A solvatochromatic approach to quantifying formulation effects on dermal permeability.

Area of Science:

• Toxicology
• Dermal Absorption
• Computational Chemistry

Background:

• Dermal risk assessments typically focus on single chemical exposure.
• Skin is often exposed to multiple chemicals that can alter permeability.
• Existing methods often use animal models or computational approaches for single solutes.

Purpose of the Study:

• To demonstrate formulation effects on dermal permeability can be modeled using linear solvation energy relationships (LSER).
• To investigate how simple and complex formulations impact dermal absorption.
• To predict dermal permeability of chemicals in occupational exposure scenarios.

Main Methods:

• Utilized linear solvation energy relationship (LSER) models with formulation-specific strength coefficients.
• Experimentally tested dermal permeability of phenolic compounds in 50% ethanol and metal-working fluid (MWF) formulations.
• Employed a membrane-coated fiber (MCF) array system with diverse membranes to correlate with skin permeability changes.

Main Results:

• Formulation-specific strength coefficients accurately predicted changes in dermal permeability (r(2) = 0.75-0.83).
• Chemical-induced skin permeability changes with 50% ethanol strongly correlated with changes in the MCF array system (r(2) = 0.91).
• Identified hydrogen donating ability and hydrophobicity as key quantitative interactions in ethanol mixtures.

Conclusions:

• LSER modeling effectively predicts formulation-driven changes in dermal permeability.
• The MCF array system serves as a viable surrogate for assessing chemical-induced skin permeability changes.
• This approach offers a promising method for predicting dermal absorption of complex chemical mixtures in occupational settings.