Organophosphorus Flame Retardant TDCPP Displays Genotoxic and Carcinogenic Risks in Human Liver Cells.

Quaiser Saquib,Maqsood A Siddiqui,Xiaowei Zhang,Abdullah M Al-Salem,Abdulaziz A Al-Khedhairy,Sabiha M Ansari

doi:10.3390/cells11020195

Abstract

Tris(1,3-Dichloro-2-propyl)phosphate (TDCPP) is an organophosphorus flame retardant (OPFR) widely used in a variety of consumer products (plastics, furniture, paints, foams, and electronics). Scientific evidence has affirmed the toxicological effects of TDCPP in in vitro and in vivo test models; however, its genotoxicity and carcinogenic effects in human cells are still obscure. Herein, we present genotoxic and carcinogenic properties of TDCPP in human liver cells (HepG2). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and neutral red uptake (NRU) assays demonstrated survival reduction in HepG2 cells after 3 days of exposure at higher concentrations (100–400 μM) of TDCPP. Comet assay and flow cytometric cell cycle experiments showed DNA damage and apoptosis in HepG2 cells after 3 days of TDCPP exposure. TDCPP treatment incremented the intracellular reactive oxygen species (ROS), nitric oxide (NO), Ca2+ influx, and esterase level in exposed cells. HepG2 mitochondrial membrane potential (ΔΨm) significantly declined and cytoplasmic localization of P53, caspase 3, and caspase 9 increased after TDCPP exposure. qPCR array quantification of the human cancer pathway revealed the upregulation of 11 genes and downregulation of two genes in TDCPP-exposed HepG2 cells. Overall, this is the first study to explicitly validate the fact that TDCPP bears the genotoxic, hepatotoxic, and carcinogenic potential, which may jeopardize human health.

Highlights

Publisher’s Note: MDPI stays neutralThe production of an alternative to flame retardants, known as organophosphorus flame retardants (OPFRs), has swiftly increased, allowing it to be used in a range of commercial products [1]
HepG2 grown in the presence of TDCPP exhibited loss in population density and cellular shrinkage
We have found a conspicuous increment in subG1peak in TDCPP-exposed cells, which confirms that the cytotoxicity observed in HepG2 cells is the outcome of apoptosis in HepG2 cells

Summary

Introduction

Publisher’s Note: MDPI stays neutralThe production of an alternative to flame retardants, known as organophosphorus flame retardants (OPFRs), has swiftly increased, allowing it to be used in a range of commercial products [1]. OPFRs are widely used in household and commercial items, including plastics, furniture, paints, foams, electronic goods, building materials, and construction materials [2]. A large amount of scientific evidence has affirmed that OPFRs can have adverse effects on humans and animals [3–6]. Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is an OPFR that is frequently added in polyvinyl chloride, rigid polyurethane foam, epoxy resin, and polyester fiber synthesis. Recent and earlier reports have confirmed the presence of TDCPP in house dust samples [9,10]. Around 96% of dust samples collected from USA households showed >2 to 50 ppm of TDCPP [11]. Dermal absorption and hand-to-mouth contact have been attributed to be a key factor for the entry of TDCPP into the human with regard to jurisdictional claims in published maps and institutional affiliations

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