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ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods

Generalized Inhalation Toxicity Model

The AFRL 711th Human Performance Wing is collaborating with EPA to create an inhalation component for the R-based httk package. The goal of this effort is to develop a computational approach to generate high-throughput toxicokinetic estimates of chemical inhalation exposures. The inhalation component of httk will have three major modules: gas, aerosol, and mixture inhalation. In combination, these modules will address the most common occupational exposure scenarios. The project utilizes open-source software, which should encourage ongoing collaborations for updating and improving the models.

The gas inhalation module utilizes physicochemical property values from the OPERA QSAR tool to estimate the time course of blood and exhaled breath concentrations. A paper describing the gas inhalation module in more detail will be published in 2020 (Linakis et al. 2020). The aerosol module currently includes updated versions of two previously published lung deposition models to allow users more flexibility in determining which region of the lungs may be affected as a result of exposures to aerosols of a certain particle size. Upon completion and release of these modules, a mixture module will be pursued utilizing the current literature on gas-aerosol/particle interactions.