Apoptosis-Inducing Potential of Selected Bromophenolic Flame Retardants 2,4,6-Tribromophenol and Pentabromophenol in Human Peripheral Blood Mononuclear Cells.

Abstract

(1) Background: 2,4,6-Tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) are utilized as brominated flame retardants (BFRs) in order to reduce the combustion of materials used in various utility products. The presence of 2,4,6-TBP and PBP has been reported in environmental samples as well as in inhaled air, dust, food, drinking water, and the human body. To date, there are limited data concerning the toxic action of 2,4,6-TBP and particularly PBP, and no study has been conducted to assess the apoptotic mechanism of action of these substances in human leukocytes. (2) Methods: PBMCs were isolated from leukocyte–platelet buffy coat and treated with tested substances in concentrations ranging from 0.01 to 50 µg/mL for 24 h. The apoptotic mechanism of action of the tested BFRs was assessed by the determination of phosphatidylserine exposure on the PBMCs surface, the evaluation of mitochondrial potential and cytosolic calcium ion levels, and the determination of caspase-8, -9, and -3 activation. Moreover, poly (ADP-ribose) polymerase-1 (PARP-1) cleavage, DNA fragmentation, and chromatin condensation were analyzed. (3) Results: 2,4,6-TBP and, more strongly, PBP induced apoptosis in PBMCs, changing all tested parameters. It was also found that the mitochondrial pathway was mainly involved in the apoptosis of PBMCs exposed to the studied compounds. (4) Conclusions: 2,4,6-TBP and PBP triggered apoptosis in human PBMCs, and some observed changes occurred at 2,4,6-TBP concentrations that were detected in humans occupationally exposed to this substance.