Potentiation of acute toxicity of 2-sec-butylphenyl N-methylcarbamate (BPMC) by fenthion in mice.
This study was undertaken to determine whether interactions of toxicologic importance might occur during combined exposure of male mice to 2-sec-butylphenyl N-methylcarbamate (BPMC) and O,O-dimethyl O-(3-methyl-4-methylthiophenyl)phosphorothioate (fenthion). The equitoxic coadministration of BPMC and fenthion resulted in only a 1.6-fold potentiation compared to the expected LD50. However, 1 hr oral pretreatment with 3 (1/100 LD50), 7.5, 15, and 30 mg/kg of fenthion resulted in 5-, 9-, 12-, and 15-fold potentiation of the acute oral toxicity of BPMC, respectively. This fenthion pretreatment caused significant increases in the BPMC plasma concentrations and in the area under the concentration-time curve. The increase of the plasma concentrations of BPMC depended upon the fenthion dose and was associated with that of the potency ratio. The pretreatment of fenthion prolonged the hexobarbital sleeping time. The plasma concentrations of BPMC after the administration of a dose of LD2.5 (20 mg/kg) in fenthion-pretreated mice were clearly lower than those of a dose of LD2.5 (195 mg/kg) in nontreated mice. These results suggested that fenthion pretreatment caused the potentiation of the acute toxicity of BPMC partially by the inhibition of detoxification of BPMC.
D000284:Administration, Oral; D000818:Animals; D002219:Carbamates / Q000097:blood / Q000633:toxicity*; D004357:Drug Synergism; D005284:Fenthion / Q000633:toxicity*; D006591:Hexobarbital / Q000494:pharmacology; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012890:Sleep / Q000187:drug effects
D002219:Carbamates; D007306:Insecticides; C019276:BPMC; D006591:Hexobarbital; D005284:Fenthion