Scientific assessment of the use of sugars as cigarette tobacco ingredients: A review of published and other publicly available studies

References

• Abdallah F. (2004). Cigarette Product Development. Raleigh, NC: Tobacco Reporter/Speccomm International.
   Google Scholar
• Adam T, Mitschke S, Streibel T, Baker RR, Zimmermann R. (2006). Puff-by-puff resolved characterisation of cigarette mainstream smoke by single photon ionisation (SPI)-time-of-flight mass spectrometry (TOFMS): comparison of the 2R4F research cigarette and pure Burley, Virginia, Oriental and Maryland tobacco cigarettes. Anal Chim Acta 572:219–229.
   PubMed Web of Science ®Google Scholar
• American Congress of Governmental Industrial Hygienists. (1991). Documentation of the Threshold Limit Value and Biological Indices. Cincinnati, OH.
   Google Scholar
• Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Cogliano V. (2008). Carcinogenicity of some aromatic amines, organic dyes, and related exposures. Lancet Oncol 9:322–323.
   PubMed Web of Science ®Google Scholar
• Baker EH, Wood DM, Brennan AL, Clark N, Baines DL, Philips BJ. (2006a). Hyperglycaemia and pulmonary infection. Proc Nutr Soc 65:227–235.
   PubMed Web of Science ®Google Scholar
• Baker RR, Chang HY. (1999). Lysophosphatidic acid, alkylglycerophosphate and alkylacetylglycerophosphate increase the neuronal nuclear acetylation of 1-acyl lysophosphatidyl choline by inhibition of lysophospholipase. Mol Cell Biochem 198:47–55.
   PubMedGoogle Scholar
• Baker RR. (2006). The generation of formaldehyde in cigarettes–Overview and recent experiments. Food Chem Toxicol 44:1799–1822.
   PubMed Web of Science ®Google Scholar
• Baker RR. (2007). Sugars, carbonyls and smoke. Food Chem Toxicol 45:1783–1786.
   PubMedGoogle Scholar
• Baker RR, Coburn S, Liu C. (2006b). The pyrolytic formation of formaldehyde from sugars and tobacco. J Anal Appl Pyrolysis 77:12–21.
   Web of Science ®Google Scholar
• Baker RR, Coburn S, Liu C, Tetteh J. (2005). Pyrolysis of saccharide tobacco ingredients: a TGA-FTIR investigation. J Anal Appl Pyrolysis 74:171–180.
   Google Scholar
• Baker RR, Dixon M. (2006). The retention of tobacco smoke constituents in the human respiratory tract. Inhal Toxicol 17:255–299.
   Web of Science ®Google Scholar
• Baker RR, Massey ED, Smith G. (2004a). An overview of the effects of tobacco ingredients on smoke chemistry and toxicity. Food Chem Toxicol 42 Suppl:S53–S83.
   Google Scholar
• Baker RR, Pereira da Silva JR, Smith G. (2004b). The effect of tobacco ingredients on smoke chemistry. Part II: casing ingredients. Food Chem Toxicol 42 Suppl:S39–S52.
   Google Scholar
• Baldrick P, Bamford DG. (1997). A toxicological review of lactose to support clinical administration by inhalation. Food Chem Toxicol 35:719–733.
   PubMed Web of Science ®Google Scholar
• Barbano MF, Cador M. (2007). Opioids for hedonic experience and dopamine to get ready for it. Psychopharmacology (Berl) 191:497–506.
   PubMed Web of Science ®Google Scholar
• Basciano H, Federico L, Adeli K. (2005). Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond) 2:5.
   PubMedGoogle Scholar
• Belluzzi JD, Wang R, Leslie FM. (2005). Acetaldehyde enhances acquisition of nicotine self-administration in adolescent rats. Neuropsychopharmacology 30:705–712.
   PubMed Web of Science ®Google Scholar
• Bernstein D. (2004). A review of the influence of particle size, puff volume, and inhalation pattern on the deposition of cigarette smoke particles in the respiratory tract. Inhal Toxicol 16:675–689.
   PubMed Web of Science ®Google Scholar
• Blackford AL, Yang G, Hernandez-Avila M, Przewozniak K, Zatonski W, Figueiredo V, Avila-Tang E, Ma J, Benowitz NL, Samet JM. (2006). Cotinine concentration in smokers from different countries: relationship with amount smoked and cigarette type. Cancer Epidemiol Biomarkers Prev 15:1799–1804.
   PubMedGoogle Scholar
• Bombick DW, Putnam K, Doolittle DJ. (1998). Comparative cytotoxicity studies of smoke condensates from different types of cigarettes and tobaccos. Toxicol In Vitro 12:241–249.
   PubMed Web of Science ®Google Scholar
• Borchers MT, Wert SE, Leikauf GD. (1998). Acrolein-induced MUC5ac expression in rat airways. Am J Physiol 274:L573–L581.
   PubMedGoogle Scholar
• Boyette MD, Hamm LA. (2001). Results of the Year 2000 TSNA sampling program in flue-cured tobacco. Rec Adv Tob Sci 27:17–22.
   Google Scholar
• Brazil National Health Monitoring Agency. (2007). Resolution RDC no. 90. Available at: Accessed on 8 November 2010.
   Google Scholar
• Britt PF, Buchanan AC, Owens CV. (2004). Does glucose enhance the formation of nitrogen containing polycyclic aromatic compounds and polycyclic aromatic hydrocarbons in the pyrolysis of proline? Fuel 83:1414–1432.
   Google Scholar
• Burley VJ. (1998). Sugar consumption and human cancer in sites other than the digestive tract. Eur J Cancer Prev 7:253–277.
   PubMedGoogle Scholar
• Burns DM, Dybing E, Gray N, Hecht S, Anderson C, Sanner T, O’Connor R, Djordjevic M, Dresler C, Hainaut P, Jarvis M, Opperhuizen A, Straif K. (2008). Mandated lowering of toxicants in cigarette smoke: a description of the World Health Organization TobReg proposal. Tob Control 17:132–141.
   PubMed Web of Science ®Google Scholar
• Byrd GD, Davis RA, Caldwell WS, Robinson JH, deBethizy JD. (1998). A further study of FTC yield and nicotine absorption in smokers. Psychopharmacology (Berl) 139:291–299.
   PubMed Web of Science ®Google Scholar
• Carmines EL. (2002). Evaluation of the potential effects of ingredients added to cigarettes. Part 1: cigarette design, testing approach, and review of results. Food Chem Toxicol 40:77–91.
   PubMed Web of Science ®Google Scholar
• Cassee FR, Groten JP, Feron VJ. (1996). Changes in the nasal epithelium of rats exposed by inhalation to mixtures of formaldehyde, acetaldehyde, and acrolein. Fundam Appl Toxicol 29:208–218.
   PubMedGoogle Scholar
• Chambers O. (2003). The Reference Cigarette. Lexington, KY: University of Kentucky, College of Agriculture.
   Google Scholar
• Chepiga TA, Morton MJ, Murphy PA, Avalos JT, Bombick BR, Doolittle DJ, Borgerding MF, Swauger JE. (2000). A comparison of the mainstream smoke chemistry and mutagenicity of a representative sample of the US cigarette market with two Kentucky reference cigarettes (K1R4F and K1R5F). Food Chem Toxicol 38:949–962.
   PubMed Web of Science ®Google Scholar
• Clapp WL, Fagg BS, Smith CJ. (1999). Reduction in Ames Salmonella mutagenicity of mainstream cigarette smoke condensate by tobacco protein removal. Mutat Res 446:167–174.
   PubMedGoogle Scholar
• Coggins CR, Wagner KA, Werley MS, Oldham MJ. (2011). A comprehensive evaluation of the toxicology of cigarette ingredients: carbohydrates and natural products. Inhal Toxicol 23 Suppl 1:13–40.
   PubMedGoogle Scholar
• Coggins CR. (2007). An updated review of inhalation studies with cigarette smoke in laboratory animals. Int J Toxicol 26:331–338.
   PubMed Web of Science ®Google Scholar
• Conolly RB, Kimbell JS, Janszen D, Schlosser PM, Kalisak D, Preston J, Miller FJ. (2004). Human respiratory tract cancer risks of inhaled formaldehyde: dose-response predictions derived from biologically-motivated computational modeling of a combined rodent and human dataset. Toxicol Sci 82:279–296.
   PubMed Web of Science ®Google Scholar
• Counts ME, Hsu FS, Tewes FJ. (2006). Development of a commercial cigarette “market map” comparison methodology for evaluating new or non-conventional cigarettes. Regul Toxicol Pharmacol 46:225–242.
   PubMed Web of Science ®Google Scholar
• Counts ME, Morton MJ, Laffoon SW, Cox RH, Lipowicz PJ. (2005). Smoke composition and predicting relationships for international commercial cigarettes smoked with three machine-smoking conditions. Regul Toxicol Pharmacol 41:185–227.
   PubMed Web of Science ®Google Scholar
• Crump KS, Chen C, Fox JF, Van Landingham C, Subramaniam R. (2008). Sensitivity analysis of biologically motivated model for formaldehyde-induced respiratory cancer in humans. Ann Occup Hyg 52:481–495.
   PubMedGoogle Scholar
• Das DK, Neogi A, Steinberg H. (1985). Nutritional and hormonal control of glucose and fructose utilization by lung. Clin Physiol Biochem 3:240–248.
   PubMedGoogle Scholar
• De Stefani E, Deneo-Pellegrini H, Mendilaharsu M, Ronco A, Carzoglio JC. (1998). Dietary sugar and lung cancer: a case-control study in Uruguay. Nutr Cancer 31:132–137.
   PubMed Web of Science ®Google Scholar
• DeMarini DM, Gudi R, Szkudlinska A, Rao M, Recio L, Kehl M, Kirby PE, Polzin G, Richter PA. (2008). Genotoxicity of 10 cigarette smoke condensates in four test systems: comparisons between assays and condensates. Mutat Res 650:15–29.
   PubMed Web of Science ®Google Scholar
• Dempsey R, Coggins CR, Roemer E. (2011). Toxicological assessment of cigarette ingredients. Regul Toxicol Pharmacol 61:119–128.
   PubMed Web of Science ®Google Scholar
• Deutsches Institut für Normung – Working Group Toxicology of Additives. (2004). Toxicological evaluation of additives for tobacco products - a guide. Berlin, Germany: Beuth Verlag.
   Google Scholar
• Dickerson JP, Roberts DL, Miller CW, Lloyd RA, Rix CE. (1976). Flue-cured tobacco flavor. II. Constituents arising from amino acid-sugar reactions. Tob Sci 20:59–63.
   Google Scholar
• Ding YS, Yan XJ, Jain RB, Lopp E, Tavakoli A, Polzin GM, Stanfill SB, Ashley DL, Watson CH. (2006). Determination of 14 polycyclic aromatic hydrocarbons in mainstream smoke from U.S. brand and non-U.S. brand cigarettes. Environ Sci Technol 40:1133–1138.
   PubMed Web of Science ®Google Scholar
• Ding YS, Zhang L, Jain RB, Jain N, Wang RY, Ashley DL, Watson CH. (2008). Levels of tobacco-specific nitrosamines and polycyclic aromatic hydrocarbons in mainstream smoke from different tobacco varieties. Cancer Epidemiol Biomarkers Prev 17:3366–3371.
   PubMed Web of Science ®Google Scholar
• Dontenwill W, Chevalier HJ, Harke HP, Klimisch HJ, Reckzeh G. (1976). [Experimental studies on tumorigenic activity of cigarette smoke condensate on mouse skin. V. Comparative studies of condensates from different modified cigarettes (author’s transl)]. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 85:141–153.
   PubMedGoogle Scholar
• Dorman DC, Struve MF, Wong BA, Marshall MW, Gross EA, Willson GA. (2008). Respiratory tract responses in male rats following subchronic acrolein inhalation. Inhal Toxicol 20:205–216.
   PubMed Web of Science ®Google Scholar
• European Commission Health,and Consumer Protection Directorate-General. (2001). Guidance on submissions for food additive evaluation by the scientific committee on food. Brussels, Belgium: Available at: http://ec.europa.eu/food/fs/sc/scf/out82_en.pdf. Accessed on 24 August 2010.
   Google Scholar
• European Commission Health and Consumer Protection Directorate-General Scientific Committee on Emerging and Newly Identified Health Risks. (2008). Health Effects of Smokeless Tobacco Products. Brussels, Belgium: European Commission. Available at: http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_013.pdf. Accessed on 28 May 2010.
   Google Scholar
• European Commission Health and Consumer Protection Directorate-General Scientific Committee on Emerging and Newly Identified Health Risks. (2010). Addictiveness and attractiveness of tobacco additives. Available at: http://ec.europa.eu/health/scientific_committees/consultations/public_consultations/scenihr_cons_12_en.htm. Accessed on 11 July 2010.
   Google Scholar
• European Parliament and Council of the European Union. (2001). Directive 2001/37/EC of the European Parliament and of the Council of 5 June 2001 on the approximation of the laws, regulations and administrative provisions of the Member States concerning the manufacture, presentation and sale of tobacco products. Off J Eur Union L194:26–34.
   Google Scholar
• Fagerström K, Furberg H. (2008). A comparison of the Fagerström Test for Nicotine Dependence and smoking prevalence across countries. Addiction 103:841–845.
   PubMed Web of Science ®Google Scholar
• Federici M, Lauro R. (2005). Review article: diabetes and atherosclerosis–running on a common road. Aliment Pharmacol Ther 22 Suppl 2:11–15.
   PubMedGoogle Scholar
• Feron VJ, Kruysse A, Til HP, Immel HR. (1978). Repeated exposure to acrolein vapour: subacute studies in hamsters, rats and rabbits. Toxicology 9:47–57.
   PubMed Web of Science ®Google Scholar
• Fisher P. (1999). Tobacco Blending. In: Davis DL, Nielsen MT eds. Tobacco: Production, Chemistry and Technology. Oxford, UK: Blackwell Science, 346–352.
   Google Scholar
• Gaby AR. (2005). Adverse effects of dietary fructose. Altern Med Rev 10:294–306.
   PubMed Web of Science ®Google Scholar
• Gager FL Jr, Nedlock JW, Martin WJ. (1971a). Tobacco additives and cigarette smoke. I. Transfer of D-glucose, sucrose, and their degradation products to the smoke. Carbohydr Res 17:327–333.
   PubMedGoogle Scholar
• Gager FL Jr, Nedlock JW, Martin WJ. (1971b). Tobacco additives and cigarette smoke. II. Organic, gas-phase products from D-glucose and sucrose. Carbohydr Res 17:335–339.
   PubMedGoogle Scholar
• Gairola C. (1982). Genetic effects of fresh cigarette smoke in Saccharomyces cerevisiae. Mutat Res 102:123–136.
   PubMedGoogle Scholar
• Gaworski CL, Heck JD, Bennett MB, Wenk ML. (1999). Toxicologic evaluation of flavor ingredients added to cigarette tobacco: skin painting bioassay of cigarette smoke condensate in SENCAR mice. Toxicology 139:1–17.
   PubMed Web of Science ®Google Scholar
• Gaworski CL, Schramke H, Diekmann J, Meisgen TJ, Tewes FJ, Veltel DJ, Vanscheeuwijck PM, Rajendran N, Muzzio M, Haussmann HJ. (2009). Effect of filtration by activated charcoal on the toxicological activity of cigarette mainstream smoke from experimental cigarettes. Inhal Toxicol 21:688–704.
   PubMed Web of Science ®Google Scholar
• German Federal Ministry for Youth Family and Health. (1977). Verordnung über Tabakerzeugnisse (Ordinance of Tobacco Products). Bundesgesetzblatt I:2831–2837.
   Google Scholar
• Gibney M, Sigman-Grant M, Stanton JL Jr, Keast DR. (1995). Consumption of sugars. Am J Clin Nutr 62:178S–193S; discussion 194S.
   PubMedGoogle Scholar
• Gori GB, Lynch CJ. (1985). Analytical cigarette yields as predictors of smoke bioavailability. Regul Toxicol Pharmacol 5:314–326.
   PubMedGoogle Scholar
• Green CR, Rodgman A. (1996). The tobacco chemists’ research conference: a half century forum for advances in analytical methodology of tobacco and its products. Rec Adv Tob Sci 22:131–304.
   Google Scholar
• Green CR, Schumacher JN, Rodgman A. (2007). The expansion of tobacco and its effect on cigarette mainstream smoke properties. Beitr Tabakforsch Int 22:317–345.
   Google Scholar
• Gregg EO, Hill C, Hollywood M, Kearney M, McAdam K, McLaughlin D, Purkis S, Williams M. (2004). The UK smoke constituents testing study. Summary of results and comparison with other studies. Beitr Tabakforsch Int 21:117–138.
   Google Scholar
• Hahn J, Schaub J. (2010). Influence of tobacco additives on the chemical composition of mainstream smoke. Beitr Tabakforsch Int 24:100–116.
   Google Scholar
• Hammond D, Fong GT, Thompson ME, Driezen P. (2004). International tobacco control policy evaluation survey (ITC 4-country survey). Wave 1 technical report. Waterloo, Canada: International Tobacco Control Policy Evaluation Survey Research Team. Available at: http://www.itcproject.org/Library/countries/4country/reports/itcw1techr. Accessed on 28 May 2010.
   Google Scholar
• Hammond D, O’Connor RJ. (2008). Constituents in tobacco and smoke emissions from Canadian cigarettes. Tob Control 17 Suppl 1:i24–i31.
   PubMedGoogle Scholar
• Health Canada. (2000). Tobacco reporting regulations. Available at: http://www.hc-sc.gc.ca/hc-ps/pubs/tobac-tabac/tir-rft/index-eng.php. Accessed on 27 May 2010.
   Google Scholar
• Hecht SS. (2006). Smoking and lung cancer–a new role for an old toxicant? Proc Natl Acad Sci USA 103:15725–15726.
   PubMedGoogle Scholar
• Heck JD. (2010). A review and assessment of menthol employed as a cigarette flavoring ingredient. Food Chem Toxicol 48 Suppl 2:S1–38.
   PubMedGoogle Scholar
• Heck JD. (2009). Smokers of menthol and nonmenthol cigarettes exhibit similar levels of biomarkers of smoke exposure. Cancer Epidemiol Biomarkers Prev 18:622–629.
   PubMed Web of Science ®Google Scholar
• Hyland A, Borland R, Li Q, Yong HH, McNeill A, Fong GT, O’Connor RJ, Cummings KM. (2006). Individual-level predictors of cessation behaviours among participants in the International Tobacco Control (ITC) Four Country Survey. Tob Control 15 Suppl 3:iii83–iii94.
   PubMed Web of Science ®Google Scholar
• Hyodo T, Maruta Y, Itaya H, Mikita A, Kodera T, Meger M. (2007). Evaluation of functional relationships for predicting mainstream smoke constituent machine yields for conventional cigarettes from the Japanese market. Regul Toxicol Pharmacol 48:194–224.
   PubMed Web of Science ®Google Scholar
• International Agency for Research on Cancer. (1982). Some Industrial Chemicals and Dyestuffs. Lyon, France: International Agency for Research on Cancer.
   Google Scholar
• International Agency for Research on Cancer. (1987). Overall evaluation of carcinogenicity: An updating of IARC Monographs Volumes 1 to 42. Lyon, France: International Agency for Research on Cancer. Available at: http://monographs.iarc.fr/ENG/Monographs/suppl7/index.php. Accessed on 20 October 2011.
   Google Scholar
• International Agency for Research on Cancer. (1999). Re-Evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide. Lyon, France: International Agency for Research on Cancer. Available at: http://monographs.iarc.fr/ENG/Monographs/vol71/index.php. Accessed on 20 October 2011.
   Google Scholar
• International Agency for Research on Cancer. (2002). Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. Lyon, France: International Agency for Research on Cancer. Available at: http://monographs.iarc.fr/ENG/Monographs/vol82/index.php. Accessed on 20 October 2011.
   Google Scholar
• International Agency for Research on Cancer. (2006). Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol. Lyon, France: International Agency for Research on Cancer.
   Google Scholar
• International Agency for Research on Cancer. (2007). Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines. Lyon, France: World Health Organization.
   Google Scholar
• International Agency for Research on Cancer. (2010). Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures. Lyon, France: World Health Organization. Available at: http://monographs.iarc.fr/ENG/Monographs/vol92/mono92.pdf. Accessed on 11 October 2011.
   Google Scholar
• International Conference on Harmonisation. (1997). Genotoxicity: a standard battery for genotoxicity testing of pharmaceuticals: S2B.
   Google Scholar
• International Organization for Standardization. (1991). International Standard 4387: Cigarettes – determination of total and nicotine-free particulate matter using a routine analytical smoking machine. Geneva, Switzerland: International Organization for Standardization.
   Google Scholar
• International Organization for Standardization. (2000). International Standard 3308: Routine analytical cigarette-smoking machine – definitions and standard conditions. Geneva, Switzerland: International Organization for Standardization.
   Google Scholar
• INVITTOX. (1990). INVITTOX protocol 3a, the FRAME modified Neutral Red uptake cytotoxicity test. Ispra, Italy: ECVAM. Available at: http://ecvam-dbalm.jrc.ec.europa.eu/. Accessed on 16 June 2010.
   Google Scholar
• Jarvis MJ, Boreham R, Primatesta P, Feyerabend C, Bryant A. (2001). Nicotine yield from machine-smoked cigarettes and nicotine intakes in smokers: evidence from a representative population survey. J Natl Cancer Inst 93:134–138.
   PubMedGoogle Scholar
• King B, Borland R, Fowles J. (2007). Mainstream smoke emissions of Australian and Canadian cigarettes. Nicotine Tob Res 9:835–844.
   PubMedGoogle Scholar
• Kobashi Y, Sakaguchi S. (1959). Free sugars in cigarette smoke. Tob Sci 3:161–163.
   Google Scholar
• Kohlhäufl M, Haidl P, Voshaar T, Häussinger K, Köhler D. (2004). [Powder inhalation systems]. Dtsch Med Wochenschr 129:2048–2052.
   PubMedGoogle Scholar
• Korte JE, Hertz-Picciotto I, Schulz MR, Ball LM, Duell EJ. (2000). The contribution of benzene to smoking-induced leukemia. Environ Health Perspect 108:333–339.
   PubMed Web of Science ®Google Scholar
• Lee PN, Forey BA, Fry JS, Hamling JS, Hamling JF, Sanders EB, Carchman RA. (2009). Does use of flue-cured rather than blended cigarettes affect international variation in mortality from lung cancer and COPD? Inhal Toxicol 21:404–430.
   PubMed Web of Science ®Google Scholar
• Leffingwell JC. (1976). Nitrogen components of leaf and their relationship to smoking quality and aroma. Rec Adv Tob Sci 2:1–31.
   Google Scholar
• Leffingwell JC. (1999). Basic Chemical Constituents of Tobacco Leaf and Differences among Tobacco Types. In: Davis DL, Nielsen MT, eds.. Tobacco: Production, Chemistry and Technology. Oxford, UK: Blackwell Sciences, 265–284.
   Google Scholar
• Life Sciences Research Office. (2004a). The LSRO report on review of ingredients added to cigarettes. Phase one: The feasibility of testing ingredients added to cigarettes. Bethesda, MD: Life Sciences Research Office.
   Google Scholar
• Life Sciences Research Office. (2004b). The LSRO report on review of ingredients added to cigarettes. Phase two: Scientific criteria for the evaluation of ingredients added to cigarettes. Bethesda, MD: Life Science Research Office.
   Google Scholar
• Lindner D, Smith S, Leroy CM, Tricker AR. (2011). Comparison of exposure to selected cigarette smoke constituents in adult smokers and nonsmokers in a European, multicenter, observational study. Cancer Epidemiol Biomarkers Prev 20:1524–1536.
   PubMed Web of Science ®Google Scholar
• Lynch AM, Sasaki JC, Elespuru R, Jacobson-Kram D, Thybaud V, De Boeck M, Aardema MJ, Aubrecht J, Benz RD, Dertinger SD, Douglas GR, White PA, Escobar PA, Fornace A Jr, Honma M, Naven RT, Rusling JF, Schiestl RH, Walmsley RM, Yamamura E, van Benthem J, Kim JH. (2011). New and emerging technologies for genetic toxicity testing. Environ Mol Mutagen 52:205–223.
   PubMed Web of Science ®Google Scholar
• MacKay J, Eriksen M. (2002). The tobacco atlas. Geneva, Switzerland: World Health Organization.
   Google Scholar
• Mariner DC, Ashley M, Shepperd CJ, Mullard G, Dixon M. (2011). Mouth level smoke exposure using analysis of filters from smoked cigarettes: A study of eight countries. Regul Toxicol Pharmacol 61:S39–S50.
   PubMed Web of Science ®Google Scholar
• Martindale W. (1993). The Extra Pharmacopoeia. London, UK: Pharmaceutical Press.
   Google Scholar
• Massachusetts General Laws Annotated. (1997). Section 307B 105, Code of Massachusetts, 660.000 et seq. (Chapter 94). Available at: http://www.mass.gov/Eeohhs2/docs/dph/regs/105cmr660.pdf. Accessed on 28 May 2010.
   Google Scholar
• Mendes P, Liang Q, Frost-Pineda K, Munjal S, Walk RA, Roethig HJ. (2009). The relationship between smoking machine derived tar yields and biomarkers of exposure in adult cigarette smokers in the US. Regul Toxicol Pharmacol 55:17–27.
   PubMed Web of Science ®Google Scholar
• Michaud DS, Fuchs CS, Liu S, Willett WC, Colditz GA, Giovannucci E. (2005). Dietary glycemic load, carbohydrate, sugar, and colorectal cancer risk in men and women. Cancer Epidemiol Biomarkers Prev 14:138–147.
   PubMed Web of Science ®Google Scholar
• Mizusaki S, Takashima T, Tomaru K. (1977). Factors affecting mutagenic activity of cigarette smoke condensate in Salmonella typhimurium TA 1538. Mutat Res 48:29–36.
   PubMed Web of Science ®Google Scholar
• Moir D, Rickert WS, Levasseur G, Larose Y, Maertens R, White P, Desjardins S. (2008). A comparison of mainstream and sidestream marijuana and tobacco cigarette smoke produced under two machine smoking conditions. Chem Res Toxicol 21:494–502.
   PubMed Web of Science ®Google Scholar
• Moldoveanu AI, Borgerding M. (2008). Formation of tobacco specific nitrosamines in mainstream cigarette smoke; part 1, FTC smoking. Beitr Tabakforsch Int 23:19–31.
   Google Scholar
• Moldoveanu SC, Byrd CH, Gerardi AR. (2011). Analysis of certain nitrogenous compounds in tobacco. Part 1: adenosine, 2,5- and 2,6-deoxyfructosazines, mannosamine and glucosamine. Beitr Tabakforsch Int 24:233–242.
   Google Scholar
• Mullings EL, Donaldson LF, Melichar JK, Munafò MR. (2010). Effects of acute abstinence and nicotine administration on taste perception in cigarette smokers. J Psychopharmacol (Oxford) 24:1709–1715.
   PubMedGoogle Scholar
• Nielsen GD, Wolkoff P. (2010). Cancer effects of formaldehyde: a proposal for an indoor air guideline value. Arch Toxicol 84:423–446.
   PubMed Web of Science ®Google Scholar
• Noguchi M, Satoh Y, Nishida K, Andoh S, Tamaki E. (1971). Studies on storage and ageing of leaf tobacco. Part ix. Changes in the content of amino acid-sugar compounds during ageing. J Agric Biol Chem 35:65–70.
   Web of Science ®Google Scholar
• O’Connor RJ, Ashare RL, Cummings KM, Hawk LW Jr (2007). Comparing smoking behaviors and exposures from flavored and unflavored cigarettes. Addict Behav 32:869–874.
   PubMedGoogle Scholar
• Olszewski PK, Levine AS. (2007). Central opioids and consumption of sweet tastants: when reward outweighs homeostasis. Physiol Behav 91:506–512.
   PubMed Web of Science ®Google Scholar
• Organization for Economic Co-operation and Development. (1997a). OECD guideline for testing of chemicals. Test No. 471: Bacterial reverse mutation test. Paris, France: OECD Publishing.
   Google Scholar
• Organization for Economic Co-operation and Development. (1997b). OECD guideline for testing of chemicals. Test No. 474: Mammalian erythrocyte micronucleus test. Paris, France: OECD Publishing.
   Google Scholar
• Organization for Economic Co-operation and Development. (2009). OECD guideline for the testing of chemicals. 413 Subchronic Inhalation Toxicity: 90-Day Study. Paris, France: OECD Publishing.
   Google Scholar
• Parliament of Canada. (2009). An act to amend the tobacco act. Available at: http://www2.parl.gc.ca/content/hoc/Bills/402/Government/C-32/C-32_4/C-32_4.PDF. Accessed on 26 May 2010.
   Google Scholar
• Parrish ME, Harward CN. (2000). Measurement of formaldehyde in a single puff of cigarette smoke using tunable diode laser infrared spectroscopy. Appl Spectrosc 54:1665–1677.
   Google Scholar
• Pasquet P, Monneuse MO, Simmen B, Marez A, Hladik CM. (2006). Relationship between taste thresholds and hunger under debate. Appetite 46:63–66.
   PubMedGoogle Scholar
• Patskan GJ, Podraza KF, Meurrens K, Coggins CR, Friedrichs B, Gerstenberg B, Gomm W, Schnell P, Stabbert R, Veltel D, Weber S, Terpstra P. (2008). Toxicological comparisons of three styles of a commercial U.S. cigarette (Marlboro with the 1R4F reference cigarette. Inhal Toxicol 20:695–721.
   PubMed Web of Science ®Google Scholar
• Phillpotts DF, Spincer D, Westcott DT. (1975). The effect of the natural sugar content of tobacco upon the acetaldehyde concentration found in cigarette smoke. Beitr Tabakforsch Int 8:7–10.
   Google Scholar
• Pickett G, Seagrave J, Boggs S, Polzin G, Richter P, Tesfaigzi Y. (2010). Effects of 10 cigarette smoke condensates on primary human airway epithelial cells by comparative gene and cytokine expression studies. Toxicol Sci 114:79–89.
   Google Scholar
• Pilcer G, Amighi K. (2010). Formulation strategy and use of excipients in pulmonary drug delivery. Int J Pharm 392:1–19.
   PubMed Web of Science ®Google Scholar
• Rabinoff M, Caskey N, Rissling A, Park C. (2007). Pharmacological and chemical effects of cigarette additives. Am J Public Health 97:1981–1991.
   PubMed Web of Science ®Google Scholar
• Rahman I, Adcock IM. (2006). Oxidative stress and redox regulation of lung inflammation in COPD. Eur Respir J 28:219–242.
   PubMed Web of Science ®Google Scholar
• Rennard SI, Basset G, Lecossier D, O’Donnell KM, Pinkston P, Martin PG, Crystal RG. (1986). Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol 60:532–538.
   PubMed Web of Science ®Google Scholar
• Renne RA, Yoshimura H, Yoshino K, Lulham G, Minamisawa S, Tribukait A, Dietz DD, Lee KM, Westerberg RB. (2006). Effects of flavoring and casing ingredients on the toxicity of mainstream cigarette smoke in rats. Inhal Toxicol 18:685–706.
   PubMed Web of Science ®Google Scholar
• Ricard JD, Martin-Lefèvre L, Dreyfuss D, Saumon G. (2000). Alveolar permeability and liquid absorption during partial liquid ventilation of rats with perflubron. Am J Respir Crit Care Med 161:44–49.
   PubMedGoogle Scholar
• Rickert WS, Trivedi AH, Momin RA, Wright WG, Lauterbach JH. (2007a). Effect of smoking conditions and methods of collection on the mutagenicity and cytotoxicity of cigarette mainstream smoke. Toxicol Sci 96:285–293.
   PubMed Web of Science ®Google Scholar
• Rickert WS, Wright WG, Trivedi AH, Momin RA, Lauterbach JH. (2007b). A comparative study of the mutagenicity of various types of tobacco products. Regul Toxicol Pharmacol 48:320–330.
   PubMed Web of Science ®Google Scholar
• Rodgman A. (2002). Some studies of the effects of additives on cigarette mainstream smoke properties. II. Casing materials and humectants. Beitr Tabakforsch Int 20:279–299.
   Google Scholar
• Rodgman A, Perfetti TA. (2009). The Chemical Components of Tobacco and Tobacco Smoke. Boca Raton, FL: CRC Press.
   Google Scholar
• Roemer E, Carchman RA. (2011). Limitations of cigarette machine smoking regimens. Toxicol Lett 203:20–27.
   PubMedGoogle Scholar
• Roemer E, Stabbert R, Rustemeier K, Veltel DJ, Meisgen TJ, Reininghaus W, Carchman RA, Gaworski CL, Podraza KF. (2004). Chemical composition, cytotoxicity and mutagenicity of smoke from US commercial and reference cigarettes smoked under two sets of machine smoking conditions. Toxicology 195:31–52.
   PubMed Web of Science ®Google Scholar
• Roemer E, Tewes FJ, Meisgen TJ, Veltel DJ, Carmines EL. (2002). Evaluation of the potential effects of ingredients added to cigarettes. Part 3: in vitro genotoxicity and cytotoxicity. Food Chem Toxicol 40:105–111.
   PubMed Web of Science ®Google Scholar
• Roemer E, Wittke S, Trelles Sticken E, Piade JJ, Bonk T, Schorp MK. (2010). The addition of cocoa, glycerol, and saccharose to the tobacco of cigarettes: Implications for smoke chemistry, in vitro cytotoxicity, mutagenicity and further endpoints. Beitr Tabakforsch Int 24:117–138.
   Google Scholar
• Rustemeier K, Stabbert R, Haussmann HJ, Roemer E, Carmines EL. (2002). Evaluation of the potential effects of ingredients added to cigarettes. Part 2: chemical composition of mainstream smoke. Food Chem Toxicol 40:93–104.
   PubMed Web of Science ®Google Scholar
• Sanders EB, Goldsmith AI, Seeman JI. (2002). A model that distinguishes the pyrolysis of D-glucose, D-fructose, and sucrose from that of cellulose. Application to the understanding of cigarette smoke formation. J Anal Appl Pyrolysis 66:29–50.
   Google Scholar
• Sato S, Ohka T, Nagao M, Tsuji K, Kosuge T. (1979). Reduction in mutagenicity of cigarette smoke condensate by added sugars. Mutat Res 60:155–161.
   PubMedGoogle Scholar
• Scherer G, Engl J, Urban M, Gilch G, Janket D, Riedel K. (2007). Relationship between machine-derived smoke yields and biomarkers in cigarette smokers in Germany. Regul Toxicol Pharmacol 47:171–183.
   PubMed Web of Science ®Google Scholar
• Schramke H, Meisgen TJ, Tewes FJ, Gomm W, Roemer E. (2006). The mouse lymphoma thymidine kinase assay for the assessment and comparison of the mutagenic activity of cigarette mainstream smoke particulate phase. Toxicology 227:193–210.
   PubMed Web of Science ®Google Scholar
• Scollo MM, Winstanley MH. (2008). Tobacco in Australia: Facts and Issues. Melbourne, Australia: Cancer Council Victoria. Available at: http://www.tobaccoinaustralia.org.au. Accessed on 6 May 2010.
   Google Scholar
• Seeman JI, Dixon M, Haussmann HJ. (2002). Acetaldehyde in mainstream tobacco smoke: formation and occurrence in smoke and bioavailability in the smoker. Chem Res Toxicol 15:1331–1350.
   PubMedGoogle Scholar
• Seeman JI, Laffoon SW, Kassman AJ. (2003). Evaluation of relationships between mainstream smoke acetaldehyde and “tar” and carbon monoxide yields in tobacco smoke and reducing sugars in tobacco blends of U.S. commercial cigarettes. Inhal Toxicol 15:373–395.
   PubMed Web of Science ®Google Scholar
• Shahab L, Hammond D, O’Connor RJ, Michael Cummings K, Borland R, King B, McNeill A. (2008). The reliability and validity of self-reported puffing behavior: evidence from a cross-national study. Nicotine Tob Res 10:867–874.
   PubMedGoogle Scholar
• Shelar GR, Bernasek PF, Furin OP. (1992). Sugar/nicotine study. Available at: http://legacy.library.ucsf.edu/tid/utq03d00/pdf?search=%22shelar%20bernasek%20furin%20sugar%20nicotine%22. Accessed on 14 April 2010.
   Google Scholar
• Shepperd CJ, Eldridge AC, Mariner DC, McEwan M, Errington G, Dixon M. (2009). A study to estimate and correlate cigarette smoke exposure in smokers in Germany as determined by filter analysis and biomarkers of exposure. Regul Toxicol Pharmacol 55:97–109.
   PubMed Web of Science ®Google Scholar
• Smith G. (1990). Review on the biological activity of smoke. Southampton, UK: BAT (UK & Export) Ltd., Research and Development Centre. Available at: Accessed on 29 May 2010.
   Google Scholar
• Soldo T, Blank I, Hofmann T. (2003). (+)-(S)-alapyridaine – a general taste enhancer? Chem Senses 28:371–379.
   PubMedGoogle Scholar
• St Charles FK, Kabbani AA, Borgerding MF. (2010). Estimating tar and nicotine exposure: human smoking versus machine generated smoke yields. Regul Toxicol Pharmacol 56:100–110.
   PubMedGoogle Scholar
• Stavanja MS, Ayres PH, Meckley DR, Bombick BR, Pence DH, Borgerding MF, Morton MJ, Mosberg AT, Swauger JE. (2003). Toxicological evaluation of honey as an ingredient added to cigarette tobacco. J Toxicol Environ Health Part A 66:1453–1473.
   PubMed Web of Science ®Google Scholar
• Stavanja MS, Ayres PH, Meckley DR, Bombick ER, Borgerding MF, Morton MJ, Garner CD, Pence DH, Swauger JE. (2006). Safety assessment of high fructose corn syrup (HFCS) as an ingredient added to cigarette tobacco. Exp Toxicol Pathol 57:267–281.
   PubMedGoogle Scholar
• Talhout R, Opperhuizen A, van Amsterdam JG. (2006). Sugars as tobacco ingredient: Effects on mainstream smoke composition. Food Chem Toxicol 44:1789–1798.
   PubMed Web of Science ®Google Scholar
• Talhout R, Opperhuizen A, van Amsterdam JG. (2007). Role of acetaldehyde in tobacco smoke addiction. Eur Neuropsychopharmacol 17:627–636.
   PubMed Web of Science ®Google Scholar
• Talhout R, Schulz T, Florek E, van Benthem J, Wester P, Opperhuizen A. (2011). Hazardous compounds in tobacco smoke. Int J Environ Res Public Health 8:613–628.
   PubMed Web of Science ®Google Scholar
• Terpstra PM, Teredesai A, Vanscheeuwijck PM, Verbeeck J, Schepers G, Radtke F, Kuhl P, Gomm W, Anskeit E, Patskan G. (2003). Toxicological evaluation of an electrically heated cigarette. Part 4: Subchronic inhalation toxicology. J Appl Toxicol 23:349–362.
   PubMed Web of Science ®Google Scholar
• Tewes FJ, Meisgen TJ, Veltel DJ, Roemer E, Patskan G. (2003). Toxicological evaluation of an electrically heated cigarette. Part 3: Genotoxicity and cytotoxicity of mainstream smoke. J Appl Toxicol 23:341–348.
   PubMed Web of Science ®Google Scholar
• Theophilus EH, Poindexter DB, Meckley DR, Bombick BR, Borgerding MF, Higuchi MA, Ayres PH, Morton MJ, Mosberg AT, Swauger JE. (2003). Toxicological evaluation of dry ice expanded tobacco. Toxicol Lett 145:107–119.
   PubMed Web of Science ®Google Scholar
• Thews G, Mutschler E, Vaupel P. (1989). Anatomie, Physiologie, Pathophysiologie des Menschen. Stuttgart, Germany: Wissenschaftliche Verlagsgesellschaft mbH.
   Google Scholar
• Thornton RE, Massey SR. (1975). Smoke effects of adding sugars to tobacco. Beitr Tabakforsch Int 8:11–15.
   Google Scholar
• Tobacco Manufacturers Association, UK Department of Health. (1997). Voluntary Agreement on the Approval and Use of New Additives in Tobacco Products in the UK. Available at: Accessed on 9 February 2010.
   Google Scholar
• Torikai K, Torikaiu K, Uwano Y, Nakamori T, Tarora W, Takahashi H. (2005). Study on tobacco components involved in the pyrolytic generation of selected smoke constituents. Food Chem Toxicol 43:559–568.
   PubMedGoogle Scholar
• Tricker AR. (2006). Biomarkers derived from nicotine and its metabolites: a review. Beitr Tabakforsch Int 22:147–175.
   Google Scholar
• Ueda K, Kawachi I, Nakamura M, Nogami H, Shirokawa N, Masui S, Okayama A, Oshima A. (2002). Cigarette nicotine yields and nicotine intake among Japanese male workers. Tob Control 11:55–60.
   PubMed Web of Science ®Google Scholar
• UK Department of Health. (2003). Permitted Additives to Tobacco Products in the United Kingdom. London, UK: Dept. of Health.
   Google Scholar
• US Consumer Product Safety Commission. (1993). Toxicity testing plan for low ignition-potential cigarettes. Washington, D.C.
   Google Scholar
• US Department of Health and Human Services. (2004). The health consequences of smoking: a report of the Surgeon General. Washington, DC: Office on Smoking and Health.
   Google Scholar
• US Department of Health Education and Welfare. (1977). Towards less hazardous cigarettes; the third set of experimental cigarettes: Report no. 3. Washington, D.C.
   Google Scholar
• US Department of Health Education and Welfare. (1980). Towards less hazardous cigarettes; the third set of experimental cigarettes: Report no. 4. Washington, D.C.
   Google Scholar
• US Environmental Protection Agency. (2003). Toxicological review of methyl ethyl ketone. Washington, D.C.: Available at: http://www.epa.gov/iris/toxreviews/0071tr.pdf. Accessed on 27 February 2011.
   Google Scholar
• US Environmental Protection Agency. (2005). Toxicological review of toluene. Washington, D.C.: Available at: http://www.epa.gov/iris/toxreviews/0118tr.pdf. Accessed on 27 February 2011.
   Google Scholar
• US Federal Trade Commission. (1967). Cigarettes: testing for tar and nicotine content. Fed Regist 32:11178.
   Google Scholar
• US Food and Drug Administration. (2000a). Invert sugar. Code of Federal Register 21:184.1859–184.1859.
   Google Scholar
• US Food and Drug Administration. (2000b). Sucrose. Code of Federal Register 21:184.1854–184.1854.
   Google Scholar
• US Food and Drug Administration. (2011). Harmful and potentially harmful constituents in tobacco products and tobacco smoke; request for comments. Fed Regist 76:50226–50230.
   Google Scholar
• US Food and Drug Administration Center for Tobacco Products. (2011). Guidance for Industry and FDA Staff – “Harmful and Potentially Harmful Constituents” in Tobacco Products as Used in Section 904(e) of the Federal Food, Drug, and Cosmetic Act. Available at: http://www.fda.gov/downloads/TobaccoProducts/GuidanceComplianceRegulatoryInformation/UCM241352.pdf. Accessed on 31 January 2011.
   Google Scholar
• US Institute of Medicine. (2001). Clearing the smoke: assessing the science base for tobacco harm reduction. Washington, DC: National Academy Press.
   Google Scholar
• US Occupational Safety and Health Administration. (2010). Occupational Safety and Health Standards, Toxic and Hazardous Substances.
   Google Scholar
• van Miert E, Vanscheeuwijck PM, Meurrens K, Gomm W, Terpstra PM. (2008). Evaluation of the micronucleus assay for the determination of cigarette mainstream smoke activity in bone marrow and peripheral blood of rats. Mutat Res 652:131–138.
   PubMedGoogle Scholar
• Vanscheeuwijck PM, Teredesai A, Terpstra PM, Verbeeck J, Kuhl P, Gerstenberg B, Gebel S, Carmines EL. (2002). Evaluation of the potential effects of ingredients added to cigarettes. Part 4: subchronic inhalation toxicity. Food Chem Toxicol 40:113–131.
   PubMed Web of Science ®Google Scholar
• Waingrow SM, Horn D, Ikard FF. (1968). Dosage patterns of cigarette smoking in American adults. Am J Public Health Nations Health 58:54–70.
   PubMedGoogle Scholar
• Walaszek Z, Hanausek M, Slaga TJ. (2007). The role of skin painting in predicting lung cancer. Int J Toxicol 26:345–351.
   PubMed Web of Science ®Google Scholar
• Wang J, Roethig HJ, Appleton S, Werley M, Muhammad-Kah R, Mendes P. (2010). The effect of menthol containing cigarettes on adult smokers’ exposure to nicotine and carbon monoxide. Regul Toxicol Pharmacol 57:24–30.
   PubMed Web of Science ®Google Scholar
• Werley MS, Coggins CR, Lee PN. (2007). Possible effects on smokers of cigarette mentholation: a review of the evidence relating to key research questions. Regul Toxicol Pharmacol 47:189–203.
   PubMed Web of Science ®Google Scholar
• Woertz HC. (1983). Evaluation of competitive brands. Available at: Accessed on 6 May 2010.
   Google Scholar
• World Health Organization. (2008). WHO report on the global tobacco epidemic, 2008: the MPOWER package. Geneva, Switzerland: World Health Organization.
   Google Scholar
• World Health Organization Study Group on Tobacco Product Regulation. (2008). The scientific basis of tobacco product regulation: second report of a WHO study group, report no. 951. Geneva, Switzerland: World Health Organization. Available at: http://www.who.int/tobacco/global_interaction/tobreg/publications/9789241209519.pdf. Accessed on 16 November 2010.
   Google Scholar
• Woutersen RA, Appelman LM, Wilmer JW, Falke HE, Feron VJ. (1987). Subchronic (13-week) inhalation toxicity study of formaldehyde in rats. J Appl Toxicol 7:43–49.
   PubMed Web of Science ®Google Scholar
• Wynder EL, Hoffmann D. (1963). Bioassays on the carcinogenicity of tobacco smoke condensates and air pollutants. Proc Am Assoc Cancer Res 4:73–73.
   Google Scholar
• Yoshida D, Matsumoto T. (1980). Amino-alpha-carbolines as mutagenic agents in cigarette smoke condensate. Cancer Lett 10:141–149.
   PubMed Web of Science ®Google Scholar
• Zilkey BF, Court WA, Binns MR, Walker EK, Dirks VA, Basrur PK. (1982). Chemical studies on Canadian tobacco and tobacco smoke. 1. Tobacco, tobacco sheet, and cigarette smoke chemical analysis on various treatments of bright and burley tobacco. Tob Sci 26:54–60.
   Google Scholar