Tobacco Documents Online

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CIG-Z~R ETTEN-FA B R I K EN GMBH ~ Dr. George Stungis BROWN & WILLIAMSON TOBACCO CORP. P.O.BOx 35090 LOUISVILLE, Kentucky 40 232 USA CF-Bm/hm CONF I DENT I AL 8999-2335 22nd February, 1983 Dear George, as I promised to you, I will give you a short report about Dr. Hoffmann's visit in Hamburg on 9th of February this year. We discussed the planned projects in detail and I can give you the following list of conclusions: Total Project Title: "On the fate of nicotine upon intake by cigarette smokers" ~rojekt I: "Nicotine Metabolism" A : "Biological Half-Life of Cotinine" AI: 12 smokers, at least five days smoking for determination of the base line level of cotinine in plasma and saliva. After cessation of smoking, plasma, saliva and urine (24-hrs-samples) will be analysed for cotinine and nicotine for the seven following days. A2:20 smokers with cotinine levels in plasma above 220 ng/ml will be engaged. ..,2

C1(3 A R ETT E N-F/:I, B R I K EN (~i M B H - 2 - % B : "Nicotine Balance", Nicotine-N'-Oxide B2: In addition to existing plans, a comparison between RIA figures and GLC figures will be performed. C : "Kinetics of Cotinine formation" No changement of existing plans. Project II: Dr. Hoffmann agreed to change the former title "On the endogenous nitrosation potential of cigarette smoke" for the new title "How to protect the smoker against possible in-vivo-nitrosation" as I proposed to him. In addition to planned studies, I proposed to study the effect of decaffeinized coffee in order to differentiate between the possible influences of caffeine and chloro- genic acid. Hoffmann agreed enthusiastically. I also proposed to control coffee consumption via determination of caffein levels in saliva by HPLC (as a result of experiments in my lab) instead of caffein metabolites determination in urine, Hoffmann found this to be an excellent idea, because it is time saving. Financing I told Hoffmann, that at the moment, we could finance the project only for on__~e year. He agreed but suggested a discussion about continuation of the study in October of this year with respect of his research fellows. ,..3

CIGARETTEN-FABRIKEN GMBH BL,~T'r NI~.: -- 3 -- With respect to cost splitting of the projects I and II, he estimated 75 % of the total poject cost for project I, because project II is more or less just "applied research", using available methodology. (75 % of 73.000 = 55.000). We feel, that we should give Dr. Hoffmann the possibility to perform project II since we got the impression, that here - perhaps for the first time - could come out a positive result, e.g.: if a smoker has an uptake of vitamine C which is sufficiently high, he is protected against in-vivo-nitrosation (see new title!). Beside of our projects, Dr. Hoffmann told us about his activities concerned with "passive smoking". He exposed non-smokers to side stream smoke under strong but still realistic conditions and determined nicotine and cotinine concentrations in saliva by RIA assay. The result was a nicotine uptake equivalent to one hundredth of one cigarette (calculated via cotinine) and led him to the conclusion, that "passive smoking is not a great risk factor". (Wynder does not believe in the importance of passive smoking and is against any research activity in this direction, as Hoffmann told us !) We also discussed the BANFF meeting on N-Nitroso-compounds (to be held at Banff/Canada, 4-9 September, 83). A symposium of 2.5 hrs is planned with special problems related to tobacco consumption (chewing, sniffing, smoking). The following topics will be discussed: I. Chemistry and formation of nitrosamines (Hoffmann) 2. Measurement in saliva (Hoffmann) 3. Metabolism of nitrosamines (Hecht) 4. Tobacco chewing and Snuff dipping (Winn) O 5. Alcohol tobacco smoking and esophagus cancer in France ~ • 6. Conclusions of the symposium (N.Wald) ~ ...4

CIGARETTEN-FABRIKEN GMBH BL~TT NR,: -- ~ -- This. list may still be incomplete or may be altered, it was just cited by heart. I hope that my letter can give you all the information you asked for. I think, that the discussion with Hoffmann was in complete agreement with our plans discussed at Brussels. In order to give you a full information, I send you a copy of the planned Hoffmann-publication (Aspen meeting) which includes some BARCLAY results and a translation of any letter to Hoffmann with our remarks to this publication. The original letter is written in German. With kindest regards, also from "AL" and Friedlieb to you and Bob Sanford, Yours sincerely, Dr. Hans Enc.