Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Nov 2016
Comparative StudyEvaluation of the Tobacco Heating System 2.2. Part 7: Systems toxicological assessment of a mentholated version revealed reduced cellular and molecular exposure effects compared with mentholated and non-mentholated cigarette smoke.
Modified risk tobacco products (MRTPs) are being developed with the aim of reducing smoking-related health risks. The Tobacco Heating System 2.2 (THS2.2) is a candidate MRTP that uses the heat-not-burn principle. Here, systems toxicology approaches were engaged to assess the respiratory effects of mentholated THS2.2 (THS2.2M) in a 90-day rat inhalation study (OECD test guideline 413). ⋯ In the lung, CS exposure induced an inflammatory response, triggered cellular stress responses, and affected sphingolipid metabolism. These responses were not observed or were much lower after THS2.2M aerosol exposure. Overall, this system toxicology analysis complements and reconfirms the results from classical toxicological endpoints and further suggests potentially reduced health risks of THS2.2M.
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Regul. Toxicol. Pharmacol. · Nov 2016
ReviewEvaluation of the Tobacco Heating System 2.2. Part 1: Description of the system and the scientific assessment program.
This publication introduces a series of eight other publications describing the non-clinical assessment and initial clinical study of a candidate modified risk tobacco product (MRTP) - the Tobacco Heating System 2.2 (THS2.2). This paper presents background information on tobacco harm reduction, to complement the approaches aimed at increasing smoking cessation and reducing smoking initiation to reduce the morbidity and mortality caused by cigarette smoking. THS2.2 heats tobacco without combustion, and the resulting formation of harmful and potentially harmful constituents (HPHC) is greatly reduced compared with cigarette smoke. ⋯ Additional mechanistic endpoints, measured as part of in vivo studies, confirmed reduced impact on smoking-related disease networks. The clinical study confirmed the reduced exposure to HPHCs in smokers switching to THS2.2, and the associated transcriptomic study confirmed the utility of a gene expression signature, consisting of only 11 genes tested in the blood transcriptome of subjects enrolled in the clinical study, as a complementary measure of exposure response. The potential of THS2.2 as an MRTP is demonstrated by the assessment and additional publications cited in this series.
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Regul. Toxicol. Pharmacol. · Nov 2016
Randomized Controlled Trial Comparative StudyEvaluation of the tobacco heating system 2.2. Part 9: Application of systems pharmacology to identify exposure response markers in peripheral blood of smokers switching to THS2.2.
As part of current harm reduction strategies, candidate modified risk tobacco products (MRTP) are developed to offer adult smokers who want to continue using tobacco product an alternative to cigarettes while potentially reducing individual risk and population harm compared to smoking cigarettes. One of these candidate MRTPs is the Tobacco Heating System (THS) 2.2 which does not burn tobacco, but instead heats it, thus producing significantly reduced levels of harmful and potentially harmful constituents (HPHC) compared with combustible cigarettes (CC). ⋯ To complement the classical exposure response measurements, we have used the previously reported whole blood derived gene signature that can distinguish current smokers from either non-smokers or former smokers with high specificity and sensitivity. We tested the small signature consisting of only 11 genes on the blood transcriptome of subjects enrolled in the clinical study and showed a reduced exposure response in subjects that either stopped smoking or switched to a candidate MRTP, the THS2.2, compared with subjects who continued smoking their regular tobacco product.
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Regul. Toxicol. Pharmacol. · Nov 2016
Randomized Controlled Trial Comparative StudyEvaluation of the Tobacco Heating System 2.2. Part 8: 5-Day randomized reduced exposure clinical study in Poland.
The Tobacco Heating System (THS) 2.2, a candidate Modified Risk Tobacco Product (MRTP), is designed to heat tobacco without burning it. Tobacco is heated in order to reduce the formation of harmful and potentially harmful constituents (HPHC), and reduce the consequent exposure, compared with combustible cigarettes (CC). In this 5-day exposure, controlled, parallel-group, open-label clinical study, 160 smoking, healthy subjects were randomized to three groups and asked to: (1) switch from CCs to THS 2.2 (THS group; 80 participants); (2) continue to use their own non-menthol CC brand (CC group; 41 participants); or (3) to refrain from smoking (smoking abstinence (SA) group; 39 participants). ⋯ Increased product consumption and total puff volume were reported in the THS group. However, exposure to nicotine was similar to CC at the end of the confinement period. Reduction in urge-to-smoke was comparable between the THS and CC groups and THS 2.2 product was well tolerated.
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Regul. Toxicol. Pharmacol. · Nov 2016
Comparative StudyEvaluation of the Tobacco Heating System 2.2. Part 3: Influence of the tobacco blend on the formation of harmful and potentially harmful constituents of the Tobacco Heating System 2.2 aerosol.
The Tobacco Heating System (THS2.2), which uses "heat-not-burn" technology, generates an aerosol from tobacco heated to a lower temperature than occurs when smoking a combustible cigarette. The concentrations of harmful and potentially harmful constituents (HPHCs) are significantly lower in THS2.2 mainstream aerosol than in smoke produced by combustible cigarettes. Different tobacco types and 43 tobacco blends were investigated to determine how the blend impacted the overall reductions of HPHCs in the THS2.2 mainstream aerosol. ⋯ Blends containing high proportions of nitrogen-rich tobacco, e.g., air-cured, and some Oriental tobaccos, produced higher acetamide, acrylamide, ammonia, and nitrogen oxide yields than did other blends. Most HPHCs were found to be released mainly through the distillation of HPHCs present in the tobacco plug or after being produced in simple thermal reactions. HPHC concentrations in the THS2.2 aerosol may therefore be further minimized by limiting the use of flue- and fire-cured tobaccos which may be contaminated by HPHCs during the curing process and carefully selecting nitrogen rich tobaccos with low concentrations of endogenous HPHCs for use in the tobacco plug blend.