TOXICOKINETIC AND BIOCHEMICAL MODELING OF HAZARDOUOS AGENTS

工作总结：该项目旨在 描述剂量、分布、新陈代谢和 消除外来生物材料。这些信息可以帮助 毒理学研究的设计和解释，并加强 低剂量外推人类风险的科学基础。 此外，生物真实的生物数学模型提供了 一种严谨的结构来制定和测试假设 环境危害的作用机制。毒代动力学 模特还可以适应不同的曝光途径和 给药方案和可以适应的因素，有助于 个体间的变异性。毒物动力学模型已经被 创建、部分开发或扩展了几个 化学品，包括甲基亮酚、扑草酮及其代谢物 苯巴比妥、异戊二烯、异丁烯、1，3-丁二烯、TCDD、艾滋病 药物单独和组合，褪黑素，和处置 孕鼠和新生儿吸入汞蒸气。为 甲基亮氨酸，生理基础上的药代动力学模型 为老鼠和人类创造的。人体模型是以血液为基础的 从服用亚甲基亮酚的志愿者那里获得的数据 商业上可以买到的含有甲基亮氨酸的饼干。

Summary of Work: This project is designed to characterize parameters of dose, distribution, metabolism, and elimination of xenobiotic materials. This information can aid in the design and interpretation of toxicology studies and to strengthen the scientific basis for low-dose extrapolation of risk to humans. Furthermore, biologically realistic biomathematical models provide a rigorous structure to formulate and test hypotheses on mechanisms of action of environmental hazards. Toxicokinetic models can also be adapted to different routes of exposure and dosage regimens and can accomodate factors that contribute to interindividual variabilities. Toxicokinetic models have been created, partially developed, or expanded upon for several chemicals, including methyleugenol, primidone and its metabolite phenobarbital, isoprene, isobutene, 1,3-butadiene, TCDD, AIDS drugs singly and in combinations, melatonin, and the disposition of inhaled mercury vapor in pregnant rats and neonates. For methyleugenol, physiologically based pharmacokinetic models were created for rats and humans. The human model was based on blood methyleugenol data obtained from volunteers who consumed commericially available cookies containing methyleugenol.