Age dependence of dithiobiuret neurotoxicity in male and female rats.

Weanling, juvenile and adult rats both sexes were treated with 1 mg/kg/day [14C] dithiobiuret (DTB) until they developed skeletal muscle weakness as detected by failure in a rotarod test. The latent period before the onset of weakness was longest in weanling animals of both sexes. The greater resistance of the weanlings, to DTB intoxication, could not be explained by differences in the cumulative body burden or tissue distribution of DTB and its metabolites. The sex of the animal was not a determinant of DTB toxicity. Urine and feces were the major and minor routes, respectively, for elimination of DTB and its metabolites in all animals. However, weanlings excreted relatively less 14C by the urinary route and more by the fecal route when compared to adults. These findings demonstrated the age dependence of DTB neurotoxicity in rats and show that it is not caused by differences in either the cumulative body burden or tissue distribution of DTB-derived [14C].