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ToxSci Advance Access originally published online on June 4, 2007
Toxicological Sciences 2007 99(1):254-259; doi:10.1093/toxsci/kfm144
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Temporal Integration in Nasal Lateralization of Homologous Alcohols

Paul M. Wise1, Sean E. Toczydlowski and Charles J. Wysocki

Monell Chemical Senses Center, 3500 Market Street, Philadelphia, Pennsylvania 19104-3308

1 To whom correspondence should be addressed. Fax: (215) 898-2084. E-mail: pwise{at}monell.org.

Received April 10, 2007; accepted May 25, 2007


  Abstract

Through temporal integration, sensory systems accumulate stimulus energy, e.g., photons, acoustic energy, or molecules, over time to detect weaker signals than they otherwise could. Past studies found imperfect temporal integration in detection of nasal irritation: To maintain a fixed level of detection, one must increase stimulus duration by more than twofold to compensate for cutting concentration in half. Despite this generality, integration varied widely among compounds, from nearly perfect, i.e., an increase in duration of slightly more than twofold could compensate for cutting concentration in half, to highly imperfect. How do such differences relate to molecular parameters? Perhaps molecules that more readily dissolve into the lipid-rich perireceptor environment will accumulate, and therefore integrate, better over time. To test this hypothesis, studies compared temporal integration for three compounds that differ systematically in lipid solubility: n-ethanol, n-butanol, and n-hexanol. Subjects were healthy, adult humans. Nasal lateralization was used to measure irritation threshold. Subjects received a fixed concentration of a single compound within each experimental session, and stimulus duration was varied to find the briefest stimulus subjects could reliably lateralize. Concentration and compound varied across sessions. Consistent with the hypothesis, integration did become closer to perfect as lipid solubility increased. That just one molecular parameter can help predict degree of integration suggests that a structure-activity approach to understanding temporal integration shows promise.

Key Words: chemical irritation; pungency; chemesthesis; volatile organic compound; inhalation toxicology.


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