Skin disease, initiated in the workplace, currently represents a major occupational health problem in the United States. Prediction of the detrimental toxic effects of hazardous chemical exposure is difficult, however, because of the complexity of the percutaneous absorption process and a lack of any consistently identifiable relationship(s) between transport rate and chemical properties. In addition, the very diverse approaches, which have been used to measure skin penetration, further complicate the problem since the extrapolation of results to the human in vivo situation is an exercise requiring often quite unreasonable (and, hence, potentially dangerous) assumptions. The ultimate goal of the research proposed here is to address this area of occupational health concern. Therefore, our specific aim is acquisition of the ability to predict accurately the toxicokinetics of occupationally-encountered molecules absorbed across human skin in vivo. The methodological approach will proceed as follows: (1) To establish from the extensive percutaneous absorption literature as broad a database as possible; to review, collate and file for future access: (a) human and animal in vivo results, (b) in vitro penetration data through excised skin, and (c) proposed pharmacokinetic and diffusional descriptions of skin transport aand biodisposition. (2) To develop, on the basis of this information, refined models of the percutaneous absorption process which incorporate both established cutaneous biology and the physicochemical interactions between the penetrant and skin. (3) To assess, in this way, the different experimental approaches to transdermal absorption; to identify, if possible, the predictive capability of the various techniques; and, hence, to specify the most appropriate studies for future determinations of potential cutaneous toxicity. In the long-term this research is designed to respond to the crucial question: """"""""Can the health hazard from dermal exposure to toxic chemicals be predicted correctly on the basis of fundamental biological and physicochemical principles?"""""""" An affirmative response, would, it is believed, lead the way to a significant decrease in skin disease of occupational origin.
