ToxSci Advance Access originally published online on August 12, 2003
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Toxicological Sciences 76, 112-120 (2003)
Copyright © 2003 by the Society of Toxicology
NEUROTOXICOLOGY |
Neurobehavioral Derangements in Adult Mice Receiving Decabrominated Diphenyl Ether (PBDE 209) during a Defined Period of Neonatal Brain Development
* Department of Environmental Toxicology, Uppsala University, Norbyvägen, Uppsala, Sweden, and
Department of Environmental Chemistry, Stockholm University, Sweden
Flame retardants are used to suppress or inhibit combustion processes in an effort to reduce the risk of fire. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), has been found to be increasing in the environment and in human milk. Previous studies have shown that lower brominated PBDEs, tetra-, penta-, and hexabrominated diphenyl ethers, can cause developmental neurotoxic effects. The present study shows that the highly brominated PBDE 2,2',3,3',4,4',5,5',6,6'-decaBDE (PBDE 209) can be absorbed during neonatal life and induce developmental neurotoxic effects in adult mice, effects that also worsen with age. These effects seem to be inducible only during a defined critical period of neonatal life. Neonatal Naval Medical Research Institute (NMRI) male mice were exposed on day 3 to 2.22 or 20.1 mg PBDE 209/kg body weight, on day 10 to 1.34, 13.4, or 20.1 mg PBDE 209/kg body weight, or on day 19 to 2.22 or 20.1 mg PBDE 209/kg body weight, or to [U-14C]-2,2',3,3',4,4',5,5',6,6'-decaBDE. The oral neonatal administration of [U-14C]PBDE 209 on day 3, 10, or 19 showed that the compound distributes throughout the body and increases in the brain, from 24 h after administration to 7 days after administration, in 3-day-old and 10-day-old mice. The spontaneous behavior tests, observed in 2-, 4-, and 6-month-old mice, showed that the effect only occurred in mice exposed on day 3 and that this effect worsened with age. We conclude that more attention should be focused on the highly brominated PBDEs as possible developmental neurotoxic agents.
Key Words: decabrominated diphenyl ether; spontaneous behavior; neonatal; flame retardants; PBDEs.
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