Physiologically based modeling of nonsteady state dermal absorption of halogenated methanes from an aqueous solution

Dermal absorption of organic chemicals from aqueous solutions are a concern in both the workplace and the home. Organic chemicals are generally not very soluble in water and the exposure may never reach steady state because the concentration of chemical decreases during the exposure. In vivo animal studies which mimic human exposures, but are carefully controlled, are one way to measure absorption. Whole animal studies are superior to excised skin measurements, because the physiological responses including blood flow, metabolism, and biological defenses are present. In this study, we develop a physiologically based model for nonsteady state exposures to organic chemicals in aqueous solutions. A key feature of this model is a compartment which describes loss of chemical in the exposure solution due to absorption into the skin. We exposed rats to a range of aqueous concentrations of dibromomethane (2.4 to 9.4 mg/ml) and bromochloromethane (3.6 to 12.8 mg/ml) and measured blood concentrations during 24-hr exposures. The blood concentrations peaked at about 1-2 hr and diminished to nearly nothing at 24 hr. Physiologically based models were used to estimate permeability coefficients for each of the exposures, although none of the exposures reached steady state due to the decreasing concentration of chemical on the surface of the skin. A constant permeability coefficient adequately described the blood concentrations during the prolonged exposure. Physiologically based models can be used to estimate permeability coefficients when the concentration of chemical on the skin is not constant. These permeability parameters can subsequently be used for assessing the risks in human exposure situations.