Dose and airflow dependence of benzyl alcohol disposition on skin

The penetration of benzyl alcohol (BA) through split-thickness cadaver skin was measured in nonoccluded Franz cells placed in a fume hood. BA, dissolved in a small volume of ethanol and spiked with C-14 radiolabel, was applied to skin at nine doses ranging from 0.9 to 10600 mu g/cm(2). The percentage of radioactivity penetrated after 24 h increased gradually with dose, ranging from 19.8 +/- 2.9% at the lowest dose to 29.2 +/- 3.0% at the highest. Less than 4% of the radioactivity was retained in the tissue at 24 h; the remainder was considered to be evaporated. These data and those from a previous study were analyzed in terms of a finite dose diffusion/evaporation model. The analysis showed that the increase in BA absorption with dose was consistent with a threefold increase in BA diffusivity in the stratum corneum, as its concentration increased from tracer levels to saturation. The variable diffusivity model was able to describe the combined observations from the two studies to within an rms error of 4.2% of dose. A method of estimating the diffusion model parameters independently of the experiment was found to yield good agreement with the experimentally-derived values at low and moderate doses. (C) 2005 Wiley-Liss, Inc. and the American Pharmacists Association.