Tobacco smoking and

R. A. Scanlan and. E. Barbour, in I. K. O NeiU,. Chen, and H. Bartsch, eds.. Relevance to Human Cancer of N-Nitroso Compounds, Tobacco Smoke and Mjcotoxins, lARC Scientific PubUcation No. 105, International Agency for Research on Cancer, Lyon, Prance, 1991, pp. 242—243. 

Compounds Affecting Rq>roduction Compounds that can affect reproductive function include several drugs and occupationally important chemicals such as solvents and pesticides as well as a number of environmentally relevant com-fxrunds. A group of chemical compounds that has received much attention recently is endocrine disrupters, many of which are halogenated hydrocarbons, e.g., PCBs. These are known to induce feminization in fish and other animal species.1.5/ There is intense debate about the significance of these compounds to human health. Tobacco smoke and ethyl alcohol also have major effects on human reproduction, the effects of alcohol being especially important. Table 5.17 lists compounds that may disturb the functions of female and male reproductive functions. 

Tobacco and its alkaloids have long ceased to have any therapeutic importance, but their extensive use as insecticides and the demand for nicotine for the manufacture of nicotinic acid have stimulated interest in processes of extraction and methods of estimation. On the latter subject there is a voluminous literature, of which critical resumes have been published by various authors.Recent work on this subject has been specially concerned with (1) the development of miero- and semi-miero-methods suitable for estimating nieotine in tobacco smoke and the distribution of nieotine on sprayed garden produce, in treated soils and in tobaeeo leaves,(2) the study of conditions necessary to ensure satisfactory results in using particular processes, " and (3) methods of separation and estimation of nicotine, nomicotine and anabasine in mixtures of these bases. ) In the United States and in Russia considerable interest is being shown in the cultivation of types of tobacco rich in nicotine, in finding new industrial uses for tobacco and its alkaloids, and in possible by-products from tobacco plants such as citric and malic acids, i " Surveys of information on tobacco alkaloids have been published by Jackson, i Marion and Spath and Kuffner. ... 

Particles are present in outdoor air and are also generated indoors from a large number of sources including tobacco smoking and other combustion processes. Particle size, generally expressed in microns (10-6 m) is important because it influences the location where particles deposit in the respiratory system (U.S. Environmental Protection Agency 1995), the efficiency of particle removal by air filters, and the rate of particle removal from indoor air by deposition on surfaces. 

Formaldehyde is a harmful compound released from walls and furnitures in new houses because adhesives containing HCHO are often used in constmction materials. In addition, H CHO is emitted by tobacco smoke and combustion exhaust gases. Long exposure to HCHO causes serious health problems called sick house diseases. In Japan, the concentration of HCHO in indoor air is regulated [54] to under 0.08 ppm based on the recommendation of the World Health Organization (WHO). 

Table 5.1. Adverse medical effects of tobacco smoking, and health benefits of smoking cessation.

Carbon monoxide A poisonous gas found in tobacco smoke and a causative factor in the cardiovascular damage arising through smoking. Carbon monoxide has also been found to function as a gaseous neuromodulator in the brain. 

Wu LT and Anthony JC (1999). Tobacco smoking and depressed mood in late childhood and early adolescence. American Journal of Public Health, 89, 1837-1840. 

Human exposure to complex mixtures of polycyclic aromatic hydrocarbons (PAH) occurs through inhalation of tobacco smoke and polluted indoor or outdoor air, through ingestion of certain foods and polluted water, and by dermal contact with soots, tars, and oils CO. Methylated PAH are always components of these mixtures and in some cases, as in tobacco smoke and in emissions from certain fuel processes, their concentrations can be in the same range as some unsubstituted PAH. The estimated emission of methylated PAH from mobile sources in the U.S. in 1979 was approximately 1700 metric tons (2). The occurrence of methylated and unsubstituted PAH has been recently reviewed (1, 2). In addition to their environmental occurrence, methylated PAH are among the most important model compounds in experimental carcinogenesis. 7,12-Dimethylbenz[a]anthracene, one of... 

The diagnosis of COPD is based in part on the patient s symptoms and a history of exposure to risk factors such as tobacco smoke and occupational exposures. 

Barrefors G, Petersson G. 1993. Assessment of ambient volatile hydrocarbons from tobacco smoke and from vehicle emissions. J Chromatogr 643 71-76. 

Tobacco smoke and iV-nitrosation are the focus of intense research activity. Workers in the field use the following concepts Tobacco-specific /V-nitrosamines (TSNA) mainstream tobacco smoke (MSTS), smoke inhaled in a puff sidestream tobacco smoke (SSTS), smoke evolved by smoldering cigarettes between puffs nitroso organic compounds (NOC), referring especially to IV-nitrosamines volatile NOC (VNOC) and iV-nitroso amino acids (NAA). 

In general, biotransformation reactions are beneficial in that they facilitate the elimination of xenobiotics from pulmonary tissues. Sometimes, however, the enzymes convert a harmless substance into a reactive form. For example, CYP-mediated oxidation often results in the generation of more reactive intermediates. Thus, many compounds that elicit toxic injury to the lung are not intrinsically pneumotoxic but cause damage to target cells following metabolic activation. A classic example of this is the activation of benzo(a)pyrene, which is a constituent of tobacco smoke and combustion products, and is... 

Lambert NM, Hartsough CS (1998) Prospective study of tobacco smoking and substance dependencies among samples of ADHD and non-ADHD participants. J Learn Disabil 31(6) 533-544 Lawrence NS, Ross TJ, Stein EA (2002) Cognitive mechanisms of nicotine on visual attention. Neuron 36(3) 539-548... 

Pauly JR, Stitzel JA, Marks MJ, Collins AC (1989) An autoradiographic analysis of cholinergic receptors in mouse brain. Brain Res BuU 22 453 59 Pauly JR, Marks MJ, Robinson SF, van de Kamp JL, Collins AC (1996) Chronic nicotine and mecamylamine treatment increase brain nicotinic receptor binding without changing alpha 4 or beta 2 mRNA levels. J Pharmacol Exp Ther 278 361-369 Perkins K, Sayette M, Conklin C, Caggiula A (2003) Placebo effects of tobacco smoking and other nicotine intake. Nicotine Tob Res 5 695-709... 

Perkins KA, Sayette M, Conklin CA, Caggiula AR (2003) Placebo effects of tobacco smoking and other nicotine intake, Nic Tob Res 5 695-709... 

Abstract Delivery of nicotine in the most desirable form is critical in maintaining people s use of tobacco products. Interpretation of results by tobacco industry scientists, studies that measure free-base nicotine directly in tobacco smoke, and the variability of free-base nicotine in smokeless tobacco products all indicate that the form of nicotine delivered to the tobacco user, in addition to the total amount, is an important factor in whether people continue to use the product following their initial exposure. The physiological impact of nicotine varies with the fraction that is in the free-base form and this leads to continued exposure to other toxic tobacco contents... 

Relative to the conjugate acid AlkH+, the conjugate base Aik is free of the H+. Hence, Aik is frequently referred to as the free-base form of the alkaloid. Reaction 1 occurs readily in many environments including cellular cytoplasm, water, the particulate matter droplets of tobacco smoke, and blood serum. 

Multiple publications (Pankow et al. 1997 Ingebrethsen et al. 2001 Pankow et al. 2003 Watson et al. 2004) have discussed measuring free-base nicotine directly, addressed the importance of free-base nicotine delivery, and examined the chemical properties of nicotine in cigarette smoke as an important determinant of the effective delivery and bioavailability of nicotine from cigarettes. Pankow et al. (1997) examined how ammonia influences nicotine delivery in tobacco smoke and concluded that conversion of nicotine to the free-base form could be facilitated by ammonia. Based on a theoretical treatment, Pankow et al. (1997) concluded that, under certain circumstances, up to 40% of the nicotine could be available as the volatile free-base form. These authors also concluded that the rate of volatilization was more rapid than that previously measured by Lewis et al. (1995) using denuder technology to examine the properties of mainstream cigarette smoke. 

Evidence from the tobacco industry documents, from research studies that measure free-base directly in tobacco smoke particulate, and from examination of smokeless tobacco products, all show that the level of free-base nicotine as delivered to the tobacco user is a critical variable in the acceptance of tobacco products and their continued use. The physiological impact of the rapid delivery of nicotine in the free-base form is a critical determinant of continued nicotine-seeking behavior, with the unintended consequences of exposure to the other toxic components of tobacco smoke and smokeless tobacco. Evaluating total delivered nicotine alone is not sufficient to characterize product differences. To fully understand the influence nicotine has on the allure of these products, both total and free-nicotine levels must be measured. A comprehensive understanding of nicotine delivery is needed to help find effective means for breaking its addictive nature and, ultimately, in reducing the morbidity and mortality associated with tobacco use. The levels of free-base nicotine must be included as part of any effort to achieve a better understanding of how tobacco products themselves influence their continued use. 

Lewis DA, Colbeck I, Mariner DC (1995) Dilution of mainstream tobacco smoke and its effects upon the evaporation and diffusion of nicotine. J Aerosol Sci 26 841-846... 

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