Document k9R5XY8w2vKJX1GGe1xZXpYbD

AR226-2921 FOR DU FONT USE ONLY cc; Haskell E. I. du Font de Nemours and Co., Inc. Laboratory for Toxicology and Industrial Elkfon Road, P. 0. Box 50 Newark, Delaware 19714 Medicine HASKELL LABORATORY REPORT NO. 5B4-84 Material Tested Haskell No. 15,588 MEDIAN LETHAL DOSE (LD50) OF IN RATS SUtWARY Single doses of] were administered by intragastric intubationto male rats. The LD50 determined to be 1900 mg/kq of body weight. Clinical signs were noted in lethally and non-lethally dosed animals. Deaths occurred within 6 days after dosing. This material is considered slightly toxic when administered as a single oral dose (i.e., LD50 between 500 and 5000 mg/kg). INTRODUCTION IIHHInin The^urpQse of this test was to determine the LD50 for] rato. The L050 is defined as that dose which, w_h_en_* Emsceredas a single dose, is expected to kill 50% of dosed animals within 14 days of dosing. While the evaluation of clinical signs of abnormality and gross pathologic changes observed after dosing are useful in assessing the toxicifcy of a test material, these data are not used in the calculation of the LD50. Company Sanitized. Does not contain TSCA CBI HLR <t584-84 Page 1 of 4 MATERIALS AND METHODS A. Animal Husbandry Male, 7-week-old, C^^^CDft(SD)BR rats 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. Animal rooms were maintained on a timer-controlled 12 hour/12 hour light/dark cycle; the relative humidity range was 32-58S and the temperature range was 23-26C. Purina Certified Rodent Chow* #5002 and water were available ad libitum. Rats were quarantined, weighed, and observed for general health approximately one week prior to testing. old when dosed. Rats were 8 weeks B. Protocol Single oral doses of the test material were made up as suspensions in Mazola* corn oil. Doses were administered to 4 groups of 10 male rats. Later in the day, rats were checked for clinical signs of toxicity. The surviving rats were weighed and observed daily, weekends excluded, during a 14-day recovery period and then sacrificed. The L050 values were calculated from the mortality data using the method of D. 3. Finney.1 C. Test Material Form: Purity: Stability: Composition; c - nifce to tan powder The material was assumed to be stable under the conditions of this study. Synonyms; Submitted by: sr Products Department Washington Works D. Raw Data and Final Rep-rt Storage All raw datu and the final report will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, E. !. du Pont delNemours and Co., Inc., Newark, Delaware, or in the Du Pont Hall of Records, Wtlmington, Delaware. Company Sanitized. Does not contain TSCA CBI HLR i?584-84 Page 2 of 4 RESULTS A. Dosing Information and Mortality Data The dosing information, fasted mean body weights, and mortality ratios are given below: Dose (mg/kg) Average Body Weight (s) Suspension (mg/ml) Average Dose (ml) Mortality Ratio 1200 254 200 1.5 0/10 1500 241 200 1.8 4/10 1800 24 J 200 2.2 6/10 2000 243 200 2.4 4/10 The LD50 for male rats was 1869 mg/kg with a 95% confidence interval of 1617-3343 mg/kg and a slope of 6.9 probits/log (mg/kg). B. Clinical Signs Non-Lethal Doses; Commonly observed clinical signs included ruffled fur, hyperactivity, limpness, hunched posture and a brown discharge from the nose. Lethal Doses; Commonly observed clinical signs included brown or yellow stained and/or wet perineum, hunched posture, diarrhea, red, yellow and/or brown discharges from the eyes, nose and mouth and moderate to severe weight loss (i.e., 5-15% of body weight) generally lasting from 1-6 days after dosing. Other clinical signs included ruffled Fur, hyperactivity, limpness, rapid and/or labored breathing, limp noise, ataxia, hair loss, low posture, general paralysis and lethargy. Deaths occurred within 3-6 days after dosing. CONCLUSION The LD50 forjJIHIHHHH^^HHHIIHIHlwas determined to be 1900 mg/kg of body weight under the conditions of this test. This material is considered slightly toxic when administered in single oral doses to male rats (i.e., LD50 between 500 and 5000). Acknowledgement; Bruce A. Burgess and Rayanne L. Ferenz also participated in this study. Company Sanitized. Does not contain TSCACBI HLR i?584-84 Page 3 of 4 Work and Report by: '/ / /">, ....... ..,, '/I ^-. - -.. talvin N. Wylie Technician Study Director: \>^ ^ Cu^/^ ' David B. Warheit, Ph.D. Research Toxicologiat Approved by: CNW/OBW/egg:8.12 Date Issued: 1/16/85 .Study Initiated/Completed; i/23/84-6/26/84 askeli Lab. Report No. !>U4-84 Niniber of pages in this report: 4 Nancy tc. unroi^ey, Section Supervisor Acute Investigations Finney, D. 3., Probit Analysis, 3d Ed., Cambridge University Press, 1971. Company Sanitized. Does not contain TSCA CBI HLR 584-84 Page 4 of 4