Chemical exposures can play a pivotal role in the etiology of human disease and it is estimated that hundreds of thousands of environmental chemicals may be linked to a large share of chronic disease. However, little is known about the complex interplay between environmental exposures, genetic susceptibility and potential adverse health outcomes. While we are constantly facing a mixture of exposures through the environment, diet, and endogenous processes, exposure and risk assessment is typically still based on the evaluation of single compounds. To address this challenge, high-resolution mass spectrometry (HR-MS) based metabolomics has been proposed as a future key technology.<br/><br/>In this contribution, an optimized untargeted metabolomics workflow is presented which provides a solution to the two key tasks in current environmental health research of (1) assessing multiple exposures simultaneously and (2) evaluating their biological/toxicological effect. Employing HR-MS and the XCMS/METLIN data processing platform, thousands of metabolic features originating from endogenous metabolites, toxicants, other xenobiotics and their biotransformation products can now be assessed simultaneously using one analytical technique. The applicability of this workflow was demonstrated in human biofluids and a cell-based model. More specifically, xenoestrogens, which are suspected to may cause endocrine disruption, have been detected at low nanomolar concentrations. Moreover, their effect on cellular metabolism was evaluated using metabolic pathway analysis. This workflow enables, for the first time, the combination of holistic, untargeted exposure assessment with changes in endogenous metabolism for deciphering specific pathways affected by individual or mixtures of toxicants.<br/><br/>The presented novel technology has many potential applications in the areas of toxicology, public health and beyond and may influence how we address the challenges in the new era of exposomics.

Exposing the exposome: Utilizing global metabolomics to characterize toxicant exposure and effect

254th National Meeting (2017)

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