Identification of Cytotoxic Flavor Chemicals in Top-Selling Electronic Cigarette Refill Fluids

Scientific Reports

Volumn 9, Issue 1, 2019, Pages

  Hua, My ^a   Omaiye, Esther E ^a   Luo, Wentai ^b   McWhirter, Kevin J ^b   Pankow, James F ^b   Talbot, Prue ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Portland State University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOTOXIN; FLAVORING AGENT;

ELECTRONIC CIGARETTE; HUMAN; QUESTIONNAIRE;

CYTOTOXINS; ELECTRONIC NICOTINE DELIVERY SYSTEMS; FLAVORING AGENTS; HUMANS; SURVEYS AND QUESTIONNAIRES;

EID: 85062147095     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-019-38978-w     Document Type: Article

References (40)

1. 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).
2. Burdock, G. A. Fenaroli’s Handbook of Flavor Ingredients (CRC Press, 2005).
3. NIOSH (National Institute for Occupational Safety and Health). NIOSH Health Hazard Evaluation Report (HETA), https://www.cdc.gov/niosh/hhe/reports/pdfs/2002-0257-2916.pdf (2005).
4. 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).
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. Pisinger, C. & Døssing, M. A systematic review of health effects of electronic cigarettes. Prev. Med. 69, 248–260 (2014).
7. Hua, M., Alfi, M. & Talbot, P. Health-related effects reported by electronic cigarette users in online forums. J. Med. Internet Res. 15, e59 (2013).
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. 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).
12. Kreiss, K. et al. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N. Engl. J. Med. 347, 330–338 (2002).
13. Egilman, D. S. & Schilling, J. H. Bronchiolitis obliterans and consumer exposure to butter-flavored microwave popcorn: a case series. Int. J. Occup. Environ. Health 18, 29–42 (2012).
14. 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. 17, 168–174 (2015).
15. 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, 733–739 (2016).
16. 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).
17. The Good Scents Company Information System. The Good Scents Company Information System, http://www.thegoodscentscompany.com (2017).
18. Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity. ISO 10993-5:2009(E), iv–34 (2009).
19. Williams et al. Metals and Silicate Particles Including Nanoparticles Are Present in Electronic Cigarette Cartomizer Fluid and Aerosol. PLoS ONE 8(3), e57987 (2013).
20. Farsalinos, K. E. et al. Impact of flavour variability on electronic cigarette use experience: an internet survey. Int. J. Environ. Res. Public Health 10, 7272–7282 (2013).
21. Pepper, J. K., Ribisl, K. M. & Brewer, N. T. Adolescents’ interest in trying flavoured e-cigarettes. Tob. Control 0, 1–5 (2016).
22. Harrell, M. B. et al. Flavored e-cigarette use: characterizing youth, young adult, and adult users. Prev. Med. Rep. 5, 33–40 (2017).
23. El Hadi, M. A. et al. Advances in fruit aroma volatile research. Molecules 18, 8200–8229 (2013).
24. Misra, M. et al. Comparative in vitro toxicity profile of electronic and tobacco cigarettes, smokeless tobacco and nicotine replacement therapy products: e-liquids, extracts and collected aerosols. Int. J. Environ. Res. Public Health 11, 11325–11347 (2014).
25. Farsalinos, K. E. et al. Comparison of the Cytotoxic Potential of Cigarette Smoke and Electronic Cigarette Vapour Extract on Cultured MyocardialCells. Int. J. Environ. Res. Public Health 10, 5146–5162 (2013).
26. Rowell, T. R. et al. Flavored e-cigarette liquids reduce proliferation and viability in the CALU3 airway epithelial cell line. Am. J. Physiol. Lung Cell Mol. Physiol. 313, L52–L66 (2017).
27. Jensen, R. P. et al. Hidden formaldehyde in e-cigarette aerosols. N. Engl. J. Med. 372, 392–394 (2015).
28. Khlystov, A. & Samburova, V. Flavoring compounds dominate toxic aldehyde production during e-cigarette vaping. Environ. Sci. Technol. 50, 13080–13085 (2017).
29. Tierney, P. A. et al. Flavour chemicals in electronic cigarette fluids. Tob Control 25, 10–5 (2015).
30. Gerloff, J. 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. 3, 28–40 (2017).
31. Gralla, E. J., Stebbins, R. B., Coleman, G. L. & Delahunt, C. S. Toxicity studies with ethyl maltol. Toxicol. Appl. Pharmacol. 15, 604–613 (1969).
32. Li, Z. et al. Toxicity studies of ethyl maltol and iron complexes in mice. Biomed. Res. Int. 2017, 1–9 (2017).
33. 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).
34. Behar, R. Z., Wang, Y. & Talbot, P. Comparing the cytotoxicity of electronic cigarette fluids, aerosols and solvents. Tob. Control 27, 325–333 (2017).
35. Behar, R. Z., Hua, M. & Talbot, P. Puffing Topography and Nicotine Intake of Electronic Cigarette Users. PLoS ONE 10, e0117222 (2015).
36. 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).
37. Riss, T. L. et al. Cell viability assays. In: Assay Guidance Manual. CDC (Centers for Disease Control and Prevention). Fixed obstructive lung disease among workers in the flavor manufacturing industry— California, 2004–2007. Morb. Mortal Wkly. Rep. 56, 289–293 (2007).
38. Cloonan, S. M. & Choi, A. M. K. Mitochondria in lung disease. J. Clinical Investigation 126, 809–820 (2016).
39. Brown, J. E., Luo, W., Isabelle, L. M. & Pankow, J. F. Candy flavorings in tobacco. N. Engl. J. Med. 23, 2250–2252 (2014).
40. Behar, R. Z. et al. Adaptation of stem cells to 96-well plate assays: use of human embryonic and mouse neural stem cells in the MTT assay. Curr. Protoc. Stem Cell Biol. Chapter 1: Unit1C.13 (2012).