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Flame Retardant TBPH Increases Permeability of Blood-Brain Barrier

While the chemical has a low penetrative ability through the blood-brain barrier, it can increase the permeability of the blood-brain barrier, potentially disrupting homeostasis.

Popular in the 1970s to 2000s, flame retardants are chemicals that are applied to materials to prevent the start or slow the spread of fire and have been used in many commercial and consumer products like furniture and building insulation. Many flame retardants are considerably toxic and can persist in the environment. Bis(2 ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) was introduced as a replacement for restricted flame retardants and has become ubiquitous in the environment, having been found accumulating in polar bears and dolphins.

In previous studies, TBPH has been found to be a structural analogue of di(2-ethylhexyl) phthalate (DEHP), a compound known to disrupt hormone synthesis and induce hepatotoxicity, reproductive, and neurobehavioural toxicity. Therefore, its potential adverse effects and evergrowing presence in our environment has been of great interest to the scientific community.

A team of scientists led by Professor Zhou Bingsheng from the Institute of Hydrobiology (IHB) of the Chinese Academy of Sciences investigated the neurotoxicity and underlying mechanisms of TBPH and found that the compound had poor penetrability through the blood-brain barrier, but could affect tight junctions and increase the permeability of the blood-brain barrier. This could disrupt homeostasis across the blood-brain barrier and cause adverse effects on the nervous system.

By using an in vitro model of human immortalised endothelial cells to evaluate the penetrability of TBPH, the scientists found that TBPH has a lower Papp during different periods, hinting at a poor penetrative ability through the blood-brain barrier. Upon further studies with transgenic zebrafish, the team was able to confirm that TBPH could affect the blood-brain barrier permeability. The group reasoned that this could be due to TBPH influencing the transcription of genes encoding tight junction proteins.

Finally, to assess the potential neurotoxicity of TBPH, the team exposed wild type zebrafish embryos/larvae to TBPH. From the results, they found that embryonic exposure to TBPH did not significantly change the hatching, signalling and malformation rates, neurotransmitter contents, or locomotor activity. This could be because TBPH can barely cross the blood-brain barrier to pose direct exposure to the central nervous system.

However, the transcription of opsin genes and visual response to light stimulation in wild type zebrafish larvae were inhibited, suggesting that there might be an additional mechanism indirectly involved in visual impairment, leaving room for investigation in future works.

For now, the study has shared some insight on the neurotoxicity and underlying mechanisms of TBPH and revealed how TBPH can impact aquatic organisms. More would have to be done to investigate the potential risk of this chemical on other organisms. [APBN]

Source: Liu et al. (2022). Bis (2-ethylhexyl)-2, 3, 4, 5-tetrabromophthalate showed poor penetrability but increased the permeability of blood brain barrier: Evidences from in vitro and in vivo studies. Journal of Hazardous Materials, 424, 127386.