Induction of hepatic cytochrome p450 activities by toxaphene in rat and japanese quail

Abstract

Several organochlorine compounds can induce hepatic cytochrome P450 activities. We exposed female Japanese quail and female rats to a single oral dose of technical toxaphene ranging from 0.012 to 40 mg/kg body weight to investigate a possible dose‐response relationship for P450 activity induction. The hepatic microsomal alkoxyresorufin dealkylation and steroid hydrox‐ylation activities (testosterone, 17β‐estradiol) were determined. Only in the highest dose groups (40 mg/kg) of rats and Japanese quail were some P450 activities induced. Pentoxyresorufin‐O‐dealkylation, formation of 15β‐hydroxytestosterone, and formation of 2‐hydroxyestradiol were induced significantly (p ≤ 0.05) in rat hepatic microsomes with a factor of 3.9, 3.1, and 2.4, respectively. In Japanese quail hepatic microsomes, the formation rates of 6β‐, 15α‐, 16β‐hydroxytestosterone and androstenedione were induced significantly (p ≤ 0.05) with a factor of 2.4, 6.5, 3.3, and 1.6, respectively. It is concluded that exposure to toxaphene can lead to specific P450 activity induction in rats and Japanese quail but only at doses near reported LD50 values. Because reported toxaphene levels in biota are lower compared with liver residue levels that we have measured in our study, we conclude that it is unlikely that P450 activity induction occurs in wildlife higher in the food chain due to environmental toxaphene exposure.