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Neonatal Developmental Neurotoxicity of Brominated Flame Retardants, the Polybrominated Diphenyl Ethers (PBDEs)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis examines developmental neurotoxic effects of polybrominated diphenyl ethers (PBDEs), PBDE 99, PBDE 153, and the fully brominated PBDE 209, after exposure during the newborn period in rodents.

Our environment contains vast numbers of contaminants, including the flame retardants, PBDEs. The PBDEs are widely found in the environment and are increasing in human milk. Individuals can be exposed to PBDEs during their whole lifetime, and especially during the lactation period. The neonatal period, coinciding with the lactation period, is characterized in many mammalian species by rapid growth and development of the immature brain. It has been shown that numerous toxicants can induce permanent disorders in brain function when administered to the neonatal mouse during the brain growth spurt (BGS). In mice and rats this period is postnatal, spanning over the first 3-4 weeks of life, while in humans, BGS begins during the third trimester of pregnancy and continues throughout the first two years of life.

The present studies identified a defined critical period during BGS in mice when the brain is vulnerable to insults of low doses of PBDEs and that it is the presence of PBDEs or their metabolites in the brain during this critical period that is crucial to evoking neurotoxic effects. The effects observed are permanent altered spontaneous behavior, reduced habituation, deficits in learning and memory, and disturbances in the cholinergic system. These effects worsen with age.

The ability of PBDEs to induce neurotoxic effects does not appear to be gender-, strain- or species-specific, because the neurotoxic effects are induced in rats and male and female mice of different strains.

The developmental neurotoxic effects of PBDEs are similar to those observed for polychlorinated biphenyls (PCBs) and possible interactive effects of PBDEs and other environmental contaminants are therefore of concern.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2004. , p. 62
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 1020
Keywords [en]
Biology, brominated flame retardants, polybrominated diphenyl ethers, PBDE, neonatal, development, neurotoxicity, behaviour, cholinergic system
Keywords [sv]
Biologi
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-4576ISBN: 91-554-6053-4 (print)OAI: oai:DiVA.org:uu-4576DiVA, id: diva2:165193
Public defence
2004-10-29, Lindahlsalen, EBC, Norbyvägen 18A, Uppsala, 09:00
Opponent
Supervisors
Available from: 2004-10-06 Created: 2004-10-06 Last updated: 2011-02-09Bibliographically approved
List of papers
1. A brominated flame-retardant, 2,2',4,4',5-pentabromodiphenyl ether: Uptake, retention and induction of neurobehavioural derangement in mice, during a critical phase of neonatal brain development.
Open this publication in new window or tab >>A brominated flame-retardant, 2,2',4,4',5-pentabromodiphenyl ether: Uptake, retention and induction of neurobehavioural derangement in mice, during a critical phase of neonatal brain development.
Show others...
2002 In: Toxicological Sciences, Vol. 67, p. 98-103Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92200 (URN)
Available from: 2004-10-06 Created: 2004-10-06Bibliographically approved
2. Neonatal exposure to 2,2´,4,4´,5-pentabromodiphenyl ether causes increased susceptibility in the cholinergic transmitter system at adult age.
Open this publication in new window or tab >>Neonatal exposure to 2,2´,4,4´,5-pentabromodiphenyl ether causes increased susceptibility in the cholinergic transmitter system at adult age.
2002 In: Toxicological Sciences, Vol. 67, p. 104-107Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92201 (URN)
Available from: 2004-10-06 Created: 2004-10-06Bibliographically approved
3. Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory and decreases hippocampal cholinergic receptors in adult mice.
Open this publication in new window or tab >>Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory and decreases hippocampal cholinergic receptors in adult mice.
2003 In: Toxicology and Applied Pharmacology, Vol. 192, p. 95-106Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92202 (URN)
Available from: 2004-10-06 Created: 2004-10-06Bibliographically approved
4. Neurobehavioral derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development.
Open this publication in new window or tab >>Neurobehavioral derangements in adult mice receiving decabrominated diphenyl ether (PBDE 209) during a defined period of neonatal brain development.
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2003 In: Toxicological Sciences, Vol. 76, p. 112-120Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92203 (URN)
Available from: 2004-10-06 Created: 2004-10-06Bibliographically approved
5. Investigations of strain and/or gender differences in developmental neurotoxic effects of polybrominated diphenyl ethers in mice
Open this publication in new window or tab >>Investigations of strain and/or gender differences in developmental neurotoxic effects of polybrominated diphenyl ethers in mice
2004 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 81, no 2, p. 344-353Article in journal (Refereed) Published
Abstract [en]

Polybrominated diphenyl ethers (PBDEs), one class of flame retardants used to suppress or inhibit the risk of fire, are regularly found in the environment and in human milk. The present study shows that neonatal exposure to a widely, environmentally found PBDE, 2,2',4,4',5-pentaBDE (PBDE 99), can induce developmental neurotoxic effects, such as changes in spontaneous behavior (hyperactivity), effects that are dose-response related and worsen with age. These changes are seen in C57/Bl mice of both sexes. Neonatal C57/Bl male and female mice were orally exposed on day 10 to 0.4, 0.8, 4.0, 8.0, or 16 mg PBDE 99/kg body weight. Spontaneous behavior (locomotion, rearing, and total activity) was observed in two-, five-, and eight-month-old mice. The behavior tests showed that the effects were dose-response and time-response related for both male and female mice. The observed developmental neurotoxic effects seen for PBDE 99, in C57/Bl mice, are similar to effects seen for 2,2',4,4'-tetraBDE (PBDE 47), PBDE 99, 2,2',4,4',5,5'- hexaBDE (PBDE 153), 2,2',3,3',4,4',5,5',6,6'-decaBDE (PBDE 209) and for certain PCBs, in male NMRI mice. Furthermore, the effects of PBDEs appear to be as potent in female mice as in male mice, and as potent in C57/Bl mice as in NMRI mice, concerning developmental neurotoxicity.

Keywords
spontaneous behavior, neonatal, flame retardants, polybrominated diphenyl ethers, gender comparison
National Category
Biological Sciences
Identifiers
urn:nbn:se:uu:diva-92204 (URN)10.1093/toxsci/kfh215 (DOI)
Available from: 2004-10-06 Created: 2004-10-06 Last updated: 2017-12-14Bibliographically approved
6. Deranged spontaneous behaviour and decrease in cholinergic muscarinic receptors in hippocampus in the adult rat, after neonatal exposure to the flame-retardant, 2,2',4,4',5-pentabromodiphenyl ether (PBDE 99).
Open this publication in new window or tab >>Deranged spontaneous behaviour and decrease in cholinergic muscarinic receptors in hippocampus in the adult rat, after neonatal exposure to the flame-retardant, 2,2',4,4',5-pentabromodiphenyl ether (PBDE 99).
Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-92205 (URN)
Available from: 2004-10-06 Created: 2004-10-06Bibliographically approved

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