APPLICATION OF A HUMAN SKIN TISSUE CULTURE MODEL IN DERMAL ABSORPTION STUDIES OF 3,3’,4,4-TETRACHLOROBIPHENYL (TCB).

TCB, one of the dioxin-like PCBs, demands much research and regulatory attention. To evaluate an in vitro generated human skin tissue culture model, cutaneous disposition of TCB under different exposure scenarios was investigated. Occlusive or non-occlusive doses of 14C-TCB were applied at 4 or 40 µg/cm2 in different vehicles including acetone, methylene chloride, a water-acetone mixture, and a soil-based mixture in flow-through diffusion cell studies (n=6~7/exposure condition). Significant exposure-dependent dermal absorption and disposition were observed. In vitro 8-hr absorption varied from 0.04% to 1.46% depending on vehicle, dosage, and occlusion. Much more TCB was absorbed into perfusate from soil than from liquid (organic or water-organic mixture) vehicles although the total penetration amount was less. Surprisingly, TCB dermal absorption/penetration ratios, which can reflect dermal absorption efficiency, were decreased by occlusion (soil dose, 0.45 –> 0. 13) or by adding water to the acetone vehicle (0.06 –> 0.02). A lower (1/10) TCB dose in soil or in acetone showed a 3-5X higher fractional dose absorption, but a lower (1/3~1/2) transderrnal flux (µg/cm2/hr), than the higher dose in each vehicle. In conclusion, this human skin tissue culture model showed similar dermal absorption and disposition characteristics for TCB when compared to an in vitro porcine skin model. Dermal absorption data from liquid TCB doses might underestimate the risk of TCB from contaminated soil. Such observed exposure-dependent dermal disposition profiles need to be considered while assessing TCB dermal risk. (Supported by EPA-CR 824007).

Acetone, Assessing dermal risk, Dermal, Dermal absorption, Dermal penetration, Dermal permeation, Dermal risk, Dioxin-like PCB, EpiDerm, Methylene chloride, PCB, Percutaneous absorption, Percutaneous penetration, Pre-validation, Prevalidation, TCB, Transdermal, Transdermal flux, Validation