A number of appendages are associated with the skin, including har follicles, sebaceous glands, eccrine and apocrine sweat glands, and nails. Recently it was found that removal of the stratum corneum does not allow complete absorption; thus it is apparent that some role, although of lesser importance, is played by other parts of the skin. The dermis and subcutaneous areas of the skin are less important in influencing penetration, and once a toxicant has penetrated the epidermis, the other layers are traversed rather easily. The dermis is highly vascular characteristic that provides maximal opportunity for further transport once molecules have gained entry through the epidermis or through skin appendages. Most of the absorption occurs at the capillary loops located at the epidermis-dermis junction. The blood supply of the dermis is under neural humoral influences whose temperature-regulating functions could thus affect penetration and distribution of toxicants. Vasoactive drugs or environmental temperature can also influence absorption by altering blood flow to these capillaries. The subcutaneous layer of the skin is highly lipid in nature and serves as a shock absorber, an insulator, and a reserve depot of energy. The pH of the skin varies between 4 and 7 and is markedly affected by hydration.
Cutaneous biotransformation is mostly associated with the stratum basale layer where there can be phase I and phase II metabolism. However, the skin is not very efficient, compared to the liver. The epidermal layer accounts for the major portion of biochemical transformations in skin. although the total skin activity is low (2-6% that of the liver). Where activity is based on epidermis alone, that layer is as active as the liver or, in the case of certain toxicants, several times more active. For some chemicals, metabolism can influence absorption, and transdermal delivery systems of drugs utilize this activity. For example prodrug such as lipid esters are applied topically, and cutaneous esterases liberate the free drug. These basal cells and extracellular esterases have been shown to be involved in detoxification of several pesticides and bioactivation of carcinogens such as benzo(a) pyrene. For rapidly penำtrating substances, metabolism by the skin is not presently considered to be of major significance, but skin may have an important first-pass metabolic function, especially for compounds that are absorbed slowly.