Toxicological Aspects Associated with Consumption from Electronic Nicotine Delivery System (ENDS): Focus on Heavy Metals Exposure and Cancer Risk

Abstract

Tobacco smoking remains one of the leading causes of premature death worldwide. Electronic Nicotine Delivery Systems (ENDSs) are proposed as a tool for smoking cessation. In the last few years, a growing number of different types of ENDSs were launched onto the market. Despite the manufacturing differences, ENDSs can be classified as "liquid e-cigarettes" (e-cigs) equipped with an atomizer that vaporizes a liquid composed of vegetable glycerin (VG), polypropylene glycol (PG), and nicotine, with the possible addition of flavorings; otherwise, the "heated tobacco products" (HTPs) heat tobacco sticks through contact with an electronic heating metal element. The presence of some metals in the heating systems, as well as in solder joints, involves the possibility that heavy metal ions can move from these components to the liquid, or they can be adsorbed into the tobacco stick from the heating blade in the case of HTPs. Recent evidence has indicated the presence of heavy metals in the refill liquids and in the mainstream such as arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), copper (Cu), and lead (Pb). The present review discusses the toxicological aspects associated with the exposition of heavy metals by consumption from ENDSs, focusing on metal carcinogenesis risk.

Keywords: ENDS; cancer; oxidative stress.

Figure 1

Schematic representation of e-cig and HTP components. E-cigs are characterized by a refillable tank (holding the e-liquid), an atomizer (activated by a button to aerosolize the e-liquid), and the battery. In HTPs, the disposable tobacco stick is heated thanks to an electronic blade, manually activated through a button (a). Alternatively, other devices use an induction heating chamber, where tobacco sticks are inserted into it (b).

Figure 2

Effects of heavy metals released by e-cigarettes. The users are exposed to many heavy metals (such as As, Cd, Cr, Ni, and Pb). These metals participate in the development of cancer, by increasing the epithelial–mesenchymal transition translocation, tumor-promoting microenvironment, and DNA mutagenesis leading to lung, breast, bladder, and oral cancer.

Figure 3

Molecular mechanisms of ENDS-induced cancer and the contribution of metals. The presence of many heavy metals (such as As, Cd, Cr, Ni, and Pb) in the ENDS mainstream contributes to the carcinogenic effects of these devices. In particular, metals are able to increase the production of ROS and oxidative stress, leading to DNA damage as well as activating cancer cell markers (like EGFR and MAP kinases) and oncogenes (c-Myc).