ToxSci Advance Access originally published online on April 12, 2006
Toxicological Sciences 2006 92(1):211-218; doi:10.1093/toxsci/kfj196
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Neonatal Exposure to Higher Brominated Diphenyl Ethers, Hepta-, Octa-, or Nonabromodiphenyl Ether, Impairs Spontaneous Behavior and Learning and Memory Functions of Adult Mice
* Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden; and Department of Environmental Chemistry, Stockholm University, Stockholm, Sweden
Received December 20, 2005; accepted March 17, 2006
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 µmol/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.
Key Words: habituation; learning and memory; Morris water maze test; polybrominated diphenyl ether; spontaneous neonatal behavior.