Percutaneous penetration and mass balance accountability: Technique and implications for dermatology

The skin maintains a complex barrier to chemical ingress while retaining fluids within the body. It would be useful to predict the rate and extent to which compounds penetrate the skin. This would allow assessment of tox-icologic hazards and the design of systems to improve topical drug delivery. Therefore, the development and application of mass balance methodology for estimating human in vivo percutaneous absorption are worthy goals. Earlier in vivo human percutaneous absorption studies have not accounted for the disposition of the applied dose. We have developed mass balance methodology for both occlusive and nonocclusive exposure conditions that allows, in addition to the estimation of percutaneous absorption, the determination of the degree to which a compound can be removed from the skin surface (decontamination) and the magnitude of chemical sequestration within the stratum corneum (substantivity). Utilizing these methods, we have studied the human in vivo percutaneous absorption of four steroids and nine para-derivatives of phenol.