Frequent occurrence of triclosan hydroxylation in mammals: A combined theoretical and experimental investigation

Triclosan (TCS) is a widespread antimicrobial agent with many adverse health risks. Its hepatoxicity invariably points to the activation of constitutive androstane receptor (CAR), which regulates cytochrome P450 (CYP) genes that are critical for oxidative metabolism. Here, we provide theoretical and experimental evidences showing metabolic TCS frequently occurs through aromatic hydroxylation in mammals. CYP-mediated oxidation was predicted take place at each C‒H bond. Molecular docking vitro approaches reveal reaction could be efficiently catalyzed by CAR-regulated CYP2B6 enzyme. Parallel monitoring (PRM) high-resolution mass spectrometry utilized identify profile metabolites paired mouse liver, bile, feces, plasma urine. We found multiple hydroxylated isomers including products generated via NIH shift chlorine, as well their subsequent conjugates. These showed isomer-specific retention mice. Glucuronide conjugates more readily excreted than sulfates. Moreover, first time, isomeric were detected urine stool human subjects used TCS-contained household personal care products. Collectively, these findings suggest an important, yet often underestimated element worth considering fully evaluate biological fates risks TCS.