title: In vitro neurotoxicity data in human risk assessment of polybrominated diphenyl ethers (PBDEs): overview and perspectives.
abstract: Polybrominated diphenyl ethers (PBDEs) are flame retardants routinely detected in samples of cord blood and breast milk. Concerns have been raised with regard to the toxicity of both pre- and postnatal exposures towards the developing nervous system. Although there is an increasing body of literature on the disruption of brain cell functions by certain PBDE congeners in vitro, some challenges have yet to be tackled to enable the translation of in vitro findings into their in vivo counterparts. In this paper, we review findings on the PBDE neurotoxicity in human cells and discuss the research gaps to be addressed. Moreover, we propose a scheme for the incorporation of in vitro data in human risk assessment, namely through (i) the determination of in vitro cell benchmark levels; (ii) the consideration of uncertainties in establishing equivalency between the in vitro and the in vivo tissue benchmark levels (e.g., chronic vs. acute exposure, interactions with other chemicals); and (iii) relating tissue benchmark levels to surrogate levels of internal exposure. Alongside the assessment of brain dosimetry following exposure to PBDEs, in vitro neurotoxicity data provide a unique opportunity to evaluate the risks of prenatal and early life exposures on children neurodevelopment.
authors.affiliation: TOXEN, Département des Sciences Biologiques, Université du Québec à Montréal, C.P. 8888 Succ. Centre-Ville, Montreal, Canada H3C 3P8. verner.marcandre@gmail.com
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Verner
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouchard
authors.forename: Ellen
authors.initials: E
authors.lastname: Fritsche
authors.forename: Michel
authors.initials: M
authors.lastname: Charbonneau
authors.forename: Sami
authors.initials: S
authors.lastname: Haddad
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005411:Flame Retardants / Q000493:pharmacokinetics / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D018570:Risk Assessment
chemical_list: D004785:Environmental Pollutants; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers