Characterizing the Metabolism of Tire Rubber-Derived p-Phenylenediamine Quinones to Identify Potential Exposure Biomarkers in Humans

Environmental Science & Technology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 5, 2024

There is growing evidence of the frequent detection tire rubber-derived contaminants

Язык: Английский

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Comparative characterization of organ-specific phase I and II biotransformation enzyme kinetics in salmonid S9 sub-cellular fractions and cell lines

Cell Biology and Toxicology, Год журнала: 2025, Номер 41(1)

Опубликована: Янв. 28, 2025

Язык: Английский

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Structure and Toxicity Characterization of Alkyl Hydroxylated Metabolites of 6PPD-Q

Environmental Science & Technology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Distinct from other nontoxic phenyl-p-phenylenediamine (PPD) quinones, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) was recently discovered to be regioselectively metabolized alkyl hydroxylated metabolites (alkyl-OH-6PPD-Q) in rainbow trout. It remains unknown whether the unique alkyl-OH-6PPD-Q contributes toxicity of 6PPD-Q. To test this, we herein synthesized chemical standards isomers and investigated their metabolic formation mechanism toxicity. The predominant confirmed on C4 tertiary carbon (C4-OH-6PPD-Q). C4-OH-6PPD-Q only observed microsomal but not cytosolic fractions trout (O. mykiss) liver S9. A general cytochrome P450 (CYP450) inhibitor fluoxetine inhibited 6PPD-Q, supporting that CYP450 catalyzed hydroxylation. This well-explained compound- regio-selective C4-OH-6PPD-Q, due weak C-H bond carbon. Surprisingly, while cytotoxicity for 6PPD-Q C3-OH-6PPD-Q a coho salmon kisutch) embryo (CSE-119) cell line, no C4-OH-6PPD-Q. further confirm this under physiologically relevant conditions, fractionated formed microsome Cytotoxicity fraction In summary, study highlighted as key moiety both metabolism hydroxylation is detoxification pathway

Язык: Английский

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Xenometabolomics in Ecotoxicology: Concepts and Applications

Environmental Science & Technology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Nontargeted high-resolution mass spectrometry (HRMS) allows for the characterization of a large fraction exposome, i.e., entirety chemicals an organism is exposed to, and helps detect important exogenous chemical compounds that could be key drivers toxicological impact. Along with these occur endogenous metabolites are essential health host organism. Chemical derived from biotransformation xenobiotics present in exposome referred to as xenometabolome, while endometabolome. Recent advancements HRMS technology allow detection features biological ecological importance context safety assessments unprecedented sensitivity resolution. In this perspective, we highlight application HRMS-based metabolomics organisms ecotoxicology, complexity comprehensively characterizing endometabolome, distinguishing xenometabolome.

Язык: Английский

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Environmental Fate, Toxicity, and Mitigation of 6PPD and 6PPD-Quinone: Current Understanding and Future Directions

Environmental Pollution, Год журнала: 2025, Номер 375, С. 126352 - 126352

Опубликована: Май 1, 2025

Язык: Английский

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Toxicity of 6PPD-quinone in European seabass (Dicentrarchus labrax) under baseline and Vibrio alginolyticus challenge conditions: Protective insights from astaxanthin mitigation

The Science of The Total Environment, Год журнала: 2025, Номер 987, С. 179821 - 179821

Опубликована: Июнь 3, 2025

Язык: Английский

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Xenometabolome of Early-Life Stage Salmonids Exposed to 6PPD-Quinone

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 14, 2024

Abstract N -(1,3-Dimethylbutyl)- N′ -phenyl- p -phenylenediamine-quinone (6PPD-Q) is a ubiquitous transformation product (TP) derived from the rubber tire antioxidant -phenylenediamine (6PPD) and acutely toxic to certain species of Salmonidae . Not all salmonids are sensitive acute lethality caused by 6PPD-Q, with 6PPD-Q potency varying several orders magnitude among teleosts. The main driver(s) sensitivity differences (are) pressing question, one area interest examining whether in teleosts ability biotransform detoxify could be key factor. This study utilized liquid-chromatography high-resolution mass spectrometry (LC-HRMS) assess biotransformation metabolome-wide effects on early-life stage salmonids, including two species, rainbow trout ( Oncorhynchus mykiss ) lake Salvelinus namaycush ), tolerant brown Salmo trutta ). Three phase I TPs seven II were detected, peak areas revealing that had greatest 6PPD-Q. Monohydroxylated verified using co-developed analytical standards will use for future biomonitoring exposure assessment. Several endogenous metabolites found dysregulated trout, indicative mitochondrial dysfunction, altered metabolism, disrupted membrane permeability. Results this indicate difference capability fish subsequent unique metabolome responses. Graphical Synopsis Inter-species salmonid leads variability

Язык: Английский

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Nontarget analysis and characterization of p-phenylenediamine-quinones and -phenols in tire rubbers by LC-HRMS and chemical species-specific algorithm

Analytica Chimica Acta, Год журнала: 2024, Номер 1326, С. 343123 - 343123

Опубликована: Авг. 22, 2024

Язык: Английский

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