Predictability of the toxicity of multiple chemical mixtures to Vibrio fischeri: Mixtures composed of similarly acting chemicals

The prediction of combined effects based on the effects of the individual c omponents of mixtures by using the pharmacological concepts of concentratio n addition and independent action might be a promising tool for the risk as sessment of pollutant mixtures. To analyze and compare the predictive capab ilities of the reference concepts for similarly acting chemicals, the overa ll toxicity of a multiple mixture was determined in a bioluminescence inhib ition assay with Vibrio fischeri. The mixture was composed of 16 similarly and specifically acting chemicals, anticipated to have a common mode of act ion via weak acid respiratory uncoupling of oxidative phosphorylation. Resu lts show that the observed mixture toxicity is rather well predicted by bot h concepts. Concentration addition shows an excellent predictive power; the median effective concentration (EC50) of the mixture is predicted with an error of about 10%. Independent action, in contrast, underestimates the EC5 0 of the mixture by a factor of a little more than three. With respect to r isk assessment procedures, it may be concluded that concentration addition gives a valid estimation of the overall toxicity for multiple mixtures with similar and specific mechanisms of action of the mixture components in thi s type of biotest.