Evidence for diazinon-mediated inhibition of cis-permethrin metabolism and its effects on reproductive toxicity in adult male mice

The potential toxicity resulting from combinatorial effects of organophosphorus and pyrethroid insecticides are not completely known. We evaluated male reproductive toxicity in mice co-exposed to diazinon and cis-permethrin. Nine-week-old male Sv/129 mice were exposed to diazinon (10 μmol/kg/day) or cis-permethrin (90 μmol/kg/day) alone or in combination (100 μmol/kg/day), or vehicle (corn oil), for 6 weeks. Diazinon and the diazinon–permethrin mixture inhibited plasma and liver carboxylesterase activities. In the mixture group, urinary excretion of cis-permethrin metabolite 3-phenoxybenzoic acid decreased along with increased plasma and testicular concentrations of cis-permethrin, while excretion of diazinon metabolites, diethylphosphate and diethylthiophosphate, did not change, versus mice exposed to each chemical alone, which suggested that inhibition of carboxylesterase decreased the metabolic capacity to cis-permethrin. Though the co-exposure decreased testosterone biosynthesis, increased degenerate germ cells in seminiferous tubule and sperm morphological abnormalities versus controls more clearly than exposure to cis-permethrin alone, the expected potentiation of toxicity was not evident.

► Diazinon suppressed co-exposed cis-permethrin metabolism by inhibiting carboxylesterase activity.
► Thereby, diazinon suppressed urinary metabolite of co-exposed cis-permethrin.
► As a result, co-exposed diazinon accentuated plasma testosterone suppression by cis-permethrin.