HBM4EU chromates study: untargeted metabolomics study of workers exposed to hexavalent chromium

Due to the wide use of Cr(VI), a large number of workers in a variety of industries are ex-posed to the potential harmful effects of this compound. The aim of this study was to inves-tigate changes in metabolic pathways in response to Cr(VI) exposure and to search for new urinary biomarkers. The study included 220 male workers who were exposed to Cr(VI) (through welding, chromium plating, surface treatment) and 102 male controls from Bel-gium, Finland, Poland, Portugal, and the Netherlands. Urinary metabolite profiles were de-termined using liquid chromatography mass spectrometry. The changes in the abundancy of excreted metabolites observed in post-shift workers vs. controls reflect fatty acid and mon-oamine neurotransmitter metabolism, oxidative modifications of amino acid residues, the excessive formation of abnormal amino acid metabolites and changes mainly in steroid hormones. We observed that: argininosuccinic acid, ubiquinone-1, indole-3-propionicacid, 6-hydroxyphenylpropionylglycine, 20-oxo-leukotriene E4, 3,4-dihydroxybenzylamine, 3,4-dimethoxyphenylethylamine and succinylacetone are potential biomarkers for Cr(VI) exposure (area under the curve > 0.9). The results of our study could form the basis for vali-dating early biomarkers of Cr(VI) exposure and their application in screening tests, and also serve as a starting point for further targeted metabolomics studies to better understand the disorders associated with Cr(VI) exposure.