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Toxicokinetics of Brominated Azo Dyes in the Early Life Stages of Zebrafish (Danio rerio) Is Prone to Aromatic Substituent Changes
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    Toxicokinetics of Brominated Azo Dyes in the Early Life Stages of Zebrafish (Danio rerio) Is Prone to Aromatic Substituent Changes
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    • Jiajun Han
      Jiajun Han
      Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada
      More by Jiajun Han
    • Diwen Yang
      Diwen Yang
      Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada
      More by Diwen Yang
    • David Ross Hall
      David Ross Hall
      Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada
      School of the Environment, University of Toronto, Toronto, ON M5S 3E8, Canada
    • Jiabao Liu
      Jiabao Liu
      The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada
      More by Jiabao Liu
    • Jianxian Sun
      Jianxian Sun
      Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada
      More by Jianxian Sun
    • Wen Gu
      Wen Gu
      Department of Environmental Toxicology, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China
      More by Wen Gu
    • Song Tang
      Song Tang
      Department of Environmental Toxicology, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China
      More by Song Tang
    • Hattan A. Alharbi
      Hattan A. Alharbi
      Department of Plant Protection, College of Food and Agriculture Sciences, King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia
    • Paul. D. Jones
      Paul. D. Jones
      Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada
    • Henry M. Krause
      Henry M. Krause
      The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada
      Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada
    • Hui Peng*
      Hui Peng
      Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada
      School of the Environment, University of Toronto, Toronto, ON M5S 3E8, Canada
      *Email: [email protected]
      More by Hui Peng
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    Environmental Science & Technology

    Cite this: Environ. Sci. Technol. 2020, 54, 7, 4421–4431
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    https://doi.org/10.1021/acs.est.9b07178
    Published March 9, 2020
    Copyright © 2020 American Chemical Society

    Abstract

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    Brominated azo dyes (BADs) have been identified as predominant indoor brominated pollutants in daycare dust; thus, their potential health risk to children is of concern. However, the toxicities of BADs remain elusive. In this study, the toxicokinetics of two predominant BADs, Disperse Blue 373 (DB373) and Disperse Violet 93 (DV93), and their suspect metabolite 2-bromo-4,6-dinitroaniline (BDNA) was investigated in embryos of zebrafish (Danio rerio). The bioconcentration factor of DV93 at 120 hpf is 6.2-fold lower than that of DB373. The nontarget analysis revealed distinct metabolism routes between DB373 and DV93 by reducing nitro groups to nitroso (DB373) or amine (DV93), despite their similar structures. NAD(P)H quinone oxidoreductase 1 (NQO1) and pyruvate dehydrogenase were predicted as the enzymes responsible for the reduction of DB373 and DV93 by correlating time courses of the metabolites and enzyme development. Further in vitro recombinant enzyme and in vivo inhibition results validated NQO1 as the enzyme specifically reducing DB373, but not DV93. Global proteome profiling revealed that the expression levels of proteins from the “apoptosis-induced DNA fragmentation” pathway were significantly upregulated by all three BADs, supporting the bioactivation of BADs to mutagenic aromatic amines. This study discovered the bioactivation of BADs via distinct eukaryotic enzymes, implying their potential health risks.

    Copyright © 2020 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.est.9b07178.

    • Exposure of embryos to BADs; sample preparation for proteome analysis; sample preparation for metabolite analysis; proteome and metabolite profiling by mass spectrometry; nontarget analysis and data processing; stability of brominated azo dyes; effects of brominated azo dyes; high-resolution MS2 spectra; analytical method validation of the quantitative proteomics strategy (PDF)

    • Metabolites detected in zebrafish embryos (XLSX)

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    Environmental Science & Technology

    Cite this: Environ. Sci. Technol. 2020, 54, 7, 4421–4431
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.est.9b07178
    Published March 9, 2020
    Copyright © 2020 American Chemical Society

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