Conventional biomonitoring programs have been criticized on the basis that they cannot include the full range of chemical pollutants that make up the exposome. Bioanalytical tools may therefore complement chemical analysis for cost-efficient and comprehensive biomonitoring in diverse tissue types. Bioanalytical tools are in vitro cell-based bioassays that target specific mechanisms of toxicity and give a measure of the toxicity of mixtures of known and unknown chemicals, such as persistent organic pollutants, pesticides, industrial chemicals, pharmaceuticals and their transformation products. We investigated human post-mortem tissues (liver, brain, adipose tissue as well as blood) from 16 individuals after dynamic equilibrium sampling by instrumental analysis with direct sample introduction (DSI) GC-MS/MS. Target analysis was complemented by bioanalytical profiling with reporter gene bioassays targeting the activation of the aryl hydrocarbon receptor (AhR) with the AhR-CALUX assay. Static equilibrium sampling with polydimethylsiloxane (silicone, PDMS) as sampling phase was possible for adipose tissue but the uptake kinetics were too slow for lipid-poor tissues. A stirring device was developed that accelerated the uptake kinetics that equilibrium was achieved within 7 days also for liver, blood and brain. Detected concentrations of 35 of 99 target analytes agreed with concentrations in literature. The detected concentrations of persistent organic pollutants increased with age while non-persistent chemicals did not show any age dependence of concentrations in blood, liver and brain and were often present at lower concentrations in adipose tissue. The activity in the AhR-CALUX bioassay also increased with age and was higher in liver and brain that in blood. The sum of concentrations of the detected chemicals was positively correlated with the bioassay responses but mixture modeling showed that the detected chemicals explained less than 2% of the activation of the AhR and less than 0.5% of cytotoxicity. This means that more than 10,000 chemicals would need to be included in an analytical method to capture all the effects with many chemicals potentially being below detection limits but still contributing to mixture effects. This comparison demonstrates how in vitro bioassays are a powerful complement to chemical analysis that captures the complexity of the exposome.
Beate Escher is Head of Department of Cell Toxicology at the Helmholtz Centre for Environmental Research in Leipzig, Germany and Professor at the Eberhard Karls University Tübingen, Germany. She is also lecturer at the Swiss Federal Institute of Technology in ETHZ, Switzerland, holds an honorary professorship at the University of Queensland and an adjunct professorship at Griffith University, Australia. She is an Associate Editor with Environmental Science and Technology. From 2011 to 2014 she held an Australian Research Council Future Fellowship and was Deputy Director of Entox at UQ from 2009 to 2013.



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