Application of a human skin tissue culture model in dermal absorption studies of 3,3',4,4'-tetrachlorobiphenyl-(TCB).
Toxicologist 2000 Mar; 54(1):150
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 ug/cm2 in different vehicles including acetone, methylene chloride, a wateracetone 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 waterorganic 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 dos, 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) transdermal flux (ug/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 non contaminated soil. Such observed exposure-dependent dermal disposition profiles need to be considered while assessing TCB dermal risk.
Models; Absorption-rates; Skin; Skin-absorption; In-vitro-studies; Tissue-culture; Risk-factors; Risk-analysis; Polychlorinated-biphenyls; Biphenyls
32598-13-3; 67-64-1; 75-09-2
The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania