Abstract SS02-03: Carcinogens and toxicants in e-cigarettes
Authors: Maciej Goniewicz L. 
Published: May 2019

Abstract
Dr. Maciej L. Goniewicz is a pharmacologist and toxicologist and Assistant Professor of Oncology at the Department of Health Behavior, Roswell Park Cancer Institute in Buffalo, NY. His primary research area is in nicotine pharmacology, with a focus on nicotine dependence and smoking cessation. He has research experience in smoking cessation behavioral treatment, pharmacotherapy, and pharmacokinetics in both clinical and community-based settings. Dr. Goniewicz's current research is focused on new nicotine-containing products and alternative forms of tobacco. He examines safety and efficacy of electronic nicotine delivery devices, commonly called e-cigarettes. These studies include the laboratory evaluation of the products, pharmacological and toxicological assessment, surveys among their users, and their potential application in harm reduction and smoking cessation.
Background
Electronic cigarettes, also known as e-cigarettes, are devices designed to imitate regular cigarettes and deliver nicotine via inhalation without combusting tobacco. When a user initiates inhalation into the device, air flow is detected by a sensor, which activates a heating element that vaporizes the nicotine solution stored in the mouthpiece cartridge. It is this vapor that is inhaled by the user. On some models an LED on the opposite end of the device is activated during inhalation to serve as an indicator of use as well as simulating the glow of burning tobacco.
E-cigarettes are purported to deliver nicotine without other toxicants and to be a safer alternative to regular cigarettes. The nicotine is extracted from tobacco leaves (in the same way the pharmaceutical industry obtains nicotine for NRT production), and is then diluted and introduced into the e-cigarette's cartridge. In addition to delivering nicotine, the vapor also provides a flavor and physical sensation sought by many smokers that is similar to that of inhaled tobacco smoke, although no tobacco or combustion is actually involved in its operation.
Different e-cigarette brands are engineered differently. The differences include the appearance, the nature of nicotine solution, the capacity of the cartridge containing the solution, the nature of the heating element, and size and type of battery. Propylene glycol or glycerin are primary used as solvents for nicotine. Solutions may contain just one or both solvents mixed with water. Various additives and flavorings are commonly added to nicotine solution, including fruit and candy flavors, ethyl alcohol, non-nicotine pharmacologically active compounds and stabilizers. The heating elements are usually thin (filament) wire made with various metals (nickel, chromium, copper coated with silver).
Toxicants in e-cigarettes
Distributors of e–cigarettes promote the product as completely free of harmful substances. However, nicotine solutions used in e-cigarettes vary with respect to concentrations of toxicants, and the quality control in e-cigarette manufacturing is questionable. Although a number of toxicants have been identified in e-cigarette vapors, the levels of these toxicants are orders of magnitude lower than those found in cigarette smoke, but higher than those found in Nicotine Replacement Therapy (NRT) products.
We generated vapors from 12 brands of e-cigarettes and the reference product, the medicinal nicotine inhaler, in controlled conditions using a modified smoking machine. The selected toxic compounds were extracted from vapors and analyzed with chromatographic and spectroscopy methods. Following carcinogens have been identified in e-cigarette vapor: formaldehyde, acetaldehyde, acrolein, tobacco specific nitrosamines (TSNAs), and some heavy metals. The levels of potentially toxic compounds in e-cigarette vapor were found to be from 9-fold to almost 450-fold lower compared with smoke from conventional cigarettes.
Williams et al. tested the hypothesis that vapors from e-cigarette contain metals derived from various components in the product. The e-cigarette vapors contained particles &gt;1 μm comprised of tin, silver, iron, nickel, aluminum, and silicate and nanoparticles (&lt;100 nm) of tin, chromium and nickel. The concentrations of nine of eleven elements in e-cigarette vapors were higher than or equal to the corresponding concentrations in conventional cigarette smoke. Many of the elements identified in vapors are known to cause respiratory distress and disease. The presence of metal and silicate particles in vapors demonstrates the need for improved quality control in e-cigarette design and manufacture.
Cytotoxicity of e-cigarettes
Some studies suggest that that vapors from e-cigarette are significantly less cytotoxic compared to tobacco smoke. Bahl et al. compared the cytotoxicity of e-cigarette refill fluids using embryonic and adult cells and examines the chemical characteristics of refill fluids. Refill solutions were tested on various cell lines. The results showed that all products from one company were cytotoxic to human embryonic stem cells and mouse neural stem cells, but non-cytotoxic to human pulmonary fibroblasts. Cytotoxicity was not due to nicotine, but was correlated with the number and concentration of chemicals used to flavor fluids.
Romagna et al. evaluated the cytotoxic potential of 21 e-cigarette liquids compared to the effects of cigarette smoke. In this study, cytotoxicity was evaluated by activating an e-cigarette device, evaporating and extracting the nicotine solution in culture medium with murine fibroblasts. Tobacco smoke extract from one cigarette was also produced. The study indicated that e-cigarette vapor is significantly less cytotoxic compared tobacco smoke; however, the results have not been validated by clinical studies yet.
Exposure reduction with e-cigarettes
One study found that after switching from tobacco to e-cigarettes nicotine exposure is unchanged while exposure to selected toxicants is substantially reduced. We recruited 20 cigarette smokers and provided all participants with e-cigarettes with cartridges containing nicotine. Smokers were asked to substitute their regular tobacco cigarettes with e-cigarettes for two weeks. Subjects provided urine samples at the day of switching (baseline) and after one and two weeks of using e-cigarettes. We analyzed urine for nicotine metabolites, NNAL (metabolite of tobacco-specific carcinogenic nitrosamine NNK), and hydroxyalkyl mercapturic acids (HAMAs, the main urinary metabolites of several alkylating substances that possess a carcinogenic potential). We found that all subjects reported significant reduction of tobacco cigarettes smoked during the study; number of tobacco cigarettes smoked per day decreased from 16.2 to 0.6 and exhaled CO decreased from 15.6 to 4.2 ppm after two weeks of using e-cigarettes. There were no significant changes in urine total nicotine metabolites (p=0.89). Urine levels of NNAL decreased by 64% (p&lt;0.05). The average reductions in HAMAs varied from 54% (metabolite of propylene oxide) to 89% (metabolite of 1,3-butadiene)(p&lt;0.05).
Conclusions
Although it cannot be said that currently marketed e-cigarettes are safe, e-cigarette vapor is likely to be much less toxic than cigarette smoke. They likely pose less direct hazard to the individual smoker than tobacco cigarettes and might help smokers quit smoking or reduce harm by smoking fewer tobacco cigarettes. The use of e-cigarettes as a harm reduction strategy among cigarette smokers who are unable to quit, warrants further study. Further research is needed to evaluate long term effects of switching, including the health effects of continued use of e-cigarettes.
Citation Format: Goniewicz L. Maciej. Carcinogens and toxicants in e-cigarettes. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr SS02-03.