基于人群生理药代动力学的优控化学品筛查研究

The evaluation and selection of priority chemicals is crucial for chemical management. However, for the priority chemicals selection method used in China, the exposure assessment and toxicity assessment is separated, which is not able to estimate the human risk posed by chemicals. Recent advance on the Expocast and toxicity prediction allow it is to use human health risk assessment to select priority chemicals. However, during this procedure, the high-throughput method to develop physiologically based pharmacokinetic model (PBPK) is crucial. Based on data availability, this project will highlight some hazard chemicals as the target chemicals. Subsequently, this project attempts to develop the Physiologically based pharmacokinetic (PBPK) models for all the target chemicals. Together with existing model parameters, experiment measurement and human survey, this project will optimize the PBPK model parameters. Meanwhile, by integrating the exposure database, fate and transport model, toxicity prediction, the priority chemicals will be selected based on risk estimation. This project will majorly focus on the development of PBPK models for target chemical, and also aims to establish the exposure database for China. These research activities potentially provide the support for chemical management in China.

优控化学品的评价和筛选是化学品管理的重要方面。目前我国的优控化学品筛选中，暴露评价与毒性评价相对独立，对化学物质的危害处于定性或者半定量阶段。近年来，暴露组学和高通量毒性预测的发展，使得估算化学品健康风险并筛选优控化学品成为可能性。在此过程中，开发高通量的人群生理药代动力学模型方法是提高暴露组学实用性的关键问题之一。本课题首先以数据可得性为基础，筛选目标物质。其次，针对目标物质，本研究将重点建立人群生理药代动力学模型，并利用以往文献模型参数，实验手段，以及人群调查数据对模型进行优化校正。同时，本课题将结合归趋模型，暴露数据库以及毒性预测技术，估算化学品健康风险并筛选优控化学品。本研究将以开发系列目标物质的体内动力学模型为核心，建立我国的暴露数据信息库，为我国的化学品筛选管理提供支持。

目前，登记在册的化学品已经有数十万种，并且每年还有大量新增。优控化学品评价和筛选是化学品管理的重要方面，而其筛查体系需全方面考虑化学品的暴露、毒性以及健康效应等。针对这一科学问题，我们首先建立了化学品动力学的仿真拟合平台，并进而开发了环境暴露与健康效应的集成平台（含毒性数据库）；利用所建成的工具平台，建立了多种化学品的动力学模型并获取了其模型参数；在此基础上，构建了以动力学为核心的多层次优控优控物质筛查体系，并且开发了我国典型优控化学品的暴露数据库；最后，我们计算了典型优控化学品的健康风险。研究拓展了化学品管理的理论体系和技术工具，有助于推动优控化学品的科学管控。