A framework for in vitro systems toxicology assessment of e-liquids

Abstract

Various electronic nicotine delivery systems (ENDS), of which electronic cigarettes (e-cigs) are the most recognized prototype, have been quickly gaining ground on conventional cigarettes because they are perceived as less harmful. Research assessing the potential effects of ENDS exposure in humans is currently limited and inconclusive. New products are emerging with numerous variations in designs and performance parameters within and across brands. Acknowledging these challenges, we present here a proposed framework for an in vitro systems toxicology assessment of e-liquids and their aerosols, intended to complement the battery of assays for standard toxicity assessments. The proposed framework utilizes high-throughput toxicity assessments of e-liquids and their aerosols, in which the device-to-device variability is minimized, and a systems-level investigation of the cellular mechanisms of toxicity is an integral part. An analytical chemistry investigation is also included as a part of the framework to provide accurate and reliable chemistry data solidifying the toxicological assessment. In its simplest form, the framework comprises of three main layers: (1) high-throughput toxicity screening of e-liquids using primary human cell culture systems; (2) toxicity-related mechanistic assessment of selected e-liquids, and (3) toxicity-related mechanistic assessment of their aerosols using organotypic air–liquid interface airway culture systems. A systems toxicology assessment approach is leveraged to enable in-depth analyses of the toxicity-related cellular mechanisms of e-liquids and their aerosols. We present example use cases to demonstrate the suitability of the framework for a robust in vitro assessment of e-liquids and their aerosols.

Overview of Electronic Nicotine Delivery Systems: A Systematic Review

“…In cellular studies, exposure to ENDS vapor increased anti-inflammatory processes, 275,278 placed oxidative stress on exposed cells, 269,279,294,301 and increased cell apoptosis and necrosis. 305 Particular ENDS flavors are more cytotoxic than others, but generally most studied ENDS liquids are much less cytotoxic than cigarette smoke extract.…”

Electronic cigarettes—A review of the physiological health effects

“…These differences could potentially explain the varying levels of the same chemical in the aerosol or a different degree of cardiac function impairment. To draw meaningful broad conclusions, there is, therefore, a need for better standardization of protocols (e.g., Azzopardi et al 2016;Farsalinos et al 2016c;Iskandar et al 2016). In addition, future researchers need to take advantage of other tools and methodologies such as randomized controlled trials (Cravo et al 2016), and develop mathematical models and new frameworks (Kalkhoran and Glantz 2015;Levy et al 2017).…”

Developing Network-Based Systems Toxicology by Combining Transcriptomics Data with Literature Mining and Multiscale Quantitative Modeling

“…The importance of this endeavor was underlined by the fact that the achievement of Step [3] was explicitly promoted as "the ultimate goal of systems toxicology." As Step [1] has been completed with the CBN database and the development of the NPA methodology, the attention now focuses on Steps [2] and [3], which have to incorporate the predictive capacity of the future qAOP.…”

“…As Step [1] has been completed with the CBN database and the development of the NPA methodology, the attention now focuses on Steps [2] and [3], which have to incorporate the predictive capacity of the future qAOP. Typical useful resources in this context are the BioModels database containing hundreds of computational models of biological processes (…”

“…The ongoing public debates on the impact on human health of glyphosate, bisphenol A, or electronic cigarettes have underlined the importance of performing reliable toxicological assessments [1][2][3]. In this context, regulatory authorities need to require evidence packages to assess the health risks associated with chemical compounds of uncertain safety risk contained in consumer products or present in the environment.…”