In Vitro Permeation of Nickel Salts Through Human Stratum Corneum

Abstract

Allergic contact dermatitis due to nickel salts is common. It is therefore important to measure the permeation of these salts through the stratum corneum (SC), the primary rate-limiting domain in skin. An advanced diffusion system and analytical techniques now enable better measurement of the flux than was possible in earlier experiments. Human SC was prepared by trypsinization of dermatomed cadaver leg skin. The diffusion system included diffusion cells with a spiral line. Aqueous solutions of nickel salts (Ni(NO3)2, NiSO 4, NiCl2 and Ni(-OOCCH3)2 at 1 % Ni2+ concentration) were used as the donor solution (400 w L/cell). The receptor fluid, pure water, was collected up to 96h after application of the donor solutions. Nickel concentrations in the donor and receptor fluid, as well as in the SC, were analysed using inductively coupled plasma mass spectrometry (ICP-MS) with a confidence limit of 0.5ppb. Based on the total recovery of nickel from the experiments, about 98 % of the dose remained in the donor solution, whereas 1 % or less was retained in SC and less than 1 % was found in the receptor fluid. Following an early surge, nickel permeates slowly across SC. The steady-state permeability coefficients of nickel were calculated from the flux data (approximately 5.2-8.5 2 10-7 cm/h) with no significant difference among the salts. The results concur in principle with earlier studies conducted using the full-thickness human skin in vitro , and suggest that in vivo nickel ions may permeate simultaneously by routes of diffusion such as the shunt pathway, apart from slow transcellular/intercellular diffusion alone.