Qiao, G.L. and J.E. Riviere. Impacts of Dermal Model and Exposure Variables on Risk Assessment of 3,3',4,4'-Tetrachlorobiphenyl (TCB). The Toxicologist 1998 42(I-S): 390.

3,3',4,4'-tetrachlorobiphenyl - 32598-13-3; methylene chloride - 00075-09-2; acetone - 00067-64-1

TCB is one of the dioxin-like PCBs which command great research and environmental interest. To quantify experimental model and exposure variable effects for risk data extrapolation, TCB dermal absorption and disposition from different vehicles were investigated in ex vivo (Isolated Perfused Porcine Skin Flap, IPPSF, n=4) and in vitro (flow through diffusion cell, n=7) porcine skin absorption models. ¹⁴C-TCB was dosed at 40 ug/cm² in different media including methylene chloride, acetone, water-based, and soil-based mixtures. Occlusion and dosage impacts were also explored. Significant vehicle-dependent model effects on dermal absorption and disposition were determined. In vitro and ex vivo absorption were averaged from 0.10 to 0.84% depending on vehicles. TCB was absorbed much more efficiently from soil than from organic vehicles and water-organic mixture in both models (p<0.05), and IPPSF showed higher absorption efficiency than the in vitro system with all formulations. Less penetration was seen from ex vivo than in vitro. Local penetration depth was water > methylene chloride > soil > acetone. Interestingly, occlusion effect was not seen with soil dose in vitro and water addition to organic vehicle did not significantly alter absorption in both systems. Low TCB soil dose showed ~ 10X higher fractional absorption (%dose) than, but identical transdermal flux (ug/cm²/hr) to, the high soil dose, suggesting a saturable absorption process. Therefore, absorption data from organic solvents might underestimate the risk of TCB from soil exposure. Such observed model-dependent vehicle effects and vehicle-dependent experimental model differences have to be taken into account while assessing TCB risk from dermal exposure. Specific mechanisms of model-exposure interactions may be better elucidated by applying pharmacokinetic principles.