A quantitative structure-activity relationship (QSAR) for a Draize eye irritation database

A collection of data on the Draize rabbit eye test (Cronin et al., 1994) has been analysed using a set of physicochemical descriptors that we have previously put forward. These descriptors are compound (or solute) parameters as follows: R(2) is an excess molar refraction, pi(2)(H) is the polarizability/dipolarity Sigma alpha(2)(H) and Sigma beta(2)(H) are the effective hydrogen bond acidity and basicity, and logL(16) is a descriptor where L(16) is the vapour-hexadecane solubility at 25 degrees C. When applied to Draize eye scores (DESs) for 38 pure bulk liquids, a very poor equation was obtained. However, when the DES values were correlated as log(DES/P(o)), where P(o) is the liquid vapour pressure, an excellent equation was found. On transforming the calculated log(DES/P(o)) values back to calculated DES values, there was good agreement with the original DES values. It is suggested that the DES/P(o) values refer to transfer of the irritant from the vapour phase to the biophase, and that the success of the present treatment demonstrates that for the pure liquids studied, a major factor in the Draize eye test is simply the transfer of the liquid (or the vapour) to the biological system. (C) 1998 Elsevier Science Ltd. All rights reserved.