RSS-Feed abonnieren
DOI: 10.1055/a-2260-5003
Gesundheitsschädliche Wirkungen von Aromen in E-Zigaretten
Harmful health effects of flavors in e-cigarettesZusammenfassung
Hintergrund Fast alle E-Zigaretten enthalten Aromastoffe, die das Produkt attraktiver machen. Bei der Bewertung von E-Zigaretten in Bezug auf die Gesundheit spielten Aromen bisher eine untergeordnete Rolle.
Methode Selektive Literaturrecherche in PubMed, ergänzt durch rechtliche Bestimmungen zur Nutzung von Aromen in E-Zigaretten.
Ergebnisse Aromen erleichtern den Einstieg in den E-Zigarettenkonsum und haben eine konsumfördernde Wirkung. Durch tieferes Inhalieren werden die Nikotinaufnahme und die Aufnahme toxischer Substanzen aus dem E-Zigaretten-Liquid gesteigert. Für einige Aromen wurden pathologische Wirkungen, additiv zu anderen toxischen Bestandteilen der E-Zigarette, nachgewiesen. Für die große Mehrzahl der in E-Zigaretten enthaltenen Aromen liegen bisher keine toxikologischen Analysen vor.
Schlussfolgerungen Die nachgewiesene konsumfördernde Wirkung und die aus präklinischen Daten extrapolierbaren Gesundheitsrisiken sind bedeutsam für die politische Diskussion eines Verbots von Aromen auch für E-Zigaretten, analog zu dem bereits geltenden Verbot von Aromen in Tabakerzeugnissen.
Abstract
Background Almost all e-cigarettes contain flavorings that make the product more attractive. In the evaluation of e-cigarettes on health, flavors have so far played a subordinate role.
Method Selective literature search in PubMed, supplemented by legal regulations on the use of flavors in e-cigarettes.
Results Flavors make it easier to start using e-cigarettes and have a consumption-promoting effect. Deeper inhalation increases nicotine uptake and the absorption of toxic substances from the e-cigarette liquid. For some flavors, pathological effects have been demonstrated in addition to other toxic components of the e-cigarette. To date, no toxicological analyses are available for the vast majority of flavors contained in e-cigarettes.
Conclusions The proven consumption-promoting effect and the health risks that can be extrapolated from preclinical data are significant for the political discussion of a ban on flavors for e-cigarettes, analogous to the ban on flavors in tobacco products already in force.
* geteilte Erstautorenschaft.
** Mitglied der Task Force Tabakentwöhnung der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP).
Publikationsverlauf
Artikel online veröffentlicht:
08. März 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
Literatur
- 1 Rauschert C, Möckl J, Seitz NN. et al. The Use of Psychoactive Substances in Germany. Dtsch Arztebl Int 2022; 119: 527-534 DOI: 10.3238/arztebl.m2022.0244.
- 2 Hanewinkel R, Hansen J. Konsum von Tabakzigaretten, E-Zigaretten und Wasserpfeifen bei Kindern und Jugendlichen. Ergebnisse des Präventionsradars von 2016 bis 2023. Pneumologie 2023; 77: 1001-1008 DOI: 10.1055/a-2146-7087.
- 3 WHO. WHO report on the global tobacco epidemic 2021: addressing new and emerging products. Geneva: WHO; 2021
- 4 Ma S, Qiu Z, Yang Q. et al. Expanding the E-Liquid Flavor Wheel: Classification of Emerging E-Liquid Flavors in Online Vape Shops. Int J Environ Res Public Health 2022; 19 DOI: 10.3390/ijerph192113953.
- 5 European C, Directorate-General for C, Directorate-General for H. et al. Attitudes of Europeans towards tobacco and electronic cigarettes – Report. European Commission. 2021. DOI: 10.2875/490366
- 6 Schröder K, Escher SE, Hoffmann-Dörr S. et al. Evaluation of route-to-route extrapolation factors based on assessment of repeated dose toxicity studies compiled in the database RepDose(®). Toxicol Lett 2016; 261: 32-40 DOI: 10.1016/j.toxlet.2016.08.013.
- 7 Staal Y, Havermans A, van Nierop L. et al. Conceptual model for the evaluation of attractiveness, addictiveness and toxicity of tobacco and related products: The example of JUUL e-cigarettes. Regul Toxicol Pharmacol 2021; 127: 105077 DOI: 10.1016/j.yrtph.2021.105077.
- 8 Pisinger C, Godtfredsen N, Bender AM. A conflict of interest is strongly associated with tobacco industry-favourable results, indicating no harm of e-cigarettes. Prev Med 2019; 119: 124-131 DOI: 10.1016/j.ypmed.2018.12.011.
- 9 Asfar T, Jebai R, Li W. et al. Risk and safety profile of electronic nicotine delivery systems (ENDS): an umbrella review to inform ENDS health communication strategies. Tob Control 2022; DOI: 10.1136/tc-2022-057495.
- 10 Feron VJ, Til HP, de Vrijer F. et al. Aldehydes: occurrence, carcinogenic potential, mechanism of action and risk assessment. Mutat Res 1991; 259: 363-385 DOI: 10.1016/0165-1218(91)90128-9.
- 11 DeJarnett N, Conklin DJ, Riggs DW. et al. Acrolein exposure is associated with increased cardiovascular disease risk. J Am Heart Assoc 2014; 3 DOI: 10.1161/jaha.114.000934.
- 12 Behar RZ, Luo W, McWhirter KJ. et al. Analytical and toxicological evaluation of flavor chemicals in electronic cigarette refill fluids. Sci Rep 2018; 8: 8288 DOI: 10.1038/s41598-018-25575-6.
- 13 Pereira EJ, Sim L, Driver H. et al. The effect of inhaled menthol on upper airway resistance in humans: a randomized controlled crossover study. Can Respir J 2013; 20: e1-e4 DOI: 10.1155/2013/383019.
- 14 Merecz-Sadowska A, Sitarek P, Zielinska-Blizniewska H. et al. A Summary of In Vitro and In Vivo Studies Evaluating the Impact of E-Cigarette Exposure on Living Organisms and the Environment. Int J Mol Sci 2020; 21: 652 DOI: 10.3390/ijms21020652.
- 15 Madsen C, Würtzen G, Carstensen J. Short-term toxicity study in rats dosed with menthone. Toxicol Lett 1986; 32: 147-152 DOI: 10.1016/0378-4274(86)90061-5.
- 16 Lin AH, Liu MH, Ko HK. et al. Menthol Cigarette Smoke Induces More Severe Lung Inflammation Than Non-menthol Cigarette Smoke Does in Mice With Subchronic Exposure – Role of TRPM8. Front Physiol 2018; 9: 1817 DOI: 10.3389/fphys.2018.01817.
- 17 Sabnis AS, Shadid M, Yost GS. et al. Human lung epithelial cells express a functional cold-sensing TRPM8 variant. Am J Respir Cell Mol Biol 2008; 39: 466-474 DOI: 10.1165/rcmb.2007-0440OC.
- 18 Leventhal AM, Tackett AP, Whitted L. et al. Ice flavours and non-menthol synthetic cooling agents in e-cigarette products: a review. Tob Control 2023; 32: 769-777 DOI: 10.1136/tobaccocontrol-2021-057073.
- 19 Wang M, Zhang Y, Xu M. et al. Roles of TRPA1 and TRPV1 in cigarette smoke -induced airway epithelial cell injury model. Free Radic Biol Med 2019; 134: 229-238 DOI: 10.1016/j.freeradbiomed.2019.01.004.
- 20 Effah F, Taiwo B, Baines D. et al. Pulmonary effects of e-liquid flavors: a systematic review. J Toxicol Environ Health B Crit Rev 2022; 25: 343-371 DOI: 10.1080/10937404.2022.2124563.
- 21 Cooper SY, Willis CV, Richardson MR. et al. Chemical Flavorants in Vaping Products Alter Neurobiology in a Sex-Dependent Manner to Promote Vaping-Related Behaviors. J Neurosci 2023; 43: 1360-1374 DOI: 10.1523/jneurosci.0755-22.2022.
- 22 Wong AL, McElroy SM, Robinson JM. et al. Flavor-specific enhancement of electronic cigarette liquid consumption and preference in mice. Drug Alcohol Depend 2020; 211: 107995 DOI: 10.1016/j.drugalcdep.2020.107995.
- 23 Patten T, Johnson NL, Shaw JK. et al. Strawberry Additive Increases Nicotine Vapor Sampling and Systemic Exposure But Does Not Enhance Pavlovian-Based Nicotine Reward in Mice. eNeuro 2023; 10 DOI: 10.1523/eneuro.0390-22.2023.
- 24 Akinola LS, Rahman Y, Ondo O. et al. Impact of tobacco flavoring on oral nicotine consumption in C57BL/6J mice. Drug Alcohol Depend 2022; 241: 109685 DOI: 10.1016/j.drugalcdep.2022.109685.
- 25 Xu Z, Tian Y, Li AX. et al. Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings. Front Mol Neurosci 2022; 15: 800406 DOI: 10.3389/fnmol.2022.800406.
- 26 Patten T, Dreier A, Herman RJ. et al. Exposure to fruit-flavoring during adolescence increases nicotine consumption and promotes dose escalation. Neuropharmacology 2021; 195: 108672 DOI: 10.1016/j.neuropharm.2021.108672.
- 27 Goldenson NI, Leventhal AM, Simpson KA. et al. A Review of the Use and Appeal of Flavored Electronic Cigarettes. Curr Addict Rep 2019; 6: 98-113 DOI: 10.1007/s40429-019-00244-4.
- 28 Russell C, McKeganey N, Dickson T. et al. Changing patterns of first e-cigarette flavor used and current flavors used by 20,836 adult frequent e-cigarette users in the USA. Harm Reduct J 2018; 15: 33 DOI: 10.1186/s12954-018-0238-6.
- 29 Pang RD, Goldenson NI, Kirkpatrick M. et al. Sex differences in the appeal of flavored e-cigarettes among young adult e-cigarette users. Psychol Addict Behav 2020; 34: 303-307 DOI: 10.1037/adb0000548.
- 30 Bono RS, Barnes AJ, Lester RC. et al. Effects of Electronic Cigarette Liquid Flavors and Modified Risk Messages on Perceptions and Subjective Effects of E-Cigarettes. Health Educ Behav 2019; 46: 197-203 DOI: 10.1177/1090198118806965.
- 31 Audrain-McGovern J, Strasser AA, Wileyto EP. The impact of flavoring on the rewarding and reinforcing value of e-cigarettes with nicotine among young adult smokers. Drug Alcohol Depend 2016; 166: 263-267 DOI: 10.1016/j.drugalcdep.2016.06.030.
- 32 Romijnders K, van Osch L, de Vries H. et al. Perceptions and Reasons Regarding E-Cigarette Use among Users and Non-Users: A Narrative Literature Review. Int J Environ Res Public Health 2018; 15 DOI: 10.3390/ijerph15061190.
- 33 Audrain-McGovern J, Rodriguez D, Pianin S. et al. Initial e-cigarette flavoring and nicotine exposure and e-cigarette uptake among adolescents. Drug Alcohol Depend 2019; 202: 149-155 DOI: 10.1016/j.drugalcdep.2019.04.037.
- 34 Garrison KA, O'Malley SS, Gueorguieva R. et al. A fMRI study on the impact of advertising for flavored e-cigarettes on susceptible young adults. Drug Alcohol Depend 2018; 186: 233-241 DOI: 10.1016/j.drugalcdep.2018.01.026.
- 35 Cadham CJ, Liber AC, Sánchez-Romero LM. et al. The actual and anticipated effects of restrictions on flavoured electronic nicotine delivery systems: a scoping review. BMC Public Health 2022; 22: 2128 DOI: 10.1186/s12889-022-14440-x.
- 36 Litt MD, Duffy V, Oncken C. Cigarette smoking and electronic cigarette vaping patterns as a function of e-cigarette flavourings. Tob Control 2016; 25: ii67-ii72 DOI: 10.1136/tobaccocontrol-2016-053223.
- 37 Bold KW, Krishnan-Sarin S, O'Malley S. et al. Examining associations of e-cigarette flavour restrictions with e-cigarette use and success quitting smoking among US adults. Tob Control 2022; 31: s184-s186 DOI: 10.1136/tobaccocontrol-2022-057458.
- 38 Liber AC, Knoll M, Cadham CJ. et al. The role of flavored electronic nicotine delivery systems in smoking cessation: A systematic review. Drug Alcohol Depend Rep 2023; 7: 100143 DOI: 10.1016/j.dadr.2023.100143.
- 39 Gerloff J, Sundar IK, Freter R. et al. Inflammatory Response and Barrier Dysfunction by Different e-Cigarette Flavoring Chemicals Identified by Gas Chromatography-Mass Spectrometry in e-Liquids and e-Vapors on Human Lung Epithelial Cells and Fibroblasts. Appl In Vitro Toxicol 2017; 3: 28-40 DOI: 10.1089/aivt.2016.0030.
- 40 Muthumalage T, Prinz M, Ansah KO. et al. Inflammatory and Oxidative Responses Induced by Exposure to Commonly Used e-Cigarette Flavoring Chemicals and Flavored e-Liquids without Nicotine. Front Physiol 2017; 8: 1130 DOI: 10.3389/fphys.2017.01130.
- 41 Lee WH, Ong SG, Zhou Y. et al. Modeling Cardiovascular Risks of E-Cigarettes With Human-Induced Pluripotent Stem Cell-Derived Endothelial Cells. J Am Coll Cardiol 2019; 73: 2722-2737 DOI: 10.1016/j.jacc.2019.03.476.
- 42 Been T, Traboulsi H, Paoli S. et al. Differential impact of JUUL flavors on pulmonary immune modulation and oxidative stress responses in male and female mice. Arch Toxicol 2022; 96: 1783-1798 DOI: 10.1007/s00204-022-03269-3.
- 43 Moshensky A, Brand CS, Alhaddad H. et al. Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice. Elife 2022; 11 DOI: 10.7554/eLife.67621.
- 44 Abouassali O, Chang M, Chidipi B. et al. In vitro and in vivo cardiac toxicity of flavored electronic nicotine delivery systems. Am J Physiol Heart Circ Physiol 2021; 320: H133-H143 DOI: 10.1152/ajpheart.00283.2020.
- 45 Han H, Peng G, Meister M. et al. Electronic Cigarette Exposure Enhances Lung Inflammatory and Fibrotic Responses in COPD Mice. Front Pharmacol 2021; 12: 726586 DOI: 10.3389/fphar.2021.726586.
- 46 Cahill KM, Johnson TK, Perveen Z. et al. In utero exposures to mint-flavored JUUL aerosol impair lung development and aggravate house dust mite-induced asthma in adult offspring mice. Toxicology 2022; 477: 153272 DOI: 10.1016/j.tox.2022.153272.
- 47 Noël A, Yilmaz S, Farrow T. et al. Sex-Specific Alterations of the Lung Transcriptome at Birth in Mouse Offspring Prenatally Exposed to Vanilla-Flavored E-Cigarette Aerosols and Enhanced Susceptibility to Asthma. Int J Environ Res Public Health 2023; 20 DOI: 10.3390/ijerph20043710.
- 48 Muthumalage T, Rahman I. Pulmonary immune response regulation, genotoxicity, and metabolic reprogramming by menthol- and tobacco-flavored e-cigarette exposures in mice. Toxicol Sci 2023; 193: 146-165 DOI: 10.1093/toxsci/kfad033.
- 49 Szafran BN, Pinkston R, Perveen Z. et al. Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model. Int J Mol Sci 2020; 21 DOI: 10.3390/ijms21176022.
- 50 Glynos C, Bibli SI, Katsaounou P. et al. Comparison of the effects of e-cigarette vapor with cigarette smoke on lung function and inflammation in mice. Am J Physiol Lung Cell Mol Physiol 2018; 315: L662-L672 DOI: 10.1152/ajplung.00389.2017.
- 51 Chapman DG, Casey DT, Ather JL. et al. The Effect of Flavored E-cigarettes on Murine Allergic Airways Disease. Sci Rep 2019; 9: 13671 DOI: 10.1038/s41598-019-50223-y.
- 52 Rubinstein ML, Delucchi K, Benowitz NL. et al. Adolescent Exposure to Toxic Volatile Organic Chemicals From E-Cigarettes. Pediatrics 2018; 141 DOI: 10.1542/peds.2017-3557.
- 53 IARC. Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, France: International Agency for Research on Cancer; 1999
- 54 Cunningham FH, Fiebelkorn S, Johnson M. et al. A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants. Food Chem Toxicol 2011; 49: 2921-2933 DOI: 10.1016/j.fct.2011.07.019.
- 55 Chandra D, Bogdanoff RF, Bowler RP. et al. Electronic cigarette menthol flavoring is associated with increased inhaled micro and sub-micron particles and worse lung function in combustion cigarette smokers. Respir Res 2023; 24: 108 DOI: 10.1186/s12931-023-02410-9.
- 56 Behar RZ, Wang Y, Talbot P. Comparing the cytotoxicity of electronic cigarette fluids, aerosols and solvents. Tob Control 2018; 27: 325-333 DOI: 10.1136/tobaccocontrol-2016-053472.
- 57 Leigh NJ, Lawton RI, Hershberger PA. et al. Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS). Tob Control 2016; 25: ii81-ii87 DOI: 10.1136/tobaccocontrol-2016-053205.
- 58 Lucas JH, Muthumalage T, Wang Q. et al. E-Liquid Containing a Mixture of Coconut, Vanilla, and Cookie Flavors Causes Cellular Senescence and Dysregulated Repair in Pulmonary Fibroblasts: Implications on Premature Aging. Front Physiol 2020; 11: 924 DOI: 10.3389/fphys.2020.00924.
- 59 Noël A, Hossain E, Perveen Z. et al. Sub-ohm vaping increases the levels of carbonyls, is cytotoxic, and alters gene expression in human bronchial epithelial cells exposed at the air-liquid interface. Respir Res 2020; 21: 305 DOI: 10.1186/s12931-020-01571-1.
- 60 O'Farrell HE, Brown R, Brown Z. et al. E-cigarettes induce toxicity comparable to tobacco cigarettes in airway epithelium from patients with COPD. Toxicol In Vitro 2021; 75: 105204 DOI: 10.1016/j.tiv.2021.105204.
- 61 Pinkston R, Zaman H, Hossain E. et al. Cell-specific toxicity of short-term JUUL aerosol exposure to human bronchial epithelial cells and murine macrophages exposed at the air-liquid interface. Respir Res 2020; 21: 269 DOI: 10.1186/s12931-020-01539-1.
- 62 Cooper SY, Akers AT, Henderson BJ. Green Apple e-Cigarette Flavorant Farnesene Triggers Reward-Related Behavior by Promoting High-Sensitivity nAChRs in the Ventral Tegmental Area. eNeuro 2020; 7 DOI: 10.1523/eneuro.0172-20.2020.
- 63 Biswas L, Harrison E, Gong Y. et al. Enhancing effect of menthol on nicotine self-administration in rats. Psychopharmacology (Berl) 2016; 233: 3417-3427 DOI: 10.1007/s00213-016-4391-x.
- 64 Henderson BJ, Wall TR, Henley BM. et al. Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability. Neuropsychopharmacology 2017; 42: 2285-2291 DOI: 10.1038/npp.2017.72.
- 65 Wang T, Wang B, Chen H. Menthol facilitates the intravenous self-administration of nicotine in rats. Front Behav Neurosci 2014; 8: 437 DOI: 10.3389/fnbeh.2014.00437.