Dermo-epidermal organotypic cultures for in vitro evaluation of skin irritation and corrosion.

In recent years, in-vitro skin models for chemical hazard identification have been developed. Most of them consist only of human keratinocytes, neglecting the contribution of other skin constituents. Cultures containing the dermal and epidermal component provide an attractive system to investigate, in a more realistic model, toxicological responses, which represents a distinct advantage over keratinocytes-based models that do not mimic faithfully the in vivo environment. This study aimed to validate dermo-epidermal organotypic cultures (ORGs) as a platform to perform irritation and corrosion tests. Skin models were constructed by seeding keratinocytes on fibroblast-containing fibrin gels. After 21 days, the ORGs were evaluated histologically, and the irritant and corrosion potential was determined by means of viability measurements (MTT assay) and cytokine release, according to 431 and 439 OECD tests guidelines. Skin models showed similar histological characteristics to native skin and were able to classify different substances with high accuracy, showing their applicability to skin irritation and corrosion tests. Although cytokines release seems to be chemical-dependent, a tendency was observed, leading to the improvement of the prediction capacity. Nevertheless, further studies should be done to reduce variability in order to increase prediction capacity. • As general mediators in injury, IL 6 and IL 8 can be a good indicator of irritation. • Most of released cytokines are likely to be chemical- and model-specific. • ORGs fulfilled the OECD performance standards. • ORGs are a useful tool for chemical hazard identification. [ABSTRACT FROM AUTHOR]