The long-term objective of the proposal is to define the physicochemica! and structural properties of volatile organic.compounds (VOCs) that govern their olfactory and trigeminal (i.e., chemesthetic or chemical sensory irritation) detectability by humans. Chemesthetic detection will include eye irritation and nasal localization (i.e., the ability to determine whether the VOC was presented to the left or right nostril when air is simultaneously presented to the contralateral nostril). Odor and irritation figure prominently among the adverse effects in certain environments of questionable air quality, both indoors (e.g., sick building syndrome and occupational settings) and outdoors (e.g., vicinity of animal farm operations, and of biosolids and wastewater treatment plants). Ameliorating such effects rests heavily in understanding the physicochemical determinants of the chemosensory potency of VOCs and the detectability of mixtures. Here, we propose to use a dynamic vapor delivery device ? designed, built, and tested in our lab ? to measure chemosensory detection of individual VOCs in terms of concentration-detection (i.e., psychometric) functions spanning the range from chance to virtually perfect detection. {The vapor delivery device was conceived and has so far proven to deliver chemosensory results of direct environmental relevance, not just relative relevance of potency across VOCs.} Selection of VOCs for testing will follow criteria of systematic chemical change (e.g., homologous series). Psychometric functions {so obtained} will be modeled by a quantitative structure-activity relationship (QSAR) of {demonstrated} success in the past to account for a simpler chemosensory detection measurement, i.e., a """"""""threshold"""""""". As a result, using the QSAR we will now be able to predict {not just a relative threshold but whole} detectability functions of environmental significance for untested VOCs. We will use the information contained in the psychometric functions for individual chemicals {(information not provided by just thresholds)} to prepare up to eight-component mixtures of selected VOCs where each single component is present at a known detectability. Then, we will test the detectability of the mixtures vis-a- vis that of the constituents, aiming to uncover the degree of dose- and response-addition attained in mixtures as a function of level of detectability and chemical identity of individual components. The outcome will allow us to make inferences about the relative breadth of chemical tuning in human olfaction and chemesthesis.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Somatosensory and Chemosensory Systems Study Section (SCS)
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Davis, Barry
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Abraham, Michael H; Sánchez-Moreno, Ricardo; Cometto-Muñiz, J Enrique et al. (2012) An algorithm for 353 odor detection thresholds in humans. Chem Senses 37:207-18
Cometto-Muñiz, J Enrique; Abraham, Michael H (2010) Odor detection by humans of lineal aliphatic aldehydes and helional as gauged by dose-response functions. Chem Senses 35:289-99
Abraham, Michael H; Gola, Joelle M R; Cometto-Muñiz, J Enrique et al. (2010) Hydrogen bonding between solutes in solvents octan-1-ol and water. J Org Chem 75:7651-8
Abraham, Michael H; Sanchez-Moreno, Ricardo; Gil-Lostes, Javier et al. (2010) The biological and toxicological activity of gases and vapors. Toxicol In Vitro 24:357-62
Cometto-Muniz, J Enrique; Abraham, Michael H (2010) Structure-activity relationships on the odor detectability of homologous carboxylic acids by humans. Exp Brain Res 207:75-84
Cometto-Muñiz, J Enrique; Abraham, Michael H (2009) Olfactory psychometric functions for homologous 2-ketones. Behav Brain Res 201:207-15
Abraham, Michael H; Acree, William E; Cometto-Muñiz, J Enrique (2009) Partition of compounds from water and from air into amides. New J Chem 33:2034-2043
Cometto-Muñiz, J E; Abraham, M H (2009) Olfactory detectability of homologous n-alkylbenzenes as reflected by concentration-detection functions in humans. Neuroscience 161:236-48
Cometto-Muniz, J Enrique; Abraham, Michael H (2008) Human olfactory detection of homologous n-alcohols measured via concentration-response functions. Pharmacol Biochem Behav 89:279-91
Cometto-Muniz, J Enrique; Cain, William S; Abraham, Michael H et al. (2008) Concentration-detection functions for the odor of homologous n-acetate esters. Physiol Behav 95:658-67

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