Tobacco Documents Online

Sl"ta r !1 , -''~' '' ~ ~T '_.~„~: OAK RIDGE IiATIC?i:U Ll1isGRAT ;'R'IES INTRODUCTIO:T The Oak Ridge progr4m protocol has been broken~down into its three phases as outlined in Tables I, II and III. During the past nine months Oak Ridge National Laboratories has underta':en the evaluation of the Walton Horizontal Smoke Er.posure 1.1achine accor3ing to the preliminary criterion developed in Appendix I and II. The Lorillard machine has been received and is being mechanically adjusted preliminary to detailed smoke analysis studies. Primary emphasis in Phase I has been made to make measurement of smoke concentration distribution, ar.d conposition in the Walton machine. Certain mechanical areas of imnortance to the manufacturer have been given priority during the first nine months, and a concurrent effort to develop more sophisticated testing methods for•the testing of the "on-stream" smoking devices has progressed well. Results in Phase I, supported by Progress Report rrl, dated November 8 (Appendix III) can be summarized as follows: Functional Renort on!Wa.1-ton Horizontal Smoking M2.chine The mixing and dilution, and purge characteristics of the Walton Horizontal Smoking i•:a.chine have been defined using analysis of C02, Nicotine and of H2 (Appendix I'v ) as indicators and are avprcjxima(;eiy as expeeteci. Compositional studies have utilized the gas chromatographic analysis of gas phase. - Results in~ Phase I to date su==ized: a. Mixing is 90 ; complete within one second after puff b. Mixing is required for optimal distribution c. Approximately 7% of smoke is lost at purge hole during the puff d. Particulate deposition on walls and stirrer amounts to approximately 2o during the 30 second exposure period e. Additional undefined losses occur during exposure period at smoke inlet hole. Purge is 90; co=lete vrithin 10 seconds, asymtotically approaching zero at 20 seconds after initiation of purge f. Positive and negative puff differences are negligible, based on analysis of gas phase constituent preliminary (Appendix III). Exact quantitation is underway. g. During the exposure period there are no appreciable changes in smoke gas phase constituent as shotm by preliminary gas chromatography experiments (Appendix I'I ) . h. There are appreciable differences when animals are inter- faced on machine (Appendix III). Quantitation and specific constituent changes are underway. I

Possible difficulties have been defined and are under study: a. Three cigarettes were found to burnmore rapidly (9 puffs) thanan individual cigarette (11 puffs). Possibly due to leakage at interface of cigarette holder and chanber, or effect of burning under increased air pressure. b. Current Walton cone holders are more stressful for hamsters thanthe "stock holder" type, as reflected by breathing rates (Appendix III),. Different types of holders being developed here and at Process and Instru.^ients will be _tested with mice. Stress measurements are being studied in a collaborative study with Dr. Walter Essman, Queens College, N'. Y. Functional Renort on Lorill2sd The machine was received on November 8, 1973. In the start-up period to date a number of mechanical malfunctions occurred. Specific items: 1. Cigarette insert and butt eject mechanism did not operate: a. Leak in pneumatic system - repaired b. Cigarette holder collet needed adjustment c. Loading piston position travel mechanism needed adjustment The machine will now load and light cigarettes properly (1/8/74). 2. Four-rray smone distribution valve assembly malfunction: a. Nylon plunger swells on alcohol mesh and stuck. Currently aluminum plungers replacing nylon. Consulted Walter Kirschstein of Lorillard. 3. Deposition on tubes and valves. Quantitation under study. Minor adjustments and calibration co.-uplete. In general the machine is working. Specific design criticisms to date are : 1. Automatic shutdown interferes with exposure cycle 2. Compactness makes service and repairs difficult Sophisticationma.kes trouble shooting a complex operation. No operation manual is available To 1. be done: Animall holders (cone type) are being developed - plethysmography and deposition studies during and following exposure will be und'ertaken as so=as possible. Depletion of smoke components, following adequate methodology development, will be undertaken.

Phase II Progress has been directed to a practical application of hich- resoluti=gas chromatographic methods for gas and semi-volatile phases. In figure I attached, an early "gc" pattern is shown. This chromatograph, along with the computerized analysis of specific components, will provide a co-marison of gas phase composition from a Walton Horizontal (push) type machine and an Oak Ridge "one lung" (pull) type machine. In~Figure II a very prelimina.ry "gc" pattern is provided comparing smoke chamber gas phase content after 25 seconds with and without 20 mice breathing from the chamber. Certain constituents change rapidly, showing preferential absorption by the lungs and trachea of exnosed animals. The technique is currently being refined and quantitative analysis of consti- tuents removed~will be presented in a future progress report. Figure III shows a preliminary "gc" pattern for human and hamster urine, and points out the possible utilization of this technique for studying the presence of tobacco smoke constituents in~the urine of smokers. This technique may ultimately be useful in defining the quantity of smoke inhaled, the actual (as contrasted to claimed) withdrawal of an individual titled "ex-smoker" in~epidemiological studies, etc. In Figure IV the preliminary "gc" profile for particulate phase is shown. Upon refinement this methodolopr will be used to show the con- stituents present inparticulate phase of the lA1 and 1R1 cigarettes used in biolooical studies. In Appendix IV is a first draft of a manuscript to be submitted describing the analysis of hydrogen as a smoke distribution monitor in various types of smoking machines. This approach has provided information as to distribution, mixing efficiency, and purge characteristics for the Walton and other machines. In Appendix V is a first draftrt of a manuscript to be submitted describing the analysis of hydrogen level as a measure of total smoke concentration in various types of smoking machines. This approzch provides information as to exact concentration and dilution within the che..uiber of the Walton and other similar machines.

. ` TABLE I PHASE'I ACTIVITIES - Preliminary Studies ANTICIPATED TIME PERIOD: 6/73 - 2/74 1. Tentative definition of an ideal exposure criterion. 2. Preliminary familiarization with operational characteristics of Walton and Lorillard devices. 3. Preliminary measurement of smoke concentration, distribution, and composition in Walton using existing methodology. 4. Preliminary respiratory characteristics and smoke deposition in hamsters + M<<-- with Walton device.

TAB LE I I PHASE II ACTIVITIES - Methodology Development and Initial Application ANTICIPATED TME PERIOD!: .11/73 - 6/75 1. Deva.sg and test concepts for, build, and'evaluate devices for continuous monitoring of smoke concentration in exposure systems. a. Select gas andiparticulate smoke indicators. b. Establish that selected indicator is relevant. c. nuild,prototype devices and test. d. Finalize application methodology. 2. Develop multicomponent analysis techniques for gas, semivolatile, and particulate phases of smoke. a. Develop high-resolution gas chromatographic methods for gas, semivolatile, and possibly particulates phases. b. Devise and test sampling methodology for Walton and Lorillard devices.' c. Develop new or apply present automatic data handling systems to high-resolution multicomponent analysis. d. Consider and~possibly develop high-resolution liquid chromatographic techniques for multicomponent analysis of particulate phase. 3. Measure selected smoke components input to exposure system. a. b. c. Correlate input with analytical delivery. Correlate input with concentration in exposure system for both Walton and Lorillard. Determine losses of smoke from both devices. 4. Develop preliminary methodology for examining particle size distribution of smoke aerosol in exposure system. a. Devise and'build samnling apparatus. b. Carry out preliminary studies,with Royco Particle Size Analyzer. c. Determine alterations in aerosol particle size due to smoke aging or animals respiration. - d. Suggest further studies. 5. Final assessment of operational characteristics. . Obtain puff profile and compare with human profile. . Assess machine reliability, ease of operation, and versatility. c. Consider animal stress. C d. Calculate cost per animal exposed. W ~ N J W _S

6. Consider criterion and experimentation on basic exposure syrtem concepts. a. Positive versus negative puffing. b. Intermittent versus continuous exposure. c. Effect of variable puff parameters on smoke concentration and comDOSition. d. Vertical versus horizontal cigarette placement. 0

C TABLE III PHASE III ACTIVITIES - Application of 'Methodology and Animal Studies ANTICIPATED TI'E PERIOD: 1/74 - 2/76 1. Detertnine composition of smoke in devices (gas, semivolatile, and particulate phases). a. Study effect of smok.e aging on composition. b. Determine effect of animals on composition. c. Compare composition in exposure environment with smoke generated by normal (negative) puffing. d. Identify acceptable cigarette-to-cigarette variability. 2. Determine concentration of respiratory gases, nitric oxide, carbon monoxide, water, and sulfur compounds in Walton and Lorillard devices. a. Adapt existing analysis methods for exposure system analysis. b. Develop-sampling methodology. c. Determine effect of smoking aging on concentration of components. d. Determine effect of animals on concentration of components - study animal depletion effects. 3. Determine concentration and distribution of gas and particulate phase in exposure environments. a. Determine concentration of smoke offered to each animal under various exposure conditions. b. Final assessment of mixing and~uniformity of smoke. c. Determine integrated exposure for each animal on both devices under various exposure conditions. d. Determine time distribution of smoke concentration in each device. e. Evaluate promising alterations in exposure systems.. f. Identify acceptabile ci-arette-to-cigarette variability. 4. Preliminary experimentation with animals. a. Respiratory characteristics of hamsters or rats under selected~ exposure cond'itioni. b. Determine smoke deposition in hamsters or rats using best available methodology. c. Determine animal stress factors under exposure conditions with~best available methodology. d. Study influence of containment devices onismol.e deposition: and animal respiration. e. Design build, and evaluate improved animal containment devices for both exposure systems. f. Measure external body exposure. 5. Formulation of a final criterion for a valid smoke exposure concept. .

TABLE IV PHASE IV ACTIVITIES - Final Conclusions and Ftecommenda.tions ANTICIPATED TIriE PERIOD!: 6/75 - 6/76 1. Final'evaluation of devices with respect of finalized criterion of phase III. 2. Formulation of recommendation for elimination of shortcoming in devices. 3. Suggestions for future studies.

C APPENDIX I PRELIMINARY CRITERION FOR Ait IDEAL SMOICE GE:TERATION-EXPOSURE DEVICE ANIMAL INDEPENDENT VARIABLES CH'EMICA7, 1. Smoke composition must simulate that produced by human conditions as closely as possible (all other criteria are designed to approxirftate this requirement or to maximize practical aspects of the use of any given device). (a) composition of generated smoke (b) composition of smoke in exposure chamber (c) composition of smoke during exposure cycle (smoke aging) (d)Y uniform.composition throughout chamber (smoke uniformity) (e) absence of artifact formation. 2. Quantity of smoke offered must be known and controllable. (a) quantity in chamber throughout exposure cycle (exposure profile) (b) accurately defined, controllable, dilution (c) minimum memory (holdup) - (d) no contamination by sidestrecLm smoke. PHYSICAL 1. -The puff profile must be known andapproximate that observed in human smoking. 2. The particle size of the smoke must be comparable to that observed in human smoking. 3. The influence of cigarette pressure drop;on puff parameters must be minimal. MECHANICAL 1. Intermittent puffing of individual cigarettes must be possible (a) Accurate, reproducible, adjustable puff volume i ~

Mechanical (continued) (b) Accurate, reproducible, adjustable pu.ff frequency (c) Accurate, reproducible, adjustable puff duration (d) Accurate, reproducible, adjustable butt length. 2.-.Presently standard puff parameters must be attainable. (a) 35 ml puff volume (b) Two second puff duration (c) One minute puff interval (d) 23 mm butt length (e) normal (suction) puff mechanism (f)- cigarette held horizontally. Must be capable of producing intermittent smoke-air cycle with adjustable durations of each. 4. Capable of being interfaced to analytical monitoring instrunentati=. 5. Adaptable to gas phase exposure by incorporation of Cambridge Filters. 6. Operational Convenience (a) Cigarette Loading (b) Cigarette Lighting (c) Butt Ejection (d) Cleanup-frequency and ease. 7. Minimum cost per animal exposed.