Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models. Environmental chemicals have been linked to TH disruption, yet the relationship between developmental exposures and decline in serum TH resulting in neurodevelopmental impairment is poorly understood. The present study developed a quantitative adverse outcome pathway (qAOP) where serum thyroxin (T4) reduction following inhibition of thyroperoxidase in the thyroid gland are described and related to deficits in fetal brain TH and the development of a brain malformation, subcortical band heterotopia. Pregnant dams were exposed to 6-propylthiouracil (PTU 0, 0.1, 0.5, 1, 2, or 3 ppm) from gestational day 6-20, increasing PTU concentrations in maternal thyroid gland and serum as well as in fetal serum. Dams exposed to 0.5 ppm PTU and higher exhibited dose-dependent decreases in thyroidal T4. Serum T4 levels in the dam were significantly decreased with exposure to 2 and 3 ppm PTU. In the fetus, T4 decrements were first observed at a lower dose of 0.5 ppm PTU. Based on these data, fetal brain T4 levels were estimated from published literature sources, and quantitatively linked to increases in the size of the heterotopia present in the brains of offspring. These data show the potential of in vivo assessments and computational descriptions of biological responses to predict the development of this structural brain malformation and use of qAOP approach to evaluate brain deficits that may result from exposure to other TH disruptors. This dataset is associated with the following publication: Hassan, I., H. El-Masri, P. Kosian, J. Ford, S. Degitz, and M. Gilbert. Neurodevelopment and Thyroid Hormone Synthesis Inhibition in the Rat: Quantitative Understanding Within the Adverse Outcome Pathway Framework. TOXICOLOGICAL SCIENCES. Society of Toxicology, 57-73, (2017).

thyroid hormone from serum of rats exposed to goitrogen. Morphometry in brain. Behavioral data. This dataset is associated with the following publication: OShaughnessy, K., P. Kosian, J. Ford, W. Oshiro, S. Degitz, and M. Gilbert. Developmental Thyroid Hormone Insufficiency Induces Cortical Brain Malformation and Learning Impairments: A Cross-Fostering Study. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 163(1): 101-115, (2018).

This file contains summary data of thyroid hormones in serum and brain in rat dams and their pups following maternal exposure to a perflorinated substance, PFHxS and an antimicrobial, Triclosan. Gene expression in thyroid glands and liver and brain were investigated. Anatomical and bahavioral indices of developmental neurotoxicity were assessed. Result so fall of these inquiries are summarized in these datasets. This dataset is associated with the following publication: Gilbert, M.E., K. OShaughnessy, S. Thomas, C. Riutta, C. Wood, A. Smith, W. Oshiro, J. Ford, A. Hotchkiss, I. Hassan, and R.L. Ford. Thyroid Disruptors: Extrathyroidal Sites of Chemical Action and Neurodevelopmental Outcome-An Examination Using Triclosan and Perfluorohexane Sulfonate. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 183(6): 195-213, (2021).

Data for O'Shaughnessy et al. 2023 - Bypassing the Brain Barriers: Upregulation of Serum miR-495 and miR-543-3p Reflects Thyroid-Mediated Developmental Neurotoxicity in the Rat. This dataset is associated with the following publication: O'Shaughnessy, K., A. Sasser, K. Bell, C. Riutta, J. Ford, R. Grindstaff, and M. Gilbert. Bypassing the Brain Barriers: Upregulation of Serum miR-495 and miR-543-3p Reflects Thyroid-Mediated Developmental Neurotoxicity in the Rat. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 198(1): 128-140, (2024).

Supplementary data for "Stephanie A. Eytcheson, Jennifer H. Olker, Katie Paul Friedman, Michael W. Hornung, Sigmund J. Degitz, Assessing utility of thyroid in vitro screening assays through comparisons to observed impacts in vivo, Regulatory Toxicology and Pharmacology, Volume 144, 2023, 105491, ISSN 0273-2300, https://doi.org/10.1016/j.yrtph.2023.105491.". Portions of this dataset are inaccessible because: N/A. They can be accessed through the following means: N/A. Format: The data used in this analysis are from publicly available sources and are cited in the references and/or the supplemental files. This dataset is associated with the following publication: Eytcheson, S., J. Olker, K. Friedman, M. Hornung, and S. Degitz. Assessing utility of thyroid in vitro screening assays through comparisons to observed impacts in vivo. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, USA, 144: 105491, (2023).

This study looked at functional endpoints in adult offspring of rats exposed in utero and postnatally to an environmentally relevant mixture of PCBs, Fox River blend. A model of neural plasticity and epilepsy, electrical kindling, was examined. Animals exposed to PCBs had slower kindling rates suggesting impaired plasticity mechanisms, consistent with previous work with PCBs where deficits were seen in another plasticity model, long-term potentiation. This dataset is associated with the following publication: Bandara, S., R. Sadowski, S. Schantz, and M. Gilbert. Developmental Exposure to an Environmental PCB Mixture Delays the Propagation of Kindling in the Amygdala. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, NETHERLANDS, n/a, (2016).

This data set is a dose response analysis of two thyroid hormone synthesis disruptors in adult male rats. Data included serum and thyroid gland concentrations of the two chemicals tested, propylthiouracil and methimazole, as well as serum and thyroid gland hormone concentrations. These data were critical for developing a model linking highthroughput assay data on synthesis inhibition to make predictions of thyroid hormone in serum. This dataset is associated with the following publication: Hassan, I., H. El-Masri, J. Ford, A. Brennan, S. Handa, K. Friedman, and M. Gilbert. Extrapolating In Vitro and Ex Vivo Screening Assay Data for Thyroperoxidase Inhibition to Predict Serum Thyroid Hormones in the Rat. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 173(2): 280-292, (2020).

Raw data to accompanying manuscript "The Pollutant Perfluorohexane Sulfonate (PFHxS) Reduces Serum Thyroxine but Does Not Alter Thyroid Hormone Action in the Postnatal Rat Brain". This dataset is associated with the following publication: O'Shaughnessy, K., K. Bell, A. Sasser, M. Gilbert, C. Riutta, J. Ford, J. McCord, and C. Wood. The Pollutant Perfluorohexane Sulfonate (PFHxS) Reduces Serum Thyroxine but Does Not Alter Thyroid Hormone Action in the Postnatal Rat Brain. ENVIRONMENT INTERNATIONAL. Elsevier B.V., Amsterdam, NETHERLANDS, 190: 108838, (2024).

This dataset was generated to support parameterization of a larval amphibian thyroid axis computational model. Specifically, plasma iodine levels were determined not only to inform a concentration value for model parameter specification in the model, but also to support the notion that aquatic and terrestrial species should be considered substantially different with regard to circulating iodide levels. Other computational model physical parameters were informed by evaluating Xenopus laevis thyroid gland histological images for morphological features including thyroid follicular cell numbers and areas. This dataset is associated with the following publication: Haselman, J., J. Nichols, K. Mattingly, M. Hornung, and S. Degitz. A biologically based computational model for the hypothalamic-pituitary-thyroid (HPT) axis in Xenopus laevis larvae. MATHEMATICAL BIOSCIENCES. Elsevier Science Ltd, New York, NY, USA, 362: 109021, (2023).

No novel data were reported in association with this product. This dataset is not publicly accessible because: The associated publication is a review/forum-type article. No novel scientific data are reported. All data cited have been previously published elsewhere. It can be accessed through the following means: Not applicable. Format: This article is a review/forum-type article. No novel scientific data are included. This dataset is associated with the following publication: Knapen, D., E. Stinckens, J. Cavallin, G. Ankley, H. Holbech, D. Villeneuve, and L. Vergauwen. Toward an AOP network-based tiered testing strategy for the assessment of thyroid hormone disruption. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, 54(16): 8491-8499, (2020).