Screening Chemicals for Estrogen Receptor Activity

We identified ER-active chemicals from the supplemental data file S2 published by Judson et al.^{73 (link)} In that study, 45 reference chemicals were tested in 18 in vitro ToxCast assays that measure ER-regulated pathways, including receptor binding and cellular proliferation, and those data were normalized to 17- $\mathrm{\alpha }$ -ethinylestradiol and integrated to produce area-under-the-curve (AUC) scores for ER agonism and antagonism.^{73 (link)} This testing and modeling approach was applied to a library of 1,812 chemicals with CR data from the 18 ToxCast assays for ER activity, and the authors used a threshold of AUC $\ge 0.1$ to define chemicals with clear agonist/antagonist activity. Here, we classified chemicals with an AUC $\ge 0.7$ as having high activity, $0.7>$ AUC $\ge 0.4$ as medium activity, and $0.4>$ AUC $\ge 0.1$ as low activity (Excel Tables S1 and S3–S5). Because Judson et al. indicated that an AUC $<0.1$ could reflect interferences in assay results,^{73 (link)} we applied a second threshold of $0.1>$ AUC $\ge 0.01$ for borderline ER agonism or antagonism. Some chemicals were borderline agonistic and antagonistic, so we designated these as having mixed borderline activity. We considered chemicals with agonist and antagonist AUCs $<0.01$ to be inactive.