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addictive. Isn't it true that while you were working at PhiUp Mor- 

 ris, you told your superiors that animals will self-administer sac- 

 charine? 



Mr. DeNoble. No, sir. I never said that they will self-administer 

 saccharine. They will work for saccharine. You can press the lever 

 and get a food pellet or get saccharine, and that is a self-adminis- 

 tration procedure. The difference between self-administration of 

 saccharine and food and nicotine is that one is delivered intra- 

 venously, the other one goes through the peripheral system. So, 

 saccharine, yes, you can self-administer it but only through the oral 

 route. It will not go intravenously. 



Mr. Bliley. Isn't it true that you conclude from your research at 

 Philip Morris that behavioral factors are primarily responsible for 

 tolerance of nicotine? 



Mr. DeNoble. No. I'd like to defer that to Dr. Mele. Paul was 

 an expert, is an expert in tolerance and nicotine. 



Mr. Mele. Well, I ran the tolerance studies anyway. Yes, we did 

 determine that under certain conditions behavioral factors contrib- 

 uted heavily to the development of tolerance to nicotine. Behavioral 

 factors were not the only component, at least back then, what was 

 termed a physiological or metabolic component. There was a duel 

 role in our studies, at least in the first studies we ran, the behav- 

 ioral component was much larger. 



Mr. Bliley. And you reported this to your superiors at Philip 

 Morris, both of you? 



Mr. Mele. Yes. 



Mr. DeNoble. Yes. 



Mr. Bliley. Isn't it true that you also concluded from your re- 

 search at Philip Morris that if there is a physiological tolerance to 

 nicotine, it is like that developed to that of saccharine or caffeine? 



Mr. Mele. I don't know that tolerance develops to saccharine. I 

 do know that tolerance develops to caffeine, yes. 



Mr. Bliley. And you reported that to your superiors? 



Mr. Mele. Tolerance to saccharine — I'm sorry, tolerance to caf- 

 feine, tolerance to nicotine, tolerance to alcohol, pentobarbital, it's 

 pretty much the same. Different mechanisms perhaps, physio- 

 logical mechanisms in the liver, but the general conditions are the 

 same, yes. 



Mr. Bliley. This subcommittee had been told by some witnesses 

 that the evidence is clear that nicotine alone is an addicting sub- 

 stance, in part because ceasing the use of nicotine causes physio- 

 logical withdrawal symptoms. Isn't it true that while you were em- 

 ployed at Philip Morris, you told your superiors that your research 

 showed that stopping nicotine use does not result in physiological 

 withdrawal? 



Mr. Mele. In rats, yes. 



Mr. Bliley. While you were employed at Philip Morris, you also 

 did experiments to determine if stopping acetaldehyde use caused 

 physiological withdrawal symptoms. And while you were working 

 at Philip Morris, you told your superiors that your experiments 

 found no physiological withdrawal resulted from stopping the use 

 of acetaldehyde, isn't that correct? 



Mr. Mele. Yes. In our experiments in rats. 



