Viberg Henrik, Fredriksson Anders, Jakobsson Eva, Orn Ulrika, Eriksson Per
Department of Environmental Toxicology, Uppsala University, Norbyvägen, Uppsala, Sweden.
Toxicol Sci. 2003 Nov;76(1):112-20. doi: 10.1093/toxsci/kfg210. Epub 2003 Aug 12.
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.
阻燃剂用于抑制或阻止燃烧过程，以降低火灾风险。一类阻燃剂，即多溴二苯醚（PBDEs），已被发现在环境和人乳中的含量不断增加。先前的研究表明，低溴化的多溴二苯醚，如四溴、五溴和六溴二苯醚，可导致发育性神经毒性效应。本研究表明，高溴化的多溴二苯醚2,2',3,3',4,4',5,5',6,6'-十溴二苯醚（PBDE 209）在新生期可被吸收，并在成年小鼠中诱发发育性神经毒性效应，且这些效应会随着年龄增长而恶化。这些效应似乎仅在新生期特定的关键时期内可诱导产生。新生期的海军医学研究所（NMRI）雄性小鼠在出生第3天接受2.22或20.1毫克PBDE 209/千克体重的暴露，在出生第10天接受1.34、13.4或20.1毫克PBDE 209/千克体重的暴露，或在出生第19天接受2.22或20.1毫克PBDE 209/千克体重的暴露，或接受[U-14C]-2,2',3,3',4,4',5,5',6,6'-十溴二苯醚。在出生第3天、第10天或第19天经口给予新生小鼠[U-14C]PBDE 209后发现，该化合物在全身分布，并在出生3天和10天的小鼠中，从给药后24小时至给药后7天，在脑中含量增加。对2个月、4个月和6个月大的小鼠进行的自发行为测试表明，这种效应仅在出生第3天暴露的小鼠中出现，且随着年龄增长而恶化。我们得出结论，应更多关注高溴化多溴二苯醚作为可能的发育性神经毒性剂。
