Distribution, excretion and skeletal muscle effects of the mycotoxin [14C]cyclopiazonic acid in rats.

The distribution of the mycotoxin, cyclopiazonic acid (CPA), in tissues and its excretion in urine and faeces was studied in male Sprague-Dawley rats. Radiolabelled CPA was biosynthetically produced by cultures of Penicillium griseofulvum and was administered to rats either intraperitoneally (ip) or intragastrically (ig). Radiolabelled material was excreted in both urine and faeces from rats dosed by either route. There was no excretion of radioactivity as expired 14CO2. Biliary excretion apparently had a major role in the disposition of CPA, since 38% of the dose of radioactivity was excreted in the faeces of ip-dosed rats within 72 hr. Skeletal muscle tissue contained 48% of the radioactive dose 6 hr after either ip or ig administration. At 72 hr, skeletal muscle of the ip-dosed rats contained 3% of the dose, whereas rats dosed ig retained 8% of the dose in muscle. Degeneration was observed in muscle from rats treated with 8 mg CPA/kg/day for 4 days. The results indicate that some of the toxic effects observed in animals exposed to CPA (hyperaesthesia, hypokinesis, abnormal posture, opisthotonos and convulsions) may be due in part to direct effects of the toxin on muscle. Furthermore, if CPA or its metabolic products distributes in the tissues of other animals as it does in the rat, the potential exists for the exposure of humans to this mycotoxin by consumption of the meat of domestic animals fed contaminated feed.