Abstract
Electronic (e-)cigarettes have emerged in recent years as putative alternative to conventional tobacco cigarettes. These products do not contain typical carcinogens that are present in tobacco smoke, due to the lack of combustion. However, besides nicotine, hazards can also arise from other constituents of liquids, such as solvents, flavors, additives and contaminants. In this study, we have analyzed 28 liquids of seven manufacturers purchased in Germany. We confirm the presence of a wide range of flavors to enhance palatability. Although glycerol and propylene glycol were detected in all samples, these solvents had been replaced by ethylene glycol as dominant compound in five products. Ethylene glycol is associated with markedly enhanced toxicological hazards when compared to conventionally used glycerol and propylene glycol. Additional additives, such as coumarin and acetamide, that raise concerns for human health were detected in certain samples. Ten out of 28 products had been declared “free-of-nicotine” by the manufacturer. Among these ten, seven liquids were identified containing nicotine in the range of 0.1–15 µg/ml. This suggests that “carry over” of ingredients may occur during the production of cartridges. We have further analyzed the formation of carbonylic compounds in one widely distributed nicotine-free brand. Significant amounts of formaldehyde, acetaldehyde and propionaldehyde were only found at 150 °C by headspace GC–MS analysis. In addition, an enhanced formation of aldehydes was found in defined puff fractions, using an adopted machine smoking protocol. However, this effect was delayed and only observed during the last third of the smoking procedure. In the emissions of these fractions, which represent up to 40 % of total vapor volume, similar levels of formaldehyde were detected when compared to conventional tobacco cigarettes. By contrast, carbonylic compounds were hardly detectable in earlier collected fractions. Our data demonstrate the necessity of standardized machine smoking protocols to reliably address putative risks of e-cigarettes for consumers.
References
Benowitz NK, Gourlay SG (1997) Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy. J Am Coll Cardiol 29:1422–1431
Benowitz NL, Hennigfield JE (1994) Establishing a nicotine threshold for addiction. The implications for tobacco regulation. N Engl J Med 331:123–125
Bullen C, McRobbie H, Thornley S, Glover M, Lin R, Laugesen M (2010) Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial. Tob Control 19:98–103
Caponnetto P, Campagna D, Papale G, Russo C, Polosa R (2012) The emerging phenomenon of electronic cigarettes. Expert Rev Respir Med 6:63–74
Cardinale A, Nastrucci C, Cesario A, Russo P (2012) Nicotine specific role in angiogenesis, proliferation and apoptosis. Crit Rev Toxicol 42:68–89
Carmines EL, Gaworski CL (2005) Toxicological evaluation of glycerin as a cigarette ingredient. Food Chem Toxicol 10:1521–1539
CDC (2013) Notes from the field: electronic cigarette use among middle and high school students—United States, 2011–2012. MMWR Morb Mortal Wkly Rep 62:729–730
Changeux JP, Taly A (2008) Nicotine receptors, allosteric proteins and medicine. Trends Mol Med 14:93–102
Counts ME, Morton MJ, Laffoon SW, Cox RH, Lipowicz PJ (2005) Smoke composition and predicting relationships for international commercial cigarettes smoked with three machine-smoking conditions. Regul Toxicol Pharmacol 41:185–227
Dawkins L, Concoran O (2014) Acute electronic cigarette use: nicotine delivery and subjective effects in regular users. Psychopharmacology 231:401–407
Dawkins L, Turner J, Hasna S, Soar K (2012) The electronic-cigarette: effects on desire to smoke, withdrawal symptoms and cognition. Addict Behav 37:970–973
Etter JF, Bullen C (2011a) Salvia cotinine levels in users of electronic cigarettes. Eur Respir J 38:1219–1236
Etter J, Bullen C (2011b) Electronic cigarette: users profile, utilization, satisfaction and perceived efficacy. Addiction 106:2017–2028
Etter JF, Bullen C, Flouris AD, Laugesen M, Eissenberg T (2011) Electronic nicotine delivery systems: a research agenda. Tob Control 20:243–248
European Parliament (2013) Amendments adopted by the European Parliament on 8 October 2013 on the proposal for a directive of the European Parliament and of the Council on the approximation of the laws, regulations and administrative provisions of the Member States concerning the manufacture, presentation and sale of tobacco and related products [COM(2012)0788–C7-0420/2012–2012/0366(COD)]
Farsalinos KE, Romagna G, Allifranchini E, Ripamonti E, Bocchietto E, Todeschi S, Tsiapras D, Kyrzopoulos S, Voudris V (2013a) Comparison of the cytotoxic potential of cigarette smoke and electronic cigarette vapour extract on cultured myocardial cells. Int J Environ Res Public Health 10:5146–5162
Farsalinos KE, Romagna G, Tsiapras D, Kyrzopoulos S, Voudris V (2013b) Evaluation of electronic cigarette use (vaping) topography and estimation of liquid consumption: implications for research protocol standards definition and for public health authorities’ regulation. Int J Environ Res Public Health 10:2500–2514
Flouris AD, Chorti MS, Poulianiti KP, Jamurtas AZ, Kostikas K, Tzatzarakis MN, Wallace Hayes A, Tsatsakis AM, Koutedakis Y (2013) Acute impact of active and passive electronic cigarette smoking on serum cotinine and lung function. Inhal Toxicol 25:91–101
Goniewicz ML, Zielinska-Danch W (2012) Electronic cigarette use among teenagers and young adults in Poland. Pediatrics 130:e879–e885
Goniewicz ML, Kuma T, Gawron M, Knysak J, Kosmider L (2012) Nicotine levels in electronic cigarettes. Nicotine Tob Res 15:158–166
Goniewicz ML, Knysak J, Gawron M, Kosmider L, Sobczak A, Kurek J, Prokopowicz A, Jablonska-Czapla M, Rosik-Dulewska C, Havel C, Jacob P III, Benowitz N (2013) Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control 23:133–139
Greenland S, Satterfield MH, Lanes SF (1998) A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch. Drug Saf 18:297–308
Hansson J, Pedersen NL, Galanti MR, Andersson T, Ahlbom A, Hallqvist J, Magnusson C (2009) Use of snus and risk for cardiovascular disease: results from the Swedish Twin Registry. J Intern Med 265:717–724
Hansson J, Galanti MR, Hergens MP, Fredlund P, Ahlbom A, Alfredsson L, Bellocco R, Eriksson M, Hallqvist J, Hedblad B, Janssom JH, Nilsson P, Pedersen N, Lagerros YT, Östergren PO, Magnusson C (2012) Use of snus and acute myocardial infarction: pooled analysis of eight prospective observational studies. Eur J Epidemiol 27:771–779
Heeschen C, Jang JJ, Weis M, Pathak A, Kaji S, Hu RS, Tsao PS, Johnson FL, Cooke JP (2001) Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis. Nat Med 7:833–839
Hess R, Bartels MJ, Pottenger LH (2004) Ethylene glycol: an estimate of tolerable levels of exposure based on a review of animal and human data. Arch Toxicol 78:671–680
Hukkanen J, Jacob P, Benowitz NL (2005) Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57:79–115
IARC monographs on the evaluation of carcinogenic risks to humans (1999) Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide, vol 71. International Agency for Research on Cancer, Lyon
Jasinska AJ, Zorick T, Brody AL, Stein EA (2013) Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans. Neuropharmacology. doi:10.1016/j.neuropharm.2013.02.015
Lee J, Cooke JP (2012) Nicotine and pathological angiogenesis. Life Sci 91:1058–1064
Lee S, Grana RA, Glantz SA (2014) Electronic cigarette use among Korean adolescents: a cross-sectional study of market penetration, dual use, and relationship to quit attempts and former smoking. J Adolesc Health 54:684–690
Mayer B (2014) How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol 88:5–7
Nimlos MR, Blanksby SJ, Qian X, Himmel ME, Johnson DK (2006) Mechanisms of glycerol dehydration. J Phys Chem A 110:6145–6156
Robertson OH, Loosli CG, Puck TT, Wise H, Lemon HM, Lester W (1947) Tests for the chronic toxicity of propylene glycol and triethylene glycol on monkeys and rats by vapor inhalation and oral administration. J Pharmacol Exp Ther 91:52–76
Schnuch A, Uter W, Geier J, Lessmann H, Frosch PJ (2007) Sensitization to 26 fragrances to be labelled according to current European regulation. Results of the IVDK and review of the literature. Contact Dermat 57:1–10
Schubert J, Heinke V, Bewersdorff J, Luch A, Schulz TG (2012) Waterpipe smoking: the role of humectants in the release of toxic carbonyls. Arch Toxicol 86:1309–1316
Uchiyama S, Inaba Y, Kunugita N (2010) Determination of acrolein and other carbonyls in cigarette smoke using coupled silica cartridges impregnated with hydroquinone and 2,4-dinitrophenylhydrazine. J Chromatogr A 1217:4383–4388
Vansickel AR, Eissenberg T (2013) Electronic cigarettes: effective nicotine delivery after acute administration. Nicotine Tob Res 15:267–270
Vansickel AR, Cobb CO, Weaver MF, Eissenberg TE (2010) A clinical laboratory model for evaluating the acute effects of electronic “cigarettes”: nicotine delivery profile and cardiovascular and subjective effects. Cancer Epidemiol Biomark Prev 19:1945–1953
Vardavas CI, Anagnostopoulos N, Kougias M, Evangelopoulou V, Connolly GN, Behrakis PK (2012) Short term pulmonary effects of using an e-cigarette: impact on respiratory flow resistance, impedance and exhaled nitric oxide. Chest 141:1400–1406
Waldum HJ, Nilsen OG, Nilsen T, Rorvik H, Syversen U, Sandvik AK, Haugen OA, Torp SH, Brenna E (1996) Long term effects of inhaled nicotine. Life Sci 58:1339–1346
Werley MS, McDonald P, Lilly P, Kirkpatrick D, Wallery J, Byron P, Venitz J (2011) Non-clinical safety and pharmacokinetic evaluations of propylene glycol aerosol in Sprague–Dawley rats and Beagle dogs. Toxicology 287:76–90
WHO (2004) WHO Study Group on tobacco product regulation. Guiding principles for the development of tobacco research and testing capacity and proposed protocols for the initiation of tobacco product testing, p 11. http://www.who.int/tobacco/global_interaction/tobreg/goa_2003_principles/en/index.html. (Accessed 8 Aug 2013)
Wieslander G, Norbäck D, Lindgren T (2001) Experimental exposure to propylene glycol mist in aviation emergency training: acute ocular and respiratory effects. Occup Environ Med 58:649–655
Wills JH, Coulston F, Harris ES, McChesney EW, Russell JC, Serrone DM (1974) Inhalation of aerosolized ethylene glycol by man. Clin Toxicol 7:463–476
Acknowledgments
This study was financially supported by intramural funding of the German Federal Institute for Risk Assessment (BfR), SFP Grant No. 1322-535.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hutzler, C., Paschke, M., Kruschinski, S. et al. Chemical hazards present in liquids and vapors of electronic cigarettes. Arch Toxicol 88, 1295–1308 (2014). https://doi.org/10.1007/s00204-014-1294-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-014-1294-7