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Draize rabbit eye test compatibility with eye irritation thresholds in humans: a quantitative structure-activity relationship analysis
journal contribution
posted on 2023-06-09, 03:26 authored by Michael H Abraham, Mostafa Hassanisadi, Mehdi Jalali-Heravi, Taravat Ghafourian, William S Cain, J Enrique Cometto-MuñizDraize 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.
History
Publication status
- Published
File Version
- Published version
Journal
Toxicological SciencesISSN
1096-6080Publisher
Oxford University PressExternal DOI
Issue
2Volume
76Page range
384-391Department affiliated with
- Biochemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2017-11-28First Compliant Deposit (FCD) Date
2017-11-28Usage metrics
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No categories selectedKeywords
acid; n methylformamide; organic solvent; wateranimal experiment; animal model; article; controlled study; data analysis; eye irritation; hydrogen bond; hydrophobicity; mathematical computing; nonhuman; passive transport; plasma; prediction; rabbit; scoring system; structure activity relation; toxicity testingAnimal Testing Alternatives; Animals; Dose-Response RelationshipDrug; Eye; Humans; Irritants; Quantitative Structure-Activity Relationship; Rabbits; Species Specificity; Toxicity Tests; VolatilizationAnimalia; Oryctolagus cuniculus
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