Document K4dEE248OD6ZRvEwenzzb9oo

AR226-3049 Study Title Approximate Lethal Dose (ALD) of H-21953 in Rats Laboratory Project ID Haskell Laboratory Report No. 795-96 Author Tracy A. Filliben Study Completed On Septembers, 1996 Performing Laboratory E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Page lel-S Company Sanitized. Does not contain TSCA CB1 Physical Form: Composition: Opaque tan to white liquid Contaminants: Punty: Submitter's Notebook .No.: CAS Registry No.: Sponsor: Study Initialed - Comp.let.ed: DuPont Specialty Chemicals P.. I. du Font de Nemours and Company Wilminglon, Delaware 6/21/96-9/3/96 Company SaniUzed. Does not contain TSuA CBi Approximate Lethal Dose (ALP) of H-21953 in Rats_______________DuPoni HLR 795-96 In Life Phase Initiated - Completed: 6/22/96 - 7/8/96 All raw data and the final report will be stored in the archives of Haskeli Laboratory for Toxicology and Industrial Medicine, E. I. du Pent de Nemours and Company, Newark. Delaware or at Iron Mountain (formerly DuPont Records Management Center, Wilmington, Delaware). -3- Company Sanitized. Does not contain T8CA CB6 SUMMARY H-21953 was administered as a single oral dose by intragastric 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 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. 4 - - Company Sanitized. Does not contain TSCA CBf Approximate Lethal Dose (ALP) ol H-21953 in Rats________________DuPont HLR 795-96 SIGNATURE PAGE .^KjUi^t^ Report by: '^JMUJLJ Q. dTracy A. Filliben Toxicology Associate ^AliL^ Work by. ^J<A/40. (] Tracy A. Filliben Toxicology Associate Reviewed and Approved for Issue: "^ lAlUji^ U.. ^JLuSw^ 0Tracy A. Filliben Study Director ^iSi^C, TF/alw 5 - - Company Sanitized. Does not contain TSCA CBS, Approximate 1-cthal Dusc (ALP) ol' H-21953 in Rats________________DuPont HLR 795-96 LNTR^DUCTION The purpose ol' this test was to determine an approximate lethal dose of H-21953 when administered as a single oral dose to male rats. The ALD was denned as ihe 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-gi 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 ofcolifonns, lead, and other contaminants. Additionally, samples from freshly washed cages and cage rucks 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. Rais were quarantined, weighed, and observed for general health for approximately one week. prior to testing. Animal rooms were maintained on a timer-controlled, 12hour light/I 2-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 23C 1"C and relative humidity of 50% 10%. Excursions outside these ranges were of small magnitude and/or brief duration and did not adversely afreet the validity of the study. B. Protocol The (CM substance was administered neat to 1 rat per dose rate by intnigastric intubation. The density of the lest substance was 1.03 g/mL. In the absence of visible evidence to the contrary, the test substance was assumed lo be stable under the conditions of administration. Dose rates administered ranged from 2300 to 11,000 h- Poapany Sanitized. Does not contain TSCA CBI Approximate Lethal Dose <Ai.D> <it H-2 \W in Ruts________________DuFuni H1.R 795-% mg/kgofhody weight in increments of approximately 50%. Additionally, I rat was dosed ai 670 mg/kg. The dosing day was lest day I; postexposure day 14 was lest day 15. Following adminisiralion of the lest substance, 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 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 MortaH'y 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) 018 0.61 0.83 1.1 1.7 2.5 Density (mg/mL) 1030 1030 1030 1030 1030 1030 Initial Body Weight (g) 280 275 250 236 234 238 Mortality No No No No No No Company Sanitized. Does not contain TSCA CBI 7 Approximate l-rlhal Dose (AI.I)i ol'H-21953 in Ral.s________________DuPont HLR 795-9f> B. Clinical Signs N011 lethal. .Doses No clinical signs of loxicily or weight losses were observed in the rats treated at 670 or 2300 mg/kg. The rats treated at 3400 and 5000 mg/kg exhibited lung noise I day after dosing: the 3400 mg/kg rat also exhibited lung noise 2 days after dosing. Weight losses of approximately 2 - 12% of initial body weight were observed in rats treated from 3400 - 11,000 mg/kg I day after dosing. CONCLUSION Under the conditions of this study, the ALD for H-21953 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. Company Sanitized. Does not contain TSCA CBI K - -