Quantitative Measurement of Inhibition of the Enzymatic Detoxification of Malathion by EPN (ethyl p-nitrophenyl thionobenzenephosphonate).

Abstract

A study of the influence of EPN on the enzymatic detoxification of the pesticide malathion was undertaken to obtain information on the mechanism responsible for the ability of EPN to potentiate the toxicity of malathion. A method for measuring the hydrolytic detoxification of malathion was developed prior to the experiments with EPN. This method involved conversion of malathion to malaoxon by bromine oxidation and subsequent incubation of malaoxon with aqueous tissue homogenates in phosphate buffer at 38[degree] C for 10 minutes. The amount of malaoxon destroyed during the incubation period was measured using a cholinesterase test system as a bioassay. A survey of the concentration of the detoxifying esterase in various tissues indicated that liver exhibits the highest activity in all species. The serum of mice and rats exhibited considerable activity but dog and guinea pig serum contained low activity. Kidney and lung of all species contained the detoxifying enzyme. Addition of EPN to the test system (2.8 x 10-5 [image]) caused 50% inhibition of the enzyme activity of male rat liver and injection of doses as low as 1 mg/kg of EPN markedly inhibited the enzyme activity of the liver of male rats. The feeding of dietary levels of 5 ppm and higher quantities of EPN to rats for 2 weeks inhibited the enzyme which detoxifies malathion.