Diffusion cell model, dermal

The primary approach to assess dermal absorption is the in vitro diffusion cell. In thi,s model, skin sections (full thickness, deimatomed to a specific thickness) are placed in a two-chambered diffusion cell in which receptor fluid is placed in a reservoir (static cells) or perfused through a receiving chamber (flow-through cells) to simulate cutaneous blood flow. Chemical may either be dosed under ambient conditions neat or dissolved in a vehicle (Franz and Bronaugh cells) or in water (sLdc-by-side diffusion... 

Dixon et al. (2001) described a preliminary PB-PK model to predict JP-8 concentrations in Air Force fuel-cell maintenance workers. The model used data from PB-PK models of naphthalene inhalation in mice and rats and nonane inhalation in rats. In addition to inhalation, a pathway of dermal exposure and a skin compartment were included. For highly exposed people, the PB-PK model was generally in agreement with exhaled-air naphthalene concentrations however, predictions for the low-exposure scenarios were grossly underestimated, especially in female workers, by a factor of 10. The model did not predict blood and urinary concentrations. The major limitation of the Dixon et al. (2001) study was the lack of appropriate human data (e.g., metabolic measures, blood and tissue partition coefficients, and diffusion rates). The Dixon et al. (2001) model predicted a rapid decline in naphthalene concentrations in all compartments after exposure except liver, fat, and brain. The model predicted accumulation in liver, brain, and fat tissues for a 7-day period that included 4-hr exposures on 5 days. Competition for enzyme does not occur only from interactions of different inhaled compounds. Interactions can also occur between inhaled compounds and metabolites formed in the body that require similar enzymes for biotransformation. Detailed kinetic studies with both benzene and -hexane show inhibition of later metabolic steps, phenol to hydroquinone or methyl -butyl ketone to 2,5-hexane dione, by high concentrations of inhaled benzene or hexane, respectively (Medinsky et al. 1989 Andersen and Clewell 1984). 

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