RESUMEN
With the wide utilization of organophosphate esters (OPEs) in recent years, OPEs have been detected more frequently in the aquatic environment. However, the distribution of OPEs in drinking source water has rarely been investigated across a large region. In this study, the occurrence and distribution of 13 OPEs were investigated in 23 source water sites from Northeast to Southeast (spacing greater than 3320 km) with a direct injection ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Total OPEs ranged from 218.8 to 636.6 ng/L, with a mean of 380.8 ng/L. The average detected concentration of OPEs in southern cities was higher than that in northern cities. Chlorinated OPEs accounted for 64.74% of the total concentration. Triethyl phosphate (TEP), tri (2-chloroethyl) phosphate (TCEP), and tri (chloropropyl) phosphate (TCPP) were detected in all water samples. Rainfall is a significant factor that affects the OPE concentration (less rainfall, higher concentration). China's OPE concentrations have rapidly reached a median level when compared to those of other countries. Ecological risk assessment showed that most OPEs have no or low risk to organisms (fish, crustacea, algae), except tricresyl phosphate (TCP), which is medium risk. The risk of OPEs in less-rain regions needs to be of greater concern, especially TCP.
Asunto(s)
Agua Potable , Retardadores de Llama , Animales , China , Cromatografía Liquida , Agua Potable/análisis , Monitoreo del Ambiente/métodos , Ésteres/análisis , Retardadores de Llama/análisis , Organofosfatos/análisis , Fosfatos/análisis , Medición de Riesgo , Espectrometría de Masas en TándemRESUMEN
As the typical aryl-organophosphate flame retardants (OPFRs), triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were reported to be estrogen disruptors. However, estrogen receptor α (ERα) binding experiments could not explain their biological effects. In this study, their action on ERα, G protein-coupled estrogen receptor (GPER) and the synthesis of 17ß-estradiol (E2) were investigated using in vitro assays and molecular docking. The results showed that TPhP acted as an ERα agonist and recruited steroid receptor co-activator 1 (SRC1) and 3 (SRC3), which was found for the first time. Unlike TPhP, TDCIPP acted as an ERα antagonist. However, both TPhP and TDCIPP activated the estrogen pathway by GPER in SKBR3 cells which were lack of ERα. Although molecular docking results revealed that both TPhP and TDCIPP could dock into ERα and GPER, their substituent groups and combination mode might affect the receptor activation. In addition, by using estrogen biosynthesis assay in H295R cells, both of TPhP and TDCIPP were found to promote E2 synthesis and E2/T ratio involving their different alteration on levels of progesterone, testosterone and estrone, and expression of various key genes. Our data proposed estrogen-disrupting mechanism frameworks of TPhP and TDCIPP. Moreover, our results will contribute to future construction of adverse outcome pathway (AOP) framework of endocrine disruptors.
Asunto(s)
Retardadores de Llama , Fosfatos , Estrógenos , Retardadores de Llama/toxicidad , Simulación del Acoplamiento Molecular , Organofosfatos , Compuestos OrganofosforadosRESUMEN
Phosphorus-containing flame retardants (PFRs) have been frequently detected in various environmental samples at relatively high concentrations and are considered emerging environmental pollutants. However, their biological effects and the underlying mechanism remain unclear, especially alkyl-PFRs. In this study, a battery of in vitro bioassays was conducted to analyze the cytotoxicity, oxidative stress, mitochondrial impairment, DNA damage and the involved molecular mechanisms of several selected alkyl-PFRs. Results showed that alkyl-PFRs induced structural related toxicity, where alkyl-PFRs with higher logKow values induced higher cytotoxicity. Long-chain alkyl-PFRs caused mitochondrial and DNA damage, resulting from intracellular reactive oxygen species (ROS) and mitochondrial superoxide overproduction; while short-chain alkyl-PFRs displayed adverse outcomes by significantly impairing mitochondria without obvious ROS generation. In addition, alkyl-PFRs caused DNA damage-induced cell cycle arrest, as determined by flow cytometry, and transcriptionally upregulated key transcription factors in p53/p21-mediated cell cycle pathways. Moreover, compared to the control condition, triisobutyl phosphate and trimethyl phosphate exposure increased the sub-G1 apoptotic peak and upregulated the p53/bax apoptosis pathway, indicating potential cell apoptosis at the cellular and molecular levels. These results provide insight into PFR toxicity and the involved mode of action and indicate the mitochondria is an important target for some alkyl-PFRs.