Toxicology of monocrotophos

Monocrotophos is a water-soluble organophosphate insecticide with high oral and moderate dermal toxicity. The toxicologically relevant mode of action is the inhibition of ChE activities. The toxicity of organophosphate metabolites of monocrotophos is comparable with the parent compound. Glycol conjugation in plant metabolism decreased the acute toxicity significantly. Dephosphorylated metabolites showed no demonstrable acute toxicity. Repeated exposure to the compound leads to initial cumulation of the single-dose effects. At moderate dose levels, the adverse effects are counteracted by an increase of tolerance through adaptation. A study in humans demonstrated no relevant ChE depression over a 30-d period at daily dose levels of up to 0.006 mg/kg. Lifetime chronic feeding studies in rodents again indicated ChE inhibition as the only specific effect. Body weight reduction was limited to high doses. No gross or microscopic specific lesions were demonstrable; especially, there was no evidence of oncogenic effects. Genotoxicity was evident in vitro, whereas comprehensive assessment of the in vivo tests indicates no toxicologically relevant mutagenic potential in mammals. This conclusion is supported by the absence of oncogenic effects in chronic feeding trials. Findings in reproduction studies were limited to secondary fetal reactions that were triggered by maternal toxicity. Acute and repeated administration studies in hens revealed no delayed (degenerative) neurotoxic potential. Monocrotophos showed no significant potentiation with 24 other ChE inhibitors. Poisoning signs after heavy doses were controlled by therapeutic doses of atropine, preferably in combination with an oxime.