DOCSLIB.ORG

Scientific-Technical Support Activities to DG

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Scientific-Technical Support Activities to DG Scientific-technical support activities to DG TAXUD-C-2 on the option to include e-cigar ettes within the scope of excisable goods for the Impact Assessment on a possible revision of Directive 2011/64/EU Administrative Arrangement TAXUD/2015/DE/329 Final report Thomas Wenzl, Zuzana Zelinkova, Jorge Regueiro, Anupam Giri 201 7 EUR 29062 This publication is a Technical report by the Joint Research Centre (JRC), the European Commission’s science and knowledge service. It aims to provide evidence-based scientific support to the European policy-making process. The scientific output expressed does not imply a policy position of the European Commission. Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use which might be made of this publication. Contact information Name: Thomas Wenzl Address: JRC Geel, Retieseweg 111, B-2440 Geel E-mail: [email protected] JRC Science Hub https://ec.europa.eu/jrc JRC105825 EUR 29062 EN PDF ISBN 978-92-79-77729-5 ISSN 1831-9424 doi:10.2760/663170 Luxembourg: Publications Office of the European Union, 2017 © European Union, 2017 The reuse of the document is authorised, provided the source is acknowledged and the original meaning or message of the texts are not distorted. The European Commission shall not be held liable for any consequences stemming from the reuse. How to cite: Wenzl, T.; Zelinkova, Z.; Regueiro, J.; Giri, A., Scientific-technical support activities to DG TAXUD-C-2 on the option to include e-cigarettes within the scope of excisable goods for the Impact Assessment on a possible revision of Directive 2011/64/EU , EUR 29062 EN, 2017. ISBN 978-92-79-77729-5, doi:10.2760/663170 All images © European Union 2017 Table of contents Acknowledgements ................................................................................................ 3 Executive summary ............................................................................................... 4 Introduction ......................................................................................................... 5 Determination of nicotine and nicotine related alkaloids in commercial e-liquids ............ 7 1.1 Samples ............................................................................................... 7 1.1.1 Sample preparation and analysis .......................................................... 7 1.1.2 Tobacco alkaloid content of liquids used in e-cigarettes ........................... 9 Volatile profiles of tobacco and non-tobacco flavoured e-liquids ................................ 13 1.2 Samples ............................................................................................. 14 1.2.1 Sample preparation and analysis ........................................................ 14 1.3 Data Analysis ...................................................................................... 14 1.3.1 Classification of samples .................................................................... 15 1.3.1.1 Partial least square discrimination ................................................. 16 1.3.1.2 Decision tree ................................................................................. 18 Conclusion.......................................................................................................... 20 ANNEX 1 – Analytical method for the determination of tobacco alkaloids in e-liquids, test samples, and results ............................................................................................ 21 A1.1. Analysis of tobacco alkaloids by HPLC-MS/MS in HILIC mode ..................... 21 A1.2. Test samples ....................................................................................... 26 A1.3. Contents of tobacco alkaloids determined in e-liquid test samples .............. 34 ANNEX 2 – Analytical method for the evaluation of flavour profiles ............................ 44 A2.1. Analysis of volatile constituents of e-liquids by thermal desorption high-resolution gas chromatography QTOF mass spectrometry ............................... 44 A2.2. Test samples ....................................................................................... 46 A2.3. Compound identification ....................................................................... 49 References ......................................................................................................... 53 List of figures ...................................................................................................... 55 List of tables ....................................................................................................... 56 Acknowledgements The authors wish to acknowledge the good collaboration with colleagues from DG TAXUD, particularly with Mrs Annerie Bouw. 3 Executive summary Electronic-cigarettes are electrical devices that produce an inhalable aerosol from a special liquid. The liquids (e-liquids) may consist of a solution of nicotine and flavourings in an appropriate solvent. Nicotine-free products are available as well. A large range of differently flavoured e-liquids is offered to the consumer. The market of electronic cigarettes and corresponding e-liquids experienced in recent years enormous growth. Some EU Member States reacted on this development and introduced excise duties on e-liquids. The partial introduction of excise duties in the common market and the lack of harmonisation of their magnitude might cause distortions of the market. For that reason, the Directorate-General Taxation and Customs Union (DG TAXUD) commissioned a study on the identification and characterisation of e-liquids, which should be based on substances naturally occurring in tobacco. The Administrative Arrangement (AA) with DG TAXUD foresaw the determination of the concentrations of nicotine and related tobacco alkaloids in e-liquid samples, and to evaluate the agreement of the measured concentrations with concentrations indicated on the product label. Additionally, the possibility of identifying e-liquids containing tobacco derived flavours had to be studied with the aim to use this information for product classification. More than 200 e-liquid samples acquired in different countries were analysed for their tobacco alkaloid contents by liquid chromatography tandem mass spectrometry. A high proportion of the investigated products contained nicotine at a level significantly different from the indicated concentration. Mostly lower concentrations were found. However, significant amounts of nicotine were determined in some products declared as "zero- nicotine". Volatile profiles of 108 e-liquid samples were measured by gas chromatography hyphenated to high-resolution quadrupole time-of-flight (QTOF) mass spectrometry. The data obtained from the analysis of was investigated with multivariate statistical methods for possibilities of discriminating tobacco- and non-tobacco flavoured e-liquids. The developed statistical models allowed identification of tobacco derived products with high probability. If a harmonized taxation of e-liquids were to be proposed, the following considerations should be taken into account in designing the tax base: • The declared nicotine content often does not match with the measured nicotine content; • Moreover, in products declared as ''zero-nicotine'' significant amounts of nicotine can be found; • Chemical analysis allows distinguishing tobacco and non-tobacco e-liquids with high probability. 4 Introduction General information about e-cigarettes Electronic (e-) cigarettes are battery-powered hand-held devices that convert a liquid into an inhalable aerosol. Attempts to produce and commercialise such aerosol dispensers are known for a long time (Robinson, 1930). However, the currently marketed e-cigarettes are based on an invention made in 2004 by the Chinese pharmacist Lik Hon (Hon, 2004). He designed a battery-powered device that aimed to supply nicotine to smokers without exposing them to the tar component of conventional smoking. E-cigarettes typically consist of a mouthpiece, an atomizer, a battery, and a tank that contains the liquid for vaporization ("e-liquid")(Famele et al., 2015). The atomizer is a heating element forming a fine mist from the e-liquid which carries the flavour, and which provides a sensation of smoking to the user. E-cigarettes might be manufactured for single use only, or might contain a replaceable or refillable e-liquid tank, and a rechargeable battery. The lack of standardization has led to various designs of e-cigarettes. Some of the e-cigarettes are in size close to tobacco containing cigarettes, while others are much larger and heavier. Similarly, the number and composition of refill solutions grew in the last decade exponentially. In contrast to tobacco containing cigarettes, for which EU legislation prohibits characterising flavours, e-liquids are marketed with a broad range of flavours and each of them is usually available with different levels of nicotine content (EU, 2014). It should be stressed that only a part of the commercialized e-liquids smells of tobacco. A big proportion of the market comprises e-liquids with non-tobacco flavours. These might taste like alcoholic and non-alcoholic beverages (coffee, wine, black tea, brandy, lemonade...), sweets (candy, cookies, chocolate, muffins...), or all kinds of fruits (cherry, strawberry, apple...). The non-tobacco flavoured e-liquids are usually manufactured from flavourings that are GRAS (generally recognized as safe) certified by the Flavour
Load more

Recommended publications
  • Roger Lee Papke Box 100267 JHM Health Science Center Gainesville, Florida 32610
    CURRICULUM VITAE Roger Lee Papke DEPARTMENT OF PHARMACOLOGY AND THERAPEUTICS UNIVERSITY OF FLORIDA SCHOOL OF MEDICINE Box 100267 J.H.M. Health Science Center Gainesville, Florida 32610 (352) 392-4712, FAX (352) 392-9696 [email protected] BIOGRAPHICAL DATA: Born: October 12, 1953, Kenmore, New York Married: December 24, 1980 to Clare Stokes Citizenship: U. S. A. EDUCATION: Starpoint Central School Pendleton, N. Y. Primary and Secondary N.Y.S. Regents Diploma 1971 New York University Washington Square College of Arts and Sciences 1971 - 1975 Majors in Biology and Classical Civilization Bachelor of Arts awarded May 1975 New York University Graduate school of Arts and Sciences 1975 - 1976 Thesis advisor: Dr. Fleur L. Strand Thesis title: An Alpha Adrenergic Response of Cardiac Muscle at an Alkaline pH Master of Science awarded May 1976 Cornell University Graduate School of Arts and Science 1976-1979: Section of Physiology Graduate Research Assistant in Reproductive Physiology Advisor: Dr. William Hansel Research topic: The endocrine control of delayed implantation in mink Cornell University Graduate School of Arts and Science 1979-1986: Section of Neurobiology and Behavior Thesis Advisor: Dr. Robert Oswald Primary research topic: Pharmacology of nicotinic acetylcholine receptors Thesis Title: The Gating of Single Channel Currents Through the Nicotinic Acetylcholine Receptors of BC3H-1 Cells: Effects of Agonists and Allosteric Ligands Ph.D. conferred January 1987 ACADEMIC APPOINTMENTS: 1987 Postdoctoral Research Associate: Department of Pharmacology,
    [Show full text]
  • Differential Effects of Alkaloids on Memory in Rodents
    www.nature.com/scientificreports OPEN Diferential efects of alkaloids on memory in rodents Patrick M. Callahan1,2, Alvin V. Terry Jr.1,2, Manuel C. Peitsch3, Julia Hoeng3* & Kyoko Koshibu3* Nicotinic acetylcholine receptors (nAChRs) play a critical role in the neuropharmacology of learning and memory. As such, naturally occurring alkaloids that regulate nAChR activity have gained interest for understanding and potentially improving memory function. In this study, we tested the acute efects of three known nicotinic alkaloids, nicotine, cotinine, and anatabine, in suppressing scopolamine-induced memory defcit in rodents by using two classic memory paradigms, Y-maze and novel object recognition (NOR) in mice and rats, respectively. We found that all compounds were able to suppress scopolamine-induced spatial memory defcit in the Y-maze spontaneous alternation paradigm. However, only nicotine was able to suppress the short-term object memory defcit in NOR, despite the higher doses of cotinine and anatabine used to account for their potential diferences in nAChR activity. These results indicate that cotinine and anatabine can uniquely regulate short-term spatial memory, while nicotine seems to have more robust and general role in memory regulation in rodents. Thus, nAChR-activating alkaloids may possess distinct procognitive properties in rodents, depending on the memory types examined. Te cholinergic system of the brain is a critical regulator of attention, memory, and higher-order cognitive processing, and its defcits are central to the etiology of dementia1. As such, nicotinic acetylcholine receptors (nAChRs) have gained much interest as a target of drug development 2. Neuronal nAChRs are pentameric pro- teins composed of various combinations of α (α2–α9) and β (β2–β4) nAChR subunits, diferentially expressed throughout the nervous system.
    [Show full text]
  • Federal Register/Vol. 82, No. 13/Monday, January 23, 2017/Proposed Rules
    8004 Federal Register / Vol. 82, No. 13 / Monday, January 23, 2017 / Proposed Rules DEPARTMENT OF HEALTH AND comment will be made public, you are www.regulations.gov. Submit both HUMAN SERVICES solely responsible for ensuring that your copies to the Division of Dockets comment does not include any Management. If you do not wish your Food and Drug Administration confidential information that you or a name and contact information to be third party may not wish to be posted, made publicly available, you can 21 CFR Part 1132 such as medical information, your or provide this information on the cover [Docket No. FDA–2016–N–2527] anyone else’s Social Security number, or sheet and not in the body of your confidential business information, such comments and you must identify this Tobacco Product Standard for N- as a manufacturing process. Please note information as ‘‘confidential.’’ Any Nitrosonornicotine Level in Finished that if you include your name, contact information marked as ‘‘confidential’’ Smokeless Tobacco Products information, or other information that will not be disclosed except in identifies you in the body of your accordance with 21 CFR 10.20 and other AGENCY: Food and Drug Administration, comments, that information will be applicable disclosure law. For more HHS. posted on http://www.regulations.gov. information about FDA’s posting of • ACTION: Proposed rule. If you want to submit a comment comments to public dockets, see 80 FR with confidential information that you 56469, September 18, 2015, or access SUMMARY: The Food and Drug do not wish to be made available to the the information at: http://www.fda.gov/ Administration (FDA) is proposing a public, submit the comment as a regulatoryinformation/dockets/ tobacco product standard that would written/paper submission and in the default.htm.
    [Show full text]
  • Evaluating the Real-World Effectiveness of Bupropion Versus Varenicline for Smoking Cessation: Exploring the Role of Nicotine Metabolism and Medication Adherence
    Evaluating the Real-World Effectiveness of Bupropion Versus Varenicline for Smoking Cessation: Exploring the Role of Nicotine Metabolism and Medication Adherence By Jiahui Zhang A thesis submitted in conformity with the requirements for the degree of Master of Science Graduate Department of Pharmacology and Toxicology University of Toronto © Copyright by Jiahui Zhang (2017) Evaluating the Real-World Effectiveness of Bupropion Versus Varenicline for Smoking Cessation: Exploring the Role of Nicotine Metabolism and Medication Adherence Jiahui Zhang Degree of Master of Science Graduate Department of Pharmacology and Toxicology University of Toronto ABSTRACT Bupropion and varenicline are effective, first-line prescription-only pharmacotherapies for smoking cessation; however, their real-world use is limited by affordability and accessibility. Using a novel internet-based randomized design, we evaluated the real-world effectiveness of mailed bupropion and varenicline, as well as the roles of nicotine metabolism (NMR) and medication adherence, in a sample of interested smokers using web-based recruitment and follow up. Quit rates at end of treatment (EOT) were significantly higher for varenicline (30.2%) compared to bupropion (19.6%). Quit rates at 6 months (14.0%) and 12 months (12.1%) were not significantly different between bupropion and varenicline. Increased medication compliance significantly improved cessation outcomes at EOT. NMR was associated with nicotine dependence. Varenicline benefited Slow Metabolizers of nicotine whilst bupropion benefited Normal Metabolizers. Even though real-world quit rates were comparable to clinical trials, improving medication compliance and implementing personalized pharmacological and behavioral interventions are promising approaches to increase efficacy of smoking cessation pharmacotherapies. ii ACKNOWLEDGEMENTS First and foremost, I would like to express my sincerest appreciation to my supervisor, Dr.
    [Show full text]
  • July 16, 2018 VIA ELECTRONIC SUBMISSION and HAND DELIVERY Division of Dockets Management Food and Drug Administration 5630 Fishe
    Jose Luis Murillo Vice President Regulatory Affairs July 16, 2018 VIA ELECTRONIC SUBMISSION AND HAND DELIVERY Division of Dockets Management Food and Drug Administration 5630 Fishers Lane, Rm. 1061 Rockville, MD 20852 Re: Docket No. FDA-2017-N-6189 (83 Fed. Reg. 11,818, March 16, 2018) Advance Notice of Proposed Rulemaking on Tobacco Product Standard for Nicotine Level of Certain Tobacco Products Altria Client Services (“ALCS”), on behalf of Philip Morris USA Inc. (“PM USA”), John Middleton Company (“JMC”), and Sherman Group Holdings LLC and its subsidiaries (“Nat Sherman”),1 submits these comments to the Food and Drug Administration’s (“FDA’s” or the “Agency’s”) Advance Notice of Proposed Rulemaking (“ANPRM”) on a Tobacco Product Standard for Nicotine Level of Certain Tobacco Products. The ANPRM comes within the context of an industry in the midst of transformative change. Cigarette smoking is at historically low levels and continues to decline. At the same time, a new market is emerging in innovative noncombustible tobacco products that are potentially less harmful than cigarettes. There is now a scientific consensus that noncombustible products, like e-vapor, are substantially less risky than conventional cigarettes. It is smoke, and not nicotine, that causes most tobacco- related harm. And adult smokers are increasingly expressing interest in switching from cigarettes to less risky alternatives. We agree that a nicotine product standard of some sort may make sense in a future regulatory system, but this requires the pre-existence of a marketplace with alternative, FDA-authorized, reduced risk products; more information about the relative risks of those products; and a regulatory system that respects the rights of adults to make decisions based on accurate information.
    [Show full text]
  • WO 2016/001643 Al 7 January 2016 (07.01.2016) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/001643 Al 7 January 2016 (07.01.2016) P O P C T (51) International Patent Classification: (74) Agents: GILL JENNINGS & EVERY LLP et al; The A61P 25/28 (2006.01) A61K 31/194 (2006.01) Broadgate Tower, 20 Primrose Street, London EC2A 2ES A61P 25/16 (2006.01) A61K 31/205 (2006.01) (GB). A23L 1/30 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/GB20 15/05 1898 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (22) International Filing Date: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 29 June 2015 (29.06.2015) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (25) Filing Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (26) Publication Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 141 1570.3 30 June 2014 (30.06.2014) GB TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 1412414.3 11 July 2014 ( 11.07.2014) GB (84) Designated States (unless otherwise indicated, for every (71) Applicant: MITOCHONDRIAL SUBSTRATE INVEN¬ kind of regional protection available): ARIPO (BW, GH, TION LIMITED [GB/GB]; 39 Glasslyn Road, London GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, N8 8RJ (GB).
    [Show full text]
  • The Letteratura a Tutti a Utomation
    THELETTERATURA US A20170296525A1 TUTTIA UTOMATION ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2017/ 0296525 A1 Moran et al. ( 43 ) Pub . Date : Oct. 19 , 2017 ( 54 ) USE OF COTININE IN TREATING OR (60 ) Provisional application No . 62 /073 ,339 , filed on Oct . PREVENTING NEUROGENESIS DEFICITS 31 , 2014 . AND ENHANCING NEUROGENESIS (71 ) Applicants : Department of Veterans Affairs , Publication Classification Washington , DC (US ) ; University of (51 ) Int . Ci. South Florida , Tampa, FL (US ) A61K 31/ 454 (2006 .01 ) A6IK 31 /55 (2006 . 01 ) (72 ) Inventors : Valentina Echeverria Moran , Largo , A61K 31 / 444 ( 2006 .01 ) FL (US ) ; Doreen Appunn , Tampa , FL .) U . S . CI. (US ) CPC .. .. .. A61K 31/ 454 ( 2013 .01 ) ; A61K 31/ 444 (2013 .01 ) ; A61K 31/ 55 (2013 .01 ) (21 ) Appl. No. : 15 /583 ,937 ( 22 ) Filed : May 1, 2017 (57 ) ABSTRACT A method of inhibiting or treating chemotherapy - induced Related U . S . Application Data cognitive dysfunction comprising administering a therapeu (63 ) Continuation - in - part of application No . PCT/ US15 / tically effective amount of cotinine to a cancer patient 58625 , filed on Nov . 2 , 2015 . experiencing chemotherapy - induced cognitive dysfunction . Percent of Neurogenesis Genes Changed by Cotinine in Forced Swimming Stress 64 % 36 % W Down Up Patent Application Publication Oct. 19 , 2017 Sheet 1 of 10 US 2017 /0296525 A1 Percent of Inflammation and Autoimmunity Genes Changed By Contine in Forced Swimming Stress 39 % n Down Up A 61% Figure 1 . Patent Application Publication Oct. 19 , 2017 Sheet 2 of 10 US 2017 /0296525 A1 Percent of Neurogenesis Genes Changed by Cotinine in Forced Swimming Stress 64 % 36 % A Down Q Up Figure 2 .
    [Show full text]
  • Solanum Alkaloids and Their Pharmaceutical Roles: a Review
    Journal of Analytical & Pharmaceutical Research Solanum Alkaloids and their Pharmaceutical Roles: A Review Abstract Review Article The genus Solanum is treated to be one of the hypergenus among the flowering epithets. The genus is well represented in the tropical and warmer temperate Volume 3 Issue 6 - 2016 families and is comprised of about 1500 species with at least 5000 published Solanum species are endemic to the northeastern region. 1Department of Botany, India Many Solanum species are widely used in popular medicine or as vegetables. The 2Department of Botany, Trivandrum University College, India presenceregions. About of the 20 steroidal of these alkaloid solasodine, which is potentially an important starting material for the synthesis of steroid hormones, is characteristic of *Corresponding author: Murugan K, Plant Biochemistry the genus Solanum. Soladodine, and its glocosylated forms like solamargine, and Molecular Biology Lab, Department of Botany, solosonine and other compounds of potential therapeutic values. India, Email: Keywords: Solanum; Steroidal alkaloid; Solasodine; Hypergenus; Glocosylated; Trivandrum University College, Trivandrum 695 034, Kerala, Injuries; Infections Received: | Published: October 21, 2016 December 15, 2016 Abbreviations: TGA: Total Glycoalkaloid; SGA: Steroidal range of biological activities such as antimicrobial, antirheumatics, Glycoalkaloid; SGT: Sergeant; HMG: Hydroxy Methylglutaryl; LDL: Low Density Lipoprotein; ACAT: Assistive Context Aware Further, these alkaloids are of paramount importance in drug Toolkit; HMDM: Human Monocyte Derived Macrophage; industriesanticonvulsants, as they anti-inflammatory, serve as precursors antioxidant or lead molecules and anticancer. for the synthesis of many of the steroidal drugs which have been used CE: Cholesterol Ester; CCl4: Carbon Tetrachloride; 6-OHDA: 6-hydroxydopamine; IL: Interleukin; TNF: Tumor Necrosis Factor; DPPH: Diphenyl-2-Picryl Hydrazyl; FRAP: Fluorescence treatments.
    [Show full text]
  • Smoking Cessation Prior to Elective Surgery
    2018 OHP Guidelines: Verification of Cessation Smoking Cessation Prior to Elective Surgery Verification of Surgery Smoking Status Cessation Cessation Scheduler Cotinine Current Smoker Options -HPCP code G0432 The scheduler Tobacco Use - Refer to Program -urine or serum sends relevant - Refer to PCP -if positive or if using chart notes and Past 30 days - Do it yourself NRT use one of these PA (prior alternate tests: Anabasine authorization) Recent Quit -HCPC code G0480 request to health Exhaled CO Tobacco Use plan along with: -CPT code 94250 -length of abstinence Past year -on-site equipment -negative lab results -for patients who have quit smoking for at Remote Quit least one year, an Tobacco Use attestation is Over 1 year ago sufficient. Verification of Cessation: Timing issues Verification of abstinence is required for at least four weeks prior to the procedure and requires objective evidence of abstinence from smoking prior to the procedure, which raises timing issues: Procedures Abstinence Requirement Testing required Elective surgical procedures are 1 month One test (urine or serum) 1 month defined as those which are flexible prior to request which starts the in their scheduling because the timeline. If the scheduled date of condition does not pose an procedure is several weeks out, an imminent threat nor does it require additional testing approximately a immediate attention within one week before procedure. month. Lung volume reduction surgery, 6 months Testing 3-4 times during the six bariatric surgery, erectile months is sufficient, again with dysfunction surgery, and spinal evidence of testing at the beginning fusion have 6-month smoking which starts the timeline and abstinence requirements approximately a week before surgery Reproductive procedures (i.e., for contraceptive purposes), cancer-related and diagnostic procedures are excluded from this guideline.
    [Show full text]
  • The Key to the Nornicotine Enantiomeric Composition in Tobacco Leaf
    University of Kentucky UKnowledge Theses and Dissertations--Plant and Soil Sciences Plant and Soil Sciences 2012 ENANTIOSELECTIVE DEMETHYLATION: THE KEY TO THE NORNICOTINE ENANTIOMERIC COMPOSITION IN TOBACCO LEAF Bin Cai University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Cai, Bin, "ENANTIOSELECTIVE DEMETHYLATION: THE KEY TO THE NORNICOTINE ENANTIOMERIC COMPOSITION IN TOBACCO LEAF" (2012). Theses and Dissertations--Plant and Soil Sciences. 5. https://uknowledge.uky.edu/pss_etds/5 This Doctoral Dissertation is brought to you for free and open access by the Plant and Soil Sciences at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Plant and Soil Sciences by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained and attached hereto needed written permission statements(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine). I hereby grant to The University of Kentucky and its agents the non-exclusive license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. I agree that the document mentioned above may be made available immediately for worldwide access unless a preapproved embargo applies.
    [Show full text]
  • Bibliography on Smoking and Health. INSTITUTION Public Health Service (DHEW), Rockville, Md
    DOCUMENT RESUME ED 068 857 CG 007 558 TITLE Bibliography on Smoking and Health. INSTITUTION Public Health Service (DHEW), Rockville, Md. National Clearinghouse for Smoking and Health. PUB DATE 71 NOTE 344p. AVAILABLE FROMSuperintendent of Documents, U. S. Government Printing Office, Washington, D. C. 20402 EDRS PRICE MF-S0.65 HC- $13.16 DESCRIPTORS Bibliographic Coupling; *Bibliographies; Booklists; Disease Control; Disease Rate; Diseases; Health; *Health Education; Indexing; Information Retrieval; *Literature Reviews; *Smoking; *Tobacco ABSTRACT This Bibliography includes all of the items added to the Technical Information Center of the National Clearinghouse for Smoking and Health from January through December 1971. The publication is broken down into eleven major categories. These are: (1) chemistry, pharmacology and toxicology; (2) mortality and morbidity;(3) neoplastic diseases;(4) non-neoplastic respiratory diseases; (5) cardiovascular diseases; (6) other diseases and conditions;(7) behavioral and educational research;(8) tobacco economics;(9) bills and legislation; and (10) general references. Also included in this bibliography are a cumulative author and organizational index and a cumulative subject index. U00 1971 NATIONAL CLEARINGHOUSE FOR SMOKING AND HEALTH BIBLIOGRAPHY on SMOKING AND HEALTH U.S. DEPARTMENT OF HEALTII. EDUCATION & WELFARE OFFICE OF EDUCATION THIS DOCUMENT HAS BEEN REPRO- DUCED EXACTLY AS RECEIVED FROM THE PERSON OR ORGANIZATION ORIG INATING IT. POINTS OF VIEW OR OPIN IONS STATED DO NOT NECESSARILY REPRESENT OFFICIAL OFFICE OF EDU- CATION POSITION OR POLICY. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service Health Services and Mental Health Administration FILMED FROM BEST AVAILABLE COPY 1 PREFACE This Bibliography includes all of the items added to theTechnical Information Center of the National Clearinghouse for Smoking and Health fromJanuary through December 1971.
    [Show full text]
  • Constitutive Activation of Nitrate Reductase in Tobacco Alters Fowering Time and Plant Biomass Jianli Lu1,3, Niharika N
    www.nature.com/scientificreports OPEN Constitutive activation of nitrate reductase in tobacco alters fowering time and plant biomass Jianli Lu1,3, Niharika N. Chandrakanth1, Ramsey S. Lewis1, Karen Andres1, Lucien Bovet2, Simon Goepfert2 & Ralph E. Dewey 1* Pyridine alkaloids produced in tobacco can react with nitrosating agents such as nitrite to form tobacco-specifc nitrosamines (TSNA), which are among the most notable toxicants present in tobacco smoke. The market type known as burley tobacco is particularly susceptible to TSNA formation because its corresponding cultivars exhibit a nitrogen-use-defciency phenotype which results in high accumulation of nitrate, which, in turn, is converted to nitrite by leaf surface microbes. We have previously shown that expression of a constitutively activated nitrate reductase (NR) enzyme dramatically decreases leaf nitrate levels in burley tobacco, resulting in substantial TSNA reductions without altering the alkaloid profle. Here, we show that plants expressing a constitutively active NR construct, designated 35S:S523D-NR, display an early-fowering phenotype that is also associated with a substantial reduction in plant biomass. We hypothesized that crossing 35S:S523D-NR tobaccos with burley cultivars that fower later than normal would help mitigate the undesirable early- fowering/reduced-biomass traits while maintaining the desirable low-nitrate/TSNA phenotype. To test this, 35S:S523D-NR plants were crossed with two late-fowering cultivars, NC 775 and NC 645WZ. In both cases, the plant biomass at harvest was restored to levels similar to those in the original cultivar used for transformation while the low-nitrate/TSNA trait was maintained. Interestingly, the mechanism by which yield was restored difered markedly between the two crosses.
    [Show full text]