Metabolomics is emerging as a powerful systems biology approach for improving preclinical drug safety assessment. This review discusses current applications and future trends of metabolomics in toxicology and drug development. Metabolomics can elucidate adverse outcome pathways by detecting endogenous biochemical alterations underlying toxicity mechanisms. Furthermore, metabolomics enables better characterization of human environmental exposures and their influence on disease pathogenesis. Metabolomics approaches are being increasingly incorporated into toxicology studies and safety pharmacology evaluations to gain mechanistic insights and identify early biomarkers of toxicity. However, realizing the full potential of metabolomics in regulatory decision making requires a robust demonstration of reliability through quality assurance practices, reference materials, and interlaboratory studies. Overall, metabolomics shows great promise in strengthening the mechanistic understanding of toxicity, enhancing routine safety screening, and transforming exposure and risk assessment paradigms. Integration of metabolomics with computational, in vitro, and personalized medicine innovations will shape future applications in predictive toxicology.
Keywords: adverse outcome pathways; drug development; metabolomics; safety; toxicity.