Electronic cigarettes (e-cigarettes) were introduced to the global market in the mid 2000’s. While it is common to hear the term “e-cigarettes”, this label is a broad term referring to a heterogeneous class of devices that differ in shape, size, and functional characteristics. Common features of e-cigarettes include a heating element that heats a propylene glycol and/or vegetable glycerin based solution (“e-liquid” /“e-juice”) that contains stabilizers, flavorings and often, nicotine. Numerous flavors are available, including tobacco, menthol, fruit, and sweet flavors. Heating of e-liquids produces an aerosol, which is then inhaled by the user. Due to their relatively short existence, data on the long-term health effects of e-cigarette use are not currently available. In the interim, evidence from animal studies, in vitro and in vivo laboratory studies, observational studies, and small-scale clinical trials may provide important information on the potential harms of e-cigarette use [1]. Many studies conducted on e-cigarettes have focused on the measurement of potentially harmful chemicals that may be produced by these products. Chemicals identified in e-cigarette aerosol include nicotine, tobacco-specific nitrosamines (TSNAs), metals, polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), and aldehydes. Within these classes, there are several respiratory irritants and toxicants, as well as carcinogenic substances linked to the development of respiratory cancers. In our work, we have tested emissions from numerous e-cigarette brands [2] and identified the presence of formaldehyde, acetaldehyde, and acrolein in e-cigarette emissions. Overall, concentrations of toxicants identified in e-cigarette aerosols were 9 to 450 times lower than in tobacco smoke [2]. Concerns have also been raised about the presence of metal particles in e-cigarette aerosol (particularly nickel and chromium, two main elements in heating coils).The inhalation of these metals in larger quantities may cause respiratory diseases, bronchitis, and pneumonia [3], however, these effects have not been definitively elucidated. The size of particulate matter generated from e-cigarettes affects pulmonary nicotine absorption and determines settlement of particulate matter into various parts of the upper or lower airways. There is likely substantial variation across generations of e-cigarette devices, and across brands. Results from laboratory studies indicate that e-cigarettes may expose users to small particles and lower amounts of particulate matter in general. While inhalation of high levels of particulate matter has been linked to greater mortality risk from cardiopulmonary illnesses, the available data indicate that e-cigarette particulate emissions expose users at a level akin to WHO guidelines and are far lower than those of conventional cigarettes. Issues raised about toxicological effects mostly question effects on cells, with a special interest in lung epithelial cells. For instance, many flavorings used in e-cigarettes (e.g. cinnamaldehyde, benaldehyde, diacetyl) are already approved for use in food, yet their impact on respiratory health via repeated inhalation is currently unknown. Several studies have shown that e-cigarette flavorings could lead to lung cell damage (mostly by releasing free radicals) and inflammation in lung tissue [4]. Studies on cytotoxic effects of e-cigarette constituents have also identified negative effects on DNA. In one in vitro research, e-cigarette liquids aerosolized at biologically relevant doses induced increased DNA strand breaks and apoptosis while decreasing survival in both normal epithelial and head and neck squamous cell carcinoma cell lines [5]. Moreover, in experiments conducted by Yu et al. [6] e-cigarettes aerosol has shown cytotoxic effects on epithelial cell lines and acted as a DNA-breaking agent. Given multiple potential etiologic mechanisms related to incident case development coupled with the long latency period in developing illness, there is currently no definitive evidence to commenting on the role of e-cigarettes in increasing lung cancer risk. As an intermediate assessment, cross-sectional biomarker data can be suggestive of possible carcinogen exposures related to cancer development. For instance, Shahab et al. [7] examined a large panel of biomarker data among e-cigarette users, cigarette users, and users of both products (“dual users”). The e-cigarette–only users had significantly lower metabolite levels for tobacco-specific nitrosamines (TSNAs), particularly NNAL, a metabolite of potent lung carcinogen NNK. Several observational longitudinal studies also showed a substantial reduction in exposure to NNK and several VOCs, including respiratory toxicants like acrolein, acrylamide, acrylonitrile, 1,3-butadiene (human carcinogen), and ethylene oxide among smokers who switched to e-cigarette [8]. Although evidence from biomarker studies are insufficient to evaluate causative mechanisms, but show users of e-cigarettes display lower levels of exposure to biomarkers of lung carcinogens when compared to smokers, such as NNK. Since e-cigarettes have only been on the market for a decade, it is presently not possible to assess all potential long-term harmful effects of e-cigarette use. To date, findings from clinical studies have demonstrated that e-cigarettes are likely less harmful compared to conventional tobacco cigarettes, and any harmful side effects are noticeably milder compared with regular cigarettes. Furthermore, it is also clear that e-cigarette aerosols are not “a harmless water vapor”, as claimed by manufacturers and retailers, and potential health effects from vaping may emerge after long-term use.

References 1. National Academies of Sciences, Engineering and Medicine. Public health consequences of e-cigarettes. Washington, DC: The National Academies Press; 2018. 2. Goniewicz et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control. 2014;23:133-139 3. Lerner et al. Environmental health hazards of e cigarettes and their components: oxidants and copper in e-cigarette aerosols. Environ Pollut. 2015;198:100-107 4. Leigh et al. Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS). Tob Control. 2016;25(Suppl 2):ii81-ii87. 5. Welz et al. Cytotoxic and genotoxic effects of electronic cigarette liquids on human mucosal tissue cultures of the oropharynx. J Environ Pathol Toxicol Oncol. 2016;35:343-354. 6. Yu et al. Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines. Oral Oncol. 2016;52:58-65. 7. Shahab et al. Nicotine, carcinogen, and toxin exposure in long-term e-cigarette and nicotine replacement therapy users: a cross-sectional study. Ann Intern Med. 2017;166:390-400. 8. Goniewicz et al. Exposure to nicotine and selected toxicants in cigarette smokers who switched to electronic cigarettes: a longitudinal within-subjects observational study. Nicotine Tob Res. 2017;19:160-167.