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

Abstract

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.