PNNL

Abstract

Realistic estimates of percutaneous absorption following exposures to solvents in the workplace, or through contaminated soil and water, are critical components in the overall understanding of human health risks. To this end, a method was developed to determine dermal uptake of solvents under nonsteady state conditions using real-time breath analysis in rats, monkeys, and human volunteers. 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 exhaled breath data were evaluated using physiologically based pharmacokinetic (PBPK) models to estimate dermal permeability constants (Kp), under various exposure conditions. Exposures have been conducted comparing the impact of exposure matrix (soil versus water), occlusion versus non-occlusion, and species-differences on the percutaneous absorption of methyl chloroform, trichloroethylene, and benzene. Exposure concentrations were analyzed before the exposure and at 0.5 hr intervals throughout the exposure to track changing exposure conditions. The percent of each chemical absorbed and their corresponding Kp values were estimated by optimization of the PBPK model to the media concentrations and the exhaled breath data. The results clearly illustrated that the methodology was sufficiently sensitive to enable the conduct of animal and human dermal studies at low exposure concentrations over small body surface areas, for short periods of time, using nonsteady state exposure conditions.