Assessment of the in vitro skin irritation of chemicals using the Vitrolife-SkinTM human skin model

Currently, the European Centre for the Validation of Alternative Methods (ECVAM) has supported formal validation studies on in vitro tests for predicting skin irritancy and corrosivity, which included three of the in vitro tests employed human skin models, EPISKINTM and EpiDermTM. When skin models are used to evaluate skin irritancy and corrosivity, it is important that suitable chemical application procedures are utilized. We used 44 chemicals and evaluated their skin irritancy using post-incubation method (10-minute treatment and 18-hour post-treatment incubation) that we have originally developed to predict skin irritancy. This method is quite similar to a refined protocol for the EPISKINTM had been proposed in the ECVAM validation study. The sensitivity, specificity, and accuracy with the MTT reduction assay-based prediction model were 77.8%, 76.9%, and 77.3%, respectively. On the other hand, the sensitivity, specificity, and accuracy with the interleukin-1α secretion assay-based prediction model were 61.1%, 92.3%, and 79.5%, respectively. Combining these endpoints, this resulted in a clear increase in sensitivity and accuracy to 94.4% and 81.8%, respectively. Vitrolife-SkinTM showed basic utility for irritancy testing by this method and it is possible to confidently predict skin irritancy, provided that the appropriate chemical application procedures are used.