Integration of metabolomics and transcriptomics reveals short-chain chlorinated paraffin-induced hepatotoxicity in male Sprague-Dawley rat
Bibliographic record
Abstract
BACKGROUND: Short-chain chlorinated paraffins (SCCPs) used in various industrial applications have been listed as new POPs. Previous studies based on high-dose exposures indicate their hepatotoxicity. However, their mechanisms of toxicity or adverse outcome pathways and health risks remain largely unknown. OBJECTIVES: This study aimed to evaluate metabolic consequences of chronic dietary exposure to SCCPs at low doses and reveal the molecular mechanisms underlying hepatotoxicity of SCCPs. METHODS: A combination of transcriptomics and metabolomics, together with general pathophysiological tests were performed to assess the hepatic response of male rats exposed to SCCPs. RESULTS: Our results highlight two major modes of action: Inhibition of energy metabolism and activation of the peroxisome proliferator-activated receptor α (PPARα). Exposure to SCCPs suppressed oxidative phosphorylation, glycolysis, gluconeogenesis and turnover of ATP-ADP-AMP and thus results in deficiencies of amino acids and nucleotides in liver of the rat. Exposure to SCCPs affected expression levels of 13 genes downstream of PPARα that encode proteins associated with metabolism of fatty acids. As a result, peroxisomal and mitochondrial fatty acid β-oxidation, microsomal fatty acid ω-oxidation, and lipogenesis were accelerated. CONCLUSIONS: Results of this work strongly support the conclusion that low-dose exposure to SCCPs can result in adverse outcomes in the rat model. Significant SCCP-induced inhibition of energy metabolism occurs at environmentally relevant dosages, which suggests that SCCPs exhibit metabolic toxicity. Interactions of SCCPs with PPARα signaling pathway can explain the disruption of lipids and amino acids metabolism.
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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 | 0.000 | 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) | 0.005 | 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 teacher head, 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".