An In Vitro and In Vivo Study of Thyroid Disruption of 1,2-Bis(2,4,6-tribromophenoxy)ethane (BTBPE)-A Novel Brominated Flame Retardant.

The novel brominated flame retardant, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), is an emerging environmental 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 bioconcentration, developmental toxicity, and thyroid endocrine disruption in zebrafish after a 14-day exposure to BTBPE (1, 3, 10 μg/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.