Biodegradation of alpha-hexachlorocyclohexane. IV. The extent of degradation of single doses in vivo.

1. Urine and stools were collected daily of 4 adult rats kept in single cages and injected once i.p. with alpha-hexachlorocyclohexane (alpha-HCH; dose per animal 126-150 mumoles), labelled uniformly with 14-C (10.8-14.0 X 10(6) dpm per animal). 2. In 4 weeks, 65% of the label was excreted through the kidneys and 16% by way of the intestine, with an estimated 8% being retained in depot fat. 3. GLC-analysis of the pooled urine showed it to contain very little unchanged drug, on average 0.05% of the dose. The time-course of the renal excretion of 14-C-labelled substance corresponded rather closely to the excretion of organically bound 36-Cl seen in earlier experiments with 36-Cl-labelled drug, indicating that the majority of urinary metabolites, presumably, still bear chlorine. 4. All or nearly all of the faecal 14-C was found by GLC to be accounted for by the stool's content of unchanged alpha-HCH. 5. Taken together, the results indicate a mean extent of alpha-HCH-degradation in the rat in the order of 80-85% of a dose. 6. Two rats were given 400 mg/kg of "cold" alpha-HCH by mouth 4 days before i.p. application of 14-C-labelled drug and were found to excrete more label through the kidneys in the first week than did the non-pretreated rats. This indicates that the drug stimulates its own degradation.