Comparative study of the percutaneous permeation and bioaccumulation of a cyclic siloxane using frozen-thawed and nonfrozen ex vivo human skin

Abstract

Literature shows contradictory information regarding the effect of freezing the excise skin ex vivo on the diffusion of substances into the skin. Few studies indicate that storing the human or animal skin in a frozen state decreases the barrier properties after thawing. Therefore, to understand the properties of frozen skin, we evaluated the effect of storage of ex vivo human skin (2 weeks at -20 °C) on the penetration of stratum corneum and permeation into deeper skin layers (epidermis, and dermis) as well as to the receptor fluid by octamethylcyclotetrasiloxane (D4) a representative test compound of cyclic siloxanes. The main research were preceded by checking the integrity of nonfrozen ex vivo human skin in comparison to the frozen-thawed one by using the Electrical Resistance technique (ER) and the fluorescence microscopy. Samples collected in the skin absorption experiment were analyzed by gas chromatography equipped with a flame ionization detector (GC-FID). The results of this study demonstrated that freezing of excised ex vivo human skin at -20 °C for up to 14 days does not alter the permeability of D4 in a statistically significant manner. Thus, our results confirmed the validity of using skin storage conditions for testing the penetration and permeation of xenobiotics recommended by the OECD, EMA, and WHO guidelines.

Keywords: Cyclic siloxane; Electrical resistance technique; Fluorescence microscopy skin imaging; Freezing of skin; Frozen skin; Frozen-thawed skin; GC-FID chromatography; Nonfrozen skin; Percutaneous permeation; Skin barrier function; Skin permeation; Skin storage conditions.