Tobacco Documents Online

2. Dose - measurements in humans Discussion: Rapporteurs Roger A. Jenkins and: Theodor D. Sterling The discussion on Pershagen's paper dealth with the accurary of estimating prevalence and amount of smoking from questionnaire studies. Sterling drew attention to the Warner study (1) showing that estimates of tobacco products consumed in US based on personal and on telephone interview, were 40 percent less than the official count based on sale of tax stamps which have to be attached to every pack sold in the US. Another point of view brought up was that reports of the amount smoked were mostly in multiples of "five" or "packs" (i.e. 10, 20 etc or one pack, 2 packs etc). Not being able to estimate more accurately from questionnaires how much people smoked, how accurately could questionnaire methods help estimate the amount of smoke to which they were exposed by the actions of others? Zober mentioned that in his experience, reports of the amount smoked were in multiples of five. Pershagen replied that in his study, there had been good agreement between self reports and that of relatives. Lebowitz added that epidemiolgocial studies of many populations showed very high reliability of smoking questions, and that a study of smelter workers has shown good recall of type and length of exposure the worker had of his experience (2). Rylander concluded that all this showed how difficult it might be to study the relation between lung cancer and exposure to environmental tobacco smoke (ETS) exposure in view of the difficulties to obtain good exposure data. In comments to Russell's presentation, Jenkins contributed that Russell's findings in human patterned what Jenkins had: observed with smoke exposed beagle dogs, namely that only 1-2% of the nicotine retained by the individual can be accounted for at any given time be measurement of plasma nicotine. First inquired if Russell's subjects were smokers or non-smokers. They'yiere mostly non-smokers although some had smoked. He

suggested that Russell's approach could be used,to study possible difference in metabolism of nicotine between smokers and non-smokers. Russell further thought that the problem might be differences in potency between mainstream and sidestream smoke. If it can be shown that exposure to ETS is related to an increased risk for lung cancer even though the exposure level is very low, then perhaps what caused lung: cancer in the smoker was not the mainstream inhaled actively but the sidestream taken passively. On the paper by Lynch, First inquired why plasma cotinine was chosen as a marker, rather than plasma nicotine. Lynch indicated that the primary reason involved the suspected rates of nicotine and cotinine decay in the plasma. The study reported was part of a larger smoking cessation experiment and thus had to work within the constriction of that experiment. The design of the main experiment involved obtaining blood and breath samples 24 hours apart. Thus nicotine, with a suspected half life of less than one hour, would nearly completely disappear from the bLood.after 24 hours. Plasma nicotine's utility as a long lived indicator of smoke exposure is minimal. Aviado indicated that the differences observed between the CO half lives of the Group I and Group II females may be due to differences in the way in which those values were determined. The former was a two point determination, the latter, an exponential decay curve fitted to four points. Jarvis was puzzled by the magnitude of the observed CO halif time value compared to other findings of 3-6 hours, and wondered if ambient CO levels were obtained during the study and if ethanol filters were employed with the Ecolyzer used to assay the breath samples. Lynch answered in the affirmative to both questions, but indicated that only ambient CO level~s were measured in the room in which blood and breath samples were taken. .2

Cosentino queried if the breath samples were true alveolar air. Lynch replied in the affirmative and described the procedure for sampling and analysis of the expired air for carbon monoxide levels.. Bake suggested that there may be another more accurate approach to obtaining C0 half life, which involved making detail~ed measurements of COHb after controlled exposure conditions. Consideration should also be given to the possible differences in COHb half lives following acute and chronic exposure, due to different equilibrium compartments. Actually, some of the differences in the literature may be accounted for on this basis. Lynch agreed, but indicatedithat he had:been interested in obtaining half life values under real life conditions, a half life which represented the average of values which could be obtained for the various activities that an individual might undergo in a given day. Cosentino indicated that different average Mhalf time values might be obtained for different individuals. Lynch agreed. Regarding Jarvis' presentation, First started by asking if cotinine levels were observed in the physiological fluids of smokers which were one hundred times larger than those found in non-smokers exposed to ETS, would it be reasonable to conclude that the latter received;about 1/100 of the dose of an active smoker? Jarvis thought that that would be a reasonable estimate of exposure level differences. Pershagen wondered about the sensitivety and specificity of the biochemical markers to distinquish between non-smokers and smokers with usually light smoking,habits, e.g. those who had not smoked a day or two before the measurements. Jarvis • responded that no biochemical marker is completely speci,fic in discriminating between smokers and non-smokers, firstly because of ETS exposure of non-smokers, and secondly, because some smokers may smoke only frequently. Neverthel~ess, of the 3

available markers, cotinine discriminates best, and is sufficiently sensitive to detect the majority of even very light smokers. Rylander askediwhat levels of plasma cotinine might be expected in smokers. Jarvis felt that 300-500 ng/ml plasma would be a reasonable estimate. REFERENCES 1. Warner K.E. Possible increases in underreporting of cigarette consumption. J Am Stat Assoc. 1978: 73:314-318'. 2. Higgins I, Welch K, Oh M, Bond G, Hurwitz P. Influence of arsenic and smoking on lung cancer among smelter workers: A pilot study. Am J Ind Med. 1981: 2:33-41. 4