Assessment of reactive oxygen species generated by electronic cigarettes using acellular and cellular approaches

Journal of Hazardous Materials

Volumn 344, Issue , 2018, Pages 549-557

  Zhao, Jiayuan ^a   Zhang, Yipei ^b   Sisler, Jennifer D ^c   Shaffer, Justine ^c   Leonard, Stephen S ^c   Morris, Anna M ^c   Qian, Yong ^c   Bello, Dhimiter ^a,b   Demokritou, Philip ^a  

^a HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^b UNIVERSITY OF MASSACHUSETTS LOWELL   (United States)

^c NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH   (United States)

Author keywords

Electronic cigarette; Nicotine; Oxidative stress; Reactive oxygen species

Indexed keywords

ELECTRON SPIN RESONANCE SPECTROSCOPY; MAGNETIC MOMENTS; MASS SPECTROMETRY; NICOTINE; OXIDATIVE STRESS; OXYGEN; TOXICITY;

CELLULAR SYSTEM; ELECTRONIC CIGARETTE; EMISSION PROFILE; HYDROXYL RADICALS; OPERATIONAL PARAMETERS; PHYSICOCHEMICAL PROPERTY; REACTIVE OXYGEN SPECIES; ROS GENERATIONS;

TOBACCO;

HYDROGEN PEROXIDE; HYDROXYL RADICAL; REACTIVE OXYGEN METABOLITE; TROLOX C; 6-HYDROXY-2,5,7,8-TETRAMETHYLCHROMAN-2-CARBOXYLIC ACID; ANTIOXIDANT; CATALASE; CHROMAN DERIVATIVE;

ASSESSMENT METHOD; BIOASSAY; CELLS AND CELL COMPONENTS; CHEMICAL COMPOUND; ELECTRONIC EQUIPMENT; HYDROGEN PEROXIDE; HYDROXYL RADICAL; OXIDATIVE STRESS; PHYSICOCHEMICAL PROPERTY; REACTIVE OXYGEN SPECIES; TOXICITY; TOXICOLOGY;

AIR POLLUTION; AIR SAMPLING; AIRWAY EPITHELIUM CELL; ARTICLE; ELECTRON SPIN RESONANCE; ENVIRONMENTAL EXPOSURE; HUMAN; IN VITRO STUDY; MASS SPECTROMETRY; OXIDATIVE STRESS; PARTICLE SIZE; SAMPLING; SPIN TRAPPING; CELL LINE; CHEMISTRY; ELECTRONIC CIGARETTE; EPITHELIUM CELL; METABOLISM;

NEPTUNIA;

ANTIOXIDANTS; CATALASE; CELL LINE; CHROMANS; ELECTRONIC NICOTINE DELIVERY SYSTEMS; EPITHELIAL CELLS; HUMANS; REACTIVE OXYGEN SPECIES;

EID: 85032667593     PISSN: 03043894     EISSN: 18733336     Source Type: Journal    
DOI: 10.1016/j.jhazmat.2017.10.057     Document Type: Article

References (72)

1. King, B.A., Patel, R., Nguyen, K.H., Dube, S.R., Trends in awareness and use of electronic cigarettes among US adults, 2010–2013. Nicotine Tob. Res. 17 (2015), 219–227, 10.1093/ntr/ntu191.
2. Singh, T., Kennedy, S., Marynak, K., Persoskie, A., Melstrom, P., King, B.A., Characteristics of electronic cigarette use among middle and high school students – United States, 2015. Morb. Mortal. Wkly. Rep. 65 (2016), 1425–1429.
3. P. Evans, E-Cigarette Makers Face Rise of Fakes. E-cigarette global sales hit $7 billion at the endof 2014, Wall Str. J. 2015.
4. Zhu, S.-H., Sun, J.Y., Bonnevie, E., Cummins, S.E., Gamst, A., Yin, L., Lee, M., Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob. Control. 23 (2014), iii3–iii9, 10.1136/tobaccocontrol-2014-051670.
5. Kim, A.E., Arnold, K.Y., Makarenko, O., E-cigarette advertising expenditures in the U.S., 2011–2012. Am. J. Prev. Med. 46 (2014), 409–412, 10.1016/j.amepre.2013.11.003.
6. 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 102 (2012), 1758–1766, 10.2105/AJPH.2011.300526.
7. Hahn, J., Monakhova, Y.B., Hengen, J., Kohl-himmelseher, M., Schüssler, J., Hahn, H., Kuballa, T., Lachenmeier, D.W., Electronic cigarettes: overview of chemical composition and exposure estimation. Tob. Induc. Dis., 2014, 1–12, 10.1186/s12971-014-0023-6.
8. Pellegrino, R.M., Tinghino, B., Mangiaracina, G., Marani, A., Vitali, M., Protano, C., Osborn, J.F., Cattaruzza, M.S., Electronic cigarettes: an evaluation of exposure to chemicals and fine particulate matter (PM). Ann. Ig. 24 (2012), 279–288.
9. Saffari, A., Daher, N., Ruprecht, A.A., De Marco, C., Pozzi, P., Boffi, R., Hamad, S.H., Shafer, M., Schauer, J.J., Westerdahl, D., Sioutas, C., Particulate metals and organic compounds from electronic and tobacco-containing cigarettes: comparison of emission rates and secondhand exposure. Environ. Sci. Process. Impacts, 2014, 2259–2267, 10.1039/C4EM00415A.
10. Farsalinos, K.E., Romagna, G., Tsiapras, D., Kyrzopoulos, S., Voudris, V., 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 (2013), 2500–2514, 10.3390/ijerph10062500.
11. Misra, M., Leverette, R.D., Cooper, B.T., Bennett, M.B., Brown, S.E., 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 (2014), 11325–11347, 10.3390/ijerph111111325.
12. Fuoco, F.C., Buonanno, G., Stabile, L., Vigo, P., Influential parameters on particle concentration and size distribution in the mainstream of e-cigarettes. Environ. Pollut. 184 (2014), 523–529, 10.1016/j.envpol.2013.10.010.
13. Marini, S., Buonanno, G., Stabile, L., Ficco, G., Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide. Toxicol. Appl. Pharmacol. 278 (2014), 9–15, 10.1016/j.taap.2014.04.004.
14. Zhang, Y., Sumner, W., Chen, D., Ph, D., Louis, S., Author, C., Sumner, W., Louis, S., In vitro particle size distributions in electronic and conventional cigarette aerosols suggest comparable deposition patterns. Nicotine Tob. Res. 15 (2013), 501–508, 10.1093/ntr/nts165.
15. Allen, J.G., Flanigan, S.S., LeBlanc, M., Vallarino, J., MacNaughton, P., Stewart, J.H., Christiani, D.C., 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 (2016), 733–739, 10.1289/ehp.1510185.
16. Herrington, J.S., Myers, C., Electronic cigarette solutions and resultant aerosol profiles. J. Chromatogr. A 2015 (1418), 192–199, 10.1016/j.chroma.2015.09.034.
17. Goniewicz, M.L., Knysak, J., Gawron, M., Kosmider, L., Sobczak, A., Kurek, J., Prokopowicz, A., Jablonska-Czapla, M., Rosik-Dulewska, C., Havel, C., Jacob, P.I., Benowitz, N., Levels of selected carcinogens and toxicants in vapor from electronic cigarettes. Tob. Control 23 (2014), 133–139, 10.1136/tobaccocontrol-2012-050859 Levels.
18. 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 8 (2013), 1–11, 10.1371/journal.pone.0057987.
19. Azzopardi, D., Patel, K., Jaunky, T., Santopietro, S., Camacho, O.M., McAughey, J., Gaça, M., Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke. Toxicol. Mech. Methods 26 (2016), 477–491, 10.1080/15376516.2016.1217112.
20. Zhao, J., Pyrgiotakis, G., Demokritou, P., Development and characterization of electronic-cigarette exposure generation system (Ecig-EGS) for the physico-chemical and toxicological assessment of electronic cigarette emissions. Inhal. Toxicol. 0 (2016), 1–12, 10.1080/08958378.2016.1246628.
21. Farsalinos, K.E., Romagna, G., Allifranchini, E., Ripamonti, E., Bocchietto, E., Todeschi, S., Tsiapras, D., Kyrzopoulos, S., Voudris, V., Comparison of the cytotoxic potential of cigarette smoke and electronic cigarette vapour extract on cultured myocardial cells. Int. J. Environ. Res. Public Health 10 (2013), 5146–5162, 10.3390/ijerph10105146.
22. Zhao, J.Y., Hopke, P.K., Concentration of reactive oxygen species (ROS) in mainstream and sidestream cigarette smoke. Aerosol Sci. Technol. 46 (2012), 191–197, 10.1080/02786826.2011.617795.
23. Lodovici, M., Bigagli, E., Oxidative stress and air pollution exposure. J. Toxicol., 2011, 2011, 10.1155/2011/487074.
24. Reuter, S., Gupta, S.C., Chaturvedi, M.M., Aggarwal, B.B., Oxidative stress, inflammation, and cancer: how are they linked?. Free Radic. Biol. Med. 49 (2010), 1603–1616, 10.1016/j.freeradbiomed.2010.09.006.
25. Faux, S.P., Tai, T., Thorne, D., Xu, Y., Breheny, D., Gaca, M., The role of oxidative stress in the biological responses of lung epithelial cells to cigarette smoke. Biomarkers 14:Suppl. 1 (2009), 90–96, 10.1080/13547500902965047.
26. Gould, N.S., Min, E., Gauthier, S., Martin, R.J., Day, B.J., Lung glutathione adaptive responses to cigarette smoke exposure. Respir. Res., 12, 2011, 133, 10.1186/1465-9921-12-133.
27. van der Toorn, M., Smit-de Vries, M.P., Slebos, D.-J., de Bruin, N., van Oosterhout, R., Kauffman, H.F., Cigarette smoke irreversibly modifies glutathione in airway epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 293 (2007), L1156–L1162, 10.1152/ajplung.00081.2007.
28. Sussan, T.E., Gajghate, S., Thimmulappa, R.K., Ma, J., Kim, J.H., Sudini, K., Consolini, N., Cormier, S.A., Lomnicki, S., Hasan, F., Pekosz, A., Biswal, S., Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model. PLoS One 10 (2015), 1–15, 10.1371/journal.pone.0116861.
29. Bodas, M., Van Westphal, C., Carpenter-Thompson, R., Mohanty, D.K., Vij, N., Nicotine exposure induces bronchial epithelial cell apoptosis and senescence via ROS mediated autophagy-impairment. Free Radic. Biol. Med. 97 (2016), 441–453, 10.1016/j.freeradbiomed.2016.06.017.
30. Shivalingappa, P.C., Hole, R., Van Westphal, C., Vij, N., Airway exposure to e-cigarette-vapors impairs autophagy and induces aggresome-formation. Antioxid. Redox Signal. 24 (2016), 186–204, 10.1089/ars.2015.6367.
31. El Golli, N., Jrad-Lamine, A., Neffati, H., Dkhili, H., Rahali, D., Dallagi, Y., El May, M.V., El Fazaa, S., Impact of e-cigarette refill liquid exposure on rat kidney. Regul. Toxicol. Pharmacol. 77 (2016), 109–116, 10.1016/j.yrtph.2016.02.012.
32. Golli, N.E., Rahali, D., Jrad-Lamine, A., Dallagi, Y., Jallouli, M., Bdiri, Y., Ba, N., Lebret, M., Rosa, J.P., El May, M., El Fazaa, S., Impact of electronic-cigarette refill liquid on rat testis. Toxicol. Mech. Methods 26 (2016), 417–424, 10.1016/j.yrtph.2016.02.012.
33. Sancilio, S., Gallorini, M., Cataldi, A., di Giacomo, V., Cytotoxicity and apoptosis induction by e-cigarette fluids in human gingival fibroblasts. Clin. Oral Investig. 20 (2016), 477–483, 10.1007/s00784-015-1537-x.
34. Anderson, C., Majeste, A., Hanus, J., Wang, S., E-cigarette aerosol exposure induces reactive oxygen species, DNA damage, and cell death in vascular endothelial cells. Toxicol. Sci., 2016, 1–9, 10.1093/toxsci/kfw166.
35. Putzhammer, R., Doppler, C., Jakschitz, T., Heinz, K., Förste, J., Danzl, K., Messner, B., Bernhard, D., Vapours of US and EU market leader electronic cigarette brands and liquids are cytotoxic for human vascular endothelial cells. PLoS One 11 (2016), 1–15, 10.1371/journal.pone.0157337.
36. Lerner, C.A., Sundar, I.K., Yao, H., Gerloff, J., Ossip, D.J., McIntosh, S., Robinson, R., Rahman, I., 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 (2015), 1–26, 10.1371/journal.pone.0116732.
37. Behar, R.Z., Davis, B., Wang, Y., Bahl, V., Lin, S., Talbot, P., Identification of toxicants in cinnamon-flavored electronic cigarette refill fluids. Toxicol. Vitr. 28 (2014), 198–208, 10.1016/j.tiv.2013.10.006.
38. Lerner, C.A., Sundar, I.K., Watson, R.M., Elder, A., Jones, R., Done, D., Kurtzman, R., Ossip, D.J., Robinson, R., McIntosh, S., Rahman, I., Environmental health hazards of e-cigarettes and their components: oxidants and copper in e-cigarette aerosols. Environ. Pollut. 198 (2015), 100–107, 10.1016/j.envpol.2014.12.033.
39. Rubenstein, D.A., Hom, S., Ghebrehiwet, B., Yin, W., Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses. Mol. Immunol. 67 (2015), 652–660, 10.1016/j.molimm.2015.05.020.
40. Taylor, M., Carr, T., Oke, O., Jaunky, T., Breheny, D., Lowe, F., Gaça, M., E-cigarette aerosols induce lower oxidative stress in vitro when compared to tobacco smoke. Toxicol. Mech. Methods 26 (2016), 465–476, 10.1080/15376516.2016.1222473.
41. Scheffler, S., Dieken, H., Krischenowski, O., Förster, C., Branscheid, D., Aufderheide, M., Evaluation of e-cigarette liquid vapor and mainstream cigarette smoke after direct exposure of primary human bronchial epithelial cells. Int. J. Environ. Res. Public Health 12 (2015), 3915–3925, 10.3390/ijerph120403915.
42. Moses, E., Wang, T., Corbett, S., Jackson, G.R., Drizik, E., Perdomo, C., Perdomo, C., Kleerup, E., Brooks, D., O'Connor, G., Dubinett, S., Hayden, P., Lenburg, M.E., Spira, A., Molecular impact of electronic cigarette aerosol exposure in human bronchial epithelium. Toxicol. Sci., 2016, 10.1093/toxsci/kfw198 kfw198.
43. Carnevale, R., Sciarretta, S., Violi, F., Nocella, C., Loffredo, L., Perri, L., Peruzzi, M., Marullo, A.G.M., De Falco, E., Chimenti, I., Valenti, V., Biondi-Zoccai, G., Frati, G., Acute impact of tobacco versus electronic cigarette smoking on oxidative stress and vascular function. Chest 150 (2016), 606–612, 10.1016/j.chest.2016.04.012.
44. Demokritou, P., Lee, S.J., Ferguson, S.T., Koutrakis, P., A compact multistage (cascade) impactor for the characterization of atmospheric aerosols. J. Aerosol Sci. 35 (2004), 281–299.
45. Pal, A.K., Watson, C.Y., Pirela, S.V., Singh, D., Chalbot, M.C.G., Kavouras, I., Demokritou, P., Linking exposures of particles released from nano-enabled products to toxicology: an integrated methodology for particle sampling, extraction, dispersion, and dosing. Toxicol. Sci. 146 (2015), 321–333, 10.1093/toxsci/kfv095.
46. Dawkins, L., Turner, J., Roberts, A., Soar, K., Vaping profiles and preferences: an online survey of electronic cigarette users. Addiction 108 (2013), 1115–1125, 10.1111/add.12150.
47. Giovenco, D.P., Lewis, M.J., Delnevo, C.D., Factors associated with e-cigarette use: a national population survey of current and former smokers. Am. J. Prev. Med. 47 (2014), 476–480, 10.1016/j.amepre.2014.04.009.
48. Invernizzi, G., Ruprecht, A., De Marco, C., Paredi, P., Boffi, R., Residual tobacco smoke: measurement of its washout time in the lung and of its contribution to environmental tobacco smoke. Tob. Control. 16 (2007), 29–33, 10.1136/tc.2006.017020.
49. Lee, Y.H., Gawron, M., Goniewicz, M.L., Changes in puffing behavior among smokers who switched from tobacco to electronic cigarettes. Addict. Behav. 48 (2015), 1–4, 10.1016/j.addbeh.2015.04.003.
50. Standardization, I.O.F., ISO 3308: Routine Analytical Cigarette-smoking Machine − Definitions and Standard Conditions. 2012, ISO, Geneva, Switzerland.
51. Pirela, S.V., Pyrgiotakis, G., Bello, D., Thomas, T., Castranova, V., Demokritou, P., Development and characterization of an exposure platform suitable for physico-chemical, morphological and toxicological characterization of printer-emitted particles (PEPs). Inhal. Toxicol. 26 (2014), 400–408, 10.3109/08958378.2014.908987.
52. Buettner, G., Spin trapping: ESR parameters of spin adducts. Free Radic. Biol. Med. 3 (1987), 259–303.
53. Janzen, E.G., Blackburn, B.J., Detection and identification of short-lived free radicals by an electron spin resonance trapping technique. J. Am. Chem. Sac. 90 (1968), 5909–5910.
54. Dahlgren, C., Karksson, A., Bylund, J., Measurement of respiratory burst products generated by professional phagocytes. Neutrophil Methods Protoc., 2007, 349–363 p. 412.
55. Pyrgiotakis, G., McDevitt, J., Bordini, A., Diaz, E., Molina, R., Watson, C., Deloid, G., Lenard, S., Fix, N., Mizuyama, Y., Yamauchi, T., Brain, J., Demokritou, P., A chemical free, nanotechnology-based method for airborne bacterial inactivation using engineered water nanostructures. Environ. Sci. Nano 1 (2014), 15–26, 10.1039/C3EN00007A.
56. Piao, C.Q., Liu, L., Zhao, Y.L., Balajee, A.S., Suzuki, M., Hei, T.K., Immortalization of human small airway epithelial cells by ectopic expression of telomerase. Carcinogenesis 26 (2005), 725–731, 10.1093/carcin/bgi016.
57. Leonard, S.S., Chen, B.T., Stone, S.G., Schwegler-Berry, D., Kenyon, A.J., Frazer, D., Antonini, J.M., Comparison of stainless and mild steel welding fumes in generation of reactive oxygen species. Part. Fibre Toxicol., 7, 2010, 32, 10.1186/1743-8977-7-32.
58. Mikheev, V.B., Brinkman, M.C., Granville, C.A., Gordon, S.M., Clark, P.I., Real-time measurement of electronic cigarette aerosol size distribution and metals content analysis. Nicotine Tob. Res, 2016, 1895–1902, 10.1093/ntr/ntw128.
59. Lerner, C.A., Rutagarama, P., Ahmad, T., Sundar, I.K., Elder, A., Rahman, I., Electronic cigarette aerosols and copper nanoparticles induce mitochondrial stress and promote DNA fragmentation in lung fibroblasts. Biochem. Biophys. Res. Commun. 477 (2016), 620–625, 10.1016/j.bbrc.2016.06.109.
60. Guan, Z.-Z., Yu, W.-F., Nordberg, A., Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells. Neurochem. Int. 43 (2003), 243–249, 10.1016/S0197-0186(03)00009-3.
61. Mosbah, R., Yousef, M.I., Mantovani, A., Nicotine-induced reproductive toxicity, oxidative damage, histological changes and haematotoxicity in male rats: the protective effects of green tea extract. Exp. Toxicol. Pathol. 67 (2015), 253–259.
62. Zhao, J., Riediker, M., Detecting the oxidative reactivity of nanoparticles: a new protocol for reducing artifacts. J. Nanoparticle Res., 16, 2014, 10.1007/s11051-014-2493-0.
63. Pirela, I.R., Miousse, X., Lu, V., Castranova, T., Thomas, Y., Qian, D., Bello, L., Kobzik, I., Koturbash, P., Effects of laser Printer–Emitted engineered nanoparticles on cytotoxicity, chemokine expression, reactive oxygen species, DNA methylation, and DNA damage: a comprehensive in vitro analysis in human small airway epithelial cells, macrophages, and lymphobla. Environ. Health Perspect. 124 (2016), 210–219.
64. Sisler, J.D., Pirela, S.V., Friend, S., Farcas, M., Schwegler-Berry, D., Shvedova, A., Castranova, V., Demokritou, P., Qian, Y., Small airway epithelial cells exposure to printer-emitted engineered nanoparticles induces cellular effects on human microvascular endothelial cells in an alveolar-capillary co-culture model. Nanotoxicology 9 (2015), 769–779, 10.3109/17435390.2014.976603.
65. Watson, C.Y., DeLoid, G.M., Pal, A., Demokritou, P., Buoyant nanoparticles implications for nano-biointeractions in cellular studies. Small, 2016, 3172–3180, 10.1002/smll.201600314.
66. Liu, H., Sun, S., Zong, Y., Li, P., Xie, J., Analysis of hydrogen peroxide in cigarette smoke from selected Chinese cigarette brands under conventional and intense machine smoking conditions. Eur. Food Res. Technol. 235 (2012), 1107–1115, 10.1007/s00217-012-1840-6.
67. Miljevic, B., Fairfull-Smith, K.E., Bottle, S.E., Ristovski, Z.D., The application of profluorescent nitroxides to detect reactive oxygen species derived from combustion-generated particulate matter: cigarette smoke − a case study. Atmos. Environ. 44 (2010), 2224–2230, 10.1016/j.atmosenv.2010.02.043.
68. Anderson, C., Majeste, A., Hanus, J., Wang, S., E-cigarette aerosol exposure induces reactive oxygen species, DNA damage, and cell death in vascular endothelial cells. ToxSci Adv. Access 154 (2016), 332–340.
69. 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. 34 (2012), 529–537, 10.1016/j.reprotox.2012.08.001.
70. Cervellati, F., Muresan, X.M., Sticozzi, C., Gambari, R., Montagner, G., Forman, H.J., Torricelli, C., Maioli, E., Valacchi, G., Comparative effects between electronic and cigarette smoke in human keratinocytes and epithelial lung cells. Toxicol. Vitr. 28 (2014), 999–1005, 10.1016/j.tiv.2014.04.012.
71. Jensen, P., Luo, W., Pankow, J.F., Strongin, R.M., Peyton, D.H., Hidden formaldehyde in E-Cigarette aerosols. N. Engl. J. Med. 372 (2015), 392–394, 10.1056/NEJMc1414731.
72. 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. 16 (2014), 1319–1326, 10.1093/ntr/ntu078.