Realistic estimates of percutaneous absorption following exposures to solvents in the workplace, or through contaminated soil and water, are critical to understanding human health risks. A method was developed to determine dermal uptake of solvents under non-steady-state conditions using real-time breath analysis in rats, monkeys, and humans. The exhaled breath was analyzed using an ion-trap mass spectrometer, which can quantitate chemicals in the exhaled breath stream in the 1-5 ppb range. The resulting data were evaluated using physiologically-based pharmacokinetic (PBPK) models to estimate dermal permeability constants (q) under various exposure conditions. The effects of exposure matrix (soil versus water), occlusion versus non-occlusion, and species differences on the absorption of methyl chloroform, trichloroethylene, and benzene were compared.
Exposure concentrations were analyzed before and at
0.5-hour intervals throughout the exposures. The percentage of
each chemical absorbed and the corresponding Kp were estimated
by optimization of the PBPKmodel to the medium concentration
and the exhaled-breath data. The method was found
to be sufficiently sensitive for animal and human dermal studies
at low exposure concentrations over small body surface areas,
for short periods, using non-steady-state exposure conditions.
Keywords percutaneous absorption; volatile organic chemicals;
rat; human; monkey; breath analysis: PBPK modeling.