Characterization of triclosan-induced hepatotoxicity and triclocarban-triggered enterotoxicity in mice by multiple omics screening

Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether, TCS) and triclocarban (3,4,4'-trichloro-carbanilide, TCC) are two antimicrobial agents commonly used for personal care products. Previous studies primarily focused on respective harmful effects of TCS and TCC. In terms of their structural similarities and differences, however, the structure-toxicity relationships on health effects of TCS and TCC exposure remain unclear. Herein, global 1H NMR-based metabolomics was employed to screen the changes of metabolic profiling in various biological matrices including liver, serum, urine, feces and intestine of mice exposed to TCS and TCC at chronic and acute dosages. Metagenomics was also applied to analyze the gut microbiota modulation by TCS and TCC exposure. Targeted MS-based metabolites quantification, histopathological examination and biological assays were subsequently conducted to supply confirmatory information on respective toxicity of TCS and TCC. We found that oral administration of TCS mainly induced significant liver injuries accompanied with inflammation and dysfunction, hepatic steatosis fatty acids and bile acids metabolism disorders; while TCC exposure caused marked intestine injuries leading to striking disruption of colonic morphology, inflammatory status and intestinal barrier integrity, intestinal bile acids metabolism and microbial community. These comparative results provide novel insights into structure-dependent mechanisms of TCS-induced hepatotoxicity and TCC-triggered enterotoxicity in mice.