Metabolomics of Childhood Exposure to Perfluorooctanoic Acid: A Cross-Sectional Study
Bibliographic record
Abstract
Background: Exposure to perfluorooctanoic acid (PFOA), a synthetic and persistent chemical used in commercial and industrial processes, is associated with reduced birth weight, increased adiposity, dyslipidemia, and liver injury. These diverse toxic effects suggest that PFOA elicits multiple biological responses. Identifying the metabolic changes induced by PFOA exposure could enhance our understanding of potential biological mechanisms.Study Objective: To identify metabolic changes associated with serum PFOA concentrations in 8-year old children using a metabolome-wide association study (MWAS).Methods: Using venous blood samples collected from 120 8-year old children in Cincinnati, OH, we quantified serum PFOA concentrations and performed untargeted metabolomic profiling by liquid chromatography-high-resolution mass spectrometry. We evaluated metabolic variations associated with PFOA concentrations using linear regression and false discovery rate (FDR) <20%. We identified associated metabolites with the METLIN mass spectral database and metabolic pathway enrichment analysis.Results: At FDR<20%, higher serum PFOA concentrations were associated with 239 detected chemical signals; 130 were positive associations. Initial annotation of the mass spectral data showed that both endogenous metabolites and perfluoroalkyl chemicals were associated with PFOA exposure. Using untargeted metabolomics, we detected PFOA, perfluorooctanesulfonic acid, and additional signals consistent with fluorinated chemicals. Biological alterations associated with PFOA concentrations included keratin sulfate degradation and metabolism of purine, caffeine, Vitamin E, linoleate, urea cycle/amino groups, glyoxylate, dicarboxylate, and galactose, consistent with changes to immunological, oxidative stress and catabolism pathways.Conclusions: This is the first study to perform a MWAS with PFOA exposure in children and provides new insights into the biological responses associated with PFOA exposure.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".