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1,4-Dioxane. I. Results of a 2-year ingestion study in rats

1974; Elsevier BV; Volume: 30; Issue: 2 Linguagem: Inglês

10.1016/0041-008x(74)90099-4

1096-0333

R.J. Kociba, Susan B. McCollister, C. Park, Theodore R. Torkelson, P.J. Gehring,

Carcinogens and Genotoxicity Assessment

Four groups of rats, 60/sex/level, were maintained on drinking water containing 0, 1.0, 0.1, or 0.01% 1,4-dioxane for up to 716 days. Male and female rats receiving 1% dioxane (equivalent to approximately 1015 and 1599 mg/kg/day, respectively) showed decreases in body weight gains, survival rates, and water consumption. Hepatocellular and renal tubular degenerative changes, accompanied by regenerative activity, were similar to those reported in previous studies following exposure to toxic levels of dioxane. Hepatocellular and nasal carcinomas, occurring at this dose level, were considered related to the lifetime exposure to these massive toxic dosages of dioxane. Male and female rats receiving 0.1% dioxane (equivalent to approximately 94 and 148 mg/kg/day, respectively) in the drinking water had variable degrees of renal and hepatic degenerative changes, but there was no indication of treatment-related tumor occurrence. Male and female rats receiving 0.01% dioxane in the drinking water (equivalent to approximately 9.6 and 19.0 mg/kg/day, respectively) showed no evidence of tumor formation or other toxic effects considered to be related to treatment. These data indicate a dose response for the toxicity of dioxane.