The physicochemical parameters of marker compounds and vehicles for use in in vitro percutaneous absorption studies.

In order to prepare for a validation study to compare percutaneous absorption through reconstructed human epidermis with ex vivo skin absorption through human and animal skin, nine test compounds, covering a wide range of physicochemical properties were selected, namely: benzoic acid; caffeine; clotrimazole; digoxin; flufenamic acid; ivermectin; mannitol; nicotine; and testosterone. The donor and receptor media for the test substances, the addition of a solubiliser for the lipophilic compounds, as well as the stability and solubility of the test substances in the vehicles, were systematically analysed. Hydrophilic molecules, being freely soluble in water, were applied in buffered saline solutions.

The use of reconstructed human epidermis for skin absorption testing: Results of the validation study.

A formal validation study was performed, in order to investigate whether the commercially-available reconstructed human epidermis (RHE) models, EPISKIN, EpiDerm and SkinEthic, are suitable for in vitro skin absorption testing. The skin types currently recommended in the OECD Test Guideline 428, namely, ex vivo human epidermis and pig skin, were used as references. Based on the promising outcome of the prevalidation study, the panel of test substances was enlarged to nine substances, covering a wider spectrum of physicochemical properties.

Permeability of the reconstructed human epidermis model Episkin in comparison to various human skin preparations.

The objective of this work was to compare the barrier function of the small diameter reconstructed human epidermis model Episkin (d=12 mm) to human skin in vitro. For that purpose a modification for the Franz diffusion cell (d=15mm) had to be developed so as to allow direct comparison with the following human skin preparations: Full thickness skin (FTS), split thickness skin (STS), heat-separated epidermis (HSE), and trypsin isolated stratum corneum (TISC). Among the tested preparations, HSE appeared to be the most preferable due to its clear morphological structure and ease of preparation.

Reconstructed human epidermis for skin absorption testing: results of the German prevalidation study.

Exposure to chemicals absorbed by the skin can threaten human health. In order to standardise the predictive testing of percutaneous absorption for regulatory purposes, the OECD adopted guideline 428, which describes methods for assessing absorption by using human and animal skin. In this study, a protocol based on the OECD principles was developed and prevalidated by using reconstructed human epidermis (RHE).