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r^:'-'-'''-la',s^-f~--rs'- AR226-3015 Study Title Approximate Lethal Dose (ALD) of H-21095 in Rats Laboratory Project ID Haskell Laboratory Report Mo. 290-95 Author M. Scott Karr Study CoBpleted On April 19. 1995 Performing Laboratory Haskell E. I. du Font de Newnirs and Company Laboratory for Toxicology and Industrial Elk^on Road, P. 0. Box 50 Newark, Delaware 19714 Medicine Medical Research No. Company Sanitized. ] psse 1 of 6 Substance Tested; Synpnygs/Codes; CTMStAL ItffORHATIOH DuPoDt BUl 2W-M Physical Form; Composition; Transparent tan liquid H-21095 contains: Contaminantsi Purityi CAS Registry No.; Sponsor; Study Initiated - Completed: In Life Phase Initiated - Completed: None 30X None available DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Vilaington, Delaware 3/13/95 - A/19/95 3/U/95 - 4/5/95 2 - net Approxiaatc Lethal Dose (ALP) of B-21095 ia 9stts SUMMARY MPMt <4.4- -s--w",%i^r ,i.-.-^ , ; 1?-' !!f 'i KM 29G-45 H-21095 vas administered as a sing'e oral dose by inti-agastric intubation to nale cats. No deaths and no clinical signs of toxicity irere observed during this study. Under the conditions of this test, the ALD vas creator than 11,000 g/kg of body weight. This substance is considered t" be very low in toxicity (ALD greater than 5000 ng/kg) when administered as a single oral dose. Work by; Toxicology Technician Reviewed and Approved for Issue: ^UdU <3. ^P^JU.L^^_____^/ ^/^S 7JTracy A. Filliben Study Director TF/alv ^"^'"------"'--------^.^ 3- SlUS DuPont BIA 290-95 INTRODUCTION The purpose of this test was to determine an approximate lethal do of The KLD vac Hde-2fi1n0e9d5 washentheadlmoiwneisstterdeodseasadamisniinsgteleredorwalhicdhosecautosed--dIeearthat3e.ither on the day of dosing or within 1A days post exposure. MATERIALS AND METHODS A- Animal Husbandry Kale Crl:CD*BR rats, approximately 7 weeks old, were received from North Carolina. Rats vere Charles River Breeding Laboratories, Raleigh, stainless steel, wire-mesh cages. Bach rat housed singly in suspended, unique identification number which was recorded on a card water-insoluble vas assigned a affixed to tic cage. The rats 3 digits were tail-marked, using a of the animal number. Purina Certified marker, with Rodent Chov* the last #5002 and water were available ad llbitum. Baskell Laboratory has an animal health monitoring program. This Laboratory Veterinarian. progran is monitored and administered by the analyzed for total bacterial counts and Water samples are periodically for the presence of conforms, lead, and other contaminants. and cage racks are Additionally, samples from fr-eshly washed cages to assure adequate sanitation by the cagevashers. periodically analyzed Data from this program are maintained separately from study records. specified Animal fead is certified by the manufacturer and to be free of a to meet list of specified nutritional requirements contaminants. On the basis of these analyses, there is no evidence in the feed or water In suggesting that contaminants were have interfered present with the results of this study. amounts which may Rats were quarantined, weighed, and observed for general health for rooms were maintained one week prior to testing. Animal light/12-hour dark cycle. Environmental aoproxiBately on a timer-controlled, 12-hour -onditlons of the rooms were targeted for a temperature of 23"C t 1"C outside these ranges and relative humidity of 50X + and/or 10!!;. brief Excursions duration and did'not adversely were of SB&II magnitude affect the validity of the study. B. Protocol S-21095 was mixed with deionized water and administered to 1 In the absence of visible rat per dose rate by intragastric intubation. the test substance was assuaed to be stable evidence to the contrary, under the eoad.'.tions of administration. Dose rates administered ranged froa 2300 to 11,000 Bg/kg of body veizht in increenf 670 ag/feg. The of appcoxiakfly docinf day -- 502. Additionally, 1 ret dva&ys 1d4ovseads atet st day 15. Pollovinf test day 1$ pcs (exposure adttini&trstlofl of the tesi substance, rats were observed Cor clinical observed at least ^ tine* a signs of toxicity. Rats verc weighed ind the 14-day observation period. Observations for veek throughout ortality were aade daily throughout the study. Pathological examinations ot test animals were not Derforaed. C. Records Retention A71 raw data and the final report will be stored in the archives of du Font HdeasHkoenlol uLrsabaonrdatoCroympfaonry, TNoexwicaorklo.,gyDealanwd aIrne dourstirnialtheMeDduiPcoinnet , REe.coIrd. s Hanagenent Center, Wilining^cp, Delavare. RESULTS A. Dosage and Mortality Data The dosage regimen and the mortality resulting over the 15-day test period are detailed below. Dosage WW 670 2300 3400 5000 7500 11,000 Dose Volume iEk) 1.! 3.7 1.6 2.6 3.8 5.4 Mixture Concentration (mg/mL) 150 150 500 500 500 500 Initial Body Weight (g) 256 243 241 262 252 245 Mortality No No No No No No B. Clinical Signs No clinical signs of toxicity were observed during' this study. DufORt ltt&2>0-5 CONCLUSIOH Under the conditions of this study, the ALD for H-21095 ma (raxr etum 11,000 w/kff of body weight. This substance is considered to be vry lov in loxiclty (ALO fr--ter than 5000 Kg/kg) when adainistered as a single oral doe to ale rats. ^^ISC-XGBI ^ s ^ - - " 6 "% c&'it^' ' ^.1^)^