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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".