Are brominated flame retardants endocrine disruptors?

Brominated flame retardants (BFRs) are a group of compounds that have received much attention recently due to their similarity with "old" classes of organohalogenated compounds such as polychlorinated biphenyls (PCBs), in terms of their fate, stability in the environment and accumulation in humans and wildlife. Toxic effects, including teratogenicity, carcinogenicity and neurotoxicity, have been observed for some BFR congeners, in particular the brominated diphenyl ethers (BDEs). This concise review focuses on the potency of BFRs and to disrupt endocrine systems, and attempts to answer the question whether or not BFRs are endocrine disruptors. Evidence is provided on the disruption of the thyroid hormone system by BFRs, with particular emphasis on the BDEs, as most recent data is available on this class of flame retardants. Similar to the hydroxylated PCBs, in vitro mechanistic studies as well as animal experiments have demonstrated the effects of BDEs on thyroid hormone transport and metabolism. An overview of possible effects of BFRs on the estrogen system is also provided. Research gaps are outlined, as well as ongoing and future studies in the European community aimed at contributing to comprehensive risk assessments based on the endocrine-disrupting effects of BFRs.

[1]  I. Meerts,et al.  Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[2]  Kevin M Crofton,et al.  Developmental exposure to brominated diphenyl ethers results in thyroid hormone disruption. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[3]  T. Visser,et al.  Inhibition of thyroid hormone sulfation by hydroxylated metabolites of polychlorinated biphenyls. , 1998, Chemico-biological interactions.

[4]  E. Jakobsson,et al.  A brominated flame retardant, 2,2',4,4',5-pentabromodiphenyl ether: uptake, retention, and induction of neurobehavioral alterations in mice during a critical phase of neonatal brain development. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[5]  I. Meerts,et al.  In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PDBEs, and polybrominated bisphenol A compounds. , 2001, Environmental health perspectives.

[6]  E. Jakobsson,et al.  Brominated flame retardants: a novel class of developmental neurotoxicants in our environment? , 2001, Environmental health perspectives.

[7]  Abraham Brouwer,et al.  Placental transfer of a hydroxylated polychlorinated biphenyl and effects on fetal and maternal thyroid hormone homeostasis in the rat. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[8]  T. Visser,et al.  Pathways of thyroid hormone metabolism. , 1996, Acta medica Austriaca.

[9]  J H Koeman,et al.  Alterations in rat brain thyroid hormone status following pre- and postnatal exposure to polychlorinated biphenyls (Aroclor 1254). , 1996, Toxicology and applied pharmacology.

[10]  S. Kitamura,et al.  Thyroid hormonal activity of the flame retardants tetrabromobisphenol A and tetrachlorobisphenol A. , 2002, Biochemical and biophysical research communications.

[11]  Sierra Rayne,et al.  Exponential increases of the brominated flame retardants, polybrominated diphenyl ethers, in the Canadian Arctic from 1981 to 2000. , 2002, Environmental science & technology.

[12]  Rosalind,et al.  Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop. , 1996, Environmental health perspectives.

[13]  J. E. Heath,et al.  Carcinogenic Activity of the Flame Retardant, 2,2-Bis(bromomethyl)-1,3-Propanediol in Rodents, and Comparison with the Carcinogenicity of Other NTP Brominated Chemicals , 1997, Toxicologic pathology.

[14]  P. Darnerud,et al.  Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and chlorinated paraffins (CPs) in rats-testing interactions and mechanisms for thyroid hormone effects. , 2002, Toxicology.

[15]  L. Hovander,et al.  Identification of Hydroxylated PCB Metabolites and Other Phenolic Halogenated Pollutants in Human Blood Plasma , 2002, Archives of environmental contamination and toxicology.

[16]  L. Johnson,et al.  Structure of human transthyretin complexed with bromophenols: a new mode of binding. , 2000, Acta crystallographica. Section D, Biological crystallography.

[17]  A. Brouwer,et al.  Binding of a 3,3', 4,4'-tetrachlorobiphenyl (CB-77) metabolite to fetal transthyretin and effects on fetal thyroid hormone levels in mice. , 1996, Toxicology.

[18]  P. Darnerud,et al.  Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice , 2001, Archives of Toxicology.

[19]  B. Southwell,et al.  Hormone delivery systems to the brain-transthyretin. , 2009, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[20]  Thomas A McDonald,et al.  A perspective on the potential health risks of PBDEs. , 2002, Chemosphere.

[21]  I. Meerts,et al.  Distribution of the flame retardant tetrabromobisphenol A in pregnant and fetal rats and effect on thyroid hormone homeostasis , 1999 .

[22]  B. Brunström,et al.  Distribution of bisphenol A and tetrabromobisphenol A in quail eggs, embryos and laying birds and studies on reproduction variables in adults following in ovo exposure , 2001, Archives of Toxicology.

[23]  S. Safe,et al.  Structure-dependent, competitive interaction of hydroxy-polychlorobiphenyls, -dibenzo-p-dioxins and -dibenzofurans with human transthyretin. , 1993, Chemico-biological interactions.

[24]  N. Kerkvliet,et al.  Immunologic and endocrine effects of the flame-retardant pentabromodiphenyl ether (DE-71) in C57BL/6J mice. , 1994, Toxicology.

[25]  J. Holme,et al.  Estrogen-like properties of brominated analogs of bisphenol A in the MCF-7 human breast cancer cell line , 2004, Cell Biology and Toxicology.

[26]  T. Visser,et al.  Interactions of Persistent Environmental Organohalogens With the Thyroid Hormone System: Mechanisms and Possible Consequences for Animal and Human Health , 1998, Toxicology and industrial health.

[27]  B. Brunström,et al.  Effects of bisphenol A and tetrabromobisphenol A on sex organ development in quail and chicken embryos , 2001, Environmental toxicology and chemistry.

[28]  J. Giesy,et al.  In vitro assessment of potential mechanism‐specific effects of polybrominated diphenyl ethers , 2002, Environmental toxicology and chemistry.

[29]  Å. Bergman Brominated flame retardants : A burning issue , 2000 .

[30]  M. Obregon,et al.  Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? , 2000, The Journal of clinical endocrinology and metabolism.

[31]  A. Brouwer,et al.  Persistent alterations in regional brain glial fibrillary acidic protein and synaptophysin levels following pre- and postnatal polychlorinated biphenyl exposure. , 1996, Toxicology and applied pharmacology.

[32]  H. Bartsch,et al.  Validation and application of a rapid in vitro assay for assessing the estrogenic potency of halogenated phenolic chemicals. , 1998, Chemosphere.

[33]  A. Brouwer,et al.  Binding of a metabolite of 3,4,3',4'-tetrachlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin. , 1986, Toxicology and applied pharmacology.

[34]  K M Crofton,et al.  Effects of short-term in vivo exposure to polybrominated diphenyl ethers on thyroid hormones and hepatic enzyme activities in weanling rats. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[35]  A D Vethaak,et al.  Development of a stably transfected estrogen receptor-mediated luciferase reporter gene assay in the human T47D breast cancer cell line. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[36]  K. Norén,et al.  Analysis of polybrominated diphenyl ethers in Swedish human milk. A time-related trend study, 1972-1997. , 1999, Journal of toxicology and environmental health. Part A.

[37]  Anders Fredriksson,et al.  Neonatal exposure to the brominated flame retardant 2,2',4,4',5-pentabromodiphenyl ether causes altered susceptibility in the cholinergic transmitter system in the adult mouse. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[38]  A. Brouwer,et al.  Fetal, neonatal, and long-term alterations in hepatic retinoid levels following maternal polychlorinated biphenyl exposure in rats. , 1995, Toxicology and applied pharmacology.

[39]  A. Brouwer,et al.  Determination of the endocrine disrupting potency of hydroxylated PCB's and flame retardants with in vitro bioassays , 2002 .

[40]  P. B. Larsen,et al.  Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology. , 2001, Environmental health perspectives.

[41]  M. Lans Thyroid hormone binding proteins as novel targets for hydroxylated polyhalogenated aromatic hydrocarbons (PHAHs) : possible implications for toxicity , 1995 .