Stressor: 259



Perflourinated chemicals

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

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.


Event Evidence


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Characterization of Exposure