Potentiated Toxicity of 2-sec-Butylphenyl Methylcarbamate (BPMC) by O,O-Dimethyl O-(3-Methyl-4-nitrophenyl)phosphorothioate (Fenitrothion) in Mice; Relationship between Acute Toxicity and Metabolism of BPMC

Potentiated Toxicity of 2-sec</it>-Butytpbenyl Methylcarbamate (BPMC) by O,O</it>-Dimethyl O</it>-(3-Methyl-4-nitrophenyl)phosphorothioate (Fenitrothion) in Mice; Relationship between Acute Toxicity and Metabolism of BPMC. TAKAHASHI, H., MIYAOKA, T., TSUDA, S., AND SHIRASU, Y. (1984). Fundam. Appl. Toxicol</it>. 4, 718–723. Fenitrothion of oral subtoxic dose (100 mg/kg; 4 hr pretreatment) decreased acute oral LD50 of BPMC from 360 to 66 mg/kg in male mice. The treatment prolonged the hexobarbital sleeping time and increased the plasma BPMC concentrations. The BPMC toxicity and its plasma concentrations were significantly reduced by phenobarbital treatment (80 mg/kg/day, 2 days, ip). This treatment diminished the effects of fenitrothion on BPMC toxicity and plasma BPMC concentrations. BPMC was metabolized by mixed-function oxidases of the liver in vitro</it>. The metabolism of BPMC was competitively inhibited by the addition of fenitrothion (5 μg/ml). Fenitrothion remained in the liver (7 μg/g liver). These results suggest that competitive inhibition of BPMC metabolism by fenitrothion may, at least in part, play a role in inhibition of BPMC detoxication, resulting in potentiation of its toxicity.