This data set describes experiments that were conducted to investigate whether exposure of male fathead minnows to environmentally-relevant estrone concentrations would result in elevated plasma 17β-estradiol concentrations in the fish. Secondly, we sought to establish whether observed elevations in plasma 17β-estradiol occurred as a result of the conversion of external estrone by the fish using an approach involving exposure of the fish to 13C-labeled estrone. Endpoints reported in the dataset include plasma 17β-estradiol and estrone concentrations, plasma vitellogenin concentrations, hepatic vitellogenin mRNA, 13C-labeled plasma 17β-estradiol and estrone concentrations, and testicular and/or hepatic expression of aromatase and several hydroxysteroid dehydrogenases involved in estrone metabolism. This dataset is associated with the following publication: Ankley, G., D. Feifarek, B. Blackwell, J. Cavallin, K. Jensen, M. Kahl, S. Poole, E. Randolph, T. Saari, and D. Villeneuve. Reevaluating the significance of estrone as an environmental estrogen (article). ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, 51: 4705-4713, (2017).

This data set describes experiments that were conducted to investigate whether exposure of male fathead minnows to environmentally-relevant estrone concentrations would result in elevated plasma 17β-estradiol concentrations in the fish. Secondly, we sought to establish whether observed elevations in plasma 17β-estradiol occurred as a result of the conversion of external estrone by the fish using an approach involving exposure of the fish to 13C-labeled estrone. Endpoints reported in the dataset include plasma 17β-estradiol and estrone concentrations, plasma vitellogenin concentrations, hepatic vitellogenin mRNA, 13C-labeled plasma 17β-estradiol and estrone concentrations, and testicular and/or hepatic expression of aromatase and several hydroxysteroid dehydrogenases involved in estrone metabolism. This dataset is associated with the following publication: Ankley, G., D. Feifarek, B. Blackwell, J. Cavallin, K. Jensen, M. Kahl, S. Poole, E. Randolph, T. Saari, and D. Villeneuve. Reevaluating the significance of estrone as an environmental estrogen (article). ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, 51: 4705-4713, (2017).

Data set to support the manuscript "Increased endocrine activity of xenobiotic chemicals as mediated by metabolic activation". Contains analytical measurement of metabolites, binding potential to the estrogen receptor, and gene activation to vitellogenin induction in the rainbow trout assays. Chemicals of interest in this study were phenolphthalein, phenolphthalin, and 4,4’-methylenedianiline. This dataset is associated with the following publication: Kolanczyk, R., J. Denny, B. Sheedy, V. Olson, J. Serrano, and M. Tapper. Increased Endocrine Activity of Xenobiotic Chemicals as Mediated by Metabolic Activation.. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 42(12): 2747-2757, (2023).

Aromatase inhibition is one of the chemical modes of action of concern to EPA's Endocrine Disruptor Screening Program (EDSP). In vitro bioassays that can detect aromatase inhibition are part of both the EDSP tier 1 screening program and are included subset of ToxCast assays employed for EDSP21 screening. An adverse outcome pathway (AOP) linking aromatase inhibition to reproductive dysfunction in fish has been described and endorsed by the OECD, establishing a scientifically sound connection between aromatase inhibition and adverse apical outcomes relevant to risk assessment and regulatory decision-making. Further, computational models that allow for quantitative prediction of dose-response time-course behaviors and the potential severity of the adverse outcome based on in vitro screening data have been developed. The present study provides further weight of evidence to support this AOP and its use in regulatory decision-making. In particular, it identifies rapid responses to aromatase inhibition that can be expected to occur within the first 24 h of exposure, examines the dynamic stability of gene expression responses over that period to help identify appropriate time periods in which characteristic gene expression responses may serve as effective biomarkers of exposure to aromatase inhibitors, and provides insights into different gene regulatory mechanisms that may be operating over the first few hours of exposure versus more systemic endocrine-related regulation that appear to take over after 6-12 h of exposure. These data continue to refine our understanding of this important mode of endocrine disruption and how to more efficiently and effectively both model and test for it to support regulatory decision-making. This dataset is associated with the following publication: Schroeder, A., G. Ankley, T. Habib, N. Garcia-Reyero, B. Escalon, K. Jensen, M. Kahl, E. Durhan, E. Makynen, J. Cavallin, D. Martinovic-Weigelt, E. Perkins, and D. Villeneuve. Rapid effects of the aromatase inhibitor fadrozole on steroid production and gene expression in the ovary of female fathead minnows (Pimephales promelas). GENERAL AND COMPARATIVE ENDOCRINOLOGY. Academic Press Incorporated, Orlando, FL, USA, 252: 79-87, (2017).

Aromatase inhibition is one of the chemical modes of action of concern to EPA's Endocrine Disruptor Screening Program (EDSP). In vitro bioassays that can detect aromatase inhibition are part of both the EDSP tier 1 screening program and are included subset of ToxCast assays employed for EDSP21 screening. An adverse outcome pathway (AOP) linking aromatase inhibition to reproductive dysfunction in fish has been described and endorsed by the OECD, establishing a scientifically sound connection between aromatase inhibition and adverse apical outcomes relevant to risk assessment and regulatory decision-making. Further, computational models that allow for quantitative prediction of dose-response time-course behaviors and the potential severity of the adverse outcome based on in vitro screening data have been developed. The present study provides further weight of evidence to support this AOP and its use in regulatory decision-making. In particular, it identifies rapid responses to aromatase inhibition that can be expected to occur within the first 24 h of exposure, examines the dynamic stability of gene expression responses over that period to help identify appropriate time periods in which characteristic gene expression responses may serve as effective biomarkers of exposure to aromatase inhibitors, and provides insights into different gene regulatory mechanisms that may be operating over the first few hours of exposure versus more systemic endocrine-related regulation that appear to take over after 6-12 h of exposure. These data continue to refine our understanding of this important mode of endocrine disruption and how to more efficiently and effectively both model and test for it to support regulatory decision-making. This dataset is associated with the following publication: Schroeder, A., G. Ankley, T. Habib, N. Garcia-Reyero, B. Escalon, K. Jensen, M. Kahl, E. Durhan, E. Makynen, J. Cavallin, D. Martinovic-Weigelt, E. Perkins, and D. Villeneuve. Rapid effects of the aromatase inhibitor fadrozole on steroid production and gene expression in the ovary of female fathead minnows (Pimephales promelas). GENERAL AND COMPARATIVE ENDOCRINOLOGY. Academic Press Incorporated, Orlando, FL, USA, 252: 79-87, (2017).

The dataset includes data from six experiments in which adult male fathead minnows were exposed to five concentrations of a per- or polyfluorinated alkyl substance (PFAS) and a 17beta-estradiol positive control for 96 hours. Meta data on each fish exposed including treatment, replicate, sex, whole body wet weight, and gonad weights are included. Endpoints measured include nuptial tubercle scores, gonadosomatic index, and hepatic expression of four estrogen regulated mRNA transcripts: vitellogenin, estrogen receptor alpha, apolipoprotein eb, and insulin-like growth factor 1. The data set also includes water quality data collected over the course of each exposure, and measured concentrations of the test chemicals in water and plasma. The PFAS tested include: Perfluorooctanoic acid; 1H,1H,8H,8H-Perfluorooctane-1,8-diol; 1H,1H,10H,10H-Perfluorodecane-1,10-diol; 1H,1H,8H,8H-Perfluoro-3,6-dioxaoctane-1,8-diol; and Perfluoro-2-methyl-3-oxahexanoic acid. This dataset is associated with the following publication: Villeneuve, D., B. Blackwell, J. Cavallin, J. Collins, J. Hoang, R. Hofer, K. Houck, K. Jensen, M. Kahl, R. Kutsi, A. Opseth, K. Santana Rodriguez, C. Schaupp, E. Stacy, and G. Ankley. Verification of In Vivo Estrogenic Activity for Four Per- and Polyfluoroalkyl Substances (PFAS) Identified as Estrogen Receptor Agonists via New Approach Methodologies. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, 57(9): 3794-3803, (2023).

Intersex in small- and largemouth bass has been observed in the upper Chesapeake Bay Watershed since 2003. This observation is indicative of exposure to estrogenic endocrine disrupting chemicals. In order to complement biological data sets and better identify the spatial and temporal nature of this end-point, discrete grab water samples were collected throughout the upper Chesapeake Bay Watershed for the evaluation of estrogenic activity. Data reported here are estrogenicity values derived from bioassay screening of OASIS-HLB extracts discrete grab water samples. Estrogenicity was determined using a bioluminescent yeast estrogen screen. Here we report estrogenicity data for selected sites in the Chesapeake Bay water shed collected between 2008 and 2011.

Intersex in small- and largemouth bass has been observed in the upper Chesapeake Bay Watershed since 2003. This observation is indicative of exposure to estrogenic endocrine disrupting chemicals. In order to complement biological data sets and better identify the spatial and temporal nature of this end-point, discrete grab water samples were collected throughout the upper Chesapeake Bay Watershed for the evaluation of estrogenic activity. Data reported here are estrogenicity values derived from bioassay screening of OASIS-HLB extracts discrete grab water samples. Estrogenicity was determined using a bioluminescent yeast estrogen screen. Here we report estrogenicity data for selected sites in the Chesapeake Bay water shed collected between 2008 and 2011.

Adult fathead minnows were exposed to dilutions of a historically estrogenic wastewater treatment plant effluent in a 21-d reproduction study. This dataset is comprised of a variety of endpoints representing key events along adverse outcome pathways linking estrogen receptor activation and other molecular initiating events to reproductive impairment. This study demonstrates the value of using an integrative approach that encompasses analytical chemistry, in vitro bioassays, and in vivo apical and pathway-based approaches with endpoints spanning from molecular- (e.g., gene expression) to organismal- (e.g., reproduction) levels of biological organization to help infer causal relationships between chemistry and potential effects on reproduction. This dataset is associated with the following publication: Cavallin , J., K. Jensen , M. Kahl , D. Villeneuve , K. Lee, A. Schroeder , J. Mayasich, E. Eid, K. Nelson, R. Milsk, B. Blackwell, J. Berninger , C. LaLone, C. Blanksma, T. Jicha , C. Elonen , R. Johnson , and G. Ankley. Pathway-based approaches for assessment of real-time exposure to an estrogenic wastewater treatment plant effluent on fathead minnow reproduction. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 35(3): 702-716, (2016).

Adult fathead minnows were exposed to dilutions of a historically estrogenic wastewater treatment plant effluent in a 21-d reproduction study. This dataset is comprised of a variety of endpoints representing key events along adverse outcome pathways linking estrogen receptor activation and other molecular initiating events to reproductive impairment. This study demonstrates the value of using an integrative approach that encompasses analytical chemistry, in vitro bioassays, and in vivo apical and pathway-based approaches with endpoints spanning from molecular- (e.g., gene expression) to organismal- (e.g., reproduction) levels of biological organization to help infer causal relationships between chemistry and potential effects on reproduction. This dataset is associated with the following publication: Cavallin , J., K. Jensen , M. Kahl , D. Villeneuve , K. Lee, A. Schroeder , J. Mayasich, E. Eid, K. Nelson, R. Milsk, B. Blackwell, J. Berninger , C. LaLone, C. Blanksma, T. Jicha , C. Elonen , R. Johnson , and G. Ankley. Pathway-based approaches for assessment of real-time exposure to an estrogenic wastewater treatment plant effluent on fathead minnow reproduction. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 35(3): 702-716, (2016).