Neurotoxicity of polybrominated diphenyl ethers (PBDEs)

Polybrominated diphenylethers (PBDEs), a class of brominated compounds used as flame retardants, are widespread and persistent contaminants, which accumulate in the environment, in animals, in the food chain, and in humans. Several studies have highlighted that the toxicity of this substances impacts the nervous system during development, as perinatal exposure to PBDEs has been shown to affect behavior, in particular motor and cognitive activities. The present research project investigated the neurotoxicity of PBDEs through an in vitro approach. The potential interactions between different PBDEs congeners, and between PBDEs and PCBs, another class of persistent contaminants, to which humans are also exposed, was assessed utilizing the Loewe additive model and the Bliss independence criterion. Additionally, a potential mechanism of PBDEs neurotoxicity was investigated, by studying the involvement of glutamate, the main neurotransmitter of central nervous system. The major findings presented in my thesis confirm the validity of in vitro models as alternatives to in vivo approaches to assess the toxicity of neurotoxicants. Results show that PBDEs cause neuronal toxicity by a mechanism involving in part the over-activation of ionotropic glutamate receptors, followed by oxidative stress leading to cell toxiucity and cell death. Moreover, co-exposure to two PBDEs congeners or a PBDe and a PCB has been shown to modify the toxicity of single compounds, suggesting that the study of interactions, supported by mathematical models, is an important issue that should be considered in risk assessment.