Document Z1nYkjZk3XkomJ43JLedE1EO

AR226-2953 FOR DU FONT USE ONLY Du Font HLR 121-91 Stady Title Approximate Lethal Dose (ALD) of in Rats Author John M. Sarver Study Completed On March 14, 1991 Performing Laboratory Haskell E. I. du Por.t de Nemours and Company Laboratory for Toxicology and Industrial Elkton Road, P. 0. Box 50 Newark, : 1aware 19714 Medn'ne Laboratory Project ID Haskell Laboratory Report No. 121-91 Page 1 of 8 ICoffipanySanitized. Does not contain TSCA '"= Naterlal Tested: Medical Research No. Hasfcell ao.: Haskell Test Code: Physical Fora: Other Codes: Synonyms: Purity: Composition: GENERAL INFORMATION Du Pont HLR 121-91 18,790 Milky white liquid t) Contaminants: Stability: In-the-absence of visible evidence to the contrary, the test material was assumed to be stable under the conditions of administration. Sponsor: Du Pont Chemicals E. I. du Pont de Nemours and Company Wilnnngton, Delaware Material Submitted By: Study Initiated - Completed: Ou Pont Cheakals I. E. du Pont de Nemours and Company Chambers Works Deepwater, N.J. 1/25/91 - 3/14/91 In-Life Phase Initiated - Completed: 1/29/91 - 2/18/91 Notebook: 2 - -^^^i^^^ffiS^i^A^^ GENERAL IHFORHATION (COMT.) There are 8 pages ^'ri this report. Distribution: Du Font HLR 121-91 - 3 ^fflpafi? Saflflzea: V6^t eonlatt TSCA CB1 Du Pont HLR 121-91 Approximate Lethal Dose (ALP) of lin Rats SUMMARY f------fU|RMas adninistered as a single oral dose by intragastrTctiitubatTonioniale rats. No deaths occurred. No clinical signs of toxicity were observed. Under the conditions of this test, the ALD was greater than 11,000 Big/kg of body weight. This material is considered to be very low in toxicity (ALD greater than 5000 ng/kg) when administered as a single oral dose. Work by: ^2x^fc- /V7- Kea^^^/^ ----------Anne M. Pessagno Technician Study Director: y^- L.J. '>CiA^v^\ John W. Sarver Technologist Approved by: /^QjgjL^y mc^ (JJL^JLA-g'-XM^___ Hancy C. Chrom^y, Ph.D. Manger Acute Toxicology 7J Reviewed and Approved for Issue: <4^t><-^ L^J . OP/Ur^'i John K. Sarver Study Director 3 /<4 /^t JWS:sf1:(144.7) ^"Panx Sanitized. Does not contain T8CA CB1 4 - - Ou Pont HLR 121-91 QUALITY ASSURANCE DOCUMENTATION STUDY: Lethal Dose (ALD) of In Rats AUDITS; Items Audited Audit Dates I Conduct Protocol, records, final report 1/29/S1 3/6/91 SHORT-TERM AUDIT REPORT NUMBER: DATE FINDINGS REPORTED TO MANAGER Q ^ ^ X ^ Reported by: /Tames Mackay ly Q-uSa'l llity... Ali.ssf.u<rranrcae'AI udi tor STUDY DIRECTOR: 3/6/91 3/t./9/ Date ^mpany Sanitized. Does not contain TCA 6i 5 - fc) Du Font HLR 121-91 INTRODUCTION Krpose of this test was to determine an approximate lethal dose of when administered as a single oral dose to gale rats. The ALD was as 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 noncoapliance are documented in the study records. No deviations existed that significantly affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Mate Cr1:CD*BR rats, approximately 7 weeks old, were received from Charles River Breeding Laboratories, 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. Purina Certified Rodent Chow ?5002 and water were available ad libitum. Rats were quarantined, weighed, and observed for general heaTth for approximately ine week prior to testing. Animal ims were maintained on a timer-contro'ned, 12-hour light/12-hour dark eye Environmental conditions of the rooms were targeted for a temperature OT 23 ^ 2C 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 material was dispersed in deionized water and administered to one rat per dose rate by intragastric intubation. Dose rates administered ranged from 2300 to 11,000 nig/kg of body weight in increments of approximately 50%. Additionally, one rat was dosed at 670 ing/kg. The dosing day was test day one; postexposure day 14 was test day 15. Foil owing administration of the test c-aterial, rats "ere observed for clinical signs of toxicity. Surviving rats were weighed and observed daily unti'1 signs of toxicity subsided, and then at least 3 times per week throughout the 14-day postexposure period. Observations for mortality were made daily throughout the study. Sanfiizea. yoss'no! -con^ri TS'CA 'CBs - 6 - Du Pont HLR 121-91 C. 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 Nemcurs and Company, Newark, Delaware or In the Du Pont Records Management Center, Wilnington, Delaware. RESULTS A. Dosage and Mortality Data The dosage regimen and the mortality resulting over the 15-day test period are detailed below. No deaths occurred. Dosage (mg/fcg) 670 2300 3400 5000 7500 11,000 Dose Volume (inL) 1.2 4.0 1.6 2.4 3.7 5.1* Emulsion Concentration {mg/mL) 150 150 500 500 500 500 Initial Body Weight (g) 274 258 231 244 244 230 Mortality No No Mo No N0 No * Administered in 2 portions, approximately 15 minutes apart. ' Sanitized. Does not contain TSCA ;ui D Du Font HLR 121-91 B. Clinical Signs There were no clinical signs of toxiclty observed throughout the study. COMCLUSIOH forf------w^ Under the conditions of this study, the ALD greater than 1-1,000 mg/kg of body weight, This.Baterja1.js considerea to be_yer,Y_low in toxiclty (ALD greater than 5000 ing/kg) when administered as a single oral dose. U^g.^j^^jeA. Pees n^t contain TSCA ; 8 -