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ICCVAM Biennial Report 2018-2019

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

In Vitro Disposition of Tox21 Chemicals

IVIVE relates chemical concentrations that induce a response in an in vitro assay to chemical exposures that induce relevant effects in vivo. IVIVE typically assumes that chemicals behave in cells in an in vitro system in the same way they behave in blood and tissue in animals. Significant differences between in vitro models and in vivo systems make this assumption inaccurate. While the nature and extent of these differences are not well characterized, it is known that a chemical’s physicochemical properties affect factors such as binding to plastic and partitioning between medium and cells. EPA and NIEHS scientists selected a group of chemicals from the Tox21 library representing a diversity of structural and physicochemical properties and are examining their in vitro disposition to better understand these factors. Work since 2018 has focused on a pilot set of 10-20 chemicals, with anticipated expansion to 100-200 chemicals in 2020. This anticipated work will represent the largest undertaking of empirical measures of in vitro disposition and inform model predictions of in vitro disposition for other chemicals beyond those tested.