The acute toxicity of oxamniquine in rats; a sex-dependent hepatotoxicity.

ABSTRACT

Toxicity studies with oxamniquine in several laboratory animal species revealed an idiosyncratic sensitivity of rats, females being much more sensitive than males. After single p.o. doses of oxamniquine, rats died up to 14 days after the dose from hepatic failure. At doses near the LD-50, serum transaminases were high and proteins low from 24 h after the dose in females and from 48 h in males; serum and liver triglycerides showed no clear changes. Histologically the livers were characterised by cytoplasmic inclusion bodies, parenchymal necrosis, and bile duct proliferation. Metabolism and pharmacokinetic data were inadequate to explain the sex-dependency of this toxicity, but tissue distribution studies with carbon-14 labelled oxamniquine showed that 72 h after a given dose livers of female rats retained more label than males, and that little of this was due to unchanged drug.