Assessment of priority tobacco additives per the requirements of the EU Tobacco Products Directive (2014/40/EU): Part 3, Smoking behavior and plasma nicotine pharmacokinetics

McEwan, Michael; Coburn, Steven; Ghosh, David; Simms, Liam; Giles, Lesley; Yuki, Dai; Ashley, Madeleine; Roemer, E.; Sohn, Hyung-Ok; Proctor, Christopher

doi:10.1016/j.yrtph.2019.02.012

Cited by 5 publications

(12 citation statements)

References 26 publications

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“…This corresponds to a breathing rate of 12 breaths per min, a tidal volume of 1.3 L, an inspiration fraction of 0.5, a pause fraction of 0.1 and finally inhalation and exhalation times of 2.5 and 2 s, respectively. This scenario was chosen as the best one based on smoking habits ( McEwan et al, 2019 ). In his review, Bernstein (2004) describes a specific pattern of smoking with 2 phases: The initial puff is first taken into the mouth and after a pause of 1–4 s, the smoke is then inhaled into the lungs.…”

Section: Methodsmentioning

confidence: 99%

Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols

Moreau,

Simms,

Andersen

et al. 2024

Front. Toxicol.

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With the use of in vitro new approach methodologies (NAMs) for the assessment of non-combustible next-generation nicotine delivery products, new extrapolation methods will also be required to interpret and contextualize the physiological relevance of these results. Quantitative in vitro to in vivo extrapolation (QIVIVE) can translate in vitro concentrations into in-life exposures with physiologically-based pharmacokinetic (PBPK) modelling and provide estimates of the likelihood of harmful effects from expected exposures. A major challenge for evaluating inhalation toxicology is an accurate assessment of the delivered dose to the surface of the cells and the internalized dose. To estimate this, we ran the multiple-path particle dosimetry (MPPD) model to characterize particle deposition in the respiratory tract and developed a PBPK model for nicotine that was validated with human clinical trial data for cigarettes. Finally, we estimated a Human Equivalent Concentration (HEC) and predicted plasma concentrations based on the minimum effective concentration (MEC) derived after acute exposure of BEAS-2B cells to cigarette smoke (1R6F), or heated tobacco product (HTP) aerosol at the air liquid interface (ALI). The MPPD-PBPK model predicted the in vivo data from clinical studies within a factor of two, indicating good agreement as noted by WHO International Programme on Chemical Safety (2010) guidance. We then used QIVIVE to derive the exposure concentration (HEC) that matched the estimated in vitro deposition point of departure (POD) (MEC cigarette = 0.38 puffs or 11.6 µg nicotine, HTP = 22.9 puffs or 125.6 µg nicotine) and subsequently derived the equivalent human plasma concentrations. Results indicate that for the 1R6F cigarette, inhaling 1/6th of a stick would be required to induce the same effects observed in vitro, in vivo. Whereas, for HTP it would be necessary to consume 3 sticks simultaneously to induce in vivo the effects observed in vitro. This data further demonstrates the reduced physiological potency potential of HTP aerosol compared to cigarette smoke. The QIVIVE approach demonstrates great promise in assisting human health risk assessments, however, further optimization and standardization are required for the substantiation of a meaningful contribution to tobacco harm reduction by alternative nicotine delivery products.

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Section: Methodsmentioning

confidence: 99%

Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols

Moreau,

Simms,

Andersen

et al. 2024

Front. Toxicol.

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“…Finally, ventilation holes in cigarette filters allow the influx of ambient air, diluting the smoke, whereas smokers tend to cover these holes with their lips and fingers (unintentionally). Thus, in real life, greater quantities of harmful substances end up in the smoke due to more intense smoking and closing of the ventilation holes 6 .…”

Section: Limitations Of the Industry Reportsmentioning

confidence: 99%

“…The submitted reports contain the results of literature searches, smoke chemistry assessments, toxicity studies, a human clinical study, and a sensory assessment. A synthesis of these reports has also been published in three journal articles [4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

Review of industry reports on EU priority tobacco additives part B: Methodological limitations

Bølling¹,

Mallock²,

Zervas³

et al. 2022

Tob. Prev. Cessation

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“…This includes recent evidence developed to fulfill the EU Tobacco Products Directive (TPD) regulatory requirement for comprehensive studies on a priority list of ingredients. [34][35][36] There is an urgent need for similar regulatory requirements for e-liquid manufacturers to generate toxicological data to support the use of flavors and other e-liquid ingredients at intended use levels. Emerging data from subchronic inhalation studies indicate that, relative to flavor-free e-vapor, the presence of flavors does not increase the biological effects of e-vapor on the respiratory tract or cardiovascular system in Apoe À/À mice 37 (Wong et al, in prep).…”

Section: E-liquidsmentioning

confidence: 99%

State-of-the-art methods and devices for generation, exposure, and collection of aerosols from e-vapor products

Boué

Goedertier

Hoeng

et al. 2020

Toxicology Research and Application

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E-vapor products (EVP) have become popular alternatives for cigarette smokers who would otherwise continue to smoke. EVP research is challenging and complex, mostly because of the numerous and rapidly evolving technologies and designs as well as the multiplicity of e-liquid flavors and solvents available on the market. There is an urgent need to standardize all stages of EVP assessment, from the production of a reference product to e-vapor generation methods and from physicochemical characterization methods to nonclinical and clinical exposure studies. The objective of this review is to provide a detailed description of selected experimental setups and methods for EVP aerosol generation and collection and exposure systems for their in vitro and in vivo assessment. The focus is on the specificities of the product that constitute challenges and require development of ad hoc assessment frameworks, equipment, and methods. In so doing, this review aims to support further studies, objective evaluation, comparison, and verification of existing evidence, and, ultimately, formulation of standardized methods for testing EVPs.

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Assessment of priority tobacco additives per the requirements of the EU Tobacco Products Directive (2014/40/EU): Part 3, Smoking behavior and plasma nicotine pharmacokinetics

Cited by 5 publications

References 26 publications

Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols

Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols

Review of industry reports on EU priority tobacco additives part B: Methodological limitations

State-of-the-art methods and devices for generation, exposure, and collection of aerosols from e-vapor products

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