Document 4JwZzEEQgZMw374ZeoggXvb8p

TRADE SECRET AR226-3081 DuPont HL-1997-00867 Study Title H-22762: Oral Approximate Lethal D ose (ALD) in Rats Laboratory Project ID: HL-1997-00867 Author: Tracy A. Fiflibeh Study Completed on: December 5,1997 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 19714-0050 W ork Request Number: Page 1 o f 7 H-22762: Oral Approximate Lethal Dose (ALP) in Rats GENERAL INFORMATION DuPont HL-1997-00867 Haskell Number: 22762 .... Puritv| Known impurities Physical Characteristics: Clear yellow liquid Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. D Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: July 17,1997 / (see report cover page) In-Life Initiated/Completed: July 17,1997 / August 20,1997 All study records, raw data, and the final report are retained at Haskell Laboratory or at Iron Mountain, 200 Todds Lane, Wilmington, Delaware 19802 (formerly known as the E. I. du Pont de Nemours and Company Records Management Center). Company Sanitized. Does not contain TSCA CB1 -2 - H-22762: Oral Approximate Lethal Dose (ALD) in Rats DuPont HL-1997-00867 SUMMARY H-22762 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 o f toxicity over a 14-day observation period. Rats dosed at 5000, 7500, or 11,000 mg/kg were found dead 1 day after dosing. Clinical signs of toxicity and body weight losses were observed in lethally and non-lethally dosed animals. Under the conditions o f this study, the oral ALD for H-22762 was 5000 mg/kg of body weight. This substance is considered to be slightly toxic (ALD 500 - 5000 mg/kg) when administered as a single oral dose to male rats. Company Sanitized. Does not contain TSCA CBt -3 - H-22762: Oral Approximate Lethal Dose (ALD) in Rats SIGNATURE PAGE DuPont H L -1997-00867 Reviewed and Approved for Issue:' Tracy A. Filliben Study Director /Z jS T iT l STUDY PERSONNEL The following individuals were responsible for conduct of the study: Manager: Nancy C. Chromey, Ph.D. Study Director: Tracy A. Filliben, Primary Technician: Tracy A. Filliben Assisting Personnel: Carol Finlay, B.A. M. Scott Karr, A.S. Toxicology Report Preparation(s): John D. Oldham, Jr., B.S. The following individual was responsible for assessing the health status of the animals on study: Laboratory Veterinarian: Charles E. Cover, V.M.D. '. Co" M"i's >id. Does n f contain TSCA CBf -4 - H-22762: Oral Approximate Lethal Dose (ALD) in Rats DuPont HL-1997-00867 INTRODUCTION The purpose o f this test was to determine an approximate lethal dose (ALD) o f H-22762 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 o f dosing or within 14 days post exposure. MATERIALS AND METHODS A. Animal H usbandry Male Crl:CD(SD)BR rats, approximately 7-10 weeks old, 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 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 administered 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 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 o f a list o f specified contaminants. On the basis o f 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 o f 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 o f 23C 1C and relative humidity o f 50% 10%. Excursions outside these ranges were o f small magnitude and/or brief duration and did not adversely affect the validity o f the study. B. Protocol The test substance administered neat to 1 rat per dose rate by intragastric intubation. The doses were calculated based on the test substance density o f 1600 mg/mL and body weights collected on the day o f dosing. Dose rates administered ranged from 2300 to 11,000 mg/kg o f body weight in increments o f 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 o f the test substance, rats were observed for clinical signs o f toxicity. CompanyS m U zrt DoK noloonte|n rsCA ^ -5 - H-22762: Oral Approximate Lethal Dose (ALP) in Rats DuPont HL-1997-00867 The rats were weighed and observed at least 3 times a week throughout the 14-day observation period. Observations for mortality and signs o f illnes?, injury, or abnormal behavior were made daily throughout the study. Pathological examinations o f test animals were not performed. RESULTS A. Dosage and M ortality Data The dosage regimen and the mortality resulting over the 15-day test period are detailed below. The lowest dose o f H-22762 which resulted in the death o f a test animal was 5000 mg/kg. Rats dosed at 5000, 7500, or 11,000 mg/kg were found dead 1 day after dosing. Dosage (mg/kg) 670 2300 3400 5000 7500 11,000 Dose Volume (mL) 0.11 0.35 0.61 0.78 1.3 2.0 Suspension Density (mg/mL) 1600 1600 1600 1600 1600 1600 Initial Body Weight (g) 257 246 285 249 279 297 Mortality No No No Yes Yes Yes B. Clinical Signs and Body Weights 1. Nonlethal Doses No clinical signs o f toxicity were observed in the rat dosed at 670 mg/kg. Wet, yellow-stained perinium was observed in the rats dosed at 2300 and 3400 mg/kg within the first 2 days after treatment. The rat treated at 3400 mg/kg exhibited a weight loss o f approximately 6% o f initial body weight by 2 days after dosing. ` 2. Lethal Doses The rat treated at 7500 mg/kg exhibited a weight loss o f approximately 12% o f initial body weight, tremors, spasms, wet underbody, and splayed hindlegs 1 day after dosing. This rat was found dead the same day. The rats treated at 5,000 and 11,000 mg/kg were found dead 1 day after dosing; no clinical signs o f toxicity or weight losses were noted. Company Sanitizeti. Does nofcontain TSCACBl 6- - H-22762: Oral Approximate Lethal Dose (ALD) in Rats DuPont HL-1997-00867 CONCLUSION Under the conditions o f this study, the oral ALD for H-22762 was 5000 mg/kg o f body weight. This substance is considered to be slightly toxic (ALD 500 - 5000 mg/kg) when administered as a single oral dose to male rats. .Company Sanitized. Does notcontaiR. f