Studies of homologous series of environmental vapors have shown that their chemesthetic (i.e., sensory irritation) potency increases with carbon chain length (that is, their detection thresholds decrease) until they reach a homolog that fails to be detected, even at vapor saturation. All ensuing homologs cannot be detected either. In this investigation, we measured concentration-detection (i.e., psychometric) functions for ocular chemesthesis from homologous alkylbenzenes (pentyl, hexyl, and heptyl benzene) and 2-ketones (undecanone, dodecanone, and tridecanone). Using a three-alternative forced-choice procedure against air blanks, we tested a total of 18 to 24 subjects, about half of them females, average age 31 years, ranging from 18 to 56 years. Stimuli were generated and presented by a computer-controlled, vapor delivery device whose output was quantified by gas chromatography. Exposure time was 6 s and delivery flow 2.5 L/min. Within the context of present and previous findings, the outcome indicated that the functions for heptylbenzene and 2-tridecanone reached a plateau where further increases in concentration did not enhance detection. We conclude that: a) a cut-off point in ocular chemesthetic detection is reached along homologous alkylbenzenes and 2-ketones at the level of heptylbenzene and 2-tridecanone, respectively, and b) the observed effect rests on the homologs exceeding a critical molecular size (or dimension) rather than on them failing to achieve a high enough vapor concentration.

As part of our systematic exploration of chemical determinants for the olfactory potency of vapors towards humans, we measured concentration-detection functions for the odor of the homologous n-alkylbenzenes toluene, ethylbenzene, butylbenzene, hexylbenzene, and octylbenzene. A vapor delivery device based on dynamic olfactometry and calibrated by gas chromatography, served to test groups of 16 to 17 participants. Subjects were young adults from both genders, normosmics, and nonsmokers. Odor functions were tightly modeled by a sigmoid (logistic) function, both at the group and the individual level. Odor detection thresholds (ODTs), defined as the concentration producing a detectability halfway between chance and perfect detection, decreased with alkyl chain length from toluene (79 ppb) to butylbenzene (2.5 ppb), and then increased form butyl to octylbenzene (89 ppb). The "U"-shaped trend of ODTs as a function of alkyl chain length indicated a loss of odor potency beyond a certain molecular size, a phenomenon recently described for chemosensory irritation (chemesthesis) and that will need consideration in structure-activity models of chemosensory potency. Interindividual ODTs' variability for any single odorant amounted to one order of magnitude, in agreement with recent studies of other homologous series but quite smaller than commonly depicted.

We measured concentration-detection (i.e., psychometric) odor functions for the homologous ketones propanone (acetone), 2-pentanone, 2-heptanone, and 2-nonanone. Under a forced-choice procedure, stimuli were presented via an 8-channel air-dilution olfactometer that allowed natural sampling of the odorant and whose output was quantified by gas chromatography. Subjects (17-22 per compound) comprised young adults from both genders, all normosmics and nonsmokers. A sigmoid (logistic) equation tightly fitted group and individual functions. The odor detection threshold (ODT) was the concentration detectable at halfway (P=0.5) between chance (P=0.0) and perfect (P=1.0) detection. Odor sensitivity increased (i.e., thresholds decreased) from acetone to heptanone, remaining constant for nonanone. This relative trend was also observed in previous work and in odor thresholds compilations, but the absolute ODTs obtained here were consistently at the lower end of those reported before. Interindividual variability of ODTs was about 1 order of magnitude. These odor functions measured behaviorally in humans were obtained at vapor concentrations 1000 times lower than functions measured via activation, with similar 2-ketones, of receptor neurons converging into individual olfactory glomeruli of mice, visualized with calcium sensitive dyes. Odorant concentrations presented as vapors (as in behavioral studies) and those presented as liquids (as in cellular/tissue studies) can be rendered equivalent via liquid-vapor partition coefficients and, then, compared in relative olfactory potency. These comparisons can reveal how sensitivity is progressively shaped across levels of the neural pathway.

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 (s) 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.

In a series of experiments, we have explored the rules of olfactory detection agonism between the odorants butyl acetate and toluene. First, we obtained the concentration-detection function for the odor of the individual compounds. Second, we selected the concentrations of the two substances producing three levels of detectability (low, medium, and high) and, for each level, tested the comparative detectability of the two single chemicals and three mixtures of varying proportions. In each case, the mixtures were prepared in such way that, if a rule of complete dose addition were to hold, all five stimuli (two single, three mixtures) should be equally detected. The outcome revealed complete dose addition at relatively low detectability levels but fell short of dose addition at medium and high levels. A recent analogous study on trigeminal chemosensory detection via nasal pungency and eye irritation of these same stimuli have shown a similar trend but showed a less dramatic loss of dose additivity with increased detectability. These results on detection of mixtures suggest a more selective window of chemical tuning (i.e., less dose-addition) in olfaction than in trigeminal chemoreception.