Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Aug 2019
The selective determination of potentially carcinogenic polycyclic aromatic compounds in lubricant base oils by the DMSO extraction method IP346 and its correlation to mouse skin painting carcinogenicity assays.
Mineral oils are produced by vacuum distillation of crude oil at temperatures from ∼300 °C to ∼600 °C. Subsequent refining processes to eliminate the carcinogenic potential of mineral oils (by extraction and/or hydrotreatment) are based on the principle of removing substances associated with carcinogenic activity; i.e. PAC (polycyclic aromatic compounds), which include PAH and N or S heterocycles. ⋯ The DMSO based IP346 is thus a simple but clear reflection of refinement efficacy. It links manufacturing conditions to carcinogenic potential of an oil, supported by solid physical-chemical and toxicological associations. In Europe it is the only legally binding method to assess, classify and label lubricating base oils and inherently more reliable for hazard assessment than the determination of an arbitrary selection of PAH.
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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.
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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. · 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.