PNNL

Abstract

Realistic estimates of dermal bioavailability following exposures to solvents through contaminated soil and water are critical components in the overall understanding of human health risk. To assess the dermal bioavailability of trichloroethylene (TCE), exhaled breath was monitored in real time using an ion trap mass spectrometer (MS/MS) to track uptake, distribution, and elimination following dermal exposures in rats and humans under various exposure scenarios. Male F344 rats were exposed to TCE in water or soil matrices under occluded or non-occluded conditions by applying a patch to a clipper-shaved area of the back. A physiologically based pharmacokinetic (PBPK) model was used to estimate total bioavailability. Rats were placed in off-gassing chambers and the chamber air TCE concentration was quantitated for 3-5 h post-dosing using the MS/MS. Human volunteers were exposed either by whole hand immersion or by attaching small patches containing TCE in soil or water on each forearm. Volunteers were provided breathing air via a facemask to eliminate inhalation exposure and exhaled breath was analyzed using the mass spectrometer. Percent absorbed and the dermal permeability coefficient (KP) were estimated for each individual by optimization of the PBPK model to the exhaled breath data and the changing media concentrations resulting from volatilization of TCE. Estimates for KP in a water matrix were 0.31 ? .014 cm/h and 0.015 ? 0.003 cm/h in rats and humans, respectively. KP estimates were more than 3-times higher from water than soil matrices in both species and KPs were always higher in rats than humans. The KP values estimated using the PBPK model were consistent, regardless of volatilization, exposure concentration, or duration. In contrast, KP values calculated using the standard Fick's Law equation were strongly affected by exposure length and volatilization of TCE.