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ToxSci Advance Access published online on April 12, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj196
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received December 20, 2005
Accepted March 17, 2006

Neurotoxicology

Neonatal Exposure to Higher Brominated Diphenyl Ethers, Heptabromo- (PBDE 183), Octabromo- (PBDE 203) or Nonabromodiphenyl Ether (PBDE 206), Impairs Spontaneous Behaviour, and Learning and Memory Functions of Adult Mice

Henrik Viberg 1, Niclas Johansson 1, Anders Fredriksson 1, Johan Eriksson 2, Göran Marsh 2, and Per Eriksson 1 *

1 Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden
2 Department of Environmental Chemistry, Stockholm University, Stockholm, Sweden

* To whom correspondence should be addressed.
Per Eriksson, E-mail: per.eriksson{at}ebc.uu.se


  Abstract

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 de-brominated) metabolite thereof. The present study revealed that 2,2',3,3',4,4',5,5',6-nonaBDE (PBDE 206), 2,2',3,4,4',5,5',6-octaBDE (PBDE 203), and to a minor extent also 2,2',3,4,4',5',6'-heptaBDE (PBDE 183), can induce developmental neurotoxic effects.

Neonatal NMRI male mice were exposed on postnatal day 3 or 10 to either PBDE 206, PBDE 203, or PBDE 183, given as a single oral dose of 21µmol/kg body weight. At the adult age of 2-3 months the mice were observed for performance in a spontaneous behaviour test and the Morris water maze test. PBDE 203 and PBDE 206, when administered on neonatal day 10, caused disturbances in spontaneous behaviour, leading to disrupted habituation and a hyperactive condition in adults at the age of 2 months. These behavioural 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 the octa-brominated diphenyl ether 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.


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