Photosafety testing is of concern for the evaluation of personal care products and pharmaceuticals. Current regulatory guidance state that photosafety should be evaluated for compounds that absorb radiation between 290 and 700 nm with relevant exposure in the skin or eyes. However, oversensitivity and the occurrence of 'pseudo-effects' with current in vitro photo(geno)toxicity assays have become a major problem. Furthermore, at this moment, there are no relevant in vitro assays available to identify the photocarcinogenic potential of compounds, which might result in unnecessary in vivo photocarcinogenicity studies for pharmaceutical ingredients or unnecessary dropouts in the development of ingredients of personal care products. For these reasons, availability of a relevant and highly predictive in vitro model from human origin to identify the photogenotoxic and/or photocarcinogenic potential of compounds is viewed as high priority. In the present study, human skin tissue obtained from surgery was used for developing a photomicronucleus test. Prior to investigations of the photogenotoxic potential of 8-methoxypsoralen, tissue viability (lactate production and lactate dehydrogenase leakage), cell proliferation (Ki-67 expression) and the effect of ultraviolet (UV) exposure on viability (MTT test), proliferation (Ki-67 expression) and p53 expression were determined. Results of the present study indicate that ex vivo human skin seems to be a relevant method for safety evaluation of compounds that reach the skin in combination with UV exposure.