507 



AFPEaiDIX B 



PLAINTIFF 

 EXHIBIT 

 NO 



TTPP'S DEPOSITION I 



BIT i^T" I 



3.27 -^. I 



^S ...J 



FMnueeklMtlea or NlcetlBi and Iti Kajor KatftboXltcs 



la N&ly* Md Itebieucted Snuff T«k«r« 



4m i ^mj^o^, t iwh 



The polynuelcar «ireMtle ^ydroc>rbon (PAH) fraction of tebtceo maokc 

 Is (enarated froa pjrrolysl* of aliphatic parafflna in tobacco l«ar (Stcdaan, 

 1968). The PAH-onrlehod fractlea of tobaeee Mokt wMeh eeaprteaa only O.df 

 Of lU enide eondenaatc woUbt (Akin ot *1.. 1976) Is lavolvotf 1a Badlatlns 

 tbo obsorvod «Xt«r«d dlspesltloa of sons druss in «ls«ratM aaokora (Juske, 

 1978). 



ConwiMrs of nokele^s tebaeaee - onufi takara and tebaeeo ohsuera > apptar 

 to b« « useful population for studyloc nicotine pharBaeoklaatlcs, reprasentlnt 

 ■ ceod cxporlJienUl aodel for delineating the orrccts of obroAle nicotine 

 Ingeatlen without being exposed to the aKnifloant Inductive stlsull of the 

 PAUs thAt are 'produced froa saoked tobaeco. 



Oaede (19i>1}. studying nlootlne abaerptloo fr«0 chewing tebaoco, observed 

 less rapid oieatlae abserptieo after chewing than after aseklng with inhalation. 

 Volff and Cllea (1950) quantitatively estimated the anounte of nicotine absorbed 

 froa chewing tebaeeo and observed that peak plasma nloetine eoneentratlens 

 aehlevad after tobaooo chewing were slightly less than those achieved after 

 »Mking ooaparable amounts of nicotine. TcBple (1976) provided evidence 

 that nicotine Is absorbed froa tobacco snuff through the nasal aueous menbrane 

 and that the urinary elialnatlon of nicotine and Its aajor oetabolltea was 

 eloilar to that following absorption of nicotine froB tobacco smoke. 



la yet, no report of an extensive pharsacoklneilc-aetabolle investigation, 

 involving aerial sanpling of both blood and wj-lne after use of eeekeless 

 tobacco, has appeared. Therefore, we undertcMk to investigate the diaposttloa 

 profile of nicotine, cotlnine and nieotlne-l*-K-oxlde in both plasna and 

 urine of naive and habituated users of tobacco snuff after a atandardlred 

 •flip- or snuff. Comparative Investigations after tobacco chewing and cU«rettc 



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