AOPs Including This Stressor
|Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity||Moderate|
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
Some PFCs have been found to bind to TTR more strongly than T4 and been implicated as thyroid toxicants that could act through transport protein displacement (Boas et al 2012; Coperchini et al 2017; Gutshall et al 1989; Ren et al 2016; Weiss et al 2015; Zhang et al 2015). Zhang et al (2016) determined the X-ray structures of TTR-PFOA and TTR-PFOS. Evidence of interference with thyroid function and/or TH concentrations has been reported in both animals (Chang et al 2008; Yu et al 2009) and human (Ballesteros et al 2016; Dallaire et al 2009; Preau et al 2014; Wang et al 2014), including evidence of transplacental transfer (Yang et al 2016).
Ballesteros, V., Costa, O., Iñiguez, C., Fletcher, T., Ballester, F., & Lopez-Espinosa, M.-J. (2016). Exposure to perfluoroalkyl substances and thyroid function in pregnant women and children: A systematic review of epidemiologic studies. Environment International. http://doi.org/10.1016/j.envint.2016.10.015
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
Chang SC, Thibodeaux JR, Eastvold ML, Ehresman DJ, Bjork JA, Froehlich JW, Lau C, Singh RJ, Wallace KB, Butenhoff JL. Thyroid hormone status and pituitary function in adult rats given oral doses of perfluorooctanesulfonate (PFOS). Toxicology. 2008 Jan 20;243(3):330-9.
Coperchini F, Awwad O, Rotondi M, Santini F, Imbriani M, Chiovato L. Thyroid disruption by perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). J Endocrinol Invest. 2017 Feb;40(2):105-121. doi: 10.1007/s40618-016-0572-z. Review.
Dallaire, R., Dewailly, É., Pereg, D., Dery, S., & Ayotte, P. (2009). Thyroid function and plasma concentrations of polyhalogenated compounds in inuit adults. Environmental Health Perspectives, 117(9), 1380–1386. http://doi.org/10.1289/ehp.0900633
Gutshall, D. M., Pilcher, G. D., & Langley, A. E. (1989). Mechanism of the serum thyroid hormone lowering effect of perfluoro-n-decanoic acid (PFDA) in rats. Journal of Toxicology and Environmental Health, 28(0098–4108; 1), 53–65. http://doi.org/10.1080/15287398909531328
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 XM, Qin WP, Cao LY, Zhang J, Yang Y, Wan B, Guo LH. Binding interactions of perfluoroalkyl substances with thyroid hormone transport proteins and potential toxicological implications. Toxicology. 2016 Jul 29;366-367:32-42. doi: 10.1016/j.tox.2016.08.011. Epub 2016 Aug 12.
Wang Y, Rogan WJ, Chen PC, Lien GW, Chen HY, Tseng YC, Longnecker MP, Wang SL. Association between maternal serum perfluoroalkyl substances during pregnancy and maternal and cord thyroid hormones: Taiwan maternal and infant cohort study. Environ Health Perspect. 2014 May;122(5):529-34. doi: 10.1289/ehp.1306925.
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
Yang L, Li J, Lai J, Luan H, Cai Z, Wang Y, Zhao Y, Wu Y. Placental Transfer of Perfluoroalkyl Substances and Associations with Thyroid Hormones: Beijing Prenatal Exposure Study. Sci Rep. 2016 Feb 22;6:21699. doi: 10.1038/srep21699.
Yu WG, Liu W, Jin YH, Liu XH, Wang FQ, Liu L, Nakayama SF. Prenatal and postnatal impact of perfluorooctane sulfonate (PFOS) on rat development: a cross-foster study on chemical burden and thyroid hormone system. Environ Sci Technol. 2009 Nov 1;43(21):8416-22. doi: 10.1021/es901602d.
Zhang, J., Kamstra, J. H., Ghorbanzadeh, M., Weiss, J. M., Hamers, T., & Andersson, P. L. (2015). In Silico Approach To Identify Potential Thyroid Hormone Disruptors among Currently Known Dust Contaminants and Their Metabolites. Environmental Science and Technology, 49(16), 10099–10107. http://doi.org/10.1021/acs.est.5b01742
Zhang J, Begum A, Brännström K, Grundström C, Iakovleva I, Olofsson A, Sauer-Eriksson AE, Andersson PL. Structure-Based Virtual Screening Protocol for in Silico Identification of Potential Thyroid Disrupting Chemicals Targeting Transthyretin. Environ Sci Technol. 2016 Nov 1;50(21):11984-11993. Epub 2016 Oct 10.
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.