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Topical Report NCI/S&HP/ORNL #54 SITE VISIT VII TO VETERAN`S ADMINISTRATION HOSPITAL East Orange, New Jersey, August 8-9, 1977 10-28-77 R. A. Jenkins, B. E. Gill, 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) Contract Charge No. 3390-0224 Intended for informal communication'with project management only. Confidential untiispublished or released by author.

SITE VISIT VII TO VAH R. A. Jenkins, B. E. Gill, and D. D. Pair Summar . Data gathered on our seventh site visit to the Veteran's Adminis- tration Hospital, East Orange, NJ, indicate that the two animal groups are being offered two distinctly different doses of nicotine but identical doses of "tar". The magnitude of this latter dose is similar to that of another NCI-sponsored beagle inhalation bioassay at Hazleton Laboratories. Measurements of carbon monoxide and carbon dioxide content of the smoke reaching the cannula indicate the smoke which the animals inhale has a gas phase:particulate phase ratio which is about twice that of the smoke which the cigarettes actually_9.enerate. Detailed chemical characterization of the particulate phase of the Code LN smoke indicates that neophytadiene is se- lectively depleted from the smoke as it passes through the exposure system. Introduction. A seventh site visit was made to the Veteran's Administration Hospital on August 8-9, 1977, to observe and document the beagle inhalation bioassay which is being conducted there. As has been the case on previous visits, our primary purpose was to collect data to enable us to better esti- mate the dose which the animals receive and to determine the extent to which certain smoking factors can contribute to the variability of that dose. Both exposure' and experimental details have been previously discussed, and can be found in reports covering previous site visits (Topical Reports NCI/ S&F{P/QRNL #6, 17, 18, 31, 32, 38, and 44). Results and Conclusions. Table I lists the measured puffing parameters for the ADL-I machines in service at the time of our visit. Puffing performance was fairly consistent in all wards. Puff volumes were close to the specified values. When judged in terms of the puff parameter measurements, the oper- ation and reliability of the machines continue to be adequate. The deliveries of total particulate matter (TPM) and nicotine of ciga- rettes smoked on the ADL-I machines at VAH are tabulated individually on Table II. In contrast to the findings ®n the previous visit, the amount of smoke generated by the exposure devices varies only slightly. Table III compares the amount of smoke generated on-site with that generated under analytical conditions (at three puffs per minute) at ORNL. The data indicate that the exposure devices generate nearly the same amount of smoke from the cigarettes as is generated under analytical conditions. The relative ratio

of the nicotine content of the exposure smokes is within a few percent of that observed analytically (2.9 vs 3.0). Table IV tabulates individually the TPM and nicotine outputs for se- lected machines as sampled at the cannula exits. There is a significant degree of variation in the values, suggesting that the amount of smoke available for inhalation will vary from machine to machine. Table V com- pares the average cannula exit values with average input values (from Table III). The results on Table V indicate that about half of the partic- ulates generated by the exposure systems actually reach the cannula and are thus available for inhalation. On-site observations indicate that a significant quantity of smoke particulates deposit in the Teflon smoke delivery tube. It is this particulate deposition which is responsible for a substantially higher than normal gas phase to particulates ratio of the smokes being offered the animal (see below). At the cannula exit, the relative ratio of the nicotine contents of the smoke of the two variants drops to about 2.4 (from 2.9 at the machine input). This phenomenon has been observed on previous monitoring visits, and appears to be a result of the ADL-I's lower efficiency of delivery of the smoke of the HN variant. Ultimately, the most important chemical parameter of the inhalation exposure is the dose which the animals receive. Our best estimate of this is the amount of smoke which the animals are offered, as measured at the cannula exit. Table VI lists our estimates of the smoke dose per animal on a weekly basis for the two variants. The doses are essentially the same as those measured on the last few visits. This suggests that the overall exposure has been relatively consistent for the past year. In this experiment, the two animal groups are being offered identical amounts of smoke particulates but two distinctly different levels of nicotine. This is the targeted dose. In an effort to more exactly define the chemical composition of the smoke which the animals are offered, we have been conducting more detailed chemical characterization studies of the particulate samples acquired on- site. Table VII compares the values of'selected constitutents in the par- ticulate phase of the Code LN'smoke, both that which is collected at the input to the ADL-I and that collected at the cannula exit. The free fatty acids and catechol pass through the machine undepleted, relative to the particulate phase as a whole. The phenol and cresols are slightly less concentrated in the smoke at the cannula exit. Most likely, this is an

artifact of the cannula exit sampling procedure, which may tend to re- volatilize some lower boiling constituents off the filter pad. Neophyta- diene, an indicator of the terpene class, appears to be the only measured component which is selectively depleted as it passes through the exposure system. Because of its relatively high molecular weight, it may more readily deposit on the tubing walls. Table VIII compares average cannula exit values for TPM, nicotine, carbon monoxide, and carbon dioxide with those obtained from analytical smoking of both variants. First, it should be noted that the CO:COz ratios obtained for both sample types are very close. This is further indication that, under exposure conditions, smoke is being generated in the specified manner (See Table III). Secondly, the amount of CO/CO2 reaching the cannula exit is essentially the same as that predicted from analytical smoking for the Code LN cigarette. For the HN cigarette, the slightly lower CO/CO2 delivery can be explained by the somewhat smaller amount of smoke generated by the ADL-I. (See Table III) The data indicate that essentially no CO or C02 are lost in the exposure system. This is in contrast to the °U50a loss of particulate phase constituents in the exposure system. Thus the smoke which animals are offered for inhalation is much different in gross chemical composition from that which the cigarettes actually generate. The gas phase: particulate phase ratio of the inhaled smoke is about twice that of normal smoke.

TABLE I Measured Puffing Parameters for ADL-I Smoking Machines in Service at VAH on August 8-9, 1977 ; Ward No. Cigarette Code Machine No. Puff Duration (sec) Puff Volume (ml) 1 HN 21 2.0 35.5 34 2.1 36.0 28 1.9 33.0 3 2.0 33.0 1 2.0 34.0 2 HN 25 1.9 33.0 20 1.4 32.0 - 2.3 31.5 10 1.8 33.0 24 1.9 33.1 3 HN 35 1.8 33.5 39 * * 37 1.9 34.5 9 2.1 35.0 38 1.7 32.0 Average for all HN Machines 1.9 ± 0.2 33.5 ± 1.3 4 LN 4 1.6 36.0 1 1.9 35.0 17 2.0 32.0 32 1.8 35.5 16 1.9 34.0 5 LN 6 2.0 36.0 40 2.1 35.5 23 1.9 35.5 19 1.9 35.0 5 2.1 31.5 6 LN 7 1.9 34.0 30 2.0 35.0 22 * * 15 1.6 34.0 2 1.7 36.0 Average for all LN Machines 1.9 ± 0.2 34.6 ± 1.4 *Mar.hine inoperative .

TABLE II Total Particulate Matter (TPM) and Nicotine Delivery of Cigarettes Smoked on Selected ADL-I Smoking Machines in Service at VAH on August 8-9, 1977 Ward No. Cigarette Code Machine No. TPM, mg/cig Nicotine, mg/cig, Nicotine:TPM Ratio 1 HN 6 87.0 6.11 .0702 31 63.5 4.54 .0715 7 63.7 4.40 .0691 14 67.3 4.92 .0731 8 69.6 4.45 .0639 Average 70.2 ± 9.7 4.88 ± 0.72 .0696 ± .0035 2 HN 25 59.4 4.54 .0764 20 61.7 5.06 .0820 10 58.6 4.32 .0737 X 64.5 5.29 .0820 24 45.0 3.35 .0744 Average 57.8 ± 7.5 4.51 ± 0.76 .0777 ± .0040 3 HN 35 57.1 4.99 .0874 39 55.8 4.17 .0747 37 56.3 4.08 .0725 9 61.7 4.32 .0700 38 56.6 3.82 .0675 Average 57.5 ± 2.4 4.28 ± 0.44 .0744 - .0077 4 LN 17 56.3 1.29 .0229 4 58.5 1.74 .0297 4 77.2 1.98 .0257 36 65.5 1.80 .0275 36 56.6 1.55 .0274 Average 62.8 ± 8.9 1.67 ± 0.26 .0266 - .0025 5 LN 19 61.0 1.39 .0228 40 63.8 1.61 .0252 40 66.9 1.86 .0278 6 57.4 1.46 .0254 6 69.1 1.61 .0233 Average 63.6 ±* 4.6 1.59 ± 0.18 .0249 ± .0020 6 LN 18 63.0 1.43 .0227 13 70.9 1.43 .0202 33 63.2 1.57 .0248 26 63.2 1.37 .0217 29 67.0 1.43 .0213 Average 65.5 ± 3.5 1.45 ±- 0.07 0.0221 ± .0017 89737754

TABLE III Comparison of Cigarette Deliveries: Input to ADL-I Smoking Machines at VAH (Site Visit VII) vs Analytical Smoking Machine Conditions Cigarette Code No. of Puffs TPM, mg/cig Nicotine, m9/cig Nicotine:TPM Ratio ADL-Ia HN 17.3 ± 1.5 61.9 ± 9.1 4.56 ± 0.66 .0732 ± .0057 Analyticalb HN 18.7 ± 1.0 71.6 ± 6.7 4.94 ± 0.60 .0688 ± .0029 ADL-Ia LN 17.5 ± 1.1 64.0 ~- 5.8 1.57 ± 0.20 .0246 ± .0027 Analyticalb LN 16.6 ± 1.0 64.9 •±4.0 1.63 ± 0.17 .0251 ± .0018 ; aVaiues given are overall averages for all input samples for a given code. bAverage results for 8 cigarettes per code on the Phipps and Bird smoking machine at 3 puffs per minute, 1 cigarette per pad

TABLE IV Total Particulate Matter (TPM) and Nicotine Output from Selected ADL-I Smoking Machines in Service at VAH on August 8-9, 1977 Ward No. Cigarette Code Machine No. TPM, mcL/cig Nicotine, mg/cig Nicotine:TPM Ratio 1 HN 6 35.5 2.42 .0682 31 35.8 2.46 .0687 7 25.7 1.64 .0638 14 29.1 1.94 .0667 8 35.6 2.09 .0587 Average 32.3 ± 4.7 2.11 ± 0.34 .0652 -.0041 2 HN 25 33.5 2.91 .0869 20 20.7 1.22 .0589 10 29.1 2.48 .0852 X 18.4 1.04 .0565 24 28.6 1.87 .0654 Average 26.1 ± 6.3 1.90 ± 0.80 .0706 ± .0145 3 HN 35 22.1 1.50 .0679 39 31.7 2.24 .0707 37 33.3 2.62 .0787 9 33.3 2.61 .0784 38 34.8 1.49 .0428 Average 31.0 ± 5.1 2.09 ± 0.57 .0677 ± .0147 4 LN 17 27.5 0.67 .0244 4 34.4 0.93 .0270 4 26.5 0.77 .0291 36 27.7 0.83 .0300 36 33.1 0.99 .0300 Average 29.8 ± 3.6 0.84 ± 0.13 .0281 ± .0024 5 LN 19 36.9 0.77 .0209 40 29.4 1.08 .0367 40 36.9 0.93 .0252 6 33.9 1.05 .0310 6 36.6 0.99 .0271 Average 34.7 +-3.2 0.96 ± 0.12 .0282 ± .0060 GD CD 6 LN 18 23.5 0.44 .0187 W ~ 13 33.5 0.67 .0200 •1 33 41.8 0.73 .0175 ~ 26 33.2 0.79 .0238 29 42.8 0.89 .0208 Average 35.0 ± 7.8 0.70 ± 0.17 .0202 ± .0024

TABLE V Comparison of Measured TPM and Nicotine Cannula Exit Values with ADL-I Input Values at VAH August 8-9, 1977 Total Particulate Matter (TPM) Nicotine Cigarette Code Input mg/cig Output mc~/c~ Output/Input Input mg/cig Output ~mg/cic...,,,.._ Output/Input _ ~ HN 61.9 ± 9.1 29.8 ± 5.7 0.48 4.56 ± 0.66 2.04 ± 0.56 0.45 LN 1 64.0 ± 5.8 33.2 ± 5.5 0.52 11 1.57 ± 0.20 0.84 ± 0.17 0.54

TABLE VI Estimate of Average Weekly Dose* of Total Particulate Matter (TPM) and Nicotine, per Dog Cicarette Code TPM, g/week Nicotine, mg/week Hhi 2.15 ± .41 147 ± 40 LN 2.39 ± .40 60 ± 12 *Dose offered, as measured at cannula exit.