Methods of assessing the percutaneous absorption of volatile chemicals in isolated perfused skin: Studies with chloropentafluorobenzene and dichlorobenzene

The experimental determination of dermal absorption of volatile chemicals i s fraught with difficulties. The isolated perfused porcine skin flap (IPPSF ) is a biologically intact, perfused skin preparation that has been employe d to predict dermal absorption of chemicals in humans. The purpose of this work was to explore various experimental dosing strategies for volatile che micals using dichlorobenzene (DCB) and chloropentafluorobenzene (CPFB) as m odel compounds. Effects of complete occlusion and various strategies of vap or trapping, vapor dosing, and solvent effects were explored. The results s uggest that dosing methodology is a major determinant of dermal absorption and could easily skew results obtained from different systems. A biological ly sensitive system such as the IPPSF is particularly sensitive to the mani pulations required to ensure precise dosing of these compounds. An interest ing finding was that the effects of solvents on compound absorption that ar e routinely described in liquid dosing scenarios were also detected when bo th the compound and solvent were exposed during the vapor phase.