Jump to:

Council for Tobacco Research

Tobacco Smoke Inhalation Bioassay Chemistry [A Report of Research Carried Out by Ornl for the Ctr-Usa in Collaboration with Mai and Process Instruments Brooklyn, Ny to Define the Characteristic of the Walton Horizontal Smoking Machine As An Inhalation Exposure Device for Mice]

Date: Oct 1979
Length: 164 pages
SF0825965-SF0826128
Jump To Images
snapshot_ctr SF0825965_6128

Fields

Type
SCIENTIFIC REPORT
ABSTRACT
GRAPHICS
CHART
DRAWING
CALCULATIONS
Depository Date
31 Jan 1996
Named Person
Griffith, G.W.
Mai
Pic
Union Carbide
Dept, O.F. Energy
Moneyhun, J.H.
Florant, L.
Greenspan, J.
Caton, J.E.
Dalbey, W.E.
Gayle, T.M.
Yeatts, L.B.
Honaker, C.B.
Horton, A.D.
Jenkins, R.A.
Holmberg, R.W.
Bayne, C.K.
Pair, D.D.
Ctr
Nci
Gori, G.
Owen, T.
Univ, K.Y.
Walton, R.R.
Morrisey, C.A.
Guerin, M.R.
Stokely, J.R.
Higgins, C.E.
Copied
Bayne, C.K.
Caton, J.E.
Clark, B.R.
Cowser, K.E.
Dalbe, W.E.
List Internal Distribution Ornl 5424 Categor, U.C. 4
Basrur, P.K., Univ, O.F. Guelph
Battista, S.P. Arthur, D. Little
Benner, J.F., Univ, O.F. Ky
Binns, R. British Amer Tobacco
Bernfeld, P., Bioresearc Consultants
List, O.F. External Distribution, A. Shown, I.N. Tid 4500
Master ID
301030963-1128

Related Documents:
Grant Number
Ct07405weng26
Request
134
Box
103
Author
Guerin, M.R., Ornl
Stokely, J.R., Ornl
Higgins, C.E., Ornl
Site
Sommers
Brand
"1r1
1a1
NCI Cigarettes (Codes 74 and 90)
Low Nicotine Series "Kentucky 1a1
85 Mm Nonfilter
2a1
Kentucky Reference 2a1"
Z00000, Reference Brands
UCSF Legacy ID
wzr1aa00

Document Images

Text Control

Highlight Text:

OCR Text Alignment:

Image Control

Image Rotation:

Image Size:

Page 31: wzr1aa00
26 OvN:-DwG 78-20r6 ,-Vd:LVE ORIVESHAFT ~ D 0 J TEFLON 1 `f; J%' PLU('v J~ i' ) n I i n J ~~ ~ ` i I_; ~ / SMOKE t_1 ~ ~ VENT TUBE Fig. 4. SEM 11 smoke distribution valve. For continuous automatic operation cigarette butis must be ejected unfailingly. Analytical smoking requires a 23-mm butt length and as individual cigaretts do not burn at the same rate, this requirement is difficult to meet. The SEM It is operated on a preset puff number basis. The same number of puffs are taken from each of the 30 cigarettes. Very short butts are not ejected efficientlyand the system is normally operated bytaking one less puff than under standard conditions. Even so, some cigarettes burn to short butts and ejection is not dependable. 1Puff duration is very close to analytical requirements. As the drum holds thirty cigarettes and makes one revolutioin per minute this sets the puff duration at near 2 sec puff. Travel time between puffs is -0.3 sec; however, the slider block is slotted so that a puff starts and stops during the travel of the drum. This results in puff duration of ^-1.85 sec or only 0.15 sec less than standard. The puffing principle of the SEM 11 depends upon constant pressure rather th,ap ftSnstant volume. A preset pressure differential is established across the cigarettes and that pressure differential is maintained by a pressure regulating system. Consequentially the puff volume developed depends on the resistance-to•draw of the individual cigarettes. SF 0825995
Page 32: wzr1aa00
27 Figure 5 shous the relationship a7f the puff volume to the resistance-to-drau• (RTD) at a pre.ct pressure differential (8.5 cm H; 0). O%cr this rather u•ide RTD range from -60-110 mm H;O RTI) the• puff volume varicti inversely from -45-30 ml puff for the unlit cigarette. As the fireconeadds -50', to the RTD of the cigarette, the puff N olumes for the same series drops to -32 22 ml puff for the burning cigarette. 50 45 • • 40 ;;: 35 ~ n ~ E W 30 2 ~ J 0 > 25 LL LL D a 0 20 w 10 5 ORNL-DWG 76-1£046 I 1 0 I I I I I I 1 1 60 70 80 90 100 110 120 130 RESISTANCE TO DRAW (mm H20) FOR UNLIT CIGARETTES Fig. 5. Relationship of puff volume to the resistance to draw of eigarcues smoked on the SEM 11 at a fixed differential pressure (8.5 cm H20). ' SFU82~996
Page 33: wzr1aa00
zx Figure 6 shoac the puff flow profile ior a series of randotnl.• selected cigarettes. This figure compares puf f s f rom t he unlit cigarett6 with puffs 2 and 7 after lighting. The line through each profile i. the mean puf7 volume for that puff. The Sr M II was calibrated in this case to generate art a%rrage 3S•nil pull t.hilc taking 10 pulls lrom the cigarette. ORNL-DwG 77-16234 55 45 43.4m 35 45 a N N u u 3 35 O ~ 31.7 m LL tL ~ a 25 50 40 34.2m 30 PUFF FLOW SEM II i- 1 UNLIT k I I i i 1 T--l 7 th PUFF If P 0 1 5 10 15 20 25 CIGARETTE POSITION I I I L 30 Fig.6. puffnow pro(ileforateriesof30randomh•sekrtedcigarettesr+okedintheSEM tlatapressurediRerentialoft7.3 cm H=0. ,t SF0S2B997
Page 34: wzr1aa00
29 The RTD of t he cigarette is a sum of the resistances offerrd hx the rod and the fire mne. As t he rod i% consumed the overall resistance drops: thus there is a change in puff t olumes on a puff-b%-puff basis (F ift. 7). The first or lighting puff is high but little smiil.c is produced. Equff 2 drops to approximatel% ? 1 ml and puff tolumes increase to -? 7 ml bx puff 10. The average om cr the 10 puffs is --3.3.7 tnI puff. !f cigarettes are selected on an RTD basis the SE X". l I max be calibrated to yield puff volumes of •-a`ml puff. Hm.+•c%er.ifrandomRTDcigarenesaresmokedthepuffsolumetitsilltarcgreath.Eten so it is possible to calibrate for smoking random RTD cigarettes to :icld an aterage puff of 35 ml. With tnirt% cigarettes smoked in a cloced space. significant heat i~ generated. During intermittent operations there is little temperature increase. During continuous operation the metal component.; of the smoking mechanism are heated and there is a gradual increase in dome temperature. Although this temperature appeai•s to have little effect upon smoke characteristicsa second effect.as yet untested. may be significant. Cigarettes stored in the hopper may dry very rapidl.•. Tests have show n cigarettes lose moisture rapidly at temperatures observed in the hopper of the SE y1 I I(Fig. 8). Analytical smoking requires cigarettes to be conditioned for at least two days at 60 r relative humidit}•and 75°F. How-ever. during continuous smoking cigarettes in the hoppercould be subjected to tem'peratures of ^ 90° F for I to 2hours. At this temperatureand time iiiten•al. there isconsiderable loss of moisture (3-4 % by weight): this loss may be signiftcant.since it has been shown that moisture content of cigarettes does affect component delivery. 40 ORNL-DWG 77- 16236 I I I I I I • ! e • • s SEM II Op= 12cm H20 0 2 4 6 8 - 10 PUFF NUMBER ' Fig. 7. Puff to puff variation of puff volume of cigarettes smoked on the SEM 11. SF 0825998
Page 35: wzr1aa00
30 ORNL-DWG 78-7008 e ~ It] 5 ' L_ ~ OVEN TEMPERATURE 81°F (AIR 60%RH AT 76.5°F) • OVEN TEMPERATURE 90°F (AIR 61.5% RH AT 75.5°F) 3 10 0 5 10 15 20 25 TIME (hr) Fig. 8. Loss of moisture from cigarettes stored at elevated temperature. Thc SEM design includes a humidification system. However. it is difficult to control the rejative humidity with the increased dome temperature. Chemical Characterization of Smoke from the SEM 11 It was recognized from the onset that the SE M 11 differed from analytical systems in several ways. First the SEM 11 is a reverse smoking system and puff volumes are not as rigid4• controlled as ih the other systems. As already described, individual puff volumes var}• inversely with resistance-to-draw of the cigarettes. Also the SE M lIisafree-smokingsystem.Thebuttsofthecigarettesareopentothedome atmosphere between puffs (Fig. 2). Most anal' ytical machines are restricted smokers, as the butt of the cigarette remains sealed between puffs. A free-smoking system is known to deliverhigherconcentra¢ions of some smoke components. Gas phase components are comparable between the two systems, except for hydrogen which is 17% higher in the SEM II smoke than in the analvtical system (Table 2). Although the total particulatesare only 5% higher in the SEM II smoke, individual components vary between the two systems ranging to 30-35 c-c greater concentrations of nicotine, phenol, and cresols (Table 3). The greatest difterences are observed for constituents present at low concentrations or for those for which standard analytical methods are lacking. These variations are not unexpected. Severad investigators have reported significantly increased delivery of particulates from smoking systems adjusted to be free smokers.t These reports indicate increases particularly of nicotine and phenol comparable ;o the increases noted here.°.It appears that undertheconditionsofthisstudythatthefreesmokingmodeoftheSEM Ilisthemajorcontributionto differences observed. I I SF 0825999
Page 36: wzr1aa00
31 Table 2. Comparison of gas phases of smoke° from b SEM II and the Filamatic An:Jytical Smoking htachine Compound SI:.111 itnl .i.erett.t Analytical 1m1 aprcttct SFNi II+Anlyncal ('O 19.0t 0.6 18.4 2 0.8 1.03 CO: 36.4 n 1. 1 36.4 * 1.4 1,00 CH4 2.0 = 0.1 1.9 ± 0.1 1.05 H2 8.1 0.4 6.9a0.5 1.17 °jA1 cit:arettes• 10 puffafciFarette. h\1• R. Guerin and R'. I). Shults. "Tobacco Smoke AnaltsisPrngram Prncress Report for the Pertod lanuary 1, 1970 to Sept. 1. 1970. ORNLd6a2. pp. 5-6. Table 3. Comparison of particulate phases of Smof,e° from the SE3f 11 and the Phipps and Bird Analytical Smoking Machine Compunent SE11II Analytical SEN1I11Analytical mg%ciEarettc TP%t 38.9 a 1.9 37.1 a 2.1 1.05 Nicotine 0.54 t 0.04 0.41 ; 0.04 1.32 N•ater 3.14 r 0.44 4.07 : 0.25 0 77 Tars 35.2 e 2.0 32.6 2.1 1.08 Glccerol 1.61 ? 0.13 1.51 ~ 0.14 1.07 Catechul 187 e 11 /1,4"1'Igare11C 176 ~ 17 1.06 Phenol 124 z 6 91 3 1.36 o-Crcwl 31 i 2 24 ± 2 1.29 m-Crewl 25 a 2 19 ' 2 1.32 p.Cresol 561 3 42 ± 2 1.33 Neophytadicnc 161 2 14 130 ! 12 1.24 Palmitic Acid 2255 14 195 x 17 1.16 Stearic Acid 63 ~ 6 65 ± 13 0.97 Oleic. Linolenic 444 ! 37 379 ! 32 1.17 and Lmoleic Acids °2A1 cigarett:s. 10 puffsJcil:arettc. This argument is not to discount the effect of varying puff volumes upon the smoke deliWery. There is the possibility that the puff volume variations observed could generate smoke greatly different in composition. The limited data available at this writing indicate that this is not a significant problem. Cigarettes aere selected at four widely separated RTD ranges. These cigarettes were smoked on the SEM 11 and the smoke analyzed (Fig. 9). TPM and nicotine decrease as the RTD increases causing lower puff volumes. Nowever, over this range. the nicotine and TPM rather closely parallel, indicating a drop in total delivery but no great shift in relative concentration. It follows that irom a scries of randomly selected cigarettes that the average delivery will be near the average for RTD selected rigarettes. The possibility still exists that the average RTD of a random set of 30 cigarettes may differ greatly from a subsequent series. For that reason, it is recorn mended that careful control and monitoring of the RTD of cigarettes used in inhalation experiments with the SEM 11 be maintained. 0 SF 0826000
Page 37: wzr1aa00
60 w 50 I- t- W X 40 ~-' --o 0 I *DELIVERY UNITS I ORNL-DWG 77-16988 ~-~-~ J i o TPM 6 NICOTINE o PUFF VOLUME 70 mg/CIGARETTE 0.01 mg/CIGARETTE mI/CIGARETTE 1-I 1-_ I I _L_L 80 90 100 '110 RESISTANCE TO DRAW (mm H20) Frg.9. (7omponent delivery of cigarenes withdifferent RTDsmoked in the SENt ll. SES1 II caIrhrated t,+dchrrr a 35•ni1 pull Irom n% er.rgc RTI) cigarettes. , Conclusions The SE M Il is anautomatic smokeeaposuremachine capable of generatinga continuous stream of fresh cigarette smoke and delivering this smoke to animals for inHalation bioassay. The smoke may be diluted in a controlled manner with little aging of the smoke. Although there is some compromise of analytical smoking parametets. the primary cause of deciatioa from analytical smoke generation appears to be the frec-smoking mode of theSFM 11. The system functions well mechanically except that it cannot eject ter) short cigarette butts. Tocotinterthisdeficiency, cigarettes are smoked taking one less puff than would be taken under analytical conditions. Puff volumes are regulated bN constant pressure resulting i n a dependency upon resistance-to-d raw of the cigarettes. Careful monitoring and control of cigarettes used for inhalation experiments u4h the SEM II should be maintained. The SEM II has operated efficiently and relatively trouble free at this site for evaluation purposes and for approximately one year in an inhalation study at Microbiological Associates, Bethesda, MD. This experience has shown the SEM II to be a reliable system, mceting the needs for which it was designed. REFERENCES i. E. L. Wynder and D. Hoffmann, Tobacco and Tobacco Stnoke, Academic Press. ?New York. 1967, pp. 113-120. : ' 2. M. R. Guerin. W. L. Maddox, J. Kendrick. D. A. Creasia. P. Nettesheim, W. Dalbey,and J. R. Stokely. "A Tobacco Smoke Inhalation Exposure Device for Rodents," .4rch. Enriron. Nealtlr, in press. ' SF 0826001
Page 38: wzr1aa00
33 3. J R. Sto}.el'v. J. H. %tonc% hun. M. R. Gucrin. L. F!orant.and J. Greenspan. "Description and Characteristics of the Walton Hoiiiontal Inhalation Expocure Smoking Machine." this report. 4. W. Dontena'ill. G. ReckzehR and L. Stadler. "BeraudrungsarJearaha (ur Lahururoriuntsliere," Be•ur. 7uhaF Jur.%e h. 40). 45 49 (1967). 5. F. J Shultz and J. R. Wagner. "A Thirt.-Port Smoking Machine for Continuous Smoke Gcneration.' Bcur. 7ahudlursch. 8(2). 53 59 (1975). 6. L. B. Yeatts: J. H. Morieyhun. and J. R. Stokelv. "A Nfethod for the Sampling and Determination ofXwcotineand IviethancasIndicatorsofTobaccoSmokeConcentrationinInhalation Ekpocurr• Systems." this report. 7. J. R. leusome and C. H. Keith. "Quantitative Studies on Cigarette Smoke II. The Effect of Phcsieal Variables on the Weight of Smoke." Tob. Sci. I, 58 63 (1957). 8. E. L. H'%nder and D. Hofl'mann. op. cit.. p. 391. 9. F. Seehofer and 11'. Schulz. "7_ur l.'rrrnretis ele,> Ghmntsrromes t•on Cigurerreu," &•iir. Tahakfe)rsch. 3(2). 151-156 (1965) '' sF08z60o2
Page 39: wzr1aa00
ANIMAL CONTAINMENT VESSELS FOR NOSE-ONLY INHALATION BIOASSAY EXPOSURE TO TOBACCO SMOKE• M. R. Guerin atdd.I. E. Caton Analytical ChcrnistrN Di%ision and W. E. Dadbel• Biology Division Oak Ridge National Laboratory Oak Ridge. Terinessee 37830 ABSTRACT N hole bod> exposure compromises the results ot inhalation bioa•sa% resting because smoke cun.ntuenrs can be tnFcstcd b% means additional to respirafton. "Nos°-only"cxposure eliminates these extraneous routes of administration but hhe restraint required produces stress which may influence dosimetq. longevity. and the resuits of the bioassa). Social animal containment mechanisms have been tested on hamsters. rau, or mice exposed to cigarette smoke from the Walton Horizontal Smoking Machine. the Maddox ORNL smoke expoiure s~stem. or the Process and Instruments Smoke Exposure Machme. Retained dose depends on containment meihbd. Stress from confinement in restratntng tubes was manifested b) weight loss. Neck-onh restraint has seteral advantages over previously used methods of containment. Introduction Whole body exposure can complicate interpreting the results of inhalation bioassays. Constituents of the smoke deposited on the exposed animal can be ingested in prccning or absorbed through the skin to add to the intended route of administration. The quantity and nature of this added exposure is beyond the control of the investigator because it depends on the behavior of individual animals in the study. The problem is expected to be particuiarly severe for bioassays of concentrated aerosols such as tobacco smoke and fumes or mists related to occupational exposure. Whole body exposure is particularly inappropriate for bioassays of concentrated aerosols known to contain toxic constituents (e.g., nicotine in tobacco smoke). Mechanisms are required to ensure that the test aerosol is inhaled but that external body exposure is minimized. "lose-on$" exposure is required to eliminate extraneous routes of administration but it also requires that the animals be restrained. Restraint is done by confining the animals inrontainment vessels -designed to position the nose so as to ensure aerosol inhalation during, nprmal •Spon.nrcd in part b% the \CI Smoking and Health Program. 35 SF o$2$0Q3
Page 40: wzr1aa00
}F respitation. Containment produces added stress which ma% influence dosimetrn. longevit.. and the results af the bio0stiay. Stress effects are particularl. detrimental to chronic r.xposu'res such as those required to e+aluatc carctnot:enicity. Seseral animal containment mechanismti have been found applicable to both short- and long-term exposures of ham,ters. rats. and mice to tobacco smoke arno.ol,. Piahabl, these desice. ,cill he gcneialh, applicable to the "nose-onh" exposure of rodent, to other aero,ols o( emironmental and occupational signififiance. Experimental The containment vessels described here are integral component, of the N'alton Horiiontal Smoking Machinct (Fig. I), the Maddox OR\L' smoke exposure ,xstem (Fie. 2). and the Process and lnstrumerits Smoke Exposure Machine' (Fig, 3). The Walton Horizontal Smoking Machinc (N'HS'vl) and the Maddox ORNL are static exposure systems in ahich the smoke aerosol is introduced into an attenuated cylindrical (visualize a coin on-end) chamber. allowed to stand for a selected time. and cleared from the chamber with fresh air until the next puff is admitted one minute atter the previous puff. The Process and Instruments Smoke Exposure Machine (P&I SEM) Fig. 1. The Walton Horizontat Smaking Machine with 20 mice in animal containment vessels. rl SF 0826004

Text Control

Highlight Text:

OCR Text Alignment:

Image Control

Image Rotation:

Image Size: