MALATHION INHIBITION OF ESTERASES AS A DETERMINANT OF MALATHION TOXICITY

¹ Department of Physiology, Harvard School of Public Health, Boston, Massachusetts

The hydrolysis of malathion by rat, mouse and guinea-pig liver homogenates and by rat plasma was inhibited after treatment of the animals with malathion. In rats and guinea pigs the hydrolysis of malathion was inhibited by doses of the insecticide below those which inhibited brain or erythrocyte cholinesterase. After single large doses of malathion, inhibition of malathion-esterase occurred sooner and persisted longer than cholinesterase inhibition. Evidence that inhibition of malathion-esterase occurs in vivo and is important in determining the toxicity of subsequent doses of malathion was obtained in experiments which showed that guinea pigs and rats that were pretreated with less than cholinesterase-inhibiting quantities of malathion were more sensitive to poisoning by subsequent doses of the insecticide. The results of several in vivo and in vitro experiments suggested that a metabolite of malathion (possibly the oxygen analog, malaoxon) was the actual inhibitor of malathion-esterase and that technical grade samples of malathion may contain a small quantity of this inhibitor. The results of this investigation indicate that an early biochemical event leading to poisoning by malathion is the inhibition of its own further hydrolytic detoxication by a metabolite (or, in cases of less pure samples, by a contaminant) of the parent insecticide.