Analysing combination effects of estrogenic compounds in aquatic organisms
Natural estrogens and synthetic chemicals that have the ability to mimic estrogens lead to reproductive dysfunction adversely affecting a variety of fish. The number and variability of these pollutants and their concentrations is such that a virtually unlimited number of different mixtures can be found. This fact renders an experimental hazard assessment of all possible mixtures impossible. However, in ecotoxicology, two different concepts, termed Concentration Addition and Independent Action allow the calculation of expected mixture toxicity on the basis of known effects of the single compounds. Concentration Addition is based on the idea of a similar mechanism of action of all hazardous substances in the examined mixture. The alternative concept of Independent Action assumes that the mixture components have dissimilar mechanisms of action. However both concepts refer to cases where all substances in a mixture affect the same experimental endpoint. In the context of the ACE project an assessment of the predictive power of both concepts has been carried out in order to identify the major issues that facilitate or hamper the successful completion of the mixture studies. The predictive power of both concepts was found to be severely limited when single substance concentration-response relationships are of low accuracy. The applicability of Concentration Addition prediction is restricted to the range of effects, which can be described for all mixture components. On the other hand, Independent Action assumes that all concentration-effect curves can be reasonably scaled to a common minimum and maximum effect. Moreover the application of the concept of Independent Action to multi-component mixtures necessitates the precise estimation of low-effect levels, which implies a high demand in terms of experimental capacity and necessary test animals. The predictive power of the methods is not affected by a high number of mixture components, thus making the available experimental capacity the decisive factor for the number of possible mixture components. Conclusions drawn and results acquired, combined with existing evidence from mixture studies in other bioassays in similar research efforts, present a formidable challenge for further investigation and development for the protection of wildlife populations and human health.
