TOXICOKINETIC AND BIOCHEMICAL MODELING OF HAZARDOUOS AGENTS

工作总结：本项目旨在表征 剂量、分布、代谢和异生物质的消除。 这些信息可以帮助设计和解释毒理学 加强低剂量外推的科学基础 对人类的风险。 此外，生物现实主义生物数学 模型提供了一个严格的结构，以制定和测试假设， 环境危害的作用机制。 毒代动力学模型可以 还应适应不同的接触途径和剂量方案， 能够适应导致个体间差异的因素。 在上一个财政年度，建立了毒代动力学模型， 部分开发或扩展了几种化学品，包括 扑米酮及其代谢物苯巴比妥，异戊二烯，异丁烯， 1，3-丁二烯、四氯二苯并对二恶英、艾滋病药物（单独使用和混合使用）、褪黑激素， 以及吸入汞蒸气在孕鼠体内的处置， 新生儿

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. During the past fiscal year, toxicokinetic models have been created, partially developed, or expanded upon for several chemicals, including 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.