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Comparative effects of PBDEs and PCBs on intracellular signaling in rat cerebellar granule neurons
KODAVANTI, PRASADA RAO S. Comparative effects of PBDEs and PCBs on intracellular signaling in rat cerebellar granule neurons. Presented at International Symposium on Halogenated Persistent Organic Pollutants (POPs), San Antonio, TX, September 12 - 17, 2010.
The objective of this study is to compare the efficacy and potency between PCB and PBDE mixtures, mixtures versus congeners, and among congeners.
Polybrominated diphenyl ethers (PBDEs) are synthetic chemicals that do not occur in nature and are structurally similar to polychlorinated biphenyls (PCBs; Figure I) and several chlorinated pesticides. They are comprised of two phenyl rings linked by oxygen and are resistant to physical, chemical and biological degradation). PBDE residues have been detected in indoor air, house dust, and foods2,3. PBDE exposure to humans may be possible via multiple sources (air, water, food and dust). PBDEs are found in higher levels in house dust in the United States than in Europe". The predominant congeners detected are PBDE-47, PBDE-99 and PBDE-209. Levels of PBDEs in human tissues, specifically blood, milk, and fat, have increased exponentially since the 1970s in several countries, including the U.S Canada, and Sweden", The doubling time for PBDE levels in the human body was estimated to be 3-5 years", Currently in Sweden, PBDE levels in breast milk are decreasing, presumably as a result ofa decrease in the use of PBDE-containing products. The EU has decreased PBDE use by two-thirds in recent years. Levels of PBDEs among individuals in North America, as measured in blood, breast milk, or adipose tissue, are 10-70 times higher than in Europe or Japans. High levels of PBDEs in North America are attributed to the greater use of penta BDE mixture (>90%) when compared to the rest of the world, Like other lipophilic compounds, PBDEs readily cross the placenta into the fetus. This provides the opportunity for PBDEs to interfere with developmental processes, possibly producing developmental effects. In spite of their widespread occurrence in the environment, only limited information is available on the toxicology of PBDEs in terms of their mode of action. Previous studies showed that PBDE exposure caused aberrations in spontaneous behavior and reduced learning and memory in mice; these effects are similar to those seen after exposure to DDT or PCBs7-9. However, the mode of action for this group of chemicals remains unclear. The underlying molecular mechanisms of the adverse health effects of PCBs have been associated with perturbations in intracellular signaling mechanisms including Ca2+ homeostasis, [3H]arachidonic acid ([3H]AA) release, mitogen-activated protein kinase (MAPK) activation, and translocation of protein kinase CIO (pKC). These intracellular signaling events are critical for learning and memory, normal function and development of the nervous system 11-12. We have extended studies to understand whether PBDEs affect intracellular signaling in a similar way to those of PCBs. The objective of this study is to compare the efficacy and potency between PCB and PBDE mixtures, mixtures versus congeners, and among congeners
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION