Toxicity Of Brominated Flame Retardant Tri (2,3-Dibroproply) Isocyanurate (TBC) On Zebrafish Embryo/ Mice And Rat

Tris-(2,3-dibromopropyl) isocyanurate (TBC) is a heterocyclic brominated flame retardant that was recently detected in the environment, and its toxic effects are still unclear. In this study, zebrafish (Danio rerio) embryo, BALB/c mice and Wistar rat were used as animal models to detect the toxic effects and its potential toxic mechanism of TBC on fish and mammal through pathological, biochemistry and molecular biology methods.Here we report that TBC could cause zebrafish gas bladder defects in inflation with pathological phenomenon of losing the ability of free motility, which can ultimately lead to the death of zebrafish larvae. TBC exposure to zebrafish embryos revealed that the phase where TBC had the most significant influence on the zebrafish larvae might be within the timeframe from 72 to 96 hour post-fertilization, which coincided with the initial inflating time of zebrafish gas bladder. Critical factors involved in the early zebrafish gas bladder development remained at the normal levels, which indicated that TBC caused a deflation of gas bladder without disrupting early organogenesis. However, the ultrastructure of gas bladder was seriously altered in the TBC-treated groups:the quantity of cytoplasmic vesicles was reduced, the electron density of inner contents in the cytoplasmic vesicles was changed, the mitochondria were distorted and the epithelial cells became apoptotic. We deduce that TBC arouses functional injury of mitochondria which influences on the secreting of mucus-like material, and results in defects in inflation of gas bladder.Our results of mice exposured to TBC for 4 weeks showed significantly changed of ALT, GLU and TG levels between control and TBC-treated groups indicated that the TBC had impact on the function of mice liver. Tistopathological observations indicated that TBC exposure caused severe injury in liver, characterized by focal necrosis, degeneration and apoptosis of hepatocyte. In addition, hyperplasia of pulmonary alveolar epithelium, congestion of bronchus, infiltration of inflammatory cells and the mitochondrial swelling were found in the lung of TBC treatment mice. While, TBC exposure did not induce significantly change in spleen. Moreover, TBC effectively activated the level of p53 gene in mice liver which enhance our result of apoptosis in the liver.A 4-week subacute oral toxicity study was performed in Wistar rats with TBC. It was observed that Free T4 level was significantly decreased in the 2 mg/kg/day TBC group and estradiol level was markedly decreased in the 50 mg/kg/day TBC group. According to histopathological observations, obvious lesions appeared in the lungs, such as diffuse thickened epithelial walls, parts fibrosis, and vasodilatation. And the marginal zone showed enlargement in spleen, as well as slight congestion accompanying inflammation existing in the kidney was found in the exposed groups.For the first time, we reported that TBC caused defects in inflation of zebrafish gas bladder, sever injury in liver and lung of BALB/c mice and impact on lung and kidney of Wistar rat. And the possible machenism of the toxic effects induced by TBC was also included in this paper. In a word, our study highlight the needed to characterize the toxic effects of noval heterocyclic brominated flame retardant (BFRs), such as TBC, as they may cause potential contamination to aquatic as well as terrestrial ecosystems.