ABSTRACT
In general, evaluations of dermal uptake of a chemical are made using animal skin (in vitro or in vivo) or human skin in vitro. However, studies conducted in our laboratory have illustrated that analysis of exhaled breath presents a useful methodology to assess dermal absorption of volatile compounds in human volunteers (1,2). Exhaled breath data is particularly useful when evaluated using some form of a kinetic model, such as a physiologically based pharmacokinetic (PBPK) model, to describe the changing kinetics over time. A PBPK model is ideally suited for integrating a variety of data, including exhaled breath measurements, to determine the penetration rate of chemicals through the skin. For instance, a PBPK model can be used to assess dermal exposures under non-steady-state conditions, where the transdermal flux is a function of the permeability coefficient (Kp), the area exposed, and the changing concentration gradient across the skin (3). The integration of realtime exhaled breath measurements and a PBPK model to determine dermal absorption has been successfully used for a number of compounds, including methyl chloroform, trichloroethylene, benzene, and toluene (1,2,4).
