The novel brominated flame retardant,1,2-bis-(2,4,6-tribromophenoxy)ethane(BTBPE),is an emerging environ-mental pollutant with undetermined toxicity.We investigated how BTBPE causes thyroid endocrine disruption with i...The novel brominated flame retardant,1,2-bis-(2,4,6-tribromophenoxy)ethane(BTBPE),is an emerging environ-mental pollutant with undetermined toxicity.We investigated how BTBPE causes thyroid endocrine disruption with integrated in silico,in vitro,and in vivo assays.In yeast two-hybrid and T-Screen assays,BTBPE interacted with zebrafish thyroid hormone receptors with binding energies weaker than the TR agonist-3,3′,5-Triiodo-L-thyronine(T3),and disrupted thyroid function as a thyroid receptor(TR)agonist.We examined the bioconcentra-tion,developmental toxicity,and thyroid endocrine disruption in zebrafish after a 14-day exposure to BTBPE(1,3,10μg/L).Thyroxine(T4)was lower in BTBPE-treated larvae,whereas corticotropin-releasing hormone(CRH)and thyroid-stimulating hormone(TSH)were higher.The gene transcription alterations along the hypothalamic-pituitary-thyroid(HPT)axis were observed.Furthermore,reduced locomotion suggested that BTBPE imparts developmental neurotoxicity at zebrafish early developmental stage.Establishing that BTBPE has thyroid endocrine-disrupting effects is an important step for understanding and managing BTBPE toxicity.展开更多
Alternative brominated flame retardants（BFRs） have become prevalent as a consequence of restrictions on the use of polybrominated diphenyl ethers（PBDEs）. For risk assessment of these alternatives, knowledge of the...Alternative brominated flame retardants（BFRs） have become prevalent as a consequence of restrictions on the use of polybrominated diphenyl ethers（PBDEs）. For risk assessment of these alternatives, knowledge of their metabolism via cytochrome P450 enzymes is needed.We have previously proved that density functional theory（DFT） is able to predict the metabolism of PBDEs by revealing the molecular mechanisms. In the current study, the reactivity of 1,2-bis（2,4,6-tribromophenoxy）ethane and structurally similar chemicals with the Compound I model representing the active site of P450 enzymes was investigated. The DFT calculations delineated reaction pathways which lead to reasonable explanations for products that were detected by wet experiments, meanwhile intermediates which cannot be determined were also proposed. Results showed that alkyl hydrogen abstraction will lead to bis（2,4,6-tribromophenoxy）ethanol, which may undergo hydrolysis yielding2,4,6-tribromophenol, a neurotoxic compound. In addition, a general pattern of oxidation reactivity regarding the 2,4,6-tribromophenyl moiety was observed among several model compounds. Our study has provided insights for convenient evaluation of the metabolism of other structurally similar BFRs.展开更多
基金supported by the National Natural Science Foundation of China (Nos.42277278,22276213).
文摘The novel brominated flame retardant,1,2-bis-(2,4,6-tribromophenoxy)ethane(BTBPE),is an emerging environ-mental pollutant with undetermined toxicity.We investigated how BTBPE causes thyroid endocrine disruption with integrated in silico,in vitro,and in vivo assays.In yeast two-hybrid and T-Screen assays,BTBPE interacted with zebrafish thyroid hormone receptors with binding energies weaker than the TR agonist-3,3′,5-Triiodo-L-thyronine(T3),and disrupted thyroid function as a thyroid receptor(TR)agonist.We examined the bioconcentra-tion,developmental toxicity,and thyroid endocrine disruption in zebrafish after a 14-day exposure to BTBPE(1,3,10μg/L).Thyroxine(T4)was lower in BTBPE-treated larvae,whereas corticotropin-releasing hormone(CRH)and thyroid-stimulating hormone(TSH)were higher.The gene transcription alterations along the hypothalamic-pituitary-thyroid(HPT)axis were observed.Furthermore,reduced locomotion suggested that BTBPE imparts developmental neurotoxicity at zebrafish early developmental stage.Establishing that BTBPE has thyroid endocrine-disrupting effects is an important step for understanding and managing BTBPE toxicity.
基金supported by the National Basic Research Program(No.2013CB430403)the National Natural Science Foundation(Nos.21137001,21325729,and 21173211)of Chinasupported by Supercomputing Center of Dalian University of Technology
文摘Alternative brominated flame retardants（BFRs） have become prevalent as a consequence of restrictions on the use of polybrominated diphenyl ethers（PBDEs）. For risk assessment of these alternatives, knowledge of their metabolism via cytochrome P450 enzymes is needed.We have previously proved that density functional theory（DFT） is able to predict the metabolism of PBDEs by revealing the molecular mechanisms. In the current study, the reactivity of 1,2-bis（2,4,6-tribromophenoxy）ethane and structurally similar chemicals with the Compound I model representing the active site of P450 enzymes was investigated. The DFT calculations delineated reaction pathways which lead to reasonable explanations for products that were detected by wet experiments, meanwhile intermediates which cannot be determined were also proposed. Results showed that alkyl hydrogen abstraction will lead to bis（2,4,6-tribromophenoxy）ethanol, which may undergo hydrolysis yielding2,4,6-tribromophenol, a neurotoxic compound. In addition, a general pattern of oxidation reactivity regarding the 2,4,6-tribromophenyl moiety was observed among several model compounds. Our study has provided insights for convenient evaluation of the metabolism of other structurally similar BFRs.
