@article {294, title = {Increased UV{\textendash}Visible Particle Absorption via Evaporation and Drying of Aqueous Droplets Containing Catechol/HONO Solutions}, journal = {Environmental Science and Technology Letters}, year = {2025}, author = {Wang, Yutong and Yang, Diwen and Fahy, William and Rivellini, Laura-Helena and Peng, Hui and Abbatt, Jonathan} } @article {289, title = {Structure and Toxicity Characterization of Alkyl Hydroxylated Metabolites of 6PPD-Q.}, journal = {Environ Sci Technol}, year = {2025}, month = {2025 Apr 08}, abstract = {

Distinct from other nontoxic phenyl--phenylenediamine (PPD) quinones, -(1,3-dimethylbutyl)-{\textquoteright}-phenyl--phenylenediamine-quinone (6PPD-Q) was recently discovered to be regioselectively metabolized to alkyl hydroxylated metabolites (alkyl-OH-6PPD-Q) in rainbow trout. It remains unknown whether the unique alkyl-OH-6PPD-Q contributes to the toxicity of 6PPD-Q. To test this, we herein synthesized chemical standards of alkyl-OH-6PPD-Q isomers and investigated their metabolic formation mechanism and toxicity. The predominant alkyl-OH-6PPD-Q was confirmed to be hydroxylated on the C tertiary carbon (C-OH-6PPD-Q). The formation of C-OH-6PPD-Q was only observed in microsomal but not in cytosolic fractions of rainbow trout () liver S9. A general cytochrome P450 (CYP450) inhibitor fluoxetine inhibited the formation of hydroxylated metabolites of 6PPD-Q, supporting that CYP450 catalyzed the hydroxylation. This well-explained the compound- and regio-selective formation of C-OH-6PPD-Q, due to the weak C-H bond on the C tertiary carbon. Surprisingly, while cytotoxicity was observed for 6PPD-Q and C-OH-6PPD-Q in a coho salmon () embryo (CSE-119) cell line, no toxicity was observed for C-OH-6PPD-Q. To further confirm this under physiologically relevant conditions, we fractionated 6PPD-Q metabolites formed in the liver microsome of rainbow trout. Cytotoxicity was observed for the fraction of 6PPD-Q, but not the fraction of C-OH-6PPD-Q. In summary, this study highlighted the C tertiary carbon as the key moiety for both metabolism and toxicity of 6PPD-Q and confirmed that alkyl hydroxylation is a detoxification pathway for 6PPD-Q.

}, issn = {1520-5851}, doi = {10.1021/acs.est.4c11823}, author = {Nair, Pranav and Barrett, Holly and Tanoto, Kaylin and Xie, Linna and Sun, Jianxian and Yang, Diwen and Yao, Han and Song, Datong and Peng, Hui} } @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 {276, title = {Structurally Selective Ozonolysis of -Phenylenediamines and Toxicity in Coho Salmon and Rainbow Trout.}, journal = {Environ Sci Technol}, year = {2024}, month = {2024 Nov 23}, abstract = {

The tire-rubber-derived ozonation product of -(1,3-dimethylbutyl)-{\textquoteright}-phenyl--phenylenediamine (6PPD), -(1,3-dimethylbutyl)-{\textquoteright}-phenyl--phenylenediamine-quinone (6PPD-Q), was recently discovered to cause acute mortality in coho salmon (). -Phenylenediamines (PPDs) with variable side chains distinct from 6PPD have been identified as potential replacement antioxidants, but their toxicities remain unclear under environmentally relevant ozone conditions. We herein tested the multiphase gas-surface ozone reactivity of four select PPDs [6PPD, -isopropyl-{\textquoteright}-phenyl--phenylenediamine (IPPD), ,{\textquoteright}-diphenyl--phenylenediamine (DPPD), and -phenyl-{\textquoteright}-cyclohexyl--phenylenediamine (CPPD)] and evaluated the toxicity of their reaction mixtures in coho salmon, rainbow trout (), and fathead minnow (). 6PPD and IPPD were found to rapidly react with ozone, while no significant multiphase ozone reactivity was observed for DPPD or CPPD. The viability of coho salmon CSE-119 cells was strongly affected by the ozonolysis products of 6PPD but not by those of the other three PPDs. Acute mortality was only observed in juvenile rainbow trout that were exposed to oxidized 6PPD, suggesting a common mechanism of toxic action in the two salmonid fish species. This study reports the structurally selective ozone reactivity of PPDs and the unique toxicity of 6PPD ozonolysis mixtures, which demonstrates that other PPDs are potential alternative antioxidants.

}, issn = {1520-5851}, doi = {10.1021/acs.est.4c04817}, author = {Xie, Linna and Yu, Jie and Nair, Pranav and Sun, Jianxian and Barrett, Holly and Meek, Oliver and Qian, Xing and Yang, Diwen and Kennedy, Lisa and Kozakiewicz, Derek and Hao, Chunyan and Hansen, John D and Greer, Justin B and Abbatt, Jonathan P D and Peng, Hui} } @article {221, title = {Declining concentrations of chlorinated paraffins in endangered St. Lawrence Estuary belugas (Delphinapterus leucas): Response to regulations or a change in diet?}, journal = {Sci Total Environ}, year = {2023}, month = {2023 Jan 07}, pages = {161488}, abstract = {

Very high levels of industrial contaminants in St. Lawrence Estuary (SLE) beluga whales represent one of the major threats to this population classified as endangered under the Species at Risk Act in Canada. Elevated concentrations of short-chained chlorinated paraffins (SCCPs) were recently reported in blubber of adult male SLE belugas. Recent regulations for SCCPs in North America, combined with their replacement by medium- (MCCPs) and long-chained chlorinated paraffins (LCCPs), highlight the importance of tracking this toxic chemical class. The objectives of this study were to evaluate (1) levels and profiles of chlorinated paraffins (CPs) in samples obtained from carcasses of adult male, adult female, juvenile, newborn, and fetus beluga, and (2) trends in adult male belugas between 1997 and 2018. Factors potentially influencing CP temporal trends such as age, feeding ecology and sampling year were also explored. SCCPs dominated (64 to 100 \%) total CP concentrations across all age and sex classes, MCCPs accounted for the remaining proportion of total CPs, and LCCPs were not detected in any sample. The chlorinated paraffin homolog that dominated the most in beluga blubber was CCl. Adult male SCCP concentrations from this study were considerably lower (\> 2000-fold) than those recently reported in Simond et al. (2020), likely reflecting a previously erroneous overestimate due to the lack of a suitable analytical method for SCCPs at the time. Both SCCPs and total CPs declined over time in adult males in our study (rate of 1.67 and 1.33 \% per year, respectively), presumably due in part to the implementation of regulations in 2012. However, there is a need to better understand the possible contribution of a changing diet to contaminant exposure, as stable isotopic ratios of carbon also changed over time.

}, issn = {1879-1026}, doi = {10.1016/j.scitotenv.2023.161488}, author = {Simond, Antoine {\'E} and Ross, Peter S and Cabrol, Jory and Lesage, V{\'e}ronique and Lair, St{\'e}phane and Woudneh, Million B and Yang, Diwen and Peng, Hui and Colbourne, Katerina and Brown, Tanya M} } @article {237, title = {Disclosing Environmental Ligands of L-FABP and PPARγ: Should We Re-evaluate the Chemical Safety of Hydrocarbon Surfactants?}, journal = {Environ Sci Technol}, year = {2023}, month = {2023 Aug 01}, abstract = {

Chemical contaminants can cause adverse effects by binding to the liver-fatty acid binding protein (L-FABP) and peroxisome proliferator-activated nuclear receptor γ (PPARγ), which are vital in lipid metabolism. However, the presence of numerous compounds in the environment has hindered the identification of their ligands, and thus only a small portion have been discovered to date. In this study, protein ffinity urification with ontargeted nalysis (APNA) was employed to identify the ligands of L-FABP and PPARγ in indoor dust and sewage sludge. A total of 83 nonredundant features were pulled-out by His-tagged L-FABP as putative ligands, among which 13 were assigned as fatty acids and hydrocarbon surfactants. In contrast, only six features were isolated when His-tagged PPARγ LBD was used as the protein bait. The binding of hydrocarbon surfactants to L-FABP and PPARγ was confirmed using both recombinant proteins and reporter cells. These hydrocarbon surfactants, along with \>50 homologues and isomers, were detected in dust and sludge at high concentrations. Fatty acids and hydrocarbon surfactants explained the majority of L-FABP (57.7 {\textpm} 32.9\%) and PPARγ (66.0 {\textpm} 27.1\%) activities in the sludge. This study revealed hydrocarbon surfactants as the predominant synthetic ligands of L-FABP and PPARγ, highlighting the importance of re-evaluating their chemical safety.

}, issn = {1520-5851}, doi = {10.1021/acs.est.3c02898}, author = {Gong, Yufeng and Yang, Diwen and Liu, Jiabao and Barrett, Holly and Sun, Jianxian and Peng, Hui} } @article {217, title = {Defining the Chemical Additives Driving In Vitro Toxicities of Plastics}, journal = {Environ. Sci. Technol.}, year = {2022}, author = {Chen, Wanzhen and Gong, Yufeng and Michael, McKie and Husein, Almuhtaram and Sun, Jianxian and Barrett, Holly and Yang, Diwen and Wu, Menghong and Andrews, Robert and Peng, Hui} } @article {215, title = {Per- and Polyfluoroalkyl Substances in North American School Uniforms.}, journal = {Environ Sci Technol}, year = {2022}, month = {2022 Sep 21}, abstract = {

We analyzed 72 children{\textquoteright}s textile products marketed as stain-resistant from US and Canadian stores, particularly school uniforms, to assess if clothing represents a significant route of exposure to per- and polyfluoroalkyl substances (PFAS). Products were first screened for total fluorine (total F) using particle-induced γ-ray emission (PIGE) spectroscopy ( = 72), followed by targeted analysis of 49 neutral and ionic PFAS ( = 57). PFAS were detected in all products from both markets, with the most abundant compound being 6:2 fluorotelomer alcohol (6:2 FTOH). Total targeted PFAS concentrations for all products collected from both countries ranged from 0.250 to 153 000 ng/g with a median of 117 ng/g (0.0281-38 100 μg/m, median: 24.0 μg/m). Total targeted PFAS levels in school uniforms were significantly higher than in other items such as bibs, hats, stroller covers, and swimsuits, but comparable to outdoor wear. Higher total targeted PFAS concentrations were found in school uniforms made of 100\% cotton than synthetic blends. Perfluoroalkyl acids (PFAAs) precursors were abundant in school uniforms based on the results of hydrolysis and total oxidizable precursor assay. The estimated median potential children{\textquoteright}s exposure to PFAS via dermal exposure through school uniforms was 1.03 ng/kg bw/day. Substance flow analysis estimated that \~{}3 tonnes/year (ranging from 0.05 to 33 tonnes/year) of PFAS are used in US children{\textquoteright}s uniforms, mostly of polymeric PFAS but with \~{}0.1 tonne/year of mobile, nonpolymeric PFAS.

}, issn = {1520-5851}, doi = {10.1021/acs.est.2c02111}, author = {Xia, Chunjie and Diamond, Miriam L and Peaslee, Graham F and Peng, Hui and Blum, Arlene and Wang, Zhanyun and Shalin, Anna and Whitehead, Heather D and Green, Megan and Schwartz-Narbonne, Heather and Yang, Diwen and Venier, Marta} } @article {218, title = {Widespread formation of toxic nitrated-bisphenols indoors by heterogeneous reactions with HONO}, journal = {Science Advances}, year = {2022}, author = {Yang, Diwen and Liu, Qifan and Wang, Sizhi and Bozorg, Martin and Liu, Jiabao and Nair, Pranav and Balaguer, Patrick and Song, Datong and Krause, Henry and Ouazia, Boualem and Abbatt, Jonathan and Peng, Hui} } @article {140, title = {Proteome-wide effects of naphthalene-derived secondary organic aerosol in BEAS-2B cells are caused by short-lived unsaturated carbonyls.}, journal = {Proc Natl Acad Sci U S A}, year = {2020}, month = {2020 Sep 28}, abstract = {

Exposure to air pollution causes adverse health outcomes, but the toxicity mechanisms remain unclear. Here, we investigated the dynamic toxicities of naphthalene-derived secondary organic aerosol (NSOA) in a human bronchial epithelial cell line (BEAS-2B) and identified the chemical components responsible for toxicities. The chemical composition of NSOA was found to vary with six simulated atmospheric aging conditions (C-C), as characterized by high-resolution mass spectrometry and ion mobility mass spectrometry. Global proteome profiling reveals dynamic evolution in toxicity: Stronger proteome-wide impacts were detected in fresh NSOA, but the effects declined along with atmospheric aging. While Nrf2-regulated proteins (e.g., ) were significantly up-regulated, the majority (78 to 97\%) of proteins from inflammation and other pathways were down-regulated by NSOA exposure (e.g., ). This pattern is distinct from the reactive oxygen species (ROS)-mediated toxicity pathway, and an alternative cysteine reaction pathway was revealed by the decreased abundance of proteins (e.g., ) prone to posttranslational thiol modification. This pathway was further validated by observing decreased Nrf2 response in reporter cells, after preincubating NSOA with cysteine. Ethynyl-naphthalene probe was employed to confirm the alkylation of cellular proteome thiols on the proteome-wide level by fresh NSOA via in-gel fluorescence imaging. Nontarget analysis identified several unsaturated carbonyls, including naphthoquinones and hydroxylated naphthoquinones, as the toxic components responsible for cysteine reactivity. Our study provides insights into the dynamic toxicities of NSOA during atmospheric aging and identifies short-lived unsaturated carbonyls as the predominant toxic components at the posttranslational level.

}, issn = {1091-6490}, doi = {10.1073/pnas.2001378117}, author = {Han, Jiajun and Wang, Shunyao and Yeung, Kirsten and Yang, Diwen and Gu, Wen and Ma, Zhiyuan and Sun, Jianxian and Wang, Xiaomin and Chow, Chung-Wai and Chan, Arthur W H 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} }