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Draize rabbit eye test compatibility with eye irritation thresholds in humans: a quantitative structure-activity
Michael H Abraham1, Mostafa Hassanisadi, Mehdi Jalali-Heravi
1Department of Chemistry, University College London, London, England, UK. m.h.abraham@ucl.ac.uk
Toxicological Sciences : an Official Journal of the Society of Toxicology
|September 30, 2003
Summary
The Draize rabbit eye test scores, adjusted for vapor pressure, align perfectly with human eye irritation thresholds for pure liquids. This finding validates the rabbit test for predicting human responses, improving chemical safety assessments.
Area of Science:
- Toxicology
- Ocular Irritation Studies
- Chemical Safety Assessment
Background:
- The Draize rabbit eye test is a standard method for assessing chemical eye irritation.
- Predicting human eye irritation from animal test data can be challenging.
- Understanding the correlation between rabbit test scores and human responses is crucial for regulatory science.
Purpose of the Study:
- To establish the compatibility between Draize rabbit eye test scores and human eye irritation thresholds (EIT) for pure bulk liquids.
- To develop a predictive model for human eye irritation based on rabbit test data and physicochemical properties.
- To elucidate the biophysical mechanism underlying ocular irritation in both rabbits and humans.
Main Methods:
- Modified maximum average score (MMAS) from the Draize test for 68 pure bulk liquids were adjusted by vapor pressure (P).
- Adjusted scores (log MMAS/P) were compared with human eye irritation thresholds (EIT) (log 1/EIT) for 23 compounds.
- A quantitative structure-activity relationship (QSAR) analysis using Abraham's general solvation equation was performed on a dataset of 91 compounds.
Main Results:
- A strong equivalence was demonstrated between adjusted rabbit eye test scores and human eye irritation thresholds.
- A five-parameter quantitative structure-activity relationship model achieved high predictive accuracy (R² = 0.936) for the combined dataset.
- The model successfully predicted EIT values for a test set with high accuracy (AAD = 0.345 log units), enabling prediction of further EIT values within 0.4 log units.
Conclusions:
- The Draize eye test in rabbits is a reliable predictor of eye irritation thresholds in humans for pure bulk liquids.
- The developed QSAR model provides a robust tool for predicting ocular irritation potential, reducing the need for animal testing.
- The mechanism of ocular irritation involves passive transfer to a polar, hydrogen-bonding, and hydrophobic biophase, distinct from water or plasma.