Evaluation of the Dermal Bioavailability of Aqueous Xylene in F344 Rats and Human Volunteers

Abstract

Xylene is a clear, colorless liquid used as a solvent in the printing, rubber, and leather industries and is commonly found in paint thinners, paints, varnishes, and adhesives. Although humans are most likely to be exposed to xylene via inhalation, xylene is also found in well and surface water. Therefore, an assessment of the dermal contribution to total xylene uptake is useful for understanding human exposures. To evaluate the significance of these exposures, the dermal absorption of o-xylene was assessed in F344 male rats and human volunteers using a combination of real-time exhaled breath analysis and physiologically based pharmacokinetic (PBPK) modeling. Animals were exposed to o-xylene dermally. Immediately following the initiation of exposure, individual animals were placed in a glass off-gassing chamber and exhaled breath was monitored. Human volunteers participating in the study placed both legs into a stainless steel hydrotherapy tub containing an initial concentration of approximately 500 w g/L o-xylene. Exhaled breath was continually analyzed from each volunteer before, during, and after exposure to track absorption and subsequent elimination of the compound in real time. In both animal and human studies, a PBPK model was used to estimate the dermal permeability coefficient (K p ) to describe each set of exhaled breath data. Rat skin was found to be approximately 12 times more permeable to aqueous o-xylene than human skin. The estimated human and rat aqueous o-xylene K p values were 0.005 - 0.001 cm/h and 0.058 - 0.009 cm/h, respectively.