John Wiley & Sons, Ltd.

Metal mixtures modeling evaluation: 1. Background

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Despite more than five decades of aquatic toxicity tests conducted with metal mixtures, there is still a need to understand how metals interact in mixtures and to predict their toxicity more accurately than currently is done. This paper provides a background for understanding the terminology, regulatory framework, qualitative and quantitative concepts, experimental approaches, and visualization and data‐analysis methods for chemical mixtures, with an emphasis on bioavailability and metal‐metal interactions in mixtures of waterborne metals. In addition, a Monte Carlo‐type randomization statistical approach to test for non‐additive toxicity is presented; and an example with a binary‐metal toxicity dataset demonstrates the challenge involved in inferring statistically significant non‐additive toxicity. This background sets the stage for the toxicity results, data analyses, and bioavailability models related to metal mixtures that are described in the remaining papers in this Special Section. It is concluded that although qualitative terminology like additive and non‐additive toxicity can be useful to convey general concepts, not expanding beyond that limited perspective could impede progress in understanding and predicting metal‐mixture toxicity. Instead of focusing on whether a given metal mixture causes additive or non‐additive toxicity, effort should be directed to develop models that can accurately predict the toxicity of metal mixtures. Environ Toxicol Chem © 2014 SETAC

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