Aims of the here presented study are, on the one hand, the establishment and demonstration of organotypic three-dimensional human skin equivalents as a new valid test system alternative to animal testing to investigate dermatological severe side-effects of the novel clinical and experimental endothelial growth factor receptor-inhibitors on human skin differentiation. On the other hand, the investigations of time-dependent toxicological properties, and carcinogenetic induction of environmental pollutant and chemotherapeutic agent arsenic trioxide in human epidermal keratinocytes in monolayer cell culture. In the end, the aim is here, the demonstration of skin-related impacts of chronic arsenic trioxide exposure in three-dimensional human skin equivalents.