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      High concentrations of flavor chemicals are present in electronic cigarette refill fluids

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          Abstract

          We characterized the flavor chemicals in a broad sample of commercially available electronic cigarette (EC) refill fluids that were purchased in four different countries. Flavor chemicals in 277 refill fluids were identified and quantified by gas chromatography-mass spectrometry, and two commonly used flavor chemicals were tested for cytotoxicity with the MTT assay using human lung fibroblasts and epithelial cells. About 85% of the refill fluids had total flavor concentrations >1 mg/ml, and 37% were >10 mg/ml (1% by weight). Of the 155 flavor chemicals identified in the 277 refill fluids, 50 were present at ≥1 mg/ml in at least one sample and 11 were ≥10 mg/ml in 54 of the refill fluids. Sixty-one% (170 out of 277) of the samples contained nicotine, and of these, 56% had a total flavor chemical/nicotine ratio >2. Four chemicals were present in 50% (menthol, triacetin, and cinnamaldehyde) to 80% (ethyl maltol) of the samples. Some products had concentrations of menthol (“Menthol Arctic”) and ethyl maltol (“No. 64”) that were 30 times (menthol) and 100 times (ethyl maltol) their cytotoxic concentration. One refill fluid contained cinnamaldehyde at ~34% (343 mg/ml), more than 100,000 times its cytotoxic level. High concentrations of some flavor chemicals in EC refill fluids are potentially harmful to users, and continued absence of any regulations regarding flavor chemicals in EC fluids will likely be detrimental to human health.

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          Most cited references39

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          A systematic review of health effects of electronic cigarettes.

          To provide a systematic review of the existing literature on health consequences of vaporing of electronic cigarettes (ECs). Search in: PubMed, EMBASE and CINAHL. Original publications describing a health-related topic, published before 14 August 2014. PRISMA recommendations were followed. We identified 1101 studies; 271 relevant after screening; 94 eligible. We included 76 studies investigating content of fluid/vapor of ECs, reports on adverse events and human and animal experimental studies. Serious methodological problems were identified. In 34% of the articles the authors had a conflict of interest. Studies found fine/ultrafine particles, harmful metals, carcinogenic tobacco-specific nitrosamines, volatile organic compounds, carcinogenic carbonyls (some in high but most in low/trace concentrations), cytotoxicity and changed gene expression. Of special concern are compounds not found in conventional cigarettes, e.g. propylene glycol. Experimental studies found increased airway resistance after short-term exposure. Reports on short-term adverse events were often flawed by selection bias. Due to many methodological problems, severe conflicts of interest, the relatively few and often small studies, the inconsistencies and contradictions in results, and the lack of long-term follow-up no firm conclusions can be drawn on the safety of ECs. However, they can hardly be considered harmless. Copyright © 2014. Published by Elsevier Inc.
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            Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation

            Introduction E-cigarettes are largely unregulated and internet sales are substantial. This study examines how the online market for e-cigarettes has changed over time: in product design and in marketing messages appearing on websites. Methods Comprehensive internet searches of English-language websites from May–August 2012 and December 2013–January 2014 identified brands, models, flavours, nicotine strengths, ingredients and product claims. Brands were divided into older and newer groups (by the two searches) for comparison. Results By January 2014 there were 466 brands (each with its own website) and 7764 unique flavours. In the 17 months between the searches, there was a net increase of 10.5 brands and 242 new flavours per month. Older brands were more likely than newer brands to offer cigalikes (86.9% vs 52.1%, p<0.01), and newer brands more likely to offer the more versatile eGos and mods (75.3% vs 57.8%, p<0.01). Older brands were significantly more likely to claim that they were healthier and cheaper than cigarettes, were good substitutes where smoking was banned and were effective smoking cessation aids. Newer brands offered more flavours per brand (49 vs 32, p<0.01) and were less likely to compare themselves with conventional cigarettes. Conclusions The number of e-cigarette brands is large and has been increasing. Older brands tend to highlight their advantages over conventional cigarettes while newer brands emphasise consumer choice in multiple flavours and product versatility. These results can serve as a benchmark for future research on the impact of upcoming regulations on product design and advertising messages of e-cigarettes.
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              Vapors Produced by Electronic Cigarettes and E-Juices with Flavorings Induce Toxicity, Oxidative Stress, and Inflammatory Response in Lung Epithelial Cells and in Mouse Lung

              Oxidative stress and inflammatory response are the key events in the pathogenesis of chronic airway diseases. The consumption of electronic cigarettes (e-cigs) with a variety of e-liquids/e-juices is alarmingly increasing without the unrealized potential harmful health effects. We hypothesized that electronic nicotine delivery systems (ENDS)/e-cigs pose health concerns due to oxidative toxicity and inflammatory response in lung cells exposed to their aerosols. The aerosols produced by vaporizing ENDS e-liquids exhibit oxidant reactivity suggesting oxidants or reactive oxygen species (OX/ROS) may be inhaled directly into the lung during a “vaping” session. These OX/ROS are generated through activation of the heating element which is affected by heating element status (new versus used), and occurs during the process of e-liquid vaporization. Unvaporized e-liquids were oxidative in a manner dependent on flavor additives, while flavors containing sweet or fruit flavors were stronger oxidizers than tobacco flavors. In light of OX/ROS generated in ENDS e-liquids and aerosols, the effects of ENDS aerosols on tissues and cells of the lung were measured. Exposure of human airway epithelial cells (H292) in an air-liquid interface to ENDS aerosols from a popular device resulted in increased secretion of inflammatory cytokines, such as IL-6 and IL-8. Furthermore, human lung fibroblasts exhibited stress and morphological change in response to treatment with ENDS/e-liquids. These cells also secrete increased IL-8 in response to a cinnamon flavored e-liquid and are susceptible to loss of cell viability by ENDS e-liquids. Finally, exposure of wild type C57BL/6J mice to aerosols produced from a popular e-cig increase pro-inflammatory cytokines and diminished lung glutathione levels which are critical in maintaining cellular redox balance. Thus, exposure to e-cig aerosols/juices incurs measurable oxidative and inflammatory responses in lung cells and tissues that could lead to unrealized health consequences.
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                Author and article information

                Contributors
                talbot@ucr.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                21 February 2019
                21 February 2019
                2019
                : 9
                : 2468
                Affiliations
                [1 ]ISNI 0000 0001 2222 1582, GRID grid.266097.c, Environmental Toxicology Graduate Program, , University of California, ; Riverside, CA 92521 United States
                [2 ]ISNI 0000 0001 2222 1582, GRID grid.266097.c, Department of Molecular, Cell and Systems Biology, , University of California, ; Riverside, CA 92521 United States
                [3 ]ISNI 0000 0001 1087 1481, GRID grid.262075.4, Department of Civil and of Environmental Engineering, , Portland State University, ; PO Box 751, Portland, OR 97207-0751 United States
                Article
                39550
                10.1038/s41598-019-39550-2
                6385236
                30792477
                f779ad1b-b524-47e0-9b7a-82cd91f8caf3
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 May 2018
                : 18 January 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000026, U.S. Department of Health &amp; Human Services | NIH | National Institute on Drug Abuse (NIDA);
                Award ID: R01DA036493-02-S1
                Award ID: R01DA036493-04-S1
                Award Recipient :
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