Neonatal Developmental Neurotoxicity of Brominated Flame Retardants, the Polybrominated Diphenyl Ethers (PBDEs)

This thesis examines developmental neurotoxic effects of polybrominated diphenyl ethers (PBDEs), PBDE 99, PBDE 153, and the fully brominated PBDE 209, after exposure during the newborn period in rodents. Our environment contains vast numbers of contaminants, including the flame retardants, PBDEs. The PBDEs are widely found in the environment and are increasing in human milk. Individuals can be exposed to PBDEs during their whole lifetime, and especially during the lactation period. The neonatal period, coinciding with the lactation period, is characterized in many mammalian species by rapid growth and development of the immature brain. It has been shown that numerous toxicants can induce permanent disorders in brain function when administered to the neonatal mouse during the brain growth spurt (BGS). In mice and rats this period is postnatal, spanning over the first 3-4 weeks of life, while in humans, BGS begins during the third trimester of pregnancy and continues throughout the first two years of life. The present studies identified a defined critical period during BGS in mice when the brain is vulnerable to insults of low doses of PBDEs and that it is the presence of PBDEs or their metabolites in the brain during this critical period that is crucial to evoking neurotoxic effects. The effects observed are permanent altered spontaneous behavior, reduced habituation, deficits in learning and memory, and disturbances in the cholinergic system. These effects worsen with age. The ability of PBDEs to induce neurotoxic effects does not appear to be gender-, strain- or species-specific, because the neurotoxic effects are induced in rats and male and female mice of different strains. The developmental neurotoxic effects of PBDEs are similar to those observed for polychlorinated biphenyls (PCBs) and possible interactive effects of PBDEs and other environmental contaminants are therefore of concern