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(13-03) Combining concentration addition and independent action for predicting mixture toxicity: studies with 40-component mixtures. Junghans, Marion*,1, Backhaus, Thomas1, Faust, Michael1, Meyer, Wiebke1, Scholze, Martin1, Grimme, L.1, 1 University of Bremen, Bremen, Germany ABSTRACT- Two concepts have shown to provide accurate predictions for mixture toxicity, concentration addition for similarly acting substances and independent action for dissimilarly acting substances. However, in environmentally relevant chemical mixtures similarly as well as dissimilarly acting substances have an impact on organisms at risk at the same time. As a step towards greater knowledge concerning the predictability of toxicity of these mixtures containing similarly as well as dissimilarly acting substances, we studied 40-component mixtures, in which the components can be clustered into four groups: chloroacetanilides, sulfonylurea, quinolones and triazines. The groups have dissimilar mechanisms of action, whereas within these groups the members act strictly similarly. Additionally, another mixture, containing as a fifth group 3 quaternary ammonium compounds, was tested in the same way. The mixtures were studied for their effects on the reproduction of the green alga Scenedesmus vacuolatus. Predictions were made according to three approaches: concentration addition, independent action, and, with a new approach, according to a two stage prediction where the mixture toxicity of each group with a similar mechanism of action is predicted by concentration addition and the overall toxicity is then predicted by assuming independent action between the groups. For all tested mixtures, concentration addition predicted a clearly higher and independent action a clearly lower toxicity than the observed mixture toxicity. In each mixture the two-stage approach led to a more accurate prediction of the observed mixture toxicity. The applicability of all three approaches for the predictive hazard assessment of mixtures composed of similarly as well as dissimilarly acting toxicants will be discussed. Key words: mixture toxicity, 40-component mixture, concentration addition, independent action |
