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 co ncern in both the workplace and the home. Organic chemicals are genera lly not very soluble in water and the exposure may never reach steady state because the concentration of chemical decreases during the expos ure. In vivo animal studies which mimic human exposures, but are caref ully controlled, are one way to measure absorption. Whole animal studi es are superior to excised skin measurements, because the physiologica l responses including blood flow, metabolism, and biological defenses are present. in this study, we develop a physiologically based model f or 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 measu red blood concentrations during 24-hr exposures. The blood concentrati ons peaked at about 1-2 hr and diminished to nearly nothing at 24 hr. Physiologically based models were used to estimate permeability coeffi cients for each of the exposures, although none of the exposures reach ed steady state due to the decreasing concentration of chemical on the surface of the skin. A constant permeability coefficient adequately d escribed the blood concentrations during the prolonged exposure. Physi ologically based models can be used to estimate permeability coefficie nts when the concentration of chemical on the skin is not constant. Th ese permeability parameters can subsequently be used for assessing the risks in human exposure situations. (C) 1997 Academic Press.