Comparison of human skin irritation and photo-irritation patch test data with cellular in vitro assays and animal in vivo data

Replacement of the rabbit Draize skin irritation test or the animal photo-irritation test is in course in Europe under the REACH chemical strategy and the Cosmetics Directive. Various in vitro protocols, including 3D skin models, have been assessed. One key difficulty in determining the validity of alternative in vitro methods is that the in vivo animal data is both scarce and often of limited utility for prediction of effects in man. Consequently, we have examined in human 4h patch tests a number of chemicals of EU borderline classification. In addition, in a specific group of cosmetic ingredients we assessed the potential of photoirritation using results obtained in 3D skin models and in human photopatch tests. Several chemicals reported to be irritant in the rabbit were found to be without effect in humans. 3D skin model assays and human patch tests provided concordant results particularly in case of non-irritating and non-phototoxic substances. In our view, skin model tests seem to be a useful tool for the prediction of human skin irritation or phototoxicity hazard, particularly for consideration of initial concentration for confirmatory human patch tests to prove substance and product safety.