Metabolomics in environmental toxicology: Applications and challenges

Metabolomics is a discipline aiming to characterize the presence of metabolites in biological matrices under specific conditions. In recent years, metabolomics has increasingly been used in environmental research to explore the metabolic changes in humans and organisms under diverse environmental exposures, mainly chemical pollutants. Hence, metabolomics has become a key tool in exposome studies, to explore the biological effects at molecular level exerted by xenobiotics. To understand the biological mechanisms triggered by specific chemical compounds, the combination of metabolomics with information about the presence of xenobiotics in the biological samples (xenometabolome), and other molecular information obtained from omics technologies (e.g. transcriptomics, proteomics) is crucial, both in exposome studies, and adverse outcome pathways (AOPs) development. This review aims to describe the main applications of metabolomics in the assessment of biological effects induced by chemical pollutants on ecosystems and human health, both in exposome studies and in laboratory-controlled assays. Different analytical aspects and recent analytical challenges are presented and discussed. Finally, the different opportunities and the current situation of metabolomics as a tool in chemical safety assessment for regulatory applications are reviewed.Thanks to Joan Meléndez Vilardell for his contribution to the graphical art of this review. Also, the financial support of Spanish MCIN/AIE/10.13039/501100011033 (Severo Ochoa Project CEX2018-000794-S) is acknowledged.Peer reviewe