Enantioselectivity in Metabolism and Toxicity of 6PPD-Quinone in Salmonids
Bibliographic record
Abstract
The toxicity of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) in salmonids has been found to be sensitive to even minor structural changes on its alkyl side chain. Inspired by this, we herein isolated the enantiomers of 6PPD-Q and tested their in vitro metabolism in liver S9 of rainbow trout (O. mykiss), along with their toxicity in a coho salmon (O. kisutch) embryo (CSE-119) cell line. (R)-6PPD-Q was found to be rapidly metabolized in rainbow trout liver S9 with a half-life (t1/2) of 12.3 minutes, which was 2.92 times faster than that of (S)-6PPD-Q. This was further evidenced by the preferential formation of an (R)-aryl-OH-6PPD-Q metabolite. Supporting this, enantioselective accumulation of (S)-6PPD-Q was found in rainbow trout in vivo. To further distinguish between kinetics and intrinsic toxicity, we tested the toxicity of 6PPD-Q enantiomers in the CSE-119 cell line with minimal metabolism of 6PPD-Q. (R)-6PPD-Q was found to strongly induce cytotoxicity in CSE-119 cells with an IC50 of 17.7 µg/L, which was 3.94 times stronger than that of (S)-6PPD-Q. In summary, this study reported the enantioselectivity in both the toxicity and metabolism of 6PPD-Q, demonstrating that its toxicity should be mediated by specific protein binding.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".