Effects of vaping-induced oxidation on nicotine analogs e-cigarettes

Univ Of North Carolina Chapel Hill, Chapel Hill NC

Investigators

Abstract

ABSTRACT The vaping landscape has significantly evolved since they were introduced, continuously gaining popularity among adolescents and young adults. Originally marketed as a smoking alternative or cessation aid, vaping devices now attract youth with various flavorings and addictive substances, including different forms of nicotine. Despite regulatory efforts, youth vaping remains a significant issue, especially with the rise of disposable devices like cool mint- and fruit-flavored vapes. Concerns about the safety of these devices compared to traditional cigarettes persist, as harmful compounds have been identified in vape emissions. The emergence of alternative nicotine formulations, such as 6-methyl nicotine, further complicates the situation. Research indicates that 6- methyl nicotine has similar physiological effects to nicotine but raises more significant safety concerns, necessitating further research and regulatory attention. Specifically, initial studies indicate that 6-methyl nicotine exhibits higher toxicity and greater activation of nicotinic receptors than nicotine, presenting a public health challenge due to gaps in understanding its long-term effects and potentially higher addictive attributes. To address these risks, this project hypothesizes that vaping-induced aerosolization of 6-methyl nicotine vaping products modifies the chemical composition of these e-liquids and generates toxic aerosol mixtures. The project aims to evaluate the chemical composition of 6-methyl nicotine and nicotinamide vapes before and after aerosolization and investigate their toxicity in human bronchial epithelial cells (hBECs), an initial target for inhaled e-cigarette aerosols. By integrating chemical characterization with in vitro exposures in our newly developed Vaping Product Exposure System (VaPES), these goals will be accomplished through two specific aims. Specific Aim 1 will analyze the chemical composition and metabolism of 6-methyl nicotine and nicotinamide vaping devices before and after vaping using targeted and nontargeted mass spectrometry. This will identify active ingredients, contaminants, and novel oxidation products formed during aerosolization. Specific Aim 2 will assess the toxicity of 6-methyl nicotine and nicotinamide compared to nicotine e-cigarettes in hBECs. This will involve evaluating cytotoxicity and gene expression, untargeted metabolomic and proteomic profiles in hBECs, and determination of chemical biomarkers of exposure. Computational modeling tools will be used to integrate chemical/transcriptomic/metabolic signatures associated with dysregulated cellular pathways in hBECs. The project's overarching goals are to provide comprehensive chemical characterization and comparative toxicity analysis of nicotine analog vaping products, inform regulatory decision-making, and lay the foundation for further toxicity testing. Utilizing advanced chemical and biological methods, this research aims to identify biomarkers of exposure and elucidate the potential health impacts of inhaling these new vaping products.