Clearing the Smoke Assessing the Science Base for Tobacco Harm Reduction (2001) / Chapter Skim
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10 Tobacco Smoke and Toxicology
10 Tobacco Smoke and Toxicology
Pages 283-308
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From page 283... ...
, smoke present in air, consists of exhaled mainstream smoke and sidestream smoke. Smoking machines are used to analyze mainstream smoke.
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From page 284... ...
The material that passes through the filter pad is the gas or vapor phase of cigarette smoke. In general, the vapor phase consists predominantly of compounds with a molecular weight <60 and the particulate phase consists of compounds with a molecular weight >200.
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From page 285... ...
However, cigarette smoke-induced tumors are more prevalent in the bronchial region, suggesting that smoke particles deposit higher up in the respiratory tract than would be predicted from the initial particle size. (Recent increases of adenocarcinomas in lower airways of smokers are hypothesized to be due to so-called smoking compensation of low-yield products.
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From page 286... ...
Cellulose acetate filters remove some of the particulate phase of the smoke but have little influence on the vapor phase. The efficiency of particle removal depends on particle size and is minimal at the numberaverage particle size found in cigarette smoke (about 0.3 ,um diameter)
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From page 287... ...
. Tobacco blends with a high sugar content produce a more acidic smoke; a basic cigarette smoke can be achieved by addition of ammonia.
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From page 288... ...
288 TABLE 10-1 Approximate Chemical Composition of Whole Mainstream Smoke CLEARING THE SMOKE Constituent % by Weight Air N2 O2 Ar Vapor Phase Water co2 CO H2 CH4 Hydrocarbons Aldehydes Ketones Nitrites He te ro cyclic s Methanol Organic acids Esters Other compounds Particulate Phase Water Alkanes Terpenoids Phenols Esters Nicotine Other alkaloids Alcohols Carbonyls Organic acids Leaf pigments Other compounds I 62 13 75.9 0.9 1.3 12.5 4 0.1 0.3 0.6 0.3 0.2 0.1 0.03 0.03 0.02 0.01 0.1 0.8 0.2 0.2 0.2 0.2 0.3 0.1 0.3 0.5 0.6 0.2 0.9 19.6 4.5 NOTE: Ar=Argon; CH4=methane; CO=carbon monoxide; CO2=carbon dioxide; H2=hydrogen; N2=nitrogen; O2=oxygen. SOURCE: Dube and Green, 1982.
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From page 289... ...
TOBACCO SMOKE AND TOXICOLOGY TABLE 10-2 Some Typical SS/MS Yield Ratios for Plain Cigarettes 289 Substance MS Yield SS/MS Small Molecules Carbonyl sulfide 18-42 ,ug 0.03-0.1 HCN 160-500 ,ug 0.06-0.5 CO 10-23 mg 2.5-4.7 Hydrazine 20-43 ,ug 3 Methane 600-1000 ,ug 3.1-4.8 Acetylene 20-40 ,ug 0.8-2.5 Nitrogen oxides 100-600 ,ug 4-13 CO2 20-50 mg 8-11 H2O (gas phase) 3-14 mg 24-30 NH3 50-130 ,ug 40-170 N2 (generated)
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From page 290... ...
290 TABLE 10-2 Continued CLEARING THE SMOKE Substance MS Yield SS/MS Lactic acid 60-170 ,ug 0.5-0.7 Benzoic acid 14-28 ,ug 0.7-1.0 Phenylacetic acid 11-38 ,ug 0.6-0.8 Succinic acid 70-140 ,ug 0.4-0.6 Glycolic acid 40-130 ,ug 0.6-1.0 Amines, Pyridines, Alkaloids Methylamine 12-29 ,ug 4.2-6.4 n-Propylamine 1.6-3.4,ug 2.8-3.8 n-Butylamine 0.5-1.5 ,ug 2.2-4.0 Aniline 360 ng 30 Pyridine 16-46,ug 6.5-20 3-Ethenylpyridine 11-30,ug 20-40 Methylpyrazine 2-5 ,ug 3-4 Pyrrole 16-23,ug 9-14 Nicotine 0.8-2.3 mg 2.6-3.3 Myomine 13-33 ,ug 4.0-7.5 Nicotyrine 4-40 ,ug 5-14 Anatabine 2-20 ,ug 0.1-0.5 2,3'-Bipyridyl 16-22 ,ug 2-3 Aza-arenes Quinoline 0.5-2.0,ug 8-11 Isoquinoline 1.6-2.0 ,ug 2.5-5 Benzo[h] quinoline 10 ng 10 Indole 16-38 ,ug 2.1-3.4 Hydrocarbons Isoprene 330-1100 ,ug 13-19 Benzene 36-68 ,ug 5-10 Toluene 100-200 ,ug 6-8 Limonene 15-50 ,ug 4-12 Neophytadiene 66-230,ug 1-2 Polynuclear Aromatic Hydrocarbons Naphthalene 2.6,ug 17 Pyrene 45-140,ug 2-11 Benzo[a]
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From page 291... ...
The major adverse tobacco smoke-induced health effects that require evaluation because of their prominence in humans are pulmonary inflammation, induction of lung cancer, chronic obstructive pulmonary disease (COPD) , cardiovascular disease, reproductive and developmental effects, and the suppression of the immune system.
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Measures of oxidized bases in DNA can be used to assay for oxidative stress (Cadet et al., 1998~. In recent comparative potency studies comparing the genotoxicity of smoke condensates from standard and new tobaccorelated PREP, a battery of in vitro assays included the Ames test, SCEs, and chromosomal aberrations (Eclipse Expert Panel, 2000~.
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From page 293... ...
ASSESSMENT OF POTENTIAL EXPOSURE REDUCTION PRODUCTS Lung Cancer Animals have not proven to be good models for the type of lung tumors induced by cigarette smoke in humans. Rodents tend to develop peripherally arising lung adenomas rather than centrally arising bronchial tumors when exposed to chemicals.
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From page 294... ...
This results in their not being able to tolerate the level of exposure to cigarette smoke that humans can. Other factors undoubtedly contribute to this species difference in response to cigarette smoke.
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Comparative potency studies for a newly developed tobacco-related PREP made use of 90-day inhalation studies in hamsters and rats to test for inflammation as well as epithelial hyperplasia and metaplasia (Eclipse Expert Panel, 2000~. The committee concludes that these studies indicate there are animal models that show promise for use in screening for development of COPDlike symptoms from the inhalation of new or existing tobacco products.
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From page 296... ...
The committee concludes that such studies suggest animal models can be used to detect the potential for tobacco products to enhance the development of atherosclerosis. Immune System Dysfunction Smoking-related changes in the peripheral immune system in humans include elevated white blood cell counts, increased cytotoxic or suppressor and decreased inducer or helper T-cell numbers, slightly suppressed T-lymphocyte activity, significantly decreased natural killer (NK)
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From page 297... ...
The primary and secondary antibody production by lymphocytes in the lung, lymph nodes, and spleen of mice exposed to tobacco smoke for longer than 26 weeks and challenged by inoculation with sheep erythrocytes was decreased (Thomas et al., 1975~. Laboratory test animals can be used to demonstrate the ability of cigarette smoke to slow the mucociliary clearance of particles from the lung and to alter the function of pulmonary macrophages.
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From page 298... ...
SYNERGISTIC EFFECTS WITH OTHER POLLUTANTS Occupational exposures to materials such as asbestos or radon daughters have proven to have a synergistic interaction with tobacco smoke leading to greatly increased production of lung tumors in exposed workers who also smoke. Although rats are not good models for detecting the induction of lung tumors from cigarette smoke alone, rats exposed to both cigarette smoke and plutonium oxide particles clearly revealed the synergistic effects of cigarette smoke on the induction of lung tumors in combined exposures (Finch et al., 1998~.
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From page 299... ...
During production, various additives are used for the desired flavor and aroma. The chemical composition of smokeless tobacco products varies due to differences in tobacco composition
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From page 300... ...
Dark tobacco has a high level of nicotine, with 3.5-4.0% reported in certain brands (Wahlberg and Ringberger, 1999~. In general the nicotine content per dose of smokeless tobacco product is higher than that of cigarettes, but the maximum serum nicotine levels are similar among all tobacco users (Benowitz, 1997~.
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From page 301... ...
should be evaluated as a possible harm reduction product since two recent epidemiological studies have suggested that it does not increase the risk of oral cancer and has favorable cardiovascular risk outcomes. More investigations into the cellular toxicity and genotoxic potential of smokeless tobacco extracts are needed.
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From page 302... ...
The same types of animal studies used to evaluate the toxicity of inhaled tobacco smoke could be done to evaluate the toxicity of smokeless tobacco products, such as Swedish snus or snuff, with a change in emphasis to the oral route of delivery. Based on known adverse health effects in humans, animal tests would be needed to evaluate the potential for smokeless tobacco to cause chronic inflammation or cancer in tissues of the oral cavity.
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From page 303... ...
It is beyond the scope of the committee's task to recommend the specific set of toxicity tests that should be done on new or existing tobacco products. The committee recommends that a panel of experts be convened to determine the specific set of toxicity tests and details of the testing regimens.
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From page 304... ...
1975. Cell-mediated immune responses to transplanted tumors in mice chronically exposed to cigarette smoke.
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Exposure to sidestream cigarette smoke alters bronchiolar epithelial cell differentiation in the postnatal rat lung. Am J Respir Cell Mol Biol 11~3~:312-320.
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From page 306... ...
l999b. Enhanced pulmonary epithelial replication and axial airway mucosubstance changes in F344 rats exposed short-term to mainstream cigarette smoke.
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1999. Perinatal sidestream cigarette smoke exposure and the developing pulmonary surfactant system in rats.
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From page 308... ...
1997. Epidemiology of cancer and other systemic effects associated with the use of smokeless tobacco.
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