Toxicokinetics and metabolism of delayed neurotoxic organophosphorus esters.
The data presented here indicate that rodents metabolize and excrete delayed neurotoxic organophosphorus esters with great efficiency. By contrast, the adult chicken seems to have difficulty carrying out these processes. The cat is intermediate between rodents and chickens. Although further studies are needed, these results suggest that the hen model may exaggerate the effect of neurotoxic organophosphorus esters. Extrapolation of findings from the chicken may thus overestimate the risk or hazard of organophosphorus esters to humans. This may explain why no human case of EPN-induced delayed neurotoxicity has been reported despite the fact that it has been in use for over a quarter of a century. Other neurotoxicity data from our laboratory seem to support the suggestion that the cat may be a better model to extrapolate neurotoxicity results to humans. The data presented in this review suggest that the pharmacokinetics and metabolism of organophosphorus esters may play a prominent role in species and age sensitivities for OPIDN. Animals that are sensitive to delayed neurotoxicity have a higher accumulation rate, coupled with slower elimination of the neurotoxic agent. These studies, however, do not rule out the possibility that the target tissue of organophosphorus delayed neurotoxicity itself is species or age specific.
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