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Activation of mouse and human Peroxisome Proliferator-Activated Receptor-alpha (PPARa) by Perfluoroalkyl Acids(PFAAs): Further investigation of C4-C12 compounds.
Citation:
WOLF, C. J., J. E. Schmid, C. LAU, AND B. D. ABBOTT. Activation of mouse and human Peroxisome Proliferator-Activated Receptor-alpha (PPARa) by Perfluoroalkyl Acids(PFAAs): Further investigation of C4-C12 compounds. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 33(4):546-51, (2012).
Impact/Purpose:
This paper represents continuing efforts of ORD to investigate the risk assessment of perfluorinated chemicals, conducted by OCSPP and OW. Perflouoroalkyl acids (PFAAs) are synthetic chemicals that are found globally in the environment and in the tissues of wildlife and humans. Many of these chemicals, especially the longer chain molecules, have been shown to adversely affect laboratory rodent development and survival. Some have been found to activate peroxisome proliferator-activated receptor alpha (PPARa) in hepatocytes and in PPARa transfected cells.
Description:
Perfluorinated alkyl acids (PFAAs) are manufactured surfactants found globally in the environment and in tissues of humans and wildlife. Several PFAAs adversely affect rodents and activation of PPARa is thought to be their mode of action. Our previous study demonstrated that some PFAAs activate mouse and human PPARa in transiently transfected COS-1 cells. Here, we test more PFAAs for PPARa activation in the same system. Cells were exposed to either vehicle, PPARa agonist (WY14643), perfluoropentanoic acid (C5), perfluoroheptanoic acid (C7), perfluorooctanoic acid (C8), perfluoroundecanoic acid (C11), or perfluorododecanoic acid (C12) at concentrations from 0.5 -100 uM and luminescence was measured. C8 induced the highest activity in human PPARa, followed by C7, C5, and C11. C12 had little activity. C8 induced the highest activity in mouse PPARa, followed by C11, C7, C12 and C5. The two studies together found increasing activity of PPARa with increasing chain length of the PFAA up to perfluorononanoic acid (C9) and lower activity with longer chain PFAAs, perfluorodecanoic acid (C10) -C12, in both mouse and human PPARa.
