Effects of Nicotine Concentration Levels in E-cigarettes on Biomarkers of Exposure to Toxicants and Tobacco Use Behaviors - Project Summary Electronic Nicotine Delivery System (ENDS, or e-cigarette) is a new class of tobacco products and may represent a reduced harm alternative for combustible cigarette smokers. In 2020, 3.7% (9.2 million) of adults aged 18 years and older reported current use of ENDS. Current everyday or some-day ENDS use is most prevalent among current cigarette smokers (13.8%) and former smokers (13.3%) and is uncommon among adult never smokers (2.2%). E-liquid nicotine concentration level is one of the primary product-level determinants of nicotine delivery and sensorimotor characteristics and there is a variety of nicotine concentration levels available in ENDS. Modern vaping products (e.g., pod-mod style like JUUL) contain nicotine in the salt formulation and tend to deliver nicotine to the lung more efficiently. Most recently, the Food and Drug Administration (FDA) has granted several ENDS products in the Premarket Tobacco Product Marketing review with varying nicotine levels, such as 0% (Logic Pro), 1.5% (Vuse Ciro), 3.0% (Vuse Viper), 4.5% (NJOY Daily Rich), and 6.0% (NJOY Daily Extra Rich). Meanwhile, FDA announced plans for proposed rules to reduce nicotine levels to minimally addictive or non-addictive levels among cigarettes (Cig). The research on the effects of e-liquid nicotine concentration levels, especially how different nicotine levels are related to health effects, tobacco use behaviors, and nicotine dependence and how nicotine levels interplay with vaping devices at the population level, can have important implications for future tobacco regulatory sciences. This large-scale population study will link the Population Assessment of Tobacco and Health (PATH) Waves 1-6 restricted biomarker with the PATH Adult Interview surveys. In Aim 1, we will analyze the pooled PATH biomarker-adult interview data to 1) examine between- subjects differences in biomarkers of exposure (BOEs) by nicotine concentration levels (e.g., zero, low, medium and high), and 2) test interaction effects of nicotine levels and vaping products on BOEs from 5 classes of FDA defined harmful and potentially harmful constituents (HPHC): nicotine metabolites, TSNAs, metals, PAHs, VOCs and the BOE of health effects (e.g., oxidative stress) in urine and serum panels using weighted multivariable regression models. In Aim 2, we will leverage the harmonized longitudinal Waves 1-6 PATH Adult Interview data to prospectively examine associations of nicotine levels in ENDS and vaping devices with tobacco use behaviors (e.g., subsequent abstinence from cigarette smoking or subsequent relapse to cigarette smoking) and nicotine dependence. This study is innovative in its focus on the effects of e-liquid nicotine concentration levels and vaping devices on population health (biomarkers), ENDS ↔ Cig use transitions and nicotine dependence by leveraging the nationally longitudinal data. Such information has important implications for future tobacco regulatory sciences at the population level and can guide FDA as to whether future Premarket Tobacco Product Application (PMTA) submissions for higher nicotine products should be authorized. 1
