Endocrine-Disrupting Chemicals: Possible Genesis of Ovarian Tumors

Background: Prolonged exposure to environmental toxicants like endocrine-disrupting chemicals has been linked to several ovarian pathologies. Exposure to endocrine-disrupting chemicals may start at any time of life from the fetal stage to adulthood resulting in various health complications The purpose of our study is to compare the concentration levels and association of benzopyrene, bisphenol A and genistein in patients with ovarian tumors and normal control group. We also sort to evaluate the predictive performance of benzopyrene, bisphenol A and genistein in patients with ovarian tumors. Methods: A case-control study was conducted for randomly selected participants involving 30 patients and 30 controls. 30 patients with radiologically diagnosed and histopathological confirmed ovarian tumors were included in the study between January 2022 and December 2022. Urine samples from each group were analyzed using liquid chromatography-mass spectrometry. Descriptive analysis for normally distributed continuous variables was done accordingly. Concentration levels of endocrine-disrupting chemicals were assessed using the Mann-Whitney test. The association of endocrine-disrupting chemicals with pathological ovarian tumors was analyzed using binary logistic regression. Evaluation of the diagnostic performance of endocrine-disrupting chemicals was analyzed using the ROC curve. Results: Overall, patients were significantly (P = 0.000) older than the healthy controls. Mean years (SD) were 36.7 (7.90) and 28.8 years (4.89) for patients and normal women respectively. Endometriomas had the highest incidence of 50%. The level of benzopyrene and bisphenol A in patients was significantly higher than those in the control group, while the level of genistein was significantly higher in normal controls. Benzopyrene and bisphenol A were significantly associated with ovarian cysts, and the incidence of pathological ovarian cysts was positively correlated to these EDCs, with OR value 64.79 (P = 0.005) for benzopyrene and 9.609 (P = 0.001) for bisphenol A. Genistein was significantly negatively correlated with the incidence of pathological ovarian tumors, with OR value of 0.153 (P = 0.007). Diagnostic performance on the AUC for benzopyrene, bisphenol A and genistein&l.

Research Development of Endocrine Disrupting Chemicals(EDCs) in Water in China

More and more importance has been attached to the problem of endocrine disrupting chemicals (EDCs) since 1960s. This article elaborates the recent research progress of EDCs in water and the trends in the near future in China.

Endocrine disrupting chemicals in mixture and obesity,diabetes and related metabolic disorders

Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading causes of morbidity and mortality. Although, different etiologic factors including excessive food intake and reduced physical activity have been well identified, they cannot explain the kinetics of epidemic evolution of obesity and diabetes with prevalence rates reaching pandemic proportions. Interestingly, convincing data have shown that environmental pollutants, specifically those endowed with endocrine disrupting activities, could contribute to the etiology of these multifactorial metabolic disorders. Within this review, we will recapitulate characteristics of endocrine disruption. We will demonstrate that metabolic disorders could originate from endocrine disruption with a particular focus on convincing data from the literature. Eventually, we will present how handling an original mouse model of chronic exposition to a mixture of pollutants allowed demonstrating that a mixture of pollutants each at doses beyond their active dose could induce substantial deleterious effects on several metabolic end-points. This proof-of-concept study, as well as other studies on mixtures of pollutants, stresses the needs for revisiting the current threshold model used in risk assessment which does not take into account potential effects of mixtures containing pollutants at environmental doses, e.g., the real life exposure. Certainly, more studies are necessary to better determine the nature of the chemicals to which humans are exposed and at which level, and their health impact. As well, research studies on substitute products are essential to identify harmless molecules.

A Toxicological Assessment of Endocrine Disrupting Chemicals Found in the BMW (Border, Midland and Western) Region of Ireland

A battery of tests was established to determine the oestrogenic, mutagenic and genotoxic potential of two categories of endocrine disrupting chemicals (EDCs), phthalates and alkylphenols. Diisononylphthalate (DINP), diethylhexylphthalate (DEHP), dibutylphthalate (DBP), diisododecylphthalate (DIDP) and 4-nonylphenol (4-NP) were oestrogenic in the yeast estrogen screen (YES) assay and potently oestrogenic in the MVLN and E-SCREEN assays at environmentally relevant concentrations. DINP and 4-NP were mutagenic in the Ames assay and also induced significant levels of unscheduled DNA synthesis and DNA strand breakage. Significant induction in the percentage of cells containing micronuclei was observed after treatment with DINP, DEHP and 4-NP. In addition, sewage effluents from sewage treatment plants (STPs) in the Border, Midlands and Western (BMW) region of Ireland were significantly oestrogenic in the YES assay. Moreover, analysis of levels of phthalates and alkylphenol identified in Irish rivers receiving treated effluent showed potent oestrogenicity in the YES assay. The proliferative and genotoxic ability of the phthalates and alkylphenol, and the oestrogenicity of the treated effluents reported here, is significant as these EDCs and EDCs within the effluent may play a role in the etiology of human abnormalities.

Screening for Genotoxicity and Oestrogenicity of Endocrine Disrupting Chemicals <i>in Vitro</i>

A diverse range of endocrine disrupting chemicals (EDCs) was examined, using an in vitro test system, for critical events required for the onset of carcinogenesis in vivo. The initiation stage of carcinogenesis is a genotoxic process. 4-Octylphenol (alkylphenol), bisphenol A (plasticiser), coumestrol and genistein (phytoestrogens), 2,4-dichlorophe- noxyacetic acid and toxaphene (pesticides) and ethinylestradiol (synthetic hormone) were investigated for potential mutagencicity, DNA strand breakage, clastogenicity and DNA repair. Significant induction in the percentage of cells containing micronuclei was observed for all the EDCs. Toxaphene and coumestrol were mutagenic in the Ames assay. They also induced significant levels of unscheduled DNA synthesis and DNA strand breakage. Bisphenol A induced low level DNA strand breakage in HepG2 cells in the comet assay. The EDCs, with the exception of toxaphene, induced transcriptional activation in the yeast estrogen screen (YES) assay. They were potently oestrogenic in the mammalian based MVLN (transactivation) and E-SCREEN (proliferation) assays. This report on the transactivational, proliferative and genotoxic ability of the EDCs suggests that these chemicals may play a role in the etiology of male and female reproductive cancers.

Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells

Endocrine-disrupting chemicals (EDCs) are known to exert estrogen-like effects that are similar to those made by naturally produced hormones or by inhibition of the receptors in the cell receiving the hormones. Recently, several reports have indicated that EDCs can affect the developing central nervous system. In our current study, we report that some EDCs induce apoptosis in cultured PC12 cells and can be classified into three groups. Bisphenol A (BPA), p-nonylphenol (NP) and tributyltin chloride (TBT) were found to induce endoplasmic reticulum (ER) stress-associated apoptosis and activate the unfolded protein response (UPR) system, whereas benomyl (beno) induced non-ER stress-associated apoptosis. The half-maximal apoptosis-inducing concentrations (IC50) of these EDCs were 160 μM for BPA, 25.6 μM for NP, 640 nM for TBT and 48 μM for beno. Although these concentrations are higher than those found in the environment, some EDCs may have apoptotic effects on various cells in the body, including neurons, through their accumulation in the body over time or condensation through the food chain. On the other hand, benzopyrene, fenvalerate, styrene monomer and bis(2-ethylhexyl)phthalate did not induce apoptosis in PC12 cells. We analyzed also whether apoptosis-inducing EDCs had an estrogen-like effect on cultured PC12 cells transfected with a luciferase reporter plasmid, the activity of which is dependent on estrogen receptor α. We found that BPA had an estrogen-like effect (EC50 = 5.9 μM) but that NP, TBT and beno did not in transfected PC12 cells. These results suggest that BPA may predomi-nantly exert estrogenic effects, but others may pre-dominantly have apoptosis-inducing effects on cells in the body exposed to a polluted environment.

Removal of endocrine disrupting chemicals from water through urethane functionalization of microfiltration membranes via electron beam irradiation

Polyethersulphone(PES)membranes modified with urethane functional groups were prepared through an interfacial reaction using electron beam irradiation.The removal of eight endocrine disrupting chemicals(EDCs)was studied using both pristine and functionalized PES membranes.The prepared membranes underwent characterization using several techniques,including attenuated total reflectance-Fourier transform infrared(ATR-FTIR)spectroscopy,scanning electron microscopy,contact angle analysis,and measurements of pure water flux.Furthermore,dynamic adsorption experiments were conducted to evaluate the adsorption mechanism of the prepared membrane toward the eight EDCs.The urethane functionalized membranes were hydrophilic(52°contact angle)and maintained a high permeate flux(26000 L/h m^(2) bar)throughout the filtration process.Dynamic adsorption results demonstrated that the introduction of urethane functional groups on the membranes significantly enhanced the removal efficiency of 17β-estradiol,estriol,bisphenol A,estrone,ethinylestradiol,and equilin.The adsorption loading of 17β-estradiol on the functionalized PES membrane was 6.7±0.7 mg/m^(2),exhibiting a 5-fold increase compared to the unmodified PES membrane.The membranes were successfully regenerated and reused for three adsorption cycles without experiencing any loss of adsorption capacity.

Analysis of Environmental Endocrine Disrupting Activities in Wastewater Treatment Plant Effluents Using Recombinant Yeast Assays Incorporated with Exogenous Metabolic Activation System

Objective To measure the endocrine disrupting chemicals （EDCs） in wastewater and evaluate the EDCs removal efficiencies in the municipal wastewater treatment plants （WWTP）. Methods A battery of in vitro recombinant yeast bioassays incorporated with exogenous metabolic activation system （rat liver preparation, S9 mix） was conducted to assess the estrogen receptor （ER）, androgen receptor （AR）, progesterone receptor （PR）, and thyroid receptor （TR） ant/agonistic activities of effluents collected from Datansha WWTP. Results The indirect estrogenic, anti‐androgenic, anti‐progesteronic, and anti‐thyroidic activities were observed in the influent. The removal efficiencies of EDCs were above 74%, suggesting that the present wastewater treatment processes were good enough to remove most of these indirect endocrine disrupting chemicals. Conclusion The incorporation of exogenous metabolic capacity into the test system was valid for the study of indirect effects on ER, AR, PR, and TR.

水体中环境内分泌干扰物(EDCs)污染现状及其对鱼类的生殖危害

越来越多的环境内分泌干扰物(EDCs)不断释放到环境,并通过大气沉降、地表径流、土壤淋溶和直接排放等方式进入水体,从而使水体成为EDCs存在的主要场所之一。为引起社会对水体EDCs污染的广泛关注,并积极采取EDCs危害防治措施,保护鱼类资源和水生态系统,本文介绍了EDCs的分类,详述了自然水体、饮用水源水以及自来水中EDCs污染情况,阐明了EDCs对鱼类的生殖危害。资料分析显示,EDCs能够扰乱生物体内分泌功能,导致生殖器官、生殖机能和生殖行为异常,引起生育力下降,甚至生物繁殖机能损害,并最终导致种群数量下降,以至物种灭绝。虽然国内外已经开展了一些关于EDCs对生物危害等方面的研究,但大都处于起步阶段,存在着基础研究薄弱、识别和鉴定困难或代价太大等问题,有关工作亟需全面、深入开展。

青鳉鱼ERRα的克隆、序列分析、组织表达及其对不同EDCs暴露的响应

内分泌干扰物质（EDCs）可以通过多种通道影响鱼类的生长、发育和繁殖,而雌激素相关受体（ERR）是一类目前没有引起足够重视的潜在致毒信号通道.本研究克隆了青鳉鱼（Oryzias latipes）ERRαmRNA全序列,并通过实时定量RT-PCR方法对其在不同组织中的表达和不同EDCs暴露下的响应进行了分析.发现青鳉鱼ERRα与其它脊椎动物ERRα氨基酸序列有较高的同源性,特别是DNA结合结构域（DBD）在从鱼类到哺乳类动物的进化过程中高度保守,配体结合结构域（LBD）序列与哺乳动物的LBD有66.4%-67.0%的序列相同.青鳉鱼ERRα与青鳉鱼雌激素受体ERα、ERβ和雄激素受体ARα、ARβ的DBD氨基酸数相同,且有较高序列相似性,但LBD的长度和序列差异较大.青鳉鱼ERRα基因有5个外显子组成,位于第14号染色体.青鳉鱼ERRα基因在各组织中广泛表达,其中在性腺、脑、脾脏、眼和肠中表达较高,且在雌雄性腺中差异表达,表明其在雌雄性别分化和性腺发育中发挥调控作用.暴露200 ng/L炔雌醇（EE2）、200 ng/L雌酮（E1）、200 ng/L己烯雌酚（DES）、100μg/L阿特拉津（AT）和200 ng/L雌二醇（E2）后,青鳉鱼精巢中ERRαmRNA水平分别显著下降至对照组的0.54、0.56、0.61、0.63和0.65倍（p〈0.05）,但暴露1μg/L三丁基锡和1μg/L三苯基锡后上升至对照组的1.34和1.35倍（p〉0.05）,表明ERRα可能参与外源EDCs影响鱼类性别分化和性腺发育的过程.此外,在青鳉鱼ERRα基因上游没有发现类似哺乳动物ERRα基因上游的类固醇激素反应元件半位点,说明鱼类ERRα基因的调控模式与哺乳类存在差异.

滇池环湖污水处理厂中酚类EDCs的存在、去除及归趋

研究了滇池环湖8座污水处理厂（Wastewater Treatment Plants,WWTPs）中酚类内分泌干扰物（Endocrine Disrupting Chemicals,EDCs）的存在、去除及归趋,阐明了该类物质的浓度水平、分布特征及环境归趋,明确了处理工艺及运行参数对酚类EDCs去除效果的影响,评估了出水和污泥外排对环境的污染负荷。结果表明：污水处理厂进水、出水和污泥中普遍检出了酚类EDCs,NP2EO、NP1EO和BPA是主要的酚类EDCs;8座污水处理厂进水中∑EDCs的质量浓度为2039～5 066 ng/L,出水中为420～1 536 ng/L,污泥中质量比为1 210～9 465 ng/g dw（dry weight,干重）,总去除率为32%～89%;不同污水处理工艺对酚类EDCs的去除效率存在较大差异,3AMBR和A2/O工艺的去除效果较氧化沟和ICEAS工艺有明显的优势;不同的工艺参数对酚类EDCs去除的影响存在一定差异,深度处理、污泥龄和辛醇-水分配系数对酚类EDCs去除效果的影响较大;降解是污水处理厂中酚类EDCs的主要去除方式;三污、五污和六污污泥对酚类EDCs的吸附作用较强;昆明市每天进入污水处理厂的酚类EDCs总量约为3771 g,经处理后,出水外排27%。研究表明,滇池环湖污水处理厂出水及其剩余污泥具有一定的环境风险。

水体中环境内分泌干扰物(EDCs)污染现状及其对鱼类的生殖危害(英文)

越来越多的环境内分泌干扰物(EDCs)不断释放到环境,并通过大气沉降、地表径流、土壤淋溶和直接排放等方式进入水体,从而使水体成为EDCs存在的主要场所之一。为引起社会对水体EDCs污染的广泛关注,并积极采取EDCs危害防治措施,保护鱼类资源和水生态系统,本文介绍了EDCs的分类,详述了自然水体、饮用水源水以及自来水中EDCs污染情况,阐明了EDCs对鱼类的生殖危害。资料分析显示,EDCs能够扰乱生物体内分泌功能,导致生殖器官、生殖机能和生殖行为异常,引起生育力下降,甚至生物繁殖机能损害,并最终导致种群数量下降,以至物种灭绝。虽然国内外已经开展了一些关于EDCs对生物危害等方面的研究,但大都处于起步阶段,存在着基础研究薄弱、识别和鉴定困难或代价太大等问题,有关工作亟需全面、深入开展。

典型EDCs在A^2/O-MBR组合工艺中的迁移行为

以环境水体中21种典型内分泌干扰物(EDCs)为目标物,对其在某城市污水处理厂厌氧-缺氧-好氧与MBR的组合工艺(A^2/O-MBR)中的迁移和归趋进行了长期研究。结果表明,该工艺对21种EDCs有很强的去除能力。EDCs在A^2/O-MBR工艺中泥水两相的迁移行为用泥水分配系数(Kd)来表示,得到的较高的泥水分配系数表明污泥对EDCs有一定的吸附作用,水相中大部分EDCs是通过污泥吸附来去除。

析因设计DLLME-SFO同时萃取水中EDCs的应用

采用全析因设计对分散液液微萃取-上浮溶剂固化（DLLME-SFO）同时萃取水中五种环境内分泌干扰物包括雌酮（E1）、雌三醇（E3）、双酚A（BPA）、己烯雌酚（DES）和壬基酚（NP）的条件进行优化,建立了预测回归方程,并分析了因素对DLLME-SFO萃取回收率的影响。利用SAS软件分析得到的最优条件为盐浓度（m/v）15%、水样体积3 mL、分散剂（甲醇）体积0.5 mL以及萃取剂（十二醇）体积120μL。在优化萃取条件下,E1、E3、BPA、DES和NP萃取回收率的预测值分别为46.17%、74.38%、79.20%、69.62%和73.05%,实验验证值分别为44.15%、87.76%、77.83%、77.68%和70.01%,实验值与预测值的相对偏差小于10%。将建立的DLLME-SFO方法用于测定实际水样中的目标化合物,结果显示实际水样中E3、BPA、DES、E1和NP同时萃取回收率分别为64.81%~76.18%,88.09%~83.15%,68.38%~70.08%,66.37%~68.72%,68.35%~72.80%,相对标准偏差（n=3）在1.47%~8.09%之间。

垃圾渗滤液中典型内分泌干扰物质(EDCs)细胞毒性分析

垃圾渗滤液的人类健康风险评估日益受到人们重视,也成为研究热点。本文采用一种新型高级氧化技术UV-Fenton处理渗滤液,并用人体乳腺癌细胞(MCF-7)评估处理过程中渗滤液原液以及渗滤液中典型内分泌干扰物质(EDCs)的细胞毒性,对垃圾渗滤液中EDCs的细胞毒性和变化规律进行了研究。结果表明渗滤液中的邻苯二甲酸二丁酯(DBP)、双酚A(BPA)、壬基酚(NP)是产生细胞毒性的主要物质,其毒性大小为DBP>BPA>NP。在同样的氧化降解过程中显示出不同毒性变化规律,通过GC-MS分析,结果显示UV-Fenton过程中产生了大量的中间产物,这也是引起毒性变化的主要原因。实验结果也说明垃圾渗滤液细胞毒性可以通过UV-Fenton过程有效去除。

Occurrence of estrogenic endocrine disrupting chemicals concern in sewage plant effluent

The purpose of this study was to give a worldwide overview of the concentrations of typical estrogenic endocrine disrupting chemicals （EDCs） in the effluent of sewage plants and then compare the concentra- tion distribution of the estrogenic EDCs in ten countries based on the survey data of the estrogenic EDCs research. The concentrations of three main categories （totally eight kinds） of estrogenic EDCs including steroidal estrogens （estrone （El）, estradiol （E2）, estriol （E3） and 17a- ethynylestradiol （EE2））, phenolic compounds （nonylphe- nol （NP） and bisphenol A （BPA）） and phthalate esters （dibutyl phthalate （DBP） and dibutyl phthalate （2- ethylhexyl） phthalate （DEHP）） in the effluents of sewage plants reported in major international journals over the past decade were collected. The statistics showed that the concentration distributions of eight kinds of EDCs were in the range of ng·L^-1 to μg·L^-1. The concentrations of steroidal estrogens mainly ranged within 50.00 ng. L-1, and the median concentrations of El, E2, E3 and EE2 were 11.00, 3.68, 4.90 and 1.00 ng·L^-1, respectively. Phenolic compounds and phthalate esters were found at pg. L-1 level （some individual values were at the high level of 40.00 μg·L^-1）. The median concentrations of BPA, NP, DBP and DEHP were 0.06, 0.55, 0.07 and 0.88 μg·L^-1, respectively. The concentrations of phenolic compounds and phthalate esters in the effluents were higher than that of steroids estrogens. The analysis of the concentration in various ten countries showed that steroids estrogens, phenolic compounds and phthalate esters in sewage plant effluents were detected with high concentration in Canada, Spain and China, respectively.

消费品中的环境内分泌干扰物(EDCs)及其对健康的危害

环境内分泌干扰物(EDCs)是一类化学品,可以冒充天然激素,混进人和动物的内分泌系统,模仿、阻断或干扰天然激素而引起内分泌紊乱,造成人类和动物体内内分泌失调、生殖能力下降、发育失衡,甚至引发恶性肿瘤和生物绝种。环境内分泌干扰物种类很多,已经确定的有邻苯二甲酸酯类、重金属类、双酚A以及溴化阻燃剂等。本文综述了近年来消费品中环境内分泌干扰物对健康危害作用的研究进展,主要包括环境内分泌干扰物的种类、环境内分泌干扰物在消费品中的分布,及其对人类健康的危害等研究进展。

Development of an analytical method to determine phenolic endocrine disrupting chemicals in sewage and sludge by GC/MS

An analytical method has been developed to determine bisphenol A and five degradation products of al-kylphenol ethoxylates in sewage and sludge. The parameters of accelerated solvent extraction (ASE) were optimized. C18 cartridge was used to clean up the sewage and the extract of sludge. The sensitivity of the mass detector was improved by adjusting the voltage of the lens manually. The instrumental detection limit was 3.2―17.8 pg. The method detection limits were 2.5―11.4 ng/L and 0.3―2.1 ng/g for sewage and sludge analysis respectively. The recovery and relative standard deviation for sewage analysis were 79.2%―111.4% and 6.9%―12.6%; for sludge analysis were 68.5%―114.0% and 8.9%―16.0%. Finally this method was applied to determin-ing the phenolic endocrine disrupting chemicals in sewage and sludge from a sewage treatment plant in Beijing.

Roles of membrane and organic fouling layers on the removal of endocrine disrupting chemicals in microfiltration

To understand the adsorption behavior of endocrine disrupting chemicals（EDCs） is important for enhancing the treatment performance and preventing potential secondary pollution caused by EDCs desorption in a microfiltration system. The dynamic adsorption of four representative EDCs, namely estriol（E3）, 17β-estradiol（E2）, 17α-ethynylestradiol（EE2）, and 4-nonylphenol（4-NP） in a microfiltration system was investigated using the Thomas＇ model.The product of the equilibrium constant and the total adsorption capacity of the membrane,Ka, for E3, E2, EE2, and 4-NP were 4.91, 9.78, 15.6, and 826, respectively, strongly correlating with the compound octanol–water partition coefficient（KOW）. Adsorption appeared to be enhanced when organic fouling formed on the surface of membrane, indicating the role of an additional adsorption column for EDCs acted by a fouling layer in microfiltration. Results of a comparison between the Ka values for clean membrane and fouled membrane illustrated that the significant contribution made by fouling layers may be attributed to the foulant layer＇s hydrophobicity（in the case of calcium humate layer） and thickness（in the case of calcium alginate layer）. This study provided a novel perspective to quantitatively analyze the dynamic adsorption behavior of trace pollutants in membrane process.

Adsorption and biodegradation of three selected endocrine disrupting chemicals in river-based artificial groundwater recharge with reclaimed municipal wastewater

Endocrine disrupting chemical（EDC） pollution in river-based artificial groundwater recharge using reclaimed municipal wastewater poses a potential threat to groundwater-based drinking water supplies in Beijing, China. Lab-scale leaching column experiments simulating recharge were conducted to study the adsorption, biodegradation, and transport characteristics of three selected EDCs： 17β-estradiol（E2）, 17α-ethinylestradiol（EE2） and bisphenol A（BPA）. The three recharge columns were operated under the conditions of continual sterilization recharge（CSR）, continual recharge（CR）, and wetting and drying alternative recharge（WDAR）. The results showed that the attenuation effect of the EDCs was in the order of WDAR 〉 CR 〉 CSR system and E2 〉 EE2 〉 BPA, which followed first-order kinetics. The EDC attenuation rate constants were 0.0783, 0.0505, and 0.0479 m-1 for E2, EE2 and BPA in the CR system, respectively. The removal rates of E2, EE2, and BPA in the CR system were 98%, 96% and 92%, which mainly depended on biodegradation and were affected by water temperature.In the CR system, the concentrations of BPA, EE2, and E2 in soil were 4, 6 and 10 times higher than in the WDAR system, respectively. According to the DGGE fingerprints, the bacterial community in the bottom layer was more diverse than in the upper layer, which was related to the EDC concentrations in the water-soil system. The dominant group was found to be proteobacteria, including Betaproteobacteria and Alphaproteobacteria, suggesting that these microbes might play an important role in EDC degradation.