A compartment model to predict in vitro finite dose absorption of chemicals by human skin

• Published in: Chemosphere (Oxford) 2024-02, Vol.349, p.140689-140689, Article 140689
• Main Authors: Fisher, H.A., Evans, M.V., Bunge, A.L., Hubal, E.A. Cohen, Vallero, D.A.
• Format: Article
• Language: English
• Subjects: Compartment modeling; Dermal absorption; Fick's law of diffusion; Human dermal permeability; In vitro model
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2023.140689

Dermal uptake is an important and complex exposure route for a wide range of chemicals. Dermal exposure can occur due to occupational settings, pharmaceutical applications, environmental contamination, or consumer product use. The large range of both chemicals and scenarios of interest makes it difficult to perform generalizable experiments, creating a need for a generic model to simulate various scenarios. In this study, a model consisting of a series of four well-mixed compartments, representing the source solution (vehicle), stratum corneum, viable tissue, and receptor fluid, was developed for predicting dermal absorption. The model considers experimental conditions including small applied doses as well as evaporation of the vehicle and chemical. To evaluate the model assumptions, we compare model predictions for a set of 26 chemicals to finite dose in-vitro experiments from a single laboratory using steady-state permeability coefficient and equilibrium partition coefficient data derived from in-vitro experiments of infinite dose exposures to these same chemicals from a different laboratory. We find that the model accurately predicts, to within an order of magnitude, total absorption after 24 h for 19 of these chemicals. In combination with key information on experimental conditions, the model is generalizable and can advance efficient assessment of dermal exposure for chemical risk assessment. [Display omitted] •Development of a flexible model to predict small dose dermal exposure.•Minimized input parameters for quick evaluation of emerging chemicals.•Both chemical and vehicle evaporation are relevant.•Dynamics of neat chemical considered when vehicle is absent.•Experimental data used to evaluate model by matching inputs to reported conditions.