Impact of Atomizer Age and Flavor on In Vitro Toxicity of Aerosols from a Third-Generation Electronic Cigarette against Human Oral Cells

Abstract

Electronic cigarettes (ECs) are categorized into generations which differ in terms of design, aerosol production, and customizability. Current and former smokers prefer third-generation devices that satisfy tobacco cravings more effectively than older generations. Recent studies indicate that EC aerosols from firstand second-generation devices contain reactive carbonyls and free radicals and can cause in vitro cytotoxicity. Third-generation ECs have not been adequately studied. Further, previous studies have focused on cells from the respiratory tract, whereas those of the oral cavity, which is exposed to high levels of EC aerosols, have been understudied. We quantified the production of reactive carbonyls and free radicals by a thirdgeneration EC and investigated the induction of cytotoxicity and oxidative stress in normal and cancerous human oral cell lines using a panel of eight commercial EC liquids. We found that EC aerosols produced using a new atomizer contained formaldehyde, acetaldehyde, and acrolein, but did not contain detectable levels of free radicals. We found that EC aerosols generated from only one of the eight liquids tested using a new atomizer induced cytotoxicity against two human oral cells in vitro. Treatment of oral cells with the cytotoxic EC aerosol caused a concomitant increase in intracellular oxidative stress. As atomizer age increased with repeated use of the same atomizer, carbonyl production, radical emissions, and cytotoxicity increased. Overall, our results suggest that thirdgeneration ECs may cause adverse effects in the oral cavity and normal EC use, which involves repeated use of the same atomizer to generate aerosol, may enhance the potential toxic effects of third-generation ECs.

Adverse effects of E‐cigarettes on head, neck, and oral cells: A systematic review

“…20,21 Seven studies were conducted in the US, 5,6,20,[22][23][24] two in Canada, 21,25 two in Switzerland, 26,27 three in Germany, [28][29][30] two in Italy, 31,32 one in Poland, 33 and one in Brazil. 34 Four studies examined e-cigarette liquid on oral cells, 28,29,[31][32][33]35,36 nine e-cigarette vapor, 5,6,[20][21][22][25][26][27]37 four tested cigarette liquid and vapor, 6,33,37,38 and one study the effects of vapor on DNA. 34 Nicotine concentration ranged from 0 to 24 mg/ml, and 12 flavors were tested for toxicity.…”

“…29 Another study used oral keratinocytes, 36 and 2 studies used premalignant keratinocytes, laryngeal lymph cells, and head and neck squamous epithelial cells. 6,23 Eight studies used donor tissue to create cell lines, [26][27][28][29][32][33][34]38 8 studies used cultured cell lines, 5,6,20,21,32,35,37,39 and 2 studies used research participants 20,36 (See Table 3).…”

“…tested four different e-cigarettes with an atomizer on HGF's. 35 They found Lava flow e-cigarettes with and without nicotine decreased cell viability in HGF's to 28% and 33%, respectively, 35 and when combined with an aged atomizer (>675 puffs), viability was further reduced by 125%. 35 Alanazi et al found reduced cell proliferation in HGF's when treated with e-cigarette vapor with and without nicotine (p = 0.001, p = 0.006, respectively).…”

“…35 They found Lava flow e-cigarettes with and without nicotine decreased cell viability in HGF's to 28% and 33%, respectively, 35 and when combined with an aged atomizer (>675 puffs), viability was further reduced by 125%. 35 Alanazi et al found reduced cell proliferation in HGF's when treated with e-cigarette vapor with and without nicotine (p = 0.001, p = 0.006, respectively). 21 According to Willershausen et al, human periodontal ligament fibroblasts (HPdLF's) showed a significant decrease in cell proliferation when treated with menthol e-cigarette liquid p < 0.001.…”

The Effects of E-Cigarette Aerosol on Oral Cavity Cells and Tissues: A Narrative Review

“…It was observed that vaping can be a reason for relapse into traditional smoking [3]. Moreover, it was found that third-generation electronic cigarettes may cause adverse effects in the oral cavity, and normal e-cigarette use, which involves repeated use of the same atomizer to generate aerosol, may enhance the potential toxic effects of third-generation e-cigarettes [4].…”