Potentiations of N-methylcarbamate toxicities by organophosphorus insecticides in male mice.
A N-methylcarbamate insecticide, 2-sec-butylphenyl N-methylcarbamate (BPMC), is markedly potentiated by low-dose treatments of P = S type organophosphorus insecticides. As a mechanism of this potentiation, the increase of plasma BPMC concentrations due to the inhibited metabolic degradation has been suggested. In this study, acute toxicities of five N-methylcarbamates structurally related to BPMC were studied after low-dose treatments of three P = S type organophosphorus insecticides (cyanophos, fenitrothion, and malathion) and one P = O type organophosphorus insecticide (dichlorvos), and the role of plasma concentrations of N-methylcarbamates in the potentiations was examined. Acute toxicities of five N-methylcarbamates were potentiated by the treatments of the P = S types, among which the potentiation of BPMC was strongest. BPMC toxicity was not potentiated by the treatment of the P = O type. Plasma concentrations of BPMC were increased by the treatments of the P = S types, but not by the treatment of the P = O type. The acute toxicity and plasma concentrations of BPMC were increased by SKF 525-A (an inhibitor of mixed-function oxidase). These results suggest that the increase of plasma BPMC concentrations may be related to the potentiation of BPMC toxicity. The treatment of fenitrothion increased plasma concentrations of other N-methylcarbamates more than those of BPMC, although the potentiation of BPMC toxicity was strongest. SKF 525-A and fenitrothion treatments increased plasma BPMC concentrations to a similar degree, but the potentiation of BPMC toxicity by SKF 525-A was significantly less than that by fenitrothion. Thus, some other mechanism(s) may be responsible for the potentiations of the N-methylcarbamate toxicities.
D000818:Animals; D002219:Carbamates / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D004357:Drug Synergism; D007306:Insecticides / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009943:Organophosphorus Compounds; D013047:Specific Pathogen-Free Organisms; D013329:Structure-Activity Relationship
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009943:Organophosphorus Compounds