有害结局路径(AOP)框架在水体复合污染监测研究中的应用

由于包含复杂的毒害化学污染物质，水体复合污染一直威胁着人类健康和水生生态安全。对复合污染水体进行监测、评估和治理是水环境管理的重点之一。监测并识别水体关键毒害污染因子是进行水质管理的前提，也是复合污染研究的难点。目前国内外在水复合污染毒性监测研究上主要基于动物活体试验或者生物体外测试。由于受限于毒理学测试方法，常见的应用通常仅关注于某方面的毒性效应或者少数的分子指标，因而受到质疑和挑战。有害结局路径(Adverse outcome pathway, AOP)的概念将化学污染物的结构、致毒的分子启动事件和生物毒性的有害结局建立关联，为污染物的毒性测试、预测和评估提供了新的模式。本文旨在论述有害结局路径在复合污染毒性评估和关键毒害物质鉴别中的指导性价值和意义。在有害结局路径的指导框架下，借助于生物体外高通量测试技术、化学分析的靶向和非靶向分析技术、和生物信息学技术，可以系统地分析化学混合物在分子、细胞水平上健康相关指标的响应水平，评估水体中复杂结构污染物，与不同生态和健康有害结局之间的关联，为水环境评价和优先污染物的筛选管理提供有效支撑。本文通过综述AOP框架在复合水体中毒害物质风险研究的现状和优势，对AOP在水环境环境管理上的应用前景提出展望。

Application of Adverse Outcome Pathways Framework in Monitoring of Toxic Chemical Pollutants from Mixtures

The complex mixture of chemicals in contaminated water threat human health and aquatic ecosystem. Monitoring and assessment of chemical mixtures is essential for water resource management, where the identification of the key pollutants that cause the adverse effects is premise of effective water quality management. Currently, toxicity monitoring of chemical mixtures has been based on animal tests or in vitro bioassays. However, due to the limitation of conventional toxicity test approaches, these applications have been questioned and challenged. Adverse outcome pathway(AOP), which combines chemical structures, molecular initial events and adverse outcomes, provides a new model for chemical toxicity test. The purpose of this paper is to discuss the guidance value and significance of AOP in the monitoring, assessment and identification of toxic chemicals in mixtures. Under the guiding framework of AOP, the effects of chemical mixture can be systematically evaluated with health relevant indicators at molecular and cellular level, followed by effective identification of key toxic chemicals, by taking advantage of in vitro high throughput screen technology, targeted and untargeted chemical analysis, bioinformatics and cheminformatics technology. Here the current research status and advantages of AOP framework in the identification of key toxic substances in mixture are summarized, and its prospect of the application in water environment monitoring and management is proposed.