Citation:

Fisher, H., M. Evans, A. Bunge, E. Cohen-Hubal, AND D. Vallero. A compartment model to predict in vitro finite dose absorption of chemicals by human skin. CHEMOSPHERE. Elsevier Science Ltd, New York, NY, 349:140689, (2024). https://doi.org/10.1016/j.chemosphere.2023.140689

Impact/Purpose:

The dermal route of exposure is an important and complex route which includes a wide range of chemicals, such as pharmaceuticals and consumer products. Dermal absorption data for this large number of chemicals is not available. Generic models developed to predict dermal absorption for chemicals has become a preferred choice. In particular, a generic dermal exposure route would be most useful when integrated with the High Throughput Toxicokinetic (httk) model that is being developed within our Center. The mass balance model evaluated in this manuscript represents the first steps towards achieving a generic dermal route.

Description:

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.

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