The Potential of Selected Brominated Flame Retardants to Affect Neurological Development

Abstract

Various brominated flame retardants (BFR), including polybrominated diphenyl ether (PBDE) congeners, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), are commonly used in household items and electronics and have been detected in the environment and/or the bodily fluids of people, including children. Some studies in animals suggest that exposure to PBDE congeners, HBCD, or TBBPA during the perinatal period may affect locomotor activity and/or memory and learning. Epidemiological studies showing similar effects in humans, however, are lacking. To assess whether an association exists between perinatal exposure and development of consistent neurobehavioral alterations, published animal studies investigating perinatal exposure to PBDE congeners, HBCD, or TBBPA with specific neurobehavioral evaluations-particularly, assessments of motor activity-were reviewed for consistency of results. Our analysis shows that although the majority of studies suggest that perinatal exposure affects motor activity, the effects observed were not consistent. This lack of consistency includes the type of motor activity (locomotion, rearing, or total activity) affected, the direction (increase or decrease) and pattern of change associated with exposure, the existence of a dose response, the permanency of findings, and the possibility of gender differences in response. Interestingly, Good Laboratory Practices (GLP)-compliant studies that followed U.S. Environmental Protection Agency (EPA)/Organization for Economic Cooperation and Development (OECD) guidelines for developmental neurotoxicity testing found no adverse effects associated with exposure to PBDE209, HBCD, or TBBPA at doses that were orders of magnitude higher and administered over longer durations than those used in the other studies examined herein. The lack of consistency across studies precludes establishment of a causal relationship between perinatal exposure to these substances and alterations in motor activity.

A reproductive, developmental and neurobehavioral study following oral exposure of tetrabromobisphenol A on Sprague-Dawley rats

“…The NOEL for these changes is 10 mg/kg BW/day. These findings are consistent with the observations of an extensive review of currently available TBBPA neurological data by Williams and DeSesso (2010) that demonstrated no adverse effects attributable to TBBPA exposures up to and including 1000 mg/kg BW/day on neurodevelopment, neuromotor functions, learning, memory, and neurobehavioral endpoints. It is noteworthy that thinning of the brain parietal cortex in the F 2 generation at post-natal day (PND) 11 was not associated with lesions or changes that were detectable by H&E histological examination.…”

Developmental Exposure to Polybrominated Diphenyl Ethers and Neurodevelopment

“…Detailed reviews of animal evidence on the effects of developmental exposure to PBDEs on neurodevelopment are available [31,32,33]. In brief, Eriksson and colleagues conducted a series of experiments exposing neonatal mice to individual PBDEs (including BDE-47, BDE-99, BDE-153, BDE-183, BDE-203, BDE-206, and BDE-209) on either postnatal day 3, 10, or 19.…”

Synergistic neurotoxicity of oxygen-glucose deprivation and tetrabromobisphenol A in vitro: role of oxidative stress

“…Experiments performed in vivo have shown that the acute exposure of adult mice to TBBPA results in its selective accumulation in the striatum, which is accompanied by significant behavioral effects [24]. There are also indications that TBBPA may act as a developmental neurotoxin [20], although there has been a lack of consistency in studies describing the neurodevelopmental effects of TBBPA [38]. Studies performed in vitro using various cell cultures demonstrated the cytotoxicity of TBBPA and have identified several putative mechanisms, including disturbances in the intracellular signaling pathways, calcium imbalance, oxidative stress and excitotoxicity in neurons [5,22,25,27,28].…”