Evaluation of the Tobacco Heating System 2.2. Part 4: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects compared with cigarette smoke

Abstract

The objective of the study was to characterize the toxicity from sub-chronic inhalation of test atmospheres from the candidate modified risk tobacco product (MRTP), Tobacco Heating System version 2.2 (THS2.2), and to compare it with that of the 3R4F reference cigarette. A 90-day nose-only inhalation study on Sprague-Dawley rats was performed, combining classical and systems toxicology approaches. Reduction in respiratory minute volume, degree of lung inflammation, and histopathological findings in the respiratory tract organs were significantly less pronounced in THS2.2-exposed groups compared with 3R4F-exposed groups. Transcriptomics data obtained from nasal epithelium and lung parenchyma showed concentration-dependent differential gene expression following 3R4F exposure that was less pronounced in the THS2.2-exposed groups. Molecular network analysis showed that inflammatory processes were the most affected by 3R4F, while the extent of THS2.2 impact was much lower. Most other toxicological endpoints evaluated did not show exposure-related effects. Where findings were observed, the effects were similar in 3R4F- and THS2.2-exposed animals. In summary, toxicological changes observed in the respiratory tract organs of THS2.2 aerosol-exposed rats were much less pronounced than in 3R4F-exposed rats while other toxicological endpoints either showed no exposure-related effects or were comparable to what was observed in the 3R4F-exposed rats.

New ideas, old problems? Heated tobacco products – a systematic review

“…However, Wong et al observed a significant increase in alanine aminotransferase (ALT), liver weights, and hepatocellular vacuolization in female rats exposed to IQOS. These effects were lower or absent in the case of cigarette-exposed rats [42]. Exposure to the IQOS aerosol did not induce lung inflammation or emphysema, nor did it consistently change the lipid profile or enhance the aortic plaque formation [66,67].…”

“…The tobacco industry has performed multiple studies regarding health consequences of HTP use. The results of in vitro and in vivo studies indicate that HTP aerosols have lower toxicity and no new hazards compared to conventional cigarette smoke [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. The results of humanbased studies also suggest that switching from conventional cigarettes to IQOS or glo leads to reductions in exposure to smoke toxicants in a manner comparable to quitting tobacco use [74][75][76][77][78].…”

“…Following the manufacturer recommendations, especially proper cleaning of the device after each 20 tobacco sticks seems to be crucial to provide proper thermal regulation and reduce emissions of harmful substances. Most of the research regarding the chemical composition of generated aerosol was carried out on brand new, never used devices [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. Independent researchers showed that the use of 1 IQOS tobacco stick left a significant amount of debris, fluid, and fragments of cast-leaf in the device holder [8].…”

Awareness and Use of 'Heat-not-burn' Tobacco Products in Great Britain

“…The manufacturer has published a host of in vitro, animal and human studies reporting that use of the heat-not-burn product is associated with reduced health risks compared with smoking cigarettes. [4][5][6] Crucially, any interpretation of these studies is limited by the researchers' and funders' conflict of interest. In one of these studies, smokers switched to using the heat-not-burn product for 5 days and were compared with smokers continuing to smoke cigarettes.…”

Possible hepatotoxicity of IQOS

“…The preclinical and clinical data PMI submitted to FDA indicate that IQOS exposure may be associated with unexpected liver toxicity. We reviewed preclinical studies conducted by PMI scientists 1 and clinical studies of 5 and 90 days of exposure to IQOS and IQOS menthol 2–5 included in PMI’s Modified Risk Tobacco Product application submitted to the US FDA.…”