@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 {290, title = {Synthesis and Toxicity Evaluation of -Phenylenediamine-Quinones.}, journal = {Environ Sci Technol}, year = {2025}, month = {2025 Apr 08}, abstract = {

-(1,3-Dimethylbutyl)--phenyl--phenylenediamine-quinone (6PPD-Q), the tire rubber-derived transformation product of 6PPD, was recently discovered to cause the acute mortality of coho salmon (). Aiming to identify potential replacement antiozonants for 6PPD that do not produce toxic quinones, seven PPD-quinones with distinct side chains were synthesized to investigate their structure-related toxicities using rainbow trout (). While 6PPD-Q exerted high toxicity (96 h LC = 0.35 μg/L), toxicity was not observed for six other PPD-quinones despite their similar structures. The fish tissue concentrations of 6PPD-Q after sublethal exposure (0.29 μg/L) were comparable to the other PPD-quinones, which indicated that bioaccumulation levels were not the reason for the selective toxicity of 6PPD-Q. Hydroxylated PPD-quinones were detected as the predominant metabolites in fish tissue. Interestingly, a single major aromatic hydroxylation metabolite was detected for the alternate PPD-quinones, but two abundant OH-6PPD-Q isomers were detected for 6PPD-Q. MS spectra confirmed that hydroxylation occurred on the alkyl side chain for one isomer. The structurally selective toxicity of 6PPD-Q was also observed in a coho salmon (CSE-119) cell line, which further supports its intrinsic toxicity. This study reported the selective toxicity of 6PPD-Q and pinpointed the possibility for other PPDs to be applied as potential substitutes of 6PPD.

}, issn = {1520-5851}, doi = {10.1021/acs.est.4c12220}, author = {Nair, Pranav and Sun, Jianxian and Xie, Linna and Kennedy, Lisa and Kozakiewicz, Derek and Kleywegt, Sonya M and Hao, Chunyan and Byun, Hannah and Barrett, Holly and Baker, Joshua and Monaghan, Joseph and Krogh, Erik T and Song, Datong and Peng, Hui} } @article {277, title = {Compound Class-Specific Temporal Trends (2021{\textendash}2023) of Tire Wear Compounds in Suspended Solids from Toronto Wastewater Treatment Plants}, journal = {ACS ES\&T Water}, year = {2024}, month = {11/2024}, author = {Xie, Linna and Yuan, Lai and Sun, Jianxian and Yang, Miqing and Khan, Ismail and Lopez, Joselyn and Gong, Yufeng and Nair, Pranav and Hao, Chunyan and Helm, Paul and Barrett, Holly and Edwards, Elizabeth and Peng, Hui} } @article {263, title = {Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands}, journal = {Nature Communications}, year = {2024}, author = {Liu, Jiabao and Malekoltojari, Aniaz and Asokakumar, Anjana and Chow, Vimanda and Li, Linhao and Li, Hao and Grimaldi, Marina and Dang, Nathanlown and Campbell, Jhenielle and Barrett, Holly and Sun, Jianxian and Navarre, William and Wilson, Derek and Wang, Hongbing and Mani, Sridhar and Balaguer, Patrick and Anakk, Sayeepriyadarshini and Peng, Hui* and Krause, Henry*} } @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 {271, title = {Identification of Hydrocarbon Sulfonates as Previously Overlooked Transthyretin Ligands in the Environment.}, journal = {Environ Sci Technol}, year = {2024}, month = {2024 May 30}, abstract = {

Incidences of thyroid disease, which has long been hypothesized to be partially caused by exposure to thyroid hormone disrupting chemicals (TDCs), have rapidly increased in recent years. However, known TDCs can only explain a small portion (\~{}1\%) of human transthyretin (hTTR) binding activities in environmental samples, indicating the existence of unknown hTTR ligands. In this study, we aimed to identify the major environmental hTTR ligands by employing protein ffinity urification with ontargeted nalysis (APNA). hTTR binding activities were detected in all 11 indoor dust and 9 out of 10 sewage sludge samples by the FITC-T displacement assay. By using APNA, 31 putative hTTR ligands were detected including perfluorooctanesulfonate (PFOS). Two of the most abundant ligands were identified as hydrocarbon surfactants ( dodecyl benzenesulfonate). Moreover, another abundant ligand was surprisingly identified as a disulfonate fluorescent brightener, 4,4{\textquoteright}-bis(2-sulfostyryl)biphenyl sodium (CBS). CBS was validated as a nM-affinity hTTR ligand with an IC of 345 nM. In total, hydrocarbon surfactants and fluorescent brighteners explain 1.92-17.0 and 5.74-54.3\% of hTTR binding activities in dust and sludge samples, respectively, whereas PFOS only contributed \<0.0001\%. Our study revealed for the first time that hydrocarbon sulfonates are previously overlooked hTTR ligands in the environment.

}, issn = {1520-5851}, doi = {10.1021/acs.est.3c10973}, author = {Gong, Yufeng and Sun, Jianxian and Wang, Xiaoyun and Barrett, Holly 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 {268, title = {Unique hepatic maternal transfer pattern of trace metals and perfluoroalkyl substances (PFAS) in a bluntnose sixgill shark (Hexanchus griseus).}, journal = {Chemosphere}, volume = {359}, year = {2024}, month = {2024 May 10}, pages = {142315}, abstract = {

The fate and distribution of environmental contaminants includes bioaccumulation within marine organisms. A deceased 4-m long adult female bluntnose sixgill shark, pregnant with 72 pups, was recovered from Coles Bay on Vancouver Island, BC, Canada in 2019. This specimen provided a unique opportunity to examine maternal transfer of contaminants in a yolk-sac viviparous shark species. Liver subsamples of the adult and offspring were analyzed for 18 targeted inorganic elements by inductively coupled plasma optical emission spectroscopy (ICP-OES) and 21 targeted perfluoroalkyl substances (PFAS) by liquid chromatography-electrospray ionization-high resolution mass spectrometry (LC-ESI-Orbitrap MS). The maternal-offspring transfer efficiencies in liver tissue were subsequently examined for both contaminant classes. Concentrations of all detectable metals apart from calcium and magnesium were found to be higher in the mother compared to the offspring, including substantial levels of toxic cadmium (6\ {\textpm}\ 2\ mg\ kg dw) and lead (7\ {\textpm}\ 3\ mg\ kg dw). Conversely, high maternal transfer efficiencies were observed for PFAS (i.e., ΣPFAS\ =\ 71\ {\textpm}\ 9\ ng\ g ww in offspring compared to 13\ {\textpm}\ 9\ ng\ g ww in the mother). This study highlighted the unique maternal transfer characteristics of PFAS in bluntnose sixgill sharks depending on the structure of the polar head group, with greater liver-to-liver transfer efficiencies observed for perfluorocarboxylic acids (PFCAs) than perfluorosulfonic acids (PFSAs) of the same fluorocarbon chain length.

}, issn = {1879-1298}, doi = {10.1016/j.chemosphere.2024.142315}, author = {Zvekic, Misha and Barrett, Holly and Diamente, Peter and Peng, Hui and Krogh, Erik T} } @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 {186, title = {Behaviors and trophodynamics of o,p{\textquoteright}-dichlorodiphenyltrichloroethane (o,p{\textquoteright}-DDT) in the aquatic food web: Comparison with p,p{\textquoteright}-DDT.}, journal = {Sci Total Environ}, year = {2022}, month = {2022 Jan 26}, pages = {153447}, abstract = {

The broad-spectrum insecticide p,p{\textquoteright}-dichlorodiphenyltrichloroethane (p,p{\textquoteright}-DDT) has been banned in most countries since the 1970s on account of its environmental persistence as well as the high biomagnification of its major metabolite 1,1-dichloro-2,2-bis(4-chorophenyl)ethylene (p,p{\textquoteright}-DDE). However, the information on the bioaccumulation and behavior of p,p{\textquoteright}-DDTs in aquatic organisms is lacking. In this study, all 6 DDT isomers were detected in biota from the food web of the Liaodong Bay, China, and the total concentrations of DDT isomers in Chinese anchovy (Thrissa kammalensis) and Japanese Spanish mackerel (Scomberomrus niphonius) were 223 {\textpm} 42 ng/g ww and 242 {\textpm} 70 ng/g ww, respectively. In biota, o,p{\textquoteright}-DDD dominated among the o,p{\textquoteright}-isomers (80.5 {\textpm} 17.3\%), while p,p{\textquoteright}-DDE dominated among the p,p{\textquoteright}-isomers (61.8 {\textpm} 15.2\%). Contrastingly, sediment from the Liaodong Bay contained similar proportions of o,p{\textquoteright}-DDT and p,p{\textquoteright}-DDTs, suggesting an isomer-specific metabolism of the compounds in biota. A well-controlled laboratory exposure experiment with Japanese medaka (Oryzias latipes) demonstrated that o,p{\textquoteright}-DDT was more difficult to metabolize to o,p{\textquoteright}-DDE compared with that of p,p{\textquoteright}-DDT. Significantly positive regressions were found between trophic levels and lipid equivalent concentrations for both o,p{\textquoteright}-DDT and o,p{\textquoteright}-DDD, and the trophic magnification factors (TMFs) were estimated as 12.3 and 9.12 (p \< 0.05), respectively. The TMFs of o,p{\textquoteright}-DDT and o,p{\textquoteright}-DDD in the aquatic food web were higher than p,p{\textquoteright}-DDT (7.76), p,p{\textquoteright}-DDD (4.17), and p,p{\textquoteright}-DDE (3.39), which may be explained by the isomer-specific metabolism differences in biota.

}, issn = {1879-1026}, doi = {10.1016/j.scitotenv.2022.153447}, author = {Sun, Jianxian and Xu, Chenke and Peng, Hui and Wan, Yi and Luo, Kai and Barrett, Holly and Hu, Jianying} } @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 {211, title = {Measuring Perfluoroalkyl Acid Contamination at a Local Hot Spot: An Authentic Field-Based Laboratory Experience in a Senior Analytical Environmental Chemistry Course}, journal = {Journal of Chemical Education}, year = {2022}, author = {Joudan, Shira and Barrett, Holly and Silva, Amila O De and Solla, Shane R and Peng, Hui and Deon, Jessica C} } @article {196, title = {Triclosan is the Predominant Antibacterial Compound in Ontario Sewage Sludge}, journal = {Environmental Science and Technology}, volume = {56}, year = {2022}, author = {Barrett, Holly and Sun, Jianxian and Gong, Yufeng and Yang, Paul and Hao, Chunyan and Verreault, Jonathan and Zhang, Yu and Peng, Hui} } @article {183, title = {Ecological Role of 6OH-BDE47: Is It a Chemical Offence Molecule Mediated by Enoyl-ACP Reductases?}, journal = {Environ. Sci. Technol.}, year = {2021}, author = {Sun, Jianxian and Barrett, Holly and Hall, David and Kutarna, Steven and Wu, Xiaoqin and Wang, Yan and Peng, Hui} } @article {145, title = {Suspect and Nontarget Screening Revealed Class-Specific Temporal Trends (2000-2017) of Poly- and Perfluoroalkyl Substances in St. Lawrence Beluga Whales.}, journal = {Environ Sci Technol}, year = {2021}, month = {2021 Jan 14}, abstract = {

The global use of \>3000 per- and polyfluoroalkyl substances (PFASs) has given rise to chemical regulatory action. However, limited information exists regarding current and historical emissions for the majority of PFASs under currently implemented regulations. This study employed suspect and nontarget screening to examine the temporal trends of legacy and unregulated PFASs in liver of the endangered beluga whale () population from the St. Lawrence Estuary in Canada collected from 2000 to 2017. A suite of 54 PFASs were tentatively identified, and were grouped into nine structurally distinct classes. Single-hydrogenated perfluoro carboxylic acids (H-PFCAs), single-hydrogenated sulfonamides (H-Sulfonamides), as well as other select sulfonamides were detected for the first time in wildlife. Greater concentrations of the majority of PFASs were determined in newborns and juveniles than in adults, suggesting effective placental and lactational transfer of PFASs. Legacy per- and polyfluoroalkyl acids and perfluorooctane sulfonamide in beluga whale liver were found to significantly decrease in concentration between 2000 and 2017, while unregulated short-chain PFAS alternatives, H-PFCAs, and odd-chain FTCAs were found to increase over time. The implementation of suspect and nontarget screening revealed class-specific temporal trends of PFASs in SLE beluga whales, and supported continuous emissions of unregulated PFASs into the environment.

}, issn = {1520-5851}, doi = {10.1021/acs.est.0c05957}, author = {Barrett, Holly and Du, Xuan and Houde, Magali and Lair, St{\'e}phane and Verreault, Jonathan and Peng, Hui} }