Long-term percutaneous triclosan exposure induces thyroid damage in mice: Interpretation of toxicity mechanism from metabolic and proteomic perspectives.

Triclosan (TCS) is an antiseptic incorporated in consumer goods and personal care products that can be absorbed via the skin, raising public health concerns for its continuous detection in human biofluids and tissues. Epidemiology has associated TCS exposure with thyroid function disturbances and decreasing serum thyroid hormone (TH) levels, but the underlying mechanism remains unclear. In this study, we revealed hypothyroidism and histological alternation in the thyroid of mice with chronic percutaneous exposure to TCS, indicating a TCS-caused thyroid impairment. Subsequently, multi-omics approaches were performed to investigate the molecular mechanism of the thyroid in response to long-term dermal TCS exposure. We discovered that TCS interfered with the TH synthesis as indicated by the changes in the levels of the synthetic materials for TH (iodide, Tg, and H2O2) and affected TH release by the downregulation of lysosomal enzymes. The upregulation of glycolysis, tricarboxylic acid cycle, fatty acid, amino acid metabolism, and adenine salvage in the thyroid was also observed after TCS exposure. All these changes led to the elevation of ATP, serving as a rescue for the decreasing thyroid functions. Together, our study demonstrated TCS-induced thyroid damage and identified the interrupted pathways, providing meaningful insight into the molecular mechanisms underpinning the potential health influence of TCS in humans.