Toxicity assessment of 6PPD-quinone in human lung cells: Insights from BEAS-2B and A549 cell lines
Bibliographic record
Abstract
N-(1,3-Dimethylbutyl)- N ′-phenyl- p -phenylenediamine-quinone (6PPD-Q), an environmental transformation product of the rubber tire antioxidant 6PPD, is increasingly detected in urban environments, yet its impact on human health. This study investigated toxicological effects of 6PPD-Q in two human lung cells: BEAS-2B (a transformed bronchial epithelial cell) and A549 (a lung adenocarcinoma cell). Cells were exposed to 6PPD-Q at concentrations of 5 to 80 ng/mL and effects on cell viability, oxidative stress by generation of reactive oxygen species (ROS), disruption of antioxidant defense response, oxidative DNA damage as determined by formation of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and biotransformation 6PPD-Q were determined. Results showed a biphasic response with an increase in cell viability at lower concentrations, suggesting an adaptive cellular response. ROS production and levels of 8-OHdG significantly increased, indicating an imbalance in redox status and induction of oxidative DNA damage. Two phase I hydroxylation products, 6PPD-Q-4-OH (TPOH1) and 6PPD-Q-phenyl-OH (TPOH2), were identified. In A549 cells, TPOH1 was only in the media, while TPOH2 was found both inside cells and in the media. Moreover, mRNA expression analysis revealed upregulation of metabolism- and oxidative stress-related genes and inflammatory cytokines. These findings suggest that 6PPD-Q may trigger oxidative stress and inflammation in lung cells. This study highlights the effects of 6PPD-Q on lung cells and underscores the need for further research on its long-term impact on human respiratory health. This study provides novel insights into the potential toxicological impacts of 6PPD-Q exposure on human lung cells, thereby contributing to hazard identification and laying a critical foundation for future research on 6PPD-Q exposure in highly affected urban environments. • 6PPD-Q increases reactive oxygen species (ROS) in human lung cells. • 8-hydroxydeoxyguanosine (8-OHdG) surge confirms DNA damage from 6PPD-Q in human lung cells. • Phase I metabolites may have a critical role in mediating toxicity under 6PPD-Q exposure. • 6PPD-Q upregulates genes linked to oxidative stress and inflammation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".