@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 = {<p>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.</p>},
	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 = {<p>-(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.</p>},
	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 {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}
}
