A Consideration of the Role of Gas/Particle Partitioning in the Deposition of Nicotine and Other Tobacco Smoke Compounds in the Respiratory Tract

Abstract

Tobacco smoke is an aerosol that contains both gaseous and suspended particulate material (PM). The particles are largely liquid droplets containing a wide variety of condensed organic compounds. Each compound in the smoke will partition between the gas and PM phases and will always seek a state of gas/particle equilibrium. When tobacco smoke is inhaled, a compound such as nicotine can deposit in the respiratory tract (RT) by four different mechanisms: (1) direct gas deposition (DGD) of the portion of the compound that is initially in the gas phase of the inhaled smoke; (2) evaporative gas deposition (EGD) of PM-phase compound by evaporation to the gas phase, then deposition; (3) particle deposition, evaporation from the deposited particle, then deposition from the gas phase (PDE); and (4) particle deposition with diffusion (PDD) into RT tissue. Three of the mechanisms (DGD, EGD, and PDE) involve volatilization from the PM phase. The relative importance of all the mechanisms is therefore greatly affected by the volatility of the compound from the PM phase as it is set by the compound's gas/particle partitioning constant K(p) through the compound's vapor pressure. For a largely nonvolatile compound such as benzo[a]pyrene, only PDD will likely be important. For a semivolatile compound such as nicotine, all four mechanisms can be important. Because tobacco smoke alkaloids such as nicotine can exist in protonated as well as free-base form, the fraction alpha(fb) of the compound that is in the neutral free-base form in the PM phase plays a critical, pH-dependent role in determining the relative importance of the four mechanisms. Equations are developed that can be used to ascertain the importance of the DGD and EGD mechanisms. The value of alpha(fb) for nicotine in a tobacco smoke PM is set by pH(eff), the effective pH of the PM phase. Historically, a primary method for measuring "smoke pH" has involved the direct exposure of a pH electrode to tobacco smoke. This method cannot yield direct insight into pH(eff) or alpha(fb) values because (1) problems exist in using such an electrode to measure smoke PM-phase pH, and (2) by itself, a measurement of the pH of tobacco smoke PM says nothing about the effects of PM-phase activity coefficients of protonated and free-base nicotine on the nicotine species distribution. The "acidic" values that have typically been measured for cigarette "smoke pH" by the direct pH electrode method are therefore neither reliable nor useful in determining the relative distribution of PM-phase nicotine among the protonated and free-base forms. The dependence of the volatility of nicotine from tobacco smoke PM on alpha(fb) means that measuring the gas/particle distribution of nicotine under equilibrium conditions in a tobacco smoke by denuder samplers (or by another method) can yield information about the nicotine K(p) for that smoke. Knowledge of K(p,fb), the partitioning constant for nicotine in the free-base form, then allows calculation of alpha(fb) through the relation K(p) = K(p,fb)/alpha(fb...

Fluorescent human lung macrophages analyzed by spectral confocal laser scanning microscopy and multispectral cytometry

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“…Particles in cigarette smoke and diverse locations have been published (Pankow, 2001). For example, the particulate matter in cigarette smoke is a thousand-to a million-fold greater than that for slightly to heavily contaminated urban air (30-500 mg/m 3 ) (Pankow, 2001).…”

Development and Initial Application of Low-Molecular Weight Organic Acids and Inorganic Ionic Species in Aerosol Particulate Matter via Ion Chromatography

“…blood and lung tissue, unprotonated nicotine is volatile and deposits into the respiratory tract at a higher percentage than the two protonated forms. 12 Greater rates of nicotine deposition increase the addictive properties of the compound by supplying the brain with nicotine at a faster rate. It is important to determine the pH level of the particulate phase in order to define the fraction of unprotonated versus protonated nicotine.…”

“…However, due to the chemical properties of tobacco smoke particulate phase, unconventional methods are required to test the pH of the solution to obtain the fraction of unprotonated nicotine. 12,13 These methods are complex and are beyond the scope of this project.…”

Acid-Base Equilibria in Organic-Solvent/Water Mixtures and Their Relevance to Gas/Particle Partitioning in the Atmosphere and in Tobacco Smoke

“…Like atmospheric PM, tobacco smoke PM is not an aqueous solution but an extremely complex liquid mixture composed primarily of condensed organic compounds. Attempts to directly measure the pH of tobacco smoke PM have been unsuccessful, except possibly as a method for measuring relative acidity between smoke samples (Pankow, 2001;Watson et al, 2004;Wayne et al, 2006). The difficulty of measuring "smoke pH" has led researchers to focus on other ways of characterizing the acid-base chemistry of tobacco smoke PM.…”