Document G5DkbyX4eGzpmVBZk1mL0rr5Y

FOR OU PONT USE ONLY Study Title AR226-2936 Du Pont HLR 805-88 Author John W. Sarver Study Completed On December 15, 1988 Performing Laboratory Haskell E L . a I. bor d at u o r P y o nt fo r d e T Nemours oxicolog y a nd an d C ompany, Industr i In al c . M e d i c i n e Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Laboratory Project ID Haskel1 Laboratory Report No. 805-88 Page 1 of 7 Company Sanitized. Does not contain TSCA CBS Material Tested: Medical Research No.; Haskell No.: Physical Form: Purity: Contaminants: GENERAL INFORMATION 17,503 White powder Du Pont HLR 805-88 Synonyms : Other Codes: Submitter's Notebook No. Stability: Sponsor: Material Submitted By: In-Life Phase Initiated - Completed: Notebook: There are 7 pages in this report Distribution: The test material was assumed to be stable under the conditions of administration. Chemical and Pigments Department E. I. du Pont de Nemours and Company, Inc. wilmington, Delaware Chemical and Pi gments Department E. I. du Pont de Nemours and Company, Chambers Works; New Jersey Inc. 11/9/88 - 12/1/88 ^p^s--------""0'----TM'06' Ou Pont HLR 805-88 Approximate Lethal Pose (ALP) of SUMMARY administered ds a single oral dose by intragastric Intubation to male rats. Deaths occurred up to 5 days after dosing. Clinical signs of toxicity were observed in lethaTTy and 'nbriTethally dosed arfimaTs. Under tne conditi 6ns of this test, the ALD was 2300 mg/kg of body weight. This material is considered to be slightly toxic (ALD 500 - 5000 mg/kg) when administered as a single oral dose. Work by: Q^yUL^ "7/9. j^JU^/JU^O Ani<e M. Grand izyo Technician6' Study Director: f}John ^-JPIA^ U bO . ^OJ^r^ W. Sarver Technologist Approved by: wi 11 i am y^Bcock, Ph.D. Researw Aoxi col ogi st Acute and Developmental Toxicology Division Reviewed and Approved for -09^ Issue: (^ ?. ("SsA-y^ John W. Sarver Study Director A3//5-'/ ^ jyS:jjb:HLR22.I8 Company Sanili^. Does not contain TSCACBB - 3 - DU Font HLR 805-88 QUALITY ASSURANCE DOCUMENTATION STUDY:) H# 17,503 AUDITS: Items Audited Test System Identification and Housing Audit Dates 11/9/88 SHORT-TERM AUDIT REPORT NUMBER:------------^ DATE FINDINGS REPORTED TO MANAGEMENT AND STUDY DIRECTOR; 11/10/88 Reported by: William J. Lynam Quality Assurance Auditor I ^/5/88 Date s^.----0-'0-1'""06' Comps"^ Du Pont HLR 805-88 INTRODUCTION The purpose of this test was to determine an approximate lethal dose of 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. This study was conducted according to the applicable EPA Good Laboratory Practice Regulations. Areas of noncompiiance are documented In the study records. No deviations existed that significantly affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Male Cr1;CO*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 was assigned a unique identification number which was recorded on a affixed to the cage. Purina Certified Rodent Chow^ #5002 and water available ad libitum. Rats were quarantined, weighed, and observed rat card were for general health for approximately one week prior to testing. Animal rooms were maintained on a timer-controned, 12-hbur light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 23 ^ 2C and relative humidity of 501 ^ 101. 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 suspended in Mazola corn oil and administered to one rat per dose rate by intragastric intubation. Dose rates administered ranged from 450 to 11,000 mg/kg of body weight in increments of approximately 501. The dosing-day was test day one; postexposure day 14 was test day 15. Following administration of the test material, 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 postexposure period. | Observations for mortality were made daily throughout the study. ; t) contain TSCACB1 seompany Sanm.ed.Doe^ot Du Font HLR 805-88 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 Nemours and Company, Inc., 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 ^|f----------BRl period are detailed below. The lowest dose of which resulted in the death of a test animal m U f t Deaths occurred up to 5 days after dosing. The survival dosed at 3400 ing/kg is attributed to animal variability, the 15-day test was 2300 ing/kg. of the aninial and does not change the ALD. Dosage (mg/kg) 450 670 1000 1500 2300 3400 5000 7500 11,000 Dose Volume (ml) 0.6 1.1 1.3 2.0 4.0 4.4 ' 4.1 5.9* 8.4* Suspension Concentration (mg/mL) 200 150 200 200 150 200 300 300 300 Initial Body wei ght (g) 264 256 265 271 264 259 247 235 230 Mortality No No No No Yes No Yes Yes Yes Administered in 2 portions, approximately 15 minutes dpart. """"'M"t""TSC'tcB' -c;py^.<. Du Pont HLR 805-88 B. Clinical Signs Nonlethal Doses The only clinical sign of toxicity observed was yellow-stained perineum in the rat dosed at 3400 ing/kg 4 days after dosing. Moderate to severe weight losses (7 to 191 of initial body weight) were observed in all rats up to 4 days after dosing. Lethal Doses The rat dosed at 2300 ing/kg exhibited lethargic behavior, hunched posture, limpness, dry brown nasal and oral discharges and brown-stained perineum on days 3 or 4 after dosing and was found dead 5 days after dosing. The rats dosed at 5000 or 7500 mg/kg died before clinical signs of toxicity were apparent. The rat dosed at 11,000 mg/kg exhibited dry red oral discharge and yellow-stained perineum one day after dosing and was found dead 2 days after dosing. Severe weight losses (up to 351 of initial body weight) were observed in most lethally dosed animals. CONCLUSION HHHHHBHB9 ___Under the conditions of this study, the ALD for f------9was 2300 mg/kg of body weight. This material is considered to be slightly toxic (ALD 500 - 5000 mg/kg) when administered as a single oral dose to male rats. ,.___.s.^.---------"^06'