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

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.

Levels of organophosphate flame retardants and their metabolites among 391 volunteers in Taiwan: difference between adults and children

“…However, our results could not clarify whether these associations are attributed to the diseases themselves or the medications used. TBEP was detected in dust from solid waste, e-waste dumpling sites, landfills, and wastewater treatment facilities (42). Previous studies from Japan revealed that TBEP was the most prevalent OPFRs in houses (43,44).…”

Tris(1,3-dichloro-2-propyl) phosphate-induced cytotoxicity and its associated mechanisms in human A549 cells

“…Toxicological studies on TDCIPP mainly focused on its endocrine disruption, neurological disorders, reproductive and developmental toxicology, as well as its potential carcinogenicity (Chen et al, 2020; Li et al, 2017; Moser et al, 2015; Rhyu et al, 2019; Saquib et al, 2022). For example, Chen et al reported TDCIPP-induced reduction of sperm motility with no obvious changes in hormone levels (Chen et al, 2020).…”

“…In the study by Rhyu et al, TDCIPP was found to cause abnormal tail fins in zebrafish embryos, which was associated with the altered expression of transcription factors involved in tail fin development (Rhyu et al, 2019). In addition, TDCIPP was shown to elicit genotoxic and carcinogenic risks in liver cells (Saquib et al, 2022). As a result, the risk of TDCIPP to human health cannot be neglected.…”

Spleen Toxicity of Organophosphorus Flame Retardant TDCPP in Mice and the Related Mechanisms

“…Furthermore, emerging evidence suggests that TDCPP exposure can cause neurological, reproductive, endocrine, hepatic and renal damage [ 1 , 8 , 9 ]. Notably, it was listed as a known carcinogen on the Proposition 65 list of substances [ 10 , 11 ].…”