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

Hongna Zhang, Katherine Z. Sanidad, Lin Zhu, Julie Parsonnet, Thomas D. Haggerty, Guodong Zhang*, Zongwei Cai*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

12 Citations (Scopus)


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

Original languageEnglish
Article number124803
JournalJournal of Hazardous Materials
Early online date9 Dec 2020
Publication statusPublished - 5 Apr 2021

Scopus Subject Areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution
  • Health, Toxicology and Mutagenesis

User-Defined Keywords

  • CYPs
  • in Silico
  • in Vitro
  • in Vivo
  • Oxidative metabolism
  • Triclosan


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