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

Scientific Reports

Volumn 9, Issue 1, 2019, Pages

  Omaiye, Esther E ^a   McWhirter, Kevin J ^b   Luo, Wentai ^b   Tierney, Peyton A ^b   Pankow, James F ^b   Talbot, Prue ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Department of Electrical and Computer Engineering   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACROLEIN; CINNAMALDEHYDE; ETHYLMALTOL; FLAVORING AGENT; MENTHOL; NICOTINE; PYRONE DERIVATIVE;

CELL CULTURE; CYTOLOGY; DRUG EFFECT; ELECTRONIC CIGARETTE; EPITHELIUM CELL; FIBROBLAST; HUMAN; LUNG; MASS FRAGMENTOGRAPHY;

ACROLEIN; CELLS, CULTURED; ELECTRONIC NICOTINE DELIVERY SYSTEMS; EPITHELIAL CELLS; FIBROBLASTS; FLAVORING AGENTS; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; HUMANS; LUNG; MENTHOL; NICOTINE; PYRONES;

EID: 85061979963     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-019-39550-2     Document Type: Article

References (52)

1. Trtchounian, A. & Talbot, P. Electronic nicotine delivery systems: is there a need for regulation? Tob Control. 20, 47–52 (2010).
2. U.S. Department of Health and Human Services (HHS), Office of the Surgeon General, Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: HHS (2016).
3. Zhu, S. H. et al. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control 23(Suppl 3), iii3–9 (2014).
4. Pisinger, C. & Døssing, M. A systematic review of health effects of electronic cigarettes. Prev Med 69, 248–260 (2014).
5. Hua, M. & Talbot, P. Potential health effects of electronic cigarettes: A systematic review of case reports. Prev Med Rep. 4, 169–178 (2016).
6. Lerner, C. et al. 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. Plos One. 10, e0116732 (2015).
7. Sussan, T. et al. Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model. Plos One. 10, e0116861 (2015).
8. Bahl, V. et al. Comparison of electronic cigarette refill fluid cytotoxicity using embryonic and adult models. Reprod Toxicol 34, 529–537 (2012).
9. Behar, R. Z. et al. Identification of toxicants in cinnamon-flavored electronic cigarette refill fluids. Toxicol in Vitro 28, 198–208 (2014).
10. Behar, R. Z. et al. Distribution, quantification and toxicity of cinnamaldehyde in electronic cigarette refill fluids and aerosols. Tob Control. 25((Suppl 2), ii94–ii102 (2016).
11. Behar, R. Z., Wang, Y. & Talbot, P. Comparing the cytotoxicity of electronic cigarette fluids, aerosols and solvents. Tob Control tobaccocontrol 2016–053472, https://doi.org/10.1136/tobaccocontrol-2016-053472 (2017).
12. Leigh, N. J., Lawton, R. I., Hershberger, P. A. & Goniewicz, M. L. Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS). Tob Control 25(Suppl 2), ii81–ii87 (2016).
13. Clapp, P. W. et al. Flavored e-cigarette liquids and cinnamaldehyde impair respiratory innate immune cell function. Am J Physiol Lung Cell Mol Physiol 313, L278–L292 (2017).
14. Hallagan J. The safety assessment and regulatory authority to use flavor—focus on e-cigarettes. http://www.femaflavor.org/safety-assessment-and-regulatory-authority-use-flavors-focus-e-cigarettes (2014).
15. Burdock G. Fenaroli’s Handbook Of Flavor Ingredients, Seventh Edition. Boca Raton : (CRC Press, 2005).
16. National Institute for Occupational Safety and Health (NIOSH) Alert. Preventing Lung Disease in Workers Who Use or Make Flavorings. Available at, https://www.cdc.gov/niosh/docs/2004-110/pdfs/2004-110.pdf?id=10.26616/NIOSHPUB2004110 (Assessed:2018) (2004).
17. Tierney, P. A., Karpinski, C. D., Brown, J. E., Luo, W. & Pankow, J. F. Flavour chemicals in electronic cigarette fluids. Tob Control 25, e10–5 (2016).
18. The Good Scents Company Information System. The Good Scents Company Information System. Available at, http://www.thegoodscentscompany.com (Accessed: 2018).
19. Dangerous Substances Directive (67/548/EEC). Available at, http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=DD:I:1967:TOC:EN (Accessed: 2018).
20. Dangerous Preparations Directive (1999/45/EC). Available at, http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:31999L0045&from=EN(Accessed: 2018).
21. Classification, Labelling and Packaging (CLP) regulation in 2008 (1272/2008). Available at, http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32008R1272&from=EN (Accessed: 2018).
22. U.S. Food and Drug Administration. “Substances Generally Regarded as Safe”. Code of Federal Regulations, title 21 C.F.R. §182.60. (2011). https://www.govinfo.gov/content/pkg/CFR-2018-title21-vol3/pdf/CFR-2018-title21-vol3-sec182-60.pdf (Accessed: 2019).
23. Gowder, S. J. T. Safety Assessment of Food Flavor - Cinnamaldehyde. Biosafety. 3, e147 (2014).
24. Kirk-Othmer Encyclopedia of Chemical Technology 4th ed. (Grayson, M. Ed). New York (John Wiley & Sons, 2001).
25. Opdyke, D. L. J. Monographs on fragrance raw materials. Food Cosmet Toxicol. 17, 241–275 (1979).
26. National Library of Medicine, Hazardous Substances Databank (HSDB). National Library of Medicine’s Toxicology Data Network (TOXNET). Available at, https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~7VEHHv:1 (Accessed: 2018).
27. Blakemore, W. M. & Thompson, H. C. Jr. Trace analysis of cinnamaldehyde in animal feed, human urine, and wastewater by electron capture gas chromatography. J Agric Food Chem. 31, 1047–1052 (1983).
28. Grundschober, F., Hall, R. L., Stofberg, J. & Vodoz, C. A. Survey of worldwide use levels of artificial flavoring substances. Flavors, 223–230 (1975).
29. Opdyke, D. L. J. Monographs of fragrance raw materials: ethyl maltol. Food Cosmet Toxicol 13, 805–806 (1975).
30. Zachary, T. B. et al. Effect of flavoring chemicals on free radical formation in electronic cigarette aerosols. Free Radic Biol Med. 120, 72–79 (2018).
31. Ai, J. et al. Menthol content in US Marketed Cigarettes. Nicotine Tob Res 18, 1575–1580 (2016).
32. Kreiss, K. et al. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N Engl J Med 347, 330–338 (2002).
33. Kullman, G. et al. Characterization of respiratory exposures at a microwave popcorn plant with cases of bronchiolitis obliterans. J Occup Environ Health 2, 169–178 (2005).
34. Lockey, J. et al. Bronchiolitis obliterans in the food flavoring manufacturing industry. Am J Respir Crit Care Med 165(suppl), A461 (2002).
35. Kanwal, R. et al. Evaluation of flavorings-related lung disease risk at six microwave popcorn plants. J Occup Environ Med 48, 149–57 (2006).
36. Allen, J. G. et al. Flavoring chemicals in e-cigarettes: diacetyl, 2, 3-pentanedione, and acetoin in a sample of 51 products, including fruit-, candy-, and cocktail-flavored e-cigarettes. Environ Health Perspect 124, 733–9 (2016).
37. Farsalinos, K., Kistler, K. A., Gillman, G. & Voudris, V. Evaluation of electronic cigarette liquids and aerosol for the presence of selected inhalation toxins. Nicotine Tob Res 17, 168–174 (2015).
38. Dawkins, L., Turner, J., Roberts, A. & Soar, K. ‘Vaping’ profiles and preferences: an online survey of electronic cigarettes users. Addiction 108(6), 1115–25 (2013).
39. National Institute for Occupational Safety and Health (NIOSH). Criteria for a recommended standard: occupational exposure to diacetyl and 2,3-Pentanedione. Available at, https://www.cdc.gov/niosh/docket/archive/pdfs/NIOSH-245/DraftDiacetylCriteriaDocument081211.pdf (Accessed: 2018) (2011).
40. U.S. Food and Drug Administration. “Substances Prohibited From Use in Human Food”. Code of Federal Regulations, title 21 C.F.R. §189.130. (2018). https://www.govinfo.gov/content/pkg/CFR-2018-title21-vol3/pdf/CFR-2018-title21-vol3-sec189-130.pdf (Accessed: 2019).
41. 2+ signaling. PhD dissertation., University of North Carolina at Chapel Hill, Carolina Digital Repository (2018).
42. Hutlzer, C. et al. Chemical hazards present in liquids and vapors of electronic cigarettes. Arch Toxicol 88, 1295–1308 (2014).
43. Gaworski, C. L., Oldham, M. J., Wagner, K. A., Coggins, C. R. E. & Patskan, G. J. An evaluation of the toxicity of 95 ingredients added individually to experimental cigarettes: approach and methods. Inhal Toxicol 23(S1), 1–12, https://doi.org/10.3109/08958378.2010.543187 (2011).
44. Muthumalage, T. et al. Inflammatory and oxidative responses induced by exposure to commonly used e-cigarette flavoring chemicals and flavored e-Liquids without nicotine. Front. Physiol. 8, 1130, 10.3389/fphys.2017.01130 (2018).
45. Sassano M. F. et al. Evaluation of e-liquid toxicity using an open-source high-throughput screening assay. Plos Biol 16(3), e2003904, 10.1371/journal.pbio.2003904 (2018).
46. Singh, J., Luquet, E., Smith, D. P. T., Potgieter, H. J. & Ragazzon, P. Toxicological and analytical assessment of e-cigarette refill components on airway epithelia. Sci Prog 99 (4), 351–398.
47. Sherwood, C. L. & Boitano, S. Airway epithelial cell exposure to distinct e-cigarette liquid flavorings reveals toxicity thresholds and activation of CFTR by the chocolate flavoring 2,5-dimethypyrazine. Respir Res 17, 57 (2016).
48. Behar, R. Z. et al. Analytical and toxicological evaluation of flavor chemicals in electronic cigarette refill fluids. Sci Reports 8, 8288, 10.1038/s41598-018-25575-6 (2018).
49. Khlystov, A. & Samburova, V. Flavoring Compounds Dominate Toxic Aldehyde Production during E-Cigarette Vaping. Environ. Sci. Technol. 50, 13080–13085 (2016).
50. Klager, S. et al. Flavoring Chemicals and Aldehydes in E-Cigarette Emissions. Environ. Sci. Technol. 51, 10806–10813 (2016).
51. Glantz, S. FDA should ban menthol as an additive not as an undefined “characterizing flavor”. [online] Center for Tobacco Control Research and Education. Available at, https://tobacco.ucsf.edu/fda-should-ban-menthol-additive-not-undefined-characterizing-flavor (Accessed 20 Oct. 2018) (2013).
52. Brown, J., Luo, W., Isabelle, L. & Pankow, J. Candy Flavorings in Tobacco. N Engl J Med. 370, 2250–2252 (2014).