A Human Mixture Risk Assessment for Neurodevelopmental Toxicity Associated with Polybrominated Diphenyl Ethers Used as Flame Retardants

 "BACKGROUND:
The European Food Safety Authority recently concluded that the exposure of small children (1–3 y old) to brominated diphenyl ether (BDE)-99 may exceed acceptable levels defined in relation to neurodevelopmental toxicity in rodents. The flame retardant BDE-209 may release BDE-99 and other lower brominated BDEs through biotic and abiotic degradation, and all age groups are exposed not only to BDE-209 and -99 but also to a cocktail of BDE congeners with evidence of neurodevelopmental toxicity. The possible risks from combined exposures to these substances have not been evaluated.

OBJECTIVES:
We performed a congener-specific mixture risk assessment (MRA) of human exposure to combinations of BDE-209 and other BDEs based on estimated exposures via diet and dust intake and on measured levels in biologic samples.


METHODS:
We employed the Hazard Index (HI) method by using BDE congener-specific reference doses for neurodevelopmental toxicity.

RESULTS:
Our HI analysis suggests that combined exposures to polybrominated diphenyl ethers (PBDEs) may exceed acceptable levels in breastfeeding infants (0–3 mo old) and in small children (1–3 y old), even for moderate (vs. high) exposure scenarios. Our estimates also suggest that acceptable levels of combined PBDEs may be exceeded in adults whose diets are high in fish. Small children had the highest combined exposures, with some estimated body burdens that were similar to body burdens associated with developmental neurotoxicity in rodents.

CONCLUSIONS:
Our estimates corroborate reports from several recent epidemiological studies of associations between PBDE exposures and neurobehavioral outcomes, and they support the inclusion of BDE-209 in the persistent organic pollutant (POP) convention as well as the need for strategies to reduce exposures to PBDE mixtures, including maximum residue limits for PBDEs in food and measures for limiting the release of PBDEs from consumer waste. "



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Banned chemicals pass through umbilical cord from mother to baby, research finds

 "Trace amounts of flame retardants, banned in the U.S. for more than a decade, are still being passed through umbilical cord blood from mothers to their babies, according to new Indiana University research. The chemicals are linked to health concerns including hormone disruption and low birth weight.
PBDEs, or polybrominated diphenyl ethers, were commonly used flame retardants in building materials, electronics and textiles until they were banned in 2004. The chemicals leach into the environment, where they persist and are found today in virtually every population worldwide."



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Related articles

• Flame retardants during pregnancy as bad as lead? Exposure linked to lower IQs in kids
• Industrial chemicals 'may cause global neurodevelopmental epidemic' - Medical News Today
• Exposure to common flame retardants may contribute to attention problems in children -- ScienceDaily

Potentially harmful chemicals widespread in household dust

Household dust exposes people to a wide range of toxic chemicals from everyday products, according to a study led by researchers at Milken Institute School of Public Health (Milken Institute SPH) at the George Washington University. The multi-institutional team conducted a first-of-a-kind meta-analysis, compiling data from dust samples collected throughout the United States to identify the top ten toxic chemicals commonly found in dust. They found that DEHP, a chemical belonging to a hazardous class called phthalates, was number one on that list. In addition, the researchers found that phthalates overall were found at the highest levels in dust followed by phenols and flame retardant chemicals."

Do flame retardants cause attention problems in children? - Medical News Today

Polybrominated diphenyl ethers are commonly used as fire retardants in many consumer goods. However, prenatal exposure to the product has now been associated with attention problems in 3-7-year-olds, according to an article the journal Neurotoxicology and Teratology.

Exposure to common flame retardants may contribute to attention problems in children -- ScienceDaily

"Prenatal exposure to some flame retardants that have been widely-used in consumer products is associated with attention problems in young children. A new study is the first to show the effects of prenatal exposure to polybrominated diphenyl ethers on children's development at ages 3, 4, and 7 years. Children with the highest exposure to certain PBDEs had approximately twice the number of maternally-reported attention problems compared to the other children in the study. PBDEs are found in textiles, plastics, wiring, and furniture containing polyurethane foam to reduce flammability."



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Selective damage to dopaminergic transporters following exposure to the brominated flame retardant, HBCDD

Over the last several decades, the use of halogenated organic compounds
has become the cause of environmental and human health concerns. Of
particular notoriety has been the establishment of the neurotoxicity of
polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers
(PBDEs). The subsequent banning of PBDEs has led to greatly increased
use of 1,2,5,6,9,10-hexabromocyclododecane (HBCDD, also known as HBCD)
as a flame retardant in consumer products. The physiochemical
similarities between HBCDD and PBDEs suggest that HBCDD may also be
neurotoxic to the dopamine system, which is specifically damaged in
Parkinson disease (PD). The purpose of this study was to assess the
neurotoxicity of HBCDD on the nigrostriatal dopamine system using an in
vitro and in vivo approach. We demonstrate that exposure to HBCDD
(0-25μM) for 24hrs causes significant cell death in the SK-N-SH
catecholaminergic cell line, as well as reductions in the growth and
viability of TH+ primary cultured neurons at lower concentrations
(0-10μM) after 72hrs of treatment. Assessment of the in vivo
neurotoxicity of HBCDD (25mg/kg for 30days) resulted in significant
reductions in the expression of the striatal dopamine transporter and
vesicular monoamine transporter 2, both of which are integral in
mediating dopamine homeostasis and neurotransmission in the dopamine
circuit. However, no changes were seen in the expression of tyrosine
hydroxylase in the dopamine terminal, or striatal levels of dopamine. To
date, these are the first data to demonstrate that exposure to HBCDD
disrupts the nigrostriatal dopamine system. Given these results and the
ubiquitous nature of HBCDD in the environment, its possible role as an
environmental risk factor for PD should be further investigated.

Scientists find link between flame retardants and obesity

"They studied the effect of two common flame retardants on sibling zebrafish and found the fish that were exposed to the compounds became heavier and longer, compared to their untreated siblings in the control group.
These flame retardants - tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) - are used to keep electronics from overheating and are found in computers, cell phones, televisions, tablets, video game consoles and other high-tech devices with electrical chips that could catch fire if they get overheated. These compounds are then released from such electronics and often end up in the dust we inhale.
A type of the much-maligned bisphenol A (BPA), which is already known to be an obesogen, these flame retardants are highly produced compounds. About 150,000 tons of TBBPA and 10,000 tons of TCBPA are produced per year.
"It's been shown that young children, who spend a lot of time on the floor, have higher levels of these compounds in their blood than adults. It has also been found to be passed through breast milk," said Maria Bondesson, a research assistant professor of biology and biochemistry with the CNRCS. "This is what led us to exposing the fish siblings to these compounds at relatively low concentrations. The fish treated with these compounds became heavier and the ones that weren't were lighter.""



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Autistic behaviours linked to banned pesticide

(Medical Xpress)—A new study co-authored by a Simon Fraser University
researcher finds the children of pregnant women exposed to high levels
of a flame retardant and a banned pesticide are more likely to exhibit
autistic-like behaviours.

The flame retardant is PBDE-28. Chlordane is the
banned pesticide. It contains the chemical trans-nonachlor, which this
study links to autistic-like behaviours.

Cognitive Deficits and Behavior Problems in Children with Prenatal Polybrominated diphenyl ethers Exposure

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are persistent chemicals that were widely used as flame retardants in furniture, carpet padding, car seats and other consumer products during the past three decades. Little is known about the impact of prenatal PBDE exposures on children's intellectual abilities or behavioral problems.
OBJECTIVE: To investigate the association between prenatal exposure to PBDEs and child neurodevelopment.
DESIGN/METHODS: We measured maternal serum concentrations of BDE-47 and the sum of 4 PBDE chemicals (-47, -99, -100, -153) in 301 women at 16 weeks of gestation and followed their children annually until 5 years of age in the HOME Study in Cincinnati, OH. We examined the associations with children's cognitive and motor abilities using the Bayley Scales of Infant Development-II at ages 1, 2, 3 years, and intelligence using the Wechsler Preschool and Primary Scale of Intelligence-III at age 5 years. We also investigated the association with children's behaviors using the Behavioral Assessment System for Children-2 at ages 2, 3, 4, and 5 years. We used linear mixed models with adjustment for maternal age, race, education, marital status, serum cotinine, IQ, blood lead, depression score, household income, child sex, and the HOME Inventory, a measure of the nurturing environment of the home. 
RESULTS: Prenatal exposure to BDE-47 and sum₄BDEs was associated with cognitive deficits at 2, 3, and 5 years; the deficits were larger in older children. The geometric mean of sum₄BDEs was 37 ng/g lipid, with BDE-47 at 20 ng/g lipid, comparable to US national average in the 2003-2004. For a 10-fold increase in BDE-47 there was a -4.6 decrement in Bayley Mental Development Index (95% CI=-8.4, -0.8) at age 3 and a -7.5 decrement in Wechsler Full Scale IQ (95% CI=-11.9, -3.1) at 5 years. Prenatal BDE-47 and sum₄BDEs exposure was also associated with an increase in hyperactivity symptoms. A ten-fold increase in BDE-47 was associated with 2.4 increment (95% CI=0.1, 4.6) in hyperactivity score.
CONCLUSIONS: Prenatal exposure to PBDEs, a group of flame retardants that are detectable in virtually all US children, was strongly associated with cognitive deficits and hyperactivity behaviors in children.

Low Levels Of Common Flame-Retardant Chemical Damages Brain Cells

Finding may have implications for autism

A common ingredient in flame retardants, BDE-49 accumulates in human blood, fat and breast milk. Despite these concentrations, little research has been done on the chemical's potential health risks. However, a study by scientists at the UC Davis MIND Institute is shedding new light on BDE-49's potential danger to brain health. The study showed that even tiny amounts of the compound damage neural mitochondria, the energy plants that power our cells. The chemical, quite literally, reduces brain power. 

Exposure to the Polybrominated Diphenyl Ether Mixture DE-71 Damages the Nigrostriatal Dopamine System: Role of Dopamine Handling in Neurotoxicity.

In the last several decades polybrominated diphenyl ethers (PBDEs) have replaced the previously banned polychlorinated biphenyls (PCBs) in multiple flame retardant utilities. As epidemiological and laboratory studies have suggested PCBs as a risk factor for Parkinson's disease (PD), the similarities between PBDEs and PCBs suggest that PBDEs have the potential to be neurotoxic to the dopamine system. The purpose of this study was to evaluate the neurotoxic effects of the PBDE mixture, DE-71, on the nigrostriatal dopamine system and address the role of altered dopamine handling in mediating this neurotoxicity. Using an in vitro model system we found DE-71 effectively caused cell death in a dopaminergic cell line as well as reducing the number of TH+ neurons isolated from VMAT2 WT and LO animals. Assessment of DE-71 neurotoxicity in vivo demonstrated significant deposition of PBDE congeners in the brains of mice, leading to reductions in striatal dopamine and dopamine handling, as well as reductions in the striatal dopamine transporter (DAT) and VMAT2. Additionally, DE-71 elicited a significant locomotor deficit in the VMAT2 WT and LO mice. However, no change was seen in TH expression in dopamine terminal or in the number of dopamine neurons in the substantia nigra pars compacta (SNpc). To date, these are the first data to demonstrate that exposure to PBDEs disrupts the nigrostriatal dopamine system. Given their similarities to PCBs, additional laboratory and epidemiological research should be considered to assess PBDEs as a potential risk factor for PD and other neurological disorders.

Futurity.org – Flame retardants linked to delays in kids

Experts report a link between exposure to a common flame retardant and deficits in motor and cognitive development among school-aged children.The findings add to growing health concerns over this class of endocrine-disrupting compounds, which are commonly found in US households. PBDEs, or polybrominated diphenyl ethers, are used in foam furniture, electronics, carpets, upholstery, and other consumer products. The chemicals easily leach out into the environment, are inhaled or ingested through dust, and then accumulate in human fat cells.