Document 9gbn1KXnag1rY1Rq37Moj9ae

AR226-2968 FOR DU PONT USE ORLY Du Font HLR 632-91 Study Title ApproximateLeHd. Dose (LD) of > in Rats Author John W. Sarver W Study Completed On February 11, 1992 I Performing Laboratory E. 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. Laboratory Project ID Haskell Laboratory Report No. 632-91 AaXt' ACn 0es m{ CB' Page 1 of 7 Substance Tested; Medical Research No.i Haskell No.; Haskell Test Code; Physical Forni Composition; Contaminants: Purity: Synonyms : GENERAL INFORMATION Du Pont HLR 632-91 19,101 Light yellov liquid J CAS Registry No.: Stability; Sponsor: Substance Submitted By: In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. Du Pont Fibers E. I. du Pont de Nemours and Company Wilmington, Delaware Study Initiated - Completed: In-Li fe Phase Initiated - Completed: Notebook: E. I. du Pont de Nemours and Company Chattanooga, Tennessee 8/9/91 - 2/11/92 8/12/91 - 9/10/91 There are 7 pages in this report. Distribution: 2- - ISC* A*0 LoVtVt<e& DO5 K\0i\c Du Pont BLR 632-91 Approximate Lethal Dose (ALP) of * in Rats SUMMARY vas administered as a single oral dose by intragastric intonation to male ravs. Clinical signs of toxicity were observed in letnally and nonlethally dosed animals. Deaths occurred up to one day after dosing. Surviving animals were observed for clinical signs of toxicity for f fer dosin8* Dnder the conditions of this test, the ALD vas 7500 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. Work by: JWS/lmr Study Director: Approved by: 0 . S,CJ\s>r-~\ John W. Sarver Technologist Manager Acute Toxicology John V. Sarver Study Director 9-1 it c 0 ntai iJ0S noi CosnPal^ Saftslio.*** Du Pont MLR 632-91 QUALITY ASSURANCE DOCUMENTATION AUDITS: Items Audited Protocol, conduct Records, final report Audit Dates 8/12/91 1/23/92 DATE FINDINGS REPORTED TO STUDY DIRECTOR: 1/23/92 DATE FINDINGS REPORTED TO MANAGEMENTl 2/6/92 Reported by: Rasies Mackay I if Quality Assurance Auditor Date Company Sanitized. Does not contain TSCA CBI Du Font HLR 632-91 INTRODUCTION purpose of this test was to determine an approximate lethal dose of l H H w h e n administered as a single oral dose to male rats. The ALD vas "definedas the lowest dose administered which caused death either on the day of dosing or within 14 days post exposure. This study was conducted according to the applicable EPA Good Laboratory Practice Regulations. Areas of noncompliance are documented in the study records. No deviations existed that affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Male Crl:CD*BR 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 vas assigned a unique identification number which was recorded on a card affixed to the cage. Purina Certified Rodent Chow #5002 and water were available ad libitum. Rats were quarantined, weighed, and observed for general 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% 10%. Excursions outside these ranges were of small magnitude and/or brief duration and d id not adversely affect the validity of the study. B. Protocol The test substance was dispersed in Mazola corn oil and administered to one rat per dose rate by intragastric intubation. Dose rates administered ranged from 2300 to 11,000 mg/kg of body weight in increments of approximately 50%. Additionally, one rat was dosed at 670 mg/kg. The dosing day was test day 1; postexposure day 14 vas test day 15. Following administration of the test substance, rats were observed for clinical signs of toxicity. Surviving rats were weighed and observed daily until signs of toxicity subsided,and then at least 3 times per week throughout the 14-day recovery period. Observations for mortality were made daily throughout the study. Pathological examinations of test animals were not performed. Company San,-fi2ed Ooesnofconfa/nTSCAcsi 5 Du Pont HLR 632-91 C. Records Retention All raw data and the final report will he 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 Du Pont Records Management Center, Wilmington, Delaware. RESULTS A. Dosage and Mortality Data The dosage regimen and the mortality resulting over the 15-day test period are detailed below. The lowest dose o f r a p H M l v h i c h resulted in the death of a test animal was 7500 mg/kg. DeTfhs occurred up to one day after dosing. Dosage igg/fcg) 670 2300 3400 5000 7500 11,000 Dose Volume (L) 1.1 3.8 2.6 3.9 5.5 8.4 Emulsion Concentration (mg/mL) 150 150 350 350 350 350 Initial Body Weight (g) 245 246 265 270 255 266 Mortality No No No No Yes Yes * Administered in two portions approximately 15 minutes apart. Company sanitized. Does not contain TSCACBf 6- - Du Pont HLR 632-91 B. Clinical Signs Nonlethal Doses No clinical signs of toxicity were observed in the rats dosed at 670, 2300, or 3400 mg/kg. Slight veight losses (up to I X of initial body weight) occurred in rats dosed at 2300 and 3400 ag/kg one day after dosing. The rat dosed at 5000 ng/kg had diarrhea and severe weight loss (10Z of initial body weight) one day after dosing. Lethal Doses The rats dosed at 7500 or 11,000 ng/kg had low posture and were lethargic one hour after dosing. Death occurred on the day of dosing in the rat dosed at 11,000 mg/kg and one day after dosing in the rat dosed at 7500 mg/kg. CONCLUSION Under the conditions of this study, the ALD f o r f ^ A v a s 7500 mg/kg of body weight. This substance is considered to be very,-Tov fir toxicity (ALD greater than 5000 mg/kg) when administered as a single oral dose to male rats. Company Sanitized. Does not contain TSCA CBI