Stereoselective Metabolism of α-, β-, and γ-Hexabromocyclododecanes (HBCDs) by Human Liver Microsomes and CYP3A4
Bibliographic record
Abstract
This is the first study investigating the in vitro metabolism of α-, β-, and γ-hexabromocyclododecane (HBCD) stereoisomers in humans and providing semiquantitative metabolism data. Human liver microsomes were incubated with individual racemic mixtures and with individual stereoisomers of α-, β-, and γ-HBCDs, the hydroxylated metabolites formed were analyzed by liquid chromatography-tandem mass spectrometry, and the value of the intrinsic in vitro clearance (Clint,vitro) was calculated. Several mono- and dihydroxylated metabolites of α-, β-, and γ-HBCDs were formed, with mono-OH-HBCDs being the major metabolites. No stereoisomerization of any of the six α-, β-, and γ-HBCD isomers catalyzed by cytochrome P450 (CYP) enzymes occurred. The value of Clint,vitro of α-HBCDs was significantly lower than that of β-HBCDs, which, in turn, was significantly lower than that of γ-HBCDs (p < 0.05). Such differences were explained by the significantly lower values of Clint,vitro of each α-HBCD stereoisomer than those of the β- and γ-HBCD stereoisomers. In addition, significantly lower values of Clint,vitro of the (-) over the (+)α- and β-HBCD stereoisomers, but not γ-HBCDs, were obtained. Our data offer a possible explanation of the enrichment of α-HBCDs over β- and γ-HBCDs on the one hand and, on the other hand, of (-)α-HBCDs over (+)α-HBCDs previously reported in human samples. It also offers information about the mechanism resulting in such enrichments, the stereoisomer-selective metabolism of α-, β-, and γ-HBCDs catalyzed by CYPs with the lack of stereoisomerization.
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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".