Polybrominated Diphenyl Ethers as Ah Receptor Agonists and Antagonists
Bibliographic record
Abstract
Polybrominated diphenyl ethers (PBDEs) have been identified in every compartment of the environment and biota due to their widespread use as flame retardants. There is debate over their potential to threaten environmental and human health due to insufficient toxicological information. The weak to moderate binding affinity of PBDE congeners to the Ah receptor (AhR) and the weak induction of EROD (ethoxyresorufin-O-deethylase) activity suggest the possibility of dioxin-like behavior. We have investigated whether PBDE congeners act as Ah receptor agonists or antagonists at sequential stages of the AhR signal transduction pathway leading to CYP1A1. PBDE congeners 77, 119, and 126 were moderately active towards DRE (dioxin response element) binding and induced responses of both CYP1A1 mRNA and CYP1A1 protein equivalent to the maximal response of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) in primary Sprague-Dawley rat hepatocytes, although at concentrations three to five orders of magnitude greater than TCDD. These congeners showed additive (throughout this article, we use additive and antagonistic as shorthand terms for increasing or decreasing the response observed with TCDD alone) behavior towards DRE binding with 10(-9) M TCDD, whereas most other PBDE congeners antagonized the action of TCDD. PBDEs 100, 153, and 183 were very weak activators of DRE binding; other congeners and the commercial "penta," "octa," and "deca" bromodiphenyl ether mixtures were inactive. The environmentally prominent congeners 47 and 99 were inactive at all stages of signal transduction, and the "penta" mixture had negligible ability to induce EROD activity. We suggest that current concentrations of PBDEs in biota contribute negligibly to dioxin-like toxicity compared with other environmental contaminants, such as polychlorinated dibenzo-p-dioxins and polychlorinated biphenyls.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.005 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.017 | 0.001 |
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; both teacher heads agree on what is shown here.
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".