Core--Exposure Assessment

描述(由申请人提供)：新中心的暴露评估核心将专注于分析化学需求和基于生理的毒物动力学(PBTK)建模。在第一个中心(1998-2003年)期间，适当收集和处理用于农药分析的现场样本(房屋灰尘、汽车灰尘和尿液)对CIP项目至关重要。由于实地研究人员现已接受了这些程序的培训，并对其他人进行了培训，因此新中心的重点将是为社区参与性研究项目和农药途径项目收集的实地样品提供分析支持。在该中心的第一个供资周期中，动力学模型对于理解和翻译关于分子机制和遗传易感性的信息也是非常宝贵的。因此，这些领域已被列为新中心的优先事项。华盛顿大学儿童环境健康风险研究中心的暴露评估核心有以下具体目标： 具体目标1：为社区参与研究项目和农药路径项目提供分析化学支持，对家庭灰尘、车辆灰尘和成人和儿童尿液的分析将包括200多个家庭的有机磷农药和代谢物。 具体目标2：协助解释基于社区的参与性研究项目和农药途径项目的接触数据。由于环境样品和尿液代谢物之间的复杂关系，对房屋粉尘、车辆粉尘和尿液分析结果的解释并不是一个简单的过程。 具体目标3：协调所有中心项目之间的暴露和剂量的机械建模，以便与风险表征核心执行的动态建模相联系。将生成随机模型，以探索测量的环境农药水平与生物监测结果之间的联系，并最终与生物效应之间的联系。这将需要对人类行为、化学转移和吸收过程以及代谢和排泄的药代动力学进行数学表示。然后，将暴露和药代动力学模型与基于生物的剂量反应模型联系起来，以更好地探索暴露反应关系。

Description (provided by applicant): The Exposure Assessment Core in the new Center will be focused on the analytical chemistry needs and physiologically based toxicokinetic (PBTK) modeling. During the first Center (1998-2003), appropriate collection and handling of field samples (house dust, car dust, and urine) for pesticide analysis was critical for the CIP project. Since field researchers have now been trained and have trained others in these procedures, the emphasis in the new Center will be on providing analytical support for field samples collected by the Community Based Participatory Research Project and the Pesticide Pathways Projects. In first funding cycle of the Center, kinetic modeling also proved invaluable for understanding and translating information on molecular mechanisms and genetic susceptibility. Thus, these areas have been prioritized for the new Center. The Exposure Assessment Core of the University of Washington Center for Child Environmental Health Risks Research has had the following specific aims: Specific aim 1: Provide analytical chemical support to the Community-Based Participatory Research (CBPR) Project and the Pesticide Pathways Project Analyses of house dust, vehicle dust, and urine from adults and children will include organophosphate (OPs) pesticides and metabolites from over 200 households. Specific aim 2: Provide assistance with the interpretation of exposure data to the Community-Based Participatory Research (CBPR) Project and the Pesticide Pathways Project. Interpretation of the results from the house dust, vehicle dust, and urinary analyses is not a straightforward process due to the complex relationship between environmental samples and urinary metabolites. Specific aim 3: Coordinate mechanistic modeling of exposure and dose among all Center projects to be linked with dynamic modeling performed by the Risk Characterization Core. Stochastic models will be generated to explore links between measured environmental pesticide levels and biomonitoring results and ultimately to biological effects. This will require mathematical representation of human behaviors, chemical transfer and absorption processes, and the pharmacokinetics of metabolism and excretion. Exposure and pharmacokinetic models with then be linked with biologically based dose response models to better explore exposure response relationships.