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VARIATIONS IN TAR, NICOTINE AND CARBON MONOXIDE DELIVERIES OBTAINED BY SMOKERS OF THE SAME BRAND B. Bentrovato, A, Porter, M. Youssef and .~, Imperial Tobacco Ltd., Montreal, Quebec, Canada J !i~?!!' < Differences exist between smokers in terms of the amounts of smoke that they obtain from a particular cigarette. To illustrate this, the puffing parameters for 13 smokers of a popular Canadian brand (15 mg tar, 1.2 mg nicotine and 16 mg carbon monoxide) were recorded. The individual puffparameters were used to duplicate the mouth deliveries of smoke obtained b7 each smoker. Individual tar deliveries ranged from 8.7 to 26.4 mg/cig with the other measured smoke components showing a similar spread in values. Resting level alveolar carbon monoxide concentrations were also measured as a marker for the efficiency of smoke uptake. The weak correlation between mouth and alveolar carbon monoxide concentrations suggested that absorption of smoke by a smoker is only partly determined by mouth levels obtained from the cigarette. It has always been understood ttmt few if any smokers exactly mJ~c the standard machine smoking pattern used m compare smoke deliveries from different cigarette. The puffing regime used for machine smoking cigarettes is an approximation to an =average" smoker and is used only to compare products so that their smoke deliveries can be zaJzkod. Although puffing behaviour can be monitored relatively eas~y provided one accepts the limitation of using a special cigaretle holder and making measurements in a controlled expcrimenta| setting, very few studies have been able to determine unambiguously the levels of smoke taken from cigarettes by smokers. There have been several methods proposed for deterraining mouth deliveries of smoke to the smoker. Thas~ include: 1) Extrapolating back from body levels of various smoke components or their metabolites 2) Collection of elgaretta butts and calculating mouth deliveries from filtered smoke component levels 5364 1SS7

3) Recording puff profilts usually by a pressure transducer/critic~d flow orifice assembly and either - Adjusting a smoking machine to smoke cigarettes with the average puff p~ameters Calculating the mouth deliveries Duplicating the puff profile on a specially designed smoking machine Of these different techniques the most accurate for determining mouth deliveries is the latter i,e. the use of a smoke duplicator. However due to the complexity of designing and building a smoking machine that can accurately duplicate human puff proFdes very few such machines have been reported in the literature (6,7) and consequently vep] few studies have been carried out, Our laboratory completnd the constraction of a 4-port puff duplicator some years ago (7) and tiffs is used in conjunction with a recording system that can monitor the poffmg behaviour of up to I0 smokers simultaneously. We have used the puff recorder and smoke duplicator to measure the amount of smoke taken from a popular Canadian brand by 13 smokers who smoke this brand regularly. By measuring the variation both within and between subjects we hoped to estimate the range of smoking topographies that exist for a group of smokers smoking their own brand and the resulting range of smoke deliveries that they obtain. We atso measured resting alveolar carbon monoxide levels to determine if absorption of this smoke component could be related to mouth deliveries of smoke. Subjects were 5 men and 8 women. They were all ITL employees and were regular smokers of the same king size filter cigarette brand with a declared package delivery of 15 nag tar. All the smokers had been smoking the same brand for at least 3 years. Reeordino Puffing Profile Each subject was recorded smoking their own brand once per day for 4 comecutive days. The recording device cortsisted of a cigarette holder containing a critical flow orifice, with either side of the orifice connected by 4 ram i.d. tygon tubing to a pressure transducer (Setra Systems Model 239E). Output from the pressure transducer was sampled at 25 times per second and saved onto the hard disc ofa Dolch portable computer. The system could record up to I0 smokers simultaneously. Puff voh~es, durations, intervals and numbers were recorded for each smoker. Butt lengths were also measured for each of the cigarettes smoked during the recording session. -- " " The recorded profiles for each smoker were averaged and then duplicated on a specially designed 4-pore smoldng machine, This smoke duplicator has been described earlier (7). Each port on the smoking machine is connected to a servo- comrolled stepping motor/piston assembly, The recorded profile drives the stepping motor/piston assembly and recreates the puff profile of the smoker. Normally each of the 4- ports is driven by the same recorded puff profile although the ports can be driven by separate F 58G471588

profiles if desired. During operation the duplicator simultaneously displays the recorded and machine generated profiles of each puff. As in a conventional smoking machine the smoke condensate was collected on a Cambridge filter pad and the vapour phase collected in a metathene bag. Following smoking, the Cambridge filters were weighed and extracted in isopropanol. The extracts were simultaneously analyzed for nicotine and water using a Hewlett-Packard 5840 gas chromatograph equipped with split columns (6' X 1/g" stainless steel with 16% apiezon L, 2% KOH, 2% Carbowax 2M on Chromosorb for nicotine and 6' x 1t8" with Poropak Q for nicotine) coupled to bid and TCD detectors respectively. The vapour phase was analyzed for carbon monoxide using an Anared AR400 infra-red gas analyzer. AlVealarCarbonMonoxideConcentratiora. Resting level alveolar carbon monoxide concentrations for each subject were ftrst measured just prior to smoking the fifth cigarette of the day and then just prior to the smoking of each subsequent cigarette until 15:30. Subjects were required to rebreatha into a plastic bag through a rubber tube which was then clamped shut. Bags were collected on a regular basis and carbon monoxide eoncentratinm determined using an Eeolyser CO Analyzer. Alveolar carbon monoxide was monitored during the 4 ~lays of the testing period. IhSS32.L3 puffin~ Behaviour The results for the puffing behaviour are summarized in Table 1. This table gives the average puff volumes, flow rates, puff durations, puff intervals and puff numbers for each of the 13 subjects. The smokers in this group had average puff volumes which ranged from a low of 18.5 ml to a high of 64.3 ml. Average flow rates were from 16.2 to 28.8 ml/s and duratinas from 0.88 to 2.98 s. For tbe group as a wbole the mean puff voinme was 46.9 ml, the mean flow rate 24.4 ml, the mean duration 1.98 s, the mean interval 40.7 s and the mean puff number 10.8. When machine smoked under standard conditions the puff number was 8.I. The profiles for each smoker were averaged on a puff by puff basis and used to drive the smoke duplicator. The smoke deliveries and resulting butt lengths are shown in Table 2 and these data are the averages of 4 ports. The average deliveries under human smoking conditions are 18.0 nag of tar (water and nicotine free), 5.5 mg of water, 1.50 nag nicotine and 18.3 mg of carbon monoxide. The machine smoked deliveries for the same cigarettes are 15.4 nag tar, 3.2 rag water, 1.43 mg nicotine and 16.0 nag carbon monoxide. The average bun: length left after human smoking was 32.8 ram compared with a bu~ length of 28 mm afar machine smoking. - 536471589

AlYenlar Carbon Monoxide The average expired air carbon monoxide concenuratlons measured at the "troughs" before the 5th through 9th cigarettes are given in Table 3. This table also shows the minimum and maximum leveis recorded and the standard deviations. A wide variety of puffprofiles were recorded for the different smokers. To illustrate some of the different profiles obtained, Figure 1 shows the 3ed puff for 3 different smokers on winch is superimposed the profile obtained from a standard smoking macinne set to deliver a 35 ml puff. Puff volumes, flow rates and puff numbers for the group of smokers as a whole are higher than the standard machine smoking conditions, while the puff interval is shorter. However the average duration of 1.98 seconds is very close to the standard duration of 2 seconds. It should be noted that these results may not represent exactly bow people smoke under natural conditions since it has been found by other investigators that smokers knowing they are in an experiment to observe or measure smoking hohavinur increase their puff numbers and reduce their puff intervals (4,5). For example Comer and Creiginoa (5) found that smokers consistently increased their puff numbers when monitored during an experiment compared with when they were monitored surreptitiously in a social setting. The magnitude of the increase in puff number in the experiment reported was of the order of 20%. Comer and Creighten however could not monitor the puff volumes surreptitiously and so could not determine if the experimental coeditiom influenced this parameter. By averaging the puff volumes for all the smokers on a puff by puff basis (Figure 2) the trend of decreasing volume with increasing puff number can be seen clearly, which is consistent with results from other studies (1-3). The large standard deviations anted for the data points illustrate the wide ranges in poffmg behaviour between subjects. In contrast, individual smokers generally showed quite consistent smoking patterns across the 4 smoking sessions in which they were recorded. For example the smoking partero~ for 3 individuals with widely different average puff volumes are shawa in Figure 3. The small standard deviations for the individual smokers show the consistency with whinh they smoke. Duplicated smoke deliveries also showed a wide range of vahies. However, the average values obtained for tar, nicotine and carbon monoxide were relatively close to the machine derived deliveries with respectively 17%, 5% and 14% higher values. The average hotl length (32.8 man) left by the smokers is considerably longer than the standard butt length of 28 roan. This is consistent with the results of an earlier study of the lengths of bum discarded by smokers in a shopping mall environment (unpublished). From several htmdred butts collected the average length was more than 4 mm longer than the ISO standard. We have found that the total volume of smoke taken by the smoker from the clgarette (i e the product of the average puff volume and the average puff number) correlates well with the mouth de lvery of tar (F~gure 4) w th a correla on cceffic ent of r - 0.96. The machine derNed total volume is 283.5 mJ which according to the regression corresponds to 10.3 mg tar. This is considerably less thaaa the measured delivery under "standard" coeditinm of 15.4 536471590

nag which suggests that h~ tend to get considerably less tar for a given puff volume than dOes a machine. The smoke duplicator measures the amount of smoke that a human smoker takes into the mouth. The amount of smoke taken up or absorbed by the smoker will depend not only on the mouth level but also on the amount of mouth spill which is the smoke lost from the mouth before inhalation, and the depth and duration of inhalation. The alveolar carbon monoxide concentrations shown in Table 3 can be used as indicators of the amount of carbon monoxide absorbed (9). If all the subjects inhaled to the same extent then there would be a good correlation between mouth deliveries of carbon monoxide and alveolar carbon monoxide concentrations. However the aca~al correlation (Figure 5) is quite poor (r2 -- 0.44) arid it must be concluded that mouth deliveries of carbon monoxide cannot be used to predict actual uptake of this smoke component. Not surprisingly the correlation between alveolar carbon monoxide and mouth tar deliveries is equally poor (Figure 6). The CORESTA, 1SO and F'rC smoking methods all specify a 35ml puff of 2 seconds duration taken once per minute until a specific butt length is reached. As noted by CORESTA (8) "Mainstrcara smoke yields detennlned by the staodard smoking methods are appropriate for the ranking of cigarettes with respect to their yield. The machine results are not necessarily predictive of yields created by individual consumers." In the present study it was found that the smokers were fairly consistent in their smoking behaviour over the time period of the experimem and that, in spite of wide differences between smokers, the average smoke deliveries were not very different from the standard machir~ derived deliveries. The amount of smoke absorbed by the smoker does not appear to be directly related to the amounts of smoke obtained from the cigarette. Guyatt, A.R., Kh-kham, A.J.T., Baldry, A.G., Dixon, M. & Cumming ,G. How does puffing behaviour alter during the smoking of a single cigaret~. Pharmacol.Biocheta. Behav. 33 (i), 189-196 (1989). Nemeth-Coslett, R. & Griffnhs, R.R. Effects of cigarette rod length oa puff volutne a~d c-re'boa monoxide delivery in cigarette smokers. Drag AJcohnl Depend. ]5 (1-2), 1-14 (1985). Kolonen, S.J., Tuomisto, P., Puustinen, P. & Aisaksinen, M.M. Puffing behavinur during the smoking of a single cigarette in a naturalistic environment. Pharmacol. Biochera. Behav. 41(4), 701-706 (1992). Schulz, W. & Seebofer, F. Smoking behaviour in Germany - the analysis of cigarette butts (KIPA). In Smoking Behaviour - Physiological and Psychological Influences. Ed. R.E.Thornton, Ch, ur¢inll Livingstone, pp. 259-276 (1978) 586471591

6. 7. g. 9. Comer, A.K. & Creighton, D.E. The effect of experimental conditions on smoking behaviour. In Smoking Behavinur - Physiological and psychological Influences. Ed. R.E.Thornton, Churchill Livingstone, pp. 76-86 (1978). Creighton, D.E., Noble, M.J. & Whewell, R.T. Instruments to measure, record and duplicate human smoking patterns. In Smoking Behaviour - Physiological and Psychological Influences. Ed. R.E.Thomton, Churchill Livingstone, pp. 277-288 (1978). McBride, C. Smoke Duplicator. Abstract No. 35, 39th Tobacco Chemists Research Conference, Montreal, Quebec, Canada. Oct. (1985). CORESTA bulletin, 1994-2, 54-57 Sinclair, N.M. The quamitation of smoke uptake. In Smoking mad the Lung, eds. G.Cumming & G.Bonsignore, pp.95-106, Plenum, New York, 1984. 536471592

Summarised Puffing Behaviour Subject Av. Puff Mean Puff Interval Puff Volume (m[) 1 54.5 2 64.3 3 1&5 4 64.8 5 51.3 6 36.6 7 28.3 8 49.1 9 22.5 10 60.8 11 49.8 12 55.9 13 53.2 Average 46.9 Standard 35.0 Flow Rate Duration (ml/sec) (sec) 27.5 2.02 27.1 2.40 16.2 1.14 26.9 2.48 26,8 2.05 27.3 1.39 22.0 1.29 16.9 2.91 25.6 0.88 29.7 2.98 27.4 1.88 24,3 2.44 28.8 1.87 24.4 1.98 17.5 2.00 Number ($ec) 23.6 13 60.3 7 28.1 15 38.7 9 26.0 13 64.3 8 35.0 12 71.4 6 20.2 18 46.6 8 34.2 11 54,3 9 28.4 11 40.7 10.8 58.0 8.1 TABLE 1: Averaged Puffing Data for Each of the 13 Subjects 536471593

Duplicated Mouth Smoke Deliveries- Subject Tar Water Nicotine CO Butt (mg/cig) (mg/cig) (mg/cig) (mg/cig) Length ~_~- 1 26.4 10.5 2.44 ~-r~i ~.1 ~0.'30~" 2 17.3 6.0 1.31 18.6 33 3 8.7 0.85 0.80 8.3 36.5 4 23.3 9.9 1.88 23.4 32.6 5 25.9 10.7 2.46 25.3 28 6 11.4 1.5 0.92 12.4 32 7 12.1 1.1 1.01 12.1 35.5 8 11.6 1.7 0.86 12.0 37 9 13.0 1.6 1.18 13.5 37.5 10 20.4 7.0 1.53 19.4 33.1 11 21.3 5.0 1.56 21.5 31 12 20.7 8.6 1.91 21,7 25.4 13 22.1 7.5 1.76 23.7 34.4 Average 18.0 5.5 1.50 18.3 32.8 Standard 15.4 3.2 1.4 3 16.0 28,0 TABLE 2: Duplicated Mouth Smoke Deliveries for Each of the 13 Subjects 5364~1594

Alveolar CO (ppm) Subject Av. Min Max Std. Dev 1 35.0 30.5 38.5 3.8 2 27.2 21.5 32.0 2.8 3 6.0 5.0 7.5 0.9 4 44.1 37,5 52.0 4.6 5 23.1 19.5 27.0 2,2 6 14.7 12.5 16.0 1.1 7 32.9 28.0 38,0 3.3 8 21.9 19,0 27.0 2.2 9 20.3 17.0 22.0 2.1 10 21.9 17.0 26.0 3,5 11 32.6 28.5 35.0 2.3 12 28.2 19.0 37,0 6.7 13 42.4 36.5 48.5 4.7 TABLE 3: Maximum,Minimum and Average Trough Levels of the Alveolar Carbon Monoxide 536471595

Puff Profile Puff #3 50 45 / \ 40 / \\ 35" ' * ~ /. " ~ "'" Standard ._.30' /: ;\\ / It , *. ~ " - Subject5 -6251 , .'~-~.\\ "-'Subject6 It. "/ ~, . 204 i! ~/ ~ ~,. ~ Subject 8 0 = i 0 0.4 0.8 1.2 1.6 2 2.4 2.8 3.2 Time (sec) FIGURE 1: The Puff Profiles of 3 Subjects (3rd Puff) with a Standard Machine Profile 536471596