Trimester-specific effects of maternal exposure to organophosphate flame retardants on offspring size at birth: A prospective cohort study in China

Luo, Dan; Liu, Wenyu; Wu, Weixiang; Tao, Ye; Hu, Li-Sheng; Wang, Limei; Yu, Meng; Zhou, Aifen; Xia, Wei; Xu, Shunqing; Li, Yuanyuan; Mei, Surong

doi:10.1016/j.jhazmat.2020.124754

Cited by 50 publications

(32 citation statements)

References 56 publications

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“… 20 Thus, adverse pregnancy outcomes and impaired glucose tolerance in offspring may occur at physiological human concentrations of EHDPP, posing notable risks to gestation and of lifelong metabolic disease in humans. Although the association of EHDPP with these diseases in humans is unclear, epidemiological studies have associated a common metabolite of several aryl-OPFRs including EHDPP with low birth weight 60 and decreased success of fertilization, implantation, and clinical pregnancy. 18 The results of this study suggest a causal relationship between EHDPP exposure and adverse pregnancy outcomes in mice, as supported by primary trophoblast organoid culture data.…”

Section: Discussionmentioning

confidence: 99%

Screening of Organophosphate Flame Retardants with Placentation-Disrupting Effects in Human Trophoblast Organoid Model and Characterization of Adverse Pregnancy Outcomes in Mice

Gao

et al. 2022

Environ Health Perspect

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Background: Abnormal placental development may result in adverse pregnancy outcomes and metabolic diseases in adulthood; however, it remains unknown whether and how xenobiotics affect human placentation. Objectives: This study aimed to screen and identify placentation-disrupting chemicals in commonly used organophosphate flame retardants (OPFRs) and, if identified, to investigate potential adverse effects on placentation in relation to adverse pregnancy outcomes and metabolic disorder in offspring in mice. Methods: We devised a high-throughput immunofluorescence screening assay based on human trophoblast organoids and used it to screen OPFRs that inhibit the proliferation of organoids. One identified chemical was assessed for its effects on placentation by evaluating villous cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts using immunofluorescence and a mitochondrial stress test after 2 d of exposure. A 10-d exposure study was further performed to observe the dynamic effect of the OPFR on the structure of the organoids. RNA-sequencing and western blotting experiments were performed to explore the associated pathways, and a potential binding protein was identified by immunoprecipitation and in vitro kinase activity assays. Animal studies were performed to determine whether the findings in organoids could be replicated in mice and to observe adverse pregnancy outcomes. Results: The proliferation of organoids exposed to three aryl-OPFRs was significantly lower than the proliferation of control organoids. Further analysis demonstrated that one such chemical, 2-ethylhexyl-diphenyl phosphate (EHDPP), disrupted placentation in organoids. Mechanistically, EHDPP interfered with insulin-like growth factor 1 receptor (IGF1R) to inhibit aerobic respiration. Mice exposed to EHDPP at a physiological human concentrations exhibited immature and mature placental disorders, which correlated with fetal growth restriction, implantation failure, stillbirth, and impaired glucose tolerance. Conclusions: The human trophoblast organoid model showed that the commonly used OPFRs disrupted placentation via IGF1R, indicating that its use may contribute to adverse pregnancy outcomes and metabolic disorders in offspring. https://doi.org/10.1289/EHP10273

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Section: Discussionmentioning

confidence: 99%

Screening of Organophosphate Flame Retardants with Placentation-Disrupting Effects in Human Trophoblast Organoid Model and Characterization of Adverse Pregnancy Outcomes in Mice

Gao

et al. 2022

Environ Health Perspect

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“…This indicates that TPPO is beginning to be exposed in humans and that people are facing TPPO exposure. Considering the structural similarity of TPPO to triphenyl phosphate (TPHP), a proven endocrine disruptor [ 20 ], the health risk of TPPO warrants further investigation.…”

Section: Resultsmentioning

confidence: 99%

Human Exposure to Chlorinated Organophosphate Ester Flame Retardants and Plasticizers in an Industrial Area of Shenzhen, China

Liu

Zhu²,

Xie

et al. 2022

IJERPH

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Human exposure to organophosphate esters (OPEs) is more pervasive in industrial areas manufacturing OPE-related products. OPE exposure is of great concern due to its associations with adverse health effects, while studies on OPE exposure in industrial districts are scarce. This study aimed to assess human exposure to OPEs in a typical industrial area producing large amounts of OPE-related products in Shenzhen, China. Tris (2-chloroethyl)-phosphate (TCEP), tris (2-chloroisopropyl) phosphate (TCPP) and other common OPEs were analyzed in urine (n = 30) and plasma (n = 21) samples. Moreover, we measured five OPE metabolites (mOPEs) in plasma samples (n = 21). The results show that TCPP and TCEP are dominant compounds, with moderate to high levels compared with those reported in urine and plasma samples from other regions. In addition, di-n-butyl phosphate (DnBP) and diethyl phosphite (DEP) were frequently detected in plasma samples and could be considered as biomarkers. Risk assessment revealed a moderate to high potential health risk from TCEP exposure. Our results provide basic data for human exposure to OPEs in industrial areas and call for the prevention and mitigation of industrial chlorinated OPE pollution.

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“…In animal studies, it was found that Cl-PFRs can accumulate in the liver and kidneys (e.g., TCPP), disrupt the functions of the endocrine system and reproductive functions (reduced fertility), and increase developmental defects (e.g., TDCPP) [143], disrupting the development of the nervous system (e.g., TClPP); many of them are carcinogenic (especially Cl-PFRs, except V6) [39,143]. TCEP, TCPP, and TDCPP are believed to exhibit neurotoxicity (associated with motor deficits and dopaminergic degeneration), cytotoxicity (reduced viability and morphological changes in human peripheral blood mononuclear cells), and developmental toxicity (associated with growth inhibition in zebrafish offspring [144,145] in relation to animal organisms.…”

Section: Environmental Impact Of Flame Retardantsmentioning

confidence: 99%

“…Luo et al [144,145] proved that exposure of women in the third trimester of pregnancy to bis (1,3-dichloro-2-propyl) phosphate (BDCIPP) may result in the impaired growth of the fetus, which is at risk of developmental toxicity (malformations).…”

Section: Environmental Impact Of Flame Retardantsmentioning

confidence: 99%

Modification of Glass/Polyester Laminates with Flame Retardants

2021

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This paper presents a review of flame retardants used for glass/polyester laminates. It concerns flame retardants withdrawn from use such as compounds containing halogen atoms and flame retardants currently used in the industry, such as inorganic hydroxides, phosphorus and nitrogen-containing compounds, antimony, and boron compounds, as well as tin–zinc compounds. Attention is also drawn to the use of nanoclays and the production of nanocomposites, intumescent flame retardant systems, and mats, as well as polyhedral oligomeric silsesquioxanes. The paper discusses the action mechanism of particular flame retardants and presents their advantages and disadvantages.

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Trimester-specific effects of maternal exposure to organophosphate flame retardants on offspring size at birth: A prospective cohort study in China

Cited by 50 publications

References 56 publications

Screening of Organophosphate Flame Retardants with Placentation-Disrupting Effects in Human Trophoblast Organoid Model and Characterization of Adverse Pregnancy Outcomes in Mice

Screening of Organophosphate Flame Retardants with Placentation-Disrupting Effects in Human Trophoblast Organoid Model and Characterization of Adverse Pregnancy Outcomes in Mice

Human Exposure to Chlorinated Organophosphate Ester Flame Retardants and Plasticizers in an Industrial Area of Shenzhen, China

Modification of Glass/Polyester Laminates with Flame Retardants

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