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437 TRADE SECRET 4*SU_ 3LT DuPont- 11269 Study Title H-25357: Oral Approximate Lethal Dose (ALD) in Rats Laboratory Project ID: DuPont-11269 A u t h o r : Carol Finlay, B.A. S t u d y C o m p l e t e d o n : August 9, 2002 P e r f o r m in g L a b o r a t o r y : E.I. du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Com paq S T tm -i. a TM>' TSC* " * Page 1 o f 8 H-25357: Oral Approximate Lethal Dose (ALD) in Rats DuPont-11269 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of the data obtained from this study. Reviewed by: JamesiC. Mackay n Associate Scientist ftrate z- Issued by Study Director: tL arol Finlay, .A. Staff Toxicologist ^ \ - l A Cyi' D atoJ -fSCA CBI Comp*1* SanRl*^.Ooe010001*40 -2- H-25357: Oral Approximate Lethal Dose (ALP) in Rats STUDY INFORMATION Substance Tested: Svnonvms/Codes: _ H-25357 Submitter's Notebook Numberfs):^ j [ [ J J p H ^ Haskell Number: 25357 CAS Registry Number: Composition:' Known Impurities DuPont-11269 Physical Characteristics: Amber liquid Sponsor: E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: June 14, 2002 / (see report cover page) In-Life Initiated/Completed: July 3, 2002 / July 22, 2002 C o w p a ^ SBn1 -3- -- fcCBI H-25357: Oral Approximate Lethal Dose (ALP) in Rats DuPont-11269 STUDY PERSONNEL Study Director: Carol Finlay, B.A. Management: Scott E. Loveless, Ph.D. Primary Technician: Diana L. Ritchie Toxicology Report Preparation: Sean M. Callaghan, B.A. Management: Nancy S. Selzer, M.S. Laboratory Veterinarian: William Singleton, D.V.M., A.C.L.A.M. tsca cbi Sanitiw d- D 06*1,010001810 Comp*" -4 - H-25357: Oral Approximate Lethal Dose (ALD) in Rats DuPont-11269 SUMMARY H-25357 was administered as a single oral dose by intragastric intubation to male rats at doses of 670, 2300, 3400, 5000, 7500, and 11,000 mg/kg. Following dosing, the rats were weighed and observed for mortality and clinical signs of toxicity over a 14-day observation period. No deaths occurred. No clinical signs were observed, and no biologically important body weight loss occurred during the study. Under the conditions o f this study, the oral ALD for H-25357 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. Co*wPaW .Does ^ c o n ta in tSCA&Bl -5 - H-25357: Oral Approximate Lethal Dose (ALD) in Rats DuPont-11269 INTRODUCTION The purpose of this test was to determine an approximate lethal dose (ALD) o f H-25357 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. Test Substance The test substance, H-25357, was supplied by the sponsor as an amber liquid. The test substance appeared to be stable under the conditions o f the study. No evidence of instability, such as a change in color or physical state, was observed. B. Animal Husbandry Male Crl:CD(SD)IGS BR rats were received from Charles River Laboratories, Inc., Raleigh, North Carolina. Rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards. 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. PMI Nutrition international, LLC Certified Rodent LabDiet 5002 and water were available ad libitum. As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrity o f the study: Water samples are analyzed for total bacterial counts, and the presence o f coliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore, and fungal counts. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations o f key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity o f the study. Cenpaay Sanitized. Does not contain TSCA CBI H-25357: Oral Approximate Lethal Dose (ALD) in Rats DuPont-11269 The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. Evaluation of these data did not indicate any conditions that affected the validity of the study. Rats were weighed and observed for general health during the 6-day quarantine period. 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 23 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 of the study. C. Protocol The test substance was administered neat to 1 rat per dose rate by intragastric intubation. The volumes administered were calculated based on the test substance density o f 1090 mg/mL and body weights collected on the day o f dosing. Doses 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 of toxicity. 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 illness, injury, or abnormal behavior were made daily throughout the study. Pathology examinations o f test animals were not performed. Com pany Sanitized. D oes not contain T S C A CB H-25357: Oral Approximate Lethal Dose (ALD) in Rats DuPont-11269 RESULTS AND DISCUSSION A. Dosing and Mortality Data No deaths occurred during the study. The dose regimen and the mortality resulting over the 15day test period are detailed below. Dose (mg/kg) 670 2300 3400 5000 7500 11,000 Volume (mL) 0.14 0.46 0.90 1.2 1.8 2.8 Density (mg/mL) 1090 1090 1090 1090 1090 1090 Initial Body Weight (g) 225.2 215.8 287.8 266.9 266.7 281.7 Mortality No No No No No No B. Clinical Signs and Body Weights No clinical signs were observed, and no biologically important body weight loss occurred during the study. CONCLUSIONS Under the conditions of this study, the oral ALD for H-25357 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. RECORDS AND SAMPLE STORAGE Specimens (if applicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. 0 ompanf Sanitized. Does not contain TSCA CBI -8-