Draize Rabbit Eye Test Compatibility with Eye Irritation Thresholds in Humans: A Quantitative Structure-Activity Relationship Analysis

Abraham, Michael H. and Hassanisadi, Mostafa and Jalali-Heravi, Mehdi and Ghafourian, Taravat and Cain, William.S. and Cometto-Mun˜iz, J.Enrique (2003) Draize Rabbit Eye Test Compatibility with Eye Irritation Thresholds in Humans: A Quantitative Structure-Activity Relationship Analysis. Toxicological Sciences, 76 (2). pp. 384-391. ISSN 1096-6080 . (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1093/toxsci/kfg242

Abstract

Draize rabbit eye test scores, as modified maximum average score (MMAS), for 68 pure bulk liquids were adjusted by the liquid-saturated vapor pressure P°. These 68 adjusted scores, as log (MMAS/P°), were shown to be completely equivalent to eye irritation thresholds (EIT), expressed as log (1/EIT), for 23 compounds in humans. Thus, for the first time the Draize eye test in rabbits for pure bulk liquids is shown to be perfectly compatible with eye irritation thresholds in humans. The total data set for 91 compounds was analyzed by the general solvation equation of Abraham. Values of log (MMAS/P°) or log (1/EIT) could be fitted to a five-parameter equation with R2 0.936, SD 0.433, AD 0.000, and AAD 0.340 over a range of 9.6 log units. When divided into a training set of 45 compounds, the corresponding equation could be used to predict the remaining 46 compounds in a test set with AD –0.037 and AAD 0.345 log units. Thus, the 91-compound equation can now be used to predict further EIT values to around 0.4 log units. It is suggested that the mechanism of action in the Draize test and in the human EIT involves passive transfer of the compound to a biophase that is quite polar, is a strong hydrogen bond base, a moderate hydrogen bond acid, and quite hydrophobic. The biophase does not resemble water or plasma, but resembles an organic solvent such as N-methylformamide.

Item Type: Article
Subjects: Q Science
Q Science > QD Chemistry
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Taravat Ghafourian
Date Deposited: 20 Oct 2008 13:28
Last Modified: 09 Apr 2014 11:08
Resource URI: http://kar.kent.ac.uk/id/eprint/10753 (The current URI for this page, for reference purposes)
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