Effects of E-Cigarette Refill Liquid Flavorings with and Without Nicotine on Human Retinal Pigment Epithelial Cells: A Preliminary Study

Overview

Journal Int J Environ Res Public Health

Publisher MDPI

Specialties Environmental Health
Public Health

Date 2021 Nov 13

PMID 34770169

Citations 3

Authors

Shilpi Goenka

Sanford R Simon

Affiliations

Soon will be listed here.

Abstract

Smoking is an etiologic factor for age-related macular degeneration (AMD). Although cigarette smoke has been extensively researched for retinal pigment epithelial (RPE) cell degeneration, the potential for adverse effects on the retinal epithelium following exposure to flavored e-cigarette refill liquid has never been explored. In this preliminary study, we have examined the effects of 20 e-liquids (10 different flavored nicotine-free and 10 nicotine-rich e-liquids) used in e-cigarettes on the metabolic activity, membrane integrity, and mitochondrial membrane potential of RPE cells. Our results showed that of the flavors studied over the concentration range: 0.5, 1, and 2% for a duration of 48 h, cinnamon was the most toxic and menthol was the second most toxic, while other flavors showed lesser or no cytotoxicity. The presence of nicotine augmented cytotoxicity for cinnamon, menthol, strawberry, vanilla, and banana while for other flavors there was no synergism. Together, our results demonstrate that exposure of RPE to flavored e-cigarette refill liquids caused significant cytotoxicity and may be a risk factor for the development of retinal pathogenesis, although further in-depth studies are necessary.

Citing Articles

Impact of nicotine-free and nicotine-rich flavored electronic cigarette refill liquids on primary human melanocyte function.

Goenka S Toxicol Rep. 2025; 14:101924.

PMID: 39949971 PMC: 11821416. DOI: 10.1016/j.toxrep.2025.101924.

E-cigarette flavoring chemicals and vehicles adversely impact the functions of pigmented human retinal ARPE-19 cells.

Goenka S Toxicol Rep. 2024; 13:101789.

PMID: 39526232 PMC: 11550671. DOI: 10.1016/j.toxrep.2024.101789.

Comparative Cytotoxicity of Menthol and Eucalyptol: An In Vitro Study on Human Gingival Fibroblasts.

Puig-Herreros C, Sanz J, Garcia-Bernal D, Rodriguez-Lozano F, Murcia L, Forner L Pharmaceutics. 2024; 16(4).

PMID: 38675182 PMC: 11054097. DOI: 10.3390/pharmaceutics16040521.

Carbonyl Profiles of Electronic Nicotine Delivery System (ENDS) Aerosols Reflect Both the Chemical Composition and the Numbers of E-Liquid Ingredients-Focus on the Toxicity of Strawberry and Vanilla Flavors.

Noel A, Ghosh A Int J Environ Res Public Health. 2022; 19(24).

PMID: 36554655 PMC: 9779252. DOI: 10.3390/ijerph192416774.

References

Leigh N, Lawton R, Hershberger P, Goniewicz M . Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS). Tob Control. 2016; 25(Suppl 2):ii81-ii87. PMC: 5784427. DOI: 10.1136/tobaccocontrol-2016-053205. View

He Y, Ge J, Burke J, Myers R, Dong Z, Tombran-Tink J . Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress. J Ocul Biol Dis Infor. 2012; 3(3):92-108. PMC: 3372610. DOI: 10.1007/s12177-011-9061-y. View

Bitzer Z, Goel R, Reilly S, Elias R, Silakov A, Foulds J . Effect of flavoring chemicals on free radical formation in electronic cigarette aerosols. Free Radic Biol Med. 2018; 120:72-79. PMC: 5940571. DOI: 10.1016/j.freeradbiomed.2018.03.020. View

Chan F, Moriwaki K, De Rosa M . Detection of necrosis by release of lactate dehydrogenase activity. Methods Mol Biol. 2013; 979:65-70. PMC: 3763497. DOI: 10.1007/978-1-62703-290-2_7. View

Merecz-Sadowska A, Sitarek P, Zielinska-Blizniewska H, Malinowska K, Zajdel K, Zakonnik L . A Summary of In Vitro and In Vivo Studies Evaluating the Impact of E-Cigarette Exposure on Living Organisms and the Environment. Int J Mol Sci. 2020; 21(2). PMC: 7013895. DOI: 10.3390/ijms21020652. View

Clapp P, Lavrich K, van Heusden C, Lazarowski E, Carson J, Jaspers I . Cinnamaldehyde in flavored e-cigarette liquids temporarily suppresses bronchial epithelial cell ciliary motility by dysregulation of mitochondrial function. Am J Physiol Lung Cell Mol Physiol. 2019; 316(3):L470-L486. PMC: 6459291. DOI: 10.1152/ajplung.00304.2018. View

Moodie C, Thrasher J, Cho Y, Barnoya J, Chaloupka F . Flavour capsule cigarettes continue to experience strong global growth. Tob Control. 2018; 28(5):595-596. DOI: 10.1136/tobaccocontrol-2018-054711. View

Patil A, Gramajo A, Sharma A, Seigel G, Kuppermann B, Kenney M . Differential effects of nicotine on retinal and vascular cells in vitro. Toxicology. 2009; 259(1-2):69-76. DOI: 10.1016/j.tox.2009.02.004. View

OFarrell H, Brown R, Brown Z, Milijevic B, Ristovski Z, Bowman R . E-cigarettes induce toxicity comparable to tobacco cigarettes in airway epithelium from patients with COPD. Toxicol In Vitro. 2021; 75:105204. DOI: 10.1016/j.tiv.2021.105204. View

10.

Larsson B, Tjalve H . Studies on the melanin-affinity of metal ions. Acta Physiol Scand. 1978; 104(4):479-84. DOI: 10.1111/j.1748-1716.1978.tb06303.x. View

11.

Kerasioti E, Veskoukis A, Skaperda Z, Zacharias A, Poulas K, Lazopoulos G . The flavoring and not the nicotine content is a decisive factor for the effects of refill liquids of electronic cigarette on the redox status of endothelial cells. Toxicol Rep. 2020; 7:1095-1102. PMC: 7484539. DOI: 10.1016/j.toxrep.2020.08.029. View

12.

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(3):e57987. PMC: 3603976. DOI: 10.1371/journal.pone.0057987. View

13.

Seiler-Ramadas R, Sandner I, Haider S, Grabovac I, Dorner T . Health effects of electronic cigarette (e‑cigarette) use on organ systems and its implications for public health. Wien Klin Wochenschr. 2020; 133(19-20):1020-1027. PMC: 8500897. DOI: 10.1007/s00508-020-01711-z. View

14.

Erythropel H, Jabba S, DeWinter T, Mendizabal M, Anastas P, Jordt S . Formation of flavorant-propylene Glycol Adducts With Novel Toxicological Properties in Chemically Unstable E-Cigarette Liquids. Nicotine Tob Res. 2018; 21(9):1248-1258. PMC: 6698951. DOI: 10.1093/ntr/nty192. View

15.

Wavreil F, Heggland S . Cinnamon-flavored electronic cigarette liquids and aerosols induce oxidative stress in human osteoblast-like MG-63 cells. Toxicol Rep. 2019; 7:23-29. PMC: 6909334. DOI: 10.1016/j.toxrep.2019.11.019. View

16.

Soneji S, Barrington-Trimis J, Wills T, Leventhal A, Unger J, Gibson L . Association Between Initial Use of e-Cigarettes and Subsequent Cigarette Smoking Among Adolescents and Young Adults: A Systematic Review and Meta-analysis. JAMA Pediatr. 2017; 171(8):788-797. PMC: 5656237. DOI: 10.1001/jamapediatrics.2017.1488. View

17.

Hazim R, Volland S, Yen A, Burgess B, Williams D . Rapid differentiation of the human RPE cell line, ARPE-19, induced by nicotinamide. Exp Eye Res. 2018; 179:18-24. PMC: 6360117. DOI: 10.1016/j.exer.2018.10.009. View

18.

Bahl V, Lin S, Xu N, Davis B, Wang Y, Talbot P . Comparison of electronic cigarette refill fluid cytotoxicity using embryonic and adult models. Reprod Toxicol. 2012; 34(4):529-37. DOI: 10.1016/j.reprotox.2012.08.001. View

19.

Leveziel N, Tilleul J, Puche N, Zerbib J, Laloum F, Querques G . Genetic factors associated with age-related macular degeneration. Ophthalmologica. 2011; 226(3):87-102. DOI: 10.1159/000328981. View

20.

Hess C, Olmedo P, Navas-Acien A, Goessler W, Cohen J, Rule A . E-cigarettes as a source of toxic and potentially carcinogenic metals. Environ Res. 2016; 152:221-225. PMC: 5135636. DOI: 10.1016/j.envres.2016.09.026. View