779 



aimed ai funher clarifying this issue, b\ measuring the undisturbed intake of individual 

 smokers in relationship to the anai\lJcaJ FTC yields of tar. nicotine, and carton mon- 

 oxide (CO) of the cigarettes smoked. 



Of the several thousand substances present in smoke, nicotine is obvioush a most 

 specific marker, in plasma it has a half-life of some 120 min (5, 6), and iu steady- 

 state levels reflect the input from cigarettes smoked during 8- 10 hr prior to sampling. 

 Toiinine, the principal metabolite of nicotine, has a terminal half-life arouiid 15 hr 

 .3, 29). and it has been suggested as a better indicator of cumuJative nkodoe intake 

 over a period of several days ( 1 9-2 1 ). 



Nicotine is delivered in close physical association with tar particles (17). OnJy a 

 negligible amount migrates as vapor, and at the average pH of cigarette srooke most 

 of it is rapidly absorbed in the lungs (2), whDe less soluble lar components ant deposited 

 on the lung surface or are partially exhaled (25). Thus, plasma nicotine aod cotinine 

 can be used to infer maximum tar intake potential, once the average ratio of tar to 

 nicotine of a cigarette's smoke is known. 



It should be kepi in mind that plasma nicotine or cotinine values art not direa 

 indicators of intake, and cannot be utilized as such to determine the validity of FTC 

 cigarette rankings, which are expressed as yields per cigarette. To this end, ibey need 

 to be transformed into estimates of mean nicotine intake per cigarette (KfNlC), ac- 

 counting for each subject's weight and cigarette consumption, and after appropriate 

 pharmacokinetic considerations. 



Blood carboxyhemoglobin is quantitatively related to the amount of inhaled carbon 

 monoxide and correlates with the concentration of CO in expired air (37). Fnere are 

 many external sources of CO besides cigarette smoke, aad endogenous formation is 

 also possible (36). For these reasons, expired CO values can be interpreted only in the 

 light of other more reliable markers, especially in studies uiilizing free ranging smokers 

 under field conditions. 



SUBJECTS AND METHODS 

 Subjects 



The subjects (397 men and 468 women) were approached randomly in five cities. 

 They were at least 21 years of age and had been smokJng only cigarettes of the same 

 brand for at least 3 months and no less than 10 cigarettes per day. Only volunteers 

 who measured at least 1 5 ppm CO of expired air were recruited, in order to eliminate 

 noninhalcrs. To ensure an even coverage of market share over the FTC range, less 

 than 10 subjects per brand were recruited (Fig. 1), with minor exceptions at very low 

 yields where few brands arc available. Subjects represenicd predominantly white collar 

 occupations and housewives. 



Only individuals in good health under no medication were recruited. Individuals 

 with alcoholic problerr»s or exceeding ±20% of ideal weight, or pregnant v«jt excluded 

 Subjects reported to the test facility and smoked one of his/her custoniary cigarettes. 

 A venous blood sample was taken 10 nodn after the last puff to allow ad»)uate time 

 for first compartment distribution (32). All subjects were sampled in midaftcmoon 

 on Wednesdays or Thursdays, and received nominal monetary compensation. 



