CHEMICAL DISPOSITION

本合同的目的是采购详细的化学品处置 从一些选定的环境污染物的研究数据或 模型化合物每年。这些研究旨在提供 应用完整动物体内化学物质命运的知识， 国家毒理学计划和基本的毒性测试 了解化学毒性的机制。大多数研究将 在完整的实验室大鼠和/或小鼠中进行。一些研究可能 需要在体外使用人类和啮齿动物肝切片孵育， 从啮齿类动物到人类的结果外推， 问题研究将动物试验结果外推至可能的人体试验 健康影响需要了解代谢途径和体内 动力学行为代谢的机制方面的研究 过程可以更好地理解异生素的代谢 可能导致解毒或反应中间体， 毒性更大。大多数研究将解决处置的有机 化学品;然而，可以进行无机化合物的研究。一 研究应包括确定吸收，分布， 化合物在给定系统中的代谢和排泄，包括 毒代动力学参数估计。这个项目的长期目标是 合同是数据的积累，将允许更好的评估 化学吸收、代谢和 在实验室动物中的分布，并更好地解释其意义 将这些数据传递给人类。

The purpose of this contract is to procure detailed chemical disposition data from a number of studies of selected environmental contaminants or model compounds per year. Such studies are designed to provide both applied knowledge of the fate of chemicals in the intact animal in support of toxicity tests conducted by the National Toxicology Program and basic knowledge of mechanisms of chemical toxicity. Most of these studies will be performed in intact laboratory rats and/or mice. Some studies may require the use of human and rodent liver slice incubations in vitro for extrapolation of results from rodents to humans and for mechanistic studies. Extrapolation of results from animal testing to possible human health effects requires knowledge of metabolic pathways and of in vivo kinetic behavior. Investigation of mechanistic aspects of metabolic processes allows greater understanding of how metabolism of a xenobiotic might lead either to detoxification or to a reactive intermediate with greater toxicity. Most studies will address the disposition of organic chemicals; however, studies of inorganic compounds may be performed. A study shall consist of the determination of the absorption, distribution, metabolism and excretion of a compound in a given system and includes estimation of toxicokinetic parameters. The long-range goal of this contract is the accumulation of data that will permit a better assessment of structure-activity relationships of chemical absorption, metabolism and disposition in laboratory animals and to better interpret the significance of these data to humans.