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.
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.
D000818:Animals; D002219:Carbamates / Q000378:metabolism / Q000633:toxicity*; D004357:Drug Synergism; D005278:Fenitrothion / Q000378:metabolism / Q000633:toxicity*; D006591:Hexobarbital / Q000494:pharmacology; D066298:In Vitro Techniques; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D006899:Mixed Function Oxygenases / Q000032:analysis; D010634:Phenobarbital / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects
D002219:Carbamates; D007306:Insecticides; C019276:BPMC; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; D005278:Fenitrothion; D010634:Phenobarbital