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Human Health Effects of Brominated Flame Retardants

Part of the The Handbook of Environmental Chemistry book series (HEC,volume 16)

Abstract

In this chapter, we review human health effects associated with the brominated flame retardants (BFRs) that have constituted the overwhelming majority of BFR production and subsequent exposure in humans. These include tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), and three commercial mixtures of polybrominated diphenyl ethers (PBDEs), or biphenyl oxides, which are known as decabromodiphenyl ether (DecaBDE), octabromodiphenyl ether (OctaBDE), and pentabromodiphenyl ether (PentaBDE). The primary endpoint of concern appears to be endocrine disruption. Other potential effects include hepatotoxicity and neurotoxicity, the later particularly during development. While the toxicological database for these chemicals is growing, further research is needed to understand potential health effects associated with less-studied PBDE congeners, examine the potential carcinogenicity of HBCD and TBBPA, and investigate the overall toxicity of a number of developing alternative BFRs. The increasing contamination of the environment and people by BFRs coupled with clear evidence of adverse health effects resulting from their exposure highlights the importance of identifying emerging issues and data gaps to fully understand the human health risks.

Keywords

  • Endocrine disruption
  • Hexabromocyclododecane
  • Polybrominated diphenyl ether
  • Tetrabromobisphenol A
  • Thyroid hormones

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References

  1. USEPA (2008) IRIS Health Assessment of 2,2',4,4'-Tetrabromodiphenyl Ether (BDE-47) CASRN 5436-43-12. U.S. Environmental Protection Agency, Washington, DC, 2008. EPA/635/R-07/005F

    Google Scholar 

  2. USEPA (2008) IRIS Health Assessment of 2',4,4',5-Pentabromodiphenyl Ether (BDE-99) CASRN 60348-60-92. U.S. Environmental Protection Agency, Washington, DC, 2008. EPA/635/R-07/006F

    Google Scholar 

  3. Birnbaum LS, Staskal DF (2004) Brominated flame retardants: cause for concern? Environ Health Perspect 112:9–17

    CrossRef  CAS  Google Scholar 

  4. Birnbaum LS, Hubal EAC (2006) Polybrominated diphenyl ethers: a case study for using biomonitoring data to address risk assessment questions. Environ Health Perspect 114:1770–1775

    CAS  Google Scholar 

  5. Dunnick JK, Nyska A (2009) Characterization of liver toxicity in F344/N rats and B6C3F1 mice after exposure to a flame retardant containing lower molecular weight polybrominated diphenyl ethers. Exp Toxicol Pathol 61(1):1–12

    CrossRef  CAS  Google Scholar 

  6. USEPA (2008) IRIS Health Assessment of 2',4,4',5,5'-Hexabromodiphenyl Ether (BDE-153) CASRN 68631-49-22. U.S. Environmental Protection Agency, Washington, DC, 2008. EPA/635/R-07/007F

    Google Scholar 

  7. Viberg H, Fredriksson A, Jakobsson E, Orn U, Eriksson P (2003) Neurobehavioral derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development. Toxicol Sci 76:112–120

    CrossRef  CAS  Google Scholar 

  8. USEPA (2008) IRIS Health Assessment of 2',3,3',4,4',5,5',6,6'-Decabromodiphenyl Ether (BDE-209) CASRN 1163-19-5. U.S. Environmental Protection Agency, Washington, DC, 2008. EPA/635/R-07/008F

    Google Scholar 

  9. Rice DC, Reeve EA, Herlihy A, Zoeller RT, Thompson WD, Markovich VP (2007) Developmental delays and locomotor activity in the C57BL6/J mouse following neonatal exposure to the fully-brominated PBDE, decabromodiphenyl ether. Neurotoxicol Teratol 29(4):511–520

    CrossRef  CAS  Google Scholar 

  10. Rice DC, Thompson WD, Reeve EA, Onos KD, Assadollahzadeh M, Markovich VP (2009) Behavioral changes in aging but not young mice after neonatal exposure to the polybrominated flame retardant decaBDE. Eviron Health Perspect 117(12):1903–1911

    CAS  Google Scholar 

  11. Viberg H, Fredriksson A, Eriksson P (2007) Changes in spontaneous behaviour and altered response to nicotine in the adult rat, after neonatal exposure to the brominated flame retardant, decabrominated diphenyl ether (PBDE 209). Neurotoxicology 28(1):136–142

    CrossRef  CAS  Google Scholar 

  12. Xing T, Chen L, Tao Y, Wang M, Chen J, Ruan DY (2010) Effects of decabrominated diphenyl ether (PBDE 209) exposure at different developmental periods on synaptic plasticity in the dentate gyrus of adult rats In vivo. Toxicol Sci 110(2):401–410

    CrossRef  Google Scholar 

  13. NTP (National Toxicology Program) (1986) Toxicology and carcinogenesis studies of decabromodiphenyl oxide (CAS No 1163-19-5) in F344/N rats and B6C3F mice (feed studies). NTP TR 309

    Google Scholar 

  14. EU (2001) European Union Risk Assessment Report (RAR): Diphenyl ether, pentabromo derivative (pentabromodiphenyl ether). EUR 19730 EN

    Google Scholar 

  15. Hagmar L, Bjork J, Sjodin A, Bergman A, Erfurth EM (2001) Plasma levels of persistent organohalogens and hormone levels in adult male humans. Arch Environ Health 56(2):138–143

    CrossRef  CAS  Google Scholar 

  16. Mazdai A, Dodder NG, Abernathy MP, Hites RA, Bigsby RM (2003) Polybrominated diphenyl ethers in maternal and fetal blood samples. Environ Health Perspect 111(9):1249–1252

    CrossRef  CAS  Google Scholar 

  17. Julander A, Karlsson M, Hagstrom K, Ohlson CG, Engwall M, Bryngelsson IL, Westberg H, van Bavel B (2005) Polybrominated diphenyl ethers-plasma levels and thyroid status of workers at an electronic recycling facility. Int Arch Occup Environ Health 78:584–592

    CrossRef  CAS  Google Scholar 

  18. Yuan J, Chen L, Chen D, Guo H, Bi X, Ju Y, Jiang P, Shi J, Li L, Jiang Q, Sheng G, Fu J, Wu T, Chen X (2008) Elevated serum polybrominated diphenyl ethers and thyroid-stimulating hormone associated with lymphocytic micronuclei in Chinese workers from an E-waste dismantling site. Environ Sci Technol 42:2195–2200

    CrossRef  CAS  Google Scholar 

  19. Wang H, Zhang Y, Liu Q, Wang F, Nie J, Qian Y (2010) Examining the relationship between brominated flame retardants (BFR) exposure and changes of thyroid hormone levels around e-waste dismantling sites. Int J Hyg Environ Health 231(5):369–380

    CrossRef  Google Scholar 

  20. Turyk ME, Persky VW, Imm P, Knobeloch L, Chatterton R, Anderson HA (2008) Hormone disruption by PBDEs in adult male sport fish consumers. Environ Health Perspect 116:1635–1641

    CrossRef  CAS  Google Scholar 

  21. Herbstman JB, Sjodin A, Apelberg BJ, Witter FR, Halden RU, Patterson DG, Panny SR, Needham LL, Goldman LR (2008) Birth delivery mode modifies the associations between prenatal polychlorinated biphenyl (PCB) and polychlorinated diphenyl ether (PBDE) and neonatal thyroid hormone levels. Environ Health Perspect 116(19):1376–1382

    CrossRef  CAS  Google Scholar 

  22. Chevrier J, Harley KG, Bradman A, Gharbi M, Sjodin A, Eskanzi B (2010) Polybrominated diphenylether (PBDE) flame retardants and thyroid hormone during pregnancy. Environ Health Perspect 118:1444–1449

    CrossRef  CAS  Google Scholar 

  23. Meeker JD, Johnson PI, Camann D, Hauser R (2009) Polybrominated diphenyl ether (PBDE) concentrations in house dust are related to hormone levels in men. Sci Total Environ 407(10):3425–3429

    CrossRef  CAS  Google Scholar 

  24. Lim JS, Lee DK, Jacobs DRJ (2008) Association of brominated flame retardants with diabetes and metabolic syndrome on the U.S. population, 2003–2004. Diabetes Care 31(9):1802–1807

    CrossRef  Google Scholar 

  25. Costa LG, Giordano G (2007) Developmental neurotoxicity of polybrominated diphenyl ether (PBDE) flame retardants. Neurotox 28(6):1047–1067

    CrossRef  CAS  Google Scholar 

  26. Roze E, Meijer L, Bakker A, Van Braeckel KN, Sauer PJ, Bos AF (2009) Prenatal exposure to organohalogens, including brominated flame retardants, influences motor, cognitive, and behavioral performance at school age. Environ Health Perspect 117:1953–1958

    CAS  Google Scholar 

  27. Herbstman JB, Sjodin A, Kurzon M, Lederman SA, Jones RS, Rauh V, Needham LL, Tang D, Niedzwiecki M, Wang RY, Perera F (2010) Prenatal exposure to PBDEs and neurodevelopment. Environ Health Perspect 118(5):712–719

    CrossRef  CAS  Google Scholar 

  28. Messer A (2010) Mini-review: polybrominated diphenyl ether (PBDE) flame retardants as potential autism risk factors. Physiol Behav 100:245–249

    CrossRef  CAS  Google Scholar 

  29. Main KM, Kiviranta H, Virtanen HE, Sundqvist E, Tuomisto JT, Tuomisto J, Vartiainen T, Skakkebaek NE, Toppari J (2007) Flame retardants in placenta and breast milk and cryptorchidism in newborn boys. Environ Health Perspect 115:1519–1526

    CAS  Google Scholar 

  30. Akutsu K, Takatori S, Noxawa S, Toshiike M, Nakazawa H, Hayakawa K, Makino T, Iwamoto T (2008) Polybrominated diphenyl ethers in human serum and sperm quality. Bull Environ Contam Toxicol 80:345–350

    CrossRef  CAS  Google Scholar 

  31. Harley K, Marks AR, Chevrier J, Bradman A, Sjodin A, Eskenazi B (2010) PBDE concentrations in women’s serum and fecundability. Environ Health Perspect 118(5):699–704

    CrossRef  CAS  Google Scholar 

  32. EU (2002) European Union Risk Assessment Report (RAR): bis(pentabromophenyl) ether. EUR 20402 EN

    Google Scholar 

  33. Yu K, He Y, Yeung LW, Lam PK, Wu RS, Zhou B (2008) DE-71-induced apoptosis involving intracellular calcium and the Bax-mitochondria-caspase protease pathway in human neuroblastoma cells in vitro. Toxicol Sci 104:341–351

    CrossRef  CAS  Google Scholar 

  34. He P, Wang AG, Xia T, Gao P, Niu Q, Guo LJ, Xu BY, Chen XM (2009) Mechanism of the neurotoxic effect of PBDE-47 and interaction of PBDE-47 and PCB153 in enhancing toxicity in SH-SY5Y cells. Neurotoxicology 30:10–15

    CrossRef  CAS  Google Scholar 

  35. Tagliaferri S, Caglieri A, Goldoni M, Pinelli S, Alinovi R, Poli D, Pellacani C, Giordano G, Mutti A, Costa LG (2010) Low concentrations of the brominated flame retardants BDE-47 and BDE-99 induce synergistic oxidative stress-mediated neurotoxicity in human neuroblastoma cells. Toxicol In Vitro 24:116–122

    CrossRef  CAS  Google Scholar 

  36. Schreiber T, Gassmann K, Gotz C, Hubenthal U, Moors M, Krause G, Merk HF, Nguyen NH, Scanlan TS, Abel J, Rose CR, Fritsche E (2010) Polybrominated diphenyl ethers induce developmental neurotoxicity in a human in vitro model: evidence for endocrine disruption. Environ Health Perspect 118:572–578

    CrossRef  CAS  Google Scholar 

  37. Song R, Duarte TL, Almeida GM, Farmer PB, Cooke MS, Zhang W, Sheng G, Fu J, Jones GD (2009) Cytotoxicity and gene expression profiling of two hydroxylated polybrominated diphenyl ethers in human H295R adrenocortical carcinoma cells. Toxicol Lett 185:23–31

    CrossRef  CAS  Google Scholar 

  38. Reistad T, Mariussen E (2005) A commercial mixture of the brominated flame retardant pentabrominated diphenyl ether (DE-71) induces respiratory burst in human neutrophil granulocytes in vitro. Toxicol Sci 87:57–65

    CrossRef  CAS  Google Scholar 

  39. He W, He P, Wang A, Xia T, Xu B, Chen X (2008) Effects of PBDE-47 on cytotoxicity and genotoxicity in human neuroblastoma cells in vitro. Mutat Res 649:62–70

    CAS  Google Scholar 

  40. Canton RF, Sanderson JT, Letcher RJ, Bergman A, van den Berg M (2005) Inhibition and induction of aromatase (CYP19) activity by brominated flame retardants in H295R human adrenocortical carcinoma cells. Toxicol Sci 88:447–455

    CrossRef  CAS  Google Scholar 

  41. Canton RF, Sanderson JT, Nijmeijer S, Bergman A, Letcher RJ, van den Berg M (2006) In vitro effects of brominated flame retardants and metabolites on CYP17 catalytic activity: a novel mechanism of action? Toxicol Appl Pharmacol 216:274–281

    CrossRef  CAS  Google Scholar 

  42. Song R, He Y, Murphy MB, Yeung LW, Yu RM, Lam MH, Lam PK, Hecker M, Giesy JP, Wu RS, Zhang W, Sheng G, Fu J (2008) Effects of fifteen PBDE metabolites, DE71, DE79 and TBBPA on steroidogenesis in the H295R cell line. Chemosphere 71:1888–1894

    CrossRef  CAS  Google Scholar 

  43. Hu XZ, Xu Y, Hu DC, Hui Y, Yang FX (2007) Apoptosis induction on human hepatoma cells Hep G2 of decabrominated diphenyl ether (PBDE-209). Toxicol Lett Jun 15;171(1-2):19–28. Epub 2007 Apr 10

    CrossRef  CAS  Google Scholar 

  44. Shao J, White CC, Dabrowski MJ, Kavanagh TJ, Eckert ML, Gallagher EP (2008) The role of mitochondrial and oxidative injury in BDE 47 toxicity to human fetal liver hematopoietic stem cells. Toxicol Sci 101:81–90

    CrossRef  CAS  Google Scholar 

  45. Stapleton HM, Kelly SM, Pei R, Letcher RJ, Gunsch C (2009) Metabolism of polybrominated diphenyl ethers (PBDEs) by human hepatocytes in vitro. Environ Health Perspect 117:197–202

    CrossRef  CAS  Google Scholar 

  46. Lupton SJ, McGarrigle BP, Olson JR, Wood TD, Aga DS (2009) Human liver microsome-mediated metabolism of brominated diphenyl ethers 47, 99, and 153 and identification of their major metabolites. Chem Res Toxicol 22:1802–1809

    CrossRef  CAS  Google Scholar 

  47. Mundy WR, Freudenrich TM, Crofton KM et al (2004) Accumulation of PBDE-47 in primary cultures of rat neocortical cells. Toxicol Sci 82:164–169

    CrossRef  CAS  Google Scholar 

  48. EU (2006) European Union Risk Assessment Report (RAR): 2,2’,6,6’-tetrabromo-4.4’isopropylindenediphenol (tetrabromobisphenol-A or TBBP-A) Part II – Health Assessment. EUR 22161 EN

    Google Scholar 

  49. Hill Top Research, Inc (1966) Acute toxicity and irritation studies in Tetrabromobisphenol A (unpublished)

    Google Scholar 

  50. International Research and Development Corporation (1978) Acute oral toxicity (LD50) study in mice (unpublished)

    Google Scholar 

  51. Leberco Laboratories (1958) Acute oral toxicity test (unpublished)

    Google Scholar 

  52. Pharmakon Laboratories (1981) Acute oral toxicity study in rats (14 day) (unpublished report no. PH 402-ET-001-81)

    Google Scholar 

  53. Pharmakon Laboratories (1981) Acute dermal toxicity study in rabbits (unpublished report no. PH 422-ET-001-81)

    Google Scholar 

  54. WHO (1995) Tetrabromobisphenol A and derivatives. Environmental Health Criteria 172. World Health Organization, Geneva

    Google Scholar 

  55. MPI Research (2002) A 90-day oral toxicity study of tetrabromobisphenol-A in rats with a recovery group (unpublished)

    Google Scholar 

  56. Noda T, Morita S, Ohgaki S, Shimizu M (1985) Safety evaluation of chemicals for use in household products (VII) teratological studies on tetrabromobisphenol-A in rats. Annual report of the Osaka Institute of Public Health and Environmental Sciences 48:106–112

    CAS  Google Scholar 

  57. MPI Research (2001) Final report – an oral prenatal developmental toxicity study with tetrabromobisphenol-A in rats (unpublished)

    Google Scholar 

  58. MPI Research (2002) An oral two generation reproductive, fertility and developmental neurobehavioural study of tetrabromobisphenol-A in rats (unpublished)

    Google Scholar 

  59. MPI Research (2003) Amendment to the final report. An oral two generation reproductive, fertility and developmental neurobehavioural study of tetrabromobisphenol-A in rats (Unpublished report)

    Google Scholar 

  60. Fukuda N, Ito Y, Yamaguchi M, Mitumori K, Koizumi M, Hasegawa R, Kamata E, Ema M (2004) Unexpected nephotoxicity induced by tetrabromobisphenol A in newborn rats. Toxicol Lett 150:145–155

    CrossRef  CAS  Google Scholar 

  61. Tada Y, Fujitani T, Yano N, Takahashi H, Yuzawa K, Ando H, Kubo Y, Nagasawa A, Ogata A, Kaminmura H (2006) Effects of tetrabromobisphenol A, brominated flame retardant, in ICR mice after prenatal and postnatal exposure. Food Chem Toxicol 44(8):1408–1413

    CrossRef  CAS  Google Scholar 

  62. Lilienthal H, Verwer CM, van der Ven LT, Piersma AH, Vos JG (2008) Exposure to tetrabromobisphenol A (TBBPA) in Wistar rats: neurobehavioral effects in offspring from a one-generation reproduction study. Toxicology 246:45–54

    CrossRef  CAS  Google Scholar 

  63. Nakajima A, Saigusa D, Tetsu N, Yamakuni T, Tomioka Y, Hishinuma T (2009) Neurobehavioral effects of tetrabromobisphenol A, a brominated flame retardant, in mice. Toxicol Lett 189(1):78–83

    CrossRef  CAS  Google Scholar 

  64. Williams AL, DeSesso JM (2010) The potential of selected brominated flame retardants to affect neurological development. J Toxicol Environ Health B Crit Rev 13(5):441–448

    Google Scholar 

  65. Ethyl Corporation (1981) Salmonella/microsomal assay-tetrabromobisphenol A EPA/OTS Doc Number 878216192

    Google Scholar 

  66. Mortelmans K, Haworth S, Lawlor T, Speck W, Tainer B, Zeigler E (1986) Salmonella mutagenicity test: II. Results from the testing of 270 Chemicals. Environ Mutagen 8(7):1–119

    CrossRef  CAS  Google Scholar 

  67. BioReliance (2001) An in vitro mammalian chromosome aberration test with tetrabromobisphenol-A (unpublished)

    Google Scholar 

  68. Helleday T, Tuominen K, Bergman A, Jenseen D (1999) Brominated flame retardants induce intragenic recombination in mammalian cells. Mutat Res 439:137–147

    CAS  Google Scholar 

  69. Mariussen E, Fonnum F (2002) The effect of pentabromodiphenyl ether, hexabromocyclododecane and tetrabromobisphenol- A on dopamine uptake into rat brain synaptosomes. Organohalogen Compounds 57:395–399

    CAS  Google Scholar 

  70. Reistad T, Mariussen E, Fonnum F (2002) The effect of brominated flame retardants on cell death and free radical formation in cerebellar granule cells. Organohalogen Compounds 57:391–394

    CAS  Google Scholar 

  71. Reistad T, Mariussen E, Ring A, Fonnum F (2007) In vitro toxicity of tetrabromobisphenol-A on cerebellar granule cells: cell death, free radical formation, calcium influx and extracellular glutamate. Toxicol Sci 96:268–278

    CrossRef  CAS  Google Scholar 

  72. Boecker RH, Schwind B, Kraus V, Pullen S, Tiegs G (2001). Cellular disturbances by various brominated flame retardants [Abstract]. Presented at the Second International Workshop on Brominated Flame Retardants, 14–16 May 2001, Stockholm, Sweden

    Google Scholar 

  73. Germer S, Piersma AH, van der Ven L, Kamyschnikov A, Fery Y, Schmitz H-J, Schrenk D (2006) Subacute effects of the brominated flame retardants hexabromocyclododecane and tetrabisphenol A on hepatic cytochrome P450 levels in rats. Toxicology 218:229–236

    CrossRef  CAS  Google Scholar 

  74. Meerts IATM, Letcher RL, Hoving S, Bergman A, Lemmen JG, van der Burg B, Brouwer A (2001) In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PBDEs and polybrominated bisphenol A compounds. Environ Health Perspect 109(4):399–407

    CrossRef  CAS  Google Scholar 

  75. Miller D, Wheals BB, Beresford N, Sumpter JP (2001) Estrogenic activity of phenolic additives determined by an in vitro yeast bioassay. Environ Health Perspect 109(2):133–138

    CrossRef  CAS  Google Scholar 

  76. Kitamura S, Kato T, Iida M, Jinno N, Suzuki T, Ohta S, Fujimoto N, Hanada H, Kashiwaga K, Kashiwaga A (2005) 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. Life Sci 76:1589–1601

    CrossRef  CAS  Google Scholar 

  77. Hamers T, Kamstra JH, Sonneveld E, Murk AJ, Kester MHA, Andersson P, Legler J, Brouwer A (2006) In vitro profiling of the endocrine disrupting potency of brominated flame retardants. Toxicol Sci 92(1):157–173

    CrossRef  CAS  Google Scholar 

  78. Li J, Ma M, Wang Z (2010) In vitro profiling of endocrine disrupting effects of phenols. Toxicol In Vitro 24(1):201–207

    CrossRef  CAS  Google Scholar 

  79. Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J et al (1999) Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 341:549–555

    CrossRef  CAS  Google Scholar 

  80. Kitamura S, Jinno N, Ohta S, Kuroki H, Fujimoto N (2002) Thyroid hormonal activity of the flame retardants tetrabromobisphenol A and tetrachlorobisphenol A. Biochem Biophys Res Commun 293:554–559

    CrossRef  CAS  Google Scholar 

  81. Freitas J, Cano P, Craig-Veit C, Goodson ML, Furlow JD, Murk AJ (2011) Detection of thyroid hormone receptor disruptors by a novel stable in vitro reporter gene assay. Toxicol In Vitro 25:257–266

    Google Scholar 

  82. Meerts IATM, Assink Y, Cenijin PH, Weijers BM, van den Berg HHJ (1999) Distribution of the flame retardant tetrabromobisphenol A in pregnant and fetal rats and effect on thyroid hormone homeostasis. Brominated Flame Retardants P068/. Organohalogen Compounds 40:375–378

    CAS  Google Scholar 

  83. Van der Ven LT, Ven de Kuil T, Verhoef A, Verwer CM, Lilienthal H, Leonards PE et al (2008) Endocrine effects of tetrabromobisphenol- A (TBBPA) in Wistar rats as tested in a one-generation reproduction study and a subacute toxicity study. Toxicology 260(1–3):150–152

    Google Scholar 

  84. Reistad T, Mariussen E, Fonnum F (2005) The effect of a brominated flame retardant, tetrabromobisphenol-A, on free radical formation in human neutrophil granulocytes: the involvement of the MAP kinase pathway and protein kinase C. Toxicol Sci 83:89–100

    CrossRef  CAS  Google Scholar 

  85. Kitamura S, Suzuki T, Sanoh S, Kohta R, Jinno N, Sugihara K, Yoshihara S, Fujimoto N, Watanabe H, Ohta S (2005) Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds. Toxicol Sci 84:249–259

    CrossRef  CAS  Google Scholar 

  86. Samuelsen M, Olsen C, Holme JA, Meussen-Elhoom E, Bergmann A, Hongslo JK (2001) Estrogen-like properties of brominated analogs of bisphenol A in the MCF-7 human breast cancer cell line. Cell Biol Toxicol 14:139–151

    CrossRef  Google Scholar 

  87. Schauer UM, Volkel W, Dekant W (2006) Toxicokinetics of tetrabromobisphenol a in humans and rats after oral administration. Toxicol Sci 91:49–58

    CrossRef  CAS  Google Scholar 

  88. Zalko D, Prouillac C, Riu A, Perdu E, Dolo L, Jouanin I, Canlet C, Debrauwer L, Cravedi JP (2006) Biotransformation of the flame retardant tetrabromo-bisphenol A by human and rat sub-cellular liver fractions. Chemosphere 64:318–327

    CrossRef  CAS  Google Scholar 

  89. Kibakaya EC, Stephen K, Whalen MM (2009) Tetrabromobisphenol A has immunosuppressive effects on human natural killer cells. J Immunotoxicol 6:285–292

    CrossRef  CAS  Google Scholar 

  90. Lewis AC, Palanker AL (1978) A dermal LD50 study in albino rabbits and an inhalation LC50 study in albino rats. Test material GLS-S6-41A. Client: Saytech Inc. (not published). 78385-2, Consumer product testing

    Google Scholar 

  91. Wilson PD, Leong BKJ (1977) Acute toxicity studies in rabbits and rats. Test material Firemaster 100 Lot 53 77.902. Sponsored by: Velsicol Chemical Corporation (not published). pp 163–499, International Research and Development Corporation

    Google Scholar 

  92. Lewis AC and Palanker AL (1978) A primary dermal irritation study, a dermal corrosion study, and an ocular irritation study in albino rabbits and an oral LD50 study in albino rats. Test material GLS-S6-41A. Client: Saytech Inc. (not published). 78385-1, Concumer Product Testing

    Google Scholar 

  93. Ogaswara S, Fukushi A, Midorikawa Y (1983) Report on acute toxicity test of pyroguard SR-103 in rats (not published)

    Google Scholar 

  94. Tobe et al (1984) Acute toxicity test of hexabromocyclododecane (not published). Research Center for Biological Safety National Public Health Research Institute

    Google Scholar 

  95. USEPA (1990) Report on the study of the acute oral toxicity of hexabromocyclododecane in the mouse. Letter from BASF. 86-900000383, EPT/OTS Doc

    Google Scholar 

  96. EU (2008) European Union Risk Assessment Report (RAR): Hexabromocyclododecane

    Google Scholar 

  97. Wenk ML (1996) Maximization test in guinea pigs. Test article: Hexabromocyclododecane; p 43. Microbiologial Associates, Inc., Rockvill, MD, USA

    Google Scholar 

  98. Wolhiser MR, Anderson PK (2003) Hexabromocyclododecane: contact sensitization potential via the local lymph node assay (including a primary irritancy screen) using CBA/J mice. Study ID 031013, p 24. Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan, USA

    Google Scholar 

  99. Zeller H, Kirsch P (1969) Hexabromocyclododecane: 28-day feeding trials with rats. BASF (not published)

    Google Scholar 

  100. Zeller H, Kirsch P (1970) Hexabromocyclododecane: 90-day feeding trials with rats. BASF (not published)

    Google Scholar 

  101. Chengelis CP (2001). A 90-day oral (gavage) toxicity study of HBCD in rats. WIL-186012, p 1527. Wil Research Laboratories, Inc., Ashland, Ohio, USA

    Google Scholar 

  102. Van der Ven LTM, Verhoef A, van de Kuil T, Slob W, Leonards PEG, Visser TJ, Hamers T, Håkansson H, Olausson H, Piersma AH, Vos JG (2006) A 28-day oral dose toxicity study of hexabromocyclododecane (HBCD) in Wistar rats. Toxicol Sci 94:281–292

    CrossRef  Google Scholar 

  103. Canton RF, Peijnenburg AA, Hoogenboom RL, Piersma AH, van der Ven LT, van den Berg M, Heneweer M (2008) Subacute effects of hexabromocyclododecane (HBCD) on hepatic gene expression profiles in rats. Toxicol Appl Pharmacol 231(2):267–272

    CrossRef  CAS  Google Scholar 

  104. Baskin AD, Phillips BM (1977) Mutagenicity of two lots of FM-100, Lot 53 and residue of lot 3322 in the absence and presence of metabolic activation. Sponsored by: Velsicol Chemical Corporation (not published). Industrial BIO TEST Laboratories, Inc

    Google Scholar 

  105. GSRI (1979) Mutagenicity test of GLS-S6-41A (not published). Gulf South Research Institute

    Google Scholar 

  106. Hossack DJN, Richold M, Jones E, Bellamy RP (1978) Ames metabolic activation test to assess the potential mutagenic effect of compound no. 49. pp 1–2. Huntingdon Research Centre

    Google Scholar 

  107. Simmon VF, Poole DC, Newell GW, Skinner WA (1976) In vitro microbiological mutagenicity studies of four CIBA-GEIGY corporation compounds. Prepared for CIBAGeigy Corporation (not published). 5702, SRI Project LSC

    Google Scholar 

  108. USEPA (1990) Ames test with hexabromides. Letter from BASF. 86-900000379, EPA/OTS Doc

    Google Scholar 

  109. Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, Speck W (1987) Salmonella mutagenicity tests: III. Results from the testing of 255 chemicals. Environ Mutagen 9(Suppl 9):1–110

    CrossRef  CAS  Google Scholar 

  110. Engelhardt and Hoffman (2000) Cytogenetic study in vivo with of hexabromocyclododecane in the mouse micronucleus test after two intraperitoneal administrations. BASF, Ludwigshafen, Germany

    Google Scholar 

  111. Ema M, Fujii S, Hirata-Koizumi M, Matsumoto M (2008) Two-generation reproductive toxicity study of the flame retardant hexabromocyclododecane in rats. Reprod Toxicol 25(3):335–351

    CrossRef  CAS  Google Scholar 

  112. Murai T, Kawasaki H, Kanoh S (1985) Studies on the toxicity of insecticides and food additives in pregnant rats (7). Fetal toxicity of hexabromocyclododekane. Oyo Yakuri 29:981–986

    CAS  Google Scholar 

  113. Stump DG (1999) Prenatal developmental toxicity study of hexabromocyclododecane (HBCD) in rats. WIL Research Laboratories, Inc, Ashland, Ohio, USA, p 410

    Google Scholar 

  114. Van der Ven LT, van de Kuil T, Leonards PEG, Slob W, Lilienthal H, Litens S, Herlin M, Hakansson H et al (2009) Endocrine effects of hexabromocyclododecane (HBCD) in a one-generation reporoduction study in Wistar rats. Toxicol Lett 185:51–62

    CrossRef  Google Scholar 

  115. Lilienthal H, van der Ven L, Roth-Haerer A, Hack A, Piersma A, Vos J (2006) Neurobehavioral toxicity of brominated flame retardants: differential effects of PBDE-99, TBBPA and HBCD and endocrine relation. Dioxin Conference 2006 Oslo. Organohalogen Compounds 68: 3 pages

    Google Scholar 

  116. Lilienthal H, van der Ven LT, Piersma AH, Vos JG (2009) Effects of the brominated flame retardant hexabromocylcododecane (HBCD) on dopamine-dependent behavior and brainstem auditory evoked potentials in a one-generation reproduction study in Wistar rats. Toxicol Lett 185(1):63–72

    CrossRef  CAS  Google Scholar 

  117. Dingemans MML, Heusinkveld HJ, de Groot A, Bergman A, van de Berg M, Westerink RHS (2009) Hexabromocylcododecane inhibits depolarization-induced increase in intracellular calcium levels and neurotransmitter release in PC12 cells. Toxicol Sci 107(2):490–497

    CrossRef  CAS  Google Scholar 

  118. Szabo DT, Diliberto JJ, Hakk H, Huwe JK, Birnbaum LS (2010) Toxicokinetics of the flame retardant hexabromocyclododecane gamma: effect of dose, timing, route, repeated exposure, and metabolism. Toxicol Sci 117(2):282–293

    CrossRef  CAS  Google Scholar 

  119. Zhang X, Yang F, Xu C, Liu W, Wen S, Xu Y (2008) Cytotoxicity evaluation of three pairs of hexabromocyclododecane (HBCD) enantiomers on Hep G2 cell. Toxicol In Vitro 22:1520–1527

    CrossRef  CAS  Google Scholar 

  120. Aniagu SO, Williams TD, Chipman JK (2009) Changes in gene expression and assessment of DNA methylation in primary human hepatocytes and HepG2 cells exposed to the environmental contaminants-Hexabromocyclododecane and 17-beta oestradiol. Toxicology 256:143–151

    CrossRef  CAS  Google Scholar 

  121. Hinkson NC, Whalen MM (2009) Hexabromocyclododecane decreases the lytic function and ATP levels of human natural killer cells. J Appl Toxicol 29:656–661

    CrossRef  CAS  Google Scholar 

  122. Hinkson NC, Whalen MM (2010) Hexabromocyclododecane decreases tumor-cell-binding capacity and cell-surface protein expression of human natural killer cells. J Appl Toxicol 30:302–309

    CrossRef  CAS  Google Scholar 

  123. Yamada-Okabe T, Sakai H, Kashima Y, Yamada-Okabe H (2005) Modulation at a cellular level of the thyroid hormone receptor-mediated gene expression by 1, 2, 5, 6, 9, 10- hexabromocyclododecane (HBCD), 4, 4´-diiodobiphenyl (DIB), and nitrofen (NIP). Toxicol Lett 155:127–133

    CrossRef  CAS  Google Scholar 

  124. McDonnell (1972) Human Patch Test, Haskell Laboratory Report. p. 185-72, Haskell Laboratory for toxicology and Industrial Medicine, E.I. du Pont de Nemours and Company

    Google Scholar 

  125. USEPA (2010) IRIS glossary/Acronyms and Abbreviations. Available: http://www.epa.gov/ncea/iris/help_gloss.htm. Accessed 29 Nov 2010

  126. Eriksson P, Jakobsson E, Fredriksson A (2001) Brominated flame retardants: a novel class of developmental neurotoxicants in our environment? Environ Health Perspect 109:903–908

    CrossRef  CAS  Google Scholar 

  127. Viberg H, Fredriksson A, Eriksson P (2004) Investigations of strain and/or gender differences in developmental neurotoxic effects of polybrominated diphenyl ethers in mice. Toxicol Sci 81:344–353

    CrossRef  CAS  Google Scholar 

  128. EU (2003) European Union Risk Assessment Report (RAR): Diphenyl ether, octabromo derivative. EUR 20403 EN

    Google Scholar 

  129. Pullen S, Boecker R, Tiegs G (2003) The flame retardants tetrabromobisphenol A and tetrabromobisphenol A-bisallylether suppress the induction of interleukin-2 receptor alpha chain (CD25) in murine splenocytes. Toxicology Feb 14;184(1):11–22

    Google Scholar 

  130. Eriksson P, Fischer C, Fredriksson A (2006) Polybrominated diphenyl ethers, a group of brominated flame retardants, can interact with polychlorinated biphenyls in enhancing developmental neurobehavioral defects. Toxicol Sci Dec;94(2):302–9. Epub 2006 Sep 15

    Google Scholar 

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Wikoff, D.S., Birnbaum, L. (2011). Human Health Effects of Brominated Flame Retardants. In: Eljarrat, E., Barceló, D. (eds) Brominated Flame Retardants. The Handbook of Environmental Chemistry(), vol 16. Springer, Berlin, Heidelberg. https://doi.org/10.1007/698_2010_97

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