Toxicokinetics and metabolism of delayed neurotoxic organophosphorus esters.
Toxicokinetics and metabolism of delayed neurotoxic organophosphorus esters.
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作者：
M. Abou‐Donia
本文所提供的数据表明，啮齿动物代谢和排泄延迟神经毒性有机磷酯的效率很高。相比之下，成年鸡似乎很难完成这些过程。猫介于啮齿动物和鸡之间。虽然需要进一步的研究，这些结果表明，母鸡模型可能夸大了神经毒性有机磷酯的影响。因此，从鸡的结果推断可能高估了有机磷酯对人类的风险或危害。这可以解释为什么没有人的情况下，EPN诱导的迟发性神经毒性的报告，尽管它已经在使用超过四分之一的世纪。我们实验室的其他神经毒性数据似乎支持猫可能是将神经毒性结果外推至人类的更好模型的建议。在这篇综述中提出的数据表明，有机磷酯的药代动力学和代谢可能在OPIDN的物种和年龄敏感性中发挥重要作用。对延迟神经毒性敏感的动物具有更高的积累率，同时神经毒剂的消除也更慢。然而，这些研究并不排除有机磷迟发性神经毒性的靶组织本身具有物种或年龄特异性的可能性。
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.