Tobacco Documents Online

JW0110.92 Jim Walker Support to XB - Effect of Levulinic and other Acids on the Perception of Nicotine - Status: Jim Walker and Roger Jennings spent the day at the lab of Dr. Don Warren at UNC-CH to conduct practice sessions in which mixtures of levulinic acid and nicotine were presented. Olfactometer modifications and changes needed to conduct the mixture experiments had been accomplished and several minor problems with the software had been corrected. These mixture experiments, in which the effect of three different levulinic acid concentrations (one just below threshold) on the perception of a range of nicotine concentrations are being quantified, were commenced and are now 1/3 complete. Significance: This research on the effects of levulinic and other acids on the intensity and/or pleasantness of sensations from nasally presented vapor phase nicotine is an important part of our effort to understand the sensory properties of nicotine in smoke. Next Steps: Over the next 5-6 weeks, the mixture studies will be completed. Contacts: Roger Jennings (5569), Jim Walker (2200) Support to XB - Effect of Levulinic and other Acids on the Olfactory Nerve Response to Nicotine Status: Jim Walker assisted Roger Jennings in the preparation of a presentation summarizing progress to date on the pigeon olfactory nerve electrophysiology experiments. Results of mixture and pre- treatment experiments, conducted investigate the effects of levulinic acid on nicotine perception, will be summarized and the rationale for future experiments will be outlined. Significance: This work is part of a systematic effort to understand the relationships between smoke chemistry, sensory nerve stimulation and perception of smoke. A key part of this effort is an understanding of the relative importance of nicotine (versus other smoke components) as a stimulus for different parts of the upper airway (from nose to tracheo-bronchial region). Next Steps: To elucidate the basis (e.g. nerve fatigue vs. change in pH of mucus) of the finding that levulinic acid pre-treatment reduces olfactory responses to nicotine, we will determine the effect of amyl acetate pre-treatment on responses to nicotine. Contacts: Roger Jennings (5569), Jim Walker (2200)

Product Understanding - Olfactory/Trigeminal Roles in Responses to Odorants Status: Dr. Amelia Drake, an ENT physician at UNC-CH with whom we collaborate, has recruited two "new" anosmics for testing at BGTC. Both of these individuals have sustained apparently complete loss of olfactory connections between nose and brain as an unavoidable consequence of medically necessary surgery. Significance: Testing of subjects that have lost olfactory connections by non-traumatic means provides a concrete means of assessing the relative roles of the olfactory and trigeminal nerves in the perception of odor and irritation. With these subjects we plan to present somewhat higher odorant concentration ranges, to ensure that we obtain more suprathreshold irritation ratings than in earlier testing. Next Steps: Permission to conduct this research will be sought at the next HRRC meeting. Contacts: Tom Guy (5175), Roger Jennings (5569), Jim Walker (2200) Miscellaneous An up-to-date collection of over 50 papers on publication bias, collected by Mr. Roger Jennings, were barcoded and entered into the R&D publication database by Ms. Nell Sizemore. These publications were used recently by RJRT scientists in their response to claims by the EPA on the adverse health affects of ETS. A book, titled "The Human Sense of Smell", has been published which contains a chapter by Jim Walker and Roger Jennings titled "Comparison of odor perception in humans and animals." The chapter describes the olfactory prowess of a variety of animals and presents the latest information on ability of humans to detect odorants and to perceive the strengths of suprathreshold concentrations and to discriminate qualitatively between odorants. JW0124.91 Jim Walker Support to XB - Effect of Levulinic and other Acids on the Perception of Nicotine - Status: Dr. Don Warren's laboratory completed almost all of the testing of 8 subjects in response to a range of nicotine concentrations in the presence or absence of a concentration of levulinic acid that, for each subject, was of low to moderate perceptual intensity. That is, odor and perceived nasal irritation ratings of response to nicotine alone were compared to those of

levulinic acid-nicotine mixtures. Significance: This research on the effects of levulinic and other acids on the sensations arising from nasally presented vapor phase nicotine is an important part of our effort to understand the sensory properties of nicotine in smoke. Next Steps: Upon completion of all of the test sessions with this mid-range levulinic acid concentration, the data will be summarized and submitted to Walker and Jennings. Then the final, and highest, levulinic acid concentration will be used in this same mixture paradigm. Contacts: Roger Jennings (5569), Jim Walker (2200) Support to XB - Effect of Levulinic and other Acids on the Olfactory Nerve Response to Nicotine Status : Roger Jennings and Tom Guy prepared the pigeon facility for upcoming electrophysiology experiments. The olfactometer was reconfigured to deliver amyl acetate instead of levulinic acid. In a test run, the olfactometer was checked for accuracy. Significance: This work is part of a systematic effort to understand the relationships between smoke chemistry, sensory nerve stimulation and perception of smoke. A key part of this effort is an understanding of the relative importance of nicotine (versus other smoke components) as a stimulus for different parts of the upper airway (from nose to tracheo-bronchial region). The pigeon model was developed to provide basic information on how levulinic acid affects nerve activity resulting from the presence of nicotine. The mixture study essentially duplicated the molar ratio of nicotine-to-levulinic acid in mainstream smoke to determine if the smoothing effect observed by smokers could be due to a general reduction in nerve traffic to the brain. Another means by which levulinic acid could cause a smoothing effect in cigarette smoke is by protonating nicotine that is deposited in the mucus overlying sensory receptors. Use of the pre-exposure paradigm with the pigeon olfactory nerve model offered a valuable way to evaluate this mechanism. Next Steps: To elucidate the basis (e.g. nerve fatigue vs. change in pH of mucus) of the finding that levulinic acid pre-treatment reduces olfactory responses to nicotine, we will determine the effect of amyl acetate pre-treatment on responses to nicotine. Contacts: Roger Jennings (5569), Jim Walker (2200) Support to XB - Critical Review of Biological Basis of

Sensory Stimulation by Cigarette Smoke Status: Tom Guy completed most of the ordering of research papers needed by Jim Walker and others for the preparation of an internal critical review paper of the literature on sensory stimulation of the respiratory airway (from the nose to the lung) by cigarette smoke. Bibliographic information on all of these papers are being entered into the BASIS system on the VAX by Sandi Ingram. Significance: This work is part of a systematic effort to understand the relationships between smoke chemistry, sensory nerve stimulation and perception of smoke. A key part of this effort is optimum use of the available information that others have gathered concerning the stimulation of sensory surfaces, in both humans and animals, by whole smoke or smoke components. Next Steps: For each part of the airway, available information will be summarized. For example, the extensive amount of published data on the pharmacological and neural mechanisms underlying the responses of the nose to nicotine and other smoke components will be illustrated. A draft of this review will be completed during May ' 92 . Contacts: Roger Jennings (5569), Jim Walker (2200), Tom Guy (5175), Sandi Ingram (0995) Product Understanding - Sensory Properties of Cigarettes with and without Nasal Stimulation Status: Jim Walker met with Harvey Gordin, Dan Kurtz, Millie Wong, Joyce Miller, and Cindy Stewart to evaluate a ballot to be used in an experiment to examine the role of nasal stimulation by smoke in the sensory properties of cigarettes. A few minor changes in the ballot were suggested by this group, based on the smoking of a Salem Lights product with and without nose "clips". Significance: This experiment is a joint Biobehavioral Division- SED-Flavor Division effort to better understand the basis of the "taste" of our cigarettes. We want to understand which attributes are most dependent on nasal (olfactory and/or trigeminal) input and relate that learning to information about smoke composition and sensory properties of individual smoke components. Initially, the focus will be on understanding the role of "smell" for nicotine and menthol. Next Steps: In approximately three weeks, the first experiment in this area will commence. A pair of products differing primarily in menthol level and a second pair differing primarily in nicotine level will be smoked with and without nose clips. Ballot ratings will be analyzed to determine the effects, on different sensory attributes, of preventing nasal stimulation. Contacts: Jim Walker (2200), John Reynolds (4390)