Fipronil metabolism, oxidative sulfone formation and toxicity among organophosphate- and carbamate-resistant and susceptible western corn rootworm populations

Fipronil toxicity and metabolism were studied in two insecticide-resistant, and one susceptible western corn rootworm (Diabrotica virgifera virgifera, LeConte) populations. Toxicity was evaluated by exposure to surface residu es and by topical application. Surface residue bioassays indicated no diffe rences in fipronil susceptibility among the three populations. Topical bioa ssays were used to study the relative toxicity of fipronil, fipronil + the mono-oxygenase inhibitor piperonyl butoxide, and fipronil's oxidative sulfo ne metabolite in two populations tone resistant with elevated mono-oxygenas e activity). Fipronil and fipronil-sulfone exhibited similar toxicity and a pplication of piperonyl butoxide prior to fipronil resulted in marginal eff ects on toxicity. Metabolism of [C-14]fipronil was evaluated ill vivo and i n vitro in the three rootworm populations. In vivo studies indicated the do minant pathway in all populations to be formation of the oxidative sulfone metabolite. Much lower quantities of polar metabolites were also identified . In vitro studies were performed using sub-cellular protein fractions (mic rosomal and cytosolic), and glutathione-agarose purified glutathione-S-tran sferase. Oxidative sulfone formation occurred almost exclusively in in vitr o microsomal reactions and was increased in the resistant populations. High ly polar metabolites were formed exclusively in in vitro cytosolic reaction s. In vitro reactions performed with purified, cytosolic glutathione-S-tran sferase (MW = 27 kDa) did not result in sulfone formation, although three a dditional polar metabolites not initially detectable in crude cytosolic rea ctions were detected. Metabolism results indicate both cytochromes P450 and glutathione-S-transferases are important to fipronil metabolism In the wes tern corn rootworm and that toxic sulfone formation by P450 does not affect net toxicity. (C) 2000 Society of Chemical Industry.