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Peer-reviewedCC BY 4.0Archives of Toxicology

Toxic in vitro effects of flavoured-air inhalers containing essential oils in differentiated human nasal epithelial cells at air–liquid interface

  • Alexander N. Larcombe1,2
  • E. E. Catchpole2
  • P. Hopper3
  • S. Stanley3
  • A. Kicic2,4,5
  • K. R. Landwehr1,2
5 affiliations
  1. 1Occupation, Environment and Safety, School of Population Health, Curtin University, GPO Box U1987, Perth, WA 6845 Australia
  2. 2Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Nedlands, Australia
  3. 3WA Organic and Isotope Geochemistry Centre, School of Earth and Planetary Sciences, Faculty of Science and Engineering, Curtin University, Bentley, WA Australia
  4. 4Department of Respiratory and Sleep Medicine, Perth Children’s Hospital, Nedlands, WA Australia
  5. 5Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Perth, WA Australia
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Abstract

Flavoured-air inhalers containing essential oils are marketed as safe, natural alternatives to smoking and vaping, yet their potential respiratory toxicity remains effectively unexamined. Manufacturers claim safety based on "100% natural" ingredients, despite evidence that essential oil inhalation can cause adverse respiratory effects. Our objective was to assess the in vitro toxicity of six commercially available flavoured-air products on human nasal airway epithelial cells. Differentiated air–liquid interface cultures of primary nasal airway epithelial cells from eight healthy adults were exposed for one hour to air (control) or flavoured air from three devices (Füm, Lio, Cigtrus; two flavours each) generated by drawing air through essential oil-infused cores at a continuous airflow of 1 L/min for one hour into an 1000 mL exposure chamber. Outcomes included transepithelial electrical resistance, cytotoxicity, protein release, cytokine/chemokine profiling and histological assessment. Chemical analysis characterised the chemical composition of device cores and identified 29 compounds across the six products, including the possible carcinogen pulegone and cytotoxic cinnamaldehyde. Five of six flavours significantly reduced transepithelial electrical resistance indicating compromised epithelial barrier integrity. Mediator responses were compartment-specific: apical surfaces showed predominantly pro-inflammatory profiles while basal release was broadly suppressed. Histological analysis revealed reduced cilia coverage, fewer mucus-producing cells, and decreased epithelial thickness across multiple treatments. This study shows that a single one-hour exposure to flavoured-air vapour led to epithelial barrier dysfunction, immune dysregulation, and structural damage in healthy human nasal airway epithelial cells, contradicting manufacturer safety claims. Rigorous toxicological evaluation of these products is urgently needed.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00204-026-04521-w.

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Cite

BibTeXRIS
BibTeX
@article{larcombe2026toxic,
  title = {{Toxic in vitro effects of flavoured-air inhalers containing essential oils in differentiated human nasal epithelial cells at air–liquid interface}},
  author = {Alexander N. Larcombe and E. E. Catchpole and P. Hopper and S. Stanley and A. Kicic and K. R. Landwehr},
  journal = {Archives of Toxicology},
  year = {2026},
  month = aug,
  doi = {10.1007/s00204-026-04521-w},
  url = {https://doi.org/10.1007/s00204-026-04521-w},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Toxic in vitro effects of flavoured-air inhalers containing essential oils in differentiated human nasal epithelial cells at air–liquid interface
AU  - Alexander N. Larcombe
AU  - E. E. Catchpole
AU  - P. Hopper
AU  - S. Stanley
AU  - A. Kicic
AU  - K. R. Landwehr
PY  - 2026
DA  - 2026/08/12
JO  - Archives of Toxicology
DO  - 10.1007/s00204-026-04521-w
UR  - https://doi.org/10.1007/s00204-026-04521-w
AB  - Flavoured-air inhalers containing essential oils are marketed as safe, natural alternatives to smoking and vaping, yet their potential respiratory toxicity remains effectively unexamined. Manufacturers claim safety based on "100% natural" ingredients, despite evidence that essential oil inhalation can cause adverse respiratory effects. Our objective was to assess the in vitro toxicity of six commercially available flavoured-air products on human nasal airway epithelial cells. Differentiated air–liquid interface cultures of primary nasal airway epithelial cells from eight healthy adults were exposed for one hour to air (control) or flavoured air from three devices (Füm, Lio, Cigtrus; two flavours each) generated by drawing air through essential oil-infused cores at a continuous airflow of 1 L/min for one hour into an 1000 mL exposure chamber. Outcomes included transepithelial electrical resistance, cytotoxicity, protein release, cytokine/chemokine profiling and histological assessment. Chemical analysis characterised the chemical composition of device cores and identified 29 compounds across the six products, including the possible carcinogen pulegone and cytotoxic cinnamaldehyde. Five of six flavours significantly reduced transepithelial electrical resistance indicating compromised epithelial barrier integrity. Mediator responses were compartment-specific: apical surfaces showed predominantly pro-inflammatory profiles while basal release was broadly suppressed. Histological analysis revealed reduced cilia coverage, fewer mucus-producing cells, and decreased epithelial thickness across multiple treatments. This study shows that a single one-hour exposure to flavoured-air vapour led to epithelial barrier dysfunction, immune dysregulation, and structural damage in healthy human nasal airway epithelial cells, contradicting manufacturer safety claims. Rigorous toxicological evaluation of these products is urgently needed.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00204-026-04521-w.
SN  - 0340-5761
SN  - 1432-0738
ER  -