Stressor: 257



Polybrominated diphenyl ethers

Stressor Overview


AOPs Including This Stressor


Events Including This Stressor


Chemical Table


AOP Evidence


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

Event Evidence


Stressor Info


Chemical/Category Description


Characterization of Exposure