The workplace is one of the most common venues for hazardous chemical contact with skin. Recognition of the dermal exposure hazard is essential for its control. Unfortunately, the present identification of chemicals as skin absorption hazards is inconsistent, poorly documented, and qualitative. As a result, those charged with protecting human health and safety in the workplace are forced to make judgments about safe or dangerous levels, and the type of personal protection required, with little or no information. The ultimate goal of this research effort is to provide occupational safety and health practitioners with improved guidance regarding potentially dangerous levels of occupational dermal exposure. While most occupational exposures of skin involve mixtures of chemicals, the interactions between multiple components and skin remain unknown. The proposed research is directed toward identifying and understanding the ? effect of exposures to chemical mixtures and especially non-aqueous solutions. Understanding that experimental evaluations will be limited to a small fraction of all mixtures encountered occupationally, we propose to develop a fundamental understanding of the underlying mechanisms by combining data with mathematical models. Specifically, we will (i) examine experimentally the extent to which several test solutes in water and in four non-aqueous solutions (toluene, n-octanol, n-octane and a selected chlorinated hydrocarbon) interact with each other or skin to alter the rate ? and/or amount of chemical absorption, (ii) develop computational procedures for estimating dermal absorption from aqueous and non-aqueous solutions containing two or more organic compounds, and (iii) demonstrate and use a new method for measuring electrochemical impedance to characterize skin barrier function and the effect of non-aqueous solutions thereon. Initial studies will involve four solutes (naphthalene, phenanthrene, 1-naphthol, and 1,3-naphthalenediol) in toluene and n-octanol. This combination of solutes and solvents were selected to examine interactions between similar and dissimilar chemicals, and to assess the importance of hydrogen bonding interactions between absorbing chemicals and skin. The ultimate goal of this research effort is a framework for relating dermal absorption measurements and predictions for liquid mixtures to industrial health scientists in the form of useful guidelines. With such information in-hand, it will be possible to plan effective exposure controls and/or interventions. ? ?