Skin Absorption of Anions: Part One. Methodology for In Vitro Cutaneous Absorption Measurements.

Abstract

Measurement of skin absorption of ions requires specific experimental protocols regarding the use of pig skin as a model, the viability of excised skin in water medium over 24h, the presence of endogenous ions, and evaluation of the contributions of facilitated transport through ion channels and ion transporters. Absorption experiments of halide anions F(-), Cl(-), Br(-) and I(-) in excised skin were performed in Franz diffusion cells. Experiments were performed on human and porcine skin under various conditions so as to define and validate experimental protocols. The distributions of endogenous ions and the absorption kinetics of halide ions were similar in both porcine and human skin models. Fresh skin kept its viability over 24h in salt-free water, allowing experiments following OECD guidelines. Permeation increased in the order F(-) < Cl(-) < Br(-) < I(-) for all receptor media and skin samples. Absorption was larger in fresh skin due to the transport through chloride channels or exchangers. Skin absorption experiments of ions in Franz cells rely on working with fresh excised skin (human or porcine) and pure water as receptor fluid. Experiments with chloride blockers or frozen/thawed skin allow discriminating passive diffusion and facilitated transport.