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Toxicological Sciences 63, 233-244 (2001)
Copyright © 2001 by the Society of Toxicology

SAFETY EVALUATION

Ocular and Nasal Trigeminal Detection of Butyl Acetate and Toluene Presented Singly and in Mixtures

J. Enrique Cometto-Muñiz*,1, William S. Cain*, Michael H. Abraham{dagger} and Joelle M. R. Gola{dagger}

* Chemosensory Perception Laboratory, Department of Surgery (Otolaryngology), University of California, San Diego, 9500 Gilman Dr. – Mail Code 0957, La Jolla, California 92093–0957; and {dagger} Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, United Kingdom

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.

Key Words: eye irritation; nasal pungency; trigeminal nerve; butyl acetate; toluene; chemosensory detection; chemical mixtures; psychometric chemosensory functions.


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