The impact of occlusion and the rôle of the counter ion on the permeation of nickel ions through skin have been examined using excised human skin. A highly sensitive electrochemical method was used to quantify the amount of nickel permeating the skin. The investigations show that nickel ions are capable of permeating the skin barrier when applied under occlusion. The process is slow, having a lag time of approximately 50 h. The permeation rate, and thus the physical amount being bioavailable, is considerably increased when aqueous nickel chloride is used in comparison with aqueous nickel sulphate. With respect to nickel permeation of the skin, we conclude that the choice of salt is an important consideration in patch testing.
The effect of the vehicle on the permeation rate of nickel ions through excised human skin was evaluated. Different hydrogels were compared with the standard patch test in petrolatum. A hydroxypropyl methylcellulose gel seemed to be the most promising alternative to petrolatum. It gave high bioavailability of the nickel and had good film forming properties leaving the nickel spread across the skin surface as a thin film without microscopically detectable crystals. The content of nickel in the various skin layers after cutaneous application was determined, and nickel was found to accumulate in the epidermis, probably due to epidermal binding. A significant amount of nickel was found also in the dermis. Occlusion and application of higher nickel concentrations increased the transport rate and must be considered in patch testing using this hydrogel. We conclude that nickel permeation is highly dependent of the choice of vehicle and the vehicle should, therefore, be an important consideration in patch testing with nickel.
Human epidermis was homogenized, dried and incubated with nickel chloride solutions in the concentration range 0.008-3.4 mM/50 mg epidermis. Nickel uptake was found to occur according to the Freundlich adsorption isotherm, giving a slope of 0.55, indicating that nickel is associatively bound to constituents of the epidermis. The binding characteristics of cobalt were very similar to those of nickel, but the two metals were not found to compete significantly for binding sites in the epidermis. The metal-chelating agents, ethylenediamine tetra-acetic acid disodium, (Na-EDTA) L-histidine and D-penicillamine were tested for ability to remove nickel from its binding sites. Na-EDTA was found to be the most efficient, removing 70-90% of the nickel bound to the tissue. The possible clinical significance of these in vitro observations are discussed in relation to percutaneous absorption and allergic contact dermatitis.
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