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Performance Summary for Estrogen and Androgen Receptor Pathway Models and Associated Assay

Version 2 2022-02-22, 21:28
Version 1 2022-02-22, 21:27
posted on 2022-02-22, 21:28 authored by EPA CCTE
Science Inventory, CCTE products:

The US EPA has developed batteries of in vitro assays to test chemicals for their potential to interact with the androgen and estrogen receptors (AR and ER). These assays have been combined using mathematical models to provide overall scores for chemicals, indicating level of agonist and antagonist activity. The combinations of assays and models are known as the AR and ER Pathway Models (Judson, Magpantay et al. 2015, Kleinstreuer, Ceger et al. 2017) because the method for combining assays makes use of the underlying biological pathways leading from the interaction of a chemical with either AR or ER through receptor dimerization and cofactor recruitment, binding to DNA, RNA and protein production and, in the case of ER, to cell proliferation. Approximately 1800 chemicals have been tested in the AR and ER assays as part of the ToxCast and Tox21 in vitro screening programs and have model scores. The AR and ER Pathway Models and associated in vitro assay data have been described in multiple peer reviewed publications (Browne, Judson et al. 2015, Judson, Magpantay et al. 2015, Browne, Judson et al. 2017, Judson, Houck et al. 2017, Kleinstreuer, Ceger et al. 2017, Browne, Kleinstreuer et al. 2018, OECD 2019, Judson, Houck et al. 2020) and FIFRA Scientific Advisory Panel (SAP) reviews (U.S. EPA 2013, U.S. EPA 2017, US EPA 2018). In these publications, the models have been evaluated against various sets of reference chemicals. This document provides a consolidated resource containing the performance metrics for each of the individual assays as well as the AR and ER Pathway Models themselves.


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