Introduction and Overview of the Key Elements of Mixture Risk Assessment
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It is said that Ginger Rogers was a better dancer than Fred Astaire. She had to match him step for step but do it backwards and in high heels. Mixture risk assessments are like Ginger Rogers: they have to address every challenge that single chemical risk assessment has but for multiple chemicals, multiple sources, chemicals that potentially interact, and all while addressing complex uncertainties. There are several challenges involved in regulatory risk assessment of combined exposures to multiple chemicals, although there is some consistency of approaches used by different countries. The influence of experimental design on modeling joint dose response is a key mathematical research area in mixture risk assessment, along with the broader issue of how to address data gaps for both the regulatory assessment as well as risk communication. Examples of such influence will be demonstrated with simple identified mixtures. An improved understanding of joint toxicity has resulted from toxicokinetic modeling of mixtures, but the huge number of possible mixtures and their exposure variations limit the improvement expected from classical in vivo testing. While new data and approaches show promise for better toxicological understanding of mixture dose response, their incorporation into regulatory strategies will take time and require careful attention to definitions and to empirical justification.