Anti-thyroid hormonal activity of tetrabromobisphenol A, a flame retardant, and related compounds: Affinity to the mammalian thyroid hormone receptor, and effect on tadpole metamorphosis

• Published in: Life sciences (1973) 2005-02, Vol.76 (14), p.1589-1601
• Main Authors: Kitamura, Shigeyuki, Kato, Teruhisa, Iida, Mitsuru, Jinno, Norimasa, Suzuki, Tomoharu, Ohta, Shigeru, Fujimoto, Nariaki, Hanada, Hideki, Kashiwagi, Keiko, Kashiwagi, Akihiko
• Format: Article
• Language: English
• Subjects: Amphibian metamorphosis; Animals; Antagonist of thyroid hormone; Antithyroid Agents - pharmacology; Chlorophenols - pharmacology; CHO Cells; Cricetinae; EcoScreen assay; Female; Flame Retardants - pharmacology; Genes, Reporter - genetics; Hamster ovary cell line CHO-K1; Larva; Metamorphosis, Biological - drug effects; Pituitary Gland - drug effects; Pituitary Gland - metabolism; Plasmids - genetics; Polybrominated Biphenyls - pharmacology; Ranidae; Rats; Receptors, Thyroid Hormone - drug effects; Receptors, Thyroid Hormone - genetics; Tadpole; Tail shortening; Tetrabromobisphenol A; Tetrachlorobisphenol A; Tetramethylbisphenol A; Thyroid hormone-disrupting activity; Thyroid Hormones - metabolism; Thyroid Hormones - pharmacology; Triiodothyronine - pharmacology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2004.08.030

The thyroid hormone-disrupting activity of tetrabromobisphenol A (TBBPA), a flame retardant, and related compounds was examined. TBBPA, tetrachlorobisphenol A (TCBPA), tetramethylbisphenol A (TMBPA) and 3,3′-dimethylbisphenol A (DMBPA) markedly inhibited the binding of triiodothyronine (T 3; 1 × 10 −10 M) to thyroid hormone receptor in the concentration range of 1 × 10 −7–1 × 10 −4 M, while bisphenol A and 2,2-diphenylpropane were inactive. TBBPA, TCBPA, TMBPA and DMBPA did not exhibit thyroid hormonal activity in a thyroid hormone-responsive reporter assay using a Chinese hamster ovary cell line (CHO-K1) transfected with thyroid hormone receptor α1 or β1, but TBBPA and TCBPA showed significant anti-thyroid hormone effects on the activity of T 3 (1 × 10 −8 M) in the concentration range of 3 × 10 −6 – 5 × 10 −5 M. The thyroid hormone-disrupting activity of TBBPA was also examined in terms of the effect on amphibian metamorphosis stimulated by thyroid hormone. TBBPA in the concentration range of 1 × 10 −8 to 1 × 10 −6 M showed suppressive action on T 3 (5 × 10 −8 M)-enhancement of Rana rugosa tadpole tail shortening. These facts suggest that TBBPA, TCBPA, TMBPA and DMBPA can act as thyroid hormone-disrupting agents.