Japan Tobacco (Switzerland)

The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to develop recommendations for optimal scientific and technical approaches for conducting in vitro assays to assess potential toxicity within and across tobacco and various next-generation products (NGPs) including heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDSs). This publication was developed by a working group of the workshop members in conjunction with the sixth workshop in that series entitled “Dosimetry for conducting in vitro evaluations” and focuses on aerosol dosimetry for aerosol exposure to combustible cigarettes, HTP, and ENDS aerosolized tobacco products and summarizes the key challenges as well as documenting areas for future research.

Abstract This publication describes a sensory assessment recommended to fulfill the regulatory requirement for Article 6(2) of the EU Tobacco Products Directive 2014/40/EU, related to whether specific cigarettes have “characterizing flavor,” which is no longer allowed in the European Union (EU) when that “characterizing flavor” results from the use of an additive or combination of additives. It describes (a) background and protocol development, (b) a proposed protocol, (c) studies to evaluate the protocol, (d) the final recommended protocol, and (e) testing results for eight priority additives that the Scientific Committee on Health, Environmental, and Emerging Risks deemed likely to provide nontobacco characterizing flavor in tobacco products. The final protocol screens assessors for sensory acuity, trains them to understand products with/without characterizing flavor, screens out assessors unable to perform the task successfully, determines which cigarette products may have a characterizing flavor, and then what, if any, characterizing flavor is present. The methodology using smell tests as suggested by regulatory staff and other authors was able to identify the positive controls included in the test and a test product containing menthol as having “characterizing flavor.”Practical Application“Characterizing flavor” in cigarettes is a sensory phenomenon. Implementation of the recommended protocol for determining “characterizing flavor” in cigarettes, whether premade or “roll your own” is needed to make an objective determination for regulatory needs. This recommended protocol is reliable as determined by various studies and can meet the needs in a reliable manner by various groups.

This publication is part of a series of three publications and describes the non-clinical assessment performed to fulfill the regulatory requirement per Art. 6 (2) of the EU Tobacco Products Directive 2014/40/EU under which Member States shall require manufacturers and importers of cigarettes and Roll Your Own tobacco containing an additive that is included in the priority list established by Commission Implementing Decision (EU) 2016/787 to carry out comprehensive studies (European Comission, 2016). This publication contains the results of a literature search, comprehensive smoke chemistry, additive transfer, and in vitro toxicity studies for the 13 priority additives (carob bean extract, cocoa powder, fenugreek extract, fig juice concentrate, geraniol, glycerol, guaiacol, guar gum, liquorice extract powder, maltol, l-menthol (synthetic), propylene glycol, and sorbitol) commissioned by the members of the Priority Additives Tobacco Consortium to independent Contract Research Organizations. Comparisons of the 39 World Health Organisation smoke emissions in smoke from cigarettes with and without priority additives identified some differences that, with few exceptions, were minor and well within the inherent variability of the analytical method observed for the 3R4F monitor cigarette. Most differences were not statistically significant and did not show consistent additive-related increases or decreases. However, test cigarettes with guar gum showed a statistically significant, additive-related increase in formaldehyde and cadmium; test cigarettes with sorbitol showed a statistically significant, additive-related increase in formaldehyde and acrolein; test cigarettes with glycerol showed a statistically significant, additive-related decrease in phenols, benzo[a]pyrene and N-nitrosoanabasine; and test cigarettes with propylene glycol showed a statistically significant, additive-related decrease in phenol and m + p-cresols. These changes were not observed when the additives were tested as a mixture. None of the increases or decreases in smoke chemistry translated into changes in the in vitro toxicity. Comparisons of the in vitro toxicity of smoke from cigarettes with and without priority additives gave some differences that were minor, well within the inherent variability of the assays, not statistically significant, and did not show consistent additive-related increases or decreases. Thus, it can be concluded that the addition of priority additives had no effect on the in vitro toxicity of the cigarette smoke. The results obtained in our studies are consistent with those in scientific literature.

This study investigated the effects of ingested meal types on the pharmacokinetics of elvitegravir (EVG), cobicistat (COBI), emtricitabine (FTC), tenofovir alafenamide (TAF), and tenofovir (TFV) following a single administration of the single-tablet regimen (STR) of EVG/COBI/FTC/TAF (150/150/200/10mg) in Japanese HIV-negative healthy subjects (n=12). In this open-label, randomized, 3-way crossover study, the bioequivalence of the EVG/COBI/FTC/TAF STR following ingestion of a nutritional protein-rich drink with a reference treatment of taking a standard breakfast was evaluated. Administration under fasted conditions, no food intake, resulted in decreases in the mean AUCinf and Cmax of EVG by 50% and 57%, respectively, relative to the administration with a standard breakfast, whereas the systemic exposure of EVG with a nutritional protein-rich drink was comparable to that with a standard breakfast. The mean AUCinf and Cmax of COBI, FTC, TAF, and TFV were comparable regardless of meal intake or meal types. Although the package insert of the EVG/COBI/FTC/TAF STR states that the medication is recommended to be taken with food, this study provides an additional insight into HIV-1-infected patients that a light meal like a nutritional protein-rich drink can be an alternative to a standard meal.

Female C57BL/6 mice were exposed to mainstream cigarette smoke at 600 μg WTPM/L, 4 h/day and 5 days/week for up to 52 weeks. At 26, 52 and 65 weeks (52 weeks of exposure plus 13 weeks of no exposure), lungs were assessed for inflammation, function, histopathology and morphometry. Structural changes were observed and accompanied by altered lung function at 26 and 52 weeks (e.g. increase of static compliance and hysteresis, and decrease of elastance). Lung morphometry quantified significant increase in airspace enlargement at 52 weeks. Chronic smoke exposure induced inflammation in respiratory organs, e.g. mixed inflammatory cell infiltrates, perivascular lymphocyte infiltrates and pigmented alveolar macrophages in the lungs. Minimal or mild alveolar emphysema was diagnosed in 70% by 26 weeks or 80% by 52 weeks. After 13 weeks of recovery, most biochemical, histopathological and morphometrical alterations were restored, while emphysema was observed to persist at 18% incidence by 65 weeks. In conclusion, the employed exposure conditions induced emphysematous changes in the lungs, accompanied by altered lung function and morphological/histopathological changes. Following the 13 weeks of no exposure, morphological changes persisted, although some functional/biochemical alterations regressed.

War Crimes in Gaza and the Zionist Fifth Column in America James Petras (Atlanta: Clear Day Books, 2010) James Petras is a teacher and humanist of a rare, encyclopaedic, analytical intelligence. He...

The Fourth Horizontal Project in the Mature Algyo Field V. Pipicz; V. Pipicz MOL Hungarian O&G Co. Search for other works by this author on: This Site Google Scholar L. Benedek; L. Benedek MOL Hungarian O&G Co. Search for other works by this author on: This Site Google Scholar Gy. Palasthy; Gy. Palasthy MOL Hungarian O&G Co. Search for other works by this author on: This Site Google Scholar T. Barodi; T. Barodi MOL Hungarian O&G Co. Search for other works by this author on: This Site Google Scholar J. Blaho; J. Blaho MOL Hungarian O&G Co Search for other works by this author on: This Site Google Scholar S.D. Joshi S.D. Joshi J.T.I. Search for other works by this author on: This Site Google Scholar Paper presented at the SPE International Thermal Operations and Heavy Oil Symposium and International Horizontal Well Technology Conference, Calgary, Alberta, Canada, November 2002. Paper Number: SPE-78953-MS https://doi.org/10.2118/78953-MS Published: November 04 2002 Cite View This Citation Add to Citation Manager Share Icon Share Twitter LinkedIn Get Permissions Search Site Citation Pipicz, V., Benedek, L., Palasthy, Gy., Barodi, T., Blaho, J., and S.D. Joshi. "The Fourth Horizontal Project in the Mature Algyo Field." Paper presented at the SPE International Thermal Operations and Heavy Oil Symposium and International Horizontal Well Technology Conference, Calgary, Alberta, Canada, November 2002. doi: https://doi.org/10.2118/78953-MS Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll ProceedingsSociety of Petroleum Engineers (SPE)SPE International Thermal Operations and Heavy Oil Symposium Search Advanced Search AbstractSince 1993, about 70 horizontal wells, have been drilled in three differentsuccessful projects. These projects were implemented in the mature AlgyÕ field.A fourth project, consisting of more than 20 new horizontal sections, kickingoff existing abandoned wells, has been developed for the thin oil rim presentin two high permeability reservoirs with top gas and bottom water The maindifference between the two reservoirs is that one has water injection and theother has two layers with strong natural bottom water drive.The first experimental wells of the 4th project were drilled tominimize the coning effects and to increase the areal recovery efficiency inthe initially 9 and 6 m thick oil zones (shrinked to 4 and 3 m in the recentstate of exploitation).To decision about the project implementation was based on reservere-evaluation. The re-evaluated reserves were determined using results of theexperimental wells, a 3D geological model, a full field 3D simulation andhorizontal well production matches with JTI software. To define saturation, neutron logs were used to determine for the gas-oil contact and carbon-oxygenlogs are used for monitoring the oil-water contact (because of the very lowsalinity of formation water). The target zone of the horizontal sections is +/-0.5 m vertically and very detailed information analysis is required to planproper trajectories.The recent state of the project, the evaluation, methods and simulationprocess used for the decision- making are presented in the paper.IntroductionThe first horizontal well was drilled in Hungary in 1989 and thereafter morethan 70 horizontal sections were completed. The 80% of these wells are in theAlgyo field, which is the largest hydrocarbon accumulation in the Pannonianbasin. After a 30-year production, the inaccessible hydrocarbons, which aredeposited in inaccessible parts of the reservoirs, have become producible byusing horizontal wells. Additionally, the target of the reservoir managementwas to maximise the long-term profit of the field by acceleration of reservesby using abandoned vertical wells.In this paper, the utilisation of horizontal wells in high permeability oilrims with gas-cap and bottom-water is discussed. The results are summarized inTable 1.The increase in the number of horizontal wells in Hungary the last years canbe seen in Fig. 1.Geological Environment of the Main Target Area, Algyo FieldThe schematic, geological cross-section of Algyo field is shown in Fig.2. Keywords: petroleum society, ultimate recovery, water cut, increment, saru, reevaluation, spe ps-cim choa 78953, horizontal section, reservoir characterization, oil rim Subjects: Reservoir Characterization, Formation Evaluation & Management This content is only available via PDF. 2002. SPE/PS-CIM/CHOA International Thermal Operations and Heavy Oil Symposium and International Horizontal Well Technology Conference You can access this article if you purchase or spend a download.