title: An analysis of nasal irritation thresholds using a new solvation equation.
abstract: In the present paper we have developed a quantitative structure-activity relationship (QSAR) equation for nasal pungency caused by nonreactive volatile organic compounds (VOCs). Our QSAR was developed upon previously published nasal pungency thresholds in anosmics, i.e., patients lacking a sense of smell and thus responding only to sensory irritation evoked by trigeminal nerve stimulation. The reported solvation equation, which fits the data with considerable precision, describes sensory potency in terms of interaction via electron pairs, dipolarity/polarizability, hydrogen bond acidity and basicity, and hydrophobicity. It correspondingly suggests relevant physicochemical properties of the biophase where the sensory response is brought about. The equation implies that in the range of molecular size where nonreactive VOCs can produce any pungency, transport from the air to the biophase strictly determines potency. In this respect, the potency of nasal pungency shares characteristics with the ability of VOCs to cause narcosis and anesthesia.
authors.affiliation: Christopher Ingold Laboratories, Department of Chemistry, University College London, London, United Kingdom.
authors.forename: M H
authors.initials: MH
authors.lastname: Abraham
authors.forename: J
authors.initials: J
authors.lastname: Andonian-Haftvan
authors.forename: J E
authors.initials: JE
authors.lastname: Cometto-Muñiz
authors.forename: W S
authors.initials: WS
authors.lastname: Cain
mesh_terms: D000328:Adult; D000368:Aged; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005260:Female; D006801:Humans; D007509:Irritants / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008970:Molecular Weight; D009297:Nasal Mucosa / Q000187:drug effects*; D000857:Olfaction Disorders / Q000523:psychology; D012684:Sensory Thresholds / Q000187:drug effects; D013329:Structure-Activity Relationship; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D007509:Irritants