Document gdapmRJeO2B94X46Mvqn2kjq

AR226-3003 '-- ' ;a -'.?""^i^(E^-.- .^ .1 Study Title Approximate Lethal Dose (ALD) of H-20431 in Rats Laboratory Project ID Haskell Laboratory Report No. 90-94 Author Carol Finlay Study Completed On March 15, 1994 Performing Laboratory Haskell I'. I. du Font de Nemours and Company Laboratory for Toxicology and Industrial Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Medicine Medical Research No. Page 1 of 7 o^pany g^,^ ^ ^ ^^ ^ ^ Substance Tested; Synonyms/Codes: GENERAL INFORMATION 0 H-2Q431 DuPont BLR 90- Physical Form; Purity! Composition; Contaminants: CAS Registry Mo. Fan milky liquid Approximately 99.5% H-20431 None available DuPont HLR 90-94 GENERAL INFORMATION (CONT.) Sponsor; Study Initiated - Completed; In Life Phase Initiated - Completed; Specialty Choicals E. I. du Font de Neoours and Conpany Vilmington, Delaware 1/6/94 - 3/15/94 1/17/94 - 2/9/94 - 3 - Company Sanitized. Does not contain TSCA CB1 Approxiaate Lethal Dose (ALP) of H-20431 in Rats SUMMARY DuPont HLR 90-94 H-20431 was administered as a to male rats. No deaths occurred observed during the study. Under greater than 11,000 ng/kg of body very low in toxicity (ALD greater single oral dose to male rats. single oral dose by intragastric Intubation and no clinical signs of toxicity were the conditions of th?s test, the ALD was weight. This substance Is considered to be than 5000 ing/kg) when administered as a _____t vork by; /JAM: _>'m.^i Carol yinlay(T Tox'.cology Associate Approved by;; /IJohn ^^--^ (^) . JO/W^-A V. Sarver ^-J Toxicologist Reviewed and Approved for Issue: _____C fi'^U^Ci^^r{roo'^]l SFLinftna\y Study Director .^/l^/^l CP/alw A - - Company Sanitized. DOBS not contain TSCA CBI INTRODUCTION DuPont HLR 90-94 The purpose ol this test was to determine an approximate lethal dose of H-20431 when administered s a single oral dose to male rats. The ALD was defined as the lowest dose administered vhich caused death either on the day of dosing or vlthin 14 days post exposure. MATERIALS AND METHODS A. Animal Husbandry Male Crl:CDBR rats, approxicately 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 vas 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 2 digits of -he animal number. Purina Certified Rodent Chov? #5002 and water wero available cd libitum. Haskell Laboratory has a monitoring program which consists periodic food and water analysis fsr contaminants. This program is monitored and administered by the Laboratory Veterinarian; data from of this program are maintained jeparattely ^rom atudy records. On the basis of these analyses, there is no evidence suggesting that contaminr.nts were present in the feed or water in amounts which may have interlered with the results of ihis study. Rats were quarantined, veighe:, and observed for generd health for approximately one 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 502 + 102. 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 mixed -.ith deionized water and administered to 1 rat per dose rate by intragasiric intubation. In the absence of visible evidence to the contrary, ;he test substance was assumed to be stable under the conditions of adainlstration. Dose rates administered ranged from 2300 to 11,000 ng/kg jf body weight in increments of approximately 50%. Additionally, 1 rat was dosed at 670 mg/kg. The dosing day was test day 1; pos (exposure 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 at Company Samtized. Does noE contain TSCA CB1 DuPont HLR 90-94 least 3 tiaea per vck throughout the 14-day recovery period. Observations for Mortality vere Bade dally throughout the study. Pathological examinations of test aniuls were not perforaed. 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 Nenours and Company, Newark, Delaware or in the OuPont Records Management Center, Uilmlngton, Delawarr. RESULTS A. Dosage and Mortality Data Thie dosage regimen and the mortal ity resulting over the 15-day test period are detailed below. No death? occurred during the study. Dosage (rng/kg: 670 Dose Volume (niL) 1.1 M1 ...ure Coiicentration (ag/nL) 150 Initial Body Weight (g) 255 2-SOO 3.6 150 235 3400 2.7 300 242 5000 A.I 300 248 7500 5 9 300 237 11.000 9.4* 300 256 Administered in 2 portions , 15 minutes apart. Mortality No No No No Mo No B. Clinical Signs No clinical signs of to;<icity were observed during the study. ^ 6 - - Company Sanitized. Does no? contain TSCA CBI DuPoRt OR 90-94 CONCLUSION Under the conditions of this tudy, the ALD for B-20431 v grufr than 11,000 g/kg of body wight. This ubjface 1 coMidrd to b vry low in toxiclty (ALD greater than 5000 f/kg) vhn dRinitrcd u a ingle oral dor to ale rats. - 7 - Conftpany Sanrfized. Doss nol contain TSCA CB1