Abraham, Michael H., Hassanisadi, Mostafa, Jalali-Heravi, Mehdi, Ghafourian, Taravat, Cain, William.S., 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. (doi:10.1093/toxsci/kfg242) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:10753)
The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. | |
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 |
---|---|
DOI/Identification number: | 10.1093/toxsci/kfg242 |
Subjects: |
Q Science Q Science > QD Chemistry |
Divisions: | Divisions > Division of Natural Sciences > Medway School of Pharmacy |
Depositing User: | Taravat Ghafourian |
Date Deposited: | 20 Oct 2008 13:28 UTC |
Last Modified: | 16 Nov 2021 09:49 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/10753 (The current URI for this page, for reference purposes) |
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