Toxicologic implications of cutaneous barriers: a molecular, cellular, and anatomical overview

The skin barrier is a complex system of chemical, biological and physical processes that together regulate the admission and expulsion of foreign agents in contact with the skin. The eggresive movement of the stratum corneum (SC) is often a measure of its integrity, and transepidermal water loss has typically been a gold standard. However, the skin barrier has several barrier systems, such as ion flux, O(2), CO(2) and pH, which can give an informative and sometimes more sensitive measure of the SC condition. Furthermore, the penetrative interactions with the barrier have focused around occlusive methods to promote drug delivery, the interactions of topically applied drugs with the barrier and the presence of environmental agents that can harm the barrier. However, the nature of penetrative barrier interactions must also be elucidated on a microscopic level. The variable nature of barrier function is demonstrated when comparing the skin properties of neonates and adults. In addition, new biochemical methods have used keratin metrics to improve diagnostic efficacy and barrier integrity analysis. This review addresses the aforementioned aspects of the skin barriers that require further study to help discern the complexity of this essential organ as it relates to dermatotoxicology and dermatopharmacology.