Semester

Fall

Date of Graduation

2019

Document Type

Thesis

Degree Type

MS

College

School of Medicine

Department

Not Listed

Committee Chair

Christopher Cuff

Committee Co-Chair

Stephen Leonard

Committee Member

Mark Olfert

Abstract

E-cigarettes and vapes are relatively new devices which are popular among young adults and teens. These devices vaporize an “e-liquid” for the user to inhale, which typically contains a mixture of propylene glycol (PG), vegetable glycerin (VG), varying concentrations of nicotine, and flavoring chemicals. Due to these flavoring chemicals being intended for ingestion as a food additive, their respiratory health effects are not well understood. Thousands of e-cigarette flavors are available on the market, many of which have the potential for toxicity. The majority of e-liquid flavoring chemicals (ELFCs) have not been tested for inhalation safety. In this study, we used pulmonary-associated cell lines to assess the in vitro effects of thirty ELFCs to determine their potential cytotoxicity at various concentrations. The ELFC vehicles PG and VG were tested individually and as mixtures that mirrored common ratios found in e-liquids (50/50 and 30/70 PG/VG, respectively). Cultured human monocytes (THP-1) were differentiated into naïve and activated macrophage phenotypes before treatment. Both cultured human bronchial epithelial cells (BEAS-2B) and differentiated macrophages were treated with 10, 100, and 1000 μM of ELFC and analyzed for cytotoxicity and inflammatory markers, including changes in viability, cell membrane damage, reactive oxygen species (ROS) production, and inflammatory cytokine release. The ELFCs which appear to affect viability the most fall into the categories of aldehydes with large carbon chains attached (decanal, hexanal, and nonanal), compounds containing benzene rings (cinnamaldehyde, eugenol, and vanillin), and chemicals classified as monoterpenes, which contain two isoprene groups (alpha-pinene, eugenol, and limonene). Cell membrane damage, as measured by lactate dehydrogenase release, was elevated in both cell lines after treatment with alpha-pinene, decanal, and nonanal. The THP-1 cells were also more sensitive to ethyl maltol and eugenol. Vanillin, ethyl maltol, and the diketones (2,3-pentanedione, 2,3-heptanedione, and 2,3-hexanedione) elicited high amounts of ROS from both cell lines. The BEAS-2B cells did not produce large amounts of inflammatory cytokines. Naïve THP-1 cells produced high levels of IL-1β, IL-8, and TNF-α when exposed to ethyl maltol and hexanal. Activated THP-1 cells also had increased IL-1β and TNF-α when exposed to ethyl maltol, but interestingly many ELFCs had a suppressive effect on inflammatory cytokines produced by activated macrophages. These findings provide insight into the potential lung pathology that e-cigarette and vape users are at risk for and provide a basis for future experiments with ELFC exposures.

Embargo Reason

Publication Pending

Available for download on Saturday, December 05, 2020

Included in

Toxicology Commons

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