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 | High |
Events Including This Stressor
Chemical Table
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