Volatile Metabolic Signatures Reveal Early Pulmonary Responses to PFAS Exposure
- 1Missouri University of Science and Technology
Abstract
Inhalation of airborne per- and polyfluoroalkyl substances (PFAS) represents an important yet understudied exposure route. While volatile organic compounds (VOCs) have been widely explored as biomarkers of toxicant exposure, their potential for early detection of PFAS-induced pulmonary toxicity remains largely unexplored. This study investigated VOC profiles in human alveolar (A549) and bronchial (BEAS-2B) epithelial cells following exposure to environmentally relevant PFAS concentrations (1, 5, and 10 ppb) for 12, 24, and 48 h. VOCs were analyzed using headspace solid-phase microextraction coupled with gas chromatography-Orbitrap mass spectrometry. We observed significant concentration- and time-dependent alterations in VOC profiles in both cell models. The principal VOCs associated with PFAS exposure include butanal, acetone, 2-butanone, 2-nonanone, (E)-2-nonenal, (E)-2-octenal, (E)-2-heptenal, 2,4-heptadienal, 2,4-nonadienal, 2,4-decadienal, 1-pentanol, and 1-hexanol. Cell type-specific regulations were observed, reflecting differential metabolic responses between transformed and non-transformed lung epithelial cells. Metabolite set enrichment analysis indicated perturbations in ketone body metabolism, consistent with altered cellular energy metabolism. Complementary qPCR analysis revealed altered expressions of CYP1A1, CYP2E1, ALDH1A1, and ALDH2, supporting a mechanistic link between PFAS exposure and oxidative stress, lipid peroxidation, and impaired aldehyde detoxification. These findings demonstrate that VOC profiling, combined with transcriptional analysis, can reveal PFAS-induced metabolic perturbations in pulmonary epithelial cells.
Related
- Validated thin-film microextraction-GC-MS reveals volatile metabolite signatures of Acinetobacter baumannii - Candida albicans interactions relevant to polymicrobial infection research
- From Food Structure to L-Cell Exposure: How Processing and Digestion Shape Endogenous GLP-1 Responses
- Metabolic signatures accompany exploratory movement in climbing plants
- Microplastic Release from Drinking Water Contact Materials: Material-Specific Responses to Chlorination and Implications for Consumer Exposure
- Sub‑chronic PFOA exposure at human‑relevant increasing doses in male mice: Role of stress‑induced gut barrier disruption in shaping intestinal and hepatic responses under high-dose conditions
BibTeX
@misc{agorsor2026volatile,
title = {{Volatile Metabolic Signatures Reveal Early Pulmonary Responses to PFAS Exposure}},
author = {P.-I. Agorsor and T.-C. Lin and Y.-W. Huang and M. O. Eze},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.23.753921},
url = {https://www.biorxiv.org/content/10.64898/2026.09.23.753921v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Volatile Metabolic Signatures Reveal Early Pulmonary Responses to PFAS Exposure
AU - P.-I. Agorsor
AU - T.-C. Lin
AU - Y.-W. Huang
AU - M. O. Eze
PY - 2026
DA - 2026/09/23
PB - bioRxiv
DO - 10.64898/2026.09.23.753921
UR - https://www.biorxiv.org/content/10.64898/2026.09.23.753921v1
AB - Inhalation of airborne per- and polyfluoroalkyl substances (PFAS) represents an important yet understudied exposure route. While volatile organic compounds (VOCs) have been widely explored as biomarkers of toxicant exposure, their potential for early detection of PFAS-induced pulmonary toxicity remains largely unexplored. This study investigated VOC profiles in human alveolar (A549) and bronchial (BEAS-2B) epithelial cells following exposure to environmentally relevant PFAS concentrations (1, 5, and 10 ppb) for 12, 24, and 48 h. VOCs were analyzed using headspace solid-phase microextraction coupled with gas chromatography-Orbitrap mass spectrometry. We observed significant concentration- and time-dependent alterations in VOC profiles in both cell models. The principal VOCs associated with PFAS exposure include butanal, acetone, 2-butanone, 2-nonanone, (E)-2-nonenal, (E)-2-octenal, (E)-2-heptenal, 2,4-heptadienal, 2,4-nonadienal, 2,4-decadienal, 1-pentanol, and 1-hexanol. Cell type-specific regulations were observed, reflecting differential metabolic responses between transformed and non-transformed lung epithelial cells. Metabolite set enrichment analysis indicated perturbations in ketone body metabolism, consistent with altered cellular energy metabolism. Complementary qPCR analysis revealed altered expressions of CYP1A1, CYP2E1, ALDH1A1, and ALDH2, supporting a mechanistic link between PFAS exposure and oxidative stress, lipid peroxidation, and impaired aldehyde detoxification. These findings demonstrate that VOC profiling, combined with transcriptional analysis, can reveal PFAS-induced metabolic perturbations in pulmonary epithelial cells.
ER -