New study from North Carolina State University shows that in utero exposure to FireMaster® 550 (FM 550) flame retardant, or its individual brominated (BFR) or organophosphate (OPFR) components, resulted in impaired brain development in newborn rats. The effects – including evidence of mitochondrial disruption and dysregulated levels of choline and triglycerides in brain tissue – were greater in male offspring than in females. The work adds to the body of evidence that OPFRs and BFRs can be neurotoxic.
FM 550 is a flame retardant blend first identified ten years ago. It was developed to replace PBDEs, a class of fire retardants being phased out for safety reasons.
“While some newer flame retardant blends still contain BFRs, OPFRs are a popular substitute for PBDEs because it is believed that OPFRs do not accumulate in the body and therefore may not be as harmful,” says Heather Patisaul, Dean associate for research in NC State’s College of Sciences and corresponding author of the study. “Specifically, OPFRs were thought to not impact acetylcholinesterase – a key neurotransmitter. But it appears that OPFRs still impact choline signaling and are just as bad, if not worse, than PBDEs for the developing brain.”
Patisaul and colleagues performed transcriptomic and lipidomic studies on the prefrontal cortices of newborn rats whose mothers had been exposed to FM550, or the BFR or OPFR elements individually, during gestation.
“Getting genetic information from transcriptomics is what researchers routinely do to unravel potential links between toxicity and health effects,” says Patisaul. “In this case, we also wanted to see if the lipid or fat composition of the brain is changed – our brains are essentially balls of fat, and lipidomics can reveal how exposure can affect the brain in its early stages of development.”
Transcriptomic and lipidomic analyzes showed evidence of mitochondrial disruption, although disruption was more pronounced in offspring that had been exposed to OPFRs. Mitochondria are found in almost all cells and serve as energy generators for cells, playing a vital role in cellular respiration.
Transcriptomic analysis revealed disruption of cellular respiration genes associated with neurodegenerative disorders like Alzheimer’s disease and ALS, while lipidomics revealed disrupted choline and triglyceride levels in the brain.
In men exposed to OPFRs, genes associated with axon guidance and choline signaling were also dysregulated. Axon guidance is the process by which neurons make the appropriate connections during neuronal development. Choline is a precursor to the neurotransmitter acetylcholine, which affects critical aspects of neuronal function and neuronal signaling.
“That so many altered genes are involved in respiration and choline, there is concern that these RFs impair autonomic function and basic cognition,” says Patisaul. “So the bottom line is that exposure to BFRs and OPFRs disrupts both neuronal signaling and the ability of cells to properly produce and use energy.”
The researchers also found that male offspring were more affected than females.
“In previous studies with rats, we found that OPFR levels are higher in attached placentas of males than in females,” says Patisaul. “So this difference in exposure could be why we’re seeing different and more severe effects in men.
“The important message here is that the presumption that OPFRs are safer than other FRs is probably false. OPFRs and BFRs can interfere with cortical development and function. And the fact that these chemicals are detectable in the placenta means they don’t break down fast enough not to do any damage.”
The book is the subject of a special issue of Neuroendocrinology, and was supported by the National Institute of Environmental Health Sciences (NIEHS) and the Environmental Protection Agency. Shannah Witchey, a former NC State postdoctoral researcher, is the first author.
Source of the story:
Material provided by North Carolina State University. Original written by Tracey Peake. Note: Content may be edited for style and length.
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