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In vitro percutaneous absorption of benzidine in complex mechanistically defined chemical mixtures
R E Baynes1, C Brownie, H Freeman
1Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Toxicology and Applied Pharmacology
|December 1, 1996
Summary
This study examined benzidine topical absorption in complex mixtures. DMSO enhanced absorption, while SnCl2 inhibited it, highlighting the need for mixture-based risk assessments.
Area of Science:
- Toxicology
- Dermal Absorption
- Chemical Mixtures
Background:
- Limited research exists on topical benzidine absorption.
- Humans are often exposed to chemical mixtures, not single toxicants.
- Understanding mixture effects is crucial for accurate risk assessment.
Purpose of the Study:
- To investigate the cumulative effects of chemical mixtures on benzidine percutaneous absorption.
- To define mixtures and evaluate interactions between components.
- To assess benzidine absorption using in vitro models.
Main Methods:
- Utilized isolated perfused porcine skin flaps (IPPSFs) and flow-through diffusion cells.
- Tested ten mixtures containing benzidine, solvents (acetone, DMSO), surfactant (SL), vasodilator (M), and reducing agent (SnCl2).
- Quantified benzidine absorption and penetration over time.
Main Results:
- Benzidine absorption extent was similar across methods, but flux profiles differed.
- DMSO enhanced benzidine dermal penetration compared to acetone.
- SnCl2 significantly inhibited benzidine absorption, while SL + M enhanced it.
- Maximum observed absorption was ~3% and penetration 22% over 8 hours.
Conclusions:
- Chemical interactions significantly influence benzidine dermal absorption.
- DMSO enhances, while SnCl2 inhibits benzidine penetration.
- Mixture exposure data is essential to avoid confounding risk assessments.