A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity

Abstract

Polybrominated diphenyl ethers (PBDEs), extensively used in the past few decades as flame retardants in a variety of consumer products, have become world-wide persistent environmental pollutants. Levels in North America are usually higher than those in Europe and Asia, and body burden is 3 to 9-fold higher in infants and toddlers than in adults. The latter has raised concern for potential developmental toxicity and neurotoxicity of PBDEs. Experimental studies in animals and epidemiological observations in humans suggest that PBDEs may be developmental neurotoxicants. Pre- and/or post-natal exposure to PBDEs may cause long-lasting behavioral abnormalities, particularly in the domains of motor activity and cognition. The mechanisms underlying the developmental neurotoxic effects of PBDEs are not known, though several hypotheses have been put forward. One general mode of action relates to the ability of PBDEs to impair thyroid hormone homeostasis, thus indirectly affecting the developing brain. An alternative or additional mode of action involves a direct effect of PBDEs on nervous system cells; PBDEs can cause oxidative stress-related damage (DNA damage, mitochondrial dysfunction, apoptosis), and interfere with signal transduction (particularly calcium signaling), and with neurotransmitter systems. Important issues such as bioavailability and metabolism of PBDEs, extrapolation of results to low level of exposures, and the potential effects of interactions among PBDE congeners and between PBDEs and other contaminants also need to be taken into account.

In vitro cytotoxicity of decabrominated diphenyl ether (PBDE-209) to human red blood cells (hRBCs)

“…Previous studies have reported that the PBDEs are toxic to the liver activity (Zhou et al, 2002), thyroid and reproduction systems (Yu et al, 2015), nervous system (Costa et al, 2014) and immune system (Lv et al, 2015). Though some highly-toxic PBDEs have been banned in many countries, other PBDEs with relatively lower toxicity, such as BDE-209, are still largely produced and used in the world (Chen et al, 2012;Akortia et al, 2016).…”

Accumulation of polybrominated diphenyl ethers in the brain compared with the levels in other tissues among different vertebrates from an e-waste recycling site

“…Despite a declining trend in the levels of PBDEs observed in certain regions, this group of persistent pollutants is still detectable in various environmental media and biotic samples (Baron et al, 2015;Hassan et al, 2013;Yu et al, 2016;Zheng et al, 2015). It has been demonstrated that PBDEs adversely affect the developing brain, resulting in neurodevelopmental disorders (Costa et al, 2014(Costa et al, , 2016Kodavanti et al, 2015). However, there is little understanding of the accumulation of PBDEs in the brain and their transfer across the blood-brain barrier (BBB).…”

Metabolic pathways of decabromodiphenyl ether (BDE209) in rainbow trout (Oncorhynchus mykiss) via intraperitoneal injection

“…such as reproductive and developmental effects, neurobehavioral toxicity and thyroid hormone disruption (Dingemans et al, 2011;Costa et al, 2014;Guyot et al, 2014;Buratovic et al, 2014). Decabromodiphenyl ether (BDE209), which is the principal component of commercial PBDEs, comprises approximately 80% of the world market demand for PBDEs (de Wit, 2002).…”