A new method for estimating dermal absorption from chemical exposure. 1. General approach

Area of Science:

• Toxicology
• Pharmacokinetics
• Chemical Engineering

Background:

• Accurate assessment of systemic chemical exposure via dermal absorption requires quantifying the total absorbed mass, including that within the skin.
• Understanding the kinetics of dermal penetration is crucial for risk assessment and predicting internal dose.

Purpose of the Study:

• To develop algebraic equations for estimating dermal absorption, incorporating exposure duration and chemical physicochemical properties.
• To model the initial rapid absorption phase and the barrier effect of the viable epidermis on lipophilic compounds.
• To propose methods for predicting necessary physicochemical data when experimental values are unavailable.

Main Methods:

• Formulation of algebraic equations based on unsteady-state diffusion principles for a two-layer skin model.
• Analysis of the influence of lipophilicity and molecular weight on dermal penetration rates.
• Adaptation of the Potts and Guy permeability correlation to separately estimate stratum corneum partitioning and diffusivity.

Main Results:

• The proposed algebraic equations adequately represent the exact solutions for unsteady-state diffusion in a composite membrane.
• The model accounts for time-dependent absorption rates and the barrier properties of the epidermis.
• A method is presented for a priori estimation of physicochemical parameters like partitioning and diffusivity.

Conclusions:

• The developed equations provide a robust method for estimating dermal absorption and systemic exposure.
• These models enhance the prediction of chemical uptake through the skin, considering key physicochemical factors.
• The study offers practical approaches for estimating essential data for toxicological and pharmacokinetic assessments.