Using representative members of each of three homologous series of chemicals-ketones, acetates and alcohols-we measured nasal pungency thresholds in anosmics via two stimulus-delivery systems. The first system consists of the fairly commonly used 270 ml, plastic 'squeeze bottles'. The second system consists of 1900 ml, glass vessels with Teflon tubing and nose-pieces. Although bulkier and more susceptible to mechanical breakage, the glass vessels possess advantages that can allow them to provide 'environmentally realistic' chemosensory thresholds, i.e. thresholds closer in absolute values to those that might be obtained under whole-body exposures. Such advantages include a larger volume of the vapor-source to accommodate whole sniffs, and a tight nose-nose-piece connection to avoid stimulus dilution. The outcome revealed that, for every chemical, the glass vessels provided nasal pungency thresholds significantly lower than those provided by the squeeze bottles. The difference amounted, on average, to a factor of 4.6, though the relative potency of the compounds remained the same under both systems. Additionally, when tested with the highest homologues used here, namely, octyl acetate and 1-octanol, anosmics using the glass vessels had little or no difficulty achieving the criterion for threshold whereas they did have difficulty when using the squeeze bottles.

We measured psychometric (i.e. concentration-response) functions for the detection of odor, nasal pungency and eye irritation from butyl acetate and toluene. Olfactory detection was measured in subjects with normal olfaction (i.e. normosmics) for whom nasal trigeminal detection does not interfere because it requires much higher concentrations. Nasal trigeminal detection, called nasal pungency, was measured only in subjects lacking olfaction (i.e. anosmics) in order to avoid odor interference. Ocular trigeminal detection, called eye irritation, was measured in both groups. The method employed entailed a two-alternative, forced-choice procedure with presentation of increasing concentrations. The outcome showed, for both chemicals, similar ocular trigeminal chemosensitivity in normosmics and anosmics and similar overall ocular and nasal trigeminal chemosensitivity. Olfactory sensitivity was much higher than both forms of trigeminal sensitivity by concentration differences of six and four orders of magnitude for butyl acetate and toluene, respectively. Detectability plots (i.e. detection performance vs log concentration) for the three sensory endpoints followed an S-shaped function with a middle range section that showed a robust linear fit (r > 0.94) on graphs of z-score vs log concentration. These detectability functions allow the calculation of olfactory and trigeminal thresholds at various levels of performance. At a point half-way between random and perfect detection, trigeminal and olfactory threshold concentrations were, respectively, 0.67 (+/-0.32) and 2.28 (+/-1.77) log units lower than those measured by us in the past for the same chemicals using an analogous procedure but under just one, fixed, level of performance. The available data suggest that, although considerably laborious, detectability functions provide chemosensory thresholds of closer relevance to environmentally realistic conditions (e.g. whole-body exposures).

To probe into the rules of trigeminal chemosensory agonism in a binary mixture of chemicals we measured, first, the detectability (i.e., psychometric) function for eye irritation and for nasal pungency of butyl acetate and toluene, singly. (To avoid olfactory biases, nasal pungency was measured in a group of anosmics, i.e., persons lacking a functional sense of smell.) Then, based on the detectability function obtained for the individual chemicals, we prepared mixtures where the 2 components varied in their relative proportions but, if a simple rule of complete sensory agonism (in the sense of dose-additivity) were to hold, the mixtures should be as detectable as the reference concentration of each of the single chemicals. For both trigeminal endpoints (i.e., eye irritation and nasal pungency), the results showed that stimuli of relatively low detectability did show complete sensory agonism, whereas stimuli of relatively high detectability fell short of complete sensory agonism when compared with the detectability of the single substances. Further testing of additional binary and higher order mixtures will confirm whether or not a structure-activity model of trigeminal chemosensory impact of single chemicals, based on selected physicochemical parameters of the stimuli, can also be applied to chemical mixtures.