Metabolism-related assays and their application to agrochemical research: Reactivity of pesticides with glutathione and glutathione transferases

An HPLC-based assay system has been developed to measure the reactivity of agrochemicals with glutathione (GSH) with and without catalysis by glutathi one transferases (GSTs). Metabolism-related parameters based on second-orde r related rate constants from non-enzymatic GSH and enzymatic GSH + GST ass ays have been derived for use in structure-activity and structure-reactivit y relationship studies of exploratory agrochemicals. The versatility and se nsitivity of the assay system has been established using a diverse range of agrochemicals and model compounds, e.g. 4-nitrobenzyl chloride, 1-chloro-2 ,4-dinitrobenzene, atrazine, acetochlor, fluorodifen, fluazifop-butyl, trid iphane, fluazinam, chlorothalonil and diazinon. For the enzymatic GSH + GST assay, second-order related rate constants, ratioed to the assay standard, 4-nitrobenzyl chloride to provide a parameter independent of assay conditi ons, spanned five orders of magnitude, fluazinam being the most reactive an d atrazine the least. Within chemical classes significant variations in rea ctivity were observed, alachlor being c.l5-fold more reactive than pretilac hlor. Applications of this assay system based on comparative measures of re activity across and within chemical classes are discussed, (C) 1998 Society of Chemical Industry.