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Toxicokinetics of Brominated Azo Dyes in the Early Life Stages of Zebrafish (Danio rerio) Is Prone to Aromatic Substituent Changes
journal contribution
posted on 2020-03-24, 16:09 authored by Jiajun Han, Diwen Yang, David Ross Hall, Jiabao Liu, Jianxian Sun, Wen Gu, Song Tang, Hattan A. Alharbi, Paul. D. Jones, Henry M. Krause, Hui PengBrominated 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.