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.

Three study groups did not differ by age, gender, BMI, tar level in their usual cigarette brand, daily cigarette consumption, and nicotine dependence score.
Participants in the CC group smoked approximately 16 cigarettes (range: 10–36) per day and kept their daily cigarette consumption within ±10% of their self-reported daily consumption throughout the investigational period. NTV group topography: The mean of the daily NTV consumption increased from 3.3 capsules (range: 1–7) on Day 1 to 6.1 capsules (range: 1.5–10) on Day 5. The mean of the total puff volume on Day 1 increased approximately by 1.5 times compared to the baseline volume and remained similar on days 3 and 5. The mean number of puffs were 16, 13.9, 14.9, and 14.9 at baseline, days 1, 3, and 5, respectively. The average puff duration increased from 1.52 seconds at baseline to 1.87, 2, and 2.13 seconds on days 1, 3, and 5, respectively. The estimated number of puffs per day were 249, 220, 307, and 344 at baseline, days 1, 3, and 5, respectively. The baseline puffing topography was similar between the NTV and CC group, but unlike for the NTV group, it remained stable in the CC group from baseline to day 5. The authors concluded that "results obtained in the present study suggest that subjects in the NTV group changed their product use behavior adapting to the NTV during the study period, and the nicotine uptake level at baseline might be one of factors of change in product use behavior. However, the fixed daily limit of capsule consumption meant that this change in product use behavior was restricted for some subjects" (p. 132).
With the exception of 1-OHP, the concentrations of the other 15 biomarkers either decreased from baseline to Day 3 and Day 5 or decreased from baseline to day 3 and then remained stable through Day 5 in both the NTV and the SA groups, and remained stable throughout the five days in the CC group. In all 3 study groups, 1-OHP decreased between baseline and Day 3 and then increased back up by Day 5 to similar levels to baseline. On Day 5, levels of the following biomarkers were reduced in the NTV group relative to the CC group, i.e. by around 63% (GM ratio 36.7, 95% CI: 30.2-44.6) in 3-HPMA, 86% (GM ratio 13.6, 95% CI: 11.8-15.7) in CEMA, 85% (GM ratio 14.9, 95% CI: 12.3-18.0) in 4-ABP, 94% (GM ratio 5.9, 95% CI: 4.5-7.7) in 1-NA, 90% (GM ratio 10.0, 95 %CI: 8.6-11.7) in 2-NA, 87% (GM ratio 13.1, 95% CI: 10.6-16.2) in S-PMA, 67% (GM ratio 33.2, 95% CI: 24.4-45.3) in 3-OHBaP, 84% (GM ratio 15.8, 95% CI: 11.5-21.6) in MHBMA, 73% (GM ratio 26.5, 95% CI: 21.6-32.3) in HBMA, 86% (GM ratio 13.8, 95% CI: 10.4-18.4) in exhaled CO, 66% (GM ratio 33.5, 95% CI: 27.2-41.3) in HEMA, 59% (GM ratio 41, 95% CI: 35.2-47.8) in total NNAL, 81% (GM ratio 19.2, 95% CI: 13.6-26.9) in total NNN, 67% (GM ratio 32.8, 95% CI: 27.6-39.0) in o-toluidine, and 39% (GM ratio 60.6, 95% CI: 46.0-79.8) in total 1-OHP. The relative changes in biomarker concentrations from baseline to Day 5 were similar between the NTV and SA group in all biomarkers, except for total NNN and 1-OHP. The
relative change was slightly smaller for NNN in the NTV group than in the SA group. The nicotine uptake, measured by nicotine equivalents was relatively stable in the CC group between baseline (10.6 ± 5.2 mg/24hr) and Day 3 (10.4 ± 5.0 mg/24hr) and Day 5 (10.5 ± 4.8 mg/24hr), but decreased in the NTV group from baseline (9.3 ± 4.0 mg/24hr) to Day 3 (4.5 ± 2.7 mg/24hr) and SA groups from baseline (9.0 ± 4.6 mg/24hr) to Day 3 (1.0 ± 0.6 mg/24hr). However, total nicotine equivalents decreased in the SA group on Day 5 (0.3 ± 0.2 mg/24hr), but increased slightly in the NTV group (5.0 ± 3.0 mg/24hr). The relative changes from baseline to Day 5 in the NTV group were approximately in the middle of those observed for the CC and SA groups. The authors concluded that "results obtained in the present study confirm that switching to the NTV for 5 days resulted in substantial reductions in subject exposure to selected HPHCs. The NTV group of subjects yielded reductions in HPHC exposure levels similar to the SA group, despite the increases in daily capsule consumption and puffing behavior after switching to the NTV" (Page 132).

Yuki, D., Takeshige, Y., Nakaya, K., & Futamura, Y. (2018). 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. Regulatory Toxicology and Pharmacology, 96, 127-134.