Toxicological comparison of cigarette smoke and e-cigarette aerosol using a 3D in vitro human respiratory model

Regul Toxicol Pharmacol. 2019 Apr:103:314-324. doi: 10.1016/j.yrtph.2019.01.036. Epub 2019 Feb 2.


With the growing prevalence of e-cigarettes as an alternative to conventional cigarettes amongst smokers worldwide, there is a need for new methods to evaluate their relative toxicological profile as part of a safety assessment. Initiatives to replace, reduce and refine animal testing have led to developments of new methodologies utilizing organotypic, in vitro tissue models. Here we use a respiratory epithelial model, EpiAirway, to examine the biological effects of nicotine-containing blu PLUS + e-cigarettes, with or without blueberry flavoring, in comparison to conventional cigarette smoke. Tissues were exposed at the air-liquid interface to cigarette smoke or e-cigarette aerosol generated using a VITROCELL VC1 smoking/vaping robot. Following exposure to cigarette smoke, there was a significant decrease in tissue viability and barrier function. Additionally, secretion of inflammatory cytokines, interleukin 6 and 8 (IL-6, IL-8) altered and a marker of DNA damage, γ-H2AX, was significantly increased. Conversely, tissues exposed to up to 400 puffs of e-cigarette aerosol with or without blueberry flavor did not differ compared to air-exposed tissues in any of the measured endpoints. Overall, the tested e-cigarette products induced significantly less cytotoxicity than conventional cigarette smoke under the conditions of test and suggest such products have the potential for reduced health risks. Our results also demonstrate that organotypic tissue models are useful for assessing the biological impact of e-cigarettes and their flavorings.

Keywords: Aerosol; Air-liquid interface; Cigarette; E-cigarette; Inflammation; Organotypic tissue model; Oxidative stress; Smoke; Toxicity.

Publication types

  • Comparative Study

MeSH terms

  • Aerosols / adverse effects*
  • Chromatography, High Pressure Liquid
  • Cigarette Smoking / adverse effects*
  • Cytokines / metabolism
  • Electronic Nicotine Delivery Systems*
  • Humans
  • Male
  • Nicotine / analysis
  • Oxidative Stress / drug effects
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Tandem Mass Spectrometry
  • Young Adult


  • Aerosols
  • Cytokines
  • Nicotine