JOURNAL OF APPLIED TOXICOLOGY
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2026
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IF 3.1
Jiuhong Zhang,Chenyang Yue,Luling Nie,Wanqi Fu,Qingsong Xie,Zhuyi Jiang,Chao Wang,Jie Jiang,Yan Wu,Jianjun Liu,Xiao Chen
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used halogen-containing organophosphate flame retardant with potential neurotoxicity, but its effects on cardiac autonomic function remain largely unexplored. This study investigated TDCIPP's impact on heart rate variability (HRV) and the underlying molecular mechanisms. Young adult male rats were treated with TDCIPP (0, 13.3, 40, 120, or 360 mg/kg/day) by gavage for 114 days. TDCIPP exposure significantly reduced multiple HRV parameters including SDRR (by 58%–62%, p < 0.005), CVRR (by 57%–64%, p < 0.01), RMSSD (by 55%–63%, p < 0.05), and SD 2 (by 59%–65%, p < 0.01) across all dose groups, indicating impaired cardiac autonomic function with a possible threshold-like pattern instead of a typical dose-dependent response. Further analyses revealed that TDCIPP decreased choline acetyltransferase (ChAT) activity (by 28%–53%, p < 0.001) and mRNA expression (by 22%–48%, p < 0.05 to p < 0.001) dose-dependently without affecting protein levels, while acetylcholinesterase (AChE) activity remained unchanged. Acetylcholine levels were significantly reduced in the 40 and 360 mg/kg/day groups (by 31% and 42%, respectively, p < 0.05). Molecular docking analysis demonstrated that TDCIPP binds to the choline binding site of ChAT, forming a hydrogen bond with His334, the same residue critical for choline binding. This suggests TDCIPP impairs cardiac autonomic function by disrupting cholinergic neurotransmission through putative competitive inhibition of ChAT activity. This novel mechanism differs from that of chlorpyrifos and provides new insights into how environmental flame retardants may impact cardiovascular health.
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Yujie Sha,Duo Zhang,Jiazichao Tu,Ruyue Zhang,Yijia Shao,Jimei Chen,Shaoyou Lu,Xiang Liu
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphate ester that can adversely affect animal or human health. The intestinal microbiota is critical to human health. High-dose exposure to TDCIPP can markedly affect the intestinal ecosystem of mice, but the effects of long-term exposure to lower concentrations of TDCIPP on the intestinal flora and body metabolism remain unclear. In this study, TDCIPP was administered to Sprague–Dawley rats by gavage at a dose of 13.3 mg/kg bw/day for 90 days. TDCIPP increased the relative weight of the kidneys ( P = 0.017), but had no effect on the relative weight of the heart, liver, spleen, lungs, testes, and ovaries ( P > 0.05). 16 S rRNA gene sequencing revealed that long-term TDCIPP exposure affected the diversity, relative abundance, and functions of rat gut microbes. The serum metabolomics of the rats showed that TDCIPP can disrupt the serum metabolic profiles, result in the up-regulation of 26 metabolites and down-regulation of 3 metabolites, and affect multiple metabolic pathways in rat sera. In addition, the disturbed genera and metabolites were correlated. The functions of some disturbed gut microbes were consistent with the affected metabolic pathways in the sera, and these metabolic pathways were all associated with kidney disease, suggesting that TDCIPP may cause kidney injury in rats by affecting the intestinal flora and serum metabolism.
研究领域:
毒理学
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微生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2024
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IF 8.2
Sujing Wang,Na Zheng,Qirui An,Xiaoqian Li,Yining Ji,Yunyang Li,Changcheng Chen,Zhifei Xiu
The flame retardant tri (1, 3-dichloro-2-propyl) phosphate (TDCIPP) is widely present in environmental media and organisms. People have paid much attention to the growth and developmental toxicity of TDCIPP, but there is little information about its cardiotoxicity and potential mechanisms. In this study, marine medaka ( Oryzias melastigma ) embryos were exposed to TDCIPP solutions (0, 0.05, 0.5, 5, and 50 μg/L) for 21 days to investigate the adverse effects of TDCIPP on cardiac development. The results showed that TDCIPP exposure altered the heart rate at different stages of embryonic development. In addition, 50 μg/L TDCIPP resulted in increased sinus venosus (SV)–bulbus arteriosus (BA) distance, pericardial cysts, and cardiac linearization in newly hatched fish. During embryonic development, the expression level of key genes regulating cardiac development is disturbed. The early stage of cardiac development is the sensitive window period for the toxic effects of TDCIPP. Oxidative stress was observed in newly hatched juveniles, but no significant lipid peroxidation damage was observed. In addition, vitellogenin (VTG) levels in juvenile fish were significantly reduced. Our results show that TDCIPP exposure induces cardiotoxicity in marine medaka embryos, which is induced in the early stages and promotes heart defects by amplifying inflammatory responses at a later stage.
研究领域:
环境毒理学
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发育生物学
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心血管毒理学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）