Regulatory toxicology and pharmacology : RTP
-
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.
-
Regul. Toxicol. Pharmacol. · Nov 2016
EditorialInvestigating a toxic risk (self-inflicted) the example of conventional and advanced studies of a novel Tobacco Heating System.
This special issue of Regulatory Toxicology and Pharmacology contains 9 scientific papers from Philip Morris International about the laboratory and 1 about early clinical investigation of a novel 'Tobacco Heating System'. The studies have employed conventional and a wide range of newer 'omics and bioinformatics techniques to seek and explore potential toxic actions of the inhalable vapour it generates. The methods of study and display of results employed are considered to be a valuable guide and model for wider application in other toxicological investigations because they are directed more to proximal causes of effects than to the cruder distal end points revealed by conventional, empirical procedures. As such they should be regarded as a paradigm for the applicability and accuracy of the testing and prediction of toxic risks.
-
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.
-
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.
-
Regul. Toxicol. Pharmacol. · Nov 2016
Comparative StudyEvaluation 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.
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. ⋯ 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.