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. 2024 Jan 4;12(1):41.
doi: 10.3390/toxics12010041.

A Practical Framework for Novel Electronic Nicotine Delivery System Evaluation: Chemical and Toxicological Characterization of JUUL2 Aerosol and Comparison with Reference Cigarettes

David K Cook  1 , Guy Lalonde  1 , Michael J Oldham  1 , Jiaming Wang  1 , Austin Bates  1 , Sifat Ullah  1 , Christina Sulaiman  1 , Karen Carter  1 , Candice Jongsma  1 , Gary Dull  1 , I Gene Gillman  1
Affiliations

A Practical Framework for Novel Electronic Nicotine Delivery System Evaluation: Chemical and Toxicological Characterization of JUUL2 Aerosol and Comparison with Reference Cigarettes

David K Cook et al. Toxics. .

Abstract

Electronic nicotine delivery systems (ENDSs) are designed as a non-combustible alternative to cigarettes, aiming to deliver nicotine without the harmful byproducts of tobacco combustion. As the category evolves and new ENDS products emerge, it is important to continually assess the levels of toxicologically relevant chemicals in the aerosols and characterize any related toxicology. Herein, we present a proposed framework for characterizing novel ENDS products (i.e., devices and formulations) and determining the reduced risk potential utilizing analytical chemistry and in vitro toxicological studies with a qualitative risk assessment. To demonstrate this proposed framework, long-term stability studies (12 months) analyzing relevant toxicant emissions from six formulations of a next-generation product, JUUL2, were conducted and compared to reference combustible cigarette (CC) smoke under both non-intense and intense puffing regimes. In addition, in vitro cytotoxicity, mutagenicity, and genotoxicity assays were conducted on aerosol and smoke condensates. In all samples, relevant toxicants under both non-intense and intense puffing regimes were substantially lower than those observed in reference CC smoke. Furthermore, neither cytotoxicity, mutagenicity, nor genotoxicity was observed in aerosol condensates generated under both intense and non-intense puffing regimes, in contrast to results observed for reference cigarettes. Following the proposed framework, the results demonstrate that the ENDS products studied in this work generate significantly lower levels of toxicants relative to reference cigarettes and were not cytotoxic, mutagenic, or genotoxic under these in vitro assay conditions.

Keywords: ENDS; aerosol; chemical; e-cigarette; electronic cigarette; framework; toxicological.

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Conflict of interest statement

At the time this work was performed, all authors were employed by Juul Labs, Inc. All testing was performed at Enthalpy Analytical LLC and Charles River Laboratories and paid for in full by Juul Labs, Inc.

Figures

Figure 1
Figure 1
Chemical and toxicological evaluation framework.
Figure 2
Figure 2
Percent reduction comparison of mean JUUL2 pod aerosol constituent aerosol levels and mean combustible cigarette smoke constituent levels under non-intense puffing regimes.
Figure 3
Figure 3
Percent reduction comparison of mean JUUL2 pod aerosol constituent aerosol levels and mean combustible cigarette smoke constituent levels under intense puffing regimes.
Figure 4
Figure 4
BALB/c 3T3 and A549 cytotoxicity of intense and non-intense ENDS aerosol and 3R4F smoke condensates, measured in the NRU assay. The dotted line represents the 70% relative viability cut-off defining cytotoxicity [98].
See this image and copyright information in PMC

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