The chemical and biochemical reactivity of dichlorvos

Abstract

The chemical structure, reactivity and metabolic fate of the insecticide dichlorvos (2,2-dichlorovinyl dimethyl phosphate) are discussed in relation to the possible genotoxicity of this and other methyl phosphate triesters. Recent attempts to demonstrate the methylation of DNA following exposure of bacteria and animals to dichlorvos are reviewed. On the basis of comparative data relating mutagenesis to methylation reactions, it seems entirely appropriate to conclude that the mutagenicity of dichlorvos to bacteria is due solely to methylation of the bacterial DNA under the conditions of these tests. However, the methylation of mammalian DNA could not be demonstrated under realistic exposure conditions (when the alkylating mutagen methyl methanesulphonate afforded clearly measurable methylation). The failure to detect methylation by dichlorvos in vivo is attributed to the operation of highly efficient enzyme-catalysed biotransformations which rely largely on the phosphorylating reactivity of dichlorvos. The biotransformation pathways, characterised mostly in the rat, appear to be common also to pig, mouse, hamster, and man.

Opinion of the Scientific Panel on Plant protection products and their residues (PPR) related to the evaluation of dichlorvos in the context of Council Directive 91/414/EEC

“…Several metabolites have been described (see Fig. 3, Addendum) (Wright et al, 1979;. Unchanged dichlorvos was not found in muscle or fat of rabbits administered dichlorvos orally at 5 mg/kg per day for 2 weeks and killed 48 hours later (Majewski et al, 1979).…”

“…3, Addendum), and thereby demethylation of dichlorvos, is thought to generate carbon dioxide and also may prevent the incorporation of the methyl group into nucleic bases due to the competing reaction (Wright et al, 1979). However, it was noted that GSH-dependent demethylation of dichlorvos may play only a minor role in terms of DNA-protection, even at high dichlorvos concentrations (Wright et al, 1979).…”

“…Apart from this reaction, dichlorvos is bound by A-esterases (non-serine esterases, arylesterases) which hydrolyse OPs and thereby are involved in dichlorvos detoxification. These enzymes occur preferentially in blood, but also in liver and many other tissues (Wright et al, 1979;Lotti, 2000). …”

Critical Evaluation of Dichlorvos’ Breast Cancer Risk

“…The DNA-methylating ability of dichlorvos in bacteria and with isolated DNA, has been implicated as the mechanism for its mutagenicity by many authors (Braun et al, 1981;Segerback and Ehrenberg, 1981;Wooder and Wright, 1981;Wright et al, 1979). However, the DNA-alkylating ability of dichlorvos in vivo has been found to be very weak (FAO/WHO, 1993;Segerback, 1981).…”

“…However, it has been argued that due to its short half-life, dichlorvos may not have a major genotoxic effect in vivo in animals (Wright et al, 1979). The genotoxic potential of dichlorvos has been studied in a variety of ways to assay DNA damage in many different animal systems: mice, rats, hamsters, and fish.…”