Chemical and in vitro toxicological comparison of emissions from a heated tobacco product and the 1R6F reference cigarette

Hashizume, Tsuneo; Ishikawa, Shinkichi; Matsumura, Kazunori; Ito, Shigeaki; Fukushima, Toshiro

doi:10.1016/j.toxrep.2023.02.005

Cited by 20 publications

(13 citation statements)

References 44 publications

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“…The heater in the device heats the tobacco stick for approximately 5 minutes (the temperature inside the tobacco stick during use is up to 295°C) to generate tobacco vapor before being inhaled. Aerosol emissions for the tobacco sticks of DT3.0a and mDT3.0a used in this study were reported by Hashizume et al 16 As an…”

Section: Investigational Tobacco Productsmentioning

confidence: 66%

“…16 In addition, the DT3.0a aerosol registered little response when investigated for mutagenic and cytotoxic effects following in vitro toxicological assays, in contrast to results obtained using the University of Kentucky reference cigarette. 16 Such results would suggest that switching from combustible cigarettes to the DT3.0a potentially reduces exposure to cigarette smoke constituents.…”

mentioning

confidence: 88%

“…In 2021, the DT3.0a (direct tobacco heating system, platform 3, generation 0, version a), which electronically heats the inside of a tobacco stick up to a temperature of 295°C, was developed and introduced by Japan Tobacco Inc. 16 The results of the chemical analysis of aerosol generated from the DT3.0a showed that most of the measured selected cigarette smoke constituents were lower levels as compared to the University of Kentucky reference cigarette. 16 In addition, the DT3.0a aerosol registered little response when investigated for mutagenic and cytotoxic effects following in vitro toxicological assays, in contrast to results obtained using the University of Kentucky reference cigarette. 16 Such results would suggest that switching from combustible cigarettes to the DT3.0a potentially reduces exposure to cigarette smoke constituents.…”

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confidence: 99%

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confidence: 99%

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A Randomized Control Study in Healthy Adult Smokers to Assess Reduced Exposure to Selected Cigarette Smoke Constituents in Switching to the Novel Heated Tobacco Product DT3.0a

Nishihara,

Yuki,

Suzuki

et al. 2023

Clinical Pharm in Drug Dev

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This was a randomized, controlled, open‐label, confinement study to assess change in exposure to selected cigarette smoke constituents in healthy adult cigarette smokers who switched to using a novel heated tobacco product (direct heating tobacco system, platform 3, generation 3, version a [DT3.0a]). Sixty nonmenthol cigarette smokers were randomized into 1 of the 4 study groups in which subjects switched to a nonmenthol type of tobacco stick used with DT3.0a, switched to a nonmenthol tobacco stick used with an in‐market heated tobacco product device (THS), continued to smoke nonmenthol cigarettes, or stopped smoking. Furthermore, 30 menthol cigarette smokers were randomized into 1 of the 2 study groups in which subjects switched to a menthol tobacco stick used with DT3.0a (mDT3.0a) or continued to smoke menthol cigarettes. Fifteen biomarkers of exposure to selected harmful and potentially harmful constituents (HPHCs) were measured during the 5‐day exposure period, followed by assessment of nicotine pharmacokinetics with the assigned product. Results indicated that switching to DT3.0a, THS, and mDT3.0a showed significant exposure reductions in most of the selected HPHCs as compared to continuing smoking cigarettes, with reductions being similar in magnitude to reductions observed with smoking cessation. For DT3.0a and mDT3.0a, nicotine pharmacokinetic parameters were not remarkably different from those obtained for cigarettes and the THS except that a longer time to maximum concentration was obtained following use of the mDT3.0a. In conclusion, switching from smoking cigarettes to DT3.0a or THS use reduced exposure to most of the selected HPHCs, and no remarkable differences were observed for the measurements obtained from different flavors of DT3.0a stick.

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Section: Investigational Tobacco Productsmentioning

confidence: 66%

mentioning

confidence: 88%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A Randomized Control Study in Healthy Adult Smokers to Assess Reduced Exposure to Selected Cigarette Smoke Constituents in Switching to the Novel Heated Tobacco Product DT3.0a

Nishihara,

Yuki,

Suzuki

et al. 2023

Clinical Pharm in Drug Dev

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“…Therefore, reduction of the causative substances of ROS may be important. The causative substances of ROS include phenolic compounds, aromatic hydrocarbons, and metals (Caliri et al, 2021), which are present in HTP aerosol at low levels (Hashizume et al, 2023; Hirn et al, 2020; Poget et al, 2021). Additionally, our preliminary experiment showed that deterioration of ROS by antioxidant treatment (i.e., N ‐acetyl‐cysteine) effectively reduced EGFR activation by CS (Figure S4).…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress‐mediated epidermal growth factor receptor activation by cigarette smoke or heated tobacco aerosol in human primary bronchial epithelial cells from multiple donors

Muratani

Ichikawa

Erami

et al. 2023

J of Applied Toxicology

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The epidermal growth factor receptor (EGFR) signaling pathway has essential roles in maintaining homeostasis of various tissues by regulating cell proliferation and differentiation. Deregulation of the EGFR signaling pathway is associated with various chronic diseases including chronic obstructive pulmonary disease. Cigarette smoke (CS) is known to activate EGFR, which is linked to chronic obstructive pulmonary disease. The biological sequence from CS exposure to EGFR activation is initiated by oxidative stress caused by intracellular reactive oxygen species (ROS) and the depletion of glutathione, which led to EGFR ligand secretion and EGFR activation.We hypothesized that reducing exposure to CS constituents contributes to preventing CS-inducible EGFR activation. Therefore, we examined the aerosol from heated tobacco products (HTPs) because the aerosol contains fewer chemical constituents at lower levels than CS. We exposed primary human bronchial epithelial cells from four donors to the extracts of CS from a 1R6F reference cigarette or HTP aerosol from three in-market products, including our DT3.0a. The biological sequence from ROS to EGFR activation was assessed. CS induced all the tested endpoints although inter-donor differences were observed, whereas HTPs elicited most of the biological events at higher concentrations; however, EGFR phosphorylation was not observed even at fivefold higher concentration than CS. Overall, our results indicate that HTPs are less effective than CS to elicit ROS-induced EGFR activation. The reduced-risk potential of HTPs on EGFR-related diseases should be investigated further. In addition, testing with multiple donors is warranted when considering the individual differences in responses of primary cells to stimuli.

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A revision of the multiple‐path particle dosimetry model focusing on tobacco product aerosol dynamics

Mori,

Ito,

Sekine

2024

Numer Methods Biomed Eng

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To assess the health impact of inhaled aerosols, it is necessary to understand aerosol dynamics and the associated dosimetry in the human respiratory tract. Although several studies have measured or simulated the dosimetry of aerosol constituents, the respiratory tract focus areas have been limited. In particular, the aerosols generated from tobacco products are complex composites and simulating their dynamics in the respiratory tract is challenging. To assess the dosimetry of the aerosol constituents of tobacco products, we developed a revised version of the Multiple‐Path Particle Dosimetry (MPPD) model, which employs (1) new geometry based on CT‐scanned human respiratory tract data, (2) convective mixing in the oral cavity and deep lung, and (3) constituent partitioning between the tissue and air, and clearance. The sensitivity analysis was conducted using aerosols composed of four major constituents of electronic cigarette (EC) aerosols to investigate the parameters that have a significant impact on the results. In addition, the revised model was run with 4 and 10 constituents in ECs and conventional cigarettes (CCs), respectively. Sensitivity analysis revealed that the new modeling and the physicochemical properties of constituents had a considerable impact on the simulated aerosol concentration and dosimetry. The simulations could be carried out within 3 min even when 10 constituents of CC aerosols were analyzed simultaneously. The revised model based on MPPD is an efficient and easy‐to‐use tool for understanding the aerosol dynamics of CC and EC constituents and their effect on the human body.

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Chemical and in vitro toxicological comparison of emissions from a heated tobacco product and the 1R6F reference cigarette

Cited by 20 publications

References 44 publications

A Randomized Control Study in Healthy Adult Smokers to Assess Reduced Exposure to Selected Cigarette Smoke Constituents in Switching to the Novel Heated Tobacco Product DT3.0a

A Randomized Control Study in Healthy Adult Smokers to Assess Reduced Exposure to Selected Cigarette Smoke Constituents in Switching to the Novel Heated Tobacco Product DT3.0a

Oxidative stress‐mediated epidermal growth factor receptor activation by cigarette smoke or heated tobacco aerosol in human primary bronchial epithelial cells from multiple donors

A revision of the multiple‐path particle dosimetry model focusing on tobacco product aerosol dynamics

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