Linking in Vitro Effects and Detected Organic Micropollutants in Surface Water Using Mixture-Toxicity Modeling

Peta A. Neale, Selim Ait-Aissa, Werner Brack, Nicolas Creusot, Michael S. Denison, Björn Deutschmann, Klára Hilscherová, Henner Hollert, Martin Krauss, Jiří Novák, Tobias Schulze, Thomas-Benjamin Seiler, Helene Serra, Ying Shao, Beate I. Escher

Surface water can contain countless organic micropollutants, and targeted chemical analysis alone may only detect a small fraction of the chemicals present. Consequently, bioanalytical tools can be applied complementary to chemical analysis to detect the effect of complex chemical mixtures. In this study, bioassays indicative of activation of the aryl hydrocarbon receptor (AhR), activation of the pregnane X receptor (PXR), activation of the estrogen receptor (ER), adaptive stress responses to oxidative stress (Nrf2), genotoxicity (p53) and inflammation (NF-κB) and fish embryo toxicity were applied along with chemical analysis to water extracts from the Danube River. Mixture toxicity modeling was applied to determine the contribution of detected chemicals to the biological effect. Effect concentrations for between 0 to 13 detected chemicals could be found in the literature for the different bioassays. Detected chemicals explained less than 0.2% of the biological effect in the PXR activation, adaptive stress response and fish embryo toxicity assays, while five chemicals explained up to 80% of ER activation and three chemicals explained up to 71% of AhR activation. This study highlights the importance of fingerprinting the effects of detected chemicals.