Enhancement of malathion toxicity to the hybrid red-legged partridge following exposure to prochloraz

The agricultural fungicide, prochloraz, which inhibits ergosterol biosynthesis in fungi, was shown to be a potent inducer of liver enzymes in the hybrid red-legged partridge. Pretreatment with a single oral dose of 180 mg/kg resulted in a dramatic potentiation of the toxicity of the organophosphorous insecticide malathion: three out of four prochloraz-pretreated birds died within 10 min from acute poisoning (82-100% inhibition of brain cholinesterase activity) following intraperitoneal administration of 3.3 or 16.7 mg/kg malathion, whereas no significant inhibition of serum cholinesterase activity was seen in control birds 1 hr after administration of the insecticide. Prochloraz pretreatment also resulted in a significant increase in susceptibility to low oral doses of malathion. In vitro metabolism of [¹⁴C]malathion by microsomes from control birds resulted largely in the formation of the malathion monoacid, whereas the anticholinesterase, malaoxon, was the main metabolite generated by microsomes from prochloraz-pretreated birds. The dramatic amplification of malathion toxicity following induction with prochloraz is attributed to an increased activation of malathion to its active metabolite malaoxon by one or more induced monooxygenase forms; inhibition of "B"-esterase activity by malaoxon may contribute to this amplification of toxicity.