Oak Ridge Associated Universities, Assigned to U.S. Environmental Protection Agency, Office of Research and Development, Center for Computational Toxicology and Exposure, Research Triangle Park, NC, USA.
U.S. Environmental Protection Agency, Office of Research and Development, Center for Computational Toxicology and Exposure, Research Triangle Park, NC, USA.
Chemosphere. 2024 Feb;349:140689. doi: 10.1016/j.chemosphere.2023.140689. Epub 2023 Nov 12.
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.
皮肤吸收是广泛的化学物质的一个重要和复杂的暴露途径。皮肤暴露可能由于职业环境、药物应用、环境污染或消费产品使用而发生。感兴趣的化学物质和情况的范围广泛使得难以进行可推广的实验,因此需要一个通用模型来模拟各种情况。在这项研究中,开发了一个由一系列四个充分混合的隔室组成的模型,代表源溶液(载体)、角质层、活组织和受体液,用于预测皮肤吸收。该模型考虑了实验条件,包括小剂量应用以及载体和化学物质的蒸发。为了评估模型假设,我们将模型对 26 种化学物质的预测与单个实验室的有限剂量体外实验进行了比较,该实验使用稳态渗透率系数和从不同实验室进行的无限剂量暴露的体外实验得出的平衡分配系数数据。我们发现,对于其中 19 种化学物质,该模型在 24 小时内准确预测了总吸收量,误差在一个数量级以内。结合实验条件的关键信息,该模型具有通用性,可以促进对化学风险评估中皮肤暴露的有效评估。