2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol

Immunotoxicity

Key value for chemical safety assessment

Effect on immunotoxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Limited data were available upon which to assess immunotoxicity of TBBPA.

  

Kibakaya et al. (2009) demonstrated that in vitro exposure of TBBPA to human natural killer (NK) cells decreased lytic function that was persistent even after the substance was removed. It must be noted that the concentrations at which function was impaired were high compared to those measured in human serum.

  

Several in vitro studies (Han et al. 2009; Reistad et al. 2005; Hurd and Whalen 2011) showed increases in cytokine mRNA, protein expression and reactive oxygen species (ROS) while cell surface proteins were reduced in NK cells at a concentration of 5 μM TBBPA.    

The ability of TBBPA to stimulate mouse immune cells was examined in vitro using splenocytes and bone marrow-derived dendritic cells (Kioke et al. 2012). In this study, TBBPA showed no cytotoxic effect on either splenocytes or bone marrow-derived dendritic cells, but could stimulate activation marker expression and IL-4 production in splenocytes.

In in vivo studies, Watanabe et al. (2010) exposed BALB/c mice to 1% TBBPA in the diet for 28 days (1887 mg/kg-bw per day). The host immunity to respiratory syncytial virus was mildly affected in lungs and bronchoalveolar lavage (BAL) fluid tested in vitro while systemic immunity was not affected.

The authors proposed that changes in cytokine production and immune (BAL) cell populations affected the immunity of the mice. Immune parameters were also investigated in a reproductive assay with rats (van der Ven et al. 2008). There was no effect upon the immunization response against sheep red blood cells in male F1 animals. Similarly, the natural killer activity test in spleen cells showed no effect in these animals.

 

Overall, although there was some indication of perturbation of immune function in in vitro studies, there was no evidence for specific effects on immune response and overall systemic immunity was not affected whole animals. 

References:

 

Kibakaya E,Stephen K, Whalen M. 2009. Tetrabromobisphenol A has immunosuppressive effects on human natural killer cells. J Immunotoxicol 6(4):285-292.

Han S-K, Sik RH, Motten AG, Chingnell CF, Bilski PJ. 2009. Photosensitized oxygen of

tetrabromobisphenol A by humic acid in aqueous solution. Photochemistry and Photobiology 85:1299-1305.

  

Reistad T, Mariussen E, Fonnum F. 2005. The effect of brominated flame retardants on cell death and free radical formation in cerebellar granule cells. Organohal Compd 57:391–394.

  

Hurd T and Whalen MM. 2011. Tetrabromobisphenol A decreases cell-surface proteins involved in human natural killer (NK) cell-dependent target cell lysis. J Immunotoxicol 8(3):219-227.

 

Koike E, Yanagisawa R, Takigami H, Takano H. 2012. Brominated flame retardants stimulate mouse immune cells in vitro. J Appl Toxicol. doi 10.1002/jat.2809.

  

Watanabe W, Shimizu T, Sawamura R, Hino A, Konno K, Hirose A, Kurokawa M. 2010. Effects of tetrabromobisphenol A, a brominated flame retardant, on the immune response to respiratory syncytial virus infection in mice. Int Immunopharmacol 10:393-397.

 

van der Ven L, Kuil T, Verhoef A, Verwer C, Lilienthal H, Leonards P, Schauer U, Canton R, Litens S, De Jong F, Visser T, Dekant W, Stern N, Hakansson H, Slob W, Van den Berg M, Vos J, Piersma A. 2008. Endocrine effects of tetrabromobisphenol-A (TBBPA) in Wistar rats as tested in a one-generation study and a subacute toxicity study. Toxicology 245(1-2):76-89.

Justification for selection of effect on immunotoxicity via oral route endpoint:
see below summary in discussion section