Chemical Boundaries for Detection of Eye Irritation in Humans from Homologous Vapors

Abstract

In a series of experiments, we looked at a "cutoff" effect for the detection of eye irritation from neat vapors of homologous n-alkylbenzenes and 2-ketones. Stimuli comprised pentyl, hexyl, and heptyl benzene, 2-dodecanone, and 2-tridecanone, presented to each eye at 4 and 8 l/min for 6 sec, using a three-alternative forced-choice procedure against blanks. Detection probability corrected for chance (i.e., detectability) decreased with carbon chain length such that heptyl benzene and 2-tridecanone were virtually undetectable, irrespective of flow rate to the eye. Heating both stimuli sources to 37 degrees C (body temperature) from 23 degrees C (room temperature) increased vapor concentration by 5.0 and 6.9 times, respectively, for heptyl benzene and 2-tridecanone. Still, both chemicals failed to show increased detection for 13 of the 21 participants. In addition, plots of experimentally measured and calculated eye irritation thresholds as a function of carbon chain length for each series indicated that, based on the trend, the concentration of the two cutoff homologs at 37 degrees C should have been high enough to allow detection. Taken together, the results suggest that these cutoffs rest on limitations related to the dimension of the molecules rather than on limitations related to their vapor concentration. For example, the stimulus molecule could exceed the size that allows it to fit into the receptor pocket of a receptive protein. Plots of calculated molecular dimensions across homologous alkylbenzenes, from ethyl to dodecylbenzene, and across 2-ketones, from 2-octanone to 2-octadecanone, provided additional support to the above conclusion.

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

“…In previous studies, only one or two concentrations per chemical were tested (ComettoMuñiz et al 2005b;Cometto-Muñiz et al 2006). These corresponded to the saturated vapor at 23°C (room temperature), at 37°C (body temperature) or both.…”

“…The cut-off points reported along these and previous series studied (ketones, alkylbenzenes, aldehydes, and carboxylic acids) (Cometto-Muñiz et al 2005b;Cometto-Muñiz et al 2006;Cometto-Muñiz et al 2007) represent the average at the group level.…”

“…Despite the prevalence of selective mechanisms to account for eye irritation potency from vapors, recent studies of homologous chemical series have shown the emergence of a cut-off point in chemesthetic detection (Cometto-Muñiz et al 2005b;Cometto-Muñiz et al 2006). In other words, a homolog is reached in the series that cannot be detected by eye irritation, even at vapor saturation.…”

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

“…What is evident (Cometto-Muñiz et al, 1998b;2005a;2005c;2006;2007a;2007b;2008b;Cometto-Muñiz et al, 2010;Cain et al, 2006) is that this increase in sensory irritation potency does not simply carry on along a homologous series, but a homolog is reached where the potency declines to zero. For each of the alcohols in Table 1, as the gaseous concentration of alcohol is increased, Q in the psychometric plots approaches unity.…”

“…We start with the psychometric plots obtained from the probability of sensory irritation detection, Q, of a given VOC as a function of its gaseous concentration, log P with P in ppm (Cometto-Muñiz et al, 1999;2001a;2002;2004a;2004b;2007b;2008;Cain et al, 2006). As for the determination of thresholds, this involves a panel of human subjects.…”