Nature of the Binding Interaction for 50 Structurally Diverse Chemicals with Rat Estrogen Receptors

This study was conducted to characterize the estrogen receptor (ER)–binding affinities of 50 chemicals selected from among the high production volume chemicals under the U.S. EPA’s (U.S. Environmental Protection Agency’s) Toxic Substances Control Act inventory. The chemicals were evaluated using the rat uterine cytosolic (RUC) ER-competitive binding assay, with secondary analysis using Lineweaver-Burk plots and slope replots to confirm true competitive inhibition and to determine an experimental Ki. Data from these ER-competitive binding assays represent the types of competitive binding curves that can be obtained when screening chemicals with broad structural diversity. True compet-itive inhibition was observed in 17 of 50 chemicals. Binding affinities were much lower than that of estradiol (E2) with Ki concentrations ranging from 0.6 to 373mM as compared with that of E2 (0.77nM). Other chemicals that appeared to displac