Mechanism of Synergism between the Pyrethroid Insecticide λ-Cyhalothrin and the Imidazole Fungicide Prochloraz, in the Honeybee (Apis mellifera L.)

Ergosterol biosynthesis-inhibiting fungicides have been found to synergize the toxicity of pyrethroid insecticides to the honeybee (Apis mellifera L.). The mechanism by which the fungicide prochloraz enhances the toxicity of the pyrethroid insecticide λ-cyhalothrin was investigated. In vitro incubations with honeybee midguts were used to study the metabolism of [14C]λ-cyhalothrin. The principal metabolite was identified as 4-hydroxy-3-phenoxybenzyl alcohol (4′-OH-3-PBAlc) with small amounts of 3-phenoxybenzoic acid (3-PBAc). Both are products of ester bond cleavage, but microsomal oxidation was implicated in the formation of 4′-OH-3-PBAlc. After treating midguts with prochloraz, metabolism was predominantly to 3-PBAc, with little formation of 4′-OH-3-PBAlc, strongly indicating an inhibition of microsomal monooxygenase activity. In vivo investigations showed the major metabolic products of [14C]λ-cyhalothrin extracted from frass of treated honeybees were 4′-OH-3-PBAlc, 2′-hydroxy-3-phenoxybenzyl alcohol, and 4′-hydroxy-3-phenoxybenzoic acid. However, when bees were simultaneously dosed with prochloraz, there was an absence of metabolites detected in the frass of bees for 16 hr post-treatment Thus, prochloraz delayed the metabolism, detoxication, and excretion of λ-cyhalothrin by inhibition of microsomal oxidation, effectively enhancing the toxicity of the pyrethroid to the honeybee.