Document YrGkY4m84eEvp7z3bmD9DMVZV

AR226-3003 i Study Title Approximate Lethal Dose (ALD) of H-20431 in Rats Laboratory Project ID Haskell Laboratory Report No. 90-94 Author Carol Finlay Study Completed On March 15, 1994 Performing Laboratory F. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Medical Research No. Page 1 o f 7 company Sanitized. Does not contain TSCA CBf Substance Tested; Synonyms/Codes: GENERAL INFORMATION DuPont HLR 90-94 Physical Form: Purity! Composition: Contaminants: CAS Registry Mo.: GENERAL INFORMATION (CONT.) Sponsor: Study Initiated - Completed; In Life Phase Initiated - Completed: Specialty Cheaicals E. I. du Pont de Nemours and Company Vilmington, Delaware 1/6/94 - 3/15/94 1/17/94 - 2/9/94 - 3- Company Sanitized. Does not contain T S C A CB1 DuPont BLR 90-94 Approximate Lethal Dose (ALP) of H-20431 in Rats SUMMARY H-20431 vas administered as a single oral dose by intragastric intubation to male rats. No deaths occurred and no clinical signs of toxicity were observed during the study. Under the conditions of this test the ALD vas greater than 11,000 mg/kg of body veight. This substance is considered to be very lov in toxicity (ALD greater than 5000 mg/kg) vhen administered as a single oral dose to male rats. f /I fTWork b y : _____________ AA-C Carol inlay Toxicology Associate Approved by: 5, John V. Sarver Toxicologist Revieved and Approved for Issue: Study Director .7 CF/alv -4- Company Sanitized. Dogs not contain TSC A CBI DuPont HLR 90-94 INTRODUCTION The purpose ot this test was to determine an approximate lethal dose of H-20431 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 Crl:CDBR rats, approximately 7 weeks old, were received from Charles River Breeding Laboratories, Kingston, New York. 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 2 digits of the animal number. Purina Certified Rodent Chov* #5002 and water -ere available cd libitum. Haskell Laboratory has a monitoring program which consists of periodic food and water analysis for contaminants. This program is monitored and administered by the laboratory Veterinarian; data from this program are maintained eparattly *rom study records. On the basis of these analyses, there is no evidence suggesting that contaminr.nts were present in the feed or water in amounts which may have interrered with the results of this study. Rats were quarantined, weighed, and observed for genercl health for approximately one week prior to testing. 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 23C 2C and relative humidity of 50% 10X. 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 mixed vith deionized water and administered to 1 rat per dose rate by intragastric intubation. In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. 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, the rats were observed for clinical signs of toxicity. The rats were weighed and observed at -5- Company Sanitized. Does not contain T S C A CB1 a DuPont BLR 90-94 least 3 tines per week throughout the 14-day recovery period. Observations for nortality were node daily throughout the study. Pathological exaninations of test aninals were not perforned. Records Retention All raw data and the final report will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Company, Newark, Delaware or in the DuPont Records Management Center, Vilmington, Delaware. RESULTS 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 mVolume i.i M '..:ure Concentration (mg/mL) 150 Initial Body Weight (g) 255 2300 3.6 " 150 235 3400 2.7 300 242 5000 4.1 300 248 7500 11,000 5 9* 9.4 300 300 237 256 Administered in 2 portions, 15 minutes apart. Mortality No No No No No No Clinical Signs No clinical signs of toxicity were observed during the study. - 6- Company Sanitized. Does not contain T S C A CB1 DuPont H I 90-94 CONCLUSIOH Under tht conditions of this study, tho ALD Cor H-20431 vas grantor than 11,000 ng/kg of body vaight. This substance is considered to be very lov in toxicity (ALD greater than 5000 ng/kg) vhen adninistered as a single oral dose to nale rats. - 7Gonftpany Sanitized. Doss not contain TSCA CB1