Document zQ9xZJvO7pkOBYwpEnkxMRjY6

TRADE SECRET AR226-3084 Study Title H-23004: ORAL APPROXIMATE LETHAL DOSE (ALD) IN RATS LABORATORY PROJECT ID: HL-1997-01291 AUTHOR: Tracy A. Filliben STUDY COMPLETED ON: December 30,1997 PERFORMING LABORATORY: E. L du Font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 WORK REQUEST NUMBER: HBR 1 Page 1 of 8 CompaniSaniteed. Does not eontainTSGACBI CERTIFICATION Study Director: ffTracy Issued by^s^^UU Q. . Q^'liUjM^________ A. Filliben Toxicology Associate /Z/g&/?7 Date -2- Company Sanitized. Does not eontain TSCA CBI STUDY INFORMATION Substance Testewlfff^f \ Synonyms/Codes: H-23004 Haskell Number: 23004 Submitter's Notebook Numberfs Known Impurities Physical Characteristics: Off-white liquid Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. Sponsor: E. I. du Font de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: November 25,1997 / (see report cover page) In-Life Initiated/Completed: November 25,1997 / December 19,1997 -3- D08S not eorti STUDY PERSONNEL Manager: Judith C. Stadler, Ph.D. Study Director: Tracy A. FiUiben Primary Technician: Tracy A. FiUiben Toxicology Report Preparation(s): Maryanne M. Wilford, B.A. Laboratory Veterinarian: Charles E. Cover, V.M.D. -4- Conapany Sanitized. Doee nQt eontain TSCA CB6 SUMMARY H-23004 was administered as a single oral dose by intragastdc intubation to male rats. Following dosing, the rats were weighed and observed for mortality and clinical signs of toxicity over a 14-day observation period. No deaths, clinical signs of toxicity, or weight losses were observed during the study. Under the conditions of this study, the ALD for H-23004 was greater than 11,000 mg/kg of body weight. This substance is considered to be very low in toxicity (ALD greater than 5000 mg/kg) when administered as a single oral dose to male rats. -5- Company Sanitized. Does not contain TSCA CB6 INTRODUCTION The purpose of this test was to determine an approximate lethal dose (ALD) ofH-23004 when administered as a single oral dose to male rats. The ALD was defined as the lowest dose administered which caused death either on the day of dosing or within 14 days post exposure. MATERIALS AND METHODS A. Animal Husbandry Male Cri:CD(SD)BR rats were received from Charles River Laboratories. Rats were housed singly in suspended, stainless steel, wire-mesh cages. Each rat was assigned a unique identification number which was recorded on a card affixed to the cage. The rats were tailmarked, using a water-insoluble marker, with the last 3 digits of the animal number. Purina Certified Rodent Chow #5002 and water were available ad libitum. HaskeJj-Laburalury has an animal health mumtormg-programr This-program-is-monitoredand-- administered by the Laboratory Veterinarian. Water samples are periodically analyzed for total bacterial counts and for the presence ofcolifonns, lead, and other contaminants. Additionally, samples from freshly washed cages and cage racks are periodically analyzed to ensure adequate sanitation by the cagewashers. Data from this program are maintained separately from study records. Animal feed is certified by the manufacturer to meet specified nutritional requirements and to be free of a list of specified contaminants. On the basis of these analyses, there is no evidence suggesting that contaminants were present in the feed or water in amounts which may have interfered with the results of this study. Rats were quarantined, weighed, and observed for general health for approximately one week. Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of23C 1C and relative humidity of 50% 10%. Excursions outside these ranges were of small magnitude and/or brief duration and did not adversely affect the validity of the study. B. Protocol The test substance was administered neat to 1 rat per dose rate by intragastric intubation. The doses were calculated based on the test substance density of 1000 mg/mL and body weights collected on the day of dosing. Dose rates administered ranged from 2300 to 11,000 mg/kg of body weight in increments of approximately 50%. Additionally, 1 rat was dosed at 670 mg/kg. The dosing day was test day 1; postexposure day 14 was test day 15. Following administration of the test substance, rats were observed for clinical signs oftoxicity. -6. Gonte.nTSCACBB Company Sanitized. Does not The rats were weighed and observed at least 2 times a week throughout the 14-day observation period. Observations for mortality and signs of illness, injury, or abnormal behavior were made daily throughout the study. Pathological examinations of test animals were not performed. RESULTS AND DISCUSSION A. Dosage and Mortality Data The dosage regimen and the mortality resulting over the 15-day test period are detailed below. No deaths occurred during the study. Dosage (mg/kg) 670 Dose Volume (mL) 0.17 Density (mg/mL) -10QO Initial Body Weight (g) 255 Mortality No 2300 0.60 1000 259 No 3400 0.92 1000 272 No A 5000 1.3 1000 266 No y 7500 1.9 1000 258 No 11,000 3.0 1000 275 No B. Clinical Signs and Body Weights No clinical signs of toxicity or body weight losses were observed during the study. CONCLUSIONS Under the conditions of this study, the ALD for H-23004 was greater than 11,000 mg/kg of body weight. This substance is considered to be very low in toxicity (ALD greater than 5000 mg/kg) when administered as a single oral dose to male rais. -7- Compan, Sanitized. Does not contain TSCACBI H-23004: Oral Approximate Lethal Dose (ALP) in Rats__________________.DuPont HL-1997-01291 RECORDS RETENTION All study records, raw data, and the final report are retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain, 200 Todds Lane, Wilmington, Delaware 19802 (formerly known as the E. L du Font de Nemours and Company Records Management Center). CompanySMitteed.DoesnotcontainTSCACBS