This dataset contains in vitro and in vivo biochemical and apical (i.e., growth/development) data pertaining to iodotyrosine deiodinase inhibition in the African clawed frog (Xenopus laevis). This dataset is associated with the following publication: Haselman, J., J. Olker, P. Kosian, J. Korte, J. Denny, J. Tietge, M. Hornung, and S. Degitz. Characterization of the Mechanistic Linkages Between Iodothyronine Deiodinase Inhibition and Impaired Thyroid-Mediated Growth and Development in Xenopus Laevis Using Iopanoic Acid. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 187(1): 139-149, (2022).

This excel file contains the resultant data from a study on iodotyrosine deiodinase in the model amphibian species, Xenopus laevis. These data include: tadpole growth and development, thyroid hormones in plasma and glands, and expression of thyroid-relevant genes. The initial worksheet tab that provides metadata for each dataset included in the other worksheets that make up the file. This dataset is associated with the following publication: Olker, J., J. Haselman, P. Kosian, K. Donnay, J. Korte, C. Blanksma, M. Hornung, and S. Degitz. Evaluating iodide recycling inhibition as a novel molecular initiating event for thyroid axis disruption in amphibians. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 166(2): 318-331, (2018).

This excel file contains the resultant data from a study on iodotyrosine deiodinase in the model amphibian species, Xenopus laevis. These data include: tadpole growth and development, thyroid hormones in plasma and glands, and expression of thyroid-relevant genes. The initial worksheet tab that provides metadata for each dataset included in the other worksheets that make up the file. This dataset is associated with the following publication: Olker, J., J. Haselman, P. Kosian, K. Donnay, J. Korte, C. Blanksma, M. Hornung, and S. Degitz. Evaluating iodide recycling inhibition as a novel molecular initiating event for thyroid axis disruption in amphibians. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 166(2): 318-331, (2018).

Supplementary materials for "Olker JH, Korte JJ, Haselman JT, Hornung MW, Degitz SJ. Cross-species comparison of chemical inhibition of human and Xenopus iodotyrosine deiodinase. Aquat Toxicol. 2022 Aug;249:106227. doi: 10.1016/j.aquatox.2022.106227. Epub 2022 Jun 15. PMID: 35767922; PMCID: PMC9887787." The excel spreadsheet contains the resultant data from an assay for chemical inhibition of amphibian Iodotyrosine Deiodinase (IYD) enzyme activity. 154 chemicals from the EPA’s ToxCast chemical library were tested in concentration-response and these amphibian IYD assay results were compared to those from the human IYD inhibition assay reported in Olker et al. 2021 (doi:10.1016/j.tiv.2020.105073). The same set of 154 chemicals were tested in both assays and compared here. This data set the median, minimum, and maximum inhibition produced at each concentration for each tested chemical. A model inhibitor (3-Nitro-L-Tyrosine) was included on each plate as a positive control, with concentration response data for those curves also included in the data set. This dataset is associated with the following publication: Olker, J., J. Korte, J. Haselman, M. Hornung, and S. Degitz. Xenopus laevis and Human iodotyrosine deiodinase enzyme cross-species sensitivity to inhibition by ToxCast chemicals.. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 249: N/A, (2022).

The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4) to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior chamber of the swim bladder, processes previously demonstrated to be thyroid-hormone regulated. Two experiments were conducted using a model deiodinase inhibitor, iopanoic acid (IOP). In the first study, fathead minnow (Pimephales promelas) embryos were exposed to 0.6, 1.9, or 6.0 mg IOP/L or control water in a flow-through system until reaching 6 days post-fertilization (dpf) at which time posterior swim bladder inflation was assessed. To examine effects on anterior swim bladder inflation, a second study was conducted with 6 dpf larvae exposed to the same IOP concentrations until reaching 21 dpf. Fish from both studies were sampled for T4/T3 measurements, gene transcription analyses, and thyroid histopathology. In the embryo study, incidence and length of inflated posterior swim bladders were significantly reduced in the 6.0 mg/L treatment at 6 dpf. Incidence of inflation and length of anterior swim bladder in larval fish were significantly reduced in all IOP treatments at 14 dpf, but inflation recovered by 18 dpf. Throughout the larval study, whole body T4 concentrations were significantly increased and T3 concentrations were significantly decreased in all IOP treatments. Consistent with hypothesized compensatory responses, significant up-regulation of deiodinase-2 mRNA was observed in the larval study, and down-regulation of thyroperoxidase mRNA was observed in all IOP treatments in both studies. Taken together, these results support the hypothesized adverse outcome pathways linking inhibition of deiodinase activity to impaired swim bladder inflation. This dataset is associated with the following publication: Cavallin, J., G. Ankley, B. Blackwell, C. Blanksma, K. Fay, K. Jensen, M. Kahl, D. Knapen, P. Kosian, S. Poole, E. Randolph, A. Schroeder, L. Vergauwen, and D. Villeneuve. Impaired swim bladder inflation in early-life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid (article). ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 36(11): 2942-2952, (2017).

The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4) to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior chamber of the swim bladder, processes previously demonstrated to be thyroid-hormone regulated. Two experiments were conducted using a model deiodinase inhibitor, iopanoic acid (IOP). In the first study, fathead minnow (Pimephales promelas) embryos were exposed to 0.6, 1.9, or 6.0 mg IOP/L or control water in a flow-through system until reaching 6 days post-fertilization (dpf) at which time posterior swim bladder inflation was assessed. To examine effects on anterior swim bladder inflation, a second study was conducted with 6 dpf larvae exposed to the same IOP concentrations until reaching 21 dpf. Fish from both studies were sampled for T4/T3 measurements, gene transcription analyses, and thyroid histopathology. In the embryo study, incidence and length of inflated posterior swim bladders were significantly reduced in the 6.0 mg/L treatment at 6 dpf. Incidence of inflation and length of anterior swim bladder in larval fish were significantly reduced in all IOP treatments at 14 dpf, but inflation recovered by 18 dpf. Throughout the larval study, whole body T4 concentrations were significantly increased and T3 concentrations were significantly decreased in all IOP treatments. Consistent with hypothesized compensatory responses, significant up-regulation of deiodinase-2 mRNA was observed in the larval study, and down-regulation of thyroperoxidase mRNA was observed in all IOP treatments in both studies. Taken together, these results support the hypothesized adverse outcome pathways linking inhibition of deiodinase activity to impaired swim bladder inflation. This dataset is associated with the following publication: Cavallin, J., G. Ankley, B. Blackwell, C. Blanksma, K. Fay, K. Jensen, M. Kahl, D. Knapen, P. Kosian, S. Poole, E. Randolph, A. Schroeder, L. Vergauwen, and D. Villeneuve. Impaired swim bladder inflation in early-life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid (article). ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 36(11): 2942-2952, (2017).

Disruption of thyroid hormone signaling is a form of endocrine disruption that is of concern to both human health and ecosystems. Research is being conducted to define the biological targets chemicals may interact with to disrupt thyroid hormone signaling and the stages in development where that disruption can most readily lead to adverse effects. The present data characterize the expression of key genes associated with thyroid hormone signaling and regulation over the course of development for two small fish widely used in aquatic ecotoxicology research. These data provide baseline information that can lead to a more complete understanding of which thyroid disrupting chemicals fish may be susceptible to and at which stages in development. This dataset is associated with the following publication: Vergauwen, L., J. Cavallin, G. Ankley, C. Bars, I. Gabriels, E. Michiels, K. Nelson, J. Periz-Stanacev, E. Randolph, S. Robinson, T. Saari, A. Schroeder, E. Stinckens, J. Swintek, S. Van Cruchten, E. Verbueken, D. Villeneuve, and D. Knapen. Gene transcription ontogeny of thyroid-axis development in early-life stage fathead minnow and zebrafish. Journal of Experimental Biology. The Company of Biologists LIMITED, Cambridge, UK, 266: 878-1002, (2018).

Disruption of thyroid hormone signaling is a form of endocrine disruption that is of concern to both human health and ecosystems. Research is being conducted to define the biological targets chemicals may interact with to disrupt thyroid hormone signaling and the stages in development where that disruption can most readily lead to adverse effects. The present data characterize the expression of key genes associated with thyroid hormone signaling and regulation over the course of development for two small fish widely used in aquatic ecotoxicology research. These data provide baseline information that can lead to a more complete understanding of which thyroid disrupting chemicals fish may be susceptible to and at which stages in development. This dataset is associated with the following publication: Vergauwen, L., J. Cavallin, G. Ankley, C. Bars, I. Gabriels, E. Michiels, K. Nelson, J. Periz-Stanacev, E. Randolph, S. Robinson, T. Saari, A. Schroeder, E. Stinckens, J. Swintek, S. Van Cruchten, E. Verbueken, D. Villeneuve, and D. Knapen. Gene transcription ontogeny of thyroid-axis development in early-life stage fathead minnow and zebrafish. Journal of Experimental Biology. The Company of Biologists LIMITED, Cambridge, UK, 266: 878-1002, (2018).

Dataset for "Combining in vitro and in silico New Approach Methods to investigate type 3 iodothyronine deiodinase chemical inhibition across species". This dataset is associated with the following publication: Mayasich, S., M. Goldsmith, K. Mattingly, and C. Lalone. Combining In Vitro and In Silico New Approach Methods to Investigate Type 3 Iodothyronine Deiodinase Chemical Inhibition Across Species. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 42(5): 1032-1048, (2023).

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).