ABSTRACT
The skin as target organ presents imponderable and wide margins of variability. In vivo, permeability is subject to homeostasis regulating the overall organism; in vitro, the sections of skin used for diffusion experiments are likely to present artifacts. To further complicate the matter, diffusion of metals appears to defy laws empirically derived for passive diffusion across biological membranes. Endeavors to define rules governing skin penetration by metals toward derivation of predictive quantitative structure-diffusion relationships for risk assessment, thus, have been unsuccessful, and penetration of the skin still needs to be determined separately for each metal compound, by in vitro or in vivo assays. Because diffusion through biological membranes is highly metal specific, and, in addition, metal ions’ valence is mutable during the process of diffusion, molecular physicochemical parameters alone do not suffice to model migration of electrolytes into and through the strata of the skin. Certain factors are closely interrelated, and their combined effects are neither entirely understood nor predictable. For example, unless the dynamics
of in situ changes in speciation (oxidation state), or electrophilic reactivity, among others, can be factored in, metal diffusivity will elude modeling. Experimental data available so far from in vitro and in vivo experimentation have been acquired under disparate conditions, and the base is too thin to allow development of a predictive algorithm considering the number of metals and metalloids of variable valence existing as free ions or forming chelates, coordination compounds, or complexes with electron donors, such as oxygen, sulfur, or phosphorus active in biological systems. The number of metals discussed in this review may appear limited; this is due to the circumstance that most scientists and government agencies so far have given priority to the limited number of industrial materials, which comport special risks from work place exposure in their investigations.
