Comparative study of the organophosphate insecticides acephate and methamidophos

Acephate and methamidophos are organophosphate insecticides that have comparable insect toxicity. However, they do not have similar mammalian toxicity. Acephate has much lower mammalian toxicity than methamidophos. Since insects and mammals can convert acephate to methamidophos, the primary goal of this project was to determine whether acephate toxicity in mammals is solely due to its metabolism to methamidophos or it is due to the differences in the stereochemistry of acephate versus methamidophos and differences in the 3-D structure of mammalian (mAChE) versus insect AChE (iAChE). The secondary goal of this project was to characterize the effects of acephate and methamidophos on mammalian endocrine parameters and amino acid concentrations.; The results of our study showed that acephate and methamidophos have similar physicochemical, molecular-orbital and electronic properties. The important differences between the two inhibitors were that acephate has an additional electron rich domain and is resistant to acid hydrolysis. Our investigation also showed that both the in vitro and in vivo insecticidal toxicity of methamidophos depends on the inhibition of the active center of iAChE. The insecticidal activity of acephate may be due to direct interaction with the active center of the iAChE. The mammalian toxicity of acephate may be due to interaction with an ‘allosteric’ reaction center in the mAChE. Our investigation supported the hypothesis that the toxicity of acephate is due to: first, the conversion of acephate to methamidophos and second, the protection of acephate against methamidophos-inhibited AChE in mammals. The endocrine effects of acephate and methamidophos differed from their cholinergic effects, and were not proportional to the amount of methamidophos present in different tissues obtained from the treatment groups. Acephate may indirectly protect the pituitary gland against the toxic effects of methamidophos. The effect of methamidophos on the adrenal cortex may be mediated by the pituitary gland, while the effect of acephate may be due to decreased metabolism of corticosteroids. Acephate and methamidophos increased the energy demands in the treatment groups.