Document zQEkn29GmQooV4689wjYJ2ajm

AR226-3048 Study Title Approximate Lethal Dose (ALD) of H-21951 in Rats Laboratory Project ID Haskell Laboratory Report No. 796-96 Author Tracy A. Filliben Study Completed On August 30, 1996 Performing Laboratory E. I. du Pont de Nemours and Company Industrial Medicine Haskell LaboratoErlyktfoonr TRooxaidc,oPlo. g0y. aBnodx 50 Newark, Delaware 19714 'ompany Sanitized. Does not contain TSCA CBI Approximar: lje\ha\ Owe (M-D) of H-21951 in Rats GENERAL INFORMATION Substance Tested: Synonyms/Codes: nuPoni HLR 796-96 physical Form: CompositioB'- Contaminants: Purity: Submitter's Notebook No.: CAS Registry No.: Sponsor: Study Initiated - Completed: In Life Phase Initiated - Completed: DuPont SpecialtyChemicals E. I. du Font de Nemours and Company Wilmington, Delaware 6/21/96-8/30/96 6/22/96 - 7/8/96 Company Sanitized. Does not contain TSCA CBt HLR 7W-9f> Approximate Lethal Dose tALD) ol H-21951 in Rats________________DuPoni (Continued) General Inl'onnauon in the archives of Haskell Laboratory for All raw data snd the final report will he stored du Pont dc Nemours and Company, Newark, Toxicology and Industrial Medicine, E. I. (formerly DuPont Records Management Center, Delaware or at Iron Mountain Wilmington. Delaware). Company Sanitized. Does not contain TSCA CBI Approximate Lethal Dose (ALD) ol H-21951 in Rats________________DuPont HLR 796-96 SUMMARY H-21951 was administered as u single oral dose by intrdga-stric intubation to male rats. No deaths occurred during the study. Clinical signs of toxicity were observed in non-lethally dosed animals. Under the conditions of this test. the ALD was greater than 11,000 ing/kg of body weight. This substance is considered to be very low in toKicily (ALD greater than 5000mg/kg) when administered as a single oral dose to male rats. Company Sanitized. Does not contain TSCA CBI 4- Approximate Lethal Dose (ALP) of H-21951 in Rah. SIGNATURE PAGE DuPont HLR 796-96 ^}^WQ.^^e^ Report by: ^TracyA.FA.i1lliben Toxicology Associate Work by^lUUM PL.-CKitMt^ QTracyA.FilBbcn v Toxicology Associate \-W.M^ Reviewed and Approved for Issae^MffjU^U. (/Tracy A. Filliben Study Director ^ ^ ?6 TF/alw Company Sanitized. Does nol contain TSCA CBI -5- Approximate Lethal Dose (ALP) olH 21951 inRais_______________DuPont HLR 79^96 INTRODUCTION The purpose of this lest was to determine an approximate lethal dose of H-21951 when administered as a single oral dose to male vats. The ALD was defined as the lowest dose administered which caused death either on the day of dosing or within 14 days post exposure. MATERIALS AND METHODS A. Animal Husbandry Male Cri:CD(SD)BR rats, approximately 7 weeks old, were received from diaries River 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. The rats were tail-marked, using a water-insoluble marker, with the last 3 digits of the animal number. Purina Certified Rodent Chow #5002 and water were available ad libitum. Haskell Laboratory has an animal health monitoring program. This program is monitored and administered by the Laboratory Veterinarian. Water samples are periodically analyzed for total bacterial counts and for the presence of colifonns, lead, and other contaminants. Additionally, samples from freshly washed cages and cage racks are periodically analyzed to assure adequate sanitation by the cagewashers. Data from this program are maintained separately from study records. Animal feed is certified by the manufacturer to meet specified nutritional requirements and to be free of a list of specified contaminants. On the basis of these analyses, there is no evidence suggesting that contaminants were present in the feed or water in amounts which may have interfered with the results of this study. Rats were quarantined, weighed, and observed for general health for approximately one week. Animal rooms were maintained on a timer-controlled. 12-hour light/I 2hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of23C 1C 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 administered neat to I ratjerdose rate by intragastric intubation. The density of the test substance wa!flB--QIn the absence of visible evidence to the contrary, the test substance was assumed to Be stable under the conditions of administration. Dose rates administered ranged from 2300 to 11,000 Company Sanitized. Does not contain TSCA CB1 ft- Approximate Lethal Dose (ALD)ofH-2l951 in Rate DuPontHLR 79646 mg/kg of body weight in increments of approximately 50%. Additionally, 1 rat was dosed at 670 mg/kg. The dosing day was test day 1; postexposure day 14 was test day 15. Following administration of the test substance, rets were observed for clinical signs of toxicity. The rats were weighed and observed daily until signs of toxidty subsided, and then at least 3 times a week throughout the 14-day observation period. Observations for mortality and signs of illness, injury, or abnormal behavior were made daily throughout the study. Pathological examinations of test animals were not performed. 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 me study. (mgflcg) 670 2300 3400 5000 7500 11.000 Dose Volume (my 0.18 0.63 0.84 1.2 1.7 2.6 Initial Body Weight (g) 271 284 253 244 237 247 Mortality No No No No No No Company Sanitized. Does not contain TSCA CB1 7- Approximate Lethal Doge (ALP) of H-21951 in Rats______________DuPont HLR 796-96 B. Ciinical Signs Nonlethal Doses Ruffled fur was observed in the rat treated at 5000 mg/kg 2 days after dosing. The rat treated at 11,000 mg/kg exhibited lethargy and low posture and carriage 1 day after dosing; no weight loss was observed. A weight loss of approximately 7% of initial body weight was observed in the rat treated at 7500 mg/kg 1 day after dosing. No clinical signs of toxicity or significant weight losses were observed in rats treated at 670.2300. or 3400 mg/kg. CONCLUSION Under the conditions of this study, the ALD for H-21951 was greater than 11,000 mg/kg of body weight. This substance is considered to be very low in toxicity (ALD greater than 5000 mg/kg) when administered as a single oral dose to male rats. C.^S.nn^.n.e-^.ln^ K-