Chemical mixture experiments approaches

In our opinion, the data are sufficiently clear to suggest that when it is not feasible to test the mixture in question, mixture extrapolation is the preferred option compared to no extrapolation. Indeed, all literature observations suggest that applying mixture extrapolation is to be preferred over not applying mixture extrapolation. Technical options for extrapolation are concentration addition, response addition, and the mixed-model approach, of which concentration addition is most often applied. Exceptions may apply in cases that are more specific. For example, when it is clear that 2 compounds precipitate (a situation of no exposure due to chemical interactions in the environment), one should acknowledge this prior to assessing mixture risks by mixture extrapolation approaches. When the data of a study allow, refined conclusions are possible. For example, when the study design is appropriate and the mathematical models are appropriate, researchers are able to discriminate between concentration addition and response addition, and (with sufficient experiment efforts) between these models and the mixed-model approach. 

In each of these disciplines several more specific goals can be identified (see text box). Because of this, a diverse set of approaches has been developed for analyzing and assessing the toxicities of chemical mixtures, which can be grouped into 3 major classes 1) mixture experiments in which the toxicity of the mixture is characterized without making any effort to connect it to the toxicities of the components 2) whole mixture approaches, that is, inferring from mixture effects the toxicity contributions of the individual components and 3) component-based approaches, that is, inferring from the mixture components their joint toxicity. 

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