The epiderm™phototoxicity test (EpiDerm™ H3D-PT)

Abstract

Assessment of the phototoxicity hazard and phototoxic potency (i.e. phototoxic risk) of topically or systemically applied compounds and mixtures is a crucial step in the safety assessment of cosmetic, pesticide and pharmaceutical products absorbing UV and visible light. The validated and regulatory accepted in vitro assay, the 3T3 NRU PT (OED TG 432), provides high level of sensitivity and thus also protection for the end-users, however, it has been reported that it also generates high rate of false positive results due to the lack of barrier properties naturally appearing in the human skin or other targeted tissues. In vitro reconstituted human skin models are increasingly being investigated for their usability in hazard identification and safety testing, because of their organotypic structure with a functional stratum corneum that allows for assessment of bioavailability of topically applied compounds and mixtures. An in vitro phototoxicity test using the human reconstructed epidermis model EpiDerm™ (EpiDerm™ H3D-PT) has been developed and pre-validated almost 20 years ago and can be used either as standalone method for the phototoxicity testing of topically applied materials, or in combination with the 3T3 NRU PT, to minimise the potentially false positive results from this assay. This chapter describes in detail the EpiDerm™ H3D-PT, which is an ECVAM pre-validated assay and accepted component of the pre-clinical testing strategy for topically applied pharmaceutical products as recommended within the ICH S10 Guideline. The chapter focuses on the technical details of the EpiDerm™ H3D-PT and also provides information about the performance of this assay during the pre-validation study. Furthermore, it discusses the follow-up work conducted by independent research teams that confirmed findings from the pre-validation study regarding high sensitivity, specificity and relevance for topically tested compounds compared to human data.