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AR226-1342 DuPont-9478 TRADE SECRET Study Title 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Volume 1 of 3 Laboratory Project ID: DuPont-9478 Te s t Gu id e l in e s : U.S. EPA Health Effects Test Guidelines OPPTS 870.3100 (1998) Au t h o r : Gregory S. Ladies, Ph.D St u d y Co m p l e t e d o n : April 1, 2003 P L :e r f o r m in g a b o r a t o r y E.I. du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 W o r k Re q u e s t Nu m b e r : 13690 Se r v ic e Co d e Nu m b e r : 1022 RECEIVED OPPTNCIC 2003JUL-7 10:59AM Page 1 of 967 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards except for the item documented below. None of the items listed impact the validity of the study. Test substance characterization was performed at Regional Analytical Services (RAS), Deepwater, NJ. None of the aforementioned analyses were performed under Good Laboratory Practice Standards; however, the analyses were conducted in compliance with ISO9002 regulations. All of the analyses are considered valid and sufficient for the purposes of this study. -2- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 24691 DuPont-9478 Dates of Inspections: Protocol: February 1,7, 2002 Conduct: February 12, 2002; March 26, 2002; April 1,2,25, 2002; May 14,23, 2002 Records, Reports: October 1-4,7-9,14-15,22-23,25,28, 2002; November 11-13,24-27 2002; December 16-19,22, 2002; January 12-15, 2003 Dates Findings Reported to: Study Director: October 9,15,28, 2002; November 13,27; January 14,15, 2003 Management: October 9,18, 2002; November 5,27, 2002; December 10, 2002; January 14,29, 2003 -3- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. -4- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT.........................................2 QUALITY ASSURANCE STATEMENT...................................................................................... 3 CERTIFICATION........................................................................................................................... 4 LIST OF TABLES...........................................................................................................................7 LIST OF FIGURES......................................................................................................................... 7 LIST OF APPENDICES................................................................................................................. 9 STUDY INFORMATION............................................................................................................. 10 STUDY PERSONNEL.................................................................................................................. 11 SUMMARY.................................................................................................................................. 12 INTRODUCTION......................................................................................................................... 15 OBJECTIVE.................................................................................................................................. 15 MATERIALS AND METHODS.................................................................................................. 15 A. Test Guidelines.................................................................................................................. 15 B. Test Substance................................................................................................................... 15 C. Test Species....................................................................................................................... 16 D. Animal Husbandry............................................................................................................. 16 E. Quarantine and Pretest Period........................................................................................... 17 F. Study Design..................................................................................................................... 17 G. Assignment to Groups....................................................................................................... 18 H. Dose Suspension Preparation............................................................................................ 18 I. Test Substance Administration.......................................................................................... 19 J. Test Substance Sampling................................................................................................... 19 K. Analytical Methods...........................................................................................................20 L. Body Weights....................................................................................................................21 M. Food Consumption and Food Efficiency...........................................................................21 N. Detailed Clinical Observations and Mortality...................................................................22 O. Ophthalmological Evaluations..........................................................................................22 P. Neurotoxicity Evaluations.................................................................................................22 Q. Clinical Pathology............................................................................................................ 23 R. Collection of Blood, Urine, Feces, and Tissue (Three-Month Recovery ) ........................25 S. Biochemical Measurements ............................................................................................. 25 T. Anatomic Pathology..........................................................................................................26 RESULTS AND DISCUSSION.................................................................................................... 29 ANALYTICAL EVALUATIONS................................................................................................29 A. Test Substance Stability....................................................................................................29 B. Chromatography............................................................................................................... 30 C. Homogeneity and Stability Samples.................................................................................. 30 D. Concentration Verification Samples.................................................................................32 -5- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 E. Discussion of Results........................................................................................................ 36 F. Analytical Conclusion....................................................................................................... 36 IN-LIFE TOXICOLOGY.............................................................................................................. 37 A. Dosage D ata...................................................................................................................... 37 B. Mean Body Weights and Body Weight Gains................................................................... 37 C. Food Consumption and Food Efficiency...........................................................................38 D. Clinical Observations and Mortality................................................................................. 38 E. In-Life Toxicology Conclusions........................................................................................ 39 NEUROBEHAVIORAL TOXICOLOGY....................................................................................39 A. Sensory Function Evaluations...........................................................................................39 B. Motor Activity.................................................................................................................. 39 C. Neurobehavioral Toxicity Conclusions.............................................................................40 CLINICAL PATHOLOGY...........................................................................................................40 A. Hematology/Coagulation...................................................................................................40 B. Clinical Chemistry.............................................................................................................42 C. Urinalysis.......................................................................................................................... 44 D. Plasma and Urine Fluoride................................................................................................45 E. Clinical Pathology Conclusions........................................................................................45 BIOCHEMICAL MEASUREMENTS..........................................................................................46 A. Biochemical Measurements..............................................................................................46 B. Biochemical Measurements Conclusions......................................................................... 47 ANATOMICAL PATHOLOGY...................................................................................................47 A. Mortality............................................................................................................................47 B. Organ Weight Data............................................................................................................47 C. Gross Observations........................................................................................................... 48 D. Microscopic Findings....................................................................................................... 48 E. Anatomical Pathology Conclusions ................................................................................. 50 CONCLUSIONS........................................................................................................................... 51 RECORDS AND SAMPLE STORAGE....................................................................................... 52 REFERENCES.............................................................................................................................. 53 TABLES........................................................................................................................................ 56 FIG U R E S.................................................................................................................................... 268 APPENDICES............................................................................................................................. 280 -6- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 LIST OF TABLES Page TABLE 1 SUMMARY OF DOSING MIXING AND STABILITY ANALYSES........................................................... 60 TABLE 2 MEAN DAILY DOSE VOLUMES FOR MALE RATS .................................................................................. 64 TABLE 3 MEAN DAILY DOSE VOLUMES FOR FEMALE R A T S ..............................................................................66 TABLE 4 MEAN BODY WEIGHTS OF MALE RATS .....................................................................................................68 TABLE 5 MEAN BODY WEIGHTS OF FEMALE R A T S ................................................................................................ 71 TABLE 6 MEAN BODY WEIGHT GAINS OF MALE R A T S .........................................................................................74 TABLE 7 MEAN BODY WEIGHT GAINS OF FEMALE RATS ....................................................................................77 TABLE 8 MEAN DAILY FOOD CONSUMPTION BY MALE RATS ......................................................................... 80 TABLE 9 MEAN DAILY FOOD CONSUMPTION BY FEMALE R A T S .....................................................................83 TABLE 10 MEAN DAILY FOOD EFFICIENCY OF MALE RATS................................................................................. 86 TABLE 11 MEAN DAILY FOOD EFFICIENCY OF FEMALE R A TS............................................................................89 TABLE 12 SUMMARY OF CLINICAL OBSERVATIONS FOR MALE RATS............................................................92 TABLE 13 SUMMARY OF CLINICAL OBSERVATIONS FOR FEMALE R ATS...................................................... 97 TABLE 14 SUMMARY OF OPHTHALMOLOGY OBSERVATIONS FOR MALE R A TS......................................103 TABLE 15 SUMMARY OF OPHTHALMOLOGY OBSERVATIONS FOR FEMALE RATS................................. 104 TABLE 16 PERCENT SURVIVAL OF MALE RATS....................................................................................................... 105 TABLE 17 PERCENT SURVIVAL OF FEMALE RATS................................................................................................. 106 TABLE 18 MEAN FORELIMB AND HINDLIMB GRIP STRENGTH FOR MALE RATS (MEAN OF THREE TRIALS)........................................................................................................................... 107 TABLE 19 MEAN FORELIMB AND HINDLIMB GRIP STRENGTH FOR FEMALE RATS (MEAN OF THREE TRIALS)........................................................................................................................... 108 TABLE 20 SUMMARY OF FUNCTIONAL OBSERVATION BATTERY FINDINGS FOR MALE R A TS 109 TABLE 21 SUMMARY OF FUNCTIONAL OBSERVATION BATTERY FINDINGS FOR FEMALE RATS ..110 TABLE 22 MOTOR ACTIVITY ASSESSEMENT: DURATION OF MOVEMENTS FOR MALE R A T S .......... 111 TABLE 23 MOTOR ACTIVITY ASSESSEMENT: DURATION OF MOVEMENTS FOR FEMALE RATS ...112 TABLE 24 MOTOR ACTIVITY ASSESSEMENT: NUMBER OF MOVEMENTS FOR MALE R A T S ...............113 TABLE 25 MOTOR ACTIVITY ASSESSEMENT: NUMBER OF MOVEMENTS FOR FEMALE RATS........114 TABLE 26 SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS...............................................................115 TABLE 27 SUMMARY OF HEMATOLOGY VALUES FOR FEMALE RATS......................................................... 119 TABLE 28 SUMMARY OF COAGULATION VALUES FOR MALE RATS..............................................................123 TABLE 29 SUMMARY OF COAGULATION VALUES FOR FEMALE R A T S........................................................ 123 TABLE 30 SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE R A T S..............................................124 TABLE 31 SUMMARY OF CLINICAL CHEMISTRY VALUES FOR FEMALE RATS......................................... 128 -7- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 LIST OF TABLES (CONTINUED) Page TABLE 32 SUMMARY OF URINALYSIS VALUES FOR MALE R A TS.................................................................... 132 TABLE 33 SUMMARY OF URINALYSIS VALUES FOR FEMALE RATS................................................................134 TABLE 34 SUMMARY OF PEROXISOMAL BETA-OXIDATION ACTIVITY IN MALE RATS........................ 136 TABLE 35 SUMMARY OF PEROXISOMAL BETA-OXIDATION ACTIVITY IN FEMALE R A T S...................137 TABLE 36 MEAN FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS.......................................................138 TABLE 37 MEAN FINAL BODY AND ORGAN WEIGHTS FOR FEMALE R A TS................................................. 145 TABLE 38 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS.................................................................154 TABLE 39 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS........................................................... 175 TABLE 40 INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS................................................................................ 197 TABLE 41 INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS................................................................................. 215 TABLE 42 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS........................................................................................................................ 231 TABLE 43 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS........................................................................................................................ 251 LIST OF FIGURES Page FIGURE 1 MEAN BODY WEIGHTS OF MALE RATS...................................................................................................270 FIGURE 2 MEAN BODY WEIGHTS OF FEMALE R A T S............................................................................................. 271 FIGURE 3 MEAN FORELIMB GRIP STRENGTH FOR MALE RATS........................................................................ 272 FIGURE 4 MEAN FORELIMB GRIP STRENGTH FOR FEMALE RATS.................................................................. 273 FIGURE 5 MEAN HINDLIMB GRIP STRENGTH FOR MALE RATS........................................................................ 274 FIGURE 6 MEAN HINDLIMB GRIP STRENGTH FOR FEMALE R A TS...................................................................275 FIGURE 7 MEAN TOTAL DURATION OF MOVEMENT FOR MALE RATS..........................................................276 FIGURE 8 MEAN TOTAL DURATION OF MOVEMENT FOR FEMALE R A TS.................................................... 277 FIGURE 9 MEAN TOTAL NUMBER OF MOVEMENTS FOR MALE R A T S...........................................................278 FIGURE 10 MEAN TOTAL NUMBER OF MOVEMENTS FOR FEMALE RATS.................................................. 279 -8- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 LIST OF APPENDICES Page APPENDIX A ANALYTICAL D A T A .................................................................................................................................. 282 VOLUME 2 ................................................................................................................................................................................. 294 APPENDIX B INDIVIDUAL DOSE VOLUMES.............................................................................................................. 295 APPENDIX C INDIVIDUAL BODY WEIGHTS................................................................................................................376 APPENDIX D INDIVIDUAL FOOD CONSUMPTION.................................................................................................... 411 APPENDIX E INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY D A T A ...................................... 436 APPENDIX F INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS................................................................ 478 APPENDIX G INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH.................490 APPENDIX H INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSM ENT...........................511 APPENDIX I INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS............................................. 522 APPENDIX J INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS................................................. 535 APPENDIX K INDIVIDUAL ANIMAL CLINICAL PATHOLOGY D A T A ................................................................ 548 VOLUME 3 ................................................................................................................................................................................. 622 APPENDIX L INDIVIDUAL ANIMAL BIOCHEMICAL DATA................................................................................... 651 APPENDIX M INDIVIDUAL ANIMAL BODY AND ORGAN WEIGHTS............................................................... 658 APPENDIX N INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS................................... 695 APPENDIX O INDIVIDUAL ANIMAL MICROSCOPIC OBSERVATIONS LISTING INDIVIDUAL ANIMALS AFFECTED.......................................................................................................................................................881 -9- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 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: C7F15CF=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: February 7, 2002 / (see report cover page) In-Life Initiated/Completed: February 12, 2002 / August 22, 2002 - 10 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats STUDY PERSONNEL Study Director: Gregory S. Ladies, Ph.D. Management: Scott E. Loveless, Ph.D. Janiee L. Connell, MS., B.A., C.I.H. Primary Technician: Deborah A. Vick, B.S. Analytical Chemist: Janet C. Maslanka, B.S. Management: S. Mark Kennedy, Ph.D. Clinical Pathologist: Nancy E. Everds, D.V.M. Management: Steven R. Frame, D.V.M., Ph.D. Neurobehavioral Toxicologist: Linda A. Malley, Ph.D. Management: Robert M. Parker, Ph.D. Biochemical Toxicologist: John C. O'Connor, M.S. Management: Matthew S. Bogdanffy, Ph.D. Pathologist: G. Tracy Makovee, D.V.M. Management: Steven R. Frame, D.V.M., Ph.D. Peer Review Pathologist: Steven R. Frame, D.V.M., Ph.D. Toxicology Report Preparation: Cecilia R. Kee, B.S. Brenda Tiffin Ophthalmologist: Nancy M. Bromberg, V.M.D., M.S. 6119 Massachusetts Avenue Bethesda, Maryland 20816 Statistical Analysis: John W. Green, Ph.D. Management: Janice L. Connell, MS., B.A., C.I.H. Laboratory Veterinarian: Thomas W. Mayer, D.V.M., A.C.L.A.M. DuPont-9478 - 11 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 SUMMARY Five groups of young adult male and female Crl:CD(SD)IGS BR rats were administered 8-2 Telomer B Alcohol daily by gavage at dosages of 0, 1, 5, 25, and 125 mg/kg/day for approximately 90 days. Body weights, food consumption, and clinical signs were evaluated weekly. Clinical pathology endpoints were evaluated on weeks 7, 13, and near the end of the three-month recovery period. Neurobehavioral assessments were also performed prior to dosing and during week 13. Biochemical evaluations (hepatic P-oxidation) were performed on animals after 10 and approximately 90 days of dosing and following the three-month recovery period. After approximately 90 days of dosing, 10 rats/sex/dose were sacrificed and given a gross and microscopic pathological examination. Approximately three months after the 90-day dosing period, 10 animals/sex in the control and high dose group were examined for recovery of toxic effects. A subgroup of 5 rats/sex/dose were designated as satellite bleed animals. An additional five animals/sex/dose were designated for hepatic biochemical analysis following a 10-day exposure to the test substance. The range of mean daily dose volumes of 8-2 Telomer B Alcohol administered to male rats was 1.2 to 3.0 ml. The range administered to female rats was 0.9 to 1.6 ml. In-Life Toxicology Parameters: No test substance-related mortality occurred in the study. A test substance-related, toxicologically significant increase in the incidence of striated teeth was observed in the 125 mg/kg/day male and female dose groups. On test day 77, all male and female high dose animals were placed on ground chow due to test substance-induced alterations to the teeth. There were no test substance-related, toxicologically significant alterations in body weight, body weight gain, food consumption, or food efficiency observed in any of the male or female dose groups. Neurotoxicology Parameters: No adverse changes in neurobehavioral parameters were observed in male or female rats in any dose group. Biochemical Toxicology: The rate of hepatic P-oxidation, a measure of peroxisome proliferation, was significantly increased in females administered 25 mg/kg/day 8-2 Telomer B Alcohol and in males and females administered 125 mg/kg/day 8-2 Telomer B Alcohol. Following a threemonth recovery period, the rate of hepatic P-oxidation was lower but still significantly increased in males administered 125 mg/kg/day 8-2 Telomer B Alcohol, and had returned to control levels in female rats. Clinical Pathology: Samples were collected at mid-study, at the end of treatment, and after three months of recovery for hematology, clinical chemistry, urinalysis, coagulation (end of study only), and plasma and urine fluoride (end of study and three-month recovery period). There were no toxicologically significant changes in clinical pathology parameters observed in rats dosed with up to 125 mg/kg/day 8-2 Telomer B Alcohol. Other changes during treatment or after a three-month recovery were considered treatment-related but non-adverse because the magnitude of change was small, transient, and/or in a direction not associated with toxicity. - 12 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Treatment-related changes observed in rats administered > 25 mg/kg/day included decreases in some red cell mass parameters along with reticulocytosis and increased serum cholesterol (females only). Test substance-related changes in clinical pathology of rats dosed with 125 mg/kg/day included transiently increased alkaline phosphatase (males only), increased phosphorus (males only), decreased triglycerides (males only), increased total protein and albumin, increased calcium (females only), increased urine volume (males only), and decreased urine ketone concentrations (males only). Plasma fluoride levels were significantly increased in males and females dosed with 125 mg/kg/day, but returned to control levels following three months of recovery. Urine fluoride excretion was increased in males and females dosed with > 5 mg/kg/day. After three months of recovery, urine fluoride levels in females returned to control levels, while levels in males were significantly reduced compared to those at the end of the exposure period. Anatomical Pathology: Test substance-related, toxicologically significant degeneration/disorganization of enamel organ ameloblast cells occurred in male rats administered 125 mg/kg/day 8-2 Telomer B Alcohol. A test substance-related, adverse increase in the incidence and severity of focal hepatic necrosis was observed in males administered 25 and 125 mg/kg/day. An increased incidence and severity of chronic progressive nephropathy occurred in the 125 mg/kg/day female group and was considered adverse. Test-substance related and statistically significant increases in liver weight parameters were present in males and females administered 25 or 125 mg/kg/day for approximately 90 days. The increased liver weights correlated with microscopic hepatocellular hypertrophy in the 125 mg/kg/day male dose group. Liver weight changes and microscopic hypertrophy were considered to be a physiological adaptive response to metabolism of the test substance and not adverse. Test-substance related and statistically significant increases in kidney weight parameters occurred in males and females administered 25 or 125 mg/kg/day. The increased kidney weights correlated with microscopic renal tubular hypertrophy in the 25 and 125 mg/kg/day male groups only. However, no correlative microscopic or clinical pathological evidence of renal toxicity were present. Therefore, kidney weight changes and microscopic tubular hypertrophy were not considered adverse findings. Altered colloid, a common spontaneous finding in rats, was increased in incidence and/or severity in treated male groups. This change was not associated with other findings in the thyroid gland and was also not considered an adverse finding. After three months of recovery, rats dosed with 125 mg/kg/day showed reversibility of some effects. The ameloblastic degeneration/disorganization persisted with decreased incidence and severity in the 125 mg/kg/day male group. Alterations in thyroid colloid persisted in male rats. Increased liver weight parameters and hepatocellular hypertrophy (males only) were no longer observed in the 125 mg/kg/day male and female groups. However, the incidence of hepatocellular necrosis in the 125 mg/kg/day male group increased after three months of recovery. Increased kidney weight parameters and renal tubular hypertrophy (males only) were not observed in rats sacrificed after three months of recovery. In contrast, the incidence and - 13 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 severity of chronic progressive nephropathy were increased in the 125 mg/kg/day female group following three months of recovery. In conclusion, the no-observed-effect level (NOEL)afor males was 5 mg/kg/day 8-2 Telomer B Alcohol based on the increased incidence of hepatic necrosis observed in males administered > 25 mg/kg/day. The NOEL for females was 25 mg/kg/day 8-2 Telomer B Alcohol based on the increased incidence and severity of chronic progressive nephropathy observed in females administered 125 mg/kg/day. a The NOEL for this study is defined as the highest dose at which toxicologically important effects attributable to the test substance were not detected. Thus, for this study, the NOEL is equivalent to the NOEL as defined by the United States Environmental Protection Agency (1985) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union (1994). - 14 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INTRODUCTION The test substance, 8-2 Telomer B Alcohol, is an organofluorine compound. The 1, 5, 25, and 125 mg/kg/day dose levels for this study were selected based on the toxicity observed in an 84day range finding study with 5, 25, and 125 mg/kg/day 8-2 Telomer B Alcohol and subchronic studies with similar fluorotelomer-based alcohols and perfluorooctanoic acid (PFOA). In the 8-2 Telomer B Alcohol range finder study, significantly lower mean body weights compared to control were observed in male rats administered 125 mg/kg/day. Similarly, significantly lower mean body weights compared to control were also observed in rats administered 100 mg/kg/day or greater of similar fluorotelomer-based alcohols. Significantly increased liver weights occurred in males dosed with 125 mg/kg/day 8-2 Telomer B Alcohol. Liver weights were also significantly increased compared to control in rats administered dose levels of fluorotelomerbased alcohols as low as 100 mg/kg/day. Furthermore, data suggest that the PFOA metabolite may accumulate in animals dosed with the 8-2 Telomer B Alcohol. In repeat dose studies, PFOA at doses of 10 mg/kg/day or lower produced the following effects: increased liver weights, increased hepatic cell proliferation and beta oxidation, and altered serum hormone levels.(1,2,3,4) The high-dose level of 125 mg/kg/day for this study was selected based on the reductions in body weight and increased liver weights observed in males dosed with 125 mg/kg/day 8-2 Telomer B Alcohol, as well as the ability of rats to tolerate a 100 mg/kg/day dose level in subchronic studies with similar fluorotelomer-based alcohols. The 125 mg/kg/day dose was expected to produce toxicity without excessive mortality. The low dose of 1 mg/kg/day was expected to be the no observed-effect level (NOEL), while the 5 and 25 mg/kg/day dose levels were expected to induce minimal to no toxicity. OBJECTIVE The objective of this study is to evaluate the potential subchronic toxicity and reversibility of 8-2 Telomer B Alcohol when administered by gavage to male and female rats. The oral route of administration was selected as the most efficient way to deliver an accurate dosage. MATERIALS AND METHODS A. Test Guidelines The subchronic toxicity study design complies with the United States Environmental Protection Agency (EPA), Office of Prevention, Pesticides, and Toxic Substances (OPPTS) Health Effects Test Guidelines, OPPTS 870.3100 90-Day Oral Toxicity in Rodents (Aug-1998). B. Test Substance The test substance, 8-2 Telomer B Alcohol, was supplied by the sponsor as a waxy solid with known purity (99.2%) and composition. A reserve sample of the test substance was collected and retained by Haskell Laboratory. - 15 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 C. Test Species On 29-Jan-2002, Crl:CD(SD)IGS BR rats with an assigned birth date of 31-Dec-2001 were received from Charles River Laboratories, Inc., Raleigh, North Carolina. One hundred five male and 105 female rats were received for the main study and 28 male and 28 female rats were received for the 10-day biochemical evaluation. The rat was selected because it is the species recommended in the subchronic toxicity guidelines. The Crl:CD(SD)IGS BR strain was chosen because extensive background information is available from the literature, the supplier, and previous studies at Haskell Laboratory. This species/strain is considered suitable relative to longevity and low incidence of spontaneous diseases. D. Animal Husbandry 1. Housing All rats were housed one per cage, sexes separate, in stainless steel, wire-mesh cages suspended above cage boards. Cage racks were relocated within the animal room and cages were repositioned on the racks every 2 weeks. 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%. Occasional excursions outside the acceptable ranges were minor and did not affect the study. 2. Feed and Water Tap water was provided ad libitum. All rats were fed pelleted PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 ad libitum. On test day 77, all rats in the male and female 125 mg/kg/day groups were placed on ground chow because of test substance-induced alterations to the teeth. 3. Identification An individual identification number was tattooed on the tail of each rat. The information on the cage labels included the unique 6-digit Haskell animal number and the individual identification number assigned to each rat. 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 of coliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore and fungal counts. - 16 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 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. E. Quarantine and Pretest Period Upon arrival at Haskell Laboratory, all rats were quarantined for 7 days, observed daily for any clinically apparent signs of disease or injury, and weighed 4 times. Rats designated for the subchronic toxicity and three-month recovery evaluations, and satellite bleeds were also examined by a veterinary ophthalmologist to identify animals with preexisting ocular lesions. Rats designated for the subchronic toxicity and three-month recovery evaluations were given a baseline neurobehavioral evaluation. On the basis of acceptable body weight gains and clinical observations, all surviving main study rats were released from quarantine by the laboratory animal veterinarian designee on test day -11; rats designated for the 10-day biochemical analysis were released on test day -4. F. Study Design Group Male Female I II III IV V VI VII VIII IX X Number/Group Male Female Dosagea 30 30 0 mg/kg/day (Control) 20 20 1 mg/kg/day 20 20 5 mg/kg/day 20 20 25 mg/kg/day 30 30 125 mg/kg/day a Weight/weight o f test substance (adjusted for sponsor-supplied purity of active ingredient). Each group of study animals, except those designated for the 10-day biochemical analysis, consisted of three subgroups: the first 10 rats/sex/dose were designated for evaluation of subchronic toxicity; the next 5 rats/sex/dose were designated as satellite bleed animals; and the last 10 rats/sex/dose (control and high-dose groups only) were designated as three-month recovery animals. An additional subgroup of 5 rats/sex/dose were designated for hepatic biochemical analysis following a 10-day exposure to the test substance. - 17 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Male and female rats designated for the subchronic toxicity evaluation were dosed through test days 92 (male) and 93 (female), and necropsied on test days 93 and 94, respectively. Male and female rats designated for the satellite bleeds were dosed through test day 90 and necropsied on test day 175 (85 days post dosing). Male and female rats designated for the three-month recovery evaluations were dosed through test day 90 and necropsied on test day 183 (93 days post dosing). Neurobehavioral evaluations were conducted on male and female animals designated for the subchronic toxicity evaluation and three-month recovery evaluation (predose and week 13). A clinical pathology evaluation was conducted on rats designated for the subchronic toxicity evaluation during week 7 and week 13 (prior to necropsy). Coagulation parameters and plasma and urine fluoride were not determined on week 7. Plasma and urine fluoride were determined for the three-month recovery animals on week 26. Biochemical evaluations were conducted on selected animals designated for the subchronic toxicity evaluation, the three-month recovery evaluations, and the 10-day exposure evaluation. In-life data (body weight, food consumption, clinical observations) for rats designated for the 10-day biochemical analysis were collected from these animals and are in study records. However, these data are not included in this report. G. Assignment to Groups 1. Rats Designated for the Subchronic Toxicity and Three-Month Recovery Evaluations, and Satellite Bleeds Rats were selected for study use on the basis of adequate body weight gain, freedom from any ophthalmological abnormalities or clinical signs of disease or injury, and a body weight within 20% of the mean within a sex. The selected rats were distributed by computerized, stratified randomization so that there were no statistically significant differences among group body weight means within a sex. On test day 0, prior to the start of test substance administration, 3 male rats and 3 female rats with out-of-range body weights, clinical signs, or neurobehavioral findings during pretest were replaced. Replacement rats were selected on the basis of freedom from any clinical signs of disease or injury and a body weight 20% of the mean within a sex. Due to technician error, one male control rat with an out-of-range body weight was used on study. H. Dose Suspension Preparation 8-2 Telomer B Alcohol was suspended in 0.5% aqueous methylcellulose. Dosing suspensions of the test substance were prepared twice per week up to day 48, then prepared daily through the remainder of the dosing period. - 18 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I. Test Substance Administration The test substance was administered daily to the study animals by oral gavage to achieve dosage levels of 1, 5, 25, or 125 mg/kg body weight/day, based on the most recently recorded body weight. Dose volumes for all groups were 5 mL/kg. Male and female control rats were similarly treated with 0.5% aqueous methylcellulose at the same dose volume as used in their respective high-dosage group. Based on the results of analytical analysis of a 4-day dose preparation obtained on test day 45, rats at all dose levels may not have received a full dose of test substance on test days 45, 46, 47, and 48. Subsequent analytical analysis on additional dose preparations (not administered to rats) indicated that the test day 45 results were due to a sampling error. 1. Rats Designated for the Subchronic Toxicity and Three-Month Recovery Evaluations, and Satellite Bleeds Oral administration of 8-2 Telomer B Alcohol began on test day 0, when the rats were approximately 50 days of age. Rats designated for the subchronic toxicity evaluation were dosed through test day 92 (males) or 93 (females). Rats designated for the three-month recovery evaluation and satellite bleeds were dosed through test day 90. Rats designated for recovery and satellite bleeds did not receive test substance during the recovery period. 2. Rats Designated for 10-Day Biochemical Analysis Oral administration of 8-2 Telomer B Alcohol began 7 days prior to study start when the rats were approximately 42 days of age and ended on test day 2. J. Test Substance Sampling Dosing suspensions for this study were prepared at the beginning of the study as a large volume mix to be used either for 3 or 4 days of dosing. Subsequently, on day 49 of the study, the dosing suspension preparation was changed to a small volume mix to be used for 1 day of dosing. Samples containing 8-2 Telomer B Alcohol at the concentrations of 0, 0.2, 1.0, 5.0, and 25.0 mg/mL were collected on test day -6 (large volume/3-4 day mix). These samples were analyzed to determine homogeneity/concentration verification and 5-hour room temperature stability. Samples from the same preparation at the 0.2 mg/mL level only, were collected on test day 0, after 7 days of refrigeration. These samples were analyzed to determine redispersion/concentration verification and refrigerated stability along with 5-hour room temperature stability. The refrigerated re-dispersion/concentration verification and stability for the other levels had been established during the mixing/stability study for a previous study.(5) On test days 48, 52, 56, 58, 65, and 91 (small volume/1 day mix), concentration verification samples for all levels were collected. The test day 48 preparation was not dosed to animals. On test days 42, 45, 63, and 73 (3-4 day mix), concentration verification samples for all levels were collected. Test day 63 and 73 preparations were not used for dosing the animals but for evaluation of the large volume mix (3-4 day). - 19 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 All dosing suspension samples were collected on the day the suspensions were dosed to the animals or at the established stability time for analysis. They were analyzed when received or frozen until analyzed. K. Analytical Methods 1. Dosing Solution Treatment Each dosing sample (10 mL for 0.2 mg/mL; 3 mL for other levels) was diluted to 100 mL with methanol and mixed to dissolve the 8-2 Telomer B Alcohol in the suspension. 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 0.03mg/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 0.04 mg/mL. Each sample (final dilution) had an equivalent amount matrix (3%) when analyzed, except the 0.2 mg/mL (10%). Samples submitted for analysis were analyzed the day the suspensions were received by the testing group or frozen until analyzed. 2. Chromatographic Conditions Instrument: Hewlett-Packard Model 6890 GC Column: J & W, DB-1701, 30 m, 0.32 mm ID, 1 um film thickness Injector: Split, 250C Detector: FID;250C Carrier Gas: Helium (2.1 mL/min) Split vent: 22.3 mL/min Injection Volume: 2 microliter Oven Program: Gradient Initial Temperature: 100C Initial Time: 1.00 min. Level 1 Rate: 20.0C/min. Level 1 Temperature: 260C Level 1 Time: 0.00 min. Total run time: 9.00 min. 3. Calibration and Quantitation A separate sample of 8-2 Telomer B Alcohol was obtained for 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 0.04 mg/mL. - 20 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 The ratio of the internal standard and 8-2 Telomer B Alcohol peak heights from replicate GC analysis of these solutions was 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/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 the standard criterion at Haskell Laboratory for 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 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 or the duplicate samples from the concentration verification as the baseline for comparing the corresponding stability results. L. Body Weights 1. Rats Designated for the Subchronic Toxicity and Three-Month Recovery Evaluations, and Satellite Bleeds Rats were weighed once per week during the approximately 90-day exposure phase of the study. In addition, the rats designated for neurobehavioral evaluations (functional observational battery and motor activity assessments) were weighed on the days of those observations. 2. Rats Designated for 10-Day Biochemical Analysis Rats were weighed on the first, eighth, and tenth day of test substance administration. M. Food Consumption and Food Efficiency The amount of food consumed by each rat over each weighing interval was determined throughout the study. Each feeder was weighed at the beginning and end of the interval and the final weight of the feeder and the amount of spillage from the feeder during the interval was subtracted from the initial feeder weight. From these measurements mean daily food consumption over the interval was determined. From the food consumption and body weight data the mean daily food efficiency was calculated. - 21 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 N. Detailed Clinical Observations and Mortality During the test period cage-site examinations to detect moribund or dead rats and abnormal behavior and/or appearance among rats were conducted at least twice daily, except on test day 46 only one cage-site examination was conducted. Moribund rats were sacrificed. At every weighing each rat was individually handled and examined for abnormal behavior and appearance. Detailed clinical observations in a standardized arena were also evaluated on rats designated for the subchronic toxicity and three-month recovery periods. Detailed clinical observations were not evaluated on rats designated for satellite bleeds. The detailed clinical observations included (but were not limited to) evaluation of fur, skin, eyes, mucous membranes, occurrence of secretions and excretions, autonomic nervous system activity (lacrimation, piloerection, and unusual respiratory pattern), changes in gait, posture, response to handling, presence of clonic, tonic, stereotypical, or unusual behavior. O. Ophthalmological Evaluations Two ophthalmological examinations were conducted by a veterinary ophthalmologist. Both eyes were examined by focal illumination and indirect ophthalmoscopy. The examinations were conducted under subdued lighting after mydriasis had been produced with a 1% tropicamide solution. On test day -11, prior to selection and grouping, the initial examination was performed on all main study rats received for the study. On test day 87, all surviving rats designated for the subchronic toxicity and three-month recovery evaluations were examined again. P. Neurotoxicity Evaluations 1. Sensory Motor Function Evaluation Prior to test substance administration and during week 13 of test substance administration, assessments of responses to approach/touch, sharp auditory stimulus, and tail pinch were made while the animal was in a standard arena. These assessments were conducted on the 10 animals per group designated for recovery from the control and high-dose groups, and on the 10 animals per group designated for subchronic toxicity from the low-dose and mid-dose groups. Fore- and hindlimb grip strength were measured by a strain gauge device (Chatillon Digital Force gauge). Pupillary constriction was measured immediately prior to removing the rats from the motor activity chambers (Section 2. below) because the darkened room in which the apparatus was located facilitated observing the response. The presence or absence of pupillary constriction was assessed after a beam of light was directed into each eye. For all these assessments, the experimenter was unaware of the group designation of the animal. 2. Motor Activity Following the evaluation of grip strength and sensory function, assessment of motor activity (MA) was conducted. Rats were individually tested in 1 of 30 nominally identical, automated - 22 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 activity monitors (Coulbourn Infrared Motor Activity System). Group and sex were counterbalanced across the monitors and time of day to the fullest extent possible. The infrared monitoring device enables measurement of 2 dependent variables: duration of movement and number of movements. A continuous movement was counted as 1 movement regardless of duration. Each test session was 60 minutes in duration, and the results were expressed for the total session as well as for 6 successive 10-minute blocks. Presence of defecation and urination on the cageboards below the motor activity monitor were also recorded following each motor activity session. 3. Test Facility Positive Control Data Data on the effects of acrylamide, carbaryl, d-amphetamine, and trimethyltin are described in four separate reports.(6,7,8,9) These positive control studies are the basis of training certification for the individuals making judgments in the neurobehavioral and neuropathology tests. The data also document that the equipment and procedures are capable of detecting effects that may be seen in neurotoxicity studies of this type. Q. Clinical Pathology A clinical pathology evaluation was conducted on all rats designated for subchronic toxicity on test days 48/49 and 93/94 in males and females, respectively. The day before collection of samples for the clinical pathology evaluation the animals were placed in metabolism cages. These animals were fasted overnight (approximately 15-17 hours) and urine was collected from each animal. Blood samples for hematology and clinical chemistry measurements were collected from the orbital sinus of each animal while the animal was under light carbon dioxide anesthesia. Blood samples for coagulation parameters and fluoride analysis were collected at sacrifice from the abdominal vena cava of each animal while the animal was under carbon dioxide anesthesia. Additional blood collected from the vena cava was placed in a serum tube, processed to serum, and frozen at -80C. Serum was discarded without analysis, however, because further tests were not required to support experimental findings. Bone marrow smears were prepared at the final sacrifice from all surviving animals. Bone marrow smears were stained with Wright's stain and coverslipped, but analysis was not necessary to support experimental findings. At the end of a 3-month recovery period, samples for hematology, clinical chemistry, urinalysis, and plasma and urine fluoride were collected and analyzed from rats designated for recovery. 1. Hematology and Coagulation Blood samples were evaluated for quality by visual examination prior to analysis. Complete blood counts, including reticulocytes, were determined on a Bayer Advia 120 hematology analyzer or determined from microscopic evaluation of the blood smear. Wright-stained blood smears from all animals were examined microscopically for confirmation of automated results and evaluation of cellular morphology. Blood smears, stained with new methylene blue, were prepared from each animal undergoing a hematology evaluation but were not needed for examination. Coagulation times were determined on a Sysmex CA-1000 Coagulation Analyzer. - 23 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 The following hematology and coagulation parameters were determined: red blood cell count hemoglobin hematocrit mean corpuscular volume mean corpuscular hemoglobin mean corpuscular hemoglobin concentration red cell distribution width absolute reticulocyte count platelet count white blood cell count differential white blood cell count microscopic blood smear examination prothrombin time activated partial thromboplastin time 2. Clinical Chemistry Serum clinical chemistry parameters were determined on a Roche Diagnostics (BMC)/Hitachi 717 clinical chemistry analyzer. Plasma fluorides were determined using a phi12 pH meter and a fluoride-selective electrode. The following clinical chemistry parameters were determined: aspartate aminotransferase alanine aminotransferase sorbitol dehydrogenase alkaline phosphatase total bilirubin urea nitrogen creatinine cholesterol triglycerides glucose total protein albumin globulin calcium inorganic phosphorus sodium potassium chloride fluoridea 3. Urinalysis Urine volume and appearance (quality, color, and clarity) were measured and evaluated visually, respectively. Urine constituents were semi-quantitatively measured on a Bayer Clinitek AtlasTM Automated Urine Chemistry analyzer. Urine protein was measured on a Roche Diagnostics (BMC)/Hitachi717 clinical chemistry analyzer. Urine osmolality was determined using an Advanced Osmometer 3900. Urine fluorides were determined using a phi12 pH meter and a fluoride-selective electrode. Sediments from all urine specimens were evaluated microscopically. a Fluoride determination was analyzed on EDTA plasma. - 24 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats The following urinalysis parameters were determined: quality color clarity volume osmolality pH glucose ketone bilirubin blood urobilinogen fluoridea protein microscopic urine sediment examination DuPont-9478 R. Collection of Blood and Tissue (Three-Month Recovery ) Blood was collected from animals (5 animals/sex/group) designated as satellite bleeds during the 90-day dosing period and recovery period and stored for possible analysis of parent compound and metabolites. Blood collection time points were: prior to dosing (test day -7), and days 0, 4, 10, 21, 35, 56, 77, 90, 94, 98, 105, 119, 133, 154, and 175. Blood (approximately 0.6 mL) was collected from the orbital sinus of designated animals while under light carbon dioxide anesthesia. On the day of blood collection, blood was collected from the animals approximately 2 hours ( 30 minutes) after dosing. For each bleeding, blood was collected at approximately the same time of day. The blood was collected in plastic tubes containing EDTA while on ice. The blood from each animal was then separated into plasma and red blood cells. The separated plasma samples were stored frozen at -80C and red blood cells were discarded. After the final bleeding (day 175), all animals were euthanatized by carbon dioxide asphyxiation and exsanguination and liver and fat were collected, weighed, and stored at -80C. The pharmacokinetic profile of 8-2 Telomer B Alcohol may be evaluated in the future and resulting data reported separately. S. Biochemical Measurements Following 10, 93 (males) or 94 (females) days of test substance administration or after threemonths (test day 183 for males and females) of recovery, five rats from each group designated for biochemical evaluation were weighed and then euthanized by CO2anesthesia and exsanguination. At each time point, the livers were removed, weighed, and then a portion was homogenized (1 gram tissue/4 mL buffer) in homogenization buffer (50 mM Tris-HCl, 50 mM Trizma-base, 0.25 M sucrose, and 5.4 mM EDTA, pH 7.4). Hepatic peroxisomes were prepared using differential centrifugation. The resulting peroxisomal pellets were resuspended in the homogenization buffer, aliquoted, and stored between -65 and -85C until analyzed for peroxisomal P-oxidation activity. The peroxisomal suspensions were diluted to a protein concentration of approximately 0.5 mg/mL. Peroxisomal P-oxidation activity was determined using [14C]palmitoyl CoA as the substrate.(10) The protein content of the peroxisomes was determined before and after analysis by the Biorad method.(11) Final rate calculations were made using the post-assay protein concentrations. a Fluoride determination was analyzed from urine with EDTA added. - 25 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 T. Anatomic Pathology After approximately 90 days of exposure to the test substance (test days 93 and 94 for males and females, respectively), groups of 10 male and 10 female rats from the 0, 1, 5, 25, and 125 mg/kg/day groups were sacrificed and necropsied. Additional groups of 10 male and 10 female rats from the 0 and 125 mg/kg/day groups were sacrificed and necropsied approximately three months after the last exposure (test day 183) to evaluate recovery of toxic effects. In addition, groups of 5 male and 5 female rats from all groups designated for hepatic biochemical analysis were sacrificed and necropsied approximately three months after the last exposure (test day 183). Rats were euthanatized by carbon dioxide anesthesia and exsanguination. Gross examinations were performed on all male and female rats. The following tissues were collected from subchronic exposure and 3-month recovery group rats sacrificed by design, or rats that were accidentally killed. D igestive System liv e r esophagus stom ach duodenum jejunum ile u m cecum colon rectum salivary glands pancreas U rinary System k id n e y s urinary bladder C ardiovascular System heart aorta H em atopoietic System sp le e n thym us m andibular lym ph node m esenteric lym ph node bone marrow3 E ndocrine System pituitary gland thyroid gland parathyroid glands adrenal glands R espiratory System N ervous System lungs brain (in clu d in g cerebrum , trachea cerebellum , m edulla/pons) nose spinal cord (3 lev els: cervical, larynx m id-thoracic, lum bar) pharynx sciatic nerve a Bone marrow was collected with the femur and sternum. M usculoskeletal System skeletal m uscle fem ur/knee j oint sternum R eproductive System M ale testes epididym ides prostate sem inal vesicles Fem ale ovaries uterus m am m ary gland M iscellaneous skin eyes (including optic nerve) gross observations The following tissues were weighed from rats sacrificed by design in the subchronic exposure group and the 3-month recovery groups: liver, kidneys, adrenal glands, thyroid (weighed after fixation), brain, spleen, thymus, heart, ovaries, uterus, epididymides, and testes. Organ weight/final body weight and organ weight/brain weight ratios were calculated. Gross lesions which were diagnosed at necropsy and for which microscopic examination was not appropriate (e.g., fluid accumulation, ruffled fur, missing anatomic parts) were generally not collected. Gross lesions for which a microscopic diagnosis would not be additive - 26 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 (e.g., osteoarthritis, pododermatitis, chronic dermatitis of the tail, urinary calculi, and deformity of the teeth, toe, tail, or pinna) were saved but were generally not processed for microscopic evaluation. Testes, epididymides, and eyes were fixed in Bouin's solution. All other tissues were fixed in 10% neutral buffered formalin. Processed tissues were embedded in paraffin, cut at a nominal thickness of 5 micrometers, stained with hematoxylin and eosin (H&E), and examined microscopically. All collected tissues from 90-day exposure group control and 125 mg/kg/day rats, and all accidentally killed rats were processed and received a full histopathological examination. Liver and kidneys were processed from 1, 5, and 25 mg/kg/day 90-day exposure group and from all 3month recovery group male and female rats. In addition, thymus, thyroid gland, and nose from 1, 5, and 25 mg/kg/day subchronic exposure group and all 3-month recovery group male rats were processed and examined microscopically. - 27 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 U. Statistical Analyses Except for Bartlett's test (p < 0.005), significance was judged at p < 0.05. Separate analyses were performed on the data for each sex. Parameter Body Weight Body Weight Gain Food Consumption Food Efficiency h-Oxidation Organ Weight Motor Activity0 Grip Strength Foot Splay Clinical Pathologyd Survival Incidence o f Clinical Observations Incidence of Ophthalmological Observations Incidence o f FOB Descriptive Parameters Incidences o f Gross and Microscopic Lesions Preliminary Test Test for lack of trend(12) Levene's test for homogeneity(15) and Shapiro-Wilk test(16) for normalityb Levene's test for homogeneity(15) and Shapiro-Wilk test(16) for normalityb Bartlett's test(23) for homogeneity o f variances Levene's test for homogeneity1-15-1and Shapiro-Wilk test(16) for normalityb Method o f Statistical Analysis If preliminary test is not If preliminary test is significant significant Sequential application1-13-1 Preliminary tests for o f the Jonckheere-Terpstra trend test(14) pairwise comparison ORa One-way analysis of variance(17) followed with Dunnett's test(18) Kruskal-Wallis test(19) followed with Dunn's test(20) Repeated measures analysis of variance(21) followed by contrasts(22) Sequential application(13) o f the Jonckheere-Terpstra trend test(14) One-way analysis of variance(17) followed with Dunnett's test(18) Kruskal-Wallis test(19) followed with Dunn's test(20) One-way analysis of variance(17) followed with Dunnett's test(18) Kruskal-Wallis test(19) followed with Dunn's test(20) None Cochran-Armitage test for trend(17)e None None a Pairwise comparisons and associated preliminary tests were only conducted if the test for lack o f trend was significant. b If the Shapiro-Wilk test was not significant but Levene's test was significant, a robust version o f Dunnett's test was used (Dunnett/Tamhane-Dunnett). c Test day and block (10-minute EPOCH) was used as repeated-measure factors. d When an individual observation was recorded as being less than a certain value, calculations were performed on half the recorded value. For example, if bilirubin was reported as <0.1, 0.05 was used for any calculations performed with that bilirubin data. e If the incidence was not significant, but a significant lack o f fit occurred, then Fisher's Exact test(24) with a Bonferroni correction was used. - 28 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 RESULTS AND DISCUSSION ANALYTICAL EVALUATIONS Dosing suspensions for this study were prepared at the beginning of the study as large volume mixes to be used either for 3 or 4 days of dosing. Samples containing 8-2 Telomer B Alcohol at the concentrations of 0, 0.2, 1.0, 5.0, and 25.0 mg/mL were collected at the initiation of the 90day study (test day -6 for large volume/3-4 day mix). These samples were analyzed to determine homogeneity/concentration verification and 5-hour room temperature stability. Samples from the same preparation at the 0.2 mg/mL level only were collected on test day 0, after 7 days of refrigeration. These samples were analyzed to determine re-dispersion/concentration verification and refrigerated stability along with 5-hour room temperature stability. The refrigerated redispersion/concentration verification and stability for the other levels had been established during the mixing/stability study for a previous study. These data indicated that the test substance was homogeneously mixed, could be re-dispersed after refrigeration to the expected concentration, and was stable in the vehicle for 5 hours after refrigeration. On test days 42 and 45 (3-4 day mix), concentration verification samples for all levels were collected. Results from analysis of the dosing suspensions collected near the mid-point of the study (test day 42) for concentration verification indicated that test substance was marginally at the targeted concentration ( 20% of nominal). In order to investigate these results, a new large volume preparation of the dosing suspensions was made and sampled on test day 45. The results for these samples were lower than expected (range: -33.4% to -66.0% of nominal) indicating a sampling problem. Investigation of the study records showed that the correct amount of test material was contained in the preparations but that a possible technician error had occurred with the re-dispersing and sampling of the test material to the analytical group. Due to the length of time needed for evaluation of the samples, the preparations had already been dosed to the animals and further sampling could not be done to define the problem with the sampling of this mix. Therefore, due to the unexpected analytical results observed on test day 45, the following study changes were implemented: 1) on test day 49 of the study, the dosing suspension preparation was changed to small volume mix to be used for 1 day of dosing and concentration verification samples for all levels were collected on test days 48 (not dosed to animals), 52, 56, 58, 65, and 91 (small volume/1 day mix); and 2) on test day 63 and 73 large volume mixes (3-4 day) were prepared and samples were collected from all levels for evaluation of the mixing and sampling for the study before test day 45. These preparations were not used for dosing the animals. A. Test Substance Stability Samples of test substance were analyzed near the beginning and the end of the study. These analyses indicated that the test substance was stable over the course of the study. The average percent of active ingredient was 99.1% 0.81 and 101.8% 2.9 for the samples analyzed on February 15, 2002, and May 30, 2002, respectively.(25) 8-2 Telomer B Alcohol was reported by - 29 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 the sponsor to have 99.2% active ingredient. The differences in values between the sponsor reported purity and the experimental data represent analytical variability. B. Chromatography 8-2 Telomer B Alcohol eluted from the GC column as resolved peak with a retention time of approximately 3.5 minutes. The internal standard eluted from the GC column as a resolved peak with a retention time of approximately 3.9 minutes. Representative GC chromatograms are shown in Appendix A, Figures 2(a - c). Test substance was not detected in the 0 mg/mL control. C. Homogeneity and Stability Samples Analytical results from dosing suspensions collected on test day -6 and test day 0 and analyzed for homogeneity and/or concentration verification and stability are shown in Appendix A, Table I and Summary Table 1. The following table summarizes the results for all homogeneity and/or concentration verification and stability analyses. Test Day Sample Type Test Day -6 Homogeneity Test Day 0 Stability 7 Day Refrigerated Nominal mg/mL 0 0.2 1.0 5.0 25 0 0.2f Measured T,M,Ba mg/mL NDd 0.163, 0.164, 0.161 0.803, 0.857, 0.890 4.55, 4.80, 4.61 19.9d, 21.9, 22.9 NDd 0.161, 0.173 Mean (T,M,B) % Nominal --81.5 85.0 93.0 86.4 --83.5 C.V.b (%) --1 5 3 7 --5 a. Mean results for the analysis of the top (T), middle (M), and bottom (B) samples. b. C.V. = Coefficient of Variation c. Samples held 5 hours at room temperature. d. Denotes none detected. e. Duplicate re-analysis of the original sample supports the original result and are not reported. f. Mean results for the analysis of duplicate concentration verification samples. Stability0 % Nominal --83.5 81.8 82.8 87.2 --79.0e The data for samples collected on test day -6 indicates that the test substance was homogeneously mixed in the vehicle at all levels (C.V.'s = 1, 5, 3 and 7, respectively). The test substance was at the targeted concentration in the samples ( 18.5% of nominal) and was stable in the vehicle when held 5 hours at room temperature. The data for 0.2 mg/mL sample collected on test day 0 after 7 days of refrigeration indicates that the test substance was homogeneously re-suspended in the vehicle (C.V. = 5). The test substance was at the targeted concentration ( 16.5% of nominal) and stable in the vehicle when held refrigerated for 7 days followed by 5 hours at room temperature. The 5-hour sample analyzed at - 30 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 79.0% of nominal appeared to be lower than expected but this can be attributed to sampling and analytical variability and not stability of the test material in the vehicle. All other concentrations in the study had been shown to be homogeneously mixed and stable in the vehicle after 7 days of refrigeration followed by 5 hours at room temperature in the mixing/stability study.(5) The following table from this study is included. Test Day Nominal Measured T,M,Ba Mean (T,M,B) C.V. Stability0 Sample Type mg/mL mg/mL % Nominal (%) % Nominal Test Day 4 Homogeneity Test Day 11 Stability 7 Day Refrigeratedf 0 1.0 5.0 25 0 1.0 5.0 25 NDc 0.944, 0.884, 0.836d 4.43, 4.37, 4.72d 22.2, 22.7, 24.2 NDc 0.900, 0.864, 0.859 4.46, 4.44 24.2, 23.9 -- 88.8 90.2 92.0 -- 87.4 89.0 96.4 ---- 6 85.4e 4 95.0 5 96.0 ---- 3 90.4g 0 84.2g 1 84.8g a Mean results for the analysis of the top (T), middle (M) and bottom (B) samples. b Samples held 5 hours at room temperature. c Denotes none detected. d Mean result of all analyses reported. e Mean result of all analyses reported except for one duplicate repeat sample which was low due to aliquot error. f Duplicate concentration verification samples analyzed except for the 1.0 mg/mL level (homogeneity). g Mean result of duplicate re-sampling from the original diluted sample. Original analysis was lower than expected due to aliquot error and not reported. - 31 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 D. Concentration Verification Samples Analytical results from dosing suspensions prepared test days 42, 45, 48, 52, 56, 58, 65, and 91 and analyzed for concentration verification are shown in Appendix A, Table II and Summary Table 1. The following table summarizes the results for concentration verification analyses of the 8-2 Telomer B Alcohol sample preparations for the above test days 42 and 45 (3/4-day mix), that were dosed to the animals. P rep a ra tio n N om inal M easured3 A verage CV Day m g/m L m g/m L % N om inal % Test D ay 42 0 .2 b 0.156, 0.169 81.5 6 1.0b 0.749, 0.776 76.3 3 5.0 3 .8 7 b, 3 .9 1 c 7 7 .8 1 2 5 .0 c 19.4, 19.1 7 7 .2 1 Test D ay 45 0 .2 b 0.0 6 6 , 0.083 37.5 13 1.0b 5 .0 b 0.676, 0.656 2.20, 2.32 6 6 .6 4 5 .2 2 4 2 5 .0b 8.34, 8.64 3 4 .0 3 a Duplicate samples per level were analyzed. C.V. calculated to verify uniformity of mixture. b Mean result of the original analysis and duplicate reanalysis of the original sample. c Mean result of duplicate re-sampling from the original diluted sample. Original analysis was lower than expected due to aliquot error and not reported. Results from analysis of the dosing suspensions collected on test day 42 for concentration verification indicated that test substance was marginally acceptable (-23.7% of nominal). Therefore, to investigate these results, a new large volume preparation (3/4-day mix) of the dosing suspensions was made and sampled on test day 45. The results for these samples were lower than expected (range: -33.4% to -66.0% of nominal) based on previously analyzed samples for the study. Additional work was then done to investigate whether the results for test day 45 were unique to the sampling for the analytical group. This involved the preparation of two large volume dose suspensions (3-4 day mixes) on test days 63 and 73 to be used only for analysis to verify the mixing and sampling procedures of the large volume dose preparations. These suspensions were not dosed to the animals. On test day 49 the dose suspensions were prepared daily for the remainder of the study. - 32 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 The following table summarizes the results for concentration verification analyses of the 8-2 Telomer B Alcohol sample preparations for the test days 48 (not dosed to animals), and 52, 56, 58, 65, and 91 (1-day mixes) that were dosed to the animals. P rep a ra tio n Day Test D ay 48b N om inal m g/m L 0.2 1.0 5.0 2 5 .0 M easured3 m g/m L 0.197, 0.219 0.865, 0.948 3.93, 3.90 2 1 .9 , 22.5 A verage % N om inal 1 0 4 .0 9 0 .7 78.3 88.8 CV % 7 6 1 2 Test D ay 52 0.2 1.0 5.0 2 5 .0 0.174, 0.184 0.8 4 5 , 0.895 4.22, 4.16 2 3 .5 , 22.3 89.5 8 7 .0 83.8 9 1 .6 4 4 1 4 Test D ay 56 0.2 1.0 5.0 2 5 .0 0.167, 0.189 0.964, 0.950 4 .4 1 , 4.31 22.8, 21.4 8 9 .0 9 5 .7 8 7 .2 8 8 .4 9 1 2 4 Test D ay 58 0.2 1.0 5.0 2 5 .0 0.174, 0.150 0.945, 0.937 4.48, 4.17 2 2 .5 , 22.1 8 1 .0 94.1 86.5 8 9 .2 10 1 5 1 T est D ay 65 0 .2 c 1.0 5.0 2 5 .0 0.159, 0.150 0.832, 0.898 4.32, 4.40 2 0 .8 , 20.5 77.5 86.5 8 7 .2 8 2 .6 4 5 1 1 T est D ay 91 0.2 0.1 6 2 , 0.165 8 2 .0 1 1.0 5 .0 c 0 .7 6 0 c, 0 .8 6 3 3.96, 3.90 8 1 .2 7 8 .6 9 1 2 5 .0 c 19.9, 18.7 7 7 .2 4 a Duplicate samples per level were analyzed. C.V. calculated to verify uniformity o f mixture. b Suspensions not dosed to animals. c Mean result o f the original analysis and duplicate reanalysis o f the original sample. Because of the results from test day 45, samples were collected from the daily mixes to verify concentration on test day 48 (not dosed to animals), 52, 56, 58, 65, and 91. With the exception of four samples, results from these analyses indicated that the dosing suspensions were at the targeted concentrations ( 20% of nominal). On test day 48, the result for the 5.0 mg/mL level was marginally acceptable at 78.3% of nominal. On test day 65, the result for the 0.20 mg/mL level was marginally acceptable at 77.5% of nominal. On test day 91, the result for the 5.0 mg/mL and the 25.0 mg/mL levels were marginally acceptable at 78.6% and 77.2% of nominal, respectively. - 33 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Based on the statistics (mean % of nominal) for all samples analyzed for the daily mixing, it can be concluded that the dosing suspensions contained the targeted amount of 8-2 Telomer B Alcohol during the period from test day 48 (not dosed to animals) until the end for the study. The following table shows the mean % of nominal for all analyzed samples at each concentration for the daily preparations and the average of the mean % of nominal, with the SD, and the CV based on this average for all the levels analyzed. Statistics for all Samples Analyzed for Small Volume Mix (1-day) Nominal Mean mg/mL 0 % Nominal --- 0.20 87.2 1.0 89.2 5.0 83.6 25 86.3 Mean: 86.6 SD 2.3 CV 3% On test day 63 and 73, dose preparations (3-4 day/large volume) were prepared but used only for verification of mixing and sampling procedures on the large volume dose preparation. These suspensions were not dosed to the animals. The following table summarizes the results for concentration verification analysis for these preparations. Preparation Day Test Day 63 Nominal mg/mL 0.2 1.0 5.0 25.0 Measureda mg/mL 0.190, 0.192 0.784, 0.792 4.12, 4.08 23.0, 21.4 Average % Nominal 95.5 78.8 82.0 88.8 CV % 1 1 1 5 Test Day 73 0.2 0.176, 0.155 82.8 9 1.0 0.980, 1.03 101.0 4 5.0 4.57, 4.60 91.8 0.4 25.0 23.3, 24.4 95.6 3 a. Duplicate samples per level were analyzed. C.V. calculated to verify uniformity of mixture. With the exception of one sample, results from these analyses indicated that the dosing suspensions were at the targeted concentrations ( 20% of nominal). On test day 63, the result for the 1.0 mg/mL level was marginally acceptable at 78.8% of nominal. Neither of these preparations were dosed to the animals but the results were used as statistical data along with the results from the previously dosed large volume preparations (test days -6, 42, and 45) to show that the dosing suspensions contained the targeted amount of test substance before test day 45 - 34 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 and that the results for that day were due to technician error while sampling for the Analytical group. Based on the statistics (mean % of nominal) for all samples analyzed for a 3-4-day preparation (large volume), it can be concluded that the dosing suspensions contained the targeted amount of 8-2 Telomer B Alcohol during the period from the initial sampling (test day -6) for the study until test day 45. The following table shows the mean % of nominal for all analyzed samples at each concentration and the average of the mean % of nominal, with the SD, and the CV based on this average for all the levels analyzed. Included are the two preparations (test day 63 and 73) that were not dosed to animals but prepared only to evaluate the mixing and sampling process. The table includes results (a) with test day 45 and (b) excluding test day 45. Statistics for all Samples Analyzed for Large Volume Mix (3-4-day) Nominal mg/mL Mean % Nominal (a) 0-- 0.20 75.8 1.0 81.5 5.0 78.0 25 76.4 Mean: 77.9 SD 2.6 CV 3% (b) 0-- 0.20 85.3 1.0 85.3 5.0 86.2 25 87.0 Mean: SD CV 85.9 0.8 1% The statistics for the large volume dose preparations with the exclusion of the test day 45 indicate that the samples were at the targeted concentrations having a mean % of nominal 85.9% 0.8, and a CV of 1%. Although the statistics based on all large volume preparations are marginally acceptable with the inclusion of test day 45 (77.9% of nominal), the test day 45 sample analysis should not be considered as part of the dose verification samples for the study and should be excluded from these statistics because: 1) previous analysis on large volume mixes indicated no problem; 2) the study notebook dose preparation sheet shows that the correct amount of test substance was present at each dosing level for the preparation, and 3) subsequently, that in sampling and analyzing the two large volume preparations after test day 45 (test days 63 and 73), the test material was dispersed properly and at the targeted concentrations. - 35 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Test substance was not found in the 0 mg/mL samples. E. Discussion of Results Based on the statistics (mean % of nominal) for all sample sets analyzed for the study and dosed to the animals, it can be concluded that the dosing suspensions contained marginally the targeted amount ( 20% of nominal) of 8-2 Telomer B Alcohol with test day 45 included and the targeted amount ( 20% of nominal) of 8-2 Telomer B Alcohol with test day 45 excluded. The following table shows the mean % of nominal for all analyzed samples at each concentration and the average of the mean % of nominal, with the SD, and the CV based on this average for all the levels analyzed (a) including test day 45 and (b) excluding test day 45. Statistics for all Samples Analyzed and Dosed to Animals Nominal Mean mg/mL % Nominal (a) 0-- 0.20 77.4 1.0 84.1 5.0 79.9 25 78.3 Mean: 79.9 SD 2.9 CV 4% (b) 0-- 0.20 83.1 1.0 86.5 5.0 84.9 25 84.9 Mean: 84.8 SD 1.4 CV 2% F. Analytical Conclusion Results from the analysis of the 8-2 Telomer B Alcohol dosing suspensions prior to the study start, at the initiation of the study, for the daily dose preparations after test day 45, and including the additional large volume dose preparation on test days 63 and 73 (not dosed to the animals) indicated that the test substance was homogeneously mixed, at the targeted concentrations and stable in the vehicle under the conditions of the study. Furthermore, the study records indicate that the correct amount of test substance was contained in the test day 45 dosing suspensions. Taken together, these data point to a problem unique to the analytical samples that were collected on test day 45. - 36 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 IN-LIFE TOXICOLOGY A. Dosage Data (Tables 2-3, Appendix B) Rats were dosed with suspensions of 8-2 Telomer B Alcohol in 0.5% aqueous methylcellulose, prepared at concentrations of 0, 0.2, 1, 5, and 25 mg/mL, designed to deliver the targeted dose of test substance at a dosing volume of 5 ml/kg body weight. The quantity of 8-2 Telomer B Alcohol administered to each rat was calculated, based on the most recent body weight for each rat, and subsequently rounded by a computer program. The range of mean daily dose volumes administered to male rats was 1.2-2.9 mL for the control group, 1.2-2.8 mL for the 1 mg/kg/day group, 1.2-3.0 mL for the 5 mg/kg/day group, 1.2-3.0 mL for the 25 mg/kg/day group, and 1.2-2.8 mL for the 125 mg/kg/day group. The range of mean daily dose volumes administered to female rats was 0.9-1.5 mL for the control group, 0.9-1.5 mL for the 1 mg/kg/day group, 0.9-1.5 mL for the 5 mg/kg/day group, 0.9-1.6 mL for the 25 mg/kg/day group, and 0.9-1.6 mL for the 125 mg/kg/day group. B. Mean Body Weights and Body Weight Gains (Tables 4-7, Figures 1-2, Appendix C) There were no test substance-related, toxicologically significant alterations in mean body weight or body weight gain observed in any of the male or female dose groups. Significant decrements of 40 and 51%, respectively, occurred in the mean body weight gain of the 25 and 125 mg/kg/day male groups during the 63-70 test day interval, while a significant increase occurred for the 125 mg/kg/day male group during the 7-14 day interval. For the 49-56 day interval, significant increases in mean body weight gain were observed for the 5 and 25 mg/kg/day male groups. On test day 77, all animals in the high-dose male and female dose groups were placed on ground chow because of test substance-induced alterations to the teeth. Once placed on ground chow, males in the 125 mg/kg/day group had a significant increase in mean body weight gain for the 84-91 test day interval. The overall (0-91 day interval) mean body weight gain of male rats, however, was similar to control across all dose levels. Over the course of the three-month recovery period, statistically significant increases in mean body weight gain occurred for the 125 mg/kg/day male group. Overall mean body weight gain for the three-month recovery period for the 125 mg/kg/day male group was significantly increased 36% compared to control. During the 77-84 test day interval, females in the 125 mg/kg/day dose group had a significant increase in mean body weight gain following their placement on ground chow. For the overall interval (0-91 days), the mean body weight gain for females was similar to control across all dose levels. A significant increase in mean body weight gain occurred for the 25 mg/kg/day female group during the 154-161 test day interval. Statistically significant increases and decreases in mean body weight gain also occasionally occurred over the three-month recovery period for the 125 mg/kg/day female group; however, the mean body weight gain for all female dose groups was similar to control for the overall recovery interval. - 37 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 C. Food Consumption and Food Efficiency (Tables 8-11, Appendix D) There were no test substance-related, toxicologically significant alterations in food consumption observed in any of the male or female dose groups. For the 98-105 and 105-112 test day intervals, males in the 125 mg/kg/day three month recovery group had statistically significant and lower food consumption of 9 and 10%, respectively. Overall (91-182 day interval), however, food consumption for the 125 mg/kg/day male three-month recovery group was similar to control. There were no test substance-related, toxicologically significant alterations in mean daily food efficiency observed in any of the male or female dose groups. Male rats in the 125 mg/kg/day group had several incidences of significantly higher mean daily food efficiency compared to control over the course of the study except during the 63-70 day interval in which significantly lower (59% compared to control) mean daily food efficiency was observed. Males in the 25 mg/kg/day dose group also had a significantly lower mean daily food efficiency of 42% during the 63-70 test day interval. Following the replacement of pelleted chow with ground chow on test day 77 for the 125 mg/kg/day male group, a significantly higher mean daily food efficiency was observed for the 84-91 day interval. For the 0-91 day study interval, however, mean daily food efficiency for male rats was similar to control, while for the overall three-month recovery interval, mean daily food efficiency was significantly increased 26% compared to control for the 125 mg/kg/day male group. Female rats in the 125 mg/kg/day group had significantly lower (60%) mean daily food efficiency during the 63-70 day interval. Following the replacement of pelleted chow with ground chow on test day 77 for the 125 mg/kg/day female group, a significantly higher mean daily food efficiency was observed for the 77-84 day interval. Overall mean daily food efficiencies for test-substance treated female groups, however, were similar to control. During the three-month recovery (test days 154-161), females in the 125 mg/kg/day group had a significant increase in mean daily food efficiency; however, for the overall three month recovery interval, mean daily food efficiency was similar to control. D. Clinical Observations and Mortality (Tables 12-17, Appendix E-F) A test substance-related, toxicologically significant increase in the incidence of striated teeth was observed in the 125 mg/kg/day male and female dose groups. In addition, there was an increase in tooth clipping required for both males and females in the 125 mg/kg/day dose group. No test substance-related ophthalmological signs of toxicity or effects on survival were observed. - 38 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 E. In-Life Toxicology Conclusions Under the conditions of this study, the NOEL for in-life toxicology parameters (body weight, body weight gain, food consumption, food efficiency, and clinical signs of toxicity) was 25 mg/kg/day for both males and females based on the increased incidence of striated teeth observed in male and female rats administered 125 mg/kg/day. NEUROBEHAVIORAL TOXICOLOGY A. Sensory Function Evaluations 1. Forelimb Grip Strength (Table 18-19, Figures 3-4, Appendix G) There were no test substance-related effects on forelimb grip strength in males or females administered any dosage of 8-2 Telomer B Alcohol. During the baseline evaluation, females in the 5 mg/kg/day group had significantly increased forelimb grip strength. However, since administration of the test material had not been initiated, this statistical difference was not test substance related. There were no statistically significant differences for males administered any dosage of the test material. 2. Hindlimb Grip Strength (Table 18-19, Figures 5-6, Appendix G) There were no test substance-related effects or statistically significant differences in hindlimb grip strength for either males or females administered any dosage of 8-2 Telomer B Alcohol. 3. Sensory Function Observation (Table 20-21, Appendix H) There were no test substance-related changes or statistically significant differences in neurobehavioral parameters in males or females administered any dosage of 8-2 Telomer B Alcohol. B. Motor Activity (Tables 22-25, Figures 7-10, Appendices I-J) There were no test substance-related effects on duration of movement or number of movements for males or females for any dosage of 8-2 Telomer B Alcohol. During the third 10-minute interval for the baseline evaluation, males in the 1 mg/kg/day group had significantly higher duration of movement compared to the control value. During the fourth 10-minute interval of the baseline evaluation, males in the 1, 5, 25, and 125 mg/kg/day groups had significantly higher duration of movement compared to the control value. During the fifth 10-minute interval of the baseline evaluation, males in the 5 mg/kg/day group had significantly higher duration of - 39 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 movement compared to the control value. However, since administration of the test material had not been initiated, these statistical differences were not test substance related. During the fifth 10-minute interval for the 13-week evaluation, duration of movement for 25 mg/kg/day males was significantly lower compared to the control value. However, since duration of movement was similar to control for 125 mg/kg/males, the statistically lower value for the 25 mg/kg/day males was not considered to be test substance-related. During the fourth 10-minute interval for the baseline evaluation, number of movements for 1, 5, and 25 mg/kg/day males was significantly higher than the control value. In addition, during the fifth 10-minute interval for the baseline evaluation, number of movements for 5 mg/kg/day males was significantly higher than the control value. However, since administration of the test material had not been initiated, these statistical differences were not test substance related. Total number of movements and the number of movements during the fifth 10-minute interval of the 13-week evaluation were significantly lower for 25 mg/kg/day males compared to the control value. However, since number of movements for 125 mg/kg/day males was similar to control, these statistical differences were not considered to be test substance related. Number of movements for 125 mg/kg/day males during the fourth 10-minute interval for the 13-week evaluation was significantly lower compared to the control value. However, since the total number of movements was similar to the control value, the statistically lower value for 125 mg/kg/day males was not considered to be test substance related. There were no statistically significant differences for females administered any dosage of the test material. C. Neurobehavioral Toxicity Conclusions Under the conditions of the study, the NOEL for neurobehavioral parameters was 125 mg/kg/day of 8-2 Telomer B Alcohol in males and females, the highest concentration tested. CLINICAL PATHOLOGY A. Hematology/Coagulation (Tables 26-29, Appendix K) There were no adverse changes in hematologic parameters in male or female rats at either time point during treatment. The following statistically significant changes in mean hematologic parameters were considered to be non-adverse. Red cell mass (red cell count, hemoglobin, hematocrit) was minimally decreased in males and females dosed with 125 mg/kg/day (at both time points during treatment, variable statistical significance for males) (Clinical Pathology Text Table 1). Decreased red cell mass was associated with regeneration of red cells (increased reticulocytes) in males (statistically significant only at 125 mg/kg/day, test days 48 and 93) and females (statistically significant at - 40 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 test day 94 only). Increased reticulocytes resulted in increased red cell distribution width and mean cell volume (variable statistical significance). However, histologically, there was no increase in extramedullary hematopoiesis. Red cell counts (males) and hematocrits (females) were minimally but statistically decreased in rats dosed with 25 mg/kg/day. These changes were sometimes associated with minimal increases in red cell distribution width and mean cell volume (variable statistical significance). In addition, minimally increased changes in red cell morphology (acanthocytes) were present in males dosed with 25 or 125 mg/kg/day at both time-points during treatment. The above changes in red cell parameters were considered to be related to treatment, and indicate minimally increased red cell turnover. However, due to the minimal nature of the changes, they were considered to be non-adverse. After approximately 90 days of recovery, red cell mass parameters, reticulocytes, red cell distribution width, and mean cell volume were similar to control group values of rats previously dosed with 125 mg/kg/day. Minimally increased mean corpuscular hemoglobin in males dosed with 125 mg/kg/day at test day 93 was considered to be possibly related to treatment, but was considered to be non adverse because minimal increases in mean corpuscular hemoglobin are not associated with adverse effects. After approximately 90 days of recovery, mean corpuscular hemoglobin concentrations were similar to control group values of rats previously dosed with 125 mg/kg/day. The following statistically significant changes in mean clinical chemistry parameters were considered to be non-adverse because they were unrelated to dose and/or occurred only at three months post dosing: Minimally and transiently decreased reticulocytes in females dosed with 25 mg/kg/day at test day 49. Minimally increased basophils in females previously dosed with 125 mg/kg/day after approximately 90 days of recovery. - 41 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Clinical Pathology Text Table 1: Red cell mass parameters and reticulocytes (expressed as a percent of control group mean)* M ales F em ales D osage (m g/kg/day): 1 5 25 125 1 5 25 125 Test Day RBC 4 8 /4 9 99% 98% 95% 93% 9 3 /9 4 100% 97% 95% 91% 183 -- -- -- 96% HGB 4 8 /4 9 101% 100% 98% 96% 9 3 /9 4 100% 98% 98% 94% 183 -- -- -- 98% HCT 4 8 /4 9 100% 100% 97% 96% 9 3 /9 4 101% 99% 98% 95% 183 -- -- -- 97% ARET 4 8 /4 9 97% 111% 113% 123% 9 3 /9 4 92% 108% 112% 126% 183 -- -- -- 105% * Statistical significance indicated by bold italicized type 98% 100% -- 99% 102% -- 98% 101% -- 88% 98% -- 98% 102% -- 99% 102% -- 99% 102% -- 97% 110% -- 97% 91% 98% 93% -- 100% 96% 91% 98% 94% -- 103% 96% 91% 97% 94% -- 103% 85% 94% 99% 125% -- 107% B. Clinical Chemistry (Tables 30-31, Appendix K) There were no adverse changes in clinical chemistry parameters in male or female rats. The following statistically significant changes in mean clinical chemistry parameters were not toxicologically significant (i.e., not adverse) or not related to exposure to test substance: Alkaline phosphatase activity was minimally and transiently increased in males dosed with 125 mg/kg/day at test day 48. At the end of dosing (test day 93), alkaline phosphatase activity was more similar to controls, although it was still minimally increased (not statistically significant). Increased alkaline phosphatase can be due to induction by a xenobiotic compound or can be due to increased biliary pressure. In this study, males dosed with 125 mg/kg/day had both increased liver weights and histologic evidence of hypertrophy, but no evidence of cholestasis. Therefore, in this study, increased alkaline phosphatase activity was probably due to induction by the test substance. Increased alkaline phosphatase activity was considered to be non-adverse because minimally increased alkaline phosphatase is not associated with adverse effects. After approximately 90 days of recovery, alkaline phosphatase activities were similar to control group values in rats previously dosed with 125 mg/kg/day. - 42 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Cholesterol was mildly increased in females dosed with 25 or 125 mg/kg/day (variable statistical significance) at test days 49 and 94 (group means were 136% to 139% of control group means). Although this change was likely due to treatment, mildly increased cholesterol does not result in adverse events. Therefore, this change was considered to be non-adverse. After approximately 90 days of recovery, cholesterol concentrations were similar to control group values in females previously dosed with 125 mg/kg/day. Triglycerides were mildly decreased in males dosed with 125 mg/kg/day at test days 48 and 93 (49 and 48% of control group means, respectively). Mildly decreased triglycerides were considered to be related to treatment; however, mildly decreased triglycerides are not associated with adverse effects, and therefore were considered non-adverse. After approximately 90 days of recovery, triglyceride concentrations were similar to control group values in males previously dosed with 125 mg/kg/day. Total protein was mildly increased due to increased albumin in males and females dosed with 125 mg/kg/day at days 48/49 and 93/94. Mildly increased total protein and albumin concentrations were likely due to treatment, but were considered to be non-adverse because mild increases in these parameters are not associated with adverse effects. After approximately 90 days of recovery, protein concentrations were similar to control group values in rats previously dosed with 125 mg/kg/day. Calcium was increased in females dosed with 125 mg/kg/day at test day 94. The increased calcium was considered to be secondary to increased albumin. Calcium exists in serum in two forms, either bound to albumin or unbound ("ionized" calcium). Ionized calcium is the physiologically active form and is tightly regulated. Increases in albumin are necessarily associated with physiologically appropriate increased bound calcium, with resultant increased total calcium. However, ionized calcium is unaffected. Therefore, this change was considered to be non-adverse. After approximately 90 days of recovery, calcium concentrations were similar to control group values in rats previously dosed with 125 mg/kg/day. Phosphorus was minimally increased in males dosed with 125 mg/kg/day at test day 48 and 93, and at the end of recovery (test day 183). Increased phosphorus was possibly due to treatment at test day 48 and 93, but was likely to be unrelated to treatment at test day 183 (after three months of recovery). Increased phosphorus is of toxicologic significance when it is associated with evidence of decreased glomerular filtration rate, but may also be affected by extrarenal factors. In this study, other indicators of glomerular filtration rate (urea nitrogen and creatinine) were unaffected by treatment. Anatomic pathology changes included increased kidney weights associated with renal tubular hypertrophy; these changes were not present after three months of recovery. However, these anatomic pathology changes are not expected to result in decreased glomerular filtration rates. Therefore, the minimally increased phosphorus was considered to be non-adverse. - 43 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 The following statistically significant changes in mean clinical chemistry parameters were considered to be non-adverse because they were unrelated to dose and/or occurred only at three months post-dosing: Decreased bilirubin in males dosed with 1 mg/kg/day at test days 48 and 93 Decreased cholesterol in males dosed with 25 mg/kg/day at test day 48 Increased urea nitrogen in males dosed with 25 mg/kg/day at test day 93 Decreased urea nitrogen and creatinine in males previously dosed with 125 mg/kg/day at recovery test day 183 Decreased cholesterol in males dosed with 1 mg/kg/day at test day 93 C. Urinalysis (Tables 32-33, Appendix K) Microscopic urine evaluation had lower priority than other urine tests. After other tests were completed on day 94, some females had insufficient urine for microscopic observation. Although no treatment-related changes were present in the samples evaluated, there were too few specimens to make unequivocal determinations. For other time-points and for males at test day 93, there were no adverse changes in urinalysis parameters. The following statistically significant changes in mean or individual urinalysis parameters were considered to be non adverse. Urine volume was increased in males dosed with 125 mg/kg/day at test day 93. Increased urine volume can be due to primary increased urine production, or can be secondary to increased water consumption. The cause of increased urine production in this study was not determined. These changes correlated with anatomic pathology findings of increased kidney weights and renal tubular hypertrophy which were considered to be non-adverse (see discussion under Microscopic Findings). Increased urine production in the absence of alterations in other renal parameters (serum urea nitrogen, serum creatinine, or adverse histologic changes in the kidney) is considered to be non-adverse. After approximately 90 days of recovery, urine volumes were similar to control group values in rats previously dosed with 125 mg/kg/day. Decreased urine ketone concentrations were present in males dosed with 125 mg/kg/day at test day 93. These decreases were likely secondary to increased urine volumes, and were considered to be non-adverse. After approximately 90 days of recovery, urine ketone concentrations were similar to control group values in rats previously dosed with 125 mg/kg/day. - 44 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 D. Plasma and Urine Fluoride (Tables 30-33, Appendix K) Plasma fluoride was increased in males dosed with 125 mg/kg/day, and in females dosed with 25 or 125 mg/kg/day at test day 93/94 (not statistically significant in females dosed with 25 mg/kg/day). After approximately 90 days of recovery, plasma fluoride concentrations were similar to control concentrations for males and females previously dosed with 125 mg/kg/day. Urine fluoride was increased in males and females dosed with 5, 25, and 125 mg/kg/day at test day 93/94 (not statistically significant in females dosed with 5 mg/kg/day). After approximately 90 days of recovery, total urine fluoride amounts were approximately 3 times greater than controls in males previously dosed with 125 mg/kg/day, but only minimally greater than controls in females. Increased plasma and urine fluoride indicates exposure to and metabolism of a fluoridecontaining compound. The presence of fluoride after 90 days of recovery indicates continued metabolism of the test substance. Clinical Pathology Text Table 2: Plasma fluoride (expressed as mean and as percent of control group mean)* Parameter Sex Test Day I/II III/IV V/VI VII/VIII 0 m g/kg/day 1 m g/kg/day 5 m g/kg/day 25 m g/kg/day P F L U (ug/m L ) M ales 93 0.1 183 0.1 -- P F L U (ug/m L ) Fem ales 94 0.1 -- 183 0.1 -- U F L U (ug) M ales 93 10.7 -- 183 9.9 -- U F L U (ug) F em ales 94 6 -- 183 11.9 -- * Statistical significance indicated by bold italicized type. 0.1 100% --0.1 100% --13 121 % --5.7 95% --- 0.1 100% --0.1 100% --3 8 .8 363% --14.1 235% --- 0.1 100% --0.2 200% --2 0 2 .4 1892% --88 1467% --- IX/X 125 m g/kg/day 0.4 400% 0.1 100% 0.5 500% 0.1 100% 997.2 9320% 2 7 .6 279% 702.6 11710% 15.7 132% E. Clinical Pathology Conclusions In conclusion, there were no adverse effects, measured by clinical pathology parameters, in rats dosed with 8-2 Telomer B Alcohol at doses up to 125 mg/kg/day. Treatment related changes in rats dosed with > 25 mg/kg/day included decreases in some red cell mass parameters along with - 45 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 regeneration (increased reticulocytes), increased serum cholesterol (females only) and increased serum phosphorus (males only). Additional treatment-related changes in clinical chemistry observed in rats dosed with 125 mg/kg/day included transiently increased alkaline phosphatase (males only), decreased triglycerides, increased total protein and albumin, and increased calcium (females only). For urinalysis parameters, males dosed with 125 mg/kg/day had increased urine volume and decreased urine ketone concentration. Treatment-related changes in fluoride measurements included increased plasma fluoride in males dosed with 125 mg/kg/day, and in females dosed with > 25 mg/kg/day (variable statistical significance). Urine fluoride excretion was increased in males and females dosed with > 5 mg/kg/day (variable statistical significance). None of the above changes are expected to be adverse. Therefore, under the conditions of this study and for the clinical pathology parameters measured, the NOEL was 125 mg/kg/day for males and females, based on the lack of adverse effects at any dose. BIOCHEMICAL MEASUREMENTS A. Biochemical Measurements (Table 34-35, Appendix L) The rate of hepatic P-oxidation, a measure of peroxisome proliferation, was determined in a subchronic oral toxicity study with 8-2 Telomer B Alcohol in male and female rats after approximately 10 or 90 days of test substance administration or following a three-month recovery period. At the 10-day, 90-day, and 3-month recovery time points in male rats, the rate of hepatic Poxidation was statistically significantly increased at 125 mg/kg/day (163, 166 and 133% of control, respectively). At the 10-day and 90-day time points, the increases in hepatic P-oxidation activity at 125 mg/kg/day in male rats were accompanied by increases in relative liver weights (133 and 152% of control, respectively). At the three-month recovery time point, the relative liver weights had returned to control levels. At the 10-day time point in female rats, the rate of hepatic P-oxidation was statistically significantly increased at 125 mg/kg/day (131% of control). At the 90-day time point, the rate of hepatic P-oxidation was statistically significantly increased at 25 and 125 mg/kg/day (116 and 152% of control, respectively). Hepatic P-oxidation returned to control levels at the three-month recovery time point. At the 10-day time point, the increase in hepatic P-oxidation activity at 125 mg/kg/day was accompanied by an increase in relative liver weight (132% of control). At the 90-day time point, the increases in hepatic P-oxidation activity at 25 and 125 mg/kg/day were accompanied by increases in relative liver weights (112 and 145% of control, respectively). At the three-month recovery time point, the relative liver weights had returned to control levels. - 46 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 B. Biochemical Measurements Conclusions Under the conditions of this study, 8-2 Telomer B Alcohol is a mild inducer of hepatic peroxisomal ^-oxidation in male and female rats. At concentrations of 125 mg/kg/day in males and 25 mg/kg/day in females, changes in the rate of hepatic peroxisome proliferation were considered to be test substance-related effects. At the three-month recovery time point, the rate of hepatic peroxisome proliferation was still slightly increased at 125 mg/kg/day in males, but had returned to control levels in female rats. ANATOMICAL PATHOLOGY A. Mortality (Appendix N) There were no test substance-related deaths. One male rat (animal number 654949) and one female rat (animal number 655071) from the control group were accidentally killed on study days 183 and 19, respectively. B. Organ Weight Data (Tables 36-37, Appendix M) Test substance-related and/or statistically significant increases, compared to controls, in liver weight parameters were present in 25 and 125 mg/kg/day males and females sacrificed at the end of the exposure period. Liver weight parameters were not significantly increased in males or females in the 125 mg/kg/day three-month recovery group (there were no recovery groups in intermediate dosed groups). In 125 mg/kg/day exposure group male rats, increased liver weight correlated with microscopic hepatocellular hypertrophy (see discussion under Microscopic Findings). Test substance-related and/or statistically significant increases, compared to controls, in one or more kidney weight parameters were present in 25 and 125 mg/kg/day males and females sacrificed at the end of the exposure period. Kidney weight parameters were not significantly increased in males or females in the 125 mg/kg/day three-month recovery group (there were no recovery groups in intermediate dosed groups). In male rats, increased kidney weights correlated with microscopic tubular hypertrophy in the 25 and 125 mg/kg/day groups sacrificed at the end of the exposure period (see discussion under Microscopic Findings). There were no other test substance-related organ weight effects. All other statistically significant organ weight changes in exposure and recovery groups were considered spurious and not biologically significant. These changes included decreased adrenal gland weight relative to body weight in 1 mg/kg/day female rats sacrificed at the end of the exposure period and decreased heart weight relative to body weight in the 125 mg/kg/day three-month recovery group females. In 125 mg/kg/day three-month recovery males, absolute, relative to body weight, and relative to brain weight thymus weights were increased; however, no test substance-related microscopic changes were present. - 47 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 C. Gross Observations (Tables 38-39, Appendix N) Gross observations noted were sporadic across groups and were not test substance related. D. Microscopic Findings (Tables 40-45, Appendix N) Test substance-related microscopic findings were present in liver, kidneys, thyroid gland, and teeth from male rats and in kidneys from female rats. A n atom ical P ath ology T ext Table: In cid en ces and A verage L esion G rades o f T est substance-R elated M icro sco p ic F in d in gs In M ale and F em ale R ats Dose (mg/kg/day): 0 1 5 25 125 Liver: Hypertrophy, hepatocellular Necrosis, focal Males: 90-Day Exposure 0/10a (0.0)b 0/10 (0.0) 0/10 (0.0) 0/10 (0.0) 0/10 (0.0) 1/10 (1.0) 0/10 (0.0) 5/10 (1.0) 10/10 (1.6) 3/10 (1.0) Kidneys: Hypertrophy, tubular 0/10 (0.0) 0/10 (0.0) 0/10 (0.0) 9/10 (1.0) 10/10 (1.0) Thyroid gland: Alteration, colloid 3/10 (1.0) 8/10 (1.1) 9/10 (1.0) 10/10 (1.0) 8/10 (2.3) Teeth: Degeneration, ameloblasts (nose) 0/10 (0.0) 0/10 (0.0) 0/10 (0.0) 0/10 (0.0) 5/10 (1.6) Liver: Necrosis, focal 3/10 (1.3) Males: Three-Month Recovery NA NA NA 7/10 (1.1) Thyroid gland: Alteration, colloid 7/10 (1.4) NA NA NA 10/10 (1.6) Teeth: Degeneration, ameloblasts (nose) 0/10 (0.0) NA NA NA 2/10 (1.0) Kidneys: Chronic progressive nephropathy 2/11 (1.0) Females: 90-Day Exposure 2/10 (1.0) 3/10 (1.0) 3/10 (1.0) 7/10 (1.0) Kidneys: Chronic progressive nephropathy 5/9 (1.0) Females: Three-Month Recovery NA NA NA 8/10 (1.4) a. Numerator indicates incidence o f rats with microscopic lesion. Denominator indicates number o f rats in group. b. Number in parentheses indicates average severity o f lesion. NA Tissue not available because there were no intermediate recovery groups. - 48 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Focal hepatocellular necrosis accompanied by a minimal inflammatory response was present in 25 and 125 mg/kg/day male 90-day exposure groups. In addition, the incidence of hepatocellular necrosis in 125 mg/kg/day three-month recovery males was increased when compared to the control group. The single occurrence of hepatocellular necrosis in males at 5 mg/kg/day was most likely not test substance-related since this lesion can occur spontaneously in control animals.(26) Focal liver necrosis was considered to be a test substance-related adverse finding in 25 and 125 mg/kg/day male rats. Hepatocellular hypertrophy was present in 125 mg/kg/day males sacrificed at the end of the exposure period. In three-month recovery male rats previously dosed with 125 mg/kg/day, hepatocellular hypertrophy was not present and appears to be reversible. Microscopically, hepatocellular hypertrophy was characterized by an increased amount of finely granular eosinophilic cytoplasm within hepatocytes. Thus, hepatocellular hypertrophy (and the associated increase in liver weights) was considered a test substance-related physiologic response to metabolism of a xenobiotic and not biologically adverse.(27,28,29) Test substance-related tooth lesions in 125 mg/kg/day exposure group male rats consisted of degeneration and/or disorganization of enamel organ ameloblast cells. This lesion was most evident in the upper incisors of the level 1 (anterior) nose section. Following a three-month recovery, ameloblastic degeneration/disorganization was still present in male rats previously dosed with 125 mg/kg/day. This tooth lesion is similar to lesions seen with fluoride toxicosis and is considered adverse.(30) In the thyroid gland, the incidence and/or relative degree of altered colloid was increased in males in all dosed groups at the end of the 90-day exposure period. Following the three-month recovery period, severity and incidence of altered colloid were increased in males at 125 mg/kg/day when compared to controls. The diagnosis of "alteration, colloid" was used for colloid changes characterized by stippled, granular, clumped, and/or diffusely basophilic colloid. A 4-level grading scheme was applied based on an estimate of the percentage of follicles that contained altered colloid. A grade of 1 was applied when 1 follicle to about 25% of the follicles were involved, with grades 2, 3, and 4 applied for each 25% increase in follicular involvement. The size, density, or staining intensity of stipples, granules, clumps, or diffuse basophilia within individual follicles did not impact the grading. Altered colloid described as clumped or granular has been reported to occur spontaneously in Sprague-Dawley rats with increasing incidence correlating to increasing age.(31) Because altered colloid occurs spontaneously in healthy Sprague-Dawley rats, and since there were no other microscopic alterations in the thyroid gland, altered colloid, although likely test substancerelated, was not considered adverse. The incidence of chronic progressive nephropathy was increased in 125 mg/kg/day 90-day exposure females when compared to controls. Incidence and severity of this lesion were increased in 125 mg/kg/day females at three months recovery when compared to controls. This lesion appears to progress after cessation of test material exposure and is considered adverse. - 49 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Renal tubular hypertrophy was present in 25 and 125 mg/kg/day male rats sacrificed at the end of the exposure period. This change was not observed in male rats sacrificed after the three-month recovery period and appears to be reversible. Microscopically, tubular hypertrophy was characterized by increased eosinophilic staining of cortical tubule epithelium and a slight increase in cell height. Cortical tubule epithelial cells appeared to contain more granular cytoplasmic material then cortical tubules of control rats. Tubular lumina of hypertrophied tubules were slightly smaller then those in control rat kidneys. Tubular hypertrophy was not associated with other histomorphologic evidence of renal damage, and renal clinical pathology parameters indicative of renal toxicity were not present (see clinical pathology section). Increased kidney weights occurring absent correlative evidence of renal toxicity commonly occur in toxicology studies and may represent a physiological response to high doses of a test material.(32) Thus, increased kidney weights and the associated renal tubular hypertrophy were likely test substance-related; however, these changes were not considered adverse but most likely represent a test substance-related physiologic response. All other microscopic observations noted are known to occur spontaneously in rats of this strain and age and were not present in a dose response fashion in either incidence or severity. E. Anatomical Pathology Conclusions Exposure to 125 mg/kg/day of the test substance for approximately 90 days produced degeneration/disorganization of enamel organ ameloblast cells in male rats. Ameloblastic degeneration/disorganization was not reversible after three months recovery. Increased incidence and severity of chronic progressive nephropathy in 125 mg/kg/day female recovery rats was considered test substance related and biologically adverse. Focal hepatic necrosis was present in 90-day males at 25 and 125 mg/kg/day and in three-month recovery males at 125 mg/kg/day. This lesion was considered test substance related and adverse. The incidence and/or severity of altered colloid in thyroid glands of male rats increased beyond control level as the dose increased; however, since there were no other microscopic alterations present this finding was not considered adverse. Increased liver weights were present in males and females at 25 and 125 mg/kg/day. The increased liver weights correlated with microscopic hepatocellular hypertrophy in males at 125 mg/kg/day. Hepatocellular hypertrophy was reversible in males following three-months recovery. These liver changes were considered to represent a physiologic response to metabolism of a xenobiotic and thus were not considered to be adverse. Increased kidney weights were present in 25 and 125 mg/kg/day males and females. In males, these kidney weight changes correlated with microscopic renal tubular hypertrophy. The increased kidney weights and renal tubular hypertrophy appeared to be reversible by three-months recovery. Increased kidney weights and microscopic tubular hypertrophy were not associated with correlative morphologic or clinical pathological changes and thus were not considered to be adverse findings. Under the conditions of this study, the NOEL for pathology for male rats was 5 mg/kg/day based on hepatic necrosis at the 25 and 125 mg/kg/day dose levels and for female rats was 25 mg/kg/day based on an increased incidence and severity of nephropathy at 125 mg/kg/day. - 50 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 CONCLUSIONS No test substance-related mortality or alterations in neurobehavioral parameters were observed in male or female rats. No test substance-related decrements in mean body weight, body weight gain, food consumption, or food efficiency were observed in male or female rats administered up to 125 mg/kg/day 8-2 Telomer B Alcohol. Test substance-related, toxicologically significant increases in the incidence of striated teeth occurred in the 125 mg/kg/day male and female dose groups. There were no toxicologically significant changes observed in clinical pathology parameters in rats dosed with up to 125 mg/kg/day 8-2 Telomer B Alcohol. A statistically significant increase in the rate of hepatic ^-oxidation occurred in the 25 mg/kg/day female and 125 mg/kg/day male and female groups. After the recovery period, the increased rate of ^-oxidation persisted, albeit at a reduced level compared to the 90-day time point, in the 125 mg/kg/day male group. Test substance-related, toxicologically significant degeneration/disorganization of enamel organ ameloblasts cells occurred in male rats dosed with 125 mg/kg/day 8-2 Telomer B Alcohol. This tooth lesion, along with the increased incidence of striated teeth, is consistent with fluoride toxicosis.(30) After three months, the degeneration/disorganization of ameloblasts persisted, at a lower incidence and severity. A test substance-related, adverse increase in the incidence and severity of focal hepatic necrosis was observed in males administered 25 and 125 mg/kg/day. An increased incidence and severity of chronic progressive nephropathy occurred in the 125 mg/kg/day female group that was considered adverse. After three months of recovery, both the incidence of hepatocellular necrosis in the 125 mg/kg/day male group and the incidence and severity of chronic progressive nephropathy in the 125 mg/kg/day female group were increased compared to control. Test-substance related and statistically significant increases in liver weight parameters were present in males and females administered 25 or 125 mg/kg/day for approximately 90 days. The increased liver weights correlated with microscopic hepatocellular hypertrophy in the 125 mg/kg/day male dose group. Liver weight changes and microscopic hypertrophy were considered to be a physiological adaptive response to metabolism of the test substance and not adverse. Test-substance related and statistically significant increases in kidney weight parameters occurred in males and females administered 25 or 125 mg/kg/day. The increased kidney weights correlated with microscopic renal tubular hypertrophy in the 25 and 125 mg/kg/day male groups only. However, no correlative microscopic or clinical pathological evidence of renal toxicity were present. Therefore, kidney weight changes and microscopic tubular hypertrophy were not considered adverse findings. Altered colloid, a common spontaneous finding in rats, was increased in incidence and/or severity in treated male groups. This change was not associated with other findings in the thyroid gland and was also not considered an adverse finding. After the three-month recovery period, increased liver weight parameters and hepatocellular hypertrophy (males only) were no longer observed in the 125 mg/kg/day male and female groups. Similarly, increased kidney weight parameters and renal tubular hypertrophy (males only) were not observed in rats sacrificed after three months of recovery. - 51 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 The no-observed-effect level (NOEL)a for 8-2 Telomer B Alcohol for the 90-day exposure period was 5 mg/kg/day 8-2 Telomer B Alcohol based on the increased incidence of hepatic necrosis observed in males administered > 25 mg/kg/day. The NOEL for females was 25 mg/kg/day 8-2 Telomer B Alcohol based on the increased incidence and severity of chronic progressive nephropathy observed in females administered 125 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 (if applicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. Test Substance characterization data 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 toxicologically important effects attributable to the test substance were not detected. Thus, for this study, the NOEL is equivalent to the NOEL as defined by the United States Environmental Protection Agency (33) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union.(34) - 52 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 REFERENCES 1. Covance study No. 6329-183 (1998). "104-week dietary carcinogenicity study with perfluorooctane sulfonic acid potassium salt (PFOS; T-6295) in rats." 2. Ikeda, T., Fukuda, K., Mori, I., Enomoto, M., Komai, T., Suga, T. (1987). Induction of cytochrome P-450 and peroxisome proliferation in rat liver by perfluorinated octanesulfonic acid. In: Fahimi HD, Sies H, eds. Peroxisomes in Biology and Medicine. Springer Verlag, New York, pp 304-308. 3. Sohlenius, A.K., Eriksson, A.M., Hogstrom, C., Kimland, M., Depierre, J.W. (1993). Perfluorooctane sulfonic acid is a potent inducer of peroxisomal fatty acid beta-oxidation and other activities known to be affected by peroxisome proliferators in mouse liver. Pharmacol. Toxicol, 72: 90-93. 4. Haughom, B., Spydevold, O. (1992). The mechanism underlying the hypolipemic effect of perfluorooctanoic acid (PFOA), perfluorooctane sulphonic acid (PFOSA) and clofibric acid. Biochem. Biophys. Acta., 1128: 65-72. 5. DuPont Haskell Laboratory Work Request 13690, Service Code 1583, Analytical Report HA-2001-037. 6. DuPont (1995). Neurotoxicity Evaluation of Trimethyltin in Rats (Positive Control Study). HLR 266-95. (MRID 44628701). 7. DuPont (1997). Neurotoxicity Evaluation of Amphetamine in Rats (Positive Control Study). HL-1997-00686. (MRID 44628703). 8. DuPont (1997). Neurotoxicity Evaluation of Carbaryl in Rats (Positive Control Study). HL-1997-00361. (MRID 44628702). 9. DuPont (1996). Neurotoxicity Evaluation of Acrylamide in Rats (Positive Control Study). HLR 293-95. (MRID 44660601). 10. Lazarow, P.B. (1981). Assay of Peroxisomal Beta-Oxidation of Fatty Acids. Methods in Enzymology 72, 315-319. 11. Bradford, M.M. (1976). A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Anal. Biochem. 72, 248-254. 12. Draper, N.R. and Smith, H. (1981). Applied Regression Analysis, 2nd edition, pp 266-273. Wiley, New York. 13. Selwyn, M.R. (1995). The use of trend tests to determine a no-observable-effect level in animal safety studies. Journal o f the American College o f Toxicology 14(2), 158-168. 14. Jonckheere, A.R. (1954). A distribution-free K-sample test against ordered alternatives. Biometrika 41, 133-145. 15. Levene, H. (1960). Robust test for equality of variances. Contributions to Probability and Statistics (J. Olkin, ed.), pp 278-292. Stanford University Press, Palo Alto. - 53 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 16. Shapiro, S.S. and Wilk., M.B. (1965). An analysis of variance test for normality (complete samples). Biometrika 52, 591-611. 17. Snedecor, G.W. and Cochran, W.G. (1967). Statistical Methods, 6th edition, pp 246-248 and 349-352. The Iowa State University Press, Ames. 18. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Amer. Statist. Assoc. 50, 1096-1121. 19. Kruskal, W.H. and Wallis, W.A. (1952). Use of ranks in one-criterion analysis of variance. J. Amer. Statist. Assoc. 47, 583-621. 20. Dunn, O.J. (1964). Multiple contrasts using rank sums. Technometrics 6, 241-252. 21. Milliken, G.A. and Johnson, D.A. (1984). Analysis of Messy Data, Volume 1.: Designed Experiments. Lifetime Learning Publications, Belmont. 22. Hocking, R.A. (1985). The Analysis of Linear Models. Brooks/Cole, Monterey. 23. Bartlett, M.S. (1937). Some examples of statistical methods of research in agriculture and applied biology. J. Royal. Statis. Soc. Suppl. 4, 137-170. 24. Fisher, R.A. (1985). Statistical Methods for Research Workers, 13th edition. Haffner, New York. 25. DuPont Haskell Laboratory Work Request 5672, Analytical Reports HA-2002-050 and HA-2002-055 26. Greaves, P. (2000). In Histopathology o fPreclinical Drug Safety Evaluation, Elsvier, Amsterdam, pp 453. 27. Sipes, G. I., and Gandolfi, A. J. (1991). In Biotransformation of Toxicants. In Casarett and Doull's Toxicology: The Basic Science of Poisons (Amdur, M. O., Doull, J., and Klaassen, C. D., Ed.), Pergamon Press, New York, pp 88-126. 28. Paynter, O.E., Harris, J.E., Burin, G.J., and Jaeger, R.B. (1985). Guidance for Analysis of Evaluation of Subchronic Exposure Studies. United States Environmental Protection Agency, EPA-540/9-85-020. 29. Greaves, P. (1990). Digestive System 2. In Histopathology o fPreclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation (P. Greaves, Ed.), Elsvier, Amsterdam, pp 393-496. 30. Reddy, C.S., and Hayes, A.W. (1989). Food Borne Toxicants. In Principles and Methods o f Toxicology (A.W. Hayes, Ed.), Raven Press, New York, pp 67-110. 31. Rao-Rupanagudi, S., Heywood, R., and Gopinah, C. (1991). "Age-related Changes in Thyroid Structures and Function in Sprague-Dawley Rats," Vet. Pathol., Vol. 29, No. 4, pp. 278-287. 32. Greaves, P. (1990). Urinary Tract. In Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation (P. Greaves, Ed.), Elsvier, Amsterdam, pp 497-583. - 54 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 33. 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., 20406. EPA-540/9-85-020. (June 1985). 34. Risk Assessment of Notified New Substances. Technical Guidance Document (XI/283/94EN), Chapter I, Sections 2.24 and 2.25. 1994. - 55 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLES - 56 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLES EXPLANATORY NOTES DuPont-9478 Critical Dates Day 91 Last day of test substance administration for rats designated for satellite bleeds and 3-month recovery. Last day of non-fasted body weight and food consumption data collection for rats designated for the 90-day exposure period. Last day of food consumption data collection for rats designated for satellite bleeds in the 1, 5, and 25 mg/kg/day dose groups. Day 92 Last day of test substance administration for male rats designated for the 90-day exposure period. Day 93 Last day of test substance administration for female rats designated for the 90-day exposure period. Male rats designated for the 90-day exposure period were sacrificed. Day 94 Female rats designated for 90-day exposure period were sacrificed. Day 175 Rats designated for satellite bleeds were sacrificed Day 182 Last day of non-fasted body weight and food consumption data collection for rats designated for the 3-month recovery period. Day 183 Male and female rats designated for the 3-month recovery period were sacrificed. Note mg/kg = mg/kg/day Notes for Clinical Pathology data: When an individual observation was recorded as being less than a certain value, calculations were performed on half the recorded value. For example, if bilirubin was reported as <0.1, 0.05 was used for any calculations performed with that bilirubin data. - 57 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLES ABBREVIATIONS: EXPLANATORY NOTES (CONTINUED) Summary of Hematology Values RBC - red blood cell count HGB - hemoglobin HCT - hematocrit MCV - mean corpuscular volume MCH - mean corpuscular hemoglobin MCHC - mean corpuscular hemoglobin concentration RDW - red cell distribution width ARET - absolute reticulocyte count PLT - platelet count WBC - white blood cell count ANEU - absolute neutrophil (all forms) ALYM - absolute lymphocyte AMON - absolute monocyte AEOS - absolute eosinophil ABAS - absolute basophil ALUC - absolute large unstained cell -- - no data Summary of Coagulation Values PT - prothrombin time APTT - activated partial thromboplastin time -- - no data DuPont-9478 - 58 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLES EXPLANATORY NOTES (CONTINUED) ABBREVIATIONS: (Continued) Summary of Clinical Chemistry Values AST - aspartate aminotransferase ALT - alanine aminotransferase SDH - sorbitol dehydrogenase ALKP - alkaline phosphatase BILI - total bilirubin BUN - urea nitrogen CREA - creatinine CHOL - cholesterol TRIG - triglycerides GLUC - glucose TP - total protein ALB - albumin GLOB - globulin CALC - calcium IPHS - inorganic phosphorous NA - sodium K - potassium CL - chloride PFLU - plasma fluoride -- - no data Summary of Urinalysis Values VOL volume UOSM urine osmolality pH the logarithm of the reciprocal of the hydrogen ion concentration URO urobilinogen UFLU urine fluoride UMTP urine protein -- - no data DuPont-9478 - 59 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 1 SUMMARY OF DOSING MIXING AND STABILITY ANALYSES Nominal: Homogeneity Samples Test Day 1/-6 Top Middle Bottom Average Measured Conc. c Average Percent Nominal Standard Deviation c Coefficient of Variation c Stability Samples 5 Hour Room Temperature Test Day 1/-6 and Test Day 4d (baseline for stability) 7-Day Refrigerated #1 #2 #3 Average Measured Conc. Average Percent Nominal Standard Deviation Coefficient of Variation Dosing Concentration of 8-2 Telomer BAlcohol (mg/mL) 0.20 1.0 5.0 25.0 0.163 (81.5) b 0.164 (82.0) 0.161 (80.5) 0.163 (81.5) 0.002 1% 0.167 (83.5) 0.163 (81.5) 0.161 (80.5) 0.173 (86.5) --- 0.167e (83.5) 0.01e 5%e 0.803 (80.3) 0.857 (85.7) 0.890 (89.0) 0.850 (85.0) 0.04 5% 0.818 (81.8) 0.888 (88.8) 0.900 (90.0) 0.864 (86.4) 0.859 (85.9) 0.874c (87.4) 0.02c 3%c 4.55 (91.0) 4.80 (96.0) 4.61 (92.2) 4.65 (93.0) 0.13 3% 4.14 (82.8) 4.51 (90.2) 4.46e (89.2) 4.44 (88.8) --- 4.45e (89.0) 0.01e 0.2%e 19.9 a (79.6) 21.9 (87.6) 22.9 (91.6) 21.6 (86.4) 1.5 7% 21.8 (87.2) 23.0 (92.0) 24.2e (96.8) 23.9 (95.6) --- 24.1ee (96.4) 0.21e 1%e 5 Hour Room Temperature 0.158a (79.0) 0.904 f (90.4) 4.21 f (84.2) 21.2 f (84.8) a Result of the original aliquot. Duplicate reanalysis o f original sample support original analysis and not reported. 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 Samples analyzed in previous study (HA-2001-037/MR 13690/SC1583). e Statistics based on the average measured concentration o f duplicate samples for the dosing level. f Mean results o f duplicate re-analysis of the original sample. Original results were low due to aliquot error - 60 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 1 (CONTINUED) SUMMARY OF DOSING MIXING AND STABILITY ANALYSES Nominal: Concentration Verification Test Day 42 #1 #2 Dosing Concentration of 8-2 Telomer BAlcohol (mg/mL) 0.20 1.0 5.0 25.0 0.156 c (78.0) b 0.169 c (84.5) 0.749 c (74.9) 0.776 c (77.6) 3.87 c (77.3) 3.91 f (78.2) 19.4 f (77.6) 19.1 f (76.2) Average Measured Conc. e Average Percent Nominal Standard Deviation e Coefficient of Variation e 0.163 (81.5) 0.01 6% 0.763 (76.3) 0.02 3% 3.89 (77.8) 0.03 1% 19.3 (77.2) 0.21 1% Test Day 45 #1 #2 Average Measured Conc. e Average Percent Nominal Standard Deviation e Coefficient of Variation e 0.066 c (33.0) 0.083 c (41.5) 0.075 (37.5) 0.01 13% 0.676 c (67.6) 0.656c (65.6) 0.666 (66.6) 0.01 2% 2.20 c (44.0) 2.32 c (46.4) 2.26 (45.2) 0.09 4% 8.34 f (33.4) 8.64 f (34.6) 8.49 (34.0) 0.21 3% Test Day 48g #1 0.197 (98.5) 0.865 (86.5) 3.93 (78.6) 21.9 (87.6) #2 0.219 0.948 3.90 22.5 (109.5) (94.8) (78.0) (90.0) Average Measured Conc. e Average Percent Nominal Standard Deviation e Coefficient of Variation e Test Day 52 #1 0.208 (104.0) 0.02 7% 0.174 (87.0) 0.907 (90.7) 0.06 6% 0.845 (84.5) 3.92 (78.3) 0.02 1% 4.22 (84.4) 22.2 (88.8) 0.42 3% 23.5 (94.0) #2 0.184 0.895 4.16 22.3 (92.0) (89.5) (83.2) (89.2) Average Measured Conc. e Average Percent Nominal Standard Deviation e Coefficient of Variation e 0.179 (89.5) 0.01 4% 0.870 (87.0) 0.04 4% 4.19 (83.8) 0.04 1% 22.9 (91.6) 0.85 4% b Numbers in parentheses are the respective percent of nominal values. c Mean result of the original analysis and duplicate reanalysis o f the original sample reported. e Statistics based on the average measured concentration o f duplicate samples for the dosing level. f Mean results o f duplicate re-analysis of the original sample. Original results were low due to aliquot error g Suspension not dosed to animals. - 61 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 1 (CONTINUED) SUMMARY OF DOSING MIXING AND STABILITY ANALYSES Nominal: Concentration Verification Test Day 56 #1 Dosing Concentration of 8-2 Telomer BAlcohol (mg/mL) 0.20 1.0 5.0 25.0 0.167 (83.5) b 0.964 (96.4) 4.41 (88.2) 22.8 (91.2) #2 Average Measured Conc. e Average Percent Nominal Standard Deviation e Coefficient of Variation e 0.189 (94.5) 0.178 (89.0) 0.02 9% 0.950 (95.0) 0.957 (95.7) 0.01 1% 4.31 (86.2) 4.36 (87.2) 0.07 2% 21.4 (85.6) 22.1 (88.4) 0.99 4% Test Day 58 #1 0.174 (87.0) 0.945 (94.5) 4.48 (89.6) 22.5 (90.0) #2 Average Measured Conc. e Average Percent Nominal Standard Deviation e Coefficient of Variation e 0.150 (75.0) 0.162 (81.0) 0.02 10% 0.937 (93.7) 0.941 (94.1) 0.01 1% 4.17 (83.4) 4.33 (86.5) 0.22 5% 22.1 (88.4) 22.3 (89.2) 0.28 1% Test Day 65 #1 #2 0.159 c (79.5) 0.150 c (75.0) 0.832 (83.2) 0.898 (89.8) 4.32 (86.4) 4.40 (88.0) 20.8 (83.2) 20.5 (82.0) Average Measured Conc. e Average Percent Nominal Standard Deviation e Coefficient of Variation e 0.155 (77.5) 0.01 4% 0.865 (86.5) 0.05 5% 4.36 (87.2) 0.06 1% b Numbers in parentheses are the respective percent of nominal values. c Mean result of the original analysis and duplicate reanalysis o f the original sample reported. e Statistics based on the average measured concentration o f duplicate samples for the dosing level. 20.7 (82.6) 0.21 1% - 62 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 1 (CONTINUED) SUMMARY OF DOSING MIXING AND STABILITY ANALYSES Nominal: Concentration Verification Test Day 91 #1 #2 Dosing Concentration of 8-2 Telomer BAlcohol (mg/mL) 0.20 1.0 5.0 25.0 0.162 (81.0) b 0.165 (82.5) 0.760 c (76.0) 0.863 (86.3) 3.96 c (79.2) 3.90 c (78.0) 19.9 c (76.4) 18.7 c (74.8) Average Measured Conc. e Average Percent Nominal Standard Deviation e Coefficient of Variation e 0.164 (82.0) 0.002 1%c 0.812 (81.2) 0.07 9% 3.93 (78.6) 0.04 1% 19.3 (77.2) 0.85 4% Test Day 63 #1 0.190 (95.0) a 0.784 (78.4) 4.12 (82.4) 23.0 (92.0) #2 Average Measured Conc. e Average Percent Nominal Standard Deviation e Coefficient of Variation e Test Day 73 #1 0.192 (96.0) 0.191 (95.5) 0.001 1% 0.176 (88.0) 0.792 (79.2) 0.788 (78.8) 0.01 1% 0.980 (98.0) 4.08 (81.8) 4.10 (82.0) 0.03 1% 4.57 (91.4) 21.4 (85.6) 22.2 (88.8) 1.1 5% 23.3 (93.2) #2 0.155 1.03 4.60 24.4 (77.5) (103.0) (92.0) (97.6) Average Measured Conc. e Average Percent Nominal Standard Deviation e Coefficient of Variation e 0.166 (82.8) 0.01 9% 1.01 (101.0) 0.04 4% 4.59 (91.8) 0.02 0.4% b Numbers in parentheses are the respective percent of nominal values. c Mean result of the original analysis and duplicate reanalysis o f the original sample reported. e Statistics based on the average measured concentration o f duplicate samples for the dosing level. 23.9 (95.6) 0.78 3% - 63 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Group: Dosage(mg/kg/day) DAY0 -DAY7 DAY7 -DAY14 DAY14 -DAY21 DAY21 -DAY28 DAY2 8 -DAY35 DAY3 5 -DAY42 DAY4 2 -DAY49 DAY4 9 -DAY56 DAY5 6 -DAY63 DAY6 3 -DAY70 DAY70 -DAY77 TABLE 2 MEAN DAILY DOSE VOLUMES FOR MALE RATS (mL) I 0 1.2 0.2(25) 1.4 0.2(25) 1.7 0.2(25) 1.9 0.2(25) 2.1 0.2(25) 2.2 0.2(25) 2.3 0.3(25) 2.4 0.3(25) 2.5 0.3(25) 2.7 0.3(25) 2.7 0.3(25) III 1 1.2 0.1(15) 1.5 0.1(15) 1.8 0.1(15) 2.0 0.1(15) 2.1 0.1(15) 2.3 0.1(15) 2.4 0.2(15) 2.4 0.2(15) 2.5 0.2(15) 2.7 0.2(15) 2.7 0.2(15) V 5 1.2 0.1(15) 1.5 0.1(15) 1.7 0.2(15) 2.0 0.2(15) 2.2 0.2(15) 2.3 0.2(15) 2.4 0.3(15) 2.5 0.2(15) 2.6 0.3(15) 2.8 0.3(15) 2.9 0.3(15) VII 25 1.2 0.1(15) 1.5 0.1(15) 1.7 0.1(15) 2.0 0.1(15) 2.1 0.2(15) 2.3 0.2(15) 2.4 0.2(15) 2.5 0.2(15) 2.6 0.2(15) 2.8 0.2(15) 2.9 0.2(15) DuPont-9478 IX 125 1.2 0.1(25) 1.5 0.1(25) 1.7 0.1(25) 1.9 0.2(25) 2.1 0.2(25) 2.2 0.2(25) 2.4 0.2(25) 2.4 0.2(25) 2.5 0.2(25) 2.6 0.2(25) 2.6 0.3(25) - 64 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Group: Dosage(mg/kg/day) DAY84 -DAY91 DAY91 DAY92 TABLE 2 (CONTINUED) MEAN DAILY DOSE VOLUMES FOR MALE RATS (mL) I 0 2.8 0.3 (25) 2.8 0.3 (25) 2.9 0.2 10) III 1 2.7 0.2'(15) 2.8 0.2'(15) 2.8 0.2'(10) V 5 2.9 0.3 15) 2.9 0.3 15) 3.0 0.3 10) VII 25 2.9 0.2'(15) 3.0 0.2'(15) 2.9 0.2'(10) DuPont-9478 IX 125 2.7 0.3 25) 2.8 0.3 25) 2.8 0.1 10) - 65 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 3 MEAN DAILY DOSE VOLUMES FOR FEMALE RATS (mL) Group: Dosage(mg/kg/day) DAY0 -DAY7 DAY7 -DAY14 DAY14 -DAY21 DAY21 -DAY28 DAY2 8 -DAY35 DAY3 5 -DAY42 DAY4 2 -DAY49 DAY4 9 -DAY56 DAY5 6 -DAY63 DAY6 3 -DAY70 DAY70 -DAY77 II 0 0.9 0.1(25) 1.0 0.1(25) 1.1 0.1(25) 1.2 0.1(24) 1.3 0.1(24) 1.3 0.1(24) 1.4 0.1(24) 1.4 0.2(24) 1.4 0.2(24) 1.4 0.2(24) 1.5 0.2(24) IV 1 0.9 0.1(15) 1.0 0.1(15) 1.1 0.1(15) 1.2 0.1(15) 1.2 0.1(15) 1.3 0.1(15) 1.4 0.1(15) 1.3 0.1(15) 1.4 0.1(15) 1.5 0.1(15) 1.5 0.1(15) VI 5 0.9 0.1(15) 1.0 0.1(15) 1.1 0.1(15) 1.2 0.1(15) 1.3 0.1(15) 1.3 0.1(15) 1.4 0.1(15) 1.4 0.1(15) 1.4 0.1(15) 1.5 0.1(15) 1.5 0.1(15) VIII 25 0.9 0.1(15) 1.0 0.1(15) 1.1 0.1(15) 1.2 0.1(15) 1.2 0.1(15) 1.3 0.1(15) 1.4 0.1(15) 1.4 0.1(15) 1.5 0.1(15) 1.5 0.1(15) 1.5 0.1(15) DuPont-9478 X 125 0.9 0.1(25) 1.0 0.1(25) 1.1 0.1(25) 1.3 0.1(25) 1.3 0.1(25) 1.3 0.1(25) 1.4 0.1(25) 1.4 0.2(25) 1.5 0.2(25) 1.5 0.2(25) 1.5 0.1(25) - 66 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 3 (CONTINUED) MEAN DAILY DOSE VOLUMES FOR FEMALE RATS (mL) Group: Dosage(mg/kg/day) DAY77 -DAY84 DAY84 -DAY91 DAY91 DAY92 -DAY93 II 0 1.5 0.2(24) 1.5 0.2(24) 1.5 0.2(24) 1.5 0.1(10) IV 1 1.5 0.1(15) 1.5 0.1(15) 1.5 0.1(15) 1.5 0.1(10) VI 5 1.5 0.1(15) 1.5 0.1(15) 1.5 0.1(15) 1.5 0.1(10) VIII 25 1.6 0.1(15) 1.6 0.1(15) 1.6 0.1(15) 1.6 0.1(10) DuPont-9478 X 125 1.5 0.2(25) 1.6 0.2(25) 1.6 0.1(25) 1.5 0.1(10) - 67 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 4 MEAN BODY WEIGHTS OF MALE RATS (g) Group: Dosage(mg/kg/day) I 0 Dosing Period for Subchronic Toxicity Evaluation DAY0 234.5 23.9(25) DAY7 288.7 29.3(25) DAY14 337.2 33.0(25) DAY21 383.6 37.5(25) DAY2 8 415.5 40.3(25) DAY3 5 445.1 48.4(25) DAY42 467.2 56.5(25) DAY4 9 483.2 52.4(25) DAY5 6 503.8 56.9(25) DAY63 520.5 58.6(25) DAY70 537.8 57.4(25) III 1 245.6 19.7(15) 299.2 24.9(15) 352.6 20.2(15) 394.9 23.2(15) 426.0 24.9(15) 455.1 27.2(15) 475.8 30.0(15) 485.0 30.8(15) 508.4 32.1(15) 523.2 34.3(15) 539.2 39.7(15) V 5 240.8 21.0(15) 295.8 26.6(15) 348.4 31.7(15) 396.1 36.4(15) 432.2 42.8(15) 464.0 47.0(15) 487.4 50.4(15) 498.4 48.7(15) 525.8 53.1(15) 545.1 56.7(15) 559.1 56.4(15) VII 25 239.4 16.0(15) 294.9 18.3(15) 345.6 22.7(15) 393.1 27.4(15) 427.1 32.0(15) 460.8 36.5(15) 489.2 37.8(15) 501.1 39.8(15) 528.5 43.0(15) 548.0 44.2(15) 558.4 45.5(15) DuPont-9478 IX 125 235.1 22.1(25) 289.2 25.7(25) 343.3 28.4(25) 387.9 32.3(25) 422.0 36.4(25) 448.9 40.7(25) 473.8 42.2(25) 486.8 45.5(25) 507.2 49.1(25) 516.0 51.9(25) 524.5 50.8(25) - 68 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 4 (CONTINUED) MEAN BODY WEIGHTS OF MALE RATS (g) Group: Dosage(mg/kg/day) I 0 III 1 Dosing Period for Subchronic Toxicity Evaluation (continued) DAY7 7 547.7 57.5(25) 544.8 36.4(15) DAY8 4 554.6 58.2(25) 549.5 39.1(15) DAY91 562.0 54.0(25) 561.0 42.2(15) Three-Month Recovery Period for Subchronic Toxicity Evaluation DAY98 568.1 55.2(15) 567.9 58.8(5) DAY105 573.3 64.3(15) 582.8 59.0(5) DAY112 581.6 63.4(15) 584.4 60.6(5) DAY119 590.9 62.8(15) 595.0 58.6(5) DAY126 605.5 62.7(15) 604.5 65.8(5) DAY133 613.7 61.8(15) 615.2 62.5(5) DAY140 612.0 64.0(15) 615.8 65.5(5) V 5 571.1 55.9(15) 582.5 58.0(15) 589.1 60.9(15) 567.0 69.6(5) 575.6 70.3(5) 579.2 72.9(5) 590.6 74.8(5) 600.6 74.0(5) 610.0 75.9(5) 608.0 87.4(5) VII 25 571.2 45.9(15) 581.2 45.7(15) 591.2 47.6(15) 606.8 59.8(5) 614.6 59.8(5) 619.3 67.0(5) 630.7 69.4(5) 646.4 70.5(5) 654.8 74.0(5) 656.8 76.7(5) DuPont-9478 IX 125 518.5 61.7(25) 531.5 53.6(25) 551.9 53.9(25) 556.0 65.4(15) 567.8 68.6(15) 573.5 67.4(15) 583.3 71.3(15) 599.3 76.1(15) 610.3 80.7(15) 612.9 81.7(15) - 69 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 4 (CONTINUED) MEAN BODY WEIGHTS OF MALE RATS (g) Group: I III V Dosage(mg/kg/day) 0 1 5 Three-Month Recovery Period for Subchronic Toxicity Evaluation continued) DAY147 617.2 65 .6 (15) 626.4 68.2' 5) 618.3 8 6 . 9 5) DAY154 625.0 68 .2 (15) 635.2 65.9' 5) 627.1 82 .4 5) DAY161 623.7 7 1 . 9 (15) 637.2 68.2' 5) 629.5 8 5 . 5 5) DAY168 629.8 7 1 . 5 (15) 642.3 65.9' 5) 631.0 88 .6 5) DAY175 631.4 79 .3 (15) 646.3 66.8' 5) 632.5 85 .8 5) DAY182 647.6 6 6 . 5 (10) . '0) 0) VII 25 665.6 79.9' 5) 681.5 82.6' 5) 678.9 83.7' 5) 690.7 85.1' 5) 693.8 81.8' 5) 0) Da ta summarized as: Mean S t a n d a r d D e v i a t i o n (n) T h e r e w e r e n o s t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e s a t p < 0. LO O by Jonckheere--Terpstra trend test. DuPont-9478 IX 125 621.5 83.0 15 635.7 81.2 15 636.5 82.0 15 649.1 85.3 15 648.1 84.3 15 634.7 86.3 10 - 70 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 5 MEAN BODY WEIGHTS OF FEMALE RATS (g) Group: Dosage(mg/kg/day) II 0 Dosing Period for Subchronic Toxicity Evaluation DAY0 186.6 15.1(25) DAY7 204.8 18.0(25) DAY14 223.5 21.1(25) DAY21 241.1 24.2(24) DAY2 8 251.8 26.5(24) DAY3 5 263.5 27.3(24) DAY42 273.0 27.6(24) DAY4 9 272.8 30.2(24) DAY5 6 284.4 30.2(24) DAY63 288.7 31.7(24) DAY70 296.1 31.0(24) IV 1 183.8 17.0(15) 205.7 15.0(15) 224.8 15.4(15) 238.7 15.9(15) 250.1 15.9(15) 264.3 17.3(15) 274.1 17.2(15) 267.2 16.9(15) 286.4 18.9(15) 291.4 21.0(15) 298.5 23.2(15) VI 5 182.2 17.0(15) 204.5 15.3(15) 223.7 17.1(15) 239.0 20.8(15) 250.9 20.0(15) 264.0 24.3(15) 274.9 24.1(15) 271.6 22.6(15) 286.8 26.2(15) 292.7 27.3(15) 297.4 26.2(15) VIII 25 182.6 14.7(15) 202.8 18.6(15) 225.7 16.7(15) 239.9 17.8(15) 252.7 21.9(15) 266.3 20.9(15) 278.5 22.0(15) 272.0 25.6(15) 292.1 27.0(15) 294.4 25.0(15) 305.1 27.4(15) DuPont-9478 X 125 188.5 16.5(25) 209.0 18.1(25) 230.4 18.6(25) 247.7 21.8(25) 259.9 24.1(25) 270.3 24.5(25) 278.2 25.4(25) 280.4 30.1(25) 292.1 29.8(25) 297.1 31.1(25) 300.0 28.6(25) - 71 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 5 (CONTINUED) MEAN BODY WEIGHTS OF FEMALE RATS (g) Group: Dosage(mg/kg/day) II 0 IV 1 Dosing Period for Subchronic Toxicity Evaluation (continued) DAY7 7 299.7 31.5(24) 302.1 22.2(15) DAY8 4 302.5 31.9(24) 305.8 25.0(15) DAY91 303.7 31.5(24) 304.9 25.4(15) Three-Month Recovery Period for Subchronic Toxicity Evaluation DAY98 310.9 38.7(14) 306.6 26.3(5) DAY105 315.8 39.9(14) 311.0 24.4(5) DAY112 318.0 37.7(14) 312.5 25.8(5) DAY119 320.2 36.9(14) 313.7 26.9(5) DAY126 327.9 38.0(14) 319.1 27.7(5) DAY133 328.9 38.6(14) 324.4 28.7(5) DAY140 331.6 36.5(14) 325.6 29.6(5) DAY147 337.0 39.2(14) 327.6 32.0(5) VI 5 301.7 27.1(15) 300.8 26.8(15) 302.5 26.5(15) 299.9 30.8(5) 299.8 34.1(5) 305.7 34.2(5) 309.2 32.0(5) 314.5 35.7(5) 319.8 38.7(5) 320.3 34.9(5) 324.5 42.0(5) VIII 25 310.5 28.9(15) 311.3 29.7(15) 310.6 29.0(15) 322.9 26.3(5) 326.9 30.0(5) 329.6 32.7(5) 340.5 32.2(5) 346.2 39.0(5) 351.3 37.4(5) 351.6 39.7(5) 354.8 39.5(5) DuPont-9478 X 125 303.0 29.5(25) 311.3 30.8(25) 310.2 29.3(25) 317.6 36.4(15) 317.8 35.1(15) 319.1 39.8(15) 324.9 40.8(15) 340.1 45.6(15) 343.9 46.4(15) 343.3 48.3(15) 349.5 50.8(15) - 72 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 5 (CONTINUED) MEAN BODY WEIGHTS OF FEMALE RATS (g) Group: II IV VI Dosage(mg/kg/day) 0 1 5 i Recovery Period for Subchronic Toxicity Evaluation (continued) DAY154 339.3 3 9 . 8 (14) 331.3 32.0' 5) 331.3 4 5 . 1 5) DAY161 333.4 3 6 . 8 (14) 330.4 28.7' 5) 327.9 4 1 . 2 5) DAY168 340.3 3 7 . 0 (14) 336.0 28.3' 5) 333.9 4 4 . 3 5) DAY175 342.3 3 8 . 6 (14) 336.2 29.3' 5) 335.9 4 4 . 6 5) DAY182 354.1 3 3 . 0 (9) 0) 0) VIII 25 359.1 42.6' 5) 361.6 47.5' 5) 368.3 48.0' 5) 366.8 53.8' 5) 0) Da ta summarized as: Mean S t a n d a r d D e v i a t i o n (n) There were no statistically significant differences at p < 0.05 by Jonckheere-Terpstra trend test. DuPont-9478 X 125 355.1 52.2 15 353.9 54.0 15 360.4 58.2 15 363.6 60.0 15 368.7 67.8 10 - 73 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 6 MEAN BODY WEIGHT GAINS OF MALE RATS (g) Group: Dosage(mg/kg/day) I 0 Dosing Period for Subchronic Toxicity Evaluation DAY0 -DAY7 54.3 7.9(25) DAY7 -DAY14 48.5 7.2(25) DAY14 -DAY21 46.4 7.8(25) DAY21 -DAY28 31.9 8.8(25) DAY2 8 -DAY35 29.5 19.4(25) DAY3 5 -DAY42 22.2 12.4(25) DAY42 -DAY49 16.0 13.0(25) DAY4 9 -DAY56 20.5 9.2(25) DAY5 6 -DAY63 16.8 6.8(25) DAY6 3 -DAY70 17.2 7.8(25) DAY70 -DAY77 9.9 5.7(25) III 1 53.6 12.0(15) 53.5 8.7(15) 42.3 4.2(15) 31.1 6.7(15) 29.0 5.3(15) 20.8 6.6(15) 9.2 6.1(15) 23.5 5.4(15) 14.8 4.5(15) 16.0 7.9(15) 5.5 11.4(15) V 5 55.0 9.3(15) 52.6 8.7(15) 47.8 7.8(15) 36.0 8.2(15) 31.8 6.0(15) 23.4 8.8(15) 11.0 8.8(15) 27.4* 8.1(15) 19.3 7.1(15) 14.0 6.6(15) 12.0 8.2(15) VII 25 55.5 6.4(15) 50.7 7.8(15) 47.6 9.2(15) 34.0 8.9(15) 33.7 7.1(15) 28.3 4.8(15) 11.9 8.7(15) 27.4* 7.5(15) 19.5 4.3(15) 10.4# 5.3(15) 12.8 5.5(15) DuPont-9478 IX 125 54.1 10.0(25) 54.1# 6.5(25) 44.6 8.1(25) 34.1 6.4(25) 26.9 6.6(25) 24.9 6.9(25) 13.0 8.5(25) 20.5 6.9(25) 8.7 15.5(25) 8.5# 16.7(25) -6.0 28.0(25) - 74 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 6 (CONTINUED) MEAN BODY WEIGHT GAINS OF MALE RATS (g) Group: Dosage(mg/kg/day) I 0 III 1 Dosing Period for Subchronic Toxicity Evaluation (continued) DAY7 7 -DAY84 6.9 6.6(25) 4.8 13.7(15) DAY8 4 -DAY91 7.5 11.0(25) 11.5 8.0(15) V 5 11.5 5.6(15) 6.6 9.9(15) VII 25 10.0 6.8(15) 10.1 6.4(15) DAY0 -DAY91 327.6 43.5(25) 315.4 35.9(15) Three-Month Recovery Period for Subchronic Toxicity Evaluation DAY91 -DAY98 13.3 6.5(15) 9.1 3.9(5) DAY9 8 -DAY105 5.3 19.1(15) 14.9 2.8(5) DAY105 -DAY112 8.3 7.1(15) 1.5 4.2(5) DAY112 -DAY119 9.3 6.9(15) 10.7 3.7(5) DAY119 -DAY126 14.6 6.7(15) 9.4 8.6(5) DAY126 -DAY133 8.2 5.7(15) 10.7 7.1(5) 348.2 50.8(15) 12.2 5.1(5) 8.6 5.1(5) 3.6 7.5(5) 11.4 5.9(5) 10.0 5.1(5) 9.4 5.4(5) 351.9 47.2(15) 9.3 3.8(5) 7.9 2.2(5) 4.6 8.6(5) 11.5 7.5(5) 15.7 5.3(5) 8.3 4.2(5) DuPont-9478 IX 125 13.1 22.4(25) 20.3# 14.2(25) 316.8 43.9(25) 11.9 6.9(15) 11.9 6.9(15) 5.6 7.2(15) 9.8 6.4(15) 16.0 7.6(15) 11.0 6.7(15) - 75 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 6 (CONTINUED) MEAN BODY WEIGHT GAINS OF MALE RATS (g) Group: I III V Dosage(mg/kg/day) 0 1 5 T h r e e - M o n t h R e c o v e r y P e r i o d f o r S u b c h r o n i c 'T o x i c i t y E v a l u a t i o n ( c o n t i n u e d ) DAY133 -DAY140 -1.7 6.4 (15) 0.6 6.7' 5) -1.9 1 6 . 5 5) DAY140 -DAY147 5.2 6.3 (15) 10.6 3.0' 5) 10.3 8.0 5) DAY147 -DAY154 7.8 8.6 (15) 8.8 2.7' 5) 8.8 6.0 5) DAY154 -DAY161 -1.3 1 1 . 9 (15) 2.0 2.5' 5) 2.4 4 . 5 5) DAY161 -DAY168 6.1 5.4 (15) 5.1 2.8' 5) 1.6 4.4 5) DAY168 -DAY175 1.5 12 .3 (15) 4.0 5.7' 5) 1.4 6.8 5) DAY175 -DAY182 2.1 5.0 (10) 0) 0) DAY91 -DAY175 DAY91 -DAY182 76.6 3 2 . 2 (15) 89.2 2 1 . 4 (10) 87.5 26.9' 5) 0) 77.7 1 8 . 0 5) 0) D a t a s u m m a r i z e d as: Mean S t a n d a r d D e v i a t i o n (n) # Statistically significant difference at p < 0.05 by Jonckheere-Terpstra trend test. * Statistically significant difference at p < 0.05 by Dunnett/Tamhane-Dunnett test. VII 25 2.0 6.0' 5) 8.9 4.9' 5) 15.9 4.5' 5) -2.6 5.6' 5) 11.8 8.8' 5) 3.1 5.0' 5) 0) 96.4 24.1' 5) 0) DuPont-9478 IX 125 2.6 7.4(15) 8.6 4.9(15) 14.2# 6.7(15) 0.8 5.6(15) 12.6# 8.5(15) -1.0 7.6(15) 11.4# 4.6(10) 104.1# 28.8(15) 108.2 31.3(10) - 76 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 7 MEAN BODY WEIGHT GAINS OF FEMALE RATS (g) Group: Dosage(mg/kg) II 0 Dosing Period for Subchronic Toxicity Evaluation DAY0 -DAY7 18.2 5.6(25) DAY7 -DAY14 18.7 7.9(25) DAY14 -DAY21 16.4 5.7(24) DAY21 -DAY28 10.7 5.7(24) DAY2 8 -DAY35 11.8 5.7(24) DAY3 5 -DAY42 9.5 5.3(24) DAY42 -DAY49 -0.2 6.2(24) DAY4 9 -DAY56 11.6 6.0(24) DAY5 6 -DAY63 4.3 5.4(24) DAY6 3 -DAY70 7.4 5.7(24) DAY70 -DAY77 3.5 4.2(24) IV 1 21.9 10.0(15) 19.1 4.1(15) 13.9 3.3(15) 11.4 5.4(15) 14.2 4.2(15) 9.8 5.6(15) -6.9 7.1(15) 19.3 7.1(15) 4.9 6.9(15) 7.2 4.3(15) 3.6 5.0(15) VI 5 22.3 9.0(15) 19.2 4.0(15) 15.2 7.6(15) 11.9 4.4(15) 13.1 6.7(15) 10.9 8.9(15) -3.3 7.2(15) 15.2 7.7(15) 5.9 7.4(15) 4.7 5.8(15) 4.3 4.5(15) VIII 25 20.2 6.9(15) 22.9 7.5(15) 14.1 7.4(15) 12.8 6.9(15) 13.6 5.9(15) 12.3 7.7(15) -6.5 9.6(15) 20.0 8.2(15) 2.3 6.4(15) 10.6 6.2(15) 5.5 4.8(15) DuPont-9478 X 125 20.5 4.8(25) 21.4 4.2(25) 17.3 6.5(25) 12.2 4.9(25) 10.4 5.9(25) 7.9 7.2(25) 2.2 9.2(25) 11.7 12.4(25) 5.0 7.6(25) 2.9 6.3(25) 3.0 5.3(25) - 77 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 7 (CONTINUED) MEAN BODY WEIGHT GAINS OF FEMALE RATS (g) Group: Dosage(mg/kg) II IV 01 Dosing Period for Subchronic Toxicity Evaluation (continued) DAY7 7 -DAY84 2.8 5.4(24) 3.7 5.2(15) DAY8 4 -DAY91 1.3 6.5(24) -0.9 5.9(15) VI 5 -0.8 3.3(15) 1.6 6.3(15) VIII 25 0.7 5.4(15) -0.7 5.8(15) DAY0 -DAY91 116.9 21.6(24) 121.1 24.6(15) Three-Month Recovery Period for Subchronic Toxicity Evaluation DAY91 -DAY98 4.5 7.4(14) 8.0 3.4(5) DAY9 8 -DAY105 4.9 6.8(14) 4.4 5.6(5) DAY105 -DAY112 2.2 5.3(14) 1.5 4.5(5) DAY112 -DAY119 2.2 6.5(14) 1.1 2.3(5) DAY119 -DAY126 7.7 6.0(14) 5.4 1.4(5) DAY126 -DAY133 1.0 6.3(14) 5.3 1.6(5) DAY133 -DAY140 2.7 6.2(14) 1.1 6.1(5) 120.2 20.5(15) 8.8 4.4(5) -0.1 6.3(5) 5.9 1.3(5) 3.5 5.3(5) 5.2 3.7(5) 5.3 6.3(5) 0.6 5.3(5) 128.0 18.2(15) 9.7 7.5(5) 3.9 6.3(5) 2.8 4.1(5) 10.9 3.3(5) 5.7 7.2(5) 5.1 4.8(5) 0.3 5.1(5) DuPont-9478 X 125 8.3# 6.2(25) -1.1 6.7(25) 121.7 19.9(25) 5.0 9.3(15) 0.2 5.3(15) 1.3 11.7(15) 5.8 10.5(15) 15.2# 7.1(15) 3.8 6.4(15) -0.6# 5.4(15) - 78 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 7 (CONTINUED) MEAN BODY WEIGHT GAINS OF FEMALE RATS (g) Group: Dosage(mg/kg) II IV VI 015 Three-Month Recovery Period for Subchronic Toxicity Evaluation (continued) DAY140 -DAY147 5.4 5.9(14) 2.0 4.5(5) 4.2 7.1(5) DAY147 -DAY154 2.4 6.2(14) 3.7 6.2(5) 6.8 7.5(5) DAY154 -DAY161 -6.0 5.2(14) -0.9 5.2(5) -3.5 5.0(5) DAY161 -DAY168 7.0 5.7(14) 5.6 4.8(5) 6.1 4.0(5) DAY168 -DAY175 2.0 3.9(14) 0.2 5.3(5) 2.0 4.2(5) DAY175 -DAY182 2.7 6.2(9) . (0) . (0) VIII 25 3.2 11.2(5) 4.4 11.0(5) 2.5# 8.3(5) 6.7 3.4(5) -1.5 7.5(5) . (0) DAY91 -DAY175 DAY91 -DAY182 36.0 13.8(14) 42.1 15.5(9) 37.5 10.7(5) . (0) 44.9 20.1(5) . (0) 53.6 24.3(5) . (0) Da ta summarized as: Mean S t a n d a r d D e v i a t i o n (n) # Statistically significant difference at p < 0.05 by Jonckheere-Terpstra trend test. DuPont-9478 X 125 6.1 6.8(15) 5.6 8.6(15) -1.2# 4.6(15) 6.5 6.9(15) 3.2 5.8(15) 2.9 7.6(10) 51.0 33.1(15 56.3 38.4(10 - 79 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 8 MEAN DAILY FOOD CONSUMPTION BY MALE RATS (g/day) Group: Dosage(mg/kg/day) I 0 Dosing Period for Subchronic Toxicity Evaluation DAY0 -DAY7 27.0 3.0(25) DAY7 -DAY14 28.3 4.1(25) DAY14 -DAY21 29.8 3.3(25) DAY21 -DAY28 30.5 3.3(25) DAY2 8 -DAY35 30.4 5.9(25) DAY3 5 -DAY42 29.5 5.2(25) DAY42 -DAY49 28.8 3.6(25) DAY4 9 -DAY56 29.4 3.2(25) DAY5 6 -DAY63 28.3 3.9(25) DAY6 3 -DAY70 29.2 3.3(25) DAY70 -DAY77 28.8 3.1(25) III 1 28.7 2.6(15) 30.1 2.1(15) 31.2 2.1(15) 29.8 1.9(15) 30.4 2.4(15) 30.0 1.7(15) 27.1 2.2(15) 29.2 1.4(15) 29.1 1.9(15) 29.6 2.5(15) 30.0 2.9(15) V 5 27.2 3.3(15) 29.6 3.6(15) 30.7 4.0(15) 31.3 3.9(15) 31.8 4.1(15) 30.9 4.2(15) 28.6 3.3(15) 30.2 3.4(15) 30.1 3.8(15) 30.2 2.8(15) 30.1 2.8(15) VII 25 27.9 2.5(15) 30.2 2.7(15) 31.2 3.4(15) 30.9 4.1(15) 32.2 4.1(15) 31.5 3.7(15) 29.1 3.7(15) 31.5 3.3(15) 31.6 3.2(15) 30.2 3.1(15) 30.3 2.8(15) DuPont-9478 IX 125 26.6 2.5(25) 29.0 2.3(25) 30.0 3.0(25) 29.1 2.9(25) 30.4 3.2(25) 29.8 3.2(25) 28.6 3.4(25) 29.1 3.3(25) 27.2 4.5(25) 26.6 4.3(25) 25.3 6.2(25) - 80 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 8 (CONTINUED) MEAN DAILY FOOD CONSUMPTION BY MALE RATS (g/day) Group: Dosage(mg/kg/day) I 0 III 1 Dosing Period for Subchronic Toxicity Evaluation (continued) DAY7 7 -DAY84 28.3 3.0(25) 28.0 1.5(15) DAY8 4 -DAY91 27.8 3.2(25) 28.9 1.9(15) V 5 29.7 2.6(15) 28.9 3.1(15) VII 25 29.2 2.2(15) 30.3 3.0(15) DAY0 -DAY91 28.9 3.0(25) 29.4 1.5(15) Three-Month Recovery Period for Subchronic Toxicity Evaluation DAY91 -DAY98 27.2 1.9(10) . (0) DAY9 8 -DAY105 28.4 2.3(10) . (0) DAY105 -DAY112 28.8 2.0(10) . (0) DAY112 -DAY119 27.6 2.9(10) . (0) DAY119 -DAY126 27.7 2.3(10) . (0) DAY126 -DAY133 28.1 2.3(10) . (0) DAY133 -DAY140 28.1 2.8(10) . (0) 30.0 3.2(15) . (0) . (0) . (0) . (0) . (0) . (0) . (0) 30.5 2.9(15) . (0) . (0) . (0) . (0) . (0) . (0) . (0) DuPont-9478 IX 125 26.6 4.6(25) 29.4 3.5(25) 28.3 2.5(25) 25.5 3.8(10) 25.9# 3.5(10) 26.0# 2.6(10) 26.6 3.3(10) 26.2 4.6(10) 27.1 3.4(10) 28.1 3.3(10) - 81 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 8 (CONTINUED) MEAN DAILY FOOD CONSUMPTION BY MALE RATS (g/day) Group: I III V Dosage (mg/kg/day) 0 1 5 Three-Month Recovery Period for Subchronic Toxicity Evaluation (continued) DAY140 -DAY147 26.8 2.9(10) . (0) . (0) DAY147 -DAY154 27.5 2.4(10) . (0) . (0) DAY154 -DAY161 28.3 2.3(10) . (0) . (0) DAY161 -DAY168 28.5 2.4(10) . (0) . (0) DAY168 -DAY175 28.2 3.0(10) . (0) . (0) DAY175 -DAY182 27.9 2.2(10) . (0) . (0) VII 25 0) 0) 0) 0) 0) 0) DAY91 -DAY175 DAY91 -DAY182 27.9 2.2(10) 27.9 2.2(10) . (0) . (0) . (0) . (0) 0) 0) Da ta summarized as: Mean S t a n d a r d D e v i a t i o n (n) # St at i s t i c a l l y significant difference at p < 0 05 by J o n c kh ee re -T er ps tra trend test. DuPont-9478 IX 125 26.4 3.9 10) 26.8 2.4 10) 26.1 2.9 10) 27.5 3.0 10) 26.4 3.1 10) 27.0 3.7 10) 26.6 3.1 10) 26.6 3.1 10) - 82 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 9 MEAN DAILY FOOD CONSUMPTION BY FEMALE RATS (g/day) Group: Dosage(mg/kg/day) II 0 Dosing Period for Subchronic Toxicity Evaluation DAY0 -DAY7 19.4 1.9(25) DAY7 -DAY14 19.5 2.2(25) DAY14 -DAY21 21.1 2.2(24) DAY21 -DAY28 20.3 2.1(24) DAY2 8 -DAY35 21.0 2.3(24) DAY3 5 -DAY42 21.3 2.1(24) DAY42 -DAY49 19.7 2.6(24) DAY4 9 -DAY56 21.2 2.2(24) DAY5 6 -DAY63 20.9 2.3(24) DAY6 3 -DAY70 20.5 2.0(24) DAY70 -DAY77 20.7 2.2(24) IV 1 19.9 1.9(15) 19.6 1.4(15) 21.0 1.9(15) 20.1 1.8(15) 20.8 1.8(14) 21.2 1.6(15) 18.9 1.4(15) 21.5 2.3(15) 20.9 2.1(15) 20.6 2.8(15) 20.6 2.1(15) VI 5 19.8 1.8(15) 19.6 2.0(15) 21.2 2.1(15) 21.0 1.7(15) 21.5 2.2(15) 21.2 2.3(15) 20.2 2.0(15) 22.1 2.0(15) 21.6 2.2(15) 20.8 1.6(15) 20.9 2.0(15) VIII 25 19.5 1.9(15) 19.5 1.6(15) 21.8 2.8(15) 20.8 2.1(15) 21.7 2.3(15) 22.0 2.7(15) 20.4 2.7(15) 23.0 1.6(15) 21.8 1.8(15) 22.1 2.2(15) 21.9 2.2(15) DuPont-9478 X 125 19.1 1.8(25) 20.2 1.8(25) 21.5 2.1(25) 21.0 2.0(25) 21.4 2.2(25) 20.7 2.2(24) 20.7 3.4(25) 21.7 2.6(25) 20.7 2.4(25) 20.5 2.2(25) 20.2 2.4(25) - 83 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 9 (CONTINUED) MEAN DAILY FOOD CONSUMPTION BY FEMALE RATS (g/day) Group: Dosage(mg/kg/day) II 0 IV 1 Dosing Period for Subchronic Toxicity Evaluation (continued) DAY7 7 -DAY84 20.4 2.6(24) 20.2 2.0(15) DAY8 4 -DAY91 19.7 2.3(24) 19.7 1.5(15) VI 5 20.3 1.5(15) 20.2 1.2(15) VIII 25 21.3 1.9(15) 20.3 1.9(15) DAY0 -DAY91 20.5 2.0(24) 20.4 1.7(14) Three-Month Recovery Period for Subchronic Toxicity Evaluation DAY91 -DAY98 19.6 2.5(9) . (0) DAY9 8 -DAY105 21.1 3.2(9) . (0) DAY105 -DAY112 21.9 2.2(9) . (0) DAY112 -DAY119 20.6 2.0(9) . (0) DAY119 -DAY126 22.0 2.4(9) . (0) DAY126 -DAY133 21.8 2.4(9) . (0) DAY133 -DAY140 22.5 2.0(9) . (0) 20.8 1.6(15) . (0) . (0) . (0) . (0) . (0) . (0) . (0) 21.2 1.7(15) . (0) . (0) . (0) . (0) . (0) . (0) . (0) DuPont-9478 X 125 20.4 4.0(25) 20.1 3.1(25) 20.6 2.1(24) 19.4 2.5(10) 20.2 2.9(10) 20.0 3.0(10) 21.1 3.8(10) 22.4 4.5(10) 22.4 4.6(10) 23.5 3.3(10) - 84 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 9 (CONTINUED) MEAN DAILY FOOD CONSUMPTION BY FEMALE RATS (g/day) Group: II IV VI Dosage(mg/kg/day) 0 1 5 Three-Month Recovery Period for Subchronic Toxicity Evaluation (continued) DAY140 -DAY147 19.9 4 . 9 (9) . (0) 0) DAY147 -DAY154 20.8 2.8 (9) . (0) 0) DAY154 -DAY161 20.6 2 . 9 (9) . (0) 0) DAY161 -DAY168 22.2 2.3 (9) . (0) 0) DAY168 -DAY175 22.4 1.9 (9) . (0) 0) DAY175 -DAY182 22.4 2.4 (9) . (0) 0) VIII 25 . (0) . (0) . (0) . (0) . (0) . (0) DAY91 -DAY175 DAY91 -DAY182 21.3 2 . 1 (9) 21.4 2 . 0 (9) . (0) . (0) 0) . (0) 0) . (0) Da ta summarized as: Mean S t a n d a r d D e v i a t i o n (n) There were no statistically significant differences at p < 0.05 by Jonckheere -Terpstra trend test. DuPont-9478 X 125 21.9 3.9 10 22.2 4.4 10 21.7 4.2 10 24.5 4.8 10 21.1 3.8 10 20.6 2.7 10 21.7 3.5 10 21.6 3.4 10 - 85 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 10 MEAN DAILY FOOD EFFICIENCY OF MALE RATS (g body weight gain/g food consumed) Group: Dosage(mg/kg/day) I 0 Dosing Period for Subchronic Toxicity Evaluation DAY0 -DAY7 0.288 0.026(25) DAY7 -DAY14 0.248 0.040(25) DAY14 -DAY21 0.222 0.027(25) DAY21 -DAY28 0.149 0.036(25) DAY2 8 -DAY35 0.104 0.235(25) DAY3 5 -DAY42 0.094 0.104(25) DAY42 -DAY49 0.079 0.067(25) DAY4 9 -DAY56 0.098 0.046(25) DAY5 6 -DAY63 0.083 0.037(25) DAY6 3 -DAY70 0.085 0.044(25) DAY70 -DAY77 0.048 0.031(25) III 1 0.265 0.050(15) 0.256 0.055(15) 0.193 0.016(15) 0.149 0.027(15) 0.136 0.023(15) 0.099 0.030(15) 0.047 0.031(15) 0.114 0.024(15) 0.072 0.019(15) 0.075 0.034(15) 0.029 0.048(15) V 5 0.288 0.027(15) 0.253 0.028(15) 0.223 0.026(15) 0.163 0.022(15) 0.142 0.018(15) 0.107 0.034(15) 0.055 0.042(15) 0.129 0.032(15) 0.090 0.027(15) 0.067 0.034(15) 0.057 0.038(15) VII 25 0.284 0.025(15) 0.239 0.023(15) 0.217 0.024(15) 0.156 0.027(15) 0.149 0.021(15) 0.129 0.022(15) 0.056 0.035(15) 0.124 0.027(15) 0.088 0.020(15) 0.049# 0.024(15) 0.061 0.026(15) DuPont-9478 IX 125 0.290 0.041(25) 0.266# 0.025(25) 0.211 0.026(25) 0.166# 0.022(25) 0.125# 0.023(25) 0.119 0.030(25) 0.063 0.037(25) 0.099 0.028(25) 0.039 0.099(25) 0.035# 0.107(25) -0.106 0.339(25) - 86 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 10 (CONTINUED) MEAN DAILY FOOD EFFICIENCY OF MALE RATS (g body weight gain/g food consumed) Group: Dosage(mg/kg/day) I 0 III 1 Dosing Period for Subchronic Toxicity Evaluation (continued) DAY77 -DAY84 0.034 0.034(25) 0.023 0.067(15) DAY84 -DAY91 0.034 0.073(25) 0.055 0.037(15) V 5 0.054 0.025(15) 0.029 0.046(15) DAY0 -DAY91 0.124 0.012(25) 0.118 0.010(15) Three-Month Recovery Period for Subchronic Toxicity Evaluation DAY91 -DAY98 0.074 0.029(10) . (0) DAY98 -DAY105 0.070 0.024(10) . (0) DAY105 -DAY112 0.030 0.022(10) . (0) DAY112 -DAY119 0.035 0.019(10) . (0) DAY119 -DAY126 0.068 0.024(10) . (0) DAY126 -DAY133 0.038 0.028(10) . (0) DAY133 -DAY140 -0.008 0.020(10) . (0) 0.128 0.010(15) . (0) . (0) . (0) . (0) . (0) . (0) . (0) VII 25 0.049 0.032(15) 0.046 0.029(15) 0.127 0.010(15) . (0) . (0) . (0) . (0) . (0) . (0) . (0) DuPont-9478 IX 125 0.059 0.133(25 0.096# 0.060(25 0.123 0.010(25 0.064 0.033(10 0.050 0.027(10 0.026 0.034(10 0.051 0.028(10 0.079 0.044(10 0.055 0.034(10 0.009 0.036(10 - 87 - LO O CM CM OO OO oo oo oo oo 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 10 (CONTINUED) MEAN DAILY FOOD EFFICIENCY OF MALE RATS (g body weight gain/g food consumed) Group: I iii V Dosage (mg/kg/day) 0 1 5 Three-Month Recovery Period for Subchronic Toxicity Evaluation (continued) DAY140 -DAY147 0.037 0.015 10 ) . (0) (0) DAY147 -DAY154 0.037 0.024 10 ) . (0) (0) DAY154 -DAY161 0.007 0.030 10 ) . (0) (0) DAY161 -DAY168 0.027 0.026 10 ) . (0) (0) DAY168 -DAY175 0.025 0.027 10 ) . (0) (0) DAY175 -DAY182 0.012 0.026 10 ) . (0) (0) DAY91 -DAY175 DAY91 -DAY182 0.037 10 ) 0.035 10 ) . (0) . (0) (0) (0) Da ta summarized as: Mean S t a n d a r d D e v i a t i o n (n ) # Statistically significant differences at p < 0.05 by Jonckheere-Terpstra trend test. VII 25 (0) (0) (0) (0) (0) (0) (0) (0) oO oo O O LO LO DuPont-9478 IX 125 0.044 0.02 5( 10) 0.078 0.03 6( 10) -0.006 0.02 9( 10) 0.049 0.03 3( 10) 0.006 10) 0.060 10) 0.043 10) 0.044# 10) - 88 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 11 MEAN DAILY FOOD EFFICIENCY OF FEMALE RATS (g body weight gain/g food consumed) Group: Dosage(mg/kg/day) II 0 Dosing Period for Subchronic Toxicity Evaluation DAY0 -DAY7 0.133 0.036(25) DAY7 -DAY14 0.134 0.053(25) DAY14 -DAY21 0.109 0.031(24) DAY21 -DAY28 0.074 0.040(24) DAY2 8 -DAY35 0.080 0.036(24) DAY3 5 -DAY42 0.064 0.034(24) DAY42 -DAY49 0.004 0.044(24) DAY4 9 -DAY56 0.078 0.040(24) DAY5 6 -DAY63 0.028 0.034(24) DAY6 3 -DAY70 0.052 0.040(24) DAY70 -DAY77 0.024 0.028(24) IV 1 0.157 0.071(15) 0.138 0.025(15) 0.095 0.023(15) 0.081 0.038(15) 0.100 0.022(14) 0.065 0.034(15) -0.054 0.057(15) 0.125 0.040(15) 0.032 0.045(15) 0.048 0.029(15) 0.025 0.037(15) VI 5 0.161 0.066(15) 0.140 0.023(15) 0.101 0.049(15) 0.082 0.032(15) 0.085 0.038(15) 0.070 0.063(15) -0.023 0.051(15) 0.097 0.045(15) 0.037 0.044(15) 0.033 0.039(15) 0.028 0.029(15) VIII 25 0.146 0.044(15) 0.168 0.056(15) 0.092 0.047(15) 0.086 0.043(15) 0.089 0.040(15) 0.078 0.044(15) -0.052 0.069(15) 0.124 0.051(15) 0.015 0.041(15) 0.068 0.034(15) 0.035 0.030(15) DuPont-9478 X 125 0.153 0.033(25) 0.152 0.028(25) 0.114 0.039(25) 0.082 0.030(25) 0.069 0.036(25) 0.053 0.047(24) 0.008 0.062(25) 0.077 0.074(25) 0.032 0.045(25) 0.021# 0.045(25) 0.020 0.038(25) - 89 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 11 (CONTINUED) MEAN DAILY FOOD EFFICIENCY OF FEMALE RATS (g body weight gain/g food consumed) Group: Dosage (mg/kg/day) II 0 IV 1 Dosing Period for Subchronic Toxicity Evaluation (continued) DAY7 7 -DAY84 0.019 0 . 0 3 8 (24) 0.024 0 . 0 3 5 (15) DAY8 4 -DAY91 0.008 0 . 0 4 5 (24) -0.007 0 . 0 4 4 (15) VI 5 -0.006 0.023(15) 0.010 0.043(15) VIII 25 0.004 0 . 0 3 7 (15) -0.006 0 . 0 4 1 (15) DAY0 -DAY91 0.062 0 . 0 0 8 (24) 0.066 0 . 0 1 0 (14) Three-Month Recovery Period for Subchronic Toxicity Evaluation DAY91 -DAY98 0.031 0 . 0 6 4 (9) 0) DAY9 8 -DAY105 0.026 0 . 0 4 2 (9) 0) DAY105 -DAY112 0.019 0 . 0 4 1 (9) 0) DAY112 -DAY119 0.013 0 . 0 4 7 (9) 0) DAY119 -DAY126 0.067 0 . 0 2 9 (9) 0) DAY126 -DAY133 0.008 0 . 0 4 7 (9) 0) DAY133 -DAY140 0.010 0 . 0 4 8 (9) 0) 0.063 0.008(15) . (0) . (0) . (0) . (0) . (0) . (0) . (0) 0.066 0 . 0 0 6 (15) 0) 0) 0) 0) 0) 0) 0) DuPont-9478 X 125 0.056# 0.041( 25 -0.009 0.047( 25 0.065 0.007( 24 0.024 0.078( 10 0.008 0.032( 10 -0.011 0.097( 10 0.046 0.081( 10 0.095 0.039( 10 0.032 0.041( 10 -0.013 0.028( 10 - 90 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 11 (CONTINUED) MEAN DAILY FOOD EFFICIENCY OF FEMALE RATS (g body weight gain/g food consumed) Group: II IV VI Dosage(mg/kg/day) 0 1 5 Three-Month Recovery Period for Subchronic Toxicity Evaluation (continued) DAY140 -DAY147 0.041 0 . 0 4 3 9) . 0) . (0) DAY147 -DAY154 0.007 0 . 0 6 3 9) . 0) . (0) DAY154 -DAY161 -0.044 0 . 0 2 7 9) . 0) . (0) DAY161 -DAY168 0.053 0 . 0 3 4 9) . 0) . (0) DAY168 -DAY175 0.013 0 . 0 2 3 9) . 0) . (0) DAY175 -DAY182 0.015 0 . 0 3 9 9) . 0) . (0) DAY91 -DAY175 DAY91 -DAY182 0.022 0 . 0 0 8 9) 0.021 0 . 0 0 7 9) . 0) . 0) . (0) . (0) VIII 25 . (0) . (0) . (0) . (0) . (0) . (0) . (0) . (0) Da ta summarized as: Mean S t a n d a r d D e v i a t i o n (n) # Statistically significant difference at p < 0.05 by Jonckheere-Terpstra trend test. DuPont-9478 X 125 0.054 0.036(10 0.032 0.029(10 -0.011# 0.030(10 0.037 0.039(10 0.026 0.035(10 0.024 0.054(10 0.028 0.018(10 0.028 0.016(10 - 91 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 12 SUMMARY OF CLINICAL OBSERVATIONS FOR MALE RATS Treatm ent Group Dosage (mg/kg/day) Animal Count I III V VII IX 0 1 5 25 125 25 15 15 15 25 Absent Toe Forepaw Right Incidence Mean o n s e t (Days) Eye O b s e r v a tio n Corneal Opacity Right 0 ( 0%) 0 '( 0%) 0 ( 0%) 1 ( 7%) 35 0 ( 0% Incidence Mean o n s e t (Days) 1 ( 4%) 91 2 '( 13%) 14 0 ( 0%) 0 ( 0%) 1 ( 4% 63 Exophthalmus Right Incidence Mean o n s e t (Days) Exophthalmus B ilateral 0 ( 0%) 0 '( 0%) 0 ( 0%) 0 ( 0%) 1 ( 4% 56 Incidence Mean o n s e t (Days) 0 ( 0%) 1 '( 7%) 21 0 ( 0%) 0 ( 0%) 0 ( 0% Enophthalmus Right Incidence Mean o n s e t (Days) 2 ( 8%) 88 2 '( 13%) 77 1 ( 7%) 35 0 ( 0%) 1 ( 4% 63 DuPont-9478 - 92 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 12 (CONTINUED) Treatm ent Group Dosage (mg/kg/day) Animal Count SUMMARY OF CLINICAL OBSERVATIONS FOR MALE RATS I III V VII 0 1 5 25 25 15 15 15 Wet F u r V entral body V entral Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 1 ( 7%) 70 0 ( 0%) General Teeth Observations S tria te d Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) Clipped Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 7%) 86 Absent Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) IX 125 25 0 ( 0%) 24 '( 96%) # 58 o\o 16 ( 84 # 1 ' 4%) 91 DuPont-9478 - 93 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 12 (CONTINUED) Treatm ent Group Dosage (mg/kg/day) Animal Count SUMMARY OF CLINICAL OBSERVATIONS FOR MALE RATS I III V VII 0 1 5 25 25 15 15 15 IX 125 25 D isch arg e Eye r i g h t Black Incidence Mean o n s e t (Days) 4 ( 16%) 98 0 ( 0%) 1 ( 7%) 91 0 ( 0%) 2 ( 8% 63 Nose Incidence Mean o n s e t (Days) 1 ( 4%) 98 0 ( 0%) 1 ( 7%) 42 0 ( 0%) 3 ( 12% 98 H air Loss Incidence Mean o n s e t (Days) 4 ( 16%) 65 5 ( 33%) 83 1 ( 7%) 25 1 ( 7%) 18 4 ( 16% 62 Wound Superficial Incidence Mean o n s e t (Days) 1 ( 4%) 112 0 ( 0%) 0 ( 0%) 0 ( 0%) 2 ( 8% 42 H yperreactive Incidence Mean o n s e t (Days) 2 ( 8%) 98 0 ( 0%) 0 ( 0%) 0 ( 0%) 2 ( 8% 116 DuPont-9478 - 94 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 12 (CONTINUED) Treatm ent Group Dosage (mg/kg/day) Animal Count SUMMARY OF CLINICAL OBSERVATIONS FOR MALE RATS I III V VII 0 1 5 25 25 15 15 15 IX 125 25 H y p eractiv e Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 4% 42 Aggressive Behavior Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 2 ( 8% 77 V ocalization No A b n o r m a l i t y D e t e c t e d Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 7%) 21 0 ( 0% Protrusion Umbilical Hernia Incidence Mean o n s e t (Days) 1 ( 4%) 21 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0% Stain Fur/Skin Incidence Mean o n s e t (Days) 5 ( 20%) 130 2 ( 13%) 131 2 ( 13%) 112 1 ( 7%) 154 6 ( 24% 150 DuPont-9478 - 95 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 12 (CONTINUED) Treatm ent Group Dosage (mg/kg/day) Animal Count SUMMARY OF CLINICAL OBSERVATIONS FOR MALE RATS I III V VII 0 1 5 25 25 15 15 15 Swollen O bservations Face Incidence Mean o n s e t (Days) 1 ( 4%) 91 0 ( 0%) 0 ( 0%) 0 ( 0% Forepaw Right Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 7% 35 IX 125 25 0 ( 0%) 0 ( 0%) In c id e n c e - The number of an im als fo r which an o b s e rv a tio n was re c o rd e d . Mean o n s e t (Days) - The mean o f t h e f i r s t t e s t d ay an o b s e r v a t i o n was r e c o r d e d f o r t h a t g r o u p . # S t a t i s t i c a l l y s ig n if ic a n t d iffe re n c e a t p < 0.05 by Cochran-Armitage tre n d t e s t . DuPont-9478 - 96 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 13 SUMMARY OF CLINICAL OBSERVATIONS FOR FEMALE RATS Treatm ent Group Dosage (mg/kg/day) Animal Count II IV VI VIII X 0 1 5 25 125 25 15 15 15 25 Eye O b s e r v a tio n s Dark Right Incidence Mean o n s e t (Days) Dark Left 1 ( 4%) 49 1 ( 7%) 91 1 ( 7%) 105 1 ( 7%) 91 0 ( 0% Incidence Mean o n s e t (Days) 0 ( 0%) 1 ( 7%) 49 0 ( 0%) 0 ( 0%) 0 ( 0% Corneal Opacity Right Incidence Mean o n s e t (Days) 1 ( 4%) 7 1 ( 7%) 140 1 ( 7%) 119 0 ( 0%) 0 ( 0% Corneal Opacity B ilateral Incidence Mean o n s e t (Days) 1 ( 4%) 35 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0% Exophthalmus Right Incidence Mean o n s e t (Days) 1 ( 4%) 7 1 ( 7%) 147 0 ( 0%) 0 ( 0%) 0 ( 0% DuPont-9478 - 97 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 13 (CONTINUED) Treatm ent Group Dosage (mg/kg/day) Animal Count SUMMARY OF CLINICAL OBSERVATIONS FOR FEMALE RATS II IV VI VIII 0 1 5 25 25 15 15 15 X 125 25 Exophthalmus Left Incidence Mean o n s e t (Days) 1 ( 4%) 28 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0% Enophthalmus Right Incidence Mean o n s e t (Days) 1 ( 4%) 21 0 ( 0%) 1 ( 7%) 112 0 ( 0%) 0 ( 0% Enophthalmus B ilateral Incidence Mean o n s e t (Days) 1 ( 4%) 42 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0% Closed B ilateral Incidence Mean o n s e t (Days) 1 ( 4%) 119 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0% Wet F u r Incidence Mean o n s e t (Days) 0 ( 0%) 1 ( 7%) 14 0 ( 0%) 0 ( 0%) 0 ( 0% DuPont-9478 - 98 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 13 (CONTINUED) Treatm ent Group Dosage (mg/kg/day) Animal Count SUMMARY OF CLINICAL OBSERVATIONS FOR FEMALE RATS II IV VI VIII 0 1 5 25 25 15 15 15 X 125 25 Scab Face Incidence Mean o n s e t (Days) 1 ( 4%) 21 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) General Teeth Observations S tria te d Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 24 ( 96%) # 53 Clipped Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 9 ( 36%) # 108 B reathing Observat ions Noise Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 7%) 63 0 ( 0%) D isch arg e Eye Incidence Mean o n s e t (Days) 2 ( 8%) 74 1 ( 7%) 91 1 ( 7%) 91 0 ( 0%) 2 ( 8%) 137 - 99 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 13 (CONTINUED) Treatm ent Group Dosage (mg/kg/day) Animal Count SUMMARY OF CLINICAL OBSERVATIONS FOR FEMALE RATS II IV VI VIII 0 1 5 25 25 15 15 15 X 125 25 Nose Black Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 4% 112 Mouth Clear Incidence Mean o n s e t (Days) 0 ( 0%) 1 ( 7%) 14 0 ( 0%) 0 ( 0%) 0 ( 0% H air Loss Incidence Mean o n s e t (Days) Wound Deep Mouth Incidence Mean o n s e t (Days) Superficial Incidence Mean o n s e t (Days) 5 ( 20%) 32 3 ( 20%) 53 1 ( 7%) 21 4 ( 27%) 64 2 ( 8% 35 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 4% 112 2 ( 8%) 11 0 ( 0%) 0 ( 0%) 1 ( 7%) 42 1 ( 4% 119 DuPont-9478 - 100 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 13 (CONTINUED) Treatm ent Group Dosage (mg/kg/day) Animal Count SUMMARY OF CLINICAL OBSERVATIONS FOR FEMALE RATS II IV VI VIII 0 1 5 25 25 15 15 15 X 125 25 Arches back during handling Incidence Mean o n s e t (Days) 2 ( 8%) 35 2 ( 13%) 25 4 ( 27%) 32 3 ( 20%) 49 6 ( 24% 42 Ear tw itch Incidence Mean o n s e t (Days) 3 ( 12%) 39 2 ( 13%) 25 3 ( 20%) 33 3 ( 20%) 54 4 ( 16% 39 H yperreactive Incidence Mean o n s e t (Days) 1 ( 4%) 42 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 4% 63 H y p eractiv e Incidence Mean o n s e t (Days) 1 ( 4%) 77 1 ( 7%) 35 1 ( 7%) 28 3 ( 20%) 49 2 ( 8% 74 V ocalization No A b n o r m a l i t y D e t e c t e d Incidence Mean o n s e t (Days) 0 ( 0%) 1 ( 7%) 35 0 ( 0%) 0 ( 0%) 0 ( 0% Comments Excessive S alivation Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 1 ( 7%) 40 0 ( 0%) 0 ( 0% DuPont-9478 - 101 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 13 (CONTINUED) Treatm ent Group Dosage (mg/kg/day) Animal Count SUMMARY OF CLINICAL OBSERVATIONS FOR FEMALE RATS I I IV VI V III 0 1 5 25 25 15 15 15 X 125 25 Comments T eeth S tuck in Cage Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 0 ( 0%) 2 ( 8%) 108 Misshapen O bservations Ear Incidence Mean o n s e t (Days) 0 ( 0%) 1 ( 7%) 21 0 ( 0%) 0 ( 0%) 0 ( 0%) Stain Fur/Skin Incidence Mean o n s e t (Days) 2 ( 8%) 147 0 ( 0%) 1 ( 7%) 42 1 ( 7%) 154 2 ( 8%) 110 Swollen O bservations Nose o\o o\o OO OO Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 1 ( 4%) 105 Face Incidence Mean o n s e t (Days) 0 ( 0%) 0 ( 0%) 0 ( 0%) 2 ( 8%) 109 In c id e n c e - The number of an im als fo r which an o b s e rv a tio n was re c o rd e d . Mean o n s e t (Days) - The mean o f t h e f i r s t t e s t day an o b s e r v a t i o n was r e c o r d e d f o r t h a t g ro u p . # S t a t i s t i c a l l y s i g n i f i c a n t d if f e r e n c e a t p < 0.05 by Cochran-A rm itage tre n d t e s t . DuPont-9478 - 102 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 14 SUMMARY OF OPHTHALMOLOGY OBSERVATIONS FOR MALE RATS (Test Day 87) Treatm ent Group Dosage (mg/kg/day) Number Examined Retina R etinal Degeneration Focal Incidence Globe Phthisis bulbi Right Incidence I 0 20 1 ( 5%) 0 ( 0%) III 1 10 1 ( 10%) 0 ( 0%) V 5 10 1 ( 10%) 0 ( 0%) VII 25 10 0 ( 0%) 0 ( 0%) IX 125 20 0 ( 0% 1 ( 5% In c id e n c e - The number of an im als (p ercen t of anim als examined) fo r which an o b s e rv a tio n was re c o rd e d . There were no s t a t i s t i c a l l y s i g n i f i c a n t d if f e r e n c e s a t p < 0.05 by Cochran-A rm itage tr e n d t e s t . - 103 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 15 SUMMARY OF OPHTHALMOLOGY OBSERVATIONS FOR FEMALE RATS (Test Day 87) Treatm ent Group Dosage (mg/kg/day) Number Examined Retina R etinal Degeneration Focal Right Incidence II 0 20 1 ( 5%) IV 1 10 0 ( 0%) VI 5 10 0 ( 0%) VIII 25 10 0 ( 0%) X 125 20 0 ( 0%) In c id e n c e - The number of an im als (p ercen t of anim als examined) fo r which an o b s e rv a tio n was re c o rd e d . There were no s t a t i s t i c a l l y s i g n i f i c a n t d if f e r e n c e s a t p < 0.05 by Cochran-A rm itage tr e n d t e s t . - 104 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 16 PERCENT SURVIVAL OF MALE RATS Treatm ent Group Dose (mg/kg/day) I III 01 V VII 5 25 DAYS ON TEST 0 100 100 100 100 7 100 100 100 100 14 100 100 100 100 21 100 100 100 100 28 100 100 100 100 35 100 100 100 100 42 100 100 100 100 49 100 100 100 100 56 100 100 100 100 63 100 100 100 100 70 100 100 100 100 77 100 100 100 100 84 100 100 100 100 91 100 100 100 100 98 a,b 100 100 100 100 105 100 100 100 100 112 100 100 100 100 119 100 100 100 100 126 100 100 100 100 133 100 100 100 100 140 100 100 100 100 147 100 100 100 100 154 100 100 100 100 161 100 100 100 100 168 100 100 100 100 175 100 100 100 100 182 100 - - - IX 125 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 Number a t s tu d y s t a r t 25 15 15 15 25 S a c r i f i c e d b y d e s i g n b,c 15 15 15 15 15 A l i v e on t e s t day 182 10 0 0 0 10 P e r c e n t S u r v i v a l = (Number o f r a t s a liv e /N u m b e r o f r a t s a t r i s k ) *100 Number of r a t s a t r i s k = Number a t stu d y s t a r t - number s a c r i f i c e d by d e sig n . a . R a t s d e s i g n a t e d f o r t h e 90 - d a y r e c o v e r y p e r i o d a n d s a t e l l i t e b l e e d s b e g a n rec o v e ry on t e s t day 92. b . R a t s d e s i g n a t e d f o r t h e 90 - d a y e x p o s u r e p e r i o d w e r e s a c r i f i c e d on te s t day 93. c . R ats d e s ig n a te d fo r s a t e l l i t e b le e d s were s a c r i f i c e d on t e s t day 175. There were no s t a t i s t i c a l l y s i g n i f i c a n t d e c re a s e s in s u r v i v a l a t p < 0.05 by Cochran-Armitage trend t e s t . - 105 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 17 PERCENT SURVIVAL OF FEMALE RATS Treatm ent Group Dose (mg/kg/day) I I IV VI V I I I 0 1 5 25 DAYS ON TEST 0 100 100 100 100 7 100 100 100 100 14 100 100 100 100 21 100 100 100 100 28 100 100 100 100 35 100 100 100 100 42 100 100 100 100 49 100 100 100 100 56 100 100 100 100 63 100 100 100 100 70 100 100 100 100 77 100 100 100 100 84 100 100 100 100 91 100 100 100 100 98 a,b 100 100 100 100 105 100 100 100 100 112 100 100 100 100 119 100 100 100 100 126 100 100 100 100 133 100 100 100 100 140 100 100 100 100 147 100 100 100 100 154 100 100 100 100 161 100 100 100 100 168 100 100 100 100 175 100 100 100 100 182 100 - - - X 125 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 Number a t s tu d y s t a r t 25 15 15 15 25 A ccidentally k illed a 1 0 0 0 0 S a c r i f i c e d b y d e s i g n b' c 15 15 15 15 15 A l i v e on t e s t day 182 9 0 0 0 10 P e r c e n t S u r v iv a l = (Number o f r a t s a liv e /N u m b e r o f r a t s a t r i s k ) *100 Number of r a t s a t r i s k = Number a t stu d y s t a r t - number a c c i d e n t a l l y k i l l e d - number s a c r i f i c e d by d esig n a . R a t s d e s i g n a t e d f o r t h e 90 - d a y r e c o v e r y p e r i o d a n d s a t e l l i t e b l e e d s b e g a n rec o v e ry on t e s t days 92. b . R a t s d e s i g n a t e d f o r t h e 90 - d a y e x p o s u r e p e r i o d w e r e s a c r i f i c e d on t e s t day 94. c. Rats d e s ig n a te d fo r s a t e l l i t e b le e d s were s a c r i f i c e d on t e s t day 175. There were no s t a t i s t i c a l l y s i g n i f i c a n t d e c re a s e s in s u r v iv a l a t p < 0.05 by Cochran-Armitage tren d t e s t. - 106 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 18 MEAN FORELIMB AND HINDLIMB GRIP STRENGTH FOR MALE RATS (MEAN OF THREE TRIALS) Assessment Dosage Forelimb Hindlimb Period______ Group (mg/kg/day) Grip Strength (kg)_______Grip Strength (kg) Baseline I III V VII IX 0 1 5 25 125 0.53 (0.08) 0.58 (0.11) 0.57 (0.11) 0.60 (0.11) 0.58 (0.11) 0.30 (0.06) 0.31 (0.06) 0.28 (0.05) 0.29 (0.06) 0.27 (0.07) Week 13 I III V VII IX 0 1 5 25 125 1.13 (0.31) 1.17 (0.17) 1.22 (0.21) 1.27 (0.18) 1.14 (0.29) 0.53 (0.15) 0.58 (0.12) 0.53 (0.10) 0.58 (0.16) 0.49 (0.14) Data arranged as : Mean (Standard Deviation) Statistical Methods: Bartlett's test for homogeneity followed by analysis o f variance and Dunnett's test. There were no statistically significant differences from control at p<0.05. - 107 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 19 MEAN FORELIMB AND HINDLIMB GRIP STRENGTH FOR FEMALE RATS (MEAN OF THREE TRIALS) Assessment Dosage Forelimb Hindlimb Period______ Group (mg/kg/day) Grip Strength (kg)_______Grip Strength (kg) Baseline II IV VI VIII X 0 1 5 25 125 0.56 (0.08) 0.63 (0.09) 0.65 (0.09) * 0.60 (0.09) 0.60 (0.10) 0.37 (0.07) 0.35 (0.05) 0.36 (0.03) 0.35 (0.09) 0.33 (0.06) Week 13 II a IV VI VIII X 0 1 5 25 125 0.88 (0.21) 1.03 (0.19) 1.05 (0.15) 0.99 (0.19) 0.97 (0.13) 0.50 (0.10) 0.40 (0.09) 0.49 (0.09) 0.47 (0.13) 0.46 (0.07) Data arranged as : Mean (Standard Deviation) a n=9 due to unscheduled death. Statistical Methods: Bartlett's test for homogeneity followed by analysis o f variance and Dunnett's test. * Statistically significant difference from control at p<0.05 by Dunnett's test. - 108 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 20 SUMMARY OF FUNCTIONAL OBSERVATION BATTERY FINDINGS FOR MALE RATS BASELINE 13-WEEK Group I III V VII IX Dosage (:mg/kg/day) 0 1 5 25 125 Number examined: 10 10 10 10 10 I III V VII IX 0 1 5 25 125 10 10 10 10 10 MANUPULATIONS: APPROACH & TOUCH: no reaction normal increased reaction (jumps away or attacks) 0 10 0 0000 9 10 10 10 10 0 0 00000 10 10 10 10 10 00000 AUDITORY STIMULUS: no reaction 00000 normal reaction (rat flinches or flicks ear) 10 10 10 10 10 exaggerated reaction (rat jumps, flips) 00000 00000 10 10 10 10 10 00000 TAIL PINCH: no response normal (turns toward site) exaggerated response 00000 9 9 10 10 10 1 10 0 0 00000 10 10 10 10 10 00000 IN MOTOR ACTIVITY MONITOR: PUPILLARY RESPONSE present absent DEFECATION present absent diarrhea URINATION: present absent 10 10 10 10 10 00000 63834 47276 00000 10 9 10 10 9 0 10 0 1 10 10 10 10 10 00000 47334 63776 00000 89979 2 113 1 There were no statistically significant differences by Cochran-Armitage test for trend at p < 0.05. - 109 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 21 SUMMARY OF FUNCTIONAL OBSERVATION BATTERY FINDINGS FOR FEMALE RATS BASELINE 13-WEEK Group II IV VI VIII X Dosage (:mg/kg/day) 0 1 5 25 125 Number examined: 10 10 10 10 10 II a IV VI VIII X 0 1 5 25 125 10 10 10 10 10 MANUPULATIONS: APPROACH & TOUCH: no reaction 00000 normal 10 10 10 10 10 increased reaction (jumps away or attacks) 0 0 0 0 0 00000 9 10 10 10 10 00000 AUDITORY STIMULUS: no reaction 00000 normal reaction (rat flinches or flicks ear) 10 10 10 10 10 exaggerated reaction (rat jumps, flips) 00000 00000 9 10 10 10 10 00000 TAIL PINCH: no response normal (turns toward site) exaggerated response 00000 10 10 10 10 10 00000 00000 9 10 10 10 10 00000 IN MOTOR ACTIVITY MONITOR: PUPILLARY RESPONSE present absent DEFECATION present absent diarrhea URINATION: present absent 10 10 10 10 10 00000 43768 67342 00000 7 9 10 10 9 3 10 0 1 9 10 10 10 10 00000 37755 63355 00000 7 10 9 9 10 2 0 1 10 a n=9 due to unscheduled death. There were no statistically significant differences by Cochran-Armitage test for trend at p < 0.05. - 110 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 22 MOTOR ACTIVITY ASSESSEMENT: DURATION OF MOVEMENTS FOR MALE RATS (sec) DuPont-9478 ASSESSMENT DOSAGE PERIOD GROUP (mg/kg/day)________________________________SUCCESSIVE lOMINUTC I N T E R V ^ BASELINE I III V VII IX O 1 5 25 125 1 383(34) 402(60) 401(39) 398(33) 402(49) 2 318(50) 344(56) 334(44) 292(71) 343(74) 3 216(90) 312(78) * 254(74) 200(108) 281(121) 4 60(67) 163(120) * 172(130) * 146(135) * 164(149) * 5 35(87) 83(138) 112(139) * 68(99) 90(123) 6 27(67) 34(52) 72(113) 60(105) 51(75) TOTAL 1039(202) 1338(354) 1346(466) 1163(430) 1331(488) 13-WEEK I III a V VII IX O 1 5 25 125 383(42) 395(39) 390(42) 413(27) 405(69) Data arranged as: Mean (Standard Deviation). 327(36) 345(27) 333(40) 308(64) 327(69) 288(52) 295(46) 244(46) 228(107) 275(115) 270(55) 277(54) 209(91) 210(93) 220(133) 226(64) 205(108) 163(96) 129(85) * 202(128) 158(96) 127(98) 105(111) 158(77) 168(108) 1652(280) 1645(310) 1443(253) 1446(364) 1596(556) a n=9 due to sensor malfunction. Statistical Methods: Shapiro-Wilk's and Levene's tests were performed. Repeated measures analysis o f variance with linear contrasts was used to identify which dosage groups, if any, were significantly different from the control group. These tests were applied to bin data and total data. * Statistically significant difference from control at p < 0.05. - lll - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 23 MOTOR ACTIVITY ASSESSEMENT: DURATION OF MOVEMENTS FOR FEMALE RATS (sec) DuPont-9478 ASSESSMENT DOSAGE PERIOD GROUP (mg/kg/day)_________________________________SUCCESSIVE 1-MINUTE INTERVALS BASELINE II IV VI VIII X 0 1 5 25 125 1 370(53) 389(61) 364(29) 373(45) 367(68) 2 265(101) 302(75) 283(94) 259(96) 321(64) 3 243(120) 244(90) 234(80) 234(75) 272(88) 4 241(83) 207(135) 256(107) 200(69) 236(112) 5 189(118) 183(163) 154(121) 153(128) 181(113) 13-WEEK II a IV VI VIII Xb 0 1 5 25 125 383(47) 408(48) 408(40) 407(64) 403(47) 289(44) 294(69) 311(58) 298(72) 302(62) 237(46) 246(65) 211(78) 234(58) 241(71) 226(59) 249(70) 166(88) 193(95) 226(71) 203(39) 182(61) 151(77) 142(78) 206(89) 6 112(92) 145(158) 140(124) 73(64) 145(116) TOTAL 1419(381) 1471(599) 1430(372) 1292(322) 1522(442) 202(85) 150(114) 170(88) 176(66) 153(114) 1540(215) 1529(288) 1418(230) 1451(321) 1531(335) Data arranged as: Mean (Standard Deviation). a n=9 due to unscheduled death. b n=9 due to sensor malfunction. Statistical Methods: Shapiro-Wilk's and Levene's tests were performed. Jonckheere's trend test was used to identify which dosage groups, if any, were significantly different from the control group. These tests were applied to bin data and total data. There were no statistically significant differences from control at p < 0.05. - 112 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 24 MOTOR ACTIVITY ASSESSEMENT: NUMBER OF MOVEMENTS FOR MALE RATS DuPont-9478 ASSESSMENT DOSAGE PERIOD GROUP (mg/kg/day)________________________________SUCCESSIVE lOMINUTC I N T E R V ^ BASELINE I III V VII IX O 1 5 25 125 1 135(19) 129(26) 132(14) 138(13) 127(26) 2 139(13) 129(26) 14O(17) 137(7) 136(27) 3 124(36) 128(25) 131(17) 1O8(47) 126(34) 4 51(50) 91(65) * 100(50) * 87(68) * 73(50) 5 21(47) 39(51) 61(61) * 46(59) 44(56) 6 21(41) 23(36) 44(57) 40(53) 28(40) TOTAL 491(141) 539(160) 609(156) 556(201) 534(162) 13-WEEK I III a V VII IX O 1 5 25 125 141(16) 142(1O) 139(12) 13O(16) 133(22) Data arranged as: Mean (Standard Deviation). 144(1O) 148(1O) 138(17) 129(14) 134(16) 134(13) 138(16) 124(19) 1O8(45) 116(33) 137(17) 133(16) 109(32) 109(43) 96(45) * 123(22) 108(47) 89(43) 73(44) * 101(57) 95(50) 76(54) 66(60) 87(47) 88(55) 773(79) 745(112) 665(78) 637(179) * 668(168) a n=9 due to sensor malfunction. Statistical Methods: Shapiro-Wilk's and Levene's tests were performed. Repeated measures analysis o f variance with linear contrasts was used to identify which dosage groups, if any, were significantly different from the control group. These tests were applied to bin data and total data. * Statistically significant difference from control at p < 0.05. - 113 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 25 MOTOR ACTIVITY ASSESSEMENT: NUMBER OF MOVEMENTS FOR FEMALE RATS DuPont-9478 ASSESSMENT DOSAGE PERIOD GROUP (mg/kg/day)_________________________________SUCCESSIVE 1-MINUTE INTERVALS BASELINE II IV VI VIII X 0 1 5 25 125 1 138(17) 131(28) 137(13) 138(17) 131(26) 2 132(32) 127(27) 125(27) 127(24) 138(32) 3 120(48) 124(27) 130(32) 132(20) 131(29) 4 130(20) 97(48) 122(43) 127(30) 124(49) 5 115(54) 85(58) 95(60) 86(66) 94(56) 6 82(58) 71(55) 84(67) 62(52) 83(68) TOTAL 717(146) 635(162) 692(160) 673(148) 702(195) 13-WEEK II a IV VI VIII Xb 0 1 5 25 125 132(25) 135(24) 125(16) 135(17) 136(11) Data arranged as: Mean (Standard Deviation). 133(14) 136(12) 138(15) 133(16) 134(19) 128(21) 128(24) 115(29) 132(20) 130(27) 126(27) 130(20) 100(36) 108(37) 126(27) 127(21) 117(22) 96(38) 96(46) 111(35) 121(35) 86(50) 101(41) 111(29) 87(55) 767(101) 732(82) 675(104) 716(78) 725(103) a n=9 due to unscheduled death. b n=9 due to sensor malfunction. Statistical Methods: Shapiro-Wilk's and Levene's tests were performed. Jonckheere's trend test was used to identify which dosage groups, if any, were significantly different from the control group. These tests were applied to bin data and total data. There were no statistically significant differences from control at p < 0.05. - 114 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 26 TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day RBC (x106/pL) DAY 48 DAY 93 DAY 183 HGB (g/dL) DAY 48 DAY 93 DAY 183 HCT (%) DAY 48 DAY 93 DAY 183 MCV (fl) DAY 48 DAY 93 DAY 183 MCH (pg) DAY 48 DAY 93 DAY 183 8.33 0.38(10) 8.57 0.32(10) 8.71 0.42(10) 15.1 0.6(10) 15.9 0.6(10) 15.4 0.6(10) 48.3 1.7(10) 47.7 1.7(10) 47.8 1.8(10) 58.0 1.4(10) 55.7 0.9(10) 54.9 1.6(10) 18.2 0.5(10) 18.6 0.5(10) 17.7 0.7(10) 8.26 0.35(10) 8.55 0.37(10) -- 15.2 0.7(10) 15.9 0.6(10) -- 48.3 2.2(10) 48.0 1.6(10) -- 58.5 1.8(10) 56.2 1.8(10) -- 18.4 0.7(10) 18.6 0.7(10) 8.18 0.13(9) 8.32 0.22(10) -- 15.1 0.4(9) 15.6 0.5(10) -- 48.4 12(9) 47.0 1.5(10) -- 59.1 12(9) 56.5 1.0(10) -- 18.5 0.4(9) 18.7 0.5(10) 7.90* 0.20(10) 8.12* 0.22(10) -- 14.8 0.5(10) 15.6 0.7(10) -- 47.0 1.4(10) 46.8 1.9(10) -- 59.5 1.7(10) 57.5* 1.4(10) -- 18.7 0.6(10) 19.1 0.5(10) 7.78* 0.42(10) 7.76* 0.44(10) 8.39 0.47(7) 14.5 0.7(10) 15.0* 0.7(10) 15.1 0.3(7) 46.4 2.4(10) 45.5* 2.5(10) 46.6 16(7) 59.7 2.0(10) 58.7* 2.4(10) 55.6 14(7) 18.7 0.5(10) 19.4* 0.6(10) 18.1 0.8(7) - 115 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 26 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day MCHC (g/dL) DAY 48 DAY 93 DAY 183 RDW (%) DAY 48 DAY 93 DAY 183 ARET (x103/pL) DAY 48 DAY 93 DAY 183 PLT (x103/pL) DAY 48 DAY 93 DAY 183 WBC (x103/pL) DAY 48 DAY 93 DAY 183 31.3 0.5(10) 33.3 0.6(10) 32.3 0.7(10) 31.5 0.5(10) 33.1 0.5(10) -- 31.3 0.4(9) 33.1 0.8(10) -- 31.5 0.7(10) 33.3 0.6(10) -- 31.3 0.5(10) 33.0 0.7(10) 32.5 0.6(7) 11.9 0.4(10) 12.8 0.6(10) 13.5 0.5(10) 11.5 0.5(10) 12.2 0.5(10) -- 11.9 0.6(9) 12.6 0.7(10) -- 12.2 0.8(10) 12.7 0.5(10) -- 12.9* 0.9(10) 13.6 1.8(10) 13.3 0.6(7) 212.6 16.7(10) 172.4 22.7(10) 179.0 24.2(10) 206.0 25.6(10) 159.2 21.2(10) -- 235.8 44.5(9) 187.0 30.8(10) -- 239.6 43.2(10) 192.6 31.2(10) -- 262.0* 26.0(10) 216.8* 53.6(10) 188.4 22.9(7) 1010 151(6) 1221 132(9) 1145 188(6) 1098 20(4) 1227 109(7) -- 1054 104(7) 1199 128(8) -- 1012 48(5) 1252 126(8) -- 950 178(5) 1275 209(9) 1074 165(7) 14.18 2.18(10) 12.19 3.55(10) 13.47 3.28(10) 15.67 3.75(10) 12.45 1.99(10) 15.12 3.70(9) 11.77 2.58(10) 15.46 3.13(10) 13.36 3.59(10) 16.29 4.01(10) 13.89 3.97(10) 13.97 2.30(7) - 116 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 26 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day ANEU (x103/pL) DAY 48 DAY 93 DAY 183 ALYM (x103/pL) DAY 48 DAY 93 DAY 183 AMON (x103/pL) DAY 48 DAY 93 DAY 183 AEOS (x103/pL) DAY 48 DAY 93 DAY 183 ABAS (x103/pL) DAY 48 DAY 93 DAY 183 1.63 0.55(10) 1.86 0.68(10) 2.75 1.37(10) 11.97 1.60(10) 9.89 3.01(10) 9.99 2.56(10) 0.30 0.13(10) 0.21 0.06(10) 0.40 0.14(10) 0.12 0.08(10) 0.14 0.07(10) 0.17 0.06(10) 0.09 0.05(10) 0.04 0.03(10) 0.11 0.05(10) 1.61 0.79(10) 1.45 0.33(10) -- 13.50 3.21(10) 10.55 1.99(10) -- 0.24 0.10(10) 0.24 0.14(10) -- 0.11 0.05(10) 0.13 0.06(10) -- 0.14 0.09(10) 0.04 0.03(10) 1.96 0.66(9) 1.81 1.04(10) -- 12.50 3.11(9) 9.49 1.45(10) -- 0.38 0.15(9) 0.24 0.12(10) -- 0.10 0.05(9) 0.14 0.12(10) -- 0.10 0.05(9) 0.04 0.01(10) 2.00 0.68(10) 2.48 1.13(10) -- 12.84 2.95(10) 10.34 2.79(10) -- 0.29 0.10(10) 0.26 0.10(10) -- 0.11 0.04(10) 0.17 0.14(10) -- 0.14 0.05(10) 0.04 0.02(10) 2.04 0.90(10) 2.17 0.79(10) 2.49 0.56(7) 13.69 3.35(10) 11.26 3.21(10) 10.67 1.74(7) 0.27 0.11(10) 0.21 0.06(10) 0.43 0.13(7) 0.12 0.04(10) 0.14 0.04(10) 0.18 0.05(7) 0.11 0.07(10) 0.04 0.01(10) 0.14 0.08(7) - 117 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 26 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day ALUC (x103/|iL) DAY 48 DAY 93 DAY 183 0.08 0.03(10) 0.06 0.03(10) 0.05 0.02(10) 0.07 0.04(10) 0.05 0.04(10) -- 0.08 0.02(9) 0.05 0.01(10) -- 0.09 0.02(10) 0.06 0.03(10) -- 0.07 0.04(10) 0.06 0.02(10) 0.07 0.02(7) Data arranged as: Mean Standard deviation (Number o f values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. - 118 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 27 TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR FEMALE RATS Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day RBC (x106/pL) DAY 49 DAY 94 DAY 183 HGB (g/dL) DAY 49 DAY 94 DAY 183 HCT (%) DAY 49 DAY 94 DAY 183 MCV (fl) DAY 49 DAY 94 DAY 183 MCH (pg) DAY 49 DAY 94 DAY 183 8.28 0.29(10) 8.24 0.26(10) 7.76 0.36(9) 15.6 0.5(10) 16.1 0.5(10) 14.7 0.6(9) 49.0 1.7(10) 47.2 1.5(10) 44.0 17(9) 59.2 0.9(10) 57.2 0.9(10) 56.8 18(9) 18.8 0.4(10) 19.6 0.3(10) 19.0 0.7(9) 8.09 0.29(9) 8.28 0.25(10) -- 15.4 0.5(9) 16.4 0.4(10) -- 48.1 17(9) 47.9 1.4(10) -- 59.5 11(9) 57.8 0.9(10) -- 19.1 0.3(9) 19.8 0.3(10) 8.14 0.36(10) 8.38 0.31(10) -- 15.5 0.6(10) 16.5 0.4(10) -- 48.3 1.7(10) 48.3 1.8(10) -- 59.4 1.6(10) 57.7 1.3(10) -- 19.0 0.4(10) 19.7 0.5(10) 8.00 0.41(10) 8.07 0.46(10) -- 14.9 0.6(10) 15.7 0.7(10) -- 46.8* 2.2(10) 45.8 2.4(10) -- 58.5 1.2(10) 56.8 0.8(10) -- 18.7 0.4(10) 19.5 0.5(10) 7.50* 0.43(10) 7.66* 0.34(10) 7.75 0.30(10) 14.2* 0.7(10) 15.1* 0.7(10) 15.1 0.5(10) 44.5* 2.5(10) 44.6* 2.1(10) 45.1 1.9(10) 59.4 1.4(10) 58.3 1.6(10) 58.2 11(10) 19.0 0.6(10) 19.8 0.6(10) 19.4 0.3(10) - 119 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 27 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR FEMALE RATS Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day MCHC (g/dL) DAY 49 DAY 94 DAY 183 RDW (%) DAY 49 DAY 94 DAY 183 ARET (x103/pL) DAY 49 DAY 94 DAY 183 PLT (x103/pL) DAY 49 DAY 94 DAY 183 WBC (x103/pL) DAY 49 DAY 94 DAY 183 31.8 0.4(10) 34.3 0.4(10) 33.4 0.3(9) 32.1 0.3(9) 34.3 0.4(10) -- 32.0 0.4(10) 34.2 0.5(10) -- 32.0 0.5(10) 34.4 0.8(10) -- 32.0 0.5(10) 34.0 0.3(10) 33.4 0.6(10) 11.7 0.6(10) 10.9 0.5(10) 11.8 0.5(9) 11.6 0.4(9) 11.0 0.4(10) -- 11.8 0.5(10) 11.0 0.4(10) -- 11.8 0.4(10) 10.8 0.3(10) -- 12.0 0.4(10) 11.6* 0.5(10) 12.1 0.8(10) 256.6 44.7(10) 141.4 31.4(10) 153.5 33.4(9) 225.4 26.9(9) 139.0 16.0(10) -- 249.0 51.4(10) 155.1 28.4(10) -- 217.1 @ 31.2(10) 140.6 19.8(10) -- 240.6 18.0(10) 176.6* 39.0(10) 164.4 27.0(10) 973 46(7) 1083 130(10) 1059 194(7) 835 175(7) 1025 174(9) -- 1095 185(8) 1158 88(7) -- 952 181(8) 1026 190(7) -- 978 160(5) 1068 88(9) 957 231(6) 13.02 4.11(10) 10.84 3.92(10) 7.29 1.97(9) 11.83 2.63(9) 9.59 2.57(10) 13.25 3.38(10) 10.57 2.47(10) 12.56 2.78(10) 9.86 2.61(10) 11.10 3.04(10) 10.26 1.38(10) 8.19 1.73(10) - 120 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 27 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR FEMALE RATS Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day ANEU (x103/pL) DAY 49 DAY 94 DAY 183 ALYM (x103/pL) DAY 49 DAY 94 DAY 183 AMON (x103/pL) DAY 49 DAY 94 DAY 183 AEOS (x103/pL) DAY 49 DAY 94 DAY 183 ABAS (x103/pL) DAY 49 DAY 94 DAY 183 1.36 0.66(10) 1.28 0.47(10) 1.33 0.49(9) 11.18 3.47(10) 9.07 3.39(10) 5.55 1.65(9) 0.22 0.15(10) 0.18 0.07(10) 0.25 0.11(9) 0.11 0.06(10) 0.18 0.07(10) 0.09 0.03(9) 0.09 0.05(10) 0.06 0.02(10) 0.04 0.04(9) 0.94 0.36(9) 1.32 0.81(10) -- 10.50 2.40(9) 7.85 2.27(10) -- 0.20 0.07(9) 0.18 0.09(10) -- 0.09 0.03(9) 0.13 0.03(10) -- 0.05 0.02(9) 0.06 0.03(10) 1.50 0.56(10) 1.45 0.51(10) -- 11.23 3.25(10) 8.70 2.48(10) -- 0.23 0.10(10) 0.15 0.08(10) -- 0.12 0.04(10) 0.17 0.06(10) -- 0.10 0.08(10) 0.05 0.05(10) 1.43 0.82(10) 1.76 1.22(10) -- 10.60 2.79(10) 7.61 2.12(10) -- 0.25 0.13(10) 0.23 0.21(10) -- 0.11 0.05(10) 0.15 0.06(10) -- 0.08 0.05(10) 0.06 0.04(10) 1.40 0.56(10) 1.74 0.68(10) 1.43 0.47(10) 9.25 2.67(10) 8.01 1.14(10) 6.27 1.67(10) 0.22 0.08(10) 0.26 0.09(10) 0.29 0.13(10) 0.10 0.05(10) 0.13 0.05(10) 0.11 0.05(10) 0.06 0.04(10) 0.06 0.02(10) 0.06@ 0.01(10) - 121 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 27 (Continued) TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR FEMALE RATS Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day ALUC (x103/|iL) DAY 49 DAY 94 DAY 183 0.07 0.03(10) 0.06 0.04(10) 0.03 0.01(9) 0.05 0.02(9) 0.05 0.03(10) -- 0.07 0.03(10) 0.04 0.03(10) -- 0.08 0.03(10) 0.05 0.04(10) -- 0.07 0.04(10) 0.05 0.02(10) 0.03 0.01(10) Data arranged as: Mean Standard deviation (Number o f values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. - 122 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 28 TEST/ PERIOD SUMMARY OF COAGULATION VALUES FOR MALE RATS Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day PT (seconds) DAY 93 APTT (seconds) DAY 93 15.9 0.8(9) 18.2 2.5(9) 16.1 0.6(10) 20.2 2.1(10) 15.9 11(9) 19.1 16(9) 15.5 0.5(10) 17.7 1.7(10) 15.9 17(9) 19.3 2.1(9) Data arranged as: Mean Standard deviation (Number o f values included in calculation) There were no statistically significant differences from control at p < 0.05. TABLE 29 TEST/ PERIOD SUMMARY OF COAGULATION VALUES FOR FEMALE RATS Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day PT (seconds) DAY 94 APTT (seconds) DAY 94 15.3 0.5(10) 15.8 1.8(10) 14.9 0.6(10) 16.2 2.0(10) 15.3 0.6(10) 15.0 1.6(10) 15.2 0.6(10) 15.4 1.7(10) 14.9 1.0(10) 14.1 2.0(10) Data arranged as: Mean Standard deviation (Number o f values included in calculation) There were no statistically significant differences from control at p < 0.05. - 123 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 30 SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day AST (U/L) DAY 48 DAY 93 DAY 183 ALT (U/L) DAY 48 DAY 93 DAY 183 SDH (U/L) DAY 48 DAY 93 DAY 183 ALKP (U/L) DAY 48 DAY 93 DAY 183 BILI (mg/dL) DAY 48 DAY 93 DAY 183 69 10(10) 85 12(10) 147 134(10) 69 5(10) 88 13(9) -- 70 6(10) 114 69(10) -- 72 9(10) 186 152(10) -- 69 6(10) 81 17(10) 134 51(10) 33 4(10) 36 5(10) 77 91(10) 33 5(10) 42 8(9) -- 32 5(10) 49 44(10) -- 33 5(10) 89 71(10) -- 34 7(10) 44 16(10) 67 26(10) 14.1 3.5(10) 18.7 3.1(10) 24.7 18.0(10) 13.2 2.8(10) 16.9 4.8(10) -- 12.6 2.4(10) 17.5 16.3(10) -- 13.2 3.0(10) 41.5 38.2(10) -- 13.3 3.5(10) 18.4 6.6(10) 21.0 6.8(10) 131 18(9) 109 25(10) 86 20(10) 114 21(10) 97 18(9) -- 126 17(9) 91 18(10) -- 135 33(10) 110 25(10) -- 165* 39(10) 136 35(10) 86 23(10) 0.11 0.04(10) 0.10 0.03(10) 0.14 0.05(10) 0.07* 0.03(10) 0.06@ 0.02(9) -- 0.10 0.03(10) 0.10 0.04(10) -- 0.10 0.04(10) 0.09 0.05(10) -- 0.07 0.03(10) 0.09 0.03(10) 0.12 0.04(10) - 124 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 30 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day BUN (mg/dL) DAY 48 DAY 93 DAY 183 CREA (mg/dL) DAY 48 DAY 93 DAY 183 CHOL (mg/dL) DAY 48 DAY 93 DAY 183 TRIG (mg/dL) DAY 48 DAY 93 DAY 183 GLUC (mg/dL) DAY 48 DAY 93 DAY 183 14 2(10) 13 2(10) 18 2(10) 14 1(10) 14 2(10) -- 14 2(10) 13 2(10) -- 14 1(10) 15* 2(10) -- 13 1(10) 13 2(10) 16* 2(10) 0.25 0.06(10) 0.42 0.06(10) 0.46 0.03(10) 0.27 0.04(10) 0.39 0.08(10) -- 0.28 0.04(10) 0.36 0.04(10) -- 0.26 0.02(10) 0.37 0.06(10) -- 0.26 0.04(10) 0.37 0.04(10) 0.41* 0.04(10) 66 9(10) 80 16(10) 76 28(10) 53 11(10) 57* 9(10) -- 62 12(10) 74 19(10) -- 52* 15(10) 66 17(10) -- 57 11(10) 65 15(10) 79 17(10) 87 24(10) 77 32(10) 81 33(10) 74 27(10) 67 23(9) -- 95 50(10) 77 28(10) -- 83 42(10) 64 26(10) -- 43* 21(10) 37* 18(10) 95 59(10) 119 7(10) 109 28(10) 129 40(10) 115 9(10) 117 32(10) -- 122 10(10) 114 24(10) -- 118 9(10) 110 29(10) -- 122 20(10) 105 22(10) 127 31(10) - 125 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 30 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day TP (g/dL) DAY 48 DAY 93 DAY 183 ALB (g/dL) DAY 48 DAY 93 DAY 183 GLOB (g/dL) DAY 48 DAY 93 DAY 183 CALC (mg/dL) DAY 48 DAY 93 DAY 183 IPHS (mg/dL) DAY 48 DAY 93 DAY 183 6.5 0.3(10) 7.2 0.4(10) 6.9 0.2(10) 4.2 0.2(10) 4.4 0.2(10) 4.2 0.2(10) 2.4 0.3(10) 2.8 0.3(10) 2.7 0.2(10) 10.8 0.4(10) 11.3 0.4(10) 11.4 0.5(10) 8.3 0.6(10) 8.1 0.6(10) 8.5 0.8(10) 6.6 0.4(10) 7.0 0.3(9) -- 4.1 0.3(10) 4.3 0.2(9) -- 2.4 0.2(10) 2.6 0.2(9) -- 10.8 0.2(10) 11.3 0.6(10) -- 7.9 0.5(10) 8.9 14(9) -- 6.6 0.4(10) 7.0 0.5(10) -- 4.2 0.2(10) 4.3 0.2(10) -- 2.5 0.3(10) 2.7 0.3(10) -- 10.8 0.5(10) 11.2 0.6(10) -- 8.4 0.7(10) 8.7 0.9(10) -- 6.5 0.3(10) 7.0 0.4(10) -- 4.2 0.2(10) 4.4 0.3(10) -- 2.3 0.2(10) 2.6 0.2(10) -- 10.5 0.4(10) 11.1 0.2(10) -- 8.4 1.0(10) 9.2 1.3(10) -- 7.0* 0.4(10) 7.6* 0.1(10) 6.8 0.1(10) 4.7* 0.2(10) 5.0@ 0.2(10) 4.2 0.1(10) 2.3 0.3(10) 2.6 0.2(10) 2.7 0.1(10) 10.8 0.4(10) 11.4 0.4(10) 11.5 0.3(10) 9.2* 0.9(10) 9.5* 1.2(10) 9.2 1.0(10) - 126 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 30 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS TEST/ PERIOD Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day NA (mmol/L) DAY 48 DAY 93 DAY 183 K (mmol/L) DAY 48 DAY 93 DAY 183 CL (mmol/L) DAY 48 DAY 93 DAY 183 PFLU (pg/mL) DAY 93 DAY 183 148.2 1.3(10) 148.4 1.3(10) 147.9 1.4(10) 149.5 4.7(10) 149.4 2.2(10) -- 148.2 2.3(10) 148.3 3.0(10) -- 148.3 1.2(10) 148.3 2.5(10) -- 147.7 1.6(10) 148.1 2.4(10) 148.4 2.2(10) 5.87 0.53(10) 6.15 0.51(10) 6.17 0.45(10) 5.68 0.47(10) 6.16 0.47(9) -- 5.76 0.62(10) 6.31 0.52(10) -- 5.52 0.43(10) 6.32 0.71(10) -- 5.74 0.34(10) 6.31 0.59(10) 6.29 0.54(10) 102.2 2.1(10) 100.7 1.9(10) 102.3 2.2(10) 103.2 3.7(10) 101.8 1.8(10) -- 101.5 2.2(10) 101.1 1.5(10) -- 101.0 2.1(10) 101.2 1.7(10) -- 101.1 2.0(10) 100.1 1.5(10) 104.1 1.9(10) 0.1 0.0(10) 0.1 0.1(9) 0.1 0.0(10) 0.1 0.0(10) 0.1 0.0(10) 0.4@ 0.0(10) 0.1 0.0(10) Data arranged as: Mean Standard deviation (Number o f values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. - 127 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 31 SUMMARY OF CLINICAL CHEMISTRY VALUES FOR FEMALE RATS TEST/ PERIOD Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day AST (U/L) DAY 49 DAY 94 DAY 183 ALT (U/L) DAY 49 DAY 94 DAY 183 SDH (U/L) DAY 49 DAY 94 DAY 183 ALKP (U/L) DAY 49 DAY 94 DAY 183 BILI (mg/dL) DAY 49 DAY 94 DAY 183 72 11(10) 85 17(10) 177 176(9) 77 15(10) 119 51(10) -- 34 8(10) 40 17(10) 96 90(9) 35 7(10) 64 46(10) -- 10.5 2.7(10) 16.7 4.4(10) 29.2 27.5(9) 10.5 4.0(10) 21.5 8.2(10) -- 83 16(10) 51 11(10) 34 8(9) 79 19(10) 52 13(10) -- 0.15 0.04(10) 0.15 0.01(10) 0.17 0.07(9) 0.15 0.03(10) 0.15 0.03(10) -- 65 6(10) 82 18(10) -- 91 89(10) 176 285(10) -- 61 9(10) 93 40(10) 103 54(10) 29 4(10) 37 10(10) -- 44 41(10) 75 106(10) -- 32 5(10) 45 16(10) 58 41(10) 7.9 0.9(10) 13.6 2.7(10) -- 21.8 41.2(10) 44.4 84.1(10) -- 10.0 2.2(10) 19.0 10.4(10) 17.5 10.4(10) 79 24(10) 54 19(10) -- 73 28(10) 49 19(10) -- 75 14(10) 53 10(10) 38 10(10) 0.13 0.03(10) 0.12 0.03(10) -- 0.14 0.04(10) 0.14 0.04(10) -- 0.16 0.03(10) 0.17 0.04(10) 0.15 0.04(10) - 128 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 31 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR FEMALE RATS TEST/ PERIOD Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day BUN (mg/dL) DAY 49 DAY 94 DAY 183 CREA (mg/dL) DAY 49 DAY 94 DAY 183 CHOL (mg/dL) DAY 49 DAY 94 DAY 183 TRIG (mg/dL) DAY 49 DAY 94 DAY 183 GLUC (mg/dL) DAY 49 DAY 94 DAY 183 15 2(10) 17 2(10) 17 2(9) 16 2(10) 17 2(10) -- 16 2(10) 17 1(10) -- 15 2(10) 17 4(10) -- 15 2(10) 17 2(10) 16 3(10) 0.33 0.05(10) 0.47 0.06(10) 0.52 0.05(9) 0.35 0.06(10) 0.49 0.03(10) -- 0.34 0.06(10) 0.44 0.06(10) -- 0.33 0.07(10) 0.48 0.10(10) -- 0.31 0.03(10) 0.46 0.06(10) 0.48 0.06(10) 77 19(10) 85 19(10) 134 26(9) 86 16(10) 97 15(10) -- 73 14(10) 79 18(10) -- 105 28(10) 125 45(10) -- 107@ 21(10) 123 39(10) 147 67(10) 44 20(10) 51 26(10) 78 14(9) 50 20(10) 66 53(10) -- 37 12(10) 39 11(10) -- 43 22(10) 41 13(10) -- 55 46(10) 42 47(10) 89 63(10) 115 10(10) 101 9(10) 121 32(9) 112 13(10) 104 12(10) -- 116 13(10) 104 9(10) -- 113 5(10) 106 16(10) -- 111 5(10) 100 5(10) 104 6(10) - 129 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 31 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR FEMALE RATS TEST/ PERIOD Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day TP (g/dL) DAY 49 DAY 94 DAY 183 ALB (g/dL) DAY 49 DAY 94 DAY 183 GLOB (g/dL) DAY 49 DAY 94 DAY 183 CALC (mg/dL) DAY 49 DAY 94 DAY 183 IPHS (mg/dL) DAY 49 DAY 94 DAY 183 7.3 0.3(10) 7.8 0.3(10) 8.5 0.3(9) 4.9 0.2(10) 5.2 0.3(10) 5.7 0.3(9) 2.4 0.2(10) 2.6 0.2(10) 2.8 0.1(9) 11.3 0.2(10) 11.7 0.4(10) 12.4 0.3(9) 7.0 1.3(10) 6.8 1.7(10) 7.1 13(9) 7.3 0.3(10) 8.0 0.3(10) -- 4.9 0.2(10) 5.4 0.3(10) -- 2.4 0.2(10) 2.6 0.1(10) -- 11.3 0.4(10) 11.5 0.2(10) -- 7.4 1.2(10) 5.9 0.8(10) -- 7.0 0.5(10) 7.6 0.5(10) -- 4.6 0.4(10) 5.0 0.3(10) -- 2.5 0.3(10) 2.7 0.3(10) -- 11.0 0.3(10) 11.3 0.4(10) -- 6.8 0.7(10) 6.8 0.9(10) -- 7.6 0.5(10) 8.3 0.7(10) -- 5.0 0.4(10) 5.5 0.5(10) -- 2.6 0.3(10) 2.7 0.4(10) -- 11.4 0.4(10) 11.8 0.5(10) -- 6.9 0.5(10) 6.7 0.9(10) -- 7.9* 0.4(10) 8.6* 0.6(10) 8.4 0.4(10) 5.5@ 0.3(10) 5.8* 0.3(10) 5.4 0.4(10) 2.4 0.2(10) 2.8 0.3(10) 2.9 0.4(10) 11.6 0.5(10) 12.2* 0.4(10) 12.2 0.3(10) 7.6 1.0(10) 7.3 0.5(10) 7.4 1.0(10) - 130 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 31 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR FEMALE RATS TEST/ PERIOD Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day NA (mmol/L) DAY 49 DAY 94 DAY 183 K (mmol/L) DAY 49 DAY 94 DAY 183 CL (mmol/L) DAY 49 DAY 94 DAY 183 PFLU (pg/mL) DAY 94 DAY 183 145.2 1.4(10) 145.6 2.1(10) 148.7 1.5(9) 145.1 1.7(10) 145.7 1.3(10) -- 145.1 1.6(10) 145.9 1.6(10) -- 144.1 2.4(10) 145.5 1.2(10) -- 144.5 1.8(10) 146.3 2.5(10) 149.6 1.5(10) 5.74 0.70(10) 5.74 0.67(10) 5.80 0.55(9) 5.59 0.48(10) 5.54 0.39(10) -- 5.50 0.38(10) 5.96 0.36(10) -- 5.36 0.27(10) 5.40 0.31(10) -- 5.55 0.38(10) 5.95 0.31(10) 5.94 0.53(10) 101.2 1.6(10) 101.1 3.0(10) 104.1 16(9) 101.6 1.3(10) 101.1 1.8(10) -- 101.9 11(10) 102.4 1.5(10) -- 100.7 2.0(10) 100.5 2.0(10) -- 100.9 1.0(10) 100.5 1.9(10) 103.9 2.3(10) 0.1 0.0(10) 0.1 0.0(9) 0.1 0.1(10) 0.1 0.0(10) 0.2 0.0(10) 0.5@ 0.1(10) 0.1 0.0(9) Data arranged as: Mean Standard deviation (Number o f values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. - 131 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 32 TEST/ PERIOD SUMMARY OF URINALYSIS VALUES FOR MALE RATS Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day VOL (mL) DAY 48 DAY 93 DAY 183 UOSM (mOsm) DAY 48 DAY 93 DAY 183 pH DAY 48 DAY 93 DAY 183 URO (EU/dL) DAY 48 DAY 93 DAY 183 UFLU fog) DAY 93 DAY 183 14.4 10.5(10) 6.8 2.5(10) 7.5 6.5(10) 10.9 5.6(10) 6.3 1.8(10) -- 11.7 6.0(10) 7.6 4.2(10) -- 13.0 7.9(10) 7.8 5.6(10) -- 17.2 5.6(10) 21.1@ 13.4(10) 7.7 4.1(10) 790 429(10) 1321 457(10) 1400 808(9) 841 341(10) 1324 323(10) -- 913 313(10) 1293 593(10) -- 840 365(10) 1549 854(10) -- 605 162(10) 703 452(10) 1322 590(10) 7.3 0.3(10) 6.8 0.7(10) 6.6 0.6(10) 7.1 0.2(10) 6.8 0.4(10) -- 7.1 0.2(10) 6.8 0.4(10) -- 7.1 0.4(10) 6.8 0.3(10) -- 7.4 0.3(10) 7.0 0.4(10) 6.6 0.4(10) 0.2 0.0(10) 0.2 0.0(9) 0.4 0.3(10) 0.2 0.0(10) 0.2 0.0(10) -- 0.2 0.0(10) 0.2 0.0(10) -- 0.2 0.0(10) 0.3 0.3(10) -- 0.2 0.0(10) 0.2 0.0(10) 0.3 0.3(10) 10.7 4.4(10) 9.9 3.1(9) 13.0 1.9(10) -- 38.8@ 10.1(9) -- 202.4@ 57.9(9) -- 997.2@ 246.3(10) 27.6* 5.1(10) - 132 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 32 (Continued) TEST/ PERIOD SUMMARY OF URINALYSIS VALUES FOR MALE RATS Group I 0 mg/kg/day Group III 1 mg/kg/day Group V 5 mg/kg/day Group VII 25 mg/kg/day Group IX 125 mg/kg/day UMTP (mg/dL) DAY 48 DAY 93 DAY 183 49 34(10) 108 87(10) 161 164(10) 48 26(10) 98 47(10) -- 55 34(10) 81 49(10) -- 47 33(10) 89 53(10) -- 43 34(10) 67 91(10) 95 91(10) Data arranged as: Mean Standard deviation (Number o f values included in calculation) * Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test. @ Statistically significant difference from control at p < 0.05 by Dunn's test. - 133 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 33 TEST/ PERIOD SUMMARY OF URINALYSIS VALUES FOR FEMALE RATS Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day VOL (mL) DAY 49 DAY 94 DAY 183 UOSM (mOsm) DAY 49 DAY 94 DAY 183 pH DAY 49 DAY 94 DAY 183 URO (EU/dL) DAY 49 DAY 94 DAY 183 UFLU fog) DAY 94 DAY 183 7.2 3.3(10) 5.0 4.5(10) 8.2 14.1(7) 7.5 5.8(10) 2.8 18(9) -- 8.2 6.2(10) 4.2 2.5(10) -- 14.4 13.3(10) 4.8 3.1(10) -- 8.2 5.2(10) 7.7 4.3(10) 4.9 4.4(10) 882 281(10) 1336 615(10) 1477 1104(7) 985 499(10) 1519 598(8) -- 1050 509(9) 1317 528(10) -- 623 257(10) 1231 493(10) -- 954 569(10) 1051 714(10) 1445 868(10) 7.1 0.2(10) 6.0 0.3(10) 5.7 0.5(7) 7.0 0.6(10) 6.1 0.4(9) -- 6.8 0.3(10) 5.9 0.4(10) -- 7.0 0.3(10) 6.4 0.3(10) -- 6.9 0.4(10) 6.2 0.3(10) 6.1 0.5(10) 0.2 0.0(10) 0.2 0.0(10) 0.2 0.0(7) 0.2 0.0(10) 0.2 0.0(9) -- 0.2 0.0(10) 0.2 0.0(10) -- 0.2 0.0(10) 0.2 0.0(10) -- 0.2 0.0(10) 0.2 0.0(10) 0.3 0.3(10) 6.0 2.3(8) 11.9 12.4(5) 5.7 14(6) -- 14.1 3.3(8) -- 88.0@ 29.0(8) -- 702.6@ 255.8(9) 15.7 3.2(7) - 134 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 33 (Continued) TEST/ PERIOD SUMMARY OF URINALYSIS VALUES FOR FEMALE RATS Group II 0 mg/kg/day Group IV 1 mg/kg/day Group VI 5 mg/kg/day Group VIII 25 mg/kg/day Group X 125 mg/kg/day UMTP (mg/dL) DAY 49 DAY 94 DAY 183 22 7(10) 33 23(10) 172 278(7) 34 24(10) 48 37(9) -- 26 18(10) 30 15(10) -- 13 6(10) 88 147(10) -- 46 35(10) 230 313(10) 588 1031(10) Data arranged as: Mean Standard deviation (Number o f values included in calculation) @ Statistically significant difference from control at p < 0.05 by Dunn's test. - 135 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 34 SUMMARY OF PEROXISOMAL BETA-OXIDATION ACTIVITY IN MALE RATS Group I Dosage (mg/kg/day) 0 Hepatic Peroxisomal Beta-Oxidation Activity _________ (nmol/min/mg protein)_________ 3-Month Recovery 10-Day Time point 90-Day Time point Time point 14.8 1.0a 12.4 1.2 11.2 1.8 III b 1 14.0 1.7 13.6 1.5 Vb 5 15.9 2.1 13.6 3.0 VII b 25 14.7 1.1 13.4 2.1 IX 125 24.1 3.7# 20.6 2.8# 14.9 2.0* a Mean standard deviation. The n = 5 for each group. b Samples were not prepared for analysis from groups III, V and VII at the 90-day recovery time points. # Statistically significant difference from control (p < 0.05) by Jonckheere's Tend test. * Statistically significant difference from control (p < 0.05) by Dunnett's test. - 136 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 35 SUMMARY OF PEROXISOMAL BETA-OXIDATION ACTIVITY IN FEMALE RATS Group II Dosage (mg/kg/day) 0 Hepatic Peroxisomal Beta-Oxidation Activity _________ (nmol/min/mg protein)_________ 3-Month Recovery 10-Day Time point 90-Day Time point Time point 22.5 2.2a 25.6 3.3 23.8 1.3 IVb 1 22.2 1.5 25.4 1.4 VIb 5 23.8 4.5 27.3 2.1 VIIIb 25 23.2 2.2 29.7 3.3# X 125 29.5 4.4# 39.1 4.7# 27.0 5.6 a Mean standard deviation. The n = 5 for each group. b Samples were not prepared for analysis from groups IV, VI and VIII at the 90-day recovery time point. # Statistically significant difference from control (p < 0.05) by Jonckheere's Tend test. - 137 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 36 Group: Dosage(mg/kg/day) MEAN FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) I III V VII 0 1 5 25 IX 125 LIVER KIDNEYS HEART SPLEEN BRAIN THYMUS ADRENAL GLANDS THYROID GLAND TESTES EPIDIDYMIDES FINAL BODY WEIGHT 14.876 1.770(10) 3.924 0.463 (10) 1.761 0.184(10) 0.913 0.137(10) 2.186 0.084(10) 0.450 0.134(10) 0.061 0.009(10) 0.024 0.004 (10) 3.588 0.228(10) 1.528 0.289(10) 552.940 49.145(10) 14.109 1.254(10) 3.804 0.263 (10) 1.832 0.095(10) 0.842 0.126(10) 2.167 0.105(10) 0.375 0.072(10) 0.048 0.013(10) 0.023 0.004 (10) 3.500 0.255(10) 1.549 0.133(10) 540.790 37.400(10) 15.575 1.744(10) 4.087 0.501(10) 1.797 0.187(10) 0.874 0.171(10) 2.234 0.089(10) 0.480 0.117(10) 0.065 0.011(10) 0.026 0.003 (10) 3.700 0.442(10) 1.623 0.160(10) 582.650 46.186(10) 17.219# 1 . 693 (10) 4.351# 0.417(10) 1.866 0.133(10) 0.919 0.102(10) 2.175 0.094 (10) 0.457 0.131(10) 0.057 0.012(10) 0.026 0.003 (10) 3.697 0 .330 (10) 1.636 0.221(10) 564.140 43.119(10) 21.976# 1.928(10) 4.636# 0.346 (10) 1.916 0.303 (10) 0.963 0.186(10) 2.175 0 .069 (10) 0.455 0.138(10) 0.062 0.014(10) 0.023 0.003 (10) 3.552 0.552(10) 1.456 0.248(10) 536.980 31.734(10) DuPont-9478 - 138 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 36 (CONTINUED) Group: Dosage(mg/kg/day) LIVER/ FINAL BODY * 100 KIDNEYS/ FINAL BODY * 100 HEART/ FINAL BODY * 100 SPLEEN/ FINAL BODY * 100 BRAIN/ FINAL BODY * 100 THYMUS/ FINAL BODY * 100 ADRENAL GLANDS/ FINAL BODY * 100 THYROID GLAND/ FINAL BODY * 100 TESTES/ FINAL BODY * 100 EPIDIDYMIDES/ FINAL BODY * 100 MEAN FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY M E A N R E L A T I V E O R G A N W E I G H T S (% of b o d y weigh t) I III V VII 0 1 5 25 2.690 0.225 (10) 2.609 0.140 10) 2.669 0.148 10) 3.050# 0.124(10) 0.712 0.091 (10) 0.707 0.076 10) 0.702 0.069 10) 0.771 0.035( 10) 0.320 0.035 (10) 0.339 0.016 10) 0.308 0.020 10) 0.331 0.013( 10) 0.165 0.021 (10) 0.156 0.023 10) 0.149 0.022 10) 0.164 0.020( 10) 0.398 0.038 (10) 0.402 0.031 10) 0.385 0.030 10) 0.387 0.030( 10) 0.081 0.021 10) 0.069 0.010 10) 0.082 0.018 10) 0.081 0.020( 10) 0.011 0.002 10) 0.009 0.002 10) 0.011 0.002 10) 0.010 0.002( 10) 0.004 0.001 10) 0.004 0.001 10) 0.004 0.001 10) 0.005 0.001( 10) 0.651 0.048 10) 0.649 0.057 10) 0.635 0.053 10) 0.657 0.054( 10) 0.279 0.060 10) 0.287 0.025 10) 0.280 0.032 10) 0.290 0.035( 10) IX 125 4.102# 0.410(10) 0.867# 0.096 (10) 0.357 0 .059 (10) 0.180 0 .037 (10) 0.406 0 .028 (10) 0.085 0 .025 (10) 0.012 0.003 (10) 0.004 0.001(10) 0.664 0.110(10) 0.273 0.054 (10) DuPont-9478 - 139 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Group: Dosage(mg/kg/day) LIVER/ BRAIN * 100 KIDNEYS/ BRAIN * 100 HEART/ BRAIN * 100 SPLEEN/ BRAIN * 100 THYMUS/ BRAIN * 100 ADRENAL GLANDS/ BRAIN * 100 THYROID GLAND/ BRAIN * 100 TESTES/ BRAIN * 100 EPIDIDYMIDES/ BRAIN * 100 TABLE 36 (CONTINUED) MEAN FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY M E A N R E L A T I V E O R G A N W E I G H T (% o r g a n to b r a i n w e i g h t ratio) I III V VII IX 0 1 5 25 125 680.794 80.3 5 6 (10) 179.350 19.0 3 4 (10) 80.545 7 . 730 (10) 41.735 5 . 680 (10) 20.511 5.854 (10) 2.794 0.360 10) 1.092 0.164 10) 164.247 10.716 10) 69.848 1 2 .791 10) 652.386 6 4 .449 10) 175.802 1 3 .117 10) 84.719 5.813 10) 38.817 5.273 10) 17.295 3.170 10) 2.230 0.622 10) 1.065 0.168 10) 161.999 15.726 10) 71.552 5.886 10) 697.513 76.846 10) 182.593 1 7 .359 10) 80.415 7.364 10) 39.063 7.279 10) 21.496 5.303 10) 2.901 0.456 10) 1.163 0.101 10) 165.628 1 8 .827 10) 72.719 7.299 10) 792.330# 78.215(10) 200.137# 18.909( 10) 85.888 6.289( 10) 42.302 4.614( 10) 21.087 6.168( 10) 2.642 0.553( 10) 1.188 0.161( 10) 170.071 14.477( 10) 75.102 8.741( 10) 1011.448# 93.8 5 3 (10) 213.371# 1 6 . 8 6 8 (10) 88.139 1 3 . 9 3 4 (10) 44.283 8.168(10) 20.829 5.858(10) 2.849 0.585(10) 1.071 0.124(10) 163.479 26.042(10) 66.885 10.870(10) - 140 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 36 (CONTINUED) Group: Dosage(mg/kg/day) MEAN FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS RATS DESIGNATED FOR RECOVERY I IX 0 125 LIVER KIDNEYS HEART SPLEEN BRAIN THYMUS ADRENAL GLANDS THYROID GLAND TESTES EPIDIDYMIDES FINAL BODY WEIGHT oo oO oo H O LD O O ccooo 15.779 2.481 9) 3.911 0.428 9) 1.799 0.161 9) 0.863 0.115 9) 2.161 9) 0.222 9) 0.055 9) 0.031 9) 3.655 0.270( 9) 1.513 0.144 9) 626.311 67.783 9) t> O o Hoos o LD i-- i O oO oO 15.067 2.7 27(:10) 3.940 0 . 5 2 0 ( :10) 1.841 0 . 2 7 6 ( :10) 0.840 :10) 2.111 0 . 0 6 7 ( :10) 0.338# 0.056( 10) 0.049 10) 0.029 10) 3.460 0.125( 10) 1.480 0.114( 10) 609.860 85.864( 10) - 141 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 36 (CONTINUED) Group: Dosage(mg/kg/day) LIVER/ FINAL BODY * 100 KIDNEYS/ FINAL BODY * 100 HEART/ FINAL BODY * 100 SPLEEN/ FINAL BODY * 100 BRAIN/ FINAL BODY * 100 THYMUS/ FINAL BODY * 100 ADRENAL GLANDS/ FINAL BODY * 100 THYROID GLAND/ FINAL BODY * 100 TESTES/ FINAL BODY * 100 EPIDIDYMIDES/ FINAL BODY * 100 MEAN FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS RATS DESIGNATED FOR RECOVERY MEAN RELATIVE ORGAN WEIGHTS ( % of body weight) I IX 0 125 2.510 0.159(9) 2.462 0.184(10) 0.625 0.027(9) 0.648 0.046 (10) 0.289 0.024(9) 0.302 0.014(10) 0.138 0.018(9) 0.139 0.015(10) 0.348 0.030(9) 0.352 0.051(10) 0.036 0.015(9) 0.056# 0.007(10) 0.009 0.002 (9) 0.008 0.001(10) 0.005 0.001(9) 0.005 0.001(10) 0.589 0.064 (9) 0.577 0.080(10) 0.244 0.032 (9) 0.248 0.045(10) - 142 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 36 (CONTINUED) Group: Dosage(mg/kg/day) MEAN FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS RATS DESIGNATED FOR RECOVERY M E A N R E L A T I V E O R G A N W E I G H T S (% o r g a n to b r a i n w e i g h t ratio) I IX 0 125 LIVER/ BRAIN * 100 KIDNEYS/ BRAIN * 100 HEART/ BRAIN * 100 SPLEEN/ BRAIN * 100 THYMUS/ BRAIN * 100 ADRENAL GLANDS/ BRAIN * 100 THYROID GLAND/ BRAIN * 100 TESTES/ BRAIN * 100 EPIDIDYMIDES/ BRAIN * 100 728.243 94.614 9) 180.855 17.182 9) 83.180 5.450( 9) 39.852 4.379 9) 10.361 4.280 9) 2.554 0.421( 9) 1.428 0.267( 9) 169.421 14.492 9) 70.022 6.365 9) 714.942 133.730( 186.766 24.848( 87.334 13.549( 39.856 5.478( 16.044# 2.650( 2.306 0.468( 1.371 0.260( 163.936 4.527( 70.171 5.982( - 143 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 36 (CONTINUED) MEAN FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS (10-DAY SACRIFICE) Group: Dosage(mg/kg/day) LIVER FINAL BODY WEIGHT LIVER/ FINAL BODY * 100 o t> O I 0 10.419 (5) 248.38 16.9 5 3 (5) 4.193 0.206 5) III 1 10.216 0.733 (5) 244.66 11.964(5) 4.174 0.164(5) V 5 10.419 1.444 5) 245.66 2 3 . 0 2 3 5) 4.232 0.2 90( 5) oo I--1 VII 25 10.703 5) 241.36 1 7 . 0 8 5 5) 4.433 0.242 5) IX 125 14.182 1.684 5) 252.94 1 7 . 8 1 9 5) 5.593 0.297( 5) RATS DESIGNATED FOR SATELLITE EVALUATIONS (FINAL SACRIFICE) Group: Dosage(mg/kg/day) LIVER FINAL BODY WEIGHT LIVER/ FINAL BODY * 100 I 0 19.628 4 . 4 0 5 (5) 603.040 98. 436 (5) 3.232 0.356 (5) III 1 20.521 3 . 768 (5) 646.340 66.8 1 4 (5) 3.157 0.296 (5) V 5 19.963 3.833' 5) 632.480 85.838' 5) 3.139 0.236' 5) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) # Statistically significant difference at p < 0.05 by Jonckheere-Terpstra trend test. VII 25 22.601 3.976 5) 693.840 8 1 . 7 7 8 5) 3.241 0.203 5) IX 125 22.559 3.686(5) 697.940# 65.719(5) 3.220 0.267(5) DuPont-9478 - 144 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 37 MEAN FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS Group: Dosage(mg/kg/day) LIVER KIDNEYS HEART SPLEEN BRAIN THYMUS ADRENAL GLANDS THYROID GLAND OVARIES UTERUS FINAL BODY WEIGHT RATS DESIGNATED FOR SUBCHRONIC TOXICITY MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) II IV VI VIII 0 1 5 25 7.904 0.849(10) 8.224 0.982(10) 8.185 0.845(10) 9.230# 1.076(10) 2.239 0.188(10) 2.147 0.239(10) 2.155 0.173(10) 2.453 0.267(10) 1.223 0.294(10) 1.108 0 .067 (10) 1.130 0.120(10) 1.161 0.125(10) 0.579 0.090(10) 0.549 0.095(10) 0.622 0.105(10) 0.574 0.073 (10) 1.967 0 .068 (10) 1.978 0.077(10) 1.931 0.085(10) 2.003 0.085(10) 0.351 0.074(10) 0.267 0 .068 (10) 0.324 0.082(10) 0.328 0.060(10) 0.076 0.012(10) 0.063 0.019(10) 0.070 0.010(10) 0.065 0.006 (10) 0.020 0.003 (10) 0.020 0.006 (10) 0.020 0.003 (10) 0.021 0.004 (10) 0.141 0.018(10) 0.132 0.025(10) 0.141 0.033 (10) 0.134 0.024(10) 0.704 0.168(10) 0.779 0.170(10) 0.738 0.300(10) 0.780 0.166(10) 286.830 25.304(10) 294.600 25.107(10) 294.090 25.820(10) 297.520 26.045(10) X 125 11.513# 0.972 (10) 2.462# 0 .265 (10) 1.150 0 .075 (10) 0.609 0 .065 (10) 2.009 0.126(10) 0.323 0.074 (10) 0.073 0.013(10) 0.022 0.004 (10) 0.140 0 .025 (10) 0.808 0.354 (10) 288.960 17.911(10) DuPont-9478 - 145 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 37 (CONTINUED) Group: Dosage(mg/kg/day) LIVER/ FINAL BODY * 100 KIDNEYS/ FINAL BODY * 100 HEART/ FINAL BODY * 100 SPLEEN/ FINAL BODY * 100 BRAIN/ FINAL BODY * 100 THYMUS/ FINAL BODY * 100 ADRENAL GLANDS/ FINAL BODY * 100 THYROID GLAND/ FINAL BODY * 100 OVARIES/ FINAL BODY * 100 MEAN FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY M E A N R E L A T I V E O R G A N W E I G H T S (% of b o d y weigh t) II IV VI VIII 0 1 5 25 2.755 0.158 10) 2.790 0.212(10) 2.784 0.161 10) 3.098# 0.171( 10) 0.782 0.043 10) 0.732 0 .087 (10) 0.734 0.043 10) 0.825 0.056( 10) 0.426 0.094 10) 0.378 0.032 (10) 0.385 0.034 10) 0.390 0.020( 10) 0.201 0.023 10) 0.186 0 .025 (10) 0.212 0.030 10) 0.194 0.028( 10) 0.689 0.049 10) 0.676 0.066 (10) 0.660 0.050 10) 0.678 0.064( 10) 0.122 0.022 10) 0.091 0.022 (10) 0.110 0.025 10) 0.111 0.023( 10) 0.027 0.004 10) 0.022* 0 .007 (10) 0.024 0.003 10) 0.022 0.003( 10) 0.007 0.001 10) 0.007 0.002 (10) 0.007 0.001 10) 0.007 0.001( 10) 0.049 0.005 10) 0.045 0 .009 (10) 0.048 0.012 10) 0.045 0.008( 10) X 125 3.988# 0.287(10) 0.852# 0.064 (10) 0.398 0.018(10) 0.212 0 .028 (10) 0.696 0 .039 (10) 0.112 0.026 (10) 0.025 0.004 (10) 0.008 0.002 (10) 0.049 0.010(10) DuPont-9478 - 146 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 37 (CONTINUED) Group: Dosage(mg/kg/day) UTERUS/ FINAL BODY * 100 MEAN FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY M E A N R E L A T I V E O R G A N W E I G H T S (% of b o d y weigh t) II IV VI VIII 0 1 5 25 0.248 0.064 (10) 0.269 0.079(10) 0.255 0.123(10) 0.262 0 .049 (10) X 125 0.277 0.111(10) Group: Dosage(mg/kg/day) LIVER/ BRAIN * 100 KIDNEYS/ BRAIN * 100 HEART/ BRAIN * 100 SPLEEN/ BRAIN * 100 THYMUS/ BRAIN * 100 ADRENAL GLANDS/ BRAIN * 100 II 0 401.348 3 4 . 7 2 7 (10) 113.798 8.306 (10) 62.105 1 4 . 5 9 8 (10) 29.353 3.943 (10) 17.870 3.645 10) 3.862 0.548 10) M E A N R E L A T I V E O R G A N W E I G H T S (% o r g a n to b r a i n w e i g h t ratio) IV VI VIII X 1 5 25 125 417.043 58.824 10) 423.342 3 3 .481 10) 461.618# 57.204(10) 573.617# 41.766(10) 108.831 1 3 .790 10) 111.492 5.931 10) 122.547 12.670(10) 122.384# 7.831(10) 56.163 4.703 10) 58.463 5.074 10) 58.037 6.592(10) 57.377 4.208(10) 27.759 4 .468 10) 32.243 5.280 10) 28.670 3.645(10) 30.410 3.442(10) 13.466 3.267 10) 16.822 4 .325 10) 16.521 3.699(10) 16.006 3.187(10) 3.188 0.905 10) 3.631 0.453 10) 3.260 0.278(10) 3.613 0.522(10) DuPont-9478 - 147 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 37 (CONTINUED) Group: Dosage(mg/kg/day) MEAN FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY M E A N R E L A T I V E O R G A N W E I G H T S (% o r g a n to b r a i n w e i g h t ratio) II IV VI VIII X 0 1 5 25 125 THYROID GLAND/ BRAIN * 100 OVARIES/ BRAIN * 100 UTERUS/ BRAIN * 100 1.018 0.159(10) 7.176 0.857(10) 35.839 8.615(10) 1.019 0 .290 (10) 6.672 1.162(10) 39.442 8.477(10) 1.045 0.144(10) 7.274 1.569(10) 38.003 14.926(10) 1.068 0.235(10) 6.658 1.112(10) 39.144 9.115(10) 1.081 0.211(10 6.994 1.301(10: 39.878 16.348(10: - 148 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 37 (CONTINUED) MEAN FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS RATS DESIGNATED FOR RECOVERY MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) Group: Dosage(mg/kg/day) II 0 X 125 LIVER KIDNEYS HEART SPLEEN BRAIN THYMUS ADRENAL GLANDS THYROID GLAND OVARIES UTERUS FINAL BODY WEIGHT I--1 o o o o oo o o 10.309 (9) 2.605 0.277 (9) 1.332 0.158 (9) 0.637 0.101 (9) 2.055 0.102 (9) 0.239 0.072 9) 0.085 0.020 9) 0.026 9) 0.131 9) 0.886 0.364 9) 334.033 3 2 . 8 4 7 9) oO o CO LD O o 10.339 1.961 10) 2.738 0.541 10) 1.234 0.175 10) 0.592 0.090 10) 1.936 0.086 10) 0.269 0.102 10) 0.075 0.013 10) 0.026 10) 0.123 0.035 10) 0.914 10) 348.920 6 5 .818 10) - 149 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 37 (CONTINUED) Group: Dosage(mg/kg/day) LIVER/ FINAL BODY * 100 KIDNEYS/ FINAL BODY * 100 HEART/ FINAL BODY * 100 SPLEEN/ FINAL BODY * 100 BRAIN/ FINAL BODY * 100 THYMUS/ FINAL BODY * 100 ADRENAL GLANDS/ FINAL BODY * 100 THYROID GLAND/ FINAL BODY * 100 OVARIES/ FINAL BODY * 100 MEAN FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS RATS DESIGNATED FOR RECOVERY M E A N R E L A T I V E O R G A N W E I G H T S (% of b o d y weig ht ) II X 0 125 3.094 0.248(9) 2.977 0.340(10) 0.783 0.079(9) 0.793 0.137(10) 0.399 0 .040 (9) 0.357# 0.031(10) 0.192 0.031(9) 0.174 0 .037 (10) 0.619 0.052(9) 0.570 0.096 (10) 0.072 0.023 (9) 0.076 0.018(10) 0.026 0.006 (9) 0.022 0.005(10) 0.008 0.002 (9) 0.008 0.002 (10) 0.039 0.010(9) 0.037 0.013(10) - 150 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 37 (CONTINUED) Group: Dosage(mg/kg/day) UTERUS/ FINAL BODY * 100 MEAN FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS RATS DESIGNATED FOR RECOVERY M E A N R E L A T I V E O R G A N W E I G H T S (% of b o d y weig ht ) II X 0 125 0.268 0.107(9) 0.278 0.130(10) Group: Dosage(mg/kg/day) M E A N R E L A T I V E O R G A N W E I G H T S (% o r g a n to b r a i n w e i g h t ratio) II X 0 125 LIVER/ BRAIN * 100 KIDNEYS/ BRAIN * 100 HEART/ BRAIN * 100 SPLEEN/ BRAIN * 100 THYMUS/ BRAIN * 100 ADRENAL GLANDS/ BRAIN * 100 501.311 39.253(9) 126.765 11.614(9) 64.848 7.420(9) 30.944 4.184(9) 11.549 3.111(9) 4.118 0.862(9) 533.737 96.914(10) 141.591 28.381(10) 63.675 8.079(10) 30.642 4.777(10) 13.835 4.955(10) 3.882 0.689(10) - 151 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 37 (CONTINUED) Group: Dosage(mg/kg/day) THYROID GLAND/ BRAIN * 100 OVARIES/ BRAIN * 100 UTERUS/ BRAIN * 100 MEAN FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS RATS DESIGNATED FOR RECOVERY M E A N R E L A T I V E O R G A N W E I G H T S (% o r g a n to b r a i n w e i g h t ratio) II X 0 125 1.261 0.297(9) 1.345 0.220(10) 6.330 1.813(9) 6.355 1.650(10) 42.819 15.794(9) 47.502 16.378(10) DuPont-9478 - 152 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 37 (CONTINUED) MEAN FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS (10-DAY SACRIFICE) Group: Dosage(mg/kg/day) LIVER FINAL BODY WEIGHT LIVER/ FINAL BODY * 100 II 0 7.185 0.785(5) 170.54 17.825(5) 4.213 0.118(5) IV 1 7.174 0.923 (5) 160.44 15.709(5) 4.473 0.355(5) VI 5 7.814 0.582(5) 170.74 16.129(5) 4.589 0.282(5) VIII 25 8.364 1.243(5) 175.58 14.315(5) 4.748 0.424(5) X 125 10.134 1.129(5) 182.52 18.060(5) 5.557 0.344(5) RATS DESIGNATED FOR SATELLITE EVALUATIONS (FINAL SACRIFICE) Group: II IV VI Dosage(mg/kg/day) 0 1 5 LIVER 12.444 2.922(5) 11.897 1.637(5) 12.711 0.553(5) FINAL BODY WEIGHT 325.900 46.602(5) 336.160 29.278(5) 335.920 44.576(5) LIVER/ FINAL BODY * 100 3.784 0.445(5) 3.537 0 .340 (5) 3.828 0.449(5) Data summarized as: Mean S t a n d a r d D e v i a t i o n (n) # Statistically significant difference at p < 0.05 by Jonckheere- Terpstra trend test. VIII 25 13.527 3.301(5) 366.840 53.771(5) 3.651 0.434(5) X 125 12.729 1.305(5) 359.320 44.287(5) 3.567 0.402(5) DuPont-9478 - 153 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS LESION INCIDENCE (Numeric) Males | TREATMENT | | | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| LIVER NO ABNORMALITY DETECTED KIDNEYS NO ABNORMALITY DETECTED DILATATION, RIGHT. LUNGS NO ABNORMALITY DETECTED HEART NO ABNORMALITY DETECTED SKELETAL MUSCLE NO ABNORMALITY DETECTED SPLEEN NO ABNORMALITY DETECTED | (10) || | 10 | | (10) || | 10 || | (10) | | 10 | | (10) | | 10 | | (10) | | 10 | | (10) | | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | | (10) |9 |1 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 154 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS AORTA NO ABNORMALITY DETECTED BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) | TREATMENT I I I I Males |0 I mg/kg II I 1 mg/kg III 5 mg/kg V 25 125 I mg/kg mg/kgI VII I IX I I I (10) II I 10 (10) I 10 I (10) I 10 I (10) I 10 I (10) I 10 I I I (10) I (10) I (10) I (10) I (10) I II I 10 I 10 I 10 I 10 I 10 I I (10) I (10) I (10) I (10) I (10) I II I 10 I 10 I 10 I 10 I 10 I I (10) I (10) I (10) I (10) I (10) I II I 10 I 10 I 10 I 10 I 10 I I (10) I (10) I (10) I (10) I (10) I II I 10 I 10 I 10 I 10 I 10 I I (10) I (10) I (10) I (10) I (10) I II I 10 I 10 I 10 I 10 I 10 I Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 155 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | LESION INCIDENCE (Numeric) | | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| ILEUM NO ABNORMALITY DETECTED PANCREAS NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED RECTUM NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED | (10) || | 10 | | (10) || | 10 | | (10) || | 10 | | (10) || | 10 | | (10) || | 10 | | (10) || | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 156 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | LESION INCIDENCE (Numeric) | | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| SALIVARY GLANDS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED PITUITARY GLAND NO ABNORMALITY DETECTED | (10) || | 10 | | (10) || | 10 | | (10) || | 10 | | (10) || | 10 | | (10) || | 10 | | (10) || | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 157 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED TRACHEA NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) | TREATMENT I I I I Males |0 I mg/kg II I 1 mg/kg III 5 mg/kg V 25 125 I mg/kg mg/kgI VII I IX I I I (10) II I 10 (10) I 10 I (10) I 10 I (10) I 10 I (10) I 10 I I I (10) I (10) I (10) I (10) I (10) I II I 10 I 10 I 10 I 10 I 10 I I (10) I (10) I (10) I (10) I (10) I II I 10 I 10 I 10 I 10 I 10 I I (10) I (10) I (10) I (10) I (10) I II I 10 I 10 I 10 I 10 I 10 I I (10) I (10) I (10) I (10) I (10) I I I 10 I 10 I 10 I 10 I 10 I I (10) I (10) I (10) I (10) I II I 10 I 10 I 10 I 10 I (9) I 9I Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 158 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS SKIN NO ABNORMALITY DETECTED ALOPECIA, RIGHT. PROSTATE NO ABNORMALITY DETECTED SEMINAL VESICLES NO ABNORMALITY DETECTED URINARY BLADDER NO ABNORMALITY DETECTED DILATATION. TESTES NO ABNORMALITY DETECTED SMALL, UNILATERAL. DISCOLORATION, OPAQUE. LESION INCIDENCE (Numeric) | TREATMENT | | | | Males |0 | mg/kg |I | 1 mg/kg III 5 mg/kg V 25 125 mg/kg mg/kg VII | IX | | (10) || | 10 || | (10) | | 10 | | (10) | | 10 | | (10) | | 10 | (10) |9 1 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) 9 1 | (10) | 10 | (10) | 10 | (10) | 10 | (10) 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) || |9 | |1 | (10) 10 | (10) 9 1 | (10) 10 | (10) |9 1 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 159 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (Numeric) Males LESIONS | TREATMENT | I | |0 | mg/kg |I | 1 |5 mg/kg mg/kg III | V 25 125 | mg/kg mg/kg| VII | IX | EPIDIDYMIDES NO ABNORMALITY DETECTED SMALL, UNILATERAL. FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED | | (10) || | 10 || | (10) | | 10 | | (10) | | 10 | | (10) | | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) |9 1 | (10) | 10 | (10) | 10 | (10) | 10 | | | | | | | | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified DuPont-9478 - 160 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR RECOVERY LESIONS LIVER NO ABNORMALITY DETECTED KIDNEYS NO ABNORMALITY DETECTED CALCULUS\CALCULI, RIGHT. LUNGS NO ABNORMALITY DETECTED HEART NO ABNORMALITY DETECTED SKELETAL MUSCLE NO ABNORMALITY DETECTED SPLEEN NO ABNORMALITY DETECTED LESION INCIDE Males | TREATMENT | I | |0 | mg/kg |I | 125 | mg/kg| IX | | | (10) || | 10 (10) | 10 | | | (10) || | 10 || | (10) | | 10 | | (10) | | 10 | | (10) || | 10 | | (10) | | 10 | (10) |9 1 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | | | | | | | | | | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 161 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR RECOVERY LESIONS AORTA NO ABNORMALITY DETECTED BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED LESION INCIDE Males | TREATMENT | I | |0 | mg/kg |I | 125 | mg/kg| IX | | | (10) || | 10 (10) | 10 | | | (10) | (10) | || | 10 | 10 | | (10) | (10) | | | 10 | 10 | | (10) | (10) | || | 10 | 10 | | (10) | (10) | || | 10 | 10 | | (10) | (10) | || | 10 | 10 | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 162 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR RECOVERY |LESION INCIDEj 1l l | Males | LESIONS | TREATMENT | | | |0 | mg/kg |I | 125 | mg/kg| IX | ILEUM NO ABNORMALITY DETECTED | | (10) || | 10 (10) | 10 | | PANCREAS NO ABNORMALITY DETECTED | (10) | (10) | || | 10 | 10 | CECUM NO ABNORMALITY DETECTED | (10) | (10) | || | 10 | 10 | COLON NO ABNORMALITY DETECTED | (10) | (10) | || | 10 | 10 | RECTUM NO ABNORMALITY DETECTED | (10) | (10) | || | 10 | 10 | MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED | (10) | | 10 | | (10) | 10 | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 163 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR RECOVERY |LESION INCIDEj 1l l | Males | LESIONS | TREATMENT | | | |0 | mg/kg |I | 125 | mg/kg| IX | SALIVARY GLANDS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED | | (10) | | 10 (10) | 10 | | (10) | (10) | | | 10 | 10 | THYMUS NO ABNORMALITY DETECTED | (10) | (10) | || | 10 | 10 | ADRENAL GLANDS NO ABNORMALITY DETECTED | (10) | (10) | | | 10 | 10 | SCIATIC NERVE NO ABNORMALITY DETECTED | (10) | (10) | | | 10 | 10 | PITUITARY GLAND NO ABNORMALITY DETECTED | (10) | | 10 | | (10) | 10 | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 164 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR RECOVERY |LESION INCIDEj 1l l | Males | LESIONS | TREATMENT | | | |0 | mg/kg |I | 125 | mg/kg| IX | THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED | | (10) | | 10 (10) | 10 | | (10) | (10) | | | 10 | 10 | TRACHEA NO ABNORMALITY DETECTED | (10) | (10) | || | 10 | 10 | ESOPHAGUS NO ABNORMALITY DETECTED | (10) | (10) | || | 10 | 10 | PHARYNX/LARYNX NO ABNORMALITY DETECTED | (10) | (10) | | | 10 | 10 | EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED | (10) || | 10 | | (10) | 10 | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 165 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR RECOVERY LESIONS SKIN NO ABNORMALITY DETECTED PROSTATE NO ABNORMALITY DETECTED SEMINAL VESICLES NO ABNORMALITY DETECTED URINARY BLADDER NO ABNORMALITY DETECTED TESTES NO ABNORMALITY DETECTED EPIDIDYMIDES NO ABNORMALITY DETECTED LESION INCIDE Males | TREATMENT | I | |0 | mg/kg |I | 125 | mg/kg| IX | | | (10) || | 10 (10) | 10 | | | (10) | (10) | || | 10 | 10 | | (10) | (10) | | | 10 | 10 | | (10) | (10) | | | 10 | 10 | | (10) | (10) | || | 10 | 10 | | (10) | (10) | | | 10 | 10 | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 166 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR RECOVERY LESIONS FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED LESION INCIDE Males | TREATMENT | I | |0 | mg/kg |I | 125 | mg/kg| IX | | | (10) | | 10 (10) | 10 | | | (10) | (10) | || | 10 | 10 | | (10) | (10) | || | 10 | 10 | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified DuPont-9478 - 167 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESION INCIDENCE (Numeric) Males LESIONS | TREATMENT | I | |0 | mg/kg |I | 1 | 5 | 25 125 | mg/kg| mg/kg mg/kg mg/kg| III | V VII | IX | | LIVER NO ABNORMALITY DETECTED | ||| (5) |5 | (5) | || 5| (5) | 5 (5) | 5 (5) | 5| KIDNEYS NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| LUNGS NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| HEART NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| SKELETAL MUSCLE NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| SPLEEN NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| || Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 168 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESION INCIDENCE (Numeric) Males LESIONS | TREATMENT | I | |0 | mg/kg |I | 1 | 5 | 25 125 | mg/kg| mg/kg mg/kg mg/kg| III | V VII | IX | | AORTA NO ABNORMALITY DETECTED | ||| (5) |5 | (5) | || 5| (5) | 5 (5) | 5 (5) | 5| BRAIN NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| SPINAL CORD NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| STOMACH NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| DUODENUM NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| JEJUNUM NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| || Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 169 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS | TREATMENT I I I | LESION INCIDENCE (Numeric) 1l I Males | |0 I mg/kg II I 1 mg/kg III 5 I 25 125 I mg/kgI mg/kg mg/kgI V I VII I IX I I ILEUM NO ABNORMALITY DETECTED I III (5) I5 (5) I 5 I (5) I II 5I (5) I 5 (5) I 5I PANCREAS NO ABNORMALITY DETECTED I (5) I (5) I (5) I (5) I (5) I II II I 5 5 5I 5 5I CECUM NO ABNORMALITY DETECTED I (5) I (5) I (5) I (5) I (5) I II II I 5 5 5I 5 5I COLON NO ABNORMALITY DETECTED I (5) I (5) I (5) I (5) I (5) I II II I 5 5 5I 5 5I RECTUM NO ABNORMALITY DETECTED I (5) I (5) I (5) I (5) I (5) I II II I 5 5 5I 5 5I MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED I (5) I (5) I (5) I (5) I (5) I II II I 5 5 5I 5 5I II Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 170 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS SALIVARY GLANDS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED PITUITARY GLAND NO ABNORMALITY DETECTED | LESION INCIDENCE (Numeric) |-----------------------------------------| Males | TREATMENT | I | |0 | mg/kg |I | 1 mg/kg III 5 | 25 125 mg/kg| mg/kg mg/kg V | VII | IX | | ||| (5) |5 (5) | 5 | (5) | || 5| (5) | 5 (5) 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5| 5 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5| 5 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5| 5 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5| 5 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5| 5 5 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 171 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED TRACHEA NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED | LESION INCIDENCE (Numeric) |-----------------------------------------| Males | TREATMENT | | | |0 | mg/kg |I | 1 mg/kg III 5 | 25 125 mg/kg| mg/kg mg/kg V | VII | IX | | ||| (5) |5 (5) | 5 | (5) | || 5| (5) | 5 (5) 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5| 5 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5| 5 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5| 5 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5| 5 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5| 5 5 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 172 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESION INCIDENCE (Numeric) Males LESIONS | TREATMENT | I | |0 | mg/kg |I | 1 | 5 | 25 125 | mg/kg| mg/kg mg/kg mg/kg| III | V VII | IX | | SKIN NO ABNORMALITY DETECTED | ||| (5) |5 | (5) | || 5| (5) | 5 (5) | 5 (5) | 5| PROSTATE NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| SEMINAL VESICLES NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| URINARY BLADDER NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| TESTES NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| EPIDIDYMIDES NO ABNORMALITY DETECTED | (5) | (5) | (5) | (5) | (5) | || || | 5 5| 5 5 5| || Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 173 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 38 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) | TREATMENT I I I I Males |0 I mg/kg II I 1 5 I 25 125 I mg/kg mg/kgI mg/kg mg/kgI III I V I VII I IX I I I III (5) I5 (5) I 5 I (5) I II 5I (5) I 5 (5) I 5I I (5) I (5) I (5) I (5) I (5) I II II I 5 5 5I 5 5I I (5) I (5) I (5) I (5) I (5) I II II I 5 5 5I 5 5I Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified DuPont-9478 - 174 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (Numeric) Females LESIONS | TREATMENT | | | | 0 1 | 5 25 125 | | mg/kg mg/kg mg/kg mg/kg mg/kg| | II | IV VI | VIII | X | | LIVER NO ABNORMALITY DETECTED | | (11) || | 11 (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | | KIDNEYS NO ABNORMALITY DETECTED | (11) | (10) | (10) | (10) | (10) | || | 11 | 10 | 10 | 10 | 10 | LUNGS NO ABNORMALITY DETECTED | (11) | (10) | (10) | (10) | (10) | || | 11 | 10 | 10 | 10 | 10 | HEART NO ABNORMALITY DETECTED LARGE. SKELETAL MUSCLE NO ABNORMALITY DETECTED | (11) || | 10 || 1 | (11) || | 11 | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | | | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 1 1 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h 90 d a y t ime p e r i o d - 175 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (Numeric) Females LESIONS | TREATMENT | | | | 0 1 | 5 25 125 | | mg/kg mg/kg mg/kg mg/kg mg/kg| | II | IV VI | VIII | X | | SPLEEN NO ABNORMALITY DETECTED | | (11) || | 11 (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | | AORTA NO ABNORMALITY DETECTED | (11) | (10) | (10) | (10) | (10) | || | 11 | 10 | 10 | 10 | 10 | BRAIN NO ABNORMALITY DETECTED | (11) | (10) | (10) | (10) | (10) | || | 11 | 10 | 10 | 10 | 10 | SPINAL CORD NO ABNORMALITY DETECTED | (11) | (10) | (10) | (10) | (10) | || | 11 | 10 | 10 | 10 | 10 | STOMACH NO ABNORMALITY DETECTED FLUID, RED. | (11) || | 10 |1 | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 1 1 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h 90 d a y t ime p e r i o d - 176 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS LESION INCIDENCE (Numeric) Females | TREATMENT | | | |0 |1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED ILEUM NO ABNORMALITY DETECTED PANCREAS NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 1 1 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h 90 d a y t ime p e r i o d - 177 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS LESION INCIDENCE (Numeric) Females | TREATMENT | | | |0 |1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| RECTUM NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED SALIVARY GLANDS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 1 1 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h 90 d a y t ime p e r i o d - 178 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS LESION INCIDENCE (Numeric) Females | TREATMENT | | | |0 |1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| SCIATIC NERVE NO ABNORMALITY DETECTED PITUITARY GLAND NO ABNORMALITY DETECTED THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED TRACHEA NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 1 1 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h 90 d a y t ime p e r i o d - 179 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (Numeric) Females LESIONS | TREATMENT | I | |0 | mg/kg | II | 1 |5 25 125 | mg/kg mg/kg mg/kg mg/kg| IV VI | VIII | X | ESOPHAGUS PERFORATION. | | (11) || |1 (10) | (10) | (10) | (10) | PHARYNX/LARYNX NO ABNORMALITY DETECTED EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED SKIN NO ABNORMALITY DETECTED STAIN, RED, NOSE. M A M MARY GLAND (FEMALE) NO ABNORMALITY DETECTED | (11) || | 11 | | (11) || | 11 | | (11) | | 10 |1 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | | | | | | | (11) || | 11 | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 1 1 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h 90 d a y t ime p e r i o d - 180 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS LESION INCIDENCE (Numeric) Females | TREATMENT | | | |0 |1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| OVARIES NO ABNORMALITY DETECTED UTERUS NO ABNORMALITY DETECTED VAGINA NO ABNORMALITY DETECTED URINARY BLADDER NO ABNORMALITY DETECTED FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | | (10) | 10 | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 | | (1 |1 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 1 1 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h 90 d a y t ime p e r i o d - 181 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT I I I II1 L E S I O N I N C I D E N C E (Numeric) I Females | | 0 I i I 5 | 25 | i25 I I mg/kgI mg/kg| mg/kg| mg/kg| mg/kg| I II I IV | VI I VIII I X | IIIII NOSE NO ABNORMALITY DETECTED I III (ii) I ii I I i (i0) I1 I i0 I I I (i0) |1 I i0 I I I (i0) |1 I i0 I I I (i0) |1 I i0 I I I Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 1 1 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h 90 d a y t ime p e r i o d DuPont-9478 - 182 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR RECOVERY LESION INCIDE Females LESIONS | TREATMENT | I | |0 | mg/kg | II | 125 | mg/kg| X| LIVER NO ABNORMALITY DETECTED KIDNEYS NO ABNORMALITY DETECTED LUNGS NO ABNORMALITY DETECTED | | (9) || |9 (10) | 10 | | (9) | (10) | || |9 10 | | (9) | (10) | || |9 10 | HEART NO ABNORMALITY DETECTED | (9) | (10) | || |9 10 | SKELETAL MUSCLE NO ABNORMALITY DETECTED | (9) | (10) | | |9 10 | SPLEEN NO ABNORMALITY DETECTED | (9) | (10) | || |9 10 | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 9 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h in 90 d a y t ime p e r i o d - 183 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR RECOVERY LESION INCIDE Females LESIONS | TREATMENT | I | |0 | mg/kg | II | 125 | mg/kg| X| AORTA NO ABNORMALITY DETECTED BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED | | (9) || |9 (10) | 10 | | (9) | (10) | || |9 10 | | (9) | (10) | | |9 10 | | (9) | (10) | || |9 10 | | (9) | (10) | || |9 10 | | (9) | (10) | || |9 10 | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 9 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h in 90 d a y t ime p e r i o d - 184 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR RECOVERY |LESION INCIDEj 1l l | Females | LESIONS | TREATMENT | | | |0 | mg/kg | II | 125 | mg/kg| X| ILEUM NO ABNORMALITY DETECTED PANCREAS NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED | | (9) || |9 (10) | 10 | | (9) | (10) | || |9 10 | | (9) | (10) | || |9 10 | COLON NO ABNORMALITY DETECTED | (9) | (10) | || |9 10 | RECTUM NO ABNORMALITY DETECTED | (9) | (10) | || |9 10 | MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED | (9) | (10) | | |9 | 10 | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 9 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h in 90 d a y t ime p e r i o d - 185 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR RECOVERY |LESION INCIDEj 1l l | Females | LESIONS | TREATMENT | | | |0 | mg/kg | II | 125 | mg/kg| X| SALIVARY GLANDS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED | | (9) | |9 (10) | 10 | | (9) | (10) | | |9 10 | | (9) | (10) | || |9 10 | ADRENAL GLANDS NO ABNORMALITY DETECTED | (9) | (10) | | |9 10 | SCIATIC NERVE NO ABNORMALITY DETECTED | (9) | (10) | | |9 10 | PITUITARY GLAND NO ABNORMALITY DETECTED | (9) | (10) | | |8 | 10 | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 9 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h in 90 d a y t ime p e r i o d - 186 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR RECOVERY |LESION INCIDEj 11 1 | Females | LESIONS | TREATMENT | | | |0 | mg/kg | II | 125 | mg/kg| X| PITUITARY GLAND LARGE. | | (9) | |1 (10) | THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED | (9) | (10) | | |9 10 | | (9) | (10) | | |9 10 | TRACHEA NO ABNORMALITY DETECTED | (9) | (10) | || |9 10 | ESOPHAGUS NO ABNORMALITY DETECTED | (9) | (10) | || |9 10 | PHARYNX/LARYNX NO ABNORMALITY DETECTED | (9) | (10) | || |9 10 | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 9 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h in 90 d a y t ime p e r i o d - 187 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR RECOVERY LESION INCIDE Females LESIONS | TREATMENT | I | |0 | mg/kg | II | 125 | mg/kg| X| EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED SKIN NO ABNORMALITY DETECTED MAMMARY GLAND (FEMALE) NO ABNORMALITY DETECTED OVARIES NO ABNORMALITY DETECTED UTERUS NO ABNORMALITY DETECTED DILATATION. | | (9) || |9 (10) | 10 | | (9) | (10) | || |9 10 | | (9) | (10) | || |9 10 | | (9) | (10) | || |9 10 | | (9) | (10) | || |8 10 | |1 | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 9 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h in 90 d a y t ime p e r i o d - 188 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR RECOVERY LESION INCIDE Females LESIONS | TREATMENT | I | |0 | mg/kg | II | 125 | mg/kg| X| VAGINA NO ABNORMALITY DETECTED URINARY BLADDER NO ABNORMALITY DETECTED FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED | | (9) || |9 (10) | 10 | | (9) | (10) | | |9 10 | | (9) | (10) | || |9 10 | | (9) | (10) | || |9 10 | | (9) | (10) | || |9 10 | | Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified N = 9 i n G r o u p II r e f l e c t s 1 e a r l y d e a t h in 90 d a y t ime p e r i o d DuPont-9478 - 189 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS LIVER NO ABNORMALITY DETECTED KIDNEYS NO ABNORMALITY DETECTED LUNGS NO ABNORMALITY DETECTED HEART NO ABNORMALITY DETECTED SKELETAL MUSCLE NO ABNORMALITY DETECTED SPLEEN NO ABNORMALITY DETECTED | TREATMENT | | | | LESION INCIDENCE (Numeric) 1l | Females | 0 1 5 25 | 125 | mg/kg mg/kg mg/kg mg/kg| mg/kg | II | IV | VI | VIII | X || | ||| (5) |5 (5) | 5 (5) | 5 | (5) | || 5| (5) 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || | 5 5 5 5| 5 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 190 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS AORTA NO ABNORMALITY DETECTED BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) Females | TREATMENT | I | |0 | mg/kg | II | 1 | 5 | 25 | 125 mg/kg| mg/kg mg/kg| mg/kg IV | VI | VIII | X || | ||| (5) |5 | (5) | || 5| (5) | 5 | (5) | || 5| (5) 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 191 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS ILEUM NO ABNORMALITY DETECTED PANCREAS NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED RECTUM NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) Females | TREATMENT | I | |0 | mg/kg | II | 1 | 5 | 25 | 125 mg/kg| mg/kg mg/kg| mg/kg IV | VI | VIII | X || | ||| (5) |5 | (5) | || 5| (5) | 5 | (5) | || 5| (5) 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 192 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS SALIVARY GLANDS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED PITUITARY GLAND NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) Females | TREATMENT | I | |0 | mg/kg | II | 1 | 5 | 25 | 125 mg/kg| mg/kg mg/kg| mg/kg IV | VI | VIII | X || | ||| (5) |5 | (5) | || 5| (5) | 5 | (5) | || 5| (5) 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 193 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED TRACHEA NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) Females | TREATMENT | I | |0 | mg/kg | II | 1 | 5 | 25 | 125 mg/kg| mg/kg mg/kg| mg/kg IV | VI | VIII | X || | ||| (5) |5 | (5) | || 5| (5) | 5 | (5) | || 5| (5) 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 194 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS SKIN NO ABNORMALITY DETECTED MAMMARY GLAND (FEMALE) NO ABNORMALITY DETECTED OVARIES NO ABNORMALITY DETECTED UTERUS NO ABNORMALITY DETECTED VAGINA NO ABNORMALITY DETECTED URINARY BLADDER NO ABNORMALITY DETECTED LESION INCIDENCE (Numeric) Females | TREATMENT | I | |0 | mg/kg | II | 1 | 5 | 25 | 125 mg/kg| mg/kg mg/kg| mg/kg IV | VI | VIII | X || | ||| (5) |5 | (5) | || 5| (5) | 5 | (5) | || 5| (5) 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 | (5) | (5) | (5) | (5) | (5) || || || |5 5| 5 5| 5 Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified - 195 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 39 (CONTINUED) INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS RATS DESIGNATED FOR SATELLITE EVALUATIONS LESIONS | TREATMENT I I | | LESION INCIDENCE (Numeric) 1l I Females | | 0 | 1 | 5 | 25 | 125 | I mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | ||||| FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED |||| ||| (5) ||| (5) | || (5) | || | 5| 5| 5| || | (5) | (5) | (5) | || || || || | 5| 5| 5| || | (5) | (5) | (5) | || || || || | 5| 5| 5| |||| Figures in parentheses is the number of animals grossly examined for this tissue The absence of a number indicates the finding specified was not identified | (5) | || 5| (5) | || 5| (5) | || 5| | (5) | 5| (5) | 5| (5) | 5| DuPont-9478 - 196 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | | LESION INCIDENCE (NUMERIC) 1l | Males | |0 | mg/kg |I | 1 mg/kg III 5 | 25 | 125 | mg/kg| mg/kg mg/kg| V | VII | IX | | DIGESTIVE SYSTEM LIVER NECROSIS, FOCAL. INFLAMMATION, SUBACUTE/CHRONIC. HYPERTROPHY, HEPATOCELLULAR. FATTY CHANGE, MEDIAN CLEFT. FATTY CHANGE, CENTRILOBULAR. PANCREAS NO ABNORMALITY DETECTED ATROPHY. ESOPHAGUS NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED | | | | | (10) || | | 10 | |2 || | (10) || |8 |2 | (10) || | 10 | (10) || | 10 | | (10) 9 2 | (10) 1 10 2 | | | | | (10) || |5 |9 | |1 ||| ||| | | | ||| | | ||| | | | (10) 3 8 | 10 1 1 | (10) 8 2 | (10) | 10 | (10) | 10 | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 197 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS DIGESTIVE SYSTEM DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED ILEUM NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED | TREATMENT | | | LESION INCIDENCE (NUMERIC) | Males |0 1 |5 | 25 | 125 | | mg/kg mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | | || | | | | | (10) | | 10 | | (10) | | 10 | | (10) | | 10 | | (10) | | 10 | | (10) | | 10 || || || || ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| || (10) | 10 | (9) | 9| (9) | 9| (9) | 9| (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 198 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Males LESIONS | TREATMENT | | | |0 | mg/kg| |I | 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| III | V | VII | IX | || DIGESTIVE SYSTEM RECTUM NO ABNORMALITY DETECTED SALIVARY GLANDS NO ABNORMALITY DETECTED | | | | | (10) | | 10 | | (10) || | 10 | | | | | | | | ||| ||| ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| ||| ||| | | (9) | 9| (10) | 10 | DuPont-9478 - 199 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED CHRONIC PROGRESSIVE NEPHROPATHY. PIGMENT, TUBULAR. HYPERTROPHY, TUBULAR. HYDRONEPHROSIS, UNILATERAL. CYST. URINARY BLADDER NO ABNORMALITY DETECTED | TREATMENT | | | LESION INCIDENCE (NUMERIC) | |0 | mg/kg |I | 1 mg/kg III Males 5 | 25 | 125 | mg/kg| mg/kg mg/kg| V | VII | IX | | | | | | ||| (10) |5 |5 | | | | | | (10) | | 10 | (10) 4 6 | (10) 3 7 | (1) 1 | | | | | (10) || |1 |4 | |9 | |1 | | | | (10) 8 1 | 10 1 | (10) | 10 | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 200 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) LESIONS | TREATMENT | | | | Males |0 1 5 | 25 | 125 | | mg/kg mg/kg mg/kg| mg/kg | mg/kg| | I | III | V | VII | IX | || RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. TRACHEA NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED | | | | | (10) || |9 || 1 | (10) || | 10 | (10) | | 10 | | | | ||| | (10) | | | 9| ||| | 1 | ||| | (10) | | | 10 | | ||| | (10) | | | 10 | NOSE NO ABNORMALITY DETECTED DEGENERATION, AMELOBLASTS. | (10) || | 10 | | | (10) | 10 | (10) | 10 | (10) || | 10 | | | (10) |5 |5 | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 201 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY | | ||1 L E S I O N I N C I D E N C E (NUMERIC) | | | Males | LESIONS | | ||1 | | CARDIOVASCULAR SYSTEM | | | HEART | NO ABNORMALITY DETECTED | CARDIOMYOPATHY. | | AORTA | NO ABNORMALITY DETECTED | | TREATMENT I | | | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| |I | III | V | VII | IX | |||| |||| |||| |||| |||| ||| (10) | || ||| ||| | 5| | | | 5| | | | || ||| (10) | || ||| ||| | 10 | | | |||| (10) | 5| 5| (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 202 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED BONE MARROW NO ABNORMALITY DETECTED | TREATMENT | | | LESION INCIDENCE (NUMERIC) | Males |0 1 |5 | 25 | 125 | | mg/kg mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | | || | | | | | (10) | | 10 | | (10) | | 10 | | (10) || | 10 | | (10) || | 10 | | (10) || | 10 || || || || ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| || (10) | 10 | (10) | 10 | (10) | 10 | (9) | 9| (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 203 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY | | | | | LESIONS | | ||| | | ENDOCRINE SYSTEM | | | PITUITARY GLAND | NO ABNORMALITY DETECTED | CYST. | | THYROID GLAND | | NO ABNORMALITY DETECTED | ALTERATION, COLLOID. | PARATHYROID GLANDS | NO ABNORMALITY DETECTED | ADRENAL GLANDS | NO ABNORMALITY DETECTED | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) | | Males | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | 1 | III | V | VII | IX | |||||| | | | | ||| (9) |8 |1 | | (10) | |7 ||| 3 ||| (9) ||| 9 ||| (10) | 10 | | | | | | || | | | (10) | |2 || 8 | || || | || | | | | | | ||| | | | (10) | |1 ||| 9 ||| ||| ||| | | | | | | ||| | | | (10) | | ||| 10 ||| ||| ||| | | | (10) | 10 | (10) |2 |8 | (9) |9 | (10) | 10 | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 204 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS NERVOUS SYSTEM BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED | TREATMENT I I I LESION INCIDENCE (NUMERIC) I |0 I mg/kg II I Males 1 I 5 I 25 I 125 I mg/kgI mg/kgI mg/kgI mg/kgI III I V I VII I IX I II I II I II I II I II I (10) I III III I 10 I I III III I (10) I II III III I 10 I I III III I (10) I II III III I 10 I I I (10) I 10 I (10) I 10 I (10) I 10 I Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 205 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | | LESION INCIDENCE (NUMERIC) 11 | Males | | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | |||| MUSCULAR AND SKELETAL SYSTEM SKELETAL MUSCLE NO ABNORMALITY DETECTED FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED | | | | | (10) || | 10 | | (10) || | 10 || | (10) || | 10 | | | | | | || | | | || | || | || | | | | | | ||| | | ||| ||| ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | ||| ||| ||| | | (10) | 10 | (10) | 10 | (10) | 10 | DuPont-9478 - 206 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY | LESION INCIDENCE (NUMERIC) | | Males | LESIONS | TREATMENT | | | |0 | mg/kg |I | 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| III | V | VII | IX | || REPRODUCTIVE SYSTEM TESTES NO ABNORMALITY DETECTED DILATATION, SEMINIFEROUS TUBULES, UNILATERAL. DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, UNILATERAL. DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL. EPIDIDYMIDES NO ABNORMALITY DETECTED OLIGOSPERMIA/GERM CELL DEBRIS, UNILATERAL. OLIGOSPERMIA/GERM CELL DEBRIS, BILATERAL. PROSTATE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. SEMINAL VESICLES NO ABNORMALITY DETECTED | | | | | (10) |8 | | | |2 | (10) |9 | |1 | (10) |7 |3 | (10) | | 10 | || || || || ||| (1) | || || | 1| | 1| || ||| ||| ||| ||| || || ||| ||| ||| ||| || ||| ||| || || || || (10) | 9| 1| (10) | 9| 1| (10) | 10 | (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 207 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS I TREATMENT I I I II1 L E S I O N I N C I D E N C E (NUMERIC) I Males | I 0 I 1 I 5 I 25 I 125 I I mg/kgI mg/kgI mg/kgI mg/kgI mg/kgI I 1 I III I V I VII I IX I I II CUTANEOUS SYSTEM SKIN NO ABNORMALITY DETECTED I I I I III (10) I 10 I I I I I I I (1) I II 1I I Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified I I I I III I I (10) I 10 I DuPont-9478 - 208 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS SPECIAL SENSES SYSTEM EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED OPTIC NERVE NOT PRESENT. FOLD/ROSETTE, RETINAL. ADHESION, RETINAL. | TREATMENT | | | LESION INCIDENCE (NUMERIC) | Males |0 | mg/kg| |I | 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| III | V | VII | IX | || | | | | | (10) || |8 |3 |1 |1 || || || || ||| ||| || || || || (10) | 10 | 1| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 209 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Males LESIONS | TREATMENT | | | |0 | mg/kg| |I | 125 | mg/kg| IX | DIGESTIVE SYSTEM LIVER NECROSIS, FOCAL. INFLAMMATION, SUBACUTE/CHRONIC. HYPERPLASIA, BILE DUCT. FATTY CHANGE, MEDIAN CLEFT. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | (10) || |3 |9 |5 |2 | (10) | 7| 9| 6| DuPont-9478 - 210 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Males LESIONS | TREATMENT I I I |0 I mg/kg II I 125 I mg/kgI IX I URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED CHRONIC PROGRESSIVE NEPHROPATHY. HYPERPLASIA, TRANSITIONAL CELL. HYDRONEPHROSIS, UNILATERAL. HYDRONEPHROSIS, BILATERAL. CYST. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified I I I I III (10) I4 I6 I I I I I (10) I 3I 5I 1I 1I 1I 1I DuPont-9478 - 211 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Males LESIONS | TREATMENT I I I | 0 I 125 I I mg/kgj mg/kgI I 1 I IX I I RESPIRATORY SYSTEM NOSE NO ABNORMALITY DETECTED ODONTODYSPLASIA. INFLAMMATION, SUBACUTE/CHRONIC. DEGENERATION, AMELOBLASTS. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified I I I I III (10) I 10 I I I I I (10) I7 1 1 2 I I I I I DuPont-9478 - 212 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Males LESIONS | TREATMENT I I I | 0 I 125 I I mg/kgI mg/kgI I 1 I IX I II LYMPHATIC AND HEMATOPOIETIC SYSTEM THYMUS NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified I I I I III (10) I 10 I I I I I I (10) I I 10 I I I DuPont-9478 - 213 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 40 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Males LESIONS | TREATMENT | I | | 0 | 125 | | mg/kg| mg/kg| |I | IX | || ENDOCRINE SYSTEM THYROID GLAND NO ABNORMALITY DETECTED ALTERATION, COLLOID. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| (10) |3 |7 | | | | | ||| (10) | | 10 | | | DuPont-9478 - 214 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY | LESION INCIDENCE (NUMERIC) 1l | Females | LESIONS | TREATMENT |0 | mg/kg | II 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| IV | VI | VIII | X | DIGESTIVE SYSTEM LIVER NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. HYPERPLASIA, BILE DUCT. FATTY CHANGE, MEDIAN CLEFT. PANCREAS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. ESOPHAGUS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. LACERATION. STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED || | (11) || |1 | 10 |2 |2 | (11) || | 11 || | (11) || | 10 |1 || 1 | (11) || | 11 | | (11) || | 11 ||| ||| ||| ||| || || || || || | ||| || | ||| | ||| || || | ||| | ||| | ||| | ||| || (10) | 1| 6| 3| 1| (10) | 9| 1| (10) | 10 | (10) | 10 | (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H - 215 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | | LESION INCIDENCE (NUMERIC) 1l | Females | |0 1 |5 | 25 | 125 | | mg/kg mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | | || DIGESTIVE SYSTEM JEJUNUM NO ABNORMALITY DETECTED ILEUM NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED RECTUM NO ABNORMALITY DETECTED SALIVARY GLANDS NO ABNORMALITY DETECTED | | | (11) || | 11 | (11) || | 11 | (11) || | 11 | (11) || | 11 | (11) || | 11 | (11) | | 11 | | | | | | | | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H | | | ||| | | ||| | | ||| | | ||| | | ||| | | | | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | - 216 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | | 0 | 1 5 25 | 125 | | mg/kg mg/kg mg/kg mg/kg mg/kg| | II IV | VI | VIII | X | | URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED CHRONIC PROGRESSIVE NEPHROPATHY. INFLAMMATION, SUBACUTE/CHRONIC. HYDRONEPHROSIS, UNILATERAL. HYDRONEPHROSIS, BILATERAL. URINARY BLADDER NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. | | | | | (11) || |7 |2 |2 | |1 | | (11) || | 10 |1 | | (10) 8 2 1 | (10) 7 3 | (10) 7 3 | (10) 1 7 1 1 (10) 10 | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H DuPont-9478 - 217 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 | mg/kg | II | 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| IV | VI | VIII | X | || RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED TRACHEA NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED | | | | | (11) || | 11 | | (11) || | 11 | (11) || | 11 | | (11) || | 11 | || || || || ||| ||| ||| ||| ||| ||| || || ||| ||| ||| ||| ||| ||| || || (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H DuPont-9478 - 218 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | | 0 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | | || CARDIOVASCULAR SYSTEM HEART NO ABNORMALITY DETECTED CARDIOMYOPATHY. AORTA NO ABNORMALITY DETECTED | | | | | (11) || |6 |5 | (11) || | 11 | | | | | | | ||| | | | ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H | | | | ||| | | | ||| | | (10) | 8| 2| (10) | 10 | DuPont-9478 - 219 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 |1 |5 | 25 | 125 | | mg/kg mg/kg| mg/kg| mg/kg| mg/kg| | II IV | VI | VIII | X | | || LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED BONE MARROW NO ABNORMALITY DETECTED HYPERPLASIA, GRANULOCYTIC. | | | | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 10 |1 | | | | | ||| ||| ||| ||| ||| ||| ||| ||| ||| | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H | | | | ||| ||| ||| ||| ||| ||| ||| ||| ||| | | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | - 220 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 | mg/kg | II | 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| IV | VI | VIII | X | || ENDOCRINE SYSTEM PITUITARY GLAND NO ABNORMALITY DETECTED THYROID GLAND NO ABNORMALITY DETECTED PARATHYROID GLANDS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED MINERALIZATION. | | | | | (11) || | 11 | | (11) || | 11 | | (9) || || 9 | (11) || | 11 | | | | | | ||| ||| ||| ||| ||| ||| ||| | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H | | | | ||| ||| ||| ||| ||| ||| ||| | | | (10) | 10 | (10) | 10 | (9) | 9| (10) | 9| 1| DuPont-9478 - 221 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | | || NERVOUS SYSTEM BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED | || | || | || | || | (11) || ||| ||| | 11 | | ||| ||| | (11) | || ||| ||| | 11 | | ||| ||| | (11) | || ||| ||| | 11 | | | | || (10) | 10 | (10) | 10 | (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H DuPont-9478 - 222 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 | mg/kg | II | 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| IV | VI | VIII | X | || MUSCULAR AND SKELETAL SYSTEM SKELETAL MUSCLE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED | | | | | (11) || | 11 || | (11) || | 11 | (11) || | 11 | || || || || ||| ||| || ||| ||| ||| ||| || || ||| ||| || || (10) | 9| 1| (10) | 10 | (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H DuPont-9478 - 223 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | | || REPRODUCTIVE SYSTEM OVARIES NO ABNORMALITY DETECTED UTERUS NO ABNORMALITY DETECTED MAMMARY GLAND (FEMALE) NO ABNORMALITY DETECTED | || | || | || | || | (11) || ||| ||| | 11 | | ||| ||| | (11) | || ||| ||| | 11 | | ||| ||| | (11) | || ||| ||| | 11 | | | | || (10) | 10 | (10) | 10 | (8) | 8| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H DuPont-9478 - 224 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT I I I | 0 I i I 5 I 25 I i25 I I mg/kgI mg/kgI mg/kgI mg/kgI mg/kgI I II I IV I VI I VIII I X I IIII CUTANEOUS SYSTEM SKIN NO ABNORMALITY DETECTED I I I I III (ii) I ii I I I I I I II I I I I I I III I I Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H I I I I III I I (i0) I i0 I DuPont-9478 - 225 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT I I I II1 L E S I O N I N C I D E N C E (NUMERIC) I Females | |0 I1 I5 | 25 | 125 | I mg/kgI mg/kg| mg/kg| mg/kg| mg/kg| I II I IV I VI I VIII I X | I II SPECIAL SENSES SYSTEM EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED OPTIC NERVE NOT PRESENT. FOLD/ROSETTE, RETINAL. I I I I III (ii) I 11 I I I i | I I I I II1 I I I I Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H I I I I II1 I I I I (10) I 9| 1I 1I DuPont-9478 - 226 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Females LESIONS | TREATMENT | I | |0 | mg/kg | II | 125 | mg/kg| X| DIGESTIVE SYSTEM LIVER NO ABNORMALITY DETECTED NECROSIS, FOCAL. INFLAMMATION, SUBACUTE/CHRONIC. HYPERPLASIA, BILE DUCT. FATTY CHANGE, MEDIAN CLEFT. ANGIECTASIS. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 9 IN G R O U P II D U E T O E A R L Y D E A T H | | | | | (9) | (10) | || |3 2| |1 |3 6| |1 1| |2 1| | 2| | DuPont-9478 - 227 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESIONS LESION INCIDENCE | | Females | | TREATMENT | | | | 0 | 125 | | mg/kg| mg/kg| | II |X | ||| URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED CHRONIC PROGRESSIVE NEPHROPATHY. HYDRONEPHROSIS, BILATERAL. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 9 IN G R O U P II D U E T O E A R L Y D E A T H || || || || ||| (9) | (10) | || | 4| 2| | 5| 8| | | 1| || DuPont-9478 - 228 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Females LESIONS | TREATMENT | | | | 0 | 125 | | mg/kg| mg/kg| | II |X | || ENDOCRINE SYSTEM PITUITARY GLAND NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 9 IN G R O U P II D U E T O E A R L Y D E A T H || || || || ||| (1) ||| | 1| || DuPont-9478 - 229 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 41 (CONTINUED) INCIDENCES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NEOPLASTIC AND NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Females LESIONS | TREATMENT I I I | 0 I 125 I I mg/kgI mg/kgI I II IX I II REPRODUCTIVE SYSTEM UTERUS DILATATION. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 9 IN G R O U P II D U E T O E A R L Y D E A T H II II II II III (i) I II I 1I II DuPont-9478 - 230 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS DIGESTIVE SYSTEM LIVER NECROSIS, FOCAL. minimal total observations per lesion INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion HYPERTROPHY, HEPATOCELLULAR. minimal mild total observations per lesion FATTY CHANGE, MEDIAN CLEFT. minimal mild total observations per lesion FATTY CHANGE, CENTRILOBULAR. minimal total observations per lesion LESION INCIDENCE (NUMERIC) I TREATMENT I I I I Males I0 1 I5 I mg/kg mg/kg I mg/kg I I I III I V I 25 I 125 mg/kg I mg/kg VII I IX I I I I I (10) II I I I I I 10 I 10 I I I I I I2 I I2 I I I I (10) 9 9 2 2 I (10) I1 I1 I 10 I 10 I1 I1 I2 I (10) 5 5 I9 I9 1 1 I (10) I3 I3 I8 I8 I4 I6 I 10 I1 I1 I1 I1 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 231 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS DIGESTIVE SYSTEM PANCREAS NO ABNORMALITY DETECTED ATROPHY. minimal total observations per lesion ESOPHAGUS NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED | TREATMENT | | | LESION INCIDENCE (NUMERIC) | |0 | mg/kg |I | Males 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| III | V | VII | IX | || | | | | | (10) || |8 | |2 |2 | | (10) || | 10 | (10) || | 10 | (10) || | 10 | (10) || | 10 || || || || ||| ||| || || || ||| ||| ||| ||| || || ||| ||| || || ||| ||| || || ||| ||| || (10) | 8| 2| 2| (10) | 10 | (10) | 10 | (10) | 10 | (9) | 9| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 232 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS DIGESTIVE SYSTEM ILEUM NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED RECTUM NO ABNORMALITY DETECTED SALIVARY GLANDS NO ABNORMALITY DETECTED | TREATMENT | | | LESION INCIDENCE (NUMERIC) | Males |0 1 |5 | 25 | 125 | | mg/kg mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | | || | | | | | (10) | | 10 | | (10) | | 10 | | (10) | | 10 | | (10) | | 10 | | (10) || | 10 || || || || ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| || (9) | 9| (9) | 9| (10) | 10 | (9) | 9| (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 233 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | ||| L E S I O N I N C I D E N C E (NUMERIC) | Males | |0 1 | mg/kg mg/kg | I | III | 5 | 25 | 125 | mg/kg| mg/kg | mg/kg| V | VII | IX | URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED CHRONIC PROGRESSIVE NEPHROPATHY. minimal total observations per lesion PIGMENT, TUBULAR. minimal total observations per lesion HYPERTROPHY, TUBULAR. minimal total observations per lesion HYDRONEPHROSIS, UNILATERAL. minimal total observations per lesion CYST. minimal total observations per lesion URINARY BLADDER NO ABNORMALITY DETECTED | | | | ||| (10) |5 | |5 |5 | | | | | | | | | | | ||| | (10) | | 10 | | (10) 4 6 6 | (10) 3 7 7 | (1) 1 | (10) |1 |4 |4 9 9 1 1 | | | (10) |8 |8 |1 |1 | 10 | 10 |1 |1 | (10) | 10 | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 234 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Males LESIONS | TREATMENT I I I |0 1 5 I mg/kg mg/kg mg/kg I I I III I V I 25 I 125 I mg/kg mg/kgI VII IX I RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion TRACHEA NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED DEGENERATION, AMELOBLASTS. minimal mild total observations per lesion I I I I III (10) I9 I I1 III 1 III (10) I 10 I III (10) I 10 I III (10) I 10 I I I I I I (10) I 10 I (10) I 10 I (10) I 10 I (10) 9 1 1 I (10) I 10 I (10) I 10 I (10) 5 2 3 5 I I I I I I I I I I I I I Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 235 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | ||| L E S I O N I N C I D E N C E (NUMERIC) | Males | | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | |||| CARDIOVASCULAR SYSTEM HEART NO ABNORMALITY DETECTED CARDIOMYOPATHY. minimal total observations per lesion AORTA NO ABNORMALITY DETECTED | | | | ||| (10) |5 | |5 ||| 5 ||| (10) | 10 | | | | | | || | | | || | || | | | | | | ||| | | | ||| ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | ||| ||| | | (10) | 5| 5| 5| (10) | 10 | DuPont-9478 - 236 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED BONE MARROW NO ABNORMALITY DETECTED | TREATMENT | | | LESION INCIDENCE (NUMERIC) | Males |0 1 |5 | 25 | 125 | | mg/kg mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | | || | | | | | (10) | | 10 | | (10) | | 10 | | (10) || | 10 | | (10) || | 10 | | (10) || | 10 || || || || ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| || (10) | 10 | (10) | 10 | (10) | 10 | (9) | 9| (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 237 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Males LESIONS | TREATMENT I I I | 0 1 I 5 25 I 125 I I mq/kq mq/kq I mq/kq mq/kq mq/kqI I I I III I V I VII IX I I ENDOCRINE SYSTEM PITUITARY GLAND NO ABNORMALITY DETECTED CYST. minimal total observations per lesion THYROID GLAND NO ABNORMALITY DETECTED ALTERATION, COLLOID. minimal mild moderate severe total observations per lesion I I I I III (9) I8 I I1 III 1 III (10) I7 I I3 I I I I3 I I (10) 2 7 1 8 I (10) I1 I9 I9 I (10) I 10 I 10 I (10) I 10 I (10) 2 3 2 1 2 8 I I I I I I I I I Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 238 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | | LESION INCIDENCE (NUMERIC) 1l | Males | |0 | mg/kg| |I | 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| III | V | VII | IX | || ENDOCRINE SYSTEM PARATHYROID GLANDS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED | | | | | (9) || || 9 | (10) || | 10 | | | | | | ||| ||| ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| ||| ||| | | (9) | 9| (10) | 10 | DuPont-9478 - 239 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS NERVOUS SYSTEM BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED | TREATMENT I I I LESION INCIDENCE (NUMERIC) I |0 I mg/kg II I Males 1 I 5 I 25 I 125 I mg/kgI mg/kgI mg/kgI mg/kgI III I V I VII I IX I II I II I II I II I II I (10) I III III I 10 I I III III I (10) I II III III I 10 I I III III I (10) I II III III I 10 I I I (10) I 10 I (10) I 10 I (10) I 10 I Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 240 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | | LESION INCIDENCE (NUMERIC) 11 | Males | | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | |||| MUSCULAR AND SKELETAL SYSTEM SKELETAL MUSCLE NO ABNORMALITY DETECTED FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED | | | | | (10) || | 10 | | (10) || | 10 || | (10) || | 10 | | | | | | || | | | || | || | || | | | | | | ||| | | ||| ||| ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | ||| ||| ||| | | (10) | 10 | (10) | 10 | (10) | 10 | DuPont-9478 - 241 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| REPRODUCTIVE SYSTEM TESTES NO ABNORMALITY DETECTED DILATATION, SEMINIFEROUS TUBULES, UNILATERAL. moderate total observations per lesion DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, UNILATERAL. mild moderate total observations per lesion DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL. minimal severe total observations per lesion (10) 8 (1) (10) 9 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 242 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | | LESION INCIDENCE (NUMERIC) 1l | Males | |0 |1 |5 | 25 | 125 | | mg/kg mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | | || REPRODUCTIVE SYSTEM EPIDIDYMIDES NO ABNORMALITY DETECTED OLIGOSPERMIA/GERM CELL DEBRIS, UNILATERAL. severe total observations per lesion OLIGOSPERMIA/GERM CELL DEBRIS, BILATERAL. severe total observations per lesion PROSTATE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion SEMINAL VESICLES NO ABNORMALITY DETECTED | | | | | (10) || |9 | | | | |1 || 1 | (10) || |7 | |3 || 3 | (10) | | 10 | | | | | ||| | | | | | | ||| ||| | | | ||| | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | | | | ||| ||| | | | ||| | | | | (10) | 9| 1| 1| (10) | 10 | (10) | 10 | DuPont-9478 - 243 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS I TREATMENT I I I II1 L E S I O N I N C I D E N C E (NUMERIC) I Males | I 0 I 1 I 5 I 25 I 125 I I mg/kgI mg/kgI mg/kgI mg/kgI mg/kgI I 1 I III I V I VII I IX I I II CUTANEOUS SYSTEM SKIN NO ABNORMALITY DETECTED I I I I III (10) I 10 I I I I I I I (1) I II 1I I Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified I I I I III I I (10) I 10 I DuPont-9478 - 244 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | | LESION INCIDENCE (NUMERIC) | | Males | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | |||| SPECIAL SENSES SYSTEM EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED OPTIC NERVE NOT PRESENT. FOLD/ROSETTE, RETINAL. minimal total observations per lesion ADHESION, RETINAL. minimal total observations per lesion | | | | ||| (10) |8 |3 | |1 |1 | |1 |1 | | | | | | || | | | | | | | | | | | | | ||| | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | | | | | | | (10) | 10 | 1| DuPont-9478 - 245 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESIONS DIGESTIVE SYSTEM LIVER NECROSIS, FOCAL. minimal mild total observations per lesion INFLAMMATION, SUBACUTE/CHRONIC. minimal mild total observations per lesion HYPERPLASIA, BILE DUCT. minimal total observations per lesion FATTY CHANGE, MEDIAN CLEFT. minimal total observations per lesion LESION INCIDENCE Males | TREATMENT | I | | 0 | 125 | | mg/kg mg/kg| | I IX | | | | | | | (10) || | |2 |1 |3 | |8 |1 |9 | |5 |5 | |2 |2 | (10) 6 1 7 9 9 6 6 | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 246 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESIONS URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED CHRONIC PROGRESSIVE NEPHROPATHY. minimal total observations per lesion HYPERPLASIA, TRANSITIONAL CELL. minimal total observations per lesion HYDRONEPHROSIS, UNILATERAL. minimal total observations per lesion HYDRONEPHROSIS, BILATERAL. minimal total observations per lesion CYST. minimal total observations per lesion LESION INCIDENCE Males | TREATMENT I I I |0 I mg/kg II I 125 mg/kg IX I I I I III (10) I4 I I6 I6 I I I I I I I I I I I I I (10) 3 5 5 1 1 1 1 1 1 1 1 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 247 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Males LESIONS | TREATMENT | | | | 0 125 | | mg/kg mg/kg| | I | IX | | RESPIRATORY SYSTEM NOSE NO ABNORMALITY DETECTED ODONTODYSPLASIA. moderate total observations per lesion INFLAMMATION, SUBACUTE/CHRONIC. mild total observations per lesion DEGENERATION, AMELOBLASTS. minimal total observations per lesion Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| (10) | 10 | | | | | | | | | | (10) |7 1 1 1 1 2 2 | | | | | | | | DuPont-9478 - 248 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Males LESIONS | TREATMENT I I I | 0 I 125 I I mg/kgI mg/kgI I 1 I IX I II LYMPHATIC AND HEMATOPOIETIC SYSTEM THYMUS NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified I I I I III (10) I 10 I I I I I I (10) I I 10 I I I DuPont-9478 - 249 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats TABLE 42 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Males LESIONS | TREATMENT | | | | 0 125 | | mg/kg mg/kg| | I | IX | | ENDOCRINE SYSTEM THYROID GLAND NO ABNORMALITY DETECTED ALTERATION, COLLOID. minimal mild moderate total observations per lesion Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | (10) || |3 | |5 |1 |1 |7 | | (10) 6 2 2 | 10 | | | | | DuPont-9478 - 250 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 1 |5 | 25 | 125 | | mg/kg mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | | || DIGESTIVE SYSTEM LIVER NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion HYPERPLASIA, BILE DUCT. minimal total observations per lesion FATTY CHANGE, MEDIAN CLEFT. minimal total observations per lesion PANCREAS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion | | | | | (11) || |1 | | 10 | 10 | |2 |2 | |2 |2 | | (11) || | 11 | | | | || || || || ||| ||| || || || || || || || || || ||| ||| ||| ||| || || || || || (10) | 1| 6| 6| 3| 3| 1| 1| (10) | 9| 1| 1| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H - 251 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | | LESION INCIDENCE (NUMERIC) ll | Females | |0 | mg/kg | II | 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| IV | VI | VIII | X | || DIGESTIVE SYSTEM ESOPHAGUS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. severe total observations per lesion LACERATION. STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED | | | | | (11) || | 10 | |1 |1 || 1 | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | | | | ||| | | | | ||| ||| ||| ||| ||| ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H | | | | ||| | | | | ||| ||| ||| ||| ||| ||| | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | - 252 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT | | | | LESION INCIDENCE (NUMERIC) 1l | Females | |0 1 |5 | 25 | 125 | | mg/kg mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | | || DIGESTIVE SYSTEM ILEUM NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED RECTUM NO ABNORMALITY DETECTED SALIVARY GLANDS NO ABNORMALITY DETECTED | | | | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | (11) || | 11 | | | | | ||| ||| ||| ||| ||| ||| ||| ||| ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H | | | | ||| ||| ||| ||| ||| ||| ||| ||| ||| | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | - 253 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | I | |0 |1 |5 25 | 125 | | mg/kg mg/kg | mg/kg mg/kg| mg/kg| | II | IV | VI | VIII | X | || URINARY SYSTEM || || KIDNEYS NO ABNORMALITY DETECTED CHRONIC PROGRESSIVE NEPHROPATHY. minimal total observations per lesion INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion HYDRONEPHROSIS, UNILATERAL. minimal total observations per lesion HYDRONEPHROSIS, BILATERAL. minimal total observations per lesion URINARY BLADDER NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion | (11) || |7 | |2 |2 | |2 |2 | | | | |1 || 1 | (11) | | 10 | |1 |1 | | (10) 8 2 2 1 1 | (10) |7 |3 |3 | (10) 7 3 3 | (10) || |1 | |7 |7 | |1 |1 | |1 |1 | | ||| | (10) | | 10 | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H - 254 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 | mg/kg | II | 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| IV | VI | VIII | X | || RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED TRACHEA NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED NOSE NO ABNORMALITY DETECTED | | | | | (11) || | 11 | | (11) || | 11 | (11) || | 11 | | (11) || | 11 | || || || || ||| ||| ||| ||| ||| ||| || || ||| ||| ||| ||| ||| ||| || || (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H - 255 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | | 0 1 | 5 | 25 | 125 | | mg/kg mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | | || CARDIOVASCULAR SYSTEM HEART NO ABNORMALITY DETECTED CARDIOMYOPATHY. minimal total observations per lesion AORTA NO ABNORMALITY DETECTED | | | | ||| (11) |6 | |5 ||| 5 ||| (11) | 11 | | | | | ||| | | | ||| ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H | | | | ||| | | | ||| ||| | | (10) | 8| 2| 2| (10) | 10 | - 256 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESIONS | TREATMENT I | | | LESION INCIDENCE (NUMERIC) | | Females | |0 | mq/kq | II | 1 | 5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| IV | VI | VIII | X | || LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED THYMUS NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED BONE MARROW NO ABNORMALITY DETECTED HYPERPLASIA, GRANULOCYTIC. mild total observations per lesion | | | | ||| (ii) ||| 11 ||| (ii) ||| 11 ||| (ii) ||| 11 ||| (11) ||| 11 ||| (11) ||| 10 |1 |1 | | | | ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H | | | | ||| ||| ||| ||| ||| ||| ||| ||| ||| ||| | | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | (10) | 10 | - 257 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY | | | | | LESIONS | | ||| | | ENDOCRINE SYSTEM | | | PITUITARY GLAND | NO ABNORMALITY DETECTED | THYROID GLAND | NO ABNORMALITY DETECTED | PARATHYROID GLANDS | NO ABNORMALITY DETECTED | ADRENAL GLANDS | NO ABNORMALITY DETECTED | MINERALIZATION. | minimal | total observations per lesion | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) | | Females | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | |||||| ||||| ||||| ||||| ||||| ||| (11) | || ||| ||| ||| (10) | ||| 11 | | ||| ||| ||| 10 | ||| (11) | || ||| ||| ||| (10) | ||| 11 | | ||| ||| ||| 10 | ||| (9) | || ||| ||| ||| (9) | ||| 9 || ||| ||| ||| 9 | ||| (11) | || ||| ||| ||| (10) | | 11 | | | | 9 | ||||| | | | | | 1| | | | | | 1| ||||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H - 258 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | | || NERVOUS SYSTEM BRAIN NO ABNORMALITY DETECTED SPINAL CORD NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED | || | || | || | || | (11) || ||| ||| | 11 | | ||| ||| | (11) | || ||| ||| | 11 | | ||| ||| | (11) | || ||| ||| | 11 | | | | || (10) | 10 | (10) | 10 | (10) | 10 | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H - 259 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 | mg/kg | II | 1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| IV | VI | VIII | X | || MUSCULAR AND SKELETAL SYSTEM SKELETAL MUSCLE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. minimal total observations per lesion FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED | | | | | (11) || | 11 | | | | (11) || | 11 | (11) || | 11 | | | | | ||| | | | | | ||| | | ||| | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H | | | | ||| | | | | | ||| | | ||| | | (10) | 9| 1| 1| (10) | 10 | (10) | 10 | - 260 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT | | | |0 1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | | || REPRODUCTIVE SYSTEM OVARIES NO ABNORMALITY DETECTED UTERUS NO ABNORMALITY DETECTED MAMMARY GLAND (FEMALE) NO ABNORMALITY DETECTED | || | || | || | || | (11) || ||| ||| | 11 | | ||| ||| | (11) | || ||| ||| | 11 | | ||| ||| | (11) | || ||| ||| | 11 | | | | || (10) | 10 | (10) | 10 | (8) | 8| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H - 261 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS | TREATMENT I I I | 0 I i I 5 I 25 I i25 I I mg/kgI mg/kgI mg/kgI mg/kgI mg/kgI I II I IV I VI I VIII I X I IIII CUTANEOUS SYSTEM SKIN NO ABNORMALITY DETECTED I I I I III (ii) I ii I I I I I I II I I I I I I III I I Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H I I I I III I I (i0) I i0 I - 262 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR SUBCHRONIC TOXICITY LESION INCIDENCE (NUMERIC) Females LESIONS TREATMENT | 0 1 I 5 I 25 I 125 I mg/kg mg/kgI mg/kgI mg/kgI mg/kg I II I IV I VI I VIII I X I II SPECIAL SENSES SYSTEM EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED OPTIC NERVE NOT PRESENT. FOLD/ROSETTE, RETINAL. minimal total observations per lesion I I I I III (ii) I 11 I I I I I I I I I III I I I I I I Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 1 1 IN G R O U P II D U E T O E A R L Y D E A T H I I I I III I I I I I I (10) 9 1 1 1 - 263 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE 1 | LESIONS | | ||| | | DIGESTIVE SYSTEM | | | LIVER Females | TREATMENT | 0 | 125 | | | mg/kg | mg/kg| | | II | X | -| | | | | | | (9) | (10) | | NO ABNORMALITY DETECTED | NECROSIS, FOCAL. | minimal | total observations per lesion | INFLAMMATION, SUBACUTE/CHRONIC. | minimal | total observations per lesion | HYPERPLASIA, BILE DUCT. | minimal | total observations per lesion | FATTY CHANGE, MEDIAN CLEFT. | minimal | mild | total observations per lesion | ANGIECTASIS. | minimal | total observations per lesion | | 3| 2| | |1 |1 | | 3| 6| | 3| 6| | | 1| 1| | 1| 1| | |1 | 1| 1| | 2| 1| | | | 2| | | 2| | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 9 IN G R O U P II D U E T O E A R L Y D E A T H - 264 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Females LESIONS | TREATMENT | | | |0 | mg/kg | II | 125 | mg/kg| X| URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED CHRONIC PROGRESSIVE NEPHROPATHY. minimal mild total observations per lesion HYDRONEPHROSIS, BILATERAL. minimal total observations per lesion | | | | | (9) | (10) | || |4 2| | |5 5| | 3| |5 8| | | 1| | 1| | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 9 IN G R O U P II D U E T O E A R L Y D E A T H - 265 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESION INCIDENCE Females LESIONS | TREATMENT | | | | 0 | 125 | | mg/kg| mg/kg| | II |X | || ENDOCRINE SYSTEM PITUITARY GLAND NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 9 IN G R O U P II D U E T O E A R L Y D E A T H || || || || ||| (1) ||| | 1| || - 266 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 TABLE 43 (CONTINUED) INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE RATS NON-NEOPLASTIC LESIONS RATS DESIGNATED FOR RECOVERY LESIONS REPRODUCTIVE SYSTEM LESION INCIDENCE |--------------| Females | TREATMENT | | | | 0 | 125 | mg/kg| mg/kg | II |X || UTERUS DILATATION. mild total observations per lesion (1) 1 1 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified N = 9 IN G R O U P II D U E T O E A R L Y D E A T H - 267 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 FIGURES - 268 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 FIGURES EXPLANATORY NOTES Critical Dates Day 91 Last day of test substance administration for rats designated for satellite bleeds and 3-month recovery. Last day of non-fasted body weight and food consumption data collection for rats designated for the 90-day exposure period. Last day of food consumption data collection for rats designated for satellite bleeds in the 1, 5, and 25 mg/kg/day dose groups. Day 92 Last day of test substance administration for male rats designated for the 90-day exposure period. Day 93 Last day of test substance administration for female rats designated for the 90-day exposure period. Male rats designated for the 90-day exposure period were sacrificed. Day 94 Female rats designated for 90-day exposure period were sacrificed. Day 175 Rats designated for satellite bleeds were sacrificed Day 182 Last day of non-fasted body weight and food consumption data collection for rats designated for the 3-month recovery period. Day 183 Male and female rats designated for the 3-month recovery period were sacrificed. - 269 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats 800 -, 700 FIGURE 1 MEAN BODY WEIGHTS OF MALE RATS Exposure Period (test days 0-92) Recovery Period (test days 92-182) DuPont-9478 600 - l'Sib &mo 500 <D 400 - 0 mg/kg/day - B - 1mg/kg/day --A--5 mg/kg/day 25 mg/kg/day 125 mg/kg/day 300 200 0 7 14 21 28 35 42 49 56 63 70 77 84 91 98 105 112 119 126 133 140 147 154 161 168 175 182 Days on Test - 270 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats FIGURE 2 MEAN BODY WEIGHTS OF FEMALE RATS 400 Exposure Period (test days 0-93) Recovery Period (test days 92-182) 350 ia 300 O PQ 250 DuPont-9478 0 mg/kg/day 1 mg/kg/day 5 mg/kg/day 25 mg/kg/day 125 mg/kg/day 200 150 -^OOU'><NO'.VOrOOt^^|--^OOU'><Na'.VOrOOt^^|--^OOU'><N Days on Test - 271 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats FIGURE 3 MEAN FORELIMB GRIP STRENGTH FOR MALE RATS 1.6 1.4 1.2 in c5 0.8 g 0.6 O<D 0.4 0.2 0 Baseline Error bars represent standard deviation Assessment Period Week 13 DuPont-9478 0 mg/kg/day 1 mg/kg/day 5 mg/kg/day 25 mg/kg/day 125 mg/kg/day - 272 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats FIGURE 4 MEAN FORELIMB GRIP STRENGTH FOR FEMALE RATS DuPont-9478 Assessment Period Error bars represent standard deviation * Statistically significant difference from control at p<0.05. - 273 - 0 mg/kg/day 1 mg/kg/day 5 mg/kg/day 25 mg/kg/day 125 mg/kg/day 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats FIGURE 5 MEAN HINDLIMB GRIP STRENGTH FOR MALE RATS DuPont-9478 0.8 0.7 0.6 0.5 IGO *oG 0.4 g 0.3 'S x 0.2 0.1 0 Baseline Error bars represent standard deviation Assessment Period - 274 - Week 13 0 mg/kg/day 1 mg/kg/day 5 mg/kg/day 25 mg/kg/day 125 mg/kg/day 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats FIGURE 6 MEAN HINDLIMB GRIP STRENGTH FOR FEMALE RATS DuPont-9478 0.7 0.6 05 I 3 0.4 55 a OG 0.3 B 'S 0.2 0.1 0 Baseline Error bars represent standard deviation Assessment Period - 275 - Week 13 0 mg/kg/day 1 mg/kg/day 5 mg/kg/day 25 mg/kg/day 125 mg/kg/day 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats FIGURE 7 MEAN TOTAL DURATION OF MOVEMENT FOR MALE RATS DuPont-9478 2500 2000 a<>OD 1500 Oo 1000 Q3 500 0 Baseline Error bars represent standard deviation Assessment Period Week 13 - 276 - 0 mg/kg/day 1 mg/kg/day 5 mg/kg/day 25 mg/kg/day 125 mg/kg/day 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats FIGURE 8 MEAN TOTAL DURATION OF MOVEMENT FOR FEMALE RATS DuPont-9478 2500 -, 2000 /o0)s 1500 <>OaD 2 '+oH 1000 'S Qa 500 0 Baseline Error bars represent standard deviation A ssessm ent Period W eek 13 - 277 - 0 mg/kg/day 1mg/kg/day 5 mg/kg/day 25 mg/kg/day 125 mg/kg/day 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats FIGURE 9 MEAN TOTAL NUMBER OF MOVEMENTS FOR MALE RATS DuPont-9478 900 800 700 <<aDD 600 500 2 400 I 300 200 100 0 Baseline Assessment Period Error bars represent standard deviation. * Statistically significant difference from control at p<0.05. - 278 - * Week 13 0 mg/kg/day 1 mg/kg/day 5 mg/kg/day 25 mg/kg/day 125 mg/kg/day 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats FIGURE 10 MEAN TOTAL NUMBER OF MOVEMENTS FOR FEMALE RATS DuPont-9478 1000 900 800 700 00 <>OD 600 500 O 400 300 200 100 0 Baseline Error bars represent standard deviation A ssessm ent Period W eek 13 - 279 - 0 mg/kg/day 1mg/kg/day 5 mg/kg/day 25 mg/kg/day 125 mg/kg/day 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDICES - 280 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Critical Dates APPENDICES EXPLANATORY NOTES Day 91 Last day of test substance administration for rats designated for satellite bleeds and 3-month recovery. Last day of non-fasted body weight and food consumption data collection for rats designated for the 90-day exposure period. Last day of food consumption data collection for rats designated for satellite bleeds in the 1, 5, and 25 mg/kg/day dose groups. Day 92 Last day of test substance administration for male rats designated for the 90-day exposure period. Day 93 Last day of test substance administration for female rats designated for the 90-day exposure period. Male rats designated for the 90-day exposure period were sacrificed. Day 94 Female rats designated for 90-day exposure period were sacrificed. Day 175 Rats designated for satellite bleeds were sacrificed Day 182 Last day of non-fasted body weight and food consumption data collection for rats designated for the 3-month recovery period. Day 183 Male and female rats designated for the 3-month recovery period were sacrificed. Note mg/kg = mg/kg/day - 281 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX A ANALYTICAL DATA - 282 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Table I. Homogeneity and Stability o f 8-2 Telomer B Alcohol in Dosing Suspensions Sample mg/mL 8-2 Telomer B Alcohol Percent Type Test Day 1/-6 Nominal Measured Nominal Homogeneity Control 0.00 N D (A) Top Middle B ottom 0.20 0.20 0.20 0.163 0.164 0.161 81.5 82.0 80.5 M ean(B): 0.163+0.002 C.V. 1% (81.5%) Top Middle B ottom 1.0 0.803 1.0 0.857 1.0 0.890 M ean(B): 0.850+0.04 C.V. 5% 80.3 85.7 89.0 (85.0%) Top Middle B ottom 5.0 4.55 5.0 4.80 5.0 4.61 Mean(B): 4.65+0.13 C.V. 3% 91.0 96.0 92.2 (93.0%) Top Middle B ottom 25.0 19.9(C) 25.0 21.9 25.0 22.9 Mean(B): 21.6+1.5 C.V. 7% 79.6 87.6 91.6 (86.4%) Stability 5 HOUR(D) 0.20 1.0 5.0 25.0 0.167 0.818 4.14 21.8 83.5 81.8 82.8 87.2 7 -D ay Refrigerated 0.2 0.2 0.161 0.173 80.5 86.5 M ean(E): 0.167+0.01 C.V. 5% (83.5%) 5 HOUR(D) 0.2 0.158(C) 79.0 (A) Denotesnotdetected. (B) Theaveragemeasuredconcentration, averagepercentofnominal (inparentheses), standarddeviation, andcoefficientofvariationoftop, middle, andbottom. (C) Duplicatereanalysisoforiginal samplesupportoriginal analysisandarenotreported. (D) Stabilitysamplesheld5hoursaroomtemperature. (E) Theaveragemeasuredconcentration, averagepercentofnominal (inparentheses), standarddeviation, andcoefficientofvariationof duplicatesamples. - 283 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Table I. Homogeneity and Stability o f 8-2 Telomer B Alcohol in Dosing Suspensions (continued) Sample Type Test Day 4(A)BCDEF) Homogeneity Control Top Middle B ottom mg/mL 8-2 Telomer B Alcohol Nominal Measured 0.00 ND(a ) 1.0 0.944 1.0 0.884 1.0 0.836 (C) Percent Nominal ---94.4 88.4 83.6 Top Middle B oTToM Mean(B): 0.888+0.05 C.V. 6% 5.0 4.43 5.0 4.37 5.0 4.72 (C) (88.8%) 88.6 87.4 94.4 Top Middle B oTToM Mean(B): 4.51+0.19 C.V. 4% 25.0 22.2 25.0 22.7 25.0 24.2 (90.2%) 88.8 90.8 96.8 Stability 5 HOUR(D) Mean(B): 23.0+1.0 C.V. 5% 1.0 0.854(G)(H) 5.0 4.75 25.0 24.0 (92.0%) 85.4 95.0 96.0 7 -D ay Refrigerated Top Middle B oTToM 1.0 1.0 1.0 0.900 0.864 0.859 90.0 86.4 85.9 Mean(B): 0.874+0.02 (87.4%) C.V. 3% #1 5.0 4.46 89.2 #2 5.0 4.44 88.8 Mean(E): 4.45+0.01 (89.0%) C.V. 0.2% #1 25.0 24.2 96.8 #2 25.0 23.9 95.6 Mean(E): 24.1+0.21 (96.4%) C.V. 1% 5 HOUR(D) 1.0 0.904(H) 90.4 5.0 4.21(H) 84.2 25.0 21.2(H) 84.8 (A) Denotesnotdetected. (B) Theaveragemeasuredconcentration, averagepercentofnominal (inparentheses), standarddeviation, andcoefficientofvariationoftop, middle, andbottom. (C) Duplicatereanalysisoforiginal samplesupportoriginal analysisandarenotreported.. (D) Stabilitysamplesheld5hoursaroomtemperature. (E) Theaveragemeasuredconcentration, averagepercentofnominal (inparentheses), standarddeviation, andcoefficientofvariationfor duplicatesamples. (F) Samplesanalyzedinapreviousstudy(HA-2001-037/MR13690/SC1583). (G) Meanresultofallreportedanalysesexceptforoneduplicaterepeatsample. Aliquoterrorcausedresulttobelow. (H) Meanresultofduplicatere-samplingfromtheoriginal dilutedsample. Originalresultwaslowerthanexpectedduetoaliquoterror. - 284 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Table II. Concentration Verification o f 8-2 Telomer B Alcohol in Dosing Solutions Preparation Day Sample Type Test Day 42 mg/mL 8-2 Telomer B Alcohol Nominal Measured Percent Nominal Concentration Verification(A) Control 0.0 N D (B) ---- 0.2-1(O) 0.2-1(1) 0.2-1(2) 0.153 0.158 0.158 76.5 79.0 79.0 0.2-2(O) 0.2-2(1) 0.2-2(2) mean(C): 0.156 0.167 0.170 0.169 78.0 83.5 85.0 84.5 mean(C): 0.169 84.5 M ean(D): 0.163 0.01 C.V. 6% (81.5) 1.0-1(O) 1.0-1(1) 1.0-1(2) 0.718 0.757 0.773 71.8 75.7 77.3 1.0-2(O) 1.0-2(1) 1.0-2(2) m ean (C): 0.749 0.764 0.779 0.784 74.9 76.4 77.9 78.4 mean(C): 0.776 77.6 M ean(D): 0.763 0.02 C.V. 3% (76.3) 5.0-1(O) 5.0-1(1) 5.0-1(2) 3.89 3.82 3.89 77.8 76.4 77.8 5.0-2(1) 5.0-2(2) mean(C): 3.87 3.89 3.93 77.3 77.8 78.6 mean(E): 3.91 78.2 M ean(D): 3.89 0.03 C.V. 1% (77.8) 25.0-1(1) 25.0-1(2) 19.4 19.4 77.6 77.6 25.0-2(1) 25.0-2(2) m ean(E): 19.4 19.3 18.8 77.6 77.2 75.2 m ean(E): 19.1 76.2 M ean(D): 19.3 0.21 (77.2) C.V. 1% (A) Duplicatesamples(-1, -2)perlevel wereanalyzed. Mean, S.D. andC.V. calculatedtoverifyuniformityofmixture. (B) Denotesnotdetected. (C) Meanresultoftheoriginal analysis [(O)], andduplicatereanalysisoftheoriginal sample[(1), (2)]. (D) Theaveragemeasuredconcentration, averagepercentofnominal(inparentheses), standarddeviation, andcoefficientofvariationfor duplicatesamples (E) Meanresultofduplicatereanalysisontheoriginal submittedsample[(1), (2)]. Original analysisnotreportedduetoaliquoterror. - 285 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Table II. Concentration Verification o f 8-2 Telomer B Alcohol in Dosing Solutions (continued) Preparation Day Sample Type Test Day 45 mg/mL 8-2 Telomer B Alcohol Nominal Measured Percent Nominal Concentration Verification(A) Control 0.0 0.2-1(O) 0.2-1(1) 0.2-1(2) N D (B) 0.065 0.067 0.065 ---32.5 33.5 32.5 m ean(C): 0.2-2(O) 0.2-2(1) 0.2-2(2) 0.066 0.081 0.083 0.084 33.0 40.5 41.5 42.0 m ean(C): 0.083 41.5 M ean(D): 0.075 0.01 C.V. 13% (37.5) 1.0-1(O) 1.0-1(1) 1.0-1(2) 0.662 0.678 0.687 66.2 67.8 68.7 m ea n (C): 1.0-2(O) 1.0-2(1) 1.0-2(2) 0.676 0.646 0.657 0.665 67.6 64.6 65.7 66.5 mean(C): 0.656 65.6 M ean(D): 5.0-1(O) 5.0-1(1) 5.0-1(2) 0.666 0.01 C.V. 2% 2.13 2.27 2.21 (66.6) 42.6 45.4 44.2 m ean(C): 5.0-2(O) 5.0-2(1) 5.0-2(2) 2.20 2.26 2.36 2.33 44.0 45.2 47.2 46.6 m ean(C): 2.32 46.4 M ean(D): 25.0-1(1) 25.0-1(2) 2.26 0.09 C.V. 4% 8.31 8.36 (45.2) 33.2 33.4 mean(): 25.0-2(1) 25.0-2(2) 8.34 8.76 8.52 33.4 35.0 34.1 m ea n (E): 8.64 34.6 M ean(D): 8.49 0.21 (34.0) C.V. 3% (A) Duplicatesamples(-1, -2)perlevelwereanalyzed. Mean, S.D. andC.V. calculatedtoverifyuniformityofmixture. (B) Denotesnotdetected. (C) Meanresultoftheoriginalanalysis[(O)], andduplicatereanalysisoftheoriginal sample[(1), (2)]. (D) Theaveragemeasuredconcentration, averagepercentofnominal (inparentheses), standarddeviation, andcoefficientofvariationfor duplicatesamples. (E) Meanresultofduplicatereanalysisontheoriginal submittedsample[(1), (2)]. Originalanalysisnotreportedduetoaliquoterror. - 286 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Table II. Concentration Verification o f 8-2 Telomer B Alcohol in Dosing Solutions (continued) Preparation Day Sample Type mg/mL 8-2 Telomer B Alcohol Nominal Measured Percent Nominal Test Day 48(F) Concentration Verification(A) Control 0.0 N D (B) ---- 0.2-1 0.2-2 1.0-1 1.0-2 5.0-1 5.0-2 25.0-1 25.0-2 Test Day 52 Concentration Verification(A) Control 0.0 0.197 0.219 M ean(D): 0.208 0.02 C.V. 7% 0.865 0.948 M ean(D): 0.907 0.06 C.V. 6% 3.93 3.90 M ean(D): 3.92 0.02 C.V. 1% 21.9 22.5 M ean(D): 22. 2 0.42 C.V. 2% N D (B) 98.5 109.5 (104.0) 86.5 94.8 (90.7) 78.6 78.0 (78.3) 87.6 90.0 (88.8) ---- 0.2-1 0.2-2 1.0-1 1.0-2 5.0-1 5.0-2 25.0-1 25.0-2 0.174 0.184 M ean(D) : 0.179 0.01 C.V. 4% 0.845 0.895 M ean(D) : 0.870 0.04 C.V. 4% 4.22 4.16 M ean(D) : 4.19 0.04 C.V. 1% 23.5 22.3 M ean(D) : 22.9 0.85 C.V. 4% 87.0 92.0 (89.5) 84.5 89.5 (87.0) 84.4 83.2 (83.8) 94.0 89.2 (91.6) (A) Duplicatesamples(-1, -2)perlevelwereanalyzed. Mean, S.D. andC.V. calculatedtoverifyuniformityofmixture. (B) Denotesnotdetected. (D) Theaveragemeasuredconcentration, averagepercentofnominal (inparentheses), standarddeviation, andcoefficientofvariationfor duplicatesamples. (F) Suspensionnotdosedtoanimals. - 287 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Table II. Concentration Verification o f 8-2 Telomer B Alcohol in Dosing Solutions (continued) Preparation Day Sample Type Test Day 56 mg/mL 8-2 Telomer B Alcohol Nominal Measured Percent Nominal Concentration Verification(A) Control 0.0 N D (B) ---- 0.2-1 0.2-2 M ean(D): 1.0-1 1.0-2 M ean(D): 5.0-1 5.0-2 M ean(D): 25.0-1 25.0-2 M ean(D): 0.167 0.189 0.178 0.02 C.V. 9% 0.964 0.950 0.957 0.01 C.V. 1% 4.41 4.31 4.36 0.07 C.V. 2% 22.8 21.4 22. 1 0.99 C.V. 4% 83.5 94.5 (89.0) 96.4 95.0 (95.7) 88.2 86.2 (87.2) 91.2 85.6 (88.4) Test Day 58 Concentration Verification(A) Control 0.0 N D (B) ---- 0.2-1 0.2-2 0.174 0.150 87.0 75.0 M ean(D): 0.162 0.02 C.V. 10% (81.0) 1.0-1 1.0-2 0.945 0.937 94.5 93.7 M ean(D): 0.941 0.01 C.V. 1% (94.1) 5.0-1 5.0-2 4.48 4.17 89.6 83.4 M ean(D): 4.33 0.22 C.V. 5% (86.5) 25.0-1 25.0-2 22.5 22.1 90.0 88.4 M ean(D): 22. 3 0.28 (89.2) C.V. 1% (A) Duplicate samples (-1, -2) per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity of mixture. (B) Denotes not detected. (D) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation for duplicate samples. - 288 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Table II. Concentration Verification o f 8-2 Telomer B Alcohol in Dosing Solutions (continued) Preparation Day Sample Type Test Day 65 mg/mL 8-2 Telomer B Alcohol Nominal Measured Percent Nominal Concentration Verification(A) Control 0.0 N D (B) ---- 0.2-1(O) 0.2-1(1) 0.2-1(2) 0.158 0.158 0.162 79.0 79.0 81.0 m ea n (C): 0.2-2(O) 0.2-2(1) 0.2-2(2) 0.159 0.148 0.149 0.153 79.5 74.0 74.5 76.5 m ean (C): M ean(D): 1.0-1 1.0-2 0.150 0.155 0.01 C.V. 4% 0.832 0.898 75.0 (77.5) 83.2 89.8 M ean(D): 5.0-1 5.0-2 0.865 0.05 C.V. 5% 4.32 4.40 (86.5) 86.4 88.0 M ean(D): 25.0-1 25.0-2 4.36 0.06 C.V. 1% 20.8 20.5 (87.2) 83.2 82.0 M ean(D): 20.7 0.21 (82.6) C.V. 1% (A) Duplicate samples (-1, -2) per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity of mixture. (B) Denotes not detected. (C) Mean result of the original analysis [(O)], and duplicate reanalysis of the original sample [(1), (2)]. (D) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation for duplicate samples. - 289 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Table II. Concentration Verification o f 8-2 Telomer B Alcohol in Dosing Solutions (continued) Preparation Day Sample Type Test Day 91 mg/mL 8-2 Telomer B Alcohol Nominal Measured Percent Nominal Concentration Verification(A) Control 0.0 N D (B) ---- 0.2-1 0.2-2 0.162 0.165 81.0 82.5 M ean(D): 0.164 0.002 C.V. 1% (82.0) 1.0-1(O) 10-1(1) 1.0-1(2) 0.781 0.744 0.754 78.1 74.4 75.4 1.0-2 mean(C): 0.760 0.863 76.0 86.3 M ean(D): 0.812 0.07 C.V. 9% (81.2) 5.0-1(O) 5.0-1(1) 5.0-1(2) 3.90 4.07 3.91 78.0 81.4 78.2 5.0-2(O) 5.0-2(1) 5.0-2(2) m ea n (C): 3.96 3.81 3.98 3.90 79.2 76.2 79.6 78.0 mean(C): 3.90 78.0 M ean(D): 3.93 0.04 C.V. 1% (78.6) 25.0-1(O) 25.0-1(1) 25.0-1(2) 19.1 20.3 20.2 76.4 81.2 80.8 25.0-2(O) 25.0-2(1) 25.0-2(2) m ea n (C): 19.9 18.8 18.9 18.4 76.4 75.2 75.6 73.6 mean(C): 18.7 74.8 M ean(D): 19.3 0.85 C.V. 4% (77.2) (A) Duplicate samples (-1,-2) per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity of mixture. (B) Denotes not detected. (C) Mean result of the original analysis [(O)], and duplicate reanalysis of the original sample [(1), (2)]. (D) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation for duplicate samples. - 290 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Table II. Concentration Verification o f 8-2 Telomer B Alcohol in Dosing Solutions (continued) Preparation Day Sample Type Test Day 63 mg/mL 8-2 Telomer B Alcohol Nominal Measured Percent Nominal Concentration V erification ^ Control 0.0 N D (B) ---- 0.2-1 0.2-2 1.0-1 1.0-2 5.0-1 5.0-2 25.0-1 25.0-2 M ean(C): M ean(C): M ean(C): M ean(C): 0.190 0.192 0.191 0.001 C.V. 1% 0.784 0.792 0.788 0.01 C.V. 1% 4.12 4.08 4.10 0.03 C.V. 1% 23.0 21.4 22.2 1.1 C.V. 5% 95.0 96.0 (95.5) 78.4 79.2 (78.8) 82.4 81.8 (82.0) 92.0 85.6 (88.8) Test Day 73 Concentration Verification^) Control 0.0 n d (C) ---- 0.2-1 0.176 88.0 0.2-2 0.155 77.5 M ean(C): 0.166 0.01 C.V. 9% (82.8) 1.0-1 1.0-2 0.980 1.03 98.0 103.0 M ean(C): 1.01 0.04 C.V. 4% (101.0) 5.0-1 5.0-2 4.57 4.60 91.4 92.0 M ean(D ): 4.59 0.02 C.V. 0.4% (91.8) 25.0-1 25.0-2 23.3 24.4 93.2 97.6 M ean(C): 23.9 0.78 C.V. 3% (95.6) (A) Duplicate samples (-1, -2) per level were analyzed. Mean, S.D. and C.V. calculated to verify uniformity of mixture. (B) Denotes not detected. (D) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation for duplicate samples. - 291 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Figure 1 Representative Analytical Calibration Curve DuPont-9478 Figure 1: C a lib r a tio n c u r v e s h o w in g lin e a r fit (lin e ) to r e p lic a te p e a k h e ig h t ra tio m e a s u r e m e n ts (squares) for calibration solutions o f 8-2 T elom er B A lco h o l diluted over a concentration range o f 0 .0 0 5 0 to 0.0453 m g/m L w ith the 0 m g/m L control diluted sam ple w as used as the zero. - 292 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 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 3.5 minutes. Retention time for internal standard is approximately 3.9 minutes. FIDI B, (020214SR\016F1603.D) pa i 40 30 20 10 0 02468 Figure 2b: Representative HPLC chromatogram o f 5.0 mg/mL 8-2 Telomer B Alcohol dosing solution diluted to a nominalconcentration o f 0.03 mg/mL. The measured concentration o f the representative solution is 4.85 mg/mL FID1 B, (020214SR\006F0603.D) PA 1 40 30 20 10 0 02468 Figure 2c: Representative HPLC chromatogram of 0.0302 mg/mL 8-2 Telomer B Alcohol analytical reference solution. - 293 - TRADE SECRET Study Title 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Volume 2 of 3 Laboratory Project ID: DuPont-9478 DuPont-9478 Te s t Gu id e l in e s : U.S. EPA Health Effects Test Guidelines OPPTS 870.3100 (1998) Au t h o r : Gregory S. Ladics, Ph.D St u d y Co m p l e t e d o n : April 1, 2003 P L :e r f o r m in g a b o r a t o r y E.I. du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 W o r k Re q u e s t Nu m b e r : 13690 Se r v i c e Co d e Nu m b e r : 1022 Page 294 of 967 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX B INDIVIDUAL DOSE VOLUMES - 295 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 0 Gavage ml Day 1 Male, I 0 mg/kg/day 654928 1.1 1.1 654993 1.0 1.0 654929 1.2 1.2 654972 1.2 1.2 654950 1.3 1.3 654953 1.5 1.5 654925 1.3 1.3 654987 1.2 1.2 654903 1.2 1.2 654966 1.1 1.1 654997 1.3 1.3 654971 1.0 1.0 654939 1.2 1.2 654919 1.2 1.2 654994 1.0 1.0 654949 1.1 1.1 654992 1.2 1.2 654909 1.1 1.1 654924 1.2 1.2 654943 1.1 1.1 654915 1.3 1.3 654927 2.1 1.2 654956 1.0 1.0 654910 1.2 1.2 654936 1.1 1.1 Gavage ml Day 2 1.1 1.0 1.2 1.2 1.3 1.5 1.3 1.2 1.2 1.1 1.3 1.0 1.2 1.2 1.0 1.1 1.2 1.1 1.2 1.1 1.3 1.2 1.0 1.2 1.1 Gavage ml Day 3 1.1 1.0 1.2 1.2 1.3 1.5 1.3 1.2 1.2 1.1 1.3 1.0 1.2 1.2 1.0 1.1 1.2 1.1 1.2 1.1 1.3 1.2 1.0 1.2 1.1 Gavage ml Day 4 1.1 1.0 1.2 1.2 1.3 1.5 1.3 1.2 1.2 1.1 1.3 1.0 1.2 1.2 1.0 1.1 1.2 1.1 1.2 1.1 1.3 1.2 1.0 1.2 1.1 Gavage ml Day 5 1.1 1.0 1.2 1.2 1.3 1.5 1.3 1.2 1.2 1.1 1.3 1.0 1.2 1.2 1.0 1.1 1.2 1.1 1.2 1.1 1.3 1.2 1.0 1.2 1.1 Gavage ml Day 6 1.1 1.0 1.2 1.2 1.3 1.5 1.3 1.2 1.2 1.1 1.3 1.0 1.2 1.2 1.0 1.1 1.2 1.1 1.2 1.1 1.3 1.2 1.0 1.2 1.1 Gavage ml Day 7 1.3 1.3 1.4 1.4 1.6 1.9 1.6 1.5 1.5 1.4 1.6 1.2 1.5 1.4 1.2 1.3 1.5 1.3 1.4 1.4 1.5 1.6 1.3 1.5 1.5 Gavage ml Day 8 1.3 1.3 1.4 1.4 1.6 1.9 1.6 1.5 1.5 1.4 1.6 1.2 1.5 1.4 1.2 1.3 1.5 1.3 1.4 1.4 1.5 1.6 1.3 1.5 1.5 Gavage ml Day 9 1.3 1.3 1.4 1.4 1.6 1.9 1.6 1.5 1.5 1.4 1.6 1.2 1.5 1.4 1.2 1.3 1.5 1.3 1.4 1.4 1.5 1.6 1.3 1.5 1.5 Gavage ml Day 10 1.3 1.3 1.4 1.4 1.6 1.9 1.6 1.5 1.5 1.4 1.6 1.2 1.5 1.4 1.2 1.3 1.5 1.3 1.4 1.4 1.5 1.6 1.3 1.5 1.5 Gavage ml Day 11 1. 3 1. 3 1. 4 1. 4 1. 6 1. 9 1. 6 1. 5 1. 5 1. 4 1. 6 1. 2 1. 5 1. 4 1. 2 1. 3 1. 5 1. 3 1. 4 1. 4 1. 5 1. 6 1. 3 1. 5 1. 5 - 296 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 12 Gavage ml D a y 13 Male, I 0 mg/kg/day 654928 1.3 1.3 654993 1.3 1.3 654929 1.4 1.4 654972 1.4 1.4 654950 1.6 1.6 654953 1.9 1.9 654925 1.6 1.6 654987 1.5 1.5 654903 1.5 1.5 654966 1.4 1.4 654997 1.6 1.6 654971 1.2 1.2 654939 1.5 1.5 654919 1.4 1.4 654994 1.2 1.2 654949 1.3 1.3 654992 1.5 1.5 654909 1.3 1.3 654924 1.4 1.4 654943 1.4 1.4 654915 1.5 1.5 654927 1.6 1.6 654956 1.3 1.3 654910 1.5 1.5 654936 1.5 1.5 Gavage ml D a y 14 1.5 1.5 1.7 1.6 1.8 2.1 1.8 1.7 1.7 1.6 1.9 1.5 1.8 1.6 1.4 1.5 1.8 1.5 1.6 1.6 1.8 1.9 1.5 1.8 1.8 Gavage ml Day 15 1.5 1.5 1.7 1.6 1.8 2.1 1.8 1.7 1.7 1.6 1.9 1.5 1.8 1.6 1.4 1.5 1.8 1.5 1.6 1.6 1.8 1.9 1.5 1.8 1.8 Gavage ml D a y 16 1.5 1.5 1.7 1.6 1.8 2.1 1.8 1.7 1.7 1.6 1.9 1.5 1.8 1.6 1.4 1.5 1.8 1.5 1.6 1.6 1.8 1.9 1.5 1.8 1.8 Gavage ml Day 17 1.5 1.5 1.7 1.6 1.8 2.1 1.8 1.7 1.7 1.6 1.9 1.5 1.8 1.6 1.4 1.5 1.8 1.5 1.6 1.6 1.8 1.9 1.5 1.8 1.8 Gavage ml Day 18 1.5 1.5 1.7 1.6 1.8 2.1 1.8 1.7 1.7 1.6 1.9 1.5 1.8 1.6 1.4 1.5 1.8 1.5 1.6 1.6 1.8 1.9 1.5 1.8 1.8 Gavage ml Day 19 1.5 1.5 1.7 1.6 1.8 2.1 1.8 1.7 1.7 1.6 1.9 1.5 1.8 1.6 1.4 1.5 1.8 1.5 1.6 1.6 1.8 1.9 1.5 1.8 1.8 Gavage ml Day 20 1.5 1.5 1.7 1.6 1.8 2.1 1.8 1.7 1.7 1.6 1.9 1.5 1.8 1.6 1.4 1.5 1.8 1.5 1.6 1.6 1.8 1.9 1.5 1.8 1.8 Gavage ml Day 21 1.7 1.7 1.8 1.8 2.0 2.4 2.1 1.9 2.0 1.8 2.1 1.8 2.1 1.8 1.6 1.7 2.1 1.7 1.9 1.8 2.0 2.1 1.7 2.1 2.1 Gavage ml D a y 22 1.7 1.7 1.8 1.8 2.0 2.4 2.1 1.9 2.0 1.8 2.1 1.8 2.1 1.8 1.6 1.7 2.1 1.7 1.9 1.8 2.0 2.1 1.7 2.1 2.1 Gavage ml D a y 23 1. 7 1. 7 1. 8 1. 8 2. 0 2. 4 2. 1 1. 9 2. 0 1. 8 2. 1 1. 8 2. 1 1. 8 1. 6 1. 7 2. 1 1. 7 1. 9 1. 8 2. 0 2. 1 1. 7 2. 1 2. 1 - 297 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 24 Gavage ml Day 25 Male, I 0 mg/kg/day 654928 1.7 1.7 654993 1.7 1.7 654929 1.8 1.8 654972 1.8 1.8 654950 2.0 2.0 654953 2.4 2.4 654925 2.1 2.1 654987 1.9 1.9 654903 2.0 2.0 654966 1.8 1.8 654997 2.1 2.1 654971 1.8 1.8 654939 2.1 2.1 654919 1.8 1.8 654994 1.6 1.6 654949 1.7 1.7 654992 2.1 2.1 654909 1.7 1.7 654924 1.9 1.9 654943 1.8 1.8 654915 2.0 2.0 654927 2.1 2.1 654956 1.7 1.7 654910 2.1 2.1 654936 2.1 2.1 Gavage ml D a y 26 1.7 1.7 1.8 1.8 2.0 2.4 2.1 1.9 2.0 1.8 2.1 1.8 2.1 1.8 1.6 1.7 2.1 1.7 1.9 1.8 2.0 2.1 1.7 2.1 2.1 Gavage ml Day 27 1.7 1.7 1.8 1.8 2.0 2.4 2.1 1.9 2.0 1.8 2.1 1.8 2.1 1.8 1.6 1.7 2.1 1.7 1.9 1.8 2.0 2.1 1.7 2.1 2.1 Gavage ml Day 28 2.0 1.8 2.0 2.0 2.2 2.7 2.2 2.0 2.2 2.0 2.2 2.0 2.2 1.9 1.8 1.9 2.2 1.9 2.1 2.0 2.2 2.3 1.8 2.2 2.3 Gavage ml Day 29 2.0 1.8 2.0 2.0 2.2 2.7 2.2 2.0 2.2 2.0 2.2 2.0 2.2 1.9 1.8 1.9 2.2 1.9 2.1 2.0 2.2 2.3 1.8 2.2 2.3 Gavage ml Day 30 2.0 1.8 2.0 2.0 2.2 2.7 2.2 2.0 2.2 2.0 2.2 2.0 2.2 1.9 1.8 1.9 2.2 1.9 2.1 2.0 2.2 2.3 1.8 2.2 2.3 Gavage ml Day 31 2.0 1.8 2.0 2.0 2.2 2.7 2.2 2.0 2.2 2.0 2.2 2.0 2.2 1.9 1.8 1.9 2.2 1.9 2.1 2.0 2.2 2.3 1.8 2.2 2.3 Gavage ml D a y 32 2.0 1.8 2.0 2.0 2.2 2.7 2.2 2.0 2.2 2.0 2.2 2.0 2.2 1.9 1.8 1.9 2.2 1.9 2.1 2.0 2.2 2.3 1.8 2.2 2.3 Gavage ml D a y 33 2.0 1.8 2.0 2.0 2.2 2.7 2.2 2.0 2.2 2.0 2.2 2.0 2.2 1.9 1.8 1.9 2.2 1.9 2.1 2.0 2.2 2.3 1.8 2.2 2.3 Gavage ml D a y 34 2.0 1.8 2.0 2.0 2.2 2.7 2.2 2.0 2.2 2.0 2.2 2.0 2.2 1.9 1.8 1.9 2.2 1.9 2.1 2.0 2.2 2.3 1.8 2.2 2.3 Gavage ml Day 35 2. 1 2. 0 2. 1 2. 1 2. 3 2. 9 2. 4 2. 2 2. 4 1. 7 2. 3 2. 2 2. 4 2. 0 1. 9 2. 1 2. 3 2. 0 2. 2 2. 1 2. 4 2. 5 2. 0 2. 5 2. 5 - 298 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 36 Gavage ml D a y 37 Male, I 0 mg/kg/day 654928 2.1 2.1 654993 2.0 2.0 654929 2.1 2.1 654972 2.1 2.1 654950 2.3 2.3 654953 2.9 2.9 654925 2.4 2.4 654987 2.2 2.2 654903 2.4 2.4 654966 1.7 1.7 654997 2.3 2.3 654971 2.2 2.2 654939 2.4 2.4 654919 2.0 2.0 654994 1.9 1.9 654949 2.1 2.1 654992 2.3 2.3 654909 2.0 2.0 654924 2.2 2.2 654943 2.1 2.1 654915 2.4 2.4 654927 2.5 2.5 654956 2.0 2.0 654910 2.5 2.5 654936 2.5 2.5 Gavage ml D a y 38 2.1 2.0 2.1 2.1 2.3 2.9 2.4 2.2 2.4 1.7 2.3 2.2 2.4 2.0 1.9 2.1 2.3 2.0 2.2 2.1 2.4 2.5 2.0 2.5 2.5 Gavage ml Day 39 2.1 2.0 2.1 2.1 2.3 2.9 2.4 2.2 2.4 1.7 2.3 2.2 2.4 2.0 1.9 2.1 2.3 2.0 2.2 2.1 2.4 2.5 2.0 2.5 2.5 Gavage ml Day 40 2.1 2.0 2.1 2.1 2.3 2.9 2.4 2.2 2.4 1.7 2.3 2.2 2.4 2.0 1.9 2.1 2.3 2.0 2.2 2.1 2.4 2.5 2.0 2.5 2.5 Gavage ml Day 41 2.1 2.0 2.1 2.1 2.3 2.9 2.4 2.2 2.4 1.7 2.3 2.2 2.4 2.0 1.9 2.1 2.3 2.0 2.2 2.1 2.4 2.5 2.0 2.5 2.5 Gavage ml D a y 42 2.3 2.0 2.2 2.2 2.4 3.0 2.5 2.4 2.5 1.6 2.4 2.3 2.6 2.1 2.0 2.1 2.5 2.1 2.4 2.2 2.6 2.6 2.1 2.6 2.6 Gavage ml D a y 43 2.3 2.0 2.2 2.2 2.4 3.0 2.5 2.4 2.5 1.6 2.4 2.3 2.6 2.1 2.0 2.1 2.5 2.1 2.4 2.2 2.6 2.6 2.1 2.6 2.6 Gavage ml D a y 44 2.3 2.0 2.2 2.2 2.4 3.0 2.5 2.4 2.5 1.6 2.4 2.3 2.6 2.1 2.0 2.1 2.5 2.1 2.4 2.2 2.6 2.6 2.1 2.6 2.6 Gavage ml Day 45 2.3 2.0 2.2 2.2 2.4 3.0 2.5 2.4 2.5 1.6 2.4 2.3 2.6 2.1 2.0 2.1 2.5 2.1 2.4 2.2 2.6 2.6 2.1 2.6 2.6 Gavage ml D a y 46 2.3 2.0 2.2 2.2 2.4 3.0 2.5 2.4 2.5 1.6 2.4 2.3 2.6 2.1 2.0 2.1 2.5 2.1 2.4 2.2 2.6 2.6 2.1 2.6 2.6 Gavage ml Day 47 2. 3 2. 0 2. 2 2. 2 2. 4 3. 0 2. 5 2. 4 2. 5 1. 6 2. 4 2. 3 2. 6 2. 1 2. 0 2. 1 2. 5 2. 1 2. 4 2. 2 2. 6 2. 6 2. 1 2. 6 2. 6 - 299 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 48 Gavage ml Day 49 Male, I 0 mg/kg/day 654928 2.3 2.3 654993 2.0 2.1 654929 2.2 2.2 654972 2.2 2.2 654950 2.4 2.4 654953 3.0 3.0 654925 2.5 2.6 654987 2.4 2.4 654903 2.5 2.5 654966 1.6 1.9 654997 2.4 2.5 654971 2.3 2.4 654939 2.6 2.8 654919 2.1 2.2 654994 2.0 2.1 654949 2.1 2.3 654992 2.5 2.6 654909 2.1 2.3 654924 2.4 2.4 654943 2.2 2.3 654915 2.6 2.7 654927 2.6 2.7 654956 2.1 2.2 654910 2.6 2.8 654936 2.6 2.6 Gavage ml D a y 50 2.3 2.1 2.2 2.2 2.4 3.0 2.6 2.4 2.5 1.9 2.5 2.4 2.8 2.2 2.1 2.3 2.6 2.3 2.4 2.3 2.7 2.7 2.2 2.8 2.6 Gavage ml Day 51 2.3 2.1 2.2 2.2 2.4 3.0 2.6 2.4 2.5 1.9 2.5 2.4 2.8 2.2 2.1 2.3 2.6 2.3 2.4 2.3 2.7 2.7 2.2 2.8 2.6 Gavage ml D a y 52 2.3 2.1 2.2 2.2 2.4 3.0 2.6 2.4 2.5 1.9 2.5 2.4 2.8 2.2 2.1 2.3 2.6 2.3 2.4 2.3 2.7 2.7 2.2 2.8 2.6 Gavage ml D a y 53 2.3 2.1 2.2 2.2 2.4 3.0 2.6 2.4 2.5 1.9 2.5 2.4 2.8 2.2 2.1 2.3 2.6 2.3 2.4 2.3 2.7 2.7 2.2 2.8 2.6 Gavage ml D a y 54 2.3 2.1 2.2 2.2 2.4 3.0 2.6 2.4 2.5 1.9 2.5 2.4 2.8 2.2 2.1 2.3 2.6 2.3 2.4 2.3 2.7 2.7 2.2 2.8 2.6 Gavage ml Day 55 2.3 2.1 2.2 2.2 2.4 3.0 2.6 2.4 2.5 1.9 2.5 2.4 2.8 2.2 2.1 2.3 2.6 2.3 2.4 2.3 2.7 2.7 2.2 2.8 2.6 Gavage ml D a y 56 2.5 2.2 2.4 2.3 2.5 3.2 2.7 2.5 2.6 1.9 2.6 2.5 2.8 2.3 2.0 2.4 2.8 2.3 2.5 2.3 2.8 2.8 2.3 2.9 2.7 Gavage ml Day 57 2.5 2.2 2.4 2.3 2.5 3.2 2.7 2.5 2.6 1.9 2.6 2.5 2.8 2.3 2.0 2.4 2.8 2.3 2.5 2.3 2.8 2.8 2.3 2.9 2.7 Gavage ml Day 58 2.5 2.2 2.4 2.3 2.5 3.2 2.7 2.5 2.6 1.9 2.6 2.5 2.8 2.3 2.0 2.4 2.8 2.3 2.5 2.3 2.8 2.8 2.3 2.9 2.7 Gavage ml Day 59 2. 5 2. 2 2. 4 2. 3 2. 5 3. 2 2. 7 2. 5 2. 6 1. 9 2. 6 2. 5 2. 8 2. 3 2. 0 2. 4 2. 8 2. 3 2. 5 2. 3 2. 8 2. 8 2. 3 2. 9 2. 7 - 300 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 60 Gavage ml D a y 61 Male, I 0 mg/kg/day 654928 2.5 2.5 654993 2.2 2.2 654929 2.4 2.4 654972 2.3 2.3 654950 2.5 2.5 654953 3.2 3.2 654925 2.7 2.7 654987 2.5 2.5 654903 2.6 2.6 654966 1.9 1.9 654997 2.6 2.6 654971 2.5 2.5 654939 2.8 2.8 654919 2.3 2.3 654994 2.0 2.0 654949 2.4 2.4 654992 2.8 2.8 654909 2.3 2.3 654924 2.5 2.5 654943 2.3 2.3 654915 2.8 2.8 654927 2.8 2.8 654956 2.3 2.3 654910 2.9 2.9 654936 2.7 2.7 Gavage ml D a y 62 2.5 2.2 2.4 2.3 2.5 3.2 2.7 2.5 2.6 1.9 2.6 2.5 2.8 2.3 2.0 2.4 2.8 2.3 2.5 2.3 2.8 2.8 2.3 2.9 2.7 Gavage ml D a y 63 2.7 2.3 2.4 2.4 2.6 3.3 2.8 2.6 2.7 1.9 2.6 2.6 2.9 2.4 2.1 2.5 2.8 2.4 2.6 2.4 2.9 2.9 2.4 3.0 2.8 Gavage ml D a y 64 2.7 2.3 2.4 2.4 2.6 3.3 2.8 2.6 2.7 1.9 2.6 2.6 2.9 2.4 2.1 2.5 2.8 2.4 2.6 2.4 2.9 2.9 2.4 3.0 2.8 Gavage ml Day 65 2.7 2.3 2.4 2.4 2.6 3.3 2.8 2.6 2.7 1.9 2.6 2.6 2.9 2.4 2.1 2.5 2.8 2.4 2.6 2.4 2.9 2.9 2.4 3.0 2.8 Gavage ml D a y 66 2.7 2.3 2.4 2.4 2.6 3.3 2.8 2.6 2.7 1.9 2.6 2.6 2.9 2.4 2.1 2.5 2.8 2.4 2.6 2.4 2.9 2.9 2.4 3.0 2.8 Gavage ml Day 67 2.7 2.3 2.4 2.4 2.6 3.3 2.8 2.6 2.7 1.9 2.6 2.6 2.9 2.4 2.1 2.5 2.8 2.4 2.6 2.4 2.9 2.9 2.4 3.0 2.8 Gavage ml Day 68 2.7 2.3 2.4 2.4 2.6 3.3 2.8 2.6 2.7 1.9 2.6 2.6 2.9 2.4 2.1 2.5 2.8 2.4 2.6 2.4 2.9 2.9 2.4 3.0 2.8 Gavage ml Day 69 2.7 2.3 2.4 2.4 2.6 3.3 2.8 2.6 2.7 1.9 2.6 2.6 2.9 2.4 2.1 2.5 2.8 2.4 2.6 2.4 2.9 2.9 2.4 3.0 2.8 Gavage ml Day 70 2.7 2.4 2.5 2.4 2.6 3.4 2.8 2.7 2.8 2.1 2.7 2.7 3.0 2.4 2.3 2.6 2.9 2.5 2.7 2.5 2.9 3.0 2.4 3.1 2.9 Gavage ml Day 71 2. 7 2. 4 2. 5 2. 4 2. 6 3. 4 2. 8 2. 7 2. 8 2. 1 2. 7 2. 7 3. 0 2. 4 2. 3 2. 6 2. 9 2. 5 2. 7 2. 5 2. 9 3. 0 2. 4 3. 1 2. 9 - 301 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 72 Gavage ml D a y 73 Male, I 0 mg/kg/day 654928 2.7 2.7 654993 2.4 2.4 654929 2.5 2.5 654972 2.4 2.4 654950 2.6 2.6 654953 3.4 3.4 654925 2.8 2.8 654987 2.7 2.7 654903 2.8 2.8 654966 2.1 2.1 654997 2.7 2.7 654971 2.7 2.7 654939 3.0 3.0 654919 2.4 2.4 654994 2.3 2.3 654949 2.6 2.6 654992 2.9 2.9 654909 2.5 2.5 654924 2.7 2.7 654943 2.5 2.5 654915 2.9 2.9 654927 3.0 3.0 654956 2.4 2.4 654910 3.1 3.1 654936 2.9 2.9 Gavage ml D a y 74 2.7 2.4 2.5 2.4 2.6 3.4 2.8 2.7 2.8 2.1 2.7 2.7 3.0 2.4 2.3 2.6 2.9 2.5 2.7 2.5 2.9 3.0 2.4 3.1 2.9 Gavage ml Day 75 2.7 2.4 2.5 2.4 2.6 3.4 2.8 2.7 2.8 2.1 2.7 2.7 3.0 2.4 2.3 2.6 2.9 2.5 2.7 2.5 2.9 3.0 2.4 3.1 2.9 Gavage ml D a y 76 2.7 2.4 2.5 2.4 2.6 3.4 2.8 2.7 2.8 2.1 2.7 2.7 3.0 2.4 2.3 2.6 2.9 2.5 2.7 2.5 2.9 3.0 2.4 3.1 2.9 Gavage ml Day 77 2.8 2.5 2.6 2.5 2.6 3.5 2.8 2.8 2.9 2.2 2.8 2.7 3.0 2.5 2.3 2.6 2.9 2.6 2.7 2.6 3.0 3.1 2.5 3.1 3.0 Gavage ml Day 78 2.8 2.5 2.6 2.5 2.6 3.5 2.8 2.8 2.9 2.2 2.8 2.7 3.0 2.5 2.3 2.6 2.9 2.6 2.7 2.6 3.0 3.1 2.5 3.1 3.0 Gavage ml Day 79 2.8 2.5 2.6 2.5 2.6 3.5 2.8 2.8 2.9 2.2 2.8 2.7 3.0 2.5 2.3 2.6 2.9 2.6 2.7 2.6 3.0 3.1 2.5 3.1 3.0 Gavage ml Day 80 2.8 2.5 2.6 2.5 2.6 3.5 2.8 2.8 2.9 2.2 2.8 2.7 3.0 2.5 2.3 2.6 2.9 2.6 2.7 2.6 3.0 3.1 2.5 3.1 3.0 Gavage ml Day 81 2.8 2.5 2.6 2.5 2.6 3.5 2.8 2.8 2.9 2.2 2.8 2.7 3.0 2.5 2.3 2.6 2.9 2.6 2.7 2.6 3.0 3.1 2.5 3.1 3.0 Gavage ml D a y 82 2.8 2.5 2.6 2.5 2.6 3.5 2.8 2.8 2.9 2.2 2.8 2.7 3.0 2.5 2.3 2.6 2.9 2.6 2.7 2.6 3.0 3.1 2.5 3.1 3.0 Gavage ml D a y 83 2. 8 2. 5 2. 6 2. 5 2. 6 3. 5 2. 8 2. 8 2. 9 2. 2 2. 8 2. 7 3. 0 2. 5 2. 3 2. 6 2. 9 2. 6 2. 7 2. 6 3. 0 3. 1 2. 5 3. 1 3. 0 - 302 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL DOSE VOLUMES Gavage ml D a y 84 Gavage ml D a y 85 Male, I 0 mg/kg/day 654928 2.9 2.9 654993 2.5 2.5 654929 2.6 2.6 654972 2.5 2.5 654950 2.6 2.6 654953 3.5 3.5 654925 2.9 2.9 654987 2.9 2.9 654903 2.9 2.9 654966 2.3 2.3 654997 2.8 2.8 654971 2.8 2.8 654939 3.1 3.1 654919 2.5 2.5 654994 2.3 2.3 654949 2.7 2.7 654992 3.0 3.0 654909 2.6 2.6 654924 2.7 2.7 654943 2.6 2.6 654915 3.1 3.1 654927 3.1 3.1 654956 2.5 2.5 654910 3.1 3.1 654936 3.0 3.0 Gavage ml D a y 86 2.9 2.5 2.6 2.5 2.6 3.5 2.9 2.9 2.9 2.3 2.8 2.8 3.1 2.5 2.3 2.7 3.0 2.6 2.7 2.6 3.1 3.1 2.5 3.1 3.0 Gavage ml Day 87 Gavage ml Day 88 2. 9 2. 5 2. 6 2. 5 2. 6 3. 5 2. 9 2. 9 2. 9 2. 3 2. 8 2. 8 3. 1 2. 5 2. 3 2. 7 3. 0 2. 6 2. 7 2. 6 3. 1 3. 1 2. 5 3. 1 3. 0 2.9 2.5 2.6 2.5 2.6 3.5 2.9 2.9 2.9 2.3 2.8 2.8 3.1 2.5 2.3 2.7 3.0 2.6 2.7 2.6 3.1 3.1 2.5 3.1 3.0 Gavage ml Day 89 2.9 2.5 2.6 2.5 2.6 3.5 2.9 2.9 2.9 2.3 2.8 2.8 3.1 2.5 2.3 2.7 3.0 2.6 2.7 2.6 3.1 3.1 2.5 3.1 3.0 Gavage ml D a y 90 2.9 2.5 2.6 2.5 2.6 3.5 2.9 2.9 2.9 2.3 2.8 2.8 3.1 2.5 2.3 2.7 3.0 2.6 2.7 2.6 3.1 3.1 2.5 3.1 3.0 Gavage ml D a y 91 2.9 2.5 2.6 2.6 2.7 3.3 3.0 2.9 3.0 2.3 2.9 2.8 3.1 2.5 2.3 2.7 3.0 2.6 2.8 2.6 3.1 3.1 2.5 3.2 3.0 Gavage ml D a y 92 2.9 2.5 2.6 2.6 2.7 3.3 3.0 2.9 3.0 3.0 DuPont-9478 - 303 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 0 Gavage ml Day 1 Male, III: 1 m g / k g / d a y 654913 1.1 1.1 654947 1.1 1.1 654995 1.2 1.2 654938 1.3 1.3 654941 1.2 1.2 654946 1.4 1.4 654960 1.4 1.4 654908 1.3 1.3 654984 1.2 1.2 654932 1.3 1.3 654948 1.3 1.3 654904 1.2 1.2 654954 1.4 1.4 654945 1.1 1.1 654988 1.2 1.2 Gavage ml Day 2 1.1 1.1 1.2 1.3 1.2 1.4 1.4 1.3 1.2 1.3 1.3 1.2 1.4 1.1 1.2 Gavage ml Day 3 1.1 1.1 1.2 1.3 1.2 1.4 1.4 1.3 1.2 1.3 1.3 1.2 1.4 1.1 1.2 Gavage ml Day 4 1.1 1.1 1.2 1.3 1.2 1.4 1.4 1.3 1.2 1.3 1.3 1.2 1.4 1.1 1.2 Gavage ml Day 5 1.1 1.1 1.2 1.3 1.2 1.4 1.4 1.3 1.2 1.3 1.3 1.2 1.4 1.1 1.2 Gavage ml Day 6 1.1 1.1 1.2 1.3 1.2 1.4 1.4 1.3 1.2 1.3 1.3 1.2 1.4 1.1 1.2 Gavage ml Day 7 1.4 1.4 1.4 1.6 1.5 1.7 1.6 1.5 1.5 1.6 1.6 1.4 1.6 1.2 1.5 Gavage ml Day 8 1.4 1.4 1.4 1.6 1.5 1.7 1.6 1.5 1.5 1.6 1.6 1.4 1.6 1.2 1.5 Gavage ml Day 9 1.4 1.4 1.4 1.6 1.5 1.7 1.6 1.5 1.5 1.6 1.6 1.4 1.6 1.2 1.5 Gavage ml Day 10 1.4 1.4 1.4 1.6 1.5 1.7 1.6 1.5 1.5 1.6 1.6 1.4 1.6 1.2 1.5 Gavage ml Day 11 1. 4 1. 4 1. 4 1. 6 1. 5 1. 7 1. 6 1. 5 1. 5 1. 6 1. 6 1. 4 1. 6 1. 2 1. 5 - 304 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 12 Gavage ml D a y 13 Male, III: 1 m g / k g / d a y 654913 1.4 1.4 654947 1.4 1.4 654995 1.4 1.4 654938 1.6 1.6 654941 1.5 1.5 654946 1.7 1.7 654960 1.6 1.6 654908 1.5 1.5 654984 1.5 1.5 654932 1.6 1.6 654948 1.6 1.6 654904 1.4 1.4 654954 1.6 1.6 654945 1.2 1.2 654988 1.5 1.5 Gavage ml D a y 14 1.7 1.6 1.7 1.8 1.8 2.0 1.8 1.8 1.8 1.8 1.9 1.7 1.8 1.6 1.7 Gavage ml Day 15 1.7 1.6 1.7 1.8 1.8 2.0 1.8 1.8 1.8 1.8 1.9 1.7 1.8 1.6 1.7 Gavage ml D a y 16 1.7 1.6 1.7 1.8 1.8 2.0 1.8 1.8 1.8 1.8 1.9 1.7 1.8 1.6 1.7 Gavage ml Day 17 1.7 1.6 1.7 1.8 1.8 2.0 1.8 1.8 1.8 1.8 1.9 1.7 1.8 1.6 1.7 Gavage ml Day 18 1.7 1.6 1.7 1.8 1.8 2.0 1.8 1.8 1.8 1.8 1.9 1.7 1.8 1.6 1.7 Gavage ml Day 19 1.7 1.6 1.7 1.8 1.8 2.0 1.8 1.8 1.8 1.8 1.9 1.7 1.8 1.6 1.7 Gavage ml Day 20 1.7 1.6 1.7 1.8 1.8 2.0 1.8 1.8 1.8 1.8 1.9 1.7 1.8 1.6 1.7 Gavage ml Day 21 1.9 1.8 1.9 2.1 2.0 2.2 2.0 2.0 2.0 2.1 2.1 1.9 2.1 1.8 1.9 Gavage ml D a y 22 1.9 1.8 1.9 2.1 2.0 2.2 2.0 2.0 2.0 2.1 2.1 1.9 2.1 1.8 1.9 Gavage ml D a y 23 1. 9 1. 8 1. 9 2. 1 2. 0 2. 2 2. 0 2. 0 2. 0 2. 1 2. 1 1. 9 2. 1 1. 8 1. 9 - 305 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 24 Gavage ml Day 25 Male, III: 1 m g / k g / d a y 654913 1.9 1.9 654947 1.8 1.8 654995 1.9 1.9 654938 2.1 2.1 654941 2.0 2.0 654946 2.2 2.2 654960 2.0 2.0 654908 2.0 2.0 654984 2.0 2.0 654932 2.1 2.1 654948 2.1 2.1 654904 1.9 1.9 654954 2.1 2.1 654945 1.8 1.8 654988 1.9 1.9 Gavage ml D a y 26 1.9 1.8 1.9 2.1 2.0 2.2 2.0 2.0 2.0 2.1 2.1 1.9 2.1 1.8 1.9 Gavage ml Day 27 1.9 1.8 1.9 2.1 2.0 2.2 2.0 2.0 2.0 2.1 2.1 1.9 2.1 1.8 1.9 Gavage ml Day 28 2.1 2.0 2.1 2.2 2.2 2.3 2.1 2.2 2.2 2.2 2.3 2.0 2.2 1.9 2.1 Gavage ml Day 29 2.1 2.0 2.1 2.2 2.2 2.3 2.1 2.2 2.2 2.2 2.3 2.0 2.2 1.9 2.1 Gavage ml Day 30 2.1 2.0 2.1 2.2 2.2 2.3 2.1 2.2 2.2 2.2 2.3 2.0 2.2 1.9 2.1 Gavage ml Day 31 2.1 2.0 2.1 2.2 2.2 2.3 2.1 2.2 2.2 2.2 2.3 2.0 2.2 1.9 2.1 Gavage ml D a y 32 2.1 2.0 2.1 2.2 2.2 2.3 2.1 2.2 2.2 2.2 2.3 2.0 2.2 1.9 2.1 Gavage ml D a y 33 2.1 2.0 2.1 2.2 2.2 2.3 2.1 2.2 2.2 2.2 2.3 2.0 2.2 1.9 2.1 Gavage ml D a y 34 2.1 2.0 2.1 2.2 2.2 2.3 2.1 2.2 2.2 2.2 2.3 2.0 2.2 1.9 2.1 Gavage ml Day 35 2. 2 2. 1 2. 2 2. 3 2. 3 2. 5 2. 2 2. 3 2. 4 2. 3 2. 4 2. 2 2. 4 2. 0 2. 2 - 306 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 36 Gavage ml D a y 37 Male, III: 1 m g / k g / d a y 654913 2.2 2.2 654947 2.1 2.1 654995 2.2 2.2 654938 2.3 2.3 654941 2.3 2.3 654946 2.5 2.5 654960 2.2 2.2 654908 2.3 2.3 654984 2.4 2.4 654932 2.3 2.3 654948 2.4 2.4 654904 2.2 2.2 654954 2.4 2.4 654945 2.0 2.0 654988 2.2 2.2 Gavage ml D a y 38 2.2 2.1 2.2 2.3 2.3 2.5 2.2 2.3 2.4 2.3 2.4 2.2 2.4 2.0 2.2 Gavage ml Day 39 2.2 2.1 2.2 2.3 2.3 2.5 2.2 2.3 2.4 2.3 2.4 2.2 2.4 2.0 2.2 Gavage ml Day 40 2.2 2.1 2.2 2.3 2.3 2.5 2.2 2.3 2.4 2.3 2.4 2.2 2.4 2.0 2.2 Gavage ml Day 41 2.2 2.1 2.2 2.3 2.3 2.5 2.2 2.3 2.4 2.3 2.4 2.2 2.4 2.0 2.2 Gavage ml D a y 42 2.3 2.2 2.3 2.5 2.4 2.6 2.3 2.4 2.5 2.5 2.6 2.3 2.6 2.1 2.3 Gavage ml D a y 43 2.3 2.2 2.3 2.5 2.4 2.6 2.3 2.4 2.5 2.5 2.6 2.3 2.6 2.1 2.3 Gavage ml D a y 44 2.3 2.2 2.3 2.5 2.4 2.6 2.3 2.4 2.5 2.5 2.6 2.3 2.6 2.1 2.3 Gavage ml Day 45 2.3 2.2 2.3 2.5 2.4 2.6 2.3 2.4 2.5 2.5 2.6 2.3 2.6 2.1 2.3 Gavage ml D a y 46 2.3 2.2 2.3 2.5 2.4 2.6 2.3 2.4 2.5 2.5 2.6 2.3 2.6 2.1 2.3 Gavage ml Day 47 2. 3 2. 2 2. 3 2. 5 2. 4 2. 6 2. 3 2. 4 2. 5 2. 5 2. 6 2. 3 2. 6 2. 1 2. 3 - 307 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 48 Gavage ml Day 49 Male, III: 1 m g / k g / d a y 654913 2.3 2.4 654947 2.2 2.2 654995 2.3 2.4 654938 2.5 2.5 654941 2.4 2.4 654946 2.6 2.7 654960 2.3 2.3 654908 2.4 2.4 654984 2.5 2.5 654932 2.5 2.5 654948 2.6 2.6 654904 2.3 2.4 654954 2.6 2.7 654945 2.1 2.1 654988 2.3 2.4 Gavage ml D a y 50 2.4 2.2 2.4 2.5 2.4 2.7 2.3 2.4 2.5 2.5 2.6 2.4 2.7 2.1 2.4 Gavage ml Day 51 2.4 2.2 2.4 2.5 2.4 2.7 2.3 2.4 2.5 2.5 2.6 2.4 2.7 2.1 2.4 Gavage ml D a y 52 2.4 2.2 2.4 2.5 2.4 2.7 2.3 2.4 2.5 2.5 2.6 2.4 2.7 2.1 2.4 Gavage ml D a y 53 2.4 2.2 2.4 2.5 2.4 2.7 2.3 2.4 2.5 2.5 2.6 2.4 2.7 2.1 2.4 Gavage ml D a y 54 2.4 2.2 2.4 2.5 2.4 2.7 2.3 2.4 2.5 2.5 2.6 2.4 2.7 2.1 2.4 Gavage ml Day 55 2.4 2.2 2.4 2.5 2.4 2.7 2.3 2.4 2.5 2.5 2.6 2.4 2.7 2.1 2.4 Gavage ml D a y 56 2.5 2.3 2.5 2.6 2.5 2.8 2.4 2.5 2.7 2.6 2.7 2.5 2.8 2.2 2.5 Gavage ml Day 57 2.5 2.3 2.5 2.6 2.5 2.8 2.4 2.5 2.7 2.6 2.7 2.5 2.8 2.2 2.5 Gavage ml Day 58 2.5 2.3 2.5 2.6 2.5 2.8 2.4 2.5 2.7 2.6 2.7 2.5 2.8 2.2 2.5 Gavage ml Day 59 2. 5 2. 3 2. 5 2. 6 2. 5 2. 8 2. 4 2. 5 2. 7 2. 6 2. 7 2. 5 2. 8 2. 2 2. 5 - 308 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 60 Gavage ml D a y 61 Male, III: 1 m g / k g / d a y 654913 2.5 2.5 654947 2.3 2.3 654995 2.5 2.5 654938 2.6 2.6 654941 2.5 2.5 654946 2.8 2.8 654960 2.4 2.4 654908 2.5 2.5 654984 2.7 2.7 654932 2.6 2.6 654948 2.7 2.7 654904 2.5 2.5 654954 2.8 2.8 654945 2.2 2.2 654988 2.5 2.5 Gavage ml D a y 62 2.5 2.3 2.5 2.6 2.5 2.8 2.4 2.5 2.7 2.6 2.7 2.5 2.8 2.2 2.5 Gavage ml D a y 63 2.6 2.4 2.5 2.8 2.6 2.8 2.5 2.6 2.8 2.7 2.8 2.5 2.9 2.3 2.6 Gavage ml D a y 64 2.6 2.4 2.5 2.8 2.6 2.8 2.5 2.6 2.8 2.7 2.8 2.5 2.9 2.3 2.6 Gavage ml Day 65 2.6 2.4 2.5 2.8 2.6 2.8 2.5 2.6 2.8 2.7 2.8 2.5 2.9 2.3 2.6 Gavage ml D a y 66 2.6 2.4 2.5 2.8 2.6 2.8 2.5 2.6 2.8 2.7 2.8 2.5 2.9 2.3 2.6 Gavage ml Day 67 2.6 2.4 2.5 2.8 2.6 2.8 2.5 2.6 2.8 2.7 2.8 2.5 2.9 2.3 2.6 Gavage ml Day 68 3.6 2.4 2.5 2.8 2.6 2.8 2.5 2.6 2.8 2.7 2.8 2.5 2.9 2.3 2.6 Gavage ml Day 69 2.6 2.4 2.5 2.8 2.6 2.8 2.5 2.6 2.8 2.7 2.8 2.5 2.9 2.3 2.6 Gavage ml Day 70 2.7 2.5 2.7 2.9 2.7 3.0 2.6 2.6 2.9 2.8 2.9 2.6 3.0 2.3 2.6 Gavage ml Day 71 2. 7 2. 5 2. 7 2. 9 2. 7 3. 0 2. 6 2. 6 2. 9 2. 8 2. 9 2. 6 3. 0 2. 3 2. 6 - 309 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 72 Gavage ml D a y 73 Male, III: 1 m g / k g / d a y 654913 2.7 2.7 654947 2.5 2.5 654995 2.7 2.7 654938 2.9 2.9 654941 2.7 2.7 654946 3.0 3.0 654960 2.6 2.6 654908 2.6 2.6 654984 2.9 2.9 654932 2.8 2.8 654948 2.9 2.9 654904 2.6 2.6 654954 3.0 3.0 654945 2.3 2.3 654988 2.6 2.6 Gavage ml D a y 74 2.7 2.5 2.7 2.9 2.7 3.0 2.6 2.6 2.9 2.8 2.9 2.6 3.0 2.3 2.6 Gavage ml Day 75 2.7 2.5 2.7 2.9 2.7 3.0 2.6 2.6 2.9 2.8 2.9 2.6 3.0 2.3 2.6 Gavage ml D a y 76 2.7 2.5 2.7 2.9 2.7 3.0 2.6 2.6 2.9 2.8 2.9 2.6 3.0 2.3 2.6 Gavage ml Day 77 2.7 2.5 2.6 2.9 2.7 3.0 2.6 2.6 3.0 2.8 2.7 2.6 3.0 2.3 2.7 Gavage ml Day 78 2.7 2.5 2.6 2.9 2.7 3.0 2.6 2.6 3.0 2.8 2.7 2.6 3.0 2.3 2.7 Gavage ml Day 79 2.7 2.5 2.6 2.9 2.7 3.0 2.6 2.6 3.0 2.8 2.7 2.6 3.0 2.3 2.7 Gavage ml Day 80 2.7 2.5 2.6 2.9 2.7 3.0 2.6 2.6 3.0 2.8 2.7 2.6 3.0 2.3 2.7 Gavage ml Day 81 2.7 2.5 2.6 2.9 2.7 3.0 2.6 2.6 3.0 2.8 2.7 2.6 3.0 2.3 2.7 Gavage ml D a y 82 2.7 2.5 2.6 2.9 2.7 3.0 2.6 2.6 3.0 2.8 2.7 2.6 3.0 2.3 2.7 Gavage ml D a y 83 2. 7 2. 5 2. 6 2. 9 2. 7 3. 0 2. 6 2. 6 3. 0 2. 8 2. 7 2. 6 3. 0 2. 3 2. 7 - 310 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL DOSE VOLUMES Gavage ml D a y 84 Gavage ml D a y 85 Male, III: 1 m g / k g / d a y 654913 2.7 2.7 654947 2.5 2.5 654995 2.6 2.6 654938 2.9 2.9 654941 2.6 2.6 654946 3.0 3.0 654960 2.6 2.6 654908 2.7 2.7 654984 3.0 3.0 654932 2.9 2.9 654948 2.9 2.9 654904 2.7 2.7 654954 3.0 3.0 654945 2.4 2.4 654988 2.7 2.7 Gavage ml D a y 86 2.7 2.5 2.6 2.9 2.6 3.0 2.6 2.7 3.0 2.9 2.9 2.7 3.0 2.4 2.7 Gavage ml Day 87 2.7 2.5 2.6 2.9 2.6 3.0 2.6 2.7 3.0 2.9 2.9 2.7 3.0 2.4 2.7 Gavage ml Day 88 2.7 2.5 2.6 2.9 2.6 3.0 2.6 2.7 3.0 2.9 2.9 2.7 3.0 2.4 2.7 Gavage ml Day 89 2.7 2.5 2.6 2.9 2.6 3.0 2.6 2.7 3.0 2.9 2.9 2.7 3.0 2.4 2.7 Gavage ml D a y 90 2.7 2.5 2.6 2.9 2.6 3.0 2.6 2.7 3.0 2.9 2.9 2.7 3.0 2.4 2.7 Gavage ml D a y 91 2.8 2.5 2.6 3.0 2.7 3.0 2.7 2.7 3.1 2.9 3.1 2.7 3.1 2.4 2.8 Gavage ml D a y 92 2. 8 2. 5 2. 6 3. 0 2. 7 3. 0 2. 7 2. 7 3. 1 2. 9 DuPont-9478 - 311 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 0 Gavage ml Day 1 Male, V 5 mg/kg/day 655005 1.2 1.2 654907 1.1 1.1 654980 1.1 1.1 654959 1.2 1.2 654961 1.3 1.3 654916 1.4 1.4 654911 1.3 1.3 654917 1.2 1.2 654998 1.2 1.2 654970 1.1 1.1 654926 1.3 1.3 654918 1.2 1.2 654981 1.0 1.0 654969 1.1 1.1 654967 1.1 1.1 Gavage ml Day 2 1.2 1.1 1.1 1.2 1.3 1.4 1.3 1.2 1.2 1.1 1.3 1.2 1.0 1.1 1.1 Gavage ml Day 3 1.2 1.1 1.1 1.2 1.3 1.4 1.3 1.2 1.2 1.1 1.3 1.2 1.0 1.1 1.1 Gavage ml Day 4 1.2 1.1 1.1 1.2 1.3 1.4 1.3 1.2 1.2 1.1 1.3 1.2 1.0 1.1 1.1 Gavage ml Day 5 1.2 1.1 1.1 1.2 1.3 1.4 1.3 1.2 1.2 1.1 1.3 1.2 1.0 1.1 1.1 Gavage ml Day 6 1.2 1.1 1.1 1.2 1.3 1.4 1.3 1.2 1.2 1.1 1.3 1.2 1.0 1.1 1.1 Gavage ml Day 7 1.4 1.4 1.4 1.5 1.7 1.7 1.6 1.5 1.6 1.2 1.6 1.5 1.3 1.3 1.4 Gavage ml Day 8 1.4 1.4 1.4 1.5 1.7 1.7 1.6 1.5 1.6 1.2 1.6 1.5 1.3 1.3 1.4 Gavage ml Day 9 1.4 1.4 1.4 1.5 1.7 1.7 1.6 1.5 1.6 1.2 1.6 1.5 1.3 1.3 1.4 Gavage ml Day 10 1.4 1.4 1.4 1.5 1.7 1.7 1.6 1.5 1.6 1.2 1.6 1.5 1.3 1.3 1.4 Gavage ml Day 11 1. 4 1. 4 1. 4 1. 5 1. 7 1. 7 1. 6 1. 5 1. 6 1. 2 1. 6 1. 5 1. 3 1. 3 1. 4 - 312 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 12 Gavage ml D a y 13 Male, V 5 mg/kg/day 655005 1.4 1.4 654907 1.4 1.4 654980 1.4 1.4 654959 1.5 1.5 654961 1.7 1.7 654916 1.7 1.7 654911 1.6 1.6 654917 1.5 1.5 654998 1.6 1.6 654970 1.2 1.2 654926 1.6 1.6 654918 1.5 1.5 654981 1.3 1.3 654969 1.3 1.3 654967 1.4 1.4 Gavage ml D a y 14 1.7 1.7 1.7 1.8 2.0 1.9 1.9 1.8 1.8 1.4 1.8 1.8 1.6 1.5 1.6 Gavage ml Day 15 1.7 1.7 1.7 1.8 2.0 1.9 1.9 1.8 1.8 1.4 1.8 1.8 1.6 1.5 1.6 Gavage ml D a y 16 1.7 1.7 1.7 1.8 2.0 1.9 1.9 1.8 1.8 1.4 1.8 1.8 1.6 1.5 1.6 Gavage ml Day 17 1.7 1.7 1.7 1.8 2.0 1.9 1.9 1.8 1.8 1.4 1.8 1.8 1.6 1.5 1.6 Gavage ml Day 18 1.7 1.7 1.7 1.8 2.0 1.9 1.9 1.8 1.8 1.4 1.8 1.8 1.6 1.5 1.6 Gavage ml Day 19 1.7 1.7 1.7 1.8 2.0 1.9 1.9 1.8 1.8 1.4 1.8 1.8 1.6 1.5 1.6 Gavage ml Day 20 1.7 1.7 1.7 1.8 2.0 1.9 1.9 1.8 1.8 1.4 1.8 1.8 1.6 1.5 1.6 Gavage ml Day 21 2.0 1.9 2.0 2.1 2.3 2.1 2.2 2.0 2.1 1.6 2.1 2.0 1.8 1.7 1.8 Gavage ml D a y 22 2.0 1.9 2.0 2.1 2.3 2.1 2.2 2.0 2.1 1.6 2.1 2.0 1.8 1.7 1.8 Gavage ml D a y 23 2. 0 1. 9 2. 0 2. 1 2. 3 2. 1 2. 2 2. 0 2. 1 1. 6 2. 1 2. 0 1. 8 1. 7 1. 8 - 313 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 24 Gavage ml Day 25 Male, V 5 mg/kg/day 655005 2.0 2.0 654907 1.9 1.9 654980 2.0 2.0 654959 2.1 2.1 654961 2.3 2.3 654916 2.1 2.1 654911 2.2 2.2 654917 2.0 2.0 654998 2.1 2.1 654970 1.6 1.6 654926 2.1 2.1 654918 2.0 2.0 654981 1.8 1.8 654969 1.7 1.7 654967 1.8 1.8 Gavage ml D a y 26 2.0 1.9 2.0 2.1 2.3 2.1 2.2 2.0 2.1 1.6 2.1 2.0 1.8 1.7 1.8 Gavage ml Day 27 2.0 1.9 2.0 2.1 2.3 2.1 2.2 2.0 2.1 1.6 2.1 2.0 1.8 1.7 1.8 Gavage ml Day 28 2.2 2.0 2.2 2.4 2.5 2.2 2.4 2.1 2.3 1.8 2.3 2.2 2.0 1.8 2.0 Gavage ml Day 29 2.2 2.0 2.2 2.4 2.5 2.2 2.4 2.1 2.3 1.8 2.3 2.2 2.0 1.8 2.0 Gavage ml Day 30 2.2 2.0 2.2 2.4 2.5 2.2 2.4 2.1 2.3 1.8 2.3 2.2 2.0 1.8 2.0 Gavage ml Day 31 2.2 2.0 2.2 2.4 2.5 2.2 2.4 2.1 2.3 1.8 2.3 2.2 2.0 1.8 2.0 Gavage ml D a y 32 2.2 2.0 2.2 2.4 2.5 2.2 2.4 2.1 2.3 1.8 2.3 2.2 2.0 1.8 2.0 Gavage ml D a y 33 2.2 2.0 2.2 2.4 2.5 2.2 2.4 2.1 2.3 1.8 2.3 2.2 2.0 1.8 2.0 Gavage ml D a y 34 2.2 2.0 2.2 2.4 2.5 2.2 2.4 2.1 2.3 1.8 2.3 2.2 2.0 1.8 2.0 Gavage ml Day 35 2. 4 2. 2 2. 4 2. 5 2. 7 2. 3 2. 6 2. 3 2. 4 1. 9 2. 5 2. 4 2. 1 2. 0 2. 1 - 314 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 36 Gavage ml D a y 37 Male, V 5 mg/kg/day 655005 2.4 2.4 654907 2.2 2.2 654980 2.4 2.4 654959 2.5 2.5 654961 2.7 2.7 654916 2.3 2.3 654911 2.6 2.6 654917 2.3 2.3 654998 2.4 2.4 654970 1.9 1.9 654926 2.5 2.5 654918 2.4 2.4 654981 2.1 2.1 654969 2.0 2.0 654967 2.1 2.1 Gavage ml D a y 38 2.4 2.2 2.4 2.5 2.7 2.3 2.6 2.3 2.4 1.9 2.5 2.4 2.1 2.0 2.1 Gavage ml Day 39 2.4 2.2 2.4 2.5 2.7 2.3 2.6 2.3 2.4 1.9 2.5 2.4 2.1 2.0 2.1 Gavage ml Day 40 2.4 2.2 2.4 2.5 2.7 2.3 2.6 2.3 2.4 1.9 2.5 2.4 2.1 2.0 2.1 Gavage ml Day 41 2.4 2.2 2.4 2.5 2.7 2.3 2.6 2.3 2.4 1.9 2.5 2.4 2.1 2.0 2.1 Gavage ml D a y 42 2.5 2.3 2.6 2.7 2.8 2.4 2.7 2.5 2.6 1.9 2.6 2.5 2.2 2.1 2.2 Gavage ml D a y 43 2.5 2.3 2.6 2.7 2.8 2.4 2.7 2.5 2.6 1.9 2.6 2.5 2.2 2.1 2.2 Gavage ml D a y 44 2.5 2.3 2.6 2.7 2.8 2.4 2.7 2.5 2.6 1.9 2.6 2.5 2.2 2.1 2.2 Gavage ml Day 45 2.5 2.3 2.6 2.7 2.8 2.4 2.7 2.5 2.6 1.9 2.6 2.5 2.2 2.1 2.2 Gavage ml D a y 46 2.5 2.3 2.6 2.7 2.8 2.4 2.7 2.5 2.6 1.9 2.6 2.5 2.2 2.1 2.2 Gavage ml Day 47 2. 5 2. 3 2. 6 2. 7 2. 8 2. 4 2. 7 2. 5 2. 6 1. 9 2. 6 2. 5 2. 2 2. 1 2. 2 - 315 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 48 Gavage ml Day 49 Male, V 5 mg/kg/day 655005 2.5 2.5 654907 2.3 2.3 654980 2.6 2.7 654959 2.7 2.7 654961 2.8 2.8 654916 2.4 2.5 654911 2.7 2.7 654917 2.5 2.5 654998 2.6 2.6 654970 1.9 2.0 654926 2.6 2.8 654918 2.5 2.6 654981 2.2 2.3 654969 2.1 2.2 654967 2.2 2.3 Gavage ml D a y 50 2.5 2.3 2.7 2.7 2.8 2.5 2.7 2.5 2.6 2.0 2.8 2.6 2.3 2.2 2.3 Gavage ml Day 51 2.5 2.3 2.7 2.7 2.8 2.5 2.7 2.5 2.6 2.0 2.8 2.6 2.3 2.2 2.3 Gavage ml D a y 52 2.5 2.3 2.7 2.7 2.8 2.5 2.7 2.5 2.6 2.0 2.8 2.6 2.3 2.2 2.3 Gavage ml D a y 53 2.5 2.3 2.7 2.7 2.8 2.5 2.7 2.5 2.6 2.0 2.8 2.6 2.3 2.2 2.3 Gavage ml D a y 54 2.5 2.3 2.7 2.7 2.8 2.5 2.7 2.5 2.6 2.0 2.8 2.6 2.3 2.2 2.3 Gavage ml Day 55 2.5 2.3 2.7 2.7 2.8 2.5 2.7 2.5 2.6 2.0 2.8 2.6 2.3 2.2 2.3 Gavage ml D a y 56 2.7 2.5 2.9 2.9 3.0 2.6 2.8 2.7 2.8 2.1 2.9 2.7 2.3 2.3 2.4 Gavage ml Day 57 2.7 2.5 2.9 2.9 3.0 2.6 2.8 2.7 2.8 2.1 2.9 2.7 2.3 2.3 2.4 Gavage ml Day 58 2.7 2.5 2.9 2.9 3.0 2.6 2.8 2.7 2.8 2.1 2.9 2.7 2.3 2.3 2.4 Gavage ml Day 59 2. 7 2. 5 2. 9 2. 9 3. 0 2. 6 2. 8 2. 7 2. 8 2. 1 2. 9 2. 7 2. 3 2. 3 2. 4 - 316 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 60 Gavage ml D a y 61 Male, V 5 mg/kg/day 655005 2.7 2.7 654907 2.5 2.5 654980 2.9 2.9 654959 2.9 2.9 654961 3.0 3.0 654916 2.6 2.6 654911 2.8 2.8 654917 2.7 2.7 654998 2.8 2.8 654970 2.1 2.1 654926 2.9 2.9 654918 2.7 2.7 654981 2.3 2.3 654969 2.3 2.3 654967 2.4 2.4 Gavage ml D a y 62 2.7 2.5 2.9 2.9 3.0 2.6 2.8 2.7 2.8 2.1 2.9 2.7 2.3 2.3 2.4 Gavage ml D a y 63 2.8 2.6 3.0 3.0 3.1 2.6 3.0 2.8 2.8 2.1 2.9 2.8 2.4 2.3 2.5 Gavage ml D a y 64 2.8 2.6 3.0 3.0 3.1 2.6 3.0 2.8 2.8 2.1 2.9 2.8 2.4 2.3 2.5 Gavage ml Day 65 2.8 2.6 3.0 3.0 3.1 2.6 3.0 2.8 2.8 2.1 2.9 2.8 2.4 2.3 2.5 Gavage ml D a y 66 2.8 2.6 3.0 3.0 3.1 2.6 3.0 2.8 2.8 2.1 2.9 2.8 2.4 2.3 2.5 Gavage ml Day 67 2.8 2.6 3.0 3.0 3.1 2.6 3.0 2.8 2.8 2.1 2.9 2.8 2.4 2.3 2.5 Gavage ml Day 68 2.8 2.6 3.0 3.0 3.1 2.6 3.0 2.8 2.8 2.1 2.9 2.8 2.4 2.3 2.5 Gavage ml Day 69 2.8 2.6 3.0 3.0 3.1 2.6 3.0 2.8 2.8 2.1 2.9 2.8 2.4 2.3 2.5 Gavage ml Day 70 2.9 2.6 3.0 3.1 3.2 2.6 3.0 2.9 2.9 2.3 3.0 3.0 2.5 2.4 2.5 Gavage ml Day 71 2. 9 2. 6 3. 0 3. 1 3. 2 2. 6 3. 0 2. 9 2. 9 2. 3 3. 0 3. 0 2. 5 2. 4 2. 5 - 317 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 72 Gavage ml D a y 73 Male, V 5 mg/kg/day 655005 2.9 2.9 654907 2.6 2.6 654980 3.0 3.0 654959 3.1 3.1 654961 3.2 3.2 654916 2.6 2.6 654911 3.0 3.0 654917 2.9 2.9 654998 2.9 2.9 654970 2.3 2.3 654926 3.0 3.0 654918 3.0 3.0 654981 2.5 2.5 654969 2.4 2.4 654967 2.5 2.5 Gavage ml D a y 74 2.9 2.6 3.0 3.1 3.2 2.6 3.0 2.9 2.9 2.3 3.0 3.0 2.5 2.4 2.5 Gavage ml Day 75 2.9 2.6 3.0 3.1 3.2 2.6 3.0 2.9 2.9 2.3 3.0 3.0 2.5 2.4 2.5 Gavage ml D a y 76 2.9 2.6 3.0 3.1 3.2 2.6 3.0 2.9 2.9 2.3 3.0 3.0 2.5 2.4 2.5 Gavage ml Day 77 2.9 2.7 3.2 3.1 3.3 2.6 3.1 3.0 3.0 2.4 3.0 3.0 2.5 2.5 2.6 Gavage ml Day 78 2.9 2.7 3.2 3.1 3.3 2.6 3.1 3.0 3.0 2.4 3.0 3.0 2.5 2.5 2.6 Gavage ml Day 79 2.9 2.7 3.2 3.1 3.3 2.6 3.1 3.0 3.0 2.4 3.0 3.0 2.5 2.5 2.6 Gavage ml Day 80 2.9 2.7 3.2 3.1 3.3 2.6 3.1 3.0 3.0 2.4 3.0 3.0 2.5 2.5 2.6 Gavage ml Day 81 2.9 2.7 3.2 3.1 3.3 2.6 3.1 3.0 3.0 2.4 3.0 3.0 2.5 2.5 2.6 Gavage ml D a y 82 2.9 2.7 3.2 3.1 3.3 2.6 3.1 3.0 3.0 2.4 3.0 3.0 2.5 2.5 2.6 Gavage ml D a y 83 2. 9 2. 7 3. 2 3. 1 3. 3 2. 6 3. 1 3. 0 3. 0 2. 4 3. 0 3. 0 2. 5 2. 5 2. 6 - 318 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL DOSE VOLUMES Gavage ml D a y 84 Gavage ml D a y 85 Male, V 5 mg/kg/day 655005 3.0 3.0 654907 2.7 2.7 654980 3.2 3.2 654959 3.2 3.2 654961 3.3 3.3 654916 2.7 2.7 654911 3.2 3.2 654917 3.0 3.0 654998 3.1 3.1 654970 2.4 2.4 654926 3.1 3.1 654918 3.1 3.1 654981 2.6 2.6 654969 2.5 2.5 654967 2.6 2.6 Gavage ml D a y 86 3.0 2.7 3.2 3.2 3.3 2.7 3.2 3.0 3.1 2.4 3.1 3.1 2.6 2.5 2.6 Gavage ml Day 87 3.0 2.7 3.2 3.2 3.3 2.7 3.2 3.0 3.1 2.4 3.1 3.1 2.6 2.5 2.6 Gavage ml Day 88 3.0 2.7 3.2 3.2 3.3 2.7 3.2 3.0 3.1 2.4 3.1 3.1 2.6 2.5 2.6 Gavage ml Day 89 3.0 2.7 3.2 3.2 3.3 2.7 3.2 3.0 3.1 2.4 3.1 3.1 2.6 2.5 2.6 Gavage ml D a y 90 3.0 2.7 3.2 3.2 3.3 2.7 3.2 3.0 3.1 2.4 3.1 3.1 2.6 2.5 2.6 Gavage ml D a y 91 2.9 2.8 3.3 3.2 3.4 2.8 3.2 3.1 3.0 2.4 3.2 3.1 2.6 2.6 2.6 Gavage ml D a y 92 2. 9 2. 8 3. 3 3. 2 3. 4 2. 8 3. 2 3. 1 3. 0 2. 6 DuPont-9478 - 319 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 0 Gavage ml Day 1 Male, VII: 25 mg/kg/day 655001 1.2 1.2 654975 1.1 1.1 654922 1.1 1.1 654940 1.2 1.2 654930 1.2 1.2 654958 1.2 1.2 654952 1.4 1.4 654923 1.3 1.3 654989 1.2 1.2 655006 1.3 1.3 654920 1.1 1.1 654912 1.1 1.1 654934 1.2 1.2 654964 1.3 1.3 654933 1.2 1.2 Gavage ml Day 2 1.2 1.1 1.1 1.2 1.2 1.2 1.4 1.3 1.2 1.3 1.1 1.1 1.2 1.3 1.2 Gavage ml Day 3 1.2 1.1 1.1 1.2 1.2 1.2 1.4 1.3 1.2 1.3 1.1 1.1 1.2 1.3 1.2 Gavage ml Day 4 1.2 1.1 1.1 1.2 1.2 1.2 1.4 1.3 1.2 1.3 1.1 1.1 1.2 1.3 1.2 Gavage ml Day 5 1.2 1.1 1.1 1.2 1.2 1.2 1.4 1.3 1.2 1.3 1.1 1.1 1.2 1.3 1.2 Gavage ml Day 6 1.2 1.1 1.1 1.2 1.2 1.2 1.4 1.3 1.2 1.3 1.1 1.1 1.2 1.3 1.2 Gavage ml Day 7 1.5 1.4 1.4 1.5 1.5 1.5 1.7 1.5 1.5 1.6 1.4 1.3 1.5 1.5 1.5 Gavage ml Day 8 1.5 1.4 1.4 1.5 1.5 1.5 1.7 1.5 1.5 1.6 1.4 1.3 1.5 1.5 1.5 Gavage ml Day 9 1.5 1.4 1.4 1.5 1.5 1.5 1.7 1.5 1.5 1.6 1.4 1.3 1.5 1.5 1.5 Gavage ml Day 10 1.5 1.4 1.4 1.5 1.5 1.5 1.7 1.5 1.5 1.6 1.4 1.3 1.5 1.5 1.5 Gavage ml Day 11 1. 5 1. 4 1. 4 1. 5 1. 5 1. 5 1. 7 1. 5 1. 5 1. 6 1. 4 1. 3 1. 5 1. 5 1. 5 - 320 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 12 Gavage ml D a y 13 Male, VII: 25 mg/kg/day 655001 1.5 1.5 654975 1.4 1.4 654922 1.4 1.4 654940 1.5 1.5 654930 1.5 1.5 654958 1.5 1.5 654952 1.7 1.7 654923 1.5 1.5 654989 1.5 1.5 655006 1.6 1.6 654920 1.4 1.4 654912 1.3 1.3 654934 1.5 1.5 654964 1.5 1.5 654933 1.5 1.5 Gavage ml D a y 14 1.7 1.6 1.6 1.7 1.8 1.6 2.0 1.8 1.8 1.8 1.6 1.5 1.7 1.8 1.8 Gavage ml Day 15 1.7 1.6 1.6 1.7 1.8 1.6 2.0 1.8 1.8 1.8 1.6 1.5 1.7 1.8 1.8 Gavage ml D a y 16 1.7 1.6 1.6 1.7 1.8 1.6 2.0 1.8 1.8 1.8 1.6 1.5 1.7 1.8 1.8 Gavage ml Day 17 1.7 1.6 1.6 1.7 1.8 1.6 2.0 1.8 1.8 1.8 1.6 1.5 1.7 1.8 1.8 Gavage ml Day 18 1.7 1.6 1.6 1.7 1.8 1.6 2.0 1.8 1.8 1.8 1.6 1.5 1.7 1.8 1.8 Gavage ml Day 19 1.7 1.6 1.6 1.7 1.8 1.6 2.0 1.8 1.8 1.8 1.6 1.5 1.7 1.8 1.8 Gavage ml Day 20 1.7 1.6 1.6 1.7 1.8 1.6 2.0 1.8 1.8 1.8 1.6 1.5 1.7 1.8 1.8 Gavage ml Day 21 2.1 1.9 1.8 1.9 2.1 1.8 2.2 2.1 2.0 2.0 1.9 1.7 1.9 2.0 2.1 Gavage ml D a y 22 2.1 1.9 1.8 1.9 2.1 1.8 2.2 2.1 2.0 2.0 1.9 1.7 1.9 2.0 2.1 Gavage ml D a y 23 2. 1 1. 9 1. 8 1. 9 2. 1 1. 8 2. 2 2. 1 2. 0 2. 0 1. 9 1. 7 1. 9 2. 0 2. 1 - 321 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 24 Gavage ml Day 25 Male, VII: 25 mg/kg/day 655001 2.1 2.1 654975 1.9 1.9 654922 1.8 1.8 654940 1.9 1.9 654930 2.1 2.1 654958 1.8 1.8 654952 2.2 2.2 654923 2.1 2.1 654989 2.0 2.0 655006 2.0 2.0 654920 1.9 1.9 654912 1.7 1.7 654934 1.9 1.9 654964 2.0 2.0 654933 2.1 2.1 Gavage ml D a y 26 2.1 1.9 1.8 1.9 2.1 1.8 2.2 2.1 2.0 2.0 1.9 1.7 1.9 2.0 2.1 Gavage ml Day 27 2.1 1.9 1.8 1.9 2.1 1.8 2.2 2.1 2.0 2.0 1.9 1.7 1.9 2.0 2.1 Gavage ml Day 28 2.4 2.1 2.0 2.1 2.3 1.9 2.3 2.2 2.2 2.2 2.1 1.8 2.0 2.2 2.3 Gavage ml Day 29 2.4 2.1 2.0 2.1 2.3 1.9 2.3 2.2 2.2 2.2 2.1 1.8 2.0 2.2 2.3 Gavage ml Day 30 2.4 2.1 2.0 2.1 2.3 1.9 2.3 2.2 2.2 2.2 2.1 1.8 2.0 2.2 2.3 Gavage ml Day 31 2.4 2.1 2.0 2.1 2.3 1.9 2.3 2.2 2.2 2.2 2.1 1.8 2.0 2.2 2.3 Gavage ml D a y 32 2.4 2.1 2.0 2.1 2.3 1.9 2.3 2.2 2.2 2.2 2.1 1.8 2.0 2.2 2.3 Gavage ml D a y 33 2.4 2.1 2.0 2.1 2.3 1.9 2.3 2.2 2.2 2.2 2.1 1.8 2.0 2.2 2.3 Gavage ml D a y 34 2.4 2.1 2.0 2.1 2.3 1.9 2.3 2.2 2.2 2.2 2.1 1.8 2.0 2.2 2.3 Gavage ml Day 35 2. 6 2. 2 2. 2 2. 2 2. 5 2. 0 2. 5 2. 4 2. 3 2. 3 2. 2 2. 0 2. 2 2. 4 2. 5 - 322 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 36 Gavage ml D a y 37 Male, VII: 25 mg/kg/day 655001 2.6 2.6 654975 2.2 2.2 654922 2.2 2.2 654940 2.2 2.2 654930 2.5 2.5 654958 2.0 2.0 654952 2.5 2.5 654923 2.4 2.4 654989 2.3 2.3 655006 2.3 2.3 654920 2.2 2.2 654912 2.0 2.0 654934 2.2 2.2 654964 2.4 2.4 654933 2.5 2.5 Gavage ml D a y 38 2.6 2.2 2.2 2.2 2.5 2.0 2.5 2.4 2.3 2.3 2.2 2.0 2.2 2.4 2.5 Gavage ml Day 39 2.6 2.2 2.2 2.2 2.5 2.0 2.5 2.4 2.3 2.3 2.2 2.0 2.2 2.4 2.5 Gavage ml Day 40 2.6 2.2 2.2 2.2 2.5 2.0 2.5 2.4 2.3 2.3 2.2 2.0 2.2 2.4 2.5 Gavage ml Day 41 2.6 2.2 2.2 2.2 2.5 2.0 2.5 2.4 2.3 2.3 2.2 2.0 2.2 2.4 2.5 Gavage ml D a y 42 2.7 2.3 2.3 2.3 2.7 2.2 2.6 2.5 2.5 2.5 2.4 2.1 2.3 2.6 2.7 Gavage ml D a y 43 2.7 2.3 2.3 2.3 2.7 2.2 2.6 2.5 2.5 2.5 2.4 2.1 2.3 2.6 2.7 Gavage ml D a y 44 2.7 2.3 2.3 2.3 2.7 2.2 2.6 2.5 2.5 2.5 2.4 2.1 2.3 2.6 2.7 Gavage ml Day 45 2.7 2.3 2.3 2.3 2.7 2.2 2.6 2.5 2.5 2.5 2.4 2.1 2.3 2.6 2.7 Gavage ml D a y 46 2.7 2.3 2.3 2.3 2.7 2.2 2.6 2.5 2.5 2.5 2.4 2.1 2.3 2.6 2.7 Gavage ml Day 47 2. 7 2. 3 2. 3 2. 3 2. 7 2. 2 2. 6 2. 5 2. 5 2. 5 2. 4 2. 1 2. 3 2. 6 2. 7 - 323 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 48 Gavage ml Day 49 Male, VII: 25 mg/kg/day 655001 2.7 2.8 654975 2.3 2.4 654922 2.3 2.4 654940 2.3 2.4 654930 2.7 2.7 654958 2.2 2.2 654952 2.6 2.6 654923 2.5 2.5 654989 2.5 2.5 655006 2.5 2.5 654920 2.4 2.5 654912 2.1 2.2 654934 2.3 2.4 654964 2.6 2.7 654933 2.7 2.9 Gavage ml D a y 50 2.8 2.4 2.4 2.4 2.7 2.2 2.6 2.5 2.5 2.5 2.5 2.2 2.4 2.7 2.9 Gavage ml Day 51 2.8 2.4 2.4 2.4 2.7 2.2 2.6 2.5 2.5 2.5 2.5 2.2 2.4 2.7 2.9 Gavage ml D a y 52 2.8 2.4 2.4 2.4 2.7 2.2 2.6 2.5 2.5 2.5 2.5 2.2 2.4 2.7 2.9 Gavage ml D a y 53 2.8 2.4 2.4 2.4 2.7 2.2 2.6 2.5 2.5 2.5 2.5 2.2 2.4 2.7 2.9 Gavage ml D a y 54 2.8 2.4 2.4 2.4 2.7 2.2 2.6 2.5 2.5 2.5 2.5 2.2 2.4 2.7 2.9 Gavage ml Day 55 2.8 2.4 2.4 2.4 2.7 2.2 2.6 2.5 2.5 2.5 2.5 2.2 2.4 2.7 2.9 Gavage ml D a y 56 2.9 2.5 2.6 2.5 2.8 2.3 2.8 2.6 2.7 2.6 2.6 2.3 2.5 2.8 3.1 Gavage ml Day 57 2.9 2.5 2.6 2.5 2.8 2.3 2.8 2.6 2.7 2.6 2.6 2.3 2.5 2.8 3.1 Gavage ml Day 58 2.9 2.5 2.6 2.5 2.8 2.3 2.8 2.6 2.7 2.6 2.6 2.3 2.5 2.8 3.1 Gavage ml Day 59 2. 9 2. 5 2. 6 2. 5 2. 8 2. 3 2. 8 2. 6 2. 7 2. 6 2. 6 2. 3 2. 5 2. 8 3. 1 - 324 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 60 Gavage ml D a y 61 Male, VII: 25 mg/kg/day 655001 2.9 2.9 654975 2.5 2.5 654922 2.6 2.6 654940 2.5 2.5 654930 2.8 2.8 654958 2.3 2.3 654952 2.8 2.8 654923 2.6 2.6 654989 2.7 2.7 655006 2.6 2.6 654920 2.6 2.6 654912 2.3 2.3 654934 2.5 2.5 654964 2.8 2.8 654933 3.1 3.1 Gavage ml D a y 62 2.9 2.5 2.6 2.5 2.8 2.3 2.8 2.6 2.7 2.6 2.6 2.3 2.5 2.8 3.1 Gavage ml D a y 63 3.1 2.7 2.7 2.6 2.9 2.4 2.9 2.7 2.8 2.7 2.7 2.4 2.6 2.9 3.2 Gavage ml D a y 64 3.1 2.7 2.7 2.6 2.9 2.4 2.9 2.7 2.8 2.7 2.7 2.4 2.6 2.9 3.2 Gavage ml Day 65 3.1 2.7 2.7 2.6 2.9 2.4 2.9 2.7 2.8 2.7 2.7 2.4 2.6 2.9 3.2 Gavage ml D a y 66 3.1 2.7 2.7 2.6 2.9 2.4 2.9 2.7 2.8 2.7 2.7 2.4 2.6 2.9 3.2 Gavage ml Day 67 3.1 2.7 2.7 2.6 2.9 2.4 2.9 2.7 2.8 2.7 2.7 2.4 2.6 2.9 3.2 Gavage ml Day 68 3.1 2.7 2.7 2.6 2.9 2.4 2.9 2.7 2.8 2.7 2.7 2.4 2.6 2.9 3.2 Gavage ml Day 69 3.1 2.7 2.7 2.6 2.9 2.4 2.9 2.7 2.8 2.7 2.7 2.4 2.6 2.9 3.2 Gavage ml Day 70 3.2 2.7 2.8 2.6 3.0 2.4 2.9 2.7 2.8 2.7 2.7 2.5 2.6 3.0 3.3 Gavage ml Day 71 3. 2 2. 7 2. 8 2. 6 3. 0 2. 4 2. 9 2. 7 2. 8 2. 7 2. 7 2. 5 2. 6 3. 0 3. 3 - 325 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 72 Gavage ml D a y 73 Male, VII: 25 mg/kg/day 655001 1.2 3.2 654975 2.7 2.7 654922 2.8 2.8 654940 2.6 2.6 654930 3.0 3.0 654958 2.4 2.4 654952 2.9 2.9 654923 2.7 2.7 654989 2.8 2.8 655006 2.7 2.7 654920 2.7 2.7 654912 2.5 2.5 654934 2.6 2.6 654964 3.0 3.0 654933 3.3 3.3 Gavage ml D a y 74 3.2 2.7 2.8 2.6 3.0 2.4 2.9 2.7 2.8 2.7 2.7 2.5 2.6 3.0 3.3 Gavage ml Day 75 3.2 2.7 2.8 2.6 3.0 2.4 2.9 2.7 2.8 2.7 2.7 2.5 2.6 3.0 3.3 Gavage ml D a y 76 3.2 2.7 2.8 2.6 3.0 2.4 2.9 2.7 2.8 2.7 2.7 2.5 2.6 3.0 3.3 Gavage ml Day 77 3.2 2.8 2.9 2.7 3.0 2.4 3.0 2.7 2.9 2.8 2.8 2.6 2.7 3.0 3.3 Gavage ml Day 78 3.2 2.8 2.9 2.7 3.0 2.4 3.0 2.7 2.9 2.8 2.8 2.6 2.7 3.0 3.3 Gavage ml Day 79 3.2 2.8 2.9 2.7 3.0 2.4 3.0 2.7 2.9 2.8 2.8 2.6 2.7 3.0 3.3 Gavage ml Day 80 3.2 2.8 2.9 2.7 3.0 2.4 3.0 2.7 2.9 2.8 2.8 2.6 2.7 3.0 3.3 Gavage ml Day 81 3.2 2.8 2.9 2.7 3.0 2.4 3.0 2.7 2.9 2.8 2.8 2.6 2.7 3.0 3.3 Gavage ml D a y 82 3.2 2.8 2.9 2.7 3.0 2.4 3.0 2.7 2.9 2.8 2.8 2.6 2.7 3.0 3.3 Gavage ml D a y 83 3. 2 2. 8 2. 9 2. 7 3. 0 2. 4 3. 0 2. 7 2. 9 2. 8 2. 8 2. 6 2. 7 3. 0 3. 3 - 326 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL DOSE VOLUMES Gavage ml D a y 84 Gavage ml D a y 85 Male, VII: 25 mg/kg/day 655001 3.2 3.2 654975 2.8 2.8 654922 2.9 2.9 654940 2.7 2.7 654930 3.0 3.0 654958 2.5 2.5 654952 3.1 3.1 654923 2.8 2.8 654989 3.0 3.0 655006 2.9 2.9 654920 2.9 2.9 654912 2.7 2.7 654934 2.7 2.7 654964 3.1 3.1 654933 3.4 3.4 Gavage ml D a y 86 3.2 2.8 2.9 2.7 3.0 2.5 3.1 2.8 3.0 2.9 2.9 2.7 2.7 3.1 3.4 Gavage ml Day 87 3.2 2.8 2.9 2.7 3.0 2.5 3.1 2.8 3.0 2.9 2.9 2.7 2.7 3.1 3.4 Gavage ml Day 88 3.2 2.8 2.9 2.7 3.0 2.5 3.1 2.8 3.0 2.9 2.9 2.7 2.7 3.1 3.4 Gavage ml Day 89 3.2 2.8 2.9 2.7 3.0 2.5 3.1 2.8 3.0 2.9 2.9 2.7 2.7 3.1 3.4 Gavage ml D a y 90 3.2 2.8 2.9 2.7 3.0 2.5 3.1 2.8 3.0 2.9 2.9 2.7 2.7 3.1 3.4 Gavage ml D a y 91 3.3 2.9 2.9 2.8 3.1 2.5 3.1 2.8 3.1 2.9 2.9 2.7 2.8 3.1 3.4 Gavage ml D a y 92 3. 3 2. 9 2. 9 2. 8 3. 1 2. 5 3. 1 2. 8 3. 1 2. 9 DuPont-9478 - 327 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 0 Gavage ml Day 1 Male, IX 125 mg/kg/day 654983 1.2 1.2 654965 1.1 1.1 654979 1.1 1.1 654986 1.2 1.2 655003 1.2 1.2 654921 1.3 1.3 654996 1.4 1.4 654951 1.2 1.2 654955 1.2 1.2 654914 1.2 1.2 654937 1.2 1.2 654962 1.3 1.3 654982 1.1 1.1 654931 1.2 1.2 654906 1.2 1.2 654985 1.0 1.0 654978 1.0 1.0 654974 1.1 1.1 654990 1.2 1.2 654976 1.1 1.1 654957 1.3 1.3 654973 1.3 1.3 654977 1.0 1.0 654942 1.2 1.2 654991 1.2 1.2 Gavage ml Day 2 1.2 1.1 1.1 1.2 1.2 1.3 1.4 1.2 1.2 1.2 1.2 1.3 1.1 1.2 1.2 1.0 1.0 1.1 1.2 1.1 1.3 1.3 1.0 1.2 1.2 Gavage ml Day 3 1.2 1.1 1.1 1.2 1.2 1.3 1.4 1.2 1.2 1.2 1.2 1.3 1.1 1.2 1.2 1.0 1.0 1.1 1.2 1.1 1.3 1.3 1.0 1.2 1.2 Gavage ml Day 4 1.2 1.1 1.1 1.2 1.2 1.3 1.4 1.2 1.2 1.2 1.2 1.3 1.1 1.2 1.2 1.0 1.0 1.1 1.2 1.1 1.3 1.3 1.0 1.2 1.2 Gavage ml Day 5 1.2 1.1 1.1 1.2 1.2 1.3 1.4 1.2 1.2 1.2 1.2 1.3 1.1 1.2 1.2 1.0 1.0 1.1 1.2 1.1 1.3 1.3 1.0 1.2 1.2 Gavage ml Day 6 1.2 1.1 1.1 1.2 1.2 1.3 1.4 1.2 1.2 1.2 1.2 1.3 1.1 1.2 1.2 1.0 1.0 1.1 1.2 1.1 1.3 1.3 1.0 1.2 1.2 Gavage ml Day 7 1.5 1.3 1.4 1.5 1.4 1.6 1.6 1.5 1.6 1.5 1.5 1.5 1.4 1.5 1.6 1.2 1.2 1.4 1.5 1.3 1.5 1.6 1.2 1.4 1.6 Gavage ml Day 8 1.5 1.3 1.4 1.5 1.4 1.6 1.6 1.5 1.6 1.5 1.5 1.5 1.4 1.5 1.6 1.2 1.2 1.4 1.5 1.3 1.5 1.6 1.2 1.4 1.6 Gavage ml Day 9 1.5 1.3 1.4 1.5 1.4 1.6 1.6 1.5 1.6 1.5 1.5 1.5 1.4 1.5 1.6 1.2 1.2 1.4 1.5 1.3 1.5 1.6 1.2 1.4 1.6 Gavage ml Day 10 1.5 1.3 1.4 1.5 1.4 1.6 1.6 1.5 1.6 1.5 1.5 1.5 1.4 1.5 1.6 1.2 1.2 1.4 1.5 1.3 1.5 1.6 1.2 1.4 1.6 Gavage ml Day 11 1. 5 1. 3 1. 4 1. 5 1. 4 1. 6 1. 6 1. 5 1. 6 1. 5 1. 5 1. 5 1. 4 1. 5 1. 6 1. 2 1. 2 1. 4 1. 5 1. 3 1. 5 1. 6 1. 2 1. 4 1. 6 - 328 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 12 Gavage ml D a y 13 Male, IX 125 mg/kg/day 654983 1.5 1.5 654965 1.3 1.3 654979 1.4 1.4 654986 1.5 1.5 655003 1.4 1.4 654921 1.6 1.6 654996 1.6 1.6 654951 1.5 1.5 654955 1.6 1.6 654914 1.5 1.5 654937 1.5 1.5 654962 1.5 1.5 654982 1.4 1.4 654931 1.5 1.5 654906 1.6 1.6 654985 1.2 1.2 654978 1.2 1.2 654974 1.4 1.4 654990 1.5 1.5 654976 1.3 1.3 654957 1.5 1.5 654973 1.6 1.6 654977 1.2 1.2 654942 1.4 1.4 654991 1.6 1.6 Gavage ml D a y 14 1.8 1.6 1.6 1.7 1.7 1.9 1.9 1.7 1.9 1.7 1.8 1.8 1.7 1.8 1.9 1.4 1.5 1.7 1.7 1.6 1.8 1.8 1.4 1.7 1.9 Gavage ml Day 15 1.8 1.6 1.6 1.7 1.7 1.9 1.9 1.7 1.9 1.7 1.8 1.8 1.7 1.8 1.9 1.4 1.5 1.7 1.7 1.6 1.8 1.8 1.4 1.7 1.9 Gavage ml D a y 16 1.8 1.6 1.6 1.7 1.7 1.9 1.9 1.7 1.9 1.7 1.8 1.8 1.7 1.8 1.9 1.4 1.5 1.7 1.7 1.6 1.8 1.8 1.4 1.7 1.9 Gavage ml Day 17 1.8 1.6 1.6 1.7 1.7 1.9 1.9 1.7 1.9 1.7 1.8 1.8 1.7 1.8 1.9 1.4 1.5 1.7 1.7 1.6 1.8 1.8 1.4 1.7 1.9 Gavage ml Day 18 1.8 1.6 1.6 1.7 1.7 1.9 1.9 1.7 1.9 1.7 1.8 1.8 1.7 1.8 1.9 1.4 1.5 1.7 1.7 1.6 1.8 1.8 1.4 1.7 1.9 Gavage ml Day 19 1.8 1.6 1.6 1.7 1.7 1.9 1.9 1.7 1.9 1.7 1.8 1.8 1.7 1.8 1.9 1.4 1.5 1.7 1.7 1.6 1.8 1.8 1.4 1.7 1.9 Gavage ml Day 20 1.8 1.6 1.6 1.7 1.7 1.9 1.9 1.7 1.9 1.7 1.8 1.8 1.7 1.8 1.9 1.4 1.5 1.7 1.7 1.6 1.8 1.8 1.4 1.7 1.9 Gavage ml Day 21 2.0 1.8 1.8 2.0 1.9 2.1 2.0 2.0 2.1 1.9 2.0 2.0 1.9 2.1 2.2 1.6 1.6 1.9 1.9 1.9 2.0 2.1 1.6 1.9 2.1 Gavage ml D a y 22 2.0 1.8 1.8 2.0 1.9 2.1 2.0 2.0 2.1 1.9 2.0 2.0 1.9 2.1 2.2 1.6 1.6 1.9 1.9 1.9 2.0 2.1 1.6 1.9 2.1 Gavage ml D a y 23 2. 0 1. 8 1. 8 2. 0 1. 9 2. 1 2. 0 2. 0 2. 1 1. 9 2. 0 2. 0 1. 9 2. 1 2. 2 1. 6 1. 6 1. 9 1. 9 1. 9 2. 0 2. 1 1. 6 1. 9 2. 1 - 329 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 24 Gavage ml Day 25 Male, IX 125 mg/kg/day 654983 2.0 2.0 654965 1.8 1.8 654979 1.8 1.8 654986 2.0 2.0 655003 1.9 1.9 654921 2.1 2.1 654996 2.0 2.0 654951 2.0 2.0 654955 2.1 2.1 654914 1.9 1.9 654937 2.0 2.0 654962 2.0 2.0 654982 1.9 1.9 654931 2.1 2.1 654906 2.2 2.2 654985 1.6 1.6 654978 1.6 1.6 654974 1.9 1.9 654990 1.9 1.9 654976 1.9 1.9 654957 2.0 2.0 654973 2.1 2.1 654977 1.6 1.6 654942 1.9 1.9 654991 2.1 2.1 Gavage ml D a y 26 2.0 1.8 1.8 2.0 1.9 2.1 2.0 2.0 2.1 1.9 2.0 2.0 1.9 2.1 2.2 1.6 1.6 1.9 1.9 1.9 2.0 2.1 1.6 1.9 2.1 Gavage ml Day 27 2.0 1.8 1.8 2.0 1.9 2.1 2.0 2.0 2.1 1.9 2.0 2.0 1.9 2.1 2.2 1.6 1.6 1.9 1.9 1.9 2.0 2.1 1.6 1.9 2.1 Gavage ml Day 28 2.2 2.0 2.0 2.2 2.0 2.3 2.1 2.2 2.3 2.1 2.2 2.2 2.1 2.3 2.4 1.7 1.8 2.1 2.1 2.0 2.2 2.2 1.7 2.0 2.4 Gavage ml Day 29 2.2 2.0 2.0 2.2 2.0 2.3 2.1 2.2 2.3 2.1 2.2 2.2 2.1 2.3 2.4 1.7 1.8 2.1 2.1 2.0 2.2 2.2 1.7 2.0 2.4 Gavage ml Day 30 2.2 2.0 2.0 2.2 2.0 2.3 2.1 2.2 2.3 2.1 2.2 2.2 2.1 2.3 2.4 1.7 1.8 2.1 2.1 2.0 2.2 2.2 1.7 2.0 2.4 Gavage ml Day 31 2.2 2.0 2.0 2.2 2.0 2.3 2.1 2.2 2.3 2.1 2.2 2.2 2.1 2.3 2.4 1.7 1.8 2.1 2.1 2.0 2.2 2.2 1.7 2.0 2.4 Gavage ml D a y 32 2.2 2.0 2.0 2.2 2.0 2.3 2.1 2.2 2.3 2.1 2.2 2.2 2.1 2.3 2.4 1.7 1.8 2.1 2.1 2.0 2.2 2.2 1.7 2.0 2.4 Gavage ml D a y 33 2.2 2.0 2.0 2.2 2.0 2.3 2.1 2.2 2.3 2.1 2.2 2.2 2.1 2.3 2.4 1.7 1.8 2.1 2.1 2.0 2.2 2.2 1.7 2.0 2.4 Gavage ml D a y 34 2.2 2.0 2.0 2.2 2.0 2.3 2.1 2.2 2.3 2.1 2.2 2.2 2.1 2.3 2.4 1.7 1.8 2.1 2.1 2.0 2.2 2.2 1.7 2.0 2.4 Gavage ml Day 35 2. 4 2. 1 2. 1 2. 4 2. 1 2. 4 2. 3 2. 3 2. 5 2. 2 2. 4 2. 4 2. 3 2. 5 2. 6 1. 8 1. 9 2. 2 2. 2 2. 1 2. 2 2. 3 1. 8 2. 1 2. 5 - 330 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 36 Gavage ml D a y 37 Male, IX 125 mg/kg/day 654983 2.4 2.4 654965 2.1 2.1 654979 2.1 2.1 654986 2.4 2.4 655003 2.1 2.1 654921 2.4 2.4 654996 2.3 2.3 654951 2.3 2.3 654955 2.5 2.5 654914 2.2 2.2 654937 2.4 2.4 654962 2.4 2.4 654982 2.3 2.3 654931 2.5 2.5 654906 2.6 2.6 654985 1.8 1.8 654978 1.9 1.9 654974 2.2 2.2 654990 2.2 2.2 654976 2.1 2.1 654957 2.2 2.2 654973 2.3 2.3 654977 1.8 1.8 654942 2.1 2.1 654991 2.5 2.5 Gavage ml D a y 38 2.4 2.1 2.1 2.4 2.1 2.4 2.3 2.3 2.5 2.2 2.4 2.4 2.3 2.5 2.6 1.8 1.9 2.2 2.2 2.1 2.2 2.3 1.8 2.1 2.5 Gavage ml Day 39 2.4 2.1 2.1 2.4 2.1 2.4 2.3 2.3 2.5 2.2 2.4 2.4 2.3 2.5 2.6 1.8 1.9 2.2 2.2 2.1 2.2 2.3 1.8 2.1 2.5 Gavage ml Day 40 2.4 2.1 2.1 2.4 2.1 2.4 2.3 2.3 2.5 2.2 2.4 2.4 2.3 2.5 2.6 1.8 1.9 2.2 2.2 2.1 2.2 2.3 1.8 2.1 2.5 Gavage ml Day 41 2.4 2.1 2.1 2.4 2.1 2.4 2.3 2.3 2.5 2.2 2.4 2.4 2.3 2.5 2.6 1.8 1.9 2.2 2.2 2.1 2.2 2.3 1.8 2.1 2.5 Gavage ml D a y 42 2.5 2.2 2.2 2.6 2.2 2.5 2.3 2.4 2.6 2.4 2.5 2.4 2.4 2.6 2.8 1.9 2.0 2.4 2.3 2.3 2.3 2.4 1.9 2.3 2.7 Gavage ml D a y 43 2.5 2.2 2.2 2.6 2.2 2.5 2.3 2.4 2.6 2.4 2.5 2.4 2.4 2.6 2.8 1.9 2.0 2.4 2.3 2.3 2.3 2.4 1.9 2.3 2.7 Gavage ml D a y 44 2.5 2.2 2.2 2.6 2.2 2.5 2.3 2.4 2.6 2.4 2.5 2.4 2.4 2.6 2.8 1.9 2.0 2.4 2.3 2.3 2.3 2.4 1.9 2.3 2.7 Gavage ml Day 45 2.5 2.2 2.2 2.6 2.2 2.5 2.3 2.4 2.6 2.4 2.5 2.4 2.4 2.6 2.8 1.9 2.0 2.4 2.3 2.3 2.3 2.4 1.9 2.3 2.7 Gavage ml D a y 46 2.5 2.2 2.2 2.6 2.2 2.5 2.3 2.4 2.6 2.4 2.5 2.4 2.4 2.6 2.8 1.9 2.0 2.4 2.3 2.3 2.3 2.4 1.9 2.3 2.7 Gavage ml Day 47 2. 5 2. 2 2. 2 2. 6 2. 2 2. 5 2. 3 2. 4 2. 6 2. 4 2. 5 2. 4 2. 4 2. 6 2. 8 1. 9 2. 0 2. 4 2. 3 2. 3 2. 3 2. 4 1. 9 2. 3 2. 7 - 331 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 48 Gavage ml Day 49 Male, IX 125 mg/kg/day 654983 2.5 2.6 654965 2.2 2.2 654979 2.2 2.3 654986 2.6 2.6 655003 2.2 2.3 654921 2.5 2.5 654996 2.3 2.3 654951 2.4 2.5 654955 2.6 2.6 654914 2.4 2.4 654937 2.5 2.6 654962 2.4 2.5 654982 2.4 2.5 654931 2.6 2.7 654906 2.8 2.9 654985 1.9 2.0 654978 2.0 2.1 654974 2.4 2.4 654990 2.3 2.4 654976 2.3 2.3 654957 2.3 2.5 654973 2.4 2.5 654977 1.9 2.0 654942 2.3 2.3 654991 2.7 2.8 Gavage ml D a y 50 2.6 2.2 2.3 2.6 2.3 2.5 2.3 2.5 2.6 2.4 2.6 2.5 2.5 2.7 2.9 2.0 2.1 2.4 2.4 2.3 2.5 2.5 2.0 2.3 2.8 Gavage ml Day 51 2.6 2.2 2.3 2.6 2.3 2.5 2.3 2.5 2.6 2.4 2.6 2.5 2.5 2.7 2.9 2.0 2.1 2.4 2.4 2.3 2.5 2.5 2.0 2.3 2.8 Gavage ml D a y 52 2.6 2.2 2.3 2.6 2.3 2.5 2.3 2.5 2.6 2.4 2.6 2.5 2.5 2.7 2.9 2.0 2.1 2.4 2.4 2.3 2.5 2.5 2.0 2.3 2.8 Gavage ml D a y 53 2.6 2.2 2.3 2.6 2.3 2.5 2.3 2.5 2.6 2.4 2.6 2.5 2.5 2.7 2.9 2.0 2.1 2.4 2.4 2.3 2.5 2.5 2.0 2.3 2.8 Gavage ml D a y 54 2.6 2.2 2.3 2.6 2.3 2.5 2.3 2.5 2.6 2.4 2.6 2.5 2.5 2.7 2.9 2.0 2.1 2.4 2.4 2.3 2.5 2.5 2.0 2.3 2.8 Gavage ml Day 55 2.6 2.2 2.3 2.6 2.3 2.5 2.3 2.5 2.6 2.4 2.6 2.5 2.5 2.7 2.9 2.0 2.1 2.4 2.4 2.3 2.5 2.5 2.0 2.3 2.8 Gavage ml D a y 56 2.7 2.2 2.4 2.8 2.4 2.7 2.4 2.6 2.7 2.5 2.7 2.7 2.6 2.8 3.0 2.1 2.2 2.5 2.5 2.4 2.5 2.6 2.1 2.4 3.0 Gavage ml Day 57 2.7 2.2 2.4 2.8 2.4 2.7 2.4 2.6 2.7 2.5 2.7 2.7 2.6 2.8 3.0 2.1 2.2 2.5 2.5 2.4 2.5 2.6 2.1 2.4 3.0 Gavage ml Day 58 2.7 2.2 2.4 2.8 2.4 2.7 2.4 2.6 2.7 2.5 2.7 2.7 2.6 2.8 3.0 2.1 2.2 2.5 2.5 2.4 2.5 2.6 2.1 2.4 3.0 Gavage ml Day 59 2. 7 2. 2 2. 4 2. 8 2. 4 2. 7 2. 4 2. 6 2. 7 2. 5 2. 7 2. 7 2. 6 2. 8 3. 0 2. 1 2. 2 2. 5 2. 5 2. 4 2. 5 2. 6 2. 1 2. 4 3. 0 - 332 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 60 Gavage ml D a y 61 Male, IX 125 mg/kg/day 654983 2.7 2.7 654965 2.2 2.2 654979 2.4 2.4 654986 2.8 2.8 655003 2.4 2.4 654921 2.7 2.7 654996 2.4 2.4 654951 2.6 2.6 654955 2.7 2.7 654914 2.5 2.5 654937 2.7 2.7 654962 2.7 2.7 654982 2.6 2.6 654931 2.8 2.8 654906 3.0 3.0 654985 2.1 2.1 654978 2.2 2.2 654974 2.5 2.5 654990 2.5 2.5 654976 2.4 2.4 654957 2.5 2.5 654973 2.6 2.6 654977 2.1 2.1 654942 2.4 2.4 654991 3.0 3.0 Gavage ml D a y 62 2.7 2.2 2.4 2.8 2.4 2.7 2.4 2.6 2.7 2.5 2.7 2.7 2.6 2.8 3.0 2.1 2.2 2.5 2.5 2.4 2.5 2.6 2.1 2.4 3.0 Gavage ml D a y 63 2.8 2.3 2.5 2.7 2.4 2.7 2.3 2.7 2.8 2.6 2.8 2.7 2.6 2.8 3.1 2.1 2.2 2.6 2.6 2.2 2.6 2.6 2.1 2.5 3.0 Gavage ml D a y 64 2.8 2.3 2.5 2.7 2.4 2.7 2.3 2.7 2.8 2.6 2.8 2.7 2.6 2.8 3.1 2.1 2.2 2.6 2.6 2.2 2.6 2.6 2.1 2.5 3.0 Gavage ml Day 65 2.8 2.3 2.5 2.7 2.4 2.7 2.3 2.7 2.8 2.6 2.8 2.7 2.6 2.8 3.1 2.1 2.2 2.6 2.6 2.2 2.6 2.6 2.1 2.5 3.0 Gavage ml D a y 66 2.8 2.3 2.5 2.7 2.4 2.7 2.3 2.7 2.8 2.6 2.8 2.7 2.6 2.8 3.1 2.1 2.2 2.6 2.6 2.2 2.6 2.6 2.1 2.5 3.0 Gavage ml Day 67 2.8 2.3 2.5 2.7 2.4 2.7 2.3 2.7 2.8 2.6 2.8 2.7 2.6 2.8 3.1 2.1 2.2 2.6 2.6 2.2 2.6 2.6 2.1 2.5 3.0 Gavage ml Day 68 2.8 2.3 2.5 2.7 2.4 2.7 2.3 2.7 2.8 2.6 2.8 2.7 2.6 2.8 3.1 2.1 2.2 2.6 2.6 2.2 2.6 2.6 2.1 2.5 3.0 Gavage ml Day 69 2.8 2.3 2.5 2.7 2.4 2.7 2.3 2.7 2.8 2.6 2.8 2.7 2.6 2.8 3.1 2.1 2.2 2.6 2.6 2.2 2.6 2.6 2.1 2.5 3.0 Gavage ml Day 70 2.8 2.4 2.6 2.5 2.5 2.8 2.4 2.8 2.9 2.7 2.8 2.8 2.7 2.7 3.2 2.2 2.3 2.6 2.6 2.4 2.6 2.6 2.1 2.5 3.0 Gavage ml Day 71 2. 8 2. 4 2. 6 2. 5 2. 5 2. 8 2. 4 2. 8 2. 9 2. 7 2. 8 2. 8 2. 7 2. 7 3. 2 2. 2 2. 3 2. 6 2. 6 2. 4 2. 6 2. 6 2. 1 2. 5 3. 0 - 333 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 72 Gavage ml D a y 73 Male, IX 125 mg/kg/day 654983 2.8 2.8 654965 2.4 2.4 654979 2.6 2.6 654986 2.5 2.5 655003 2.5 2.5 654921 2.8 2.8 654996 2.4 2.4 654951 2.8 2.8 654955 2.9 2.9 654914 2.7 2.7 654937 2.8 2.8 654962 2.8 2.8 654982 2.7 2.7 654931 2.7 2.7 654906 3.2 3.2 654985 2.2 2.2 654978 2.3 2.3 654974 2.6 2.6 654990 2.6 2.6 654976 2.4 2.4 654957 2.6 2.6 654973 2.6 2.6 654977 2.1 2.1 654942 2.5 2.5 654991 3.0 3.0 Gavage ml D a y 74 2.8 2.4 2.6 2.5 2.5 2.8 2.4 2.8 2.9 2.7 2.8 2.8 2.7 2.7 3.2 2.2 2.3 2.6 2.6 2.4 2.6 2.6 2.1 2.5 3.0 Gavage ml Day 75 2.8 2.4 2.6 2.5 2.5 2.8 2.4 2.8 2.9 2.7 2.8 2.8 2.7 2.7 3.2 2.2 2.3 2.6 2.6 2.4 2.6 2.6 2.1 2.5 3.0 Gavage ml D a y 76 2.8 2.4 2.6 2.5 2.5 2.8 2.4 2.8 2.9 2.7 2.8 2.8 2.7 2.7 3.2 2.2 2.3 2.6 2.6 2.4 2.6 2.6 2.1 2.5 3.0 Gavage ml Day 77 2.9 2.3 2.6 2.5 2.5 2.9 2.5 2.8 2.8 2.8 2.9 2.8 2.6 2.3 3.2 1.8 2.3 2.2 2.7 2.4 2.6 2.7 2.1 2.6 3.1 Gavage ml Day 78 2.9 2.3 2.6 2.5 2.5 2.9 2.5 2.8 2.8 2.8 2.9 2.8 2.6 2.3 3.2 1.8 2.3 2.2 2.7 2.4 2.6 2.7 2.1 2.6 3.1 Gavage ml Day 79 2.9 2.3 2.6 2.5 2.5 2.9 2.5 2.8 2.8 2.8 2.9 2.8 2.6 2.3 3.2 1.8 2.3 2.2 2.7 2.4 2.6 2.7 2.1 2.6 3.1 Gavage ml Day 80 2.9 2.3 2.6 2.5 2.5 2.9 2.5 2.8 2.8 2.8 2.9 2.8 2.6 2.3 3.2 1.8 2.3 2.2 2.7 2.4 2.6 2.7 2.1 2.6 3.1 Gavage ml Day 81 2.9 2.3 2.6 2.5 2.5 2.9 2.5 2.8 2.8 2.8 2.9 2.8 2.6 2.3 3.2 1.8 2.3 2.2 2.7 2.4 2.6 2.7 2.1 2.6 3.1 Gavage ml D a y 82 2.9 2.3 2.6 2.5 2.5 2.9 2.5 2.8 2.8 2.8 2.9 2.8 2.6 2.3 3.2 1.8 2.3 2.2 2.7 2.4 2.6 2.7 2.1 2.6 3.1 Gavage ml D a y 83 2. 9 2. 3 2. 6 2. 5 2. 5 2. 9 2. 5 2. 8 2. 8 2. 8 2. 9 2. 8 2. 6 2. 3 3. 2 1. 8 2. 3 2. 2 2. 7 2. 4 2. 6 2. 7 2. 1 2. 6 3. 1 - 334 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL DOSE VOLUMES Gavage ml D a y 84 Gavage ml D a y 85 Male, IX 125 mg/kg/day 654983 2.9 2.9 654965 2.4 2.4 654979 2.6 2.6 654986 2.7 2.7 655003 2.6 2.6 654921 2.8 2.8 654996 2.6 2.6 654951 2.8 2.8 654955 2.7 2.7 654914 2.9 2.9 654937 2.8 2.8 654962 2.7 2.7 654982 2.5 2.5 654931 2.7 2.7 654906 3.2 3.2 654985 1.9 1.9 654978 2.3 2.3 654974 2.5 2.5 654990 2.8 2.8 654976 2.5 2.5 654957 2.7 2.7 654973 2.8 2.8 654977 2.2 2.2 654942 2.6 2.6 654991 3.1 3.1 Gavage ml D a y 86 2.9 2.4 2.6 2.7 2.6 2.8 2.6 2.8 2.7 2.9 2.8 2.7 2.5 2.7 3.2 1.9 2.3 2.5 2.8 2.5 2.7 2.8 2.2 2.6 3.1 Gavage ml Day 87 2.9 2.4 2.6 2.7 2.6 2.8 2.6 2.8 2.7 2.9 2.8 2.7 2.5 2.7 3.2 1.9 2.3 2.5 2.8 2.5 2.7 2.8 2.2 2.6 3.1 Gavage ml Day 88 2.9 2.4 2.6 2.7 2.6 2.8 2.6 2.8 2.7 2.9 2.8 2.7 2.5 2.7 3.2 1.9 2.3 2.5 2.8 2.5 2.7 2.8 2.2 2.6 3.1 Gavage ml Day 89 2.9 2.4 2.6 2.7 2.6 2.8 2.6 2.8 2.7 2.9 2.8 2.7 2.5 2.7 3.2 1.9 2.3 2.5 2.8 2.5 2.7 2.8 2.2 2.6 3.1 Gavage ml D a y 90 2.9 2.4 2.6 2.7 2.6 2.8 2.6 2.8 2.7 2.9 2.8 2.7 2.5 2.7 3.2 1.9 2.3 2.5 2.8 2.5 2.7 2.8 2.2 2.6 3.1 Gavage ml D a y 91 3.0 2.6 2.7 3.0 2.7 2.9 2.7 2.9 2.8 3.0 2.9 2.8 2.7 2.8 3.4 2.1 2.4 2.7 2.9 2.7 2.7 2.8 2.2 2.6 3.2 Gavage ml D a y 92 3. 0 2. 6 2. 7 3. 0 2. 7 2. 9 2. 7 2. 9 2. 8 3. 0 DuPont-9478 - 335 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 0 Gavage ml Day 1 Female, II 0 m g / k g / d a y 655031 0.9 0.9 655107 0.9 0.9 655098 0.8 0.8 655016 0.9 0.9 655079 0.9 0.9 655036 1.1 1.1 655025 0.9 0.9 655099 1.0 1.0 655032 1.0 1.0 655083 1.0 1.0 655093 0.8 0.8 655045 0.9 0.9 655065 0.9 0.9 655074 1.0 1.0 655035 0.9 0.9 655009 0.9 0.9 655068 1.0 1.0 655019 1.0 1.0 655062 1.0 1.0 655109 1.0 1.0 655101 1.0 1.0 655072 1.0 1.0 655015 0.8 0.8 655071 0.9 0.9 655022 0.9 0.9 Gavage ml Day 2 0.9 0.9 0.8 0.9 0.9 1.1 0.9 1.0 1.0 1.0 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 1.0 1.0 1.0 1.0 0.8 0.9 0.9 Gavage ml Day 3 0.9 0.9 0.8 0.9 0.9 1.1 0.9 1.0 1.0 1.0 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 1.0 1.0 1.0 1.0 0.8 0.9 0.9 Gavage ml Day 4 0.9 0.9 0.8 0.9 0.9 1.1 0.9 1.0 1.0 1.0 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 1.0 1.0 1.0 1.0 0.8 0.9 0.9 Gavage ml Day 5 0.9 0.9 0.8 0.9 0.9 1.1 0.9 1.0 1.0 1.0 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 1.0 1.0 1.0 1.0 0.8 0.9 0.9 Gavage ml Day 6 0.9 0.9 0.8 0.9 0.9 1.1 0.9 1.0 1.0 1.0 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 1.0 1.0 1.0 1.0 0.8 0.9 0.9 Gavage ml Day 7 0.9 1.0 0.9 1.0 0.9 1.2 1.0 1.1 1.1 1.1 0.8 1.0 1.0 1.1 1.0 1.0 1.1 1.1 1.0 1.1 1.2 1.2 0.9 1.0 1.0 Gavage ml Day 8 0.9 1.0 0.9 1.0 0.9 1.2 1.0 1.1 1.1 1.1 0.8 1.0 1.0 1.1 1.0 1.0 1.1 1.1 1.0 1.1 1.2 1.2 0.9 1.0 1.0 Gavage ml Day 9 0.9 1.0 0.9 1.0 0.9 1.2 1.0 1.1 1.1 1.1 0.8 1.0 1.0 1.1 1.0 1.0 1.1 1.1 1.0 1.1 1.2 1.2 0.9 1.0 1.0 Gavage ml Day 10 0.9 1.0 0.9 1.0 0.9 1.2 1.0 1.1 1.1 1.1 0.8 1.0 1.0 1.1 1.0 1.0 1.1 1.1 1.0 1.1 1.2 1.2 0.9 1.0 1.0 Gavage ml Day 11 0. 9 1. 0 0. 9 1. 0 0. 9 1. 2 1. 0 1. 1 1. 1 1. 1 0. 8 1. 0 1. 0 1. 1 1. 0 1. 0 1. 1 1. 1 1. 0 1. 1 1. 2 1. 2 0. 9 1. 0 1. 0 - 336 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 12 Gavage ml D a y 13 Female, II 0 m g / k g / d a y 655031 0.9 0.9 655107 1.0 1.0 655098 0.9 0.9 655016 1.0 1.0 655079 0.9 0.9 655036 1.2 1.2 655025 1.0 1.0 655099 1.1 1.1 655032 1.1 1.1 655083 1.1 1.1 655093 0.8 0.8 655045 1.0 1.0 655065 1.0 1.0 655074 1.1 1.1 655035 1.0 1.0 655009 1.0 1.0 655068 1.1 1.1 655019 1.1 1.1 655062 1.0 1.0 655109 1.1 1.1 655101 1.2 1.2 655072 1.2 1.2 655015 0.9 0.9 655071 1.0 1.0 655022 1.0 1.0 Gavage ml D a y 14 1.0 1.0 1.0 1.1 1.0 1.3 1.1 1.2 1.1 1.2 0.9 1.1 1.1 1.2 1.1 1.1 1.2 1.2 1.2 1.2 1.3 1.2 1.0 1.0 1.1 Gavage ml Day 15 1.0 1.0 1.0 1.1 1.0 1.3 1.1 1.2 1.1 1.2 0.9 1.1 1.1 1.2 1.1 1.1 1.2 1.2 1.2 1.2 1.3 1.2 1.0 1.0 1.1 Gavage ml D a y 16 1.0 1.0 1.0 1.1 1.0 1.3 1.1 1.2 1.1 1.2 0.9 1.1 1.1 1.2 1.1 1.1 1.2 1.2 1.2 1.2 1.3 1.2 1.0 1.0 1.1 Gavage ml Day 17 1.0 1.0 1.0 1.1 1.0 1.3 1.1 1.2 1.1 1.2 0.9 1.1 1.1 1.2 1.1 1.1 1.2 1.2 1.2 1.2 1.3 1.2 1.0 1.0 1.1 Gavage ml Day 18 1.0 1.0 1.0 1.1 1.0 1.3 1.1 1.2 1.1 1.2 0.9 1.1 1.1 1.2 1.1 1.1 1.2 1.2 1.2 1.2 1.3 1.2 1.0 1.0 1.1 Gavage ml Day 19 1.0 1.0 1.0 1.1 1.0 1.3 1.1 1.2 1.1 1.2 0.9 1.1 1.1 1.2 1.1 1.1 1.2 1.2 1.2 1.2 1.3 1.2 1.0 1.1 Gavage ml Day 20 1.0 1.0 1.0 1.1 1.0 1.3 1.1 1.2 1.1 1.2 0.9 1.1 1.1 1.2 1.1 1.1 1.2 1.2 1.2 1.2 1.3 1.2 1.0 1.1 Gavage ml Day 21 1.1 1.0 1.1 1.1 1.0 1.3 1.2 1.3 1.2 1.3 1.0 1.2 1.2 1.3 1.2 1.2 1.3 1.4 1.2 1.2 1.4 1.4 1.0 1.2 Gavage ml D a y 22 1.1 1.0 1.1 1.1 1.0 1.3 1.2 1.3 1.2 1.3 1.0 1.2 1.2 1.3 1.2 1.2 1.3 1.4 1.2 1.2 1.4 1.4 1.0 1.2 Gavage ml D a y 23 1. 1 1. 0 1. 1 1. 1 1. 0 1. 3 1. 2 1. 3 1. 2 1. 3 1. 0 1. 2 1. 2 1. 3 1. 2 1. 2 1. 3 1. 4 1. 2 1. 2 1. 4 1. 4 1. 0 1. 2 - 337 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 24 Gavage ml Day 25 Female, II 0 m g / k g / d a y 655031 1.1 1.1 655107 1.0 1.0 655098 1.1 1.1 655016 1.1 1.1 655079 1.0 1.0 655036 1.3 1.3 655025 1.2 1.2 655099 1.3 1.3 655032 1.2 1.2 655083 1.3 1.3 655093 1.0 1.0 655045 1.2 1.2 655065 1.2 1.2 655074 1.3 1.3 655035 1.2 1.2 655009 1.2 1.2 655068 1.3 1.3 655019 1.4 1.4 655062 1.2 1.2 655109 1.2 1.2 655101 1.4 1.4 655072 1.4 1.4 655015 1.0 1.0 655071 655022 1.2 1.2 Gavage ml D a y 26 1.1 1.0 1.1 1.1 1.0 1.3 1.2 1.3 1.2 1.3 1.0 1.2 1.2 1.3 1.2 1.2 1.3 1.4 1.2 1.2 1.4 1.4 1.0 1.2 Gavage ml Day 27 1.1 1.0 1.1 1.1 1.0 1.3 1.2 1.3 1.2 1.3 1.0 1.2 1.2 1.3 1.2 1.2 1.3 1.4 1.2 1.2 1.4 1.4 1.0 1.2 Gavage ml Day 28 1.3 1.1 1.1 1.2 1.1 1.4 1.3 1.3 1.3 1.3 1.0 1.2 1.3 1.3 1.3 1.3 1.3 1.4 1.3 1.3 1.5 1.4 1.0 1.3 Gavage ml Day 29 1.3 1.1 1.1 1.2 1.1 1.4 1.3 1.3 1.3 1.3 1.0 1.2 1.3 1.3 1.3 1.3 1.3 1.4 1.3 1.3 1.5 1.4 1.0 1.3 Gavage ml Day 30 1.3 1.1 1.1 1.2 1.1 1.4 1.3 1.3 1.3 1.3 1.0 1.2 1.3 1.3 1.3 1.3 1.3 1.4 1.3 1.3 1.5 1.4 1.0 1.3 Gavage ml Day 31 1.3 1.1 1.1 1.2 1.1 1.4 1.3 1.3 1.3 1.3 1.0 1.2 1.3 1.3 1.3 1.3 1.3 1.4 1.3 1.3 1.5 1.4 1.0 1.3 Gavage ml D a y 32 1.3 1.1 1.1 1.2 1.1 1.4 1.3 1.3 1.3 1.3 1.0 1.2 1.3 1.3 1.3 1.3 1.3 1.4 1.3 1.3 1.5 1.4 1.0 1.3 Gavage ml D a y 33 1.3 1.1 1.1 1.2 1.1 1.4 1.3 1.3 1.3 1.3 1.0 1.2 1.3 1.3 1.3 1.3 1.3 1.4 1.3 1.3 1.5 1.4 1.0 1.3 Gavage ml D a y 34 1.3 1.1 1.1 1.2 1.1 1.4 1.3 1.3 1.3 1.3 1.0 1.2 1.3 1.3 1.3 1.3 1.3 1.4 1.3 1.3 1.5 1.4 1.0 1.3 Gavage ml Day 35 1. 3 1. 1 1. 2 1. 2 1. 2 1. 5 1. 4 1. 4 1. 3 1. 4 1. 0 1. 3 1. 4 1. 4 1. 4 1. 3 1. 4 1. 4 1. 3 1. 3 1. 6 1. 4 1. 1 1. 3 - 338 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 36 Gavage ml D a y 37 Female, II 0 m g / k g / d a y 655031 1.3 1.3 655107 1.1 1.1 655098 1.2 1.2 655016 1.2 1.2 655079 1.2 1.2 655036 1.5 1.5 655025 1.4 1.4 655099 1.4 1.4 655032 1.3 1.3 655083 1.4 1.4 655093 1.0 1.0 655045 1.3 1.3 655065 1.4 1.4 655074 1.4 1.4 655035 1.4 1.4 655009 1.3 1.3 655068 1.4 1.4 655019 1.4 1.4 655062 1.3 1.3 655109 1.3 1.3 655101 1.6 1.6 655072 1.4 1.4 655015 1.1 1.1 655071 655022 1.3 1.3 Gavage ml D a y 38 1.3 1.1 1.2 1.2 1.2 1.5 1.4 1.4 1.3 1.4 1.0 1.3 1.4 1.4 1.4 1.3 1.4 1.4 1.3 1.3 1.6 1.4 1.1 1.3 Gavage ml Day 39 1.3 1.1 1.2 1.2 1.2 1.5 1.4 1.4 1.3 1.4 1.0 1.3 1.4 1.4 1.4 1.3 1.4 1.4 1.3 1.3 1.6 1.4 1.1 1.3 Gavage ml Day 40 1.3 1.1 1.2 1.2 1.2 1.5 1.4 1.4 1.3 1.4 1.0 1.3 1.4 1.4 1.4 1.3 1.4 1.4 1.3 1.3 1.6 1.4 1.1 1.3 Gavage ml Day 41 1.3 1.1 1.2 1.2 1.2 1.5 1.4 1.4 1.3 1.4 1.0 1.3 1.4 1.4 1.4 1.3 1.4 1.4 1.3 1.3 1.6 1.4 1.1 1.3 Gavage ml D a y 42 1.4 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.3 1.5 1.4 1.4 1.3 1.4 1.5 1.4 1.4 1.6 1.5 1.2 1.3 Gavage ml D a y 43 1.4 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.3 1.5 1.4 1.4 1.3 1.4 1.5 1.4 1.4 1.6 1.5 1.2 1.3 Gavage ml D a y 44 1.4 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.3 1.5 1.4 1.4 1.3 1.4 1.5 1.4 1.4 1.6 1.5 1.2 1.3 Gavage ml Day 45 1.4 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.3 1.5 1.4 1.4 1.3 1.4 1.5 1.4 1.4 1.6 1.5 1.2 1.3 Gavage ml D a y 46 1.4 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.3 1.5 1.4 1.4 1.3 1.4 1.5 1.4 1.4 1.6 1.5 1.2 1.3 Gavage ml Day 47 1. 4 1. 1 1. 2 1. 3 1. 2 1. 5 1. 4 1. 4 1. 4 1. 4 1. 0 1. 3 1. 5 1. 4 1. 4 1. 3 1. 4 1. 5 1. 4 1. 4 1. 6 1. 5 1. 2 1. 3 - 339 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 48 Gavage ml Day 49 Female, II 0 m g / k g / d a y 655031 1.4 1.3 655107 1.1 1.1 655098 1.2 1.2 655016 1.3 1.3 655079 1.2 1.2 655036 1.5 1.5 655025 1.4 1.4 655099 1.4 1.4 655032 1.4 1.4 655083 1.4 1.4 655093 1.0 1.0 655045 1.3 1.4 655065 1.5 1.5 655074 1.4 1.4 655035 1.4 1.4 655009 1.3 1.4 655068 1.4 1.4 655019 1.5 1.5 655062 1.4 1.4 655109 1.4 1.4 655101 1.6 1.7 655072 1.5 1.6 655015 1.2 1.1 655071 655022 1.3 1.4 Gavage ml D a y 50 1.3 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.4 1.4 1.7 1.6 1.1 1.4 Gavage ml Day 51 1.3 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.4 1.4 1.7 1.6 1.1 1.4 Gavage ml D a y 52 1.3 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.4 1.4 1.7 1.6 1.1 1.4 Gavage ml D a y 53 1.3 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.4 1.4 1.7 1.6 1.1 1.4 Gavage ml D a y 54 1.3 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.4 1.4 1.7 1.6 1.1 1.4 Gavage ml Day 55 1.3 1.1 1.2 1.3 1.2 1.5 1.4 1.4 1.4 1.4 1.0 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.4 1.4 1.7 1.6 1.1 1.4 Gavage ml D a y 56 1.4 1.2 1.2 1.3 1.3 1.6 1.5 1.5 1.5 1.5 1.1 1.4 1.6 1.4 1.5 1.4 1.5 1.6 1.4 1.4 1.7 1.6 1.2 1.4 Gavage ml Day 57 1.4 1.2 1.2 1.3 1.3 1.6 1.5 1.5 1.5 1.5 1.1 1.4 1.6 1.4 1.5 1.4 1.5 1.6 1.4 1.4 1.7 1.6 1.2 1.4 Gavage ml Day 58 1.4 1.2 1.2 1.3 1.3 1.6 1.5 1.5 1.5 1.5 1.1 1.4 1.6 1.4 1.5 1.4 1.5 1.6 1.4 1.4 1.7 1.6 1.2 1.4 Gavage ml Day 59 1. 4 1. 2 1. 2 1. 3 1. 3 1. 6 1. 5 1. 5 1. 5 1. 5 1. 1 1. 4 1. 6 1. 4 1. 5 1. 4 1. 5 1. 6 1. 4 1. 4 1. 7 1. 6 1. 2 1. 4 - 340 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 60 Gavage ml D a y 61 Female, II 0 m g / k g / d a y 655031 1.4 1.4 655107 1.2 1.2 655098 1.2 1.2 655016 1.3 1.3 655079 1.3 1.3 655036 1.6 1.6 655025 1.5 1.5 655099 1.5 1.5 655032 1.5 1.5 655083 1.5 1.5 655093 1.1 1.1 655045 1.4 1.4 655065 1.6 1.6 655074 1.4 1.4 655035 1.5 1.5 655009 1.4 1.4 655068 1.5 1.5 655019 1.6 1.6 655062 1.4 1.4 655109 1.4 1.4 655101 1.7 1.7 655072 1.6 1.6 655015 1.2 1.2 655071 655022 1.4 1.4 Gavage ml D a y 62 1.4 1.2 1.2 1.3 1.3 1.6 1.5 1.5 1.5 1.5 1.1 1.4 1.6 1.4 1.5 1.4 1.5 1.6 1.4 1.4 1.7 1.6 1.2 1.4 Gavage ml D a y 63 1.4 1.2 1.3 1.4 1.3 1.6 1.5 1.4 1.5 1.5 1.1 1.4 1.6 1.5 1.5 1.5 1.5 1.6 1.4 1.5 1.8 1.6 1.2 1.4 Gavage ml D a y 64 1.4 1.2 1.3 1.4 1.3 1.6 1.5 1.4 1.5 1.5 1.1 1.4 1.6 1.5 1.5 1.5 1.5 1.6 1.4 1.5 1.8 1.6 1.2 1.4 Gavage ml Day 65 1.4 1.2 1.3 1.4 1.3 1.6 1.5 1.4 1.5 1.5 1.1 1.4 1.6 1.5 1.5 1.5 1.5 1.6 1.4 1.5 1.8 1.6 1.2 1.4 Gavage ml D a y 66 1.4 1.2 1.3 1.4 1.3 1.6 1.5 1.4 1.5 1.5 1.1 1.4 1.6 1.5 1.5 1.5 1.5 1.6 1.4 1.5 1.8 1.6 1.2 1.4 Gavage ml Day 67 1.4 1.2 1.3 1.4 1.3 1.6 1.5 1.4 1.5 1.5 1.1 1.4 1.6 1.5 1.5 1.5 1.5 1.6 1.4 1.5 1.8 1.6 1.2 1.4 Gavage ml Day 68 1.4 1.2 1.3 1.4 1.3 1.6 1.5 1.4 1.5 1.5 1.1 1.4 1.6 1.5 1.5 1.5 1.5 1.6 1.4 1.5 1.8 1.6 1.2 1.4 Gavage ml Day 69 1.4 1.2 1.3 1.4 1.3 1.6 1.5 1.4 1.5 1.5 1.1 1.4 1.6 1.5 1.5 1.5 1.5 1.6 1.4 1.5 1.8 1.6 1.2 1.4 Gavage ml Day 70 1.5 1.2 1.3 1.4 1.3 1.6 1.6 1.5 1.5 1.5 1.1 1.5 1.7 1.5 1.5 1.5 1.5 1.6 1.5 1.5 1.8 1.7 1.2 1.4 Gavage ml Day 71 1. 5 1. 2 1. 3 1. 4 1. 3 1. 6 1. 6 1. 5 1. 5 1. 5 1. 1 1. 5 1. 7 1. 5 1. 5 1. 5 1. 5 1. 6 1. 5 1. 5 1. 8 1. 7 1. 2 1. 4 - 341 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 72 Gavage ml D a y 73 Female, II 0 m g / k g / d a y 655031 1.5 1.5 655107 1.2 1.2 655098 1.3 1.3 655016 1.4 1.4 655079 1.3 1.3 655036 1.6 1.6 655025 1.6 1.6 655099 1.5 1.5 655032 1.5 1.5 655083 1.5 1.5 655093 1.1 1.1 655045 1.5 1.5 655065 1.7 1.7 655074 1.5 1.5 655035 1.5 1.5 655009 1.5 1.5 655068 1.5 1.5 655019 1.6 1.6 655062 1.5 1.5 655109 1.5 1.5 655101 1.8 1.8 655072 1.7 1.7 655015 1.2 1.2 655071 655022 1.4 1.4 Gavage ml D a y 74 1.5 1.2 1.3 1.4 1.3 1.6 1.6 1.5 1.5 1.5 1.1 1.5 1.7 1.5 1.5 1.5 1.5 1.6 1.5 1.5 1.8 1.7 1.2 1.4 Gavage ml Day 75 1.5 1.2 1.3 1.4 1.3 1.6 1.6 1.5 1.5 1.5 1.1 1.5 1.7 1.5 1.5 1.5 1.5 1.6 1.5 1.5 1.8 1.7 1.2 1.4 Gavage ml D a y 76 1.5 1.2 1.3 1.4 1.3 1.6 1.6 1.5 1.5 1.5 1.1 1.5 1.7 1.5 1.5 1.5 1.5 1.6 1.5 1.5 1.8 1.7 1.2 1.4 Gavage ml Day 77 1.5 1.2 1.3 1.4 1.4 1.6 1.6 1.5 1.6 1.6 1.2 1.5 1.7 1.5 1.5 1.5 1.5 1.6 1.6 1.5 1.8 1.7 1.2 1.5 Gavage ml Day 78 1.5 1.2 1.3 1.4 1.4 1.6 1.6 1.5 1.6 1.6 1.2 1.5 1.7 1.5 1.5 1.5 1.5 1.6 1.6 1.5 1.8 1.7 1.2 1.5 Gavage ml Day 79 1.5 1.2 1.3 1.4 1.4 1.6 1.6 1.5 1.6 1.6 1.2 1.5 1.7 1.5 1.5 1.5 1.5 1.6 1.6 1.5 1.8 1.7 1.2 1.5 Gavage ml Day 80 1.5 1.2 1.3 1.4 1.4 1.6 1.6 1.5 1.6 1.6 1.2 1.5 1.7 1.5 1.5 1.5 1.5 1.6 1.6 1.5 1.8 1.7 1.2 1.5 Gavage ml Day 81 1.5 1.2 1.3 1.4 1.4 1.6 1.6 1.5 1.6 1.6 1.2 1.5 1.7 1.5 1.5 1.5 1.5 1.6 1.6 1.5 1.8 1.7 1.2 1.5 Gavage ml D a y 82 1.5 1.2 1.3 1.4 1.4 1.6 1.6 1.5 1.6 1.6 1.2 1.5 1.7 1.5 1.5 1.5 1.5 1.6 1.6 1.5 1.8 1.7 1.2 1.5 Gavage ml D a y 83 1. 5 1. 2 1. 3 1. 4 1. 4 1. 6 1. 6 1. 5 1. 6 1. 6 1. 2 1. 5 1. 7 1. 5 1. 5 1. 5 1. 5 1. 6 1. 6 1. 5 1. 8 1. 7 1. 2 1. 5 - 342 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL DOSE VOLUMES Gavage ml D a y 84 Gavage ml D a y 85 Female, II 0 m g / k g / d a y 655031 1.5 1.5 655107 1.3 1.3 655098 1.3 1.3 655016 1.5 1.5 655079 1.4 1.4 655036 1.7 1.7 655025 1.6 1.6 655099 1.5 1.5 655032 1.5 1.5 655083 1.6 1.6 655093 1.1 1.1 655045 1.4 1.4 655065 1.7 1.7 655074 1.5 1.5 655035 1.6 1.6 655009 1.5 1.5 655068 1.5 1.5 655019 1.6 1.6 655062 1.6 1.6 655109 1.5 1.5 655101 1.9 1.9 655072 1.6 1.6 655015 1.2 1.2 655071 655022 1.5 1.5 Gavage ml D a y 86 1.5 1.3 1.3 1.5 1.4 1.7 1.6 1.5 1.5 1.6 1.1 1.4 1.7 1.5 1.6 1.5 1.5 1.6 1.6 1.5 1.9 1.6 1.2 1.5 Gavage ml Day 87 1.5 1.3 1.3 1.5 1.4 1.7 1.6 1.5 1.5 1.6 1.1 1.4 1.7 1.5 1.6 1.5 1.5 1.6 1.6 1.5 1.9 1.6 1.2 1.5 Gavage ml Day 88 1.5 1.3 1.3 1.5 1.4 1.7 1.6 1.5 1.5 1.6 1.1 1.4 1.7 1.5 1.6 1.5 1.5 1.6 1.6 1.5 1.9 1.6 1.2 1.5 Gavage ml Day 89 1.5 1.3 1.3 1.5 1.4 1.7 1.6 1.5 1.5 1.6 1.1 1.4 1.7 1.5 1.6 1.5 1.5 1.6 1.6 1.5 1.9 1.6 1.2 1.5 Gavage ml D a y 90 1.5 1.3 1.3 1.5 1.4 1.7 1.6 1.5 1.5 1.6 1.1 1.4 1.7 1.5 1.6 1.5 1.5 1.6 1.6 1.5 1.9 1.6 1.2 1.5 Gavage ml D a y 91 1.5 1.3 1.3 1.5 1.4 1.7 1.6 1.5 1.6 1.6 1.1 1.5 1.8 1.5 1.6 1.6 1.5 1.6 1.6 1.5 1.8 1.6 1.3 1.5 Gavage ml D a y 92 1.5 1.3 1.3 1.5 1.4 1.7 1.6 1.5 1.6 1.6 Gavage ml D a y 93 1. 5 1. 3 1. 3 1. 5 1. 4 1. 7 1. 6 1. 5 1. 6 1. 6 DuPont-9478 - 343 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 0 Gavage ml Day 1 Female, IV 1 mg/kg/day 655086 0.9 0.9 655041 0.9 0.9 655108 0.8 0.8 655040 0.9 0.9 655044 0.9 0.9 655013 1.0 1.0 655089 0.8 0.8 655091 0.9 0.9 655033 1.0 1.0 655090 1.1 1.1 655051 0.9 0.9 655018 1.0 1.0 655096 1.0 1.0 655057 0.8 0.8 655028 1.0 1.0 Gavage ml Day 2 0.9 0.9 0.8 0.9 0.9 1.0 0.8 0.9 1.0 1.1 0.9 1.0 1.0 0.8 1.0 Gavage ml Day 3 0.9 0.9 0.8 0.9 0.9 1.0 0.8 0.9 1.0 1.1 0.9 1.0 1.0 0.8 1.0 Gavage ml Day 4 0.9 0.9 0.8 0.9 0.9 1.0 0.8 0.9 1.0 1.1 0.9 1.0 1.0 0.8 1.0 Gavage ml Day 5 0.9 0.9 0.8 0.9 0.9 1.0 0.8 0.9 1.0 1.1 0.9 1.0 1.0 0.8 1.0 Gavage ml Day 6 0.9 0.9 0.8 0.9 0.9 1.0 0.8 0.9 1.0 1.1 0.9 1.0 1.0 0.8 1.0 Gavage ml Day 7 1.0 1.0 1.0 1.0 1.0 1.2 1.0 1.0 1.1 1.2 1.0 1.1 1.0 0.9 1.1 Gavage ml Day 8 1.0 1.0 1.0 1.0 1.0 1.2 1.0 1.0 1.1 1.2 1.0 1.1 1.0 0.9 1.1 Gavage ml Day 9 1.0 1.0 1.0 1.0 1.0 1.2 1.0 1.0 1.1 1.2 1.0 1.1 1.0 0.9 1.1 Gavage ml Day 10 1.0 1.0 1.0 1.0 1.0 1.2 1.0 1.0 1.1 1.2 1.0 1.1 1.0 0.9 1.1 Gavage ml Day 11 1. 0 1. 0 1. 0 1. 0 1. 0 1. 2 1. 0 1. 0 1. 1 1. 2 1. 0 1. 1 1. 0 0. 9 1. 1 - 344 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 12 Gavage ml D a y 13 Female, IV 1 mg/kg/day 655086 1.0 1.0 655041 1.0 1.0 655108 1.0 1.0 655040 1.0 1.0 655044 1.0 1.0 655013 1.2 1.2 655089 1.0 1.0 655091 1.0 1.0 655033 1.1 1.1 655090 1.2 1.2 655051 1.0 1.0 655018 1.1 1.1 655096 1.0 1.0 655057 0.9 0.9 655028 1.1 1.1 Gavage ml D a y 14 1.0 1.0 1.1 1.1 1.2 1.3 1.1 1.1 1.2 1.3 1.0 1.2 1.1 1.0 1.1 Gavage ml Day 15 1.0 1.0 1.1 1.1 1.2 1.3 1.1 1.1 1.2 1.3 1.0 1.2 1.1 1.0 1.1 Gavage ml D a y 16 1.0 1.0 1.1 1.1 1.2 1.3 1.1 1.1 1.2 1.3 1.0 1.2 1.1 1.0 1.1 Gavage ml Day 17 1.0 1.0 1.1 1.1 1.2 1.3 1.1 1.1 1.2 1.3 1.0 1.2 1.1 1.0 1.1 Gavage ml Day 18 1.0 1.0 1.1 1.1 1.2 1.3 1.1 1.1 1.2 1.3 1.0 1.2 1.1 1.0 1.1 Gavage ml Day 19 1.0 1.0 1.1 1.1 1.2 1.3 1.1 1.1 1.2 1.3 1.0 1.2 1.1 1.0 1.1 Gavage ml Day 20 1.0 1.0 1.1 1.1 1.2 1.3 1.1 1.1 1.2 1.3 1.0 1.2 1.1 1.0 1.1 Gavage ml Day 21 1.1 1.1 1.1 1.2 1.2 1.3 1.2 1.2 1.2 1.3 1.1 1.2 1.2 1.1 1.2 Gavage ml D a y 22 1.1 1.1 1.1 1.2 1.2 1.3 1.2 1.2 1.2 1.3 1.1 1.2 1.2 1.1 1.2 Gavage ml D a y 23 1. 1 1. 1 1. 1 1. 2 1. 2 1. 3 1. 2 1. 2 1. 2 1. 3 1. 1 1. 2 1. 2 1. 1 1. 2 - 345 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 24 Gavage ml Day 25 Female, IV 1 mg/kg/day 655086 1.1 1.1 655041 1.1 1.1 655108 1.1 1.1 655040 1.2 1.2 655044 1.2 1.2 655013 1.3 1.3 655089 1.2 1.2 655091 1.2 1.2 655033 1.2 1.2 655090 1.3 1.3 655051 1.1 1.1 655018 1.2 1.2 655096 1.2 1.2 655057 1.1 1.1 655028 1.2 1.2 Gavage ml D a y 26 1.1 1.1 1.1 1.2 1.2 1.3 1.2 1.2 1.2 1.3 1.1 1.2 1.2 1.1 1.2 Gavage ml Day 27 1.1 1.1 1.1 1.2 1.2 1.3 1.2 1.2 1.2 1.3 1.1 1.2 1.2 1.1 1.2 Gavage ml Day 28 1.1 1.2 1.2 1.2 1.3 1.3 1.2 1.3 1.3 1.4 1.2 1.3 1.3 1.1 1.3 Gavage ml Day 29 1.1 1.2 1.2 1.2 1.3 1.3 1.2 1.3 1.3 1.4 1.2 1.3 1.3 1.1 1.3 Gavage ml Day 30 1.1 1.2 1.2 1.2 1.3 1.3 1.2 1.3 1.3 1.4 1.2 1.3 1.3 1.1 1.3 Gavage ml Day 31 1.1 1.2 1.2 1.2 1.3 1.3 1.2 1.3 1.3 1.4 1.2 1.3 1.3 1.1 1.3 Gavage ml D a y 32 1.1 1.2 1.2 1.2 1.3 1.3 1.2 1.3 1.3 1.4 1.2 1.3 1.3 1.1 1.3 Gavage ml D a y 33 1.1 1.2 1.2 1.2 1.3 1.3 1.2 1.3 1.3 1.4 1.2 1.3 1.3 1.1 1.3 Gavage ml D a y 34 1.1 1.2 1.2 1.2 1.3 1.3 1.2 1.3 1.3 1.4 1.2 1.3 1.3 1.1 1.3 Gavage ml Day 35 1. 2 1. 2 1. 3 1. 3 1. 4 1. 4 1. 3 1. 4 1. 4 1. 5 1. 2 1. 4 1. 3 1. 2 1. 3 - 346 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 36 Gavage ml D a y 37 Female, IV 1 mg/kg/day 655086 1.2 1.2 655041 1.2 1.2 655108 1.3 1.3 655040 1.3 1.3 655044 1.4 1.4 655013 1.4 1.4 655089 1.3 1.3 655091 1.4 1.4 655033 1.4 1.4 655090 1.5 1.5 655051 1.2 1.2 655018 1.4 1.4 655096 1.3 1.3 655057 1.2 1.2 655028 1.3 1.3 Gavage ml D a y 38 1.2 1.2 1.3 1.3 1.4 1.4 1.3 1.4 1.4 1.5 1.2 1.4 1.3 1.2 1.3 Gavage ml Day 39 1.2 1.2 1.3 1.3 1.4 1.4 1.3 1.4 1.4 1.5 1.2 1.4 1.3 1.2 1.3 Gavage ml Day 40 1.2 1.2 1.3 1.3 1.4 1.4 1.3 1.4 1.4 1.5 1.2 1.4 1.3 1.2 1.3 Gavage ml Day 41 1.2 1.2 1.3 1.3 1.4 1.4 1.3 1.4 1.4 1.5 1.2 1.4 1.3 1.2 1.3 Gavage ml D a y 42 1.2 1.3 1.3 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.3 1.5 1.4 1.3 1.3 Gavage ml D a y 43 1.2 1.3 1.3 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.3 1.5 1.4 1.3 1.3 Gavage ml D a y 44 1.2 1.3 1.3 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.3 1.5 1.4 1.3 1.3 Gavage ml Day 45 1.2 1.3 1.3 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.3 1.5 1.4 1.3 1.3 Gavage ml D a y 46 1.2 1.3 1.3 1.4 1.5 1.4 1.4 1.4 1.4 1.5 1.3 1.5 1.4 1.3 1.3 Gavage ml Day 47 1. 2 1. 3 1. 3 1. 4 1. 5 1. 4 1. 4 1. 4 1. 4 1. 5 1. 3 1. 5 1. 4 1. 3 1. 3 - 347 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 48 Gavage ml Day 49 Female, IV 1 mg/kg/day 655086 1.2 1.1 655041 1.3 1.3 655108 1.3 1.2 655040 1.4 1.3 655044 1.5 1.4 655013 1.4 1.4 655089 1.4 1.4 655091 1.4 1.4 655033 1.4 1.4 655090 1.5 1.5 655051 1.3 1.3 655018 1.5 1.4 655096 1.4 1.4 655057 1.3 1.2 655028 1.3 1.4 Gavage ml D a y 50 1.1 1.3 1.2 1.3 1.4 1.4 1.4 1.4 1.4 1.5 1.3 1.4 1.4 1.2 1.4 Gavage ml Day 51 1.1 1.3 1.2 1.3 1.4 1.4 1.4 1.4 1.4 1.5 1.3 1.4 1.4 1.2 1.4 Gavage ml D a y 52 1.1 1.3 1.2 1.3 1.4 1.4 1.4 1.4 1.4 1.5 1.3 1.4 1.4 1.2 1.4 Gavage ml D a y 53 1.1 1.3 1.2 1.3 1.4 1.4 1.4 1.4 1.4 1.5 1.3 1.4 1.4 1.2 1.4 Gavage ml D a y 54 1.1 1.3 1.2 1.3 1.4 1.4 1.4 1.4 1.4 1.5 1.3 1.4 1.4 1.2 1.4 Gavage ml Day 55 1.1 1.3 1.2 1.3 1.4 1.4 1.4 1.4 1.4 1.5 1.3 1.4 1.4 1.2 1.4 Gavage ml D a y 56 1.2 1.5 1.3 1.4 1.5 1.4 1.5 1.5 1.5 1.6 1.3 1.5 1.5 1.3 1.4 Gavage ml Day 57 1.2 1.5 1.3 1.4 1.5 1.4 1.5 1.5 1.5 1.6 1.3 1.5 1.5 1.3 1.4 Gavage ml Day 58 1.2 1.5 1.3 1.4 1.5 1.4 1.5 1.5 1.5 1.6 1.3 1.5 1.5 1.3 1.4 Gavage ml Day 59 1. 2 1. 5 1. 3 1. 4 1. 5 1. 4 1. 5 1. 5 1. 5 1. 6 1. 3 1. 5 1. 5 1. 3 1. 4 - 348 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 60 Gavage ml D a y 61 Female, IV 1 mg/kg/day 655086 1.2 1.2 655041 1.5 1.5 655108 1.3 1.3 655040 1.4 1.4 655044 1.5 1.5 655013 1.4 1.4 655089 1.5 1.5 655091 1.5 1.5 655033 1.5 1.5 655090 1.6 1.6 655051 1.3 1.3 655018 1.5 1.5 655096 1.5 1.5 655057 1.3 1.3 655028 1.4 1.4 Gavage ml D a y 62 1.2 1.5 1.3 1.4 1.5 1.4 1.5 1.5 1.5 1.6 1.3 1.5 1.5 1.3 1.4 Gavage ml D a y 63 1.3 1.4 1.4 1.4 1.5 1.5 1.6 1.5 1.5 1.6 1.3 1.6 1.5 1.3 1.4 Gavage ml D a y 64 1.3 1.4 1.4 1.4 1.5 1.5 1.6 1.5 1.5 1.6 1.3 1.6 1.5 1.3 1.4 Gavage ml Day 65 1.3 1.4 1.4 1.4 1.5 1.5 1.6 1.5 1.5 1.6 1.3 1.6 1.5 1.3 1.4 Gavage ml D a y 66 1.3 1.4 1.4 1.4 1.5 1.5 1.6 1.5 1.5 1.6 1.3 1.6 1.5 1.3 1.4 Gavage ml Day 67 1.3 1.4 1.4 1.4 1.5 1.5 1.6 1.5 1.5 1.6 1.3 1.6 1.5 1.3 1.4 Gavage ml Day 68 1.3 1.4 1.4 1.4 1.5 1.5 1.6 1.5 1.5 1.6 1.3 1.6 1.5 1.3 1.4 Gavage ml Day 69 1.3 1.4 1.4 1.4 1.5 1.5 1.6 1.5 1.5 1.6 1.3 1.6 1.5 1.3 1.4 Gavage ml Day 70 1.3 1.5 1.4 1.5 1.6 1.5 1.6 1.6 1.5 1.6 1.3 1.6 1.5 1.3 1.5 Gavage ml Day 71 1. 3 1. 5 1. 4 1. 5 1. 6 1. 5 1. 6 1. 6 1. 5 1. 6 1. 3 1. 6 1. 5 1. 3 1. 5 - 349 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 72 Gavage ml D a y 73 Female, IV 1 mg/kg/day 655086 1.3 1.3 655041 1.5 1.5 655108 1.4 1.4 655040 1.5 1.5 655044 1.6 1.6 655013 1.5 1.5 655089 1.6 1.6 655091 1.6 1.6 655033 1.5 1.5 655090 1.6 1.6 655051 1.3 1.3 655018 1.6 1.6 655096 1.5 1.5 655057 1.3 1.3 655028 1.5 1.5 Gavage ml D a y 74 1.3 1.5 1.4 1.5 1.6 1.5 1.6 1.6 1.5 1.6 1.3 1.6 1.5 1.3 1.5 Gavage ml Day 75 1.3 1.5 1.4 1.5 1.6 1.5 1.6 1.6 1.5 1.6 1.3 1.6 1.5 1.3 1.5 Gavage ml D a y 76 1.3 1.5 1.4 1.5 1.6 1.5 1.6 1.6 1.5 1.6 1.3 1.6 1.5 1.3 1.5 Gavage ml Day 77 1.3 1.5 1.4 1.5 1.6 1.5 1.6 1.5 1.5 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml Day 78 1.3 1.5 1.4 1.5 1.6 1.5 1.6 1.5 1.5 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml Day 79 1.3 1.5 1.4 1.5 1.6 1.5 1.6 1.5 1.5 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml Day 80 1.3 1.5 1.4 1.5 1.6 1.5 1.6 1.5 1.5 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml Day 81 1.3 1.5 1.4 1.5 1.6 1.5 1.6 1.5 1.5 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml D a y 82 1.3 1.5 1.4 1.5 1.6 1.5 1.6 1.5 1.5 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml D a y 83 1. 3 1. 5 1. 4 1. 5 1. 6 1. 5 1. 6 1. 5 1. 5 1. 7 1. 4 1. 7 1. 5 1. 4 1. 5 - 350 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL DOSE VOLUMES Gavage ml D a y 84 Gavage ml D a y 85 Female, IV 1 mg/kg/day 655086 1.3 1.3 655041 1.5 1.5 655108 1.4 1.4 655040 1.5 1.5 655044 1.6 1.6 655013 1.5 1.5 655089 1.7 1.7 655091 1.6 1.6 655033 1.6 1.6 655090 1.7 1.7 655051 1.4 1.4 655018 1.7 1.7 655096 1.5 1.5 655057 1.4 1.4 655028 1.5 1.5 Gavage ml D a y 86 1.3 1.5 1.4 1.5 1.6 1.5 1.7 1.6 1.6 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml Day 87 1.3 1.5 1.4 1.5 1.6 1.5 1.7 1.6 1.6 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml Day 88 1.3 1.5 1.4 1.5 1.6 1.5 1.7 1.6 1.6 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml Day 89 1.3 1.5 1.4 1.5 1.6 1.5 1.7 1.6 1.6 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml D a y 90 1.3 1.5 1.4 1.5 1.6 1.5 1.7 1.6 1.6 1.7 1.4 1.7 1.5 1.4 1.5 Gavage ml D a y 91 1.3 1.5 1.4 1.5 1.6 1.5 1.7 1.6 1.6 1.7 1.4 1.7 1.6 1.4 1.5 Gavage ml D a y 92 1.3 1.5 1.4 1.5 1.6 1.5 1.7 1.6 1.6 1.7 Gavage ml D a y 93 1. 3 1. 5 1. 4 1. 5 1. 6 1. 5 1. 7 1. 6 1. 6 1. 7 DuPont-9478 - 351 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 0 Gavage ml Day 1 Female, VI 5 mg/kg/day 655054 0.8 0.8 655038 0.9 0.9 655034 0.9 0.9 655039 0.9 0.9 655029 0.9 0.9 655067 1.0 1.0 655020 0.7 0.7 655087 0.9 0.9 655066 1.0 1.0 655042 1.1 1.1 655059 0.8 0.8 655064 1.0 1.0 655050 1.0 1.0 655021 0.8 0.8 655017 0.9 0.9 Gavage ml Day 2 0.8 0.9 0.9 0.9 0.9 1.0 0.7 0.9 1.0 1.1 0.8 1.0 1.0 0.8 0.9 Gavage ml Day 3 0.8 0.9 0.9 0.9 0.9 1.0 0.7 0.9 1.0 1.1 0.8 1.0 1.0 0.8 0.9 Gavage ml Day 4 0.8 0.9 0.9 0.9 0.9 1.0 0.7 0.9 1.0 1.1 0.8 1.0 1.0 0.8 0.9 Gavage ml Day 5 0.8 0.9 0.9 0.9 0.9 1.0 0.7 0.9 1.0 1.1 0.8 1.0 1.0 0.8 0.9 Gavage ml Day 6 0.8 0.9 0.9 0.9 0.9 1.0 0.7 0.9 1.0 1.1 0.8 1.0 1.0 0.8 0.9 Gavage ml Day 7 1.0 1.0 1.0 1.0 1.0 1.1 1.0 1.1 1.1 1.2 0.9 1.0 1.0 0.9 1.0 Gavage ml Day 8 1.0 1.0 1.0 1.0 1.0 1.1 1.0 1.1 1.1 1.2 0.9 1.0 1.0 0.9 1.0 Gavage ml Day 9 1.0 1.0 1.0 1.0 1.0 1.1 1.0 1.1 1.1 1.2 0.9 1.0 1.0 0.9 1.0 Gavage ml Day 10 1.0 1.0 1.0 1.0 1.0 1.1 1.0 1.1 1.1 1.2 0.9 1.0 1.0 0.9 1.0 Gavage ml Day 11 1. 0 1. 0 1. 0 1. 0 1. 0 1. 1 1. 0 1. 1 1. 1 1. 2 0. 9 1. 0 1. 0 0. 9 1. 0 - 352 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 12 Gavage ml D a y 13 Female, VI 5 mg/kg/day 655054 1.0 1.0 655038 1.0 1.0 655034 1.0 1.0 655039 1.0 1.0 655029 1.0 1.0 655067 1.1 1.1 655020 1.0 1.0 655087 1.1 1.1 655066 1.1 1.1 655042 1.2 1.2 655059 0.9 0.9 655064 1.0 1.0 655050 1.0 1.0 655021 0.9 0.9 655017 1.0 1.0 Gavage ml D a y 14 1.0 1.1 1.1 1.1 1.1 1.2 1.1 1.2 1.2 1.3 1.0 1.1 1.2 1.0 1.1 Gavage ml Day 15 1.0 1.1 1.1 1.1 1.1 1.2 1.1 1.2 1.2 1.3 1.0 1.1 1.2 1.0 1.1 Gavage ml D a y 16 1.0 1.1 1.1 1.1 1.1 1.2 1.1 1.2 1.2 1.3 1.0 1.1 1.2 1.0 1.1 Gavage ml Day 17 1.0 1.1 1.1 1.1 1.1 1.2 1.1 1.2 1.2 1.3 1.0 1.1 1.2 1.0 1.1 Gavage ml Day 18 1.0 1.1 1.1 1.1 1.1 1.2 1.1 1.2 1.2 1.3 1.0 1.1 1.2 1.0 1.1 Gavage ml Day 19 1.0 1.1 1.1 1.1 1.1 1.2 1.1 1.2 1.2 1.3 1.0 1.1 1.2 1.0 1.1 Gavage ml Day 20 1.0 1.1 1.1 1.1 1.1 1.2 1.1 1.2 1.2 1.3 1.0 1.1 1.2 1.0 1.1 Gavage ml Day 21 1.1 1.2 1.1 1.2 1.2 1.3 1.1 1.3 1.3 1.4 1.0 1.3 1.2 1.1 1.1 Gavage ml D a y 22 1.1 1.2 1.1 1.2 1.2 1.3 1.1 1.3 1.3 1.4 1.0 1.3 1.2 1.1 1.1 Gavage ml D a y 23 1. 1 1. 2 1. 1 1. 2 1. 2 1. 3 1. 1 1. 3 1. 3 1. 4 1. 0 1. 3 1. 2 1. 1 1. 1 - 353 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 24 Gavage ml Day 25 Female, VI 5 mg/kg/day 655054 1.1 1.1 655038 1.2 1.2 655034 1.1 1.1 655039 1.2 1.2 655029 1.2 1.2 655067 1.3 1.3 655020 1.1 1.1 655087 1.3 1.3 655066 1.3 1.3 655042 1.4 1.4 655059 1.0 1.0 655064 1.3 1.3 655050 1.2 1.2 655021 1.1 1.1 655017 1.1 1.1 Gavage ml D a y 26 1.1 1.2 1.1 1.2 1.2 1.3 1.1 1.3 1.3 1.4 1.0 1.3 1.2 1.1 1.1 Gavage ml Day 27 1.1 1.2 1.1 1.2 1.2 1.3 1.1 1.3 1.3 1.4 1.0 1.3 1.2 1.1 1.1 Gavage ml Day 28 1.2 1.2 1.2 1.2 1.3 1.4 1.2 1.3 1.4 1.4 1.1 1.3 1.3 1.2 1.2 Gavage ml Day 29 1.2 1.2 1.2 1.2 1.3 1.4 1.2 1.3 1.4 1.4 1.1 1.3 1.3 1.2 1.2 Gavage ml Day 30 1.2 1.2 1.2 1.2 1.3 1.4 1.2 1.3 1.4 1.4 1.1 1.3 1.3 1.2 1.2 Gavage ml Day 31 1.2 1.2 1.2 1.2 1.3 1.4 1.2 1.3 1.4 1.4 1.1 1.3 1.3 1.2 1.2 Gavage ml D a y 32 1.2 1.2 1.2 1.2 1.3 1.4 1.2 1.3 1.4 1.4 1.1 1.3 1.3 1.2 1.2 Gavage ml D a y 33 1.2 1.2 1.2 1.2 1.3 1.4 1.2 1.3 1.4 1.4 1.1 1.3 1.3 1.2 1.2 Gavage ml D a y 34 1.2 1.2 1.2 1.2 1.3 1.4 1.2 1.3 1.4 1.4 1.1 1.3 1.3 1.2 1.2 Gavage ml Day 35 1. 2 1. 3 1. 2 1. 3 1. 3 1. 4 1. 3 1. 4 1. 4 1. 6 1. 1 1. 4 1. 3 1. 2 1. 2 - 354 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 36 Gavage ml D a y 37 Female, VI 5 mg/kg/day 655054 1.2 1.2 655038 1.3 1.3 655034 1.2 1.2 655039 1.3 1.3 655029 1.3 1.3 655067 1.4 1.4 655020 1.3 1.3 655087 1.4 1.4 655066 1.4 1.4 655042 1.6 1.6 655059 1.1 1.1 655064 1.4 1.4 655050 1.3 1.3 655021 1.2 1.2 655017 1.2 1.2 Gavage ml D a y 38 1.2 1.3 1.2 1.3 1.3 1.4 1.3 1.4 1.4 1.6 1.1 1.4 1.3 1.2 1.2 Gavage ml Day 39 1.2 1.3 1.2 1.3 1.3 1.4 1.3 1.4 1.4 1.6 1.1 1.4 1.3 1.2 1.2 Gavage ml Day 40 1.2 1.3 1.2 1.3 1.3 1.4 1.3 1.4 1.4 1.6 1.1 1.4 1.3 1.2 1.2 Gavage ml Day 41 1.2 1.3 1.2 1.3 1.3 1.4 1.3 1.4 1.4 1.6 1.1 1.4 1.3 1.2 1.2 Gavage ml D a y 42 1.2 1.4 1.3 1.4 1.3 1.4 1.4 1.5 1.5 1.6 1.2 1.5 1.4 1.2 1.3 Gavage ml D a y 43 1.2 1.4 1.3 1.4 1.3 1.4 1.4 1.5 1.5 1.6 1.2 1.5 1.4 1.2 1.3 Gavage ml D a y 44 1.2 1.4 1.3 1.4 1.3 1.4 1.4 1.5 1.5 1.6 1.2 1.5 1.4 1.2 1.3 Gavage ml Day 45 1.2 1.4 1.3 1.4 1.3 1.4 1.4 1.5 1.5 1.6 1.2 1.5 1.4 1.2 1.3 Gavage ml D a y 46 1.2 1.4 1.3 1.4 1.3 1.4 1.4 1.5 1.5 1.6 1.2 1.5 1.4 1.2 1.3 Gavage ml Day 47 1. 2 1. 4 1. 3 1. 4 1. 3 1. 4 1. 4 1. 5 1. 5 1. 6 1. 2 1. 5 1. 4 1. 2 1. 3 - 355 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 48 Gavage ml Day 49 Female, VI 5 mg/kg/day 655054 1.2 1.2 655038 1.4 1.3 655034 1.3 1.2 655039 1.4 1.4 655029 1.3 1.3 655067 1.4 1.4 655020 1.4 1.4 655087 1.5 1.4 655066 1.5 1.4 655042 1.6 1.5 655059 1.2 1.2 655064 1.5 1.6 655050 1.4 1.4 655021 1.2 1.3 655017 1.3 1.3 Gavage ml D a y 50 1.2 1.3 1.2 1.4 1.3 1.4 1.4 1.4 1.4 1.5 1.2 1.6 1.4 1.3 1.3 Gavage ml Day 51 1.2 1.3 1.2 1.4 1.3 1.4 1.4 1.4 1.4 1.5 1.2 1.6 1.4 1.3 1.3 Gavage ml D a y 52 1.2 1.3 1.2 1.4 1.3 1.4 1.4 1.4 1.4 1.5 1.2 1.6 1.4 1.3 1.3 Gavage ml D a y 53 1.2 1.3 1.2 1.4 1.3 1.4 1.4 1.4 1.4 1.5 1.2 1.6 1.4 1.3 1.3 Gavage ml D a y 54 1.2 1.3 1.2 1.4 1.3 1.4 1.4 1.4 1.4 1.5 1.2 1.6 1.4 1.3 1.3 Gavage ml Day 55 1.2 1.3 1.2 1.4 1.3 1.4 1.4 1.4 1.4 1.5 1.2 1.6 1.4 1.3 1.3 Gavage ml D a y 56 1.3 1.4 1.3 1.5 1.4 1.5 1.4 1.5 1.5 1.7 1.2 1.6 1.4 1.3 1.3 Gavage ml Day 57 1.3 1.4 1.3 1.5 1.4 1.5 1.4 1.5 1.5 1.7 1.2 1.6 1.4 1.3 1.3 Gavage ml Day 58 1.3 1.4 1.3 1.5 1.4 1.5 1.4 1.5 1.5 1.7 1.2 1.6 1.4 1.3 1.3 Gavage ml Day 59 1. 3 1. 4 1. 3 1. 5 1. 4 1. 5 1. 4 1. 5 1. 5 1. 7 1. 2 1. 6 1. 4 1. 3 1. 3 - 356 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 60 Gavage ml D a y 61 Female, VI 5 mg/kg/day 655054 1.3 1.3 655038 1.4 1.4 655034 1.3 1.3 655039 1.5 1.5 655029 1.4 1.4 655067 1.5 1.5 655020 1.4 1.4 655087 1.5 1.5 655066 1.5 1.5 655042 1.7 1.7 655059 1.2 1.2 655064 1.6 1.6 655050 1.4 1.4 655021 1.3 1.3 655017 1.3 1.3 Gavage ml D a y 62 1.3 1.4 1.3 1.5 1.4 1.5 1.4 1.5 1.5 1.7 1.2 1.6 1.4 1.3 1.3 Gavage ml D a y 63 1.3 1.5 1.3 1.5 1.4 1.5 1.5 1.6 1.6 1.7 1.3 1.6 1.5 1.3 1.3 Gavage ml D a y 64 1.3 1.5 1.3 1.5 1.4 1.5 1.5 1.6 1.6 1.7 1.3 1.6 1.5 1.3 1.3 Gavage ml Day 65 1.3 1.5 1.3 1.5 1.4 1.5 1.5 1.6 1.6 1.7 1.3 1.6 1.5 1.3 1.3 Gavage ml D a y 66 1.3 1.5 1.3 1.5 1.4 1.5 1.5 1.6 1.6 1.7 1.3 1.6 1.5 1.3 1.3 Gavage ml Day 67 1.3 1.5 1.3 1.5 1.4 1.5 1.5 1.6 1.6 1.7 1.3 1.6 1.5 1.3 1.3 Gavage ml Day 68 1.3 1.5 1.3 1.5 1.4 1.5 1.5 1.6 1.6 1.7 1.3 1.6 1.5 1.3 1.3 Gavage ml Day 69 1.3 1.5 1.3 1.5 1.4 1.5 1.5 1.6 1.6 1.7 1.3 1.6 1.5 1.3 1.3 Gavage ml Day 70 1.3 1.5 1.4 1.6 1.4 1.6 1.5 1.6 1.5 1.7 1.3 1.6 1.5 1.4 1.4 Gavage ml Day 71 1. 3 1. 5 1. 4 1. 6 1. 4 1. 6 1. 5 1. 6 1. 5 1. 7 1. 3 1. 6 1. 5 1. 4 1. 4 - 357 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 72 Gavage ml D a y 73 Female, VI 5 mg/kg/day 655054 1.3 1.3 655038 1.5 1.5 655034 1.4 1.4 655039 1.6 1.6 655029 1.4 1.4 655067 1.6 1.6 655020 1.5 1.5 655087 1.6 1.6 655066 1.5 1.5 655042 1.7 1.7 655059 1.3 1.3 655064 1.6 1.6 655050 1.5 1.5 655021 1.4 1.4 655017 1.4 1.4 Gavage ml D a y 74 1.3 1.5 1.4 1.6 1.4 1.6 1.5 1.6 1.5 1.7 1.3 1.6 1.5 1.4 1.4 Gavage ml Day 75 1.3 1.5 1.4 1.6 1.4 1.6 1.5 1.6 1.5 1.7 1.3 1.6 1.5 1.4 1.4 Gavage ml D a y 76 1.3 1.5 1.4 1.6 1.4 1.6 1.5 1.6 1.5 1.7 1.3 1.6 1.5 1.4 1.4 Gavage ml Day 77 1.3 1.5 1.4 1.6 1.5 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml Day 78 1.3 1.5 1.4 1.6 1.5 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml Day 79 1.3 1.5 1.4 1.6 1.5 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml Day 80 1.3 1.5 1.4 1.6 1.5 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml Day 81 1.3 1.5 1.4 1.6 1.5 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml D a y 82 1.3 1.5 1.4 1.6 1.5 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml D a y 83 1. 3 1. 5 1. 4 1. 6 1. 5 1. 6 1. 5 1. 6 1. 6 1. 8 1. 3 1. 7 1. 5 1. 4 1. 4 - 358 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL DOSE VOLUMES Gavage ml D a y 84 Gavage ml D a y 85 Female, VI 5 mg/kg/day 655054 1.4 1.4 655038 1.5 1.5 655034 1.4 1.4 655039 1.6 1.6 655029 1.4 1.4 655067 1.6 1.6 655020 1.5 1.5 655087 1.6 1.6 655066 1.6 1.6 655042 1.8 1.8 655059 1.3 1.3 655064 1.7 1.7 655050 1.5 1.5 655021 1.4 1.4 655017 1.4 1.4 Gavage ml D a y 86 1.4 1.5 1.4 1.6 1.4 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml Day 87 1.4 1.5 1.4 1.6 1.4 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml Day 88 1.4 1.5 1.4 1.6 1.4 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml Day 89 1.4 1.5 1.4 1.6 1.4 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml D a y 90 1.4 1.5 1.4 1.6 1.4 1.6 1.5 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml D a y 91 1.3 1.5 1.4 1.5 1.5 1.6 1.6 1.6 1.6 1.8 1.3 1.7 1.5 1.4 1.4 Gavage ml D a y 92 1.3 1.5 1.4 1.5 1.5 1.6 1.6 1.6 1.6 1.8 Gavage ml D a y 93 1. 3 1. 5 1. 4 1. 5 1. 5 1. 6 1. 6 1. 6 1. 6 1. 8 DuPont-9478 - 359 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 0 Gavage ml Day 1 Female, VIII 25 mg/kg/day 655058 0.9 0.9 655076 0.9 0.9 655047 0.8 0.8 655055 0.9 0.9 655105 0.9 0.9 655078 1.0 1.0 655073 0.9 0.9 655011 0.9 0.9 655085 1.0 1.0 655012 1.0 1.0 655043 0.9 0.9 655082 1.0 1.0 655060 0.9 0.9 655056 0.8 0.8 655081 0.9 0.9 Gavage ml Day 2 0.9 0.9 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 0.9 1.0 0.9 0.8 0.9 Gavage ml Day 3 0.9 0.9 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 0.9 1.0 0.9 0.8 0.9 Gavage ml Day 4 0.9 0.9 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 0.9 1.0 0.9 0.8 0.9 Gavage ml Day 5 0.9 0.9 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 0.9 1.0 0.9 0.8 0.9 Gavage ml Day 6 0.9 0.9 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 0.9 1.0 0.9 0.8 0.9 Gavage ml Day 7 1.0 1.0 0.9 1.0 1.0 1.2 1.0 1.0 1.1 1.1 1.0 1.0 1.0 0.8 1.1 Gavage ml Day 8 1.0 1.0 0.9 1.0 1.0 1.2 1.0 1.0 1.1 1.1 1.0 1.0 1.0 0.8 1.1 Gavage ml Day 9 1.0 1.0 0.9 1.0 1.0 1.2 1.0 1.0 1.1 1.1 1.0 1.0 1.0 0.8 1.1 Gavage ml Day 10 1.0 1.0 0.9 1.0 1.0 1.2 1.0 1.0 1.1 1.1 1.0 1.0 1.0 0.8 1.1 Gavage ml Day 11 1. 0 1. 0 0. 9 1. 0 1. 0 1. 2 1. 0 1. 0 1. 1 1. 1 1. 0 1. 0 1. 0 0. 8 1. 1 - 360 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 12 Gavage ml D a y 13 Female, VIII 25 mg/kg/day 655058 1.0 1.0 655076 1.0 1.0 655047 0.9 0.9 655055 1.0 1.0 655105 1.0 1.0 655078 1.2 1.2 655073 1.0 1.0 655011 1.0 1.0 655085 1.1 1.1 655012 1.1 1.1 655043 1.0 1.0 655082 1.0 1.0 655060 1.0 1.0 655056 0.8 0.8 655081 1.1 1.1 Gavage ml D a y 14 1.1 1.1 1.0 1.1 1.1 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 1.0 1.1 Gavage ml Day 15 1.1 1.1 1.0 1.1 1.1 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 1.0 1.1 Gavage ml D a y 16 1.1 1.1 1.0 1.1 1.1 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 1.0 1.1 Gavage ml Day 17 1.1 1.1 1.0 1.1 1.1 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 1.0 1.1 Gavage ml Day 18 1.1 1.1 1.0 1.1 1.1 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 1.0 1.1 Gavage ml Day 19 1.1 1.1 1.0 1.1 1.1 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 1.0 1.1 Gavage ml Day 20 1.1 1.1 1.0 1.1 1.1 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 1.0 1.1 Gavage ml Day 21 1.2 1.2 1.1 1.2 1.1 1.3 1.2 1.2 1.3 1.3 1.1 1.2 1.2 1.0 1.3 Gavage ml D a y 22 1.2 1.2 1.1 1.2 1.1 1.3 1.2 1.2 1.3 1.3 1.1 1.2 1.2 1.0 1.3 Gavage ml D a y 23 1. 2 1. 2 1. 1 1. 2 1. 1 1. 3 1. 2 1. 2 1. 3 1. 3 1. 1 1. 2 1. 2 1. 0 1. 3 - 361 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 24 Gavage ml Day 25 Female, VIII 25 mg/kg/day 655058 1.2 1.2 655076 1.2 1.2 655047 1.1 1.1 655055 1.2 1.2 655105 1.1 1.1 655078 1.3 1.3 655073 1.2 1.2 655011 1.2 1.2 655085 1.3 1.3 655012 1.3 1.3 655043 1.1 1.1 655082 1.2 1.2 655060 1.2 1.2 655056 1.0 1.0 655081 1.3 1.3 Gavage ml D a y 26 1.2 1.2 1.1 1.2 1.1 1.3 1.2 1.2 1.3 1.3 1.1 1.2 1.2 1.0 1.3 Gavage ml Day 27 1.2 1.2 1.1 1.2 1.1 1.3 1.2 1.2 1.3 1.3 1.1 1.2 1.2 1.0 1.3 Gavage ml Day 28 1.2 1.2 1.1 1.2 1.1 1.4 1.3 1.3 1.4 1.3 1.2 1.3 1.3 1.1 1.3 Gavage ml Day 29 1.2 1.2 1.1 1.2 1.1 1.4 1.3 1.3 1.4 1.3 1.2 1.3 1.3 1.1 1.3 Gavage ml Day 30 1.2 1.2 1.1 1.2 1.1 1.4 1.3 1.3 1.4 1.3 1.2 1.3 1.3 1.1 1.3 Gavage ml Day 31 1.2 1.2 1.1 1.2 1.1 1.4 1.3 1.3 1.4 1.3 1.2 1.3 1.3 1.1 1.3 Gavage ml D a y 32 1.2 1.2 1.1 1.2 1.1 1.4 1.3 1.3 1.4 1.3 1.2 1.3 1.3 1.1 1.3 Gavage ml D a y 33 1.2 1.2 1.1 1.2 1.1 1.4 1.3 1.3 1.4 1.3 1.2 1.3 1.3 1.1 1.3 Gavage ml D a y 34 1.2 1.2 1.1 1.2 1.1 1.4 1.3 1.3 1.4 1.3 1.2 1.3 1.3 1.1 1.3 Gavage ml Day 35 1. 3 1. 3 1. 2 1. 3 1. 2 1. 5 1. 3 1. 3 1. 5 1. 4 1. 2 1. 4 1. 3 1. 2 1. 4 - 362 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 36 Gavage ml D a y 37 Female, VIII 25 mg/kg/day 655058 1.3 1.3 655076 1.3 1.3 655047 1.2 1.2 655055 1.3 1.3 655105 1.2 1.2 655078 1.5 1.5 655073 1.3 1.3 655011 1.3 1.3 655085 1.5 1.5 655012 1.4 1.4 655043 1.2 1.2 655082 1.4 1.4 655060 1.3 1.3 655056 1.2 1.2 655081 1.4 1.4 Gavage ml D a y 38 1.3 1.3 1.2 1.3 1.2 1.5 1.3 1.3 1.5 1.4 1.2 1.4 1.3 1.2 1.4 Gavage ml Day 39 1.3 1.3 1.2 1.3 1.2 1.5 1.3 1.3 1.5 1.4 1.2 1.4 1.3 1.2 1.4 Gavage ml Day 40 1.3 1.3 1.2 1.3 1.2 1.5 1.3 1.3 1.5 1.4 1.2 1.4 1.3 1.2 1.4 Gavage ml Day 41 1.3 1.3 1.2 1.3 1.2 1.5 1.3 1.3 1.5 1.4 1.2 1.4 1.3 1.2 1.4 Gavage ml D a y 42 1.4 1.4 1.3 1.4 1.3 1.6 1.4 1.4 1.5 1.4 1.3 1.5 1.4 1.2 1.4 Gavage ml D a y 43 1.4 1.4 1.3 1.4 1.3 1.6 1.4 1.4 1.5 1.4 1.3 1.5 1.4 1.2 1.4 Gavage ml D a y 44 1.4 1.4 1.3 1.4 1.3 1.6 1.4 1.4 1.5 1.4 1.3 1.5 1.4 1.2 1.4 Gavage ml Day 45 1.4 1.4 1.3 1.4 1.3 1.6 1.4 1.4 1.5 1.4 1.3 1.5 1.4 1.2 1.4 Gavage ml D a y 46 1.4 1.4 1.3 1.4 1.3 1.6 1.4 1.4 1.5 1.4 1.3 1.5 1.4 1.2 1.4 Gavage ml Day 47 1. 4 1. 4 1. 3 1. 4 1. 3 1. 6 1. 4 1. 4 1. 5 1. 4 1. 3 1. 5 1. 4 1. 2 1. 4 - 363 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 48 Gavage ml Day 49 Female, VIII 25 mg/kg/day 655058 1.4 1.3 655076 1.4 1.3 655047 1.3 1.2 655055 1.4 1.3 655105 1.3 1.2 655078 1.6 1.6 655073 1.4 1.3 655011 1.4 1.3 655085 1.5 1.5 655012 1.4 1.4 655043 1.3 1.2 655082 1.5 1.5 655060 1.4 1.5 655056 1.2 1.2 655081 1.4 1.5 Gavage ml D a y 50 1.3 1.3 1.2 1.3 1.2 1.6 1.3 1.3 1.5 1.4 1.2 1.5 1.5 1.2 1.5 Gavage ml Day 51 1.3 1.3 1.2 1.3 1.2 1.6 1.3 1.3 1.5 1.4 1.2 1.5 1.5 1.2 1.5 Gavage ml D a y 52 1.3 1.3 1.2 1.3 1.2 1.6 1.3 1.3 1.5 1.4 1.2 1.5 1.5 1.2 1.5 Gavage ml D a y 53 1.3 1.3 1.2 1.3 1.2 1.6 1.3 1.3 1.5 1.4 1.2 1.5 1.5 1.2 1.5 Gavage ml D a y 54 1.3 1.3 1.2 1.3 1.2 1.6 1.3 1.3 1.5 1.4 1.2 1.5 1.5 1.2 1.5 Gavage ml Day 55 1.3 1.3 1.2 1.3 1.2 1.6 1.3 1.3 1.5 1.4 1.2 1.5 1.5 1.2 1.5 Gavage ml D a y 56 1.4 1.4 1.3 1.4 1.4 1.8 1.4 1.5 1.6 1.5 1.3 1.5 1.6 1.3 1.6 Gavage ml Day 57 1.4 1.4 1.3 1.4 1.4 1.8 1.4 1.5 1.6 1.5 1.3 1.5 1.6 1.3 1.6 Gavage ml Day 58 1.4 1.4 1.3 1.4 1.4 1.8 1.4 1.5 1.6 1.5 1.3 1.5 1.6 1.3 1.6 Gavage ml Day 59 1. 4 1. 4 1. 3 1. 4 1. 4 1. 8 1. 4 1. 5 1. 6 1. 5 1. 3 1. 5 1. 6 1. 3 1. 6 - 364 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 60 Gavage ml D a y 61 Female, VIII 25 mg/kg/day 655058 1.4 1.4 655076 1.4 1.4 655047 1.3 1.3 655055 1.4 1.4 655105 1.4 1.4 655078 1.8 1.8 655073 1.4 1.4 655011 1.5 1.5 655085 1.6 1.6 655012 1.5 1.5 655043 1.3 1.3 655082 1.5 1.5 655060 1.6 1.6 655056 1.3 1.3 655081 1.6 1.6 Gavage ml D a y 62 1.4 1.4 1.3 1.4 1.4 1.8 1.4 1.5 1.6 1.5 1.3 1.5 1.6 1.3 1.6 Gavage ml D a y 63 1.4 1.4 1.3 1.4 1.4 1.7 1.5 1.5 1.6 1.5 1.3 1.6 1.6 1.3 1.6 Gavage ml D a y 64 1.4 1.4 1.3 1.4 1.4 1.7 1.5 1.5 1.6 1.5 1.3 1.6 1.6 1.3 1.6 Gavage ml Day 65 1.4 1.4 1.3 1.4 1.4 1.7 1.5 1.5 1.6 1.5 1.3 1.6 1.6 1.3 1.6 Gavage ml D a y 66 1.4 1.4 1.3 1.4 1.4 1.7 1.5 1.5 1.6 1.5 1.3 1.6 1.6 1.3 1.6 Gavage ml Day 67 1.4 1.4 1.3 1.4 1.4 1.7 1.5 1.5 1.6 1.5 1.3 1.6 1.6 1.3 1.6 Gavage ml Day 68 1.4 1.4 1.3 1.4 1.4 1.7 1.5 1.5 1.6 1.5 1.3 1.6 1.6 1.3 1.6 Gavage ml Day 69 1.4 1.4 1.3 1.4 1.4 1.7 1.5 1.5 1.6 1.5 1.3 1.6 1.6 1.3 1.6 Gavage ml Day 70 1.4 1.5 1.4 1.5 1.4 1.8 1.5 1.5 1.7 1.6 1.3 1.6 1.6 1.4 1.6 Gavage ml Day 71 1. 4 1. 5 1. 4 1. 5 1. 4 1. 8 1. 5 1. 5 1. 7 1. 6 1. 3 1. 6 1. 6 1. 4 1. 6 - 365 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 72 Gavage ml D a y 73 Female, VIII 25 mg/kg/day 655058 1.4 1.4 655076 1.5 1.5 655047 1.4 1.4 655055 1.5 1.5 655105 1.4 1.4 655078 1.8 1.8 655073 1.5 1.5 655011 1.5 1.5 655085 1.7 1.7 655012 1.6 1.6 655043 1.3 1.3 655082 1.6 1.6 655060 1.6 1.6 655056 1.4 1.4 655081 1.6 1.6 Gavage ml D a y 74 1.4 1.5 1.4 1.5 1.4 1.8 1.5 1.5 1.7 1.6 1.3 1.6 1.6 1.4 1.6 Gavage ml Day 75 1.4 1.5 1.4 1.5 1.4 1.8 1.5 1.5 1.7 1.6 1.3 1.6 1.6 1.4 1.6 Gavage ml D a y 76 1.4 1.5 1.4 1.5 1.4 1.8 1.5 1.5 1.7 1.6 1.3 1.6 1.6 1.4 1.6 Gavage ml Day 77 1.5 1.5 1.4 1.5 1.4 1.9 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml Day 78 1.5 1.5 1.4 1.5 1.4 1.9 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml Day 79 1.5 1.5 1.4 1.5 1.4 1.9 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml Day 80 1.5 1.5 1.4 1.5 1.4 1.9 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml Day 81 1.5 1.5 1.4 1.5 1.4 1.9 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml D a y 82 1.5 1.5 1.4 1.5 1.4 1.9 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml D a y 83 1. 5 1. 5 1. 4 1. 5 1. 4 1. 9 1. 6 1. 6 1. 7 1. 6 1. 4 1. 6 1. 7 1. 4 1. 7 - 366 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL DOSE VOLUMES Gavage ml D a y 84 Gavage ml D a y 85 Female, VIII 25 mg/kg/day 655058 1.5 1.5 655076 1.5 1.5 655047 1.4 1.4 655055 1.4 1.4 655105 1.4 1.4 655078 1.8 1.8 655073 1.6 1.6 655011 1.6 1.6 655085 1.7 1.7 655012 1.6 1.6 655043 1.4 1.4 655082 1.6 1.6 655060 1.7 1.7 655056 1.4 1.4 655081 1.7 1.7 Gavage ml D a y 86 1.5 1.5 1.4 1.4 1.4 1.8 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml Day 87 1.5 1.5 1.4 1.4 1.4 1.8 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml Day 88 1.5 1.5 1.4 1.4 1.4 1.8 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml Day 89 1.5 1.5 1.4 1.4 1.4 1.8 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml D a y 90 1.5 1.5 1.4 1.4 1.4 1.8 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml D a y 91 1.5 1.5 1.3 1.5 1.4 1.8 1.6 1.6 1.7 1.6 1.4 1.6 1.7 1.4 1.7 Gavage ml D a y 92 1.5 1.5 1.3 1.5 1.4 1.8 1.6 1.6 1.7 1.6 Gavage ml D a y 93 1. 5 1. 5 1. 3 1. 5 1. 4 1. 8 1. 6 1. 6 1. 7 1. 6 DuPont-9478 - 367 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 0 Gavage ml Day 1 Female, X 125 mg/kg/day 655097 0.9 0.9 655052 1.0 1.0 655063 0.8 0.8 655103 0.9 0.9 655026 0.9 0.9 655095 1.0 1.0 655023 0.9 0.9 655007 0.9 0.9 655053 1.0 1.0 655092 1.0 1.0 655046 0.9 0.9 655027 1.0 1.0 655104 0.9 0.9 655106 0.8 0.8 655024 1.0 1.0 655037 0.9 0.9 655088 1.0 1.0 655010 1.0 1.0 655077 1.0 1.0 655030 1.0 1.0 655075 1.0 1.0 655100 1.1 1.1 655049 0.8 0.8 655084 0.8 0.8 655061 0.8 0.8 Gavage ml Day 2 0.9 1.0 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 0.9 1.0 0.9 0.8 1.0 0.9 1.0 1.0 1.0 1.0 1.0 1.1 0.8 0.8 0.8 Gavage ml Day 3 0.9 1.0 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 0.9 1.0 0.9 0.8 1.0 0.9 1.0 1.0 1.0 1.0 1.0 1.1 0.8 0.8 0.8 Gavage ml Day 4 0.9 1.0 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 0.9 1.0 0.9 0.8 1.0 0.9 1.0 1.0 1.0 1.0 1.0 1.1 0.8 0.8 0.8 Gavage ml Day 5 0.9 1.0 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 0.9 1.0 0.9 0.8 1.0 0.9 1.0 1.0 1.0 1.0 1.0 1.1 0.8 0.8 0.8 Gavage ml Day 6 0.9 1.0 0.8 0.9 0.9 1.0 0.9 0.9 1.0 1.0 0.9 1.0 0.9 0.8 1.0 0.9 1.0 1.0 1.0 1.0 1.0 1.1 0.8 0.8 0.8 Gavage ml Day 7 1.0 1.1 0.9 1.1 1.1 1.1 1.0 1.0 1.1 1.1 1.0 1.1 1.0 0.8 1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.2 0.9 1.0 0.9 Gavage ml Day 8 1.0 1.1 0.9 1.1 1.1 1.1 1.0 1.0 1.1 1.1 1.0 1.1 1.0 0.8 1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.2 0.9 1.0 0.9 Gavage ml Day 9 1.0 1.1 0.9 1.1 1.1 1.1 1.0 1.0 1.1 1.1 1.0 1.1 1.0 0.8 1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.2 0.9 1.0 0.9 Gavage ml Day 10 1.0 1.1 0.9 1.1 1.1 1.1 1.0 1.0 1.1 1.1 1.0 1.1 1.0 0.8 1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.2 0.9 1.0 0.9 Gavage ml Day 11 1. 0 1. 1 0. 9 1. 1 1. 1 1. 1 1. 0 1. 0 1. 1 1. 1 1. 0 1. 1 1. 0 0. 8 1. 1 1. 1 1. 1 1. 1 1. 1 1. 1 1. 1 1. 2 0. 9 1. 0 0. 9 - 368 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 12 Gavage ml D a y 13 Female, X 125 mg/kg/day 655097 1.0 1.0 655052 1.1 1.1 655063 0.9 0.9 655103 1.1 1.1 655026 1.1 1.1 655095 1.1 1.1 655023 1.0 1.0 655007 1.0 1.0 655053 1.1 1.1 655092 1.1 1.1 655046 1.0 1.0 655027 1.1 1.1 655104 1.0 1.0 655106 0.8 0.8 655024 1.1 1.1 655037 1.1 1.1 655088 1.1 1.1 655010 1.1 1.1 655077 1.1 1.1 655030 1.1 1.1 655075 1.1 1.1 655100 1.2 1.2 655049 0.9 0.9 655084 1.0 1.0 655061 0.9 0.9 Gavage ml D a y 14 1.1 1.1 1.0 1.2 1.2 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 0.9 1.2 1.2 1.2 1.2 1.1 1.3 1.2 1.3 1.0 1.1 1.0 Gavage ml Day 15 1.1 1.1 1.0 1.2 1.2 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 0.9 1.2 1.2 1.2 1.2 1.1 1.3 1.2 1.3 1.0 1.1 1.0 Gavage ml D a y 16 1.1 1.1 1.0 1.2 1.2 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 0.9 1.2 1.2 1.2 1.2 1.1 1.3 1.2 1.3 1.0 1.1 1.0 Gavage ml Day 17 1.1 1.1 1.0 1.2 1.2 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 0.9 1.2 1.2 1.2 1.2 1.1 1.3 1.2 1.3 1.0 1.1 1.0 Gavage ml Day 18 1.1 1.1 1.0 1.2 1.2 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 0.9 1.2 1.2 1.2 1.2 1.1 1.3 1.2 1.3 1.0 1.1 1.0 Gavage ml Day 19 1.1 1.1 1.0 1.2 1.2 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 0.9 1.2 1.2 1.2 1.2 1.1 1.3 1.2 1.3 1.0 1.1 1.0 Gavage ml Day 20 1.1 1.1 1.0 1.2 1.2 1.3 1.1 1.1 1.2 1.2 1.1 1.2 1.1 0.9 1.2 1.2 1.2 1.2 1.1 1.3 1.2 1.3 1.0 1.1 1.0 Gavage ml Day 21 1.2 1.2 1.1 1.3 1.3 1.4 1.2 1.1 1.3 1.3 1.2 1.3 1.2 1.0 1.3 1.3 1.3 1.3 1.3 1.4 1.4 1.4 1.1 1.2 1.2 Gavage ml D a y 22 1.2 1.2 1.1 1.3 1.3 1.4 1.2 1.1 1.3 1.3 1.2 1.3 1.2 1.0 1.3 1.3 1.3 1.3 1.3 1.4 1.4 1.4 1.1 1.2 1.2 Gavage ml D a y 23 1. 2 1. 2 1. 1 1. 3 1. 3 1. 4 1. 2 1. 1 1. 3 1. 3 1. 2 1. 3 1. 2 1. 0 1. 3 1. 3 1. 3 1. 3 1. 3 1. 4 1. 4 1. 4 1. 1 1. 2 1. 2 - 369 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 24 Gavage ml Day 25 Female, X 125 mg/kg/day 655097 1.2 1.2 655052 1.2 1.2 655063 1.1 1.1 655103 1.3 1.3 655026 1.3 1.3 655095 1.4 1.4 655023 1.2 1.2 655007 1.1 1.1 655053 1.3 1.3 655092 1.3 1.3 655046 1.2 1.2 655027 1.3 1.3 655104 1.2 1.2 655106 1.0 1.0 655024 1.3 1.3 655037 1.3 1.3 655088 1.3 1.3 655010 1.3 1.3 655077 1.3 1.3 655030 1.4 1.4 655075 1.4 1.4 655100 1.4 1.4 655049 1.1 1.1 655084 1.2 1.2 655061 1.2 1.2 Gavage ml D a y 26 1.2 1.2 1.1 1.3 1.3 1.4 1.2 1.1 1.3 1.3 1.2 1.3 1.2 1.0 1.3 1.3 1.3 1.3 1.3 1.4 1.4 1.4 1.1 1.2 1.2 Gavage ml Day 27 1.2 1.2 1.1 1.3 1.3 1.4 1.2 1.1 1.3 1.3 1.2 1.3 1.2 1.0 1.3 1.3 1.3 1.3 1.3 1.4 1.4 1.4 1.1 1.2 1.2 Gavage ml Day 28 1.2 1.2 1.1 1.4 1.3 1.4 1.3 1.2 1.4 1.4 1.3 1.4 1.3 1.0 1.3 1.4 1.4 1.3 1.3 1.5 1.4 1.5 1.1 1.2 1.2 Gavage ml Day 29 1.2 1.2 1.1 1.4 1.3 1.4 1.3 1.2 1.4 1.4 1.3 1.4 1.3 1.0 1.3 1.4 1.4 1.3 1.3 1.5 1.4 1.5 1.1 1.2 1.2 Gavage ml Day 30 1.2 1.2 1.1 1.4 1.3 1.4 1.3 1.2 1.4 1.4 1.3 1.4 1.3 1.0 1.3 1.4 1.4 1.3 1.3 1.5 1.4 1.5 1.1 1.2 1.2 Gavage ml Day 31 1.2 1.2 1.1 1.4 1.3 1.4 1.3 1.2 1.4 1.4 1.3 1.4 1.3 1.0 1.3 1.4 1.4 1.3 1.3 1.5 1.4 1.5 1.1 1.2 1.2 Gavage ml D a y 32 1.2 1.2 1.1 1.4 1.3 1.4 1.3 1.2 1.4 1.4 1.3 1.4 1.3 1.0 1.3 1.4 1.4 1.3 1.3 1.5 1.4 1.5 1.1 1.2 1.2 Gavage ml D a y 33 1.2 1.2 1.1 1.4 1.3 1.4 1.3 1.2 1.4 1.4 1.3 1.4 1.3 1.0 1.3 1.4 1.4 1.3 1.3 1.5 1.4 1.5 1.1 1.2 1.2 Gavage ml D a y 34 1.2 1.2 1.1 1.4 1.3 1.4 1.3 1.2 1.4 1.4 1.3 1.4 1.3 1.0 1.3 1.4 1.4 1.3 1.3 1.5 1.4 1.5 1.1 1.2 1.2 Gavage ml Day 35 1. 3 1. 3 1. 1 1. 4 1. 4 1. 4 1. 3 1. 3 1. 4 1. 4 1. 4 1. 4 1. 4 1. 1 1. 4 1. 4 1. 4 1. 4 1. 4 1. 5 1. 5 1. 5 1. 1 1. 2 1. 2 - 370 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 36 Gavage ml D a y 37 Female, X 125 mg/kg/day 655097 1.3 1.3 655052 1.3 1.3 655063 1.1 1.1 655103 1.4 1.4 655026 1.4 1.4 655095 1.4 1.4 655023 1.3 1.3 655007 1.3 1.3 655053 1.4 1.4 655092 1.4 1.4 655046 1.4 1.4 655027 1.4 1.4 655104 1.4 1.4 655106 1.1 1.1 655024 1.4 1.4 655037 1.4 1.4 655088 1.4 1.4 655010 1.4 1.4 655077 1.4 1.4 655030 1.5 1.5 655075 1.5 1.5 655100 1.5 1.5 655049 1.1 1.1 655084 1.2 1.2 655061 1.2 1.2 Gavage ml D a y 38 1.3 1.3 1.1 1.4 1.4 1.4 1.3 1.3 1.4 1.4 1.4 1.4 1.4 1.1 1.4 1.4 1.4 1.4 1.4 1.5 1.5 1.5 1.1 1.2 1.2 Gavage ml Day 39 1.3 1.3 1.1 1.4 1.4 1.4 1.3 1.3 1.4 1.4 1.4 1.4 1.4 1.1 1.4 1.4 1.4 1.4 1.4 1.5 1.5 1.5 1.1 1.2 1.2 Gavage ml Day 40 1.3 1.3 1.1 1.4 1.4 1.4 1.3 1.3 1.4 1.4 1.4 1.4 1.4 1.1 1.4 1.4 1.4 1.4 1.4 1.5 1.5 1.5 1.1 1.2 1.2 Gavage ml Day 41 1.3 1.3 1.1 1.4 1.4 1.4 1.3 1.3 1.4 1.4 1.4 1.4 1.4 1.1 1.4 1.4 1.4 1.4 1.4 1.5 1.5 1.5 1.1 1.2 1.2 Gavage ml D a y 42 1.3 1.4 1.2 1.4 1.4 1.5 1.4 1.3 1.4 1.5 1.4 1.4 1.4 1.1 1.4 1.5 1.5 1.4 1.4 1.5 1.6 1.6 1.1 1.3 1.3 Gavage ml D a y 43 1.3 1.4 1.2 1.4 1.4 1.5 1.4 1.3 1.4 1.5 1.4 1.4 1.4 1.1 1.4 1.5 1.5 1.4 1.4 1.5 1.6 1.6 1.1 1.3 1.3 Gavage ml D a y 44 1.3 1.4 1.2 1.4 1.4 1.5 1.4 1.3 1.4 1.5 1.4 1.4 1.4 1.1 1.4 1.5 1.5 1.4 1.4 1.5 1.6 1.6 1.1 1.3 1.3 Gavage ml Day 45 1.3 1.4 1.2 1.4 1.4 1.5 1.4 1.3 1.4 1.5 1.4 1.4 1.4 1.1 1.4 1.5 1.5 1.4 1.4 1.5 1.6 1.6 1.1 1.3 1.3 Gavage ml D a y 46 1.3 1.4 1.2 1.4 1.4 1.5 1.4 1.3 1.4 1.5 1.4 1.4 1.4 1.1 1.4 1.5 1.5 1.4 1.4 1.5 1.6 1.6 1.1 1.3 1.3 Gavage ml Day 47 1. 3 1. 4 1. 2 1. 4 1. 4 1. 5 1. 4 1. 3 1. 4 1. 5 1. 4 1. 4 1. 4 1. 1 1. 4 1. 5 1. 5 1. 4 1. 4 1. 5 1. 6 1. 6 1. 1 1. 3 1. 3 - 371 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 48 Gavage ml Day 49 Female, X 125 mg/kg/day 655097 1.3 1.3 655052 1.4 1.3 655063 1.2 1.1 655103 1.4 1.4 655026 1.4 1.4 655095 1.5 1.5 655023 1.4 1.4 655007 1.3 1.3 655053 1.4 1.4 655092 1.5 1.4 655046 1.4 1.5 655027 1.4 1.5 655104 1.4 1.4 655106 1.1 1.1 655024 1.4 1.5 655037 1.5 1.5 655088 1.5 1.6 655010 1.4 1.5 655077 1.4 1.4 655030 1.5 1.6 655075 1.6 1.7 655100 1.6 1.6 655049 1.1 1.1 655084 1.3 1.3 655061 1.3 1.3 Gavage ml D a y 50 1.3 1.3 1.1 1.4 1.4 1.5 1.4 1.3 1.4 1.4 1.5 1.5 1.4 1.1 1.5 1.5 1.6 1.5 1.4 1.6 1.7 1.6 1.1 1.3 1.3 Gavage ml Day 51 1.3 1.3 1.1 1.4 1.4 1.5 1.4 1.3 1.4 1.4 1.5 1.5 1.4 1.1 1.5 1.5 1.6 1.5 1.4 1.6 1.7 1.6 1.1 1.3 1.3 Gavage ml D a y 52 1.3 1.3 1.1 1.4 1.4 1.5 1.4 1.3 1.4 1.4 1.5 1.5 1.4 1.1 1.5 1.5 1.6 1.5 1.4 1.6 1.7 1.6 1.1 1.3 1.3 Gavage ml D a y 53 1.3 1.3 1.1 1.4 1.4 1.5 1.4 1.3 1.4 1.4 1.5 1.5 1.4 1.1 1.5 1.5 1.6 1.5 1.4 1.6 1.7 1.6 1.1 1.3 1.3 Gavage ml D a y 54 1.3 1.3 1.1 1.4 1.4 1.5 1.4 1.3 1.4 1.4 1.5 1.5 1.4 1.1 1.5 1.5 1.6 1.5 1.4 1.6 1.7 1.6 1.1 1.3 1.3 Gavage ml Day 55 1.3 1.3 1.1 1.4 1.4 1.5 1.4 1.3 1.4 1.4 1.5 1.5 1.4 1.1 1.5 1.5 1.6 1.5 1.4 1.6 1.7 1.6 1.1 1.3 1.3 Gavage ml D a y 56 1.4 1.4 1.2 1.5 1.4 1.6 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.4 1.1 1.3 1.4 Gavage ml Day 57 1.4 1.4 1.2 1.5 1.4 1.6 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.4 1.1 1.3 1.4 Gavage ml Day 58 1.4 1.4 1.2 1.5 1.4 1.6 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.4 1.1 1.3 1.4 Gavage ml Day 59 1. 4 1. 4 1. 2 1. 5 1. 4 1. 6 1. 4 1. 4 1. 6 1. 5 1. 6 1. 5 1. 5 1. 1 1. 5 1. 6 1. 6 1. 5 1. 5 1. 7 1. 8 1. 4 1. 1 1. 3 1. 4 - 372 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml Day 60 Gavage ml D a y 61 Female, X 125 mg/kg/day 655097 1.4 1.4 655052 1.4 1.4 655063 1.2 1.2 655103 1.5 1.5 655026 1.4 1.4 655095 1.6 1.6 655023 1.4 1.4 655007 1.4 1.4 655053 1.6 1.6 655092 1.5 1.5 655046 1.6 1.6 655027 1.5 1.5 655104 1.5 1.5 655106 1.1 1.1 655024 1.5 1.5 655037 1.6 1.6 655088 1.6 1.6 655010 1.5 1.5 655077 1.5 1.5 655030 1.7 1.7 655075 1.8 1.8 655100 1.4 1.4 655049 1.1 1.1 655084 1.3 1.3 655061 1.4 1.4 Gavage ml D a y 62 1.4 1.4 1.2 1.5 1.4 1.6 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.4 1.1 1.3 1.4 Gavage ml D a y 63 1.5 1.4 1.2 1.5 1.5 1.7 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.6 1.2 1.3 1.4 Gavage ml D a y 64 1.5 1.4 1.2 1.5 1.5 1.7 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.6 1.2 1.3 1.4 Gavage ml Day 65 1.5 1.4 1.2 1.5 1.5 1.7 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.6 1.2 1.3 1.4 Gavage ml D a y 66 1.5 1.4 1.2 1.5 1.5 1.7 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.6 1.2 1.3 1.4 Gavage ml Day 67 1.5 1.4 1.2 1.5 1.5 1.7 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.6 1.2 1.3 1.4 Gavage ml Day 68 1.5 1.4 1.2 1.5 1.5 1.7 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.6 1.2 1.3 1.4 Gavage ml Day 69 1.5 1.4 1.2 1.5 1.5 1.7 1.4 1.4 1.6 1.5 1.6 1.5 1.5 1.1 1.5 1.6 1.6 1.5 1.5 1.7 1.8 1.6 1.2 1.3 1.4 Gavage ml Day 70 1.5 1.4 1.3 1.5 1.5 1.7 1.5 1.4 1.6 1.5 1.6 1.5 1.6 1.2 1.6 1.6 1.6 1.5 1.4 1.6 1.8 1.6 1.2 1.4 1.4 Gavage ml Day 71 1. 5 1. 4 1. 3 1. 5 1. 5 1. 7 1. 5 1. 4 1. 6 1. 5 1. 6 1. 5 1. 6 1. 2 1. 6 1. 6 1. 6 1. 5 1. 4 1. 6 1. 8 1. 6 1. 2 1. 4 1. 4 - 373 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL DOSE VOLUMES Gavage ml D a y 72 Gavage ml D a y 73 Female, X 125 mg/kg/day 655097 1.5 1.5 655052 1.4 1.4 655063 1.3 1.3 655103 1.5 1.5 655026 1.5 1.5 655095 1.7 1.7 655023 1.5 1.5 655007 1.4 1.4 655053 1.6 1.6 655092 1.5 1.5 655046 1.6 1.6 655027 1.5 1.5 655104 1.6 1.6 655106 1.2 1.2 655024 1.6 1.6 655037 1.6 1.6 655088 1.6 1.6 655010 1.5 1.5 655077 1.4 1.4 655030 1.6 1.6 655075 1.8 1.8 655100 1.6 1.6 655049 1.2 1.2 655084 1.4 1.4 655061 1.4 1.4 Gavage ml D a y 74 1.5 1.4 1.3 1.5 1.5 1.7 1.5 1.4 1.6 1.5 1.6 1.5 1.6 1.2 1.6 1.6 1.6 1.5 1.4 1.6 1.8 1.6 1.2 1.4 1.4 Gavage ml Day 75 1.5 1.4 1.3 1.5 1.5 1.7 1.5 1.4 1.6 1.5 1.6 1.5 1.6 1.2 1.6 1.6 1.6 1.5 1.4 1.6 1.8 1.6 1.2 1.4 1.4 Gavage ml D a y 76 1.5 1.4 1.3 1.5 1.5 1.7 1.5 1.4 1.6 1.5 1.6 1.5 1.6 1.2 1.6 1.6 1.6 1.5 1.4 1.6 1.8 1.6 1.2 1.4 1.4 Gavage ml Day 77 1.5 1.4 1.3 1.5 1.5 1.7 1.5 1.5 1.6 1.5 1.7 1.5 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.7 1.8 1.7 1.2 1.4 1.5 Gavage ml Day 78 1.5 1.4 1.3 1.5 1.5 1.7 1.5 1.5 1.6 1.5 1.7 1.5 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.7 1.8 1.7 1.2 1.4 1.5 Gavage ml Day 79 1.5 1.4 1.3 1.5 1.5 1.7 1.5 1.5 1.6 1.5 1.7 1.5 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.7 1.8 1.7 1.2 1.4 1.5 Gavage ml Day 80 1.5 1.4 1.3 1.5 1.5 1.7 1.5 1.5 1.6 1.5 1.7 1.5 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.7 1.8 1.7 1.2 1.4 1.5 Gavage ml Day 81 1.5 1.4 1.3 1.5 1.5 1.7 1.5 1.5 1.6 1.5 1.7 1.5 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.7 1.8 1.7 1.2 1.4 1.5 Gavage ml D a y 82 1.5 1.4 1.3 1.5 1.5 1.7 1.5 1.5 1.6 1.5 1.7 1.5 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.7 1.8 1.7 1.2 1.4 1.5 Gavage ml D a y 83 1. 5 1. 4 1. 3 1. 5 1. 5 1. 7 1. 5 1. 5 1. 6 1. 5 1. 7 1. 5 1. 6 1. 2 1. 6 1. 7 1. 6 1. 5 1. 5 1. 7 1. 8 1. 7 1. 2 1. 4 1. 5 - 374 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL DOSE VOLUMES Gavage ml D a y 84 Gavage ml D a y 85 Female, X 125 mg/kg/day 655097 1.6 1.6 655052 1.5 1.5 655063 1.3 1.3 655103 1.6 1.6 655026 1.5 1.5 655095 1.7 1.7 655023 1.5 1.5 655007 1.5 1.5 655053 1.7 1.7 655092 1.6 1.6 655046 1.7 1.7 655027 1.6 1.6 655104 1.6 1.6 655106 1.2 1.2 655024 1.6 1.6 655037 1.7 1.7 655088 1.6 1.6 655010 1.5 1.5 655077 1.5 1.5 655030 1.8 1.8 655075 1.9 1.9 655100 1.7 1.7 655049 1.2 1.2 655084 1.5 1.5 655061 1.4 1.4 Gavage ml D a y 86 1.6 1.5 1.3 1.6 1.5 1.7 1.5 1.5 1.7 1.6 1.7 1.6 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.8 1.9 1.7 1.2 1.5 1.4 Gavage ml Day 87 1.6 1.5 1.3 1.6 1.5 1.7 1.5 1.5 1.7 1.6 1.7 1.6 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.8 1.9 1.7 1.2 1.5 1.4 Gavage ml Day 88 1.6 1.5 1.3 1.6 1.5 1.7 1.5 1.5 1.7 1.6 1.7 1.6 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.8 1.9 1.7 1.2 1.5 1.4 Gavage ml Day 89 1.6 1.5 1.3 1.6 1.5 1.7 1.5 1.5 1.7 1.6 1.7 1.6 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.8 1.9 1.7 1.2 1.5 1.4 Gavage ml D a y 90 1.6 1.5 1.3 1.6 1.5 1.7 1.5 1.5 1.7 1.6 1.7 1.6 1.6 1.2 1.6 1.7 1.6 1.5 1.5 1.8 1.9 1.7 1.2 1.5 1.4 Gavage ml D a y 91 1.5 1.4 1.4 1.6 1.5 1.6 1.5 1.6 1.7 1.6 1.8 1.6 1.6 1.3 1.6 1.7 1.6 1.6 1.5 1.7 1.8 1.7 1.2 1.4 1.4 Gavage ml D a y 92 1.5 1.4 1.4 1.6 1.5 1.6 1.5 1.6 1.7 1.6 Gavage ml D a y 93 1. 5 1. 4 1. 4 1. 6 1. 5 1. 6 1. 5 1. 6 1. 7 1. 6 DuPont-9478 - 375 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX C INDIVIDUAL BODY WEIGHTS - 376 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 0 Body Weight g Day 7 Body Weight g D a y 14 Body Weight g Day 21 Body Weight g Day 28 Body Weight g Day 35 Body Weight g D a y 42 Body Weight g Day 49 Body Weight g D a y 56 Male, I 0 mg/kg/day 654928 654993 654929 654972 654950 654953 654925 654987 654903 654966 654997 654971 654939 654919 654994 654949 654992 654909 654924 654943 654915 654927 654956 654910 654936 214.3 208.4 237.6 242.9 264.2 299.7 251.3 237.7 243.4 223.6 267.8 202.9 244.9 235.7 195.0 213.4 238.8 213.7 231.3 229.2 254.3 249.5 196.5 239.4 225.8 256.8 260.0 289.7 288.4 318.2 371.8 311.3 292.6 300.3 277.5 322.2 247.4 307.0 277.0 238.9 261.1 301.7 261.7 284.6 283.3 309.9 317.7 252.3 295.6 291.6 296.8 298.1 330.0 329.9 363.6 423.6 369.5 344.3 345.0 318.5 372.9 294.7 363.7 317.6 286.9 307.6 357.0 307.7 326.7 329.5 360.2 374.1 298.7 358.6 355.5 346.6 337.2 367.3 369.6 409.3 483.6 418.0 387.3 397.7 360.3 412.9 351.2 416.4 358.5 327.9 349.8 410.3 344.3 372.7 362.2 407.8 426.9 340.8 421.7 410.2 390.4 362.3 396.1 393.9 439.0 536.8 448.0 395.9 441.1 397.0 437.5 391.9 443.1 384.9 360.9 379.3 438.2 376.1 412.2 390.6 446.7 460.2 369.3 446.5 450.2 428.1 391.9 421.9 415.9 461.3 575.9 486.3 447.2 471.9 341.5 462.9 434.8 483.4 407.4 384.2 410.4 469.5 403.6 439.8 419.6 481.7 495.5 406.5 492.5 492.6 457.1 407.2 433.4 434.4 482.9 607.2 502.6 474.3 492.3 313.3 483.8 460.9 519.7 425.5 407.0 428.7 495.8 429.8 477.3 441.8 514.4 517.6 428.6 521.4 524.2 469.5 417.1 441.4 441.6 482.8 607.1 517.9 483.9 503.8 374.6 496.6 482.4 550.9 438.6 414.0 450.7 521.8 451.6 485.8 457.7 531.3 543.9 444.8 550.1 521.3 500.8 448.9 471.7 457.5 499.7 638.8 537.5 505.4 529.8 384.8 514.7 497.2 568.9 461.3 402.4 475.9 550.4 467.0 503.0 467.7 557.3 568.1 466.0 576.8 542.6 - 377 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 63 Body Weight g D a y 70 Body Weight g D a y 77 Body Weight g D a y 84 Body Weight g D a y 91 Body Weight g D a y 93 Body Weight g D a y 98 Body Weight g Day 105 Body Weight g Day 112 Male, I 0 mg/kg/day 654928 654993 654929 654972 654950 654953 654925 654987 654903 654966 654997 654971 654939 654919 654994 654949 654992 654909 654924 654943 654915 654927 654956 654910 654936 530.1 468.0 487.0 472.9 512.6 660.1 550.6 528.0 545.6 380.8 525.5 512.1 575.1 477.5 423.2 501.7 563.4 486.1 522.5 486.8 574.5 579.3 481.9 601.7 566.6 547.1 482.5 501.2 481.8 525.2 680.6 563.0 539.3 569.4 424.8 545.8 536.1 591.0 489.2 450.4 522.0 575.8 497.3 539.2 498.5 589.8 600.7 485.2 619.5 588.9 556.8 494.9 510.6 492.8 512.9 692.0 566.9 556.6 580.8 442.1 557.7 545.6 606.1 500.0 458.3 527.7 586.2 510.6 544.7 510.0 603.9 614.1 495.9 626.5 597.8 574.1 500.9 516.0 499.3 526.8 698.3 584.1 571.1 589.2 454.8 562.0 558.3 617.0 498.7 460.1 533.7 596.6 520.6 532.7 515.6 611.7 614.3 494.7 626.6 606.8 586.7 507.2 525.3 512.3 548.5 659.9 596.2 580.5 603.1 468.7 572.4 562.4 629.9 504.1 466.3 539.1 601.6 529.1 556.8 516.4 619.4 621.7 498.9 634.7 609.6 566.3 486.8 506.1 498.8 520.7 646.3 575.8 566.4 578.5 583.7 493.6 578.2 577.3 634.9 511.2 484.7 557.8 609.5 535.1 576.1 538.5 630.0 632.3 509.8 651.9 448.9 586.1 543.7 647.2 509.2 497.1 563.7 626.5 554.8 592.2 552.2 652.6 644.8 519.9 660.8 473.1 606.2 548.7 660.2 511.3 503.0 572.9 636.3 567.2 597.0 551.0 653.6 656.2 523.1 664.9 - 378 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 119 Body Weight g Day 126 Body Weight g Day 133 Body Weight g Day 140 Body Weight g Day 147 Body Weight g Day 154 Body Weight g Day 161 Body Weight g Day 168 Body Weight g Day 175 Male, I 0 mg/kg/day 654928 654993 654929 654972 654950 654953 654925 654987 654903 654966 654997 654971 654939 654919 654994 654949 654992 654909 654924 654943 654915 654927 654956 654910 654936 490.9 610.7 576.2 676.0 518.5 508.7 579.9 644.3 567.2 605.2 560.2 666.4 657.3 529.0 673.5 523.5 628.5 591.9 687.7 526.4 520.9 586.7 662.5 572.5 619.4 569.7 680.4 671.8 547.3 693.8 541.4 632.0 600.3 697.7 533.1 527.8 597.1 661.3 576.4 627.6 583.3 697.0 684.3 553.9 692.3 540.8 619.5 590.3 712.4 528.9 520.0 597.8 656.4 576.1 623.0 585.5 694.1 685.2 555.6 694.4 552.8 624.7 576.7 715.1 529.8 526.3 602.4 659.4 578.9 629.5 592.9 705.6 693.8 562.9 707.3 537.5 635.0 598.8 728.6 541.7 530.6 606.8 669.6 583.4 628.6 605.6 721.5 703.9 572.1 710.7 509.9 643.9 572.2 738.8 544.9 529.5 609.7 667.7 592.2 637.3 609.7 723.0 691.9 574.0 710.7 528.0 649.3 577.9 741.9 548.7 536.6 613.3 674.5 591.0 647.6 621.5 732.9 701.9 570.5 712.0 489 655 575 743 551 535 614 683 593 658 625 751 703 569 718 - 379 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Body Weight g Day 182 Body Weight g Day 183 Male, I 0 mg/kg/day 654928 654993 654929 654972 654950 654953 654925 654987 654903 654966 654997 654971 654939 654919 654994 654949 654992 654909 654924 654943 654915 654927 654956 654910 654936 543.9 623.7 680.7 598.6 658.6 631.2 754.8 697.7 570.9 715.8 521.1 601.2 656.3 578.3 631.4 605.8 725.9 674.6 551.9 691.5 INDIVIDUAL BODY WEIGHTS - 380 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 0 Body Weight g Day 7 Body Weight g D a y 14 Body Weight g Day 21 Body Weight g Day 28 Body Weight g Day 35 Body Weight g D a y 42 Body Weight g Day 49 Body Weight g D a y 56 Male, III 1 m g / k g / d a y 654913 654947 654995 654938 654941 654946 654960 654908 654984 654932 654948 654904 654954 654945 654988 224.8 221.2 230.5 250.0 241.2 271.8 283.0 255.8 236.4 252.4 255.3 233.0 272.2 217.1 239.2 280.3 273.5 287.2 311.2 305.9 337.5 325.6 302.9 302.8 314.8 315.7 281.2 319.0 236.8 292.9 334.3 323.4 342.4 367.5 358.2 393.7 361.3 356.4 352.7 365.7 372.2 336.5 363.6 314.6 347.1 376.2 361.7 381.4 415.0 404.4 436.3 401.6 396.6 396.1 413.7 417.5 370.5 411.7 352.0 388.8 410.8 391.3 411.4 441.2 437.0 465.8 417.9 438.4 437.7 441.8 454.2 401.4 448.5 376.1 416.7 436.6 416.2 446.8 467.2 468.2 501.0 440.7 458.1 471.7 467.5 489.5 436.5 481.4 400.2 444.2 464.0 433.4 469.3 493.6 472.2 525.5 457.6 476.0 491.5 493.2 512.0 459.5 511.7 412.7 465.0 473.1 445.9 472.3 504.9 476.9 532.1 455.4 475.4 501.5 500.2 524.8 477.7 530.1 425.4 478.9 499.7 467.2 495.0 527.8 498.0 556.7 484.5 503.2 535.5 519.1 542.7 490.4 557.7 443.3 505.9 - 381 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 63 Body Weight g D a y 70 Body Weight g D a y 77 Body Weight g D a y 84 Body Weight g D a y 91 Body Weight g D a y 93 Body Weight g D a y 98 Body Weight g Day 105 Body Weight g Day 112 Male, III 1 m g / k g / d a y 654913 654947 654995 654938 654941 654946 654960 654908 654984 654932 654948 654904 654954 654945 654988 515.5 479.9 508.9 552.8 514.0 568.8 498.9 510.6 556.7 533.5 561.4 500.8 574.5 454.4 517.3 537.1 491.3 532.7 570.4 533.4 596.3 512.7 513.9 584.5 554.7 574.7 511.7 590.1 455.1 529.9 546.9 502.3 529.8 576.3 543.9 598.8 522.9 529.7 594.0 561.5 543.2 528.4 593.5 464.4 535.8 537.9 503.4 526.5 574.6 524.3 599.0 529.5 532.0 607.4 570.6 587.4 532.0 600.9 471.9 545.4 557.6 509.0 528.2 600.7 540.3 595.3 540.5 541.0 623.1 584.8 610.0 543.5 611.1 474.7 554.9 534.1 489.6 514.1 579.4 515.8 577.7 513.2 516.1 601.8 566.1 625.3 551.0 618.2 480.0 565.1 640.9 563.6 636.0 497.2 576.4 649.3 565.5 635.0 498.1 573.9 - 382 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 119 Body Weight g Day 126 Body Weight g Day 133 Body Weight g Day 140 Body Weight g Day 147 Body Weight g Day 154 Body Weight g Day 161 Body Weight g Day 168 Body Weight g Day 175 Male, III 1 m g / k g / d a y 654913 654947 654995 654938 654941 654946 654960 654908 654984 654932 654948 654904 654954 654945 654988 661.4 576.0 642.5 514.3 580.9 674.0 590.0 661.2 511.1 586.0 689.4 601.9 661.0 529.0 594.5 699.6 598.8 661.2 532.4 586.9 713.9 606.3 674.3 540.4 597.1 721.2 614.0 680.2 553.0 607.6 727.0 613.7 683.1 553.0 609.3 729.2 619.9 687.6 562.3 612.5 738.3 616.7 690.9 572.6 613.2 - 383 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 0 Body Weight g Day 7 Body Weight g D a y 14 Body Weight g Day 21 Body Weight g Day 28 Body Weight g Day 35 Body Weight g D a y 42 Body Weight g Day 49 Body Weight g D a y 56 Male, V 5 mg/kg/day 655005 654907 654980 654959 654961 654916 654911 654917 654998 654970 654926 654918 654981 654969 654967 235.1 226.4 227.0 249.3 268.1 275.8 260.6 238.8 248.3 213.2 269.8 243.5 208.9 227.6 220.2 288.9 281.8 289.9 309.6 330.2 333.7 327.3 298.7 311.9 249.9 320.4 297.7 260.2 261.4 275.8 345.7 333.3 348.4 366.6 396.3 375.8 388.8 355.2 368.1 285.6 369.1 350.8 316.9 297.3 327.9 400.1 375.6 405.5 424.4 452.5 413.1 439.2 400.3 415.5 325.6 423.4 399.6 368.8 330.8 367.7 439.5 405.3 448.1 474.2 497.7 441.6 486.0 426.6 453.5 353.2 467.2 435.4 394.6 360.3 399.2 470.0 433.5 487.2 504.7 537.0 466.1 517.7 457.5 489.3 372.3 509.6 471.6 424.1 390.2 428.5 498.9 453.0 522.5 536.3 552.1 478.3 546.5 497.5 519.9 385.7 529.6 493.6 435.9 414.9 446.3 509.4 455.9 535.6 547.4 558.7 491.4 539.7 508.7 518.5 399.8 554.3 518.5 453.2 433.9 451.7 538.2 493.7 576.4 572.2 600.3 514.0 566.6 536.4 550.2 413.6 574.7 545.7 469.9 456.8 478.5 - 384 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 63 Body Weight g D a y 70 Body Weight g D a y 77 Body Weight g D a y 84 Body Weight g D a y 91 Body Weight g D a y 93 Body Weight g D a y 98 Body Weight g Day 105 Body Weight g Day 112 Male, V 5 mg/kg/day 655005 654907 654980 654959 654961 654916 654911 654917 654998 654970 654926 654918 654981 654969 654967 565.3 510.3 597.7 600.2 621.6 519.9 591.9 568.1 565.0 429.4 589.1 569.9 483.1 468.4 496.6 576.2 520.3 607.4 613.6 642.9 516.2 606.7 580.2 575.8 451.8 606.6 590.0 500.8 489.6 508.2 589.4 530.4 630.1 623.7 653.1 522.9 622.8 597.8 598.2 474.4 598.7 596.8 503.8 505.5 518.3 596.5 544.2 645.1 633.9 666.1 544.1 638.2 600.9 617.8 481.7 614.0 610.1 513.0 508.3 523.8 587.6 553.5 661.6 649.1 672.7 550.2 638.0 613.3 608.2 477.3 641.3 619.2 524.7 511.5 528.0 567.8 532.9 626.5 621.1 643.3 526.3 619.9 587.8 587.6 513.3 496.9 651.0 632.2 530.5 524.5 508.6 657.1 646.2 531.6 534.4 513.4 667.4 648.6 540.8 525.8 - 385 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 119 Body Weight g Day 126 Body Weight g Day 133 Body Weight g Day 140 Body Weight g Day 147 Body Weight g Day 154 Body Weight g Day 161 Body Weight g Day 168 Body Weight g Day 175 Male, V 5 mg/kg/day 655005 654907 654980 654959 654961 654916 654911 654917 654998 654970 654926 654918 654981 654969 654967 517.6 675.5 667.3 550.7 542.0 529.2 691.2 669.2 560.0 553.3 535.6 697.0 686.6 572.5 558.1 532.9 703.6 699.5 575.7 528.4 540.7 719.7 704.8 577.1 549.4 550.4 718.6 713.5 588.5 564.5 545.6 724.1 719.0 589.1 569.6 546.2 726.6 727.2 585.3 569.9 542.4 722.1 726.8 589.1 582.0 - 386 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 0 Body Weight g Day 7 Body Weight g D a y 14 Body Weight g Day 21 Body Weight g Day 28 Body Weight g D a y 35 Body Weight g D a y 42 Body Weight g Da y 49 Body Weight g D a y 56 Male, VII 25 mg/kg/day 655001 654975 654922 654940 654930 654958 654952 654923 654989 655006 654920 654912 654934 654964 654933 230.8 219.2 218.7 238.9 238.0 248.9 277.3 251.5 236.3 251.9 227.9 217.7 235.0 252.8 245.5 290.9 275.1 270.6 296.2 305.2 290.8 334.9 308.3 297.2 310.4 274.7 264.6 294.2 307.4 302.8 348.1 327.6 317.5 340.6 360.9 325.6 390.1 363.6 357.6 363.7 325.5 305.4 334.8 357.6 364.8 417.7 378.0 366.2 387.5 416.1 358.7 437.8 412.8 399.0 409.5 376.6 339.8 371.1 405.7 420.4 470.7 410.7 400.7 414.2 464.1 382.3 459.7 447.4 438.7 440.2 416.1 364.9 396.6 443.2 457.7 517.2 433.2 433.9 442.2 502.8 409.2 494.7 477.5 469.4 467.9 448.6 395.6 433.3 480.6 506.4 543.8 467.4 469.1 467.8 534.6 432.1 523.0 498.3 496.0 495.4 475.6 423.6 455.8 510.9 543.9 552.5 473.0 480.1 474.4 542.1 439.1 526.6 503.8 503.6 500.1 491.0 441.8 474.9 534.2 578.7 588.9 502.7 523.7 496.5 566.8 454.9 556.7 519.7 533.0 522.7 523.6 466.6 500.1 558.2 613.0 - 387 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g D a y 63 Body Weight g D a y 70 Body Weight g D a y 77 Body Weight g D a y 84 Body Weight g D a y 91 Body Weight g D a y 93 Body Weight g D a y 98 Body Weight g Day 105 Body Weight g Da y 112 Male, VII 25 mg/kg/day 655001 654975 654922 654940 654930 654958 654952 654923 654989 655006 654920 654912 654934 654964 654933 612.3 530.6 543.4 516.2 584.3 471.2 576.2 533.3 557.2 542.3 540.6 488.8 510.8 576.1 636.1 630.5 542.1 555.8 529.8 597.7 480.7 575.4 533.8 565.1 549.1 549.9 504.1 520.1 590.3 651.0 641.2 553.4 572.5 543.7 598.8 486.6 592.7 548.5 582.9 556.4 560.1 527.0 531.3 604.1 668.5 646.1 558.9 580.3 542.2 602.4 496.9 617.2 560.9 600.2 573.2 576.8 532.7 544.2 611.0 674.3 661.8 580.6 583.5 554.6 619.4 506.6 620.7 566.3 612.7 575.2 588.0 531.7 554.7 627.4 685.4 641.7 554.9 555.6 534.8 596.1 483.1 598.4 539.3 580.5 557.0 591.8 543.3 566.6 639.7 692.4 602.8 551.8 571.7 646.5 700.4 607.2 554.7 563.4 655.8 715.2 - 388 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 119 Body Weight g Day 126 Body Weight g Day 133 Body Weight g Day 140 Body Weight g Day 147 Body Weight g Day 154 Body Weight g Day 161 Body Weight g Day 168 Body Weight g Day 175 Male, VII 25 mg/kg/day 655001 654975 654922 654940 654930 654958 654952 654923 654989 655006 654920 654912 654934 654964 654933 619.8 555.9 583.1 662.7 732.1 638.2 576.0 591.9 674.0 752.0 648.3 581.7 597.4 679.4 767.0 642.3 580.2 604.5 681.3 775.5 652.4 590.0 607.1 687.5 791.1 672.1 606.0 616.0 702.3 811.1 676.8 595.3 614.4 701.3 806.9 680.0 617.5 616.4 717.7 821.9 688.0 622.5 618.7 723.2 816.8 - 389 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 0 Body Weight g Day 7 Body Weight g D a y 14 Body Weight g Day 21 Body Weight g Day 28 Body Weight g D a y 35 Body Weight g D a y 42 Body Weight g Da y 49 Body Weight g D a y 56 Male, IX 125 m g / k g / d a y 654983 654965 654979 654986 655003 654921 654996 654951 654955 654914 654937 654962 654982 654931 654906 654985 654978 654974 654990 654976 654957 654973 654977 654942 654991 236.6 211.9 218.3 243.8 231.8 269.5 275.4 248.9 238.8 248.3 234.6 266.3 222.9 240.9 248.1 194.0 201.7 214.6 234.9 216.4 253.6 261.7 194.1 234.0 236.1 298.9 260.9 273.2 295.7 278.0 323.2 325.6 296.2 310.9 298.9 298.6 299.4 280.1 301.6 316.0 233.5 248.2 276.1 290.2 269.2 308.8 316.6 232.0 286.6 311.4 351.7 315.8 329.8 346.1 334.5 377.7 371.5 349.4 376.9 344.1 358.5 353.6 338.7 364.4 379.6 274.6 291.0 334.6 336.2 326.6 360.2 368.2 285.7 339.5 374.3 396.7 357.0 363.5 405.8 374.5 416.7 400.9 392.1 428.6 383.8 409.9 406.5 386.1 421.9 438.7 318.9 329.7 378.2 373.7 373.6 400.5 411.9 321.6 377.2 429.1 437.1 393.1 391.5 444.3 401.3 454.1 426.4 430.6 462.1 414.0 446.6 443.9 419.8 462.7 476.0 345.1 357.4 421.2 415.0 404.8 431.4 446.6 344.5 403.1 476.6 470.5 412.9 423.4 480.5 421.6 481.8 454.4 456.4 490.2 441.9 476.5 472.2 456.2 496.5 516.8 359.8 378.7 447.9 440.9 424.6 449.4 465.3 367.9 425.9 509.2 504.4 438.7 446.2 516.1 449.2 501.6 460.2 487.3 513.9 475.5 500.0 485.6 477.5 519.5 550.3 387.4 398.2 471.4 462.8 455.3 469.0 488.9 388.8 455.8 540.8 510.9 438.7 459.9 518.9 456.5 503.4 457.6 499.1 522.5 486.5 518.8 505.6 500.1 541.3 581.1 395.9 410.4 488.3 481.6 469.7 493.1 496.6 404.3 462.4 566.0 530.4 442.8 484.1 553.3 473.7 533.9 485.6 522.7 544.3 503.8 538.8 530.0 527.8 562.7 607.8 416.2 430.3 506.6 495.4 482.4 505.7 510.2 414.4 484.5 593.6 - 390 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g D a y 63 Body Weight g D a y 70 Body Weight g D a y 77 Body Weight g D a y 84 Body Weight g D a y 91 Body Weight g D a y 93 Body Weight g D a y 98 Body Weight g Day 105 Body Weight g Da y 112 Male, IX 125 m g / k g / d a y 654983 654965 654979 654986 655003 654921 654996 654951 654955 654914 654937 654962 654982 654931 654906 654985 654978 654974 654990 654976 654957 654973 654977 654942 654991 555.0 462.0 497.6 538.3 486.4 546.9 462.4 541.0 557.4 516.7 557.9 536.4 519.9 569.0 623.5 427.9 443.6 528.9 516.2 438.9 516.7 523.6 425.4 500.3 606.9 559.3 478.9 516.0 508.0 499.3 553.6 485.1 552.8 571.8 538.0 564.1 561.4 536.7 537.5 647.3 435.0 456.5 520.9 529.9 486.5 519.5 527.8 414.0 503.6 608.1 570.3 460.1 522.0 493.1 500.1 570.7 495.8 558.1 562.0 553.7 576.3 561.9 511.2 464.6 641.8 369.9 456.3 438.2 537.5 484.2 529.4 548.4 427.8 512.1 616.5 574.4 488.1 525.7 536.4 511.6 567.4 520.6 565.7 533.8 576.1 569.1 545.9 501.1 541.0 639.7 388.5 464.9 497.8 555.9 506.1 537.3 557.3 441.9 513.0 629.3 596.3 510.5 546.5 605.1 530.9 579.7 534.8 573.2 568.1 591.0 581.8 550.5 531.5 559.7 672.1 421.4 484.4 533.0 583.6 531.0 544.9 560.7 444.1 522.3 639.3 569.9 483.6 512.4 575.0 506.1 553.2 508.6 555.0 542.5 563.5 588.8 570.6 533.4 580.1 687.9 430.8 499.1 560.5 589.4 539.0 556.5 566.6 456.9 528.5 651.3 611.2 580.8 543.9 600.7 713.8 441.1 504.3 566.6 592.8 549.0 558.9 579.8 472.5 536.8 665.5 622.2 579.7 564.9 608.1 712.5 446.5 514.1 579.6 587.6 542.4 568.3 587.2 477.4 542.3 669.6 - 391 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 119 Body Weight g Day 126 Body Weight g Day 133 Body Weight g Day 140 Body Weight g Day 147 Body Weight g Day 154 Body Weight g Day 161 Body Weight g Day 168 Body Weight g Day 175 Male, IX 125 m g / k g / d a y 654983 654965 654979 654986 655003 654921 654996 654951 654955 654914 654937 654962 654982 654931 654906 654985 654978 654974 654990 654976 654957 654973 654977 654942 654991 633.6 581.9 575.0 610.9 734.9 451.3 513.6 585.4 603.0 558.7 581.2 602.5 482.1 551.5 683.4 657.6 594.1 584.2 627.6 758.8 449.4 535.0 606.4 621.5 574.2 588.9 612.2 496.5 574.4 708.6 665.9 596.4 595.4 642.0 777.3 451.7 540.1 625.0 639.3 574.9 604.5 630.7 501.9 582.6 726.6 670.1 592.2 613.8 645.2 773.5 456.4 539.3 633.9 631.2 580.7 612.3 637.0 492.8 579.4 735.7 684.6 595.8 627.8 653.8 778.0 460.7 545.5 640.1 648.9 587.1 619.2 648.2 494.6 595.1 742.9 704.4 606.0 636.5 672.1 785.7 492.5 556.7 658.8 668.4 601.1 623.5 660.9 504.0 608.9 756.1 703.1 613.0 646.3 678.2 786.0 490.3 562.6 662.0 678.0 593.9 619.8 656.9 499.0 606.2 752.7 725.9 626.7 678.3 690.1 796.4 498.5 566.6 683.2 690.1 605.5 617.9 665.0 502.2 624.6 766.2 704.7 623.3 667.9 692.3 801.5 498.8 565.4 685.6 682.1 603.8 622.2 662.4 508.4 630.8 772.8 - 392 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Body Weight g Day 182 Body Weight g Day 183 Male, IX 125 mg/kg/day 654983 654965 654979 654986 655003 654921 654996 654951 654955 654914 654937 654962 654982 654931 654906 654985 654978 654974 654990 654976 654957 654973 654977 654942 654991 505.5 572.6 702.9 694.3 613.5 635.5 669.1 517.4 651.0 784.9 475.3 552.6 673.0 667.9 597.1 616.9 642.7 492.6 620.8 759.7 INDIVIDUAL BODY WEIGHTS - 393 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 0 Body Weight g Day 7 Body Weight g D a y 14 Body Weight g Day 21 Body Weight g Day 28 Body Weight g D a y 35 Body Weight g D a y 42 Body Weight g Da y 49 Body Weight g D a y 56 Female, II 0 m g / k g / d a y 655031 655107 655098 655016 655079 655036 655025 655099 655032 655083 655093 655045 655065 655074 655035 655009 655068 655019 655062 655109 655101 655072 655015 655071 655022 174.3 174.0 163.3 181.5 174.1 214.7 179.5 195.9 200.4 203.8 163.7 183.9 188.4 193.6 181.4 177.0 200.3 200.2 191.7 191.6 208.8 204.6 155.1 179.2 183.5 187.9 190.1 181.6 199.3 183.3 232.8 203.7 212.1 213.9 220.3 168.4 202.2 207.9 219.9 202.6 195.3 217.0 218.6 203.6 210.7 238.4 233.3 172.4 202.6 201.9 207.2 199.3 203.1 212.7 194.9 252.5 226.1 242.5 223.6 234.0 180.5 226.7 229.5 236.5 220.7 219.0 242.1 247.3 231.5 235.9 261.6 248.9 190.9 196.4 224.1 229.7 206.5 216.3 218.3 205.2 266.2 247.6 256.9 245.6 250.7 193.1 241.9 247.0 259.4 242.6 241.5 257.9 270.2 245.1 247.7 285.8 271.7 198.2 240.6 251.4 214.1 222.5 233.8 220.2 285.0 257.6 267.1 256.0 259.0 194.9 244.2 260.7 262.8 252.3 252.2 267.9 276.3 261.1 256.6 302.3 286.4 198.6 259.0 257.8 219.5 232.1 239.1 233.0 299.1 271.3 276.4 266.2 275.1 200.1 261.1 283.5 278.2 273.5 261.2 285.5 289.9 268.9 267.9 313.6 286.7 218.9 265.9 275.0 226.9 241.5 255.6 242.5 301.2 283.8 287.8 282.4 280.2 207.3 269.7 296.5 286.9 276.0 265.4 284.5 299.1 275.4 278.6 329.7 305.4 231.9 269.6 267.8 220.2 239.1 251.6 238.2 294.8 277.1 276.3 278.3 278.2 209.2 271.6 305.1 284.7 285.0 274.4 287.2 301.6 280.1 279.1 338.2 312.0 223.5 274.9 285.6 234.4 246.0 269.8 258.4 315.7 295.7 292.3 298.1 295.8 213.2 274.5 314.5 284.1 294.3 286.6 294.4 311.8 288.9 288.1 344.1 320.4 232.5 286.4 - 394 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g D a y 63 Body Weight g D a y 70 Body Weight g D a y 77 Body Weight g D a y 84 Body Weight g D a y 91 Body Weight g D a y 94 Body Weight g D a y 98 Body Weight g Day 105 Body Weight g Da y 112 Female, II 0 m g / k g / d a y 655031 655107 655098 655016 655079 655036 655025 655099 655032 655083 655093 655045 655065 655074 655035 655009 655068 655019 655062 655109 655101 655072 655015 655071 655022 287.2 234.3 250.9 282.6 259.3 320.5 299.9 289.8 300.1 297.3 213.3 286.6 326.0 294.0 297.8 292.2 294.0 315.8 289.7 292.5 362.5 315.2 239.8 288.6 301.3 245.5 265.5 282.6 267.0 325.7 317.2 299.5 302.4 308.8 224.2 294.4 340.7 297.4 298.4 296.4 301.7 321.1 299.9 299.7 358.6 330.2 240.4 288.5 306.4 245.3 264.8 289.4 272.3 329.4 319.9 302.1 312.1 314.7 231.1 294.5 339.3 309.5 305.0 294.5 298.5 322.6 310.2 297.9 366.5 331.2 241.0 293.9 309.2 251.9 266.3 301.1 276.4 337.3 315.7 302.9 300.8 324.0 229.4 289.8 340.2 308.2 311.2 304.3 306.0 322.2 315.2 304.2 374.1 328.6 243.8 296.6 300.2 250.1 268.3 296.1 282.0 338.7 320.7 302.1 317.3 326.0 229.3 300.5 352.2 305.0 311.1 312.4 298.6 326.5 312.1 306.9 366.5 323.7 250.5 293.1 292.6 238.5 261.1 286.5 266.8 322.5 301.7 284.9 302.9 310.8 236.7 298.2 356.0 305.9 309.7 314.7 304.6 331.7 319.9 308.1 381.8 343.4 240.0 301.2 234.5 313.2 362.6 318.1 321.4 318.5 317.5 333.1 332.4 311.4 381.9 338.9 238.1 298.9 234.7 310.9 365.0 316.0 324.8 328.3 324.2 332.0 330.9 308.5 377.8 340.7 251.4 306.5 - 395 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 119 Body Weight g Day 126 Body Weight g Day 133 Body Weight g Day 140 Body Weight g Day 147 Body Weight g Day 154 Body Weight g Day 161 Body Weight g Day 168 Body Weight g Day 175 Female, II 0 m g / k g / d a y 655031 655107 655098 655016 655079 655036 655025 655099 655032 655083 655093 655045 655065 655074 655035 655009 655068 655019 655062 655109 655101 655072 655015 655071 655022 237.8 306.1 377.4 316.1 321.1 324.2 319.7 337.2 342.1 313.5 375.5 338.6 265.3 308.3 240.9 307.3 377.0 325.7 333.2 328.7 327.1 340.5 358.8 320.8 387.9 356.0 278.6 308.3 242.9 305.7 372.3 326.9 331.8 327.4 330.8 343.9 349.0 314.9 404.7 357.5 286.1 310.5 246.6 308.7 377.4 336.3 331.6 334.2 335.3 353.9 353.1 321.0 395.7 345.5 290.3 312.4 246.5 321.1 387.8 341.1 335.3 338.5 340.5 352.2 349.6 324.8 411.0 360.6 295.2 313.4 248.8 325.4 395.2 341.4 319.6 339.4 339.7 362.1 358.0 328.8 409.7 366.4 300.7 315.4 245.3 321.9 376.6 338.8 313.6 331.8 339.1 352.3 355.0 321.5 400.7 354.9 299.2 316.4 249.3 330.4 371.7 348.9 326.8 337.9 347.8 362.7 365.4 322.9 413.7 354.0 313.1 320.1 252.5 336.3 378.0 345.8 329.5 338.1 347.0 365.3 367.3 326.1 420.9 360.7 308.3 316.9 - 396 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Body Weight g Day 182 Body Weight g Day 183 Female, II 0 m g / k g / d a y 655031 655107 655098 655016 655079 655036 655025 655099 655032 655083 655093 655045 655065 655074 655035 655009 655068 655019 655062 655109 655101 655072 655015 655071 655022 343.5 329.2 352.1 370.7 371.5 328.7 420.5 364.0 306.9 322.8 317.1 329.8 347.7 344.4 309.3 405.9 340.9 288.4 INDIVIDUAL BODY WEIGHTS - 397 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 0 Body Weight g Day 7 Body Weight g D a y 14 Body Weight g Day 21 Body Weight g Day 28 Body Weight g D a y 35 Body Weight g D a y 42 Body Weight g Da y 49 Body Weight g D a y 56 Female, IV 1 mg/kg/day 655086 655041 655108 655040 655044 655013 655089 655091 655033 655090 655051 655018 655096 655057 655028 172.1 186.9 168.1 182.6 177.2 201.2 152.0 181.2 194.4 211.0 171.3 203.4 199.8 161.4 195.0 191.8 192.1 192.3 205.2 203.1 231.3 200.2 207.8 214.2 235.2 191.4 220.4 206.0 183.4 211.3 209.5 209.7 213.6 229.5 230.9 254.4 221.6 221.3 232.0 250.7 205.2 239.6 225.0 203.6 224.9 218.3 229.6 225.4 243.5 243.4 269.5 237.3 239.5 249.0 267.0 217.8 247.2 238.6 217.2 237.0 223.5 238.3 243.0 247.5 255.7 269.4 245.3 255.9 265.3 281.1 234.7 264.6 250.1 226.8 250.4 235.8 246.0 257.1 267.5 274.5 283.7 262.8 274.9 276.6 297.9 249.3 281.6 258.1 241.7 257.2 241.8 267.6 261.6 275.8 293.0 289.3 275.5 282.6 283.3 301.5 254.6 294.0 275.9 250.8 264.2 228.4 260.9 248.1 264.5 278.5 274.7 273.6 274.9 272.8 291.6 256.0 287.1 277.2 245.0 274.5 248.7 292.3 266.6 286.7 296.3 287.2 304.5 292.8 298.5 315.2 259.9 307.2 290.3 262.4 288.0 - 398 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g D a y 63 Body Weight g D a y 70 Body Weight g D a y 77 Body Weight g D a y 84 Body Weight g D a y 91 Body Weight g D a y 94 Body Weight g D a y 98 Body Weight g Day 105 Body Weight g Da y 112 Female, IV 1 mg/kg/day 655086 655041 655108 655040 655044 655013 655089 655091 655033 655090 655051 655018 655096 655057 655028 254.2 287.3 281.7 283.5 307.4 295.3 318.6 300.7 292.5 326.6 263.5 316.0 294.8 261.6 286.6 256.6 293.9 284.7 295.5 318.7 303.8 325.7 310.7 306.5 329.3 262.0 326.8 305.0 266.7 292.2 257.5 298.3 289.9 299.9 324.4 306.1 327.4 305.5 309.0 333.4 274.8 332.9 297.7 273.1 301.7 258.6 299.9 284.7 301.5 324.6 302.6 338.3 318.6 317.0 343.5 277.0 337.2 303.0 273.4 307.2 254.3 290.0 284.7 305.6 329.3 309.3 340.1 315.0 310.2 342.6 283.8 331.1 310.2 270.0 298.0 243.3 276.1 269.3 293.1 317.2 299.4 317.9 302.6 303.6 323.5 290.6 344.4 319.3 276.5 302.4 300.6 349.6 314.3 283.4 307.3 299.0 349.4 320.6 280.2 313.5 - 399 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 119 Body Weight g Day 126 Body Weight g Day 133 Body Weight g Day 140 Body Weight g Day 147 Body Weight g Day 154 Body Weight g Day 161 Body Weight g Day 168 Body Weight g Day 175 Female, IV 1 mg/kg/day 655086 655041 655108 655040 655044 655013 655089 655091 655033 655090 655051 655018 655096 655057 655028 298.8 353.8 321.6 282.2 311.9 305.4 361.1 326.2 286.7 316.1 311.5 367.0 332.7 289.2 321.7 306.3 364.0 342.1 288.3 327.1 307.9 373.5 341.5 290.1 325.0 313.2 370.2 354.7 290.1 328.3 318.0 368.6 345.7 292.6 327.3 322.0 367.9 356.3 296.4 337.4 322.3 364.3 365.1 296.2 332.9 - 400 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 0 Body Weight g Day 7 Body Weight g D a y 14 Body Weight g Day 21 Body Weight g Day 28 Body Weight g D a y 35 Body Weight g D a y 42 Body Weight g Da y 49 Body Weight g D a y 56 Female, VI 5 mg/kg/day 655054 655038 655034 655039 655029 655067 655020 655087 655066 655042 655059 655064 655050 655021 655017 169.6 183.2 170.3 178.4 185.3 204.8 148.6 189.3 196.1 210.9 162.7 190.0 193.3 162.5 188.6 193.7 207.6 192.7 202.9 206.4 225.5 197.9 219.2 212.6 235.6 182.2 205.7 209.3 177.7 198.8 209.4 224.7 211.7 218.8 222.8 244.7 222.6 241.6 241.7 254.1 197.0 226.5 231.5 194.7 214.1 214.5 242.6 223.0 240.8 246.5 267.9 221.8 252.5 260.3 274.8 206.4 252.3 241.9 213.0 226.3 231.6 248.6 231.7 249.8 255.9 274.9 237.4 261.0 274.3 286.7 218.4 269.6 258.5 232.2 232.7 237.2 261.0 243.3 261.8 263.9 285.9 254.5 287.3 289.1 311.4 226.5 286.7 269.6 232.7 249.6 239.9 277.4 257.6 284.6 251.3 288.9 277.7 298.0 298.1 317.8 240.5 302.3 280.1 248.6 261.3 236.1 264.7 248.5 277.5 262.6 286.0 274.5 288.8 286.9 308.3 239.3 311.5 275.9 254.2 259.9 260.6 280.2 258.6 295.5 279.5 301.7 282.3 296.9 309.6 343.4 246.8 324.5 289.9 265.9 266.6 - 401 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g D a y 63 Body Weight g D a y 70 Body Weight g D a y 77 Body Weight g D a y 84 Body Weight g D a y 91 Body Weight g D a y 94 Body Weight g D a y 98 Body Weight g Day 105 Body Weight g Da y 112 Female, VI 5 mg/kg/day 655054 655038 655034 655039 655029 655067 655020 655087 655066 655042 655059 655064 655050 655021 655017 261.8 293.6 265.3 296.6 279.3 305.0 300.6 321.7 314.3 347.2 251.2 324.0 295.5 264.4 269.7 261.7 302.4 270.1 313.2 288.1 311.8 307.1 319.1 306.9 349.3 257.6 329.6 293.9 271.6 278.3 269.8 306.1 275.8 318.4 291.2 314.5 306.2 312.7 318.1 359.2 259.4 339.4 296.8 276.1 281.2 273.1 302.2 271.6 315.3 287.2 311.1 306.9 311.4 324.2 355.6 258.5 338.2 301.5 277.2 278.6 266.6 307.1 277.5 309.4 290.1 311.6 312.6 329.0 326.1 351.9 260.6 333.6 301.8 273.7 285.4 252.3 292.7 259.1 301.3 279.9 291.4 301.6 314.7 308.1 339.8 268.0 346.7 313.1 284.3 287.2 259.2 351.8 308.8 290.2 289.0 263.7 356.7 316.5 296.4 295.3 - 402 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 119 Body Weight g Day 126 Body Weight g Day 133 Body Weight g Day 140 Body Weight g Day 147 Body Weight g Day 154 Body Weight g Day 161 Body Weight g Day 168 Body Weight g Day 175 Female, VI 5 mg/kg/day 655054 655038 655034 655039 655029 655067 655020 655087 655066 655042 655059 655064 655050 655021 655017 272.6 358.5 317.0 293.6 304.5 273.2 369.3 322.6 297.1 310.2 277.4 382.3 318.4 302.7 318.0 278.1 373.9 323.8 305.6 320.2 274.3 389.2 329.2 306.0 324.0 284.8 405.2 325.3 309.6 331.8 283.3 393.7 327.5 305.9 328.9 287.0 405.7 328.9 312.6 335.4 286.6 408.4 328.5 321.6 334.5 - 403 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 0 Body Weight g Day 7 Body Weight g D a y 14 Body Weight g Day 21 Body Weight g Day 28 Body Weight g Day 35 Body Weight g D a y 42 Body Weight g Day 49 Body Weight g D a y 56 Female, VIII 25 mg/kg/day 655058 655076 655047 655055 655105 655078 655073 655011 655085 655012 655043 655082 655060 655056 655081 172.7 184.2 161.2 177.3 177.2 208.8 171.7 185.1 200.2 197.9 173.4 196.7 187.1 155.7 189.4 197.1 204.8 177.4 204.5 192.8 235.6 199.8 206.6 223.6 226.6 190.0 205.0 203.3 161.9 213.2 220.3 211.7 207.8 225.1 212.1 260.2 226.4 226.3 248.5 245.8 214.5 239.0 220.7 198.7 228.8 233.6 243.5 210.3 240.1 225.6 266.7 236.2 239.5 267.3 259.1 223.6 248.3 243.2 209.2 251.6 245.9 249.5 224.3 246.7 227.4 288.6 251.7 260.9 288.3 264.5 232.9 268.7 261.8 213.6 265.5 265.0 252.8 233.1 261.0 248.1 300.6 260.7 269.8 303.0 278.1 248.4 284.9 266.5 238.3 283.6 272.3 271.1 255.5 273.5 251.2 329.8 276.1 277.4 308.7 286.4 257.5 291.8 289.7 248.2 288.8 251.8 258.7 242.3 254.7 243.7 321.8 266.6 267.9 296.7 279.9 249.7 302.7 297.7 247.4 298.9 272.1 279.2 269.2 275.9 272.7 350.1 287.2 296.8 321.6 307.9 259.7 309.4 316.8 251.9 310.7 - 404 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 63 Body Weight g D a y 70 Body Weight g D a y 77 Body Weight g D a y 84 Body Weight g D a y 91 Body Weight g D a y 94 Body Weight g D a y 98 Body Weight g Day 105 Body Weight g Day 112 Female, VIII 25 mg/kg/day 655058 655076 655047 655055 655105 655078 655073 655011 655085 655012 655043 655082 655060 655056 655081 281.5 277.7 264.1 281.4 275.6 340.3 291.4 301.6 324.2 299.9 261.0 311.0 320.5 263.9 322.1 289.4 290.4 273.3 293.8 283.4 368.1 309.2 304.4 331.3 312.3 264.8 319.4 329.5 278.0 328.5 294.3 298.5 278.6 294.1 278.8 370.5 317.3 311.6 340.0 317.8 273.1 321.0 339.1 279.6 343.8 290.1 303.8 274.0 287.4 283.6 364.9 318.0 319.9 347.3 320.6 277.9 327.0 337.5 271.9 345.3 293.1 303.3 264.8 292.5 279.2 361.4 313.9 319.5 339.3 326.1 273.4 325.2 342.6 283.8 341.0 278.2 297.0 264.9 279.5 268.8 351.3 305.3 306.7 317.9 305.6 293.8 335.1 349.5 295.5 340.8 295.9 340.5 349.9 293.2 354.9 292.0 348.0 353.1 296.2 358.9 - 405 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 119 Body Weight g Day 126 Body Weight g Day 133 Body Weight g Day 140 Body Weight g Day 147 Body Weight g Day 154 Body Weight g Day 161 Body Weight g Day 168 Body Weight g Day 175 Female, VIII 25 mg/kg/day 655058 655076 655047 655055 655105 655078 655073 655011 655085 655012 655043 655082 655060 655056 655081 303.1 363.4 363.6 307.6 364.9 300.0 377.3 373.3 307.2 373.2 304.7 382.0 370.8 317.0 381.9 300.4 383.3 379.2 316.9 378.2 315.8 395.1 369.5 309.7 383.8 306.2 393.4 388.7 319.5 387.9 302.9 401.0 383.6 318.2 402.3 313.1 410.0 387.4 320.6 410.5 305.6 405.8 393.7 311.8 417.3 - 406 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 0 Body Weight g Day 7 Body Weight g D a y 14 Body Weight g Day 21 Body Weight g Day 28 Body Weight g D a y 35 Body Weight g D a y 42 Body Weight g Da y 49 Body Weight g D a y 56 Female, X 125 mg/kg/day 655097 655052 655063 655103 655026 655095 655023 655007 655053 655092 655046 655027 655104 655106 655024 655037 655088 655010 655077 655030 655075 655100 655049 655084 655061 179.5 193.1 165.6 189.9 181.1 209.1 180.1 186.9 203.7 204.9 183.8 202.5 183.9 151.4 192.9 187.2 204.4 198.9 195.4 205.8 207.0 210.3 160.3 168.8 165.4 195.9 211.4 185.0 218.5 211.1 222.4 201.6 207.2 218.3 226.2 203.3 221.5 205.6 161.7 213.5 211.9 223.2 225.3 210.5 229.0 228.1 237.5 177.9 195.1 182.8 216.7 227.1 204.1 239.8 231.4 255.7 227.4 225.8 236.6 248.5 218.6 244.8 228.5 184.0 230.9 241.1 244.6 240.1 229.9 252.5 248.1 260.0 198.9 214.9 209.5 233.9 234.1 211.0 258.5 253.0 275.5 236.2 228.5 258.6 261.7 247.4 259.7 246.2 194.2 254.3 262.4 261.9 257.4 250.0 275.7 275.3 279.1 210.3 236.8 230.7 239.1 249.3 219.7 274.5 260.5 283.9 250.9 247.9 277.3 274.1 263.5 270.7 255.3 202.5 267.2 273.0 284.1 266.7 265.9 294.1 287.2 293.0 212.7 241.8 242.5 252.7 258.5 229.9 278.4 281.7 283.6 263.8 262.1 288.1 287.1 280.9 280.9 277.2 210.9 274.2 287.0 285.8 281.1 272.5 301.6 306.2 300.6 222.1 243.1 247.1 267.5 272.2 233.8 282.3 277.6 309.2 271.9 264.3 286.6 291.0 284.1 286.2 280.1 218.4 284.1 297.2 294.2 280.5 271.8 309.5 326.2 314.3 229.1 261.0 262.3 264.0 261.0 223.3 281.2 273.8 302.3 270.4 258.3 273.8 282.3 300.0 290.2 289.7 216.1 295.2 303.9 310.9 294.6 284.3 317.0 340.3 319.5 223.4 267.8 266.3 283.3 279.4 245.3 294.7 288.7 319.4 277.5 277.4 310.6 303.5 313.0 302.9 299.9 225.6 307.4 317.3 311.6 298.0 290.6 338.6 355.4 285.3 229.5 267.4 279.0 - 407 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 63 Body Weight g D a y 70 Body Weight g D a y 77 Body Weight g D a y 84 Body Weight g D a y 91 Body Weight g D a y 94 Body Weight g D a y 98 Body Weight g Day 105 Body Weight g Day 112 Female, X 125 mg/kg/day 655097 655052 655063 655103 655026 655095 655023 655007 655053 655092 655046 655027 655104 655106 655024 655037 655088 655010 655077 655030 655075 655100 655049 655084 655061 290.0 280.3 246.8 302.5 294.7 334.2 285.6 288.3 315.0 304.4 324.0 303.3 301.6 227.5 304.1 322.6 315.2 301.7 292.4 334.7 363.5 318.9 235.0 265.1 275.7 294.2 288.4 250.7 303.6 307.5 332.3 292.3 286.2 313.8 296.5 324.2 306.7 310.4 234.1 314.7 327.1 310.3 302.3 285.1 329.2 359.2 324.9 240.4 278.4 288.3 301.8 278.6 251.7 305.8 296.8 336.6 292.1 290.3 317.9 308.0 332.4 309.5 314.0 239.8 323.3 335.2 311.1 297.5 291.2 331.9 359.8 333.1 242.0 284.7 290.5 315.9 293.4 265.8 314.5 300.9 336.1 298.1 307.2 332.0 315.6 343.5 317.8 329.6 248.3 323.8 342.3 315.0 306.1 291.8 352.0 371.3 341.4 241.0 293.2 285.5 309.7 289.8 272.2 310.1 298.8 324.6 304.2 310.1 333.9 310.7 350.9 318.6 326.3 251.0 319.5 349.9 314.7 318.0 299.2 343.6 360.3 332.1 241.5 280.7 283.8 294.8 277.8 251.5 294.3 283.1 317.1 282.7 283.0 305.9 299.4 357.2 314.6 335.7 263.2 333.0 349.3 322.2 297.1 304.4 364.8 366.4 335.7 246.8 286.2 288.1 354.4 304.1 332.4 264.1 340.7 348.7 328.0 302.3 305.3 358.0 361.9 337.8 244.2 291.6 294.2 371.1 314.9 340.0 256.5 340.4 351.0 294.0 300.5 311.1 364.5 374.6 341.1 245.6 292.6 288.9 - 408 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL BODY WEIGHTS Body Weight g Day 119 Body Weight g Day 126 Body Weight g Day 133 Body Weight g Day 140 Body Weight g Day 147 Body Weight g Day 154 Body Weight g Day 161 Body Weight g Day 168 Body Weight g Day 175 Female, X 125 mg/kg/day 655097 655052 655063 655103 655026 655095 655023 655007 655053 655092 655046 655027 655104 655106 655024 655037 655088 655010 655077 655030 655075 655100 655049 655084 655061 375.6 322.7 334.0 262.5 342.9 350.9 332.5 301.6 323.7 376.1 384.1 342.4 246.5 289.5 289.1 389.0 336.4 354.6 273.7 355.2 372.5 358.3 311.3 332.0 406.1 402.6 358.0 252.7 294.5 304.9 388.9 336.7 347.7 282.5 355.1 384.5 373.6 314.6 324.8 413.5 410.2 359.8 253.9 304.1 308.6 397.5 332.8 356.8 281.3 351.8 379.0 368.1 312.2 319.2 420.4 409.1 362.6 253.0 305.7 300.5 398.5 335.3 348.1 288.1 357.5 384.0 382.1 318.0 332.9 438.7 422.3 370.6 259.1 304.8 302.1 400.2 340.0 380.4 286.5 357.7 395.5 381.9 324.2 338.2 449.3 427.5 364.7 263.2 311.7 305.7 405.5 334.7 384.9 283.6 353.2 395.8 386.5 313.1 333.9 444.3 429.5 365.1 258.5 313.8 306.0 415.1 340.3 381.0 290.9 365.2 402.3 395.3 314.8 331.2 467.0 445.4 369.5 261.1 314.2 313.3 418.3 346.2 372.1 296.0 364.0 403.2 404.3 323.1 339.1 479.5 449.4 376.6 262.2 312.2 308.4 - 409 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Body Weight g Day 182 Body Weight g Day 183 Female, X 125 mg/kg/day 655097 655052 655063 655103 655026 655095 655023 655007 655053 655092 655046 655027 655104 655106 655024 655037 655088 655010 655077 655030 655075 655100 655049 655084 655061 416.9 391.8 327.7 347.2 480.0 456.5 370.6 266.5 320.3 309.7 394.4 374.8 306.3 326.6 455.3 432.2 358.5 249.7 302.1 289.3 INDIVIDUAL BODY WEIGHTS - 410 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX D INDIVIDUAL FOOD CONSUMPTION - 411 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 14 Food Cons. g/anm/day Day 21 Food Cons. g/anm/day Day 28 Food Cons. g/anm/day Day 35 Food Cons. g/anm/day D a y 42 Food Cons. g/anm/day Day 49 Food Cons. g/anm/day D a y 56 Food Cons. g/anm/day D a y 63 Food Cons g/anm/day Day 70 Male, I 0 mg/kg/day 654928 654993 654929 654972 654950 654953 654925 654987 654903 654966 654997 654971 654939 654919 654994 654949 654992 654909 654924 654943 654915 654927 654956 654910 654936 22.6 23.2 28.5 25.7 27.7 34.9 28.4 30.0 28.6 27.6 29.0 22.9 30.5 25.3 21.9 25.1 28.0 23.8 25.3 26.0 28.3 30.3 24.6 28.9 26.9 14.2 24.5 28.2 25.6 28.5 35.8 30.4 29.7 30.0 28.7 29.7 25.4 33.2 26.2 25.3 25.5 30.3 27.5 27.1 28.3 29.5 31.9 26.9 31.4 34.0 25.7 25.8 28.5 26.9 30.3 35.9 30.6 30.4 33.3 28.6 29.6 30.0 34.1 28.0 24.3 26.6 30.3 27.5 28.3 28.2 31.0 37.5 27.7 34.0 31.9 28.1 26.8 30.3 26.9 31.5 38.6 30.1 26.4 36.0 31.8 31.2 31.7 34.5 29.0 25.2 27.8 30.6 26.9 30.1 29.9 33.4 34.5 27.5 30.8 32.7 29.5 27.4 30.3 26.4 32.2 40.7 30.3 29.0 34.7 7.8 31.2 33.6 36.4 28.1 24.9 28.2 31.1 27.7 29.8 30.6 37.2 34.6 30.5 34.2 33.3 28.6 26.1 28.0 26.1 32.8 38.5 29.2 29.6 34.4 10.4 29.9 31.5 38.6 29.3 25.4 27.2 29.3 27.9 28.3 28.9 32.6 31.6 28.3 32.5 33.6 25.7 22.9 25.5 23.6 27.5 33.2 27.9 26.9 30.6 25.8 30.1 32.0 37.8 29.8 24.1 28.7 30.8 26.0 27.5 29.9 32.8 31.6 27.5 34.9 27.8 28.8 26.5 29.7 26.1 29.9 36.2 30.7 28.9 31.7 26.2 30.4 30.9 35.8 28.9 23.0 29.5 31.4 25.0 26.1 27.1 31.1 32.0 27.9 33.9 28.6 28.8 25.8 28.6 25.0 29.1 36.3 28.8 28.8 30.8 16.3 27.2 29.1 31.4 28.1 20.9 30.2 29.6 26.3 26.0 28.1 31.0 30.2 27.7 33.9 30.2 28.0 24.5 28.1 25.0 29.4 37.8 26.5 28.2 34.1 24.6 30.2 32.2 33.9 29.0 25.3 29.5 29.8 27.0 27.2 28.6 29.6 32.7 27.1 32.1 30.5 - 412 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day D a y 77 Food Cons. g/anm/day D a y 84 Food Cons. g/anm/day D a y 91 Food Cons. g/anm/day D a y 98 Food Cons. g/anm/day Day 105 Food Cons. g/anm/day Day 112 Food Cons. g/anm/day Day 119 Food Cons. g/anm/day Day 126 Food Cons. g/anm/day Day 133 Food Cons g/anm/day Day 140 Male, I 0 mg/kg/day 654928 654993 654929 654972 654950 654953 654925 654987 654903 654966 654997 654971 654939 654919 654994 654949 654992 654909 654924 654943 654915 654927 654956 654910 654936 27.5 24.8 28.7 26.0 22.8 36.1 28.5 29.8 31.9 27.1 30.8 30.6 34.3 29.2 23.3 27.6 30.5 26.9 26.8 28.2 30.3 32.6 26.9 29.9 29.5 28.0 23.7 28.6 24.7 31.8 34.8 28.0 28.2 33.1 28.7 28.7 29.3 33.7 25.7 23.1 27.8 29.0 26.2 24.4 26.8 29.1 28.5 25.5 29.4 30.4 28.1 23.6 28.2 26.5 30.6 18.9 28.1 28.0 32.3 28.2 30.1 30.7 34.5 27.4 24.2 27.9 29.5 25.8 25.8 24.9 29.2 28.6 24.6 29.4 30.6 25.1 28.1 27.0 24.5 26.2 27.5 29.0 29.5 25.1 29.9 23.7 26.5 29.6 27.6 27.9 28.5 31.4 30.6 27.4 30.6 24.9 27.7 30.8 28.4 28.6 28.5 30.8 31.5 26.8 30.0 23.2 27.0 29.9 26.7 28.5 23.1 30.4 31.0 26.1 30.1 24.7 27.3 31.0 24.9 26.6 27.1 29.7 30.0 25.8 29.7 25.5 27.3 30.0 25.5 26.7 29.1 31.6 31.6 26.2 27.5 22.4 26.9 29.2 26.2 25.9 28.4 29.9 31.7 28.5 31.6 - 413 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 147 Food Cons. g/anm/day Day 154 Food Cons. g/anm/day Day 161 Food Cons. g/anm/day Day 168 Food Cons. g/anm/day Day 175 Food Cons. g/anm/day Day 182 Male, I 0 mg/kg/day 654928 654993 654929 654972 654950 654953 654925 654987 654903 654966 654997 654971 654939 654919 654994 654949 654992 654909 654924 654943 654915 654927 654956 654910 654936 23.2 26.8 28.8 21.8 25.5 25.3 30.0 30.6 26.6 29.5 23.6 26.8 28.4 24.9 25.3 28.5 30.9 30.4 26.8 29.3 24.2 26.9 28.6 26.3 28.0 28.3 32.1 30.3 27.3 30.6 25.5 28.3 30.7 25.6 28.6 30.4 31.9 29.1 25.0 29.7 24.8 26.6 30.4 24.5 29.6 26.5 33.8 29.9 25.7 30.4 25.0 26.6 27.7 26.3 27.6 26.8 32.4 29.9 26.6 29.9 - 414 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 14 Food Cons. g/anm/day Day 21 Food Cons. g/anm/day Day 28 Food Cons. g/anm/day Day 35 Food Cons. g/anm/day D a y 42 Food Cons. g/anm/day Day 49 Food Cons. g/anm/day D a y 56 Food Cons. g/anm/day D a y 63 Food Cons g/anm/day Day 70 Male, III 1 m g / k g / d a y 654913 654947 654995 654938 654941 654946 654960 654908 654984 654932 654948 654904 654954 654945 654988 26.4 27.2 27.2 28.9 30.8 33.7 30.0 29.2 30.8 29.9 30.6 26.6 28.2 22.7 28.0 30.2 29.7 29.5 31.6 32.0 35.0 29.4 30.6 30.9 30.6 31.0 27.3 29.0 25.7 29.3 30.2 29.8 30.5 32.2 34.2 33.9 29.3 35.4 29.7 31.7 32.1 28.2 31.7 28.7 31.0 29.2 29.2 27.1 30.4 32.6 29.7 26.7 31.3 30.8 30.4 32.3 28.3 31.4 26.9 30.2 30.8 28.0 29.1 25.1 34.2 31.9 28.3 31.9 31.6 30.2 32.7 30.3 33.1 28.1 30.6 29.8 27.0 28.9 30.4 30.4 32.4 27.7 32.8 31.5 29.8 30.4 29.7 32.0 28.2 29.3 25.3 24.4 25.2 27.0 25.6 28.6 24.1 27.0 25.3 27.5 30.2 28.4 31.1 27.6 29.8 29.4 27.8 26.9 30.1 28.9 30.5 29.9 30.4 30.3 29.3 29.2 27.0 32.0 28.3 28.7 29.2 26.7 27.9 30.7 28.9 29.7 29.0 30.0 32.2 30.4 30.2 25.3 31.0 26.2 28.5 29.8 27.4 29.6 31.9 30.9 33.1 27.0 28.8 33.4 30.6 30.3 27.0 31.6 24.1 28.9 - 415 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Food Cons. g/anm/day D a y 77 Food Cons. g/anm/day D a y 84 Food Cons g/anm/day D a y 91 Male, III 1 m g / k g / d a y 654913 654947 654995 654938 654941 654946 654960 654908 654984 654932 654948 654904 654954 654945 654988 29.2 26.9 27.1 30.7 31.3 30.7 28.2 30.0 32.4 29.9 37.7 30.4 31.8 25.3 28.5 27.1 27.1 26.2 28.7 26.8 28.3 27.2 28.6 30.3 29.1 29.9 26.9 28.8 25.3 29.6 30.0 27.0 28.1 31.7 27.3 28.3 28.1 27.4 29.2 30.6 31.4 28.0 31.7 25.1 30.0 INDIVIDUAL FOOD CONSUMPTION DuPont-9478 - 416 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 14 Food Cons. g/anm/day Day 21 Food Cons. g/anm/day Day 28 Food Cons. g/anm/day Day 35 Food Cons. g/anm/day D a y 42 Food Cons. g/anm/day Day 49 Food Cons. g/anm/day D a y 56 Food Cons. g/anm/day D a y 63 Food Cons g/anm/day Day 70 Male, V 5 mg/kg/day 655005 654907 654980 654959 654961 654916 654911 654917 654998 654970 654926 654918 654981 654969 654967 26.5 25.5 28.4 31.3 29.5 30.5 30.7 28.4 29.6 21.4 27.3 27.4 22.7 21.1 27.4 28.9 28.8 30.6 34.0 33.7 30.1 35.4 31.3 31.1 23.2 28.7 30.6 25.6 22.6 29.9 30.6 27.6 32.4 35.0 36.9 31.3 36.7 30.5 31.8 24.7 32.1 31.6 27.4 22.6 29.3 31.7 27.9 33.2 36.1 36.6 30.6 37.7 29.5 32.9 26.1 33.4 32.8 28.1 23.7 29.6 30.7 27.3 35.0 35.1 38.3 30.7 36.9 31.5 33.6 25.2 35.8 33.8 27.9 25.7 30.3 30.9 27.9 34.8 35.3 34.4 30.5 37.5 33.8 32.1 23.3 32.3 31.5 25.9 24.2 29.0 28.5 23.5 30.2 31.9 30.4 27.4 31.2 30.1 30.1 24.5 33.8 32.2 25.8 24.5 25.2 31.2 28.0 33.9 32.1 33.2 30.1 34.7 30.6 31.5 23.6 32.2 32.6 24.6 25.3 29.2 32.3 27.0 32.4 33.7 34.0 28.0 34.0 32.9 32.1 23.8 32.2 32.0 24.5 24.0 28.6 31.0 27.4 31.1 31.8 35.3 28.3 32.3 30.0 32.4 26.3 33.8 32.1 27.1 26.1 28.6 - 417 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Food Cons. g/anm/day D a y 77 Food Cons. g/anm/day D a y 84 Food Cons g/anm/day D a y 91 Male, V 5 mg/kg/day 655005 654907 654980 654959 654961 654916 654911 654917 654998 654970 654926 654918 654981 654969 654967 32.0 25.3 33.4 32.0 33.5 29.2 32.7 30.7 32.7 27.2 30.5 30.8 25.9 26.7 28.4 30.3 26.6 31.3 31.0 32.0 31.4 34.2 30.3 32.1 26.1 28.9 31.4 26.4 25.8 27.4 27.4 26.6 32.9 33.3 30.2 30.4 32.0 31.0 25.4 24.6 33.6 28.0 27.2 25.4 26.0 INDIVIDUAL FOOD CONSUMPTION DuPont-9478 - 418 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 14 Food Cons. g/anm/day Day 21 Food Cons. g/anm/day Day 28 Food Cons. g/anm/day D a y 35 Food Cons. g/anm/day D a y 42 Food Cons. g/anm/day Day 49 Food Cons. g/anm/day D a y 56 Food Cons. g/anm/day D a y 63 Food Cons g/anm/day D a y 70 Male, VII 25 mg/kg/day 655001 654975 654922 654940 654930 654958 654952 654923 654989 655006 654920 654912 654934 654964 654933 31.6 26.2 25.5 28.7 28.2 26.4 27.9 26.9 30.2 31.7 24.8 23.4 27.8 29.7 30.2 34.0 29.5 28.1 30.3 32.6 27.7 31.1 31.9 33.7 31.3 27.7 24.4 27.8 29.8 33.3 38.6 30.8 30.0 31.2 33.7 28.0 31.1 32.4 31.9 31.2 29.5 24.1 28.6 30.6 35.8 40.9 28.4 28.2 29.7 34.8 27.6 30.1 32.9 32.1 30.6 29.7 24.5 26.8 30.9 36.2 41.3 28.3 30.2 32.2 36.8 30.0 32.7 31.4 32.2 31.5 30.1 24.8 29.5 33.4 38.6 37.6 28.4 30.5 30.9 35.8 28.2 32.0 30.5 32.0 32.1 30.1 24.8 27.6 34.0 38.1 33.5 26.0 27.4 27.5 31.7 25.6 28.2 26.5 27.6 26.9 29.2 24.8 29.2 33.6 38.5 37.5 28.8 34.1 28.8 31.9 27.6 31.6 29.7 33.1 31.1 30.9 26.3 30.1 32.8 37.9 37.9 30.5 33.2 30.6 34.2 27.5 31.2 28.8 32.7 29.9 30.8 26.7 29.3 34.3 36.7 37.4 27.6 30.5 31.1 33.8 27.5 29.2 26.5 31.0 29.7 29.2 26.1 28.1 30.8 34.4 - 419 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Food Cons. g/anm/day D a y 77 Food Cons. g/anm/day D a y 84 Food Cons g/anm/day D a y 91 Male, VII 25 mg/kg/day 655001 654975 654922 654940 654930 654958 654952 654923 654989 655006 654920 654912 654934 654964 654933 36.4 27.7 32.1 30.4 32.2 27.0 32.4 27.9 31.3 27.7 29.2 27.7 27.8 30.9 34.3 32.7 27.0 29.7 28.4 28.3 26.9 31.0 29.1 30.9 28.5 28.9 24.7 29.1 29.6 33.3 35.3 30.5 30.2 28.7 30.5 27.6 30.3 27.2 32.3 27.5 29.7 24.3 31.5 34.2 34.5 INDIVIDUAL FOOD CONSUMPTION DuPont-9478 - 420 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 14 Food Cons. g/anm/day Day 21 Food Cons. g/anm/day Day 28 Food Cons. g/anm/day Day 35 Food Cons. g/anm/day D a y 42 Food Cons. g/anm/day Day 49 Food Cons. g/anm/day D a y 56 Food Cons. g/anm/day D a y 63 Food Cons g/anm/day Day 70 Male, IX 125 m g / k g / d a y 654983 654965 654979 654986 655003 654921 654996 654951 654955 654914 654937 654962 654982 654931 654906 654985 654978 654974 654990 654976 654957 654973 654977 654942 654991 28.5 23.7 24.8 28.5 26.2 29.5 28.0 27.7 30.4 27.4 27.0 26.4 25.4 26.5 28.9 22.3 23.2 25.7 26.0 23.6 27.8 28.5 20.8 27.9 30.1 30.9 26.9 26.5 29.3 29.5 31.7 29.0 28.8 33.1 29.1 29.7 30.4 28.0 29.8 31.7 24.1 24.8 29.0 27.0 28.9 30.4 28.8 25.5 30.1 33.2 31.4 28.1 26.3 31.8 28.6 31.7 28.6 30.2 37.1 27.9 31.5 33.7 30.4 32.6 34.5 26.2 26.0 29.1 27.1 29.6 30.2 28.3 25.0 30.4 34.6 31.2 27.5 25.7 31.9 27.9 31.6 27.0 30.8 34.6 28.3 30.3 32.2 29.5 31.3 32.2 25.0 25.0 29.2 27.6 26.7 28.7 28.0 23.5 28.2 34.6 33.4 27.7 27.9 33.5 27.6 34.1 29.9 31.6 33.7 30.5 31.3 33.6 31.6 32.0 36.9 23.9 25.2 29.8 28.0 27.7 29.7 29.9 26.2 29.2 35.4 33.7 27.5 27.4 33.4 28.6 28.7 26.5 31.3 33.0 29.4 31.2 32.0 30.7 32.6 36.7 26.9 25.1 29.4 26.9 27.0 28.7 27.6 24.5 29.9 35.6 29.5 24.6 26.1 28.5 26.9 28.1 24.9 28.5 29.2 27.1 30.8 31.7 31.4 32.2 38.0 26.1 24.1 28.6 27.7 26.8 28.9 25.7 23.9 29.5 35.6 30.0 23.6 27.3 32.9 29.3 32.7 29.6 29.6 31.2 27.9 29.2 32.2 31.0 30.3 35.5 25.3 26.1 27.5 26.2 26.3 28.2 26.3 23.8 28.5 36.3 31.5 27.4 27.6 24.7 27.8 31.9 21.1 29.3 31.0 28.8 30.8 29.8 23.7 28.1 34.9 25.6 24.5 28.4 27.8 19.3 27.3 13.9 24.3 32.1 28.9 30.2 25.7 28.1 17.4 25.1 29.8 25.9 27.4 31.6 27.2 29.6 31.2 27.7 17.7 35.8 22.5 25.9 24.8 27.6 26.8 25.7 26.7 17.9 27.9 28.8 - 421 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day D a y 77 Food Cons. g/anm/day D a y 84 Food Cons. g/anm/day D a y 91 Food Cons. g/anm/day D a y 98 Food Cons. g/anm/day Day 105 Food Cons. g/anm/day Day 112 Food Cons. g/anm/day Day 119 Food Cons. g/anm/day Day 126 Food Cons. g/anm/day Day 133 Food Cons g/anm/day Day 140 Male, IX 125 m g / k g / d a y 654983 654965 654979 654986 655003 654921 654996 654951 654955 654914 654937 654962 654982 654931 654906 654985 654978 654974 654990 654976 654957 654973 654977 654942 654991 29.8 19.5 26.8 22.6 26.3 31.6 25.9 27.8 26.4 30.1 29.7 30.4 20.8 11.6 33.7 12.0 25.6 9.5 27.4 25.1 27.4 29.0 24.2 28.5 29.6 26.0 31.9 26.1 33.3 26.6 28.4 29.9 24.9 12.2 29.5 24.6 25.4 27.3 31.8 26.3 17.1 25.4 23.7 29.8 29.9 27.3 27.4 23.5 24.6 32.0 30.2 30.6 27.8 36.5 28.1 30.4 30.1 28.8 35.2 30.6 28.8 30.3 31.7 28.1 35.6 23.9 25.9 30.7 29.7 29.3 26.2 26.0 21.5 25.7 32.7 18.6 25.1 28.2 25.6 25.4 25.5 26.2 22.0 25.5 33.3 19.8 25.2 27.5 26.2 25.4 26.2 26.2 23.4 25.1 33.9 22.5 26.3 27.8 27.4 25.1 26.7 25.4 23.1 24.6 31.6 22.5 24.3 26.0 29.0 26.6 27.4 27.2 22.8 25.8 33.8 14.9 25.7 28.2 29.0 26.6 27.2 27.2 23.4 27.0 32.6 22.6 25.0 29.2 30.3 25.3 28.3 27.5 22.9 26.5 33.7 24.5 25.7 30.2 29.2 26.9 31.3 29.7 23.0 26.4 33.8 - 422 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 147 Food Cons. g/anm/day Day 154 Food Cons. g/anm/day Day 161 Food Cons. g/anm/day Day 168 Food Cons. g/anm/day Day 175 Food Cons. g/anm/day Day 182 Male, IX 125 mg/kg/day 654983 654965 654979 654986 655003 654921 654996 654951 654955 654914 654937 654962 654982 654931 654906 654985 654978 654974 654990 654976 654957 654973 654977 654942 654991 19.0 24.1 28.7 30.0 26.1 28.9 28.0 21.8 25.6 31.7 28.1 24.8 27.6 29.5 25.8 26.4 27.2 21.7 26.8 30.4 23.5 24.5 28.0 30.1 24.5 25.9 25.7 21.8 26.2 31.1 25.1 24.5 31.1 30.5 26.4 26.6 28.2 23.0 27.6 32.2 22.4 23.5 29.0 27.5 25.7 26.5 25.8 23.3 27.0 33.0 21.0 24.8 30.2 28.1 25.8 28.2 26.6 22.8 28.5 33.8 - 423 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 14 Food Cons. g/anm/day Day 21 Food Cons. g/anm/day Day 28 Food Cons. g/anm/day Day 35 Food Cons. g/anm/day D a y 42 Food Cons. g/anm/day Day 49 Food Cons. g/anm/day D a y 56 Food Cons. g/anm/day D a y 63 Food Cons g/anm/day Day 70 Female, II 0 m g / k g / d a y 655031 655107 655098 655016 655079 655036 655025 655099 655032 655083 655093 655045 655065 655074 655035 655009 655068 655019 655062 655109 655101 655072 655015 655071 655022 16.7 17.6 18.2 19.2 16.1 20.4 19.5 23.1 20.1 20.3 14.9 18.8 20.5 19.7 19.6 19.9 20.7 21.1 20.8 20.4 22.0 21.4 18.2 18.1 18.4 19.3 16.8 18.0 18.2 15.0 19.7 20.0 23.7 19.8 19.4 15.2 19.5 20.8 20.1 21.0 20.9 22.2 21.2 20.1 20.5 21.6 21.1 18.4 14.8 19.3 21.5 16.6 19.1 18.9 17.1 22.2 21.9 22.8 22.1 20.8 17.2 21.7 22.4 22.1 22.5 23.6 23.0 24.1 21.8 21.2 23.0 22.5 17.7 20.8 20.8 16.3 18.7 19.6 16.8 21.4 21.1 22.6 21.4 20.3 15.7 20.3 22.8 21.1 20.2 22.3 20.5 23.1 19.8 20.8 23.5 21.7 17.6 20.0 21.4 16.0 17.9 19.3 16.9 20.9 21.4 23.7 21.7 20.4 16.9 21.4 24.6 22.1 21.3 22.2 22.5 23.4 22.8 20.4 25.1 21.6 19.8 20.0 22.8 17.7 18.6 20.8 17.6 22.5 22.5 23.9 23.5 21.1 17.4 20.5 23.8 21.9 22.3 23.4 20.2 23.5 22.5 20.1 24.0 22.0 18.7 19.5 19.1 14.4 15.3 18.4 16.6 20.1 19.8 22.2 21.2 19.9 15.7 20.2 23.1 20.8 21.6 24.1 19.7 21.4 20.9 18.9 23.9 20.6 15.8 18.6 22.4 17.9 18.8 21.2 18.3 21.8 21.4 23.0 23.5 23.4 17.9 21.9 27.0 19.3 19.9 23.8 21.6 22.4 21.8 20.5 23.1 20.2 18.6 19.8 22.2 17.3 17.3 22.1 17.5 21.3 22.0 21.6 21.5 20.8 17.2 21.8 26.2 21.1 21.7 24.9 20.0 21.2 22.0 19.6 23.0 20.4 18.9 19.2 22.0 17.7 17.8 20.6 17.4 19.6 22.3 22.3 21.8 22.2 17.5 19.5 24.0 21.1 21.5 23.0 20.4 21.0 22.2 18.7 22.9 20.5 17.1 18.7 - 424 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day D a y 77 Food Cons. g/anm/day D a y 84 Food Cons. g/anm/day D a y 91 Food Cons. g/anm/day D a y 98 Food Cons. g/anm/day Day 105 Food Cons. g/anm/day Day 112 Food Cons. g/anm/day Day 119 Food Cons. g/anm/day Day 126 Food Cons. g/anm/day Day 133 Food Cons g/anm/day Day 140 Female, II 0 m g / k g / d a y 655031 655107 655098 655016 655079 655036 655025 655099 655032 655083 655093 655045 655065 655074 655035 655009 655068 655019 655062 655109 655101 655072 655015 655071 655022 21.5 16.6 17.0 19.8 18.1 21.4 22.0 21.8 22.3 22.1 18.0 20.3 23.8 21.7 23.3 24.0 19.7 20.2 24.0 18.6 21.9 20.7 18.0 20.2 20.2 16.5 17.3 20.9 17.0 22.3 21.2 22.0 18.0 22.1 17.4 20.7 25.9 20.1 21.5 24.1 20.0 19.5 24.3 19.6 24.8 19.5 17.3 18.3 18.1 16.4 15.9 19.7 16.9 20.5 21.7 17.9 21.7 21.4 16.9 20.1 25.0 21.7 19.8 22.9 17.5 20.2 21.6 18.0 22.3 19.0 18.4 18.2 18.3 20.9 19.0 19.6 22.0 16.2 22.3 22.0 15.6 22.6 23.5 21.0 20.1 26.1 19.0 22.6 20.3 14.8 20.6 25.1 23.3 20.4 25.1 20.1 22.3 21.0 19.2 20.4 20.2 19.2 19.4 25.6 18.8 20.8 20.8 20.2 21.9 21.3 21.2 21.7 27.3 18.8 23.0 23.0 20.2 21.2 22.6 21.8 21.8 24.1 17.3 26.0 20.6 21.3 20.9 24.7 22.4 24.2 24.9 19.2 23.3 21.0 21.4 - 425 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 147 Food Cons. g/anm/day Day 154 Food Cons. g/anm/day Day 161 Food Cons. g/anm/day Day 168 Food Cons. g/anm/day Day 175 Food Cons g/anm/day Day 182 Female, II 0 m g / k g / d a y 655031 655107 655098 655016 655079 655036 655025 655099 655032 655083 655093 655045 655065 655074 655035 655009 655068 655019 655062 655109 655101 655072 655015 655071 655022 7.3 22.2 21.6 22.1 23.8 18.5 22.4 21.0 20.5 15.1 20.5 19.7 23.9 23.9 18.4 22.4 21.7 21.3 16.2 21.2 21.4 21.7 25.8 17.1 22.3 20.5 18.8 22.0 22.3 22.1 24.4 26.1 18.1 22.6 20.2 21.5 21.4 21.4 23.0 23.8 25.0 18.9 24.4 22.6 21.1 24 20 21 24 25 18 23 23 20 - 426 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 14 Food Cons. g/anm/day Day 21 Food Cons. g/anm/day Day 28 Food Cons. g/anm/day Day 35 Food Cons. g/anm/day D a y 42 Food Cons. g/anm/day Day 49 Food Cons. g/anm/day D a y 56 Food Cons. g/anm/day D a y 63 Food Cons g/anm/day Day 70 Female, IV 1 mg/kg/day 655086 655041 655108 655040 655044 655013 655089 655091 655033 655090 655051 655018 655096 655057 655028 18.0 18.1 18.8 22.0 20.3 22.4 19.8 20.4 19.1 23.2 18.1 22.5 18.9 17.3 19.1 18.2 18.9 19.2 21.9 21.1 21.3 20.2 20.3 19.1 20.8 16.5 20.4 19.1 17.9 19.3 18.8 20.9 20.5 23.9 22.9 23.0 22.4 19.6 20.6 23.9 17.9 22.1 20.0 18.6 19.9 17.3 19.0 20.4 20.6 21.7 19.8 20.7 22.2 20.1 22.7 17.6 22.7 18.6 18.1 19.5 18.1 a 19.3 23.5 21.4 20.4 22.2 22.8 20.5 23.0 18.7 23.3 19.1 19.9 19.6 18.7 23.9 19.1 23.1 22.1 19.8 22.3 22.2 21.8 22.2 19.3 22.4 20.8 20.1 20.8 16.0 19.5 16.9 18.9 18.8 17.6 21.0 20.1 18.5 20.7 18.0 20.5 19.1 18.6 18.8 19.4 24.6 20.5 21.8 20.6 19.8 24.4 23.4 21.2 23.6 17.5 25.5 20.5 20.6 19.5 18.5 20.8 20.3 21.7 22.1 19.3 24.2 22.6 20.3 23.0 17.4 24.7 20.9 19.0 19.3 18.9 21.4 19.5 22.2 21.3 19.6 23.7 21.9 21.2 22.4 13.2 26.1 20.1 18.8 19.5 a Inaccurate data; food consumption value not calculated. - 427 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Food Cons. g/anm/day D a y 77 Food Cons. g/anm/day D a y 84 Food Cons g/anm/day D a y 91 Female, IV 1 mg/kg/day 655086 655041 655108 655040 655044 655013 655089 655091 655033 655090 655051 655018 655096 655057 655028 18.1 20.2 20.2 22.0 21.2 19.9 23.5 20.6 18.9 23.9 18.3 24.3 18.4 18.7 21.0 17.3 19.0 18.5 21.8 19.2 20.1 23.1 21.3 20.8 22.5 17.6 24.3 20.1 18.4 19.9 17.1 17.0 18.6 22.5 20.1 19.0 20.5 21.0 20.1 20.2 19.1 22.2 19.9 19.0 19.3 INDIVIDUAL FOOD CONSUMPTION DuPont-9478 - 428 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 14 Food Cons. g/anm/day Day 21 Food Cons. g/anm/day Day 28 Food Cons. g/anm/day Day 35 Food Cons. g/anm/day D a y 42 Food Cons. g/anm/day Day 49 Food Cons. g/anm/day D a y 56 Food Cons. g/anm/day D a y 63 Food Cons g/anm/day Day 70 Female, VI 5 mg/kg/day 655054 655038 655034 655039 655029 655067 655020 655087 655066 655042 655059 655064 655050 655021 655017 19.6 21.1 19.5 19.6 20.3 20.1 19.1 21.0 22.6 23.5 17.3 17.9 19.7 16.6 19.0 19.5 20.0 18.0 19.3 19.5 19.5 20.1 21.6 23.7 23.1 18.0 18.4 19.4 15.9 18.2 20.0 21.8 20.2 21.0 22.5 21.6 18.4 21.5 25.5 25.5 18.8 21.5 21.3 19.0 19.6 20.5 21.0 19.8 20.9 20.6 21.3 20.2 22.2 24.3 24.6 19.1 21.3 21.0 19.3 18.7 19.8 20.8 20.6 21.0 21.1 20.6 22.8 23.9 26.0 25.3 19.3 22.6 20.9 17.7 20.6 18.9 22.4 20.9 23.8 16.0 21.4 22.9 20.9 24.1 24.1 19.2 22.8 21.2 18.9 20.4 18.7 18.7 18.5 20.5 18.9 18.9 21.7 20.3 21.4 25.3 17.9 23.5 20.1 19.1 19.4 20.8 22.7 20.4 22.0 20.8 21.3 25.1 23.2 23.3 25.8 19.2 24.1 22.1 18.9 21.8 20.0 23.0 20.8 23.7 18.5 21.1 24.7 24.3 21.8 23.8 18.7 23.9 21.4 18.4 20.1 20.8 21.4 20.1 22.7 20.6 19.7 21.9 21.0 21.2 23.3 19.1 22.8 20.4 16.9 19.5 - 429 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Food Cons. g/anm/day D a y 77 Food Cons. g/anm/day D a y 84 Food Cons g/anm/day D a y 91 Female, VI 5 mg/kg/day 655054 655038 655034 655039 655029 655067 655020 655087 655066 655042 655059 655064 655050 655021 655017 20.7 21.6 20.6 22.2 19.4 18.6 23.3 20.0 23.3 24.1 18.7 22.9 21.4 17.0 20.4 19.2 21.8 20.5 20.2 19.0 18.5 22.9 21.2 22.0 22.2 19.3 21.1 20.1 17.3 19.5 19.8 20.8 20.6 19.4 20.1 19.7 20.6 22.1 20.4 21.4 18.7 21.4 21.2 17.1 20.2 INDIVIDUAL FOOD CONSUMPTION DuPont-9478 - 430 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 14 Food Cons. g/anm/day Day 21 Food Cons. g/anm/day Day 28 Food Cons. g/anm/day Day 35 Food Cons. g/anm/day D a y 42 Food Cons. g/anm/day Day 49 Food Cons. g/anm/day D a y 56 Food Cons. g/anm/day D a y 63 Food Cons g/anm/day Day 70 Female, VIII 25 mg/kg/day 655058 655076 655047 655055 655105 655078 655073 655011 655085 655012 655043 655082 655060 655056 655081 19.6 19.4 16.6 19.6 18.0 23.1 20.3 19.3 21.7 22.0 18.5 21.2 18.0 16.5 19.4 19.0 18.7 18.2 18.8 17.4 22.8 21.0 19.8 21.4 20.9 17.9 20.8 17.4 18.3 20.8 20.3 22.3 17.7 28.3 20.9 25.4 22.1 21.3 23.6 22.2 18.7 21.4 19.6 18.3 24.4 19.5 19.9 18.1 20.0 17.8 25.1 22.0 21.8 24.5 21.5 19.9 22.1 19.4 19.3 21.2 21.8 20.2 19.0 20.7 19.8 27.4 21.1 21.2 24.7 21.6 20.5 23.9 19.0 21.3 22.8 19.5 21.4 20.3 20.4 19.7 30.7 23.1 20.9 22.9 21.5 19.9 22.1 22.8 20.7 23.8 17.0 18.6 17.4 19.0 17.7 25.1 20.3 19.1 21.2 19.9 18.7 25.3 21.6 20.2 24.4 20.8 21.3 20.5 22.4 22.8 26.4 24.0 24.3 22.9 24.2 21.8 22.8 24.5 22.6 23.7 21.2 21.3 18.8 20.0 20.0 25.4 23.0 23.1 22.8 21.6 18.7 23.2 22.2 22.5 22.9 23.7 22.8 18.5 20.4 19.5 26.5 23.1 20.9 23.4 21.8 20.1 20.6 22.3 22.9 25.2 - 431 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Food Cons. g/anm/day D a y 77 Food Cons. g/anm/day D a y 84 Food Cons g/anm/day D a y 91 Female, VIII 25 mg/kg/day 655058 655076 655047 655055 655105 655078 655073 655011 655085 655012 655043 655082 655060 655056 655081 21.8 22.3 18.6 20.4 17.9 26.2 21.5 22.1 24.8 21.8 19.8 21.8 23.2 22.2 24.7 19.7 21.6 17.4 19.9 19.0 23.5 22.2 21.9 24.2 21.8 19.9 22.6 22.6 20.4 23.3 18.8 23.1 16.9 19.4 17.7 18.5 20.1 21.9 22.4 21.5 18.2 22.0 21.0 21.4 21.9 INDIVIDUAL FOOD CONSUMPTION DuPont-9478 - 432 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 7 Food Cons. g/anm/day D a y 14 Food Cons. g/anm/day Day 21 Food Cons. g/anm/day Day 28 Food Cons. g/anm/day Day 35 Food Cons. g/anm/day D a y 42 Food Cons. g/anm/day Day 49 Food Cons. g/anm/day D a y 56 Food Cons. g/anm/day D a y 63 Food Cons g/anm/day Day 70 Female, X 125 mg/kg/day 655097 655052 655063 655103 655026 655095 655023 655007 655053 655092 655046 655027 655104 655106 655024 655037 655088 655010 655077 655030 655075 655100 655049 655084 655061 18.4 18.6 16.2 19.9 18.8 20.2 19.4 18.4 19.7 19.6 19.3 19.3 19.5 14.7 19.7 19.5 22.0 21.1 18.6 20.7 20.7 22.6 16.0 18.3 17.3 19.3 18.9 16.7 21.3 19.1 23.1 20.0 19.2 20.2 20.1 20.6 20.5 21.3 16.7 19.6 22.1 22.8 21.4 20.1 21.6 22.2 23.0 18.2 18.6 18.7 21.2 19.4 18.2 22.3 20.7 23.5 21.6 19.5 22.9 21.5 24.5 20.3 22.1 16.9 21.4 23.3 26.4 21.9 20.9 22.8 23.8 23.4 18.6 19.8 20.1 19.2 20.4 17.3 20.6 20.1 23.6 21.8 20.9 22.2 21.3 23.3 20.2 22.7 16.4 20.4 23.3 24.0 21.1 20.7 22.2 23.2 23.2 17.9 18.6 19.7 20.8 19.1 17.2 20.4 21.5 22.8 21.1 22.9 23.1 20.7 23.9 20.2 24.4 16.9 21.5 23.8 23.8 21.6 20.2 21.1 25.9 23.7 18.8 20.0 20.5 22.2 19.6 17.7 19.9 20.6 24.5 21.1 19.8 22.2 19.6 21.8 19.6 22.2 15.7 a 22.8 22.5 20.9 19.2 21.6 24.7 23.2 17.2 19.1 20.0 19.8 18.0 15.2 18.6 17.7 21.7 20.0 18.9 19.8 19.1 23.8 20.8 24.3 15.8 22.1 22.5 28.0 22.8 20.4 21.4 28.2 23.5 15.1 19.7 19.1 22.0 21.1 18.7 21.4 21.8 25.8 20.6 21.7 24.2 21.4 24.5 20.7 24.3 16.6 21.2 23.3 21.2 22.1 19.7 23.8 25.9 26.1 16.6 17.5 21.2 21.3 20.2 16.7 21.3 20.1 25.9 20.2 21.5 22.2 19.6 21.2 19.0 21.9 16.5 19.7 22.1 23.3 20.9 18.8 20.1 23.9 25.4 16.9 18.7 20.1 21.0 19.9 17.8 19.5 21.5 24.4 20.0 19.1 21.5 19.3 22.6 18.4 23.1 16.5 21.5 22.0 21.5 22.3 19.2 17.8 22.7 24.1 16.4 19.9 20.5 a Inaccurate data; food consumption value not calculated. - 433 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day D a y 77 Food Cons. g/anm/day D a y 84 Food Cons. g/anm/day D a y 91 Food Cons. g/anm/day D a y 98 Food Cons. g/anm/day Day 105 Food Cons. g/anm/day Day 112 Food Cons. g/anm/day Day 119 Food Cons. g/anm/day Day 126 Food Cons. g/anm/day Day 133 Food Cons g/anm/day Day 140 Female, X 125 mg/kg/day 655097 655052 655063 655103 655026 655095 655023 655007 655053 655092 655046 655027 655104 655106 655024 655037 655088 655010 655077 655030 655075 655100 655049 655084 655061 22.0 18.4 17.2 19.3 19.0 26.2 19.3 20.3 22.6 20.1 23.5 18.3 22.9 15.7 19.9 21.4 20.3 19.1 19.6 20.2 20.7 23.7 16.1 18.7 19.5 23.7 18.5 20.4 20.8 6.1 18.6 20.7 23.8 21.8 20.3 24.4 19.7 25.3 17.5 20.1 22.6 21.1 20.7 18.4 23.4 27.2 22.1 15.0 19.8 19.2 20.5 19.0 20.7 19.3 18.6 23.5 21.0 23.5 21.4 18.4 24.0 12.7 25.2 16.8 20.1 22.3 19.4 23.2 18.9 24.4 19.2 20.8 14.4 16.2 17.8 20.5 21.2 17.2 18.1 22.6 22.4 21.5 15.2 17.0 18.5 19.0 24.1 19.4 18.2 22.4 22.2 23.3 14.8 20.5 17.7 19.7 17.9 21.6 20.3 20.6 24.4 24.6 14.9 18.9 17.2 21.3 21.8 20.0 20.1 24.3 27.9 24.8 14.8 18.2 18.1 23.4 25.6 22.4 18.7 28.1 27.0 26.6 15.0 17.7 19.6 23.5 26.6 23.5 17.8 27.5 26.0 27.4 14.9 18.4 18.5 22.6 24.6 25.9 18.7 26.9 24.5 28.8 18.6 21.7 22.5 - 434 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FOOD CONSUMPTION Food Cons. g/anm/day Day 147 Food Cons. g/anm/day Day 154 Food Cons. g/anm/day Day 161 Food Cons. g/anm/day Day 168 Food Cons. g/anm/day Day 175 Food Cons g/anm/day Day 182 Female, X 125 mg/kg/day 655097 655052 655063 655103 655026 655095 655023 655007 655053 655092 655046 655027 655104 655106 655024 655037 655088 655010 655077 655030 655075 655100 655049 655084 655061 22.0 22.5 23.9 19.4 26.9 25.2 26.5 15.4 20.0 17.1 23.4 24.9 24.5 18.8 28.6 24.9 26.0 15.7 17.9 17.4 22.3 22.4 24.6 18.3 24.5 26.5 27.5 15.3 17.9 17.6 22.3 26.3 29.6 18.6 29.3 27.5 29.2 16.3 25.5 20.5 21.4 23.2 20.9 18.8 28.7 23.2 23.6 15.4 18.2 17.6 17 21 20 18 24 22 23 17 20 17 - 435 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX E INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA - 436 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal MI 654928 MI 654993 MI 654929 MI 654972 MI 654950 MI 654953 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Stain Fur/Skin, Shoulder, Bilateral, Brown Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hyperreactive Hair Loss, Forepaw, Bilateral Protrusion, Umbilical Hernia Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design Days 0-42,49-93 48,93 93 0-42,49-93 48,93 93 0-21,91-93 48,93 28-42,49-84 93 0-42,49-93 48,93 93 0-14 48,93 70-93 28-42,49-93 21-42,49-93 93 0-42,49-93 48,93 93 - 437 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal MI 654925 MI 654987 MI 654903 MI 654966 MI 654997 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Right Discharge, Eye right, Black Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right MI 654971 Sacrificed by design General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Right Days 0-42,49-93 48.93 93 0-21,35-42,49-93 28 48.93 28 93 0-42,49-93 48.93 93 0,7,14-84,91,98-175 10,21 0-4,35,56,77,90,94-105,119,133,154,175 175 0,7,14-84,91,98-175 56 0-4,10,21,35,77,90,94-105,119,133,154, 175 175 0,7,14-84,91,98-133 147-175 0-4,10,21,35,56,77,90,94-105,119,133, 154,175 - 438 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal MI 654971 MI 654939 MI 654919 Observation Discharge, Eye right, Black Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Corneal Opacity, Right Discharge, Eye right, Black Hair Loss, Forelimb, Bilateral Hair Loss, Forelimb, Left Hair Loss, Forepaw, Bilateral Hair Loss, Forepaw, Left Swollen Observations, Face Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Right Discharge, Nose, Black Hair Loss, Nose Wound, Superficial, Nose Sacrificed by design Days 140-147 175 0,7,14-21 94-105,119,133,154 0 - 4 , 1 0 , 2 1 , 3 5 , 5 6 , 77, 90,1 7 5 91,98-175 91,98-105 42-84,91,98-175 28-35 42-84,91,98-175 28-35 91,98 175 0,7,14-84,91,105 ,126-140,168-175 35 0 - 4 , 1 0 , 2 1 , 5 6 , 7 7 , 90, 9 4 - 1 0 5 , 1 1 9 , 1 3 3 , 1 5 4 175 98 119 112,147-161 175 - 439 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal MI 654994 MI 654949 MI 654992 MI 654909 MI 654924 MI 654943 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Stain Fur/Skin, Face, Red Stain Fur/Skin, Head, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Accidentally killed General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Stain Fur/Skin, Face, Red Stain Fur/Skin, Head, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hyperreactive Stain Fur/Skin, Dorsal Body, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Days 0-140 183 147-183 147-183 183 0-183 183 183 0-140 183 147-183 147-183 183 0-119,133 183 126 147-183 183 0-183 183 183 0-126 - 440 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal MI 654943 MI 654915 MI 654927 MI 654956 MI 654910 MI 654936 Observation Eye Observations, Bled via Orbital for Clin Path, Right Discharge, Eye right, Black Hair Loss, Face, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Stain Fur/Skin, Dorsal Body, Red Stain Fur/Skin, Face, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design Days 183 133-161 168-183 183 0-183 183 183 0-183 183 183 0-119 183 147-183 126-183 183 0-183 183 183 0-42,49 48,93 93 - 441 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M III 654913 M III 654947 M III 654995 M III 654938 M III 654941 M III 654946 M III 654960 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Sacrificed by design Days 0-42,49-93 48,93 93 0-42,49-93 48,93 93 0-42,49-93 48,93 93 0-42,49-93 48,93 93 0-42,49-93 48,93 93 0-42,49-93 48,93 93 0-35 48,93 49-93 42,49-93 93 - 442 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M III 654908 M III 654984 M III 654932 M III 654948 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Side, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right M III 654904 Hair Loss, Forepaw, Bilateral Hair Loss, Forepaw, Right Stain Fur/Skin, Forelimb, Left, Brown Stain Fur/Skin, Shoulder, Left, Red Stain Fur/Skin, Ventral body, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Days 0-42,49-70 48.93 77-93 93 0-42,49-93 93 48 93 0-42,49-93 48.93 93 0,7,14-56,98-126 0-4,10,21,35,56,77,90,94-105,119,133, 154,175 161-175 133-154 63-84,91 154-175 154-175 175 0,7,14-84,91,98-175 10 - 443 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal Observation M III 654904 Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design M III 654954 General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Right M III 654988 Hair Loss, Forelimb, Bilateral Sacrificed by design General observation, No Abnormality Detected Eye Observations, Exophthalmus, Bilateral Eye Observations, Bled viaOrbital forClinPath, Eye Observations, Bled viaOrbital forClinPath, Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Corneal Opacity, Right Stain Fur/Skin, Dorsal Body, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Corneal Opacity, Right Hair Loss, Forepaw, Left Hair Loss, Forepaw, Right Sacrificed by design Days 0-4,21,35,56,77,90,94-105,119,133,154,175 175 0,7,28-84,91,98-105 112-175 0-4,10,21,35,56,77,90,94-105,119,133, 154,175 14-21 175 0,7 21 B i l a t3e5r a l Left 10 0-4,21,56,77,90,94-105,119,133,154,175 14-84,91,98-175 154-175 175 0,7,49-77,91,98,133-175 42 0-4,10,21,35,56,77,90,94-105,119,133,154,175 14-42 105-126 84 175 - 444 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal MV 655005 MV 654907 MV 654980 MV 654959 MV 654961 MV 654916 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Comments, animal out of cage Stain Fur/Skin, Ventral body, Brown Stain Fur/Skin, Face, Brown Wet Fur, Ventral body, Ventral Sacrificed by design Days 0-42,49-93 48,93 93 0-42,49-93 48,93 93 0-42,49-93 48,93 93 0-42,49-93 48,93 93 0-42,49-93 48,93 93 0-42,49-63,77 48,93 70 70 70 70 93 - 445 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal MV 654911 MV 654917 MV 654998 MV 654970 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Forelimb, Left Hair Loss, Forepaw, Bilateral Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right MV 654926 Discharge, Nose, Black Discharge, Eye right, Black Sacrificed by design General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design Days 0-7 48.93 35-42,49-93 14-42,49-93 93 0-42,49-93 48.93 93 0-42,49-93 48.93 93 0,7,14-35,56-84,105-175 0-4,10,21,35,56,77,90,94-105,119,133, 154.175 42-49,98 91 175 0,7,14-28,42-84,91,98-175 35 0-4,10,21,35,56,77,90,94-105,119,133, 154.175 175 - 446 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal MV 654918 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right MV 654981 Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right MV MV 654969 654967 Stain Fur/Skin, Dorsal Body, Red Stain Fur/Skin, Face, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, excessive bleeding Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design Days 0,7,14-84, 91, 98-1 7 5 0-4,10,21, 35,.56,77,90, 94-1 0 5 ,119 ,133, 154,175 175 0,7,14-84, 91, 98-1 4 7 0-4,10,21, 35,.56,77,90, 94-1 0 5 ,119 ,133, 154,175 154-175 154-175 175 0,7,14-84, 91, 98-1 7 5 105,154 0-4,10,21, 35,.56,77,90,.94-98, 119, 1 3 3 , 1 7 5 133 175 0-42,49-93 48,93 93 - 447 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M VII 655001 M VII 654975 M VII 654922 M VII 654940 M VII 654930 M VII 654958 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Vocalization, No Abnormality Detected Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design Days 0-42,49-93 93 48 93 0-42,49-93 93 48 93 0-42,49-93 48,93 93 0 48,93 21,28,35,42 28-42,49-93 7-42,49-93 93 0-42,49-93 48,93 93 0-42,49-93 48,93 93 - 448 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M VII 654952 M VII 654923 M VII 654989 M VII 655006 M VII 654920 Observation General observation, No Abnormality Detected Absent, Toe, Forepaw Right Eye Observations, Bled via Orbital for Clin Path, Right Swollen Observations, Forepaw, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right M VII 654912 Stain Fur/Skin, Head, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped Sacrificed by design Days 0-28 35-42,49-93 48.93 35-42,49-63 93 0-42,49-93 48.93 93 0-42,49-93 48.93 93 0-42,49-93 48.93 93 0,7,14-84,91,98-147 0-4,10,21,35,56,77,90,94-105,119,133, 154.175 154-175 175 0,7,14-84 0-4,10,21,35,56,77,90,94-105,119,133, 154.175 86,91,98-175 175 - 449 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA DuPont-9478 Sex Group Animal M VII 654934 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Right M VII 654964 Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right M VII 654933 Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design Days 0,7, 14-84,.91, 98-1 7 5 56 0-4, 10,21, 35,.7 7 , 9 0 , 9 4 - 1 0 5 , 1 1 9 ,133,154 175 175 0,7, 14-84,.91, 98-1 7 5 0-4, 10,21, 35,.5 6 , 7 7 , 9 0 , 9 4 - 1 0 5 , 119,133, 154, 175 175 0,7, 14-84,.91, 98-1 7 5 0-4, 10,21, 35,.5 6 , 7 7 , 9 0 , 9 4 - 1 0 5 , 119,133, 154, 175 175 - 450 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M IX 654983 M IX 654965 M IX 654979 M IX 654986 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Hyperactive Sacrificed by design General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Eye Observations, Exophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Corneal Opacity, Right General Teeth Observations, Clipped General Teeth Observations, Striated Discharge, Eye right, Black Hair Loss, Face, Right Wound, Superficial, Head Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Days 0-35 48,93 49-93 42,49-84 93 0-42 63-93 56 93 48 63-93 77-93 84-93 49-56 63-93 70-77 93 0-42 48,93 49-93 93 0-42,49-70 48,93 - 451 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M IX 654986 M IX 655003 M IX 654921 M IX 654996 M IX 654951 M IX 654955 Observation General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped Days 75-93 75-93 93 0-42 48,93 49-93 93 0-42 48,93 49-93 93 0-42 48,93 75-93 49-93 93 0-42,49 48,93 63-93 93 0-42,49 48,93 77-93 - 452 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M IX 654955 M IX 654914 M IX 654937 M IX 654962 Observation General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Aggressive Behavior Hyperreactive Discharge, Nose, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Bled via Orbital for Clin Path General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design Days 77-93 93 0-35 48,93 49-93 42,84-93 70-93 42 93 0,7,14-42 77 0-4, 1 0 , 2 1 , 3 5 , 5 6 , 90,. 9 4 - 1 0 5 , 1 1 9 , 1 3 3 , 1 5 4 175 126-175 49-84,91,98-175 175 0,7,14-42 0-4, 1 0 , 2 1 , 3 5 , 5 6 , .77,. 9 0 , 9 4 - 1 0 5 , 1 1 9 , 1 3 3 , 154,175 77-84,91,98-175 49-84,91,98-175 175 - 453 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M IX 654982 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right M IX General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design 654931 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right M IX M IX General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design 654906 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design 654985 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Absent General Teeth Observations, Clipped General Teeth Observations, Striated Days 0,7,14-42 0-4,10,21,35,56,77,90,94-105,119,133, 154.175 63-84,91,98-175 49-84,91,98-175 175 0,7,14-56 0-4,10,21,35,56,77,90,94-105,119,133, 154.175 74- 84,91,98-175 63-84,91,98-175 175 0,7,14-70 133,154 90 0-4,10,21,35,56,77,94-105,119,175 75- 84,91,98-175 84,91,98-175 175 0-7 183 91-183 77-183 49-183 - 454 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M IX 654985 M IX 654978 M IX 654974 M IX 654990 Observation Discharge, Nose, Black Discharge, Eye right, Black Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Aggressive Behavior Hyperreactive Stain Fur/Skin, Dorsal Body, Red Stain Fur/Skin, Face, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Hair Loss, Forelimb, Bilateral Days 77 77-98 35-147 14-147 183 0-42,183 183 49-182 183 0-42 183 75-183 49-183 112-119 161-168 147-183 175-183 183 0-42 183 112-183 49-183 56-175 - 455 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M IX 654990 M IX 654976 M IX 654957 M IX 654973 Observation Hair Loss, Forelimb, Left Hair Loss, Forepaw, Bilateral Stain Fur/Skin, Dorsal Body, Red Stain Fur/Skin, Face, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Discharge, Nose, Black Hair Loss, Forelimb, Right Hair Loss, Forepaw, Bilateral Hair Loss, Forepaw, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Wound, Superficial, Shoulder, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Days 182-183 70-183 147-183 147-183 183 0-14 183 77-183 175-183 56 21-56 63-84 183 0-7 183 91-183 49-183 14-56 183 0-42 183 126-183 49-182 - 456 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal M IX 654973 M IX 654977 M IX 654942 M IX 654991 Observation Stain Fur/Skin, Dorsal Body, Red Stain Fur/Skin, Head, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Stain Fur/Skin, Head, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Stain Fur/Skin, Dorsal Body, Red Stain Fur/Skin, Head, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Stain Fur/Skin, Dorsal Body, Red Stain Fur/Skin, Head, Red Sacrificed by design Days 147-183 147-183 183 0-140,175-183 183 147-168 183 0-42 183 84-183 49-183 147-183 147-182 183 0-56 183 63-183 77-182 147-183 147-183 183 - 457 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F II 655031 F II 655107 F II 655098 F II 655016 F II 655079 F II 655036 F II 655025 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Wound, Superficial, Shoulder, Left Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Dark, Right Days 0-94 49,94 94 0-94 49,94 94 0,21-94 49,94 7-14 94 0-94 49 94 94 0-94 49,94 94 0-94 49,94 94 0-42,56-94 49,94 49 - 458 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F II 655025 F II 655099 F II 655032 F II 655083 F II 655093 Observation Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Wound, Superficial, Shoulder, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Closed, Bilateral Eye Observations, Enophthalmus, Bilateral Eye Observations, Enophthalmus, Right Eye Observations, Exophthalmus, Left Eye Observations, Exophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Corneal Opacity, Bilateral Eye Observations, Corneal Opacity, Right Eye Observations, tail vein Days 94 0-7,21-94 49,94 14 94 0-35,49-94 49,94 42 94 0-94 49,94 94 0 119-175 42-84,91,98-112 21-35 28-35 7,14 10,21 0-4,35,56 35-84,91,98-175 7,14-28 77,90,94-105,119,133,154,175 - 459 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F II 655093 F II 655045 Observation Discharge, Eye left, Black Discharge, Eye right, Black Hair Loss, Face, Left Hair Loss, Face, Right Scab, Face Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right F II 655065 Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right F II 655074 Hair Loss, Inguen, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right F II 655035 Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Ear twitch, Bilateral Days 28-35 7,14 35-42 21-28 21-49 175 0,7,14-84,.91, 98-1 7 5 0-4,10,21, 35,. 5 6 , 7 7 ,90,94-105, 119, 133 154,175 175 0,7,14-28, 49-- 8 4 , 9 1 , 9 8 - 1 7 5 0-4,10,21, 35,. 5 6 , 7 7 ,90,94-105, 119, 133 154,175 35-42 175 0,7,14-84,.91, 98-1 7 5 0-4,10,21, 35,. 5 6 , 7 7 ,90,94-105, 119, 133 154,175 175 0-35 183 56-183 56-183 42-49 - 460 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F II 655035 F II 655009 F II 655068 F II 655019 F II 655062 Observation Ear twitch Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hyperactive Hyperreactive Discharge, Eye bilateral, Black Discharge, Eye right, Black Discharge, Eye right, Red Ear twitch, Bilateral Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Sacrificed by design Days 63-70 183 0-14,28-35,56 183 77-140 42-49 98-105,183 112 126-147 21 183 0-183 183 183 0-183 183 183 0-7 183 14-183 28-183 183 - 461 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F II 655109 F II 655101 F II 655072 F II 655015 F II 655071 F II 655022 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Ear twitch, Bilateral Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Stain Fur/Skin, Head, Red Sacrificed by design General observation, No Abnormality Detected Accidentally killed General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Stain Fur/Skin, Head, Red Sacrificed by design Days 0-21,35-183 183 28 28 183 0-7,70-77,154-183 183 14-63,84-147 28-63 183 0-183 183 183 0-147,182-183 183 154-175 183 0-14 19 0,7,14-84,91,98-133 0-4,10,21,35,56,77,90,94-105,119,133, 154,175 140-175 175 - 462 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F IV 655086 F IV 655041 F IV 655108 F IV 655040 F IV 655044 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Forelimb, Left Hair Loss, Forepaw, Left Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Vocalization, No Abnormality Detected Hyperactive Ear twitch, Bilateral Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Ear twitch, Bilateral Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Misshapen Observations, Ear, Bilateral Days 0-94 49,94 94 0-14,70-94 49,94 21-63 21-63 94 0-14,28,49-70,84,94 49,94 35,42 35-42 21,77 21,77,91 94 0-21,35-70,84-94 49,94 28 28,77 94 0 49,94 35-94 - 463 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F IV 655044 F IV 655013 F IV 655089 F IV 655091 F IV 655033 F IV 655090 F IV 655051 Observation Misshapen Observations, Ear, Left Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Discharge, Mouth, Clear Wet Fur, Hindpaw, Bilateral Wet Fur, Thoracic, Ventral Wet Fur, Face, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Dark, Left Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Days 7-28 94 0-94 49,94 94 0-94 49,94 94 0-7,2149,94 14 14 14 14 94 0-42,56 49,94 49 94 0-94 49,94 94 0,7,14- - 464 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F IV 655051 F IV 655018 F IV 655096 F IV 655057 F IV 655028 Observation Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Dark, Right Discharge, Eye right, Black Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Forelimb, Right Hair Loss, Forepaw, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Exophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Corneal Opacity, Right Hair Loss, Face, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design Days 0-4,10,21,35,56,77,90,94-105,119,133,154,175 175 0,7,14-84,98-105,133-175 90 0-4,10,21,35,56,77,94-105,119,133,154,175 91,112-126 91 175 0,7,14-28,49-56,119-175 0-4,10,21,35,56,77,90,94-105,119,133,154,175 35-42 63-84,91,98-112 175 0,7,14-84,91,98-119,133 147-175 154,175 0-4,10,21,35,56,77,90,94-105,119,133 140-175 126 175 0,7,14-84,91,98-175 0-4,10,21,35,56,77,90,94-105,119,133,154,175 175 - 465 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F VI 655054 F VI 655038 F VI 655034 F VI 655039 F VI 655029 F VI 655067 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Ear twitch, Bilateral Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Comments, excessive salivation Stain Fur/Skin, Chin, Red Stain Fur/Skin, Face, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Ear twitch, Bilateral Days 0-94 49,94 94 0-94 49,94 94 0-21,35-77,94 49,94 28 28,84-91 94 0-94 49,94 94 0-35,49-94 49,94 40 42 42 94 0-35,49-94 49,94 42 - 466 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F VI 655067 F VI 655020 F VI 655087 F VI 655066 F VI 655042 F VI 655059 Observation Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Ear twitch, Bilateral Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hyperactive Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Days 42 94 0-21,35-94 49,94 28 28 94 0-21,35-94 49,94 28 28 94 0-94 49,94 94 0-94 49,94 94 0,56-84,91,98 112-175 133 0-4,10,21,35,56,77,90,94 175 - 467 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F VI 655059 F VI 655064 Observation Eye Observations, Corneal Opacity, Right Eye Observations, Dark, Right Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Hair Loss, Forepaw, Left Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right F VI 655050 Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right F VI 655021 Discharge, Eye right, Black Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right F VI 655017 Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design Days 119-175 105-133 28-49 28-49 7,14-21 175 0,7,14-84,.91, 98-1 7 5 0-4,10,21, 35,.56,77,90,.94-105,.119, 133 154,175 175 0,7,14-84, 98- 175 0-4,10,21, 35,.56,77,90,.94-105,.119, 133 154,175 91 175 0,7,14-84,.91, 98-1 7 5 0-4,10,21, 35,.56,77,90,.94-105,.119, 133 154,175 175 0,7,14-84,.91, 98-1 7 5 0-4,10,21,.35,.56,77,90,.94-105,.119, 133 154,175 175 - 468 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F VIII 655058 F VIII 655076 F VIII 655047 F VIII 655055 F VIII 655105 Observation General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Breathing Observations, Noise Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Ear twitch, Bilateral Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hyperactive Ear twitch, Bilateral Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hyperactive Days 0-56,70-94 49,94 63 94 0-35 49,94 49-94 42 94 0-28,42-94 49,94 35 35 94 0-77,91-94 49,94 84 84 84 94 0-21,35-94 49,94 28 - 469 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F VIII 655105 F VIII 655078 F VIII 655073 F VIII 655011 F VIII 655085 F VIII 655012 F VIII 655043 Observation Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hyperactive Ear twitch, Bilateral Ear twitch Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Shoulder, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Days 28 94 0-28,42-56,70-9. 49,94 35,63 35 63 94 0-94 49,94 94 0-94 49,94 94 0-94 49,94 94 0-7,21-94 49,94 14 94 0,7,14-84,91,98 175 - 470 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal F VIII 655043 Observation Eye Observations, Bled via Orbital for Clin Path, Right F VIII 655082 Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right F VIII 655060 Hair Loss, Forelimb, Left Stain Fur/Skin, Head, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right F VIII F VIII 655056 655081 Eye Observations, Dark, Right Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Face, Right Wound, Superficial, Face Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design Days 0-4,10,21,35,56,77,90,94-105,119,133, 154 175 0,7,14-84,91,98-147 0-4,10,21,35,56,77,90,94-105,119,133, 154.175 175 154-175 175 0,7,14-84,105-175 0-4,10,21,35,56,77,90,94-105,119,133, 154.175 91,98 175 0,7,14-35,56-84,91,98-175 35,56 0-4,10,21,77,90,94-105,119,133,154,175 42-49 42 175 0,7,14-84,91,98-175 0-4,10,21,35,56,77,90,94-105,119,133, 154.175 175 - 471 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal Observation FX 655097 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design FX 655052 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design FX 655063 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design FX 655103 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Hyperreactive Sacrificed by design FX 655026 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design FX 655095 General observation, No Abnormality Detected Days 0-42 49,94 49-94 94 0-42 49,94 49-94 94 0-42 49,94 49-94 94 0-56 49,94 84-94 77-94 63-94 94 0-42 49,94 49-94 94 0-14 - 472 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal FX 655095 FX 655023 FX 655007 FX 655053 FX 655092 Observation Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Hair Loss, Forelimb, Bilateral Ear twitch, Bilateral Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Hyperactive Days 49,94 49-94 21-42 35 35 94 0-21,35 49,94 49-94 28,84 94 0-42 49,94 49-94 94 0-42 49,94 49-94 94 0-42 49,94 77-94 77-84 - 473 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal FX 655092 FX 655046 FX 655027 FX 655104 Observation Hair Loss, Forepaw, Bilateral Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bledvia Orbital for Clin Path, Bilateral Eye Observations, Bledvia Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bledvia Orbital for Clin Path, Bilateral Eye Observations, Bledvia Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Discharge, Eye right, Black Wound, Deep, Mouth Comments, animal caught teeth on cage, nose was stuck Swollen Observations, Face Swollen Observations, Nose Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Days 49-94 70 94 0,7,14-70 133 0-4,10,21,35,56,77,90,94-105,119,154 175 77-84,91,98-175 175 0,7,14-42 133,154,175 0-4,10,21,35,56,77,90,94-98,105,119 104- 175 49-84,91,98-140 161-175 112-119 104 105- 119 105 175 0,7,14-42 0-4,10,21,35,56,77,90,94-105,119,133 154,175 126-175 49-84,91,98-175 - 474 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal FX 655104 FX 655106 FX 655024 FX 655037 FX 655088 Observation Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Discharge, Eye bilateral, Black Discharge, Nose, Black Comments, teeth caught in cage Stain Fur/Skin, Forepaw, Bilateral, Red Stain Fur/Skin, Face, Red Days 175 0,7,14-42 0-4,10,21 49-84,91, 175 0,7,14-42 0-4,10,21 147-175 49-84,91, 175 0-42 183 49-183 183 0-42 183 112-183 49-183 112 112 112 112 112 - 475 - DuPont-9478 154,175 154,175 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Sex Group Animal FX 655088 FX 655010 FX 655077 FX 655030 FX 655075 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Observation Swollen Observations, Face Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Wound, Superficial, Mouth Ear twitch, Bilateral Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Hyperactive Ear twitch, Bilateral Days 112 183 0-35 183 77-183 49-183 119-126 42 42-49 183 0-35 183 49-183 70-140 42,70 Arches back during handling Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right 42,70 183 0-42 183 105-183 49-183 183 0-42 183 - 476 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA Sex Group Animal FX 655075 FX 655100 FX 655049 FX 655084 FX 655061 Observation General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Clipped General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Stain Fur/Skin, Head, Red Stain Fur/Skin, Neck, Red Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right General Teeth Observations, Striated Sacrificed by design General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Ear twitch, Bilateral Arches back during handling Sacrificed by design Days 112-183 49-183 183 0-42 183 105-183 49-183 183 0-49 183 56-182 91-183 126-183 183 0-42 183 49-183 183 0-28,42183 35,91 35,91 183 - 477 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX F OPHTHALMOLOGY REPORT AND INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS - 478 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 - 479 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS ( T e s t D ay 87) Sex Group Animal MI 654928 MI 654993 MI 654929 MI 654972 MI 654950 MI 654953 MI 654925 MI 654987 MI 654903 MI 654994 MI 654949 MI 654992 MI 654909 MI 654924 MI 654943 MI 654915 MI 654927 MI 654956 MI 654910 MI 654936 Observation No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Retina, Retinal Degeneration Focal, Right No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Days 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 - 480 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS ( T e s t D ay 87) Sex Group Animal M III 654913 M III 654947 M III 654995 M III 654938 M III 654941 M III 654946 M III 654960 M III 654908 M III 654984 M III 654932 Observation No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Retina, Retinal Degeneration Focal, Left Days 87 87 87 87 87 87 87 87 87 87 DuPont-9478 - 481 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS ( T e s t D ay 87) Sex Group Animal MV 655005 MV 654907 MV 654980 MV 654959 MV 654961 MV 654916 MV 654911 MV 654917 MV 654998 MV 654967 Observation No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Retina, Retinal Degeneration Focal, Left No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Days 87 87 87 87 87 87 87 87 87 87 DuPont-9478 - 482 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS ( T e s t D ay 87) Sex Group Animal M VII 655001 M VII 654975 M VII 654922 M VII 654940 M VII 654930 M VII 654958 M VII 654952 M VII 654923 M VII 654989 M VII 655006 Observation No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Days 87 87 87 87 87 87 87 87 87 87 DuPont-9478 - 483 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS ( T e s t D ay 87) Sex Group Animal M IX 654983 M IX 654965 M IX 654979 M IX 654986 M IX 655003 M IX 654921 M IX 654996 M IX 654951 M IX 654955 M IX 654914 M IX 654985 M IX 654978 M IX 654974 M IX 654990 M IX 654976 M IX 654957 M IX 654973 M IX 654977 M IX 654942 M IX 654991 Observation No Ophthalmological Abnormalities Detected Globe, Phthisis bulbi, Right No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Days 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 - 484 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS ( T e s t D ay 87) Sex Group Animal F II 655031 F II 655107 F II 655098 F II 655016 F II 655079 F II 655036 F II 655025 F II 655099 F II 655032 F II 655083 F II 655035 F II 655009 F II 655068 F II 655019 F II 655062 F II 655109 F II 655101 F II 655072 F II 655015 F II 655071 Observation No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Retina, Retinal Degeneration Focal, Right No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Days 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 - 485 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS ( T e s t D ay 87) Sex Group Animal F IV 655086 F IV 655041 F IV 655108 F IV 655040 F IV 655044 F IV 655013 F IV 655089 F IV 655091 F IV 655033 F IV 655090 Observation No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Days 87 87 87 87 87 87 87 87 87 87 DuPont-9478 - 486 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS ( T e s t D ay 87) Sex Group Animal F VI 655054 F VI 655038 F VI 655034 F VI 655039 F VI 655029 F VI 655067 F VI 655020 F VI 655087 F VI 655066 F VI 655042 Observation No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Days 87 87 87 87 87 87 87 87 87 87 DuPont-9478 - 487 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS ( T e s t D ay 87) Sex Group Animal F VIII 655058 F VIII 655076 F VIII 655047 F VIII 655055 F VIII 655105 F VIII 655078 F VIII 655073 F VIII 655011 F VIII 655085 F VIII 655012 Observation No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Days 87 87 87 87 87 87 87 87 87 87 DuPont-9478 - 488 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL OPHTHALMOLOGICAL OBSERVATIONS ( T e s t D ay 87) Sex Group Animal FX 655097 FX 655052 FX 655063 FX 655103 FX 655026 FX 655095 FX 655023 FX 655007 FX 655053 FX 655092 FX 655037 FX 655088 FX 655010 FX 655077 FX 655030 FX 655075 FX 655100 FX 655049 FX 655084 FX 655061 Observation No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected No Ophthalmological Abnormalities Detected Days 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 87 - 489 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX G INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH -490- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Male Rats/Group I 0 mg/kg/day BASELINE Animal Number 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 Trial 1 0.63 0.66 0.46 0.46 0.56 0.51 0.41 0.49 0.72 0.41 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.53 0.46 0.54 0.62 0.62 0.63 0.65 0.65 0.59 0.53 0.58 0.52 0.52 0.40 0.49 0.66 0.66 0.61 0.41 0.32 0.38 0.40 0.41 0.43 0.61 0.52 0.62 0.56 0.45 0.47 Trial 1 0.26 0.48 0.24 0.27 0.23 0.48 0.31 0.22 0.39 0.23 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.38 0.41 0.35 0.41 0.27 0.39 0.27 0.29 0.27 0.38 0.22 0.29 0.22 0.23 0.23 0.29 0.27 0.35 0.40 0.35 0.35 0.31 0.23 0.25 0.26 0.38 0.34 0.22 0.20 0.22 -49 1- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Male Rats/Group III 1 mg/kg/day BASELINE Animal Number 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 Trial 1 0.77 0.57 0.47 0.42 0.70 0.52 0.62 0.80 0.64 0.61 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.46 0.56 0.60 0.37 0.54 0.49 0.58 0.69 0.58 0.40 0.36 0.39 0.46 0.45 0.54 0.39 0.60 0.50 0.74 0.64 0.67 0.76 0.72 0.76 0.72 0.82 0.73 0.48 0.63 0.57 Trial 1 0.28 0.26 0.32 0.19 0.46 0.40 0.31 0.38 0.28 0.47 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.27 0.36 0.30 0.25 0.36 0.29 0.20 0.21 0.24 0.27 0.25 0.24 0.36 0.23 0.35 0.43 0.42 0.42 0.38 0.28 0.32 0.37 0.30 0.35 0.18 0.26 0.24 0.33 0.29 0.36 -492- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Male Rats/Group V 5 mg/kg/day BASELINE Animal Number 654911 654916 654917 654959 654961 654967 654998 654907 654980 655005 Trial 1 0.68 0.56 0.61 0.56 0.76 0.56 0.45 0.52 0.61 0.76 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.85 0.71 0.75 0.42 0.58 0.52 0.59 0.56 0.59 0.64 0.48 0.56 0.85 0.69 0.77 0.56 0.45 0.52 0.53 0.52 0.50 0.37 0.38 0.42 0.44 0.42 0.49 0.53 0.56 0.62 Trial 1 0.23 0.29 0.36 0.34 0.35 0.22 0.23 0.35 0.23 0.20 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.27 0.32 0.27 0.25 0.26 0.27 0.24 0.22 0.27 0.31 0.30 0.32 0.27 0.30 0.31 0.18 0.20 0.20 0.22 0.22 0.22 0.47 0.28 0.37 0.25 0.28 0.25 0.46 0.28 0.31 -493- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Male Rats/Group VII 25 mg/kg/day BASELINE Animal Number 654922 654923 654952 654958 654975 654989 655001 655006 654930 654940 Trial 1 0.70 0.53 0.72 0.61 0.54 0.45 0.44 0.47 0.54 0.69 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.45 0.61 0.59 0.64 0.76 0.64 0.85 1.01 0.86 0.56 0.48 0.55 0.55 0.49 0.53 0.66 0.51 0.54 0.58 0.56 0.53 0.49 0.56 0.51 0.53 0.51 0.53 0.71 0.65 0.68 Trial 1 0.32 0.19 0.29 0.45 0.36 0.31 0.21 0.26 0.29 0.34 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.32 0.30 0.31 0.20 0.23 0.21 0.35 0.41 0.35 0.25 0.31 0.34 0.20 0.29 0.28 0.25 0.21 0.26 0.22 0.31 0.25 0.20 0.24 0.23 0.22 0.25 0.25 0.49 0.33 0.39 -494- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Male Rats/Group IX 125 mg/kg/day BASELINE Animal Number 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 Trial 1 0.67 0.60 0.91 0.60 0.35 0.57 0.41 0.67 0.40 0.51 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.48 0.59 0.58 0.57 0.76 0.64 0.72 0.75 0.79 0.61 0.66 0.62 0.28 0.63 0.42 0.69 0.61 0.62 0.36 0.47 0.41 0.73 0.53 0.64 0.60 0.50 0.50 0.50 0.65 0.55 Trial 1 0.19 0.65 0.34 0.29 0.26 0.23 0.33 0.31 0.30 0.25 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.18 0.19 0.19 0.37 0.34 0.45 0.26 0.22 0.27 0.38 0.26 0.31 0.20 0.30 0.25 0.19 0.28 0.23 0.18 0.20 0.24 0.22 0.28 0.27 0.35 0.25 0.30 0.18 0.19 0.21 -495- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Male Rats/Group I 0 mg/kg/day WEEK 13 Animal Number 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 Trial 1 1.85 1.58 1.46 1.31 0.97 0.85 1.52 0.59 1.08 0.59 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 1.55 1.19 1.53 1.37 1.20 1.38 0.75 0.84 1.02 1.76 1.40 1.49 1.16 1.11 1.08 1.32 0.94 1.04 1.31 1.19 1.34 1.07 1.02 0.89 1.06 1.00 1.05 0.46 0.52 0.52 Trial 1 0.46 0.66 0.34 0.73 0.67 0.46 0.30 0.39 0.79 0.34 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.47 0.61 0.51 0.69 0.55 0.63 0.38 0.44 0.39 0.63 0.61 0.66 0.74 0.58 0.66 0.38 0.41 0.42 0.53 0.51 0.45 0.29 0.44 0.37 0.95 0.65 0.80 0.53 0.22 0.36 -496- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Male Rats/Group III 1 mg/kg/day WEEK 13 Animal Number 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 Trial 1 1.47 1.35 0.77 0.78 0.97 0.95 0.95 1.52 1.52 1.43 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 1.01 1.19 1.22 0.75 0.75 0.95 1.34 1.45 1.19 1.12 1.07 0.99 1.00 0.97 0.98 1.07 1.23 1.08 1.28 1.05 1.09 0.96 1.46 1.31 1.09 1.58 1.40 1.59 1.28 1.43 Trial 1 0.66 0.22 0.61 0.77 0.63 0.49 0.52 0.51 0.58 0.85 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.54 0.75 0.65 0.42 0.41 0.35 0.76 0.66 0.68 0.51 0.47 0.58 0.58 0.55 0.59 0.59 0.48 0.52 0.36 0.37 0.42 0.67 0.65 0.61 0.71 0.65 0.65 0.71 0.72 0.76 -497- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Male Rats/Group V 5 mg/kg/day WEEK 13 Animal Number 654911 654916 654917 654959 654961 654967 654998 654907 654980 655005 Trial 1 1.06 0.92 1.52 0.96 1.56 1.06 1.07 1.44 1.15 1.60 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 1.59 1.22 1.29 1.14 0.87 0.98 1.03 1.48 1.34 1.25 1.67 1.29 1.80 1.03 1.46 1.27 0.94 1.09 1.09 0.95 1.04 1.11 1.19 1.25 0.72 0.81 0.89 1.55 1.41 1.52 Trial 1 0.62 0.38 0.54 0.58 0.66 0.57 0.33 0.45 0.55 0.59 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.67 0.56 0.62 0.51 0.53 0.47 0.39 0.49 0.47 0.74 0.42 0.58 0.62 0.71 0.66 0.61 0.50 0.56 0.31 0.42 0.35 0.33 0.51 0.43 0.53 0.41 0.50 0.74 0.59 0.64 -498- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Male Rats/Group VII 25 mg/kg/day WEEK 13 Animal Number 654922 654923 654952 654958 654975 654989 655001 655006 654930 654940 Trial 1 1.01 1.27 1.45 0.95 1.67 0.99 1.29 0.96 1.27 1.51 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 1.33 0.85 1.06 1.09 1.64 1.33 1.67 1.24 1.45 1.20 0.71 0.95 1.62 1.19 1.49 1.38 1.18 1.18 1.25 1.50 1.35 0.95 1.56 1.16 1.44 0.98 1.23 1.38 1.49 1.46 Trial 1 0.40 0.63 0.84 0.60 0.63 0.51 0.31 0.35 0.51 0.81 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.46 0.54 0.47 0.71 0.68 0.67 0.56 0.57 0.66 0.51 0.46 0.52 0.57 0.85 0.68 0.65 0.69 0.62 0.43 0.31 0.35 0.31 0.41 0.36 0.65 0.55 0.57 0.90 0.85 0.85 -499- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Male Rats/Group IX 125 mg/kg/day WEEK 13 Animal Number 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 Trial 1 1.56 1.24 1.30 1.16 1.36 0.66 1.00 0.57 0.75 1.23 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 1.18 1.51 1.42 1.32 1.33 1.30 1.73 1.41 1.48 1.32 1.04 1.17 1.55 1.22 1.38 1.03 0.66 0.78 1.29 1.31 1.20 0.46 0.72 0.58 0.99 1.13 0.96 1.31 0.88 1.14 Trial 1 0.46 0.95 0.59 0.42 0.65 0.31 0.48 0.35 0.44 0.40 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.51 0.42 0.46 0.61 0.64 0.73 0.56 0.56 0.57 0.40 0.42 0.41 0.49 0.49 0.54 0.25 0.31 0.29 0.47 0.44 0.46 0.19 0.27 0.27 0.62 0.61 0.56 0.65 0.82 0.62 -500- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Female Rats/Group II 0 mg/kg/day BASELINE Animal Number 655019 655071 655062 655068 655009 655015 655035 655072 655101 655109 Trial 1 0.65 0.73 0.44 0.45 0.51 0.72 0.47 0.60 0.54 0.54 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.41 0.63 0.56 0.76 0.67 0.72 0.41 0.55 0.47 0.54 0.48 0.49 0.43 0.67 0.54 0.57 0.50 0.60 0.56 0.40 0.48 0.67 0.51 0.59 0.62 0.79 0.65 0.50 0.59 0.54 Trial 1 0.69 0.45 0.37 0.29 0.27 0.33 0.36 0.39 0.46 0.42 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.35 0.43 0.49 0.36 0.36 0.39 0.25 0.31 0.31 0.29 0.37 0.32 0.34 0.35 0.32 0.27 0.27 0.29 0.32 0.33 0.34 0.38 0.20 0.32 0.53 0.47 0.49 0.42 0.40 0.41 -50 1- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Female Rats/Group IV 1 mg/kg/day BASELINE Animal Number 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 Trial 1 0.74 0.60 0.71 0.61 0.59 0.57 0.73 0.66 0.73 0.44 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.66 0.76 0.72 0.51 0.46 0.52 0.57 0.45 0.58 0.75 0.77 0.71 0.56 0.50 0.55 0.70 0.52 0.60 0.69 0.57 0.66 0.72 0.77 0.72 0.73 0.72 0.73 0.55 0.56 0.52 Trial 1 0.39 0.50 0.31 0.35 0.32 0.22 0.45 0.32 0.34 0.41 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.46 0.31 0.39 0.28 0.24 0.34 0.28 0.26 0.28 0.34 0.28 0.32 0.34 0.31 0.32 0.32 0.44 0.33 0.42 0.35 0.41 0.29 0.30 0.30 0.49 0.51 0.45 0.32 0.29 0.34 -502- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Female Rats/Group VI 5 mg/kg/day BASELINE Animal Number 655020 655029 655034 655039 655042 655066 655067 655087 655038 655054 Trial 1 0.61 0.43 0.58 0.66 0.66 0.70 0.57 0.61 0.73 0.78 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.63 0.44 0.56 0.64 0.43 0.50 0.71 0.70 0.66 0.75 0.85 0.75 0.76 0.55 0.66 0.51 0.62 0.61 0.65 0.57 0.60 0.91 0.73 0.75 0.57 0.59 0.63 0.93 0.68 0.80 Trial 1 0.34 0.43 0.42 0.34 0.27 0.42 0.39 0.31 0.51 0.33 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.24 0.39 0.32 0.44 0.31 0.39 0.38 0.33 0.38 0.44 0.28 0.35 0.41 0.32 0.33 0.28 0.26 0.32 0.36 0.32 0.36 0.36 0.36 0.34 0.30 0.39 0.40 0.49 0.26 0.36 -503- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Female Rats/Group VIII 25 mg/kg/day BASELINE Animal Number 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 Trial 1 0.90 0.80 0.59 0.66 0.56 0.45 0.56 0.62 0.59 0.44 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.72 0.56 0.73 0.62 0.66 0.69 0.49 0.65 0.58 0.57 0.48 0.57 0.79 0.65 0.67 0.38 0.58 0.47 0.66 0.75 0.66 0.61 0.53 0.59 0.44 0.79 0.61 0.49 0.44 0.46 Trial 1 0.50 0.44 0.22 0.36 0.23 0.36 0.47 0.58 0.31 0.28 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.43 0.51 0.48 0.40 0.41 0.42 0.26 0.26 0.25 0.37 0.26 0.33 0.31 0.32 0.29 0.31 0.34 0.34 0.34 0.35 0.39 0.41 0.42 0.47 0.36 0.28 0.32 0.20 0.22 0.23 -504- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Female Rats/Group X 125 mg/kg/day BASELINE Animal Number 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 Trial 1 0.42 0.58 0.61 0.54 0.67 0.69 0.80 0.59 0.71 0.71 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.50 0.51 0.48 0.65 0.51 0.58 0.41 0.46 0.49 0.66 0.36 0.52 0.46 0.48 0.54 0.69 0.75 0.71 0.68 0.72 0.73 0.66 0.53 0.59 0.58 0.45 0.58 0.72 0.75 0.73 Trial 1 0.23 0.40 0.31 0.28 0.35 0.38 0.20 0.26 0.27 0.45 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.29 0.25 0.26 0.44 0.38 0.41 0.29 0.28 0.29 0.27 0.41 0.32 0.44 0.41 0.40 0.34 0.32 0.35 0.22 0.41 0.28 0.34 0.33 0.31 0.31 0.21 0.26 0.38 0.45 0.427 -505- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Female Rats/Group II 0 mg/kg/day WEEK 13 Forelimb Grip Strength (kg) Animal Number Trial 1 Trial 2 Trial 3 Mean of Three Trials 655019 1.02 0.88 0.74 0.88 655071 1 655062 1.04 0.76 0.80 0.87 655068 0.85 0.53 0.58 0.65 655009 1.24 0.94 0.82 1.00 655015 0.99 0.70 0.76 0.82 655035 1.23 1.23 1.13 1.20 655072 1.21 1.34 0.96 1.17 655101 0.74 0.75 0.78 0.76 655109 0.62 0.53 0.66 0.60 Trial 1 0.56 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.70 0.76 0.67 0.47 0.49 0.38 0.28 0.54 0.51 0.41 0.69 0.49 0.44 0.33 0.57 0.61 0.59 0.38 0.45 0.45 0.36 0.49 0.45 0.68 0.52 0.67 0.36 0.47 0.34 0.51 0.52 0.54 0.47 0.62 0.40 1Rat accidentally killed on test day 19. -506- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Female Rats/Group IV 1 mg/kg/day WEEK 13 Animal Number 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 Trial 1 1.23 0.57 1.20 0.84 1.40 0.71 1.21 1.22 0.97 1.16 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 1.10 0.81 1.05 1.10 1.09 0.92 0.99 0.53 0.91 1.36 0.96 1.05 1.05 1.10 1.18 0.61 0.50 0.61 1.05 1.14 1.13 1.10 0.97 1.10 1.55 1.46 1.33 0.83 1.01 1.00 Trial 1 0.51 0.34 0.45 0.35 0.35 0.31 0.43 0.26 0.61 0.24 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.52 0.51 0.51 0.45 0.29 0.36 0.37 0.40 0.41 0.60 0.31 0.42 0.41 0.32 0.36 0.22 0.29 0.27 0.47 0.48 0.46 0.27 0.39 0.31 0.56 0.57 0.58 0.38 0.46 0.36 -507- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Female Rats/Group VI 5 mg/kg/day WEEK 13 Animal Number 655020 655029 655034 655039 655042 655066 655067 655087 655038 655054 Trial 1 1.29 1.05 1.05 1.42 0.95 1.19 1.12 0.73 1.27 0.83 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.64 1.07 1.00 1.30 0.92 1.09 0.84 0.80 0.90 1.12 1.36 1.30 0.89 1.20 1.01 0.98 1.24 1.14 0.88 0.84 0.95 0.92 0.98 0.88 1.18 1.42 1.29 1.08 0.88 0.93 Trial 1 0.55 0.46 0.44 0.62 0.70 0.73 0.29 0.34 0.47 0.30 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.60 0.54 0.56 0.53 0.68 0.56 0.48 0.48 0.47 0.61 0.46 0.56 0.45 0.44 0.53 0.54 0.43 0.57 0.48 0.41 0.39 0.37 0.41 0.37 0.62 0.56 0.55 0.39 0.30 0.33 -50 8- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Female Rats/Group VIII 25 mg/kg/day WEEK 13 Animal Number 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 Trial 1 1.18 1.21 1.19 1.00 0.99 0.72 0.71 1.24 0.88 0.77 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 1.23 1.34 1.25 0.82 1.00 1.01 1.13 0.96 1.09 1.10 0.90 1.00 1.26 1.52 1.26 0.77 0.66 0.72 0.92 0.78 0.80 1.19 0.95 1.13 0.63 0.90 0.80 0.96 0.79 0.84 Trial 1 0.75 0.39 0.28 0.58 0.34 0.50 0.59 0.65 0.28 0.42 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.84 0.73 0.77 0.42 0.41 0.41 0.30 0.37 0.32 0.43 0.46 0.49 0.33 0.35 0.34 0.42 0.39 0.44 0.45 0.56 0.53 0.61 0.50 0.59 0.41 0.54 0.41 0.46 0.36 0.41 -50 9- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Female Rats/Group X 125 mg/kg/day WEEK 13 Animal Number 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 Trial 1 0.96 1.08 0.96 1.03 1.10 0.95 1.15 1.01 0.88 0.85 Forelimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.65 0.68 0.76 1.06 0.81 0.98 1.15 0.94 1.02 1.19 1.13 1.12 0.76 1.05 0.97 0.81 0.80 0.85 0.88 0.91 0.98 0.94 1.46 1.14 0.84 0.63 0.78 1.24 1.11 1.07 Trial 1 0.33 0.59 0.46 0.44 0.52 0.61 0.44 0.57 0.31 0.65 Hindlimb Grip Strength (kg) Trial 2 Trial 3 Mean of Three Trials 0.34 0.56 0.41 0.51 0.49 0.53 0.52 0.55 0.51 0.55 0.38 0.46 0.56 0.41 0.50 0.46 0.47 0.51 0.43 0.31 0.39 0.45 0.41 0.48 0.33 0.28 0.31 0.45 0.46 0.52 -5 10- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX H INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT -5 11- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT Male Rats/Group I: 0 mg/kg/day MANIPULATIONS MOTOR ACTIVITY ANIMAL ASSESSMENT APPROACH & NUMBER PERIOD TOUCH 654909 Baseline 0 Week 13 0 654910 Baseline 0 Week 13 0 654915 Baseline 0 Week 13 0 654924 Baseline 0 Week 13 0 654927 Baseline 0 Week 13 0 654943 Baseline 0 Week 13 0 654949 Baseline 0 Week 13 0 654956 Baseline 0 Week 13 0 654992 Baseline 0 Week 13 0 654994 Baseline 0 Week 13 0 AUDITORY STIMULUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 PUPILLARY RESPONSE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DEFECATION 1 1 0 0 1 0 1 0 1 1 1 0 0 1 1 0 0 0 0 1 URINATION 1 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 1 0 1 1 DuPont-9478 -5 12- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Male Rats/Group III: 1 mg/kg/day INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT MANIPULATIONS MOTOR ACTIVITY ANIMAL ASSESSMENT APPROACH & NUMBER PERIOD TOUCH 654908 Baseline 0 Week 13 0 654913 Baseline 0 Week 13 0 654932 Baseline 0 Week 13 0 654938 Baseline 0 Week 13 0 654941 Baseline 0 Week 13 0 654946 Baseline 0 Week 13 0 654947 Baseline 1 Week 13 0 654960 Baseline 0 Week 13 0 654984 Baseline 0 Week 13 0 654995 Baseline 0 Week 13 0 AUDITORY STIMULUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 PUPILLARY RESPONSE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DEFECATION 1 1 0 1 0 1 0 1 0 1 0 0 0 1 1 1 0 0 1 0 URINATION 1 1 1 1 1 1 0 1 1 1 1 1 1 1 1 1 1 0 1 1 DuPont-9478 -5 13- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Male Rats/Group V: 5 mg/kg/day INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT MANIPULATIONS MOTOR ACTIVITY ANIMAL ASSESSMENT APPROACH & NUMBER PERIOD TOUCH 654911 Baseline 0 Week 13 0 654916 Baseline 0 Week 13 0 654917 Baseline 0 Week 13 0 654959 Baseline 0 Week 13 0 654961 Baseline 0 Week 13 0 654967 Baseline 0 Week 13 0 654998 Baseline 0 Week 13 0 654907 Baseline 0 Week 13 0 654980 Baseline 0 Week 13 0 655005 Baseline 0 Week 13 0 AUDITORY STIMULUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PUPILLARY RESPONSE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DEFECATION 0 0 1 0 1 1 1 0 0 1 1 0 1 0 1 0 1 0 1 1 URINATION 1 1 1 1 1 1 1 0 1 1 1 1 1 1 1 1 1 1 1 1 DuPont-9478 -5 14- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT Male Rats/Group VII: 25 mg/kg/day MANIPULATIONS MOTOR ACTIVITY ANIMAL ASSESSMENT APPROACH & NUMBER PERIOD TOUCH 654922 Baseline 0 Week 13 0 654923 Baseline 0 Week 13 0 654952 Baseline 0 Week 13 0 654958 Baseline 0 Week 13 0 654975 Baseline 0 Week 13 0 654989 Baseline 0 Week 13 0 655001 Baseline 0 Week 13 0 655006 Baseline 0 Week 13 0 654930 Baseline 0 Week 13 0 654940 Baseline 0 Week 13 0 AUDITORY STIMULUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PUPILLARY RESPONSE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DEFECATION 1 0 0 0 0 0 1 0 0 1 0 0 1 1 0 0 0 0 0 1 URINATION 1 1 1 0 1 1 1 1 1 1 1 1 1 0 1 0 1 1 1 1 DuPont-9478 -5 15- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT Male Rats/Group IX: 125 mg/kg/day MANIPULATIONS MOTOR ACTIVITY ANIMAL ASSESSMENT APPROACH & NUMBER PERIOD TOUCH 654942 Baseline 0 Week 13 0 654957 Baseline 0 Week 13 0 654973 Baseline 0 Week 13 0 654974 Baseline 0 Week 13 0 654976 Baseline 0 Week 13 0 654977 Baseline 0 Week 13 0 654978 Baseline 0 Week 13 0 654985 Baseline 0 Week 13 0 654990 Baseline 0 Week 13 0 654991 Baseline 0 Week 13 0 AUDITORY STIMULUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PUPILLARY RESPONSE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DEFECATION 0 0 1 0 1 1 1 0 0 0 0 0 0 1 1 1 0 1 0 0 URINATION 1 1 1 0 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 DuPont-9478 -5 16- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT Female Rats/Group II: 0 mg/kg/day MANIPULATIONS MOTOR ACTIVITY ANIMAL ASSESSMENT APPROACH & NUMBER PERIOD TOUCH 655019 Baseline 0 Week 13 0 655071 Baseline 0 Week 13 a 655062 Baseline 0 Week 13 0 655068 Baseline 0 Week 13 0 655009 Baseline 0 Week 13 0 655015 Baseline 0 Week 13 0 655035 Baseline 0 Week 13 0 655072 Baseline 0 Week 13 0 655101 Baseline 0 Week 13 0 655109 Baseline 0 Week 13 0 AUDITORY STIMULUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PUPILLARY RESPONSE 0 0 0 DEFECATION 1 1 0 URINATION 1 0 1 0 11 00 1 00 1 00 1 0 10 0 11 000 00 1 00 1 000 00 1 0 11 00 1 00 1 0 11 00 1 aRat accidentally killed on test day 19. -5 17- DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT Female Rats/Group IV: 1 mg/kg/day MANIPULATIONS MOTOR ACTIVITY ANIMAL ASSESSMENT APPROACH & NUMBER PERIOD TOUCH 655013 Baseline 0 Week 13 0 655033 Baseline 0 Week 13 0 655040 Baseline 0 Week 13 0 655041 Baseline 0 Week 13 0 655044 Baseline 0 Week 13 0 655086 Baseline 0 Week 13 0 655089 Baseline 0 Week 13 0 655090 Baseline 0 Week 13 0 655091 Baseline 0 Week 13 0 655108 Baseline 0 Week 13 0 AUDITORY STIMULUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PUPILLARY RESPONSE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DEFECATION 1 0 0 1 0 1 0 1 1 0 0 0 0 1 0 1 1 1 0 1 URINATION 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 1 1 1 1 1 DuPont-9478 -5 18- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT Female Rats/Group VI: 5 mg/kg/day MANIPULATIONS MOTOR ACTIVITY ANIMAL ASSESSMENT APPROACH & NUMBER PERIOD TOUCH 655020 Baseline 0 Week 13 0 655029 Baseline 0 Week 13 0 655034 Baseline 0 Week 13 0 655039 Baseline 0 Week 13 0 655042 Baseline 0 Week 13 0 655066 Baseline 0 Week 13 0 655067 Baseline 0 Week 13 0 655087 Baseline 0 Week 13 0 655038 Baseline 0 Week 13 0 655054 Baseline 0 Week 13 0 AUDITORY STIMULUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PUPILLARY RESPONSE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DEFECATION 1 0 0 1 1 0 1 1 0 1 1 1 1 1 1 0 1 1 0 1 URINATION 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 DuPont-9478 -5 19- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT Female Rats/Group VIII: 25 mg/kg/day MANIPULATIONS MOTOR ACTIVITY ANIMAL ASSESSMENT APPROACH & NUMBER PERIOD TOUCH 655011 Baseline 0 Week 13 0 655012 Baseline 0 Week 13 0 655047 Baseline 0 Week 13 0 655055 Baseline 0 Week 13 0 655058 Baseline 0 Week 13 0 655073 Baseline 0 Week 13 0 655076 Baseline 0 Week 13 0 655078 Baseline 0 Week 13 0 655085 Baseline 0 Week 13 0 655105 Baseline 0 Week 13 0 AUDITORY STIMULUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PUPILLARY RESPONSE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DEFECATION 1 1 0 0 1 1 1 1 0 1 1 0 1 0 0 0 1 0 0 1 URINATION 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 DuPont-9478 -520- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT Female Rats/Group X: 125 mg/kg/day MANIPULATIONS MOTOR ACTIVITY ANIMAL ASSESSMENT APPROACH & NUMBER PERIOD TOUCH 655010 Baseline 0 Week 13 0 655030 Baseline 0 Week 13 0 655037 Baseline 0 Week 13 0 655049 Baseline 0 Week 13 0 655061 Baseline 0 Week 13 0 655075 Baseline 0 Week 13 0 655077 Baseline 0 Week 13 0 655084 Baseline 0 Week 13 0 655088 Baseline 0 Week 13 0 655100 Baseline 0 Week 13 0 AUDITORY STIMULUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 TAIL PINCH 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PUPILLARY RESPONSE 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DEFECATION 1 0 1 1 1 1 1 1 0 0 1 1 1 0 0 0 1 1 1 0 URINATION 1 1 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 1 1 1 DuPont-9478 -52 1- 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX I INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS - 522 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Baseline Male Rats/Group I: 0 mg/kg/day Ammal Number 1 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 395 398 440 359 383 324 396 419 363 350 Successive 10-Minute Intervals 2345 336 162 0 14 273 151 13 389 282 59 1 325 246 22 0 364 35 1 36 247 215 214 280 288 201 30 3 375 260 66 0 259 373 99 17 321 230 112 0 6 1 10 2 0 12 217 0 12 6 11 Baseline Male Rats/Group III: 1 mg/kg/day Animal Number 1 Successive 10-Minute Intervals 2345 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 345 270 249 236 4 442 366 384 213 19 423 307 262 40 3 420 397 254 202 6 322 311 195 0 2 377 340 321 364 175 353 280 316 188 13 409 368 394 276 125 396 345 295 23 45 535 457 449 85 439 6 145 12 3 0 0 73 8 0 3 95 Total 908 836 1173 952 831 1497 918 1132 1117 1024 Total 1249 1436 1038 1279 830 1650 1158 1572 1107 2060 - 523 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Baseline Male Rats/Group V: 5 mg/kg/day Animal Number 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 Successive 10-Minute Intervals 1 23456 420 292 160 77 3 3 370 323 211 40 19 0 431 320 356 321 331 266 357 314 168 22 12 4 324 271 243 96 9 4 420 426 387 326 319 279 411 361 267 235 268 129 426 342 284 328 35 7 405 315 216 239 119 6 450 374 247 38 8 21 Baseline Male Rats/Group VII: 25 mg/kg/day Animal Number 12 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 393 345 384 260 384 233 328 196 405 299 434 295 398 314 399 197 454 392 400 391 Successive 10-Minute Intervals 345 323 344 103 288 216 34 141 0 0 31 3 0 249 231 245 229 270 245 205 35 0 220 275 79 2 252 280 48 6 48 2 13 0 181 316 15 5 14 6 Total 955 963 2025 877 947 2157 1671 1422 1300 1138 Total 1556 1184 771 558 1610 1789 967 605 1216 1377 - 524 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Baseline Male Rats/Group IX: 125 mg/kg/day Ammal Successive 10-Minute Intervals Number 12 34 5 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 413 328 72 67 3 500 471 478 420 231 415 310 343 226 222 390 359 257 11 1 351 265 111 0 0 337 320 331 334 120 451 390 317 315 316 355 233 304 51 4 416 438 374 119 2 388 315 227 94 5 6 0 77 220 20 0 40 142 4 1 5 Total 883 2177 1736 1038 727 1482 1931 951 1350 1034 - 525 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Baseline Female Rats/Group II: 0 mg/kg/day Ammal Number 1 Successive 10-Minute Intervals 2345 655009 655015 655019 655035 655062 655068 655071 655072 655101 655109 329 155 279 215 232 317 118 2 145 189 324 262 261 234 126 425 377 283 336 31 351 247 172 101 2 407 313 322 261 198 460 443 380 355 400 326 314 380 175 208 338 243 248 306 188 424 178 101 277 314 6 103 141 4 7 1 155 157 66 217 265 Baseline Female Rats/Group IV: 1 mg/kg/day Animal Number 12 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 446 365 363 288 388 312 322 266 361 294 370 216 357 239 336 284 525 482 424 278 Successive 10-Minute Intervals 345 305 361 338 160 187 310 229 20 8 337 243 254 212 174 4 106 288 130 191 53 185 231 81 1 419 444 484 254 222 116 6 339 157 3 66 0 68 158 1 481 176 Total 1313 912 1211 1459 874 1656 2195 1469 1540 1559 Total 2154 1465 960 1488 1045 1178 1183 934 2835 1470 - 526 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Baseline Female Rats/Group VI: 5 mg/kg/day Animal Number 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 Successive 10-Minute Intervals 12 34 56 413 63 59 330 290 158 334 233 207 198 13 341 322 181 5 6 10 349 289 194 272 152 268 339 350 263 263 38 11 339 307 283 247 40 2 371 269 216 313 299 285 404 344 317 258 247 164 392 410 307 422 237 299 362 239 311 248 231 196 Baseline Female Rats/Group VIII: 25 mg/kg/day Animal Number 12 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 301 123 400 290 329 360 394 264 306 198 385 243 384 331 391 91 433 334 410 359 Successive 10-Minute Intervals 345 178 111 7 291 192 205 262 223 319 191 144 0 97 160 190 196 198 288 307 265 231 192 312 34 290 116 2 340 275 252 6 66 11 98 0 107 175 47 56 1 168 Total 1313 976 865 1524 1264 1218 1753 1734 2067 1587 Total 786 1389 1591 993 1058 1485 1565 1076 1176 1804 - 527 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Baseline Female Rats/Group X: 125 mg/kg/day Ammal Number 12 Successive 10-Minute Intervals 345 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 392 345 285 77 0 336 285 188 312 263 466 472 428 410 255 423 286 272 271 267 303 283 200 264 205 391 337 353 311 276 274 257 119 36 49 294 285 300 192 43 337 286 266 225 148 453 369 313 266 308 6 0 187 105 246 298 243 0 1 120 246 Total 1099 1571 2136 1765 1553 1911 735 1115 1382 1955 - 528 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Week 13 Male Rats/Group I: 0 mg/kg/day Animal Number 1 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 405 317 417 371 394 411 415 431 358 312 Successive 10-Minute Intervals 2345 324 313 227 249 276 191 215 96 371 259 280 170 315 245 169 196 384 368 318 287 341 283 254 258 333 277 350 213 349 341 321 331 284 268 289 231 295 335 276 229 6 3 27 185 77 263 254 217 255 128 173 Week 13 Male Rats/Group III: 1 mg/kg/day Animal Number 1 Successive 10-Minute Intervals 2345 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 a 386 368 294 273 299 390 365 258 282 274 388 350 343 237 100 428 365 261 302 334 320 281 206 164 24 415 358 344 296 252 381 346 312 283 130 463 346 331 363 291 385 329 307 295 140 518 529 469 441 516 6 200 238 42 180 15 250 50 162 10 459 Total 1521 1122 1682 1373 2014 1801 1805 2028 1558 1620 Total 1820 1807 1460 1870 1010 1915 1502 1956 1466 2932 aData inaccurate due to sensor malfunction; data excluded from summary table and statistical analysis - 529 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Week 13 Male Rats/Group V: 5 mg/kg/day Animal Number 654911 654916 654917 654959 654961 654967 654998 654907 654980 655005 Successive 10-Minute Intervals 1 23456 309 301 200 248 104 9 446 360 338 226 130 278 414 328 290 273 147 9 363 278 210 38 55 157 375 332 264 206 203 281 455 353 220 131 265 144 385 375 252 166 206 131 370 264 262 163 3 7 379 373 191 265 195 5 401 362 211 371 324 26 Week 13 Male Rats/Group VII: 25 mg/kg/day Animal Number 12 654922 654923 654952 654958 654975 654989 655001 655006 654930 654940 395 320 455 361 399 321 459 381 387 224 398 180 417 295 381 335 433 367 410 292 Successive 10-Minute Intervals 345 229 244 188 138 256 20 208 114 70 318 236 232 162 194 90 020 337 280 94 272 262 218 351 186 205 264 324 175 6 236 65 172 186 202 1 113 149 224 230 Total 1171 1778 1461 1101 1661 1568 1515 1069 1408 1695 Total 1612 1295 1284 1812 1259 581 1536 1617 1766 1695 - 530 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Week 13 Male Rats/Group IX: 125 mg/kg/day Ammal Successive 10-Minute Intervals Number 12 34 5 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 290 236 61 21 0 456 372 314 348 328 391 380 276 276 236 339 303 288 151 202 340 232 98 21 8 476 423 385 379 336 472 317 369 378 239 360 252 228 243 109 460 393 388 232 206 466 358 340 155 357 6 119 250 170 254 2 317 261 2 119 182 Total 727 2068 1729 1537 701 2316 2036 1194 1798 1858 - 531 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Week 13 Female Rats/Group II: 0 mg/kg/day Animal Number 12 655019 655071 a 655062 655068 655009 655015 655035 655072 655101 655109 368 267 390 227 378 244 347 345 342 279 362 283 357 289 406 305 497 365 Successive 10-Minute Intervals 345 237 233 206 210 252 166 236 246 204 292 311 256 140 156 136 238 291 239 258 203 185 231 219 187 292 126 245 6 157 246 247 215 32 201 128 308 281 Total 1468 1491 1555 1766 1085 1614 1420 1656 1806 Week 13 Female Rats/Group IV: 1 mg/kg/day Animal Number 12 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 385 272 358 278 375 298 431 306 387 356 367 141 471 259 463 340 477 402 364 289 Successive 10-Minute Intervals 345 256 211 174 139 227 74 317 293 274 206 250 185 282 180 142 195 270 135 221 310 226 364 279 172 261 358 265 215 114 173 6 Total 243 1541 56 1132 319 1876 182 1560 184 1531 34 1142 0 1487 26 1644 281 2044 179 1334 aRat accidentally killed on test day 19. - 532 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Week 13 Female Rats/Group VI: 5 mg/kg/day Animal Number 655020 655029 655034 655039 655042 655066 655067 655087 655038 655054 Successive 10-Minute Intervals 12 34 56 451 307 263 49 10 229 380 349 287 227 223 119 398 233 142 67 200 5 419 259 102 118 38 191 356 265 157 322 187 181 393 381 243 204 180 114 460 332 135 102 216 284 348 261 172 118 218 181 413 315 318 205 110 107 458 412 293 251 127 292 Week 13 Female Rats/Group VIII: 25 mg/kg/day Animal Number 12 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 369 250 447 327 378 290 348 217 284 152 464 352 457 318 415 370 415 332 496 376 Successive 10-Minute Intervals 345 175 228 18 243 210 194 211 216 15 171 121 137 147 144 71 313 288 201 321 197 178 250 103 206 243 377 191 266 47 212 6 148 218 142 103 83 260 198 239 113 251 Total 1309 1585 1045 1127 1468 1515 1529 1298 1468 1833 Total 1188 1639 1252 1097 881 1878 1669 1583 1671 1648 - 533 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS Week 13 Female Rats/Group X: 125 mg/kg/day Animal Number 12 655010 655030 655037 a 655049 655061 655075 655077 655084 655088 655100 381 297 394 295 493 484 396 333 400 204 454 352 381 279 470 326 313 228 439 405 Successive 10-Minute Intervals 345 235 261 177 257 260 201 427 503 408 255 260 188 169 276 190 331 64 291 105 187 49 274 247 351 219 187 135 322 292 272 6 66 202 95 129 268 222 1 169 0 321 Total 1417 1609 2410 1561 1507 1714 1002 1837 1082 2051 aData inaccurate due to sensor malfunction; data excluded from summary table and statistical analysis - 534 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX J INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS - 535 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Baseline Male Rats/Group I: 0 mg/kg/day Ammal Number 1 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 132 146 88 146 138 129 137 139 135 159 Successive 10-Minute Intervals 2345 141 86 2 10 165 133 2 5 115 128 42 3 132 143 19 1 148 36 1 20 138 145 144 153 141 154 39 7 133 150 58 0 127 124 97 13 146 142 103 2 6 5 10 6 2 9 136 2 16 9 17 Baseline Male Rats/Group III: 1 mg/kg/day Animal Number 1 Successive 10-Minute Intervals 2345 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 141 135 126 159 9 119 139 139 140 15 146 151 132 38 5 145 145 131 97 8 137 119 118 14 150 133 143 177 158 125 121 131 113 10 130 139 134 143 96 134 146 159 26 35 59 62 64 15 54 6 97 17 7 0 0 84 5 0 11 8 Total 376 461 382 443 352 845 480 496 505 569 Total 667 569 479 526 379 845 505 642 511 262 - 536 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Baseline Male Rats/Group V: 5 mg/kg/day Animal Number 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 Successive 10-Minute Intervals 1 23456 134 140 91 67 5 7 138 162 141 53 17 3 124 163 143 141 157 151 149 138 128 30 14 15 157 136 140 92 19 6 122 116 126 128 126 131 130 136 148 133 147 92 128 161 146 159 31 8 129 132 120 159 84 17 109 120 129 38 9 14 Baseline Male Rats/Group VII: 25 mg/kg/day Animal Number 12 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 158 143 120 123 157 135 141 136 142 137 128 138 126 142 141 130 130 134 133 150 Successive 10-Minute Intervals 345 153 142 88 130 152 30 100 4 4 40 5 2 134 151 159 136 161 130 113 42 1 933 134 80 6 135 131 37 6 63 3 10 1 145 124 15 10 14 13 Total 444 514 879 474 550 749 786 633 641 419 Total 747 558 410 325 868 817 439 296 498 599 - 537 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Baseline Male Rats/Group IX: 125 mg/kg/day Ammal Successive 10-Minute Intervals Number 12 34 5 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 133 137 67 52 5 66 76 69 67 43 110 121 141 137 121 152 161 163 18 1 144 157 110 14 151 172 162 134 98 121 143 131 142 145 138 135 138 54 12 117 120 123 47 4 141 141 151 77 6 6 1 9 124 19 2 35 72 7 2 12 Total 395 330 754 514 418 752 754 484 413 528 - 538 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Baseline Female Rats/Group II: 0 mg/kg/day Ammal Number 1 Successive 10-Minute Intervals 2345 655009 655015 655019 655035 655062 655068 655071 655072 655101 655109 174 97 150 127 147 135 94 4 108 124 135 158 163 142 103 121 122 132 120 33 144 144 108 95 4 133 179 142 153 128 118 126 128 137 144 152 152 138 140 149 148 162 160 159 163 120 87 74 116 156 6 101 113 7 7 9 116 108 60 172 131 Baseline Female Rats/Group IV: 1 mg/kg/day Animal Number 12 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 124 126 153 139 138 129 105 126 126 130 149 128 150 131 150 165 66 59 151 139 Successive 10-Minute Intervals 345 163 127 132 105 134 133 139 27 8 125 139 122 133 104 4 104 136 130 106 45 127 151 43 3 74 62 73 143 155 116 6 154 98 5 62 1 85 99 5 57 141 Total 796 578 708 535 504 851 761 791 964 684 Total 826 762 446 679 498 732 658 517 391 845 - 539 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Baseline Female Rats/Group VI: 5 mg/kg/day Animal Number 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 Successive 10-Minute Intervals 1 23456 148 57 54 163 157 111 118 125 136 112 3 2 128 126 127 8 10 16 134 147 143 139 143 153 134 136 138 141 43 11 153 140 154 139 60 3 129 101 106 134 117 121 147 146 168 146 142 139 123 128 123 108 126 111 156 139 147 131 149 168 Baseline Female Rats/Group VIII: 25 mg/kg/day Animal Number 12 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 137 119 130 130 118 96 134 131 151 132 172 146 146 149 150 79 120 137 124 154 Successive 10-Minute Intervals 345 113 77 11 132 111 131 130 134 136 135 108 4 89 139 120 143 146 150 132 154 141 156 146 26 132 85 3 159 166 141 6 58 13 90 1 86 144 39 53 3 137 Total 690 496 415 859 603 649 708 888 719 890 Total 515 647 704 513 717 901 761 610 480 881 - 540 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Baseline Female Rats/Group X: 125 mg/kg/day Ammal Number 12 Successive 10-Minute Intervals 345 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 146 139 143 72 0 133 122 125 126 111 64 61 67 60 38 137 154 138 152 125 129 152 124 144 163 148 147 140 181 145 155 184 107 42 42 146 150 177 177 54 133 137 141 143 120 123 136 151 142 145 6 2 133 13 148 151 137 0 4 110 132 Total 502 750 303 854 863 898 530 708 784 829 - 541 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Week 13 Male Rats/Group I: 0 mg/kg/day Animal Number 1 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 120 155 140 142 120 129 158 126 166 150 Successive 10-Minute Intervals 2345 133 125 101 143 152 147 148 70 131 119 126 109 151 125 128 128 132 114 126 121 142 139 155 139 148 131 141 114 136 146 143 124 155 139 141 145 158 150 157 137 6 7 32 100 53 127 150 122 150 88 124 Week 13 Male Rats/Group III: 1 mg/kg/day Animal Number 1 Successive 10-Minute Intervals 2345 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 a 151 156 148 151 150 135 134 128 125 123 144 151 138 125 73 136 164 155 141 139 152 149 101 102 23 154 146 139 124 148 132 132 137 146 78 128 149 141 135 158 146 152 151 151 78 58 65 55 60 59 6 138 133 22 95 30 112 26 121 7 58 Total 629 704 725 727 740 854 814 825 834 876 Total 894 778 653 830 557 823 651 832 685 355 aData inaccurate due to sensor malfunction; data excluded from summary table and statistical analysis - 542 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Week 13 Male Rats/Group V: 5 mg/kg/day Animal Number 654911 654916 654917 654959 654961 654967 654998 654907 654980 655005 Successive 10-Minute Intervals 1 23456 144 124 118 142 53 11 124 133 127 131 86 164 134 157 134 135 104 13 154 162 124 34 45 127 131 132 135 108 116 124 120 119 104 74 120 86 150 151 149 113 138 97 154 156 151 113 3 4 142 137 99 110 100 19 136 113 98 126 129 16 Week 13 Male Rats/Group VII: 25 mg/kg/day Animal Number 12 654922 654923 654952 654958 654975 654989 655001 655006 654930 654940 145 147 104 121 133 124 136 143 150 124 138 100 103 119 133 141 123 135 134 139 Successive 10-Minute Intervals 345 130 134 108 67 133 12 100 82 53 144 104 101 93 117 60 330 121 99 58 150 158 128 132 116 108 141 144 106 6 128 23 123 80 124 2 43 111 115 121 Total 592 765 677 646 746 623 798 581 607 618 Total 792 460 615 708 668 246 543 821 729 785 - 543 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Week 13 Male Rats/Group IX: 125 mg/kg/day Ammal Successive 10-Minute Intervals Number 12 34 5 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 148 129 63 19 1 119 113 116 111 143 136 149 151 133 161 148 140 146 89 134 172 138 66 31 10 131 155 146 159 145 111 153 137 130 139 148 124 108 114 77 117 136 132 105 86 101 106 91 66 117 6 86 82 131 168 3 151 108 6 68 72 Total 446 684 861 825 420 887 778 577 644 553 - 544 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Week 13 Female Rats/Group II: 0 mg/kg/day Animal Number 12 655019 655071 a 655062 655068 655009 655015 655035 655072 655101 655109 148 145 124 127 134 123 143 136 147 149 120 117 161 150 138 139 74 110 Successive 10-Minute Intervals 345 158 114 153 127 141 132 146 163 134 134 142 142 118 137 114 116 125 124 152 136 149 100 104 108 100 71 89 6 124 149 158 117 37 109 140 136 121 Total 842 800 858 814 702 711 888 725 565 Week 13 Female Rats/Group IV: 1 mg/kg/day Animal Number 12 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 165 143 168 146 148 126 100 135 149 155 144 117 105 135 129 145 118 118 125 140 Successive 10-Minute Intervals 345 156 123 108 135 144 81 108 163 153 118 111 107 140 138 104 140 138 146 87 103 108 159 152 136 103 124 103 138 105 121 6 Total 116 811 79 753 127 825 120 691 106 792 22 707 1 539 28 749 131 697 129 758 aRat accidentally killed on test day 19. - 545 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Week 13 Female Rats/Group VI: 5 mg/kg/day Animal Number 655020 655029 655034 655039 655042 655066 655067 655087 655038 655054 Successive 10-Minute Intervals 12 34 56 108 139 129 44 15 132 125 122 141 128 127 86 124 123 89 34 107 6 131 112 84 105 47 103 131 152 112 137 116 106 103 141 118 127 99 94 107 151 61 88 128 122 155 159 128 96 132 139 142 143 132 118 93 74 125 136 156 122 99 145 Week 13 Female Rats/Group VIII: 25 mg/kg/day Animal Number 12 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 143 133 123 117 119 116 153 141 160 109 121 154 116 138 149 156 146 132 120 137 Successive 10-Minute Intervals 345 132 163 25 141 123 110 132 122 19 109 80 105 109 98 61 133 144 141 146 101 103 161 77 135 101 139 143 155 37 120 6 132 145 67 92 92 129 103 145 76 131 Total 567 729 483 582 754 682 657 809 702 783 Total 728 759 575 680 629 822 707 823 737 700 - 546 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Week 13 Female Rats/Group X: 125 mg/kg/day Animal Number 12 655010 655030 655037 a 655049 655061 655075 655077 655084 655088 655100 135 123 135 123 57 56 137 133 156 103 135 147 136 128 134 171 145 137 113 140 Successive 10-Minute Intervals 345 122 157 109 118 120 118 66 56 45 128 139 101 118 135 127 168 63 154 74 119 36 143 127 124 143 128 88 155 150 144 6 52 124 11 92 139 140 5 95 2 133 Total 698 738 291 730 778 807 498 794 643 835 aData inaccurate due to sensor malfunction; data excluded from summary table and statistical analysis - 547 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX K INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA - 548 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES ABBREVIATIONS: General: ADEQ - adequate CLOT - sample clotted DECR - decreased INCR - increased NSR - no sample received for testing NT - not taken or not performed NT-HEMOL - not taken due to hemolysis OK - sample condition OK for testing QNS - quantity not sufficient for testing RNV - result not valid UTD - unable to determine > - greater than < - less than Individual Hematology Values: COND - sample condition RBC - red blood cell count HGB - hemoglobin HCT - hematocrit MCV - mean corpuscular volume MCH - mean corpuscular hemoglobin MCHC - mean corpuscular hemoglobin concentration RDW - red cell distribution width ARET - absolute reticulocyte count PLT - platelet count WBC - white blood cell count ANEU - absolute neutrophil (all forms) ALYM - absolute lymphocyte AMON - absolute monocyte AEOS - absolute eosinophil ABAS - absolute basophil ALUC - absolute large unstained cell SPEC - special observations Individual NORM ANIS MIC MAC POLY HYPO ECHI ACAN TARG RX HJB - Red Blood Cell Morphology Values: - Normal - anisocytosis - microcytes - macrocytes - polychromasia - hypochromasia - echinocytes - acanthocytes - Target cells - rouleaux - Howell-Jolly body - not observed or not examined see whole blood sample condition - 549 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) ABBREVIATIONS: (Continued) Individual NORM SM TOX DB VC BC PCE GP BP SPEC - White Blood Cell / Platelet Morphology Values: - Normal - Smudge white blood cells - toxic neutrophils - Dhle bodies - vacuolated cytoplasm - basophilic cytoplasm - platelet clumps / estimate - giant platelets - bizarre platelets - special observations - not observed or not examined; see whole blood sample condition Individual PHEM PLIP PICT PT APTT Coagulation Values: - plasma hemolysis - plasma lipemia - plasma icterus - prothrombin time - activated partial thromboplastin time Individual SHEM SLIP SICT AST ALT SDH ALKP BILI BUN CREA CHOL TRIG GLUC TP ALB GLOB CALC IPHS NA K CL PHEM PLIP PICT PFLU Clinical Chemistry Values: - serum hemolysis - serum lipemia - serum icterus - aspartate aminotransferase - alanine aminotransferase - sorbitol dehydrogenase - alkaline phosphatase - total bilirubin - urea nitrogen - creatinine - cholesterol - triglycerides - glucose - total protein - albumin - globulin - calcium - inorganic phosphorous - sodium - potassium - chloride - plasma hemolysis from blood sample for fluoride determination - plasma lipemia from blood sample for fluoride determination - plasma icterus from blood sample for fluoride determination - plasma fluoride - 550 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) ABBREVIATIONS: (Continued) Individual Urinalysis Values: QUAL - quality (modifies color) COL - color CLAR - clarity VOL - volume UOSM - urine osmolality pH - the logarithm of the reciprocal of the hydrogen ion concentration UGLU - urine glucose KET - ketone UBIL - urine bilirubin BLD - blood URO - urobilinogen UFLU - urine fluoride UMTP - urine protein SPEC - special observations Individual Urine Microscopic Examination Values: EPIT - epithelial cells UWBC - urine white blood cells URBC - urine red blood cells NCRY - normal crystals MICR - microorganisms SPER - sperm SPEC - special observations KEY: Special 1234- Observations: trace few moderate many Urine Microscopic Values: EPIT/UWBC/URBC NCRY/MICR per high power field per high power field (40x) (4 0x) 1 - 1-10 1 - 1-25%/field 2 - 11-50 2 - 26-50%/field 3 - >50 3 - >50%/field SPERM/MUCUS per low power field (10x) 1 - 1-5 2 - 6-20 3 - >20 NOTES: When individual animal data are not reported, it may be due to one of the following reasons or other reasons, all of which are explained in the study records: the sample was c l o t t e d (CLOT) t h e r e w a s i n s u f f i c i e n t s a m p l e for t e s t i n g (QNS) a v a l i d r e s u l t c o u l d n o t b e o b t a i n e d (RNV) the sample was not suitable for testing the animal died prior to sample collection n o s a m p l e w as a v a i l a b l e for t e s t i n g (NSR) When an individual observation was recorded as being less than a certain value, calculations were performed on half the recorded value. For example, if bilirubin was reported as <0.1, 0.05 was used for any calculations performed with that bilirubin data. - 551 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number COND RBC x 1 0 6/uL HGB g/dL Male, Group I - 0 mg/kg/day - Day 48 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 OK OK OK OK OK OK OK OK OK OK 7.83 8.48 7.98 8. 68 8.10 8.48 8.10 8.86 7.98 8.82 14.5 15.7 15.1 15.4 15.0 15.3 14.7 15.4 14.1 16. 2 Male, Group III - 1 mg/kg/day - Day 48 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 OK OK OK OK OK OK OK OK OK OK 8. 61 7.91 8.88 8.15 8.04 8.03 8.56 8.40 8.21 7.77 15.3 14.9 16. 4 14.6 14.1 14.6 16. 2 15.1 15.3 15.4 Male, Group V - 5 mg/kg/day - Day 48 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 OK OK OK OK OK OK OK OK OK OK 8.24 8.29 8.26 8.05 NT 8.08 8.33 8.32 8.07 8.01 15.5 15.1 14.9 15.3 NT 14.7 15.8 15.2 14.9 14.8 HCT % 46. 0 49.8 47.3 49.8 48.3 48.2 46.6 48.8 46.7 51.3 49.5 46.2 52.2 45.9 45.3 47.5 51.2 48.4 48.2 48.5 50.1 47.6 48.2 49.2 NT 47.8 49.8 48.6 47.7 46.4 Individual Hematology Values MCV fL MCH pg MCHC g/dL RDW % ARET x 1 0 9/L PLT x 1 0 3/uL WBC x 1 0 3/uL 58.8 58.7 59.3 57.3 59.7 56.8 57.6 55.1 58.6 58.2 18.5 18.5 18.9 17.7 18.6 18.0 18.1 17.4 17.7 18.3 31.4 31.5 31.8 31.0 31.1 31.7 31.5 31.6 30.2 31.5 12.1 11.5 12.2 11.6 12.5 11.2 11.8 11.9 12.3 12.1 211.0 215.8 191.6 193.9 194.0 205.0 221.1 231.9 240.9 220.5 847 1106 1184 814 RNV 998 RNV RNV 1110 RNV 17.02 15.00 13.95 12.96 12.79 14.01 12.51 10.54 17.84 15.17 57.5 58.4 58.8 56.3 56.3 59.1 59.8 57.6 58.7 62.3 17.8 18.9 18.5 17.9 17.5 18.2 18.9 17.9 18.6 19.8 30.9 32.3 31.4 31.8 31.0 30.9 31.6 31.1 31.7 31.8 11.4 11.2 11.1 11.2 11.9 12.1 11.6 12.1 12.0 10.8 207.7 174.9 193.7 196.3 247.6 210.1 250.3 185.2 183.7 210.6 RNV 1073 1094 RNV RNV RNV RNV RNV 1104 1122 9.81 16.38 17.29 17.48 18.44 13.28 22.51 13.97 11.01 16.52 60.7 57.4 58.4 61.1 NT 59.1 59.8 58.4 59.1 58.0 18.8 18.2 18.0 19.0 NT 18.2 19.0 18.2 18.5 18.5 30.9 31.7 30.9 31.1 NT 30.7 31.7 31.2 31.2 31.9 11.4 10.8 12.5 12.4 NT 11.9 11.6 12.6 11.3 12.5 213.4 172.4 280.9 310.7 NT 250.3 183.9 248.0 214.1 248.2 961 RNV RNV 1026 NT 1102 1008 1267 1029 983 16.45 17.07 10.00 15.65 NT 12.57 12.82 22.89 12.92 15.71 DuPont-9478 - 552 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number COND RBC x 1 0 6/uL HGB g/dL Male, G r o u p VII - 25 m g / k g / d a y - D a y 48 HCT % 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 OK OK OK OK OK OK OK OK OK OK 8.03 7.99 8.01 7.83 7.87 8.04 7.88 8.14 7.73 7.46 14.4 15.1 15.1 14.4 14.8 14.4 14.6 15.9 14.4 14.8 46.4 46.6 47.4 45.2 47.3 48.1 46.3 50.0 45.4 47.0 Male, Group IX - 125 mg/kg/day - Day 48 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 OK OK OK OK OK OK OK OK OK OK 8.44 7.74 8.38 7.51 7.48 7.04 7.93 7.61 7.76 7.88 15.1 14.6 15.5 14.3 14.0 13.3 15.3 14.8 14.2 14.2 49.6 46.4 49.5 45.9 44.8 42.7 48.6 47.9 43.8 44.9 Individual Hematology Values MCV fL MCH pg MCHC g/dL RDW % ARET x 1 0 9/L PLT x 1 0 3/uL WBC x 1 0 3/uL 57.8 58.4 59.1 57.6 60.0 59.9 58.8 61.5 58.7 63.0 17.9 18.9 18.9 18.4 18.8 17.9 18.6 19.5 18.6 19.8 31.0 32.4 31.9 32.0 31.3 29.9 31.6 31.8 31.7 31.4 12.5 12.3 11.7 12.8 11.9 13.9 11.6 11.1 12.6 11.7 256.4 237.1 265.4 291.8 207.7 309.1 249.9 212.6 188.1 178.2 987 997 RNV RNV RNV RNV 954 RNV 1046 1074 13.14 17.40 18.46 17.96 11.37 15.08 16.02 20.45 11.26 13.48 58.8 60.0 59.0 61.1 59.9 60.7 61.3 63.0 56.4 56.9 17.9 18.8 18.5 19.1 18.7 18.9 19.3 19.4 18.3 18.0 30.4 31.3 31.3 31.2 31.2 31.1 31.4 30.9 32.5 31.6 13.5 12.1 13.0 13.4 13.6 13.2 11.4 11.6 14.4 13.1 276.3 244.0 258.2 247.1 237.7 309.0 244.1 231.1 291.0 281.9 985 RNV RNV 1207 RNV RNV 718 880 959 RNV 20.10 13.31 18.02 22.06 18.80 11.74 16.60 11.31 19.49 11.49 DuPont-9478 - 553 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Hematology Values Animal Number ANEU x 1 0 3/uL ALYM x 1 0 3/uL AMON x 1 0 3/uL AEOS x 1 0 3/uL ABAS x 1 0 3/uL ALUC x 1 0 3/uL Male, Group I - 0 mg/kg/day - Day 48 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 1.60 1.99 1.23 1.36 1.28 1.96 1.42 1.16 2.98 1.35 14.54 12.37 12.12 10.98 11.09 11.42 10.59 9.38 14.04 13.13 0.40 0.28 0.33 0.24 0.27 0.30 0.30 0.00 0.49 0.37 0.29 0.13 0.11 0.13 0.05 0.14 0.06 0.00 0.12 0.12 0.08 0.16 0.09 0.15 0.04 0.11 0.06 0.00 0.10 0.12 0.10 0.07 0.07 0.10 0.07 0.07 0.08 0.00 0.11 0.09 Male, Group III - 1 mg/kg/day - Day 48 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 1.51 1.84 0.77 1.55 1.83 1.12 3.60 1.26 0.97 1.63 7.93 13.79 16.12 15.14 15.96 11.58 18.46 12.20 9.56 14.28 0.13 0.20 0.12 0.31 0.32 0.26 0.45 0.18 0.24 0.23 0.09 0.16 0.09 0.09 0.09 0.18 0.00 0.15 0.10 0.13 0.09 0.30 0.09 0.26 0.15 0.08 0.00 0.11 0.09 0.18 0.06 0.09 0.10 0.14 0.09 0.07 0.00 0.07 0.05 0.07 Male, Group V - 5 mg/kg/day - Day 48 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 1.42 2.89 0.93 2.54 NT 1.38 1.55 2.55 2.06 2.29 14.36 13.40 8.81 12.25 NT 10.67 10.59 19.35 10.17 12.89 0.31 0.55 0.14 0.54 NT 0.24 0.44 0.47 0.49 0.23 0.13 0.05 0.06 0.10 NT 0.11 0.07 0.20 0.07 0.13 0.11 0.09 0.03 0.14 NT 0.08 0.10 0.21 0.07 0.10 0.11 0.08 0.05 0.08 NT 0.08 0.07 0.11 0.06 0.08 - 554 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Hematology Values Animal Number ANEU x 1 0 3/uL ALYM x 1 0 3/uL AMON x 1 0 3/uL AEOS x 1 0 3/uL ABAS x 1 0 3/uL ALUC x 1 0 3/uL Male, Group VII - 25 mg/kg/day - Day 48 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 0.89 2.43 2.19 3.13 1.76 1.23 1.49 2.28 2.62 1.98 11.75 14.22 15.43 14.05 9.01 13.43 14.02 17.64 7.94 10.94 0.17 0.37 0.40 0.40 0.20 0.19 0.19 0.22 0.38 0.38 0.08 0.14 0.14 0.14 0.12 0.10 0.06 0.12 0.14 0.04 0.16 0.17 0.16 0.15 0.21 0.07 0.18 0.11 0.11 0.07 0.10 0.08 0.13 0.10 0.07 0.06 0.08 0.09 0.07 0.07 Male, Group IX - 125 mg/kg/day - Day 48 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 3.01 1.75 3.70 2.98 1.26 0.99 2.22 1.53 1.55 1.39 16.26 11.08 13.59 18.25 16.93 10.45 13.74 9.41 17.28 9.88 0.40 0.28 0.37 0.44 0.22 0.12 0.28 0.19 0.28 0.11 0.18 0.12 0.15 0.15 0.08 0.05 0.18 0.09 0.10 0.11 0.15 0.04 0.11 0.12 0.23 0.07 0.12 0.05 0.16 0.00 0.10 0.06 0.10 0.11 0.08 0.06 0.06 0.04 0.12 0.00 - 555 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number COND RBC x106/uL HGB g/dL Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 OK OK OK OK OK OK OK OK OK OK 8.29 8.66 8.08 8.93 8.46 8.28 8.75 9.04 8.37 8.82 15.4 16.5 15.7 16.3 15.7 15.0 15.6 16.4 15.4 16.8 Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 OK OK OK OK OK OK OK OK OK OK 8.69 8.20 8.99 8.81 8.70 8.71 8.03 8.93 8.44 7.96 15.7 15.1 16.9 15.5 15.5 16.4 15.5 16.4 16.1 15.6 Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 OK OK OK OK OK OK OK OK OK OK 8.27 8.38 8.64 7.96 8.18 8.42 8.54 8.44 8.41 7.98 16.3 15.1 15.7 15.4 15.6 15.6 16.2 15.5 15.7 14.6 HCT % 46.1 48.7 46.3 48.8 47.8 44.8 48.4 50.1 46.4 49.8 47.0 45.9 50.4 48.2 47.0 50.7 46.8 49.5 47.5 47.1 47.8 46.8 48.1 45.5 44.9 47.7 49.0 47.6 48.4 44.6 Individual Hematology Values MCV fL MCH pg MCHC g/dL RDW % ARET x103/uL PLT x103/uL WBC x103/uL 55.6 56.2 57.2 54.6 56.5 54.1 55.3 55.4 55.5 56.5 18.6 19.1 19.5 18.2 18.5 18.1 17.9 18.2 18.4 19.1 33.4 34.0 34.0 33.3 32.8 33.5 32.3 32.8 33.1 33.7 13.5 12.1 13.3 11.9 13.4 13.2 12.9 12.4 12.8 12.9 209.40 184.00 161.20 131.40 186.30 179.70 141.10 177.50 172.50 180.80 1142 1377 1390 1019 1187 1120 1233 RNV 1369 1149 18.08 12.47 15.58 9.18 12.86 9.73 10.40 6.75 16.24 10.61 54.1 56.0 56.1 54.7 54.0 58.2 58.3 55.5 56.3 59.2 18.0 18.4 18.8 17.6 17.8 18.8 19.3 18.3 19.1 19.6 33.3 32.8 33.6 32.2 33.0 32.3 33.1 33.0 34.0 33.2 12.3 12.0 11.8 12.7 12.9 11.7 12.2 12.8 12.2 11.4 170.10 136.50 149.10 202.20 161.20 134.60 182.10 162.20 143.70 150.60 1102 1245 1300 1411 1222 RNV RNV 1103 RNV 1203 9.48 12.48 14.29 15.40 12.23 11.46 13.29 11.01 10.09 14.78 57.8 55.8 55.7 57.1 54.9 56.7 57.4 56.3 57.6 55.9 19.7 18.0 18.2 19.4 19.1 18.5 19.0 18.4 18.6 18.4 34.0 32.3 32.7 34.0 34.7 32.7 33.1 32.7 32.3 32.8 12.4 12.0 12.3 12.4 12.3 12.6 12.2 14.1 12.0 13.8 171.70 146.20 193.90 235.00 186.00 201.50 141.80 219.20 209.50 165.30 1165 1244 RNV 1315 1096 1379 966 1216 1211 RNV 10.27 11.22 9.77 15.92 12.37 10.57 11.44 16.81 9.67 9.62 DuPont-9478 - 556 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number COND RBC x106/uL HGB g/dL Male, G r o u p VII - 25 m g / k g / d a y - D a y 93 HCT % 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 OK OK OK OK OK OK OK OK OK OK 7.99 8.32 8.02 7.86 7.97 8.14 8.05 8.63 8.19 8.07 15.2 15.7 14.8 14.6 15.4 15.6 15.5 17.1 15.4 16.3 44.7 47.0 45.3 44.7 46.6 46.1 47.8 51.1 46.4 47.9 Male, G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 OK OK OK OK OK OK OK OK OK OK 8.19 8.09 8.08 6.96 7.82 7.07 8.07 7.53 7.73 8.05 15.9 15.6 15.4 14.1 15.0 13.9 16.1 15.1 14.3 14.9 49.1 46.7 46.9 42.0 45.1 42.5 47.7 47.7 42.9 44.4 Individual Hematology Values MCV fL MCH pg MCHC g/dL RDW % ARET x103/uL PLT x103/uL WBC x103/uL 56.0 56.5 56.4 56.9 58.4 56.7 59.4 59.2 56.6 59.3 19.0 18.9 18.5 18.6 19.3 19.1 19.2 19.8 18.8 20.2 34.0 33.4 32.8 32.6 33.1 33.8 32.3 33.5 33.3 34.1 12.8 12.6 12.5 12.7 12.5 13.5 13.2 12.0 13.2 12.2 172.20 229.40 197.60 202.40 160.70 229.00 224.00 195.10 181.50 134.00 1332 1398 1348 1376 1106 1094 RNV RNV 1153 1205 9.19 17.36 10.48 9.14 8.86 16.48 15.11 17.91 14.40 14.62 59.9 57.7 58.1 60.4 57.6 60.1 59.1 63.3 55.6 55.1 19.4 19.2 19.0 20.2 19.1 19.7 20.0 20.0 18.5 18.5 32.3 33.3 32.8 33.5 33.2 32.8 33.8 31.6 33.3 33.6 12.2 12.7 12.8 18.2 13.3 12.6 12.7 13.7 14.9 13.3 158.10 180.70 187.00 324.30 165.10 253.40 217.80 278.20 216.40 187.40 1190 1406 1178 1686 1454 1232 1003 1084 RNV 1239 16.26 12.94 14.26 22.59 13.10 9.25 13.11 10.10 16.98 10.26 DuPont-9478 - 557 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Hematology Values Animal Number ANEU x!03/uL ALYM x103/uL AMON x103/uL AEOS x103/uL ABAS x103/uL ALUC SPEC x103/uL Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 2.47 2.19 1.51 2.04 1.68 1.91 1.59 0.81 3.21 1.20 14.84 9.88 13.60 6.84 10.71 7.44 8.39 5.67 12.47 9.04 0.31 0.14 0.15 0.12 0.28 0.21 0.21 0.20 0.24 0.22 0.31 0.16 0.15 0.15 0.06 0.13 0.11 0.07 0.17 0.08 0.06 0.05 0.09 0.02 0.05 0.02 0.03 0.00 0.05 0.03 0.09 0.06 0.08 0.03 0.08 0.03 0.06 0.00 0.09 0.04 BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 1.81 1.29 1.00 1.63 1.90 1.49 1.06 1.35 1.14 1.78 7.40 10.79 12.97 13.18 9.94 9.51 11.56 9.23 8.38 12.51 0.15 0.09 0.12 0.33 0.21 0.23 0.53 0.14 0.38 0.23 0.07 0.19 0.08 0.10 0.06 0.23 0.13 0.19 0.12 0.10 0.03 0.07 0.05 0.04 0.06 0.00 0.00 0.04 0.02 0.08 0.03 0.06 0.07 0.12 0.06 0.00 0.00 0.05 0.05 0.08 BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 0.98 1.13 1.34 4.05 2.03 1.39 1.40 3.33 1.29 1.14 8.99 9.73 8.04 11.18 9.76 8.80 9.68 12.51 8.13 8.03 0.10 0.22 0.23 0.47 0.34 0.20 0.20 0.41 0.16 0.11 0.12 0.07 0.09 0.11 0.17 0.09 0.06 0.43 0.03 0.24 0.04 0.04 0.02 0.05 0.03 0.03 0.04 0.05 0.03 0.06 0.04 0.05 0.04 0.06 0.05 0.06 0.06 0.08 0.04 0.05 BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED DuPont-9478 - 558 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Hematology Values Animal Number ANEU x!03/uL ALYM x103/uL AMON x!03/uL AEOS x103/uL ABAS x103/uL ALUC SPEC x103/uL Male, G r o u p VII - 25 m g / k g / d a y - D a y 93 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 1.53 4.05 1.85 2.09 1.44 4.65 1.58 2.73 3.13 1.77 7.40 12.45 8.26 6.71 7.07 11.19 12.58 14.66 10.70 12.36 0.14 0.38 0.19 0.17 0.15 0.38 0.35 0.24 0.39 0.25 0.06 0.34 0.11 0.10 0.14 0.16 0.48 0.11 0.08 0.09 0.03 0.05 0.04 0.03 0.03 0.05 0.05 0.05 0.03 0.08 0.04 0.09 0.04 0.03 0.04 0.05 0.08 0.12 0.07 0.08 BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED Male, G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 2.27 2.31 2.88 3.70 1.39 0.95 2.20 1.46 2.56 2.00 13.42 10.17 10.95 18.24 11.27 8.01 10.50 8.38 13.87 7.79 0.24 0.20 0.15 0.32 0.22 0.13 0.18 0.14 0.26 0.23 0.18 0.18 0.15 0.19 0.12 0.10 0.12 0.06 0.17 0.17 0.05 0.02 0.03 0.06 0.05 0.03 0.04 0.03 0.05 0.03 0.09 0.06 0.10 0.08 0.06 0.03 0.06 0.03 0.06 0.04 BLOOD VOLUME SIGNIFICANTLY MORE THAN SPECIFIED DuPont-9478 - 559 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number COND RBC x106/uL HGB g/dL Male, G r o u p I - 0 m g / k g / d a y - :D a y 183 HCT % 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 OK OK OK OK OK OK OK OK OK OK 8.80 8.98 8.20 9.50 8.82 8.74 7.95 8.66 8.81 8.63 16.2 15.8 15.0 16.0 15.0 14.8 14.8 15.3 16.3 14.8 49.4 48.6 46.7 49.8 46.9 48.4 44.7 47.3 50.1 45.8 Male, Group IX - 125 mg/kg/day - Day 183 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 OK OK OK OK CLOT OK CLOT CLOT OK OK 8.17 7.74 8.98 8.53 NT 9.00 NT NT 8.28 8.04 15.0 14.6 15.2 15.6 NT 15.4 NT NT 15.2 15.0 45.8 44.0 47.8 47.8 NT 48.8 NT NT 46.2 45.9 Individual Hematology Values MCV fL MCH pg MCHC g/dL RDW % ARET x103/uL PLT x103/uL WBC x103/uL 56.1 54.1 56.9 52.5 53.2 55.3 56.3 54.6 56.9 53.1 18.4 17.6 18.2 16.9 17.0 16.9 18.7 17.7 18.5 17.2 32.8 32.6 32.0 32.2 32.0 30.6 33.2 32.4 32.5 32.4 12.8 13.7 13.5 13.8 14.4 14.2 13.6 12.9 13.4 13.1 150.30 150.50 192.20 175.80 186.90 174.80 236.20 170.80 178.60 174.00 RNV RNV 1100 RNV 1420 1265 1151 866 RNV 1065 12.34 12.68 17.42 18.99 14.48 15.79 10.29 8.00 12.36 12.30 56.1 56.8 53.2 56.0 NT 54.2 NT NT 55.8 57.0 18.4 18.9 16.9 18.3 NT 17.1 NT NT 18.4 18.6 32.8 33.2 31.7 32.6 NT 31.6 NT NT 33.0 32.7 13.5 14.1 13.0 13.9 NT 13.0 NT NT 12.6 12.8 203.20 225.90 179.50 185.30 NT 153.50 NT NT 195.70 175.70 1063 1302 861 1092 NT 967 NT NT 957 1276 15.54 15.89 15.42 16.17 NT 12.25 NT NT 10.57 11.95 DuPont-9478 - 560 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Hematology Values Animal Number ANEU x!03/uL ALYM x!03/uL AMON x103/uL AEOS x103/uL ABAS x103/uL ALUC x103/y Male, Group I - 0 mg/kg/day - Day 183 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 2.02 3.08 6.08 2.60 3.30 3.38 2.18 1.64 1.41 1.76 9.71 9.09 10.38 15.52 10.20 11.55 7.39 5.75 10.34 9.94 0.33 0.31 0.64 0.34 0.58 0.48 0.42 0.42 0.20 0.24 0.16 0.11 0.13 0.26 0.17 0.18 0.21 0.09 0.26 0.14 0.08 0.04 0.13 0.19 0.16 0.14 0.05 0.06 0.12 0.17 0.04 0.05 0.07 0.08 0.06 0.06 0.05 0.04 0.03 0.06 Male, Group IX - 125 mg/kg/day - Day 183 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 2.43 3.36 2.80 2.95 NT 2.03 NT NT 1.92 1.94 12.26 11.65 11.78 12.27 NT 9.62 NT NT 7.90 9.21 0.51 0.59 0.37 0.33 NT 0.24 NT NT 0.44 0.55 0.16 0.15 0.14 0.28 NT 0.18 NT NT 0.19 0.14 0.12 0.08 0.25 0.25 NT 0.14 NT NT 0.06 0.05 0.07 0.07 0.08 0.09 NT 0.04 NT NT 0.07 0.06 - 561 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number COND RBC x 1 0 6/uL HGB g/dL Female, G r o u p II - 0 m g / k g / d a y - D a y 49 HCT % 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 OK OK OK OK OK OK OK OK OK OK 8.75 8.21 8.50 8.49 8.38 8.19 7.79 7.98 8.04 8.51 16.4 15.5 15.8 15.3 16.2 15.5 14.7 15.2 15.5 15.6 52.0 48.0 49.6 49.5 50.8 48.6 46.3 47.2 48.8 49.4 Female, Group IV - 1 mg/kg/day - Day 49 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 OK OK OK OK OK OK OK OK OK OK 8.39 8.36 8.07 7.89 8.36 8.32 NT 7.58 7.81 8.03 16.2 15.9 15.0 15.0 15.6 16.0 NT 14.6 15.3 15.2 50.1 49.8 46.3 46.9 49.0 49.2 NT 45.1 48.0 48.2 Female, Group VI - 5 mg/kg/day - Day 49 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 OK OK OK OK OK OK OK OK OK OK 8.70 7.62 8.02 8.18 8.34 7.83 8.44 7.95 8.53 7.75 16.5 14.5 14.9 15.9 15.9 15.2 15.5 15.5 15.7 14.9 51.7 45.7 47.0 48.4 49.0 47.9 48.2 49.5 48.9 46.7 Individual Hematology Values MCV fL MCH pg MCHC g/dL RDW % ARET x 1 0 9/L PLT x 1 0 3/uL WBC x 1 0 3/uL 59.5 58.5 58.4 58.3 60.6 59.3 59.4 59.2 60.6 58.0 18.8 18.9 18.6 18.0 19.3 18.9 18.8 19.0 19.3 18.3 31.6 32.4 31.8 30.9 31.9 31.9 31.7 32.1 31.8 31.5 11.6 11.4 11.2 13.2 11.5 11.5 11.8 11.6 11.9 11.1 348.0 259.0 209.0 269.2 284.3 281.5 257.2 195.2 250.9 211.4 RNV 1015 971 965 RNV 1043 908 978 933 RNV 11.06 11.70 17.04 19.84 5.29 13.14 15.98 14.70 11.73 9.76 59.8 59.6 57.4 59.5 58.6 59.2 NT 59.5 61.5 60.1 19.3 19.1 18.6 19.0 18.6 19.2 NT 19.3 19.6 19.0 32.4 32.0 32.4 32.0 31.8 32.5 NT 32.5 31.9 31.6 11.1 11.6 11.5 12.2 11.6 11.2 NT 11.8 11.9 11.3 196.9 204.5 194.7 257.4 206.4 225.8 NT 264.6 226.7 251.6 567 1024 945 910 957 630 NT 811 RNV RNV 11.92 14.85 9.99 14.33 8.16 13.69 NT 13.78 11.93 7.85 59.4 60.0 58.7 59.2 58.8 61.2 57.1 62.3 57.4 60.3 19.0 19.0 18.6 19.4 19.0 19.4 18.3 19.6 18.4 19.2 32.0 31.7 31.7 32.8 32.4 31.7 32.1 31.4 32.1 31.8 11.7 12.7 11.2 11.4 11.6 12.3 11.9 11.6 12.1 11.2 266.6 356.0 222.4 192.8 206.4 261.7 312.7 232.0 226.3 213.1 918 1512 1112 934 1021 1041 1118 RNV 1106 RNV 10.80 8.46 20.09 15.74 11.33 15.95 11.50 14.85 11.27 12.49 DuPont-9478 - 562 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number COND RBC x 1 0 6/pL HGB g/dL HCT % Female, Group VIII - 25 mg/kg/day - Day 49 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 OK OK OK OK OK OK OK OK OK OK 7.64 7.95 7.59 7.42 8.06 7.84 8.41 8.58 8.60 7.93 14.6 14.8 14.5 14.4 15.0 14.2 15.4 15.7 15.9 14.9 46.1 46.4 45.3 44.0 46.6 44.2 47.7 50.1 50.8 46.4 Female, Group X - 125 mg/kg/day - Day 49 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 OK OK OK OK OK OK OK OK OK OK 7.90 7.85 6.99 6.89 7.40 7.53 8.30 7.24 7.49 7.36 14.3 15.1 13.9 13.1 14.6 13.8 15.2 13.4 14.6 14.2 44.9 47.6 42.5 41.0 44.9 43.1 49.2 42.4 45.0 43.9 Individual Hematology Values MCV fL MCH pg MCHC g/dL RDW % ARET x 1 0 9/L PLT x 1 0 3/pL WBC x 1 0 3/pL 60.4 58.4 59.6 59.3 57.8 56.4 56.7 58.4 59.1 58.5 19.2 18.6 19.0 19.4 18.7 18.2 18.4 18.3 18.5 18.8 31.8 31.8 31.9 32.7 32.3 32.2 32.4 31.3 31.3 32.1 11.9 11.1 11.8 12.0 11.5 11.7 11.3 12.0 11.9 12.5 248.1 205.1 210.6 239.6 193.9 198.1 208.3 189.4 192.2 286.0 889 1014 959 1259 RNV RNV 1055 635 831 975 10.07 12.16 16.11 13.50 14.86 9.32 10.55 17.03 12.57 9.38 56.9 60.7 60.9 59.6 60.7 57.3 59.3 58.6 60.0 59.7 18.2 19.3 19.9 19.0 19.8 18.4 18.3 18.6 19.5 19.2 31.9 31.8 32.7 31.9 32.6 32.1 30.9 31.7 32.5 32.2 11.7 12.0 11.4 12.4 12.5 11.6 11.7 12.4 12.2 11.7 252.2 202.8 228.3 265.8 239.9 252.4 251.4 251.0 233.6 228.6 RNV 806 RNV 1059 RNV 1213 908 RNV 902 RNV 10.93 7.74 9.54 9.40 11.07 10.39 14.89 9.84 17.93 9.29 DuPont-9478 - 563 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Hematology Values Animal Number ANEU x 1 0 3/uL ALYM x 1 0 3/uL AMON x 1 0 3/uL AEOS x 1 0 3/uL ABAS x 1 0 3/uL ALUC x 1 0 3/uL Female, G r o u p II - 0 m g / k g / d a y - D a y 49 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 0.48 1.76 1.12 2.16 0.37 2.06 2.19 1.26 1.06 1.10 10.21 9.53 15.22 16.77 4.79 10.58 13.09 12.97 10.26 8.35 0.18 0.24 0.17 0.57 0.06 0.21 0.35 0.13 0.19 0.08 0.09 0.09 0.26 0.15 0.04 0.09 0.10 0.13 0.10 0.07 0.04 0.03 0.16 0.11 0.01 0.15 0.13 0.12 0.07 0.09 0.06 0.05 0.11 0.10 0.02 0.05 0.13 0.10 0.05 0.07 Female, Group IV - 1 mg/kg/day - Day 49 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 0.74 0.99 0.91 1.40 0.65 0.63 NT 1.65 0.72 0.76 10.78 13.39 8.77 12.34 7.20 12.71 NT 11.73 10.83 6.75 0.25 0.24 0.13 0.33 0.16 0.12 NT 0.23 0.14 0.18 0.06 0.13 0.08 0.07 0.05 0.13 NT 0.09 0.12 0.10 0.05 0.05 0.05 0.10 0.06 0.05 NT 0.04 0.05 0.02 0.05 0.05 0.05 0.10 0.03 0.05 NT 0.05 0.06 0.03 Female, Group VI - 5 mg/kg/day - Day 49 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 1.29 1.42 1.32 1.65 2.40 2.04 1.10 2.19 0.90 0.70 8.97 6.71 18.22 13.36 8.46 13.30 9.78 12.07 9.97 11.43 0.26 0.11 0.24 0.31 0.15 0.38 0.11 0.39 0.19 0.18 0.18 0.11 0.08 0.17 0.11 0.08 0.13 0.09 0.13 0.08 0.07 0.06 0.13 0.15 0.13 0.07 0.30 0.05 0.04 0.03 0.03 0.05 0.10 0.11 0.08 0.08 0.09 0.07 0.04 0.05 - 564 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Hematology Values Animal Number ANEU x 1 0 3/uL ALYM x 1 0 3/pL AMON x 1 0 3/pL AEOS x 1 0 3/pL ABAS x 1 0 3/pL ALUC x 1 0 3/pL Female, Group VIII - 25 mg/kg/day - Day 49 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 1.33 0.57 0.88 1.08 1.11 1.13 0.66 2.29 3.14 2.11 8.35 11.16 14.66 11.92 13.28 7.65 9.58 13.98 8.58 6.84 0.20 0.20 0.19 0.13 0.15 0.38 0.12 0.42 0.48 0.25 0.09 0.07 0.12 0.13 0.09 0.10 0.05 0.15 0.23 0.09 0.03 0.04 0.16 0.15 0.13 0.02 0.09 0.11 0.08 0.03 0.06 0.12 0.11 0.10 0.10 0.04 0.05 0.08 0.06 0.05 Female, Group X - 125 mg/kg/day - Day 49 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 1.64 0.57 0.75 1.33 1.07 2.27 1.20 1.26 2.16 1.78 8.82 6.82 8.38 7.79 9.55 7.76 13.18 8.10 14.90 7.15 0.29 0.20 0.16 0.12 0.31 0.16 0.24 0.20 0.38 0.16 0.11 0.10 0.12 0.06 0.07 0.08 0.07 0.08 0.22 0.11 0.04 0.02 0.05 0.05 0.02 0.07 0.09 0.13 0.13 0.04 0.04 0.04 0.08 0.05 0.05 0.05 0.12 0.08 0.15 0.05 - 565 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number COND RBC x106/uL HGB g/dL Female, G r o u p II - 0 m g / k g / d a y - D a y 94 HCT % 655031 655016 655025 655032 655036 655079 655083 655098 655099 655107 OK OK OK OK OK OK OK OK OK OK 8.10 8.00 8.06 8.59 8.33 8.08 8.60 8.48 8.34 7.84 15.5 15.8 15.9 16.2 16.7 16.1 16.7 16.7 16.3 15.5 45.8 45.3 46.6 48.2 48.7 46.8 48.2 49.2 48.0 44.8 Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 OK OK OK OK OK OK OK OK OK OK 8.28 8.47 8.23 8.17 8.32 8.38 8.69 8.13 7.74 8.39 16.4 16.7 16.0 16.1 16.5 16.2 17.1 16.3 15.8 16.7 48.6 49.0 46.8 46.2 47.8 47.9 50.5 47.8 45.9 48.0 Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 OK OK OK OK OK OK OK OK OK OK 8.42 8.13 8.90 8.31 8.58 7.91 8.53 8.10 8.75 8.19 16.9 16.0 17.1 16.5 17.1 15.7 16.4 16.7 16.5 16.4 49.2 46.5 52.0 47.8 49.5 45.3 48.4 48.8 48.4 47.5 Individual Hematology Values MCV fL MCH pg MCHC g/dL RDW % ARET x103/uL PLT x103/uL WBC x103/uL 56.6 56.6 57.8 56.1 58.5 57.9 56.1 58.1 57.5 57.1 19.2 19.8 19.7 18.9 20.0 19.9 19.4 19.7 19.6 19.8 33.9 34.9 34.2 33.7 34.2 34.4 34.6 34.0 34.0 34.6 10.8 11.0 10.3 11.7 11.2 10.3 11.0 11.3 11.4 10.2 104.40 207.80 136.00 173.20 161.50 133.70 137.70 120.70 128.50 110.00 1201 925 1197 928 1196 1248 942 976 1067 1153 13.17 6.41 8.01 19.52 7.89 11.65 13.05 9.80 11.73 7.16 58.7 57.8 56.9 56.5 57.4 57.2 58.2 58.8 59.2 57.3 19.9 19.7 19.5 19.7 19.9 19.3 19.7 20.1 20.4 19.9 33.8 34.1 34.3 34.9 34.7 33.7 33.9 34.1 34.4 34.7 11.0 11.0 11.0 11.2 10.8 10.7 11.2 10.8 12.0 10.4 121.80 132.00 139.60 115.40 135.00 155.30 126.10 151.80 165.70 147.10 1138 1177 1040 899 1192 RNV 860 687 1164 1072 8.61 12.58 5.94 12.09 6.69 10.04 11.50 12.78 8.70 6.95 58.5 57.2 58.5 57.5 57.7 57.2 56.7 60.3 55.3 58.0 20.1 19.7 19.2 19.8 19.9 19.9 19.3 20.6 18.9 20.0 34.3 34.4 32.9 34.5 34.5 34.8 34.0 34.2 34.1 34.5 10.7 11.6 11.3 10.9 10.6 11.7 10.9 11.2 10.5 10.8 180.60 133.10 194.80 143.40 147.70 162.90 163.20 184.30 98.20 143.10 1039 1274 RNV RNV 1220 1177 1065 RNV 1112 1219 8.41 8.69 14.43 12.22 9.18 13.19 8.94 10.59 7.10 12.94 DuPont-9478 - 566 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number COND RBC x106/pL HGB g/dL HCT % Female, G r o u p VIII - 25 m g / k g / d a y - D a y 94 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 OK OK OK OK OK OK OK OK OK OK 7.30 7.92 7.78 7.56 8.49 8.09 8.40 8.49 8.74 7.90 14.6 15.4 15.5 15.1 16.5 15.5 16.1 15.9 16.8 15.9 42.3 44.4 44.7 43.3 48.6 46.0 46.4 48.1 49.7 44.2 Female, G r o u p X - 125 m g / k g / d a y - D a y 94 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 OK OK OK OK OK OK OK OK OK OK 8.11 7.87 7.90 7.30 7.56 7.55 8.14 7.08 7.53 7.56 15.3 15.9 15.9 14.4 15.6 14.6 15.8 13.7 14.9 15.3 45.9 46.9 46.1 42.5 46.2 42.5 46.6 40.6 43.8 45.2 Individual Hematology Values MCV fL MCH pg MCHC g/dL RDW % ARET x103/pL PLT x103/pL WBC x103/pL 57.9 56.1 57.4 57.3 57.2 56.9 55.2 56.6 56.9 56.0 20.0 19.5 19.9 19.9 19.4 19.1 19.2 18.7 19.2 20.2 34.4 34.8 34.7 34.7 34.0 33.6 34.7 33.1 33.8 36.0 11.1 10.6 10.5 10.8 10.4 10.6 10.8 11.4 11.3 10.8 170.40 130.00 120.70 139.70 133.30 151.80 153.10 164.20 137.80 105.30 1057 1321 811 RNV 1042 RNV 1204 824 923 RNV 10.13 10.27 12.05 7.43 13.41 8.51 8.30 8.77 13.87 5.81 56.5 59.6 58.4 58.3 61.1 56.2 57.2 57.3 58.2 59.8 18.8 20.2 20.1 19.8 20.7 19.3 19.4 19.3 19.8 20.3 33.3 33.9 34.4 33.9 33.9 34.4 34.0 33.7 34.1 33.9 11.2 12.1 11.0 10.8 11.4 11.2 12.0 12.4 11.8 11.6 145.40 185.00 151.90 136.80 148.00 131.90 240.90 223.70 195.90 206.80 1214 962 RNV 1186 1037 1112 1061 980 1060 997 11.74 7.21 9.29 9.71 11.18 10.25 11.77 9.69 11.15 10.59 DuPont-9478 - 567 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Hematology Values Animal Number ANEU x103/uL ALYM x!03/uL AMON x!03/uL AEOS x103/uL ABAS x103/uL ALUC x103/y Female, G r o u p II - 0 m g / k g / d a y - D a y 94 655031 655016 655025 655032 655036 655079 655083 655098 655099 655107 1.29 0.88 1.21 2.07 0.52 1.70 1.20 1.37 1.75 0.84 11.28 5.21 6.42 16.57 7.02 9.46 11.36 8.06 9.36 6.00 0.19 0.13 0.14 0.34 0.15 0.22 0.17 0.12 0.25 0.11 0.29 0.13 0.15 0.26 0.11 0.12 0.23 0.17 0.22 0.11 0.05 0.02 0.04 0.10 0.04 0.07 0.05 0.05 0.08 0.06 0.06 0.04 0.04 0.18 0.04 0.07 0.04 0.04 0.08 0.03 Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 0.76 1.47 0.47 3.09 0.82 1.08 0.88 1.43 0.88 2.29 7.49 10.50 5.27 8.40 5.55 8.41 10.19 10.85 7.52 4.35 0.11 0.29 0.09 0.33 0.18 0.15 0.18 0.25 0.08 0.11 0.09 0.18 0.08 0.13 0.09 0.16 0.15 0.16 0.15 0.12 0.08 0.07 0.01 0.07 0.04 0.14 0.05 0.05 0.03 0.06 0.07 0.08 0.02 0.07 0.02 0.11 0.05 0.04 0.04 0.02 Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 1.38 1.22 1.15 1.10 2.34 1.99 1.20 2.16 1.02 0.98 6.65 6.88 12.70 10.88 6.60 10.74 7.28 8.08 5.74 11.42 0.06 0.26 0.29 0.12 0.09 0.19 0.10 0.09 0.10 0.21 0.24 0.17 0.29 0.12 0.07 0.16 0.13 0.13 0.19 0.20 0.05 0.10 0.00 0.00 0.03 0.06 0.16 0.05 0.02 0.06 0.03 0.06 0.00 0.00 0.04 0.06 0.07 0.06 0.03 0.06 - 568 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Hematology Values Animal Number ANEU x103/uL ALYM x103/pL AMON x103/pL AEOS x103/pL ABAS x103/pL ALUC x103/y Female, G r o u p VIII - 25 m g / k g / d a y - D a y 94 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 1.94 0.47 1.93 1.08 1.29 2.21 0.82 1.68 4.87 1.29 7.70 9.32 9.58 5.98 11.59 6.13 7.17 6.71 7.78 4.14 0.29 0.14 0.26 0.18 0.15 0.08 0.10 0.13 0.81 0.14 0.13 0.21 0.09 0.11 0.15 0.09 0.06 0.15 0.25 0.21 0.03 0.06 0.08 0.04 0.12 0.00 0.09 0.06 0.07 0.02 0.04 0.06 0.10 0.04 0.10 0.00 0.06 0.04 0.09 0.01 Female, G r o u p X - 125 m g / k g / d a y - D a y 94 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 2.29 1.01 0.76 1.69 1.64 1.51 1.92 1.90 1.44 3.21 8.76 5.81 7.92 7.45 9.19 8.44 9.35 7.36 8.99 6.87 0.38 0.20 0.31 0.31 0.16 0.10 0.26 0.22 0.37 0.28 0.21 0.13 0.19 0.10 0.09 0.09 0.14 0.09 0.18 0.12 0.05 0.03 0.05 0.10 0.04 0.05 0.05 0.06 0.08 0.06 0.04 0.03 0.05 0.06 0.06 0.05 0.05 0.05 0.09 0.05 - 569 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number COND RBC x106/uL HGB g/dL HCT % Female, G r o u p II - 0 m g / k g / d a y - D a y 183 655009 655015 655019 655035 655062 655068 655072 655101 655109 OK OK OK OK OK OK OK OK OK 8.46 7.47 7.32 7.90 7.43 7.49 7.92 8.01 7.81 16.0 13.8 14.7 15.1 14.2 14.9 14.4 14.9 14.3 47.7 41.6 43.7 44.7 43.0 44.4 43.4 44.9 42.8 Female, Group X - 125 mg/kg/day - Day 183 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 OK OK OK OK OK OK OK OK OK OK 7.76 7.59 8.07 7.93 7.63 7.57 8.22 7.84 7.78 7.12 15.1 15.0 15.4 15.2 14.7 14.8 15.4 15.6 15.4 13.9 45.5 44.2 47.0 45.4 42.6 45.3 47.4 45.8 46.0 41.4 Individual Hematology Values MCV fL MCH pg MCHC g/dL RDW % ARET x103/uL PLT x103/uL WBC x103/uL 56.3 55.7 59.7 56.6 57.9 59.3 54.8 56.1 54.8 18.9 18.4 20.1 19.1 19.1 19.9 18.2 18.6 18.3 33.6 33.1 33.6 33.8 33.0 33.5 33.1 33.2 33.4 11.2 11.8 12.4 12.5 12.0 11.3 12.0 11.1 11.7 111.60 144.80 158.50 216.50 188.40 169.50 123.40 135.70 132.90 956 RNV RNV 1357 861 877 999 1283 1082 11.29 6.67 8.98 6.56 4.32 5.84 7.73 7.24 6.94 58.6 58.2 58.2 57.3 55.9 59.8 57.7 58.5 59.1 58.2 19.5 19.7 19.0 19.2 19.3 19.5 18.8 19.9 19.7 19.6 33.3 33.8 32.7 33.5 34.5 32.7 32.6 34.0 33.4 33.6 12.6 13.0 12.5 11.2 11.1 12.7 11.6 11.4 11.9 13.1 213.60 138.20 183.00 183.40 133.10 162.00 179.10 150.60 128.30 172.70 RNV 761 1026 1191 1250 RNV RNV 786 726 RNV 8.39 7.79 7.54 8.26 7.11 9.99 6.18 9.13 11.63 5.92 DuPont-9478 - 570 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Hematology Values Animal Number ANEU x103/uL ALYM x!03/uL AMON x!03/uL AEOS x103/uL ABAS x103/uL ALUC x103/y Female, G r o u p II - 0 m g / k g / d a y - D a y :183 655009 655015 655019 655035 655062 655068 655072 655101 655109 2.23 1.29 1.35 1.09 0.79 1.46 0.63 1.85 1.24 8.45 5.09 7.21 5.11 3.26 3.77 6.75 5.06 5.28 0.40 0.14 0.22 0.19 0.19 0.44 0.11 0.21 0.31 0.11 0.11 0.14 0.11 0.04 0.10 0.07 0.08 0.05 0.06 0.01 0.04 0.04 0.03 0.04 0.13 0.02 0.03 0.04 0.03 0.03 0.03 0.02 0.02 0.03 0.02 0.03 Female, Group X - 125 mg/kg/day - Day 183 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 2.33 1.53 1.12 2.14 1.20 1.61 1.11 1.11 1.22 0.96 5.22 5.81 6.10 5.84 5.40 7.74 4.61 7.61 9.87 4.48 0.58 0.19 0.17 0.17 0.32 0.42 0.18 0.23 0.30 0.35 0.16 0.15 0.07 0.06 0.09 0.09 0.19 0.07 0.15 0.07 0.07 0.07 0.06 0.04 0.04 0.08 0.07 0.06 0.07 0.04 0.03 0.03 0.02 0.02 0.05 0.04 0.01 0.04 0.03 0.02 - 571 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number NORM ANIS MIC Male, Group I - 0 mg/kg/day - Day 48 654903 NO - - 654925 NO - - 654928 NO - - 654929 NO - - 654936 NO - - 654950 NO - - 654953 NO - - 654972 NO - - 654987 NO - - 654993 NO - - Male, Group III - 1 mg/kg/day - Day 48 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 NO NO NO NO NO NO NO NO NO NO - TRACE - - - TRACE - - Male, Group V - 5 mg/kg/day - Day 48 654907 NO - - 654911 NO - - 654916 NO - - 654917 NO - - 654959 NO - - 654961 NO - - 654967 NO - - 654980 NO - - 654998 NO - - 655005 NO - - Individual Red Blood Cell Morphology Values MAC POLY HYPO ECHI ACAN TARG - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - FEW - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - - FEW - - - FEW - - FEW FEW - - TRACE TRACE - - - FEW - ---- - - MODERATE - - TRACE FEW - - - FEW - - TRACE FEW - - FEW TRACE - - - FEW - ---- - TRACE FEW - - - TRACE - - - FEW - ---- ---- - - MODERATE - ---- - - TRACE - - - TRACE - - - FEW - - - MODERATE - ---- - - MODERATE - - FEW MODERATE - - TRACE FEW - ---- - TRACE TRACE - RX - - - HJB - - - DuPont-9478 - 572 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Red Blood Cell Morphology Values Animal Number NORM ANIS MIC MAC POLY HYPO ECHI ACAN TARG Male, Group VII - 25 mg/kg/day - Da y 48 654922 NO - - - TRACE - - MODERATE - 654923 NO - - - TRACE - TRACE FEW - 654930 NO - - - TRACE - TRACE FEW - 654940 NO - - - FEW - - MODERATE - 654952 NO - - - TRACE - - FEW - 654958 NO - - - TRACE - FEW Many - 654975 NO - - - TRACE - - TRACE - 654989 NO - - - TRACE - - - - 655001 NO - - - TRACE - - FEW - 655006 NO - - - TRACE - - - - Male, Group IX - 125 mg/kg/day - Da y 48 654914 NO - - - TRACE - - MODERATE - 654921 NO - - - TRACE - - MODERATE - 654951 NO - - - TRACE - - FEW - 654955 NO - - - TRACE - FEW FEW - 654965 NO - - - TRACE - TRACE MODERATE - 654979 NO - - - FEW - - TRACE - 654983 NO - - - TRACE - - - - 654986 NO - - - TRACE - - - - 654996 NO - - - TRACE - FEW MODERATE - 655003 NO - - - TRACE - - MODERATE - RX - - HJB - - DuPont-9478 - 573 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number NORM ANIS MIC Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654903 NO - - 654925 NO - - 654928 NO - - 654929 NO - - 654936 NO - - 654950 NO - - 654953 NO - - 654972 NO - - 654987 NO - - 654993 NO - - Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 NO - - 654913 NO - - 654932 NO - - 654938 NO - - 654941 NO - - 654946 NO - - 654947 NO - - 654960 NO - - 654984 NO - - 654995 NO - - Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 NO - - 654911 NO - - 654916 NO - - 654917 NO - - 654959 NO - - 654961 NO - - 654967 NO - - 654980 NO - - 654998 NO - - 655005 NO - - Individual Red Blood Cell Morphology Values MAC POLY HYPO ECHI ACAN TARG - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - MODERATE - - MANY TRACE - MANY - - TRACE - - FEW - - TRACE - - MANY TRACE - TRACE FEW - MODERATE TRACE - MANY TRACE - MODERATE TRACE - MANY TRACE --- - MODERATE - - TRACE TRACE - MANY TRACE - FEW - --- - MANY FEW - TRACE - - FEW - - MODERATE - - MODERATE TRACE - MODERATE TRACE - MODERATE TRACE - MANY TRACE - MANY FEW - MANY TRACE --- - MANY TRACE - - - RX HJB ----------- ---------- TRACE ----------- DuPont-9478 - 574 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Red Blood Cell Morphology Values Animal Number NORM ANIS MIC MAC POLY HYPO ECHI ACAN TARG Male, G r o u p VII - 25 m g / k g / d a y - D a y 93 654922 NO - - - TRACE - MANY TRACE - 654923 NO - - - TRACE - MODERATE TRACE - 654930 NO - - - TRACE - MANY TRACE - 654940 NO - - - TRACE - MODERATE TRACE - 654952 NO - - - TRACE - MANY TRACE - 654958 NO - - - TRACE - MANY TRACE - 654975 NO - - - TRACE - MANY TRACE - 654989 NO - - - TRACE - - - - 655001 NO - - - TRACE - MODERATE TRACE - 655006 NO - - - TRACE - TRACE - - Male, G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 NO NO NO NO NO NO NO NO NO NO -- --FEW FEW ----FEW FEW -- - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - MANY FEW - MANY TRACE - MODERATE TRACE - MANY FEW - MANY TRACE - MANY TRACE - MANY - - MANY TRACE - MODERATE MODERATE - MANY TRACE - - RX - - HJB DuPont-9478 - 575 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Red Blood Cell Morphology Values Animal Number NORM ANIS MIC MAC POLY HYPO ECHI ACAN TARG Male, Group I - 0 mg/kg/day - Day 183 654909 NO - - - TRACE - TRACE MODERATE - 654910 NO - - - TRACE - MODERATE MODERATE - 654915 NO - - - TRACE - MANY FEW - 654924 NO - - - TRACE - FEW MODERATE - 654927 NO - - - TRACE - MODERATE MANY - 654943 NO - - - TRACE - FEW MODERATE - 654949 NO - - - FEW - MODERATE MODERATE - 654956 NO - - - TRACE - FEW FEW - 654992 NO - - - TRACE - MODERATE MODERATE - 654994 NO - - - TRACE - MODERATE MODERATE - Male, Group IX - 125 mg/kg/day - Day 183 654942 NO - - - TRACE - MODERATE MODERATE - 654957 NO - - - TRACE - MODERATE MANY - 654973 NO - - - TRACE - FEW MODERATE - 654974 NO - - - TRACE - FEW MODERATE - 654976 NT NT NT NT NT NT NT NT NT 654977 NO - - - TRACE - FEW MODERATE - 654978 NT NT NT NT NT NT NT NT NT 654985 NT NT NT NT NT NT NT NT NT 654990 NO - - - TRACE - MODERATE FEW - 654991 NO - - - TRACE - MODERATE FEW - RX HJB -- TRACE -------- TRACE ----NT NT -NT NT NT NT --- DuPont-9478 - 576 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Red Blood Cell Morphology Values Animal Number NORM ANIS MIC MAC POLY HYPO ECHI ACAN TARG Female, G r o u p II - 0 m g / k g / d a y - D a y 49 655016 NO - - - FEW - FEW - - 655025 NO - - - TRACE - - - - 655031 NO - - - TRACE - - TRACE - 655032 NO - - - TRACE - - TRACE - 655036 NO - - - TRACE - MODERATE FEW - 655079 NO - - - TRACE - - FEW - 655083 NO - - - TRACE - - - - 655098 NO - - - TRACE - - TRACE - 655099 NO - - - TRACE - - - - 655107 NO TRACE Female, Group IV - 1 mg/kg/day - Da y 49 655013 NO - - - TRACE - - FEW - 655033 NO - - - TRACE - TRACE FEW - 655040 NO - - - TRACE - TRACE MODERATE - 655041 NO - - - TRACE - - FEW - 655044 NO - - - TRACE - - - - 655086 NO - - - TRACE - TRACE FEW - 655089 NO - - - TRACE - - FEW - 655090 NO - - - FEW - - FEW - 655091 NO - - - TRACE - FEW FEW - 655108 NO TRACE TRACE TRACE Female, Group VI - 5 mg/kg/day - Da y 49 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 NO NO NO NO NO NO NO NO NO NO - TRACE - - TRACE - - TRACE - FEW - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - - ---- ---- - - FEW - - TRACE - - - - FEW - - FEW MODERATE - ---- - FEW FEW - ---- RX - - - HJB - - - DuPont-9478 - 577 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Red Blood Cell Morphology Values Animal Number NORM ANIS MIC MAC POLY HYPO ECHI ACAN TARG Female, Group VIII - 25 mg/kg/day - Day 49 655011 NO 655012 NO - - - 655047 NO - - - 655055 NO - - - 655058 NO - - - 655073 NO - - - 655076 NO - - - 655078 NO - - - 655085 NO - - - 655105 NO - - - Female, Group X - 125 mg/kg/day - Day 49 TRACE TRACE TRACE FEW TRACE TRACE TRACE TRACE TRACE TRACE FEW FEW --- --- - TRACE MODERATE - TRACE TRACE - MODERATE FEW - TRACE - --- - - TRACE - - FEW - - 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 NO NO NO NO NO NO NO NO NO NO TRACE - TRACE - TRACE - TRACE - - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE - TRACE FEW FEW - FEW FEW - MODERATE FEW - TRACE TRACE - - FEW - - TRACE --- - MODERATE MODERATE - FEW FEW - - TRACE - RX - - HJB - - DuPont-9478 - 578 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Red Blood Cell Morphology Values Animal Number NORM ANIS MIC MAC POLY HYPO ECHI ACAN TARG Female, G r o u p II - 0 m g / k g / d a y - D a y 94 655016 NO - - - FEW - MODERATE - - 655025 NO - - - FEW - FEW - - 655031 NO - - - FEW - MODERATE - - 655032 NO - - - FEW - FEW FEW - 655036 NO - - - FEW - MANY TRACE - 655079 NO - - - FEW - FEW TRACE - 655083 NO - - - FEW - MODERATE TRACE - 655098 NO - - - FEW - MODERATE TRACE - 655099 NO - - - FEW - FEW - - 655107 NO FEW Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 NO - - - FEW - MANY TRACE - 655033 NO - - - FEW - FEW FEW - 655040 NO - - - FEW - MANY FEW - 655041 NO - - - FEW - MODERATE - - 655044 NO - - - FEW - FEW - - 655086 NO - - - FEW - FEW - - 655089 NO - - - FEW - FEW - - 655090 NO - - - FEW - MODERATE FEW - 655091 NO - - - FEW - MANY FEW - 655108 NO FEW MODERATE Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 NO - - - FEW - - - - 655029 NO - - - FEW - FEW - - 655034 NO - - - FEW - - - - 655038 NO - - - FEW - MODERATE - - 655039 NO - - - FEW - MANY - - 655042 NO - - - FEW - - FEW - 655054 NO - - - FEW - MANY - - 655066 NO - - - FEW - FEW TRACE - 655067 NO - - - FEW - MODERATE FEW - 655087 NO - - - FEW - - - - RX - - - HJB - - - DuPont-9478 - 579 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Red Blood Cell Morphology Values Animal Number NORM ANIS MIC MAC POLY HYPO ECHI ACAN TARG Female, G r o u p VIII - 25 m g / k g / d a y - D a y 94 655011 NO 655012 NO - - - 655047 NO - - - 655055 NO - - - 655058 NO - - - 655073 NO - - - 655076 NO - - - 655078 NO - - - 655085 NO - - - 655105 NO - - - Female, G r o u p X - 125 m g / k g / d a y - D a y 94 FEW FEW FEW FEW FEW FEW FEW FEW FEW FEW MANY TRACE - FEW FEW - FEW - - MANY TRACE - MODERATE - - MANY FEW - FEW - --- - MODERATE FEW - MODERATE TRACE - - 655007 NO FEW MANY 655023 NO - - - FEW - MANY FEW - 655026 NO - - - FEW - MANY - - 655052 NO - - - FEW - FEW - - 655053 NO - - - FEW - MANY TRACE - 655063 NO - - - FEW - MANY FEW - 655092 NO - - - FEW - - - - 655095 NO - - - FEW - MANY MODERATE - 655097 NO - - - FEW - MANY FEW - 655103 NO - - - FEW - MANY FEW - RX - - HJB - - DuPont-9478 - 580 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Red Blood Cell Morphology Values Animal Number NORM ANIS MIC MAC POLY HYPO ECHI ACAN TARG Female, G r o u p II - 0 m g / k g / d a y - D a y 183 655009 NO - - - TRACE - TRACE TRACE - 655015 NO - - - TRACE - TRACE TRACE - 655019 NO - - - TRACE - TRACE FEW - 655035 NO - - - TRACE - TRACE TRACE - 655062 YES - - - - - - - - 655068 NO - - - TRACE - TRACE TRACE - 655072 NO - - - TRACE - FEW FEW - 655101 NO - - - TRACE - TRACE TRACE - 655109 NO - - - TRACE - MODERATE TRACE - Female, Group X - 125 mg/kg/day - Day 183 655010 NO - - - TRACE - MANY MANY - 655030 NO - - - TRACE - FEW TRACE - 655037 NO - - - TRACE - FEW MODERATE - 655049 NO - - - TRACE - - - - 655061 NO - - - TRACE - - - - 655075 NO - - - TRACE - TRACE TRACE - 655077 NO - - - TRACE - MODERATE FEW - 655084 NO - - - TRACE - TRACE - - 655088 NO - - - TRACE - MODERATE MODERATE - 655100 NO - - - TRACE - MODERATE MANY - RX - - HJB - - DuPont-9478 - 581 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual White Blood Cell / Platelet Morphology Values Animal NORM SM TOX DB VC BC PCE GP BP Number Male, Group I - 0 mg/kg/day - Day 48 654903 YES - - - - - - - - 654925 YES - - - - - - - - 654928 YES - - - - - - - - 654929 YES - - - - - - - - 654936 NO - - - - - YES/ADEQ - - 654950 YES - - - - - - - - 654953 NO - - - - - YES/ADEQ - - 654972 NO - - - - - YES/DECR - - 654987 YES - - - - - - - - 654993 NO - - - - - YES/ADEQ - - Male, Group III - 1 mg/kg/day - Day 48 654908 NO - - - - - YES/ADEQ - - 654913 YES - - - - - - - - 654932 YES - - - - - - - - 654938 NO - - - - - YES/ADEQ - - 654941 NO - - - - - YES/ADEQ - - 654946 NO - - - - - YES/ADEQ - - 654947 NO - - - - - YES/UTD - - 654960 NO - - - - - YES/ADEQ - - 654984 YES - - - - - - - - 654995 YES - - - - - - - - Male, Group V - 5 mg/kg/day - Day 48 654907 YES - - - - - - - - 654911 NO - - - - - YES/ADEQ - - 654916 NO - - - - - YES/ADEQ - - 654917 YES - - - - - - - - 654959 NO - - - - - YES/UTD - - 654961 YES - - - - - - - - 654967 YES - - - - - - - - 654980 YES - - - - - - - - 654998 YES - - - - - - - - 655005 YES - - - - - - - - - 582 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual White Blood Cell / Platelet Morphology Values Animal NORM SM TOX DB VC BC PCE GP BP Number Male, Group VII - 25 mg/kg/day - Da y 48 654922 YES - - - - - - - - 654923 YES - - - - - - - - 654930 NO - - - - - YES/ADEQ - - 654940 NO - - - - - YES/ADEQ - - 654952 NO - - - - - YES/ADEQ - - 654958 NO - - - - - YES/DECR - - 654975 YES - - - - - - - - 654989 NO - - - - - YES/ADEQ - - 655001 YES - - - - - - - - 655006 YES - - - - - - - - Male, Group IX - 125 mg/kg/day - Da y 48 654914 YES - - - - - - - - 654921 NO - - - - - YES/UTD - - 654951 NO - - - - - YES/DECR - - 654955 YES - - - - - - - - 654965 NO - - - - - YES/ADEQ - - 654979 NO - - - - - YES/ADEQ - - 654983 YES - - - - - - - - 654986 YES - - - - - - - - 654996 YES - - - - - - - - 655003 NO - - - - - YES/UTD - - DuPont-9478 - 583 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual White Blood Cell / Platelet Morphology Values Animal NORM SM TOX DB VC BC PCE GP BP Number Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654903 YES - - - - - - - - 654925 YES - - - - - - - - 654928 YES - - - - - - - - 654929 YES - - - - - - - - 654936 YES - - - - - - - - 654950 YES - - - - - - - - 654953 YES - - - - - - - - 654972 NO - - - - - YES/DECR - - 654987 YES - - - - - - - - 654993 YES - - - - - - - - Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 YES - - - - - - - - 654913 YES - - - - - - - - 654932 YES - - - - - - - - 654938 YES - - - - - - - - 654941 YES - - - - - - - - 654946 NO - - - - - YES/DECR - - 654947 NO - - - - - YES/DECR - - 654960 YES - - - - - - - - 654984 NO - - - - - YES/ADEQ - - 654995 YES - - - - - - - - Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 YES - - - - - - - - 654911 YES - - - - - - - - 654916 NO - - - - - YES/ADEQ - - 654917 YES - - - - - - - - 654959 YES - - - - - - - - 654961 YES - - - - - - - - 654967 YES - - - - - - - - 654980 YES - - - - - - - - 654998 YES - - - - - - - - 655005 NO - - - - - YES/ADEQ - - - 584 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual White Blood Cell / Platelet Morphology Values Animal NORM SM TOX DB VC BC PCE GP BP Number M a l e , G r o u p VII - 25 m g / k g / d a y - D a y 93 654922 YES - - - 654923 YES - - - 654930 YES - - - 654940 YES - - - 654952 YES - - - 654958 YES - - - 654975 NO - - - 654989 NO - - - 655001 YES - - - 655006 YES - - - YES/ADEQ YES/DECR M a l e , G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 YES - - - 654921 YES - - - 654951 YES - - - 654955 YES - - - 654965 YES - - - 654979 YES - - - 654983 YES - - - 654986 YES - - - 654996 NO - - - 655003 YES - - - YES/ADEQ DuPont-9478 - 585 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual White Blood Cell / Platelet Morphology Values Animal NORM SM TOX DB VC BC PCE GP BP SPEC Number M a l e , G r o u p I - 0 m g / k g / d a y - :D a y 183 654909 NO - - - - - YES/UTD - - 654910 NO - - - - - YES/ADEQ - - 654915 YES - - - - 654924 NO - - - - - YES/UTD - - 654927 YES - - - - - - - - TRACE-SPHEROCYTE 654943 YES - - - - 654949 YES - - - - 654956 YES - - - - 654992 NO - - - - - YES/UTD - - 654994 YES - - - - Male, Group IX - 125 mg/kg/day - Day 183 654942 YES - - - - 654957 YES - - - - 654973 YES - - - - 654974 YES - - - - 654976 NT NT NT NT NT NT NT NT NT 654977 YES - - - - 654978 NT NT NT NT NT NT NT NT NT 654985 NT NT NT NT NT NT NT NT NT 654990 YES - - - - 654991 YES - - - - DuPont-9478 - 586 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual White Blood Cell / Platelet Morphology Values Animal NORM SM TOX DB VC BC PCE GP BP Number Female, G r o u p II - 0 m g / k g / d a y - D a y 49 655016 NO - - - - - YES/UTD 655025 YES - - - - - - 655031 YES - - - - - - 655032 YES - - - - - - 655036 NO - - - - - YES/ADEQ 655079 YES - - - - - - 655083 YES - - - - - - 655098 YES - - - - - - 655099 YES - - - - - - 655107 NO - - - - - YES/ADEQ Female, Group IV - 1 mg/kg/day - Day 49 655013 YES - - - - - - 655033 YES - - - - - - 655040 YES - - - - - - 655041 YES - - - - - - 655044 YES - - - - - - 655086 YES - - - - - - 655089 NO - - - - - YES/ADEQ 655090 YES - - - - - - 655091 NO - - - - - YES/ADEQ 655108 NO - - - - - YES/UTD Female, Group VI - 5 mg/kg/day - Day 49 655020 YES - - - - - - 655029 YES - - - - - - 655034 YES - - - - - - 655038 YES - - - - - - 655039 YES - - - - - - 655042 YES - - - - - - 655054 YES - - - - - - 655066 NO - - - - - YES/ADEQ 655067 YES - - - - - - 655087 NO - - - - - YES/UTD - 587 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual White Blood Cell / Platelet Morphology Values Animal NORM SM TOX DB VC BC PCE GP BP Number Female, Group VIII - 25 mg/kg/day - Day 49 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 YES YES YES YES NO NO YES YES YES YES - - YES/ADEQ YES/ADEQ Female, Group X - 125 mg/kg/day - Day 49 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 NO YES NO YES NO YES YES NO YES NO - - YES/ADEQ YES/INCR YES/UTD YES/DECR YES/DECR DuPont-9478 - 588 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual White Blood Cell / Platelet Morphology Values Animal NORM SM TOX DB VC BC PCE GP BP Number Female, G r o u p II - 0 m g / k g / d a y - D a y 94 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 YES YES YES YES YES YES YES YES YES YES --------------- --------------------------------------------------------- Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 YES - - - - - - - - 655033 YES - - - - - - - - 655040 YES - - - - - - - - 655041 YES - - - - - - - - 655044 YES - - - - - - - - 655086 NO - - - - - YES/ADEQ - - 655089 YES - - - - - - - - 655090 YES - - - - - - - - 655091 YES - - - - - - - - 655108 YES - - - - - - - - Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 YES - - - - - - - - 655029 YES - - - - - - - - 655034 NO - - - - - YES/DECR - - 655038 NO - - - - - YES/DECR - - 655039 YES - - - - - - - - 655042 YES - - - - - - - - 655054 YES - - - - - - - - 655066 NO - - - - - YES/ADEQ - - 655067 YES - - - - - - - - 655087 YES - - - - - - - - - 589 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual White Blood Cell / Platelet Morphology Values Animal NORM SM TOX DB VC BC PCE GP BP Number Female, G r o u p V III - 25 m g / k g / d a y - D a y 94 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 YES YES YES NO YES NO YES YES YES NO - - YES/ADEQ YES/DECR YES/ADEQ Female, G r o u p X - 125 m g / k g / d a y - D a y 94 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 YES YES NO YES YES YES YES YES YES YES - - YES/ADEQ DuPont-9478 - 590 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual White Blood Cell / Platelet Morphology Values Animal NORM SM TOX DB VC BC PCE GP BP Number Female, G r o u p II - 0 m g / k g / d a y - D a y 183 655009 655015 655019 655035 655062 655068 655072 655101 655109 YES NO NO YES YES YES YES YES YES - - YES/UTD YES/UTD Female, Group X - 125 mg/kg/day - Day 183 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 YES YES YES YES YES YES NO YES YES NO - - YES/ADEQ YES/ADEQ DuPont-9478 - 591 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number PHEM PLIP PICT Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 NONE NONE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE PT sec 16.2 15.5 15.4 16.8 16.7 16.6 15.8 15.9 NT 14.4 15.5 16.2 15.7 15.9 15.6 17.2 16.0 17.1 15.5 15.9 15.1 16.3 18.6 15.2 15.7 15.9 15.6 15.5 15.1 QNS Individual Coagulation Values APTT sec 18.2 19.9 22.3 15.2 19.7 16.9 19.7 17.0 NT 14.7 19.3 24.2 23.5 19.8 17.7 20.8 18.0 19.8 19.3 19.9 18.0 19.0 20.8 16.1 19.1 18.4 19.4 19.3 21.8 QNS - 592 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number PHEM PLIP PICT PT sec Male, G r o u p VII - 25 m g / k g / d a y - D a y 93 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 15.4 15.5 15.9 15.1 16.0 15.0 15.0 15.7 15.1 16.7 Male, G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 NONE NONE NONE TRACE NSR NONE NONE NONE NONE NONE NONE NONE NONE NONE NT NONE NONE NONE NONE NONE NONE NONE NONE NONE NT NONE NONE NONE NONE NONE 20.2 15.1 16.2 15.7 NT 15.3 15.4 14.3 14.7 15.8 Individual Coagulation Values APTT sec 15.0 19.1 20.2 17.4 18.5 16.2 16.3 19.7 16.9 17.8 22.4 16.9 22.0 19.8 NT 19.9 20.2 17.1 18.2 17.4 - 593 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number PHEM PLIP PICT PT sec Female, G r o u p II - 0 m g / k g / d a y - D a y 94 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 14.7 14.9 15.3 16.0 14.6 15.0 15.5 16.0 15.7 15.1 Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 NONE NONE NONE NONE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 15.5 16.3 14.3 15.3 14.5 15.0 14.9 14.6 14.7 14.2 Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 NONE NONE NONE NONE NONE NONE NONE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 15.1 15.9 14.8 15.9 15.5 14.6 15.0 14.8 14.8 16.4 Individual Coagulation Values APTT sec 19.3 12.9 17.7 15.0 16.8 15.4 15.7 15.6 14.5 14.9 18.1 19.1 15.2 16.1 13.2 14.7 19.2 15.0 16.6 15.0 18.6 12.8 14.2 13.8 13.8 16.4 16.0 14.7 15.0 15.0 - 594 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number PHEM PLIP PICT PT sec Female, G r o u p VIII - 25 m g / k g / d a y - D a y 94 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 14.6 15.5 15.9 15.9 15.7 15.1 15.5 14.1 14.9 14.7 Female, G r o u p X - 125 m g / k g / d a y - D a y 94 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 13.1 15.5 16.3 14.9 14.4 14.6 15.9 15.5 13.8 15.0 Individual Coagulation Values APTT sec 15.0 18.9 15.1 14.1 13.0 14.9 13.7 17.0 16.5 15.3 10.6 13.9 13.7 11.9 14.3 14.5 17.9 16.2 13.3 15.0 - 595 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number SHEM SLIP SICT Male, Group I - 0 mg/kg/day - Day 48 654928 654903 654925 654929 654936 654950 654953 654972 654987 654993 TRACE NONE TRACE TRACE NONE TRACE TRACE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group III - 1 mg/kg/day - Day 48 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 NONE TRACE NONE TRACE NONE NONE TRACE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group V - 5 mg/kg/day - Day 48 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 TRACE TRACE TRACE NONE NONE NONE NONE TRACE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE AST U/L 83 61 65 68 57 86 70 56 77 66 62 70 71 71 73 66 79 69 61 71 59 77 78 77 67 63 68 71 71 71 Individual Clinical Chemistry Values ALT SDH ALKP BILI U/L U/L U/L mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 39 21.6 131 0.13 15 0.27 84 36 11.9 114 <0.10 14 0.22 66 32 9.3 96 0.13 19 0.39 74 33 14.3 145 0.11 12 0.18 61 28 11.1 137 0.12 16 0.26 68 36 17.4 143 0.13 15 0.28 63 32 14.5 QNS 0.14 12 0.24 66 28 14.5 120 0.10 16 0.21 52 31 13.8 151 <0.10 11 0.21 66 30 12.3 138 0.15 14 0.28 56 30 15.6 97 <0.10 14 0.23 55 35 13.9 127 <0.10 15 0.29 33 26 10.5 112 <0.10 14 0.32 55 34 11.0 112 0.10 13 0.27 60 40 17.5 75 0.10 12 0.22 45 28 14.9 111 <0.10 12 0.24 50 44 14.2 127 0.10 14 0.29 57 31 7.8 157 <0.10 15 0.29 43 32 12.2 106 <0.10 14 0.33 70 34 14.1 119 0.11 15 0.26 61 23 11.0 142 0.10 11 0.25 77 29 11.5 124 0.13 13 0.25 49 33 13.7 137 <0.10 16 0.31 37 36 16.5 147 0.15 15 0.31 71 34 14.9 112 0.11 12 0.22 62 28 8.2 QNS 0.11 10 0.23 61 33 14.2 108 0.10 14 0.32 56 38 13.5 106 0.10 15 0.29 74 27 10.9 113 <0.10 15 0.26 60 39 11.3 146 <0.10 17 0.34 70 DuPont-9478 - 596 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number SHEM SLIP SICT AST U/L Male, Group VII - 25 mg/kg/day - Day 48 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 TRACE TRACE NONE TRACE NONE TRACE TRACE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 69 69 62 84 88 61 79 72 70 65 Male, Group IX - 125 mg/kg/day - Day 48 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 NONE SMALL NONE TRACE TRACE NONE TRACE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 67 61 82 65 70 69 70 72 62 75 Individual Clinical Chemistry Values ALT SDH ALKP BILI U/L U/L U/L mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 32 10.4 169 0.13 16 0.29 42 36 11.5 112 0.18 15 0.22 76 28 10.2 111 0.12 14 0.25 80 34 16.9 208 0.13 14 0.27 49 34 14.3 101 <0.10 15 0.27 41 27 11.4 124 0.11 14 0.25 58 36 12.6 115 0.10 13 0.30 47 33 13.5 118 0.11 15 0.24 39 44 11.7 138 <0.10 15 0.27 43 27 19.7 155 <0.10 13 0.25 47 28 12.7 243 <0.10 13 0.26 51 31 11.1 130 0.11 12 0.23 52 48 22.1 191 <0.10 13 0.26 44 31 10.1 192 <0.10 14 0.21 51 28 13.3 135 <0.10 13 0.26 57 37 10.0 165 <0.10 11 0.25 52 45 13.0 149 0.11 13 0.24 78 32 11.7 167 <0.10 13 0.29 72 34 13.8 101 0.10 12 0.22 51 30 15.1 172 0.12 16 0.34 61 DuPont-9478 - 597 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL Male, Group I - 0 mg/kg/day - Day 48 654928 78 115 6.4 654903 77 118 6.7 654925 58 122 6.7 654929 83 116 6.4 654936 111 117 7.1 654950 100 112 6.7 654953 132 134 6.5 654972 103 123 6.4 654987 78 123 6.1 654993 54 112 6.3 Male, Group III - 1 mg/kg/day - Day 48 654908 27 126 6.7 654913 60 113 6.5 654932 51 127 7.4 654938 120 114 6.6 654941 80 107 6.5 654946 75 113 5.9 654947 92 105 6.8 654960 55 105 6.3 654984 102 125 6.9 654995 75 110 6.2 Male, Group V - 5 mg/kg/day - Day 48 654907 91 108 6.0 654911 48 128 6.4 654916 18 145 6.7 654917 88 126 6.9 654959 142 116 7.4 654961 125 115 6.6 654967 57 120 6.4 654980 106 121 7.2 654998 80 124 6.4 655005 193 119 6.3 ALB g/dL 4.2 4.2 4.1 4.2 4.4 3.9 4.0 4.2 4.0 4.3 4.2 4.2 4.6 4.1 4.0 3.7 4.4 4.0 4.3 3.9 4.1 3.9 4.1 4.4 4.6 4.2 4.2 4.4 4.0 3.9 Individual Clinical Chemistry Values GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L 2.2 11.5 9.0 147.5 6.08 97.9 2.5 10.3 8.2 149.1 5.23 101.4 2.6 10.5 8.0 148.5 5.91 101.8 2.2 10.8 7.8 149.2 6.12 101.3 2.7 11.1 9.2 149.3 5.47 102.3 2.8 10.6 8.3 147.4 6.03 102.1 2.5 11.1 8.7 146.7 6.36 102.7 2.2 10.3 8.4 146.6 6.81 106.3 2.1 10.4 7.1 150.7 5.10 104.1 2.0 11.0 8.2 147.3 5.55 101.6 2.5 10.5 7.5 148.0 6.04 103.8 2.3 10.9 8.6 147.2 5.96 98.1 2.8 10.8 7.7 162.6 5.98 112.4 2.5 11.1 7.8 148.3 6.04 102.2 2.5 10.6 7.8 148.2 5.07 104.8 2.2 10.5 7.2 149.7 5.10 103.2 2.4 11.2 8.5 146.2 6.42 100.8 2.3 10.6 8.2 147.6 5.22 101.8 2.6 10.9 7.1 148.2 5.33 101.5 2.3 10.6 8.5 149.3 5.61 102.9 1.9 10.3 7.8 147.0 5.75 100.9 2.5 10.1 8.3 144.0 5.94 101.6 2.6 10.6 9.6 147.0 7.27 104.5 2.5 11.1 7.5 149.5 5.48 101.7 2.8 11.4 8.2 147.0 6.09 102.2 2.4 11.0 8.8 151.1 5.61 100.8 2.2 10.3 7.2 150.0 5.19 103.6 2.8 11.4 8.5 148.4 5.25 98.3 2.4 10.7 8.9 151.6 5.14 103.8 2.4 10.9 8.7 146.6 5.90 97.6 - 598 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL ALB g/dL Male, Group VII - 25 mg/kg/day - Day 48 654922 34 109 6.5 4.3 654923 85 109 6.3 4.2 654930 173 126 6.9 4.3 654940 56 113 6.1 4.2 654952 51 117 6.7 4.1 654958 43 133 6.4 4.1 654975 77 112 6.9 4.4 654989 89 127 6.5 4.3 655001 129 110 6.1 3.8 655006 93 119 6.6 4.2 Male, Group IX - 125 mg/kg/day - Day 48 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 32 38 89 42 27 23 71 47 26 38 123 7.1 4.8 138 6.9 4.6 112 7.6 4.8 111 6.2 4.4 115 6.8 4.4 94 6.5 4.5 119 7.0 4.6 122 7.0 5.0 118 7.3 5.0 170 7.2 4.9 Individual Clinical Chemistry Values GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L 2.2 10.6 8.6 147.2 5.62 99.7 2.1 10.4 10.7 146.6 5.86 99.7 2.6 10.7 7.7 148.8 5.53 102.6 1.9 10.2 8.3 147.8 6.32 104.2 2.6 10.2 7.5 150.1 4.80 101.3 2.3 10.3 8.0 148.5 5.54 103.5 2.5 11.3 8.7 148.6 5.38 99.4 2.2 10.3 7.7 148.3 5.55 100.0 2.3 11.2 9.0 147.2 5.66 97.7 2.4 10.1 7.7 150.3 4.91 102.3 2.3 10.2 8.3 151.3 5.56 102.0 2.3 11.0 10.4 146.3 6.37 102.8 2.8 11.2 9.8 148.4 5.64 102.1 1.8 10.3 9.4 147.1 5.49 100.7 2.4 10.7 9.0 146.5 5.59 97.9 2.0 10.6 8.5 148.6 5.50 100.9 2.4 11.2 8.4 146.5 5.92 98.6 2.0 10.8 9.1 146.0 5.36 104.1 2.3 11.0 8.2 147.7 5.70 99.3 2.3 11.3 10.8 148.4 6.24 102.2 DuPont-9478 - 599 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Clinical Chemistry Values Animal Number SHEM SLIP SICT AST U/L ALT U/L SDH U/L ALKP U/L BILI mg/dL Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 NONE TRACE SMALL TRACE NONE TRACE SMALL SMALL NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 69 74 108 94 84 93 73 80 86 84 31 18.3 111 <0.10 28 16.5 76 0.10 40 13.1 128 0.15 38 22.8 135 0.11 37 18.8 107 0.12 34 17.6 120 <0.10 39 16.7 74 0.10 32 18.4 101 0.11 46 23.2 150 0.12 38 21.7 85 0.11 Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 SMALL SMALL NONE TRACE NONE MODERATE TRACE TRACE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 93 96 65 109 78 NT-HEMOL 95 79 83 90 39 57 32 49 45 NT-HEMOL 41 35 34 42 17.6 23.2 11.5 21.7 18.9 7.1 20.4 15.5 15.5 17.7 84 110 85 93 80 NT-HEMOL 111 130 79 105 <0.10 <0.10 0.10 <0.10 0.10 NT-HEMOL <0.10 <0.10 <0.10 <0.10 Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 TRACE NONE SMALL SMALL TRACE TRACE NONE TRACE NONE SMALL NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 163 88 91 293 111 66 73 79 75 100 35 10.4 123 0.11 33 18.2 91 0.11 37 13.1 104 <0.10 173 63.0 115 0.17 47 12.3 80 <0.10 32 13.4 81 0.13 31 11.5 76 0.11 32 14.3 68 0.11 29 12.1 81 0.10 45 6.6 91 0.10 BUN mg/dL 11 14 17 11 13 12 11 14 12 14 14 14 13 17 12 12 18 13 14 15 12 13 14 14 14 10 12 15 12 15 CREA mg/dL 0.34 0.50 0.42 0.44 0.37 0.36 0.46 0.52 0.36 0.47 0.36 0.43 0.28 0.47 0.29 0.44 0.39 0.44 0.52 0.29 0.37 0.30 0.37 0.37 0.33 0.32 0.37 0.41 0.35 0.44 CHOL mg/dL 70 81 112 71 94 74 78 56 93 74 63 40 61 65 49 49 54 56 73 57 81 61 36 100 59 81 67 96 78 83 DuPont-9478 - 600 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number SHEM SLIP SICT AST U/L Male, G r o u p VII - 25 m g / k g / d a y - D a y 93 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 SMALL NONE TRACE SMALL TRACE TRACE SMALL TRACE SMALL NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 295 495 62 135 94 387 134 92 83 80 Male, G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 NONE SMALL TRACE SMALL TRACE SMALL TRACE TRACE NONE SMALL NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 83 64 93 72 87 119 75 78 64 70 Individual Clinical Chemistry Values ALT U/L SDH U/L ALKP U/L BILI mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 167 51.3 147 0.13 213 116.8 107 0.20 28 11.8 88 <0.10 83 37.6 142 <0.10 33 14.4 72 <0.10 188 103.6 108 0.12 57 22.1 91 <0.10 42 14.9 87 <0.10 43 18.9 125 <0.10 39 24.0 128 0.11 14 17 12 15 16 16 15 16 16 13 0.39 0.42 0.30 0.36 0.35 0.39 0.47 0.29 0.32 0.36 57 104 78 60 42 80 63 54 58 61 46 19.5 194 <0.10 12 0.39 58 27 11.8 96 0.11 11 0.35 63 60 22.6 176 0.10 14 0.37 51 42 13.7 171 0.10 16 0.37 91 34 18.0 101 0.10 14 0.40 55 78 33.7 142 0.11 13 0.37 56 42 20.4 138 <0.10 13 0.36 77 28 17.1 136 <0.10 15 0.45 86 44 16.0 95 0.10 10 0.28 50 34 10.9 113 0.12 12 0.37 66 DuPont-9478 - 601 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Clinical Chemistry Values Animal Number TRIG mg/dL GLUC mg/dL TP g/dL ALB g/dL GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654903 56 97 7.5 4.5 3.0 11.5 8.3 148.2 5.65 99.4 654925 51 92 7.5 4.5 3.0 11.1 7.9 148.8 6.09 99.3 654928 82 105 7.0 4.3 2.7 11.0 8.9 146.5 6.16 97.7 654929 40 94 6.9 4.5 2.4 11.1 8.3 148.1 6.89 103.0 654936 148 100 7.6 4.6 3.0 12.1 8.2 149.8 6.26 101.0 654950 95 101 6.9 3.9 3.0 11.1 8.8 148.7 7.03 103.0 654953 83 106 7.5 4.5 3.0 11.8 7.6 147.0 6.13 99.1 654972 43 186 7.2 4.5 2.7 11.2 8.4 149.6 5.40 103.0 654987 80 115 7.0 4.4 2.6 11.4 7.5 150.6 5.71 100.1 654993 89 89 6.5 4.3 2.2 10.9 6.8 147.1 6.17 101.0 Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 40 94 7.2 4.5 2.7 11.2 8.9 146.5 7.24 102.8 654913 49 95 6.6 4.2 2.4 10.4 8.5 148.4 5.85 98.4 654932 67 102 7.3 4.5 2.8 11.5 7.3 151.4 5.94 101.6 654938 89 165 7.3 4.4 2.9 11.8 9.6 147.9 6.20 102.4 654941 92 92 6.9 4.2 2.7 11.1 8.1 152.0 6.02 103.9 654946 NT-HEMOL 149 NT-HEMOL NT-HEMOL NT-HEMOL 11.3 NT-HEMOL 147.2 NT-HEMOL 101.5 654947 52 115 6.8 4.5 2.3 11.4 9.4 148.6 6.20 99.4 654960 36 96 6.8 4.2 2.6 11.2 8.0 148.1 5.51 103.3 654984 88 170 7.2 4.4 2.8 12.6 12.1 153.1 6.28 101.4 654995 92 91 6.6 4.0 2.6 10.8 7.9 150.8 6.23 103.6 Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 74 96 6.6 4.2 2.4 10.1 7.5 147.1 6.22 102.9 654911 61 112 6.9 4.2 2.7 11.6 9.6 148.8 7.09 100.4 654916 18 178 6.7 4.1 2.6 11.1 10.0 145.4 6.45 101.4 654917 60 111 6.9 4.2 2.7 11.3 9.0 145.9 7.04 101.4 654959 102 122 7.0 4.3 2.7 11.0 9.6 146.3 6.41 101.7 654961 86 109 7.7 4.6 3.1 11.8 8.2 152.8 6.12 101.1 654967 67 103 6.8 4.4 2.4 11.4 8.6 152.3 6.18 103.7 654980 84 107 7.6 4.5 3.1 11.3 8.2 147.6 6.45 99.5 654998 95 98 7.6 4.5 3.1 12.1 8.2 151.6 5.71 100.2 655005 120 105 6.4 3.8 2.6 10.2 7.6 144.9 5.38 98.8 PHEM NONE NONE NONE NONE NONE NONE TRACE NONE TRACE NONE NONE NONE NONE NONE TRACE TRACE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE DuPont-9478 - 602 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL ALB g/dL Male, G r o u p VII - 25 m g / k g / d a y - D a y 93 654922 35 88 7.1 4.7 654923 55 96 7.3 4.7 654930 91 117 7.2 4.4 654940 37 101 6.4 4.3 654952 62 106 6.8 4.1 654958 42 119 6.9 4.2 654975 48 188 7.2 4.5 654989 113 96 6.9 4.5 655001 87 94 6.5 4.0 655006 74 99 7.6 4.7 Male, G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 23 38 80 50 27 26 37 34 15 35 103 7.6 5.0 104 7.8 5.0 110 7.8 4.9 99 7.5 5.0 89 7.5 4.7 89 7.4 4.9 102 7.7 4.9 164 7.6 5.3 92 7.4 5.1 102 7.6 5.1 Individual Clinical Chemistry Values GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L PHEM 2.4 11.1 9.0 149.7 6.17 100.9 NONE 2.6 11.2 9.7 147.4 6.73 99.3 NONE 2.8 11.2 8.1 152.7 6.45 103.5 NONE 2.1 10.8 7.8 149.7 6.15 103.1 NONE 2.7 11.0 9.6 148.3 6.50 100.8 NONE 2.7 10.6 8.2 145.4 5.53 100.9 TRACE 2.7 11.4 11.5 146.1 5.52 99.4 NONE 2.4 11.3 10.3 145.7 7.89 102.6 NONE 2.5 11.1 10.4 146.3 6.60 98.8 NONE 2.9 11.3 7.8 151.5 5.64 102.4 NONE 2.6 11.4 10.1 150.3 7.20 101.3 NONE 2.8 12.1 11.0 144.7 7.44 99.9 TRACE 2.9 11.6 9.3 149.4 5.93 100.3 NONE 2.5 11.8 10.6 150.8 6.41 99.2 NONE 2.8 10.7 8.4 146.1 5.85 97.9 NONE 2.5 11.3 9.3 150.2 5.99 100.3 NONE 2.8 10.9 8.4 145.2 6.15 99.1 NONE 2.3 11.5 11.0 148.0 5.83 101.9 NONE 2.3 11.5 9.7 145.8 6.51 98.3 NONE 2.5 11.3 7.6 150.3 5.75 102.4 NONE DuPont-9478 - 603 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number PLIP PICT PFLU Ug/mL Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Individual Clinical Chemistry Values - 604 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number PLIP PICT PFLU ug/mL Male, G r o u p VII - 25 m g / k g / d a y - D a y 93 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 Male, G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.3 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.3 0.4 Individual Clinical Chemistry Values DuPont-9478 - 605 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number SHEM SLIP SICT AST U/L Male, G r o u p I - 0 m g / k g / d a y - :D a y 183 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 TRACE NONE TRACE TRACE NONE TRACE TRACE TRACE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 89 81 523 89 142 133 83 106 140 84 Male, Group IX - 125 mg/kg/day - Day 183 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 SMALL TRACE NONE TRACE SMALL TRACE TRACE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 146 235 72 132 91 157 88 143 188 92 Individual Clinical Chemistry Values ALT SDH ALKP BILI U/L U/L U/L mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 42 19.2 63 0.12 19 0.47 54 30 11.0 76 0.12 18 0.41 78 332 74.0 129 0.26 17 0.44 148 41 18.7 82 0.10 18 0.44 54 85 24.2 76 0.11 19 0.45 92 62 26.9 73 0.14 16 0.51 80 32 21.2 110 0.11 15 0.44 76 46 16.4 70 0.11 18 0.47 63 65 21.5 99 0.18 15 0.50 66 39 13.7 82 0.13 20 0.45 53 89 18.2 134 0.14 16 78 33.1 109 0.11 12 33 11.8 92 0.11 15 79 17.4 81 0.17 17 39 15.2 70 <0.10 15 95 20.8 72 0.15 16 38 22.0 77 <0.10 15 73 21.8 66 0.13 18 101 31.8 58 0.17 18 41 17.6 97 0.13 14 0.38 0.38 0.39 0.45 0.38 0.37 0.41 0.46 0.41 0.46 87 89 71 91 75 55 58 72 112 77 DuPont-9478 - 606 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL ALB g/dL Male, G r o u p I - 0 m g / k g / d a y - :D a y 183 654909 48 156 6.6 4.3 654910 130 144 6.9 4.2 654915 97 102 6.7 3.7 654924 66 196 6.9 4.2 654927 55 92 7.3 4.4 654943 100 188 7.3 4.3 654949 132 104 7.0 4.2 654956 83 104 6.6 4.0 654992 38 119 7.0 4.2 654994 60 82 6.9 4.3 Male, Group IX - 125 mg/kg/day - Day 183 654942 191 99 6.9 4.3 654957 48 152 6.8 4.1 654973 73 105 7.0 4.1 654974 104 163 6.9 4.2 654976 50 184 6.6 4.0 654977 50 122 6.7 4.1 654978 57 127 6.9 4.3 654985 45 128 6.9 4.3 654990 149 94 6.7 4.2 654991 186 91 7.0 4.3 Individual Clinical Chemistry Values GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L 2.3 11.2 8.8 147.0 6.47 102.7 2.7 11.5 9.4 146.9 6.78 105.0 3.0 11.9 9.6 149.9 6.28 102.0 2.7 11.7 9.0 146.9 6.05 101.5 2.9 11.7 8.8 148.1 6.87 103.5 3.0 12.1 8.7 148.7 5.61 102.5 2.8 10.6 7.3 147.0 5.60 98.8 2.6 11.2 7.9 150.1 6.06 105.7 2.8 11.3 8.3 146.1 6.29 101.5 2.6 10.8 7.4 148.5 5.71 99.3 2.6 11.3 9.0 148.3 6.48 105.5 2.7 11.5 10.3 147.3 5.95 105.2 2.9 11.5 10.3 151.0 7.32 106.6 2.7 11.7 8.7 145.7 5.68 102.9 2.6 11.4 11.0 148.1 5.89 104.5 2.6 11.6 8.4 150.0 6.09 106.5 2.6 11.5 8.8 145.3 6.57 101.8 2.6 11.6 9.0 149.6 6.56 100.9 2.5 10.6 8.4 146.7 6.72 103.7 2.7 11.9 7.8 152.0 5.59 103.5 PHEM NONE NONE NONE NONE NONE NONE NSR NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE DuPont-9478 - 607 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number PLIP PICT PFLU Ug/mL Male, G r o u p I - 0 m g / k g / d a y - :D a y 183 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 NONE NONE NONE NONE NONE NONE NT NONE NONE NONE NONE NONE NONE NONE NONE NONE NT NONE NONE NONE 0.1 0.0 0.0 0.0 0.0 0.0 NT 0.0 0.1 0.4 Male, Group IX - 125 mg/kg/day - Day 183 o o 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 Individual Clinical Chemistry Values - 608 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number SHEM SLIP SICT AST U/L Female, G r o u p II - 0 m g / k g / d a y - D a y 49 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 TRACE TRACE TRACE NONE TRACE NONE TRACE TRACE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 75 58 76 80 85 62 70 55 70 89 Female, Group IV - 1 mg/kg/day - Day 49 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 TRACE NONE NONE TRACE NONE TRACE TRACE TRACE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 83 83 80 72 61 110 52 69 80 75 Female, Group VI - 5 mg/kg/day - Day 49 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 TRACE NONE TRACE TRACE NONE TRACE TRACE TRACE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 68 65 68 73 66 70 68 60 53 58 Individual Clinical Chemistry Values ALT SDH ALKP BILI U/L U/L U/L mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 36 13.9 109 0.13 15 0.34 98 33 7.3 89 0.16 17 0.34 64 36 11.4 83 0.12 17 0.38 101 28 13.2 62 0.12 14 0.25 54 29 12.6 62 0.10 17 0.41 69 22 10.5 79 0.13 16 0.36 99 44 8.6 79 0.13 15 0.32 50 32 6.0 70 0.18 14 0.29 90 28 9.0 105 0.21 12 0.30 82 51 12.7 95 0.19 15 0.34 64 28 6.9 105 0.13 16 0.32 98 36 10.4 82 0.13 16 0.36 60 49 11.4 59 0.15 17 0.34 65 34 9.5 75 0.17 13 0.27 78 28 7.4 53 0.11 15 0.33 90 43 20.9 85 0.16 19 0.45 91 31 8.6 65 0.15 16 0.32 104 27 7.7 87 0.16 14 0.38 73 34 9.7 109 0.21 13 0.34 97 38 12.2 65 0.15 18 0.44 104 30 7.8 85 0.13 18 0.28 67 30 7.6 92 0.14 12 0.34 58 35 7.0 59 0.10 16 0.32 62 27 7.8 71 0.14 17 0.35 71 32 7.7 66 0.16 16 0.41 92 25 7.9 62 0.11 15 0.40 70 31 9.5 139 0.12 19 0.41 87 30 7.3 78 0.14 15 0.25 90 29 9.5 68 0.16 15 0.35 81 20 7.1 65 <0.10 16 0.29 53 DuPont-9478 - 609 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number SHEM SLIP SICT AST U/L Female, Group VIII - 25 mg/kg/day - Day 49 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 NONE TRACE TRACE NONE SMALL NONE NONE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 50 96 66 60 63 52 66 60 342 57 Female, Group X - 125 mg/kg/day - Day 49 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 TRACE TRACE TRACE TRACE TRACE NONE TRACE TRACE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 56 74 53 53 73 68 54 50 68 56 Individual Clinical Chemistry Values ALT SDH ALKP BILI U/L U/L U/L mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 26 7.9 62 0.18 14 0.29 123 48 14.0 50 0.13 17 0.36 102 34 8.9 92 0.13 18 0.35 102 27 6.2 62 0.12 17 0.28 91 26 9.3 78 0.12 12 0.40 75 30 7.0 42 0.10 18 0.32 101 26 7.7 72 0.10 15 0.25 84 35 8.7 62 0.13 11 0.21 84 158 139.0 142 0.23 15 0.39 172 33 9.7 66 0.13 17 0.42 114 33 8.0 54 0.19 13 0.30 120 33 12.7 104 0.12 18 0.31 94 27 8.8 70 0.16 20 0.39 96 33 8.1 79 0.18 16 0.31 92 30 10.4 67 0.14 15 0.30 102 27 9.4 91 0.13 14 0.32 77 26 8.2 62 0.15 14 0.29 105 34 9.4 80 0.13 15 0.29 98 41 14.6 69 0.19 12 0.31 146 37 10.4 71 0.16 13 0.32 135 DuPont-9478 - 610 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL ALB g/dL Female, G r o u p II - 0 m g / k g / d a y - D a y 49 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 64 38 34 29 42 27 25 89 56 31 116 7.3 4.8 114 7.3 5.1 104 7.3 4.8 106 6.9 4.5 129 7.2 4.9 126 7.6 5.1 113 7.0 4.7 123 7.0 4.8 117 7.7 5.0 100 7.6 5.3 Female, Group IV - 1 mg/kg/day - Day 49 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 35 29 36 95 56 49 74 41 46 39 101 7.5 4.9 104 7.0 4.5 107 7.0 4.8 123 7.0 5.0 116 7.5 4.9 84 7.5 5.0 122 7.5 5.0 120 7.1 4.7 116 7.5 5.1 122 7.6 5.0 Female, Group VI - 5 mg/kg/day - Day 49 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 22 44 30 44 36 34 26 64 33 39 112 6.5 4.1 108 6.9 4.2 112 6.6 4.5 103 6.7 4.4 117 8.3 5.3 119 6.9 4.4 103 7.0 4.6 121 6.9 4.5 116 7.5 5.3 147 7.1 4.4 Individual Clinical Chemistry Values GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L 2.5 11.4 7.9 145.4 7.05 100.2 2.2 11.4 9.1 143.4 5.15 100.1 2.5 11.2 6.9 144.9 6.44 98.5 2.4 11.0 7.1 147.3 5.76 103.9 2.3 11.6 9.0 145.6 6.16 103.0 2.5 11.3 6.0 145.1 5.16 100.2 2.3 11.0 6.5 146.5 5.25 101.4 2.2 10.9 5.9 143.1 5.37 102.1 2.7 11.5 6.0 146.9 4.87 102.0 2.3 11.4 5.7 143.8 6.20 100.7 2.6 11.2 6.9 146.1 5.17 100.0 2.5 10.8 6.6 147.3 5.18 102.5 2.2 10.9 6.2 143.4 5.75 102.5 2.0 11.1 6.9 143.4 5.49 100.4 2.6 11.3 6.4 146.6 5.34 101.5 2.5 12.0 10.2 147.3 6.74 101.6 2.5 11.5 7.0 142.5 5.55 102.8 2.4 10.9 7.4 144.3 5.16 103.8 2.4 11.7 7.8 144.6 5.89 100.7 2.6 11.9 8.6 145.2 5.65 99.7 2.4 10.9 7.7 144.2 6.10 103.4 2.7 10.8 6.2 145.2 5.61 103.0 2.1 10.6 6.3 144.4 5.18 100.3 2.3 10.9 7.4 142.2 5.31 99.8 3.0 11.6 6.0 146.5 5.78 101.6 2.5 10.8 6.8 146.9 4.98 102.7 2.4 10.7 6.3 145.4 5.64 101.8 2.4 11.4 6.8 147.8 5.02 102.3 2.2 11.4 6.3 144.0 5.50 102.1 2.7 11.1 8.1 144.1 5.91 101.9 - 611 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL ALB g/dL Female, Group VIII - 25 mg/kg/day - Day 49 655011 50 121 7.7 5.1 655012 41 109 7.0 4.7 655047 33 110 7.5 5.0 655055 36 110 7.6 4.7 655058 32 115 6.7 4.6 655073 31 119 7.6 5.2 655076 30 107 7.2 4.7 655078 104 114 8.0 5.5 655085 40 118 8.1 5.0 655105 30 106 8.4 5.8 Female, Group X - 125 mg/kg/day - Day 49 655007 51 109 8.1 5.7 655023 62 121 7.2 5.1 655026 34 111 7.4 5.2 655052 39 103 7.8 5.5 655053 30 112 7.7 5.2 655063 26 117 8.0 5.6 655092 43 109 7.4 5.1 655095 40 108 8.5 5.8 655097 183 116 8.3 5.8 655103 39 107 8.3 5.8 Individual Clinical Chemistry Values GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L 2.6 11.8 6.8 146.8 5.01 101.8 2.3 10.7 6.6 145.1 4.98 102.6 2.5 11.7 7.3 141.6 5.09 104.0 2.9 11.4 7.4 145.4 5.57 100.5 2.1 10.7 7.3 143.5 5.63 100.2 2.4 11.5 7.4 139.1 5.71 100.4 2.5 11.1 6.0 144.6 5.44 100.5 2.5 11.9 6.7 142.9 5.39 96.7 3.1 11.7 6.9 147.1 5.59 100.8 2.6 11.7 6.3 145.3 5.16 99.2 2.4 11.6 7.1 144.5 5.27 101.1 2.1 10.7 7.5 143.9 5.05 101.9 2.2 11.5 8.7 144.3 5.66 101.6 2.3 11.7 7.1 146.4 5.05 100.6 2.5 11.2 9.7 144.6 6.06 101.7 2.4 11.4 6.1 147.8 5.79 100.7 2.3 11.0 8.2 145.7 5.32 101.5 2.7 12.1 7.0 143.0 5.49 100.0 2.5 12.4 7.3 141.2 6.11 98.5 2.5 11.9 7.0 143.7 5.67 101.5 DuPont-9478 - 612 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number SHEM SLIP SICT AST U/L Female, G r o u p II - 0 m g / k g / d a y - D a y 94 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 NONE NONE TRACE NONE TRACE NONE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 118 66 89 77 101 66 72 73 92 92 Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 90 126 195 221 106 108 59 94 86 100 Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 TRACE NONE NONE TRACE TRACE NONE NONE TRACE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 73 83 122 89 76 77 98 74 70 58 Individual Clinical Chemistry Values ALT U/L SDH U/L ALKP U/L BILI mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 78 22.9 62 0.16 19 0.51 106 35 13.4 41 0.14 17 0.45 89 32 21.3 56 0.14 20 0.50 108 25 16.3 47 0.14 13 0.43 60 58 21.5 37 0.13 18 0.51 95 23 11.0 45 0.14 18 0.50 99 41 11.5 43 0.14 15 0.32 59 29 12.7 42 0.17 18 0.48 94 32 17.3 64 0.14 16 0.55 77 46 18.8 70 0.17 18 0.45 66 37 15.2 77 0.12 19 0.47 90 72 20.5 55 0.18 17 0.47 70 179 40.1 35 0.13 19 0.47 99 100 28.3 43 0.21 13 0.46 112 52 25.6 36 0.12 17 0.51 86 43 22.9 55 0.15 16 0.54 102 24 16.9 48 0.17 18 0.48 113 39 13.6 58 0.12 19 0.47 84 38 18.3 66 0.17 18 0.48 95 54 13.4 43 0.15 17 0.56 116 33 14.2 63 0.10 20 0.40 65 40 15.6 55 0.15 18 0.45 83 61 15.8 44 0.13 18 0.50 73 31 10.2 49 0.14 17 0.47 73 44 13.9 47 0.12 17 0.51 96 35 13.1 32 0.12 18 0.32 72 36 18.1 102 0.13 17 0.45 81 33 9.3 58 0.13 15 0.46 114 28 14.3 39 0.13 16 0.44 88 26 11.1 49 <0.10 18 0.36 49 DuPont-9478 - 613 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number SHEM SLIP SICT AST U/L Female, G r o u p VIII - 25 m g / k g / d a y - D a y 94 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 54 73 95 140 76 70 71 110 984 83 Female, G r o u p X - 125 m g / k g / d a y - D a y 94 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 TRACE NONE TRACE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 150 65 61 97 92 79 96 55 174 64 Individual Clinical Chemistry Values ALT U/L SDH U/L ALKP U/L BILI mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 33 11.0 33 0.14 14 32 13.1 43 0.15 20 44 20.0 58 0.18 17 53 24.9 42 0.14 20 31 17.0 49 <0.10 15 36 17.0 33 0.14 16 31 17.3 57 0.14 15 77 29.4 39 0.13 12 374 283.2 99 0.20 17 35 11.5 41 0.14 26 0.42 0.50 0.37 0.42 0.45 0.53 0.40 0.46 0.57 0.71 170 121 107 93 80 108 100 98 228 140 75 35.4 44 0.19 12 0.46 144 32 17.3 72 0.18 17 0.43 95 31 10.7 54 0.22 18 0.50 125 50 22.0 66 0.21 18 0.43 89 39 18.3 52 0.13 17 0.46 105 35 12.9 55 0.13 15 0.43 105 30 7.3 49 0.18 17 0.39 84 38 12.7 47 0.11 18 0.44 106 69 38.6 36 0.23 14 0.43 195 47 14.5 58 0.16 21 0.60 184 DuPont-9478 - 614 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL ALB g/dL Female, G r o u p II - 0 m g / k g / d a y - D a y 94 655016 64 105 8.1 5.5 655025 42 92 8.4 5.9 655031 71 96 7.7 5.0 655032 34 90 7.6 4.8 655036 36 95 7.5 5.0 655079 24 105 7.7 5.1 655083 33 99 7.4 5.1 655098 111 117 7.6 5.2 655099 44 114 8.3 5.2 655107 49 92 7.8 5.4 Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 35 93 7.7 5.1 655033 33 92 7.6 5.0 655040 50 108 8.2 5.7 655041 85 108 7.9 5.4 655044 47 115 8.0 5.2 655086 61 89 7.8 5.2 655089 212 124 8.2 5.6 655090 41 117 7.5 5.1 655091 44 100 8.1 5.7 655108 55 97 8.5 5.8 Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 24 35 44 41 40 32 37 54 27 57 97 6.9 4.5 107 7.9 5.1 110 7.8 5.2 94 7.2 4.7 107 8.6 5.5 108 7.3 4.9 86 7.2 4.6 115 7.9 5.0 105 7.6 5.3 113 7.7 4.7 Individual Clinical Chemistry Values GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L PHEM 2.6 11.6 6.0 142.3 5.03 100.2 NONE 2.5 11.7 6.3 144.6 5.00 98.1 TRACE 2.7 11.5 6.2 144.8 6.11 97.4 NONE 2.8 11.7 7.3 146.7 5.73 102.5 NONE 2.5 11.4 6.9 144.9 5.77 98.6 NONE 2.6 11.5 6.3 146.1 5.66 99.0 NONE 2.3 11.5 7.2 146.3 6.27 105.8 TRACE 2.4 11.2 4.6 144.7 5.18 102.8 NONE 3.1 12.8 11.1 150.3 7.19 105.3 NONE 2.4 11.6 6.3 144.9 5.44 101.4 NONE 2.6 11.1 6.2 145.4 5.44 98.1 NONE 2.6 11.6 7.0 145.0 5.39 101.7 NONE 2.5 11.7 5.2 146.4 5.11 101.3 NONE 2.5 11.2 4.6 144.1 5.26 101.1 NONE 2.8 11.5 5.8 147.2 5.87 102.8 NONE 2.6 11.5 5.5 146.8 5.51 100.3 NONE 2.6 11.8 6.6 144.0 6.30 100.4 TRACE 2.4 11.4 6.8 147.0 5.73 104.6 TRACE 2.4 11.7 6.5 146.7 5.77 100.9 NONE 2.7 11.6 5.0 143.9 5.02 99.3 NONE 2.4 11.0 7.2 145.7 6.39 102.3 TRACE 2.8 11.5 6.8 146.5 5.55 104.2 NONE 2.6 11.9 7.7 144.7 6.32 101.0 NONE 2.5 11.2 7.0 144.8 5.57 102.4 NONE 3.1 11.9 6.2 148.9 6.07 102.1 NONE 2.4 11.2 7.9 145.9 6.01 104.5 NONE 2.6 10.8 5.6 146.1 5.81 103.4 NONE 2.9 11.7 7.1 147.9 6.25 103.3 NONE 2.3 10.8 5.2 143.5 5.36 99.6 NONE 3.0 11.4 7.2 145.1 6.23 101.3 TRACE DuPont-9478 - 615 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL ALB g/dL Female, G r o u p VIII - 25 m g / k g / d a y - D a y 94 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 33 43 54 28 29 27 35 64 56 43 104 8.7 5.9 104 7.7 5.3 98 7.8 5.1 91 7.9 5.2 95 7.3 4.9 147 8.0 5.6 97 7.8 5.0 116 9.0 6.3 108 9.3 5.6 101 9.0 6.2 Female, G r o u p X - 125 m g / k g / d a y - D a y 94 655007 30 99 8.5 5.8 655023 20 102 7.9 5.6 655026 23 101 9.1 6.2 655052 26 90 8.8 6.0 655053 37 102 8.7 5.7 655063 19 108 8.4 5.8 655092 29 103 7.7 5.3 655095 31 98 8.4 5.4 655097 175 94 8.9 6.0 655103 34 98 9.6 6.4 Individual Clinical Chemistry Values GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L PHEM 2.8 12.2 6.9 144.5 5.12 97.7 TRACE 2.4 11.5 7.2 146.1 5.82 100.1 TRACE 2.7 11.6 6.1 143.8 5.20 102.2 NONE 2.7 11.4 6.7 144.5 5.37 103.2 NONE 2.4 11.0 6.0 145.3 5.93 100.6 NONE 2.4 11.9 8.6 146.0 5.05 102.0 NONE 2.8 11.4 6.0 146.4 5.65 99.5 NONE 2.7 12.0 6.0 144.2 5.39 97.9 NONE 3.7 12.8 7.6 147.2 5.43 98.7 NONE 2.8 12.3 6.0 147.1 5.08 103.0 NONE 2.7 12.1 7.9 146.2 6.25 101.5 NONE 2.3 11.7 7.9 146.6 5.80 100.9 TRACE 2.9 12.6 7.5 148.0 5.94 100.5 NONE 2.8 12.3 6.9 144.6 5.95 97.2 NONE 3.0 12.4 7.3 150.8 5.31 100.6 TRACE 2.6 12.2 7.4 146.0 5.94 99.9 NONE 2.4 11.7 7.7 147.8 6.47 104.6 NONE 3.0 11.9 6.5 142.8 6.16 100.8 NONE 2.9 12.5 6.8 142.5 5.81 98.8 NONE 3.2 13.0 6.9 147.2 5.84 100.6 NONE DuPont-9478 - 616 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number PLIP PICT PFLU ug/mL Female, G r o u p II - 0 m g / k g / d a y - D a y 94 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.2 Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.1 0.1 0.1 0.1 0.1 0.3 0.1 0.1 0.1 0.1 Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 Individual Clinical Chemistry Values - 617 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number PLIP PICT PFLU ug/mL Female, G r o u p V III - 25 m g / k g / d a y - D a y 94 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.2 0.2 0.2 0.2 0.2 0.1 0.1 0.2 0.2 0.2 Female, G r o u p X - 125 m g / k g / d a y - D a y 94 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE LD LD LD O OO 0.6 0.6 0.6 0.4 0.3 0.3 0.3 Individual Clinical Chemistry Values DuPont-9478 - 618 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number SHEM SLIP SICT AST U/L Female, G r o u p II -- 0 m g / k g / d a y - D a y 183 655009 655015 655019 655035 655062 655068 655072 655101 655109 TRACE NONE TRACE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 626 104 128 114 90 244 85 79 119 Female, Group X - 125 mg/kg/day - Day 183 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 NONE NONE TRACE TRACE TRACE TRACE NONE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 253 76 102 68 91 68 79 105 91 95 Individual Clinical Chemistry Values ALT SDH ALKP BILI U/L U/L U/L mg/dL BUN mg/dL CREA mg/dL CHOL mg/dL 323 98.0 47 0.34 13 0.52 126 77 17.7 30 0.12 18 0.45 132 58 24.3 43 0.19 18 0.60 153 61 24.0 40 0.16 17 0.49 109 62 14.6 26 0.15 15 0.49 153 136 42.2 29 0.15 21 0.54 186 36 11.0 28 0.14 18 0.57 121 45 11.8 37 0.12 17 0.54 108 65 19.2 24 0.13 19 0.50 118 167 44.9 43 19.9 64 20.1 25 8.4 49 12.6 30 11.9 32 12.4 46 11.0 64 18.7 56 14.9 29 <0.10 18 32 0.14 11 37 0.15 15 43 0.14 17 29 0.17 21 37 0.18 12 39 0.13 15 60 0.20 19 47 0.16 13 30 0.15 17 0.48 0.42 0.55 0.43 0.57 0.43 0.53 0.50 0.39 0.47 255 265 93 74 129 127 86 113 151 180 DuPont-9478 - 619 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number TRIG mg/dL GLUC mg/dL TP g/dL ALB g/dL Female, G r o u p II -- 0 m g / k g / d a y - D a y 183 655009 64 97 8.0 5.2 655015 83 99 8.5 5.7 655019 78 196 8.6 5.7 655035 75 95 8.9 5.9 655062 79 124 9.0 6.2 655068 101 129 8.4 5.7 655072 54 108 8.4 5.7 655101 93 133 8.1 5.6 655109 75 105 8.2 5.5 Female, Group X - 125 mg/kg/day - Day 183 655010 100 99 8.6 5.0 655030 245 100 8.4 4.7 655037 52 107 7.9 5.3 655049 50 95 8.1 5.4 655061 50 111 9.0 6.2 655075 140 107 8.6 5.9 655077 41 110 7.9 5.3 655084 49 110 8.5 5.8 655088 81 102 8.1 5.4 655100 84 95 8.5 5.4 Individual Clinical Chemistry Values GLOB g/dL CALC mg/dL IPHS mg/dL NA mmol/L K mmol/L CL mmol/L 2.8 12.0 6.2 148.3 6.00 103.2 2.8 12.1 6.5 149.6 4.94 104.7 2.9 12.8 9.6 149.6 6.16 103.5 3.0 12.3 5.9 148.9 5.37 100.9 2.8 12.9 5.8 149.8 5.11 104.4 2.7 12.5 8.3 146.0 5.92 102.9 2.7 12.5 7.9 150.7 6.30 105.3 2.5 12.3 7.2 146.8 6.56 105.7 2.7 12.5 6.5 148.5 5.81 105.9 3.6 12.2 8.0 147.1 5.67 101.2 3.7 12.6 7.3 148.7 5.78 100.4 2.6 11.8 6.1 149.2 5.57 103.8 2.7 11.9 6.7 150.9 5.48 106.4 2.8 12.7 7.5 151.6 5.32 106.2 2.7 12.6 9.3 149.8 6.93 102.3 2.6 11.9 6.5 150.8 6.69 107.2 2.7 12.2 8.5 151.2 5.70 104.6 2.7 12.3 7.9 147.9 6.22 102.5 3.1 12.2 6.5 149.0 6.01 104.1 PHEM NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NSR NONE NONE NONE DuPont-9478 - 620 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number PLIP PICT PFLU ug/mL Female, G r o u p II - 0 m g / k g / d a y - D a y 183 oo oo 655009 655015 655019 655035 655062 655068 655072 655101 655109 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Female, Group X - 125 mg/kg/day - Day 183 o o 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 NONE NONE NONE NONE NONE NONE NT NONE NONE NONE NONE NONE NONE NONE NONE NONE NT NONE NONE NONE 0.1 0.1 0.1 0.1 0.1 NT 0.1 0.1 0.1 Individual Clinical Chemistry Values DuPont-9478 - 621 - TRADE SECRET Study Title 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Volume 3 of 3 Laboratory Project ID: DuPont-9478 DuPont-9478 Te s t Gu id e l in e s : U.S. EPA Health Effects Test Guidelines OPPTS 870.3100 (1998) Au t h o r : Gregory S. Ladics, Ph.D St u d y Co m p l e t e d o n : April 1, 2003 P L :e r f o r m in g a b o r a t o r y E.I. du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 W o r k Re q u e s t Nu m b e r : 13690 Se r v i c e Co d e Nu m b e r : 1022 Page 622 of 967 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal QUAL COL CLAR Number Male, Group I - 0 mg/kg/day - Day 48 654928 654903 654925 654929 654936 654950 654953 654972 654987 654993 MEDIUM LIGHT MEDIUM LIGHT LIGHT LIGHT LIGHT MEDIUM LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLOUDY HAZY CLOUDY HAZY CLOUDY HAZY HAZY CLOUDY HAZY CLOUDY Male, Group III - 1 mg/kg/day - Day 48 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 MEDIUM LIGHT MEDIUM MEDIUM LIGHT LIGHT LIGHT MEDIUM LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLOUDY CLOUDY HAZY HAZY HAZY CLOUDY HAZY HAZY HAZY Male, Group V - 5 mg/kg/day - Day 48 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 LIGHT MEDIUM MEDIUM MEDIUM MEDIUM MEDIUM LIGHT MEDIUM LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLOUDY HAZY CLOUDY HAZY CLEAR HAZY CLOUDY CLEAR CLOUDY CLEAR VOL mL 4.2 9.0 10.8 15.4 11.0 16.4 19.4 5.0 41.0 12.0 7.0 22.0 5.4 10.8 17.2 6.2 12.0 5.6 14.6 8.4 14.0 9.2 5.2 6.9 12.6 9.8 27.0 10.0 10.6 11.2 Individual Urinalysis Values UOSM mOsm/kg pH UGLU mg/dL KET mg/dL UBIL BLD URO EU/dL 1781 856 840 492 822 533 593 1144 233 603 7.0 NEGATIVE 15 NEGATIVE NEGATIVE 7.5 NEGATIVE 5 NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 8.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE Moderate 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE 15 NEGATIVE NEGATIVE 7.5 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 1203 358 1431 949 461 925 660 1056 536 828 7.0 NEGATIVE 15 NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 619 1027 1409 1300 782 860 351 1036 1004 742 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE 15 NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.5 NEGATIVE 15 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 DuPont-9478 - 623 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal QUAL COL CLAR VOL Number mL Male, Group VII - 25 mg/kg/day - Day 48 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 MEDIUM LIGHT LIGHT MEDIUM MEDIUM MEDIUM MEDIUM LIGHT LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLOUDY HAZY CLOUDY CLEAR HAZY HAZY HAZY HAZY CLOUDY HAZY 7.2 29.0 19.4 5.6 6.8 11.6 10.4 21.0 14.4 5.0 Male, Group IX - 125 mg/kg/day - Day 48 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 LIGHT MEDIUM LIGHT MEDIUM LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLOUDY CLOUDY HAZY HAZY CLOUDY HAZY HAZY CLOUDY HAZY HAZY 13.8 13.0 10.4 11.0 22.2 27.0 15.6 23.0 20.5 15.0 Individual Urinalysis Values UOSM mOsm/kg pH UGLU mg/dL KET mg/dL UBIL BLD URO EU/dL 928 378 589 1283 1301 627 839 477 610 1364 7.0 NEGATIVE 15 NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 6.5 NEGATIVE 15 NEGATIVE NEGATIVE 7.0 NEGATIVE 15 NEGATIVE NEGATIVE 7.5 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.5 NEGATIVE 15 NEGATIVE NEGATIVE 6.5 NEGATIVE 15 NEGATIVE NEGATIVE 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 691 7.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 751 7.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 695 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 896 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 481 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 355 8.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 622 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 530 7.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 432 7.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 601 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 DuPont-9478 - 624 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number UMTP mg/dL Male, Group I - 0 mg/kg/day - Day 48 654928 654903 654925 654929 654936 654950 654953 654972 654987 654993 118 55 27 20 54 77 24 76 10 28 Male, Group III - 1 mg/kg/day - Day 48 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 62 21 91 52 24 30 77 72 19 32 Male, Group V - 5 mg/kg/day - Day 48 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 21 53 78 105 41 32 13 114 60 34 Individual Urinalysis Values - 625 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number UMTP mg/dL Male, Group VII - 25 mg/kg/day - Day 48 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 75 13 19 99 49 25 28 24 41 101 Male, Group IX - 125 mg/kg/day - Day 48 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 42 35 39 130 64 12 27 29 19 37 Individual Urinalysis Values - 626 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal QUAL COL CLAR Number Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654928 654903 654925 654929 654936 654950 654953 654972 654987 654993 MEDIUM LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT MEDIUM LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLEAR CLEAR CLEAR HAZY CLEAR CLEAR HAZY HAZY HAZY Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 MEDIUM LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLEAR HAZY CLOUDY CLEAR CLEAR CLEAR CLEAR HAZY CLEAR Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 LIGHT LIGHT LIGHT MEDIUM LIGHT LIGHT LIGHT MEDIUM MEDIUM MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR HAZY CLEAR CLEAR CLEAR HAZY HAZY HAZY CLEAR VOL mL 5.5 5.0 9.6 5.8 7.6 8.2 8.0 4.0 10.8 3.0 5.0 8.0 4.8 6.8 5.4 8.6 5.0 3.6 6.8 8.8 7.6 16.8 8.2 4.2 10.4 7.4 7.2 9.0 3.0 1.8 Individual Urinalysis Values UOSM mOsm/kg pH UGLU mg/dL KET mg/dL UBIL BLD URO EU/dL 1475 1424 676 1415 1177 879 1323 1648 908 2283 7.0 NEGATIVE 5 NEGATIVE NEGATIVE O. 2 6.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE 15 NEGATIVE NEGATIVE 0.2 8.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE 15 NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE 5 NEGATIVE TRACE 0.2 1574 1033 1516 1645 1613 798 1125 1690 1258 989 6.5 NEGATIVE 15 NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE 15 NEGATIVE NEGATIVE 0.2 7.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE 15 NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE 15 NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE 5 NEGATIVE MODERATE 0.2 7.0 NEGATIVE 15 NEGATIVE NEGATIVE 0.2 1117 536 1248 1886 947 1069 590 1226 2013 2301 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 6.5 NEGATIVE 5 NEGATIVE NEGATIVE 6.5 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEG A T I V E 15 NEG A T I V E NEG A T I V E 7.0 NEGATIVE NEGATIVE NEGATIVE TRACE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 6.5 NEG A T I V E 15 NEG A T I V E NEG A T I V E 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 DuPont-9478 - 627 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal QUAL COL CLAR VOL Number mL Male, G r o u p VII - 25 m g / k g / d a y - D a y 93 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 MEDIUM LIGHT LIGHT LIGHT LIGHT MEDIUM MEDIUM LIGHT LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR HAZY CLEAR CLEAR CLEAR CLEAR HAZY HAZY HAZY 3.6 19.6 6.8 5.8 5.6 2.0 5.8 16.0 7.4 5.2 Male, G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 LIGHT LIGHT LIGHT MEDIUM LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY HAZY HAZY CLEAR HAZY HAZY CLEAR CLEAR CLEAR HAZY 17.8 29.0 7.2 6.2 12.6 31.5 10.8 41.0 41.0 14.0 Individual Urinalysis Values UOSM mOsm/kg pH UGLU mg/dL KET mg/dL UBIL BLD URO EU/dL 1813 484 1285 1501 1454 3643 1618 687 1242 1766 6.5 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEG A T I V E 15 NEG A T I V E NEG A T I V E 7.0 NEG A T I V E 15 NEG A T I V E NEG A T I V E 7.0 NEGATIVE 5 SMALL NEGATIVE 6.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.0 NEG A T I V E 15 NEG A T I V E NEG A T I V E 6.5 NEG A T I V E 15 NEG A T I V E NEG A T I V E 0.2 0.2 0.2 0.2 0.2 1.0 0.2 0.2 0.2 0.2 567 400 1487 1480 588 350 922 284 324 623 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.5 NEGATIVE 5 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE SMALL 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE LARGE 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 DuPont-9478 - 628 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number UFLU ug UMTP mg/dL Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654928 654903 654925 654929 654936 654950 654953 654972 654987 654993 4.4 7.5 8.7 11.3 20.5 9.6 12.5 8.6 14.3 9.2 74 103 22 74 95 328 71 146 27 139 Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 654913 654932 654938 654941 654946 654947 654960 654984 654995 12.7 13.6 14.1 16.2 14.9 11.8 9.5 11.0 13.0 13.0 100 63 129 116 112 29 171 148 77 36 Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 654911 654916 654917 654959 654961 654967 654980 654998 655005 39.3 46.7 38.9 33.1 36.6 51.1 21.6 52.3 29.3 QNS 37 26 68 139 46 74 27 114 163 119 Individual Urinalysis Values - 629 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number UFLU ug UMTP mg/dL Male, G r o u p VII - 25 m g / k g / d a y - D a y 93 654922 654923 654930 654940 654952 654958 654975 654989 655001 655006 282.4 236.0 131.5 135.5 126.1 QNS 242.3 195.1 231.7 240.8 158 16 69 112 67 184 75 34 60 115 Male, G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 1203.7 915.4 895.7 879.9 716.7 893.4 958.5 1158.1 1557.8 793.1 36 29 90 314 68 10 47 9 14 52 Individual Urinalysis Values - 630 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal QUAL COL CLAR VOL Number mL Male, Group I - 0 mg/kg/day - Day 183 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 LIGHT MEDIUM MEDIUM LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY HAZY HAZY HAZY CLOUDY CLEAR CLEAR CLEAR CLEAR HAZY 5.8 3.6 3.0 22.0 3.6 10.0 4.8 5.8 15.2 1.0 Male, Group IX - 125 mg/kg/day - Day 183 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 MEDIUM LIGHT LIGHT MEDIUM LIGHT LIGHT LIGHT LIGHT MEDIUM LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR HAZY CLEAR CLEAR 4.8 15.6 3.8 9.0 13.2 8.6 6.8 6.0 2.8 6.4 Individual Urinalysis Values UOSM mOsm/kg pH UGLU mg/dL KET mg/dL UBIL BLD URO EU/dL 913 2189 2545 457 2552 923 1095 1219 709 QNS 6.5 NEGATIVE 15 NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE 5 NEGATIVE NEGATIVE 1.0 6.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 8.0 NEGATIVE 15 NEGATIVE NEGATIVE 1.0 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 1788 693 1387 1375 671 752 1012 1486 2594 1461 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE 15 NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE 5 NEGATIVE NEGATIVE 1.0 6.5 NEGATIVE 5 NEGATIVE NEGATIVE 0.2 DuPont-9478 - 631 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number UFLU ug UMTP mg/dL Male, Group I - 0 mg/kg/day - Day 183 654909 654910 654915 654924 654927 654943 654949 654956 654992 654994 6.8 10.3 7.5 15.9 11.7 9.5 6.4 8.4 13 QNS 52.0 196.0 600.0 21.0 110.0 113.0 143.0 139.0 52.0 180.0 Male, Group IX - 125 mg/kg/day Day 183 654942 654957 654973 654974 654976 654977 654978 654985 654990 654991 30.5 26.2 20.5 36 33.3 26.4 19.2 27.4 28.1 28.1 107.0 22.0 115.0 71.0 21.0 23.0 31.0 100.0 140.0 320.0 Individual Urinalysis Values - 632 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal QUAL COL CLAR VOL Number mL Female, G r o u p II - 0 m g / k g / d a y - D a y 49 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 MEDIUM MEDIUM MEDIUM LIGHT MEDIUM MEDIUM MEDIUM MEDIUM MEDIUM LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR CLEAR HAZY CLEAR CLEAR CLEAR CLEAR CLOUDY CLEAR 5.2 8.8 8.6 15.0 4.0 3.6 5.2 6.0 7.4 7.8 Female, Group IV - 1 mg/kg/day - Day 49 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 LIGHT LIGHT MEDIUM MEDIUM MEDIUM MEDIUM MEDIUM MEDIUM MEDIUM LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLOUDY CLOUDY CLEAR CLOUDY CLEAR CLEAR CLEAR CLEAR HAZY CLEAR 14.2 18.8 4.2 4.6 2.0 3.8 2.0 4.2 11.8 9.6 Female, Group VI - 5 mg/kg/day - Day 49 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 MEDIUM LIGHT MEDIUM MEDIUM LIGHT LIGHT MEDIUM MEDIUM LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR HAZY CLOUDY CLEAR 3.2 9.0 3.6 5.2 21.0 14.6 2.0 6.6 13.0 3.8 Individual Urinalysis Values UOSM mOsm/kg pH UGLU mg/dL KET mg/dL UBIL BLD URO EU/dL 909 599 780 497 825 1385 1293 879 970 681 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE Moderate 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE Trace 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 420 432 1037 1005 1537 1182 1835 1336 620 449 8.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 8.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE Trace 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE 5 NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 1828 828 1113 1128 276 NT 1706 968 450 1150 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 DuPont-9478 - 633 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal QUAL COL CLAR VOL Number mL Female, Group VIII - 25 mg/kg/day - Day 49 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 LIGHT LIGHT MEDIUM LIGHT LIGHT LIGHT LIGHT MEDIUM MEDIUM MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR 8.8 9.2 8.0 7.8 19.0 10.8 50.0 8.4 18.0 4.2 Female, Group X - 125 mg/kg/day - Day 49 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 MEDIUM LIGHT MEDIUM MEDIUM MEDIUM LIGHT LIGHT MEDIUM MEDIUM MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLOUDY CLEAR CLEAR CLEAR CLEAR HAZY CLEAR CLEAR CLEAR 4.0 20.0 7.0 5.6 3.0 11.0 13.0 4.6 8.4 5.4 Individual Urinalysis Values UOSM mOsm/kg pH UGLU mg/dL KET mg/dL UBIL BLD URO EU/dL 858 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 679 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 870 7.0 NEGATIVE NEGATIVE NEGATIVE Trace 0.2 655 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 321 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 648 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 125 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 744 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 427 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 906 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 1156 296 849 1223 2185 324 469 1362 758 920 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 DuPont-9478 - 634 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number UMTP mg/dL SPEC Female, G r o u p II - 0 m g / k g / d a y - D a y 49 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 26 16 F E C A L C O N T A M I N A T I O N O B S E R V E D 27 9 19 27 24 22 35 FECAL C O N T AMINATION O B S E R V E D 15 Female, Group IV 1 mg/kg/day - Day 49 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 16 10 25 40 FECAL CONTAMINATION OBSERVED 52 33 69 74 15 8 Female, Group VI - 5 mg/kg/day - Day 49 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 57 57 21 21 5 12 F E C A L C O N T A M I N A T I O N O B S E R V E D 37 17 13 21 Individual Urinalysis Values - 635 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number UMTP mg/dL Female, Group VIII - 25 mg/kg/day - Day 49 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 18 11 18 13 6 13 2 18 11 18 Female, Group X - 125 mg/kg/day - Day 49 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 95 12 17 28 74 21 12 104 59 33 Individual Urinalysis Values - 636 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal QUAL COL CLAR VOL Number mL Female, G r o u p II - 0 m g / k g / d a y - D a y 94 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 MEDIUM LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR HAZY CLEAR HAZY CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR 1.8 3.6 4.8 6.4 2.0 3.0 5.8 3.2 17.0 2.6 Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT NT LIGHT LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW NT YELLOW YELLOW YELLOW CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR NT CLEAR CLEAR CLEAR 3.0 3.4 1.8 1.0 2.8 2.6 QNS 2.6 7.2 1.0 Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR HAZY CLEAR HAZY CLEAR CLEAR CLEAR CLEAR HAZY 4.4 10.0 2.0 6.8 3.4 4.0 3.0 2.8 4.0 o LD co i--i Individual Urinalysis Values UOSM mOsm/kg pH UGLU mg/dL KET mg/dL UBIL BLD URO EU/dL 2486 864 1088 1075 2137 1078 1217 1344 393 1678 5.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE TRACE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 5.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 1176 1181 2122 QNS 1548 1044 NT 1800 755 2528 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 5.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 NT NT NT NT NT NT 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 1464 460 2243 768 940 1394 1136 1941 1374 1452 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 5.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 DuPont-9478 - 637 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal QUAL COL CLAR VOL Number mL Female, G r o u p VIII - 25 m g / k g / d a y - D a y 94 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 MEDIUM LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY HAZY HAZY HAZY CLEAR CLOUDY HAZY CLEAR CLEAR CLEAR 2.8 3.4 10.8 8.6 2.6 4.6 2.0 2.0 7.4 3.4 Female, G r o u p X - 125 m g / k g / d a y - D a y 94 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 LIGHT LIGHT LIGHT LIGHT LIGHT MEDIUM LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY HAZY CLEAR HAZY HAZY CLEAR HAZY CLEAR HAZY CLEAR 14.2 9.0 4.4 8.8 4.6 1.6 13.0 2.4 11.0 8.0 Individual Urinalysis Values UOSM mOsm/kg pH UGLU mg/dL KET mg/dL UBIL BLD URO EU/dL 2013 1690 686 578 1272 1004 1639 1655 833 939 6.0 NEGATIVE NEGATIVE SMALL NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE NEGATIVE NEGATIVE MODERATE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 345 625 1367 718 1244 2593 542 1848 557 674 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 DuPont-9478 - 638 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Urinalysis Values Animal Number UFLU ug UMTP mg/dL SPEC Female, G r o u p II - 0 m g / k g / d a y - D a y 94 655016 655025 655031 655032 655036 655079 655083 655098 655099 655107 QNS 4.1 5.3 8.7 QNS 3.7 7.6 4.4 9.7 4.4 85 30 FECAL CONTAMINATION OBSERVED 20 20 FECAL CONTAMINATION OBSERVED 59 24 27 24 8 29 Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 655033 655040 655041 655044 655086 655089 655090 655091 655108 4.9 6.3 QNS QNS 6.4 3.4 NT 5.8 7.6 QNS 30 19 44 45 36 22 NT 112 16 111 Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 655029 655034 655038 655039 655042 655054 655066 655067 655087 12.4 15.7 QNS 16.7 9.0 17.3 10.3 14.1 QNS 17.5 27 12 54 12 16 32 25 31 56 34 - 639 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Individual Urinalysis Values Animal Number UFLU ug UMTP mg/dL SPEC Female, G r o u p V III - 25 m g / k g / d a y - D a y 94 655011 655012 655047 655055 655058 655073 655076 655078 655085 655105 144.9 61.6 71.0 70.6 83.8 78.6 QNS QNS 119.9 73.2 496 34 F E C A L C O N T A M I N A T I O N O B S E R V E D 15 FECAL C O N T A M I N A T I O N OB S E R V E D 11 22 58 FECAL C O N T A M I N A T I O N OB S E R V E D 51 115 50 24 Female, G r o u p X - 125 m g / k g / d a y - D a y 94 655007 655023 655026 655052 655053 655063 655092 655095 655097 655103 873.5 766.5 436.4 883.7 1096.9 QNS 514.7 346.3 888.0 517.0 128 21 33 40 46 840 11 756 310 111 DuPont-9478 - 640 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal QUAL COL CLAR VOL Number mL Female, G r o u p II - 0 m g / k g / d a y - D a y 183 655009 655015 655019 655035 655062 655068 655072 655101 655109 NT NT MEDIUM LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT NT NT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW NT NT CLEAR CLEAR CLEAR HAZY CLEAR CLEAR HAZY QNS QNS 1.0 3.6 3.6 4.0 1.4 4.0 40.0 Female, Group X - 125 mg/kg/day - Day 183 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 MEDIUM LIGHT LIGHT LIGHT MEDIUM MEDIUM LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR HAZY CLEAR HAZY CLEAR CLEAR HAZY CLEAR HAZY 2.4 11.8 2.2 2.8 1.0 5.8 4.4 13.8 1.0 4.2 Individual Urinalysis Values UOSM mOsm/kg pH UGLU mg/dL KET mg/dL UBIL BLD URO EU/dL NT NT 3391 1540 1616 269 2072 1306 142 NT NT NT NT NT NT NT NT NT NT 6.0 NEGATIVE NEGATIVE SMALL NEGATIVE 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 5.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE NT NT 0.2 0.2 0.2 0.2 0.2 0.2 0.2 1753 502 2187 1447 3195 1151 1053 261 1972 925 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.5 NEGATIVE NEGATIVE SMALL TRACE 1.0 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 7.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 5.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 6.0 NEGATIVE NEGATIVE NEGATIVE NEGATIVE 0.2 DuPont-9478 - 641 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number UFLU ug UMTP mg/dL Female, G r o u p II - 0 m g / k g / d a y - D a y 183 655009 655015 655019 655035 655062 655068 655072 655101 655109 QNS QNS QNS 5.6 7.3 5.4 QNS 7 34 QNS QNS 780 31 220.0 85 47.0 37.0 2.0 Female, Group X - 125 mg/kg/day - Day 183 655010 655030 655037 655049 655061 655075 655077 655084 655088 655100 13.7 18.8 QNS 11.4 QNS 18.7 16.4 18.3 QNS 12.3 3380 990.0 62 22.0 135.0 181.0 156.0 21.0 230 700.0 Individual Urinalysis Values - 642 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number EPIT UWBC URBC Male, Group I - 0 mg/kg/day - Day 48 654903 1 0 0 654925 1 0 0 654928 1 0 0 654929 1 0 0 654936 1 0 0 654950 1 0 0 654953 1 0 0 654972 1 0 0 654987 1 0 0 654993 1 0 0 Male, Group III - 1 mg/kg/day - Day 48 654908 1 0 0 654913 1 0 0 654932 1 0 0 654938 1 0 0 654941 1 0 0 654946 1 0 0 654947 1 0 0 654960 1 0 0 654984 1 0 0 654995 1 0 0 Male, Group V - 5 mg/kg/day - Day 48 654907 1 0 0 654911 1 0 0 654916 1 0 0 654917 1 0 0 654959 1 0 0 654961 1 0 0 654967 1 0 0 654980 1 0 0 654998 1 0 0 655005 1 0 0 NCRY 1 3 1 1 2 1 2 2 1 1 1 0 2 1 1 1 1 2 1 1 1 1 2 1 1 2 1 2 2 1 Individual Urine Microscopic Values MICR SPER 32 32 22 31 31 32 31 32 33 31 21 32 31 22 33 33 21 32 33 32 31 31 23 32 21 21 31 23 33 33 - 643 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number EPIT UWBC URBC NCRY Male, Group VII - 25 mg/kg/day - Da y 48 654922 1 0 0 2 654923 1 0 0 1 654930 1 0 0 1 654940 1 0 0 1 654952 1 0 0 1 654958 1 0 0 1 654975 1 0 0 1 654989 1 0 0 1 655001 1 0 0 2 655006 1 0 0 1 Male, Group IX - 125 mg/kg/day - Da y 48 654914 1 0 0 2 654921 1 0 0 1 654951 1 0 0 1 654955 1 1 0 1 654965 1 0 0 2 654979 1 0 0 1 654983 1 0 0 1 654986 1 0 0 1 654996 1 0 0 1 655003 1 0 0 1 Individual Urine Microscopic Values MICR SPER 31 31 33 21 21 22 22 32 33 33 33 33 32 22 33 23 30 33 23 22 - 644 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number EPIT UWBC URBC Male, G r o u p I - 0 m g / k g / d a y - D a y 93 654903 1 0 0 654925 1 0 0 654928 1 0 0 654929 0 0 0 654936 1 0 0 654950 1 0 0 654953 1 0 0 654972 0 0 0 654987 1 0 0 654993 QNS QNS QNS Male, G r o u p III - 1 m g / k g / d a y - D a y 93 654908 1 0 0 654913 1 0 0 654932 1 0 0 654938 0 0 0 654941 1 0 0 654946 0 0 0 654947 1 0 0 654960 0 0 0 654984 1 0 2 654995 0 0 0 Male, G r o u p V - 5 m g / k g / d a y - D a y 93 654907 1 0 0 654911 0 0 0 654916 0 0 0 654917 0 0 1 654959 0 0 0 654961 0 0 0 654967 1 0 0 654980 0 0 0 654998 QNS QNS QNS 655005 QNS QNS QNS NCRY 1 1 1 1 1 1 1 1 1 QNS 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 QNS QNS Individual Urine Microscopic Values MICR SPER SPEC 1 1 BELOW RECOMMENDED VOLUME 1 1 1-MUCUS STRANDS 1 3 1-MUCUS STRANDS 1 2 1-MUCUS STRANDS 1 0 1-MUCUS STRANDS 1 0 1-MUCUS STRANDS 1 1 1-MUCUS STRANDS 1 2 1-MUCUS STRANDS; BELOW RECOMMENDED VOLUME 1 3 1-MUCUS STRANDS QNS QNS 12 13 1 3 BELOW RECOMMENDED VOLUME 21 13 12 11 1 3 BELOW RECOMMENDED VOLUME 1 2 1-MUCUS STRANDS 12 1 1 1-MUCUS STRANDS 12 13 12 1 1 1-MUCUS STRANDS 13 1 1 1-MUCUS STRANDS 1 3 1-MUCUS STRANDS QNS QNS QNS QNS - 645 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number EPIT UWBC URBC NCRY M a l e , G r o u p VII - 25 m g / k g / d a y - D a y 93 654922 1 0 0 1 654923 1 0 0 1 654930 0 0 0 1 654940 0 0 0 1 654952 1 0 0 1 654958 QNS QNS QNS QNS 654975 0 0 0 1 654989 1 0 0 1 655001 0 0 0 1 655006 0 0 0 1 M a l e , G r o u p IX - 125 m g / k g / d a y - D a y 93 654914 0 0 0 1 654921 0 0 0 0 654951 1 0 0 2 654955 1 0 0 1 654965 0 0 0 1 654979 0 0 0 1 654983 0 0 0 1 654986 0 0 0 1 654996 1 0 0 1 655003 1 0 2 1 Individual Urine Microscopic Values MICR SPER SPEC 1 2 BELOW RECOMMENDED VOLUME 12 13 1 2 1-MUCUS STRANDS 1 2 1-MUCUS STRANDS QNS QNS 12 21 13 1 3 BELOW RECOMMENDED VOLUME 33 23 13 11 13 23 11 11 22 1 1 1-MUCUS STRANDS DuPont-9478 - 646 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number EPIT UWBC URBC Female, G r o u p II - 0 m g / k g / d a y - D a y 655016 1 0 0 655025 1 0 0 655031 1 0 1 655032 1 0 0 655036 0 0 0 655079 1 0 0 655083 1 0 0 655098 1 1 0 655099 1 1 0 655107 1 0 0 Female, Group IV - 1 mg/kg/day - Day 655013 0 0 0 655033 1 0 0 655040 1 1 0 655041 1 0 0 655044 1 1 0 655086 1 0 0 655089 1 0 0 655090 1 0 0 655091 1 0 0 655108 1 0 0 Female, Group VI - 5 mg/kg/day - Day 655020 1 1 0 655029 0 0 0 655034 1 0 0 655038 1 0 0 655039 1 0 0 655042 0 0 0 655054 1 0 0 655066 1 0 0 655067 1 0 0 655087 1 0 0 NCRY 1 1 1 2 0 0 1 1 1 1 1 1 0 2 0 0 0 1 1 0 0 0 0 0 0 3 0 2 1 0 Individual Urine Microscopic Values MICR SPER SPEC 20 20 30 30 30 10 10 20 30 30 30 30 30 30 2 0 BELOW RECOMMENDED VOLUME 20 3 0 BELOW RECOMMENDED VOLUME 20 30 20 3 0 BELOW RECOMMENDED VOLUME 20 1 0 BELOW RECOMMENDED VOLUME 10 30 30 1 0 BELOW RECOMMENDED VOLUME 30 30 10 - 647 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number EPIT UWBC URBC NCRY Female, Group VIII - 25 mg/kg/day - Day 49 655011 1 0 0 2 655012 1 0 0 0 655047 1 0 0 0 655055 1 1 0 0 655058 0 0 0 0 655073 0 0 0 1 655076 1 0 0 0 655078 1 0 0 1 655085 1 0 0 2 655105 1 0 0 1 Female, Group X - 125 mg/kg/day - Day 49 655007 1 0 0 2 655023 1 0 0 1 655026 1 0 0 0 655052 1 0 0 0 655053 1 0 0 0 655063 1 0 0 0 655092 1 0 0 2 655095 1 0 0 0 655097 1 0 0 0 655103 1 0 0 1 Individual Urine Microscopic Values MICR SPER SPEC 30 20 20 30 20 30 30 20 20 20 30 3 0 EPITHELIAL CELLS APPEAR DEGENERATED 1 0 EPITHELIAL CELLS APPEAR DEGENERATED 3 0 1-MUCUS STRANDS 2 0 BELOW RECOMMENDED VOLUME 10 30 2 0 1-MUCUS STRANDS 30 20 DuPont-9478 - 648 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number EPIT UWBC URBC NCRY Female, G r o u p II - 0 m g / k g / d a y - D a y 94 655031 0 0 0 1 655016 QNS QNS QNS QNS 655025 QNS QNS QNS QNS 655032 1 0 0 1 655036 QNS QNS QNS QNS 655079 QNS QNS QNS QNS 655083 1 0 0 0 655098 QNS QNS QNS QNS 655099 0 0 0 0 655107 QNS QNS QNS QNS Female, G r o u p IV - 1 m g / k g / d a y - D a y 94 655013 QNS QNS QNS QNS 655033 0 0 0 0 655040 QNS QNS QNS QNS 655041 QNS QNS QNS QNS 655044 QNS QNS QNS QNS 655086 QNS QNS QNS QNS 655089 QNS QNS QNS QNS 655090 QNS QNS QNS QNS 655091 1 0 0 0 655108 QNS QNS QNS QNS Female, G r o u p VI - 5 m g / k g / d a y - D a y 94 655020 0 0 0 0 655029 0 0 0 0 655034 QNS QNS QNS QNS 655038 1 0 0 1 655039 QNS QNS QNS QNS 655042 1 0 0 1 655054 QNS QNS QNS QNS 655066 QNS QNS QNS QNS 655067 QNS QNS QNS QNS 655087 1 0 0 1 Individual Urine Microscopic Values MICR SPER SPEC 1 0 1-MUCUS STANDS; BELOW RECOMMENDED VOLUME QNS QNS QNS QNS 10 QNS QNS QNS QNS 10 QNS QNS 10 QNS QNS QNS QNS 1 0 BELOW RECOMMENDED VOLUME QNS QNS QNS QNS QNS QNS QNS QNS QNS QNS QNS QNS 1 0 BELOW RECOMMENDED VOLUME QNS QNS 1 0 BELOW RECOMMENDED VOLUME 1 0 BELOW RECOMMENDED VOLUME QNS QNS 10 QNS QNS 1 0 BELOW RECOMMENDED VOLUME QNS QNS QNS QNS QNS QNS 1 0 BELOW RECOMMENDED VOLUME - 649 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Animal Number EPIT UWBC URBC NCRY Female, G r o u p VIII - 25 m g / k g / d a y - D a y 94 655011 QNS QNS QNS QNS 655012 QNS QNS QNS QNS 655047 1 0 0 1 655055 1 0 0 1 655058 QNS QNS QNS QNS 655073 0 0 0 1 655076 QNS QNS QNS QNS 655078 QNS QNS QNS QNS 655085 0 0 0 0 655105 QNS QNS QNS QNS Female, G r o u p X - 125 m g / k g / d a y - D a y 94 655007 0 0 0 0 655023 0 0 0 1 655026 1 0 0 1 655052 0 0 1 1 655053 1 0 0 0 655063 QNS QNS QNS QNS 655092 0 0 0 1 655095 QNS QNS QNS QNS 655097 0 0 0 1 655103 0 0 0 1 Individual Urine Microscopic Values MICR SPER SPEC QNS QNS QNS QNS 10 10 QNS QNS 2 0 BELOW RECOMMENDED VOLUME QNS QNS QNS QNS 10 QNS QNS 10 10 1 0 BELOW RECOMMENDED VOLUME 10 1 0 BELOW RECOMMENDED VOLUME QNS QNS 10 QNS QNS 1 0 1 -MUCUS STRANDS 10 DuPont-9478 - 650 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX L INDIVIDUAL ANIMAL BIOCHEMICAL DATA - 651 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL ANIMAL BIOCHEMICAL DATA IN MALE RATS AT THE 10-DAY TIME POINT Group I III V VII IX Animal Number 655115 655119 655124 655135 655137 655144 655118 655120 655132 655139 655121 655126 655127 655131 655138 655112 655116 655125 655129 655133 655113 655122 655123 655128 655130 Beta-Oxidation Rate (nmol/min/mg protein) 13.71 14.73 16.45 14.21 14.97 11.31 13.43 15.37 15.52 14.59 18.35 17.77 13.89 15.53 14.12 16.17 14.27 14.32 13.34 15.19 26.88 25.23 26.16 17.65 24.61 - 652 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL ANIMAL BIOCHEMICAL DATA IN MALE RATS AT THE 90-DAY TIME POINT Group I III V VII IX Animal Number 654928 654929 654950 654972 654993 654913 654938 654941 654947 654995 655005 654907 654959 654961 654980 654922 654930 654940 654975 655001 654965 654979 654983 654986 655003 Beta-Oxidation Rate (nmol/min/mg protein) 12.52 13.02 11.22 11.35 14.00 15.49 12.41 11.97 14.65 13.25 13.02 11.62 11.01 13.92 18.59 12.69 14.15 15.82 10.15 14.04 22.46 17.74 23.81 17.57 21.58 - 653 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL ANIMAL BIOCHEMICAL DATA IN MALE RATS AT THE 3-MONTH RECOVERY TIMEPOINT Group I IX Animal Number 654994 654992 654909 654924 654943 Beta-Oxidation Rate (nmol/min/mg protein) 11.86 8.05 11.90 12.53 11.59 654978 654974 654985 654990 654976 12.48 15.32 16.42 17.03 13.27 - 654 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL ANIMAL DATA IN FEMALE RATS AT THE 10-DAY TIME POINT Group II IV VI VIII X Animal Number 655141 655149 655152 655155 655159 655142 655160 655162 655164 655165 655140 655145 655154 655158 655167 655144 655148 655161 655163 655166 655143 655146 655147 655150 655151 Beta-Oxidation Rate (nmol/min/mg protein) 24.98 21.43 19.38 24.16 22.38 22.73 23.21 23.58 21.46 19.99 26.61 19.16 29.66 19.81 24.01 22.45 23.27 21.53 21.82 27.02 22.76 28.39 34.45 30.13 31.75 DuPont-9478 - 655 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL ANIMAL DATA IN FEMALE RATS AT THE 90-DAY TIME POINT Group II IV VI VIII X Animal Number 655016 655031 655079 655098 655107 655040 655041 655044 655086 655108 655029 655034 655038 655039 655054 655047 655055 655058 655076 655105 655026 655052 655063 655097 655103 Beta-Oxidation Rate (nmol/min/mg protein) 25.67 29.04 24.65 20.73 28.10 25.00 25.98 24.60 24.00 27.46 30.69 25.64 25.24 27.33 27.36 28.24 33.60 32.41 28.80 25.35 35.00 42.79 33.28 43.57 40.78 DuPont-9478 - 656 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats INDIVIDUAL ANIMAL DATA IN FEMALE RATS AT THE 3-MONTH RECOVERY TIMEPOINT Group II VIII Animal Number 655035 655015 655009 655068 655062 Beta-Oxidation Rate (nmol/min/mg protein) 23.78 21.61 25.06 23.75 24.62 655088 655077 655010 655030 655049 25.91 25.38 32.42 18.98 32.17 DuPont-9478 - 657 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX M INDIVIDUAL ANIMAL BODY AND ORGAN WEIGHTS - 658 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Subchronic Toxicity Group : I 0 mg/kg/day Sex :MALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | EPIDIDYMIDES | | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS % F B W % B R A I N | (Gms) % F B W % B R A I N | 654903 |578.50 | 2.187 0.3780 | 0.057 0.0099 2.6063 | 1.634 0.2825 74.714 | 1.885 0.3258 86.191 | 4.177 0.7220 190.99 | 654925 |575.80 | 2.190 0.3803 | 0.065 0.0113 2.9680 | 1.735 0.3013 79.224 | 1.652 0.2869 75.434 | 3.551 0.6167 162.15 | 654928 |566.30 | 2.123 0.3749 | 0.061 0.0108 2.8733 | 1.651 0.2915 77.767 | 1.785 0.3152 84.079 | 3.885 0.6860 183.00 | 654929 |506.10 | 2.184 0.4315 | 0.063 0.0124 2.8846 | 1.783 0.3523 81.639 | 1.847 0.3649 84.570 | 3.745 0.7400 171.47 | 654936 |583.70 | 2.137 0.3661 | 0.048 0.0082 2.2461 | 0.791 0.1355 37.015 | 1.555 0.2664 72.766 | 3.497 0.5991 163.64 | 654950 |520.70 | 2.139 0.4108 | 0.058 0.0111 2.7115 | 1.609 0.3090 75.222 | 1.901 0.3651 88.873 | 4.513 0.8667 210.99 | 654953 |646.30 | 2.175 0.3365 | 0.072 0.0111 3.3103 | 1.555 0.2406 71.494 | 1.921 0.2972 88.322 | 4.361 0.6748 200.51 | 654972 |498.80 | 2.341 0.4693 | 0.063 0.0126 2.6912 | 1.655 0.3318 70.696 | 1.678 0.3364 71.679 | 4.197 0.8414 179.28 | 654987 |566.40 | 2.316 0.4089 | 0.077 0.0136 3.3247 | 1.561 0.2756 67.401 | 1.981 0.3498 85.535 | 4.268 0.7535 184.28 | 654993 |486.80 | 2.066 0.4244 | 0.048 0.0099 2.3233 | 1.308 0.2687 63.311 | 1.405 0.2886 68.006 | 3.041 0.6247 147.19 | | Mean | S.D. || |552.94 | 2.186 0.3981 | 0.061 0.0111 2.7939 | 1.528 0.2789 69.848 | 1.761 0.3196 80.545 | 3.924 0.7125 179.35 |49.145 | 0.084 0.0383 | 0.009 0.0016 0.3601 | 0.289 0.0595 12.791 | 0.184 0.0345 7.7301 | 0.463 0.0912 19.034 G r o u p : III 1 m g / k g / d a y S e x :M A L E S | ANIMAL | FBW | BRAIN | | (Gms) |(Gms) % F B W | ADRENAL GLANDS | EPIDIDYMIDES | | (Gms) % F B W %B R A I N | (Gms) % F B W % B R A I N | (Gms) HEART | KIDNEYS % F B W % B R A I N | (Gms) % F B W %B R A I N 654908 |516.10 | 2.313 0.4482 | 0.031 0.0060 1.3403 | 1.372 0.2658 59.317 | 1.736 0.3364 75.054 | 3.872 0.7502 167.40 654913 |534.10 | 2.149 0.4024 | 0.035 0.0066 1.6287 | 1.605 0.3005 74.686 | 1.820 0.3408 84.691 | 3.455 0.6469 160.77 654932 |566.10 | 2.082 0.3678 | 0.035 0.0062 1.6811 | 1.573 0.2779 75.552 | 1.856 0.3279 89.145 | 4.174 0.7373 200.48 654938 |579.40 | 2.213 0.3819 | 0.038 0.0066 1.7171 | 1.536 0.2651 69.408 | 2.031 0.3505 91.776 | 3.756 0.6483 169.72 654941 |515.80 | 2.229 0.4321 | 0.045 0.0087 2.0188 | 1.650 0.3199 74.024 | 1.766 0.3424 79.228 | 4.177 0.8098 187.39 654946 |577.70 | 2.175 0.3765 | 0.065 0.0113 2.9885 | 1.775 0.3073 81.609 | 1.856 0.3213 85.333 | 3.673 0.6358 168.87 654947 |489.60 | 1.999 0.4083 | 0.051 0.0104 2.5513 | 1.355 0.2768 67.784 | 1.688 0.3448 84.442 | 3.737 0.7633 186.94 654960 |513.20 | 2.030 0.3956 | 0.053 0.0103 2.6108 | 1.458 0.2841 71.823 | 1.889 0.3681 93.054 | 3.658 0.7128 180.20 FBW - Final Body Weight - 659 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Subchronic Toxicity Group : III 1 mg/kg / d a y Sex :MALES ANIMAL | FBW | BRAIN | (Gms) | (Gms) %FBW | ADRENAL GLANDS | EPIDIDYMIDES | | (Gms) % F B W %B R A I N | (Gms) % F B W % B R A I N | (Gms) HEART | KIDNEYS % F B W % B R A I N | (Gms) %FBW %BRAIN 654984 |601.80 | 2.184 0.3629 | 0.066 0.0110 3.0220 | 1.498 0.2489 68.590 | 1.879 0.3122 86.035 | 3.475 0.5774 159.11 654995 |514.10 | 2.295 0.4464 | 0.063 0.0123 2.7451 | 1.669 0.3246 72.723 | 1.800 0.3501 78.431 | 4.065 0.7907 177.12 Mean S.D. |540.79 | 2.167 0.4022 | 0.048 0.0089 2.2304 | 1.549 0.2871 71.552 | 1.832 0.3394 84.719 | 3.804 0.7073 175.80 |37.400 | 0.105 0.0313 | 0.013 0.0024 0.6217 | 0.133 0.0251 5.8859 | 0.095 0.0160 5.8132 | 0.263 0.0764 13.117 Group : V 5 mg/kg/day Sex :MALES ANIMAL | FBW | BRAIN | ADRENAL GLANDS | EPIDIDYMIDES | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS % F B W % B R A I N | (Gms) % F B W % B R A I N 654907 |532.90 | 2.138 0.4012 | 0.055 0.0103 2.5725 | 1.368 0.2567 63.985 | 1.555 0.2918 72.732 | 3.747 0.7031 175.26 654911 |619.90 | 2.419 0.3902 | 0.061 0.0098 2.5217 | 1.706 0.2752 70.525 | 1.981 0.3196 81.893 | 4.815 0.7767 199.05 654916 |526.30 | 2.329 0.4425 | 0.066 0.0125 2.8338 | 1.674 0.3181 71.876 | 1.703 0.3236 73.122 | 4.286 0.8144 184.03 654917 |587.80 | 2.187 0.3721 | 0.071 0.0121 3.2465 | 1.846 0.3141 84.408 | 1.816 0.3089 83.036 | 4.109 0.6990 187.88 654959 |621.10 | 2.271 0.3656 | 0.067 0.0108 2.9502 | 1.747 0.2813 76.926 | 1.763 0.2839 77.631 | 4.601 0.7408 202.60 654961 |643.30 | 2.228 0.3463 | 0.062 0.0096 2.7828 | 1.570 0.2441 70.467 | 1.943 0.3020 87.208 | 4.430 0.6886 198.83 654967 |513.30 | 2.171 0.4229 | 0.059 0.0115 2.7176 | 1.545 0.3010 71.165 | 1.549 0.3018 71.350 | 3.372 0.6569 155.32 654980 |626.50 | 2.248 0.3588 | 0.091 0.0145 4.0480 | 1.530 0.2442 68.061 | 1.981 0.3162 88.123 | 3.928 0.6270 174.73 654998 |587.60 | 2.214 0.3768 | 0.061 0.0104 2.7552 | 1.434 0.2440 64.770 | 2.055 0.3497 92.818 | 4.282 0.7287 193.41 655005 |567.80 | 2.134 0.3758 | 0.055 0.0097 2.5773 | 1.814 0.3195 85.005 | 1.627 0.2865 76.242 | 3.304 0.5819 154.83 Mean S.D. || |582.65 | 2.234 0.3852 | 0.065 0.0111 2.9006 | 1.623 0.2798 72.719 | 1.797 0.3084 80.415 | 4.087 0.7017 182.59 |46.186 | 0.089 0.0296 | 0.011 0.0016 0.4555 | 0.160 0.0317 7.2988 | 0.187 0.0199 7.3639 | 0.501 0.0689 17.359 FBW - Final Body Weight - 660 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Subchronic Toxicity Group : VII 25 mg/kg/day Sex :MALES ANIMAL | FBW | BRAIN | ADRENAL GLANDS | EPIDIDYMIDES | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS % F B W % B R A I N | (Gms) % F B W % B R A I N 654922 |555.60 | 2.183 0.3929 | 0.049 0.0088 2.2446 | 1.487 0.2676 68.117 | 1.764 0.3175 80.806 | 4.301 0.7741 197.02 654923 |539.30 | 2.242 0.4157 | 0.059 0.0109 2.6316 | 1.728 0.3204 77.074 | 1.821 0.3377 81.222 | 4.319 0.8009 192.64 654930 |596.10 | 2.234 0.3748 | 0.035 0.0059 1.5667 | 1.663 0.2790 74.440 | 2.048 0.3436 91.674 | 4.331 0.7266 193.87 654940 |534.80 | 2.330 0.4357 | 0.066 0.0123 2.8326 | 1.760 0.3291 75.536 | 1.709 0.3196 73.348 | 4.014 0.7506 172.27 654952 |598.40 | 2.126 0.3553 | 0.076 0.0127 3.5748 | 1.446 0.2416 68.015 | 1.978 0.3305 93.039 | 4.656 0.7781 219.00 654958 |483.10 | 1.979 0.4096 | 0.055 0.0114 2.7792 | 1.325 0.2743 66.953 | 1.630 0.3374 82.365 | 3.399 0.7036 171.75 654975 |554.90 | 2.120 0.3821 | 0.048 0.0087 2.2642 | 1.336 0.2408 63.019 | 1.877 0.3383 88.538 | 4.435 0.7992 209.20 654989 |580.50 | 2.181 0.3757 | 0.057 0.0098 2.6135 | 1.888 0.3252 86.566 | 1.915 0.3299 87.804 | 4.571 0.7874 209.58 655001 |641.70 | 2.139 0.3333 | 0.057 0.0089 2.6648 | 1.896 0.2955 88.640 | 1.971 0.3072 92.146 | 4.952 0.7717 231.51 655006 |557.00 | 2.214 0.3975 | 0.072 0.0129 3.2520 | 1.830 0.3285 82.656 | 1.947 0.3496 87.940 | 4.528 0.8129 204.52 Mean S.D. |564.14 | 2.175 0.3873 | 0.057 0.0102 2.6424 | 1.636 0.2902 75.102 | 1.866 0.3311 85.888 | 4.351 0.7705 200.14 |43.119 | 0.094 0.0299 | 0.012 0.0022 0.5534 | 0.221 0.0347 8.7412 | 0.133 0.0130 6.2888 | 0.417 0.0345 18.909 Group : IX 125 mg/kg/day Sex :MALES | ANIMAL | FBW | BRAIN | (Gms) |(Gms) %FBW | ADRENAL GLANDS | EPIDIDYMIDES | | (Gms) % F B W %B R A I N | (Gms) % F B W % B R A I N | (Gms) HEART | KIDNEYS % F B W % B R A I N | (Gms) % F B W % B R A I N 654914 |563.50 | 2.298 0.4078 | 0.096 0.0170 4.1775 | 1.610 0.2857 70.061 | 1.869 0.3317 81.332 | 4.636 0.8227 201.74 654921 |553.20 | 2.064 0.3731 | 0.054 0.0098 2.6163 | 1.421 0.2569 68.847 | 1.819 0.3288 88.130 | 4.372 0.7903 211.82 654951 |555.00 | 2.159 0.3890 | 0.056 0.0101 2.5938 | 1.549 0.2791 71.746 | 1.870 0.3369 86.614 | 4.618 0.8321 213.90 654955 |542.50 | 2.226 0.4103 | 0.066 0.0122 2.9650 | 1.543 0.2844 69.317 | 2.121 0.3910 95.283 | 4.895 0.9023 219.90 654965 |483.60 | 2.132 0.4409 | 0.070 0.0145 3.2833 | 1.507 0.3116 70.685 | 1.480 0.3060 69.418 | 4.681 0.9679 219.56 654979 |512.40 | 2.185 0.4264 | 0.052 0.0101 2.3799 | 1.446 0.2822 66.178 | 2.590 0.5055 118.54 | 4.605 0.8987 210.76 654983 |569.90 | 2.139 0.3753 | 0.061 0.0107 2.8518 | 0.807 0.1416 37.728 | 1.841 0.3230 86.068 | 4.557 0.7996 213.04 654986 |575.00 | 2.130 0.3704 | 0.050 0.0087 2.3474 | 1.364 0.2372 64.038 | 2.012 0.3499 94.460 | 4.308 0.7492 202.25 654996 |508.60 | 2.156 0.4239 | 0.067 0.0132 3.1076 | 1.670 0.3284 77.458 | 1.968 0.3869 91.280 | 5.452 1.0720 252.88 FBW - Final Body Weight - 661 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Subchronic Toxicity Group : IX 125 mg/kg/day Sex :MALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | EPIDIDYMIDES | I I (Gms) |(Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) HEART | KIDNEYS % F B W % B R A I N | (Gms) % F B W % B R A I N | 655003 |506.10 | 2.257 0.4460 | 0.049 0.0097 2.1710 | 1.643 0.3246 72.796 | 1.586 0.3134 70.270 | 4.240 0.8378 187.86 | | Mean I S.D. || | | | | |536.98 | 2.175 0.4063 | 0.062 0.0116 2.8494 | 1.456 0.2732 66.885 | 1.916 0.3573 88.139 | 4.636 0.8673 213.37 I31.7 3 4 | 0.06 9 0.02 8 2 | 0. 014 0.0 026 0.58 5 4 | 0.248 0.05 4 2 1 0 . 8 7 0 | 0.303 0.0 593 1 3 . 9 3 4 | 0.346 0.09 5 9 1 6 . 8 6 8 FBW - Final Body Weight - 662 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Subchronic Toxicity Group : I 0 mg/kg/day Sex :MALES ANIMAL | (Gms) LIVER SPLEEN TESTES THYMUS THYROID GLAND % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) % F B W %B R A I N | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N 654903 | 16.824 2.9082 769.27 | 1.074 0.1857 49.108 | 3.893 0.6729 178.01 | 0.359 0.0621 16.415 | 0.024 0.0041 1.0974 654925 | 13.693 2.3781 625.25 | 0.885 0.1537 40.411 | 3.365 0.5844 153.65 | 0.496 0.0861 22.648 | 0.017 0.0030 0.7763 654928 | 15.743 2.7800 741.54 | 0.960 0.1695 45.219 | 3.759 0.6638 177.06 | 0.274 0.0484 12.906 | 0.021 0.0037 0.9892 654929 | 13.187 2.6056 603.80 | 0.853 0.1685 39.057 | 3.669 0.7250 167.99 | 0.387 0.0765 17.720 | 0.024 0.0047 1.0989 654936 | 15.095 2.5861 706.36 | 0.811 0.1389 37.950 | 3.715 0.6365 173.84 | 0.541 0.0927 25.316 | 0.024 0.0041 1.1231 654950 | 15.783 3.0311 737.87 | 0.942 0.1809 44.039 | 3.490 0.6703 163.16 | 0.498 0.0956 23.282 | 0.028 0.0054 1.3090 654953 | 17.121 2.6491 787.17 | 0.952 0.1473 43.770 | 3.691 0.5711 169.70 | 0.621 0.0961 28.552 | 0.027 0.0042 1.2414 654972 | 14.283 2.8635 610.12 | 0.822 0.1648 35.113 | 3.512 0.7041 150.02 | 0.387 0.0776 16.531 | 0.024 0.0048 1.0252 654987 | 15.690 2.7701 677.46 | 1.156 0.2041 49.914 | 3.681 0.6499 158.94 | 0.655 0.1156 28.282 | 0.030 0.0053 1.2953 654993 | 11.344 2.3303 549.08 | 0.677 0.1391 32.769 | 3.101 0.6370 150.10 | 0.278 0.0571 13.456 | 0.020 0.0041 0.9681 Mean S.D. | | 14.876 2.6902 680.79 | 0.913 0.1653 41.735 | 3.588 0.6515 164.25 | 0.450 0.0808 20.511 | 0.024 0.0043 1.0924 | 1.770 0.2248 80.356 | 0.137 0.0212 5.6798 | 0.228 0.0478 10.716 | 0.134 0.0206 5.8536 | 0.004 0.0007 0.1639 Group : III 1 mg/kg / d a y Sex :MALES ANIMAL | | (Gms) LIVER %FBW %BRAIN | | (Gms) SPLEEN %FBW %BRAIN | | (Gms) TESTES %FBW %BRAIN | | (Gms) THYMUS %FBW %BRAIN | THYROID GLAND | (Gms) %FBW %BRAIN 654908 | 13.521 2.6198 584.57 | 0.793 0.1537 34.284 | 2.930 0.5677 126.68 | 0.309 0.0599 13.359 | 0.025 0.0048 1.0808 654913 | 13.493 2.5263 627.87 | 0.845 0.1582 39.321 | 3.529 0.6607 164.22 | 0.312 0.0584 14.518 | 0.020 0.0037 0.9307 654932 | 15.900 2.8087 763.69 | 0.761 0.1344 36.551 | 3.830 0.6766 183.96 | 0.364 0.0643 17.483 | 0.029 0.0051 1.3929 654938 | 16.451 2.8393 743.38 | 1.094 0.1888 49.435 | 3.529 0.6091 159.47 | 0.518 0.0894 23.407 | 0.024 0.0041 1.0845 654941 | 13.863 2.6877 621.94 | 0.989 0.1917 44.370 | 3.384 0.6561 151.82 | 0.354 0.0686 15.882 | 0.022 0.0043 0.9870 654946 | 14.040 2.4303 645.52 | 0.844 0.1461 38.805 | 3.450 0.5972 158.62 | 0.423 0.0732 19.448 | 0.027 0.0047 1.2414 654947 | 13.017 2.6587 651.18 | 0.637 0.1301 31.866 | 3.359 0.6861 168.03 | 0.266 0.0543 13.307 | 0.019 0.0039 0.9505 654960 | 13.151 2.5625 647.83 | 0.857 0.1670 42.217 | 3.652 0.7116 179.90 | 0.385 0.0750 18.966 | 0.020 0.0039 0.9852 FBW - Final Body Weight - 663 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Subchronic Toxicity Group : III 1 mg/kg / d a y Sex :MALES ANIMAL | | (Gms) LIVER %FBW %BRAIN | | (Gms) SPLEEN %FBW %BRAIN | | (Gms) TESTES %FBW %BRAIN | | (Gms) THYMUS %FBW %BRAIN | THYROID GLAND | (Gms) %FBW %BRAIN 654984 | 14.923 2.4797 683.29 | 0.764 0.1270 34.982 | 3.533 0.5871 161.77 | 0.424 0.0705 19.414 | 0.018 0.0030 0.8242 654995 | 12.728 2.4758 554.60 | 0.834 0.1622 36.340 | 3.799 0.7390 165.53 | 0.394 0.0766 17.168 | 0.027 0.0053 1.1765 Mean S.D. | 14.109 2.6089 652.39 | 0.842 0.1559 38.817 | 3.500 0.6491 162.00 | 0.375 0.0690 17.295 | 0.023 0.0043 1.0654 | 1.254 0.1403 64.449 | 0.126 0.0226 5.2729 | 0.255 0.0568 15.726 | 0.072 0.0103 3.1698 | 0.004 0.0007 0.1678 Group : V 5 mg/kg/day Sex :MALES ANIMAL | (Gms) LIVER SPLEEN TESTES THYMUS THYROID GLAND % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N 654907 | 13.279 2.4918 621.09 | 0.621 0.1165 29.046 | 3.202 0.6009 149.77 | 0.529 0.0993 24.743 | 0.027 0.0051 1.2629 654911 | 15.581 2.5135 644.11 | 0.893 0.1441 36.916 | 3.803 0.6135 157.21 | 0.457 0.0737 18.892 | 0.028 0.0045 1.1575 654916 | 14.164 2.6912 608.16 | 0.786 0.1493 33.748 | 3.555 0.6755 152.64 | 0.420 0.0798 18.033 | 0.031 0.0059 1.3310 654917 | 16.489 2.8052 753.96 | 1.014 0.1725 46.365 | 3.729 0.6344 170.51 | 0.646 0.1099 29.538 | 0.026 0.0044 1.1888 654959 | 17.731 2.8548 780.76 | 1.120 0.1803 49.317 | 3.871 0.6232 170.45 | 0.602 0.0969 26.508 | 0.028 0.0045 1.2329 654961 | 17.017 2.6453 763.78 | 0.941 0.1463 42.235 | 3.879 0.6030 174.10 | 0.519 0.0807 23.294 | 0.025 0.0039 1.1221 654967 | 12.452 2.4259 573.56 | 0.753 0.1467 34.684 | 3.281 0.6392 151.13 | 0.355 0.0692 16.352 | 0.023 0.0045 1.0594 654980 | 16.952 2.7058 754.09 | 1.112 0.1775 49.466 | 4.728 0.7547 210.32 | 0.601 0.0959 26.735 | 0.022 0.0035 0.9786 654998 | 16.528 2.8128 746.52 | 0.796 0.1355 35.953 | 3.268 0.5562 147.61 | 0.313 0.0533 14.137 | 0.025 0.0043 1.1292 655005 | 15.559 2.7402 729.10 | 0.702 0.1236 32.896 | 3.682 0.6485 172.54 | 0.357 0.0629 16.729 | 0.025 0.0044 1.1715 Mean S.D. | | 15.575 2.6687 697.51 | 0.874 0.1492 39.063 | 3.700 0.6349 165.63 | 0.480 0.0822 21.496 | 0.026 0.0045 1.1634 | 1.744 0.1475 76.846 | 0.171 0.0218 7.2788 | 0.442 0.0529 18.827 | 0.117 0.0180 5.3033 | 0.003 0.0006 0.1008 FBW - Final Body Weight - 664 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Subchronic Toxicity Group : VII 25 mg/kg/day Sex :MALES ANIMAL | (Gms) LIVER SPLEEN TESTES THYMUS THYROID GLAND % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N 654922 | 16.414 2.9543 751.90 | 0.760 0.1368 34.814 | 3.552 0.6393 162.71 | 0.269 0.0484 12.322 | 0.023 0.0041 1.0536 654923 | 16.965 3.1457 756.69 | 0.822 0.1524 36.664 | 3.816 0.7076 170.21 | 0.370 0.0686 16.503 | 0.027 0.0050 1.2043 654930 | 18.546 3.1112 830.17 | 1.134 0.1902 50.761 | 4.003 0.6715 179.19 | 0.523 0.0877 23.411 | 0.031 0.0052 1.3876 654940 | 15.957 2.9837 684.85 | 0.970 0.1814 41.631 | 3.522 0.6586 151.16 | 0.366 0.0684 15.708 | 0.026 0.0049 1.1159 654952 | 17.594 2.9402 827.56 | 0.888 0.1484 41.769 | 3.328 0.5561 156.54 | 0.339 0.0567 15.945 | 0.031 0.0052 1.4581 654958 | 14.340 2.9683 724.61 | 0.895 0.1853 45.225 | 3.312 0.6856 167.36 | 0.437 0.0905 22.082 | 0.027 0.0056 1.3643 654975 | 17.187 3.0973 810.71 | 0.968 0.1744 45.660 | 3.706 0.6679 174.81 | 0.486 0.0876 22.925 | 0.022 0.0040 1.0377 654989 | 16.625 2.8639 762.27 | 0.980 0.1688 44.934 | 3.395 0.5848 155.66 | 0.673 0.1159 30.857 | 0.023 0.0040 1.0546 655001 | 20.773 3.2372 971.15 | 0.877 0.1367 41.000 | 4.203 0.6550 196.49 | 0.647 0.1008 30.248 | 0.022 0.0034 1.0285 655006 | 17.787 3.1934 803.39 | 0.898 0.1612 40.560 | 4.131 0.7417 186.59 | 0.462 0.0829 20.867 | 0.026 0.0047 1.1743 Mean S.D. | 17.219 3.0495 792.33 | 0.919 0.1636 42.302 | 3.697 0.6568 170.07 | 0.457 0.0808 21.087 | 0.026 0.0046 1.1879 | 1.693 0.1237 78.215 | 0.102 0.0196 4.6142 | 0.330 0.0543 14.477 | 0.131 0.0204 6.1679 | 0.003 0.0007 0.1611 Group : IX 125 mg/kg/day Sex :MALES ANIMAL | | (Gms) LIVER %FBW %BRAIN | (Gms) SPLEEN %FBW %BRAIN | (Gms) TESTES %FBW %BRAIN | (Gms) THYMUS %FBW %BRAIN THYROID GLAND | (Gms) %FBW %BRAIN 654914 | 22.509 3.9945 979.50 | 0.921 0.1634 40.078 | 3.548 0.6296 154.40 | 0.618 0.1097 26.893 | 0.026 0.0046 1.1314 654921 | 21.736 3.9291 1053.1 | 0.949 0.1715 45.979 | 3.541 0.6401 171.56 | 0.289 0.0522 14.002 | 0.023 0.0042 1.1143 654951 | 22.546 4.0623 1044.3 | 0.862 0.1553 39.926 | 4.169 0.7512 193.10 | 0.443 0.0798 20.519 | 0.023 0.0041 1.0653 654955 | 23.398 4.3130 1051.1 | 1.449 0.2671 65.094 | 3.883 0.7158 174.44 | 0.725 0.1336 32.570 | 0.027 0.0050 1.2129 654965 | 19.727 4.0792 925.28 | 0.959 0.1983 44.981 | 3.651 0.7550 171.25 | 0.378 0.0782 17.730 | 0.019 0.0039 0.8912 654979 | 21.382 4.1729 978.58 | 1.000 0.1952 45.767 | 3.302 0.6444 151.12 | 0.265 0.0517 12.128 | 0.023 0.0045 1.0526 654983 | 20.456 3.5894 956.33 | 0.732 0.1284 34.222 | 2.192 0.3846 102.48 | 0.474 0.0832 22.160 | 0.020 0.0035 0.9350 654986 | 22.395 3.8948 1051.4 | 0.928 0.1614 43.568 | 3.976 0.6915 186.67 | 0.431 0.0750 20.235 | 0.022 0.0038 1.0329 654996 | 26.082 5.1282 1209.7 | 0.943 0.1854 43.738 | 3.890 0.7648 180.43 | 0.451 0.0887 20.918 | 0.028 0.0055 1.2987 FBW - Final Body Weight - 665 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Subchronic Toxicity G r o u p : IX 125 m g / k g / d a y S e x :M A L E S | ANIMAL | I |(Gms) LIVER I SPLEEN I TESTES I THYMUS I THYROID GLAND % F B W %rBRAIN I(Gms) % F B W % B R A I N I(Gms) % F B W % B R A I N I(Gms) % F B W % B R A I N I(Gms) % F B W % B R A I N | 655003 I 19.526 3.8581 865.13 I 0.891 0.1761 39.477 I 3.371 0.6661 149.36 I 0.477 0.0943 21.134 I 0.022 0.0043 0.9747 | | Mean |IIII I 21.976 4.1022 1011.4 I 0.963 0.1802 44.283 I 3.552 0.6643 163.48 I 0.455 0.0846 20.829 I 0.023 0.0043 1.0709 I S.D. I 1.928 0.4098 93.853 I 0.186 0.0367 8.1682 I 0.552 0.1104 26.042 I 0.138 0.0246 5.8581 I 0.003 0.0006 0.1245 FBW - Final Body Weight - 666 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Recovery Group : I 0 mg/kg/day Sex :MALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | EPIDIDYMIDES | | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS | % F B W % B R A I N | (Gms) %FBW %BRAIN | | 654909 |578.30 | 2.124 0.3673 | 0.041 0.0071 1.9303 | 1.533 0.2651 72.175 | 1.733 0.2997 81.591 | 3.825 0.6614 180.08 | | 654910 |691.50 | 2.184 0.3158 | 0.055 0.0080 2.5183 | 1.706 0.2467 78.114 | 1.907 0.2758 87.317 | 4.529 0.6550 207.37 | | 654915 |725.90 | 2.295 0.3162 | 0.062 0.0085 2.7015 | 1.611 0.2219 70.196 | 1.857 0.2558 80.915 | 4.260 0.5869 185.62 | | 654924 |631.40 | 2.074 0.3285 | 0.041 0.0065 1.9769 | 1.479 0.2342 71.311 | 1.728 0.2737 83.317 | 4.031 0.6384 194.36 | | 654927 |674.60 | 2.356 0.3492 | 0.060 0.0089 2.5467 | 1.496 0.2218 63.497 | 2.037 0.3020 86.460 | 4.138 0.6134 175.64 | | 654943 |605.80 | 2.106 0.3476 | 0.060 0.0099 2.8490 | 1.398 0.2308 66.382 | 1.615 0.2666 76.686 | 3.879 0.6403 184.19 | | 654956 |551.90 | 2.124 0.3849 | 0.068 0.0123 3.2015 | 1.717 0.3111 80.838 | 1.854 0.3359 87.288 | 3.232 0.5856 152.17 | | 654992 |656.30 | 2.123 0.3235 | 0.050 0.0076 2.3552 | 1.329 0.2025 62.600 | 1.931 0.2942 90.956 | 4.033 0.6145 189.97 | | 654994 |521.10 | 2.065 0.3963 | 0.060 0.0115 2.9056 | 1.344 0.2579 65.085 | 1.530 0.2936 74.092 | 3.269 0.6273 158.31 | | Mean | S.D. |626.31 | 2.161 0.3477 | 0.055 0.0089 2.5539 | 1.513 0.2436 70.022 | 1.799 0.2886 83.180 | 3.911 0.6248 180.86 | |67.783 | 0.100 0.0298 | 0.009 0.0020 0.4205 | 0.144 0.0319 6.3647 | 0.161 0.0238 5.4505 | 0.428 0.0271 17.182 | Group : IX 125 mg/kg/day Sex :MALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | EPIDIDYMIDES | | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS | % F B W % B R A I N | (Gms) %FBW %BRAIN | | 654942 |620.80 | 2.113 0.3404 | 0.041 0.0066 1.9404 | 1.548 0.2494 73.261 | 1.788 0.2880 84.619 | 4.126 0.6646 195.27 | | 654957 |616.90 | 2.080 0.3372 | 0.039 0.0063 1.8750 | 1.451 0.2352 69.760 | 1.864 0.3022 89.615 | 4.567 0.7403 219.57 | | 654973 |642.70 | 2.202 0.3426 | 0.064 0.0100 2.9064 | 1.582 0.2461 71.844 | 1.847 0.2874 83.878 | 4.389 0.6829 199.32 | | 654974 |673.00 | 2.081 0.3092 | 0.062 0.0092 2.9793 | 1.503 0.2233 72.225 | 2.076 0.3085 99.760 | 4.187 0.6221 201.20 | | 654976 |597.10 | 2.192 0.3671 | 0.051 0.0085 2.3266 | 1.481 0.2480 67.564 | 1.742 0.2917 79.471 | 3.784 0.6337 172.63 | | 654977 |492.60 | 2.180 0.4425 | 0.042 0.0085 1.9266 | 1.530 0.3106 70.183 | 1.453 0.2950 66.651 | 3.039 0.6169 139.40 | | 654978 |552.60 | 2.091 0.3784 | 0.033 0.0060 1.5782 | 1.218 0.2204 58.250 | 1.617 0.2926 77.331 | 3.551 0.6426 169.82 | | 654985 |475.30 | 1.995 0.4197 | 0.048 0.0101 2.4060 | 1.603 0.3373 80.351 | 1.553 0.3267 77.845 | 3.212 0.6758 161.00 | | 654990 |667.90 | 2.044 0.3060 | 0.050 0.0075 2.4462 | 1.516 0.2270 74.168 | 2.136 0.3198 104.50 | 4.213 0.6308 206.12 | FBW - Final Body Weight - 667 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Recovery Group : IX 125 mg/kg/day Sex :MALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | EPIDIDYMIDES | I I (Gms) |(Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) HEART I KIDNEYS I % F B W % B R A I N I (Gms) % F B W % B R A I N I I 654991 I759.70 1 2.131 0.2805 I 0.057 0.0075 2.6748 I 1.366 0.1798 64.101 I 2.337 0.3076 109.67 I 4.333 0.5704 203.33 I I I Mean I S.D. I1 I I I I I I609.86 1 2.111 0.3524 I 0.049 0.0080 2.3060 I 1.480 0.2477 70.171 I 1.841 0.3020 87.334 I 3.940 0.6480 186.77 I I85.864 0.067 0.0508 I 0.010 0.0015 0.4682 I 0.114 0.0454 5.9824 I 0.276 0.0136 13.549 I 0.520 0.0459 24.848 I FBW - Final Body Weight - 668 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Recovery Group : I 0 mg/kg/day Sex :MALES ANIMAL | (Gms) LIVER %FBW %BRAIN | (Gms) SPLEEN %FBW %BRAIN | (Gms) TESTES %FBW %BRAIN | (Gms) THYMUS %FBW %BRAIN THYROID GLAND | (Gms) %FBW %BRAIN 654909 | 13.874 2.3991 653.20 | 0.788 0.1363 37.100 | 3.814 0.6595 179.57 | 0.159 0.0275 7.4859 | 0.021 0.0036 0.9887 654910 | 19.106 2.7630 874.82 | 1.040 0.1504 47.619 | 4.242 0.6134 194.23 | 0.374 0.0541 17.125 | 0.026 0.0038 1.1905 654915 | 19.298 2.6585 840.87 | 1.028 0.1416 44.793 | 3.522 0.4852 153.46 | 0.139 0.0191 6.0566 | 0.031 0.0043 1.3508 654924 | 16.367 2.5922 789.15 | 0.748 0.1185 36.066 | 3.659 0.5795 176.42 | 0.296 0.0469 14.272 | 0.037 0.0059 1.7840 654927 | 17.544 2.6007 744.65 | 0.916 0.1358 38.879 | 3.520 0.5218 149.41 | 0.149 0.0221 6.3243 | 0.031 0.0046 1.3158 654943 | 15.294 2.5246 726.21 | 0.723 0.1193 34.330 | 3.819 0.6304 181.34 | 0.170 0.0281 8.0722 | 0.031 0.0051 1.4720 654956 | 13.066 2.3675 615.16 | 0.866 0.1569 40.772 | 3.512 0.6363 165.35 | 0.155 0.0281 7.2976 | 0.030 0.0054 1.4124 654992 | 14.895 2.2695 701.60 | 0.783 0.1193 36.882 | 3.423 0.5216 161.23 | 0.234 0.0357 11.022 | 0.039 0.0059 1.8370 654994 | 12.566 2.4114 608.52 | 0.872 0.1673 42.228 | 3.382 0.6490 163.78 | 0.322 0.0618 15.593 | 0.031 0.0059 1.5012 Mean S.D. | 15.779 2.5096 728.24 | 0.863 0.1384 39.852 | 3.655 0.5885 169.42 | 0.222 0.0359 10.361 | 0.031 0.0050 1.4280 | 2.481 0.1587 94.614 | 0.115 0.0176 4.3789 | 0.270 0.0643 14.492 | 0.088 0.0149 4.2803 | 0.005 0.0009 0.2668 Group : IX 125 mg/kg/day Sex :MALES ANIMAL | | (Gms) LIVER %FBW %BRAIN | (Gms) SPLEEN %FBW %BRAIN | (Gms) TESTES %FBW %BRAIN | (Gms) THYMUS %FBW %BRAIN THYROID GLAND | (Gms) %FBW %BRAIN 654942 | 16.631 2.6790 787.08 | 0.872 0.1405 41.268 | 3.560 0.5735 168.48 | 0.414 0.0667 19.593 | 0.029 0.0047 1.3725 654957 | 14.671 2.3782 705.34 | 0.916 0.1485 44.038 | 3.385 0.5487 162.74 | 0.317 0.0514 15.240 | 0.033 0.0053 1.5865 654973 | 14.447 2.2479 656.09 | 0.904 0.1407 41.054 | 3.715 0.5780 168.71 | 0.388 0.0604 17.620 | 0.025 0.0039 1.1353 654974 | 17.388 2.5837 835.56 | 0.940 0.1397 45.171 | 3.480 0.5171 167.23 | 0.414 0.0615 19.894 | 0.034 0.0051 1.6338 654976 | 13.934 2.3336 635.68 | 0.773 0.1295 35.265 | 3.458 0.5791 157.76 | 0.288 0.0482 13.139 | 0.026 0.0044 1.1861 654977 | 10.701 2.1724 490.87 | 0.635 0.1289 29.128 | 3.436 0.6975 157.61 | 0.251 0.0510 11.514 | 0.025 0.0051 1.1468 654978 | 13.068 2.3648 624.96 | 0.694 0.1256 33.190 | 3.542 0.6410 169.39 | 0.345 0.0624 16.499 | 0.040 0.0072 1.9130 654985 | 12.493 2.6284 626.22 | 0.823 0.1732 41.253 | 3.260 0.6859 163.41 | 0.291 0.0612 14.586 | 0.023 0.0048 1.1529 654990 | 17.770 2.6606 869.37 | 0.924 0.1383 45.205 | 3.364 0.5037 164.58 | 0.314 0.0470 15.362 | 0.026 0.0039 1.2720 FBW - Final Body Weight - 669 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Male Rats Designated for Recovery Group : IX 125 mg/kg/day Sex :MALES | ANIMAL | | |(Gms) LIVER | SPLEEN | TESTES | THYMUS | THYROID GLAND | %FBW %BRAIN |(Gms) %FBW %BRAIN |(Gms) %FBW %BRAIN |(Gms) %FBW %BRAIN |(Gms) %FBW %BRAIN | | 654991 | 19.568 2.5758 918.25 | 0.916 0.1206 42.985 | 3.398 0.4473 159.46 | 0.362 0.0477 16.987 | 0.028 0.0037 1.3139 | | | Mean | S.D. |||||| | 15.067 2.4624 714.94 | 0.840 0.1385 39.856 | 3.460 0.5772 163.94 | 0.338 0.0557 16.044 | 0.029 0.0048 1.3713 | | 2.727 0.1840 133.73 | 0.106 0.0148 5.4785 | 0.125 0.0796 4.5266 | 0.056 0.0074 2.6500 | 0.005 0.0010 0.2603 | FBW - Final Body Weight - 670 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Male Rats Designated for Satellite Evaluation (10-Day Sacrifice) Group : I 0 mg/kg/day Sex :MALES ANIMAL | FBW | (Gms) (Gms) LIVER %FBW 655115 655119 655124 655135 655137 |254.1 |241.7 |266.0 |222.4 |257.7 | 11 .566 9 .945 | 11 .053 9 .158 | 10 .375 4.552 4.115 4.155 4.118 4.026 Mean S.D. |248.38 | 10 .419 4.193 | 16.953 0 .940 0.206 roup : III 1 mg/kg / d a y Sex :MALES ANIMAL | FBW | (Gms) (Gms) LIVER %FBW 655114 655118 655120 655132 655139 |247.2 |247.9 |226.2 |242.8 |259.2 | 9. 848 10. 209 | 9. 572 | 9. 991 11. 460 3.984 4.118 4.232 4.115 4.421 Mean S.D. |244.66 10. 216 | 11.9 6 4 | 0. 733 4.174 0.164 FBW - Final Body Weight - 671 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Male Rats Designated for Satellite Evaluation (10-Day Sacrifice) Group : V 5 mg/kg/day Sex :MALES ANIMAL | FBW | (Gms) |(Gms) LIVER %FBW 655121 655126 655127 655131 655138 |271.9 |209.0 |249.7 |253.9 |243.8 |12.100 | 8.676 | 9.924 |n.717 | 9.680 4.450 4.151 3.974 4.615 3.970 Mean S.D. |245.66 |10.419 4.232 | 23.023 | 1.444 0.290 | | | | | | | Group : VII 25 mg/kg/day Sex :MALES ANIMAL | FBW | (Gms) |(Gms) LIVER %FBW 655112 655116 655125 655129 655133 |212.9 |254.1 |238.0 |251.9 |249.9 | 9.320 |10.352 |10.490 |n.846 |n.508 4.378 4.074 4.408 4.703 4.605 Mean S.D. |241.36 |10.703 4.433 | 17.085 | 1.004 0.242 | | | | | | | | | FBW - Final Body Weight - 672 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Male Rats Designated for Satellite Evaluation (10-Day Sacrifice) Group : IX 125 mg/kg/day Sex :MALES ANIMAL | FBW | (Gms) (Gms) LIVER %FBW 655113 655122 655123 655128 655130 |238.1 |276.2 |245.5 |237.4 |267.5 12.784 16.404 12.838 13.321 15.563 5.369 5.939 5.229 5.611 5.818 Mean S.D. |252.94 | 17.81 14.182 5.593 1.684 0.297 DuPont-9478 FBW - Final Body Weight - 673 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Male Rats Designated for Satellite Evaluation (Final Sacrifice) Group : I 0 mg/kg/day Sex :MALES | ANIMAL | FBW | | (Gms) |(Gms) LIVER %FBW 654919 654939 654966 654971 654997 551.10 743.60 489.70 575.70 655.10 19.363 24.134 12.940 18.670 23.031 3.5135 3.2456 2.6424 3.2430 3.5156 Mean S.D. 603.04 98.436 19.628 3.2320 4.405 0.3562 Group : III 1 mg/kg / d a y Sex :MALES ANIMAL | FBW | (Gms) (Gms) LIVER %FBW 654904 654945 654948 654954 654988 |616.70 |572.60 |738.30 |690.90 |613.20 18.945 17.032 24.199 24.931 17.496 3.0720 2.9745 3.2777 3.6085 2.8532 Mean S.D. |646.34 |66.814 20.521 3.1572 3.768 0.2963 FBW - Final Body Weight - 674 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Male Rats Designated for Satellite Evaluation (Final Sacrifice) Group : V 5 mg/kg/day Sex :MALES ANIMAL | FBW | (Gms) (Gms) LIVER %FBW 654918 654926 654969 654970 654981 |726.80 |722.10 |582.00 |542.40 |589.10 23.418 24.295 19.389 15.430 17.283 3.2221 3.3645 3.3314 2.8448 2.9338 Mean S.D. |632.48 |85.838 19.963 3.1393 3.833 0.2364 Group : VII 25 mg/kg/day Sex :MALES ANIMAL | FBW | (Gms) (Gms) LIVER %FBW 654912 654920 654933 654934 654964 |622.50 |688.00 |816.80 |618.70 |723.20 19.039 21.986 28.040 18.824 25.118 3.0585 3.1956 3.4329 3.0425 3.4732 Mean S.D. |693.84 |81.778 22.601 3.2405 3.976 0.2034 FBW - Final Body Weight - 675 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Male Rats Designated for Satellite Evaluation (Final Sacrifice) Group : IX 125 mg/kg/day Sex :MALES ANIMAL FBW (Gms) (Gms) LIVER %FBW 654906 654931 654937 654962 654982 801.50 692.30 704.70 623.30 667.90 28.596 21.588 20.829 18.843 22.940 3.5678 3.1183 2.9557 3.0231 3.4346 Mean S.D. 697.94 65.719 22.559 3.2199 3.686 0.2674 DuPont-9478 FBW - Final Body Weight - 676 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Subchronic Toxicity G r o u p : II 0 m g / k g / d a y Sex :FEMALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) LIVER | %FBW %BRAIN | | 655016 |286.50 | 1.957 0.6831 | 0.074 0.0258 3.7813 | 1.971 0.6880 100.72 | 2.378 0.8300 121.51 | 8.877 3.0984 453.60 | | 655025 |301.70 | 2.094 0.6941 | 0.072 0.0239 3.4384 | 1.286 0.4263 61.414 | 2.252 0.7464 107.55 | 8.737 2.8959 417.24 | | 655031 |292.60 | 1.964 0.6712 | 0.060 0.0205 3.0550 | 1.141 0.3900 58.096 | 2.174 0.7430 110.69 | 7.403 2.5301 376.93 | | 655032 |302.90 | 2.002 0.6609 | 0.098 0.0324 4.8951 | 1.277 0.4216 63.786 | 2.246 0.7415 112.19 | 8.256 2.7257 412.39 | | 655036 |322.50 | 2.043 0.6335 | 0.086 0.0267 4.2095 | 1.243 0.3854 60.842 | 2.521 0.7817 123.40 | 8.859 2.7470 433.63 | | 655079 |266.80 | 1.982 0.7429 | 0.080 0.0300 4.0363 | 1.046 0.3921 52.775 | 2.201 0.8250 111.05 | 7.413 2.7785 374.02 | | 655083 |310.80 | 1.948 0.6268 | 0.081 0.0261 4.1581 | 1.230 0.3958 63.142 | 2.459 0.7912 126.23 | 8.359 2.6895 429.11 | | 655098 |261.10 | 1.879 0.7196 | 0.059 0.0226 3.1400 | 1.042 0.3991 55.455 | 2.220 0.8502 118.15 | 7.334 2.8089 390.31 | | 655099 |284.90 | 1.925 0.6757 | 0.074 0.0260 3.8442 | 1.135 0.3984 58.961 | 2.068 0.7259 107.43 | 7.526 2.6416 390.96 | | 655107 |238.50 | 1.873 0.7853 | 0.076 0.0319 4.0577 | 0.859 0.3602 45.862 | 1.869 0.7836 99.786 | 6.280 2.6331 335.29 | | | Mean | S.D. || | |286.83 | 1.967 0.6893 | 0.076 0.0266 3.8616 | 1.223 0.4257 62.105 | 2.239 0.7819 113.80 | 7.904 2.7549 401.35 | |25.304 | 0.068 0.0488 | 0.012 0.0039 0.5481 | 0.294 0.0940 14.598 | 0.188 0.0428 8.3064 | 0.849 0.1580 34.727 | Group : IV 1 mg/kg/day Sex :FEMALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS | % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) LIVER | %FBW %BRAIN | | 655013 |299.40 | 2.040 0.6814 | 0.079 0.0264 3.8725 | 1.073 0.3584 52.598 | 2.252 0.7522 110.39 | 8.222 2.7462 403.04 | | 655033 |303.60 | 2.052 0.6759 | 0.094 0.0310 4.5809 | 1.136 0.3742 55.361 | 2.012 0.6627 98.051 | 8.763 2.8864 427.05 | | 655040 |293.10 | 1.842 0.6285 | 0.040 0.0136 2.1716 | 1.207 0.4118 65.527 | 2.253 0.7687 122.31 | 8.498 2.8994 461.35 | | 655041 |276.10 | 2.028 0.7345 | 0.067 0.0243 3.3037 | 1.092 0.3955 53.846 | 2.557 0.9261 126.08 | 8.085 2.9283 398.67 | | 655044 |317.20 | 2.059 0.6491 | 0.032 0.0101 1.5542 | 1.073 0.3383 52.113 | 1.928 0.6078 93.638 | 7.659 2.4146 371.98 | | 655086 |243.30 | 1.977 0.8126 | 0.071 0.0292 3.5913 | 1.023 0.4205 51.745 | 1.766 0.7259 89.327 | 6.383 2.6235 322.86 | | 655089 |317.90 | 1.872 0.5889 | 0.074 0.0233 3.9530 | 1.053 0.3312 56.250 | 2.346 0.7380 125.32 | 10.197 3.2076 544.71 | | 655090 |323.50 | 2.027 0.6266 | 0.055 0.0170 2.7134 | 1.137 0.3515 56.093 | 2.088 0.6454 103.01 | 8.578 2.6516 423.19 | FBW - Final Body Weight - 677 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Subchronic Toxicity Group : IV 1 mg/kg/day Sex :FEMALES ANIMAL | FBW | BRAIN | (Gms) | (Gms) %FBW | ADRENAL GLANDS | | (Gms) % F B W % B R A I N | (Gms) HEART | KIDNEYS | % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) LIVER %FBW %BRAIN 655091 |302.60 | 1.933 0.6388 | 0.066 0.0218 3.4144 | 1.228 0.4058 63.528 | 2.318 0.7660 119.92 | 8.370 2.7660 433.01 655108 |269.30 | 1.946 0.7226 | 0.053 0.0197 2.7235 | 1.062 0.3944 54.573 | 1.951 0.7245 100.26 | 7.484 2.7791 384.58 Mean S.D. |294.60 | 1.978 0.6759 | 0.063 0.0216 3.1878 | 1.108 0.3781 56.163 | 2.147 0.7317 108.83 | 8.224 2.7903 417.04 |25.107 | 0.077 0.0656 | 0.019 0.0067 0.9046 | 0.067 0.0319 4.7035 | 0.239 0.0872 13.790 | 0.982 0.2122 58.824 Group : VI 5 mg/kg/day Sex :FEMALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) LIVER | %FBW %BRAIN | | 655020 |301.60 | 1.931 0.6403 | 0.063 0.0209 3.2626 | 0.987 0.3273 51.113 | 2.149 0.7125 111.29 | 8.880 2.9443 459.87 | | 655029 |279.90 | 1.831 0.6542 | 0.068 0.0243 3.7138 | 1.078 0.3851 58.875 | 2.021 0.7220 110.38 | 7.202 2.5731 393.34 | | 655034 |259.10 | 1.758 0.6785 | 0.056 0.0216 3.1854 | 0.941 0.3632 53.527 | 1.845 0.7121 104.95 | 6.924 2.6723 393.86 | | 655038 |292.70 | 2.025 0.6918 | 0.082 0.0280 4.0494 | 1.111 0.3796 54.864 | 2.116 0.7229 104.49 | 8.505 2.9057 420.00 | | 655039 |301.30 | 1.989 0.6601 | 0.060 0.0199 3.0166 | 1.101 0.3654 55.354 | 2.170 0.7202 109.10 | 7.750 2.5722 389.64 | | 655042 |339.80 | 1.950 0.5739 | 0.087 0.0256 4.4615 | 1.206 0.3549 61.846 | 2.339 0.6883 119.95 | 9.454 2.7822 484.82 | | 655054 |252.30 | 1.948 0.7721 | 0.064 0.0254 3.2854 | 1.094 0.4336 56.160 | 2.090 0.8284 107.29 | 7.625 3.0222 391.43 | | 655066 |308.10 | 1.959 0.6358 | 0.070 0.0227 3.5733 | 1.312 0.4258 66.973 | 2.186 0.7095 111.59 | 8.270 2.6842 422.15 | | 655067 |291.40 | 1.890 0.6486 | 0.075 0.0257 3.9683 | 1.177 0.4039 62.275 | 2.139 0.7340 113.17 | 7.990 2.7419 422.75 | | 655087 |314.70 | 2.030 0.6451 | 0.077 0.0245 3.7931 | 1.292 0.4105 63.645 | 2.491 0.7915 122.71 | 9.248 2.9387 455.57 | | | Mean | S.D. || | |294.09 | 1.931 0.6600 | 0.070 0.0239 3.6309 | 1.130 0.3849 58.463 | 2.155 0.7342 111.49 | 8.185 2.7837 423.34 | |25.820 | 0.085 0.0502 | 0.010 0.0025 0.4529 | 0.120 0.0336 5.0742 | 0.173 0.0426 5.9315 | 0.845 0.1615 33.481 | FBW - Final Body Weight - 678 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Subchronic Toxicity Group : VIII 25 mg/kg/day Sex :FEMALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS | % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) LIVER | %FBW %BRAIN | | 655011 |306.70 | 1.958 0.6384 | 0.073 0.0238 3.7283 | 1.060 0.3456 54.137 | 2.627 0.8565 134.17 | 10.728 3.4979 547.91 | | 655012 |305.60 | 1.998 0.6538 | 0.056 0.0183 2.8028 | 1.293 0.4231 64.715 | 2.347 0.7680 117.47 | 9.551 3.1253 478.03 | | 655047 |264.90 | 1.895 0.7154 | 0.056 0.0211 2.9551 | 1.012 0.3820 53.404 | 2.134 0.8056 112.61 | 7.515 2.8369 396.57 | | 655055 |279.50 | 2.107 0.7538 | 0.067 0.0240 3.1799 | 1.069 0.3825 50.736 | 2.234 0.7993 106.03 | 8.585 3.0716 407.45 | | 655058 |278.20 | 2.042 0.7340 | 0.063 0.0226 3.0852 | 1.090 0.3918 53.379 | 2.301 0.8271 112.68 | 8.310 2.9871 406.95 | | 655073 |305.30 | 1.974 0.6466 | 0.064 0.0210 3.2421 | 1.159 0.3796 58.713 | 2.353 0.7707 119.20 | 9.671 3.1677 489.92 | | 655076 |297.00 | 2.108 0.7098 | 0.075 0.0253 3.5579 | 1.173 0.3949 55.645 | 2.864 0.9643 135.86 | 8.930 3.0067 423.62 | | 655078 |351.30 | 2.069 0.5890 | 0.067 0.0191 3.2383 | 1.399 0.3982 67.617 | 2.897 0.8247 140.02 | 10.928 3.1107 528.18 | | 655085 |317.90 | 1.855 0.5835 | 0.062 0.0195 3.3423 | 1.275 0.4011 68.733 | 2.529 0.7955 136.33 | 9.605 3.0214 517.79 | | 655105 |268.80 | 2.019 0.7511 | 0.070 0.0260 3.4671 | 1.076 0.4003 53.294 | 2.243 0.8344 111.09 | 8.475 3.1529 419.76 | | Mean | S.D. |297.52 | 2.003 0.6775 | 0.065 0.0221 3.2599 | 1.161 0.3899 58.037 | 2.453 0.8246 122.55 | 9.230 3.0978 461.62 | |26.045 | 0.085 0.0638 | 0.006 0.0027 0.2784 | 0.125 0.0200 6.5924 | 0.267 0.0564 12.670 | 1.076 0.1713 57.204 | Group : X 125 mg/kg/day Sex :FEMALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS | % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) LIVER | %FBW %BRAIN | | 655007 |283.00 | 1.923 0.6795 | 0.070 0.0247 3.6401 | 1.232 0.4353 64.067 | 2.522 0.8912 131.15 | 11.585 4.0936 602.44 | | 655023 |282.70 | 1.860 0.6579 | 0.050 0.0177 2.6882 | 1.064 0.3764 57.204 | 2.159 0.7637 116.08 | 10.675 3.7761 573.92 | | 655026 |283.10 | 2.001 0.7068 | 0.077 0.0272 3.8481 | 1.172 0.4140 58.571 | 2.496 0.8817 124.74 | 10.693 3.7771 534.38 | | 655052 |277.80 | 2.076 0.7473 | 0.063 0.0227 3.0347 | 1.094 0.3938 52.697 | 2.563 0.9226 123.46 | 12.457 4.4842 600.05 | | 655053 |305.90 | 2.126 0.6950 | 0.097 0.0317 4.5626 | 1.235 0.4037 58.090 | 2.435 0.7960 114.53 | 12.127 3.9644 570.41 | | 655063 |251.50 | 1.912 0.7602 | 0.066 0.0262 3.4519 | 1.002 0.3984 52.406 | 2.079 0.8266 108.73 | 10.581 4.2072 553.40 | | 655092 |299.40 | 2.031 0.6784 | 0.080 0.0267 3.9389 | 1.143 0.3818 56.278 | 2.464 0.8230 121.32 | 10.646 3.5558 524.18 | | 655095 |317.10 | 2.249 0.7092 | 0.083 0.0262 3.6905 | 1.191 0.3756 52.957 | 3.048 0.9612 135.53 | 13.348 4.2094 593.51 | | 655097 |294.80 | 1.850 0.6275 | 0.062 0.0210 3.3514 | 1.186 0.4023 64.108 | 2.306 0.7822 124.65 | 12.171 4.1286 657.89 | FBW - Final Body Weight - 679 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing F e m a l e R a t s D e s i g n a t e d for S u b c h r o n i c 1T o x i c i t y G r o u p : X 125 m g / k g / d a y ,S e x :FEMALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | I I (Gms) |(Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) HEART | KIDNEYS | % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) LIVER | %FBW %BRAIN | | 655103 |294.30 | 2.063 0.7010 | 0.081 0.0275 3.9263 | 1.184 0.4023 57.392 | 2.551 0.8668 123.65 | 10.851 3.6871 525.98 | | | Mean I S.D. || | | | | | |288.96 | 2.009 0.6963 | 0.073 0.0252 3.6133 | 1.150 0.3984 57.377 | 2.462 0.8515 122.38 | 11.513 3.9883 573.62 | |l7.911 | 0.126 0.0391 | 0.013 0.0039 0.5220 | 0.075 0.0182 4.2082 | 0.265 0.0640 7.8306 | 0.972 0.2870 41.766 | FBW - Final Body Weight - 680 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Subchronic Toxicity G r o u p : II 0 m g / k g / d a y Sex :FEMALES | ANIMAL | | (Gms) OVARIES %FBW %BRAIN | (Gms) SPLEEN %FBW %BRAIN | (Gms) THYMUS %FBW %BRAIN THYROID GLAND | (Gms) % F B W % B R A I N | UTERUS | (Gms) %FB W %B R A I N | | | 655016 | 0.131 0.0457 6.6939 | 0.634 0.2213 32.397 | 0.290 0.1012 14.819 | 0.022 0.0077 1.1242 | 0.818 0.2855 41.799 | | 655025 | 0.116 0.0384 5.5396 | 0.614 0.2035 29.322 | 0.242 0.0802 11.557 | 0.018 0.0060 0.8596 | 0.708 0.2347 33.811 | | 655031 | 0.143 0.0489 7.2811 | 0.583 0.1992 29.684 | 0.372 0.1271 18.941 | 0.022 0.0075 1.1202 | 0.937 0.3202 47.709 | | 655032 | 0.167 0.0551 8.3417 | 0.715 0.2361 35.714 | 0.395 0.1304 19.730 | 0.021 0.0069 1.0490 | 0.944 0.3117 47.153 | | 655036 | 0.163 0.0505 7.9785 | 0.650 0.2016 31.816 | 0.513 0.1591 25.110 | 0.018 0.0056 0.8811 | 0.542 0.1681 26.530 | | 655079 | 0.144 0.0540 7.2654 | 0.618 0.2316 31.181 | 0.312 0.1169 15.742 | 0.020 0.0075 1.0091 | 0.525 0.1968 26.488 | | 655083 | 0.159 0.0512 8.1622 | 0.598 0.1924 30.698 | 0.373 0.1200 19.148 | 0.020 0.0064 1.0267 | 0.589 0.1895 30.236 | | 655098 | 0.134 0.0513 7.1315 | 0.466 0.1785 24.800 | 0.377 0.1444 20.064 | 0.018 0.0069 0.9580 | 0.549 0.2103 29.218 | | 655099 | 0.135 0.0474 7.0130 | 0.461 0.1618 23.948 | 0.327 0.1148 16.987 | 0.026 0.0091 1.3506 | 0.588 0.2064 30.545 | | 655107 | 0.119 0.0499 6.3534 | 0.449 0.1883 23.972 | 0.311 0.1304 16.604 | 0.015 0.0063 0.8009 | 0.841 0.3526 44.901 | | | Mean | S.D. | | 0.141 0.0492 7.1760 | 0.579 0.2014 29.353 | 0.351 0.1225 17.870 | 0.020 0.0070 1.0179 | 0.704 0.2476 35.839 | | 0.018 0.0047 0.8570 | 0.090 0.0233 3.9433 | 0.074 0.0219 3.6447 | 0.003 0.0010 0.1592 | 0.168 0.0645 8.6153 | Group : IV 1 mg/kg/day Sex :FEMALES | ANIMAL | | | (Gms) OVARIES %FBW %BRAIN | | (Gms) SPLEEN %FBW %BRAIN | | (Gms) THYMUS %FBW %BRAIN | THYROID GLAND | (Gms) %FBW %BRAIN | | (Gms) UTERUS %FBW %BRAIN | | | 655013 | 0.153 0.0511 7.5000 | 0.590 0.1971 28.922 | 0.326 0.1089 15.980 | 0.014 0.0047 0.6863 | 0.720 0.2405 35.294 | | 655033 | 0.169 0.0557 8.2359 | 0.728 0.2398 35.478 | 0.360 0.1186 17.544 | 0.024 0.0079 1.1696 | 1.051 0.3462 51.218 | | 655040 | 0.107 0.0365 5.8089 | 0.462 0.1576 25.081 | 0.180 0.0614 9.7720 | 0.024 0.0082 1.3029 | 0.788 0.2689 42.780 | | 655041 | 0.095 0.0344 4.6844 | 0.523 0.1894 25.789 | 0.242 0.0876 11.933 | 0.022 0.0080 1.0848 | 0.816 0.2955 40.237 | | 655044 | 0.133 0.0419 6.4594 | 0.523 0.1649 25.401 | 0.161 0.0508 7.8193 | 0.020 0.0063 0.9713 | 0.662 0.2087 32.152 | | 655086 | 0.158 0.0649 7.9919 | 0.465 0.1911 23.520 | 0.256 0.1052 12.949 | 0.017 0.0070 0.8599 | 1.086 0.4464 54.932 | | 655089 | 0.140 0.0440 7.4786 | 0.599 0.1884 31.998 | 0.305 0.0959 16.293 | 0.016 0.0050 0.8547 | 0.728 0.2290 38.889 | | 655090 | 0.139 0.0430 6.8574 | 0.621 0.1920 30.636 | 0.350 0.1082 17.267 | 0.017 0.0053 0.8387 | 0.542 0.1675 26.739 | FBW - Final Body Weight - 681 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Subchronic Toxicity Group : IV 1 mg/kg/day Sex :FEMALES | ANIMAL | | | (Gms) OVARIES %FBW %BRAIN | | (Gms) SPLEEN %FBW %BRAIN | | (Gms) THYMUS %FBW %BRAIN | THYROID GLAND | (Gms) %FBW %BRAIN | | (Gms) UTERUS %FBW %BRAIN | | | 655091 | 0.123 0.0406 6.3632 | 0.584 0.1930 30.212 | 0.230 0.0760 11.899 | 0.015 0.0050 0.7760 | 0.679 0.2244 35.127 | | 655108 | 0.104 0.0386 5.3443 | 0.400 0.1485 20.555 | 0.257 0.0954 13.207 | 0.032 0.0119 1.6444 | 0.721 0.2677 37.050 | | Mean | S.D. 0.020| 0.132 0.0451 6.6724 | 0.550 0.1 862 2 7 . 7 5 9 | 0.267 0.0908 13.466 | 0.0069 1.0189 | 0.779 0.2695 39.442 | 0.0220 0.0022| 0.025 0.0095 1.1622 | 0.095 0.0254 4.4680 | 0.068 3.2670 | 0.006 0.2898 | 0.170 0.0792 8.4771 | Group : VI 5 mg/kg/day Sex :FEMALES | ANIMAL | | (Gms) OVARIES %FBW %BRAIN | (Gms) SPLEEN %FBW %BRAIN | (Gms) THYMUS %FBW %BRAIN THYROID GLAND | (Gms) % F B W % B R A I N | UTERUS | (Gms) %FB W %B R A I N | | 0.1001| 655020 | 0.144 0.0477 7.4573 | 0.703 0.2331 36.406 | 0.302 15.640 | 0.024 0.0080 1.2429 | 0.560 0.1857 29.001 | | 655029 | 0.127 0.0454 6.9361 | 0.510 0.1822 27.854 | 0.321 0.1147 17.531 | 0.014 0.0050 0.7646 | 0.539 0.1926 29.437 | | 655034 | 0.127 0.0490 7.2241 | 0.643 0.2482 36.576 | 0.324 0.1250 18.430 | 0.019 0.0073 1.0808 | 0.438 0.1690 24.915 | 0.020| 6 5 5 0 3 8 | 0.164 0.0560 8 . 0 9 8 8 | 0.555 0.1 896 2 7 . 4 0 7 | 0.337 0.1151 1 6 .642 | 0.0068 0.9877 | 0.754 0.2576 37.235 | | 655039 | 0.104 0.0345 5.2288 | 0.580 0.1925 29.160 | 0.193 0.0641 9.7034 | 0.024 0.0080 1.2066 | 1.067 0.3541 53.645 | | 655042 | 0.163 0.0480 8.3590 | 0.821 0.2416 42.103 | 0.520 0.1530 26.667 | 0.023 0.0068 1.1795 | 0.754 0.2219 38.667 | | 655054 | 0.170 0.0674 8.7269 | 0.593 0.2350 30.441 | 0.347 0.1375 17.813 | 0.019 0.0075 0.9754 | 1.435 0.5688 73.665 | 0.021| 6 5 5066 | 0.161 0.0523 8 . 2 1 8 5 | 0.548 0.1779 2 7 . 9 7 3 | 0.322 0.1045 1 6 . 4 3 7 | 0.0068 1.0720 | 0.656 0.2129 33.486 | 0.2111| 6 5 5 0 6 7 | 0.074 0.0254 3 . 9153 | 0.521 0.1788 2 7 . 5 6 6 | 0.310 0.1 064 1 6 .402 | 0.019 0.0065 1 . 0053 | 0.615 32.540 | | 655087 | 0.174 0.0553 8.5714 | 0.750 0.2383 36.946 | 0.263 0.0836 12.956 | 0.019 0.0060 0.9360 | 0.557 0.1770 27.438 | | | Mean | S.D. 0.020| 0.141 0.0481 7 . 2736 | 0.622 0.2117 3 2 .243 | 0.324 0.1 104 1 6 .822 | | 0.0069 1.0451 | 0.738 0.2551 38.003 | | 0.033 0.0116 1.5691 | 0.105 0.0296 5.2803 | 0.082 0.0255 4.3252 | 0.003 0.0009 0.1436 | 0.300 0.1226 14.926 | FBW - Final Body Weight - 682 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Subchronic Toxicity Group : VIII 25 mg/kg/day Sex :FEMALES | ANIMAL | | (Gms) OVARIES %FBW %BRAIN | (Gms) SPLEEN %FBW %BRAIN | (Gms) THYMUS %FBW %BRAIN THYROID GLAND | (Gms) % F B W % B R A I N | UTERUS | (Gms) %FB W %B R A I N | | | 655011 | 0.120 0.0391 6.1287 | 0.660 0.2152 33.708 | 0.364 0.1187 18.590 | 0.019 0.0062 0.9704 | 0.801 0.2612 40.909 | | 655012 | 0.165 0.0540 8.2583 | 0.666 0.2179 33.333 | 0.283 0.0926 14.164 | 0.031 0.0101 1.5516 | 0.560 0.1832 28.028 | | 655047 | 0.112 0.0423 5.9103 | 0.580 0.2190 30.607 | 0.427 0.1612 22.533 | 0.019 0.0072 1.0026 | 0.847 0.3197 44.697 | | 655055 | 0.156 0.0558 7.4039 | 0.535 0.1914 25.392 | 0.298 0.1066 14.143 | 0.016 0.0057 0.7594 | 0.525 0.1878 24.917 | | 655058 | 0.124 0.0446 6.0725 | 0.617 0.2218 30.215 | 0.249 0.0895 12.194 | 0.017 0.0061 0.8325 | 0.613 0.2203 30.020 | | 655073 | 0.166 0.0544 8.4093 | 0.527 0.1726 26.697 | 0.301 0.0986 15.248 | 0.022 0.0072 1.1145 | 0.972 0.3184 49.240 | | 655076 | 0.156 0.0525 7.4004 | 0.655 0.2205 31.072 | 0.275 0.0926 13.046 | 0.022 0.0074 1.0436 | 0.827 0.2785 39.231 | | 655078 | 0.116 0.0330 5.6066 | 0.530 0.1509 25.616 | 0.331 0.0942 15.998 | 0.023 0.0065 1.1116 | 0.962 0.2738 46.496 | | 655085 | 0.112 0.0352 6.0377 | 0.506 0.1592 27.278 | 0.422 0.1327 22.749 | 0.025 0.0079 1.3477 | 0.948 0.2982 51.105 | | 655105 | 0.108 0.0402 5.3492 | 0.460 0.1711 22.784 | 0.334 0.1243 16.543 | 0.019 0.0071 0.9411 | 0.743 0.2764 36.800 | | Mean | S.D. | 0.134 0.0451 6.6577 | 0.574 0.1940 28.670 | 0.328 0.1111 16.521 | 0.021 0.0071 1.0675 | 0.780 0.2618 39.144 | | 0.024 0.0085 1.1116 | 0.073 0.0282 3.6453 | 0.060 0.0231 3.6987 | 0.004 0.0012 0.2351 | 0.166 0.0493 9.1149 | Group : X 125 mg/kg/day Sex :FEMALES | ANIMAL | | | (Gms) OVARIES %FBW %BRAIN | | (Gms) SPLEEN %FBW %BRAIN | | (Gms) THYMUS %FBW %BRAIN | THYROID GLAND | (Gms) %FBW %BRAIN | | (Gms) UTERUS %FBW %BRAIN | | | 655007 | 0.111 0.0392 5.7722 | 0.561 0.1982 29.173 | 0.310 0.1095 16.121 | 0.028 0.0099 1.4561 | 0.468 0.1654 24.337 | | 655023 | 0.157 0.0555 8.4409 | 0.576 0.2037 30.968 | 0.273 0.0966 14.677 | 0.020 0.0071 1.0753 | 0.570 0.2016 30.645 | | 655026 | 0.169 0.0597 8.4458 | 0.753 0.2660 37.631 | 0.222 0.0784 11.094 | 0.022 0.0078 1.0995 | 0.530 0.1872 26.487 | | 655052 | 0.152 0.0547 7.3218 | 0.624 0.2246 30.058 | 0.414 0.1490 19.942 | 0.028 0.0101 1.3487 | 0.821 0.2955 39.547 | | 655053 | 0.151 0.0494 7.1025 | 0.594 0.1942 27.940 | 0.266 0.0870 12.512 | 0.023 0.0075 1.0818 | 0.548 0.1791 25.776 | | 655063 | 0.141 0.0561 7.3745 | 0.624 0.2481 32.636 | 0.361 0.1435 18.881 | 0.016 0.0064 0.8368 | 0.503 0.2000 26.308 | | 655092 | 0.178 0.0595 8.7642 | 0.618 0.2064 30.428 | 0.388 0.1296 19.104 | 0.023 0.0077 1.1324 | 1.484 0.4957 73.067 | | 655095 | 0.121 0.0382 5.3802 | 0.646 0.2037 28.724 | 0.430 0.1356 19.120 | 0.018 0.0057 0.8004 | 1.262 0.3980 56.114 | | 655097 | 0.103 0.0349 5.5676 | 0.594 0.2015 32.108 | 0.237 0.0804 12.811 | 0.016 0.0054 0.8649 | 0.850 0.2883 45.946 | FBW - Final Body Weight - 683 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Subchronic Toxicity Group : X 125 mg/kg/day Sex :FEMALES | ANIMAL | I |(Gms) OVARIES %FBW %BRAIN | |(Gms) SPLEEN %FBW %BRAIN | |(Gms) THYMUS %FBW %BRAIN | THYROID GLAND |(Gms) %FBW %BRAIN | |(Gms) UTERUS %FBW %BRAIN | | | 655103 I 0.119 0.0404 5.7683 | 0.504 0.1713 24.430 | 0.326 0.1108 15.802 | 0.023 0.0078 1.1149 | 1.043 0.3544 50.557 | | | Mean I S.D. |||||| I 0.140 0.0488 6.9938 | 0.609 0.2118 30.410 | 0.323 0.1120 16.006 | 0.022 0.0075 1.0811 | 0.808 0.2765 39.878 | | 0.025 0.0096 1.3010 | 0.065 0.0275 3.4424 | 0.074 0.0263 3.1870 | 0.004 0.0016 0.2112 | 0.354 0.1109 16.348 | FBW - Final Body Weight - 684 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Recovery G r o u p : II 0 m g / k g / d a y Sex :FEMALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS | % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) LIVER | %FBW %BRAIN | | 655009 |317.10 | 1.939 0.6115 | 0.090 0.0284 4.6416 | 1.165 0.3674 60.083 | 2.266 0.7146 116.86 | 8.669 2.7338 447.09 | | 655015 |288.40 | 1.944 0.6741 | 0.087 0.0302 4.4753 | 1.208 0.4189 62.140 | 2.580 0.8946 132.72 | 9.943 3.4476 511.47 | | 655019 |347.70 | 2.218 0.6379 | 0.128 0.0368 5.7710 | 1.506 0.4331 67.899 | 2.890 0.8312 130.30 | 11.718 3.3701 528.31 | | 655035 |322.80 | 2.005 0.6211 | 0.060 0.0186 2.9925 | 1.503 0.4656 74.963 | 2.396 0.7423 119.50 | 9.806 3.0378 489.08 | | 655062 |344.40 | 2.091 0.6071 | 0.092 0.0267 4.3998 | 1.433 0.4161 68.532 | 3.128 0.9082 149.59 | 11.122 3.2294 531.90 | | 655068 |329.80 | 1.950 0.5913 | 0.075 0.0227 3.8462 | 1.346 0.4081 69.026 | 2.501 0.7583 128.26 | 9.951 3.0173 510.31 | | 655072 |340.90 | 2.148 0.6301 | 0.090 0.0264 4.1899 | 1.343 0.3940 62.523 | 2.620 0.7686 121.97 | 11.076 3.2490 515.64 | | 655101 |405.90 | 2.063 0.5083 | 0.062 0.0153 3.0053 | 1.428 0.3518 69.220 | 2.730 0.6726 132.33 | 11.298 2.7834 547.65 | | 655109 |309.30 | 2.138 0.6912 | 0.080 0.0259 3.7418 | 1.053 0.3404 49.252 | 2.338 0.7559 109.35 | 9.201 2.9748 430.36 | | Mean | S.D. |334.03 | 2.055 0.6192 | 0.085 0.0257 4.1182 | 1.332 0.3995 64.848 | 2.605 0.7829 126.77 | 10.309 3.0937 501.31 | |32.847 | 0.102 0.0524 | 0.020 0.0063 0.8616 | 0.158 0.0404 7.4199 | 0.277 0.0795 11.614 | 1.040 0.2483 39.253 | Group : X 125 mg/kg/day Sex :FEMALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | | | (Gms) | (Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) HEART KIDNEYS | % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) LIVER | %FBW %BRAIN | | 655010 |306.30 | 1.816 0.5929 | 0.074 0.0242 4.0749 | 1.192 0.3892 65.639 | 3.426 1.1185 188.66 | 11.589 3.7835 638.16 | | 655030 |455.30 | 2.008 0.4410 | 0.071 0.0156 3.5359 | 1.472 0.3233 73.307 | 3.615 0.7940 180.03 | 13.781 3.0268 686.30 | | 655037 |394.40 | 1.968 0.4990 | 0.092 0.0233 4.6748 | 1.245 0.3157 63.262 | 2.503 0.6346 127.18 | 10.562 2.6780 536.69 | | 655049 |249.70 | 1.863 0.7461 | 0.062 0.0248 3.3280 | 0.977 0.3913 52.442 | 2.027 0.8118 108.80 | 7.045 2.8214 378.15 | | 655061 |289.30 | 1.786 0.6174 | 0.076 0.0263 4.2553 | 1.022 0.3533 57.223 | 2.218 0.7667 124.19 | 8.489 2.9343 475.31 | | 655075 |432.20 | 1.968 0.4553 | 0.089 0.0206 4.5224 | 1.491 0.3450 75.762 | 2.920 0.6756 148.37 | 11.180 2.5868 568.09 | | 655077 |326.60 | 2.010 0.6154 | 0.081 0.0248 4.0299 | 1.181 0.3616 58.756 | 2.312 0.7079 115.02 | 9.701 2.9703 482.64 | | 655084 |302.10 | 2.012 0.6660 | 0.075 0.0248 3.7276 | 1.162 0.3846 57.753 | 2.425 0.8027 120.53 | 8.440 2.7938 419.48 | | 655088 |374.80 | 2.010 0.5363 | 0.047 0.0125 2.3383 | 1.188 0.3170 59.104 | 2.705 0.7217 134.58 | 10.908 2.9104 542.69 | FBW - Final Body Weight - 685 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Recovery Group : X 125 mg/kg/day Sex :FEMALES | ANIMAL | FBW | BRAIN | ADRENAL GLANDS | | | (Gms) |(Gms) % F B W | (Gms) % F B W % B R A I N | (Gms) HEART | KIDNEYS | % F B W % B R A I N | (Gms) % F B W % B R A I N | (Gms) LIVER | %FBW %BRAIN | | 655100 |358.50 | 1.917 0.5347 | 0.083 0.0232 4.3297 | 1.409 0.3930 73.500 | 3.231 0.9013 168.54 | 11.691 3.2611 609.86 | | | Mean | S.D. || | | | | | |348.92 | 1.936 0.5704 | 0.075 0.0220 3.8817 | 1.234 0.3574 63.675 | 2.738 0.7935 141.59 | 10.339 2.9766 533.74 | |65.818 | 0.086 0.0956 | 0.013 0.0045 0.6889 | 0.175 0.0314 8.0787 | 0.541 0.1374 28.381 | 1.961 0.3399 96.914 | FBW - Final Body Weight - 686 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Recovery G r o u p : II 0 m g / k g / d a y Sex :FEMALES ANIMAL | (Gms) OVARIES %FBW %BRAIN | (Gms) SPLEEN %FBW %BRAIN THYMUS | (Gms) %FBW %BRAIN THYROID GLAND | (Gms) %FBW %BRAIN | (Gms) UTERUS %FBW %BRAIN 655009 | 0.142 0.0448 7.3234 | 0.622 0.1962 32.078 | 0.164 0.0517 8.4580 | 0.027 0.0085 1.3925 | 0.721 0.2274 37.184 655015 | 0.099 0.0343 5.0926 | 0.646 0.2240 33.230 | 0.204 0.0707 10.494 | 0.013 0.0045 0.6687 | 0.910 0.3155 46.811 655019 | 0.164 0.0472 7.3940 | 0.819 0.2355 36.925 | 0.359 0.1032 16.186 | 0.037 0.0106 1.6682 | 1.811 0.5209 81.650 655035 | 0.100 0.0310 4.9875 | 0.648 0.2007 32.319 | 0.221 0.0685 11.022 | 0.025 0.0077 1.2469 | 0.725 0.2246 36.160 655062 | 0.079 0.0229 3.7781 | 0.601 0.1745 28.742 | 0.165 0.0479 7.8910 | 0.027 0.0078 1.2912 | 0.784 0.2276 37.494 655068 | 0.100 0.0303 5.1282 | 0.503 0.1525 25.795 | 0.261 0.0791 13.385 | 0.029 0.0088 1.4872 | 0.904 0.2741 46.359 655072 | 0.196 0.0575 9.1248 | 0.749 0.2197 34.870 | 0.247 0.0725 11.499 | 0.020 0.0059 0.9311 | 0.782 0.2294 36.406 655101 | 0.175 0.0431 8.4828 | 0.631 0.1555 30.587 | 0.183 0.0451 8.8706 | 0.028 0.0069 1.3572 | 0.536 0.1321 25.982 655109 | 0.121 0.0391 5.6595 | 0.512 0.1655 23.948 | 0.345 0.1115 16.137 | 0.028 0.0091 1.3096 | 0.798 0.2580 37.325 Mean S.D. | 0.131 0.0389 6.3301 | 0.637 0.1916 30.944 | 0.239 0.0723 11.549 | 0.026 0.0078 1.2614 | 0.886 0.2677 42.819 | 0.040 0.0105 1.8133 | 0.101 0.0310 4.1837 | 0.072 0.0232 3.1108 | 0.007 0.0018 0.2972 | 0.364 0.1069 15.794 Group : X 125 mg/kg/day Sex :FEMALES | ANIMAL | | | (Gms) OVARIES %FBW %BRAIN | | (Gms) SPLEEN %FBW %BRAIN | THYMUS | (Gms) %FBW %BRAIN | THYROID GLAND | (Gms) %FBW %BRAIN | | (Gms) UTERUS %FBW %BRAIN | | | 655010 | 0.111 0.0362 6.1123 | 0.623 0.2034 34.306 | 0.249 0.0813 13.711 | 0.026 0.0085 1.4317 | 1.109 0.3621 61.068 | | 655030 | 0.085 0.0187 4.2331 | 0.591 0.1298 29.432 | 0.439 0.0964 21.863 | 0.025 0.0055 1.2450 | 0.776 0.1704 38.645 | | 655037 | 0.134 0.0340 6.8089 | 0.702 0.1780 35.671 | 0.336 0.0852 17.073 | 0.024 0.0061 1.2195 | 0.711 0.1803 36.128 | | 655049 | 0.114 0.0457 6.1192 | 0.585 0.2343 31.401 | 0.210 0.0841 11.272 | 0.026 0.0104 1.3956 | 1.329 0.5322 71.337 | | 655061 | 0.103 0.0356 5.7671 | 0.471 0.1628 26.372 | 0.157 0.0543 8.7906 | 0.027 0.0093 1.5118 | 0.760 0.2627 42.553 | | 655075 | 0.092 0.0213 4.6748 | 0.511 0.1182 25.965 | 0.405 0.0937 20.579 | 0.030 0.0069 1.5244 | 0.816 0.1888 41.463 | | 655077 | 0.195 0.0597 9.7015 | 0.595 0.1822 29.602 | 0.232 0.0710 11.542 | 0.021 0.0064 1.0448 | 1.376 0.4213 68.458 | | 655084 | 0.168 0.0556 8.3499 | 0.516 0.1708 25.646 | 0.171 0.0566 8.4990 | 0.026 0.0086 1.2922 | 0.706 0.2337 35.089 | | 655088 | 0.132 0.0352 6.5672 | 0.560 0.1494 27.861 | 0.331 0.0883 16.468 | 0.035 0.0093 1.7413 | 0.433 0.1155 21.542 | FBW - Final Body Weight - 687 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 Organ Weight Listing Female Rats Designated for Recovery Group : X 125 mg/kg/day Sex :FEMALES | ANIMAL | OVARIES | |(Gms) %FBW %BRAIN | |(Gms) SPLEEN %FBW %BRAIN | |(Gms) THYMUS %FBW %BRAIN | THYROID GLAND |(Gms) %FBW %BRAIN | |(Gms) UTERUS %FBW %BRAIN | | | 6 5 5 1 0 0 | 0.10 0 0.02 7 9 5 . 2 1 6 5 | 0.77 0 0.21 4 8 40 .167 | 0.164 0.04 5 7 8. 5550 | 0.020 0.0 056 1 . 0 4 3 3 | 1.126 0.31 4 1 5 8 . 7 3 8 | | | Mean | S.D. |||||| | 0.123 0.0370 6.3550 | 0.592 0.1744 30 .642 | 0.269 0.0757 13 .835 | 0.026 0.0077 1.3450 | 0.914 0.2781 47.502 | | 0.03 5 0. 0134 1 . 6 5 0 3 | 0.09 0 0.0 366 4. 7768 | 0.102 0.01 7 8 4. 9551 | 0.004 0.00 1 8 0.22 0 3 | 0.305 0.1296 1 6 . 3 7 8 | FBW - Final Body Weight - 688 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Female Rats Designated for Satellite Evaluations (10-Day Sacrifice) G r o u p : II 0 m g / k g / d a y Sex :FEMALES ANIMAL | FBW | (Gms) |(Gms) LIVER %FBW 655141 655149 655152 655155 655159 |148.6 |184.2 |192.1 |168.9 |158.9 |6.422 |7.580 |8.276 |7.192 |6.454 4.322 4.115 4.308 4.258 4.062 Mean S.D. |170.54 |7.185 | 17.825 |o.785 4.213 0.118 Group : IV 1 mg/kg/day Sex :FEMALES ANIMAL | FBW | (Gms) |(Gms) LIVER %FBW 655142 655160 655162 655164 655165 |163.8 |135.6 |159.1 |178.8 |164.9 |7.398 |6.456 |6.247 |8.583 |7.188 4.516 4.761 3.926 4.800 4.359 Mean S.D. |160.44 |7.174 | 15.709 |0.923 4.473 0.355 | | | | | | | | | | | | | | | FBW - Final Body Weight - 689 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Female Rats Designated for Satellite Evaluations (10-Day Sacrifice) Group : VI 5 mg/kg/day Sex :FEMALES ANIMAL | FBW | (Gms) |(Gms) LIVER %FBW 655140 655145 655154 655158 655167 |146.6 |167.3 |170.8 |190.3 |178.7 |6.848 |8.360 |7.907 |8.156 |7.798 4.671 4.997 4.629 4.286 4.364 Mean S.D. |170.74 |7.814 | 16.129 |0.582 4.589 0.282 | | | | | | | Group : VIII 25 mg/kg/day Sex :FEMALES ANIMAL | FBW | (Gms) |(Gms) LIVER %FBW | | 655144 655148 655161 655163 655166 |177.0 |179.5 |152.3 |177.5 |191.6 |8.157 |9.610 |6.735 |7.720 |9.596 4.608 5.354 4.422 4.349 5.008 | | | | | Mean S.D. |175.58 |8.364 | 14.315 |1.243 4.748 0.424 | | FBW - Final Body Weight - 690 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Female Rats Designated for Satellite Evaluations (10-Day Sacrifice) Group : X 125 mg/kg/day Sex :FEMALES ANIMAL | FBW | | (Gms) |(Gms) LIVER %FBW 655143 655146 655147 655150 655151 |190.1 |170.2 |206.8 |185.3 |160.2 | 9.516 | 9.894 |12.044 |10.084 | 9.130 5.006 5.813 5.824 5.442 5.699 Mean S.D. |182.52 |10.134 5.557 | 18.06 | 1.129 0.344 | | | | | | | DuPont-9478 FBW - Final Body Weight - 691 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Female Rats Designated for Satellite Evaluations (Final Sacrifice) G r o u p : II 0 m g / k g / d a y Sex :FEMALES ANIMAL | FBW | | (Gms) | (Gms) LIVER %FBW 655022 655045 655065 655074 655093 |316.90 |336.30 |378.00 |345.80 |252.50 | 10.043 | 13.912 | 15.652 | 13.889 | 8.723 3.1691 4.1368 4.1407 4.0165 3.4547 Mean S.D. |325.90 | 12.444 3.7836 |46.602 | 2.922 0.4451 Group : IV 1 mg/kg/day Sex :FEMALES ANIMAL | FBW | (Gms) (Gms) LIVER %FBW 655018 655028 655051 655057 655096 |364.30 |332.90 |322.30 |296.20 |365.10 14.077 11.003 9.970 11.429 13.007 3.8641 3.3052 3.0934 3.8585 3.5626 Mean S.D. |336.16 |29.278 11.897 3.5368 1.637 0.3397 FBW - Final Body Weight - 692 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Female Rats Designated for Satellite Evaluations (Final Sacrifice) Group : VI 5 mg/kg/day Sex :FEMALES ANIMAL | FBW | (Gms) (Gms) LIVER %FBW 655017 655021 655050 655059 655064 |334.50 |321.60 |328.50 |286.60 |408.40 11.964 13.230 13.097 12.290 12.973 3.5767 4.1138 3.9869 4.2882 3.1765 Mean S.D. |335.92 U4.576 12.711 3.8284 0.553 0.4490 Group : VIII 25 mg/kg/day Sex :FEMALES | ANIMAL | FBW | | (Gms) |(Gms) LIVER %FBW 655043 655056 655060 655081 655082 |305.60 |311.80 |393.70 |417.30 |405.80 | 10.699 | 9.860 | 13.407 | 16.478 | 17.192 3.5010 3.1623 3.4054 3.9487 4.2366 Mean S.D. |366.84 | 13.527 3.6508 |53.771 | 3.301 0.4339 FBW - Final Body Weight - 693 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Organ Weight Listing Female Rats Designated for Satellite Evaluations (Final Sacrifice) Group : X 125 mg/kg/day Sex :FEMALES | ANIMAL | FBW | (Gms) |(Gms) LIVER %FBW | 655024 | 655027 | 655046 | 655104 | 655106 | | Mean | S.D. 364.00 346.20 |4 1 8 . 3 0 372.10 296.00 359.32 44.287 | 12.552 | 10.958 | 14.617 | 12.954 | 12.562 3.4484 3.1652 3.4944 3.4813 4.2439 | | 12.729 3.5666 | 1.305 0.4020 | | | | | | | | | | DuPont-9478 FBW - Final Body Weight - 694 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX N INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS - 695 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS EXPLANTORY NOTES Accidently killed (includes animals presented dead or moribund that have injured themselves or were inadvertently injured when being handled. In-life and necropsy findings may be used to make this determination.) Lesion Grading Histopathological changes are described according to their morphologic character, distribution and severity. The distribution (extent of tissue involvement) is indicated, where appropriate, by modifiers such as focal, multifocal, diffuse, unilateral, bilateral, etc.; A severity score, if appropriate, is also assigned as follows: Minimal: the amount of change present barely exceeds that which is considered to be within normal limits. Mild: in general, the lesion is easily identified but of limited severity. The lesion probably does not produce any functional impairment. Moderate: the lesion is prominent but there is significant potential for increased severity. Limited tissue or organ dysfunction is possible. Severe: the degree of change is either as complete as considered possible or great enough in intensity or extent to expect significant tissue or organ dysfunction. Comment: grades minimal through severe represent progressive involvement/severity along a continuum with minimal lesions being the least severe and severe lesions being the most severe. While the grades refer to the morphological characteristics of lesions, they also indicate their relative biological significance. Gross observations listing multiple masses for a tissue are distinguished with letters (i.e., a, b, c, d, etc.) Neoplasm Designations *B: Benign neoplasm, primary site *M: Malignant neoplasm, primary site - 696 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654903 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V ESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE - 697 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654909 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . NECROSIS, FOCAL, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, THYMUS, NOSE - 698 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654910 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i l d . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, THYMUS, NOSE - 699 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654915 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i l d . NECROSIS, FOCAL, m i l d . HYPERPLASIA, BILE DUCT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, NOSE - 700 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654919 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654924 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654924 C ontinued on th e n ext page . . . . - 701 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654924 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, THYROID GLAND, NOSE 654925 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 654925 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 702 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654925 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, PITUITARY GLAND : NOT PRESENT. EYE(S) WITH OPTIC NERVE : OPTIC NERVE NOT PRESENT. m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V ESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE - 703 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654927 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . NECROSIS, FOCAL, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m o d e r a t e . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, NOSE - 704 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654928 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654928 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . PANCREAS : ATROPHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . EYE(S) WITH OPTIC NERVE : OPTIC NERVE NOT PRESENT. C o n t i n u e d o n t h e n e x t p a g e ........ - 705 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654928 C ontinued from p re v io u s page H istopathology : PROSTATE : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE 654929 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654929 C ontinued on th e n ext page . . . . - 706 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654929 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V ESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE - 707 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654936 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : TESTES : DISCOLORATION, OPAQUE. No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654936 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL, severe. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, BILATERAL, s e v e r e . C ontinued on th e n ext page . . . . - 708 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654936 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V ESICLES, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE 654939 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE - 709 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654943 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : HYPERPLASIA, BILE DUCT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, NOSE - 710 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654949 A ccidentally K illed D u r a tio n o f d o s i n g - d a y s : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from n ecro p sy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, THYROID GLAND, NOSE - 711 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654950 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654950 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . PARATHYROID GLANDS : NOT PRESENT. EYE(S) WITH OPTIC NERVE : FOLD/ROSETTE, RETINAL, m in im a l. TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, m inim al. C o n t i n u e d o n t h e n e x t p a g e ........ BILATERAL, - 712 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654950 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE 654953 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654953 C ontinued on th e n ext page . . . . - 713 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654953 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . PANCREAS : ATROPHY, m i n i m a l . PITUITARY GLAND : CYST, m i n i m a l . EYE(S) WITH OPTIC NERVE : OPTIC NERVE NOT PRESENT. PROSTATE : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE - 714 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654956 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, THYMUS, NOSE - 715 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654966 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654971 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654971 C ontinued on th e n ext page . . . . - 716 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654971 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654972 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654972 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . C o n t i n u e d o n t h e n e x t p a g e ........ - 717 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654972 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, EYE(S) WITH OPTIC NERVE : ADHESION, RETINAL, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE 654987 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 654987 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 718 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654987 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, HEART : CARDIOMYOPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V ESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE - 719 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654992 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, THYROID GLAND, NOSE - 720 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654993 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . PROSTATE : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . 654993 No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, C ontinued on th e n ext page . . . . - 721 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654993 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , SEMINAL V E SICL E S, BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , BONE MARROW, NOSE URINARY STERNUM, 654994 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . 654994 C ontinued on th e n ext page . . . . - 722 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I 0 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654994 C ontinued from p re v io u s page H istopathology : THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, THYMUS, NOSE 654997 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE - 723 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654904 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654908 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : SKIN : ALOPECIA, RIGHT, SIDE. 654908 C ontinued on th e n ext page . . . . - 724 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654908 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : SK IN , NOSE - 725 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654913 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE - 726 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654932 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, NOSE - 727 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654938 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, NOSE - 728 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654941 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, m i l d . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, NOSE - 729 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654945 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654946 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654946 C ontinued on th e n ext page . . . . - 730 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654946 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 654947 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 654947 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 731 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654947 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 654948 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : 654948 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 732 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654948 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654954 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE - 733 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654960 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, THYROID GLAND, NOSE - 734 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654984 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, NOSE - 735 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654988 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654995 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654995 C ontinued on th e n ext page . . . . - 736 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : I I I 1 m g/kg/day Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654995 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE - 737 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654907 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, NOSE - 738 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654911 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . FATTY CHANGE, MEDIAN CLEFT, m i l d . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE - 739 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654916 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, NOSE - 740 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654917 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . NECROSIS, FOCAL, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE - 741 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654918 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654926 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654926 C ontinued on th e n ext page . . . . - 742 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654926 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654959 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . 654959 C ontinued on th e n ext page . . . . - 743 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654959 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 654961 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654961 C ontinued on th e n ext page . . . . - 744 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654961 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 654967 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654967 C ontinued on th e n ext page . . . . - 745 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654967 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, NOSE 654969 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE - 746 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654970 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654980 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : TESTES : SMALL, UNILATERAL. 654980 C ontinued on th e n ext page . . . . - 747 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654980 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, UNILATERAL, m ild. DILATATION, SEMINIFEROUS TUBULES, UNILATERAL, m o d e r a t e . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE - 748 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654981 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654998 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : URINARY BLADDER : DILATATION, m o d e r a te . 654998 C ontinued on th e n ext page . . . . - 749 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654998 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, TESTES, EPIDIDYMIDES, FEMUR/KNEE JO IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : URINARY BLADDER, NOSE - 750 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 S how ing STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V 5 m g/kg/day I n d iv id u a l Animal L is tin g anim al d ata fo r in d iv id u a l Sex: M ales anim als Animal Ref M icroscopic & M acroscopic Findings 655005 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, NOSE - 751 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654912 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654920 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654920 C ontinued on th e n ext page . . . . - 752 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654920 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654922 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654922 LIVER : NECROSIS, FOCAL, m i n i m a l . INFLAMMATION, SUBACUTE/CHRONIC, C o n t i n u e d o n t h e n e x t p a g e ........ m inim al. - 753 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654922 C ontinued from p re v io u s page H istopathology : THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, NOSE 654923 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654923 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, NECROSIS, FOCAL, m i n i m a l . C o n t i n u e d o n t h e n e x t p a g e ........ m inim al. - 754 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654923 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 654930 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654930 C ontinued on th e n ext page . . . . - 755 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654930 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 654933 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE - 756 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654934 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654940 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654940 C ontinued on th e n ext page . . . . - 757 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654940 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, NECROSIS, FOCAL, m i n i m a l . KIDNEYS : HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 654952 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 654952 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 758 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654952 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, KIDNEYS : HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 654958 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 654958 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 759 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654958 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . NECROSIS, FOCAL, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE - 760 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654964 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654975 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654975 C ontinued on th e n ext page . . . . - 761 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654975 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : NECROSIS, FOCAL, m i n i m a l . KIDNEYS : HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 654989 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 654989 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 762 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654989 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 655001 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655001 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 763 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 655001 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, KIDNEYS : HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE 655006 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655006 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 764 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : V II 25 m g /k g /d ay Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 655006 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, KIDNEYS : CYST, m i n i m a l . HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : NOSE - 765 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654906 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654914 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654914 C ontinued on th e n ext page . . . . - 766 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654914 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : HYPERTROPHY, HEPATOCELLULAR, m i n i m a l . KIDNEYS : HYPERTROPHY, TUBULAR, m i n i m a l . CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . JEJUNUM : NOT PRESENT. ILEUM : NOT PRESENT. CECUM : NOT PRESENT. RECTUM : NOT PRESENT. MESENTERIC LYMPH NODE : NOT PRESENT. THYROID GLAND : ALTERATION, COLLOID, m i l d . 654914 C ontinued on th e n ext page . . . . - 767 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654914 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, PANCREAS, COLON, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE 654921 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654921 C ontinued on th e n ext page . . . . - 768 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654921 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERTROPHY, HEPATOCELLULAR, m i l d . NECROSIS, FOCAL, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HYPERTROPHY, TUBULAR, m i n i m a l . PANCREAS : ATROPHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, s e v e r e . NOSE : DEGENERATION, AMELOBLASTS, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW - 769 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654931 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654937 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 654937 C ontinued on th e n ext page . . . . - 770 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654937 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654942 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654942 LIVER : HYPERPLASIA, BILE DUCT, m i n i m a l . NECROSIS, FOCAL, m i n i m a l . C o n t i n u e d o n t h e n e x t p a g e ........ - 771 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654942 C ontinued from p re v io u s page H istopathology : THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, THYMUS, NOSE 654951 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654951 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . C o n t i n u e d o n t h e n e x t p a g e ........ - 772 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654951 C ontinued from p re v io u s page H istopathology : LIVER : HYPERTROPHY, HEPATOCELLULAR, m i l d . NECROSIS, FOCAL, m i n i m a l . KIDNEYS : HYPERTROPHY, TUBULAR, m i n i m a l . CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . PANCREAS : ATROPHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, s e v e r e . NOSE : DEGENERATION, AMELOBLASTS, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW - 773 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654955 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : KIDNEYS : DILATATION, RIGHT, s e v e r e . No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V ESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JO IN T , STERNUM, NOSE H istopathology : 654955 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERTROPHY, HEPATOCELLULAR, m i l d . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HYDRONEPHROSIS, UNILATERAL, m i n i m a l . HYPERTROPHY, TUBULAR, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . C o n t i n u e d o n t h e n e x t p a g e ........ - 774 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654955 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V ESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 654957 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : 654957 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE C ontinued on th e n ext page . . . . - 775 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654957 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . NECROSIS, FOCAL, m i l d . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i l d . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, NOSE 654962 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE - 776 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654965 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : EYE(S) WITH OPTIC NERVE : MISSING, RIGHT. No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654965 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERTROPHY, HEPATOCELLULAR, m i l d . NECROSIS, FOCAL, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m o d e r a t e . C o n t i n u e d o n t h e n e x t p a g e ........ - 777 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654965 C ontinued from p re v io u s page H istopathology : EYE(S) WITH OPTIC NERVE : OPTIC NERVE NOT PRESENT. NOSE : DEGENERATION, AMELOBLASTS, m ild. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW 654973 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : 654973 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C ontinued on th e n ext page . . . . - 778 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654973 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . NECROSIS, FOCAL, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m o d e r a t e . NOSE : DEGENERATION, AMELOBLASTS, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, THYMUS - 779 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654974 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . NECROSIS, FOCAL, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HYDRONEPHROSIS, BILATERAL, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, NOSE - 780 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654976 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . NECROSIS, FOCAL, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . NOSE : DEGENERATION, AMELOBLASTS, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS - 781 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654977 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : KIDNEYS : CALCULUS\CALCULI, RIGHT. No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V ESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JO IN T , STERNUM, NOSE H istopathology : 654977 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . NECROSIS, FOCAL, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . KIDNEYS : HYPERPLASIA, TRANSITIONAL CELL, m i n i m a l . HYDRONEPHROSIS, UNILATERAL, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . C o n t i n u e d o n t h e n e x t p a g e ....... - 782 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654977 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, NOSE 654978 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654978 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . C o n t i n u e d o n t h e n e x t p a g e ........ - 783 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654978 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, THYMUS, NOSE 654979 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 654979 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERTROPHY, HEPATOCELLULAR, m i n i m a l . KIDNEYS : PIGMENT, TUBULAR, m i n i m a l . HYPERTROPHY, TUBULAR, m i n i m a l . C o n t i n u e d o n t h e n e x t p a g e ........ - 784 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654979 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, HEART : CARDIOMYOPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE 654982 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : 654982 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C ontinued on th e n ext page . . . . - 785 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654982 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654983 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : TESTES : SMALL, UNILATERAL. EPIDIDYMIDES : SMALL, UNILATERAL. 654983 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, NOSE C o n t i n u e d o n t h e n e x t p a g e ........ - 786 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654983 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERTROPHY, HEPATOCELLULAR, m i n i m a l . KIDNEYS : HYPERTROPHY, TUBULAR, m i n i m a l . LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, UNILATERAL, m oderate. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, UNILATERAL, s e v e r e . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE - 787 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654985 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, KIDNEYS : CYST, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . NOSE : ODONTODYSPLASIA, m o d e r a t e . INFLAMMATION, SUBACUTE/CHRONIC, m inim al. m ild. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS - 788 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654986 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : HYPERTROPHY, HEPATOCELLULAR, m i l d . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HYPERTROPHY, TUBULAR, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i l d . NOSE : DEGENERATION, AMELOBLASTS, m i l d . 654986 C ontinued on th e n ext page . . . . - 789 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654986 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW 654990 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654990 C ontinued on th e n ext page . . . . - 790 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654990 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . NECROSIS, FOCAL, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m o d e r a t e . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, NOSE 654991 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : 654991 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE C o n t i n u e d o n t h e n e x t p a g e ........ - 791 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654991 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i l d . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYMUS, NOSE 654996 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE 654996 C ontinued on th e n ext page . . . . - 792 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 654996 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERTROPHY, HEPATOCELLULAR, m i l d . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HYPERTROPHY, TUBULAR, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . THYROID GLAND : ALTERATION, COLLOID, m i n i m a l . PARATHYROID GLANDS : NOT PRESENT. NOSE : DEGENERATION, AMELOBLASTS, m i l d . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V ESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW - 793 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 655003 Term inal S a c rific e K i l l e d o n Day : 93 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V E SICL E S, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : FATTY CHANGE, CENTRILOBULAR, m i n i m a l . INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERTROPHY, HEPATOCELLULAR, m i n i m a l . KIDNEYS : HYPERTROPHY, TUBULAR, m i n i m a l . 655003 No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, C ontinued on th e n ext page . . . . - 794 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 In d iv id u a l Showing anim al d a ta STUDY : 1 3 6 9 0 / 2 4 6 9 1 / m a l e Dose Group : IX 125 m g /k g /d a y Sex: Animal L is tin g for individual M ales anim als Animal Ref M icroscopic & M acroscopic Findings 655003 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , PROSTATE, SEMINAL V ESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE - 795 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655009 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : NECROSIS, FOCAL, m i n i m a l . INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS - 796 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655015 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : FATTY CHANGE, MEDIAN CLEFT, m i l d . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655016 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : HEART : LARGE. 655016 C ontinued on th e n ext page . . . . - 797 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655016 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE - 798 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655019 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : UTERUS : DILATATION. No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . UTERUS : DILATATION, m ild . - 799 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655022 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655025 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655025 C ontinued on th e n ext page . . . . - 800 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655025 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE - 801 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655031 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . KIDNEYS : HYDRONEPHROSIS, BILATERAL, m i n i m a l . CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . 655031 C ontinued on th e n ext page . . . . - 802 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655031 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655032 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655032 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE C ontinued on th e n ext page . . . . - 803 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655032 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, HEART : CARDIOMYOPATHY, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655035 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : 655035 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 804 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655035 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS 655036 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655036 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE C ontinued on th e n ext page . . . . - 805 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655036 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, PARATHYROID GLANDS : NOT PRESENT. m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655045 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : 655045 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 806 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655045 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655062 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : PITUITARY GLAND : LARGE. No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, NOSE 655062 C ontinued on th e n ext page . . . . - 807 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655062 C ontinued from p re v io u s page H istopathology : LIVER : FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : PITUITARY GLAND 655065 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE - 808 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655068 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER 655071 A ccidentally K illed D u r a t i o n o f d o s i n g - d a y s : 19 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from n ecro p sy Gross Pathology : STOMACH : FLUID, RED. 6 5 5 0 7 1 C o n t i n u e d o n t h e n e x t p a g e ........ - 809 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655071 C ontinued from p re v io u s page Gross Pathology : ESOPHAGUS : PERFORATION, LARGE CLOTTING IN AREA OF PUNCTURE. SKIN : STAIN, RED, NOSE. No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . ESOPHAGUS : INFLAMMATION, SUBACUTE/CHRONIC, s e v e r e . LACERATION. BONE MARROW : HYPERPLASIA, GRANULOCYTIC, m i l d . 655071 C ontinued on th e n ext page . . . . - 810 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655071 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655072 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655072 C ontinued on th e n ext page .. - 811 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655072 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655074 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE - 812 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655079 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . HEART : CARDIOMYOPATHY, m i n i m a l . PARATHYROID GLANDS : NOT PRESENT. 655079 C ontinued on th e n ext page . . . . - 813 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655079 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE 655083 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655083 C ontinued on th e n ext page . . . . - 814 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655083 C ontinued from p re v io u s page H istopathology : LIVER : INFLAMMATION, KIDNEYS : INFLAMMATION, SUBACUTE/CHRONIC, SUBACUTE/CHRONIC, m inim al. m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655093 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : 655093 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 815 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655093 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655098 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . 655098 C ontinued on th e n ext page . . . . - 816 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655098 C ontinued from p re v io u s page H istopathology : HEART : CARDIOMYOPATHY, m i n i m a l . URINARY BLADDER : INFLAMMATION, SUBACUTE/CHRONIC, m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE 655099 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655099 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 817 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655099 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE - 818 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655101 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER - 819 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655107 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE - 820 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : I I 0 m g/kg/day Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655109 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : HYPERPLASIA, BILE DUCT, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS - 821 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655013 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655018 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : 655018 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C ontinued on th e n ext page . . . . - 822 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655018 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655028 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE - 823 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655033 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655040 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655040 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 824 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655040 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655041 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655041 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE C ontinued on th e n ext page . . . . - 825 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655041 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655044 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS - 826 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655051 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655057 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655057 C ontinued on th e n ext page . . . . - 827 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655057 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655086 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS - 828 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655089 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655090 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655090 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C ontinued on th e n ext page . . . . - 829 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655090 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655091 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655091 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE C ontinued on th e n ext page . . . . - 830 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655091 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . 655096 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE - 831 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : IV 1 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655108 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS - 832 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655017 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655020 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655020 C ontinued on th e n ext page . . . . - 833 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655020 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655021 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE - 834 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655029 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655034 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655034 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 835 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655034 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655038 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655038 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE C ontinued on th e n ext page . . . . - 836 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655038 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655039 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS - 837 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655042 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655050 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : 655050 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C ontinued on th e n ext page . . . . - 838 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655050 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655054 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . - 839 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655059 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655064 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655064 C ontinued on th e n ext page . . . . - 840 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655064 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655066 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS - 841 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655067 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655087 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655087 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C ontinued on th e n ext page . . . . - 842 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : VI 5 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655087 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . - 843 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655011 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655012 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655012 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 844 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655012 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655043 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE - 845 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655047 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655055 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655055 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C ontinued on th e n ext page . . . . - 846 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655055 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655056 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE - 847 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655058 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655060 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : 655060 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C ontinued on th e n ext page . . . . - 848 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655060 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655073 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS - 849 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655076 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655078 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655078 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 850 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655078 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655081 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE - 851 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655082 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655085 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655085 C ontinued on th e n ext page . . . . - 852 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655085 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655105 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655105 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE C ontinued on th e n ext page . . . . - 853 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : V III 25 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655105 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d KIDNEYS DuPont-9478 - 854 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655007 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : HYPERPLASIA, BILE DUCT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, HEART : CARDIOMYOPATHY, m i n i m a l . m inim al. 655007 C ontinued on th e n ext page . . . . - 855 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655007 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655010 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : 655010 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE C ontinued on th e n ext page . . . . - 856 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655010 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i l d . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER 655023 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . 6 5 5 0 2 3 C o n t i n u e d o n t h e n e x t p a g e ........ - 857 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655023 C ontinued from p re v io u s page H istopathology : KIDNEYS : HYDRONEPHROSIS, UNILATERAL, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655024 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655024 C ontinued on th e n ext page . . . . - 858 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655024 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655026 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 655026 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . C o n t i n u e d o n t h e n e x t p a g e ........ - 859 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655026 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655027 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655027 C ontinued on th e n ext page . . . . - 860 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655027 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655030 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : ANGIECTASIS, m in im a l. 655030 C ontinued on th e n ext page . . . . - 861 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655030 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i l d . HYDRONEPHROSIS, BILATERAL, m i n i m a l . 655037 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS - 862 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655046 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655049 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655049 C ontinued on th e n ext page . . . . - 863 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655049 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . HYPERPLASIA, BILE DUCT, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS 655052 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : 655052 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C o n t i n u e d o n t h e n e x t p a g e ........ - 864 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655052 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . ADRENAL GLANDS : MINERALIZATION, m in im a l. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE - 865 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655053 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, HEART : CARDIOMYOPATHY, m i n i m a l . m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : KIDNEYS, LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, 655053 C ontinued on th e n ext page - 866 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655053 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655061 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . 655061 C ontinued on th e n ext page . . . . - 867 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655061 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655063 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : 655063 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . SKELETAL MUSCLE : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . C o n t i n u e d o n t h e n e x t p a g e ........ - 868 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655063 C ontinued from p re v io u s page H istopathology : EYE(S) WITH OPTIC NERVE : OPTIC NERVE NOT PRESENT. FOLD/ROSETTE, RETINAL, m in im a l. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655075 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 6 5 5 0 7 5 C o n t i n u e d o n t h e n e x t p a g e ........ - 869 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655075 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655077 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655077 C ontinued on th e n ext page . . . . - 870 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655077 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . ANGIECTASIS, m in im a l. KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655084 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 6 5 5 0 8 4 C o n t i n u e d o n t h e n e x t p a g e ........ - 871 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655084 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : FATTY CHANGE, MEDIAN CLEFT, m i l d . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655088 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655088 C ontinued on th e n ext page . . . . - 872 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655088 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655092 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, 655092 C ontinued on th e n ext page . . . . - 873 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655092 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, KIDNEYS : INFLAMMATION, SUBACUTE/CHRONIC, PANCREAS : INFLAMMATION, SUBACUTE/CHRONIC, MAMMARY GLAND (FEMALE) : NOT PRESENT. m inim al. m inim al. m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE - 874 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655095 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : FATTY CHANGE, MEDIAN CLEFT, m i n i m a l . KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, 655095 C ontinued on th e n ext page . . . . - 875 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655095 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655097 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i n i m a l . 655097 C ontinued on th e n ext page . . . . - 876 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655097 C ontinued from p re v io u s page H istopathology : No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE JO IN T , STERNUM, BONE MARROW, NOSE 655100 Term inal S a c rific e K i l l e d on Day : 183 E x p o s u r e G r o u p : RECOV Animal is sig n e d o f f from necropsy Gross Pathology : 655100 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE C ontinued on th e n ext page . . . . - 877 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655100 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE NEPHROPATHY, m i l d . No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER 655103 Term inal S a c rific e K i l l e d on Day : 94 E x p o s u r e G r o u p : 90DAY Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE H istopathology : LIVER : HYPERPLASIA, BILE DUCT, m i n i m a l . 6 5 5 1 0 3 C o n t i n u e d o n t h e n e x t p a g e ........ - 878 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655103 C ontinued from p re v io u s page H istopathology : KIDNEYS : CHRONIC PROGRESSIVE PARATHYROID GLANDS : NOT PRESENT. MAMMARY GLAND (FEMALE) : NOT PRESENT. NEPHROPATHY, m inim al. No M i c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIA TIC NERVE, PITUITARY GLAND, THYROID GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , OVARIES, UTERUS, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, BONE MARROW, NOSE 655104 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : 655104 No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, C ontinued on th e n ext page . . . . - 879 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 I n d iv id u a l Animal L is tin g Showing anim al d a ta fo r in d iv id u a l STUDY : 1 3 6 9 0 / 2 4 6 9 1 / f e m Dose Group : X 125 m g /k g /d ay Sex: Fem ales anim als Animal Ref M icroscopic & M acroscopic Findings 655104 C ontinued from p re v io u s page Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE 655106 Term inal S a c rific e K ille d on Day : 175 E x p o s u r e G r o u p : SATEL Animal is sig n e d o f f from necropsy Gross Pathology : No M a c r o s c o p i c A b n o r m a l i t y O b s e r v e d : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SC IA T IC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SK IN , MAMMARY GLAND (FEMALE), OVARIES, UTERUS, VAGINA, URINARY BLADDER, FEMUR/KNEE J O IN T , STERNUM, NOSE - 880 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats DuPont-9478 APPENDIX O INDIVIDUAL ANIMAL MICROSCOPIC OBSERVATIONS LISTING INDIVIDUAL ANIMALS AFFECTED - 881 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | LESIONS | | | | TREATMENT | | | LESION INCIDENCE (NUMERIC) 1 | Males | i1 | |0 |1 |5 | 25 | 125 | | mg/kg | mg/kg | mg/kg | mg/kg | mg/kg| | I | III | V | VII | IX | | || | | DIGESTIVE | | | LIVER SYSTEM | NECROSIS, FOCAL. | | | | | | | | | | INFLAMMATION, SUBACUTE/CHRONIC. | | | | | | | | | | | | | || | || | || | | (20) | (10) || |654909 || | (10) | (10) | (20) | || || |654917 |654922 |654921| |654915 |654923 |654942| |654927 |654940 |654951| | |654958 |654957| | |654975 |654965| | |654973| | |654974| | |654976| | |654977| | |654990| |654903 |654908 |654907 |654922 |654921| |654909 |654913 |654911 |654923 |654951| |654910 |654932 |654916 |654930 |654955| |654915 |654938 |654917 |654940 |654957| |654924 |654941 |654959 |654952 |654965| |654925 |654946 |654961 |654958 |654973| |654927 |654947 |654967 |654989 |654974| |654928 |654960 |654980 |655001 |654976| |654929 |654995 |654998 |655006 |654977| |654936 |655005 |654978| |654949 |654979| |654950 |654983| | || Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 882 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | LESIONS | | | || | | DIGESTIVE SYSTEM | | | LIVER | INFLAMMATION, SUBACUTE/CHRONIC. | | | | | | | HYPERTROPHY, HEPATOCELLULAR. | | | | | | | | | | HYPERPLASIA, BILE DUCT. | | | | | | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) i1 | Males | 11 || |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg mg/kg| mg/kg | mg/kg| | I | III | V | VII | IX | || ||| || || ||| || ||| || ||| || ||| | (20) | (10) | (10) | (10) | (20) | |654953| |654956| |654972| |654987| |654992| |654993| |654994| || || || || || || || || || || |654915| |654927| |654943| |654949| |654992| || | |654985| | |654990| | |654991| | |654996| | |655003| ||| ||| | |654914| | |654921| | |654951| | |654955| | |654965| | |654979| | |654983| | |654986| | |654996| | |655003| | |654942| | |654973| | |654974| | |654977| | |654978| | |654990| || ||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 883 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | | LESION INCIDENCE (NUMERIC) 11 | Males | |0 |1 |5 | 25 | 125 | | mg/kg | mg/kg | mg/kg| mg/kg | mg/kg| | I | III | V | VII | IX | | |||| DIGESTIVE SYSTEM LIVER FATTY CHANGE, MEDIAN CLEFT. FATTY CHANGE, CENTRILOBULAR. | |||| | |||| | |||| | |||| | (20) | (10) | (10) | (10) | (20) | || || || || || |654909 |654984 |654907| 654958 |654951| |654910 |654995 |654911| |654929 |654972 || || | || || || || |655003| | |||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 884 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS DIGESTIVE SYSTEM PANCREAS NO ABNORMALITY DETECTED ATROPHY. | TREATMENT | | | LESION INCIDENCE (NUMERIC) 1 | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| | I | III | V | VII | IX | |||||| |||||| |||||| |||||| |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |654955| |654929| | | |654965| |654936| | | |654979| |654950| | | |654983| |654972| | | |654986| |654987| | | |654996| |654993| | | |655003| |654928| | | |654921| |654953| | | |654951| 111111 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 885 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | LESIONS | | | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) ll | Males | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| |1 | III | V | VII | IX | |||||| | | DIGESTIVE | | | ESOPHAGUS SYSTEM | NO ABNORMALITY DETECTED | | | | | | | | | | || || || || | (10) | || || |654903| |654925| |s5492s| |654929| |s5493s| |654950| |654953| |654972| |s5498v| |654993| || | | | | ||| | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | | | | | | | | | || || || || | (10) | || || |654914| |65492l| |65495l| |654955| |654965| |654979| |654983| |s5498s| |s5499s| |655003| || DuPont-9478 - 886 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | LESIONS | | | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) ll | Males | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| |1 | III | V | VII | IX | |||||| | | DIGESTIVE | | | STOMACH SYSTEM | NO ABNORMALITY DETECTED | | | | | | | | | | || || || || | (10) | || || |654903| |654925| |s5492s| |654929| |s5493s| |654950| |654953| |654972| |s5498v| |654993| || | | | | ||| | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | | | | | | | | | || || || || | (10) | || || |654914| |65492l| |65495l| |654955| |654965| |654979| |654983| |s5498s| |s5499s| |655003| || DuPont-9478 - 887 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | LESIONS | | | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) ll | Males | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| |1 | III | V | VII | IX | |||||| | | DIGESTIVE | | | DUODENUM SYSTEM | NO ABNORMALITY DETECTED | | | | | | | | | | || || || || | (10) | || || |654903| |654925| |s5492s| |654929| |s5493s| |654950| |654953| |654972| |s5498v| |654993| || | | | | ||| | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | | | | | | | | | || || || || | (10) | || || |654914| |65492l| |65495l| |654955| |654965| |654979| |654983| |s5498s| |s5499s| |655003| || DuPont-9478 - 888 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| DIGESTIVE SYSTEM JEJUNUM NO ABNORMALITY DETECTED (10) 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 (9) 654921 654951 654955 654965 654979 654983 654986 654996 655003 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 889 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | LESIONS | | | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) i1 | Males | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| |1 | III | V | VII | IX | |||||| | | DIGESTIVE | | | ILEUM SYSTEM | NO ABNORMALITY DETECTED | | | | | | | | | | || || || || | (10) | || || |654903| |654925| |s5492s| |654929| |s5493s| |654950| |654953| |654972| |s5498v| |654993| || | | | | ||| | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | | | | | | | | | || || || || | (9) | || || |654921| |65495l| |654955| |654965| |654979| |654983| |s5498s| |s5499s| |655003| || || DuPont-9478 - 890 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | LESIONS | | | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) i1 | Males | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| |1 | III | V | VII | IX | |||||| | | DIGESTIVE | | | CECUM SYSTEM | NO ABNORMALITY DETECTED | | | | | | | | | | || || || || | (10) | || || |654903| |654925| |s5492s| |654929| |s5493s| |654950| |654953| |654972| |s5498v| |654993| || | | | | ||| | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | | | | | | | | | || || || || | (9) | || || |654921| |65495l| |654955| |654965| |654979| |654983| |s5498s| |s5499s| |655003| || || DuPont-9478 - 891 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | LESIONS | | | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) ll | Males | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| |1 | III | V | VII | IX | |||||| | | DIGESTIVE | | | COLON SYSTEM | NO ABNORMALITY DETECTED | | | | | | | | | | || || || || | (10) | || || |654903| |654925| |s5492s| |654929| |s5493s| |654950| |654953| |654972| |s5498v| |654993| || | | | | ||| | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | | | | | | | | | || || || || | (10) | || || |654914| |65492l| |65495l| |654955| |654965| |654979| |654983| |s5498s| |s5499s| |655003| || DuPont-9478 - 892 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| DIGESTIVE SYSTEM RECTUM NO ABNORMALITY DETECTED (10) 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 (9) 654921 654951 654955 654965 654979 654983 654986 654996 655003 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 893 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS DIGESTIVE SYSTEM SALIVARY GLANDS NO ABNORMALITY DETECTED | TREATMENT | | | LESION INCIDENCE (NUMERIC) 1 | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| | I | III | V | VII | IX | |||||| |||||| |||||| |||||| |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |654921| |654928| | | |654951| |654929| | | |654955| |654936| | | |654965| |654950| | | |654979| |654953| | | |654983| |654972| | | |654986| |654987| | | |654996| |654993| | | |655003| 111111 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 894 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | | LESIONS | | | || | | URINARY SYSTEM | | | KIDNEYS 11 | NO ABNORMALITY DETECTED | | | | | | | | | CHRONIC PROGRESSIVE NEPHROPATHY. | | | | | | | | | | | | | | LESION INCIDENCE (NUMERIC) | |------------------------------------------ 1 | Males | | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | |||||| || ||| || ||| || ||| || ||| | ( 2 0 ) | (10) | (10) | (10) | (20) | 11 11 || || |654903| 654932| 654907|654922 |654942| |654909| 654938| 654967| |654973| |654910| 654941| 655005| |654978| |654925| 654960| ||| |654929| ||| |654936| ||| |654956| ||| |654987| ||| |654994| ||| |654915| 654908| 654911|654923 |654914| |654924| 654913| 654916|654930 |654921| |654927| 654946| 654917|654958 |654951| |654928| 654947| 654959|654989 |654955| |654943| 654984| 654961| |654957| |654949| 654995| 654980| |654965| |654950| 654998| |654974| |654953| |654972| |654992| |654993| || || | |654976| | |654979| | |654986| | |654990| | |654991| | |654996| || ||| Figure in parentheses is number of animals m i c r o scopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 895 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | LESIONS | | | | | | URINARY SYSTEM | | | KIDNEYS | PIGMENT, TUBULAR. | HYPERTROPHY, TUBULAR. | | | | | | | | | | HYPERPLASIA, TRANSITIONAL CELL. | HYDRONEPHROSIS, UNILATERAL. | | HYDRONEPHROSIS, BILATERAL. | CYST. | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) |- | 11 | M a l e s ||| |0 |1 5 | 25 | 125 | | mg/kg| mg/kg mg/kg | mg/kg | mg/kg| |I | III V | VII | IX | || ||| || || ||| || ||| || ||| | ||| (20) | | | | | | | | | | | | | | | | | | (10) || | | | | | | | | | | | | | | | | | (10) ||| | (10) | (20) | || || | |654979| |654923 |654914| |654930 |654921| |654940 |654951| |654952 |654955| |654958 |654965| |654975 |654979| |654989 |654983| |655001 |654986| |655006 |654996| | |655003| | |654977| | |654955| | |654977| | |654974| |655006 |654985| || ||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 896 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| URINARY SYSTEM URINARY BLADDER NO ABNORMALITY DETECTED (10) 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 (1) 654998 (10) 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 897 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. | TREATMENT | | | LESION INCIDENCE (NUMERIC) 1 | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| | I | III | V | VII | IX | |||||| |||||| |||||| |||||| |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |654921| |654928| | | |654951| |654929| | | |654955| |654936| | | |654965| |654950| | | |654979| |654972| | | |654986| |654987| | | |654996| |654993| | | |655003| |654953| | | |654983| 111111 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 898 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| RESPIRATORY SYSTEM TRACHEA NO ABNORMALITY DETECTED (10) 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 (10) 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 899 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | | LESIONS | | | || | | RESPIRATORY SYSTEM | | | PHARYNX/LARYNX | NO ABNORMALITY DETECTED | | | | | | | | | | | LESION INCIDENCE (NUMERIC) |------------------------- | Males | | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | |||||| |||||| |||||| |||||| |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |654921| |654928| | | |654951| |654929| | | |654955| |654936| | | |654965| |654950| | | |654979| |654953| | | |654983| |654972| | | |654986| |654987| | | |654996| |654993| | | |655003| |||||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 900 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | | LESIONS | | | | | | RESPIRATORY | | | NOSE SYSTEM | NO ABNORMALITY DETECTED | | | | | | | | | | | | | | | | | | | | ODONTODYSPLASIA. | INFLAMMATION, SUBACUTE/CHRONIC. | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) | |------------------------- --------------- 1 | Males | --------------- 1 |0 |1 |5 25 | 125 | | mg/kg| mg/kg| mg/kg mg/kg| mg/kg| | I | III | V | VII | IX | ||| || li ||| | ||| | ||| | ||| | | (20) | (10) | (10) | (10) | (20) | || || || || |654903| 654908| 654907 654922| 654914| |654909| 654913| 654911 654923| 654942| |654910| 654932| 654916 654930| 654955| |654915| 654938| 654917 654940| 654957| |654924| 654941| 654959 654952| 654974| |654925| 654946| 654961 654958| 654977| |654927| 654947| 654967 654975| 654978| |654928| 654960| 654980 654989| 654979| |654929| 654984| 654998 655001| 654983| |654936| 654995| 655005 655006| 654990| |654943| |654949| |654950| |654953| |654956| |654972| |654987| |654992| |654993| |654994| || || | | | | | | | | | | | | 654991| 655003| | | | | | | | | 654985| 654985| ||| | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 901 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | |||| RESPIRATORY SYSTEM NOSE DEGENERATION, AMELOBLASTS. (20) (10) (10) (10) (20) 654921 654951 654965 654973 654976 654986 654996 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 902 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| CARDIOVASCULAR SYSTEM HEART NO ABNORMALITY DETECTED CARDIOMYOPATHY. |||| | (10) | || || ||| ||| |654903| || |654925| || |654929| || |654972| || |654993| || |654928| || |654936| || |654950| || |654953| || |654987| || |||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified || | (10) | || || |654914| |654921| |654965| |654986| |655003| |654951| |654955| |654979| |654983| |654996| || DuPont-9478 - 903 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| CARDIOVASCULAR SYSTEM 1 | AORTA | NO ABNORMALITY DETECTED | | | | | | | | | | 11 | (1 0 ) | || || |654903| |654925| |654928| |654929| |654936| |654950| |654953| |654972| |654987| |654993| || 1 | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 1 | | | | | | | | | | | | | (10) | || || |654914| |654921| |654951| |654955| |654965| |654979| |654983| |654986| |654996| |655003| || DuPont-9478 - 904 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED (10) 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 (10) 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 905 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | | LESIONS | | | || | | LYMPHATIC AND | | | THYMUS HEMATOPOIETIC SYSTEM | NO ABNORMALITY DETECTED | | | | | | | | | | | | | | | | | | | | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) | |------------------------- --------------- 1 | Males | --------------- 1 | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | |||||| 11 |||||| |||||| |||||| |||||| | (20) | || || ||| ||| | (20) | || || |654903| | | |654914| |654909| | | |654921| |654910| | | |654942| |654915| | | |654951| |654924| | | |654955| |654925| | | |654957| |654927| | | |654965| |654928| | | |654973| |654929| | | |654974| |654936| | | |654976| |654943| | | |654977| |654949| | | |654978| |654950| | | |654979| |654953| | | |654983| |654956| | | |654985| |654972| | | |654986| |654987| | | |654990| |654992| | | |654991| |654993| | | |654996| |654994| | | |655003| |||||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 906 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| LYMPHATIC AND HEMATOPOIETIC SYSTEM MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED (10) 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 (10) 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 907 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| LYMPHATIC AND HEMATOPOIETIC SYSTEM MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED (10) 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 (9) 654921 654951 654955 654965 654979 654983 654986 654996 655003 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 908 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| LYMPHATIC AND HEMATOPOIETIC SYSTEM | | BONE MARROW | NO ABNORMALITY DETECTED | | | | | | | | | | || | (10) | || || |654903| |654925| |654928| |654929| |654936| |654950| |654953| |654972| |654987| |654993| || | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | || | (10) | || || |654914| |654921| |654951| |654955| |654965| |654979| |654983| |654986| |654996| |655003| || DuPont-9478 - 909 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| ENDOCRINE SYSTEM PITUITARY GLAND NO ABNORMALITY DETECTED CYST. (9) 654903 654928 654929 654936 654950 654972 654987 654993 654953 (10) 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 910 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | | LESIONS | | | || | | ENDOCRINE SYSTEM | | | THYROID GLAND | NO ABNORMALITY DETECTED | | | | | | | | | | ALTERATION, COLLOID. | | | | | | | | | | | | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) | |------------------------- --------------- 1 | Males | --------------- 1 |0 |1 |5 25 | 125 | | mg/kg| mg/kg| mg/kg mg/kg| mg/kg| | I | III | V | VII | IX | ||| || li ||| | ||| | ||| | ||| | (20) | (10) | (10) | (10) || || || |654903| 654960| 654916 | | (20) | || 654955| |654924| 654984| 655003| |654925| | |654936| | |654949| | |654950| | |654953| | |654972| | |654992| | |654993| | |654909| 654908| 654907 | | | | | | | | 654922| 654914| |654910| 654913| 654911 654923| 654921| |654915| 654932| 654917 654930| 654942| |654927| 654938| 654959 654940| 654951| |654928| 654941| 654961 654952| 654957| |654929| 654946| 654967 654958| 654965| |654943| 654947| 654980 654975| 654973| |654956| 654995| 654998 654989| 654974| |654987| |654994| || || |6 5 5005 | | | 655001| 654976| 655006| 654977| 654978| 654979| ||| | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 911 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) 1 | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | |||| ENDOCRINE SYSTEM THYROID GLAND ALTERATION, COLLOID. (20) (10) (10) (10) (20) 654983 654985 654986 654990 654991 654996 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 912 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| ENDOCRINE SYSTEM 1 | PARATHYROID GLANDS | NO ABNORMALITY DETECTED | | | | | | | | | 11 | (9) | || || |654903| |654925| |654928| |654929| |654936| |654953| |654972| |654987| |654993| || 1 | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 1 | | | | | | | | | | | | (9) | || || |654914| |654921| |654951| |654955| |654965| |654979| |654983| |654986| |655003| || DuPont-9478 - 913 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS ENDOCRINE SYSTEM ADRENAL GLANDS NO ABNORMALITY DETECTED | TREATMENT | | | LESION INCIDENCE (NUMERIC) 1 | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| | I | III | V | VII | IX | |||||| |||||| |||||| |||||| |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |654921| |654928| | | |654951| |654929| | | |654955| |654936| | | |654965| |654950| | | |654979| |654953| | | |654983| |654972| | | |654986| |654987| | | |654996| |654993| | | |655003| 111111 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 914 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| NERVOUS SYSTEM 1 | BRAIN | NO ABNORMALITY DETECTED | | | | | | | | | | 11 | (1 0 ) | || || |654903| |654925| |654928| |654929| |654936| |654950| |654953| |654972| |654987| |654993| || 1 | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 1 | | | | | | | | | | | | | (10) | || || |654914| |654921| |654951| |654955| |654965| |654979| |654983| |654986| |654996| |655003| || DuPont-9478 - 915 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS NERVOUS SYSTEM SPINAL CORD NO ABNORMALITY DETECTED | TREATMENT | | | LESION INCIDENCE (NUMERIC) 1 | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| | I | III | V | VII | IX | |||||| |||||| |||||| |||||| |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |654921| |654928| | | |654951| |654929| | | |654955| |654936| | | |654965| |654950| | | |654979| |654953| | | |654983| |654972| | | |654986| |654987| | | |654996| |654993| | | |655003| 111111 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 916 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS NERVOUS SYSTEM SCIATIC NERVE NO ABNORMALITY DETECTED | TREATMENT | | | LESION INCIDENCE (NUMERIC) 1 | Males |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| | I | III | V | VII | IX | |||||| |||||| |||||| |||||| |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |654921| |654928| | | |654951| |654929| | | |654955| |654936| | | |654965| |654950| | | |654979| |654953| | | |654983| |654972| | | |654986| |654987| | | |654996| |654993| | | |655003| 111111 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 917 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | | LESIONS | | | || | | MUSCULAR AND SKELETAL SYSTEM | | | SKELETAL MUSCLE | NO ABNORMALITY DETECTED | | | | | | | | | | | LESION INCIDENCE (NUMERIC) |------------------------- | Males | | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | |||||| |||||| |||||| |||||| |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |654921| |654928| | | |654951| |654929| | | |654955| |654936| | | |654965| |654950| | | |654979| |654953| | | |654983| |654972| | | |654986| |654987| | | |654996| |654993| | | |655003| |||||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 918 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| MUSCULAR AND SKELETAL SYSTEM FEMUR/KNEE JOINT NO ABNORMALITY DETECTED (10) 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 (10) 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 919 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | | LESIONS | | | || | | MUSCULAR AND SKELETAL SYSTEM | | | STERNUM | NO ABNORMALITY DETECTED | | | | | | | | | | | LESION INCIDENCE (NUMERIC) |------------------------- | Males | | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | I | III | V | VII | IX | |||||| |||||| |||||| |||||| |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |654921| |654928| | | |654951| |654929| | | |654955| |654936| | | |654965| |654950| | | |654979| |654953| | | |654983| |654972| | | |654986| |654987| | | |654996| |654993| | | |655003| |||||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 920 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | 1 LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | 1|||| REPRODUCTIVE SYSTEM TESTES NO ABNORMALITY DETECTED DILATATION, SEMINIFEROUS TUBULES, UNILATERAL. DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, UNILATERAL. DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL. || | (10) | || || |654903| |654925| |654928| |654929| |654953| |654972| |654987| |654993| || || || 11 654936 654950 || | (1) | || || || || || || || || || || || |654980| |654980| 11 || | (10) | || || |654914| |654921| |654951| |654955| |654965| |654979| |654986| |654996| |655003| || |654983| 11 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 921 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | LESIONS | | | | TREATMENT | | | | LESION INCIDENCE (NUMERIC) | 11 i1 | Males | -------- | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| | I | III | V | VII | IX | |||||| | | REPRODUCTIVE | | | EPIDIDYMIDES SYSTEM | NO ABNORMALITY DETECTED | | | | | | | | | OLIGOSPERMIA/GERM CELL DEBRIS, UNILATERAL. | OLIGOSPERMIA/GERM CELL DEBRIS, BILATERAL. | || || || || | (10) | || || |654903| |654925| |654928| |654929| |654950| |654953| |654972| |654987| |654993| || |654936| || | | | | ||| | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | | | | | | | | | | || || || || | (10) | || || |654914| |654921| |654951| |654955| |654965| |654979| |654986| |654996| |655003| |654983| || || DuPont-9478 - 922 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| REPRODUCTIVE SYSTEM PROSTATE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |654921| |654929| | | |654951| |654936| | | |654955| |654950| | | |654965| |654972| | | |654979| |654987| | | |654983| | | | | |654986| | | | | |654996| | | | | |655003| |654928| |||| 654953 654993 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 923 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | | LESION INCIDENCE (NUMERIC) | | Males | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | I | III | V | VII | IX | ||||| REPRODUCTIVE SYSTEM SEMINAL VESICLES NO ABNORMALITY DETECTED (10) 654903 654925 654928 654929 654936 654950 654953 654972 654987 654993 (10) 654914 654921 654951 654955 654965 654979 654983 654986 654996 655003 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 924 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESION INCIDENCE (NUMERIC) Males LESIONS | TREATMENT | I | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| |I | III | V | VII | IX | |||||| CUTANEOUS SYSTEM SKIN NO ABNORMALITY DETECTED ||| ||| ||| ||| | (10) | (1) | || || || |654903| 654908| |654925| |s5492s| |654929| |s5493s| |654950| |654953| |654972| |s5498v| |654993| | | | | | | | | | ||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | ||| | | | | | | | | | | | || || || || | (10) | || || |654914| 65492l| |65495l| |654955| |654965| |654979| |654983| |s5498s| |s5499s| |655003| || DuPont-9478 - 925 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Male Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS ]CIAL SENSES SYSTEM ](S) W I T H O P T I C N E R V E NO ABNORMALITY DETECTED OPTIC NERVE NOT PRESENT. FOLD/ROSETTE, RETINAL. ADHESION, RETINAL. LESION INCIDENCE (NUMERIC) Males | TREATMENT | I | |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| |I | III | V | VII | IX | |||||| |||||| |||||| |||||| |||||| | (10) | || || ||| ||| | (10) | || || |654903| | | |654914| |654925| | | |65492l| |s5492s| | | |65495l| |654929| | | |654955| |s5493s| | | |654965| |654953| | | |654979| |s5498v| | | |654983| |654993| | | |s5498s| | | | | |s5499s| | | | | |655003| |654925| | | |654965| |654928| |||| |654953| |||| |654950| |||| |654972| |||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 926 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | | LESIONS | | | || | | LIVER | NO ABNORMALITY DETECTED | | | | NECROSIS, FOCAL. | INFLAMMATION, SUBACUTE/CHRONIC. | | | | | | | | | | | | | HYPERPLASIA, BILE DUCT. | | | | FATTY CHANGE, MEDIAN CLEFT. | | | | TREATMENT | | | | L E S I O N I N C I D E N C E (Animal #) | |------------------------- --------------- 1 | Females | --------------- 1 | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | |||||| ii |||||| | (20) | || || ||| ||| | (20) | || || |655035| | | |655010| |655068| | | |655097| |655098| | | |655100| |655101| |||| |655009| |||| |655009| | | |655023| |655016| | | |655026| |655019| | | |655037| |655025| | | |655049| |655031| | | |655052| |655032| | | |655053| |655036| | | |655061| |655071| | | |655063| |655072| | | |655075| |655079| | | |655077| |655083| | | |655088| |655099| | | |655092| |655107| |||| |655031| | | |655007| |655079| | | |655026| |655109| | | |655049| | | | | |655103| |655015| | | |655084| |655016| | | |655095| |655025| |||| |||||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 927 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS LIVER FATTY CHANGE, MEDIAN CLEFT. ANGIECTASIS. L E S I O N I N C I D E N C E (Animal #) Females | TREATMENT | | | |0 |1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg | II | IV | VI | VIII | X ||||| ||||| | (20) | | | | (20) |655062| ||| | | | | |655030 | | | | |655077 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 928 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | | LESIONS | | | || | | KIDNEYS | NO ABNORMALITY DETECTED | | | | | | | | | | | CHRONIC PROGRESSIVE NEPHROPATHY. | | | | | | | | | | | | | | | LESION INCIDENCE (Animal #) | |------------------------------------------ 1 | Females | ------------------------------------------------------------- 1 | TREATMENT | | | 0 | 1 | 5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg| | II | IV | VI | VIII | X | | |||||| 11 | || | ( 2 0 ) | (10) | (10) | (10) | (20) | || || || |655009 |655013 |655020 |655012 |655037| |655016 |655040 |655034 |655047 |655049| |655025 |655041 |655038 |655055 |655053| |655032 |655044 |655039 |655058 | | |655035 |655086 |655042 |655073 | | |655036 |655089 |655066 |655085 | | |655071 |655090 |655067 |655105 | | |655072 |655108 || |655079 || |655107 || |655109 || |655015 |655033 |655029 |655011 |655007| |655019 |655091 |655054 |655076 |655010| |655031 |655087 |655078 |655026| |655062 |655030| |655068 |655052| |655099 |655061| |655101 |655063| | |655075| | |655077| | |655084| | |655088| | |655095| | |655097| | |655100| | || Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified - 929 - DuPont-9478 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS L E S I O N I N C I D E N C E (Animal #) Females | TREATMENT | | | |0 |1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X | ||| KIDNEYS CHRONIC PROGRESSIVE NEPHROPATHY. INFLAMMATION, SUBACUTE/CHRONIC. HYDRONEPHROSIS, UNILATERAL. HYDRONEPHROSIS, BILATERAL. | ( 2 0 ) | ( 1 0 ) | (10) ||| |655083|655091 | |655098| | || |655031| ii | |i | (10) | | | | |1 | (20) |655103 |655092 | |655023 |655030 i Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 930 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | LUNGS | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 931 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS HEART NO ABNORMALITY DETECTED CARDIOMYOPATHY. L E S I O N I N C I D E N C E (Animal #) Females | TREATMENT | I | |0 |1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg | II | IV | VI | VIII | X ||||| ||||| ||| (11) ||| ||| ||| | (10) |655016| | | |655023 |655036| | | |655026 |65507l| | | |655052 |655083| | | |655063 |655099| | | |655092 |655107| | | |655095 | | | | |655097 | | | | |655103 |655025| | | |655007 655031 | | |655053 |655032| ||| |655079| ||| |655098| ||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 932 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS SKELETAL MUSCLE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. L E S I O N I N C I D E N C E (Animal #) Females | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| ||||| ||| (11) ||| ||| ||| | (10) || |655016| | | |655007 |655025| | | |655023 |655031| | | |655026 |655032| | | |655052 |655036| | | |655053 |655071| | | |655092 |655079| | | |655095 |655083| | | |655097 |655098| | | |655103 |655099| ||| |655107| ||| | | | | |655063 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 933 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | SPLEEN | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 934 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | AORTA | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 935 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | BRAIN | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 936 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | SPINAL CORD | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 937 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | STOMACH | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 938 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | DUODENUM | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 939 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | JEJUNUM | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 940 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | ILEUM | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 941 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS PANCREAS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. L E S I O N I N C I D E N C E (Animal #) Females | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| ||||| | (11) | || || ||| ||| | (10) || |655016| | | |655007 |655025| | | |655023 |655031| | | |655026 |655032| | | |655052 |655036| | | |655053 |655071| | | |655063 |655079| | | |655095 |655083| | | |655097 |655098| | | |655103 |655099| ||| |655107| ||| | | | | |655092 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 942 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | CECUM | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 943 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | COLON | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 944 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | RECTUM | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 945 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | MESENTERIC LYMPH NODE | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 946 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | SALIVARY GLANDS | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 947 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | MANDIBULAR LYMPH NODE | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 948 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | THYMUS | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 949 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | LESIONS | | | | TREATMENT | | | | L E S I O N I N C I D E N C E (Animal #) | i1 | Females |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| | 11 | IV | VI | VIII | X | |||||| | | ADRENAL GLANDS | NO ABNORMALITY DETECTED | | | | | | | | | | | MINERALIZATION. | || ||| (11) ||| |655016| |655025| |65503l| |655032| |655036| |65507l| |655079| |655083| |655098| |655099| |655107| || || | ||| | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | ||| | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655053| |655063| |655092| |655095| |655097| |655103| || || |655052| || DuPont-9478 - 950 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | SCIATIC NERVE | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 951 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | LESIONS | | | | TREATMENT | | | | L E S I O N I N C I D E N C E (Animal #) | i1 | Females |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| | II | IV | VI | VIII | X | |||||| | | PITUITARY GLAND | NO ABNORMALITY DETECTED | | | | | | | | | | | | || | (12) | || || |655016| |655025| |65503l| |655032| |655036| |655062| |65507l| |655079| |655083| |655098| |655099| |655107| || | ||| | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | ||| | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || || DuPont-9478 - 952 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | THYROID GLAND | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 953 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS PARATHYROID GLANDS NO ABNORMALITY DETECTED L E S I O N I N C I D E N C E (Animal #) Females | TREATMENT | | | |0 |1 |5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| ||||| | (9) | || || ||| ||| | (9) || |655016| | | |655007 |655025| | | |655023 |655031| | | |655026 |655032| | | |655052 |655071| | | |655053 |655083| | | |655063 |655098| | | |655092 |655099| | | |655095 |655107| | | |655097 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 954 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | TRACHEA | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 955 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS ESOPHAGUS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. LACERATION. L E S I O N I N C I D E N C E (Animal #) Females | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| ||||| ||| (11) ||| ||| ||| | (10) || |655016| | | |655007 |655025| | | |655023 |655031| | | |655026 |655032| | | |655052 |655036| | | |655053 |655079| | | |655063 |655083| | | |655092 |655098| | | |655095 |655099| | | |655097 |655107| | | |655103 |655071| ||| |655071| ||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 956 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | PHARYNX/LARYNX | NO ABNORMALITY DETECTED | | | | | | | | | | | || | (1 1 ) | || || |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 957 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | L E S I O N I N C I D E N C E (Animal #) |------------------------- | Females LESIONS | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED OPTIC NERVE NOT PRESENT. FOLD/ROSETTE, RETINAL. || | (11) | || || |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || || || | ||| | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | ||| | | | | | | | | | | | | | | | | (10) || |655007 |655023 |655026 |655052 |655053 |655092 |655095 |655097 |655103 | | |655063 |655063 | DuPont-9478 - 958 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | SKIN | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 959 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS MAMMARY GLAND (FEMALE) NO ABNORMALITY DETECTED L E S I O N I N C I D E N C E (Animal #) Females | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| ||||| ||| (11) ||| ||| ||| | (8) || |655016| | | |655007 |655025| | | |655023 |655031| | | |655026 |655032| | | |655052 |655036| | | |655053 |655071| | | |655063 |655079| | | |655095 |655083| | | |655097 |655098| ||| |655099| ||| |655107| ||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 960 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | OVARIES | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 961 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions | | | | LESIONS | | | | TREATMENT | | | | L E S I O N I N C I D E N C E (Animal #) | i1 | Females |0 |1 |5 | 25 | 125 | | mg/kg| mg/kg| mg/kg| mg/kg | mg/kg| | II | IV | VI | VIII | X | |||||| | | UTERUS | NO ABNORMALITY DETECTED | | | | | | | | | | | DILATATION. | || | (12) | || || |655016| |655025| |65503l| |655032| |655036| |65507l| |655079| |655083| |655098| |655099| |655107| |655019| || | ||| | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | ||| | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || || DuPont-9478 - 962 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS URINARY BLADDER NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. L E S I O N I N C I D E N C E (Animal #) Females | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| ||||| ||| (11) ||| ||| ||| | (10) || |655016| | | |655007 |655025| | | |655023 |655031| | | |655026 |655032| | | |655052 |655036| | | |655053 |655071| | | |655063 |655079| | | |655092 |655083| | | |655095 |655099| | | |655097 |655107| | | |655103 |655098| ||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 963 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | FEMUR/KNEE JOINT | NO ABNORMALITY DETECTED | | | | | | | | | | | || | (1 1 ) | || || |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 964 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | STERNUM | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 965 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS BONE MARROW NO ABNORMALITY DETECTED HYPERPLASIA, GRANULOCYTIC. L E S I O N I N C I D E N C E (Animal #) Females | TREATMENT | | | | 0 | 1 | 5 | 25 | 125 | mg/kg| mg/kg| mg/kg| mg/kg| mg/kg | II | IV | VI | VIII | X ||||| ||||| ||| (11) ||| ||| ||| | (10) || |655016| | | |655007 |655025| | | |655023 |655031| | | |655026 |655032| | | |655052 |655036| | | |655053 |655079| | | |655063 |655083| | | |655092 |655098| | | |655095 |655099| | | |655097 |655107| | | |655103 |655071| ||| Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified DuPont-9478 - 966 - 8-2 Telomer B Alcohol: Subchronic Toxicity 90-Day Oral Gavage Study in Rats Microscopic Observations in Female Rats Listing Individual Animals Affected Neoplastic and Non-Neoplastic Lesions LESIONS | TREATMENT | | L E S I O N I N C I D E N C E (Animal #) Females 0 mg/kg II 1 mg/kg IV 5 mg/kg VI 25 mg/kg VIII 125 mg/kg X | | NOSE | NO ABNORMALITY DETECTED | | | | | | | | | | | || ||| (1 1 ) ||| |655016| |655025| |655031| |655032| |655036| |655071| |655079| |655083| |655098| |655099| |655107| || | | | | | | | | | | | | | | Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified | | | | | | | | | | | | | | || | (10) | || || |655007| |655023| |655026| |655052| |655053| |655063| |655092| |655095| |655097| |655103| || || DuPont-9478 - 967 -