API
Stressor: 261

Title

To create a new stressor, from the Listing Stressors page at https://aopwiki.org/stressors click ‘New stressor.’ This will bring you to a page entitled “New Stressor” where a stressor title can be entered. Click ‘Create stressor’ to create a new Stressor page listing the stressor title at the top. More help

Tetrabromobisphenol A

Stressor Overview

The stressor field is a structured data field that can be used to annotate an AOP with standardised terms identifying stressors known to trigger the MIE/AOP. Most often these are chemical names selected from established chemical ontologies. However, depending on the information available, this could also refer to chemical categories (i.e., groups of chemicals with defined structural features known to trigger the MIE). It can also include non-chemical stressors such as genetic or environmental factors. More help

AOPs Including This Stressor

This table is automatically generated and lists the AOPs associated with this Stressor. More help
AOP Name Evidence
Interference with thyroid serum binding protein transthyretin and subsequent adverse human neurodevelopmental toxicity Not Specified

Events Including This Stressor

This table is automatically generated and lists the Key Events associated with this Stressor. More help
Event Name
Activation of specific nuclear receptors, PPAR-gamma activation
Activation of PPARγ
Activation, EGFR

Chemical Table

The Chemical Table lists chemicals associated with a stressor. This table contains information about the User’s term for a chemical, the DTXID, Preferred name, CAS number, JChem InChIKey, and Indigo InChIKey.To add a chemical associated with a particular stressor, next to the Chemical Table click ‘Add chemical.’ This will redirect you to a page entitled “New Stressor Chemical.’ The dialog box can be used to search for chemical by name, CAS number, JChem InChIKey, and Indigo InChIKey. Searching by these fields will bring forward a drop down list of existing stressor chemicals formatted as  Preferred name, “CAS- preferred name,” “JChem InChIKey – preferred name,” or “Indigo InChIKey- preferred name,” depending on by which field you perform the search. It may take several moments for the drop down list to display. Select an entity from the drop down list and click ‘Add chemical.’ This will return you to the Stressor Page, where the new record should be in the ‘Chemical Table’ on the page.To remove a chemical associated with a particular stressor, in the Chemical Table next to the chemical you wish to delete, click ‘Remove’ and then click 'OK.' The chemical should no longer be visible in the Chemical table. More help
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

This table is automatically generated and includes the AOPs with this associated stressor as well as the evidence term and evidence text from this AOP Stressor. More help
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

This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor. More help
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).

Activation, EGFR

EGFR phosphorylation increased significantly in human immortalized bronchial epithelial BEAS-2B cells following exposure to 10 μg/mL tetrabromobisphenol A for 15 min (Koike et al., 2016).  

Stressor Info

Text sections under this subheading include the Chemical/Category Description and Characterization of Exposure. More help
Chemical/Category Description
To edit the Chemical/Category Description” section, on a KER page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “Chemical/Category Description” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “Chemical/Category Description”  section on the page. More help
Characterization of Exposure
To edit the “Characterization of Exposure” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “Characterization of Exposure”  section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “Characterization of Exposure” section on the page. More help

References

List of the literature that was cited for this Stressor description. Ideally, the list of references, should conform, to the extent possible, with the OECD Style Guide (https://www.oecd.org/about/publishing/OECD-Style-Guide-Third-Edition.pdf) (OECD, 2015).To edit the “References” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “References” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “References” section on the page. More help

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.