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

Fundam Appl Toxicol. 1984 Oct;4(5):718-23. doi: 10.1016/0272-0590(84)90092-7.

Abstract

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. The metabolism of BPMC was competitively inhibited by the addition of fenitrothion (5 micrograms/ml). Fenitrothion remained in the liver (7 micrograms/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbamates / metabolism
  • Carbamates / toxicity*
  • Drug Synergism
  • Fenitrothion / metabolism
  • Fenitrothion / toxicity*
  • Hexobarbital / pharmacology
  • In Vitro Techniques
  • Insecticides / toxicity*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mixed Function Oxygenases / analysis
  • Phenobarbital / pharmacology
  • Sleep / drug effects

Substances

  • Carbamates
  • Insecticides
  • BPMC
  • Hexobarbital
  • Mixed Function Oxygenases
  • Fenitrothion
  • Phenobarbital