Brominated flame retardants: a novel class of developmental neurotoxicants in our environment?

Brominated flame retardants are a novel group of global environmental contaminants. Within this group the polybrominated diphenyl ethers (PBDE) constitute one class of many that are found in electrical appliances, building materials, and textiles. PBDEs are persistent compounds that appear to have an environmental dispersion similar to that of polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT). Levels of PBDEs are increasing in mother's milk while other organohalogens have decreased in concentration. We studied for developmental neurotoxic effects two polybrominated diphenyl ethers, 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47) and 2,2',4,4',5-pentabromodiphenyl ether (PBDE 99)--congeners that dominate in environmental and human samples--together with another frequently used brominated flame retardant, tetrabromo-bis-phenol-A (TBBPA). The compounds were given to 10-day-old NMRI male mice, as follows: PBDE 47, 0.7 mg (1.4 micromol), 10.5 mg (21.1 micromol)/kg body weight (bw); PBDE 99, 0.8 mg (1.4 micromol), 12.0 mg (21.1 micromol)/kg bw; TBBPA, 0.75 mg (1.4 micromol), 11.5 mg (21.1 micromol)/kg bw. Mice serving as controls received 10 mL/kg bw of the 20% fat emulsion vehicle in the same manner. The present study has shown that neonatal exposure to PBDE 99 and PBDE 47 can cause permanent aberrations in spontaneous behavior, evident in 2- and 4-month-old animals. This effect together with the habituation capability was more pronounced with increasing age, and the changes were dose-response related. Furthermore, neonatal exposure to PBDE 99 also affected learning and memory functions in adult animals. These are developmental defects that have been detected previously in connection with PCBs.

[1]  R. Morris,et al.  Place navigation impaired in rats with hippocampal lesions , 1982, Nature.

[2]  L. A. Gallenberg,et al.  Transfer of persistent chemicals in milk. , 1989, Drug metabolism reviews.

[3]  H. Kunkel GENERAL INTRODUCTION , 1971, The Journal of experimental medicine.

[4]  J. Coyle,et al.  Neurochemical aspects of the ontogenesis of cholinergic neurons in the rat brain , 1976, Brain Research.

[5]  P. Eriksson,et al.  Exposure to nicotine during a defined period in neonatal life induces permanent changes in brain nicotinic receptors and in behaviour of adult mice , 2000, Brain Research.

[6]  B. Campbell,et al.  Ontogeny of Adrenergic Arousal and Cholinergic Inhibitory Mechanisms in the Rat , 1969, Science.

[7]  R. Bartus,et al.  The cholinergic hypothesis of geriatric memory dysfunction. , 1982, Science.

[8]  A. Fredriksson MPTP-induced behavioural deficits in mice : validity and utility of a model of Parkinsonism , 1994 .

[9]  P. Eriksson,et al.  Changes in behavior and muscarinic receptor density after neonatal and adult exposure to bioallethrin , 1998, Neurobiology of Aging.

[10]  G. Marsh,et al.  Synthesis and Characterization of 32 Polybrominated Diphenyl Ethers , 1999 .

[11]  P. Eriksson,et al.  Exposure to DDT during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice , 1992, Brain Research.

[12]  H. Tilson,et al.  Developmental neurotoxicology of polychlorinated biphenyls and related compounds , 1992 .

[13]  P. Eriksson Neuroreceptor and Behavioral Effects of DDT and Pyrethroids in Immature and Adult Mammals , 1992 .

[14]  P. Eriksson,et al.  Neonatal exposure to 2,2',5,5'-tetrachlorobiphenyl causes increased susceptibility in the cholinergic transmitter system at adult age. , 1996, Environmental toxicology and pharmacology.

[15]  H. Tilson,et al.  Polychlorinated biphenyls and the developing nervous system: cross-species comparisons. , 1990, Neurotoxicology and teratology.

[16]  R. Seegal Epidemiological and laboratory evidence of PCB-induced neurotoxicity. , 1996, Critical reviews in toxicology.

[17]  D. Drachman,et al.  Memory and cognitive function in man , 1977, Neurology.

[18]  A. Nordberg Neuronal nicotinic receptors and their implications in ageing and neurodegenerative disorders in mammals. , 1993, Journal of reproduction and fertility. Supplement.

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

[20]  J. Coyle,et al.  Neurochemical aspects of the ontogenesis of gabanergic neurons in the rat brain , 1976, Brain Research.

[21]  R. Morris Spatial Localization Does Not Require the Presence of Local Cues , 1981 .

[22]  P. Eriksson,et al.  Differential expression of muscarinic subtype mRNAs after exposure to neurotoxic pesticides , 1998, Neurobiology of Aging.

[23]  P. Eriksson Perinatal developmental neurotoxicity of PCBs , 1998 .

[24]  oseph,et al.  INTELLECTUAL IMPAIRMENT IN CHILDREN EXPOSED TO POLYCHLORINATED BIPHENYLS IN UTERO , 2000 .

[25]  P. Eriksson,et al.  Neonatal exposure to paraquat or MPTP induces permanent changes in striatum dopamine and behavior in adult mice. , 1993, Toxicology and applied pharmacology.

[26]  P. Eriksson,et al.  Neonatal exposure to 3,3',4,4'-tetrachlorobiphenyl: changes in spontaneous behaviour and cholinergic muscarinic receptors in the adult mouse. , 1991, Toxicology.

[27]  A. C. Collins,et al.  Postnatal Development of Cholinergic Enzymes and Receptors in Mouse Brain , 1987, Journal of neurochemistry.

[28]  J. Gray,et al.  Effects of cholinergic-rich neural grafts on radial maze performance of rats after excitotoxic lesions of the forebrain cholinergic projection system—II. Cholinergic drugs as probes to investigate lesion-induced deficits and transplant-induced functional recovery , 1991, Neuroscience.

[29]  S. Schantz,et al.  Neurochemical and Behavioral Sequelae of Exposure to Dioxins and PCBs , 1994 .

[30]  D. Rice,et al.  Effects of postnatal exposure to a PCB mixture in monkeys on nonspatial discrimination reversal and delayed alternation performance. , 1997, Neurotoxicology.

[31]  P. Eriksson,et al.  Exposure to an organophosphate (DFP) during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice , 1995, Brain Research.

[32]  P. Eriksson,et al.  Neonatal exposure to neurotoxic pesticides increases adult susceptibility: a review of current findings. , 2000, Neurotoxicology.

[33]  L. Hagmar,et al.  Flame retardant exposure: polybrominated diphenyl ethers in blood from Swedish workers. , 1999, Environmental health perspectives.

[34]  J. Boer,et al.  Do flame retardants threaten ocean life? , 1998, Nature.

[35]  C. A. Wit,et al.  Polybrominated diphenyl ethers (PBDE) in biological samples from the Swedish environment , 1993 .

[36]  T. Lewander,et al.  Marble burying and spontaneous motor activity in mice: interactions over days and the effect of diazepam. , 1987, Scandinavian journal of psychology.

[37]  J. Jacobson,et al.  Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive functioning in young children. , 1990, The Journal of pediatrics.

[38]  P. Eriksson,et al.  Neurotoxic effects in adult mice neonatally exposed to 3,3'4,4'5-pentachlorobiphenyl or 2,3,3'4,4'-pentachlorobiphenyl. Changes in brain nicotinic receptors and behaviour. , 1998, Environmental toxicology and pharmacology.

[39]  H. Fibiger,et al.  The organization and some projections of cholinergic neurons of the mammalian forebrain , 1982, Brain Research Reviews.

[40]  U. Sellström Determination of some polybrominated flame retardants in biota, sediment and sewage sludge , 1999 .

[41]  J. R. James,et al.  Genetic and environmental aspects of the role of nicotinic receptors in neurodegenerative disorders: Emphasis on Alzheimer's disease and Parkinson's disease , 1995, Behavior genetics.

[42]  J. Jacobson,et al.  Prenatal exposure to polychlorinated biphenyls: effects on birth size and gestational age. , 1984, The Journal of pediatrics.

[43]  K. Norén,et al.  Certain organochlorine and organobromine contaminants in Swedish human milk in perspective of past 20-30 years. , 2000, Chemosphere.

[44]  G. Blomkvist,et al.  Polybrominated aromatic pollutants found in fish in Sweden , 1981 .

[45]  R. Bolles,et al.  The ontogeny of behaviour in the albino rat , 1964 .

[46]  P. Eriksson,et al.  Developmental neurotoxicity of four ortho-substituted polychlorinated biphenyls in the neonatal mouse. , 1996, Environmental toxicology and pharmacology.

[47]  J S Taylor,et al.  Congenital poisoning by polychlorinated biphenyls and their contaminants in Taiwan. , 1988, Science.

[48]  Children Pesticides in the Diets of Infants and Children , 1993 .

[49]  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.