Document 4QQZyR9zLyJgEZDoQVKkvbb9R

AR226-2998 Study Title Approxinate Lethal Dose (ALD) of H-20349 in Rats Laboratory Project ID Hasksll Laboratory Report No. 752-93 Author Carol Finlay Study Coepleted On December 21, 1993 Performing Laboratory Haskell E. I. du Laboratory Font de Nenuurs and Cospsny for Toxicology and Industrial Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Medicine SanHized. Does not contain TSCA CBfi Company Pag 1 of 8 DuPorl HLX 752-93 GOOD-LABORATORY PRACTICE COMPLIANCE STATEMENT This study vas conducted in compliance with BPA TSCA Good Laboratory Practice Standards (40 CFB 792). Submit ter: E. I. du Pont de Nenours and Company Sponsor: DuPont Specialty Chemicals E. I. du Pont de Nenours and Company Study Director: /ti/^ A^ (f /hiA ^^'tkkjJtt ^tt^_____/2 fCarol Pluday Toxicology Associate Acute, IniBuno-, and Neuro toxicology .Company Sanitized. Does not contain TSCA CB1 2 - - '^''^a.?'^'^"! Substance Tested; Synonyms/Codes; GENERAL INl-OJUtATION DuPont HLR 752-93 Physical Fern: Composition: Contaminants: Purity: CAS Registry No.; Sponsor: Study Initiated - Completed; In Life Phase Initiated - Coapleced: Opsgueyfaitesgai-solid at_roo_-- ceBperature.Opaque vhi te liquid after liquefied for dosing. DuPont Specialty Chenicals E. I. du Pent de Nenours and Cosrany Vilaington, Delaware 10/18/93 - 12/21/93 10/19/93 - 11/11/93 Company Sanitized. Does not contain TSCA CBI 3 - DuPont HLR 752-93 Approximate Lethal Dose (ALP) of H-20349 in gats SOHMARY H-20349 vas administered as a fingle oral dose by intragastric intubation to Bale rats. No deaths occurred curing the study. Clinical signs of toxicity rare observed in sooe animals. Under the conditions of this test, t^~3ffiD^vas-=greB^eT-^han^^T^0^g^fcg-^--b^'*^t^=^^ considered to be very low in toxicity (ALD greater than 5000 Bg/kg) when adBinistered as a single oral dose. Vork by; ^/l^ ^'MJA^ CaarrooQO. Finlay // Toxicology Associate Approved by: Reviewed and Approved for Issue: -/^J- QQ/L^/i^ John V. Sarver Toxicologist f fl^LfaC, *^L h^A^ C^rol Finlay Study Director 11/^l/^ CF/alv Company Sanitized. Does not contain TSCA CBI ^-^ 1^ DuPoot RU 752-93 QUALITY ASSURANCE DOCUMBnATIOM (8-20349) Pates of Inspection; Conduct - 10/20/93 Records, Report(s) - l2/l&'93 Pate(s) Findings ReporteJ to; Study Director - 12/14/93 Management - 12/14/93 Reported by: [^Jff>f^(^^ t' Jerf Chapoan Quality Assurance Auditor l^/^ Date Company Sanitized. Does notcoRSa'm TSCACSg 5 - - ........ .^...--..-.^ .....,,,,......_,,_.. ,.if^^-^..^;i^^i^M^: Bi'?"''i^^'%^'?''l%i^^ ^ DuPont HLR 752-93 INTRODUCTION The purpose of this test was to determine an approximate lethal dose of H-20349 when administered as a single oral dose to alc rats. The ALD vas defined as the lowest dose administered which caused death either on the day of dosing or vlthin 14 days post exposure. This study vas conducted in coBpliance vith the applicable EPA Good Laboratory Practice Standards. 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 was assigned a unique identification number which was recorded on a card affixed to the cage. The rats were tail-marked with the last 2 digits of the identification nuuber. Purina Certified Rodent Chow* #5002 and water were available ad libitus. Rats were quarantined, weighed, and observed for general health for approximately 1 week prior to testing. Animal rooas vere maintained on a tiner-controlled. 12-hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of ^C 2Cand relative humidity of 50Z 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 liquefied by heating it up to and at approximately 5Q*'C in a vaterbath. The test substance was then mixed vith Mazola* corn oil and administered to 1 rat per dose rate by intragastric intubation. The flask containing the nixture was placed in a waterbath (approximately 40C) to keep it hosogeneous during the dosing procedure. In the absence of visible evidence -'. the contrary, the test substance was assueed to be stable under th- .unditions of administration. Dose rates administered ranged from 2300 to 11,000 mg/kg of body weight in increments of approximately 50X. Additionally, 1 rat was dosed at 670 sg/kg. The dosing day "as test day Is 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 dally 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 ^rformed. -- 6 -- Company Sanitized. Does "oi contain TSCA CBE ''-'T^'?^?"-CT-^Tp7HW--T-"~^^i'RT3' '^^^S^'^^-'^WT^iiaair^-^r--' - -;-.. "A-^M DuPont HLR 752-&J C. Records Retention All raw data and the final report will be stored in the archives of Baskell Laboratory for Toxicology and Industrial Medicine, E. I. du Font de Neaours and Company, Newark, Delaware or in the DuPont Records Management Center, Vllaington, 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 during the study. Dosage (mg/kg) 670 2300 3400 5000 7500 11,000 Dose Volume (BL) 1.1 3.9 3.1 4.4 7.19.4 Mixture Concentration (ag/mL) 150 150 300 300 300 300 Initial Body Weight (g) 253 252 277 267 285 257 Mortality No No No No No No Administered in 2 portions approximately 15 minutes apart. B. Clinical Signs No clinlchi -igns of toxicity were observed in the rat dosed at 670 mg/kg. Yellow-stained perineum and hunched posture were observed the day after dosing in the rat dosed at 2300 mg/kg. The rats dosed at 3400 or 5000 mg/kg each exhibited diarrhea and yellow-stained perineuR up to 3 days after dosing. Yellow-stained perineir, dry red ocular discharge, and red-stained face were observed the day after dosing in the rats dosed at 7500 or 11,000 mg/kg. Alopecia of the paw was observed 14 days after dosing in the rat dosed at 7500 mg/kg. The rat dosed at 11,000 g/kg exhibited yellow-stained perineum, dry red ocular discharge, or diarrhea 2. 3, and 4 days after dosing. Weight loaa of approximately 32 of initial body weight occurred by the day after dosing in the rat dosed at QOSSpasy S--ifeed. Does s-.c^-aa^ TSCA CB5 DuPont HLR 752-93 f/kf. 2300 The rats dosed at 7500 or approximately 4 and 5Z of initial body 11,000 g/kg had weight losses of weight, respectively, by 2 days after dosing. , CONCLUSION Under the conditions of this study, fhe ALD for H-20349 was greater than 11,000 off/kg of body weight. This substance is considered to be very low in toxicity (ALP greater than 5000 Bg/kg) when administered as a single oral dose to Bale rats. fe) 8 - - smTSCACBB