CHEMICAL DISPOSITION IN MAMMALS

本合同的目的是采购详细的化学处理 来自选定环境污染物的多项研究的数据或 每年的化合物模型。这类研究的目的是既提供 化学物质在完好动物体内命运的应用知识 由国家毒理学计划和基础毒理学项目进行的毒性测试 了解化学毒性的机理。大多数这些研究都将 在完整的实验大鼠和/或小鼠身上进行。一些研究可能 要求使用人和啮齿动物肝脏切片体外孵育 从啮齿动物到人类和机械学的结果的外推 学习。将动物试验结果外推到可能的人类身上 对健康的影响需要了解代谢途径和体内的 动力学行为。新陈代谢的机制研究 过程允许更好地了解异种生物的代谢 可能会导致解毒或产生活性中间体 毒性更大。大多数研究将解决有机污染物的处置问题 化学物质；但是，可以对无机化合物进行研究。一个 研究应包括测定药物的吸收、分布、 化合物在特定系统中的新陈代谢和排泄，包括 毒物动力学参数的估算。这样做的长期目标是 合同是数据的积累，将允许进行更好的评估 化学吸收、代谢和代谢的构效关系 并更好地解释实验动物的性情倾向 将这些数据提供给人类。

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.