Document 3eKogvwGG3KpZ8R4n4ZY5EaBO

AR226-3039 Study Title Approximate Lethal Dose (ALD) of H-2I460 in Rats Laboratory Project ID Haskell Laboratory Report No. 176-96 Author Tracy A. Fiiliuen Study Completed On February 29, 1996 Performing Laboratory E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road. P. O. Box 50 Newark, Delaware 19714 I Page I 17 Company Sanitized. Does not contain TSCA CBI Approximate L-elhal Dose (AI.D) ol H-2I4W) in Rats r.FNFRAL INFORMATION DaPont HLR 176-96 Substance Tested: Synnnvms/Codes: Physical Form: Composition: Contaminants: Purity: Submitter's Notebook No,: CAS Registrd^ 'Sponsor: Study Initiated - Compieteti: In Life Phase initiated - ComBeted: DuPont Specialty Chemicals E. I. du Pont de Nemours and Company Wilmington, Delaware 1/ 17/9 6 - 2/ 29/96 1/ 18/96 - 2/5/96 San2" ' not contain Approximate Lethal Dose (ALD) nl'H-21460 in Rats DuPont HLR 176-96 Approximate Lethal Dose (ALD) o f H-21460 in Rats SUMMARY H -21460 was administered as a single oral dose by intragastric intubation to male rats. No deaths occurred, and no clinical signs o f toxicity were observed in any 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. }- Company Sanitized. Does not contain TSCA CBI Approximate Lethul Dose (ALD) ol'H-21460 in Rats SIGNATURE PAGE DuPont HLR 176-96 Report by: Technical Assistant Work by: Technical Assistant '~j"LfReviewed and Approved for Issue fl. Tracy A. Filliben Study Director 2 a-Wc, TF/alw 4- Company Sanitized. Does not contain TSC CB1 Approximate Lethal Dose (AI.D) of H-21460 in Rats INTRODUCTION DuPr.nl HLR 176-96 The purpose o f this test was to determine an approximate lethal dose o f H-21460 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. A. Animal Husbandry MATERIALS AND METHODS Male Crl:CDBR rats, approximately 7 weeks old, were received from Charles River Breeding 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 adminis. .od by the Laboratory Veterinarian. Water samples are periodically analyzed for total bacterial counts and for the presence o f coliforms, 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 o f a list o f 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 prior to testing. Animal rooms were maintained on a timer-controlled, 12hour light/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature o f 23C lC 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 dosed neat and administered to I rat per dose rate by intragastric intubation. The density of the test substance was 1.1 g/mL or 1100 mg/niL. In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. Dose rates administered -5 - Company Sanitized. Does not contain TSCA CBI Approximate Lelhal Dose (ALD) oi H-21460 in Rais DuPtmt HLR 176-% ranged from 2300 to 11,000 mg/kg of body weight in increments o f approximately 50%. Additionally, I rat was dosed at 670 mg/kg. The dosing day was test day I; postexposure day 14 was test day 15. Following administration o f the test rats were observed for clinical signs of toxicity. Rats were weigheri 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. C. Records Retention All raw data and the final report will be stored in the archives o f Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Company, Newark, Delaware o r in the DuPont Records Management Center, Wilmington! Delaware. 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 the study. Dosage (mg/kg) 670 2300 3400 5000 7500 11.000 Dose Volume (mL) 0.16 0.54 0.79 1.2 1.6 2.5 Density Concentration (me/mL) 1100 1100 100 1100 1100 1100 Initial Body Weight (g) 260 259 256 260 237 247 Mortality No No No No No No B. Clinical Signs No clinical signs of toxicity were observed during the tudy. Company Sanitized. Does not contain TSCA CBI Approximate Lethal Doe (ALD) ofH-2!460 in DuPont HLBl7iLaft 8to?y***" ALDfor H-214fi0 was greater than I l.flon *.*. * OTootfyweight This substance is consideredto be vmrylow in toxicity (A ll 5000mg^kg) when administered as a single oral dose to nude rats. . 1.' . ** , -r i r 'N ; 'f . H .' i r- ` : :i' : - * t \ K V ' - l;< W' i v . v L ? r - r l : ' , :,< - if} : -`" i f - i - ' - i f >V - . ,,V -v jI if r f ' f / j T f - ' r ^ fe .3 1 s i.- .,: *?T*gS -?-,r 1 * 4 * . i- ;;;&$ 'iv ) .-V