Phenones and hydroxy benzophenones are widely used as UV radiation filters, and in the manufacturing of insecticides and pharmaceuticals. Understanding the ability of these chemicals to mimic the effects of the steroid estrogen is of interest to the US Environmental Protection Agency and other international environmental organizations. The current study sequentially combined complementary in vitro (outside a living organism) rainbow trout estrogen receptor (rtER) binding and liver slice vitellogenin (Vtg) mRNA induction assays in the context of a defined ER-mediated adverse outcome pathway (AOP). Cyclic phenones, branched phenones, and hydroxybenzophenones bound to rtER with relative potency ranging from no affinity to high binding affinity of 0.11%, and many induced Vtg, an egg yolk protein, gene expression in rt liver slices. In addition, cyclohexylphenylketone which did not bind rtER binding in cytosol was biotransformed within liver tissue to a chemical that induced Vtg expression. Cyclic phenones, branched phenones and hydroxybenzophenones produced estrogen like responses in these rainbow trout in vitro assays. This dataset is associated with the following publication: Tapper, M., J. Denny, J. Serrano, R. Kolanczyk, B. Sheedy, G. Overland, M. Hornung, and P. Schmieder. Phenone, hydroxybenzophenone, and branched phenone estrogen receptor binding and vitellogenin agonism in rainbow trout in vitro models. Applied In Vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, USA, 5(1): 62-74, (2019).

Screening certain environmental chemicals for their ability to interact with endocrine targets, including the androgen receptor (AR), is an important global concern. We previously developed a model using a battery of eleven in vitro AR assays to predict in vivo AR activity. Here we describe a revised mathematical modelling approach that also incorporates data from newly available assays and demonstrate that subsets of assays can provide close to the same level of predictivity. These subset models are evaluated against the full model using 1820 chemicals, as well as in vitro and in vivo reference chemicals from the literature. This dataset is associated with the following publication: Judson, R., K. Houck, K. Friedman, J. Brown, P. Browne, P. Johnston, D. Close, K. Mansouri, and N. Kleinstreuer. Selecting a Minimal set of Androgen Receptor Assays for Screening Chemicals. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, USA, 117(November 2020): 104764, (2020).

Screening certain environmental chemicals for their ability to interact with endocrine targets, including the androgen receptor (AR), is an important global concern. We previously developed a model using a battery of eleven in vitro AR assays to predict in vivo AR activity. Here we describe a revised mathematical modelling approach that also incorporates data from newly available assays and demonstrate that subsets of assays can provide close to the same level of predictivity. These subset models are evaluated against the full model using 1820 chemicals, as well as in vitro and in vivo reference chemicals from the literature. This dataset is associated with the following publication: Judson, R., K. Houck, K. Friedman, J. Brown, P. Browne, P. Johnston, D. Close, K. Mansouri, and N. Kleinstreuer. Selecting a Minimal set of Androgen Receptor Assays for Screening Chemicals. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, USA, 117(November 2020): 104764, (2020).

Microarray experiments examined in the study. This dataset is associated with the following publication: Rooney, J., N. Ryan, J. Liu, R. Houtman, R. van Beuningen, J. Hsieh, G. Chang, S. Chen, and J. Corton. A Gene Expression Biomarker Identifies Chemical Modulators of Estrogen Receptor α in an MCF-7 Microarray Compendium. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, USA, 34(2): 313-329, (2021).

Microarray experiments examined in the study. This dataset is associated with the following publication: Rooney, J., N. Ryan, J. Liu, R. Houtman, R. van Beuningen, J. Hsieh, G. Chang, S. Chen, and J. Corton. A Gene Expression Biomarker Identifies Chemical Modulators of Estrogen Receptor α in an MCF-7 Microarray Compendium. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, USA, 34(2): 313-329, (2021).

A representative group of multicyclic aromatic hydrocarbons (MAHC) which can be further classified as bridged-ring (bridged-MAHC) or fused-ring (fused-MAHC) were examined for their ability to interact with the estrogen receptor of rainbow trout (rtER) in a hepatic cytosolic estrogen receptor competitive binding assay (cyto rtERαβ) and the vitellogenin (Vtg) mRNA gene activation liver slice assay. All five fused-MAHCs; naphthalene (NAFT), fluorene (FE), Fluoranthene (FAT), pyrene (PY), and 9,10-dihydroanthracene (DAC) had no estrogenic activity in the in vitro assays used. Five of the eight bridged-MAHCs; triphenylethylene (3PE), o-terphenyl (OTP), triphenylmethane (TPM), 1,1-diphenylethylene (DPE), and cis-stilbene (CSB) were estrogenic in these assays. The additional three bridged-MAHC’s; trans-stilbene (TSB), tetraphenylethylene (4PE), and 4,4-di-tertbutylphenyl (DtBB) were determined to be non-binders due to isomeric configuration, solubility limitation, and possible steric hinderance. This first report of the rtER-binding of bridged-MAHCs in fish demonstrates binding for a class of chemicals normally not thought of as having an affinity for the estrogen receptor and further supports the versatility or promiscuity of ER ligand selectivity. This dataset is associated with the following publication: Kolanczyk, R., J. Denny, B. Sheedy, P. Schmieder, and M. Tapper. Estrogenic activity of multicyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) in vitro assays. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 207: 43-51, (2019).

A representative group of multicyclic aromatic hydrocarbons (MAHC) which can be further classified as bridged-ring (bridged-MAHC) or fused-ring (fused-MAHC) were examined for their ability to interact with the estrogen receptor of rainbow trout (rtER) in a hepatic cytosolic estrogen receptor competitive binding assay (cyto rtERαβ) and the vitellogenin (Vtg) mRNA gene activation liver slice assay. All five fused-MAHCs; naphthalene (NAFT), fluorene (FE), Fluoranthene (FAT), pyrene (PY), and 9,10-dihydroanthracene (DAC) had no estrogenic activity in the in vitro assays used. Five of the eight bridged-MAHCs; triphenylethylene (3PE), o-terphenyl (OTP), triphenylmethane (TPM), 1,1-diphenylethylene (DPE), and cis-stilbene (CSB) were estrogenic in these assays. The additional three bridged-MAHC’s; trans-stilbene (TSB), tetraphenylethylene (4PE), and 4,4-di-tertbutylphenyl (DtBB) were determined to be non-binders due to isomeric configuration, solubility limitation, and possible steric hinderance. This first report of the rtER-binding of bridged-MAHCs in fish demonstrates binding for a class of chemicals normally not thought of as having an affinity for the estrogen receptor and further supports the versatility or promiscuity of ER ligand selectivity. This dataset is associated with the following publication: Kolanczyk, R., J. Denny, B. Sheedy, P. Schmieder, and M. Tapper. Estrogenic activity of multicyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) in vitro assays. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 207: 43-51, (2019).

This is an original dataset generated at the U.S. EPA. Data was analyzed with the ToxCast Pipeline and deposited for release in invitroDB accessible via the U.S. EPA CompTox Chemicals Dashboard. Dataset is a zip file containing two Excel spreadsheets titled AIME-ERTA_384_Tables_All_Submission_v2 and README_AIME-ERTA_384_Manuscript_Sup_Data_v2. This dataset is associated with the following publication: Hopperstad, K., D. DeGroot, T. Zurlinden, C. Brinkman, R. Thomas, and C. Deisenroth. Chemical Screening in an Estrogen Receptor Transactivation Assay with Metabolic Competence. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 187(1): 112-126, (2022).

This is an original dataset generated at the U.S. EPA. Data was analyzed with the ToxCast Pipeline and deposited for release in invitroDB accessible via the U.S. EPA CompTox Chemicals Dashboard. Dataset is a zip file containing two Excel spreadsheets titled AIME-ERTA_384_Tables_All_Submission_v2 and README_AIME-ERTA_384_Manuscript_Sup_Data_v2. This dataset is associated with the following publication: Hopperstad, K., D. DeGroot, T. Zurlinden, C. Brinkman, R. Thomas, and C. Deisenroth. Chemical Screening in an Estrogen Receptor Transactivation Assay with Metabolic Competence. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 187(1): 112-126, (2022).

Data are summarized in a two-dimensional data matrix that was developed for each substance for hazard characterization (Tables S1–S3). In the horizontal direction of the matrix, read-across of the target phenol to the source analogues was performed for the purpose of data-gap filling, whereas in the vertical direction, data from different streams (traditional and NAM) were compared and contrasted, to evaluate concordance of orthogonal approaches for evaluating potential estrogenicity. The greater the degree of agreement in orthogonal approaches for determining bioactivity, the greater the confidence one has in using the collective results of such NAMs in hazard characterization of the target phenol. This dataset is associated with the following publication: Webster, F., M. Gagne, G. Patlewicz, P. Pradeep, N. Trefiak, R. Judson, and T. Barton-Maclaren. Predicting estrogen receptor activation by a group of substituted phenols: An integrated approach to testing and assessment case study. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, USA, 106: 278-291, (2019).