Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphorus flame retardant and has been detected in various environmental matrices including indoor dust. Inhalation of indoor dust is one of the most important pathways for human exposure to TDCIPP. However, its adverse effects on human lung cells and potential impacts on respiratory toxicity are largely unknown. In the current study, human non-small cell carcinoma (A549) cells were selected as a cell model, and the effects of TDCIPP on cell viability, cell cycle, cell apoptosis, and underlying molecular mechanisms were investigated. Our data indicated a concentration-dependent decrease in the cell viability of A549 cells after exposure to TDCIPP for 48 h, with half lethal concentration (LC50) being 82.6 µM. In addition, TDCIPP caused cell cycle arrest mainly in the G0/G1 phase by down-regulating the mRNA expression of cyclin D1, CDK4, and CDK6, while up-regulating the mRNA expression of p21 and p27. In addition, cell apoptosis was induced via altering the expression levels of Bcl-2, BAX, and BAK. Our study implies that TDCIPP may pose potential health risks to the human respiratory system and its toxicity should not be neglected.
CanbazDLogiantaraAvan ReeR, et al. (2017) Immunotoxicity of organophosphate flame retardants TPHP and TDCIPP on murine dendritic cells in vitro. Chemosphere177: 56–64.
2.
ChenHWangPDuZ, et al. (2018) Oxidative stress, cell cycle arrest, DNA damage and apoptosis in adult zebrafish (Danio rerio) induced by tris(1,3-dichloro-2-propyl) phosphate. Aquatic Toxicology194: 37–45.
3.
ChenRHongXYanS, et al. (2020) Three organophosphate flame retardants (OPFRs) reduce sperm quality in Chinese rare minnows (Gobiocypris rarus). Environmental Pollution263: 114525.
4.
ChenYLiuQMaJ, et al. (2020) A review on organophosphate flame retardants in indoor dust from China: implications for human exposure. Chemosphere260: 127633.
5.
CuiDBiJZhangZN, et al. (2020) Organophosphorus flame retardant TDCPP-induced cytotoxicity and associated mechanisms in normal human skin keratinocytes. The Science of the Total Environment726: 138526.
6.
FengYShiJLiM, et al. (2023) Evaluation of the cytotoxic activity of triphenyl phosphate on mouse spermatocytes cells. Toxicology in Vitro: An International Journal Published in Association with BIBRA90: 105607.
7.
GreavesAKLetcherRJ (2017) A review of organophosphate esters in the environment from biological effects to distribution and fate. Bulletin of Environmental Contamination and Toxicology98: 2–7.
8.
GwonHROhHJChangKH, et al. (2021) Occurrence, distribution, and potential exposure risk of organophosphate flame retardants in house dust in South Korea. The Science of the Total Environment770: 144571.
9.
HaoCHelmPAMorseD, et al. (2018) Liquid chromatography-tandem mass spectrometry direct injection analysis of organophosphorus flame retardants in Ontario surface water and wastewater effluent. Chemosphere191: 288–295.
10.
HarrisMHThompsonCB (2000) The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death & Differentiation7: 1182–1191.
11.
KillileaDWChowDXiaoSQ, et al. (2017) Flame retardant tris(1,3-dichloro-2-propyl)phosphate (TDCPP) toxicity is attenuated by N-acetylcysteine in human kidney cells. Toxicology Reports4: 260–264.
12.
KuwanaTNewmeyerDD (2003) Bcl-2-family proteins and the role of mitochondria in apoptosis. Current Opinion in Cell Biology15: 691–699.
13.
LiRZhouPGuoY, et al. (2017) Tris (1,3-dichloro-2-propyl) phosphate-induced apoptotic signaling pathways in SH-SY5Y neuroblastoma cells. Neurotoxicology58: 1–10.
14.
LiJZhangZMaL, et al. (2018) Implementation of USEPA RfD and SFO for improved risk assessment of organophosphate esters (organophosphate flame retardants and plasticizers). Environment International114: 21–26.
15.
LiRZhangLShiQ, et al. (2018) A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae. Aquatic Toxicology199: 46–54.
16.
LiuWLiuXPanZ, et al. (2019) Ailanthone induces cell cycle arrest and apoptosis in melanoma B16 and A375 cells. Biomolecules9(7): 275.
17.
MengYXuXXieG, et al. (2022) Alkyl organophosphate flame retardants (OPFRs) induce lung inflammation and aggravate OVA-simulated asthmatic response via the NF-кB signaling pathway. Environment International163: 107209.
18.
MoserVCPhillipsPMHedgeJM, et al. (2015) Neurotoxicological and thyroid evaluations of rats developmentally exposed to tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) and tris(2-chloro-2-ethyl)phosphate (TCEP). Neurotoxicology and Teratology52: 236–247.
19.
NgabireDSeongYAPatilMP, et al. (2018) Induction of apoptosis and G1 phase cell cycle arrest by Aster incisus in AGS gastric adenocarcinoma cells. International Journal of Oncology53: 2300–2308.
20.
RhyuDLeeHTanguayRL, et al. (2019) Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) disrupts zebrafish tail fin development. Ecotoxicology and Environmental Safety182: 109449.
21.
SaillenfaitAMNdawSRobertA, et al. (2018) Recent biomonitoring reports on phosphate ester flame retardants: a short review. Archives of Toxicology92: 2749–2778.
22.
SaquibQAl-SalemAMSiddiquiMA, et al. (2022) Organophosphorus flame retardant TDCPP displays genotoxic and carcinogenic risks in human liver cells. Cells11(2): 195.
23.
SchrederEDLa GuardiaMJ (2014) Flame retardant transfers from U.S. households (dust and laundry wastewater) to the aquatic environment. Environmental Science & Technology48: 11575–11583.
24.
SchrederEDUdingNLa GuardiaMJ (2016) Inhalation a significant exposure route for chlorinated organophosphate flame retardants. Chemosphere150: 499–504.
25.
ShiSFengQZhangJWangXZhaoLFanYHuPWeiPBuQCaoZ (2024) Global patterns of human exposure to flame retardants indoors. The Science of the Total Environment912: 169393.
26.
WangXSongF (2024) The neurotoxicity of organophosphorus flame retardant tris (1,3-dichloro-2-propyl) phosphate (TDCPP): main effects and its underlying mechanisms. Environmental Pollution346: 123569.
27.
XiWSLiJBLiuYY, et al. (2021) Cytotoxicity and genotoxicity of low-dose vanadium dioxide nanoparticles to lung cells following long-term exposure. Toxicology459: 152859.
28.
XiangPLiuRYLiC, et al. (2017) Effects of organophosphorus flame retardant TDCPP on normal human corneal epithelial cells: implications for human health. Environmental Pollution230: 22–30.
29.
XiangPLiuRYSunHJ, et al. (2017) Effects of novel brominated flame retardant TBPH and its metabolite TBMEHP on human vascular endothelial cells: implication for human health risks. Environmental Research156: 834–842.
30.
YanSWangQYangL, et al. (2020) Comparison of the toxicity effects of tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) with tributyl phosphate (TNBP) reveals the mechanism of the apoptosis pathway in asian freshwater clams (corbicula fluminea). Environmental Science & Technology54: 6850–6858.
31.
YuXYinHPengH, et al. (2019) OPFRs and BFRs induced A549 cell apoptosis by caspase-dependent mitochondrial pathway. Chemosphere221: 693–702.
32.
ZhangWWangRGiesyJP, et al. (2019) Tris (1,3-dichloro-2-propyl) phosphate treatment induces DNA damage, cell cycle arrest and apoptosis in murine RAW264.7 macrophages. Journal of Toxicological Sciences44: 134–144.
33.
ZhangZNYangDLLiuH, et al. (2023) Effects of TCPP and TCEP exposure on human corneal epithelial cells: oxidative damage, cell cycle arrest, and pyroptosis. Chemosphere331: 138817.
34.
ZhongXQiuJKangJ, et al. (2019) Exposure to tris(1,3-dichloro-2-propyl) phosphate (TDCPP) induces vascular toxicity through Nrf2-VEGF pathway in zebrafish and human umbilical vein endothelial cells. Environmental Pollution247: 293–301.
35.
ZubiagaAM (2020) Foreword special issue cell cycle and regulation. Genes11(3): 254.
