@article {130, title = {Toxicokinetics of Brominated Azo Dyes in the Early Life Stages of Zebrafish () Is Prone to Aromatic Substituent Changes.}, journal = {Environ Sci Technol}, volume = {54}, year = {2020}, month = {2020 04 07}, pages = {4421-4431}, abstract = {

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 (). 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.

}, keywords = {Animals, Azo Compounds, Child, Dust, Embryo, Nonmammalian, Humans, Mutagens, Toxicokinetics, Zebrafish}, issn = {1520-5851}, doi = {10.1021/acs.est.9b07178}, author = {Han, Jiajun and Yang, Diwen and Hall, David Ross and Liu, Jiabao and Sun, Jianxian and Gu, Wen and Tang, Song and Alharbi, Hattan A and Jones, Paul D and Krause, Henry M and Peng, Hui} } @article {93, title = {Identification of Chemicals that Cause Oxidative Stress in Oil Sands Process-Affected Water.}, journal = {Environ Sci Technol}, volume = {51}, year = {2017}, month = {2017 Aug 01}, pages = {8773-8781}, abstract = {

Oil sands process-affected water (OSPW) has been reported to cause oxidative stress in organisms, yet the causative agents remain unknown. In this study, a high-throughput in vitro Nrf2 reporter system was used, to determine chemicals in OSPW that cause oxidative stress. Five fractions, with increasing polarity, of the dissolved organic phase of OSPW were generated by use of solid phase extraction cartridges. The greatest response of Nrf2 was elicited by F2 (2.7 {\textpm} 0.1-fold), consistent with greater hydroperoxidation of lipids in embryos of Japanese medaka (Oryzias latipes) exposed to F2. Classic naphthenic acids were mainly eluted in F1, and should not be causative chemicals. When F2 was fractionated into 60 subfractions by use of HPLC, significant activation of Nrf2 was observed in three grouped fractions: F2.8 (1.30 {\textpm} 0.01-fold), F2.16 (1.34 {\textpm} 0.05-fold), and F2.25 (1.28 {\textpm} 0.15-fold). 54 compounds were predicted to be potential chemicals causing Nrf2 response, predominated by SO and O species. By use of high-resolution MS spectra, these SO and O species were identified as hydroxylated aldehydes. This study demonstrated that polyoxygenated chemicals, rather than classic NAs, were the major chemicals responsible for oxidative stress in the aqueous phase of OSPW.

}, keywords = {Animals, Carboxylic Acids, Oil and Gas Fields, Oryzias, Oxidative Stress, Water, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/acs.est.7b01987}, author = {Sun, Jianxian and Peng, Hui* and Alharbi, Hattan A and Jones, Paul D and Giesy, John P and Wiseman, Steve B} } @article {99, title = {Peroxisome Proliferator-Activated Receptor γ is a Sensitive Target for Oil Sands Process-Affected Water: Effects on Adipogenesis and Identification of Ligands.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 07 19}, pages = {7816-24}, abstract = {

Identification of toxic components of complex mixtures is a challenge. Here, oil sands process-affected water (OSPW) was used as a case study to identify those toxic components with a known protein target. Organic chemicals in OSPW exhibited dose-dependent activation of peroxisome proliferator-activated receptor γ (PPARγ) at concentrations less than those currently in the environment (0.025{\texttimes} equivalent of full-strength OSPW), by use of a luciferase reporter gene assay. Activation of PPARγ-mediated adipogenesis by OSPW was confirmed in 3T3L1 preadipocytes, as evidenced by accumulation of lipids and up-regulation of AP2, LPL, and PPARγ gene expression after exposure to polar fractions of OSPW. Unexpectedly, the nonpolar fractions of OSPW inhibited differentiation of preadipocytes via activation of the Wnt signaling pathway. Organic chemicals in OSPW that were ligands of PPARγ were identified by use of a pull-down system combined with untargeted chemical analysis (PUCA), with a recombinant PPARγ protein. Thirty ligands of PPARγ were identified by use of the PUCA assay. High resolution MS(1) and MS(2) spectra were combined to predict the formulas or structures of a subset of ligands, and polyoxygenated or heteroatomic chemicals, especially hydroxylated carboxylic/sulfonic acids, were the major ligands of PPARγ.

}, keywords = {Adipogenesis, Ligands, Oil and Gas Fields, PPAR gamma, Water}, issn = {1520-5851}, doi = {10.1021/acs.est.6b01890}, author = {Peng, Hui and Sun, Jianxian and Alharbi, Hattan A and Jones, Paul D and Giesy, John P and Wiseman, Steve} }