Particle-Gas Equilibria of Ammonia and Nicotine in Mainstream Cigarette Smoke

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1 Aerosol Science & Technology ISSN: (Print) (Online) Journal homepage: Particle-Gas Equilibria of Ammonia and Nicotine in Mainstream Cigarette Smoke Bradley J. Ingebrethsen, Cynthia S. Lyman, Charles H. Risner, Patricia Martin & Bert M. Gordon To cite this article: Bradley J. Ingebrethsen, Cynthia S. Lyman, Charles H. Risner, Patricia Martin & Bert M. Gordon (2001) Particle-Gas Equilibria of Ammonia and Nicotine in Mainstream Cigarette Smoke, Aerosol Science & Technology, 35:5, , DOI: / To link to this article: Published online: 30 Nov Submit your article to this journal Article views: 397 Citing articles: 13 View citing articles Full Terms & Conditions of access and use can be found at

2 Aerosol Science and Technology 35: (2001) c 2001 American Association for Aerosol Research Published by Taylor and Francis =01=$12.00 C.00 Particle-Gas Equilibria of Ammonia and Nicotine in Mainstream Cigarette Smoke Bradley J. Ingebrethsen, Cynthia S. Lyman, Charles H. Risner, Patricia Martin, and Bert M. Gordon Bowman Gray Technical Center, R. J. Reynolds Tobacco Company, Winston-Salem, North Carolina The particle-gas equilibria of ammonia and nicotine in mainstream cigarette smoke have been studied by diffusion denuder collection. The surface deposition rate of nicotine is observed to decrease as the smoke traverses the denuder, and this effect is attributed to a changing particle nicotine vapor pressure driven by the measured rapid loss of volatile ammonia from the particles, an interpretation that differs from that of prior studies. The rapid ammonia deposition is observed to be complete at a length-to- ow rate ratio of 28 s/cm 2 for an American blended cigarette, and 38% of the total ammonia analyzed in the collected smoke appears to be nonvolatile in the aerosol, possibly bound in the particles by reaction with acids. Fitting of a theoretical model that predicts the rapid ammonia loss and changing nicotine vapor pressure to the measurements predicts that the nicotine vapor pressure over the particles in fresh smoke is about 6% of the pure component nicotine value, and the ammonia vapor pressure over the smoke particulate is considerably less than that predicted by its aqueous Henry s law coef cient. Dilution of mainstream smoke enhanced the fractional deposition of both ammonia and nicotine in the denuder tubes and provided a means to estimate the nonvolatile ammonia fraction, which varied considerably in cigarettes made with different tobacco types. Among the different tobacco type cigarettes, smoke ammonia concentration, smoke ph, and smoke nicotine-to-particulate ratio varied with ammonia and nicotine deposition from diluted smoke when extreme values for an all burley tobacco cigarette were included in the analysis, but no trends were apparent when only the more typical range of the other cigarettes was considered. INTRODUCTION It has been suggested that the chemical state of nicotine in mainstream cigarette smoke in uences the rate and extent of nicotine uptake during smoking (Pankow et al. 1997). It has also been proposed that the addition of ammonia and/or ammoniayielding compounds to tobacco in uences the chemical state of nicotine in cigarette smoke (Pankow et al. 1997). However, though experimental demonstrations of an effect of nicotine s Received 2 December 1999; accepted 29 August Address correspondence to Bradley J. Ingebrethsen, 2 Prospect Street, Rhinebeck, NY chemical state on its uptake during cigarette smoking have not been reported, there are a number of published observations that suggest that nicotine uptake may be determined by other factors. Studies of inhaled mainstream smoke report that from 86% to 99% of inhaled nicotine is deposited, i.e., not exhaled, regardless of cigarette type (Armitage et al. 1975; Greenberg et al. 1952; Ingebrethsen 1989; Isaac and Rand 1972; Landahl and Tracewell 1957). These measurements suggest that if inhaled nicotine deposition varies with cigarette properties, it does so over a very narrow range in the vicinity of near complete deposition. In addition, the rate of nicotine uptake during cigarette smoking has been observed to be at least as rapid as that during intravenous injection (Russell and Feyerabend 1978; Henning eld et al. 1993; Rose et al. 1999). This suggests that any hypothesized variation in rate with cigarette properties may not be resolvable experimentally. In a study comparing acidic to basic smoke, Schievelbein (1982) reported no effect of smoke type on uptake rate in smoke-ventilated dogs. Moreover, he noted that, in contrast to oral absorption, the in uence of smoke ph on lung absorption appeared to be negligible. From a practical point of view, basic cigarette smoke, like cigar smoke, is very harsh on the throat. Consequently, inhalability becomes an important consideration in assessing nicotine uptake during normal smoking. In the absence of experimental veri cation of the hypothesis that nicotine s chemical form in uences uptake during smoking, discussions have focused on relating cigarette smoke properties to proposed mechanisms of nicotine deposition and transport during smoking. One effect that has been suggested to play a role is the rapid diffusion of gas-phase nicotine base to respiratory tract surfaces as contrasted with the less rapid diffusion of nonvolatile protonated nicotine residing in smoke particles (Pankow et al. 1997). Evaluation of this hypothesis has drawn upon the limited number of diffusion denuder studies, the preferred method for measurement of nicotine gas-particulate equilibrium in aerosols. Hager and Niessner (1997) studied nicotine partitioning in simple model aerosol systems but did not study cigarette smoke. Several studies of nicotine partitioning in environmental tobacco smoke (ETS) have been reported, e.g., 874

3 PARTICLE-GAS EQUILIBRIA OF AMMONIA AND NICOTINE 875 Eatough et al. (1989), but ETS is both chemically different and orders of magnitude more dilute than mainstream smoke. With regard to nicotine uptake during smoking, the denuder studies of mainstream smoke by Lewis (1994) and Lewis et al. (1994, 1995) are by far the most relevant. However, the distribution of ammonia between the gas and particulate phases of cigarette smoke, and the resultant interaction with nicotine distribution, has not been carefully examined. In this paper we give an alternative theoretical interpretation of the Lewis et al. (1995) denuder measurements and present new results on simultaneous ammonia and nicotine collection in denuder tubes. Data on the effects of smoke dilution and tobacco type on the gas-particle equilibria are discussed, and the in uence of several smoke properties on the equilibria are examined. THEORETICAL Lewis (1994) developed a theoretical treatment of vapor deposition in a cylindrical denuder from an aerosol with evaporating particles and used this analysis to interpret measurements on mainstream cigarette smoke (Lewis 1994; Lewis et al. 1994, 1995). The model tracks nicotine mass elements evaporated at incremental positions along a tube and describes deposition of vapor attributable to each mass element by an approximation to the Gormley-Kennedy (G-K) equation (Gormley and Kennedy 1949). Total deposition in the tube is calculated as the sum of that deposited from the individual mass elements. These computer simulations predict that the mass deposition of nicotine from the aerosol, as a function of tube position, should follow the same rst order exponential pattern predicted by the approximation to the G-K equation used for vapor diffusion within the model. However, experimental measurements of nicotine deposition along the denuder tube length indicated a double exponential decay pattern (Lewis et al. 1995). To explain these experimental results, it was proposed that nicotine initially present in the vapor phase at the denuder inlet is removed at a rate faster than the nicotine evaporating from the smoke particles. Speci cally, it was suggested that the nicotine vapor initially present is removed as predicted by the G-K approximation with the standard nicotine gas diffusion coef cient. Simultaneously, nicotine evaporating from the particles deposits at a rate predicted by G-K using a smaller apparent nicotine diffusion coef cient and a preexponential factor that differs from the expected value (i.e., the total nicotine mass). The combination of fast and slow rst-order decays gives a good numerical t to the data. However, the possibilty of rapid equilibration of evaporating nicotine with the bulk vapor concentration in the smoke suggests that the independent deposition of initially present vapor and evaporating vapor may not be physically reasonable. In order to evaluate the consistency between the proposed initial vapor effect and the physical mechanisms of the model, the full numerical simulation from Lewis (1994) was reproduced and the in uence of varying the nicotine vapor concentration at the tube inlet was assessed. No initial vapor level, including those exceeding the particle surface equilibrium value, i.e., supersaturated levels, yielded the double exponential pattern obtained in Lewis (1994) by the simple sum of two rst order terms. These simulations predict that all initial vapor levels rapidly equilibrate to the particle surface vapor pressure value yielding a single exponential deposition pattern along the tube length. The simulations also predict that the surface deposition rate is directly proportional to the vapor concentration at a given axial position. This is illustrated by the constant ratio of surface deposition rate to nicotine vapor concentration across the tube length as plotted in Figure 1 for three particle number concentrations covering the full range of deposition patterns predicted by the simulations. The multicomponent model described below also predicts a constant ratio of deposition rate to nicotine vapor concentration, except for a very short initial length. The gas-particle equilibration time scale is expected to be much more rapid than that for diffusion of vapor to the tube wall. In all simulations, vapor at the particle surface equilibrates rapidly with the bulk gas. Surface deposition is then driven by the bulk gas concentration. The implication for the experimental observations is that the elevated and steeply varying deposition rate at short lengths is the result of rapidly varying vapor concentration. In other words, the deposition data seem to imply a changing smoke particle surface-vapor concentration similar in pattern to the surface deposition curve. A likely physical mechanism for the changing surface vapor concentration is the rapid loss of components more volatile than nicotine that changes the particle composition and alters the nicotine surface-vapor concentration. In order to test this alternative physical interpretation, we have developed an alternative description of the nicotine gasparticle equilibrium in cigarette smoke that allows for an evolving particle-surface nicotine vapor pressure as deposition takes place along the tube and smoke-particle composition changes. We employ a more complex particulate and particle-gas Figure 1. Ratio of nicotine-deposition rate to nicotine-vapor concentration plotted versus denuder tube section endpoint length divided by volumetric ow rate.

4 876 B. J. INGEBRETHSEN ET AL. partitioning description than that in Lewis (1994) to calculate particulate concentrations and particle-surface vapor pressures. Evaporation rates and denuder surface deposition rates are then calculated essentially as in Lewis (1994). It should be noted that the theoretical model to be described is but one of many possible ways of testing the proposed physical mechanism of a changing nicotine vapor pressure driven by loss of other components from the particles. Mainstream cigarette smoke contains numerous volatile basic components that can adsorb to the acidic surface of a denuder tube. The evaporative loss of particulate components can conceivably alter the nicotine vapor pressure through effects on the particulate chemistry beyond that expected by the simple change in concentration through depletion of nicotine, the only effect allowed in the Lewis (1994) simulations. In our description, the particulate composition is approximated as an aqueous solution and several smoke components are allowed to partition between the gas and particulate phases and to ionize in the particulate solutions. With this approach the vapor pressure of nicotine at the particle surface is predicted to vary over a greater range than in the Lewis (1994) model. This mechanism suggests an alternative interpretation of the deposition curves that avoids some of the dif culties discussed above. Cigarette smoke particulate matter is sometimes assumed to behave as an aqueous solution, e.g., Pankow et al. (1997), but the nature and complexity of smoke chemistry and the presence of a substantial amount of aqueous-insoluble material in the particles render the aqueous approximation a recognized oversimpli cation. Our description of mainstream smoke in a denuder tube includes carbon dioxide and ammonia in addition to nicotine as volatile species that distribute between the gas and particulate phases. The phase distributions are as predicted by Henry s law behavior where appropriate information is available and by ideal solution predictions where information is not available. The surface of the denuder is treated as a perfect sink for both ammonia and nicotine but as unreactive toward carbon dioxide. The smoke particles are treated as aqueous solutions in which carbon dioxide, nicotine, ammonia, and a generic organic acid are in ionic equilibria. The solution concentration of the volatile form of a compound isin uenced by ionization and that, in turn, in uences the vapor concentration. The rate of particle equilibration with the gas phase is calculated with a standard isothermal particle evaporation equation (Hinds 1982). The expressions for solution and gas-particle equilibria, along with mass balance and electroneutrality expressions, are solved simultaneously to provide both solution and gas-phase species concentrations. This procedure for concentration calculations was combined with a numerical surface-deposition algorithm similar to that used in Lewis (1994) and is based on an incremental solution of the full G-K equation. The primary adjustable parameters used to t the model to measured deposition patterns were multiplicative vapor-pressure correction factors for both ammonia and nicotine particlesurface vapor pressures. These factors modi ed the particlesurface vapor pressure values predicted by the dilute solution equilibrium approximation. Such an adjustment is reasonable given the high concentrations calculated for the particle solutions (greater than one molar in several species), and was needed to t the simulations to experimental data. Smoke concentration levels of total particulate matter (TPM), ammonia, nicotine, and carbon dioxide were set to experimentally measured values. The organic acids present in smoke particulate matter were collectively represented by a generic acid of xed molecular weight and pk a. Acid concentration was set by means of an adjustable acid-to-nicotine mass ratio. Table 1 lists the chemical species, reactions, values for the equilibrium constants, and several other parameters required to calculate the solution equilibria, the particle-gas equilibria, and the surface deposition rates employed in the model. The equations required to reproduce the Lewis (1994) model can be found in that reference and the additional expressions needed for the multicomponent model can be found in Seinfeld and Pandis (1998). NUMERICAL SIMULATION RESULTS Figure 2 reproduces the nicotine deposition data from Lewis et al. (1995) as fraction of nicotine deposited (amount deposited on each 5 cm tube section divided by the sum of amounts on all tube sections and the backup lter) versus tube endpoint length divided by volumetric ow rate, hereafter referred to as length divided by ow rate. The best t of the Lewis numerical simulation to the unvented, no mouth end ventilation, cigarette data (lower points) is shown as the lower solid curve. The initial nicotine vapor concentration has no signi cant effect on the simulation predictions as shown by the superposition in Figure 2 of the curves for VAPOR, initial vapor at saturation concentration, and NO VAPOR, initial vapor concentration set to zero. The upper solid curve in Figure 2 is a prediction for the vented, mouth end ventilation cigarette data based on best- t parameters from the unvented data. Only the smoke concentration has been adjusted by the reported dilution factor. Clearly the simulation does not produce a double exponential decay and the initial nicotine vapor concentration has an insigni cant effect. In Figure 3 the same data from Lewis et al. (1995) are compared to the multicomponent model simulations. The best t to the unvented data is shown as the lower solid curve and was obtained with vapor-pressure correction factors of 6.75 for nicotine and 0.1 for ammonia. The acid-to-nicotine mass ratio was optimized at The upper solid curve in Figure 3 was obtained by holding all parameters derived from the lower curve simulation constant, except for the smoke-concentration level, which was adjusted by the experimentally determined dilution factor. The respectable prediction of the vented data using the same tting parameters as those for the unvented data provides a degree of support for the reasonableness of the physical model. Shown in Figure 3 as dashed lines are simulation results where the ammonia concentration has been set to zero with all other parameters held constant at the values for the best- t

5 PARTICLE-GAS EQUILIBRIA OF AMMONIA AND NICOTINE 877 Table 1 Chemical species, reactions, equilibrium constants, and parameter values for the multicomponent simulation of nicotine and ammonia particle-gas equilibria in mainstream smoke Chemical species Symbol Water H 2 O Hydronium ion H C Hydroxyl ion OH Nicotine NIC Single protonated nicotine NICH C Double protonated nicotine NICH CC 2 Carbon dioxide CO 2 Carbonate ion CO 3 Bicarbonate ion HCO 3 Ammonia NH 3 Ammonium ion NH C 4 Organic acid AH Ionized acid A Reaction Equilibrium constant H 2 O, H C C OH K 298 D M a NICH C, H C C NIC K 298 D M b NICH CC 2, H C C NICH C K 298 D M b CO 2 H 2 O, H C C CO 3 H K 298 D M a CO 3 H, H C C CO 3 K 298 D M a NH C 4, HC C NH 3 K 298 D M a AH, H C C A K 298 D M c CO 2gas C H 2 O, CO 2 H 2 O H 298 D M atm 1a NH 3gas C H 2 O, NH 3 H 2 O H 298 D 62 M atm 1a NIC gas C H 2 O, NIC H 2 O Ideal behavior assumed Parameter Value Nicotine vapor pressure at 298 ± C Smoke particle average mass diameter Molecular weight generic acid Range acid to nicotine mass ratio Nicotine diffusion coef cient Ammonia diffusion coef cient a Seinfeld and Pandis (1998). b Weast (1972). c Measured in this study. d Ingebrethsen (1989) torr c 0.3 ¹m d 94 g/mole c c cm 2 /s c 0.22 cm 2 /s c values. The absence of ammonia yields predictions of slightly lower total nicotine deposition, 2.81% versus 4.01% unvented and 20.8% versus 21.3% vented. The smaller proportional impact of ammonia for the more dilute smoke is attributable to the even more rapid loss of ammonia in the dilute case than in the more concentrated unvented measurements. The fraction of total nicotine deposition associated with the rapid evaporation of ammonia, 1.2% and 0.5% for unvented and vented cigarettes, respectively, corresponds very closely to that attributed by Lewis et al. (1995) to initially present nicotine vapor, % and %. While the details of the aqueous equilibria model are certainly an oversimpli cation, mechanistically the rapid evaporation of ammonia interpretation seems more physically reasonable than the initial-vapor hypothesis. Logically the effect of rapid ammonia evaporation would remain small and decrease slightly as the smoke is diluted fteenfold. This is because ammonia is expected to leave the particles even more rapidly at the higher dilution and therefore exert less effect on the nicotine vapor pressure. It seems less likely that the fraction of nicotine initially in the vapor phase would remain constant when the smoke undergoes a fteenfold dilution. EXPERIMENTAL METHODS Mainstream cigarette smoke measurements were made with three denuder tube con gurations. The rst set of conditions were very close to those for the continuous draw measurements reported in Lewis et al. (1995). Our apparatus for this con guration consisted of a 0.8 cm i.d., 120 cm length glass tube with a phosphoric acid coating on the inner surface. An ammonia and nicotine penetration trap of wash bottles and a lter, described below, was connected at the lower end of the vertically positioned tube. A mass ow controller maintained a 5.0 cm 3 /s ow rate through the tube and trap. Smoke was introduced into the denuder tube by placing the cigarette directly into the top opening of the tube and allowing a continuous ow to be drawn through the cigarette for the length of time required to consume 2.0 cm of cigarette length. After smoking, the tube was separated into six 20 cm sections that were extracted and analyzed for ammonia and nicotine as described below. The trap solutions and lter extracts were also analyzed to determine material passing through the tube. The other two denuder con gurations employed are depicted in Figure 4 and allowed mainstream smoke to be generated by intermittent puf ng of the cigarette rather than by a continuous ow. In the undiluted smoke arrangement, Figure 4a, a threeway solenoid valve was used to alternate the denuder ow from cigarette to clean air (through a scrubbing lter and a ow resistance). The ow through the cigarette was switched on for a 2 s puff once per minute. With a denuder ow of 17.5 cm 3 /s, the 2 s puff had a total volume of 35 cm 3. In order to study variable denuder ow rates, the outlet ow from the solenoid could be split to a bypass and a denuder ow thereby maintaining a 35 cm 3 puff at the cigarette with a reduced ow rate through the denuder tube. Measurements at ow rates of 17.5 and 8.75 cm 3 /s were made with the undiluted con guration. The denuder tube in these experiments was 0.5 cm i.d. and 120 cm in length and was coated with phosphoric acid. The

6 878 B. J. INGEBRETHSEN ET AL. Figure 2. Comparison of reproductions of Lewis simulations without initial vapor assumption to Lewis data for nicotine deposition versus denuder length divided by ow rate for vented and unvented cigarettes with initial vapor concentration set to zero or to the equilibrium value. The ordinate values are the amounts on each 5 cm tube section divided by the total on all tube sections plus that on the backup lter. penetration trap was identical to that in the rst con guration. The intermittent injection of smoke into the laminar ow through the denuder tube resulted in some dilution of the smoke by axial dispersion as the injected puff traveled the length of the tube with a typical parabolic ow pro le. For the 17.5 cm 3 /s ow rate and a 2 s puff, the smoke concentration was calculated to be reduced to 43% of the initial value by dispersion dilution. The diluted smoke denuder con guration, Figure 4b, was identical to the undiluted arrangement, Figure 4a, except for the two 500 cm 3 dilution vessels positioned between the solenoid outlet and the denuder tube inlet and the absence of a bypass split. During the experiment, smoke owed into the rst vessel, through a short connecting tube to the second vessel, and then into the denuder inlet. The ow rates and vessel volumes were such that smoke from a given puff was not completely cleared from the vessels prior to the next puff 60 s later. This arrangement was designed to produce a relatively steady smoke concentration at the exit of the second vessel after two puf ng cycles. For a 17.5 cm 3 /s ow and 500 cm 3 vessel volume, the smoke concentration at the exit of the second vessel after two puf ng cycles was calculated to be about 3% of the inlet value. Both polyvinyl chloride vessels and the connecting tube were extracted and analyzed for ammonia and nicotine. The collection ef ciency and capacity of the denuder for ammonia and nicotine were determined by collection of standard gas samples. Nicotine gas standards were generated by a continuous ow of air through an isothermal nicotine reservoir, and ammonia gas standards were obtained from calibrated ammoniaair mixtures. Figure 5 shows a plot of the logarithm of the fraction of total reactant deposited versus the tube section endpoint length divided by the ow rate for ammonia and nicotine gas standards. The gas standards contained at least ten times the total mass of ammonia and nicotine present in the smoking experiments. The diffusion coef cients calculated from the slopes of the lines in Figure 5 are 0.22 cm 2 /s for ammonia (versus 0.24 cm 3 /s calculated from Perry and Green (1984)) and cm 2 /s for nicotine (versus cm 2 /s reported by Eatough et al. (1989)). The penetration trap consisted of two gas wash bottles containing aqueous phosphoric acid solution with a glass- ber lter in series between the bottles. This arrangement was suf cient to capture all the ammonia and nicotine exiting the denuder tube at the ow rates employed. After smoke collection the trap lter pad and the denuder tube sections were extracted with water to provide an aqueous acidic solution that, along with the wash bottle solutions, contained the collected smoke components. A

7 PARTICLE-GAS EQUILIBRIA OF AMMONIA AND NICOTINE 879 Figure 3. Comparison of multicomponent simulations to Lewis data for vented and unvented cigarettes for nicotine deposition versus denuder length divided by ow rate with and without ammonia present. The ordinate values are the amounts on each 5 cm tube section divided by the total on all tube sections plus that on the backup lter. Figure 4. Diagram of apparatus for denuder collection of ammonia and nicotine from puffed mainstream smoke for: A.) undiluted smoke; B.) diluted smoke; with a.) cigarette; b.) solenoid valve; c.) acid-coated lter; d.) ow resistance; e.) dilution vessels; f.) acid-coated denuder tube; g.) gas wash-bottle containing acid solution; h.) uncoated lter; i.) by-pass ow. portion of each aqueous solution was taken directly for cation exchange ion chromatography (CEIC) analysis of ammonium ion. CEIC analysis of ammonium ion was performed on a cation exchange column with a conductivity detector under isocratic conditions of 22 mn H 2 SO 4. The remainder of each aqueous solution was made basic with sodium hydroxide solution and partitioned with hexane to extract nicotine. The hexane solutions were then analyzed by gas chromatography (GC) for nicotine. The GC analysis was performed on a Carbowax fused silica capillary column with a ame ionization detector under a programmed temperature pro le and splitless injection. With the denuder con gured to approximate the conditions of Lewis et al.(1995), a commercial, full- avor, lter-tipped, 12 mg tar (by Federal Trade Commission (FTC) standard method), English-blend cigarette was studied. This cigarette was similar to that described in Lewis et al. (1995). With the undiluted puf ng con guration, a commercial lter tipped, light, 10 mg tar (by FTC method), American-blend cigarette was studied. With the diluted-smoke con guration the commercial American blend cigarette and 3 single-tobacco, nonblended ( ue cured, Burley, and Oriental) test cigarettes were studied. For these latter four cigarette types both the FTC yield data and yields collected during the denuder measurements are given in Table 2.

8 880 B. J. INGEBRETHSEN ET AL. Figure 5. Logarithm of fraction of ammonia and nicotine deposited versus denuder tube-section endpoint length divided by volumetric ow rate for test gas samples. Smoke ph measurements were performed by a method described by Harris and Hayes (1977). In this procedure the whole smoke from 20 sequentially puffed cigarettes is scrubbed by 50 cm 3 of water in a stirred trap. After smoking, the stirred trap liquid is purged for 10 min with nitrogen to remove dissolved carbon dioxide. The ph of the residual liquid is measured by electrode. The value so obtained is termed smoke ph. Nicotine vapor pressure was measured by GC analysis of nicotine scrubbed from gas samples drawn from isothermal vessels containing liquid nicotine that had equilibrated with the gas in the vessel. EXPERIMENTAL RESULTS Figure 6 shows the results of the experiments with the English blend cigarette under denuder conditions that approximated those of Lewis et al. (1995). The fractions of total ammonia and nicotine deposited in each tube section (amounts deposited on each 20 cm tube section divided by total of amounts on all tubes and the backup lter) are plotted versus length divided by ow rate. The difference in tube lengths analyzed for the data in Figure 3 versus that in Figure 6 results in the different magnitudes for the y axes in the plots. No theoretical comparison was made for these data and the curves shown in Figure 6 simply connect the points. Figure 6 shows that the ammonia and nicotine deposition patterns are of similar shape. For both species, larger fractions were deposited in the rst two sections, but the magnitude of the ammonia fraction deposited is signi cantly greater than that of nicotine. The total fraction of nicotine deposited in this experiment is about twice that reported for the unvented case in Lewis et al. (1995), 8% versus 4%. We do not know if we accurately reproduced all of the experimental details of the prior work in our measurements, including the exact cigarette type, and cannot ascribe any signi cance to the different results for the total fraction of nicotine deposited. Our multicomponent model analysis predicts that about 95% of the total ammonia should deposit Table 2 Yields from test cigarettes for FTC and denuder measurement smoking Smoking method Measure Flue cured Burley Turkish American blended FTC puffs/cigarette tar /puff ¹g Nicotine/puff ¹g TPM/puff ¹g CO 2 /puff ¹g Nicotine/TPM smoke ph Denuder Nicotine/puff ¹g Ammonia/puff ¹g

9 PARTICLE-GAS EQUILIBRIA OF AMMONIA AND NICOTINE 881 Figure 6. Measured fraction of ammonia and nicotine deposited per tube section versus denuder tube section endpoint length divided by volumetric ow rate for a replication of Lewis experimental conditions on unvented cigarettes. The ordinate values are the amounts on each 20 cm tube section divided by the total on all tube sections plus that on the backup lter. Error bars indicate one standard deviation. Solid lines simply connect the experimental data points. under these conditions, whereas we observe only about 40% deposition. This discrepancy appears to be due to a fraction of the ammonia being bound in the particles as nonvolatile, an effect which was not included in the original theoretical analysis. The results for measurements in the undiluted puf ng con g- uration, Figure 4a, on the commercial American-blend cigarette are presented in Figure 7. The results of separate experimental runs at 17.5 and 8.75 cm 3 /s denuder ow rates are combined on Figure 7. Cumulative fraction ammonia and cumulative fraction nicotine deposited versus denuder tube section endpoint length divided by volumetric ow rate for blended cigarettes collected under puf ng conditions. The ordinate values are the amounts on each 20 cm tube section divided by the total on all tube sections plus that on the backup lter. Error bars indicate one standard deviation. Solid lines are best- t curves of multicomponent model to data.

10 882 B. J. INGEBRETHSEN ET AL. Figure 8. Measured cumulative fraction of ammonia deposited versus denuder tube section endpoint length under diluted smoke conditions. (Cigarettes are made from blended, ue-cured, burley, and Oriental tobaccos. Error bars indicate one standard deviation.) the plot to achieve the range of length divided by ow rate values shown. The measurements at the two ow rates yielded data at overlapping length divided by ow rate values and were mutually consistent. The tendency for the cumulative ammonia deposition to plateau at less than 100% deposition is evident. This experimental observation was the basis for introducing a nonvolatile ammonia factor into the multicomponent model. Formation of ammonium salts with organic acids in the particles is not an unreasonable possibility and will be discussed further below. The best t of the multicomponent model to the data yielded the predictions for ammonia and nicotine fractions deposited and are shown as solid lines in Figure 7. The best theoretical t Figure 9. Measured cumulative fraction of nicotine deposited versus denuder tube section endpoint length under diluted smoke conditions. (Cigarettes are made from blended, ue-cured, burley, and Oriental tobaccos. Error bars indicate one standard deviation.)

11 PARTICLE-GAS EQUILIBRIA OF AMMONIA AND NICOTINE 883 was achieved with an acid-to-nicotine mass ratio of 0.35, a nonvolatile ammonia fraction of 0.38, and vapor pressure correction factors of 3.15 for nicotine and for ammonia. In Figure 8 the cumulative fraction of ammonia deposited in the diluted-smoke denuder con guration is plotted as a function of tube length for the commercial American blend and three single-tobacco-type test cigarettes. The analagous plot for cumulative fraction of nicotine deposited is shown in Figure 9. In these plots the mass quantities deposited in the dilution vessels are included in the rst tube-section data values. The absolute mass quantities of ammonia and nicotine in these experiments varied even more among the cigarettes than the fractional amounts, as indicated by considering the yield data in Table 2 in combination with the fractional deposition. Because the ow and deposition in this denuder con guration is not consistent with the model assumptions, no tting of the model to these data are presented. DISCUSSION Our replication of the Lewis (1994) numerical model does not support the initial vapor hypothesis proposed to explain the observed denuder nicotine deposition pattern in Lewis et al. (1995). The numerical simulations are insensitive to the value chosen for the initial nicotine vapor concentration and fail to reproduce the observed two-stage decay. The separation of deposition terms for initially present vapor and evaporated vapor represents an arti cial maintenance of a vapor concentration exceeding the particle surface vapor concentration, i.e., a supersaturated initial vapor level. This supersaturation is proposed to be maintained for 3 4 s, while reasonable estimates of particle-vapor equilibration time scales are on the order of 0.1 s or less (e.g., Hinds (1982, p. 268) using nicotine s properties). The numerical simulations predict that supersaturation is rapidly relieved and the gas-phase nicotine concentration quickly assumes the particle surface value. Since the nicotine surface deposition rate is predicted to be directly dependent on the gas-phase concentration as illustrated in Figure 1, and the particles are predicted to rapidly equilibrate with the gas phase, the rate of surface deposition is expected to be directly dependent on the particle-surface vapor concentration. Consequently, the rapidly decreasing deposition rate at short denuder lengths appears to be attributable to a rapidly decreasing particle- surface nicotine vapor pressure. The small fraction of total nicotine deposition attributed by Lewis (1994) to initially present vapor is accounted for, in this analysis, by a small and transitory elevation of particle-nicotine vapor pressure. The multicomponent model provides a physically reasonable explanation for a rapidly decreasing particle surface nicotine vapor concentration across the initial denuder section in the rapid loss of ammonia from the particles. The implementation of the Lewis (1994) model uses three adjustable parameters to t the experimental deposition data. Two of these parameters k A and D A, the preexponential and exponential factors in the term for evaporated vapor removal in Lewis et al. (1995), are not strictly de ned, but rather phenomenologically represent the combined, net effects of the physical mechanisms modeled in Lewis (1994) and consequently do not lend themselves to independent experimental veri cation. Although the multicomponent model introduces several additional physical processes and a more complex description of composition, only four adjustable parameters were used to t the model to the experiments: vapor pressure correction factors for ammonia and nicotine; the fraction of nonvolatile ammonia in the particles; and the organic acid concentration. The nonvolatile ammonia fraction is material that the CEIC method analyzes as ammonium ion but appears not to vaporize in the denuder experiments. This material may well be attributable to nonvolatile ammonium salts of organic acids formed in the smoke particles, but the current ndings allow only speculation regarding this possibility. The fraction of nonvolatile ammonia could reasonably have been treated as a separately determined experimental value determined from the data in Figure 8 under the assumption that complete evaporation has taken place under high dilution. For example, the value of 0.62 for the volatile fraction of ammonia for the blended cigarette determined from the model agrees well with the value derived directly from Figure 8, where the asymptotic level of ammonia loss is about 60% for this cigarette. Effectively, the tting of the model involves varying three adjustable parameters to t two independently measured sets of data, the nicotine and the ammonia measurements, which strengthens con dence in the meaningfulness of the analysis somewhat. However, it must be recognized that separate experimental veri cation of the tting parameters is the only valid test of the physical mechanisms embodied in the theoretical model. Fortunately, each of the parameters has a wellde ned physical meaning and can be accessed experimentally in separate experiments, as the nonvolatile ammonia fraction is in Figure 8. For example, the vapor correction factors are simple predictions of the vapor pressures over the particulate matter and could be measured as the vapor concentrations of the respective compounds over bulk samples of the smoke particulate matter. The acid concentration in the smoke could be addressed by direct chemical analysis or titration, but it should be noted that the nicotine-to-acid ratio in the model predicts only dissolved acid concentration and total acid analyses are likely to include additional acids present that are bound as insoluble salts. Regarding the details of the theoretical model, it should be remembered that mainstream cigarette smoke contains components spanning a range of volatility from those exclusively in the gas phase to nonvolatile particulate material. That the physicochemical properties of the particles should change as evaporation proceeds and particle composition changes in a denuder is not unexpected. That the particle properties change exactly as predicted by the aqueous approximation and solely due to ammonia loss is less likely. Smoke particulate matter contains substantial amounts of aqueous-insoluble compounds as well as aqueous-soluble volatile compounds other than

12 884 B. J. INGEBRETHSEN ET AL. ammonia and nicotine. The presence of such compounds logically suggests a smoke chemistry and physics more complex than the aqueous solution description assumed in the multicomponent model. Nevertheless, our denuder deposition measurements clearly indicate that the quantity of volatile ammonia lost as a function of tube length correlates closely with a decrease in the rate of nicotine loss from the smoke. That is, ammonia, and possibly other compounds that deposit in the denuder at about the same rate as ammonia, are changing the volatility of nicotine in the particles and, consequently, its rate of loss by adsorption. A simpli ed analysis of the denuder measurements can be made by ignoring the details of particle composition and viewing the deposition patterns as the result of particles evaporating at a rate determined by a surface vapor pressure. In this way the vapor pressure over the smoke particles, however it is achieved, required to yield the observed deposition rates can be calculated. Taken in this way, the measurements indicate for the blended cigarette smoke at the inlet of the denuder a nicotine vapor pressure of about 6% of the pure component value at 298 ± C (no nicotine Henry s law constant was available for comparison), or about torr, which drops to about 3.5% of the pure component value at a tube length of 40 cm. The ammonia vapor pressure above the particles appears to be about 1% of that predicted by its Henry s law coef cient at 298 ± C. Figures 8 and 9 indicate that after the approximately thirtyfold dilution, ammonia loss has essentially reached a plateau for all four cigarette types, with little additional deposition after the rst denuder section. Nicotine, on the other hand, continues to be lost as the smoke travels through the denuder. This pattern suggests that the nal fraction of ammonia deposited in these experiments might be an estimate of the volatile fraction of ammonia, but that the nal fraction of nicotine deposited should be taken as the fraction deposited only under these particular experimental conditions. Signi cant variation among cigarette types is observed. The Burley cigarette deposited a greater fraction of the total ammonia and nicotine than the other cigarette types. The blended and ue-cured cigarettes revealed the smallest fraction of ammonia deposited, with Oriental intermediate. The blended and Oriental were lowest on fraction of nicotine deposited, with ue-cured intermediate. The asymptotic level of volatile ammonia for the blended cigarette indicated by the diluted smoke measurements (i.e., about 60%) agrees well with the value for nonvolatile fraction found by tting the multicomponent model to the undiluted smoke measurements. By considering the absolute smoke yields of ammonia and nicotine, Table 2, together with the data in Figures 9 and 10, we nd that the Burley cigarette stands apart even further from the others, depositing 9.5 times more ammonia and 4.5 times more nicotine in the diluted smoke experiments. Examination of the total fractions of ammonia and nicotine deposited in the diluted smoke experiments reveals some correlation of these values with other smoke properties. However, these correlations appear to be driven by the extreme values obtained from the Burley cigarette. Figure 10 shows the fractions of total ammonia and nicotine deposited in the diluted smoke experiments (i.e., the highest cumulative data points in Figures 8 and 9) plotted as a function of the ammonia-per-puff level for the four cigarettes of different tobacco type. The same fractional yields as a function of smoke ph and ratio of nicotine to TPM are given in Figures 11 and 12, respectively. In each case the blended, ue-cured, and Oriental cigarettes cluster together and Figure 10. Fractions of total ammonia and nicotine deposited (in diluted smoke measurements on blended, ue-cured, burley, and Oriental tobacco cigarettes) versus mass of ammonia per puff in smoke.

13 PARTICLE-GAS EQUILIBRIA OF AMMONIA AND NICOTINE 885 Figure 11. Fractions of total ammonia and nicotine deposited (in diluted smoke measurements on blended, ue-cured, burley, and Oriental tobacco cigarettes) versus smoke ph. show a weak relationship with the x axis parameter, while the Burley cigarette stands apart and drives the correlation. Whether or not mainstream smoke chemical properties are potential predictors of nicotine uptake during smoking will not be addressed here. However, some hypotheses regarding ammonia and nicotine mass transport from mainstream smoke in the respiratory tract can be inferred from the present ndings. The measurements in the present study span a denuder length/ owrate range of 0 to 28 s/cm 2. This range corresponds (assuming a typical inhalation ow rate of 200 cm 3 /s) to a penetration depth of generation 13 (bronchi with muscle) in the idealized Weibel airway model (Witschi and Nettesheim 1982). To the extent that human airway ows and surfaces approximate denuder conditions, the present ndings suggest that for undiluted Figure 12. Fractions of total ammonia and nicotine deposited (in diluted smoke measurements on blended, ue-cured, burley, and Oriental tobacco cigarettes) versus ratio of mass of nicotine to mass of TPM in smoke.

14 886 B. J. INGEBRETHSEN ET AL. blended cigarette smoke almost all of the volatile ammonia and approximately 10% of the total nicotine would have deposited in the lung at this stage. The dilution level in the present diluted smoke measurements, about thirtyfold, is on the order of what might be achieved during smoking when a puff of mainstream smoke mixes with inhaled air and nonexchanged air in the lung. At this dilution level several smoke properties appear to vary with total fraction nicotine deposited, Figures 10 12, and could conceivably have implications for nicotine mass transport during inhalation. However, these apparent trends are driven by the extreme burley cigarette properties. Smoke from the burley cigarette has ten times the ammonia level of the commercial blended cigarette and a smoke ph value a full ph unit above the normal range for blended cigarettes. As a consequence, burley smoke has the taste properties of cigar smoke and would be considered noninhalable by American blend cigarette smokers. Excluding the burley cigarette, neither the smoke ammonia concentration, the smoke ph, nor the smoke nicotine to TPM ratio show a relationship to the fraction of ammonia and nicotine deposited. The implications of these results for mass transport of nicotine and ammonia in the lung require further investigation. REFERENCES Armitage, A. K., Dollery, C. T., George, C. F., Houseman, T. H., Lewis, P. J., and Turner, D. M. (1975). Absorption and Metabolism of Nicotine from Cigarettes, Brit. Med. Jour. 4: Eatough, D. J., Benner, C. L., Bayona, J. M., Richards, G., Lamb, J. D., Lee, M. L., Lewis, E. A., and Hansen, L. D. (1989). Chemical Composition of Environmental Tobacco Smoke. 1. Gas-Phase Acids and Bases, Environ. Sci. Technol. 23: Gormley, P. G., and Kennedy, M. (1949). Diffusion From a Stream Flowing Through a Cylindrical Tube, Proc. R. Ir. Acad. 52A: Greenberg, L. A., Lester, D., and Haggard, H. W. (1952). The Absorption of Nicotine in Tobacco Smoking, J. Pharmacol. Exp. Ther. 104: Hager, B., and Niessner, R. (1997). On the Distribution of Nicotine Between the Gas and Particle Phase and Its Measurement, Aerosol Sci. Technol. 26: Harris, J. L., and Hayes, L. E. (1977). A Method for Measuring the ph Value of Whole Smoke, Tob. Sci. 21: Henning eld, J. E., Stapleton, J. M., Benowitz, N. L., Grayson, R. F., and London, E. D. (1993). Higher Levels of Nicotine in Artial than in Venous Blood after Cigarette Smoking, Drug Alcohol Depend. 33: Hinds, W. C. (1982). Aerosol Technology, John Wiley & Sons, New York, pp Ingebrethsen, B. J. (1989). The Physical Properties of Mainstream Cigarette Smoke and their Relationship to Deposition in the Respiratory Tract. In Extrapolation of Dosimetric Relationships for Inhaled Particles and Gases, edited by J. D. Crapo, E. D. Smolko, F. J. Miller, J. A. Graham, and A. W. Haye. Academic Press, San Diego, pp Isaac, P. F., and Rand, M. J. (1972). Cigarette Smoking and Plasma Levels of Nicotine, Nature (London) 236: Landahl, M. D., and Tracewell, T. N. (1957). An Investigation of Cigarette Smoke as an Aerosol with Special Reference to Retention in the Lungs in Human Subjects, Trans. III. State Acad. Sci. 50: Lewis, D. A. (1994). The Evaporation and Diffusion of Nicotine from Mainstream Tobacco Smoke, Ph.D. thesis, University of Essex, Colchester. Lewis, D. A., Colebeck, I., and Mariner, D. C. (1994). Diffusion Denuder Method for Sampling Vapor-Phase Nicotine in Mainstream Tobacco Smoke, Anal. Chem. 66: Lewis, D. A., Colebeck, I., and Mariner, D. C. (1995). Dilution of Mainstream Tobacco Smoke and its Effects Upon the Evaporation and Diffusion of Nicotine, J. Aerosol Sci. 26: Pankow, J. F., Mader, B. T., Isabelle, L. M., Luo, W., Pavlick, A., and Liang, C. (1997). Conversion of Nicotine in Tobacco to its Volatile and Available Free- Base Form through the Action of Gaseous Ammonia, Environ. Sci. Technol. 31: Perry, R. H., and Green, D. W. (1984). Perry s Chemical Engineers Handbook, 6th ed., McGraw Hill, New York, pp Rose, J. E., Behm, F. M., Westman, E. C., and Coleman, R. E. (1999). Arterial Nicotine Kinetics During Cigarette Smoking and Intravenous Nicotine Administration: Implications for Addiction, Drug Alcohol Depend. 56: Russell, M. A. H., and Feyerabend, C. (1978). Cigarette Smoking: A Dependence on High-Nicotine Boli, Drug Metab. Rev. 8: Schievelbein, H. (1982). Nicotine, Resorption and Fate, Pharmac. Ther. 18: Seinfeld, J. H., and Pandis, S. N. (1998). Atmospheric Chemistry and Physics, John Wiley & Sons, New York, pp. 341, 391. Weast, R. C. (1972). Handbook of Chemistry and Physics, 53rd ed., The Chemical Rubber Company, Cleveland, OH, p. D-118. Witschi, H., and Nettesheim, P. (1982). Mechanisms in Respiratory Toxicology, CRC Press, Boca Raton, FL, p. 44.