Accumulation and biotransformation of BDE-47 by zebrafish larvae and teratogenicity and expression of genes along the hypothalamus-pituitary-thyroid axis.

Accumulation and effects of BDE-47 and two analogues, 6-OH-BDE-47 and 6-MeO-BDE-47, on ontogeny and profiles of transcription of genes along the hypothalamus-pituitary-thyroid (HPT) axis of zebrafish (Danio rerio) embryos exposed from 4 h post fertilization (hpf) to 120 hpf were investigated. The 96 h-LC(50) of the most toxic compound, based on teratogenicity, was 330 μg of 6-OH-BDE-47/L. 6-OH-BDE-47 significantly down-regulated expression of mRNA of thyroid stimulating hormone receptor (TSHR), thyroid hormone receptors (TRs, including TRα and TRβ), sodium/iodide symporter (NIS), and transthyretin (TTR) while up-regulating expression of thyroglobulin (TG) and thyrotropin-releasing hormone (TRH). Spontaneous movement was affected by 1 mg of 6-OH-BDE-47/L or 5 mg of 6-MeO-BDE-47/L. BDE-47 did not alter activity of larvae at any concentration tested. 6-MeO-BDE-47 significantly up-regulated expression of mRNA of TRH, TRα, TRβ and NIS. Both 6-OH-BDE-47 and 6-MeO-BDE-47 affected the thyroid hormone pathway. BDE-47 and 6-MeO-BDE-47 were accumulated more than 6-OH-BDE-47. 6-MeO-BDE-47 was transformed into 6-OH-BDE-47, but BDE-47 was not transformed into it. In summary, the synthetic brominated flame retardant, BDE-47, did not elicit the adverse effects caused by the other two analogues and appeared to have less toxicological relevance than the two natural product analogues 6-OH- and 6-MeO-BDE-47.