Flavor-Toxicant Correlation in E-cigarettes: A Meta-Analysis

Abstract

Flavors in electronic cigarette (ECIG) liquids may increase ECIG aerosol toxicity via intact distillation or chemical transformation. For this report, we performed a meta-analysis of the literature to categorize the compounds found in flavored ECIG liquids into a few chemical classes and to predict their possible chemical transformations upon ECIG liquid aerosolization. This analysis allowed us to propose specific correlations between flavoring chemicals and aerosol toxicants. A literature search was conducted in November 2019 using PubMed. Keywords included terms related to ECIGs and flavors. Studies were included if they reported chemical ingredients of flavored liquids and clearly stated the commercial names of these liquids. The obtained data were visualized on a network diagram to show the common chemical compounds identified in flavored ECIG liquids and categorize them into different chemical classes. The systematic literature review included a total of 11 articles. Analysis of the data reported gave a total of 189 flavored liquids and 173 distinct chemical compounds that were categorized into 22 chemical classes according to their functional groups. The subsequent prediction of chemical transformations of these functional groups highlighted the possible correlation of flavor compounds to aerosol toxicants.

Emerging ENDS products and challenges in tobacco control toxicity research

“…Typically, flavourings promote the production of free radicals and elevated levels of HPHCs during vaping 52. However, individual ENDS flavourants induce toxicity in the respiratory tract, cardiovascular and circulatory systems, and in the skeletal system and skin 53.…”

Evaluation of Inhalation Exposures and Potential Health Impacts of Ingredient Mixtures Using in vitro to in vivo Extrapolation

“…Nicotine is considered the active ingredient in the e-liquid while flavors are added to accommodate user’s sensory preference. Hundreds of unique flavor ingredients are identified based on reviews of e-liquids on the market ( Hua et al, 2019 ; Krüsemann et al, 2021 ; Salam et al, 2020 ), with acids (such as lactic, benzoic, levulinic, salicyclic, malic, and tartaric acids) in some EC products converting nicotine to nicotine salts ( Harvanko et al, 2020 ). The combinations of these ingredients lead to a myriad of e-liquids in the market.…”

Characterizing the Chemical Landscape in Commercial E-Cigarette Liquids and Aerosols by Liquid Chromatography–High-Resolution Mass Spectrometry

“…E-liquid typically contains propylene glycol (PG), vegetable glycerin (VG), nicotine, flavorants, and other chemicals, although information about chemical additives is not typically disclosed by manufacturers. , Thus, aerosols inhaled during e-cig use are complex mixtures of solvents and additives as well as compounds formed during the vaping process . Multiple generations of e-cig devices and a wide variety of e-liquid formulations are commercially available, and new e-cig devices and liquids are rapidly proliferating, including over 8000 e-liquid flavors. , While the FDA enacted some sales bans in the United States in 2020, the policies only restrict a subset of flavors and products. − As a result of the heterogeneity, complexity, and lack of transparency associated with e-cig products, exposures from e-cig use are poorly understood and their health effects difficult to predict, as exemplified by the “e-cigarette, or vaping, product use associated lung injury” (EVALI) outbreak of 2019 . Thus, there is a need for the development of new analytical approaches that can identify a wide spectrum of chemicals that are present in e-cig liquids and aerosols.…”

“…Numerous known toxicants have been identified and measured in e-cig liquids and aerosols to date, including metals, carbonyls, free radicals, and phthalates. ,, Most existing studies investigating e-cig exposures have focused on quantifying specific, known constituents in e-liquids, especially those present at high levels in combustible cigarettes such as tobacco alkaloids, polycyclic aromatic hydrocarbons, and formaldehyde. ,, However, a growing number of studies have investigated chemicals unique to e-cigs, including compounds that are formed by thermal decomposition of e-liquid solvents (PG and VG), ,, contaminants from e-liquid packaging and e-cig device components, , and flavorants. ,− …”

“…6 Multiple generations of ecig devices and a wide variety of e-liquid formulations are commercially available, and new e-cig devices and liquids are rapidly proliferating, 1 including over 8000 e-liquid flavors. 7,8 While the FDA enacted some sales bans in the United States in 2020, the policies only restrict a subset of flavors and products. 9−11 As a result of the heterogeneity, complexity, and lack of transparency associated with e-cig products, exposures from e-cig use are poorly understood and their health effects difficult to predict, as exemplified by the "ecigarette, or vaping, product use associated lung injury" (EVALI) outbreak of 2019.…”