A Metabolomic Perspective of Small Molecule Toxicity

Recent advances in small molecule profiling, including ultraperformance liquid chromatography and time-of-flight mass spectrometry, have given unprecedented views of the metabolic response to toxic stimuli. Metabolomics, the process of measuring the concentration changes in metabolites of biofluids such as urine, serum, sweat or saliva or that of intact cells, tissues or single-celled organisms, is the missing piece of the omics puzzle (genomics, transcriptomics, proteomics) necessary for providing a holistic view (DNA, RNA, protein and metabolites) of the biological response to a toxicant. Furthermore, metabolomics is an essential addition to any toxicity biomarker-screening programme, as evidenced by its strong foothold in both pharmaceutical and academic settings. Here we discuss metabolomic science with respect to its past and future contributions to the field of toxicology and describe blueprints necessary for conducting a well-designed and robust metabolomics experiment from sample collection to data acquisition and analysis. Metabolomics holds great promise as a tool for advancing the field of toxicology by uncovering novel biomarkers of toxic responses and by significantly improving xenobiotic metabolite identification.