Toxicity assessment of refill liquids for electronic cigarettes

International Journal of Environmental Research and Public Health

Volumn 12, Issue 5, 2015, Pages 4796-4815

  Varlet, Vincent ^a   Farsalinos, Konstantinos ^b,c   Augsburger, Marc ^a   Thomas, Aurélien ^a,d   Etter, Jean François ^e  

^a UNIVERSITY CENTER OF LEGAL MEDICINE   (Switzerland)

^b ONASSIS CARDIAC SURGERY CENTER   (Greece)

^c UNIVERSITY OF PATRAS   (Greece)

^d UNIVERSITY OF LAUSANNE   (Switzerland)

^e UNIVERSITY OF GENEVA   (Switzerland)

Author keywords

E cigarette; E liquid; Electronic cigarette; Electronic nicotine delivery systems; Quality control

Indexed keywords

1,3 BUTADIENE; ACETONE; ACROLEIN; ALCOHOL; ALDEHYDE; CHEMICAL COMPOUND; CYCLOHEXANE; DIETHYLENE GLYCOL; E-LIQUID; ETHYLENE GLYCOL; FORMALDEHYDE; HYDROCARBON; NITROSAMINE; REFILL LIQUID; SOLVENT; TERPENE; UNCLASSIFIED DRUG; AIR POLLUTANT; ORGANIC COMPOUND;

ALDEHYDE; LIQUID; QUALITY CONTROL; SOLVENT; TERPENE; TOXIC SUBSTANCE; TOXICITY;

ACUTE TOXICITY; ANAEROBIC BACTERIUM; ARTICLE; CONTROLLED STUDY; ELECTRONIC CIGARETTE; FLAVOR; LIMIT OF DETECTION; LONG TERM EXPOSURE; MICROORGANISM; MOULD; PSEUDOMONAS AERUGINOSA; STAPHYLOCOCCUS AUREUS; TOXICITY TESTING; YEAST; AIR POLLUTANT; ANALYSIS; MICROBIOLOGY;

NICOTIANA TABACUM; PSEUDOMONAS AERUGINOSA; STAPHYLOCOCCUS AUREUS;

AIR MICROBIOLOGY; AIR POLLUTANTS; ELECTRONIC CIGARETTES; ORGANIC CHEMICALS; SOLVENTS;

EID: 84929359064     PISSN: 16617827     EISSN: 16604601     Source Type: Journal    
DOI: 10.3390/ijerph120504796     Document Type: Article

References (42)

1. Brown, J.; West, R.; Beard, E.; Michie, S.; Shahab, L.; McNeill, A. Prevalence and characteristics of e-cigarette users in Great Britain: Findings from a general population survey of smokers. Addict. Behav. 2014, 39, 1120-1125.
2. Hajek, P.; Etter, J.F.; Benowitz, N.; Eissenberg, T.; McRobbie, H. Electronic cigarettes: Review of use, content, safety, effects on smokers and potential for harm and benefits. Addiction 2014, 109, 1801-1810.
3. Etter, J.F.; Bullen, C.; Flouris, A.D.; Laugesen, M.; Eissenberg, T. Electronic nicotine delivery systems: A research agenda. Tob. Control 2011, 20, 243-248.
4. Regan, A.K.; Promoff, G.; Dube, S.R.; Arrazola, R. Electronic nicotine delivery systems: Adult use and awareness of the “e-cigarette” in the USA. Tob. Control 2011, 22, 19-23.
5. Pearson, J.L.; Richardson, A.; Niaura, R.S.; Vallone, D.M.; Abrams, D.B. E-Cigarette awareness, use, and harm perceptions in US adults. Am. J. Public Health 2012, 102, 1758-1766.
6. King, B.A.; Alam, S.; Promoff, G.; Arrazola, R.; Dube, S.R. Awareness and ever use of electronic cigarettes among U.S. adults, 2010-2011. Nicotine Tob. Res. 2013, 15, 1623-1627.
7. Adkison, S.E.; O’Connor, R.J.; Bansal-Travers, M.; Hyland, A.; Borland, R.; Yong, H.H.; Cummings, K.M.; McNeill, A.; Thrasher, J.F.; Hammond, D.; et al. Electronic nicotine delivery systems: International tobacco control four-country survey. Am. J. Prev. Med. 2013, 44, 207-215.
8. Etter, J.F.; Zather, E.; Svensson, S. Analysis of refill liquids for electronic cigarettes. Addiction 2013, 108, 1671-1679.
9. Vakkalanka, J.P.; Hardison, L.S., Jr.; Holstege, C.P. Epidemiological trends in electronic cigarette exposures reported to U.S. Poison Centers. Clin. Toxicol. (Phila) 2014, 52, 542-548.
10. Martinez, R.E.; Dhawan, S.; Sumner, W.; Williams, B.J. On-line chemical composition analysis of refillable electronic cigarette aerosol-measurement of nicotine and nicotyrine. Nicotine Tob. Res. 2014, doi:10.1093/ntr/ntu334.
11. Etter, J.F. Electronic cigarettes: A survey of users. BMC Public Health 2010, doi:10.1186/1471-2458-10-231.
12. Etter, J.F.; Bullen, C. Electronic cigarette: Users profile, utilization, satisfaction and perceived efficacy. Addiction 2011, 106, 2017-2028.
13. EDQM. European Pharmacopeia 7.0; European Directorate for the Quality of Medicines and Healthcare: Strasbourg, France, 2012.
14. ICH. ICH Topic Q 3 B (R2) Impurities in New Drug Products. In Proceedings of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Step 4 Version, Geneva, Switzerland, 2006; pp. 1-12.
15. EU Commission. Report EUR 14482 EN Food Science and techniques. In Reports of the Scientific Committee for Food, Twenty-Ninth Series; EU Commission: Brussels, Belgium, 1992; pp.1-37.
16. Good Scents Company. The Good Scents Company Information Database. Available online: http://www.thegoodscentscompany.com/# (accessed on 27 November 2014).
17. Farsalinos, K.E.; Romagna, G.; Tsiapras, D.; Kyrzopoulos, S.; Voudris, V. Characteristics, perceived side effects and benefits of electronic cigarette use: A worldwide survey of more than 19,000 consumers. Int. J. Environ. Res. Public Health 2014, 11, 4356-4373.
18. WHO. Electronic Nicotine Delivery Systems, Including Electronic Cigarettes. Report by the Convention Secretariat. In Proceedings of the Conference of the Parties to the WHO Framework Convention on Tobacco Control, Geneva, Switzerland, 18 June 2012.
19. FDA. Guidance for industry. In Testing of Glycerin for Diethylene Glycol; US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER): Rockville MD, USA, 2007.
20. US_Pharmacopeial_Convention. (467) Residual solvents. In United States Pharmacopeia 30; United States Pharmacopeial Convention: Rockville, MD, USA, 2007.
21. Lim, H.; Shin, H. Measurement of aldehydes in replacement liquids of electronic cigarettes by headspace gas chromatography-mass spectrometry. Korean Chem. Soc. 2013, 2691-2696.
22. IARC. N’-nitrosonornicotine and 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone. Iarc Monogr. Eval. Carcinog. Risks Hum. 2012, 100, 319-331.
23. Stepanov, I.; Jensen, J.; Hatsukami, D.; Hecht, S.S. Tobacco-specific nitrosamines in new tobacco products. Nicotine Tob. Res. 2006, 8, 309-313.
24. Kim, H.J.; Shin, H.S. Determination of tobacco-specific nitrosamines in replacement liquids of electronic cigarettes by liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 2013, 1291, 48-55.
25. Farsalinos, K.E.; Polosa, R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: A systematic review. Ther. Adv. Drug Saf. 2014, 5, 67-86.
26. Schuster, B. AAPCC and Poison Centers Issue Warning about Electronic Cigarette Devices and Liquid Nicotine American Association of Poison Control Centers. Available online: http://www.aapcc.org/press/29/ (accessed on 27 November 2014).
27. Christensen, L.B.; van’t Veen, T.; Bang, J. XXXIII International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 28-31 May 2013, Copenhagen, Denmark (85. Three cases of attempted suicide by ingestion of nicotine liquid used in e-cigarettes.). Clin. Toxicol. 2013, 51, 252-378.
28. Kosmider, L.; Sobczak, A.; Fik, M.; Knysak, J.; Zaciera, M.; Kurek, J.; Goniewicz, M.L. Carbonyl compounds in electronic cigarette vapors: Effects of nicotine solvent and battery output voltage. Nicotine Tob. Res. 2014, 16, 1319-1326.
29. Jensen, R.P.; Luo, W.; Pankow, J.F.; Strongin, R.M.; Peyton, D.H. Hidden formaldehyde in e-cigarette aerosols. N. Engl. J. Med. 2015, 372, 392-394.
30. Goniewicz, M.L.; Knysak, J.; Gawron, M.; Kosmider, L.; Sobczak, A.; Kurek, J.; Prokopowicz, A.; Jablonska-Czapla, M.; Rosik-Dulewska, C.; Havel, C.; et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob. Control 2014, 23, 133-139.
31. EFSA. Scientific Opinion on Flavouring Group Evaluation 20, Revision 2 (FGE.20Rev2): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30. EFSA J. 2009, 8, 1405.
32. EFSA. EFSA Scientific Opinion on Flavouring Group Evaluation 78, Revision 1 (FGE.78Rev1). Consideration of aliphatic and alicyclic and aromatic hydrocarbons evaluated by JECFA (63rd meeting) structurally related to aliphatic and aromatic hydrocarbons evaluated by EFSA in FGE.25Rev2. EFSA J. 2011, 9, doi:10.2903/j.efsa.2011.2178.
33. Farsalinos, K.E.; Kistler, K.A.; Gillman, G.; Voudris, V. Evaluation of electronic cigarette liquids and aerosol for the presence of selected inhalation toxins. Nicotine Tob. Res. 2014, 17, 168-174.
34. EPA. Non-Carcinogen Tolerable Daily Intake (TDI) Values from US EPA. Available online: http://www-esdworldbankorg/popstoolkit/POPsToolkit/POPSTOOLKIT_COM/TOOLS/HHRA/TDI_USEPAHTM (accessed on 27 November 2014).
35. EFSA. Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to use of formaldehyde as a preservative during the manufacture and preparation of food additives. EFSA J. 2006, 415, 1-10.
36. Van Andel, I.; Sleijffers, A.; Schenk, E. Adverse Health Effects of Cigarette Smoke: Aldehydes. RIVM Report 340603002; The Netherlands National Institute for Public Health and the Environment (RIVM): Bilthoven, The Netherlands, 2006; pp. 1-65.
37. EPA. Ambient Water Quality Criteria for Acrolein; US Environmental Protection Agency EPA: Washington, DC, USA, 1980; pp. 1-102.
38. Council of Europe. Flavouring Substances and Natural Sources of Flavourings, 3rd ed.; Council of Europe: Strasbourg, France, 1981
39. WHO. Safety evaluation of certain food additives and contaminants. In International Programme on Chemical Safety; World Health Organization: Geneva, Switzerland, 1998.
40. Bahl, V.; Lin, S.; Xu, N.; Davis, B.; Wang, Y.H.; Talbot, P. Comparison of electronic cigarette refill fluid cytotoxicity using embryonic and adult models. Reprod. Toxicol. 2012, 34, 529-537.
41. Etter, J.; Bullen, C. Cotinine levels in users of electronic cigarettes. Eur. Respir. J. 2011, 38, 1219-1220.
42. Williams, M.; Villarreal, A.; Bozhilov, K.; Lin, S.; Talbot, P. Metal and silicate particles including nanoparticles are present in electronic cigarette cartomizer fluid and aerosol. PLoS One 2013, 8, doi:10.1371/journal.pone.0057987.