Epithelial Cell Regulation & Transformation Program, Integrative Biology and Infectious Diseases Branch, DER, NIDCR
The goal of this initiative is to encourage studies aimed at assessing the effects of aerosol mixtures produced by electronic cigarettes (ECs) on oral and periodontal epithelial cells. This initiative will support 1) comprehensive identification of chemicals produced by electronic cigarettes using state of the art analytical methods; 2) analysis of synergistic effects of e-cigarette aerosol mixtures on oral and periodontal epithelia with an emphasis on effects that include genotoxicity, mutagenicity, proliferation, cell death, and transformation using appropriate in vitro and/or in vivo model systems; and 3) effects of ECs on oral homeostasis and factors that maintain oral homeostasis (e.g. cytokines). This initiative will emphasize the use of novel 3D cultures that are representative of the oral mucosa and other clinically-relevant model systems.
ECs are battery operated devices that consist of a metal heating element that vaporizes a solution containing a mixture of chemicals that may include nicotine, propylene glycol, glycerine, flavors and other additives. The recent introduction of electronic cigarettes (ECs) also known as electronic nicotine delivery systems (ENDS) in the US has led to their widespread use by smokers and non-smokers alike. Data indicate that 20.1% of adult smokers tried ECs in 2011 with a higher number of women compared to men in the US. Disturbingly, the rate of EC use by middle school and high school children doubled during 2011-2012 alone (3.3% to 6.8%) in the US.
EC sales in 2012 were estimated at $1.7 billion in the US. If unregulated, the economics of ECs are expected to have tremendous growth potential for the tobacco industry and surpass the sales of conventional tobacco smoking cigarettes in the next decade. While these devices have escaped initial scrutiny for safety standards and regulation, the FDA has very recently initiated efforts to establish rules that would regulate the marketing of these products as tobacco products. In view of their rapid acceptance and use, the NIH held a workshop in November 2013 to identify future research priorities relating to the effects of ECs on safety, addictiveness, potential use in smoking cessation, and public safety. In addition, there is evidence for an increasing rate of queries from patients to health practitioners relating to the safety and efficacy of ECs as smoking cessation devices.
While perceived as safe by most users, there is no scientific evidence to support the safety of ECs and initial studies indicate that a variety of chemicals and metal particles are produced during the vaporization of nicotine and additives by these devices. The chemicals identified in the aerosols of ECs include but are not limited to propylene glycol, glycerine, formaldehyde, acetaldehyde, acrolein, toluene, nitrosamines, nickel, cadmium, aluminum, silicon and lead (Fig.1). While levels of many of the identified compounds and metals in ECs are much lower than tobacco smoke produced by conventional cigarettes, some of them have been shown to be carcinogenic and/or genotoxic in earlier studies. Furthermore smoking characteristics and potential for abuse by users of ECs, physical characteristics of vaporized nicotine and other chemical products, nicotine yield, and degree of exposure of oral, periodontal and upper aerodigestive tract epithelial cells are profoundly different when compared to conventional cigarettes.
Gaps and Opportunities
The rapidly increasing acceptability of ECs as safe products or as aides to tobacco cessation, and their widespread use among smokers, non-smokers, teenagers and adolescents indicate a troubling trend that might pose a public health problem in the future. There is an urgent need to determine the biological effects of chemical mixtures in ECs for generating evidence-based public health policies and regulations. To date, there have been no systematic studies conducted to analyze the synergistic effects of chemical mixtures (as opposed to effects of individual components) generated by ECs on oral and periodontal epithelial cells. Specifically the effects of long term exposure to ECs are completely unknown and present a potential oral cancer and periodontal disease risk for users due to their higher exposure to such chemical mixtures. This initiative will provide important and much needed preliminary data on the effects of ECs on oral health.
Current Portfolio Overview
An NIH grant portfolio analysis was performed in April 2014 for research on electronic cigarettes. Two R21 grants and two supplements to currently funded grants were identified that deal with the effects of ECs on mouse lung cells, human lung fibroblasts, airway epithelial cells and the influence of advertising on EC demand among smokers. None of the projects focus on oral and periodontal epithelial cells of the oral cavity.
Individuals and Groups Whose Input was Solicited for This Initiative
The recommendations of the NIH workshop (Electronic Cigarettes: Developing a Research Agenda) provided the impetus and the basis for this initiative. Public comments were also solicited when NIDCR posted the list of FY2016 research themes on our website in August 2014.
Alignment with Institute Goals and Strategic Plan
This initiative is aligned with the NIDCR Strategic Plan 2014-2019, Goal 1, Objective 1-1: Enable basic research to advance knowledge of dental, oral, and craniofacial health; and Goal 3, Objective 3-3: Provide science-based information about oral health and disease to health care providers, patients and caregivers, policy makers, and the general public.
Brown CJ, Cheng JM. Electronic cigarettes: product characterisation and design considerations. Tob Control. 2014 May;23 Suppl 2:ii4-10.
Centers for Disease Control and Prevention (CDC). Notes from the field: electronic cigarette use among middle and high school students - United States, 2011-2012. MMWR Morb Mortal Wkly Rep. 2013 Sep 6;62(35):729-30.
Evans SE, Hoffman AC. Electronic cigarettes: abuse liability, topography and subjective effects. Tob Control. 2014 May;23 Suppl 2:ii23-9.
Goniewicz ML, Knysak J, Gawron M, Kosmider L, Sobczak A, Kurek J, Prokopowicz A, Jablonska-Czapla M, Rosik-Dulewska C, Havel C, Jacob P 3rd, Benowitz N. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control. 2014 Mar;23(2):133-9.
Goniewicz ML, Kuma T, Gawron M, Knysak J, Kosmider L. Nicotine levels in electronic cigarettes. Nicotine Tob Res. 2013 Jan;15(1):158-66.
Popova L, Ling PM. Alternative tobacco product use and smoking cessation: a national study. Am J Public Health. 2013 May;103(5):923-30.
Pötschke-Langer M., et al. Electronic Cigarettes - An Overview. Red Series Tobacco Prevention and Tobacco Control. Volume 19, German Cancer Research Center (DKFZ), Heidelberg.2013
Williams M, Villarreal A, Bozhilov K, Lin S, Talbot P. Metal and silicate particles including nanoparticles are present in electronic cigarette cartomizer fluid and aerosol. PLoS One. 2013;8(3):e57987.
NIH Workshop on Electronic Cigarettes: Developing a Research Agenda.
Proposed Rule by the Food and Drug Administration. “Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Regulations on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products.” 04/25/2014