S01-02 Whole mixture assessments of water, food and human blood

In vitro bioassays have a long tradition for hazard assessment of chemicals as well as for water quality monitoring. Here we apply these tools to mixtures extracted from pooled samples covering the continuum of environment to human, including water, fish, milk and human serum. We developed a test battery of 22 in vitro bioassays that broadly covered developmental neurotoxicity, thyroid hormone system disruption, reproductive toxicity, genotoxicity and adaptive stress responses. Putative adverse outcome pathways synthesized from diverse literature sources served as a starting point for the selection of the bioassays. Most assays responded to wastewater with effecs and cytotoxicity decreasing from wastewater over surface water to drinking water. Serum samples pooled from diverse population groups in Australia and Europe were extracted with solid-phase extraction yielding broad-spectrum extracts of chemicals of a medium hydrophobicity range including neutral and charged organic chemicals. 50-60 % of the bioassays responded to the dosed serum extracts. All groups of mode of action were affected with the exception of genotoxicity. High specificity was observed for disruption on thyroid hormone system and neurotoxicity. Through a global profiling approach (suspect screening), 24 endogenous chemicals and environmental pollutants were identified with high confidence and were quantified, among many more qualitatively confirmed. Mixture modelling using detected concentrations and bioassay data for single chemicals demonstrated that little of the effect could be explained by the quantified chemicals. Endogenous compounds also contributed to mixture effects and future work will need to establish a baseline of effects caused by endogenous compounds and differentiate those from the effects triggered by environmental pollutants. Bioassays are a promising tool to identify bioactive chemical mixtures in environmental and human biomonitoring.