AOPs Including This Stressor
|Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity||Strong|
Events Including This StressorThis table is automatically generated and lists KE’s including this stressor.
Chemical TableThe Chemical Table lists chemicals associated with a stressor. This table contains information about the User’s term for a chemical, the DTXID, Preferred name, CAS number, JChem InChIKey, and Indigo InChIKey. Instructions To add a chemical associated with a particular stressor, next to the Chemical Table click ‘Add chemical.’ This will redirect you to a page entitled “New Stressor Chemical.’ The dialog box can be used to search for chemical by name, CAS number, JChem InChIKey, and Indigo InChIKey. Searching by these fields will bring forward a drop down list of existing stressor chemicals formatted as “CAS- preferred name” “JChem InChIKey – preferred name” or “Indigo InChIKey- preferred name” depending on which field you perform the search. Select an entity from the drop down list and click ‘Add chemical.’ This will return you to the Stressor Page, where the new record should be in the ‘Chemical Table’ on the page.
Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
It has been shown that many PBDE congeners and/or metabolites (including hydroxylated metabolites of PBDE congeners) can bind to TTR, in some cases more strongly than T4 (Hallgren and Darnerud 2002; Marchesini et al 2008; Ren and Guo 2012; Weiss et al 2015), and this class of congeners has been implicated as a thyroid toxicant (Boas et al 2012; Gore et al 2015; Miller et al 2009; Murk et al 2013). In rats, certain PBDEs have been found to impact learning and memory ability via damage to hippocampal neurons, perhaps through a TTR-mediated transport process as described in this AOP (Driscoll et al 2009; Kato et al 2009; Sun et al 2017). In humans, PBDEs and/or metabolites affect TH during vulnerable windows (i.e. pregnancy) and have been associated with pediatric neurobehavioral development and the developing nervous system, with particular emphasis on the hydroxylated metabolites that have been found to bioaccumulate in serum in children (Athanasiadou et al 2008; Chevrier et al 2010; Dingemans et al 2011; Eskenazi et al 2013; Preau et al 2015).
Athanasiadou, M., Cuadra, S. N., Marsh, G., Bergman, A., & Jakobsson, K. (2008). Polybrominated diphenyl ethers (PBDEs) and bioaccumulative hydroxylated PBDE metabolites in young humans from Managua, Nicaragua. Environmental Health Perspectives, 116(3), 400–408. http://doi.org/10.1289/ehp.10713
Boas, M., Feldt-Rasmussen, U., & Main, K. M. (2012). Thyroid effects of endocrine disrupting chemicals. Molecular and Cellular Endocrinology, 355(2), 240–248. http://doi.org/10.1016/j.mce.2011.09.005
Chevrier, J., Harley, K. G., Bradman, A., Gharbi, M., Sjödin, A., & Eskenazi, B. (2010). Polybrominated diphenyl ether (PBDE) flame retardants and thyroid hormone during pregnancy. Environmental Health Perspectives, 118(10), 1444–1449. http://doi.org/10.1289/ehp.1001905
Dingemans, M. M. L., van den Berg, M., & Westerink, R. H. S. (2011). Neurotoxicity of brominated flame retardants: (In)direct effects of parent and hydroxylated polybrominated diphenyl ethers on the (Developing) nervous system. Environmental Health Perspectives, 119(7), 900–907. http://doi.org/10.1289/ehp.1003035
Driscoll, L. L., Gibson, A. M., & Hieb, A. (2009). Chronic postnatal DE-71 exposure: Effects on learning, attention and thyroxine levels. Neurotoxicology and Teratology, 31(2), 76–84. http://doi.org/10.1016/j.ntt.2008.11.003
Eskenazi, B., Chevrier, J., Rauch, S. A., Kogut, K., Harley, K. G., Johnson, C., … Bradman, A. (2013). In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study. Environmental Health Perspectives, 121(2), 257–262. http://doi.org/10.1289/ehp.1205597
Gore, a. C., Chappell, V. a., Fenton, S. E., Flaws, J. a., Nadal, a., Prins, G. S., … Zoeller, R. T. (2015). Executive Summary to EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocrine Reviews, (October), er.2015-1093. http://doi.org/10.1210/er.2015-1093
Hallgren, S., & Darnerud, P. O. (2002). Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and chlorinated paraffins (CPs) in rats—testing interactions and mechanisms for thyroid hormone effects. Toxicology, 177(2–3), 227–243. http://doi.org/10.1016/S0300-483X(02)00222-6
Kato, Y., Haraguchi, K., Kubota, M., Seto, Y., Ikushiro, S. I., Sakaki, T., … Degawa, M. (2009). 4-Hydroxy-2,2’,3,4’,5,5’,6-heptachlorobiphenyl-mediated decrease in serum thyroxine level in mice occurs through increase in accumulation of thyroxine in the liver. Drug Metabolism and Disposition, 37(10), 2095–2102. http://doi.org/10.1124/dmd.109.028621
Marchesini, G. R., Meimaridou, A., Haasnoot, W., Meulenberg, E., Albertus, F., Mizuguchi, M., … Murk, A. J. (2008). Biosensor discovery of thyroxine transport disrupting chemicals. Toxicology and Applied Pharmacology, 232(1), 150–160. http://doi.org/10.1016/j.taap.2008.06.014
Miller, M. D., Crofton, K. M., Rice, D. C., & Zoeller, R. T. (2009). Thyroid-disrupting chemicals: Interpreting upstream biomarkers of adverse outcomes. Environmental Health Perspectives, 117(7), 1033–1041. http://doi.org/10.1289/ehp.0800247
Murk, A. J., Rijntjes, E., Blaauboer, B. J., Clewell, R., Crofton, K. M., Dingemans, M. M. L., … Gutleb, A. C. (2013). Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals. Toxicology in Vitro, 27(4), 1320–1346. http://doi.org/10.1016/j.tiv.2013.02.012
Préau, L., Fini, J. B., Morvan-Dubois, G., & Demeneix, B. (2014). Thyroid hormone signaling during early neurogenesis and its significance as a vulnerable window for endocrine disruption. Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, 1849(2), 112–121. http://doi.org/10.1016/j.bbagrm.2014.06.015
Ren, X. M., & Guo, L. H. (2012). Assessment of the binding of hydroxylated polybrominated diphenyl ethers to thyroid hormone transport proteins using a site-specific fluorescence probe. Environmental Science and Technology, 46(8), 4633–4640. http://doi.org/10.1021/es2046074
Sun W, Du L, Tang W, Kuang L, Du P, Chen J, Chen D. PBDE-209 exposure damages learning and memory ability in rats potentially through increased autophagy and apoptosis in the hippocampus neuron. Environ Toxicol Pharmacol. 2017 Mar;50:151-158. doi: 10.1016/j.etap.2017.02.006.
Weiss, J. M., Andersson, P. L., Zhang, J., Simon, E., Leonards, P. E. G., Hamers, T., & Lamoree, M. H. (2015). Tracing thyroid hormone-disrupting compounds: database compilation and structure-activity evaluation for an effect-directed analysis of sediment. Analytical and Bioanalytical Chemistry, 5625–5634. http://doi.org/10.1007/s00216-015-8736-9
This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor.
Chemical/Category DescriptionInstructions To edit the “ Stressor Description” section, on a KER page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “Stressor Description” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “Stressor Description” section on the page.
Characterization of ExposureInstructions To edit the “Characterization of Exposure” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “Characterization of Exposure” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “Characterization of Exposure” section on the page.
List the bibliographic references to original papers, books or other documents used to support the Stressor. Instructions To edit the “References” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “References” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “References” section on the page.