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AR226-2830 Material Tested: Material Submitted by Copies Co: E. I. du Font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine HASKELL LABORATORY REPORT NO. 245-71 rganic Chemicals Department [Jackson Laboratory Haskell No.: Otner Codes: 6918 ACUTE ORAL TEST Procedure: The test material, as an aqueous suspension, was administered by intragastric intubation ChR-CD male rats in single doses. Survivors were sacrificed 14 days later; the livers were removed analysis. Results: Suspension ^ Dose ('"R/kg) Mortality* Weight When Killed (g) Body Liver 25 11,000+ 25 7,500+ 25 5,000 25 3,400 15 2,250 25 1,500 25 1,000 15 670 14 d. 14 d. 14 d. 14 d. 14 d. 14 d. 14 d. 14 d. 325 330 334 343 345 318 331 364 16.20 16.38 15.27 16.18 14.62 13.22 13.65 16.00 * S - ( ) d. = Sacrificed ( ) days after dosing + Administered in divided doses L.W./B.W. X 100 5.0 5.0 4.6 4.7 4.2 4.2 4.1 4.4 Clinical Sign None TEN-DOSE ORAL SUBACUTE TEST Procedure: The test material was administered by intragastric intubation, as a 15% aqueous suspensi six young adult ChR-CD male rats, five times a week for two weeks; another group cf six rats served and was intubated with water. Three test and three control rats from each group were sacrificed app four hours and 14 days after the last dose. Results: Dose (mg/kg/day) Mortality Weight of Animals After lUth Dose Liver (s) Killed: 14 Days After 10th Dose L.W./B.W. X 100 Animals Killed: After 14 Days 10th After Dose 10th Dose Gross Pathology^ on Liver Animals Killed; After 14 Days 10th Dose After 10th Dose 2200 0/6 18.2 14.3 19.7 17.6 21.2 18.2 5.9 3.6 6.0 4.8 7.2 5.4 0 (Control) 0/6 13.0 17.1 13.9 13.3 8.4 18.1 4.2 4.3 4.2. 4.0 3.6 4.1 In addition, the following organs were examined histologically: brain, eyes, stomach, du spleen, bone marrow, pancreas, adrenal, kidney, testis, epididymis, lung, and trachea; no compound histologic changes were observed in any of these organs. Gross and histopathologic code No abnormality detected Large and heavy Slightly ' -ge and heavy Reduction jf number of centrilobular Focal RE cell hyperplasia cytoplasmic vesicles ^ ^ R4 .Sunimar^:!|HBHHH^BI^Bi^HilB^HHBQhas low toxicity when administered orally to young ad male raw; its Approximate Lethal Dose (ALD) ft greater than 11,000 mg/kg of body weight. There was gross nor gravimetric evidence of liver enlargement 14 days after dosing. Repeated administration of the test compound to rats at a rate of 2200 mg/kg/day for ten large and heavy livers at the end of the test phase, but these livers were within the normal range the 14-day recovery phase. Histologically, the compound caused a reduction of the number of centril cytoplasmic vesicles after the tenth dose and after the 14-day recovery period. This type of liver considered reversible; this reversibility probably would have been manifest with a longer recovery Da te: July 20. 1971 Report by: Joan A.. Oral Toxico ^'JIof hn/A. Approved by: _____^JfjL-H . .... /./ '/;cs / ..'Dir