This project is a continuation of NIOSH 5-RO1-OH03658-02, """"""""Dermatopharmacokinetics of paint solvents."""""""" The overall research objective for this continuation project is to expand prior studies to evaluate the percutaneous absorption of compounds commonly encountered within similar industries (styrene and ethylbenzene) along with focused studies to evaluate the dermal bioavailability of compounds with both lipophilic and hydrophilic properties. The first part of this study demonstrated that the dermal absorption of toluene in an aqueous matrix was substantially less than previous estimates, and that aqueous methyl ethyl ketone was absorbed to a much greater degree than previously determined. Additionally, studies conducted to evaluate the dermal absorption of methyl ethyl ketone have revealed a biphasic absorption pattern, with an initial rapid appearance of compound in the exhaled breath, indicative of high permeability, followed by a more sustained moderate permeability. Furthermore, our studies with complex paint matrices indicate that the matrix impacts toluene dermal absorption to a lesser degree than concentration within the matrix. The next phase of study, as proposed here, will explore the biphasic absorption in more detail by evaluating additional compounds with both lipophilic and hydrophilic properties, will evaluate the dermal bioavailability of additional compounds commonly encountered in the occupational setting, and will evaluate the dermal bioavailability of solvents as vapors. This continuation proposal has the following Specific Aims: 1. To compare the dermal absorption of compounds with both lipophilic and hydrophilic properties with prior studies using methyl ethyl ketone in F344 rats; 2.To evaluate the kinetics and dermal bioavailability of ethylbenzene and styrene in an aqueous matrix using F344 rats; 3.To evaluate the kinetics and dermal bioavailability of ethylbenzene, styrene, and toluene vapor using F344 rats.
