Document RjVw2ndRXXen7DEpey6BMk3zE

AR226-3056 Study Title Approximate Lethal Dose (ALD) ofH-21987 in Rats Laboratory Project ID Haskell Laboratory Report No. 783-96 Author Tracy A. Filliben Study Completed On September 24,1996 Performing Laboratory E. I. du Font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Medical Research No.L^^^--^i <c ^n^^ _A 0^ Corft-P^^ Sa^- Page 1 of 8 Substance Tested: Synonyms: GENERAL INFORMATION H-21987 Physical Form: Composition: Known Impurities: Purity: Structure: Tan liquid dispersion Submitter's Notebook No.: CAS Registry No.: Sponsor: Study Initiated - Completed: In Life Phase Initiated - Completed: (? Not applicable DuPont Specialty Chemicals E. I. du Font de Nemours and Company Wilmington, Delaware 7/11/96-9/24/96 7/15/96-8/6/96 Company Sanitized. Does not contain TSCACB1 -2- GENERAL INFORMATION (Continued) All raw data and the final report will be stored in the archives ofHaskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Company, Newark, Delaware or in the DuPont Records Management Center, Wilmington, Delaware. Company Sanitized. Does not contain TSCA CBI -3- -SUMMARY" H-21987 was administered as a single oral dose by intragastric intubation to male rats. No deaths occurred, and no clinical signs oftoxicity were observed during this study. Under the conditions of this test, the ALD was greater than 11,000 mg/kg of body weight. This substance is considered to be very low in toxicity (ALD greater than 5,000 mg/kg) when administered as a single oral dose to male rats. ^^^^'^r^ SIGNATURE PAGE ^ Report By:: M. Scott Karr Toxicology Technician Work by: A^. M.Scott Karr Toxicology Technician '^U'^AMlLin^ r^ Reviewed and Approved for Issue:VA?<l^U/.. ^_ (/"Tracv Tracy A. Filliben Study Director 9 l^f^Ca UnTSCACBl 5- INTRODUCTION The purpose of this test was to determine an approximate lethal dose ofH-21987 when administered as a single oral dose 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. MATERIALS AND METHODS A. Animal Husbandry Male Crl:CD(SD)BR rats, approximately 7 weeks old, were received from Charles 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 ofcoliforms, 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 2- hour 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 1 rat per dose rate by intragastric intubation. The density was determined by weighing 3, 1 mL aliquots ofH-21987 and averaging the 3 weights. The density was calculated to be 1.0655 g/mL or 1065.5 mg/mL. hi the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. Dose rates administered Company Sanitized Oooeesan"otf contain TSCA CBf -6- ranged from 2300 to 11,000 mg/kg of body weight in increments of approximately ^O'^T'Additionally^n'at was dosed~aT670 mg/lcg^The'dosiiig'day was test day 1; postexposure day 14 was test day 15. Following administration of the test substance, rats were observed for clinical signs oftoxicity. The rats were weighed and observed 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 this study. Dosage (mg/kg) 670 2300 3400 5000 7500 11,000 Dose Volume (mL) 0.15 0.52 0.78 1.1 1.9 2.6 Density Concentration (mg/mL) 1065.5 1065.5 1065.5 1065.5 1065.5 1065.5 Initial Body Weight (g) 240 241 245 244 265 248 Mortality no no no no no no ^'""""--------------rsc^B, 7- B. Clinical Signs No clinical signs of toxi city were observed during this study. CONCLUSION Under the conditions of this study, the ALD for H-21987 was greater than 11,000 mg/kg of body weight. This substance is considered to be very low in toxicity (ALD greater than 5,000 mg/kg) when administered as a single oral dose to male rats. ^-----^ 8- ________^'"^,