Evaluation of a Flow-ThroughIn VitroSkin Penetration Chamber Method Using Acetone-Deposited Organic Solids

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Abstract
A systematic evaluation of a flow-through skin penetration chamber, obtained from Oak Ridge National Laboratory, was conducted by measuring in vitro cutaneous penetration with five organic chemicals: urea, caffeine, benzoic acid (BA), salicylic acid (SA), and acetylsalicylic acid (ASA). These hydrophilic test materials were selected for evaluation since it has been established by several investigators that the highly lipophilic compounds are difficult to study in any in vitro absorption system. They were also selected because of their known penetration of the skin of several species, including humans. Each chemical was applied in 5–10 µg/cm2 amounts as 14C-labeled chemicals in 10 µl volumes of acetone. The extent and rate of cutaneous penetration were compared using full-thickness skin from both HRS/J hairless mice and Fischer 344 rats. A rank order for the extent of penetration (percentage of dose absorbed over a uniform time period) was established using Fischer rat skin: caffeine > BA > SA > urea > ASA. A rank order using hairless mouse skin was not possible because the results were only statistically different from each other for urea vs. the other chemicals in this group. High-performance liquid chromatographic (HPLC) analysis for the chemical identity of penetrant molecules entering the effluent media revealed differences in the chemical moiety that penetrated compared with the chemical applied. Penetration by ASA from both hairless mouse and Fischer rat skin following application of ASA resulted in increasing proportions of the cleavage product, SA, in the effluent at later time points of these measurements, indicating a chemical transformation during penetration. Moreover, a species difference was observed (rat > mouse) in the degree to which either type of skin preparation cleaved the applied ASA to SA. In summary, our evaluation of this chamber has confirmed that several types of polar solid materials can penetrate skin in vitro and be readily quantified in this system. In addition, these results have further shown that stirring of the media receptor wells may be critical to making valid measurements for several chemicals in a flow-through design skin chamber, and that detection of the particular chemical species that penetrates skin (compared with the chemical applied) may be important to the characterization of radioactive skin penetration profiles.