The toxicology of the three commercial polybrominated diphenyl oxide (ether) flame retardants.

Three commercial polybrominated diphenyl oxide flame retardants (PBDPO, PBDE) are manufactured: decabromodiphenyl oxide (DBDPO), octabromodiphenyl oxide (OBDPO) and pentabromodiphenyl oxide (PeBDPO). The composition, production volumes, uses and toxicology of the three products differ. In 1999, DBDPO accounted for approximately 82% of the global PBDPO usage. DBDPO has been extensively tested. DBDPO was not acutely toxic, was not irritating to the skin or eye, and did not induce skin sensitization. No evidence of genotoxic effects was detected in the Ames Salmonella, chromosome aberration, mouse lymphoma, or sister chromatid exchange tests. No cytogenic changes were observed in the bone marrow of rats (parents and offspring) undergoing a one-generation reproduction test. DBDPO did not adversely affect development or reproduction in rats. DBDPO's no-adverse-effect-level (NOAEL) in repeated dose studies was > or = 1000 mg/kg body weight. No, equivocal, or some evidence of carcinogenicity, dependent on genus and sex, was found in mice and rats at 2.5% and 5% of the diet administered for 2 years. DBPDO was poorly absorbed from the gastrointestinal tract (< 0.3-2% oral dose), had a short half-life (< 24 h) compared to PCB 153 (only 2% of an oral dose eliminated by rats in 21 days), and was rapidly eliminated via the feces (> 99% in 72 h). In contrast, components of the PeBDPO product were well absorbed and slowly eliminated, OBDPO's effect level in a 90-day study was approximately 100 mg/kg, PeBDPO's no-effect-level (NOEL) in a 30-day study was 1 mg/kg, and OBDPO induced developmental toxicity in the rat. In aquatic species, neither DBDPO nor OBDPO were toxic to aquatic organisms or bioconcentrating. Components of the PeBDPO product bioconcentrated in fish but produced little evidence of adverse effects.

[1]  S. E. el Dareer,et al.  Disposition of decabromobiphenyl ether in rats dosed intravenously or by feeding. , 1987, Journal of toxicology and environmental health.

[2]  M W Hornung,et al.  Toxic equivalency factors of polybrominated dibenzo-p-dioxin, dibenzofuran, biphenyl, and polyhalogenated diphenyl ether congeners based on rainbow trout early life stage mortality. , 1996, Toxicology and applied pharmacology.

[3]  E. Lores,et al.  Responses of marine unicellular algae to brominated organic compounds in six growth media. , 1987, Ecotoxicology and environmental safety.

[4]  J. Giesy,et al.  Comparison of Ah receptor-mediated luciferase and ethoxyresorufin-O-deethylase induction in H4IIE cells: implications for their use as bioanalytical tools for the detection of polyhalogenated aromatic hydrocarbons. , 1996, Toxicology and applied pharmacology.

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

[6]  I. Meerts,et al.  Polybrommated diphenyl ethers (PCDs) as Ah-receptor agonists and antagonists. , 1998 .

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

[8]  Tommy Andersson,et al.  Liver morphology and cytochrome P450 activity in fry of rainbow trout after microinjection of lipid-soluble xenobiotics in the yolk-sac embryos , 1993 .

[9]  P. Darnerud,et al.  Lack of effects of some individual polybrominated diphenyl ether (PBDE) and polychlorinated biphenyl (PCB) congeners on human lymphocyte functions in vitro. , 1997, Toxicology letters.

[10]  Dag Broman,et al.  Dietary uptake in pike (Esox lucius) of some polychlorinated biphenyls, polychlorinated naphthalenes and polybrominated diphenyl ethers administered in natural diet , 1997 .

[11]  M L Hardy,et al.  Prenatal Oral (Gavage) Developmental Toxicity Study of Decabromodiphenyl Oxide in Rats , 2002, International journal of toxicology.

[12]  Eva Jakobsson,et al.  Interaction of polybrominated biphenyls ether metabolites (PBDE-OH) with human transthyretin in vitro. , 1998 .

[13]  C. D. Klaasen Casarett & Doull's Toxicology: The Basic Science of Poisons , 1980 .

[14]  J. Palha,et al.  Transthyretin is not essential for thyroxine to reach the brain and other tissues in transthyretin-null mice. , 1997, The American journal of physiology.

[15]  H. Tilson,et al.  Congener-specific distribution of polychlorinated biphenyls in brain regions, blood, liver, and fat of adult rats following repeated exposure to Aroclor 1254. , 1998, Toxicology and applied pharmacology.

[16]  A Schmoldt,et al.  Induction of rat liver microsomal cytochrome P-450 by the pentabromo diphenyl ether Bromkal 70 and half-lives of its components in the adipose tissue. , 1990, Toxicology.

[17]  Bo Jansson,et al.  Dietary Uptake and Biological Effects of Decabromodiphenyl Ether in Rainbow Trout (Oncorhynchus mykiss) , 1999 .

[18]  E. Mcconnell,et al.  National Toxicology Program Nomenclature for Hepatoproliferative Lesions of Rats , 1986, Toxicologic pathology.

[19]  C. Capen,et al.  Mechanistic Data and Risk Assessment of Selected Toxic End Points of the Thyroid Gland , 1997, Toxicologic pathology.

[20]  U. Orn,et al.  Metabolism of 2,2',4,4'-tetrabromodiphenyl ether in rat and mouse. , 1998, Xenobiotica; the fate of foreign compounds in biological systems.

[21]  M. Gottesman,et al.  Transthyretin Regulates Thyroid Hormone Levels in the Choroid Plexus, But Not in the Brain Parenchyma: Study in a Transthyretin-Null Mouse Model. , 2000, Endocrinology.

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

[23]  C. Owman,et al.  Transthyretin expression in the rat brain: effect of thyroid functional state and role in thyroxine transport , 1993, Brain Research.

[24]  G. Schussler,et al.  Thyroxine-binding proteins. , 2000, Thyroid : official journal of the American Thyroid Association.

[25]  D. L. McAllister,et al.  A preliminary report on the investigation of the comparative toxicity of combustion products of high impact polystyrene with and without decabromodiphenyloxide/antimony trioxide as a flame retardant using 2,3,7,8-tetrabromodibenzo-p-dioxin and 2,3,7,8-tetrabromodibenzofuran as positive controls , 1989 .

[26]  G. Carlson,et al.  Induction of xenobiotic metabolism in rats by brominated diphenyl ethers administered for 90 days. , 1980, Toxicology letters.

[27]  Eva Jakobsson,et al.  Developmental neurotoxicity of brominated flame-retardants, polybrominated diphenyl ethers and tetrabromo-bis-phenol A , 1998 .

[28]  G. Carlson,et al.  Induction of xenobiotic metabolism in rats by short-term administration of brominated diphenyl ethers. , 1980, Toxicology letters.

[29]  J. Koeman,et al.  Different competition of thyroxine binding to transthyretin and thyroxine-binding globulin by hydroxy-PCBs, PCDDs and PCDFs. , 1994, European journal of pharmacology.

[30]  B. Schwetz,et al.  Toxicology of octabromobiphenyl and decabromodiphenyl oxide. , 1975, Environmental health perspectives.

[31]  L. G. Davis,et al.  Detection of thyroid toxicants in a tier I screening battery and alterations in thyroid endpoints over 28 days of exposure. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[32]  Tommy Andersson,et al.  Effects of exposure to food contaminated with PBDE, PCN or PCB on reproduction, liver morphology and cytochrome P450 activity in the three-spined stickleback, Gasterosteus aculeatus , 1993 .

[33]  W J Breslin,et al.  Teratogenic evaluation of a polybromodiphenyl oxide mixture in New Zealand white rabbits following oral exposure. , 1989, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[34]  R. Tatsukawa,et al.  Formation of brominated dibenzofurans from the photolysis of flame retardant decabromobiphenyl ether in hexane solution by UV and sun light , 1987, Bulletin of environmental contamination and toxicology.

[35]  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.