Flammability Standards – A Major Role in Flame Retardant Exposure? Televisions as a case study.

Flame retardants (FRs) are added to materials to enhance the fire safety level of readily combustible polymers. Although they have been purported to aid in preventing fires in some cases, they have also become a significant cause for concern given the vast data on environmental persistence and human and animal adverse health effects. Evidence since the 1980s has shown that Canadian, American and Europeans have detectable levels of FRs in their bodies. North Americans in particular have high levels of these chemicals due to stringent flammability standards and the higher use of polybrominated diphenyl ethers (PBDEs) in North America as opposed to Europe. FRs have been detected in household dust and some evidence suggests that TVs could be a significant source of exposure to FRs. It is imperative to re-visit the flammability standard (UL94V) that allows for FR use in TVs plastic materials by providing a risk versus benefit analysis to determine if this standard provides a fire safety benefit and if it plays a major role in FR exposure. This report first examined the history of televisions and the progression to the UL94V flammability test standard to understand why FRs were first added to polymers used in the manufacturing of TVs. It has been demonstrated to be due to fire hazards resulting from the use of plastic materials in cathode-ray tube (CRT) TVs that had an “instant-on” feature and high voltage and operating temperatures. In providing a risk versus benefit analysis, this paper presents the argument that 1) by providing a market survey the current flammability test standard (UL94V) is outdated and lacks relevance to current technology as flat, thin, energy efficient Liquid Crystal Displays (LCDs) dominate over traditionally used heavy, bulky and energy-intensive CRTs; 2) FRs do not impart fire safety benefits considering that there is a lack of valid fire safety concern, such as reduced internal and external ignition and fire hazard, and a lack of valid fire data and hazard for television fires in general and finally; 3) the standard is overly stringent as it does not consider the risk due to exposure to FRs in household dust due to the proliferation and greater use of televisions in households. Therefore, this report argues that the UL94V standard has become trapped in history and needs to be updated as it may play a major role in FR exposure.

β-Arrestin-mediated Regulation of the Human Ether-a-go-go-Related Gene (hERG) Potassium Channel

The human ether-a-go-go-related gene (hERG) encodes the voltage-gated K+ channel, hERG (Kv11.1). This channel passes the rapidly-activating delayed rectifier K+ current (IKr), which is important for cardiac repolarization. A reduction in IKr due to loss-of-function mutations or drug interactions causes long QT syndrome (LQTS), which can lead to cardiac arrhythmias and sudden cardiac death. The density of hERG channels in the plasma membrane is a key determinant of normal physiological function, and is balanced by trafficking to and from the cell surface. Many LQTS-associated hERG mutations result in a trafficking deficiency of otherwise functional channels. Thus, elucidating mechanisms of hERG regulation at the plasma membrane is useful for the prevention and treatment of LQTS. We previously demonstrated that M3 muscarinic receptor activation increases mature hERG expression through a Gq protein-dependent protein kinase C (PKC) pathway. In addition to conventional Gq protein-coupling, M3 receptors recruit β-arrestins upon agonist binding. Traditionally known for their role in receptor desensitization and internalization, β-arrestins also act as adaptor proteins to facilitate G protein-independent signaling. In the present work, I investigated the exclusive effect of β-arrestin signaling on hERG expression by utilizing an arrestin-biased M3 designer receptor (M3D-arr) exclusively activated by clozapine-N-oxide (CNO). By expressing M3D-arr in hERG-HEK cells and treating with CNO under various conditions, I found that M3D-arr activation increased mature hERG expression and current. Within this paradigm, M3D-arr recruited β-arrestin to the plasma membrane, and promoted the PI3K-dependent activation of Akt. I further found that the activated Akt acted through phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) and Rab11 to facilitate endosomal recycling of hERG channels to the plasma membrane.