RESTRICTED GR&DC PROGRAMME REVIEW 11 th-15th June, 1984 SLPIMARY OF DISCUSSIONS These summaries have been specifically written to describe delegates' suggestions on modifications to the GR&DC programme. For the sake of brevity, they generally do not indicate the high level of support for the bulk of the programme. c0 0 1984 BdUsh Ametican Tobawo Co. LAd. Thb must not be copkd or shmn to =uuWwdsW Pefwrm BATCo document for Province of British Columbia 5 November 1999 - 1 - WORK AREA 01: BIOLOGICAL RESEARCH (1) Delegates accepted that a "balanced portfolio" of tests should be used to assess biological activity. Too much reliance should not be placed on the Ames test, or indeed on any one test. Ideally, of course, tests should be meaningful in terms of human disease. (See note below.) (2) Inhalation should be the follow-up test to the Ames test (a) if this latter indicates significant differences between cigarette candidates and (b) if equal dose to the animal can be achieved. (3) The Ames results on all the commercial cigarettes should be brought together in a single report. If necessary, further tests should be carried out to check ranking between cigarettes from different countries. (4) Tests for specific biological activity should relate to human smoking patterns (e.g. puff volume) and should compare. for example, the last'and first puffs. (5) A priority ranking for the cigarette design variables should be established. (6) The confusing results from the inhalation studies on Duolite/carbon filters should be re-studied. (7) The confusing picture regarding the influence of nitrate was noted; results to date should be summarised and reported. Note: In Project RIO, commercial cigarettes are first examined by the Ames test and then by a whole smoke animal inhalati model, the end point being the induction of two enzyme systems. With regard to the Ames test--.-'a mutagenicity ~e, difference of only 0.1 is statistically signifi-~;nt, which_sug~e~sts scatter is minimal. In comparing a given product fr'om-diTferent countries, broad conclusions can be made from the available data but, ideally, the cigarettes should be compared in a single experiment. (This applies to all toxicology, not just the Ames test.) In the past, inhalation work has been used for specific. tasks (e.g. syn- thetic tobacco, eugenol). Thus a broad data base does not yet exist. The use of several dose markers suggests that the animals respond to the smoke in a similar manner. This is substantiated by respiratory monitoring data. Work is proceeding, however, to develop a particulate phase marker - (a) catechol and (b) joint studies with Harwell, radio-labelled smoke. It is recognised that short term inhalation tests are not predictive of carcinogenicity, only of inhalation toxicity. Commercial samples of Project RIO should be completed by September/October 1984 and all assays established by the end of the year. 0 1984 British American Tobacco Co. tAd. This must rot be copied or ShOWD to UnSUOKWiSW PUMM. co BATCo document for Province of British Columbia 5 November 1999 - 2 - WORK AREA 02: SMOKE RESEARCH Nitrosamine Formation (1) An understanding should be gained of how processing can chemically affect nitrosamine levels in both own and competition tobacco blends. (2) Work on nitrosamine formation in both model experiments and during curing, processing, etc., should include monitoring of as many components as possible which may be related to the underlying forma- tion mechanisms, e.g. redox system components. (3) Model studies on nitrosamine formation should initially be chemical systems - the inclusion of enzymes should be a second phase study. (4) Attempts should be made to establish'whether products high in nitros- amine give higher biological. activity. (Since the Ames test is not sensitive to nitrosamines, other tests should be pursued.) Combustion (1) Despite the difficulties in developing semi-theoretical/semi-experi- mental models (such as the puff-by-puff), such models should be brought into practical use and based on scientific know-how to allow prediction beyond the experimental data. (2) The continuous feed pyrolysis system for animal inhalation studies does not exactly simulate all the processes in a burning cigarette. Its use should be to asses separately aspects of smoke formation on biological activity, e.g. importance of temperature, pure pyrolysis Y. combustion, flow rate through generation zone. (3) The multicell model should be used to assess the effects/differences of the various methods of producing filter ventilation: electro- static perforation, on-line and off-line laser, etc. (4) The multicell model should be used to give the manufacturing toler- ances for the B&W Gemini filter. (5) The ID combustion model should be used to predict factors important in cigarette burn rate and the consumption of specific materials in tobacco such as sheet. (Empirical kinetic data will be needed for the latter application.) (6) The puff-by-puff delivery model should be used to predict how the transfer of nicotine to mainstream smoke could be improved. (Although the model can be used to assess combined effects of tobacco consump- tion, nicotine release, filtration, etc., these parameters are not related back directly to chemical parameters of the tobacco.) (7) The modelling work of the Physical Properties of Tobacco group should be more closely integrated with this group. Further work was reques- ted on shredded stem, relating to the reduction of carbon monoxide and increase in nicotine transfer, to be done jointly with the Chemistry of Processing group. CC) U1 0 1984 British American Tobacco Co. L&d. This must not be copied or shown to V10&U1h0riZ6d a L BATCo document for Province of British Columbia 5 November 1999 3 Sidestream There should be a better balance of effort between sidestream reduction and ambient smoke studies. Self-Extinguishing Cigaretes There is no work at GRADC, nor plans to start any. Aerosol Formation (1) Studies on the formation of the smoke aerosol in the thermal analysis/pyrolysis system should aim to clarify the relative impor- tance of the various combustion conditions on aerosol formation: temperature, heating rate. atmosphere, flow rate. A clearer pro- gramme definition is required. L (2) Work is planned to asse'ss the taste perception of two component monodisperse aerosols generated over the size range 0.1 to lpm. These aerosols have number concentrations of "105 particles/ cm3, compared to -j109 in smoke.- It was suggested that the emphasis of this work should be changed so that polydisperse aerosols of -V109 particles/cm3 should be used. Effects of chemical parameters such as pH on taste should then be assessed. (3) The classical aerosol equations refer to stable aerosols, but the particulate and vapour phases of smoke are not in equilibrium - there is a continuous transfer between the two phases. It was suggested, therefore, that the rates of evaporation and condensation of particl es should be examined. Smoke Filtration (1) The filter modelling work should now start turning towards practical application (e.g. the definition of filter tolerances, the develop- ment of novel filters). (2) Both present measurements and thi filtration model relate to fibre filters. It was suggested that measurements on open cellular filters should be made. However, direct application of the present filtration model is not practical because of the different physical structure of cellular filters. (3) Velocities used in the filtration efficiency/velocity studies should cover: (a) the range of filtration mechanisms (diffusion-impaction); (b) the velocities encountered in human smoking regimes; (c) -the velocities encountered in the grooves and channels of novel filters. (Baffle-filters may be usiful if they filter by impaction. However, high velocities would be needed to produce the impaction.) (4) Celanese Fibers are producing filters designed for high velocities., Some calculations/assessments of these filters would be useful. C:> (B&W to supply details to Martin Duke.) CO 0 1994 ElTitish American Tobacco Co. Ud. This must not be copied or ihown to unauthorised Perm" BATCo document for Province of British Columbia 5 November 1999 - 4 - (5) Measurements should be made to see how far back in the filter smoke and air mix to produce swirl. (6) Three approaches should be pursued to manufacture filters which generate swirl: 0) Manufacture at GR&DC - John Luke. (ii) Filtrona "deep groove". (iii) Mardens injection moulding of the "deep groove" (but not the "2-tube" filter). Selective Filtration (1) Delegates were uncomfortable in the knowledge that direct work on selective filtration at GROC has terminated. BAT Germany wished for some work to continue, for specific chemical reduction (possi- bility of Herzfeld league table introduction) and for modification of smoke sensory characteristics. The small effort by external consultants ends in August. -Consideration should be given to further (limited) Work. (2) Any development-on graft polymerisation of cellulose acetate should be done jointly with a fibre company. Celanese Fibers already have an interest in this approach - a joint venture with them should be considered. (3) The Duolite filter is known to improve smoke taste. A smoke scan of the filter should be made to attempt to correlate reduced irrita- tion with reduced levels of dienes. C=) 110 CO 0 1994 British American Tobnew Co. UA 11sis must rM be cooed or shown to =authorised BATCo document for Province of British Columbia 5 November 1999 - 5 - WORK AREA 03: SMOKER BEHAVIOUR (1) Puff-by-puff duplication was endorsed and should aim to identify the significance of the smoke dose and quality relative to smoke sensations and product attributes. (2) The direct estimation of human smoke uptake is the key to identifying the specific relationship between dose and subjective properties of smoke. Smoker response to the inherent delivery fluctuations of the product should be researched. (3) The "remote monitor" device for smoking behaviour, although having little application for monitoring individual puffing events, offers considerable potential for obtaining an "average' of smoking beha- viour over extended time periods. The device might provide an event marker for puffing frequency and the time of day smoking. It might also have application for m6nitoring third-party smoking. (4) It was considered important to identify as far as possible the factor5 (either individual, specific or environment-based) that prompt a smoking event. Because the proposed diary approach of Gale would present too long a time scale, there is a need for alter- native immediate action. (5) An attempt should be made to establish the degree of tolerable change (through cigarette design parameter modification) in terms of puffing and inhalation parameters that would or could be accepted by the consumer. (This may provide some insight into the cigarette design criteria that contribute to product acceptability. The observation of a lack of a substantial change in either puffing or inhalation pattern following a relatively large change in product deliveries. at least for some smokers, suggested a possible low level of sensi- tivity to dose on a per puff/inhalation basis. This finding focused attention on the possible role of puff frequency and position along the rod as a basis of dose manipulation.) (6) The aerosol -retenti on/aerosol -se.nsory characteristic is of vital importance. Studies should concentrate on understanding how different Nsimple" aerosols of known characteristics can influence retention. before moving to studies on real smoke. (7) Considerable importance was attached to the observed differences in the aerosol composition from the first and second halves of the cigarette - which is probably related to the mean residence time of smoke in the rod. (8) The relationship between aerosol composition and the effect of mouth humidity serve to highlight the massive gaps in our understanding between "conventional thinking" and reality. In view of the observa- tion that the smoke aerosol appears to be in an unstable state Immediately post-puffing, it should be seen whether filters giving rise to turbulent and swirling effects may have a positive effect on stabilising the aerosol. (9) The ability to manipulate and control the retention characteristics of a product through the identification of the smoke aerosol proper- ties within the respiratory tract should be considered as an area of importance for future product design. 0 1984 British American Tobacco Co. lAd. Ills mum not be copied or shown to =authorised ;*rsons. cc U1 C=> BATCo document for Province of British Columbia 5 November 1999 Additional Comments 6 Concern was re-stated on the use of holders for assessing smoke-dose in the retention studies. as this could lead to "non-natural" smoking. The whole smoker behaviour programme was considered to be too broad; effort should be concentrated on the above-stated key needs - with shorter time-scales. Wherever possible, in studies investigating smoker responses to pro- duct changes, the products should have only one changed variable (e.g. nicotine). 0 1994 Mtish American Tobacco Co. LAd. This must no be copied or shown to unauthorised personL BATCo document for Province of British Columbia 5 November 1999 cc - 7 - WORK AREA 04: FLAVOUR RESEARCH (1) There was criticism of the amount of effort expended on leaf studies. It was recommended that there should be a review of the direction of this effort in relation to the needs of the Operating Companies and of the Leaf Steering Committee. (2) The preliminary findings on tobacco sulphur compounds should be followed up on selected brands, e.g. Marlboro. Whilst recognising that PFW would be unlikely to work exclusively with BAT, collabora- tive work with PFW should continue, at least for the short term, to determine the usefulness of sulphur compounds. (3) There is a need to develop careful ly-designed experiments to maximise the early use of XRF and FTIR. A chemometrics technical exchange meeting in 1984/85 was supported. (4) Doubts were expressed regarding the flavour stabilisation work: careful selection of goals is vital. Physico-chemico methods of flavou'r stabilisation should be- considered, but there should first be a literature review of available fixatives, e.g. glycozides, pectins, carbohydrates. (5) The work on tobacco extraction was seriously questioned. Work at Harwell was not supported. However, as the Svenska Tabaks project has reached the 'commercial isation possibility' stage, this project should continue for the short term, at least. (6) Work on terpenes should be reduced. As an alternative to tobacco gum. effort should be directed to flavour products using abienol as the raw material. Cost data should be obtained with respect to this approach. 110 co 0 1984 British American Tobacco Co. Ud. This must not be copied or Am w wouthorised persons. C\ BATCo document for Province of British Columbia 5 November 1999 - 8 - WORK AREA 05: PROCESS RESEARCH . (A) PHYSICS OF TOBACCO (1) Mechanical Strength of Cigarettes and Filters The effects of circumference and cigarette paper grammage on rod firmness, and on firmness during smoking, should be investigated. Further work on subjective response to firmness is required. (Both CRA and BAT Germany are investigating this.) Work on the mechanical strength of cigarettes and filters should be extended to include different diameters, hot collapse and shredded stem. Computer programs based on mathematiial models are needed. (2) Effect of Particulate Size and Shape on Physical Properties of Cigarettes The effects of mixing reconstituted tobacco shapes with normal tobacco should be investigated. (The mechanical effects of changing particle shape 'have to be separated from the pure geometrical effects.) Effects of broad spectrum and narrow spectrum particle size and shape should be studied. Attempts should be made to extend the studies to shredded stem. (3) Fundamentals of Tobacco Degradation Possible areas of application should be considered - e.g. pattern of degradation needs study (corners breaking off or particles breaking in half); classifying tobaccos in terms of susceptibility to degra- dation; expansion, drying and threshing processes. (4) Relation of Process Conditions to Plant Settings There is a need to relate filling value improvement to practical equipment design. The work relating plant settings to process conditions (i.e. the true conditions experienced by the tobacco) should be extended to include studies on degradation. loose ends, firmness, etc. \0 Un 0 1984 British America Tobacco Co. LAd. This must not be copied or shown to unauthorised PffsonL BATCO document for Province of BritiSh Columbia 5 November 1999 - 9 - WORK AREA 05: PROCESS RESEARCH (B) CHEMISTRY OF PROCESSING (1) The programme as presented was criticised for being poorly planned. executed and analysed. There is too much emphasis on multi-variate mapping; raw chemical data must be presented/ reported. Wherever possible, 'simple' changes to tobacco chemistry should be studied. (2) All delegates wish to influence the work on the new tobacco treatment cylinder, which can operate over a wide range of closely controlled conditions. There must be a clear definition of objectives (e.g. specific biological activity, nitrosamines reduction, irritation amelioration, specific flavour precursor breakdown/generation and loss of flavours). GR&DC will correspond with edch CAC country, detailing the character- istics of the equipment and reviewing past knowledge and experience and requesting each country to submit their work priorities. Follow- ing this, a detailed prograffme with time scales will be circulated to CAC countries for comment. In view of the fact that blended cigarettes are becoming more popu- lar world-wide, GR&DC should be better equipped to evaluate such products. 0 1984 British American Tobacco Co. LA This must not be copied or shown to unauthorized Persons. co => 00 BATCo document for Province of British Columbia 5 November 1999 10 - WORK AREA 05: PROCESS RESEARCH (B) EXPANSION STUDIES (1) Two principal points were raised in discussions: (i) Will the theory developed to explain the experimental results obtained with different solvent s/expansi on agents predict whether combinations of inorganic agents could show similar synergistic effects? 00 There is a need to assess commercial prospects soon, before much more work is done. (2) The concept of using an outside - consultancy to assess safety/ economics was considered. I*n any event, any new process must be cheaper and/or simpler than existing processes. Subjective and chemical studies of products should not be. pursued until commercial prospects are confirmed. (3) Further limited work should be done with inorganic agents within the limits of existing equipment. (Deeper studies would require the construction' of an apparatus to operate at higher pressures than at present.) 0 1984 British Amcrican Tobacco Co. Ltd. 'nis must riot be copied or khown to unauthorind persom c0 N-0 BATCo document for Province of British Columbia 5 November 1999 WORK AREA 05: PROCESS RESEARCH (C) NOVEL CIGARETTE TECHNOLOGY (1) It is vital to establish close interactive links between CAC research groups and PAG to exploiting significant findings. (2) Areas of potential importance are: (a) Rapid exploitation of mature products/technologies, e.g. tow selection. thermoformable plugwrap. M Commercial isation of promising novel products, e.g. thermo- formable tipping, polypropylene. (c) Fundamental research to provide innovative products which offer enhanced smoker benefits, low weight/cost opportunities or the reduction of biological'activity. (3) BAT Germany indicated renewed interest in polypropylene fibre as a filter material and will hold further discussions with GR&DC. B&W suggested a possible hybrid fibre with CA and PP. (4) B&W suggested that if carbonyls were not formed, metals in tobacco might be a valid route to reducing sidestream irritation. Work should also continue to investigate carbon as a conductor. The effect of metal additions on biological activity should be examined. (5) The effect of tobacco density on harshness and smoke temperature should be studied. (This could apply to all low-weight products, and concepts would need to be developed to deal with this effect.) (6) Observations of reduced -CO/tar ratio, and the decrease in visible sidestream in an experimental foamed cigarette, justify further work on closed-cell foam rods. (A narrow peripheral coal might burn more efficiently.) (7) Estimates for costs of producing segmented, annular and variable density cigarettes are wanted, taking into account processing prob- lems, machine speeds, etc. (8) BAW expressed the hope that one day we might develop the technology to design cigarettes with a 'clean' substrate with only nicotine and flavours added. C=) 00 0 1984 British American Tobacco Co. Ltd. This must not be copied or shown to onauthorised persons. BATCo document for Province of British Columbia 5 November 1999 - 12 - WORK AREA 06: ANALYSIS AND TEST METHOD DEVELOPMENT Sidestream Smoke Analysis Delegates would see some advantages if the fishtail chimney system and the new 20-port smoking machine which has been developed for sidestream work could be adopted on a wider scale as standard industry equipment. Further consideration should be given to the advisability of trying to encourage this, possibly through publication or by direct contact with individual paper manufacturers. Future sidestream method development should include analysis of NO, pH and other "non-routine" constituents as guided by the Sidestream, Research group. Ambient Smoke - Collection and Analysis There is an interest in using the airborne vapour monitor (AVM) for the continuous monitoring of ambient concentrations.of nicotine in factories. Furthermore, the instrument might be used to detect ambient menthol. It was also noted that nicotine levels obtained using the AVM should correspond to those obtained by more conventional analytical methods, such as adsorption followed by thermal desorption/GC. With respect to monitoring carbon monoxide, it was thought that perhaps it would also be informative to check whether an oxygen deficiency could be detected under certain conditions in enclosed spaces. Metals in Smoke The discussion centred on the extent to which we need to measure metals in smoke and the choice of which metals should be determined. The possible inclusion of selenium was raised by BAT Germany. The possibility of determining the trace metals in various novel cigarette papers was raised, and it was agreed that this was likely to be necessary. Development of Analytical Procedures for Measuring TPM and Nicotine Retention in the Lung There was general interest in the hood collection system and procedures used for collecting smoke exhalates - but the trapping efficiency for nicotine at the high flow rate used was questioned. General opinion was that this work on individual smoke constituents would probably need to be expanded. B&W suggested that care should be taken to preclude the trapping of ambient nicotine and TPM when sampling. The Simultaneous Determination of Nicotine and Cotinine in Plasma at Nanogram Levels by HPLC Due to th6 low levels of nicotine being determined (generally 50 ng per ml) in smokers' plasma, it was suggested that doing the work in an Isolated anicotine freeo laboratory may be advantageous. Since preparation is the rate limiting stage of the method, the possible use of radio immuno assay (RIA) for nicotine and cotinine determinations should be explored. co 0 1984 Brifish American Tobacco Co. tAd. This mua tot be copied or thown to mmu&"isw pe.ML BATCO document for Province of British Columbia 5 November 1999 0 CL 0 CD r+ A VE RA GE O F P RI O RI T I ES GI ( V R EN ev e P BY nu R e OG I b R ND u A I d M V g 14 I e E DU ts RE AL a V r I C e E A W M C C Ind E O i ET U c I NT at N R e G I d . E J S fo U T r N O E i 1 n 198 984 for 4 G ma R t OU io P n) R& D P R OG R AM ME ' P R OJ E C T S P P Av v ri r, er r or or a9 q it i e y A O H ig h A D Hi 9 h /M e di u m 0 0 M ed i u m 0 0 LO W W W 0 or r 1 k k B Ar r LUL ea a OG IC A L 8 6 9. Pr Sh 0 j o r ec t t To R io m T s t s 69 13 5 0 . Hu m a n S tu di e s 44 No n e 0 U Z W wA E RE S EA RC H 1 2 2 4 Co m a b p us p1 ti i o ca n, ti 14 o od n e l Ii n g: 1 6 Co m b b a u si st c i on st M ud o i d e e s 1 l i n g: 1 7 0 X Mi t r o sa m in es / C a d mi u m 2 45 No n e Si d b e a st si r c ea /r m i : du ct i o n 1 22 Si d e s tr e am : a m b i en t 1 96 F il t ra t l o n: n o v el 12 2 F i lt me r c at h l an on is : m & s e le c ti v e. 7 7 84 9 0 o u s % mA L K 5 w i m u m L i u Be Ph Re h y t a s e vi i n o vl ti u o o r gi n St ca u T d ie St s u di e s 3 2 2 4b 30 88 P N ha ic r o ipa ti c n o e l og y 11 17 5 3 0 4 t LA VM K 1 1 1Z ma p p i ng 1 67 S en s or y P er c e p t io n 3 34 L e af ad d S i tu ti di ve e s s: /e x t r ac t s 3 2 M 89 22 T N on e E, 0 5 P RU CE SSI N G 1 7 W P hy b s a l s Cs ic : . 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