Reconstructed Human Epidermis for Skin Absorption Testing: Results of the German Prevalidation Study

Abstract

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). The permeation of the OECD standard compounds, caffeine and testosterone, through commercially available RHE models was compared to that of human epidermis and animal skin. In comparison to human epidermis, the permeation of the chemicals was overestimated when using RHE. The following ranking of the permeation coefficients for testosterone was obtained: SkinEthic > EpiDerm, EPISKIN > human epidermis, bovine udder skin, pig skin. The ranking for caffeine was: SkinEthic, EPISKIN > bovine udder skin, EpiDerm, pig skin, human epidermis. The inter-laboratory and intra-laboratory reproducibility was good. Long and variable lag times, which are a matter of concern when using human and pig skin, did not occur with RHE. Due to the successful transfer of the protocol, it is now in the validation process.

The Role of Corneocytes in Skin Transport Revised—A Combined Computational and Experimental Approach

“…The magnitude of the affinity constant k, representing the ratio of the rate constant of adsorption and desorption and thus being an indicator of the binding strength, will influence the extent to which the effective diffusion coefficient will be reduced compared to a pure partitioning process. Furthermore, a large German multicentre-study aiming at a validation of reconstructed human epidermis models failed irrespective of the skin model investigated to predict experimental apparent permeability coefficient of a set of test compounds by established QSPR (quantitative structure activity relationship)-analyses that base only on molecular weight and lipophilicity parameters such as those mentioned above, or open-source software such as DermWin and Skinperm (80). It may be speculated that predictions may be improved when taking into account protein binding and hydration effects with the help of the theoretical analysis or the proposed experimental procedure.…”

Evaluation of 3D-human skin equivalents for assessment of human dermal absorption of some brominated flame retardants

“…Mouse skin showed higher permeability to several chemicals, in vitro, than either rat, pig or human skin (Hughes et al, 2001). A comparative study conducted in 2006 according to OECD guidelines reported less penetration of testosterone in pig and bovine skin (0.07 and 0.13% of applied dose) compared to human skin (0.32%), while EPISKIN™ and EpiDerm™ models showed higher permeations (0.53 and 2.36, respectively) (Schafer-Korting et al, 2006). It is noteworthy that both 3D-HSE producers claim that their skin models were further developed since 2006 to improve the barrier function.…”

Suitability of skin integrity tests for dermal absorption studies in vitro

“…The protocol was subject of multicenter validation studies as laid down (van de Sandt et al, 2004) and following specifications of e.g. skin type and handling (Schäfer-Korting et al, 2006. To avoid unsuitable over-prediction of the dermal absorption by the use of impaired skin preparations, the OECD guideline requires a skin integrity check.…”