Fundamental Toxicology

The skin is the largest organ of the human body and interfaces with the environment, maintaining the equilibrium of the internal milieu and preventing the ingress of environmental toxins. Toxicity results when physical or chemical agents breach this normally effective barrier. Advances in molecular biology have both increased our understanding of the physical and biological elements that contribute to this skin barrier function and helped in the development of tools for more reliable dermato-toxicological risk assessment.
The skin consists of an inner layer called the dermis that sits astride the subcutaneous fat and adjoins the overlying epidermis. The cellular content of the dermis comprises predominantly fibroblasts and mast cells. The fibroblasts produce the collagen and elastin fibres that give the skin its tensile strength. These fibres are embedded in a ground substance of sugar-containing molecules known as glycosaminoglycans, which are also produced by the fibroblasts. This extracellular matrix situated at the dermoepidermal junction is now known to have a significant effect on growth of cells of the epidermis. The dermis also contains cells of the monocyte/macrophage system, which together with the dendritic, antigen-presenting cells of the epidermis are part of the body's cellular immune defence mechanism, and are involved with both allergic and irritant dermatitis responses.
The epidermis covers the dermis and contains a basal layer of replicating cells. Above the basal layer, several layers of terminally differentiating cells evolve into the stratum corneum. The latter is a water-impenetrable,...