Dataset for: An Approach for Using In Vitro and In Silico Data to Identify Pharmaceuticals with Potential (Anti-)Estrogenic Activity in Aquatic Vertebrates at Environmentally Relevant Concentrations

Endocrine-active pharmaceuticals can cause adverse reproductive and developmental effects in non-target organisms. Aquatic vertebrates may be susceptible to the effects of such pharmaceuticals given that the structure of hormone receptors and the physiology of the endocrine system are highly conserved across vertebrates. To aid in the regulatory review of the environmental impact of drugs, we demonstrate an approach to screen and support the prioritization of pharmaceuticals based on their ability to interact with estrogen receptors (ERs) at environmentally relevant concentrations. Tox21 in vitro results from ER agonist and antagonist assays were retrieved for 1,123 pharmaceuticals. In silico predictions from the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) models were used to estimate ER agonist and antagonist activity for an additional 170 pharmaceuticals not tested in the Tox21 assay platform. The “estrogenic effect ratio” (EER) and “anti-estrogenic effect ratio” (AEER) were calculated by comparing the activity concentration at half-maximal response (AC50) for ER agonism and antagonism, respectively, to estimated pharmaceutical concentrations in fish tissue based on estimates of environmental exposures. A total of 73 and 127 pharmaceuticals were identified as ER agonists and antagonists, respectively. As expected, 17β-estradiol and 17α-ethinylestradiol displayed EERs > 1, and raloxifene and bazedoxifene acetate displayed AEERs > 1, thus indicating that these pharmaceuticals have potential to reach fish tissue levels that exceed concentrations estimated to interact with ERs. Four pharmaceuticals displayed EERs between 0.1 and 1, while six displayed AEERs between 0.1 and 1. This approach may help determine the need for submission of environmental assessment data for new drug applications and support prioritization of pharmaceuticals with potential to disrupt endocrine signaling in vertebrates.