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

DOI: 10.1016/j.jhazmat.2020.124803

Source and publish data:

Journal of Hazardous Materials (2021)

Update date:2022-08-11

Topics:

Authors:

Zhang, Hongna

Sanidad, Katherine Z.

Zhu, Lin

Parsonnet, Julie

Haggerty, Thomas D.

Zhang, Guodong

Cai, Zongwei

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Article abstract of DOI:10.1016/j.jhazmat.2020.124803

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.

Full text of DOI:10.1016/j.jhazmat.2020.124803

Journal Pre-proof

Frequent occurrence of triclosan hydroxylation in

mammals:

combined theoretical and

experimental investigation

Hongna Zhang, Katherine Z. Sanidad, Lin Zhu,

Julie Parsonnet, Thomas D. Haggerty, Guodong

Zhang, Zongwei Cai

PII:

S0304-3894(20)32794-1

DOI:

https://doi.org/10.1016/j.jhazmat.2020.124803

HAZMAT124803

Reference:

To appear in:

Journal of Hazardous Materials

Received date: 25 June 2020

Revised date: 7 November 2020

Accepted date: 6 December 2020

Please cite this article as: Hongna Zhang, Katherine Z. Sanidad, Lin Zhu, Julie

Parsonnet, Thomas D. Haggerty, Guodong Zhang and Zongwei Cai, Frequent

occurrence of triclosan hydroxylation in mammals: A combined theoretical and

experimental

investigation, Journal of Hazardous Materials, (2020)

doi:https://doi.org/10.1016/j.jhazmat.2020.124803

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