ABSTRACT
INTRODUCTION Diffusion of many topically applied molecules, drug, or chemical through the stratum corneum is mainly a passive process influenced by dose and concentration gradient through the skin, and diffusion obeys Fick’s law. The physicochemical properties of the chemical influence absorption, and for nonlipophilic molecules (log p 0-3.3) there is a linear relationship with lipophilicity. For highly lipophilic drugs and chemicals, affinity for the lipophilic stratum corneum may reduce diffusion resulting in a reservoir in the stratum corneum, some of which may be available for diffusion at a later time. Having crossed the stratum corneum, the absorbed drug must diffuse through the viable epidermis to reach the papillary layer of the upper dermis, and hence the systemic circulation. There are, however, further processes that might influence the availability of chemicals for penetration into the systemic circulation as well as their disposition and toxicity in the cutaneous tissues. These include physical barrier processes in the basal layer of the epidermis, transport processes into and out of the basal layer, and metabolic transformation (which occurs mainly in the basal layer and appendages). This chapter describes the current understanding of these processes and their importance in toxicity. A greater understanding of these processes may help to explain interindividual variation in absorption, metabolism, and efficacy, or toxicity locally in the skin.
