toxicometabolomics

Toxicometabolomics is a discipline that applies metabolomics to toxicology in order to understand how exposure to chemicals perturbs endogenous metabolism. It seeks to identify metabolic signatures of exposure (biomarkers of exposure), the resulting biological effects (biomarkers of effect), and the underlying mechanisms of toxicity. The field supports studies in humans, animals, and in vitro models and is often integrated with exposomics and systems toxicology to place metabolite changes in a broader context.

Analytical workflows typically involve collecting biological samples such as blood, urine, or tissue, followed by measurement with platforms including LC-MS, GC-MS, and NMR. Both untargeted and targeted approaches are used to detect wide metabolite changes and to quantify specific compounds. Data processing, quality control, normalization, and batch correction are essential, as is metabolite identification and annotation. Statistical methods range from multivariate analyses to pathway and network analyses, with machine learning aiding biomarker discovery and interpretation. In some studies, stable isotope tracing is used to investigate metabolic fluxes related to toxicant exposure.

Applications of toxicometabolomics span environmental and occupational health, pharmacology, and food safety. It is employed to discover biomarkers of exposure to metals, solvents, pesticides, and persistent organic pollutants, as well as to investigate drug-induced toxicity. Insights include perturbations in energy and lipid metabolism, amino acid turnover, bile acid pathways, and oxidative stress responses, contributing to mechanistic understanding and risk assessment. Cross-species and dose–response comparisons are common and can inform regulatory toxicology.

Challenges include metabolite identification, standardization across laboratories, reproducibility, and accounting for confounders such as diet and microbiome. Future directions emphasize integration with other omics and exposomics, improved databases and annotations, and advancing quantitative, mechanism-based toxicology.