In Vitro Permeation of Metals through Human Skin: A Review and Recommendations

During the last few decades, the interest in skin permeation of, specifically, metals has increased with the in vitro method utilizing diffusion cells as the prominent method of investigating permeability. This review provides a systematic synopsis focused on an in vitro diffusion cell method utilizing human skin and examines the differences in experimental design as this could influence the results obtained. The permeation of metals such as chromium, cobalt, copper, gold, lead, mercury, nickel, palladium, platinum, rhodium, silver, titanium, and zinc are discussed. The metals included in this review, except for titanium and zinc, can permeate through intact human skin under physiological conditions. On the basis of flux values, the order of permeability could be summarized as Cu > Pb > Cr > Ni > Co > Pt > Hg > Rh (excluding nanoparticles). Permeability of metals through human skin is highly variable with the different methodologies as a contributing factor. Furthermore, metals are retained in the skin which could lead to reservoir (depot) formation and extended exposure even after the removal thereof from the outer surface of the skin. Finally, recommendations are provided on the standardization of experimental design and format of data reporting to enable the comparison of results from future in vitro metal permeation studies.