Tobacco Documents Online

Topical Report NCI/S&HP/ORNL #62 SITE VISIT II TO BORRISTON RESEARCH LABORATORIES Temple Hills, Maryland, November 7-9, 1977 2-3-78 R. A. Jenkins, B. E. Gill, R. B. Quincy, and D. D. Pair Tobacco Smoke Research Program Bio/Organic Analysis Section Analytical Chemistry Division Oak Ridge National Laboratory Oak Ridge, Tennessee 37830 Interagency Agreement (ERDA-NIH/NCI) No. 40-485-74, Part II Internal (ORNL) Charge No. 3390-0224 Intended for informal communication with project management only. Confidential until published.or released by author.

SITE VISIT II TO BRL R. A. Jenkins, B. E. Gill,--R. B. Quincy, and D. D. Pair Summary. A second working site visit has been made to Borriston Research Laboratories. Changing to the ADL/II-cuffed cannula exposure system has resulted in a dramatic improvement in the mechanical reliability of the exposures at BRL. The smoke particulate doses offered the animals are near those determined on the previous visit. Carbon monoxide content of the Code 13 and 04 smoke at the cannula suggests that the animals are being of- fered the targeted level of gas phase constituents. Detailed characterization of the Code 11 smoke indicates that it has very little interaction with the exposure system during normal residence time. In general, animals in the BRL bioassay are being offered a consistent smoke dose,which is near the proper magnitude and chemically similar to that anticipated for the cigarette vari- ants. Introduction. A second site visit was made to Borriston Research Laboratories on November 7-9, 1977, to observe and document the chronic exposure of male beagles to the smoke of several types of cigarettes. Our primary purpose was to collect data to enable us to better estimate the smoke dose which the animals receive and to determine the extent to which certain smoking factors contribute to the variability in that dose. This was our first visit to BRL since the Code 11, 13, and 32 (SEB-IV) exposure groups had been switched to the ADL/II-cuffed cannula exposure system from the BNW-uncuffed cannula sys- tem. Many of the exposure details and experimental methods have been discussed previously, and can be found in the report covering Site Visit I (Topical Report NCI/S&HP/ORNL #48). Experimental. We have been placing greater emphasis in our monitoring effort on a more detailed chemical characterization of the whole smoke offered the animal. On this visit, several samples of the smoke generated by the Code 11 variant (including both AaL/II'input and cannula exit samples) were returned and subjected to a multi-component, mull<i-aliguot analysis. This permits a much more detailed chemical description of the smoke, as several of the com- ponents correlate highly with the presence of entire classes of smoke consti- tuents.

In addition, this was our first opportunity to sample, at Borriston the cannula exit for carbon monoxide (CO) and carbon dioxide (C02). CO is important because of its physiological impact, and the ratio of CO to COG content in the gas phase gives an indication of pyrolysis conditions in the burning cone of the cigarette. Briefly, the procedure and apparatus for taking a gas phase sample from the cannula exit are similar to that for ob- taining a particulate phase sample, except that the effluent from the respir- ator (ventilator) is expelled into a large, evacuated Saran gas sampling bag. Following completion of smoking, the contents of the bag are mixed, and a portion is drawn into a small glass gas sampling bulb. The bulb is returned to ORNL for analysis, which is performed by gas chromatography using Amberlyst ion-exchange resin in the Ni-form as the "stationary phase". Results and Discussion. The mechanical operation and reliability of the ADL/II machines now in use at BRL represent a dramatic improvement over the exposure systems previously used. Very little mechanical binding or total machine failure was observed. Table I lists the puffing parameters for se- lected ADL/II exposure systems in service at the time of the visit. (Note that values given on this and all other tables are means ± standard deviation.) The puff volumes average about 10-15% lower than the specified 35.0 rErl, and a few machines were observed to have exceeding low puff volumes. Puff volumes should be carefully measured prior to placing the machine back in service after cleaning. In addition, puff volumes should be spot checked between cleaning intervals. Table II compares static burn rates of Code 04 (SEB IV) cigarettes mea- sured in several wards at BRL with those determined under analytical conditions at ORNL with cigarettes from the same batch. There is some variation of the values among the wards, but on the average, cigarettes are consumed more slowly at Borriston than under analytical conditions. Since the time of the previous visit, the ventilation air flow in the exposure wards has been increased, re- sulting in a greater degree of comfort for the exposure technicians. All sidestream smoke is now exhausted into the hoods. However, relative humidity levels were somewhat higher.than those of analytical conditions (70-'5°0' vs 60®;). This may account for the lower static burn rate. Individual values for total particulate matter (TPM) and nicotine deliver- ies of cigarettes smoked on selected ADL/II exposure systems at BRL are tabu- lated on Table III. With the exception of cigarettes smoked on machines with

abnormally low puff volumes (e.g., ADL/II #87 smoking Code 67 cigarettes), the smoke deliveries for a given code are fairly consistent from machine to machine. In addition, average cigarette deliveries for a given code are quite similar to those obtained on Site Visit I. The exception to this is the Code 13 variant. On the previous visit, the Code 13 cigarettes delivered unexpectedly high levels of nicotine. On this visit, Code 13 nicotine deliv- eries were at the targeted level. That smoke deliveries of cigarettes were essentially the same on both visits for Codes 11, SEB IV, and 67 is particu- larly important, since the exposure systems were changed after Site Visit I for Codes 11 and SEB IV. Table IV compares the average per cigarette deliveries of TPM and nico- tine determined on-site with those of cigarettes from the same batch returned to ORNL and smoked under analytical conditions. In all cases, cigarettes smoked by the ADL/II systems yielded somewhat less TPM and nicotine, but for Codes 11, 13, and 04, differences in the nicotine deliveries are not statis- tically significant. At BRL, the Code 67 variant produced significantly less nicotine than under analytical conditions. The same phenomenon was noted on Site Visit I, and cannot be entirely attributed to the somewhat-lower-than- specified puff volume of exposure systems smoking the Code 67 variant. Table IV tabulates the TPM and nicotine content of the smoke reaching the cannula exit for individual exposure devices. For any given code, the TPM and nicotine levels in this output smoke is relatively consistent, sug- gesting that particulate dosages offered the animals will not change radically as they are shifted to various exposure systems. Table VI compares average levels of TPM and nicotine of the smoke generated by the exposure devices with those of smoke actually reaching the cannula exit. Clearly, the ADL/II-cuffed cannula system is about 65-90'Z' efficient in its delivery of the smoke partic- ulate phase to the cannula. This is a very good efficiency, and is typical of that observed at another inhalation bioassay laboratory using the same exposure system. Table VII compares the PMO content of the Code 67 smoke generated analyt- ically with that generated by the ADL/IT and that arriving at the cannula exit. The efficiency of delivery (output/input) of PMO is apparently significantly lower than that for nicotine (68% vs 88%), but this may be an artifact of the cannula exit sampling procedure. The highly volatile PMO may be partially

evaporated from the filter pad as large amounts of air are drawn through the exposure system stand tube. That the PMO content of smoke generated analyt- ically is substantially greater than that generated under exposure conditions was also observed on the previous visit. Sonie of the PMO probably evaporates from the cigarette between the time that it is opened for conditioning and when its smoked under exposure conditions. For analytical smoking, fresh, unopened packages of Code 67 cigarettes are used, and smoked after only two hours of conditioning at the proper humidity. Of course, the most important chemical parameter relating to the chronic exposure is the smoke dose which the animals receive. At present, our best estimate of this dose is the amount of smoke offered the animals at the exit of the cannula. For the ADL/II, cuffed-cannula system, we believe that the dose offered approximates well the amount of smoke inhaled. Actual retention of the inhaled smoke is probably a much more individual matter, depending on such factors as individual volume and rate of respiration. Table VIII lists our estimates of the amount of smoke offered each variant group on a weekly basis. The Code 67 exposure group is being offered the same amount of nico- tine as the SEB IV (Code 04) group, but about 13% more TPM. The Code 11 and 13 groups are offered about 14% less TPM than the SEB IV group. Three distinct nicotine dose groups are being maintained, with a dose ratio of approximately 2:7:21. In general, offered dose levels for each group were comparable to those observed on the previous visit. However, the retained dose was proba- bly substantially greater than that observed previously for the Code 11, 13, and SEB IV groups, because the use of the ADLOII-cuffed cannula exposure system should insure that a greater fraction of the available smoke is inhaled than did the BNW-uncuffed cannula system. For the purpose of more exactly defining the chemical composition of the smoke offered the animals, we have been conducting detailed chemical charac- terizations of some of the smoke particulate phase samples acquired on site. In addition, comparison of smoke samples before and after passage through the exposure system help determine- the extent to which, if any, certain constituents or classes of constituents selectively Interact with the system. Table IX compares relative constituent'concentrations in TPM samples taken at the machine input and cannula exit for the Code 11 variant. With the exception of phenol, the relative concentrations are the same in both input and output

samples, suggesting that very little selective depletion occurs as the smoke passes through the system. The slight depletion of phenol has been observed for other cigarette codes and at other bioassay sites, and is thought to be chiefly an artifact of the high air flow required to sample the cannula exit. Table X compares the average deliveries to the cannula exit of systems smoking the Code 13 and 04 variants with deliveries of cigarettes from the same batch smoked under analytical conditions at ORNL. Analytical results are included for the Code 11 and 67 variants for the sake of completeness. For the Code 13 variant, about as much CO and C02 reach the cannula as would have been predicted from analytical smoking (assuming no gas phase losses to the exposure system). For the Code 04 variant, carbon monoxide levels are as expected, but C02 in the cannula exit smoke is somewhat lower than what would have been expected. However, the C0:C02 ratios for a given Code are statistically the same as those determined analytically. That this is the case indicates that there are no gross differences between the overall cigarette combustion process in the bioassay and that in the analytical smoking situation. The fact that CO and COL levels in the bioassay smoke are near those of analytically generated smoke suggest that the animals are being offered the targeted levels of gas phase constituents. Combined with the good efficiency of delivery of particulate phase constituents, the results from this site visit indicate that animals in the BRL bioassay.are being offered a smoke dose which is consistent, chemically similar to that expected from the cigarette variants, and near the proper magnitude. f .

Table I Measured Puffing Parameters for Selected ADL-II Exposure Devices in Service at BRL on November 7-9, 1977 Ward No. Cigarette Code Machine No. Puff Duration (sec) Puff Volume (r~l ) 6 11 77 2.0 33.0 85 2.0 33.0 27 2.0 32.0 14 2.0 33.0 23 2.1 32.0 13 11 33 2.0 23.0 17 2.0 31.0 11 1.9 32.0 5 2.0 32.5 69 2.0 32.0 20 2.0 32.0 16 11 37 2.0 33.0 48 2.0 33.0 61 1.9 33.0 82 2.0 22.0 84 2.0 34.5 56 2.0 34.0 - 2.0 34.0 Average Puff Volume for Selected Code 11 Machi nes : 31.6 ± 3.4 ml 7 13 41 2.0 33.0 81 2.1 29.5 68 2.0 33.0 63 2.0 33.5 39 2.0 33.5 4 13 34 2.1 32.0 53 2.0 30.0 8 2.0 34.0 42 2.0 33.0 38 2.0 32.5 Average Puff Volume for Selected Code 13 Machines: 32.4 ± 1.5 m 1 7 4

Table I - (Cont'd) Ward No. Cigarette Code hlachine No. Puff Duration (sec) Puff Volume (mlL 8 04 54 2.0 32.0 (SEB IV) 73 2.1 28.0 3 2.0 30.0 26 2.0 32.0 71 2.0 34.0 2 2.1 28.0 46 2.0 28.0 52 2.0 32.5 64 2.0 28.0 66 2.0 33.0 Average Puff Volume for Selected Code 04 Machines: 30.6 ± 2.4 ml 10 67 22 2.0 34.0 87 2.0 20.0 16 2.1 33.5 31 2.0 33.5 45 2.0 33.0 67 2.0 31.0 83 2.0 31.5 44 1.9 33.0 49 2.1 33.0 75 2.0 32.0 15 67 58 2.1 32.0 43 Inoperative - 1 2.0 20.0 36 1.9 34.5 57 2.1 29.0 18 2.0 34.0 76 2.0 35.0 70 2.1 31.0 9 2.0 33.0 29 2.0 30.0 Average Puff Volume for Selected Code 67 Machines: 31.2 ± 4.2 ml ,•

Table II Comparison of Code-04 Static Burn Rates: Exposure Conditions at BRL vs Analytical Smoking Conditions at ORNL Site Burn Ratea mm/min Burn Rateb m,c/min BRL, Ward 4 4.60 _~ ± 0.11 64.9 ± 3.2 Ward 6 3.99 ± 0.16 57.3 ± 0.4 Ward 7 4.06 ± 0.08 58.3 ± 0.7 Ward 8 4.53 ± 0.09 62.3 ± 1.1 Ward 10 4.12 ± 0.14 58.8 ± 2.0 Ward 15 4.06 ± 0.08 59.7 ± 0.9 Ward 16 4.20 ± 0.30 60.8 ± 4.5 ORNL 4.80 ± 0.14 67.3 ± 1.2 aBurn rate given in terms of actual length of cigarette burned. bBurn rate given in terms of actual weight of cigarette burned.

Table III Total Particulate Matter (TPh9)Yand Nicotine Delivery of Cigarettes Smoked on Selected ADL-II Exposure Systems in Service at BRL on November 7-9, 1977 Cigarette Code Ward No. Machine No. TPM mc/ci~ Nicotine mg/cig Nicotine:TPM Ratio 11 6 77 47.1 0.94 .0200 6 77 54.6 1.09 .0200 6 85 42.5 0.87 .0205 6 85 48.5 0.87 .0179 6 27 46.4 0.95 .0205 6 27 45.3 1.25 .0276 6 14 34.3 0.66 .0192 6 14 36.8 0.82 .0223 13 33 40.1 0.79 .0197 13 17 50.2 0.97 .0193 13 11 44.4 0.88 .0198 16 37 50.8 0.84 .0165 16 48 48.4 0.95 .0196 16 56 47.6 0.97 .0204 16 - 48.7 0.95 .0195 Average 45.7 ± 5.4 0.92 ± 0.13 .0202 ± .0024 13 7 41 45.8 0.24 .0052 7 81 42.8 0.20 .0047 7 68 49.1 0.20 .0041 7 63 44.0 0.18 .0041 7 39 43.2 0.18 .0042 4 34 39.7 0.19 .0048 4 53 43.4 0.21 .0048 4 8 52.6 0.24 .0046 4 42 40.2 0.20 .0050 4 38 44.7 0.22 .0049 Average 44.6 ± 3.9 0.21 ± 0.02 .0046 ± .0004 04 8 54 48.1 2.60 .0541 (SEB IV) 8 73 53.8 2.55 .0474 8 3 60.2 2.60 .0432 8 26 54.1 2.55 .0471 8 2 44.0 2.52 .0573 8 46 50.0 2.52 .0504 8 52 54.0 2.94 .0544 8 64 ' 52.7 2.64 .0501 8 66 48.5 2.76 .0569 Average 51.7 ± 4.7 2.63 ± 0.14 .0512 ± .0048