Mixture component effects on the in vitro dermal absorption of pentachlorophenol

Interactions between chemicals in a mixture and interactions of mixture com ponents with the skin can significantly alter the rate and extent of percut aneous absorption, as well as the cutaneous disposition of a topically appl ied chemical. The predictive ability of dermal absorption models, and conse quently the dermal risk assessment process, would be greatly improved by th e elucidation and characterization of these interactions. Pentachlorophenol (PCP), a compound known to penetrate the skin readily, was used as a marke r compound to examine mixture component effects using in vitro porcine skin models. PCP was administered in ethanol or in a 40% ethanol/60% water mixt ure or a 40% ethanol/60% water mixture containing either the rubefacient me thyl nicotinate (MNA) or the surfactant sodium lauryl sulfate (SLS), or bot h MNA and SLS. Experiments were also conducted with C-14-labelled 3,3 ' ,4, 4 ' -tetrachlorobiphenyl (TCB) and 3,3 ' ,4,4 ' ,5-pentachlorobiphenyl (PCB ). Maximal PCP absorption was 14.12% of the applied dose from the mixture c ontaining SLS, MNA, ethanol and water. However, when PCP was administered i n ethanol only, absorption was only 1.12% of the applied dose. There were a lso qualitative differences among the absorption profiles for the different PCP mixtures. In contrast with the PCP results, absorption of TCB or PCB w as negligible in perfused porcine skin, with only 0.14% of the applied TCB dose and 0.05% of the applied PCB dose being maximally absorbed. The low ab sorption levels for the PCB congeners precluded the identification of mixtu re component effects. These results suggest that dermal absorption estimate s from a single chemical exposure may not reflect absorption seen after exp osure as a chemical mixture and that absorption of both TCB and PCB are min imal in this model system.