浓度加和模型在化学混合物毒性评估中的应用

Application of the Concentration Addition Model in the Assessment of Chemical Mixture Toxicity

化学污染物总是以混合物形式存在于实际环境体系中.化学混合物的毒性评估与预测是环境化学领域当前的研究热点与难题.要评估与预测一个化学混合物的毒性效应,首先要证明其是否具有加和性.目前有3个加和参考模型即浓度加和模型(CA)、独立作用模型(IA)与效应相加模型(ES)用于化学混合物毒性的加和性检验.如果混合物效应明显偏离加和参考模型预测效应,则认为该混合物产生毒性相互作用,即协同或拮抗.选择不同的加和参考模型可能得出不同的相互作用结论.ES模型最早广泛应用,但不能解释由同一化合物构成的所谓虚拟组合现象,应用已开始受到限制.IA模型被认为适用于具有相异作用模式的化学物构成的混合物,而CA模型适用于相似作用模式化学物构成的混合物并能合理解释ES模型不能解释的虚拟组合现象,常常认为是化学混合物毒性预测的标准模型.然而,由于CA模型目前没有坚实的理论支持,也不能直接联系混合物毒性作用机理,同时在浓度-效应曲线的部分区域存在不能预测的所谓"预测盲区",因此,CA模型也只是一个工作模型,需谨慎使用.

Various chemical pollutants are always existing as mixtures in real environment. Currently, the assessment and prediction of chemical mixture toxicity is the hotspots and difficulties in environmental chemistry. To accurately assess and predict the toxicity of a chemical mixture, it is necessary to validate whether the toxicities of various components in the mix ture is additive or not. Three common additive reference models, the effect summation （ES）, concentration addition （CA）, and independent action （IA）, are available to determine the toxicity interaction. Synergism or antagonism between the compo- nents in a mixture can be identified if the observed toxicity of the mixture deviates from the prediction in terms of ES, CA, or IA. The resulting interaction type （synergism or antagonism） may be inconsistent according to those reference models ap- plied. Although the ES model is the earliest application model proposed to assess and predict mixture toxicity, its application in environmental chemistry was affected due to its limit in the interpretation of the so-called sham combination constructed by the same compound. The IA model is suitable to model the toxicities of mixtures consisting of the components showing dissimilar modes of actions. The CA can predict the toxicities of the mixtures consisting of the chemicals with similar modes of actions and can rationally interpret the sham combination which is impossible to be depicted by the ES model. The CA is therefore often considered as a standard additive model for the toxicity prediction of a chemical mixture. However, the CA is only a pragmatic model because it has no solid theory basis and no direct connection with the mechanism of action resulting in toxicity. Furthermore, there are so-called predictive blind zones in some concentration intervals on the concentration-response curve where the toxicities of mixtures cannot be predicted by the CA. So, it is necessary to carefully use the CA model.