Studies on the Mode of Action of Organophosphorus Compounds

Abstract

In order to further elucidate the mechanism of metabolic difference between sumithion and methylparathion, distribution of sumithion and methylparathion into several tissues, activation, that is, conversion into more toxic oxygen analogs, and degradation into non-toxic compounds were examined in vivo following the intravenous administration of the phosphorothioates to Guinea pigs and white rats. Sumioxon and methylparaoxon were detected in all tissues tested, among which lung and liver were richest in them. More sumioxon than methylparaoxon was found. Chese organophosphorus compounds were found to be decomposed to non-toxic desmethyl compounds and dimethyl phosphorothioic acid mainly in liver and kidney. From these results it seems improbable that the lower toxicity of sumithion than that of methylparathion results from the different in their rate of metabolism. As reported previously, sumithion and sumioxon inhibit brain cholinesterase activity of mammals less potently in vivo than methylparathion and methylparaoxon respectively. Phosphorus content and inhibition of cholinesterase in Guinea pig brain were investigated in vivo after the intravenous administration of phosphorus labeled phosphorothioates and their oxygen analoges, in order to clarify if any relationships be observed between phosphorus content and inhibition. Although content of phosphorus derived from sumithion was not significantly different from that obtained from methylparathion, reduction of cholinesterase activity by methylparathion was strikingly larger than that by sumithion. On the other hand, phosphorus derived from sumioxon was found to penetrate into Guinea pig brain less than methylparaoxon phosphorus, and as the result the former hindered the enzyme activity less effectively. From these results, the mechanism of lower toxicity of sumithion toward mammals was presumed.