데이터셋 상세
미국
Rapid Effects of the Aromatase Inhibitor Fadrozole on Steroid Production and Gene Expression in the Ovary of Female Fathead Minnows (Pimephales promelas)
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).
데이터 정보
연관 데이터
Case study in 21st century ecotoxicology: Using in vitro aromatase inhibition data to predict reproductive outcomes in fish, in vivo.
공공데이터포털
Data set includes empirical results from 60 h, 10 d, and 21 d exposures of female fathead minnows to the fungicide imazalil as well as simulations from predictive models anchored to an established adverse outcome pathway (https://aopwiki.org/aops/25). Contents are organized into multiple tabs: (1) Simulated effects on plasma 17b-estradiol and vitellogenin used to inform experimental design. (2) Model simulations based on nominal concentrations used in the 60 h, 10 d, and 21 d exposures. (3) Biological effects data from the 60 h experiment. (4) Analytical exposure verification from the 60 h experiment. (5) Biological effects data from the 10 d exposure. (6) Biological effects data from 21 d exposure. (7) Analytical exposure verification from the 10 d and 21 d exposures. (8) Reproduction data from the 10 d and 21 d exposures. (9) Simulated reproduction results based on nominal exposure concentrations used in the 10 d and 21 d exposures. (10) Histopathology evaluations for selected females from the 10 d and 21 d exposures. This dataset is associated with the following publication: Villeneuve, D., B. Blackwell, C. Blanksma, J. Cavallin, W. Cheng, R. Conolly, K. Conrow, D. Feifarek, L. Heinis, K. Jensen, M. Kahl, R. Milsk, S. Poole, E. Randolph, T. Saari, K. Watanabe, and G. Ankley. Case Study in 21st-Century Ecotoxicology: Using In Vitro Aromatase Inhibition Data to Predict Reproductive Outcomes in Fish In Vivo. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 42(1): 100-116, (2023).
Case study in 21st century ecotoxicology: Using in vitro aromatase inhibition data to predict reproductive outcomes in fish, in vivo.
공공데이터포털
Data set includes empirical results from 60 h, 10 d, and 21 d exposures of female fathead minnows to the fungicide imazalil as well as simulations from predictive models anchored to an established adverse outcome pathway (https://aopwiki.org/aops/25). Contents are organized into multiple tabs: (1) Simulated effects on plasma 17b-estradiol and vitellogenin used to inform experimental design. (2) Model simulations based on nominal concentrations used in the 60 h, 10 d, and 21 d exposures. (3) Biological effects data from the 60 h experiment. (4) Analytical exposure verification from the 60 h experiment. (5) Biological effects data from the 10 d exposure. (6) Biological effects data from 21 d exposure. (7) Analytical exposure verification from the 10 d and 21 d exposures. (8) Reproduction data from the 10 d and 21 d exposures. (9) Simulated reproduction results based on nominal exposure concentrations used in the 10 d and 21 d exposures. (10) Histopathology evaluations for selected females from the 10 d and 21 d exposures. This dataset is associated with the following publication: Villeneuve, D., B. Blackwell, C. Blanksma, J. Cavallin, W. Cheng, R. Conolly, K. Conrow, D. Feifarek, L. Heinis, K. Jensen, M. Kahl, R. Milsk, S. Poole, E. Randolph, T. Saari, K. Watanabe, and G. Ankley. Case Study in 21st-Century Ecotoxicology: Using In Vitro Aromatase Inhibition Data to Predict Reproductive Outcomes in Fish In Vivo. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 42(1): 100-116, (2023).
Derivation and Evaluation of Putative Adverse Outcome Pathways for Effects of Cycylooxygenase inhibitors on Reproductive Processes in Female Fish
공공데이터포털
Fathead minnows (Pimephales promelas) were exposed to 100 ug/L indomethacin, 200 ug/L ibuprofen, or 20 ug/L celecoxib for 96 h. Effects on cycloxygenase enzyme activity in ovary, prostaglandin F2alpha concentrations in plasma, 17beta-estradiol concentrations in plasma, and vitellogenin concentrations in plasma were measured. Gene expression in ovary samples was evaluated using a 15,000 probe oligonucleotide microarray. Transcriptomics data (raw data and normalized) are available through the National Center for Biotechnology Information, Gene Expression Omnibus (GEO), accession number GSE72976. Metabolite profiles in liver tissue were measured by proton nuclear magnetic resonance. In addition to these data, the data set also contains identification of differentially expressed genes, pathway enrichment and gene set enrichment analyes, ToxCast data for indomethacin and celecoxib, chemical-gene interaction data derived from the Comparative Toxicogenomics database, and results from Level 1, Level 2, and Level 3 SeqAPASS analyses that examine conservation of target proteins across species (https://seqapass.epa.gov/seqapass/). This dataset is associated with the following publication: Martinovic-Weigelt, D., A. Mehinto, G. Ankley , J. Berninger, T. Collette , J. Davis , N. Denslow, E. Durhan, E. Eid, D. Ekman , K. Jensen , M. Kahl , C. LaLone , Q. Teng , and D. Villeneuve. Derivation and evaluation of putative adverse outcome pathways for the effects of cyclooxygenase inhibitors on reproductive processes in female fish. TOXICOLOGICAL SCIENCES. Society of Toxicology, 156(2): 344-361, (2017).
Differential Sensitivity to In Vitro Inhibition of Cytochrome P450 Aromatase (CYP19) Activity Among 18 Freshwater Fishes
공공데이터포털
There is significant concern regarding potential impairment of fish reproduction associated with endocrine disrupting chemicals. Aromatase (CYP19) is a steroidogenic enzyme involved in the conversion of androgens to estrogens. Inhibition of aromatase by chemicals can result in reduced concentrations of estrogens leading to adverse reproductive effects. These effects have been extensively investigated in a small number of laboratory model fishes, but differences in sensitivity among species is largely unknown. Therefore, this study took a first step towards understanding potential differences in sensitivity to aromatase inhibitors among fishes. Specifically, a standard in vitro aromatase inhibition assay using subcellular fractions of whole tissue homogenates was used to evaluate the potential sensitivity of eighteen phylogenetically diverse species of freshwater fish to the nonsteroidal aromatase inhibitor fadrozole. Sensitivity to fadrozole ranged by more than 52-fold among these species. Five species were further investigated for sensitivity to up to four additional nonsteroidal aromatase inhibitors, letrozole, imazalil, prochloraz, and propiconazole. Potencies of each of these chemicals relative to fadrozole ranged by up to two orders of magnitude among the five species. Commonly investigated laboratory model species were among the least sensitive to all the investigated chemicals; therefore, ecological risks of aromatase inhibitors derived from these species might not be adequately protective of more sensitive native fishes. This information could guide more objective ecological risk assessments of native fishes to chemicals that inhibit aromatase. This dataset is associated with the following publication: Doering, J., D. Villeneuve, K. Fay, E. Randolph, K. Jensen, M. Kahl, C. LaLone, and G. Ankley. Differential sensitivity to in vitro inhibition of cytochrome P450 aromatase (CYP19) activity among 18 freshwater fishes. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 170(2): 394-403, (2019).
Case study in 21st century ecotoxicology: using in vitro aromatase inhibition data to predict short term in vivo responses in adult female fish
공공데이터포털
This research was designed to evaluate whether a biologically-based computational model aligned with an adverse outcome pathway (AOP) could effectively predict animal (in vivo) responses to chemicals shown to inhibit the enzyme aromatase in a non-animal (in vitro) screening assays. Aromatase is an enzyme that plays a critical role in the synthesis of estrogens, an important class of hormones, and chemicals that inhibit aromatase are viewed as probable endocrine disrupting compounds. Although the model was not able to accurately predict the average in vivo responses observed for all chemicals tested, there was strong qualitative to semi-quantitative agreement with the proposed AOP and predictions did fall within the distribution of measured values. Consequently, this “new approach methodology” likely has utility for screening-level assessments. This work helps to establish the confidence and limitations of this approach. The data set includes: 1) High throughput screening results for chemicals identified as aromatase inhibitors. 2) Novel in vitro aromatase inhibition data for six chemicals. 3) Modeled predictions of impacts on 17b-estradiol and vitellogenin concentrations over a range of concentrations. 4) Measured biological effects of 3 aromatase inhibitors in fathead minnows exposed for 24 h. 5) Measured plasma and water concentrations of the test chemicals. This dataset is associated with the following publication: Villeneuve, D., B. Blackwell, J. Cavallin, W. Cheng, R. Conolly, D. Feifarek, K. Jensen, M. Kahl, R. Milsk, S. Poole, E. Randolph, T. Saari, and G. Ankley. Case study in 21st century ecotoxicology: Using in vitro aromatase inhibition data to predict short term in vivo responses in adult female fish. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 40(4): 1155-1170, (2021).
Case study in 21st century ecotoxicology: using in vitro aromatase inhibition data to predict short term in vivo responses in adult female fish
공공데이터포털
This research was designed to evaluate whether a biologically-based computational model aligned with an adverse outcome pathway (AOP) could effectively predict animal (in vivo) responses to chemicals shown to inhibit the enzyme aromatase in a non-animal (in vitro) screening assays. Aromatase is an enzyme that plays a critical role in the synthesis of estrogens, an important class of hormones, and chemicals that inhibit aromatase are viewed as probable endocrine disrupting compounds. Although the model was not able to accurately predict the average in vivo responses observed for all chemicals tested, there was strong qualitative to semi-quantitative agreement with the proposed AOP and predictions did fall within the distribution of measured values. Consequently, this “new approach methodology” likely has utility for screening-level assessments. This work helps to establish the confidence and limitations of this approach. The data set includes: 1) High throughput screening results for chemicals identified as aromatase inhibitors. 2) Novel in vitro aromatase inhibition data for six chemicals. 3) Modeled predictions of impacts on 17b-estradiol and vitellogenin concentrations over a range of concentrations. 4) Measured biological effects of 3 aromatase inhibitors in fathead minnows exposed for 24 h. 5) Measured plasma and water concentrations of the test chemicals. This dataset is associated with the following publication: Villeneuve, D., B. Blackwell, J. Cavallin, W. Cheng, R. Conolly, D. Feifarek, K. Jensen, M. Kahl, R. Milsk, S. Poole, E. Randolph, T. Saari, and G. Ankley. Case study in 21st century ecotoxicology: Using in vitro aromatase inhibition data to predict short term in vivo responses in adult female fish. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 40(4): 1155-1170, (2021).
Verification of in vivo estrogenic activity for four per- and polyfluoroalkyl substances (PFAS) identified as estrogen receptor agonists via new approach methodologies (v4)
공공데이터포털
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).
Conversion of environmental estrone to estradiol by male fathead minnows
공공데이터포털
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).
Assessing reproductive effects of aromatase inhibition on fishes with group-synchronous oocyte development using western mosquitofish (Gambusia affinis) as a model
공공데이터포털
Predictive models and frameworks for linking inhibition of the enzyme aromatase, as measured in non-animal high throughput screening assays, to adverse effects on reproduction in fish have been established. However, those models were established using data from several fish species commonly reared in the laboratory that employ a particular reproductive strategy involving asynchronous oocyte development and repeat spawning. Many fish species employ synchronous oocyte development and spawn annually. This product was intended to help address the question of whether the current approaches for predicting impacts of aromatase inhibitors are applicable to fish with a synchronous/annual spawning reproduction strategy. The study establishes the mosquitofish as a viable laboratory model with synchronous oocyte development and provides preliminary evidence that exposure to aromatase inhibitors during a critical period of the reproductive cycle can lead to adverse effects on fish reproduction. This dataset provides all the data used to generate the tables and figures presented in Doering et al. "Assessing reproductive effects of aromatase inhibition on fishes with group-synchronous oocyte development using Western Mosquitofish (Gambusia affinis) as a model." Data are organized as separate tabs in an Excel spreadsheet with a cover sheet, followed by a separate tab for each Figure and Table from the manuscript.
Assessing reproductive effects of aromatase inhibition on fishes with group-synchronous oocyte development using western mosquitofish (Gambusia affinis) as a model
공공데이터포털
Predictive models and frameworks for linking inhibition of the enzyme aromatase, as measured in non-animal high throughput screening assays, to adverse effects on reproduction in fish have been established. However, those models were established using data from several fish species commonly reared in the laboratory that employ a particular reproductive strategy involving asynchronous oocyte development and repeat spawning. Many fish species employ synchronous oocyte development and spawn annually. This product was intended to help address the question of whether the current approaches for predicting impacts of aromatase inhibitors are applicable to fish with a synchronous/annual spawning reproduction strategy. The study establishes the mosquitofish as a viable laboratory model with synchronous oocyte development and provides preliminary evidence that exposure to aromatase inhibitors during a critical period of the reproductive cycle can lead to adverse effects on fish reproduction. This dataset provides all the data used to generate the tables and figures presented in Doering et al. "Assessing reproductive effects of aromatase inhibition on fishes with group-synchronous oocyte development using Western Mosquitofish (Gambusia affinis) as a model." Data are organized as separate tabs in an Excel spreadsheet with a cover sheet, followed by a separate tab for each Figure and Table from the manuscript.
목록