Biotransformation of 6PPD-quinone <i>In Vitro</i> Using RTL-W1 Cell Line
Why this work is in the frame
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Bibliographic record
Abstract
Urban stormwater runoff contains the tire-derived transformation product N -(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine-quinone (6PPD-quinone), which poses significant environmental risks due to its high toxicity toward certain salmonids. 6PPD-quinone biotransformation has been investigated to explain some of the stark interspecies differences in sensitivity across different fishes; however, the primary mechanisms of 6PPD-quinone biotransformation remain unclear. This work aimed to explore the toxicokinetics of 6PPD-quinone in immortalized rainbow trout ( Oncorhynchus mykiss ) liver cells (RTL-W1) to identify transformation products, using coexposure with different enzyme inhibitors and inducers. Using high-resolution mass spectrometry, we identified three phase I 6PPD-quinone transformation products, with phenyl ring hydroxylation dominating, followed by hydroxylation of the alkyl side chain, and an unknown transformation product after 4 h of exposure. Co-exposing RTL-W1 cells with α-naphthoflavone and quercetin greatly inhibited the biotransformation of 6PPD-quinone, revealing that CYP1A is primarily involved in phase I biotransformation. Hepatic clearance predicted from in vitro results was further verified based on isolated perfused trout liver experiments. Further studies are necessary on the biotransformation and kinetics of 6PPD-quinone and the detoxification pathways involved in a wide phylogenetic space in fishes.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| 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 it