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Evaluating the Cytotoxicity of Electronic Cigarette Refill Fluids and Aerosols and Identifying Flavor Chemicals That May Cause Harm
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Evaluating the Cytotoxicity of Electronic Cigarette Refill Fluids and Aerosols and Identifying Flavor Chemicals That May Cause Harm
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Dissertation
Evaluating the Cytotoxicity of Electronic Cigarette Refill Fluids and Aerosols and Identifying Flavor Chemicals That May Cause Harm
2018
Overview
Electronic cigarettes (EC) have become part of mainstream culture. In 2016, the FDA classified EC as tobacco products and deemed they should be regulated as such. EC produce an aerosol from fluids that expose users to flavor chemicals generally regarded as safe for ingestion. When first introduced, little was known about how consumers would use these products or how they would affect human health. This project sought to assess EC topography, adapt 96-well plate assays for use with human embryonic stem cells (hESC), evaluate the cytotoxicity of EC refill fluids and aerosols, and identify flavor chemicals that may cause harm. Topography varied among users, but was often consistent within an individual between brands or days. Moreover, nicotine consumption and total puff volume were consistent with compensatory usage. hESC serve as an important model for evaluating the effects of EC on prenatal development that would be relevant for pregnant women who use these products. hESC, which are typically difficult to work with in quantitative assays, were adapted and validated for use in 96-well plate assays. Refill fluids and aerosols were then screened for cytotoxicity. Flavors, brands and solvent mixtures ranged in cytotoxicity with glycerin based products and cinnamon-flavored fluids being the most potent. To identify the cause of cytotoxicity, flavor chemicals were identified in a convenience sample of products. Twelve dominant flavor chemicals were found at concentrations >1 mg/ml. Cinnamaldehyde (CAD) was identified as a dominant flavor chemical in cinnamon-flavored products, and cytotoxicity was correlated with the amount of CAD/product. In several products, CAD was found at extremely high concentrations in both refill fluids (>100 mg/ml) and their aerosols. CAD was further tested in cell-based assays, and the overall impact of CAD on respiratory cells was studied at the air-liquid interface in a 3D model using a proteomics pathway analysis. CAD was genotoxic, impacted the cytoskeleton, and affected growth, motility and apoptosis, and upregulated several cell stress-based pathways in the human bronchial epithelium. This project found that some flavor chemicals, such as CAD, are present in EC products at high concentrations that could be harmful to human health. EC products, including flavor chemicals, should be regulated to insure user safety.
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
9780438430266, 0438430263
