有机污染物的混合毒性QSAR模型及其机制研究进展  

QSAR models and their corresponding toxicity mechanism for mixture toxicity of organic pollutants

作　　者：王婷[1] 林志芬[1,2] 田大勇[3] 王大力[1] 孔令云[1] 仇雁翎[4] 

机构地区：[1]同济大学污染控制与资源化研究国家重点实验室,上海200092 [2]区域环境质量协同创新中心,北京100084 [3]安阳工学院化学与环境工程学院,安阳455000 [4]同济大学上海市化学品分析、风险评估与控制重点实验室,上海200092

出　　处：《科学通报》2015年第19期1771-1780,共10页Chinese Science Bulletin

基　　金：国家自然科学基金(201177092,21377096,U1404217);同济大学污染控制与资源化研究国家重点实验室自主研究(重点)项目(PCRRY11003);同济大学英才(攀登)计划(0400219287);上海市科学技术委员会(14DZ2261100)资助

摘　　要：环境有机污染物的联合暴露是一条普遍规律.化合物定量结构与活性相关研究(quantitative structure-activity relationship,QSAR)模型是研究有机污染物毒性的重要方法.本文以有机污染物的混合毒性及其机制研究为主线,将化合物按照毒性作用方式分为3类:非极性麻醉型、极性麻醉型和反应性化合物,并概述了3类化合物基于毒性作用机制的混合毒性QSAR模型.简单综述了非极性麻醉型化合物混合毒性的定量预测方法,发现非极性麻醉型化合物的毒性预测方法最为简单,仅由混合体系的总疏水性决定,可通过统一的QSAR模型预测;概述了极性麻醉型化合物混合毒性的定量预测方法,指出极性麻醉型化合物的混合毒性由混合体系总疏水性和氢键效应共同决定;重点解析了反应性化合物的混合毒性QSAR模型,发现由于反应性化合物作用机制较为复杂,目前仍缺乏统一的混合毒性定量预测方法.进一步从混合物组分、化合物之间相互作用和化合物与靶蛋白的相互作用3方面入手,综述了反应性化合物混合毒性QSAR模型的最新研究进展.最后指出,采用基因组学和代谢组学等更为先进的实验手段进一步揭示化合物的分子生物学机制,进而建立更为通用的有机污染物混合毒性预测方法是今后发展的方向.Environmental contaminants are frequently encountered as mixtures rather than single chemicals. However, current environmental quality standards and ecological risk assessments are mainly based on single toxicities, and pay little attention to the potential hazards of mixture exposure. The study of mixture toxicity is therefore not only of theoretical value, but also of deep practical significance. This review mainly focuses on quantitative structure-activity relationship（QSAR） models for mixture toxicities of organic pollutants and the corresponding toxicity mechanisms. The organic pollutants are classified as non-polar narcosis chemicals, polar narcosis chemicals, and reactive chemicals, according to their modes of action. QSAR models of the three types of chemical are described based on their toxicity mechanisms respectively. QSAR models of non-polar narcosis chemicals are described. The QSAR models of the mixture toxicities of non-polar narcosis chemicals are the simplest. The toxicity only depends on the total hydrophobicity of the mixture and can be predicted using a uniform model. QSAR models for polar narcosis chemicals are summarized. The toxicities of narcosis chemicals are determined not only by the total hydrophobicity but also by hydrogen-bonding effects. QSAR models for reactive chemicals are described in detail. There is no uniform model, because the toxicity mechanisms of the reactive chemicals are complicated. However, three aspects of the latest research on quantitative prediction methods for toxicities of mixtures containing reactive chemicals are summarized： the factors affecting multicomponent mixtures containing reactive chemicals; the interactions among the single chemicals in the mixture; and the interactions between the chemicals and the target protein. It is pointed out that identifying the molecular biological mechanisms of chemicals using advanced experimental methods（such as genomics and metabolomics） and formulating a common prediction model based on these mechanisms should

关 键 词：混合毒性 毒性作用方式 毒性机制 疏水性 氢键 

分 类 号：X171.5[环境科学与工程—环境科学]