The tire rubber antioxidant -(1,3-dimethylbutyl)--phenyl--phenylenediamine (6PPD) and its quinone product (6PPDQ) are prevalent emerging contaminants, yet their biotransformation profiles remain poorly understood, hampering the assessment of environmental and health risks. This study investigated the phase-I metabolism of 6PPD and 6PPDQ across aquatic and mammalian species through liver microsome (LM) incubations and simulations. A total of 40 metabolites from seven pathways were identified using the highly sensitive nano-electrospray ionization mass spectrometry. Notably, 6PPDQ was consistently detected as a 6PPD metabolite with an approximate 2% yield, highlighting biotransformation as a neglected indirect exposure pathway for 6PPDQ in organisms. 6PPDQ was calculated to form through a facile two-step phenyl hydroxylation of 6PPD, catalyzed by cytochrome P450 enzymes. Distinct species-specific metabolic kinetics were observed, with fish LM demonstrating retarded biotransformation rates for 6PPD and 6PPDQ compared to mammalian LM, suggesting the vulnerability of aquatic vertebrates to these contaminants. Intriguingly, two novel coupled metabolites were identified for 6PPD, which were predicted to exhibit elevated toxicity compared to 6PPDQ and result from C-N oxidative coupling by P450s. These unveiled metabolic profiles offer valuable insights for the risk assessment of 6PPD and 6PPDQ, which may inform future studies and regulatory actions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.est.4c03361 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Prediction of p-phenylenediamine antioxidant concentrations in human urine using machine learning models.
J Hazard Mater
January 2025
Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China. Electronic address:
p-phenylenediamine antioxidants (PPDs) are extensively used in rubber manufacturing for their potent antioxidative properties, but PPDs and 2-anilino-5-[(4-methylpentan-2yl)amino]cyclohexa-2,5-diene-1,4-dione (6PPDQ) pose potential environmental and health risks. Existing biomonitoring methods for assessing human exposure to PPDs are labor-intensive, costly, and provide limited data. Thus, there is a critical need to develop predictive models for evaluating PPDs and 6PPDQ exposure levels to facilitate health risk assessments.
View Article and Find Full Text PDFLong-Term Exposure to Tire-Derived 6-PPD Quinone Causes Neurotoxicity and Neuroinflammation via Inhibition of HTR2A in C57BL/6 Mice.
Environ Sci Technol
January 2025
School of Basic Medical Sciences, Shandong Second Medical University, 7166 Baotong West Street, Weicheng District, Weifang, Shandong 261053, China.
-(1,3-dimethylbutyl)-'-phenyl--phenylenediamine quinone (6-PPDQ), a novel contaminant derived from tire wear, has raised concerns due to its potential neurotoxicity, yet its long-term effects on mammalian neurological health remain poorly understood. This study investigates the neurotoxic and neuroinflammatory impacts of prolonged 6-PPDQ exposure using male C57BL/6 mice. Behavioral assessments revealed significant cognitive deficits, while biochemical analyses demonstrated increased levels of reactive oxygen species, apoptosis, and blood-brain barrier (BBB) disruption.
View Article and Find Full Text PDFMolecule self-assembly of hydrangea-shaped hollow O, Cl -codoped graphite-phase carbon nitride microspheres for efficient N-(1,3-dimethyl butyl)-N'-phenyl-p-phenylenediamine quinone photodegradation and bacteria disinfection.
J Colloid Interface Sci
January 2025
College of Materials and Chemistry, China Jiliang University, 258 Xueyuan Street, Xiasha Higher Education Zone, Hangzhou 310018, China. Electronic address:
6PPD-quinone (6PPD-Q) as a derivative of the rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), is attracting intensive attention due to the significant hazard to ecosystems. However, the effective management of this type of contaminant has been scarcely reported. Hydrangea-like hollow O, Cl-codoped graphite-phase carbon nitride microspheres (HHCN), featuring open pores were readily prepared by molecular self-assembly and utilized to address 6PPD-Q in an aqueous system for the first time.
View Article and Find Full Text PDFExposure to 6PPD-Q induces dysfunctions of ovarian granulosa cells: Its potential role in PCOS.
J Hazard Mater
December 2024
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China. Electronic address:
N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), an environmental pollutant derived from the ozonolysis of the widely used tire rubber antioxidant 6PPD, has been found to accumulate in air, dust, and water, posing significant health risks. While its reproductive toxicity in male organisms has been established, its effects on female reproductive health remain unclear. Polycystic ovary syndrome (PCOS), a common endocrine disorder in premenopausal women, is known to be influenced by environmental pollutants.
View Article and Find Full Text PDFAcute and Subchronic Toxicity of 6PPD-Quinone to Early Life Stage Lake Trout ().
Environ Sci Technol
January 2025
Toxicology Centre, University of Saskatchewan, Saskatoon S7N 5B3, Canada.
-(1,3-Dimethylbutyl)-'-phenyl--phenylenediamine-quinone (6PPD-Q) is a rubber-tire derivative which leaches into surface waters from roadway runoff, from tire particles and has been identified as a possible driver of urban runoff mortality syndrome in coho salmon. Sensitivity to this toxicant is highly variable across fish species and life stages. With environmental concentrations meeting or exceeding toxicity thresholds in sensitive fishes, the potential for ecologically relevant effects is significant.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!