Interactions between chemicals in a mixture and interactions of mixture components with the skin, can significantly alter the rate and extent of percutaneous absorption, as well as the cutaneous diposition of a xenobiotic. The predictive ability of dermal absorption models, and consequently, the dermal risk assessment process would be greatly improved through the elucidation and characterization of these interactions. As a first step, the effects of several generalized mixture components, on the percutaneous absorption of 3,3' ,4,4', 5-pentachloro biphenyl (PCB), 3,3',4,4'-tetrachloro biphenyl (3,3',4,4'-TCB), and pentachlorophenol (PCP) were examined using isolated perfused porcine skin flap (IPPSF) and porcine skin flow through (PSFT) diffusion cell systems. Mixtures containing combinations of the surfactant sodium lauryl sulfate (SLS), the vasodilator methyl nicotinate (MNA), ethanol, and water were studied. With all mixtures studied, PCB, and TCB absorption was negligible (approximately 0.1 % of the applied dose) as quantified using both radiolabel and an HPLC method. In contrast, the absorption of PCP occurred to a much greater extent (-14% of the applied dose), and showed significant mixture effects. Not only was the magnitude of PCP absorption altered, but the absorption profiles, and the disposition within the stratum corneum, dermis, epidermis, and subcutaneous fat were highly dependent on mixture components. The contrast of the results obtained for PCB and PCP, illustrate an area of interaction between the structural and chemical parameters that dictate the amount of chemical absorbed into the systemic circulation.
The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania