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

Area of Science:

• Pharmacology
• Toxicology
• Dermatology

Background:

• Percutaneous absorption is crucial for understanding chemical exposure and drug delivery.
• In vitro models using animal skin are common for assessing chemical penetration.
• Comparing different diffusion systems is essential for reliable in vitro absorption data.

Purpose of the Study:

• To compare the in vitro percutaneous absorption of phenol and eight p-substituted phenolic derivatives.
• To evaluate the performance of static and flow-through diffusion systems for absorption studies.
• To examine the variability of cumulative percentage absorption data.

Main Methods:

• Utilized clipped dorsal skin from female Fischer 344 rats, sectioned to approximately 350 µm thickness.
• Applied phenol compounds at 4 µg/cm² in ethanol to the skin in diffusion cells.
• Measured 72-hour cumulative absorption in receptor fluid using both static and flow-through diffusion systems.

Main Results:

• 72-hour cumulative absorption ranged from 15.4% to 97.6% across phenols and systems.
• High absorption (>70%) was observed for phenols with a log octanol:water partition coefficient (log P) between 1.4 and 3.5.
• Significant absorption differences between systems were noted for five phenols, with lower absorption in the static system for acetamidophenol, chlorophenol, and cyanophenol, and in the flow-through system for phenol and heptyloxyphenol.

Conclusions:

• Both static and flow-through diffusion systems are viable for in vitro percutaneous absorption studies.
• Chemical properties, particularly log P, significantly influence absorption rates and variability.
• Data variability is higher for poorly absorbed chemicals, necessitating careful interpretation of results from different systems.