Document NeKdM5j47bmQqd2eQDq2YDmDE

mm AR226-2998 Study Title Approximate Lethal Dose (ALD) of H-20349 in Rats Laboratory Project ID Haskell Laboratory Report No. 752-93 Author Carol Finlay Study Completed On December 21, 1993 Haskell Performing Laboratory B. I. du Pont de Nemours and Company Moratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 ..I____ 1A1U not contain T S C A CBS Company Sanitized. Does Page 1 of 8 imiiiki DuPorl Htl 752-93 GOOD '.ARARATARY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with BFA TSCA Good Laboratory Practice Standards (40 CFR 792). Submi tier: S. I. du Pont de Nemours and Company Sponsor: DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Study Director: L M / L j U 7'2 /li / l i Toxicology Associate Acute. Inumino-. and Neurotoxicology i CompanySanitized.DoesnotcortanTSCACB - 2- Substance Tested: Synonyas/Codes; GENERAL INFORMATInw DuPont HLA 752-93 Physical Form: Composition: Contaminants: Purity: CAS Registry No.: Sponsor: Study Initiated - Completed: In Life Phase Initiated - Completed: Opaque white semi-solid at r o n e .... temperature. Opaque white liquid after liquefied for dosing. DuPont Specialty Chemicals E. I. du Pent de Nemours and Company Vilmington, Delaware 10/18/93 - 12/21/93 10/19/93 - 11/11/93 Company Sanitized. Does not contain TSCA CBI -3- Approximate Lethal Dose (ALP) of H-20349 in Rats SUHNARY H-20349 vas administered as a single oral dose by intragastrie intubation to male rats. No deaths occurred during the study. Clinical signs of toxicity were observed in some animals. Under the conditions of this test t h e A L D v a s g r e a t e r t h a n l l sv?0Ong/kgobodyveight. This substance is considered to be very lov in toxicity (ALD greater than 5000 mg/kg) when administered as a single oral dose. t 6A H .Jtl HllLLi. ,, CaroQ. Finlay / Toxicology Associate il Approved by: John V. Sarver Toxicologist Reviewed and Approved for Issue: Study Director IZ / ' U / U CF/alw I Company Sanitized. Does not contain TSCA CBI -4- DuPont B 752-93 QUALITY ASSURANCE DOCUMEHTATIOH (B-20349) Dates of Inspection: Conduct - 10/20/93 Records, Report(s) - 12/14 '93 Date(s) Findings Reporte 1 to; Study Director - 12/14/93 Management - 12/14/93 Reported by: fog- pPjerfChapman Quality Assurance Auditor Date Company Sanitized. Does not co^!afn TSCACffg -5- S iv r liE ^ t* 4 r S t m DuPont BLR 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 sale 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 in compliance with the applicable EPA Good Laboratory Practice Standards. MATERIALS AMD 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 number. Purina Certified Rodent Chow* #5002 and water were available ad libitum. Rats were quarantined, weighed, and observed for general health for approximately 1 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 did not adversely affect the validity of the study. B. Protocol The test substance was liquefied by heating it up to and at . approximately 50eC in a waterbath. The test substance was then mixed with Mazla* corn oil and administered to 1 rat per dose rate by intragastric intubation. The flask containing the mixture was placed in a waterbath (approximately 40C) to keep it homogeneous during the dosing procedure. In the absence of visible evidence the contrary, the test substance was assumed 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 50*. Additionally, 1 rat was dosed at 670 sg/kg. The dosing day was test day 1| 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 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 ver not performed. -6- Company Sanitized. Does noi contain TSCA CBS r^nat-f l T j r w i j - ' .... .................... ";*/";4l5g5 DuPont HLR 752-9J 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 Neaours and Coapany, Newark, Delavare or in the DuPont 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. No deaths occurred during the study. Dosage (mg/kg) 670 2300 3400 5000 7500 11,000 Dose Volume (mL) 1.1 3.9 3.1 4.4 7.1* 9.4* Mixture Concentration (isg/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 clinical ~lgns of toxicity were observed in the rat dosed at 670 ng/kg. Yellow-stained perineum and hunched posture were observed the day after dosing in the rat dosed at 2300 ng/kg. The rats dosed at 3400 or 5000 ng/kg each exhibited diarrhea and yellow-stained perineum up to 3 dayg -ftsr dosing. Yellow-stained perineum, dry red ocular discharge, and red-stained fact were observed the day after dosing in the rats dosed at 7500 or 11,000 mg/kg. Alopecia of the paw was observed l * d ays *ter dosing in the rat dosed at 7500 ng/kg. The rat dosed at 11,000 ng/kg exhibited yellow-stained perineum, dry red ocular discharge, or diarrhea 2, 3, and 4 days after dosing. Weight loss of approximately 3* o*. initial body weight occurred by the day after dosing in the rat dosed at -7- Sompany Smmftized. Does noXcca*01 c  i DuPont HLR 752-93 2300 mg/kg. The rats dosed at 7500 or 11,000 mg/kg had weight losses of approxiaately 4 and 5X of initial body weight, respectively, by 2 days after dosing. , CONCLUSION Under the conditions of this study, the ALD for H-20349 was greater than 11,000 mg/kg of body weight. This substance is considered to be very low in toxicity (ALD greater than 5000 ng/kg) when administered as a single oral dose to male rats. 8- - Company Sanitized. D ees rqI contain TSC A CBS!