The Correlation and Prediction of VOC Thresholds for Nasal Pungency, Eye Irritation and Odour in Humans

Abraham, Michael H.; Gola, Jo&euml;lle M.R.; Cometto-Mu&ntilde;iz, J. Enrique; Cain, William S.

doi:10.1159/000049244

Cited by 17 publications

(27 citation statements)

References 35 publications

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“…This possibility is consistent with the success achieved by a QSAR model based on selective, rather than specific, chemical determinants of human chemesthetic potency (Abraham et al 2001), as noted in the Introduction. All chemesthetic receptors are thought to be proteins.…”

Section: Discussionsupporting

confidence: 86%

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

et al. 2007

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We measured concentration-detection (i.e., psychometric) functions for the eye irritation evoked by three homologous n-alcohols (1-nonanol, 1-decanol, and 1-undecanol) and two homologous acetates (nonyl and decyl acetate). A vapor delivery device based on a dynamic dilution of stimuli in nitrogen served to present various concentrations of each compound, including the undiluted vapor, to the subjects (n≥26).Delivered concentrations were quantified by gas chromatography. Detection probability (P) was assessed via a three-alternative, forced-choice procedure, and quantified on a scale ranging from P = 0.0 (chance detection) to P = 1.0 (perfect detection). Flowrate to the eye equaled 2.5 L/min and time of exposure was 6 sec. The functions for 1-undecanol and decyl acetate plateau at P ≈ 0.5 and P ≈ 0.25, respectively, such that further increases in concentration failed to increase detection notably. Thus, both series reached a break-point, or cut-off, in detection of ocular irritation. The present outcome provides additional evidence that the cut-off does not rest on the low vapor concentration of the homolog but, more likely, on the homolog exceeding a critical molecular dimension(s) which prevents it from interacting effectively with the appropriate receptors.

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Section: Discussionsupporting

confidence: 86%

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

et al. 2007

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“…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).…”

Section: Structure-activity Relationships: Previous Thresholds Vs Psmentioning

confidence: 99%

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

Cometto‐Muñiz

Abraham

2008

Pharmacology Biochemistry and Behavior

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We explored in humans concentration-detection functions for the odor of the homologous n-alcohols ethanol, 1-butanol, 1-hexanol, and 1-octanol. These functions serve to establish structure-activity relationships, and reflect the pharmacology of the olfactory sense at the behavioral level. We tested groups of 14 to 17 subjects (half of them females), averaging 31 to 35 years old. An 8-station vapor delivery device (VDD8) presented the stimulus under a three-alternative forced-choice procedure against carbon-filtered air. The VDD8 was built to meet the demands of typical human sniffs in a short-term (<5 sec) olfactory detection task, and to accurately control odorant generation, delivery, and stability. Actual stimulus concentration was quantified by gas chromatography before and during testing. The functions obtained were log normally distributed and were accurately modeled by a sigmoid (logistic) function, both at the group and at the individual level. Sensitivity to ethanol was the lowest and to 1-octanol the highest. Functions became steeper with increasing carbon chain length. For all alcohols the concentration detected halfway between chance and perfect detection (threshold) was at the ppb (or nM) level. Females were slightly more sensitive than males. Intersubject variability across participants was between one and two orders of magnitude. The present odor thresholds were lower than many reported in the past but their relative pattern across alcohols paralleled that in our earlier data and in compilation studies. A previously described quantitative structure-activity relationship for odor potency holds promise to model thresholds that, like those obtained here, best reflect the intrinsic sensitivity of human olfaction.

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“…VOCs led to creation of a QSAR in the form of a linear free energy relationship (LFER) [23][24][25]:…”

Section: Quantitative Structure-activity Relationship (Qsar)mentioning

confidence: 99%

Chemesthesis from volatile organic compounds: Psychophysical and neural responses

Cain

Lee

Wise

et al. 2006

Physiology & Behavior

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In Experiment 1, subjects sought to localize the nostril stimulated, left or right, in tests with nine esters (acetates, propionates, and butyrates) at concentrations meant to trigger chemesthesis (pungency, irritation). The task produced psychometric functions for chemesthetic detection unconfounded by olfactory sensations. The functions indicated a sharp transition from no detection to perfect detection, rather uniform across the esters, which themselves varied in potency by two log units. The correlation between the thresholds for the eight materials that yielded thresholds and predictions from a published linear free energy relationship (LFER) equaled 0.99. In Experiment 2, amplitude of the negative mucosal potential (NMP) was recorded from the septum. The resulting functions also increased with concentration sharply. Against a criterion amplitude of the NMP, thresholds measured in the first experiment (and predictions from the LFER) correlated 0.99. The NMP seems to offer an adequate objective measure of sensory irritation. The LFER, although effective predictively, could stand to have a parameter to anticipate that molecules beyond a certain size fail to trigger irritation. In the present case, a cut-off of chemesthetic potency occurred between butyl butyrate and hexyl butyrate for the group of subjects, with some variation of the boundary among individuals.

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The Correlation and Prediction of VOC Thresholds for Nasal Pungency, Eye Irritation and Odour in Humans

Cited by 17 publications

References 35 publications

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

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

Chemesthesis from volatile organic compounds: Psychophysical and neural responses

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