Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke

Abstract

Electronic cigarettes (E-cigarettes) are a potential means of addressing the harm to public health caused by tobacco smoking by offering smokers a less harmful means of receiving nicotine. As e-cigarettes are a relatively new phenomenon, there are limited scientific data on the longer-term health effects of their use. This study describes a robust in vitro method for assessing the cytotoxic response of e-cigarette aerosols that can be effectively compared with conventional cigarette smoke. This was measured using the regulatory accepted Neutral Red Uptake assay modified for air–liquid interface (ALI) exposures. An exposure system, comprising a smoking machine, traditionally used for in vitro tobacco smoke exposure assessments, was adapted for use with e-cigarettes to expose human lung epithelial cells at the ALI. Dosimetric analysis methods using real-time quartz crystal microbalances for mass, and post-exposure chemical analysis for nicotine, were employed to detect/distinguish aerosol dilutions from a reference Kentucky 3R4F cigarette and two commercially available e-cigarettes (Vype eStick and ePen). ePen aerosol induced 97%, 94% and 70% less cytotoxicity than 3R4F cigarette smoke based on matched EC50 values at different dilutions (1:5 vs. 1:153 vol:vol), mass (52.1 vs. 3.1 μg/cm2) and nicotine (0.89 vs. 0.27 μg/cm2), respectively. Test doses where cigarette smoke and e-cigarette aerosol cytotoxicity were observed are comparable with calculated daily doses in consumers. Such experiments could form the basis of a larger package of work including chemical analyses, in vitro toxicology tests and clinical studies, to help assess the safety of current and next generation nicotine and tobacco products.

Reduced biological effect of e-cigarette aerosol compared to cigarette smoke evaluated in vitro using normalized nicotine dose and RNA-seq-based toxicogenomics

“…The toxicological assessment of e-cigarettes has so far reported fewer biological responses on cellular functions compared to conventional cigarettes 6,12,[25][26][27] , however, approaches for dose and matrices have been inconsistent. Yu and colleagues compared e-cigarette aerosol extracts with cigarette smoke extracts generated in media applied to both primary and immortalized epithelial cells.…”

“…In our recent e-cigarette studies, we have shown the importance of expressing dose as a function of delivered nicotine, when conducting comparative studies across different tobacco and nicotine product categories. Azzopardi et al 25 and Adamson et al 7,28 showed how deposited mass and nicotine quantification at the cellular exposure interface enable appropriate extrapolation and comparisons in an aerosol matrix. Different types of e-cigarettes and e-liquids generate different volumes of aerosol and deliver different amounts of nicotine, however typically smokers who switch from cigarette to nicotine delivery devices adapt their behavior to potentially titrate for nicotine 18,19 .…”

Electronic cigarettes—A review of the physiological health effects

“…These differences could potentially explain the varying levels of the same chemical in the aerosol or a different degree of cardiac function impairment. To draw meaningful broad conclusions, there is, therefore, a need for better standardization of protocols (e.g., Azzopardi et al 2016;Farsalinos et al 2016c;Iskandar et al 2016). In addition, future researchers need to take advantage of other tools and methodologies such as randomized controlled trials (Cravo et al 2016), and develop mathematical models and new frameworks (Kalkhoran and Glantz 2015;Levy et al 2017).…”

In VitroandEx VivoApproaches to Evaluate Next-Generation Tobacco and Non-Tobacco Products on Human Blood Platelets

“…7,8 Complex in vitro tissue and organ models have been established that include assessment of cardiovascular and vascular systems. 9 …”