Mixture Toxicity and Gene Inductions: Can We Predict the Outcome?
As a consequence of the nature of most real life exposure scenarios, the last decade of ecotoxicology research has seen an increased interest in the assessment of mixture ecotoxicology. Often mixtures are considered to follow one of two models, either concentration (CA) or response addition (RA), both of which have been described in literature. Nevertheless mixtures that deviate from either of both models exist, they typically exhibit phenomena like synergism, ratio or concentration dependency, inhibition. Moreover both CA and RA were mainly challenged and evaluated for acute responses at relatively high levels of biological organization, e.g. whole organism mortality, and applicability to genetic responses has not received much attention. Genetic responses are considered the primary reaction in case of toxicant exposure and carry valuable mechanistic information. Effects at the gene expression level, are at the heart of the mode of action of toxicants and mixtures. The ability to predict mixture responses at this primary response level is an important asset in predicting and understanding mixture effects at different levels of biological organization. This study evaluates the applicability of mixture models to stress gene inductions in Escherichia coli employing model toxicants with known mode of action in binary combinations. The research showed that even if the maximum of the dose response curve is not known, making a classical ECx (concentration causing x % effect) approach impossible, mixture models can predict the responses to the binary mixtures from the single toxicant response curves well. In most cases the mode of action of the toxicants does not determine the optimal choice of model, i.e. concentration addition or response addition or a deviation thereof.
PMID: 17983273 [PubMed - as supplied by publisher]
