A protocol to determine dermal absorption of xenobiotica through human skin in vitro

Abstract

Determination of the absorption through the skin is of utmost importance for predictions of benefits and of risks of dermal exposure to xenobiotica. In order to allow for flexibility, the OECD guideline for the determination of skin absorption for different purposes and use conditions (OECD guideline 428 combined with the Technical Guidance Document 28) is inexplicit; hence, different experimental procedures are used which may lead to limited comparability of study results. The here described protocol provides explicit guidance, whereas it does not invalidate other procedures within the frame of the OECD guideline since uncritical versus critical steps are differentiated. Optimizations are presented which finally led to a precisely defined protocol allowing for enhanced comparability of future study results. Some salient properties of this protocol are the storage of the prepared diffusion cell overnight refrigerated in the presence of a protease inhibitor cocktail and include investigation of the integrity of the skin sample as well as the removal of the upper stratum corneum by tape strips under standardized conditions.

Keywords: Dermal absorption; Protocol; Transdermal kinetics.