A Real-Time In-vivo Method for Studying the Percutaneous Absorption of Volatile Chemicals

Abstract

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 (K_p) 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 O.5-hour intervals throughout the exposures. The percentage of each chemical absorbed and the corresponding K_p were estimated by optimization of the PBPK model to the medium concentration and the exhaled-breath data. The method was found to be sufficiendy 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