title: Temporal integration in nasal lateralization of homologous propionates.
abstract: For nasal irritation from volatile chemicals, a version of Haber's rule (k = C(n)T) can model the trade-off between concentration (C) and duration of exposure (T) to achieve a fixed sensory impact, e.g. threshold-level irritation or a fixed suprathreshold intensity. The term k is a constant. The exponent, n, represents how well the system integrates over time. An exponent of 1 indicates complete temporal integration: an x-fold increase in stimulus duration exactly compensates for cutting the concentration 1/x. An exponent greater than 1 indicates incomplete temporal integration: more than an x-fold increase in duration is needed. In a previous study of homologous alcohols, n varied systematically with number of methylene units: integration became more complete as the length of the carbon chain increased. To explore the generality of this finding, we tested homologous esters that differ in the number of methylene units: n-ethyl propionate, n-propyl propionate, and n-butyl propionate. Nasal lateralization was used to measure irritation thresholds. Human subjects received a fixed concentration of a single compound within each experimental session. Stimulus duration was varied to find the briefest stimulus that caused lateralizable irritation. Concentration and compound varied across sessions. Consistent with results with n-alcohols, integration became more complete as the number of methylene units increased. Lipid solubility varies with chain length; hence, solubility in the nasal mucosa may play a role in the dynamics of irritation. Further, preliminary analyses suggest that, for data pooled across both chemical series, n varies systematically with molecular parameters related to solubility and diffusion.
authors: Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104-3308, USA. pwise@monell.org
authors: Paul M
authors: PM
authors: Wise
authors: Sean E
authors: SE
authors: Toczydlowski
authors: Kai
authors: K
authors: Zhao
authors: Charles J
authors: CJ
authors: Wysocki
mesh_terms: D000293:Adolescent; D000328:Adult; D000438:Alcohols / Q000378:metabolism; D000465:Algorithms; D000704:Analysis of Variance; D002138:Calibration; D016208:Databases, Factual; D005260:Female; D006801:Humans; D019570:Inhalation Exposure; D007509:Irritants / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D009296:Nasal Cavity / Q000378:metabolism*; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism; D011422:Propionates / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D055815:Young Adult
chemical_list: D000438:Alcohols; D007509:Irritants; D011422:Propionates