Potentiations of N-Methylcarbamate Toxicities by Organophosphorus Insecticides in Male Mice

Abstract

Potentiations of N-Methylcarbamate Toxicities by Organophosphorus Insecticides in Male Mice. TAKAHASHI, H., KATO, A., YAMASHITA, E., NAITO, Y., TSUDA, S., and SHIRASU, Y. (1987). Fundam. Appl. Toxicol. 8, 139–146. A N-methylcarbamate insecticide, 2-sec-butylphe-nyl 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, feni-trothion, 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.