Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Jul 2018
Randomized Controlled Trial Comparative StudyAssessment of the exposure to harmful and potentially harmful constituents in healthy Japanese smokers using a novel tobacco vapor product compared with conventional cigarettes and smoking abstinence.
The objectives of this clinical study were to demonstrate a reduction in exposure to selected harmful and potentially harmful constituents (HPHCs), and to assess product use behavior, in Japanese healthy adult smokers who switched to a novel tobacco vapor product (NTV). 60 smokers were randomly assigned for 5 days to either (a) a group who switched to an NTV (n = 20), (b) a group who continued to smoke their own brand of conventional cigarettes (CC, n = 20) or (c) a smoking abstinence group (SA, n = 20). Fifteen biomarkers of exposure (BoEs) to 14 HPHCs and pyrene were measured at baseline, day 3 and 5. Product use behavior was assessed by measuring product consumption, nicotine uptake and puffing topography. ⋯ Additionally, nicotine uptake in the NTV group was approximately half that observed in the CC group. BoE values were significantly reduced in the NTV group as compared to those in the CC group. Significantly, the magnitude of the reduction in exposure to HPHCs observed in the NTV group (49-94%) was close to that observed for the SA group (39-95%).
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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
Randomized Controlled Trial Comparative StudyAssessment of the reduction in levels of exposure to harmful and potentially harmful constituents in Japanese subjects using a novel tobacco heating system compared with conventional cigarettes and smoking abstinence: A randomized controlled study in confinement.
Smoking conventional cigarettes (CCs) exposes smokers to harmful and potentially harmful constituents (HPHCs). The Tobacco Heating System 2.2 (THS 2.2), a candidate modified risk tobacco product, was developed to reduce or eliminate the formation of HPHCs, while preserving as much as possible the taste, sensory experience, nicotine delivery profile and ritual characteristics of CC. This randomized, controlled, open-label study in confinement for 5 day exposure aimed to demonstrate the reduction in exposure to selected HPHCs, to assess nicotine uptake and subjective effects, in participants switching to THS 2.2 (n = 80) compared to participants continuing smoking CCs (n = 40) and abstaining from smoking (n = 40). ⋯ More importantly, the magnitude of exposure reduction observed was close to that which was seen in participants who abstained from smoking for 5 days, while nicotine uptake was maintained. Reduction in urge-to-smoke was comparable between THS and CC groups, however THS 2.2 was slightly less satisfactory than CCs. The new, alternative tobacco product THS 2.2 was well tolerated.
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Regul. Toxicol. Pharmacol. · Apr 2015
Randomized Controlled Trial Multicenter Study Comparative StudyA study to investigate changes in the levels of biomarkers of exposure to selected cigarette smoke constituents in Japanese adult male smokers who switched to a non-combustion inhaler type of tobacco product.
In a clinical study, changes in 14 biomarkers of exposures (BOEs) from 10 tobacco smoke constituents and mutagens detected by the urine mutagenicity test were investigated using a non-combustion inhaler type of tobacco product (NCIT) by switching from a conventional cigarette. This study was conducted in 80 Japanese healthy adult males with a 4-week residential, controlled, open-label, parallel group design. After randomization, 40 smokers used NCIT with approximately 750 aspirations, other 20 smokers smoked approximately 20 pieces of an assigned 1-mg ISO tar conventional cigarette (CC1) every day. ⋯ On day 29, the levels of these BOEs were almost the same as those in the NS group, except BOEs of nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). This suggested that the exposure to 8 constituents and mutagens in the NCIT group was similar to that in the NS group, while the exposure to nicotine was higher. Although the precise exposure level to NNK was not estimated because of the long half-life of its BOE, it would be substantially lower in the NCIT group than in the CC1 group.