RECONSTRUCTED HUMAN SKIN EQUIVALENTS-THEIR VALUE FOR SCREENING OF SKIN IRRITATION.

Advances in techniques for culturing human skin cells have led to the development of reconstructed human skin equivalents that closely resemble native human skin. These in vitro models offer a variety of approaches to investigate wound healing, skin ageing, pigmentation, skin penetration, transdermal drug delivery, cutaneous metabolism and toxicity. Skin corrosion and irritation due to chemical exposure are important toxicological concerns and since animal testing has drastically been restrained by regulatory demands, much effort has been applied to provide reproducible, reliable and consistent human skin models to predict the potential of chemicals to induce skin irritation in humans. The ultimate aim of the thesis is to evaluate reconstructed human skin equivalents as tools for screening and predicting skin irritation in humans, addressing the following questions: 1) What biological parameters are suited to detect skin irritation in vitro and in vivo, and can these endpoints be used to identify compounds that are likely to induce skin irritation in humans? 2) What are the characteristics of present-day skin models, both industrial and in-house, and to what extent do they resemble native human skin? 3) Can the reproducibility and the standardization of skin models be improved by using immortalized human skin cell lines? 4) Can the microdialysis technique be used as a tool to facilitate in vitro – in vivo correlations?

Cutaneous irritancy, Cutaneous irritation, Cutaneous toxicity, Dermal irritancy, Dermal irritancy testing, Dermal irritation, EpiDerm, MTT, MTT ET-50 tissue viability assay, MTT assay, Metabolism, Reconstructed human skin equivalents, Skin irritancy, Skin irritation