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• W2076515629 abstract "The organophosphorus insecticide, demeton-S-methyl (DSM), is considered as a good surrogate of the highly toxic nerve agent VX for skin absorption studies due to similar physico-chemical properties and in vitro percutaneous penetration profile. But, when skin distribution was estimated by measuring inhibition of cholinesterase activity, the results were poorly reproducible. The various grades of commercial DSM solutions were suspected to be the origin of the discrepancies. This hypothesis was tested by measuring inhibition of human acetyl- and butyrylcholinesterase by two commercial DSM solutions. The inhibition rate was independent on the enzyme concentration confirming pseudo-first order conditions. But complete inhibition of butyrylcholinesterase activity was achieved only when the DSM concentration was at least 1500-fold higher than the enzyme concentration. Besides, complete inhibition of acetylcholinesterase was never achieved. Mass spectrometry analysis of the inhibited butyrylcholinesterase adducts identified monomethoxyphosphorylated-serine, the aged product of inhibition by DSM or a derivative with a modified leaving group. Neither spontaneous reactivation nor aging of the dimethoxyphosphorylated-serine could account for the inhibition kinetics observed, suggesting an overly complicated kinetic scheme not compatible with the requirement of a titration experiment. In conclusion, cholinesterase-based analytical methods should be avoided for DSM titration in skin penetration studies." @default.
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• W2076515629 date "2011-04-01" @default.
• W2076515629 modified "2023-09-30" @default.
• W2076515629 title "The kinetic study of the inhibition of human cholinesterases by demeton-S-methyl shows that cholinesterase-based titration methods are not suitable for this organophosphate" @default.
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• W2076515629 doi "https://doi.org/10.1016/j.tiv.2011.01.006" @default.
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