Watanabe P G, Schumann A M, Reitz R H
Mammalian and Environmental Toxicology Research Laboratory, Dow Chemical Company, Midland, Michigan 48674.
Regul Toxicol Pharmacol. 1988 Dec;8(4):408-13. doi: 10.1016/0273-2300(88)90039-6.
Toxicokinetics provides a powerful tool, which is not used sufficiently in the conduct and interpretation of animal toxicity studies. In selecting doses for toxicity studies toxicokinetic data can be used effectively. The tools of toxicokinetics are limited only by the toxicologists' understanding of basic biologic mechanisms. More knowledge on mechanisms of action implicates the possibility of more detailed toxicokinetic models. Physiologically based pharmacokinetic models are valuable in the interpretation of animal toxicity studies. They provide a physiological basis for extrapolating between species and routes of administration, and the future use of these models in setting acceptable levels of exposure for non-cancer toxicity in humans deserves serious consideration.
毒代动力学提供了一个强大的工具,但在动物毒性研究的实施和解释中并未得到充分利用。在为毒性研究选择剂量时,毒代动力学数据可以得到有效利用。毒代动力学工具仅受毒理学家对基本生物学机制理解的限制。对作用机制的更多了解意味着可能建立更详细的毒代动力学模型。基于生理学的药代动力学模型在解释动物毒性研究方面很有价值。它们为种属间和给药途径间的外推提供了生理学基础,并且这些模型未来在设定人类非癌症毒性的可接受暴露水平方面的应用值得认真考虑。