Comparative in vitro percutaneous absorption of p-substituted phenols through rat skin using static and flow-through...

The objective of this study was to compare the in vitro percutaneous absorption of phenol and eight p-substituted phenolic derivatives using the static and flow-through diffusion systems. The variability of the cumulative percentage absorption data was also examined. Clipped dorsal skin was removed from female Fischer 344 rats (90 days old), cut on a dermatome to approximately 350 mum thick, placed in a diffusion cell and treated with chemical (4 mug/cm(2), ethanol). The 72-hr cumulative absorption into the receptor fluid for the phenols in both systems ranged from 15.4 to 97.6% of the dose. Absorption was greater than 70% in both systems for phenols with a log octanol: water partition coefficient (log P) value between 1.4 and 3.5. The percentage of the dose remaining in the skin and washed from the skin and cell top at 72 hr in both systems ranged from 1.8 to 56.2% and from 0.7 to 45.2%, respectively. There were significant differences in absorption between the two systems with five of the phenols. Absorption was significantly lower for acetamido-, chloro- and cyanophenol in the static system and phenol and heptyloxyphenol in the flow-through system. However, the differences in absorption for phenol and chlorophenol were small (<4%) and may not be that biologically relevant. Phenols absorbed the least (<70%), were also on the extremes of the log P range examined and had the most variable absorption data. Both systems appear to be equivalent means to investigate in vitro percutaneous absorption of chemicals, but it is critical to recognize that the data can vary, especially for chemicals not absorbed well.