Stressor: 258
Title
Stressor Overview
AOPs Including This Stressor
| AOP Name | Evidence |
|---|---|
| Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity | Strong |
Events Including This Stressor
This table is automatically generated and lists KE’s including this stressor.Chemical Table
The 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.AOP Evidence
Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
Soy isoflavones, such as genistein, have been found to bind to TTR (Radovic et al 2006) and have been noted as thyroid toxicants (Miller et al 2009; Murk et al 2013). Synthetic flavonoids, such as EMD 21388 have also been found to interfere with TH transport via TTR binding and have been well-studied in rats (Leuprasitsakul et al 1990; Mendel et al 1992; Pedraza et al 1996; Schröder-van der Elst et al 1997; Schröder-van der Elst et al 1998). This early work in rats helped refine knowledge of the TTR interference pathway and its important to brain and fetal thyroid function.
Lueprasitsakul, W., Alex, S., Fang, S. L., Pino, S., Irmscher, K., Köhrle, J., & Braverman, L. E. (1990). Flavonoid administration immediately displaces thyroxine (T4) from serum transthyretin, increases serum free T4, and decreases serum thyrotropin in the rat. Endocrinology.
Mendel, C. M., Cavalieri, R. R., & Kohrle, J. (1992). Thyroxine (T4) transport and distribution in rats treated with EMD 21388, a synthetic flavonoid that displaces T4 from transthyretin. Endocrinology, 130(3), 1525–1532.
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
Pedraza, P., Calvo, R., Obregón, M. J., Asuncion, M., Escobar Del Rey, F., & Morreale De Escobar, G. (1996). Displacement of T4 from transthyretin by the synthetic flavonoid EMD 21388 results in increased production of T3 from T4 in rat dams and fetuses. Endocrinology, 137(11), 4902–4914. http://doi.org/10.1210/en.137.11.4902
Radović, B., Mentrup, B., & Köhrle, J. (2006). Genistein and other soya isoflavones are potent ligands for transthyretin in serum and cerebrospinal fluid. The British Journal of Nutrition, 95(6), 1171–1176. http://doi.org/10.1079/BJN20061779
Schröder-Van Der Elst, J. P., Van Der Heide, D., Rokos, H., Köhrle, J., & Morreale De Escobar, G. (1997). Different tissue distribution, elimination, and kinetics of thyroxine and its conformational analog, the synthetic flavonoid EMD 49209 in the rat. Endocrinology, 138(1), 79–84. http://doi.org/10.1210/en.138.1.79
Schröder-van der Elst, J. P., van der Heide, D., Rokos, H., Morreale de Escobar, G., & Köhrle, J. (1998). Synthetic flavonoids cross the placenta in the rat and are found in fetal brain. The American Journal of Physiology, 274(2 Pt 1), E253-6. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9486155
Event Evidence
This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor.
Stressor Info
Chemical/Category Description
Instructions 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 Exposure
Instructions 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.References
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.