Application of dosimetry tools for the assessment of e-cigarette aerosol and cigarette smoke generated on two different in vitro exposure systems

Abstract

The diluted aerosols from a cigarette (3R4F) and an e-cigarette (Vype ePen) were compared in two commercially available in vitro exposure systems: the Borgwaldt RM20S and Vitrocell VC10. Dosimetry was assessed by measuring deposited aerosol mass in the exposure chambers via quartz crystal microbalances, followed by quantification of deposited nicotine on their surface. The two exposure systems were shown to generate the same aerosols (pre-dilution) within analytically quantified nicotine concentration levels (p = 0.105). The dosimetry methods employed enabled assessment of the diluted aerosol at the exposure interface. At a common dilution, the per puff e-cigarette aerosol deposited mass was greater than cigarette smoke. At four dilutions, the RM20S produced deposited mass ranging 0.1–0.5 µg/cm2/puff for cigarette and 0.1–0.9 µg/cm2/puff for e-cigarette; the VC10 ranged 0.4–2.1 µg/cm2/puff for cigarette and 0.3–3.3 µg/cm2/puff for e-cigarette. In contrast nicotine delivery was much greater from the cigarette than from the e-cigarette at a common dilution, but consistent with the differing nicotine percentages in the respective aerosols. On the RM20S, nicotine ranged 2.5–16.8 ng/cm2/puff for the cigarette and 1.2–5.6 ng/cm2/puff for the e-cigarette. On the VC10, nicotine concentration ranged 10.0–93.9 ng/cm2/puff for the cigarette and 4.0–12.3 ng/cm2/puff for the e-cigarette. The deposited aerosol from a conventional cigarette and an e-cigarette in vitro are compositionally different; this emphasises the importance of understanding and characterising different product aerosols using dosimetry tools. This will enable easier extrapolation and comparison of pre-clinical data and consumer use studies, to help further explore the reduced risk potential of next generation nicotine products.Graphical abstractA cigarette and an e-cigarette (top left) were assessed on two different in vitro exposure systems, the Borgwaldt RM20S (top right) and the VC 10 (bottom right). Compositionally the product aerosols were different, but there was no difference between the same product on different machines (bottom left).

Reduced biological effect of e-cigarette aerosol compared to cigarette smoke evaluated in vitro using normalized nicotine dose and RNA-seq-based toxicogenomics

“…In our recent e-cigarette studies, we have shown the importance of expressing dose as a function of delivered nicotine, when conducting comparative studies across different tobacco and nicotine product categories. Azzopardi et al 25 and Adamson et al 7,28 showed how deposited mass and nicotine quantification at the cellular exposure interface enable appropriate extrapolation and comparisons in an aerosol matrix. Different types of e-cigarettes and e-liquids generate different volumes of aerosol and deliver different amounts of nicotine, however typically smokers who switch from cigarette to nicotine delivery devices adapt their behavior to potentially titrate for nicotine 18,19 .…”

Characterization of a Vitrocell VC1 Using Nicotine Dosimetry: An Essential Component Toward StandardizedIn VitroAerosol Exposure of Tobacco and Next Generation Nicotine Delivery Products

“…However, while numerous studies have analyzed the aerosol constitu-ents generated by tobacco products and NGPs, [12][13][14] the exposure dosimetry at the ALI and the consistency of in vitro puff-to-puff aerosol production have only recently been realised. [15][16][17] Reproducible aerosol generation is crucial to developing standardized dosimetry measurements. In addition, measuring appropriate markers, for example, nicotine, at the cellular/tissue target is essential to understanding subsequent biological responses.…”

“…A number of dosimetry tools can be used to support the assessment of aerosols generated using in vitro exposure systems and include particle size and number evaluation, analytical chemical quantitation of exposure constituents, and mass deposition either by gravimetric means or analytical quantification. [15][16][17][18][19] For example, Neilson et al, 20 as part of an in vitro assessment of e-cigarettes in RhuA using a VC1 Smoking Robot, employed the use of quartz crystal microbalances (QCMs) to measure deposited mass and confirm aerosol delivery to the tissues. In another example, using a VC1 smoking robot, Fields et al, 21 assessed aerosols from reference 3R4F cigarette smoke and e-cigarettes by fluorometric analysis of aerosols collected at generation source and cellular exposure.…”

“…In this study, we have assessed 3R4F reference cigarette and NGP (e-cigarette and THP) aerosols in the VC1 at the generation source and at the exposure interface in the cellular media. Nicotine was quantified using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), as described in Adamson et al (2016). The use of nicotine as a surrogate marker of aerosol exposure allows for a direct comparison across the different products.…”

“…These data were then compared to previously published dosimetry data for the same products, generated at a different laboratory (BAT R&D, Southampton, UK) and on different exposure systems to confirm repeatability. 16,17 FIG. 1.…”