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Development and Initial Results from the Inclusion of Evaporation into a 2D dermal absorption model
Citation:
Deacon, B., S. Silva, G. Lian, M. Evans, AND T. Chen. Development and Initial Results from the Inclusion of Evaporation into a 2D dermal absorption model. SOT, Nashville, TN, March 19 - 23, 2023. https://doi.org/10.23645/epacomptox.22207186
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. Model evaluation is an important step needed to increase confidence in our effort. This work produces a collection of dermal absorption data in combination with molecular descriptors and parameters from the CompTox Dashboard.
Description:
Computational models, alongside experiments, have been used to assess skin permeation of chemicals. The Surrey model, a mechanistic model for predicting transdermal and systemic kinetics of chemicals diffusing through various skin layers, has been used and validated with infinite dose methods to assess chemical permeation. To replicate published experiments and real-life exposure scenarios, this research further develops the Surrey model. An evaporation module will be developed and integrated into the Surrey model to improve the finite dose method. The latest iteration of the Surrey model will provide simulations of experimental conditions where the vehicle will be in contact with the air instead of being covered. We will then compare the model to previous versions of the Surrey model, US EPA high throughput, generic, and physiologically based toxicokinetic (httk) model and to experimental finite dose data, taken from Aggarwal et al, 2015 and Hewitt et al, 2020. Development of the model has been carried out in Python and improves upon the Surrey model reported in Chen et al, 2016. The module has considered both ideal and non-ideal evaporation. An ideal solution involves calculating the flux into the atmosphere, whereas a non-ideal solution involves both the flux and the activity. The evaporation model mainly considers a vehicle of water plus one active ingredient (e.g., water: nitrobenzene), with the capability to model a three-component system (e.g., water: ethanol: nitrobenzene). Validation has been performed for the individual evaporation module and the Surrey model. We present comparisons between models and experimental data. The Surrey model is compared against the Surrey model without evaporation to highlight the improvement seen. This comparison approach with both comparing to our previous model and to experiment results in a higher confidence level of the model. Comparing the model to Aggarwal et al, 2015 and Hewitt et al, 2020 demonstrates that our model can apply to a wide range of chemicals (cosmetics and pesticides); the model previously tested only pharmaceutical chemicals. Several improvements have been made to the Surrey model and the current version has been validated to allow application of the model.
URLs/Downloads:
DOI: Development and Initial Results from the Inclusion of Evaporation into a 2D dermal absorption model
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