Abraham, MH; Kumarsingh, R; Cometto-Muniz, JE; Cain, WS

Archives of Toxicology [Arch. Toxicol.], vol. 72, no. 4, pp. 227-232, Mar 1998

Nasal pungency thresholds (NPT) in man have been determined by Cometto-Muniz and Cain for 44 varied compounds, including esters, aldehydes, ketones, alcohols, carboxylic acids, aromatic hydrocarbons and pyridine. With the exclusion of acetic acid, 43 of these NPT values are well correlated through the general linear free energy equation of Abraham, leading to the algorithm, log(1/NPT) = -8.519 + 2.154 pi sub(2) super(H) + 3.522 capital sigma alpha sub(2) super(H) + 1.397 capital sigma beta sub(2) super(H) + 0.860 logL super(16) n = 43, r super(2) = 0.955, SD = 0.27, F = 201 (i) where the independent variables are solute descriptors: pi sub(2) super(H) is the dipolarity/polarizability, capital sigma alpha sub(2) super(H) and capital sigma beta sub(2) super(H) are the overall or effective hydrogen-bond acidity and basicity, and L super(16) is the solute Ostwald solubility coefficient on hexadecane at 25 degree C. Surprisingly, the aliphatic aldehydes and carboxylic acids fit the correlation and with respect to nasal pungency thresholds in man for brief (1-3 s) presentations must be regarded as 'nonreactive' compounds. It is suggested mere transport of the compound from the air stream to the receptor area largely determines the potency to produce pungency. Various chemical properties of the receptor area are deduced from the coefficients in Eq. i.