Exposure to the Tire Rubber-Derived Contaminant 6PPD-Quinone Causes Mitochondrial Dysfunction <i>In Vitro</i>
Bibliographic record
Abstract
N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-quinone), a rubber tire oxidation product found in road runoff, is highly and acutely toxic to selected salmonids including coho salmon, brook trout, and rainbow trout but not other fish species and invertebrates studied to date. Sensitive species displayed increased ventilation and gasping, suggesting a possible impact on respiration. Here, adherent cell lines RTL-W1 and RTgill-W1 were exposed to 5–80 μg/L 6PPD-quinone, and cytotoxicity, oxygen consumption rate (OCR), and biotransformation of 6PPD-quinone were measured to assess the ability of 6PPD-quinone to uncouple mitochondrial respiration in vitro . RTL-W1 cells were not sensitive to 6PPD-quinone, and exposure did not result in significant impacts on cytotoxicity or OCR. In contrast, RTgill-W1 cells demonstrated decreased cell viability at 80 μg/L and a 2-fold increase in OCR at 20 μg/L. Effects appear to be partly driven by toxicokinetic differences where incubation of RTL-W1 cells with 6PPD-quinone led to almost quantitative conversion of 6PPD-quinone into a suspected hydroxy-metabolite, which was not observed in RTgill-W1 cells. Exposure studies with primary cultures of rainbow trout gill cells indicated that 6PPD-quinone increased OCR by uncoupling the mitochondrial electron transport chain. Together, these findings suggest that 6PPD-quinone toxicity might be driven by a tissue-specific disruption of mitochondrial respiration.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.001 | 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".