组合指数在环境混合物联合毒性研究中的初步应用

化学品在实际环境中总是以组分繁杂多变的混合物形式存在,其混合物的毒性评估与预测一直是环境毒理学研究重点。在环境毒理学领域,浓度加和(concentration addition,CA)及独立作用(independent action,IA)是评估与预测化学混合物联合毒性的经典模型,一般认为CA适用于作用模式相似的混合物体系而IA适用于作用模式相异的混合物体系,但如何使用CA与IA一直存在争议。组合指数(combination index,CI)是在半数效应方程基础上发展起来的不依赖于作用模式的用于混合物联合毒性评估的混合物毒性指数,具有坚实的理论基础,不仅能定性地评估毒理学相互作用,也能定量地评估相互作用的大小,已在药物组合研究中得以广泛应用,近年来已引起环境毒理学研究者兴趣。本文就组合指数及药物组合应用、进入环境毒理学领域、与CA及IA的关系、存在的问题等几个方面进行评述,以期推进CI在化学混合物毒性评估与预测领域中的应用。

Application of the Combination Index in the Assessment of Combined Toxicity of Environmental Mixture

Various chemicals always exist as complex mixtures in real environment. The assessment and prediction of toxicity for chemical mixtures has been the research focus in environmental toxicology. The concentration addition (CA) and independent action (IA) are the classic additive reference models for the toxicity assessment and prediction of chemical mixture. It is generally recognized that the IA model is suitable to estimate the toxicities of the mixtures of the components showing dissimilar modes of actions (MOA), and the CA to the mixtures consisting of the chemicals with similar MOA. But how to correctly use CA and IA has been controversial for a long time. Combination index (CI) has solid theory basis for the reason that it is based on the median-effect equation and independent of the toxic MOA, and CI could qualitatively determine the toxicological interactions and quantitatively evaluate the degree of interaction. The CI has been widely used in drug combination. In recent years, CI is increasingly attracting interests of environmental toxicology researchers. In this review, the fundamental concepts and its application to drug combination and environmental toxicology field, the differences between CI and CA (or IA),and the existing problems are summarized, aiming to propel the applications of CI in mixture toxicity assessment and prediction.