Stressor: 261
Title
Stressor Overview
AOPs Including This Stressor
| AOP Name | Evidence |
|---|---|
| Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity | Not Specified |
Events Including This Stressor
Chemical Table
| User term | DTXID | Preferred name | Casrn | jchem_inchi_key | indigo_inchi_key |
|---|---|---|---|---|---|
| Tetrabromobisphenol A | DTXSID1026081 | 3,3',5,5'-Tetrabromobisphenol A | 79-94-7 | VEORPZCZECFIRK-UHFFFAOYSA-N | VEORPZCZECFIRK-UHFFFAOYSA-N |
AOP Evidence
Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity
Tetrabromobisphenol A (TBBPA) has been found to competitively bind to TTR (Meerts et al 2000; Weiss et al 2015) and other bisphenols have been implicated as thyroid toxicants (Boas et al 2012). Iakovleva et al (2016) recently reported the crystal structure of TTR-TBBPA
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
Iakovleva, I., Begum, A., Brännström, K., Wijsekera, A., Nilsson, L., Zhang, J., … Olofsson, A. (2016). Tetrabromobisphenol a is an efficient stabilizer of the transthyretin tetramer. PLoS ONE, 11(4), 1–16. http://doi.org/10.1371/journal.pone.0153529
Meerts, I. a, van Zanden, J. J., Luijks, E. a, van Leeuwen-Bol, I., Marsh, G., Jakobsson, E., … Brouwer, a. (2000). Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. Toxicological Sciences : An Official Journal of the Society of Toxicology, 56(1), 95–104. http://doi.org/10.1093/toxsci/56.1.95
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
Activation of specific nuclear receptors, PPAR-gamma activation
TBBPA binds to PPARγ in vitro, with a Kd of 0.78 µM and in vivo in zebrafish, with a LOEL of 100 nM (Fang et al., 2015; Riu et al., 2011; Riu et al., 2014). Mild activation has also been reported in vitro in several research papers and in ToxCast assays as well, with effective doses ranging from 0.3 to 10 µM (Riu et al., 2011; Riu et al., 2014; Suzuki et al., 2013; ToxCastTM Data; Watt and Schlezinger, 2015).
Activation of PPARγ
TBBPA binds to PPARγ in vitro, with a Kd of 0.78 µM and in vivo in zebrafish, with a LOEL of 100 nM (Fang et al., 2015; Riu et al., 2011; Riu et al., 2014). Mild activation has also been reported in vitro in several research papers and in ToxCast assays as well, with effective doses ranging from 0.3 to 10 µM (Riu et al., 2011; Riu et al., 2014; Suzuki et al., 2013; ToxCastTM Data; Watt and Schlezinger, 2015).
Stressor Info
Chemical/Category Description
Characterization of Exposure
References
Fang, M., Webster, T. F., Ferguson, P. L. and Stapleton, H. M. (2015). Characterizing the peroxisome proliferator-activated receptor (PPARg) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust. Environ. Health Perspect. 123, 166–172.
Riu, A., Grimaldi, M., le Maire, A., Bey, G., Phillips, K., Boulahtouf, A., Perdu, E., Zalko, D., Bourguet, W. and Balaguer, P. (2011). Peroxisome Proliferator-Activated Receptor [ gamma ] Is a Target for Halogenated Analogs of Bisphenol A. Perspect. Environ. Heal. Collect. Proquest Hosp. 119, 1227–1232.
Riu, A., Mccollum, C. W., Pinto, C. L., Grimaldi, M., Hillenweck, A., Perdu, E., Zalko, D., Bernard, L., Laudet, V., Balaguer, P., et al. (2014). Halogenated bisphenol-a analogs act as obesogens in zebrafish larvae (Danio rerio). Toxicol. Sci. 139, 48–58.
Suzuki, G., Tue, N. M., Malarvannan, G., Sudaryanto, A., Takahashi, S., Tanabe, S., Sakai, S. I., Brouwer, A., Uramaru, N., Kitamura, S., et al. (2013). Similarities in the endocrine-disrupting potencies of indoor dust and flame retardants by using human osteosarcoma (U2OS) cell-based reporter gene assays. Environ. Sci. Technol. 47, 2898–2908.
ToxCastTM Data. “ToxCastTM Data.” US Environmental Protection Agency. http://www.epa.gov/ncct/toxcast/data.html.
Watt, J. and Schlezinger, J. J. (2015). Structurally-diverse, PPARγ-activating environmental toxicants induce adipogenesis and suppress osteogenesis in bone marrow mesenchymal stromal cells. Toxicology 331, 66–77.