Assessment of the exposure to harmful and potentially harmful constituents in healthy Japanese smokers using a novel tobacco vapor product compared with conventional cigarettes and smoking abstinence

Yuki, Dai; Takeshige, Yuki; Nakaya, Kyoko; Futamura, Yasuyuki

doi:10.1016/j.yrtph.2018.05.001

Cited by 25 publications

(39 citation statements)

References 28 publications

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“…Because the risk of smoking-related diseases is dose-dependent [ [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] ], a significant reduction in toxicant emission can be expected to result in a significant reduction in toxicant exposure in human subjects who switch from cigarette smoking to a candidate MRTP in clinical studies. Ideally, this exposure reduction should approach the effect of complete smoking abstinence [ [37] , [38] , [39] , [40] , [41] , [42] ].…”

Section: Introductionmentioning

confidence: 99%

Comparing the preclinical risk profile of inhalable candidate and potential candidate modified risk tobacco products: A bridging use case

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Comparing the preclinical risk profile of inhalable candidate and potential candidate modified risk tobacco products: A bridging use case

et al. 2020

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“…A short-term clinical study reported that smokers who switched to NTV showed a decrease in levels for biomarkers that indicate CS exposure (Yuki et al, 2018). The study provides the difference in the state of exposure, whereas in vitro studies using 3D cells provide the difference in functional change and organizational morphology.…”

Section: Biological Implications Of the Resultsmentioning

confidence: 99%

LC/MS analysis of three-dimensional model cells exposed to cigarette smoke or aerosol from a novel tobacco vapor product

2020

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A novel tobacco vapor product (NTV) contains tobacco leaves and generates nicotinecontaining aerosols using heating elements. Subchronic biological effects have been evaluated previously using three-dimensional bronchial epithelial model cells by repeated exposure to cigarette smoke (CS) and the NTV aerosols; however, the intracellular exposure characteristics have not been studied in detail. In this study, cells were initially exposed to an aqueous extract (AqE) of cigarette smoke (CS) at two concentration levels, and the cell lysate underwent untargeted analysis by LC-high resolution mass spectrometry to determine the exogenous compounds present in the cells. Among the thousands of peaks detected, four peaks showed a CS-dependency, which were reproducibly detected. Two of the peaks were nicotine and nicotine N-oxide, and the other two putative compounds were myosmine and norharman. The cells were then exposed to an AqE of CS in various combinations of exposure and post-exposure culture durations. Post-exposure culturing of cells with fresh medium markedly decreased the peak areas of the four compounds. The in-vitro switching study of CS to NTV aerosols was investigated by intermittently exposing cells to an AqE of CS four times, followed by exposure to either an AqE of CS, NTV aerosol or medium another four times. Switching to NTV reduced myosmine and norharman levels, which are known CS constituents. The results indicate that extracellular compounds inside cells reflect the exposure state outside cells. Thus, monitoring functional changes to cells in these exposure experiments is feasible.

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“… Exposure to carcinogenic toxicants A significant reduction in carcinogenic toxicant emission should then lead to a significant reduction in exposure to these substances in human subjects who switch from cigarette smoking to using a cMRTP in clinical studies. Ideally, these levels of exposure reduction should approach the levels of reduction observed in study subjects who abstained from smoking for the duration of the study [36–39]. As a direct consequence of a reduction in exposure to carcinogenic toxicants, switching to a cMRTP use should also lead to a significant reduction in urinary genotoxicity (a biomarker of total genotoxic exposure) compared with continued smoking and approach the urinary genotoxicity observed upon smoking abstinence [37].…”

Section: The Approachmentioning

confidence: 99%

Assessing the lung cancer risk reduction potential of candidate modified risk tobacco products

et al. 2019

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Smoking is the major cause of lung cancer. While the risk of lung cancer increases with the number of cigarettes smoked and the duration of smoking, it also decreases upon smoking cessation. The development of candidate modified risk tobacco products (cMRTP) is aimed at providing smokers who will not quit with alternatives to cigarettes that present less risk of harm and smoking-related disease. It is necessary to assess the risk reduction potential of cMRTPs, including their potential to reduce the risk of lung cancer. Assessing the lung cancer risk reduction potential of cMRTPs is hampered by (i) the absence of clinical risk markers that are predictive of future lung cancer development, (ii) the latency of lung cancer manifestation (decades of smoking), and (iii) the slow reduction in excess risk upon cessation and a fortiori upon switching to a cMRTP. It is, therefore, likely that only long-term epidemiology will provide definitive answers to this question and allow to first verify that a cMRTP reduces the risk of lung cancer and if it does, to quantify the reduction in excess lung cancer risk associated with a cMRTP. For this to be possible, the cMRTP would need to be available in the market and used exclusively by a large portion of current smokers. Here, we propose that a mechanism-based approach represents a solid alternative to show in a pre-market setting that switching to a cMRTP is likely to significantly reduce the risk of lung cancer. This approach is based on the causal chain of events that leads from smoking to disease and leverages both non-clinical and clinical studies as well as the principles of systems toxicology. We also discuss several important challenges inherent to the assessment of cMRTPs as well as key aspects regarding product use behavior.

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Assessment of the exposure to harmful and potentially harmful constituents in healthy Japanese smokers using a novel tobacco vapor product compared with conventional cigarettes and smoking abstinence

Cited by 25 publications

References 28 publications

Comparing the preclinical risk profile of inhalable candidate and potential candidate modified risk tobacco products: A bridging use case

Comparing the preclinical risk profile of inhalable candidate and potential candidate modified risk tobacco products: A bridging use case

LC/MS analysis of three-dimensional model cells exposed to cigarette smoke or aerosol from a novel tobacco vapor product

Assessing the lung cancer risk reduction potential of candidate modified risk tobacco products

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