Stereoselective toxicity of malathion and its metabolites, malaoxon and isomalathion

Abstract

In recent years, the stereoselective toxicity of chiral organophosphorus pesticides has received increasing attention from environmental toxicology scientists. In an attempt to explore the stereoselective effects of chiral organophosphorus pesticides on non-target organisms and enzymes, this work investigated the stereoselective toxicity and inhibition of malathion, malaoxon and isomalathion on Daphnia magna and on acid a-naphthyl acetate esterase extracted from wheat flour, respectively. Toxicity differences were observed between the two enantiomers of malathion and malaoxon and among the four stereoisomers of isomalathion in the LC50 values on D. magna and the IC50 values on acid a-naphthyl acetate esterase. Enantiomers with (R)-configuration in all the tested compounds showed higher toxicity to D. magna than their (S)-forms and racemic forms. Racemic malaoxon and isomalathion showed the strongest inhibition on acid a-naphthyl acetate esterase compared to their respective enantiomers and stereoisomers.

Enantioselective behavior of malathion enantiomers in toxicity to beneficial organisms and their dissipation in vegetables and crops

“…This result is consistent with that from an assay for stereoselective toxicity of malathion toward Daphnia magna, and its inhibition of acid ␣-naphthyl acetate esterase extracted from wheat flour, by Zhang et al [31]. Poiec investigated the enantioselective toxicity in rats, house-flies, cockroaches, granary weevils, and the twospotted spider mite; in all these bioassays, the R-configuration on the chiral carbon atom caused the highest toxicity, while the Sconfiguration caused the lowest toxicity [32].…”

Enantiomer‐specific profenofos‐induced cytotoxicity and DNA damage mediated by oxidative stress in rat adrenal pheochromocytoma (PC12) cells

“…A number of previous studies have appeared to address the enantioselective toxicity of chiral OPs in recent years (Emerick et al, 2012;Liu et al, 2006;Nillos et al, 2010;Sun et al, 2010;Wang et al, 2010;Zhang et al, 2011). However, research on the molecular mechanisms of enantioselective toxicity of OPs has been limited.…”

Chemoenzymatic resolution of rac-malathion

“…However, malathion can be oxidatively converted into malaoxon 2 , 7 which is a potent inhibitor of acetylcholinesterases (AChEs) and carboxyesterases (CaEs). 8,9 Moreover, ( R )-malaoxon (Scheme 1) had demonstrated up to 22-fold greater inhibition of mammalian AChE than the corresponding ( S )-isomer, 10-13 ( R )-malaoxon (88% ee; LD 50 23.1 mg/kg) is twice as toxic as the ( S )-isomer (90% ee; LD 50 48.0 mg/kg) to rats. 13,14 Based on this data, ( S )-malathion ( S )- 1 is expected to be safer to humans since it metabolizes into ( S )-malaoxon.…”

“…8,9 Moreover, ( R )-malaoxon (Scheme 1) had demonstrated up to 22-fold greater inhibition of mammalian AChE than the corresponding ( S )-isomer, 10-13 ( R )-malaoxon (88% ee; LD 50 23.1 mg/kg) is twice as toxic as the ( S )-isomer (90% ee; LD 50 48.0 mg/kg) to rats. 13,14 Based on this data, ( S )-malathion ( S )- 1 is expected to be safer to humans since it metabolizes into ( S )-malaoxon. The enantiomers of malathion and malaoxon (Scheme 1) were first synthesized in the author’s lab 12,15,16 although O,O -diethyl phosphate analogs of malathion and malaoxon have been previously prepared.…”

“…12,16 Other groups have improved upon these synthetic approaches, 13,14 and introduced chiral HPLC as a useful alternative for separating racemic malathion into the ( R )- and ( S )-isomers. 18,19 However, these approaches may not be amenable for large scale preparation.…”