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Copper (Cu) is toxic to humans and animals as a result of the generation of reactive oxygen species (ROS) through Fenton reactions and abnormal alterations in metabolism and biological processes. For the general population, diet and drinking water are the main sources of Cu exposure, and the intestinal tract is therefore the first barrier against Cu-induced toxicity. Previous studies have demonstrated the cytotoxicity of Cu exposure with a focus on specific aspects such as oxidative stress and Cu transportation. But the information on the global response of cells to Cu exposure is limited. Metabolomic methods, featuring the high-flux detection of whole metabolites in cells and organisms, provide promising alternatives to conventional methods in the study of global cytotoxicity response. In this study, the human colon carcinoma cell line HT-29 was selected and a metabolomic method based on liquid chromatography …