An approach to the prediction of chemosensory effects of volatile organic compounds on humans

The aim of this project was to construct equations to predict the mechanism of threshold values of sensory irritation (nose and eye irritation) caused by Volatile Organic Compounds (VOCs). Mathematical models were established to predict Nasal pungency thresholds (NPTs) and odour detection thresholds (ODTs). Firstly, the Abraham Solvation Equation was used to determine the octanol/water partition coefficient (log Poct) for fluorescein. A similar equation was used to characterize several Gas-Liquid Chromatography (GLC) stationary phases. Abraham descriptors were determined for several VOC compounds using data obtained from experiments using GLC and data on water-solvent partition coefficients. The QSAR analysis on NPTs and ODTs revealed that "selective" processes (i.e., chemically-broad, transfer driven effects) overwhelmingly dominate chemesthetic detection, whereas both selective and "specific" (i.e., chemically-narrow, ligand-receptor interactions) processes control olfactory potency. To understand further the nature of the chemical factors that influence ODT values, the possibility was explored that NPT values could be used to estimate "selective" effects in ODTs. In the present study, concentration-detection, i.e., detectability, functions for the human olfactory detection of some chemical vapours of diverse chemical structures were analyzed. The functions cover the complete peri-threshold range from chance to almost perfect detection and provide much more information than can be conveyed by a single "threshold value". These odour functions have been modeled with a uniform approach: a simplified sigmoid equation, y = 1 / (1 + e*"0), and have been correlated with the set of up to five physicochemical descriptors taken from the Abraham solvation equation that has quite successfully described the simpler "odour threshold" and "nasal pungency" psychophysical outcome. Previous studies of ocular and nasal chemesthetic thresholds along and across homologous chemical series have suggested the existence of a "cut-off, i.e., a point where a homolog fails to stimulate even at vapor saturation. All larger homologs fail as well. The present study sought, first, to identify the particular cut-off member along homologous alkylbenzenes and 2-ketones and, second, to probe the likely basis for the effect