The profile of rat liver enzyme induction produced by prochloraz and its major metabolites.

Abstract

1. The profile of the hepatic mixed-function oxidase system of male rats has been examined following treatment with prochloraz (I) and three of its major metabolites (II, III and IV). 2. The overall induction profile of prochloraz reflected the contribution of the individual metabolites. There was a slight increase of lauric acid hydroxylase, but by far the major induction was seen in the activity of aldrin epoxidase and 7-pentoxyresorufin-O-dealkylase (7- and 14-fold respectively). 3. N-Propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]urea (II), a primary intermediate in the metabolism of prochloraz, was a phenobarbitone-type inducer, increasing the activity of aldrin epoxidase and 7-pentoxyresorufin-O-dealkylase by 120% and 8-fold respectively. 4. The prochloraz metabolites, trichlorophenoxyethanol (III) and trichlorophenoxyacetic acid (IV) were both inducers of the clofibrate type, increasing the activity of lauric acid 12-hydroxylase. 5. The induction profile of prochloraz was of a mixed type, but the predominant characteristics were those of phenobarbitone induction.