Draize eye scores and eye irritation thresholds in man can be combined into one QSAR

Draize eye scores (DES) of 37 pure organic liquids have been converted into scores for the corresponding vapors, DES/P0, where P0 is the liquid vapor pressure in atmospheres at 298 K. It is shown that there is a constant difference of 6.7 between values of log(DES/P0) and log (1/EIT), where EIT is the eye irritation threshold in parts per million (ppm, by volume) of eight vapors for human subjects. The 37 log(DES/P0) values can be combined with log(1/EIT) values for 17 vapors into one quantitative structure-activity relationship (QSAR) for sensory potency (SP) using our general solvation equation, [formula: see text] where R2 is an excess molar refraction, pi 2H is the compound polarizability/dipolarity, sigma alpha 2H and sigma beta 2H are the compound hydrogen-bond acidity and basicity, and L16 is the gas-hexadecane partition coefficient at 298 K. n is the number of data points, r the correlation coefficient, SD the standard deviation, and F the F-statistic. LogSP is then either [log(DES/P0) - 0.66] or log (1/EIT), confirming the result for the eight common compounds. It is suggested that the equation can be used to predict eye irritancy of organic vapors and pure liquids. It is further suggested that for the compounds in the data set, the main process in eye irritation is transfer of the compound from the vapor or pure liquid to a biological phase, and a number of chemical properties of the biological phase have been mapped out through the equation. These properties are consistent with corresponding properties for a number of organic liquid phases.