Triclocarban (TCC) is a widely used antimicrobial agent added to consumer and personal care products. It has been classified as an emerging contaminant of concern due to its widespread occurrence, environmental persistence, bioaccumulation, and potential toxicity. Recent studies have shown liver toxicity related to TCC exposure, but the toxicological effects and potential mechanism induced by TCC is largely unknown. After TCC enters animal or human body, the chemical can be metabolized to hydroxylated triclocarbans (OH-TCCs) that may possess higher toxicity. However, current studies largely neglected the potential toxicity related to OH-TCCs. Therefore, this proposal attempts to combine advanced mass spectrometry (MS) and related omics techniques to investigate the underlying mechanism of liver toxicity induced by TCC and OH-TCCs. Both cell and animal models will be used. Chemical synthesis has been utilized to obtain OH-TCC standards because of their commercially unavailability. The metabolomics and lipidomics will be applied to study the changes of endogenous metabolic profiles related to TCC/OH-TCC exposures. Specifically, non-targeted analysis will be conducted to identify small molecule biomarkers, metabolic pathways and networks related to liver toxicity. Targeted metabolomics/lipidomics analysis will be performed to clarify the metabolic changes of selected biomarkers and to investigate the potential target sites of TCC/OH-TCC. Moreover, matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) will be used to reveal distribution difference of endogenous metabolites in animal liver tissue. Biological verification of the proposed hypothesis will be carried out throughout the study. The proposed research will be an important step towards the understanding of mechanism of liver toxicity induced by TCC and OH-TCCs at cellular and molecular levels, providing scientific basis for human health risk assessments. The platform established in this project can help shed light on the investigation of toxicological effects of other environmental contaminants.
|Effective start/end date||1/01/20 → 31/12/22|
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