Robustness of HPHC Reduction in THS 2.2 Aerosol Relative to 3R4F Reference Cigarette Smoke under Extreme Climatic Conditions

Abstract

Summary In order to assess robustness for the reduction of harmful and potentially harmful constituent (HPHC) levels generated by the Tobacco Heating System 2.2 (THS 2.2), a heated tobacco product, we compared the aerosol of this product with mainstream smoke from the 3R4F reference cigarette under different conditions of temperature and humidity. The desired climatic conditions were achieved by using an air-conditioning system coupled with the smoking-machine housing. Two extreme climatic conditions were selected, representing a “Hot and Dry” climate (30 °C and 35% relative humidity RH) and a “Hot and Very Humid” climate (30 °C and 75% RH). In addition, aerosol and smoke were generated using the standard conditions recognized for smoking-machine analyses of tobacco products (22 °C and 60% RH), which were close to the climatic conditions defined for “Subtropical and Mediterranean” environments (25 °C and 60% RH). The experimental conditions were chosen to simulate the use of THS 2.2 and cigarettes under extreme conditions of temperature and humidity. HeatSticks and cigarettes taken from freshly opened packs were subjected to short-term conditioning from two to a few more days under the same experimental conditions. We analyzed 54 HPHCs in THS 2.2 aerosol and 3R4F cigarette smoke, generated in accordance with the Health Canada Intense (HCI) standard, using modified temperature and humidity conditions for sample conditioning and machine-smoking experiments. We used a volume-adjusted approach for comparing HPHC reductions across the different climatic conditions investigated. Although a single puffing regimen was used, the total puff volume recorded for the 3R4F cigarette smoke varied due to the influence of temperature and humidity on combustion rate, which justified the use of a volume-adjusted approach. Volume-adjusted yields were derived from HPHC yields expressed in mass-per-tobacco stick normalized per total puff volume. The results indicated that, regardless of the considered climatic conditions, the HPHC levels investigated in THS 2.2 aerosol were reduced by at least 90%, on average, when compared with the concentrations in 3R4F cigarette mainstream smoke. This confirmed the robustness in performance for THS 2.2 to deliver reduced levels of HPHCs under the extreme climatic conditions investigated in this study. In order to further characterize the robustness of these reductions, the lowest reduction performance achieved for individual HPHCs across all climatic conditions was used to define the threshold for a robust reduction. The majority of the 54 HPHCs investigated in THS 2.2 aerosol showed more than 90% reduction. Calculations derived from nicotine-adjusted yields also confirmed robust reductions for all investigated HPHCs. The small differences in absolute reduction between the volume- and nicotine-adjusted approaches were predominantly attributed to a combination of the differences in both nominal nicotine deliveries and total puff volumes between THS 2.2 and 3R4F cigarettes; however, this did not influence the determination of robustness. Our findings confirm the value of this approach for assessing the robustness of a product’s performance under different climatic conditions.

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

“…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).…”

“…The U.S. Food and Drug Administration (U.S. FDA, 2012) has proposed guidance for assessing the harm reduction potential of a “modified risk tobacco product” (MRTP) based on the possibility that decreased toxicant exposure may lead to health benefits. One of the expected MRTPs is heated tobacco products (HTPs), which generate vapor by heating but not combusting tobacco leaves; thus, the aerosol contains lower levels of harmful constituents than CS (Hirn et al, 2020; Poget et al, 2021). Several previous studies showed that the aerosol of HTP elicited less biological effects in in vitro and in vivo studies, as well as clinical testing (Ito et al, 2019; Phillips et al, 2016; Thorne et al, 2020; Yuki et al, 2022).…”

The Product Science of Electrically Heated Tobacco Products: An Updated Narrative Review of the Scientific Literature

“…This observation is supported by the majority of newly identified studies and reviews. Quantified levels of the HPHCs investigated were either substantially lower from HTPs than from cigarettes [34][35][36][37][38][39][40] or undetectable or unquantifiable for HTPs [41]. The observed reduction in HPHC yields for HTPs when compared to cigarettes remains even when experimental machine smoking of the products is conducted under a range of extreme conditions of temperature and humidity [36].…”

“…Quantified levels of the HPHCs investigated were either substantially lower from HTPs than from cigarettes [ 34 - 40 ] or undetectable or unquantifiable for HTPs [ 41 ]. The observed reduction in HPHC yields for HTPs when compared to cigarettes remains even when experimental machine smoking of the products is conducted under a range of extreme conditions of temperature and humidity [ 36 ]. A small number of additional identified studies or reviews reported levels of chemical constituents to be higher with HTPs than with cigarettes for some, but not all, of the HTPs investigated [ 39 , 42 ].…”

Non-targeted analytical comparison of a heated tobacco product aerosol against mainstream cigarette smoke: does heating tobacco produce an inherently different set of aerosol constituents?

“…The relevance of this product category lies in its potential as a harm reduction strategy, as HTPs have been shown to release lower levels of harmful and potentially harmful constituents (HPHCs) than cigarettes. For one of the marketleading HTPs, the Tobacco Heating System 2.2 (THS 2.2) developed by Philip Morris International (PMI) and marketed under the brand name IQOS™ [1], analytical studies have substantiated its potential for harm reduction by demonstrating that it releases on average > 90% lower levels of HPHCs versus a reference cigarette, even when using extreme puffing regimens and climatic conditions [2,3].…”