Document 2JzyLR85Da8NeKdQmoZLxXaZN

AR226-3143 DuPont-3628 TRADE SECRET Study Title H-24256: Oral Approximate Lethal Dose (ALD) in Rats Laboratory Project ID: DuPont-3628 Author: Carol Finlay, B.A. Study Completed on: December 14,1999 Performing Laboratory: E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Work Request Number^ Service Code Number: Company Sanitized. Does not contain TSCA CB1 Page 1 of 7 H-24256: Oral Approximate Lethal D ose (ALP) in Rats DuPont-3628 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of the data obtained from this study. Reviewed by: QnJtxOc . C J t / c L P . Deborah A. Vick, A.A.S. Associate Scientist Issued by Study D irector: (faro! Finlay,*.A/ . Associate Scientist A/-hsc.-/W Date h . i*ni Date Company Sanitized. Does not contain TSC A CBl -2 - H-24256: Oral Approximate Lethal Dose (ALD) in Rats STUDY INFORMATION DuPont-3628 Haskell Number: 24256 Known Impurities: Physical Characteristics Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: October 19,1999 / (see report cover page) In-Life Initiated/Completed: October 20,1999/ November 10,1999 Company Sanitized. Does not contain TSC A CB1 -3 - % H-24256: Oral Approximate Lethal Dose (ALP) in Rats DuPont-3628 SUMMARY H-24256 was administered as a single oral dose by intragastric intubation to male rats at doses of 670, 2300,3400,5000,7500, and 11,000 mg/kg. Following dosing, the rats were weighed and observed for mortality and clinical signs of toxicity over a 14- or 17-day period. No deaths occurred. No clinical signs of toxicity or body weight losses were observed during the study. Under the conditions of this study, the oral ALD for H-24256 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. Company Sanitized. Does not contain TSCA CBt -4 - H-24256: Oral Approximate Lethal D ose (ALP) in Rats DuPont-3628 INTRODUCTION The purpose of this test was to determine an approximate lethal dose (ALD) of H-24256 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. Test Substance The test substance,, was supplied by the sponsor as a n | m m | ^ ^ H | j ^ H H l T h e test substance appeared to be stable under the conditions orthe study. No evidence of instability, such as a change in color or physical state, was observed. B. Animal Husbandry Male Crl:CD(SD)IGS BR rats were received from Charles River Laboratories, Inc., Raleigh, North Carolina. 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 tail-marked, using a water-insoluble marker, with the last 3 digits of the animal number. PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 and water were available ad libitum. Hgskell Laboratory has an animal health monitoring program. This program is monitored and administered by the Laboratory Veterinarian. Water samples are periodically analyzed for total bacterial counts and for the presence of coliforms, 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 6 days. 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 of 23 l'C 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. Company Sanitized. Does not contain T S C A C W -5 - H-24256: Oral Approximate Lethal D ose (ALD) in Rats C. Protocol DuPont-3628 The test substance was administered neat to 1 rat per dose rate by intragastricintutaation. The volumes administered were calculated based on the test substance density o f * ( m ig /m L and body weights collected on the day of dosing. Doses 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 of toxicity. The rats were weighed and observed 2 or 3 times a week throughout the 14-day (rats dosed at 3400, 5000,7500, or 11,000 mg/kg) or 17-day (rats dosed at 670 or 2300 mg/kg) 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. Dosing and Mortality Data The dose regimen and the mortality resulting over the 14- or 17-day observation period are detailed below. No deaths occurred during the study. Dose (mg/kg) 670 2300 3400 5000 7500 11,000 Volume (mL) 0.17 0.59 0.73 1.3 1.9 2.7 Density (mg/mLL 1 i MM\ Initial Body Weight (g) 280 279 233 279 275 264 Mortality No No No No No No B. Clinical Signs and Body Weights No clinical signs of toxicity or body weight losses were observed during the study. Company Sanitized. Does not contain TSCA C H -6 - H-24256: Oral Approximate Lethal D ose (ALP) in Rats DuPont-3628 CONCLUSIONS Under the conditions of this study, the oral ALD for was greater than 11,000 mg/kg of body weight. This substance is considered to be very low in toxicity (A ID greater than 5000 mg/kg) when administered as a single oral dose to male rats. Company Sanitized. Does not contain TSCA CB1 -7 -