Stressor: 260




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Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity

Some phthalates have been found to competitively bind to TTR (Ishihara et al 2003; Weiss et al 2015) and have been implicated as thyroid toxicants (Boas et al 2012; Gore et al 2015; Miller et al 2009). While both animal and human data is scarce, there is some evidence for dose-dependent biochemical and morphological changes in animals (Howarth et al 2001; Liu et al 2015; O'Connor et al 2002) as well as in humans (Huang et al 2007; Meeker et al 2007).


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

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

Howarth JA, Price SC, Dobrota M, Kentish PA, Hinton RH. Effects on male rats of di-(2-ethylhexyl) phthalate and di-n-hexylphthalate administered alone or in combination. Toxicol Lett. 2001 Apr 8;121(1):35-43.

Huang PC, Kuo PL, Guo YL, Liao PC, Lee CC. Associations between urinary phthalate monoesters and thyroid hormones in pregnant women. Hum Reprod. 2007 Oct;22(10):2715-22.

Ishihara A1, Nishiyama N, Sugiyama S, Yamauchi K. The effect of endocrine disrupting chemicals on thyroid hormone binding to Japanese quail transthyretin and thyroid hormone receptor. Gen Comp Endocrinol. 2003 Oct 15;134(1):36-43.

Liu, C., Zhao, L., Wei, L., & Li, L. (2015). DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats. Environmental Science and Pollution Research. http://doi.org/10.1007/s11356-015-4567-7

Meeker JD, Calafat AM, Hauser R. Di(2-ethylhexyl) phthalate metabolites may alter thyroid hormone levels in men. Environ Health Perspect. 2007 Jul;115(7):1029-34.

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

O'Connor JC, Frame SR, Ladics GS. Evaluation of a 15-day screening assay using intact male rats for identifying steroid biosynthesis inhibitors and thyroid modulators. Toxicol Sci. 2002 Sep;69(1):79-91.

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


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