Modeling the Physiology and Toxicology of Metals

Most bioaccumulation models in current use were originally developed for organic chemicals and subsequently applied to metals. As a result, they do not typically incorporate metal-specific features that affect how metals are taken up, metabolized, detoxified, and eliminated. This review describes models that are used to evaluate metal accumulation, from waterborne and dietary exposure, by aquatic organisms. It considers whole-body models (including single-compartment and multicompartment variations), physiologically based pharmacokinetic models (providing an explicit representation of individual organs), and food chain or food web models. A representative model framework and example application are described for each model. Variations are also discussed. Metal bioaccumulation models have not typically been developed to predict effects on aquatic organisms. However, several that were developed for this purpose are described herein. These include damage–repair models, biotic ligand models, physiologically based mechanistic models, and intracellular speciation models. While some effects models incorporate relatively unique metal-specific features, they have primarily been applied to waterborne exposures, and received limited use for predicting effects resulting from both waterborne and dietary exposures. Studies that facilitate the refinement of both bioaccumulation and effects models, and the unification of such models, will likely benefit both the scientific and regulatory communities.