Coexposure of neonatal mice to a flame retardant PBDE 99 (2,2',4,4',5-pentabromodiphenyl ether) and methyl mercury enhances developmental neurotoxic defects

Toxicol Sci. 2008 Feb;101(2):275-85. doi: 10.1093/toxsci/kfm271. Epub 2007 Nov 2.

Abstract

Epidemiological studies indicate that exposure to environmental pollutants during early human development can have deleterious effects on cognitive development. The interaction between environmental pollutants is suggested as one reason for the observed defective neurological development in children from the Faeroe Islands as compared to children from the Seychelles. We have previously seen in mice that polychlorinated biphenyls (PCBs) can interact together with methyl mercury (MeHg), as well as PCB together with polybrominated diphenyl ether (PBDE 99) to exacerbate developmental neurotoxic effects when present during a critical period of neonatal brain development. PBDEs are a new class of global environmental contaminants. The present study shows that neonatal coexposure to PBDE 99 (0.8 mg/kg body weight) and MeHg (0.4 or 4.0 mg/kg body weight) can exacerbate developmental neurotoxic effects. These effects are manifested as disrupted spontaneous behavior, reduced habituation, and impaired learning/memory abilities. This is seen in the low dose range, where the sole compounds do no give rise to developmental neurotoxic effects. The effects seen are more than just additive. Furthermore, a significant effect of interaction was seen on the cholinergic nicotinic receptors in the cerebral cortex and hippocampus. This suggests that a mechanism for the observed cognitive defects is via the cholinergic system. Furthermore, PBDE can interact with MeHg causing developmental neurotoxic effects similar to those we previously have observed between PCB 153 + MeHg and PCB 52 + PBDE 99. This is of vital importance, as the levels of PBDEs are increasing in mother's milk and in the environment generally.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Behavior, Animal / drug effects*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / metabolism
  • Drug Synergism
  • Female
  • Flame Retardants / toxicity*
  • Halogenated Diphenyl Ethers
  • Hippocampus / drug effects
  • Hippocampus / growth & development
  • Hippocampus / metabolism
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Methylmercury Compounds / toxicity*
  • Mice
  • Mice, Inbred Strains
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / physiopathology
  • Phenyl Ethers / toxicity*
  • Polybrominated Biphenyls / toxicity*
  • Receptors, Nicotinic / metabolism

Substances

  • Flame Retardants
  • Halogenated Diphenyl Ethers
  • Methylmercury Compounds
  • Phenyl Ethers
  • Polybrominated Biphenyls
  • Receptors, Nicotinic
  • pentabromodiphenyl ether