PBDEs: Small differences, big toxic changes.

Kim, KH, DD Bose, A Ghogha, J Riehl, R Zhang, CD Barnhart, PJ Lein and IN Pessah. 2011. Para- and Ortho-Substitutions are key determinants of polybrominated diphenyl ether activity toward ryanodine receptors and neurotoxicity. Environmental Health Perspectives. http://dx.doi.org/10.1289/ehp.1002728.

The types of chemical attachments and their arrangement in brominated flame retardant molecules can predict how toxic the compounds are to rat brain cells, according to results of a human and rat cell study.

Small changes in the chemical structures of flame retardants – specifically, the number and location of attached groups – determined how they interacted with key cell receptors, report researchers in the journal Environmental Health Perspectives. The chemicals with fewer groups in specific locations changed receptor activity in ways that altered human kidney cells and affected the survival of rat brain cells. These are the same types of flame retardents that accumulate the most in human and animal tissues.

This study is important because it furthers our understanding of the toxic effects of widely-used flame retardants by identifying which types are potentially most dangerous. The research has broad implications for regulation of currently used flame retardants and the design of next generation chemicals. In other words, by understanding what types of chemical structures are more toxic, researchers can design safer chemicals and government agencies can tighten restrictions surrounding the use of their more toxic counterparts.

Polybrominated diphenyl ethers (PBDEs) are widely used to slow burning and suppress flames in textiles, furniture, electronics and many other consumer products. These flame retardants can bioaccumulate – or build up – in human tissues.

The chemicals differ in their ability to amass in tissue. The PBDEs that bioaccumulate the most have fewer than five bromine groups. However, the PBDE types with more than five bromine groups can be altered – debrominated – in tissues to yield the more toxic structures.

People are exposed mainly through eating and breathing PBDEs that escape from products and contaminate food, dust and other parts of the environment. For the past two decades, concentrations in people and the environment have been climbing. For instance, breast milk levels of PBDEs have roughly doubled every five years since 1972.

A growing body of animal and human studies show brominated flame retardants affect the brain and cognitive function. One example of this, a 2010 study, reported that increased levels of the most abundant types of PBDEs are associated with decreases in cognitive, behavioral and physical development in children less than six years old.

In this study, researchers at the University of California-Davis used human and rat cells to test whether PBDE toxicity can be predicted based on the number and location of bromine groups in the chemical structure of multiple widely used PBDEs. They specifically assessed how PBDEs impact a class of cell receptors called ryanodine receptors that enrich brain and skeletal muscle cells. Ryanodine receptors are targets of another class of bioaccumulative neurotoxicant: polychlorinated biphenyls (PCBs).

Researchers identified which different types of PBDEs activate or inhibit ryanodine receptors in human kidney cells. The PBDEs that inappropriately activated the ryanodine receptor in the kidney cells also caused cell death in neurons isolated from rat brains. Ryanodine receptors are found in human brains, too.

The results suggest that testing flame retardants for receptor activity offers an accurate first step to test their neurotoxicity.

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Based on a work at www.environmentalhealthnews.org.