Organophosphorus flame-retardant tris(1-chloro-2-propyl)phosphate is genotoxic and apoptotic inducer in human umbilical vein endothelial cells.

Abstract

Tris(1-chloro-2-propyl)phosphate (TCPP) is a chlorinated organophosphorus flame retardant (OPFR) widely used in consumer goods after the phaseout of brominated flame retardants (BFRs). TCPP can percolate into the indoor and outdoor dusts, leading to its detection in the human body fluids (urine, breast milk) and placenta. However, TCPP has not been studied so far for its toxicity in the human vascular system. Hence, we have used human umbilical vein endothelial cells (HUVECs) and exposed them to TCPP ranging from low to high (5-400 μM) concentrations for 24 h. Cytotoxicity analysis by MTT and NRU assays exhibited 15.27% and 20.56%, 21.67%, and 48.67% survival decline of cells only at 200 and 400 μM. Comet assay data showed DNA damage from 50 to 400 μM with Olive tail moment (OTM) values between 1.03 and 35.59, respectively. TCPP-exposed HUVECs exhibited 1.09 and 1.39-fold greater intracellular reactive oxygen species (ROS) at 25 and 400 μM, indicating oxidative stress. HUVEC mitochondrial membrane potential (ΔΨm) measurements showed 1.16 and 1.48-fold higher fluorescence of Rh123 dye at 25 and 400 μM, confirming mitochondrial dysfunction. Flow cytometric data demonstrated 5.1%-58.8% cells in SubG1 apoptotic phase at 5 and 400 μM TCPP. Our novel data revealed that TCPP is a genotoxic and apoptotic inducer, which may trigger alike responses in human vascular system. Overall, detailed in vivo studies are warranted on the transcriptional and translations effects of TCPP.