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      Considerations on dosimetry for in vitro assessment of e-cigarette toxicity

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          Abstract

          Electronic cigarettes (or e-cigarettes) can be used as smoking cessation aid. Some studies tend to show that they are less hazardous than tobacco cigarettes, even if it does not mean they are completely safe. The huge variation in study designs assessing in vitro toxicity of e-cigarettes aerosol makes it difficult to make comparisons and draw robust and irrefutable conclusions. In this paper, we review this heterogeneity (in terms of e-cigarette products, biological models, and exposure conditions) with a special focus on the wide disparity in the doses used as well as in the way they are expressed. Finally, we discuss the major issue of dosimetry and show how dosimetry tools enable to align data between different exposure systems or data from different laboratories and therefore allow comparisons to help further exploring the risk potential of e-cigarettes.

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          Most cited references72

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          A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy

          E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine products approved as smoking-cessation treatments.
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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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              Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages

              Objective Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function. Methods AMs were treated with ECVC and nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species (ROS) release and bacterial phagocytosis were assessed. Results Macrophage culture with ECL or ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL and resulted in increased apoptosis and necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide 3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage viability and apoptosis. Secretion of interleukin 6, tumour necrosis factor α, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9 was significantly increased following ECVC challenge. Treatment with the anti-oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC to levels not significantly different from baseline and restored phagocytic function. Conclusions ECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. While further research is needed to fully understand the effects of e-cigarette exposure in humans in vivo, we caution against the widely held opinion that e-cigarettes are safe.
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                Author and article information

                Contributors
                vforest@emse.fr
                Journal
                Respir Res
                Respir Res
                Respiratory Research
                BioMed Central (London )
                1465-9921
                1465-993X
                17 December 2022
                17 December 2022
                2022
                : 23
                : 358
                Affiliations
                GRID grid.7429.8, ISNI 0000000121866389, Mines Saint-Etienne, , Univ Jean Monnet, INSERM, U1059 Sainbiose, Centre CIS, ; 158 Cours Fauriel, CS 62362, 42023 Saint-Etienne Cedex 2, France
                Article
                2286
                10.1186/s12931-022-02286-1
                9758947
                36528600
                7ab66bde-8e24-428f-821b-c43e7d7aa162
                © The Author(s) 2022

                Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 30 August 2022
                : 9 December 2022
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Respiratory medicine
                in vitro inhalation toxicology,e-cigarette toxicity,dosimetry,physiological doses

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