Factors determining percutaneous metal absorption

Metals play a vital role in human, animal and plant physiology, and important research, past and ongoing, is directed towards exploring the interrelated mechanisms that govern their penetration through skin. Much insight has been gained through these efforts, but our understanding of the process is still incomplete, mainly due to the failure to allow for the effects of chemical speciation of metallic elements, especially the transition metals. Also, 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. Endeavors to define rules governing skin penetration to give predictive quantitative structure-diffusion relationships for metallic elements for risk assessment purposes have been unsuccessful, and penetration of the skin still needs to be determined separately for each metal species, either by in vitro or in vivo assays. Phenomena observed by us and other investigators, which appear to determine the process of skin permeation for a number of metals, are reviewed, separating the exogenous factors from the characteristics of the skin or other endogenous factors.