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.
Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame retardant additives. In a recent study, we have seen that neonatal exposure to some brominated flame retardants can cause permanent aberrations in spontaneous motor behavior that seem to worsen with age. In view of an increasing amount of PBDEs in mother's milk and in the environment, the present study was undertaken to investigate whether there is a critical and limited phase, during neonatal life, for induction of persistent neurotoxic effects of 2,2',4,4',5-pentaBDE (PBDE 99). Neonatal NMRI male mice were exposed on day 3, 10, or 19 to 8 mg 2,2',4,4',5-pentaBDE/kg body weight. Uptake and retention of 2,2',4,4',5-penta[(14)C]BDE were studied in the mouse brain after exposure to 1.5 M becquerel (Bq) 2,2',4,4',5-penta[(14)C]BDE /kg body weight (bw) on postnatal day 3, 10, or 19. Spontaneous motor behavior was observed in 4-month-old mice. Mice exposed to 2,2',4,4',5-pentaBDE on day 3 or 10 showed significantly impaired spontaneous motor behavior, whereas no effect was seen in mice exposed on day 19. Neonatal mice exposed to 2,2',4,4',5-penta[(14)C]BDE 99 on postnatal day 3, 10, or 19 were sacrificed 24 h or 7 days posttreatment. The amount of radioactivity, given as per mille ( per thousand) of total amount administered, was between 3.7 and 5.1 per thousand in the three different age categories at 24 h after administration. Seven days after the administration, 2,2',4,4',5-penta[(14)C]BDE or its metabolites could still be detected in the brain. The amount of radioactivity in the brain was not higher in mice exposed on day 3 or 10 when compared to exposure on day 19. Thus, the behavioral disturbances observed in adult mice following neonatal exposure to 2,2',4,4',5-pentaBDE are induced during a defined critical period of neonatal brain development.
Eriksson
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P
Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, S-752 36, Uppsala, Sweden. per.eiksson@ebc.uu.se
Viberg
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H
Jakobsson
E
E
Orn
U
U
Fredriksson
A
A
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005260:Female; D005411:Flame Retardants / Q000493:pharmacokinetics* / Q000633:toxicity; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D010647:Phenyl Ethers / Q000493:pharmacokinetics* / Q000633:toxicity; D011075:Polybrominated Biphenyls; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; C086401:pentabromodiphenyl ether