Our goal in this article is to provide a perspective on how to understand the nature of responses to chemical mixtures. In studying responses to mixtures, researchers often identify “mixture interactions”—responses to mixtures that are not accurately predicted from the responses to the mixture’s individual components. Critical in these studies is how to predict responses to mixtures and thus to identify a mixture interaction. We explore this issue with a focus on olfaction and on the first level of neural processing—olfactory sensory neurons—although we use examples from taste systems as well and we consider responses beyond sensory neurons, including behavior and psychophysics. We provide a broadly comparative perspective that includes examples from vertebrates and invertebrates, from genetic and nongenetic animal models, and from literature old and new. In the end, we attempt to recommend how to approach these problems, including possible future research directions.

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