Viberg Henrik, Johansson Niclas, Fredriksson Anders, Eriksson Johan, Marsh Göran, Eriksson Per
Department of Environmental Toxicology, Uppsala University, Norbyvagen 18A, S-752 36 Uppsala, Sweden.
Toxicol Sci. 2006 Jul;92(1):211-8. doi: 10.1093/toxsci/kfj196. Epub 2006 Apr 12.
Polybrominated diphenyl ethers (PBDEs), used as flame retardants, have been shown to be increasing in the environment and in human mother's milk. We have earlier reported that lower brominated PBDEs, such as tetra-, penta-, and hexa-brominated diphenyl ethers, can cause developmental neurotoxic effects in mice. Recently, this was also observed with the full-brominated PBDE, deca-brominated diphenyl ether (PBDE 209), although it was suggested that the effects were caused by a (possibly debrominated) metabolite thereof. The present study revealed that 2,2',3,3',4,4',5,5',6-nonabromodiphenyl ether (PBDE 206), 2,2',3,4,4',5,5',6-octabromodiphenyl ether (PBDE 203), and to a minor extent also 2,2',3,4,4',5',6'-heptabromodiphenyl ether (PBDE 183) can induce developmental neurotoxic effects. Neonatal Naval Medical Research Institute male mice were exposed on postnatal day 3 or 10 to PBDE 206, PBDE 203, or PBDE 183, given as a single oral dose of 21 mumol/kg body weight. At the adult age of 2-3 months, the mice were observed for performance in a spontaneous behavior test and the Morris water maze test. PBDE 203 and PBDE 206, when administered on neonatal day 10, caused disturbances in spontaneous behavior, leading to disrupted habituation and a hyperactive condition in adults at the age of 2 months. These behavioral changes were also seen in 2-month-old mice exposed to PBDE 203 on neonatal day 3. Furthermore, exposure to PBDE 203 on neonatal day 10 affected learning and memory functions in adult mice. The developmental neurotoxic effects were most pronounced in mice exposed to PBDE 203. These developmental neurobehavioral defects were in agreement with those we observed previously with lower brominated PBDEs and with PBDE 209. It is important to consider the fact that different PBDE congeners can have differing degrees of potency, when comparing levels of PBDEs in the environment and in mother's milk.
多溴二苯醚(PBDEs)作为阻燃剂,已被证明在环境和人类母乳中的含量不断增加。我们之前曾报道,低溴代多溴二苯醚,如四溴、五溴和六溴二苯醚,可对小鼠产生发育神经毒性作用。最近,全溴代多溴二苯醚十溴二苯醚(PBDE 209)也观察到了这种情况,尽管有人认为这些影响是由其(可能脱溴的)代谢产物引起的。本研究表明,2,2',3,3',4,4',5,5',6-九溴二苯醚(PBDE 206)、2,2',3,4,4',5,5',6-八溴二苯醚(PBDE 203),以及在较小程度上2,2',3,4,4',5',6'-七溴二苯醚(PBDE 183)均可诱导发育神经毒性作用。新生期的海军医学研究所雄性小鼠在出生后第3天或第10天接受PBDE 206、PBDE 203或PBDE 183单次口服给药,剂量为21 μmol/kg体重。在2至3个月大的成年期,观察小鼠在自发行为测试和莫里斯水迷宫测试中的表现。在出生后第10天给予PBDE 203和PBDE 206,会导致自发行为紊乱,导致成年小鼠(2个月大时)习惯化破坏和多动状态。在出生后第3天接触PBDE 203的2个月大小鼠中也观察到了这些行为变化。此外,在出生后第10天接触PBDE 203会影响成年小鼠的学习和记忆功能。发育神经毒性作用在接触PBDE 203的小鼠中最为明显。这些发育神经行为缺陷与我们之前在低溴代多溴二苯醚和PBDE 209中观察到的一致。在比较环境和母乳中多溴二苯醚的水平时,考虑到不同的多溴二苯醚同系物可能具有不同程度的效力这一事实很重要。