Irritant contact dermatitis (ICD) is a common occupational disease associated with exposure to multiple chemical and environmental agents. Prolonged water exposure exacerbates susceptibility to ICD via maceration of the stratum corneum and subsequent loss of a competent epidermal barrier. This proposal focuses on the unexpected finding that the skin of the term human infant exhibits extraordinary epidermal barrier properties despite development under aqueous conditions and exposure to potentially noxious agents such as urine. It is hypothesized that the human fetus generates a hydrophobic mantle which overlies and protects the developing stratum corneum before birth. This mantle is the putative result of a surge in sebaceous gland activity in the last trimester of pregnancy and production of a thick, lipid-rich, hydrophobic film (vernix caseosa). Droplets of distilled water or water containing 25 mg/ml lecithin with or without surfactant protein B (100 ng/ml) will be overlaid on the outer vernix surface. We propose that understanding fetal protective mechanisms will allow reapplication in the field of adult occupational dermatoses. Data supporting this proposal have been developed in the context of irritant contact (diaper) dermatitis in infancy. The specific aims of this pilot project are: 1) to develop methods for handling and spreading vernix in vitro given its unusual rheological properties; 2) to apply vernix in the form of a biofilm to cultured skin substitutes and to test the hypothesis that vernix stimulates epidermal metabolism and barrier maturation under aqueous culture conditions; 3) to determine the ability of vernix to act as an epidermal protectant against noxious environmental agents using a standard newborn rat model of human skin. In summary, this proposal builds on the working hypothesis that human vernix constitutes a naturally occurring biofilm with unique barrier properties preventing maceration under aqueous conditions. Information resulting from this proposal may lead to development of new treatment modalities such as natural wound dressings or topical barrier creams for protection of preterm and term infant skin, the female perineum, and occupational hand dermatoses secondary to irritant exposure.