Lipophiles tobacco smoke

The acid-base chemistry of nicotine is now well known and investigations have shown that nicotine in tobacco smoke or in smokeless tobacco prodncts can exist in pH-dependent protonated or nnprotonated free-base forms. In tobacco smoke, only the free-base form can volatilize readily from the smoke particnlate matter to the gas phase, with rapid deposition in the respiratory tract. Using volatility-based analytical measurements, the fraction of nicotine present as the free-base form can be quantitatively determined. For smokeless tobacco products, the situation differs because the tobacco is placed directly in the oral cavity. Hence, the pH of smokeless tobacco prodncts can be measured directly to yield information on the fraction of nicotine available in the nnprotonated free-base form. It is important to characterize the fraction of total nicotine in its conjugate acid-base states as this dramatically affects nicotine bioavailability, because the protonated form is hydrophilic while the nnprotonated free-base form is lipophilic and thus readily diffuses across membranes (Armitage and Turner 1970 Schievelbein et al. 1973). As drug delivery rate and addiction potential are linked (Henningfield and Keenan 1993), increases in delivery rate due to increased free-base levels affect the addiction potential. 

There are no known direct studies on the toxic effects of chemical exposures on the developing fetus. It is known, however, that children of tobacco smokers (tobacco smoke is a mixture of multiple lipophiles and hydrophiles) have unusually high incidences of ADHD, autism, and other developmental disorders. These and other mixture effects are examined more closely in subsequent chapters. This chapter has aimed to alert the reader to the fact that toxic exposure begins at conception and impacts the fetus throughout gestation and beyond. 

Cigarettes, cigars, pipe tobacco, and smokeless tobacco are made up of dried tobacco leaves and hundreds of other components added for flavor and other properties. More than 4000 individual toxic lipophilic and hydrophilic chemical compounds, of which greater than 60 are carcinogens, have been identified in tobacco and tobacco smoke. I35 36 Accordingly, all tobacco and tobacco smoke exposure is, of necessity, to mixtures of toxic chemicals. 

Tobacco smoke contains hundreds of different lipophiles and hydrophiles. Children and adolescents are particularly sensitive to chemical-induced asthma. One study has found that children and teens who smoke cigarettes have nearly four times the risk of developing asthma in their teens than their cohorts who do not smoke. I59l... 

The continuing worldwide increase in respiratory disease corresponds to increases in the release of chemicals into the atmosphere. Respiratory irritation, sensitization, asthma, RADS, and lung cancer can be attributed to numerous single chemicals whose toxicological properties are, for the most part, well known. Many unexplained incidences of respiratory disease cannot be attributed to single chemical exposures, but have been shown to occur when exposures are to chemical mixtures that are composed of at least one lipophile and one hydrophile. The sources of such mixtures include diesel exhausts, tobacco smoke, carpet emissions, paint fumes, and cleaning products. Prevention of chemically induced respiratory diseases should include limiting exposures to these chemical mixtures. 

Human exposure to a combination of tobacco smoke and the house dust mites has been shown to result in allergic sensitization. It is believed that tobacco smoke impairs the barrier function of the airway epithelium, leading to increased access of allergens contained in the house dust mite. In vitro studies with human bronchial epithelial cells have confirmed this hypothesis. I42,43l In this instance it is believed that lipophiles in tobacco smoke serve to facilitate the permeation of toxic allergens. 

Subsequent studies indicated the major precursors in tobacco of PAHs in its smoke were not cellulose and lignin but were the lipophilic tobacco components. Rodgman and Cook (3269, 3286, 3291) and Severson et al. (3616) reported that terpenoids, phytosterols, and saturated hydrocarbons were PAH precursors... 

Snook ME, Chortyk OT (1986) Advances in lipophilic gel chromatography of tobacco and tobacco smoke components. Rec Adv Tob Sci 12 237-297 Stephens RL, Weybrew JA (1959) Isatin a color reagent for nomicotine. Tob Sci 3 48-51... 

Ketamine can be taken by intravenous, intramuscular, nasal or oral means and sometimes it can be smoked with tobacco. With nasal intake, plasmatic peak concentration is reached after about an hour, but results can be seen earlier within approximately 20 min if the intake is intramuscular [25], Due to its high lipophilicity, ketamine is rapidly distributed in the brain and is then distributed to less vascularized organs and adipose tissue, where its accumulation is possible. Ketamine is also responsible for the increased adrenergic tone and cardiovascular symptoms activating [26]. 

Biological activity of CSC from extracted tobacco was decreased but to a much lesser extent than decrease in MSS PAH (and B[a]P) yields. This resulted from two unanticipated effects of extraction on the tobacco and its smoke Extracted lipophilic compounds included various inhibitors (saturated hydrocarbons) and anticarcinogens (a-tocopherol, P-sitosterol, cholesterol, H-Umonene, duvanediols) which have been reported to offset the mmorigenicity of PAHs. 

Personnel from Wynder s laboratory subsequently recommended the addition of lipophilic compounds, e.g., n-hentriacontane, to tobacco [Bmnnemann and Hoffmann (480)] to reduce the generation during the smoking process of nitrate-derived nitrogen oxide which was postulated as a reactant in the formation of NNAs. 

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