@article {275, title = {Emerging investigator series: nontargeted screening of aryl hydrocarbon receptor agonists in endangered beluga whales from the St. Lawrence Estuary: beyond legacy contaminants.}, journal = {Environ Sci Process Impacts}, volume = {26}, year = {2024}, month = {2024 Sep 18}, pages = {1451-1464}, abstract = {

The elevated concentrations of organohalogen contaminants in the endangered St. Lawrence Estuary (SLE) belugas have prompted the hypothesis that aryl hydrocarbon receptor (AhR) activity may be a contributor towards their potential adverse effects. While indirect associations between AhR and contaminant levels have been reported in SLE beluga tissues, AhR activity was never directly measured. Using bioassays and nontargeted analysis, this study contrasted AhR activity and agonist profiles between pooled tissue extracts of endangered SLE and non-threatened Arctic belugas. Tissue extracts of SLE belugas exhibited significantly higher overall AhR activity than that of Arctic belugas, with a 2000s SLE beluga liver extract exerting significantly higher activity than blubber extracts of SLE and Arctic belugas from the same time period. Contrary to our expectations, well-known AhR agonists detected by nontargeted analysis, including polychlorinated biphenyls (PCBs), were only minor contributors to the observed AhR activity. Instead, Tox21 suspect screening identified more polar chemicals, such as dyes and natural indoles, as potential contributors. Notably, the natural product bromoindole was selectively detected in SLE beluga liver at high abundance and was further confirmed as an AhR agonist. These findings highlighted the significance of the AhR-mediated toxicity pathway in belugas and underscored the importance of novel AhR agonists, particularly polar compounds, in its induction.

}, keywords = {Animals, Beluga Whale, Endangered Species, Environmental Monitoring, Estuaries, Liver, Polychlorinated Biphenyls, Receptors, Aryl Hydrocarbon, Water Pollutants, Chemical}, issn = {2050-7895}, doi = {10.1039/d4em00243a}, author = {Barrett, Holly and Sun, Jianxian and Chen, Yuhao and Yang, Diwen and Verreault, Jonathan and Houde, Magali and Wania, Frank and Peng, Hui} } @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 {100, title = {Combined Transcriptomic and Proteomic Approach to Identify Toxicity Pathways in Early Life Stages of Japanese Medaka (Oryzias latipes) Exposed to 1,2,5,6-Tetrabromocyclooctane (TBCO).}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 07 19}, pages = {7781-90}, abstract = {

Currently, the novel brominated flame retardant 1,2,5,6-tetrabromocyclooctane (TBCO) is considered a potential replacement for hexabromocyclododecane (HBCD). Therefore, use of TBCO could increase in the near future. To assess potential toxicological risks to aquatic organisms, embryos of Japanese medaka (Oryzias latipes) were exposed to 10, 100, or 1000 μg/L TBCO from 2 h postfertilization until 1 day post-hatch. TBCO accumulated in embryos in the order of 0.43-1.3 {\texttimes} 10(4)-fold, and the rate constant of accumulation was 1.7-1.8 per day. The number of days to hatch and the hatching success of embryos exposed to the medium and the greatest concentrations of TBCO were impaired. Responses of the transcriptome (RNA-seq) and proteome were characterized in embryos exposed to 100 μg/L TBCO because this was the least concentration of TBCO that caused an effect on hatching. Consistent with effects on hatching, proteins whose abundances were reduced by exposure to TBCO were enriched in embryo development and hatching pathways. Also, on the basis of the responses of transcriptome and proteome, it was predicted that TBCO might impair vision and contraction of cardiac muscle, respectively, and these effects were confirmed by targeted bioassays. This study provided a comprehensive understanding of effects of TBCO on medaka at early life stages and illustrated the power of "omics" to explain and predict phenotypic responses to chemicals.

}, keywords = {Animals, Oryzias, Proteomics, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/acs.est.6b01249}, author = {Sun, Jianxian and Tang, Song and Peng, Hui* and Saunders, David M V and Doering, Jon A and Hecker, Markus and Jones, Paul D and Giesy, John P and Wiseman, Steve} } @article {101, title = {High Conservation in Transcriptomic and Proteomic Response of White Sturgeon to Equipotent Concentrations of 2,3,7,8-TCDD, PCB 77, and Benzo[a]pyrene.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 05 03}, pages = {4826-35}, abstract = {

Adverse effects associated with exposure to dioxin-like compounds (DLCs) are mediated primarily through activation of the aryl hydrocarbon receptor (AHR). However, little is known about the cascades of events that link activation of the AHR to apical adverse effects. Therefore, this study used high-throughput, next-generation molecular tools to investigate similarities and differences in whole transcriptome and whole proteome responses to equipotent concentrations of three agonists of the AHR, 2,3,7,8-TCDD, PCB 77, and benzo[a]pyrene, in livers of a nonmodel fish, the white sturgeon (Acipenser transmontanus). A total of 926 and 658 unique transcripts were up- and down-regulated, respectively, by one or more of the three chemicals. Of the transcripts shared by responses to all three chemicals, 85\% of up-regulated transcripts and 75\% of down-regulated transcripts had the same magnitude of response. A total of 290 and 110 unique proteins were up- and down-regulated, respectively, by one or more of the three chemicals. Of the proteins shared by responses to all three chemicals, 70\% of up-regulated proteins and 48\% of down-regulated proteins had the same magnitude of response. Among treatments there was 68\% similarity between the global transcriptome and global proteome. Pathway analysis revealed that perturbed physiological processes were indistinguishable between equipotent concentrations of the three chemicals. The results of this study contribute toward more completely describing adverse outcome pathways associated with activation of the AHR.

}, keywords = {Animals, Benzo(a)pyrene, Dioxins, Fishes, Polychlorinated Dibenzodioxins, Proteomics}, issn = {1520-5851}, doi = {10.1021/acs.est.6b00490}, author = {Doering, Jon A and Tang, Song and Peng, Hui and Eisner, Bryanna K and Sun, Jianxian and Giesy, John P and Wiseman, Steve and Hecker, Markus} } @article {104, title = {p,p{\textquoteright}-DDE Induces Gonadal Intersex in Japanese Medaka (Oryzias latipes) at Environmentally Relevant Concentrations: Comparison with o,p{\textquoteright}-DDT.}, journal = {Environ Sci Technol}, volume = {50}, year = {2016}, month = {2016 Jan 05}, pages = {462-9}, abstract = {

Previous studies have reported high body burdens of dichlorodiphenyltrichloroethane (DDT) and its metabolites in wild fishes worldwide. This study evaluated the adverse effects of 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p{\textquoteright}-DDE) and o,p{\textquoteright}-DDT on gonadal development and reproduction by exposing transgenic Japanese medaka (Oryzias latipes) from hatch for 100 days. While both p,p{\textquoteright}-DDE and o,p{\textquoteright}-DDT induced intersex in male medaka, the lowest observable effective concentration (LOEC) of o,p{\textquoteright}-DDT was 57.7 ng/g ww, about 5-fold lower than that (272 ng/g ww) of p,p{\textquoteright}-DDE. Since LOECs of both chemicals were comparable to the body concentrations in wild fish, DDT contamination would likely contribute to the occurrence of intersex observed in wild fish. Exposure to o,p{\textquoteright}-DDT resulted in much higher expression of vitellogenin in liver of males than p,p{\textquoteright}-DDE, accordant with the higher potency of o,p{\textquoteright}-DDT than p,p{\textquoteright}-DDE to induce intersex. This phenomenon could be partly explained by the significantly elevated levels of 17β-estradiol in plasma of males exposed to o,p{\textquoteright}-DDT, in addition to its estrogenic activity via the estrogen receptor. Significantly lower fertilization (p = 0.006) and hatchability (p = 0.019) were observed in the 13 intersex males. This study for the first time demonstrated the induction of intersex and reproductive effects of p,p{\textquoteright}-DDE and o,p{\textquoteright}-DDT at environmentally relevant concentrations.

}, keywords = {Animals, DDT, Dichlorodiphenyl Dichloroethylene, Disorders of Sex Development, Estradiol, Gonads, Male, Oryzias, Vitellogenins, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/acs.est.5b05042}, author = {Sun, Jianxian and Wang, Chen and Peng, Hui and Zheng, Guomao and Zhang, Shiyi and Hu, Jianying} } @article {112, title = {Isomer-specific accumulation of perfluorooctanesulfonate from (N-ethyl perfluorooctanesulfonamido)ethanol-based phosphate diester in Japanese Medaka (Oryzias latipes).}, journal = {Environ Sci Technol}, volume = {48}, year = {2014}, month = {2014 Jan 21}, pages = {1058-66}, abstract = {

While (N-ethyl perfluorooctanesulfonamido)ethanol (FOSE) -based phosphate diester (diSPAP) has been proposed as a candidate precursor of perfluorooctanesulfonate (PFOS), its potential biotransformation to PFOS has not been verified. Metabolism of diSPAP was investigated in Japanese medaka ( Oryzias latipes ) after exposure in water for 10 days, followed by 10 days of depuration. Branched isomers of diSPAP (B-diSPAP) were preferentially enriched in medaka exposed to diSPAP, with the proportion of branched isomers (BF) ranging from 0.56 to 0.80, which was significantly greater than that in the water to which the medaka were exposed (0.36) (p \< 0.001). This enrichment was due primarily to preferential uptake of B-diSPAP. PFOS together with perfluorooctanesulfonamide (PFOSA), N-ethyl perfluorooctanesulfonamide (NEtFOSA), 2-(perfluorooctanesulfonamido)acetic acid (FOSAA), NEtFOSAA, FOSE, and NEtFOSE were detected in medaka exposed to diSPAP, which indicated the potential for biotransformation of diSPAP to PFOS via multiple intermediates. Due to preferential metabolism of branched isomers, FOSAA and PFOSA exhibited greater BF values (\>0.5) than those of NEtFOSA, NEtFOSAA, and NEtFOSE (\<0.2). Such preferential metabolism of branched isomers along the primary pathway of metabolism and preferential accumulation of B-diSPAP led to enrichment of branched PFOS (B-PFOS) in medaka. Enrichment of B-PFOS was greater for 3-, 4-, and 5-perfluoromethyl PFOS (P3MPFOS, P4MPFOS, and P5MPFOS), for which values of BF were 0.58 {\textpm} 0.07, 0.62 {\textpm} 0.06, and 0.61 {\textpm} 0.05 (day 6), respectively; these values are 5.8-, 7.8-, and 6.4-fold greater than those of technical PFOS. This work provides evidence on the isomer-specific accumulation of PFOS from diSPAP and will be helpful to track indirect sources of PFOS in the future.

}, keywords = {Alkanesulfonic Acids, Animals, Biotransformation, Chromatography, High Pressure Liquid, Environmental Monitoring, Esters, Fluorocarbons, Gas Chromatography-Mass Spectrometry, Half-Life, Hydrocarbons, Fluorinated, Isomerism, Kinetics, Metabolic Networks and Pathways, Organophosphorus Compounds, Oryzias, Phosphates, Reference Standards, Sulfonamides}, issn = {1520-5851}, doi = {10.1021/es404867w}, author = {Peng, Hui and Zhang, Shiyi and Sun, Jianxian and Zhang, Zhong and Giesy, John P and Hu, Jianying} } @article {111, title = {Trophic transfer of dechloranes in the marine food web of Liaodong Bay, north China.}, journal = {Environ Sci Technol}, volume = {48}, year = {2014}, month = {2014 May 20}, pages = {5458-66}, abstract = {

Dechloranes are of particular concern because of their ubiquity in environmental matrices, but little is known about their trophic transfer in aquatic food web. This study investigated the trophic transfer of seven dechloranes in a marine food web from Liaodong Bay, China. Dechloranes were determined in sediments and 15 marine species including benthic invertebrates, fish and gulls collected from Liaodong Bay. Biomagnification factors (BMFTL) of dechloranes in black-headed gulls were calculated to be 6.4, 1.7, 0.45, 0.36, 0.14, and 0.11 for mirex, Dechlorane 602 (Dec 602), Dechlorane 603 (Dec 603), antiundecachloropentacyclooctadecadiene (anti-Cl11DP), syn-dechlorane plus (syn-DP), and anti-DP. Significantly positive relationships were found between lipid equivalent concentrations of mirex, Dec 602, and anti-Cl11DP and trophic levels, and the trophic magnification factors (TMFs) were 13, 3.7, and 5.6, respectively, indicating that these compounds undergo trophic magnification in the aquatic food web. Lipid equivalent concentrations of Dec 603 and DP isomers did not exhibit a statistically significant correlation with trophic levels. The relatively low trophic magnification potentials of Dec 603 and DP isomers were possibly due to their extreme hydrophobicity (logKOW: 11.2-11.3) and subsequent low bioavailabilities compared with mirex (7.0), Dec 602 (8.1) and anti-Cl11DP. The results provided important information for understanding the ecological risk of dechloranes.

}, keywords = {Animals, Aquatic Organisms, Bays, Charadriiformes, China, Environmental Monitoring, Fishes, Food Chain, Geologic Sediments, Hydrocarbons, Chlorinated, Invertebrates, Ontario, Regression Analysis, Water Pollutants, Chemical}, issn = {1520-5851}, doi = {10.1021/es500229y}, author = {Peng, Hui and Wan, Yi and Zhang, Kun and Sun, Jianxian and Hu, Jianying} }