Quantitative structure–activity and quantitative structure–property relationship approaches as alternative skin sensitization risk assessment methods

Abstract

ABSTRACTThis study aimed to predict skin sensitization potency of selected chemicals by quantitatively analyzing their physicochemical properties by employing quantitative structure–activity relationship (QSAR) and quantitative structure–property relationship (QSPR) approaches as alternative risk assessment methods to animal testing. Correlations between effective concentration for a stimulation index of 3 (EC3) (%), the amount of a chemical required to elicit a threefold increase in lymph node cell proliferative activity (stimulation index, ≥3), were calculated using local lymph node assay (LLNA) and physicochemical properties of 212 skin sensitizers and 38 non-sensitizers were investigated. The correlation coefficients between melting point (MP) and EC3 and between surface tension (ST) and EC3 were 0.65 and 0.69, respectively. The correlation coefficient for MP + ST and EC3 was estimated to be 0.72. Thus, correlation coefficients between EC3 and MP, ST, and MP + ST reliably predicted the skin sensitization potential of the chemicals with sensitivities of 72% (126/175), 70% (122/174), and 73% (116/158); specificities of 77% (27/35), 69% (22/32), and 81% (26/32); and accuracies of 73% (153/210), 70% (144/206), and 75% (142/190), respectively. Our findings suggest that the EC3 value may be more accurately predicted using the ST values of chemicals as opposed to MP values. Thus, information on MP and ST parameters of chemicals might be useful for predicting the EC3 values as not only an alternative approach to animal testing, but as a risk assessment method for skin sensitization.