The focus of regulatory chemical risk assessment has been mainly placed on single chemicals rather than mixtures. However, living organisms and the environment might be exposed to mixtures of chemicals. Many scientific studies have revealed that mixture toxicity can arise from the combined effects of components present at levels below their individual no-effect concentrations. Predictive approaches will be essential for estimating mixture toxicity, as the number of possible mixtures is extremely large. Although predictive models are virtually indispensable for estimating mixture toxicity for both scientific and regulatory purposes, risk assessors encounter substantial difficulties in using conventional models, mainly due to the lack of information on the modes of toxic action of the mixture constituents. Alternative models that use different information instead of the modes of action thus need to be developed. The objective of this study is to investigate the state of the art in predictive models based on quantitative structure-activity relationship techniques for estimating the toxicity of mixture components, and to identify future challenges hindering more reliable mixture risk assessment for environmental risk assessment. Alternative models need to be developed not only to overcome the limitations of conventional models, but also to improve their performance.
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