Draize rabbit eye test compatibility with eye irritation thresholds in humans: a quantitative structure-activity relationship analysis

Abraham, Michael H, Hassanisadi, Mostafa, Jalali-Heravi, Mehdi, Ghafourian, Taravat, Cain, William S and Cometto-Muñiz, 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

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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
Keywords: acid; n methylformamide; organic solvent; water, animal 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 testing, Animal Testing Alternatives; Animals; Dose-Response Relationship, Drug; Eye; Humans; Irritants; Quantitative Structure-Activity Relationship; Rabbits; Species Specificity; Toxicity Tests; Volatilization, Animalia; Oryctolagus cuniculus
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Taravat Ghafourian
Date Deposited: 28 Nov 2017 14:59
Last Modified: 02 Jul 2019 17:18
URI: http://sro.sussex.ac.uk/id/eprint/64161

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