Comparative In Vitro Toxicity Profile of Electronic and Tobacco Cigarettes, Smokeless Tobacco and Nicotine Replacement Therapy Products: E-Liquids, Extracts and Collected Aerosols

Abstract

The use of electronic cigarettes (e-cigs) continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT) products and a nicotine replacement therapy (NRT) product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic.

A comparative study of electronic cigarette vapor extracts on airway-related cell lines in vitro

“…Bahl et al (2012) and Misra et al (2014)). Unlike tobacco cigarettes, which have defined nicotine yields on the packaging, the nicotine content of E-liquids is simply labelled as 'low', 'medium', or 'high'; the precise concentration is not defined.…”

Electronic cigarettes—A review of the physiological health effects

“…For instance, Misra et al (2014) found no cytotoxicity or mutagenicity of EC aerosols, but found high cytotoxicity and mutagenicity of CC smoke in human lung epithelial cells (A549). Also, Scheffler et al (2015b) discovered reduced viability and increased oxidative stress when human bronchial epithelial (NHBE) cells were exposed to EC humectants, but much lower viability and higher oxidative stress when the same cells were exposed to CC smoke (see also Taylor et al 2016 for similar results).…”

Investigations into the pituri plant: nicotine content, nicotine conversion to nornicotine, nicotine release and cytotoxicity of Australian native Nicotiana spp.

“…There have been reports of cytotoxicity caused by smokeless tobacco products such as gutkha (Avti et al, 2010), khaini (Das et al, 2013), Sudanese toombak (Costea et al, 2010), American moist snuff (Misra et al, 2014), Swedish moist snuff (Coggins et al, 2012, Costea et al, 2010, Kentucky reference moist smokeless tobacco product (Lombard et al, 2010) and commercial chewing tobacco (Coppe et al, 2008). The present study is the first assessment of cytotoxicity induced by tobacco constituents of pituri as a means of investigating its potential carcinogenicity.…”

“…There are numerous reports on in vitro cytotoxic effects of commercially available smokeless tobacco products such as Swedish snus (Coggins et al, 2012, Costea et al, 2010, American moist snuff (Misra et al, 2014), commercial chewing tobacco (Coppe et al, 2008) and Kentucky reference smokeless tobacco product (Lombard et al, 2010). There have been reports of cytotoxicity caused by Indian manufactured smokeless tobacco such as gutka (Avti et al, 2010) and khaini (Das et al, 2013).…”

“…Determining the chemistry of the different types of the ash used in pituri especially in regard to the toxic chemicals such as the polycyclic aromatic hydrocarbons (PAHs) or heavy metals that might affect cell survival will help to get a better understanding of the extent of toxicity as well as the pathways involved in cytotoxicity. Also parallel to this would be applying a range of other cell assays such as mutagenicity assays (Wan et al, 2009) to detect genetic damage that leads to gene mutations, genotoxicity (Misra et al, 2014) to investigate DNA damage as an indication of potential carcinogenicity, apoptosis assays (Bagchi et al, 1999) to look for higher than normal apoptosis that can be attributed to pituri chemicals, and assays that evaluate the inflammatory response (Nordskog et al, 2003) to exposure with pituri chemicals.…”