||Comparative In vitro Percutaneous Absorption of p-Substituted Phenols through Rat Skin Using Static and Flow-Through Diffusion Systems.
Hughes, M. F. ;
Shrivastava, S. P. ;
Fisher, H. L. ;
Hall, L. L. ;
||ManTech Environmental Technology, Inc., Research Triangle Park, NC.;Health Effects Research Lab., Research Triangle Park, NC. Environmental Toxicology Div.
Dermal absorption ;
In vitro analysis ;
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The objective of this study was to determine the in vitro percutaneous absorption of (14)C-phenol and eight p-substituted derivatives and to examine the variability of this data. Two diffusion systems, the static and flow-through, were used. Clipped dorsal skin was removed from female F344 rats (90 days old), dermatomed to a thickness of approximately 350 micrometer, placed in a diffusion cell and treated with chemical (4 microgram/sq cm, in ethanol). The cumulative absorption at 72 hr for the phenols in both systems ranged from 15.4 to 97.6%. Greater than 70% of the chemical was absorbed in both systems when the chemical had a log P value between 1.4-3.5. Significant differences in percent absorption between the two diffusion systems were observed with 5 of the compounds. Absorption of acetamidophenol, chlorophenol and cyanophenol were significantly lower in the static system. Absorption of phenol and heptyloxyphenol were significantly lower in the flow-through system. The most variable absorption data in both systems were with the phenols that were absorbed the least (70%). These same chemicals were also on the extremes of the log P scale for the phenols examined. Controlling for the variability of in vitro percutaneous absorption of chemicals is necessary when using the data for human risk assessment.