Targeted Cell Assays test the ability of a chemical to directly interact with a nuclear hormone receptor. These tests will include the receptors for reproductive hormones (estrogen, androgen, progesterone), thyroid hormone, adrenal steroids and others, as well as other components of endocrine signaling pathways.
Chemical interactions with nuclear receptors include binding interactions (competitive and non-competitive), and activational interactions (agonist and antagonist). There are many ways to quantitatively measure the binding affinity of a compound, and different approaches can provide different kinds of information important to the chemist.
Activational assays also employ different technologies, and provide information that can supplement data collection. These assays typically utilize a cell-based system and a very specific nuclear receptor targeting. Tier 2 testing can quickly screen for possible agonist or antagonist activities of new compounds across multiple nuclear receptors. Based on the outcome of the assays, one can obtain an indication of which nuclear receptors (and thereby endocrine signaling pathways) may be affected by the new compound.
This tier represents a relatively comprehensive analysis of the ability of a chemical to interact with one or more of the 48 different nuclear receptors, providing a fairly rapid and cost-effective way to screen for chemicals that may be free of EDC activity.