Pentachlorophenol has earlier been shown to be metabolized in mammals to tetrachloro-p-hydroquinone. The metabolite possesses pronounced inhibitory activity on bacterial/3-glucuronidase but not on/5-glucuronidase from liver. Indirect evidence for the occurrence of both pentachlorophenol and tetraehloro-p-hydroquinone as conjugates with glueuronic acid in the urine from pentachlorophenol-treated rats is now presented. Bovine liver/3-glucuronidase has been utilized to split the conjugates present.
The in vivo metabolism of pentachlorophenol has also been studied in rats treated with phenobarbital and/3-diethylarninoethyldiphenyl propylacetate (SKF 525-A). In vitro metabolism has been studied using liver mierosomes from rats pretreated with phenobarbital. Quantitative analysis of the compounds occurring in extracts of urine or extracts from the mierosomal incubates was performed by means of mass fragmentography. Pretreatment with phenobarbital increased the metabolism of pentachlorophenol to tetrachloro-p-hydroquinone both in vivo and in vitro. SKF 525-A, however, inhibited the metabolism in vitro but enhanced the metabolism in vivo when given less frequently than every 6th h. Dechlorination of pentachlorophenol is mediated by microsomal enzymes that can be induced by phenobarbital. SKF 525-A does not inhibit the dechlorination in vivo but does so in vitro.