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Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS)
  1. Noel J Leigh1,
  2. Ralph I Lawton1,
  3. Pamela A Hershberger2,
  4. Maciej L Goniewicz1
  1. 1Department of Health Behavior, Roswell Park Cancer Institute, Buffalo, New York, USA
  2. 2Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, USA
  1. Correspondence to Dr Maciej L Goniewicz, Division of Cancer Prevention and Population Sciences, Department of Health Behavior, Roswell Park Cancer Institute, Elm and Carlton Streets, Carlton House A320, Buffalo, NY 14263, USA; maciej.goniewicz{at}


Background E-cigarettes or electronic nicotine delivery systems (ENDS) are designed to deliver nicotine-containing aerosol via inhalation. Little is known about the health effects of flavoured ENDS aerosol when inhaled.

Methods Aerosol from ENDS was generated using a smoking machine. Various types of ENDS devices or a tank system prefilled with liquids of different flavours, nicotine carrier, variable nicotine concentrations and with modified battery output voltage were tested. A convenience sample of commercial fluids with flavour names of tobacco, piña colada, menthol, coffee and strawberry were used. Flavouring chemicals were identified using gas chromatography/mass spectrometry. H292 human bronchial epithelial cells were directly exposed to 55 puffs of freshly generated ENDS aerosol, tobacco smoke or air (controls) using an air–liquid interface system and the Health Canada intense smoking protocol. The following in vitro toxicological effects were assessed: (1) cell viability, (2) metabolic activity and (3) release of inflammatory mediators (cytokines).

Results Exposure to ENDS aerosol resulted in decreased metabolic activity and cell viability and increased release of interleukin (IL)-1β, IL-6, IL-10, CXCL1, CXCL2 and CXCL10 compared to air controls. Cell viability and metabolic activity were more adversely affected by conventional cigarettes than most tested ENDS products. Product type, battery output voltage and flavours significantly affected toxicity of ENDS aerosol, with a strawberry-flavoured product being the most cytotoxic.

Conclusions Our data suggest that characteristics of ENDS products, including flavours, may induce inhalation toxicity. Therefore, ENDS users should use the products with caution until more comprehensive studies are performed.

  • Electronic nicotine delivery devices
  • Toxicology
  • Harm Reduction

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  • Contributors MLG contributed to the conception of the work. MLG, PAH, NJL and RIL contributed to data analysis and drafted the manuscript. NJL and RIL ran experiments. All authors approved the final version of the manuscript. MLG has full access to all study data and takes responsibility for the integrity of the data and accuracy of the data analysis.

  • Funding Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01DA037446, the National Cancer Institute under Award Number P30 CA016056 and the Roswell Park Alliance Foundation.

  • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • Competing interests MLG reports grants from and served as an advisory board member to pharmaceutical companies that manufacture smoking cessation drugs. Other authors declare no conflict of interest.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data could be made available to qualified researchers by request to the corresponding author.