Application of metallomics to understand environmental metal exposure

Environmental metal exposure is rarely a single-element event and even more rarely a single-chemical-species event. Metals and metalloids circulate as dynamic mixtures whose toxicity, transport, and biological effects are governed by speciation, binding to biomolecules, subcellular localization, and interactions with endogenous metal homeostasis. Metallomics, the comprehensive study of elemental distributions, metal species, and metal–biomolecule interactions across biological systems has emerged as a powerful framework for moving exposure science beyond “total metal concentration” toward mechanistically meaningful measurements. Metallomics integrates high-sensitivity multi-element quantification (ICP-MS), elemental speciation (LC/CE–ICP-MS coupled to molecular MS), metalloproteomics, metallometabolomics, spatial metal imaging (LA-ICP-MS and complementary mass spectrometry imaging), and single-cell elemental analysis. Together, these tools enable investigators to trace environmental exposures from external sources to internal dose, then to biologically effective dose, and finally to downstream pathway disruption. This review synthesizes peer-reviewed evidence on metallomics platforms and study designs used to understand environmental exposures, with emphasis on how speciation and ligand binding control toxicity, how spatial mapping reveals tissue and cell-type vulnerability, how single-cell metallomics resolves heterogeneity masked by bulk averaging, and how integrative “metallomics + other omics” strategies illuminate causal pathways linking exposure to disease. We discuss best practices in sampling, quality assurance, contamination control, and data integration, and we highlight emerging directions such as non-targeted speciation, isotope tracing, and multiscale exposure-to-biology pipelines.