Concentrations of hazardous chemicals in mainstream aerosol generated by heat-not-burn tobacco

Background The Japanese government is trying to establish effective countermeasures for avoidance of secondhand smoke in indoor environments for tobacco-free Tokyo Olympic and Paralympic games 2020, as requested by the International Olympic Committee (IOC) and the World Health Organization (WHO). On the other hand, the tobacco industries have launched heat-not-burn (HNB) tobacco products which it claims is designed to produce less harmful components in Japan recently. Smokers strongly demand for products claiming or implying reduced health risks. There is little scientific data, however, of the hazards and toxicity of HNB tobacco. Methods In this study, we evaluated several harmful compounds (nicotine, tar, carbon monoxide (CO) and tobacco-specific nitrosamines (TSNAs)) in the mainstream aerosol and fillers of iQOS produced by Philip Morris International (PMI), and compared their concentrations with those from conventional combustion cigarettes. Mainstream aerosol was collected under the conditions of 55 ml puff volume, 2 s puff duration, 30 s puff interval, and 100% blocking of the filter ventilation holes according to the Health Canada, Official Method T-115. Results The concentrations of nicotine in tobacco fillers and the mainstream aerosol of iQOS were almost the same as those of conventional combustion cigarettes, while the concentration of TSNAs was one fifth and CO was one hundredth of those of conventional combustion cigarettes. Conclusions "Tobacco companies continue reassuring health concerned smokers by offering with their new products the illusion of safety (WNTD 2006)." The market share of HNB tobaccos have been rapidly increased in Japan. One reason why HNB may be gaining market share is that nicotine-containing ENDS are prohibited for sale in Japan. PMI applied for US-FDA approval of the heat-not-burn tobacco product "iQOS" as a modified risk tobacco product in 2016. Although it is low concentration in this study, toxic compounds are definitely included in the mainstream aerosol of iQOS

Evaluation of toxic activities of polycyclic aromatic hydrocarbon derivatives using in vitrobioassays

金沢大学医薬保健研究域薬学系金沢大学自然科学研究科Several polycyclic aromatic hydrocarbons and nitrated polycyclic aromatic hydrocarbons (PAHs/NPAHs) such as benzo[a]pyrene and 1-nitropyrene are mutagens and/or carcinogens. These compounds secondarily generate PAH hydroxides, ketones, and quinones through atmospheric and metabolic reactions. The health effects of these compounds is now an important social concern. For example, lung cancer, bronchitis, whistling and so on. In this work, we evaluated toxicities of 25 PAH derivatives (hydroxides, ketones and quinones) in terms of aryl hydrocarbon receptor (AhR) binding and thyroid hormone-related endpoints using three in vitro bioassays: dioxinresponsive chemical-activated luciferase gene expression (DR-CALUX), thyroid receptor β chemical-activated luciferase gene expression (TRβ-CALUX), and competitive human transthyretin-binding (TTR-binding) assays. Eleven of the 25 PAH derivatives had AhR agonist activity, six had AhR antagonist activity and seven had TRpotentiation activity in the TR-CALUX. Furthermore, PAH quinones and hydroxides had strong TTR-binding activity. 3,4-Dihydrobenz[a]anthracen-1(2 H)-one had the strongest agonist activity (EC20: 0.4μM) as determined by DR-CALUX. PAH ketones showed stronger activity than the control and significant difference by statistical analysis. Benzo[c]phenanthrene-[1,4]-quinone was the most TTR-active compound (IC50: 2.5μM). Both PAH ketones and quinones, which have functional groups with low polarity, had significant activities in all tested assays. These in vitro results suggest that PAH derivatives might have various toxic activities in animals. For estimating the health effects and accessing the environmental risks of PAHs, further studies on the toxicity mechanisms are necessary. ©2009 The Pharmaceutical Society of Japan