New insights into the cellular mechanism of triclosan-induced dermal toxicity from a combined metabolomic and lipidomic approach

Triclosan (TCS), an antimicrobial chemical, has been widely used in consumer goods and personal care products. Despite skin is the crucial entry of TCS into human body, previous studies mainly focused on the potential health risks after TCS absorption. Considering in vivo evidences have indicated that topical use of TCS could lead to serious skin lesions, it is thus in urgent need to unveil the underlying mechanisms of dermal toxicity caused by TCS application. In this study, mass spectrometry-based metabolomics and lipidomics were applied to investigate TCS-induced changes of endogenous small molecular metabolites and lipids in human HaCaT keratinocytes. Metabolic biomarker analysis revealed that TCS exposure was associated with the elevation of purine and glutathione metabolism, down-regulation of amino acid metabolism and dysregulation of lipid metabolism in keratinocytes. These intracellular metabolic disorders consequently led to the overproduction of reactive oxygen species (ROS) and accumulation of ammonia. TCS-induced oxidative stress was further validated in human HaCaT cells, functioning as the crucial factor for the generation of pro-inflammatory cytokines that triggered inflammation and lipid disturbances related to cell apoptosis. Our findings update the existing understanding of skin health risks of TCS application at the molecular level.