Effect of phenobarbital pretreatment on the metabolism of DDT in the rat and the bovine

Abstract

Lactating cows receiving 100 mg of DDT/day in the feed during 63 days were given daily ip injections of phenobarbital sodium at a dose of 5 mg/kg, from day 28 until day 49. During the period of treatment with phenobarbital, a decrease was noted in the fat-soluble residues of DDT and its metabolites in the milk, owing to a significant reduction in the presence of p,p′-DDD. Young bulls pretreated with phenobarbital at the same dose, during 7 or 14 days, prior to a single iv injection of 2 g DDT, showed a marked increase in the rate of urinary excretion of the water-soluble metabolite DDA as compared with unpretreated animals. Similar results were also observed in rats. Enzyme induction appeared to be present in the liver of pretreated bulls, as evidenced by an increased rate of in vitro metabolism of parathion and paraoxon. Similarly, pretreatment of adult female rats with phenobarbital (50 mg/kg/day for 7 days) stimulated the in vitro degradation, by liver homogenates, of p,p′-DDT to p,p′-DDD but not to p,p′-DDE. These results suggest that bovine liver is susceptible to enzyme induction and that phenobarbital stimulates the hepatic biotransformation of DDT to DDD and, possibly, to DDA.