Nontargeted Metabolomics and Machine Learning Reveal Associations Between 6:2 Fluorotelomer Ethoxylate Exposure and Intracranial Aneurysm Risk.

Authors

Weijian Fan, Kaiyuan Huang, Yuxiang Weng, Zebin Fang, Luyuan Zhang, Feng Xiao, Tianxiang Zhan, Chao Zhang, Jianwei Pan

Published in

Environmental pollution (Barking, Essex : 1987). Pages 129368. Oct 20, 2026. Epub Oct 20, 2026.

Abstract

6:2 Fluorotelomer ethoxylates (6:2 FTEOs) are an emerging class of polyfluoroalkyl substances widely used in anti-fog products. Their increasing detection in environmental media and human serum has raised concerns regarding their potential toxicity and associated health risks. The association between 6:2 FTEO exposure and intracranial aneurysm (IA) risk has not been evaluated in any epidemiological study to date. Here, we conducted a case-control study (137 IA patients and 274 healthy controls), quantified seven serum 6:2 FTEO homologues, and performed metabolomic profiling of human serum samples. 6:2 FTEO6, 6:2 FTEO9, and 6:2 FTEO11 dominated the 6:2 FTEO profile in human serum. Serum levels of 6:2 FTEO6, 6:2 FTEO8, and 6:2 FTEO9 showed significant (p < 0.01) associations with IA risk, with adjusted odds ratios comparing the highest versus lowest quartile of 2.68 (95% CI: 1.61-3.70), 2.78 (1.78-3.81), and 1.98 (1.10-3.58), respectively. Weighted quantile sum analysis indicated a significant effect of the combined 6:2 FTEO exposure on IA risk, driven mainly by 6:2 FTEO6. Random forest showed the strongest apparent discrimination, and its top-ranked metabolites were enriched in arachidonic acid metabolism and phosphatidylcholine biosynthesis. In exploratory mediation analyses, the observed indirect-effect estimates for 6:2 FTEO6 and 6:2 FTEO8 were statistically compatible with mediation through arachidonic acid metabolism and phosphatidylcholine biosynthesis. This study is the first to provide epidemiological evidence linking 6:2 FTEO exposure to increased IA risk, and provides hypothesis-generating evidence linking serum 6:2 FTEO concentrations, lipid metabolic perturbations, and IA status.

PMID:
42901465
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.

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