Document dMDZy69ZwEy9GEKmR5JMXQX6

TRADE SECRET AR226-3084 DuPont HL-1997-01291 Study Title H-23004: Oral Approximate Lethal Dose (ALD) in Rats Laboratory Project ID: HL-1997-01291 Author: Tracy A. Filliben Study Com pleted on: December 30,1997 P erforming Laboratory: E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Work Request Number: w Page 1 of 8 Company Sanitized. Does not contain TSCA CBt H-23004: Oral Approximate Lethal Dose (ALD) in Rats DuPont HL-1997-01291 Study D irector: Issued b C E R T IF IC A T IO N CL ' , yv / y ' Tracy A. Filliben Toxicology Associate ____________ """ /Z J"3C>lCl'7 D ate W -2 - Company Sanitized. Does not contain TSCA CBi H-23004: Oral Approximate Lethal D ose (ALP) in Rats STUDY INFORM ATION Substance T e s te d M ^ M M ^ Svnonvms/Codes: H-23004 Haskell Number: 23004 Submitter's Notebook Number(s) Compositio: DuPont HL-1997-01291 Known Impurities: Physical Characteristics: Off-white liquid Stability: The test substance appeared to be stable under the conditions o f the study; no evidence of instability was observed. Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: November 25,1997 / (see report cover page) Tn-LifeInitiated/Completed: November25, 1997/D ecem ber 19,1997 -3 - C om pany Sanitized. Does n ot contain TSCA CBI H-23004: Oral Approximate Lethal Dose (ALP) in Rats DuPont HL-1997-01291 STUDY PERSONNEL Manager: Judith C. Stadler, Ph.D. Study Director: Tracy A. Filliben Primary Technician: Tracy A. Filliben Toxicology Report Preparation(s): Maryanne M. Wilford, B.A. Laboratory Veterinarian: Charles B. Cover, V.M.D. -4 - Company Sanitized. Does not contain TSCA CBI H-23004: Oral Approximate Lethal D ose (ALD) in Rats DuPont HL-1997-01291 I SUMMARY H-23004 was administered as a single oral dose by intragastric intubation to male rats. Following dosing, the rats were weighed and observed for mortality and clinical signs of toxicity over a 14-day observation period. No deaths, clinical signs of toxicity, or weight losses were observed during the study. Under the conditions o f this study, the ALD for H-23004 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 H-23004: Oral Approximate Lethal Dose (ALP) in Rats DuPont HL-1997-01291 IN T R O D U C T IO N The purpose of this test was to determine an approximate lethal dose (ALD) of H-23004 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 M ETHODS A. Animal H usbandry Male Crl:CD(SD)BR rats were received from Charles River Laboratories. 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 tailmarked, 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. rThis^jrogram is^m onitoredcind----administered by the Laboratory Veterinarian. W ater samples are periodically analyzed for total bacterial counts and for the presence of coliforms, lead, and other contaminants. Additionally, samples from freshly washed cages and cage racks are periodically analyzed to ensure 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/12-hour dark cycle. Environmental conditions o f the rooms were targeted for a temperature of 23C 1C and relative humidity of 50% 10%. Excursions outside these ranges were o f 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 doses were calculated based on the test substance density of 1000 mg/mL and body weights collected on the day o f dosing. Dose rates administered ranged from 2300 to 11,000 mg/kg of body weight in increments of approximately 50%. Additionally, 1 rat was dosed at 670 mg/kg. The dosing day was test day 1; postexposure day 14 was test day 15. Following administration of the test substance, rats were observed for clinical signs of toxicity. 6- - Company Sanitized. Does not contain TSCA CBS H-23004: Oral Approximate Lethal Dose (ALD) in Rats DuPont HL-1997-01291 The rats were weighed and observed at least 2 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 o f test animals were not performed. RESULTS AND DISCUSSION A. Dosage and M ortality D ata 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) ..... 0.17............ 0.60 0.92 1.3 1.9 3.0 Density (mg/mL) 100 1000 1000 1000 1000 1000 Initial Body W eight (g) . ____ 255____ 259 272 266 258 275 M ortality No No No No No No B. Clinical Signs an d Body W eights No clinical signs of toxicity or body weight losses were observed during the study. CONCLUSIONS Under the conditions o f this study, the ALD for H-23004 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. Conwan, Sanitized. Does not contain TSCA CBI H-23004: Oral Approximate Lethal Dose (ALP) in Rats .DuPont HL-1997-01291 RECORDS RETENTION All study records, raw data, and the final report are retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain, 200 Todds Lane, W ilmington, Delaware 19802 (formerly known as the E. I. du Pont de Nemours and Company Records Management Center). Company Sanitized. Does not contain TSCACBI