Modeling mixtures interactions in environmental toxicology

Abstract

In the environment, organisms are exposed to mixtures of different toxicants, which may interact in ways that are difficult to predict when only considering each component individually. Adapting and expanding tools from pharmacology, the toxicology field uses analytical, graphical, and computational methods to identify and quantify interactions in multi-component mixtures. The two general frameworks are concentration addition, where components have similar modes of action and their effects sum together, or independent action, where components have dissimilar modes of action and do not interact. Other interaction behaviors include synergism and antagonism, where the combined effects are more or less than the additive sum of individual effects. This review covers foundational theory, methods, an in-depth survey of original research from the past 20 years, current trends, and future directions. As humans and ecosystems are exposed to increasingly complex mixtures of environmental contaminants, analyzing mixtures interactions will continue to become a more critical aspect of toxicological research.

Keywords: Antagonism; Environmental exposure; Isobologram; Mixtures interactions; Regression; Synergism.