Toxicity studies of epichlorohydrin in Sprague-Dawley rats.
Adult male and female Sprague-Dawley rats received epichlorohydrin via gavage in distilled water for 10 consecutive days at dose levels of 3, 7, 19, and 46 mg/kg-day, and for 90 days at dose levels of 1, 5, and 25 mg/kg-day. Epichlorohydrin did not adversely effect mortality, but toxicity, at the higher doses, was evident by: 1) losses in body weight gain and organ weights, 2) reductions in food and water consumption, and 3) in the hematological and microscopic examinations in both study periods. Significant decreases in erythrocyte count, hemoglobin, and hematocrit levels were found in the high dose level in males after 10 and 90 days. Dose-related increases in kidney and liver weights were observed in both sexes at 25 mg/kg-day in the 90-day study and in various organs for both 19 and 46 mg/kg-day in the 10-day study. Histopathological examination identified the forestomach as the primary target organ for both sexes and in both studies with significant dose-related increases in mucosal hyperplasia (acanthosis) and hyperkeratosis. Based on the data presented, a lowest observable adverse effect level (LOAEL) for oral exposure of Sprague-Dawley rats to epichlorohydrin is 3 mg/kg-day for 10 days and 1 mg/kg-day is suggested as the no observed adverse effect level (NOAEL) for a 90 day oral exposure. These conclusions were the same whether the lesions were analyzed for each sex individually or whether the data in each study was pooled.
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Environmental Monitoring Systems Laboratory, U. S. Environmental Protection Agency, Cincinnati, Ohio 45268, USA.
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D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D001774:Blood Chemical Analysis; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004811:Epichlorohydrin / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000254:growth & development; D008099:Liver / Q000187:drug effects / Q000254:growth & development; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*; D013270:Stomach / Q000002:abnormalities / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000254:growth & development; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
D002273:Carcinogens; D012997:Solvents; D004811:Epichlorohydrin