Toxicology of Chemical Mixtures

The toxicity of chemical mixtures is determined by the effects of components as well as interactions, if any, among components occurring at the exposure, toxicokinetic or toxicodynamic phases. This chapter describes the concepts and methods essential for evaluating the toxicity of chemical mixtures. Approaches applicable to in vitro and in vivo conditions are discussed with particular emphasis on the assessment approaches that use whole mixtures, similar mixtures or mixture components. The approaches based on mixture components require a thorough understanding of the theory and models of additivity (dose, response). Accordingly, the notions of additivity for similarly acting and dissimilarly acting chemicals are considered and their use in the prediction of the toxicity of chemical mixtures discussed. An illustrative example of an in vitro evaluation of a ternary mixture of rotenone, deguelin and pyridaben is also presented.

Keywords: chemical mixtures; dose additivity; response additivity; potentiation; antagonism; synergism; supra-additivity; infra-additivity; toxic equivalency factor; comparative potency method