A Quantitative Structure Activity Analysis on the Relative Sensitivity of the Olfactory and the Nasal Trigeminal Chemosensory Systems

Abstract

We have applied a quantitative structure-activity relationship (QSAR) approach to analyze the chemical parameters that determine the relative sensitivity of olfaction and nasal chemesthesis to a common set of volatile organic compounds (VOCs). We used previously reported data on odor detection thresholds (ODTs) and nasal pungency thresholds (NPTs) from 64 VOCs belonging to 7 chemical series (acetate esters, carboxylic acids, alcohols, aliphatic aldehydes, alkylbenzenes, ketones, and terpenes). The analysis tested whether NPTs could be used to separate out "selective" chemosensory effects (i.e., those resting on the transfer of VOCs from the gas phase to the receptor phase) from "specific" chemosensory effects in ODTs. Previous work showed that selective effects overwhelmingly dominate chemesthetic potency whereas both selective and specific effects control olfactory potency. We conclude that it is indeed possible to use NPTs to separate out selective from specific effects in ODTs. Among the series studied, aldehydes and acids, except for formic acid, show clear specific effects in their olfactory potency. Furthermore, for VOCs whose odor potency rests mainly on selective effects, we have developed a QSAR equation that can predict their ODTs based on their NPTs.

Human olfactory detection of homologous n-alcohols measured via concentration–response functions

“…The model is not only descriptive and predictive (Abraham MH et al, 2001), it also has mechanistic significance. It quantifies the characteristics and relative role of transfer processes governing the transport of odorants from the air phase, when they enter the nose, to the biophase where reception takes place (Abraham MH et al, 2007). In other words, the QSAR quantifies the physicochemical properties that make a VOC a potent (low threshold) or a weak (high threshold) odorant, and also serves to define the complementary properties of the receptor environment .…”

“…Even fewer have measured these functions for a number of odorants in the context of addressing structure-activity, e.g., (Cometto-Muñiz JE et al, 2004;Wise PM et al, 2007). Our own previous work has included measuring odor thresholds along and across homologous series, using a uniform procedure , with the goal of studying enough odorants to propose a structureactivity model for the short-term (1-3 sec) odor detection of volatile organic compounds (VOCs) by humans Abraham MH et al, 2007). Compared to other thresholds in the literature (Devos M et al, 1990), our values captured well the relative odor potency across VOCs but lay at the high end of the reported range.…”

Prediction of Partition Coefficients and Permeability of Drug Molecules in Biological Systems with Abraham Model Solute Descriptors Derived from Measured Solubilities and Water-to-Organic Solvent Partition Coefficients

“…To date mathematical expressions have been reported for predicting water-to-organic solvent partition coefficients and solubilities in more than 70 organic solvents, air-to-tissue and blood-to-tissue partition coefficients for 5 human and rat tissues, water-to-human skin and blood-to-rat/rabbit skin partitions, human skin permeability coefficients, and rat (Zhao et al, 2003) and human (Zhao et al, 2002) intestinal absorption. Expressions are also available for estimating Draize rabbit eye test scores for pure liquids and eye irritation thresholds in humans , odor detection thresholds and nasal pungency of volatile organic compounds (VOCs) (Abraham et al, 2007b), and the minimum alveolar concentration (MAC) for inhalation anesthetics in rats (Abraham et al, 2008b). The number of derived Abraham model correlations is expected in future years as more experimental data becomes available.…”

An assessment of air quality reflecting the chemosensory irritation impact of mixtures of volatile organic compounds

“…VOCs have been divided into those that act by a 'physical' and those that act by a 'chemical' mechanism (Abraham et al, 2010a;Alarie et al 1995Alarie et al , 1996Alarie et al , 1998 noting that in the mouse assay test, it was possible to account for the RD 50 end point only for VOCs that acted by a 'physical' mechanism. A rather different terminology has been used in classifying the effect of VOCs on odor detection thresholds, ODTs (Abraham et al 2007). VOCs were divided into those that acted by 'physical' effects (e.g., transfer driven effects in which small structural changes in VOC evoke predictable, and rather small, changes in biological activity) and 'specific' effects (e.g., those in which small structural changes in the VOC may evoke less predictable, and often large, changes in biological activity).…”