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.

Tris (2-chloroisopropyl) phosphate and Tris (nonylphenyl) phosphite Promote Human Renal Cell Apoptosis through the ERK/CEPBA/Long Non-Coding RNA Cytoskeleton Regulator Axis

“…These results were consistent with some experimental results [26] that indicated that renal cell viability was negatively correlated with the concentration of TCPP. One study found that low concentrations of TCPP had pro-apoptotic and pro-activating effects on venous endothelial cells [27], but another study did not detect a significant increase in the rate of apoptosis and ROS in TCPPtreated hepatocytes [28], suggesting that the toxic effects of OPs are somewhat tissue/cell specific. ROS production is usually caused by a change in mitochondrial permeability [29].…”

Skeletal effects following developmental flame-retardant exposure are specific to sex and chemical class in the adult Wistar rat

“…Endothelial cells (ECs) release angiocrine factors, which include vascular endothelial growth factors (VEGFs) and fibroblast growth factors (FGFs), to promote and regulate bone growth ( Hu and Olsen, 2016 ; Kaigler et al, 2003 ; Ramasamy et al, 2016 ; Owen-Woods and Kusumbe, 2022 ). Limited studies exist on the ability of FRs to impact EC function, although BFRs and OPFRs have been shown to induce apoptosis and genotoxicity in human umbilical vein ECs ( Chen et al, 2020 ; Saquib et al, 2021 ). Deletion of bone-derived VEGF in osteoblasts obtained from male mice produced immature mineral precursors in culture, whereas it produced mature mineral precursors from female-derived osteoblasts, suggesting a role of VEGF in influencing the skeletal matrix independent of sex hormones in a sex-specific manner ( Goring et al, 2019 ).…”