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

• Published in: Journal of hazardous materials 2022-02, Vol.424 (Pt A), p.127386-127386, Article 127386
• Main Authors: Liu, Sitian, Song, Guili, Li, Fan, Li, Ruiwen, Chen, Xiangping, Guo, Yongyong, Zhou, Fang, Wang, Qiangwei, Yang, Lihua, Zhou, Bingsheng
• Format: Article
• Language: English
• Subjects: Animals; Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate; Blood-Brain Barrier; Flame Retardants - toxicity; Neurotoxicity; Penetrability; Permeability; Phthalic Acids - toxicity; Zebrafish
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2021.127386

Bis(2ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a replacement for restricted flame retardants, has become ubiquitous in the environment. To reveal the neurotoxicity and underlying mechanism of TBPH, we first evaluated its penetrability through the blood-brain barrier (BBB) using hCMEC/D3 cells as in vitro model, and found TBPH had poor penetrability through BBB with a maximum Papp of 14.8 × 10−6 cms−1. Further study using transgenetic zebrafish (Tg flk1: EGFP) as in vivo model confirmed that TBPH could affect the BBB permeability, probably via affecting the transcription of genes encoding tight junction proteins. Finally, wild type zebrafish embryos/larvae were exposed to TBPH to evaluate the neurotoxicity. The neurodevelopment, neurotransmitters and locomotor activity of zebrafish larvae did not changed, which may be because TBPH can hardly cross the BBB to pose direct exposure to the central nervous system. However, the transcription of opsins genes and visual response to light stimulation in zebrafish larvae were inhibited, pointing to additional mechanism that may cause visual impairment indirectly. Above all, these results can help further understand the neurotoxicity and underlying mechanism by TBPH, and also pointed out potential risk of this chemical to aquatic organisms. [Display omitted] •The neurotoxicity and underlying mechanisms of TBPH were characterized.•TBPH showed poor penetrability to cross the BBB in vitro.•TBPH increased the BBB permeability both in vitro and in vivo.•TBPH did not affect the neurotransmitters and locomotor of zebrafish larvae.•TBPH affected the visual response via inhibiting the transcription of opsins genes.