Effect of O, O-dimethyl O- (3-methyl-4-nitrophenyl) phosphorothioate (fenitrothion) treatment on acute toxicity of 2-sec-butylphenyl methylcarbamate (BPMC) in dogs.

Abstract

The effects of O, O-dimethyl O-(3-methyl-4-nitrophenyl) phosphorothioate (fenitrothion) on the acute toxicity of 2-sec-butylphenyl methylcarbamate (BPMC) were investigated in dogs. The plasma concentration of BPMC and the erythrocyte cholinesterase (ChE) activity were measured to examine whether these parameters were appropriate indicators for the toxic effects. The increase of BPMC dose (50-400mg/kg, p.o.) aggravated the toxic symptom accompanied with the increase of plasma concentrations of BPMC and ChE inhibition. Oral coadministration of fenitrothion (100mg/kg; no effective dose) greatly extended the duration of toxic symptom of BPMC (50mg/kg; minimum effective dose) to 2-fold (5h). The plasma level of BPMC in the eliminating phase was increased by the coadministration and began to decrease after 6h, while ChE inhibition continued for 8h. Pretreatment with fenitrothion 5mg/kg/day for 7 days caused one death out of 3 dogs after the administration of BPMC (100mg/kg), while the same dose of BPMC without pretreatment did not cause any death. The pretreatment of fenitrothion increased the duration of toxic symptom of BPMC by 2.5-fold. The time course of the toxic symptom was similar to that of plasma concentration of BPMC but the inhibition of ChE in surviving dog was greater than that in dead one. These results suggested that the acute toxicity of BPMC was potentiated by fenitrothion and that the plasma concentration of BPMC was a better indicator of the potentiation than ChE activity.