Pollution of Environmental Endocrine Disrupting Chemicals(EDCs) in Water and Its Adverse Reproductive Effect on Fish

Environmental endocrine disrupting chemicals （EDCs）, commonly found in the environment, come from industry and agriculture, including pesticides, fungicides, insecticides, herbicides, and other chemicals. Nowadays, more and more EDCs were released into the environment. EDCs go into water body via atmosphere sedi-mentation, surface runoff, soil eluviation, etc., so water body becomes the main place for existing. In order to attract scientific and public attention worldwide and to prevent EDCs pol ution, in this study we reviewed the classification of EDCs and their concentrations in natural water bodies, drinking water sources and water plants, and the reproductive toxicity of EDCs to fish were reviewed. EDCs could disturb the endocrine system and make reproductive organs and reproduction abnor-mal, resulting in fertility descending, reproduction function damage, community quan-tity decrease and even species extinction. In addition, EDCs could disrupt the homeostasis maintained by hormones, which would result in defects of neural de-velopment and abnormalities of the endocrine and reproductive systems. The exact molecular mechanisms have not been completely reported, but researches have suggested that multiple mechanisms were involved in the action of EDCs. Although there have been researches on the biohazard of EDCs, there stil exist problems of weakness in fundamental researches, difficulties in recognizing and identifying EDCs and high cost, which restraint the knowledge on them.

Progress in study on endocrine disrupting pesticides (EDPs) in aquatic environment

Background on the generation of the problems of endocrine disrupting pesticides (EDPs) in aquatic environment, characteristics of EDPs, adverse effects and their effect mechanism of EDPs on human and wildlife, the transportation and degradation pathways of EDPs in water and analysis methods of EDPs in water were reviewed. The importance of EDPs in water should be attached to adverse effects on wildlife and human health. It was advised to estab- lish research programs on EDPs in aquatic environment es- pecially in water supply source.

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.

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.

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.

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.

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.

Studies on the testicular toxicity of 2-bromopropane,an environmental endocrine disrupter

Aim: 2-bromopropane (2-BP) is known as an environmentalendocrine disrupter. Recently its reproductive and hematopoitic tox-icity has aroused the attention of the toxicologists. The presentstudy was designed to study its testicular toxicity in male rats.Methods; Forty male SD rats were divided into four groups of10 rats each. 2-BP was administered intraperitoneally at doses of1800 mg, 600 mg or 200 mg per kg body weight per day for 5days. The control rats were given a similar volume of the vehicle.The animals were sacrificed two days after the last dose. Results: With increasing doses, the seminiferous tubular damage wasgradually increased and the percentage of spermatogonia in the totalgerm cells gradually decreased ( P < 0. 05). The seminiferoustubular area of rats taking 1800 mg/kg was also reduced significant-ly . The body weight, testicular weight and relative testicular weightof rats taking the highest dose level were all significantly decreasedas compared with the controls. (Reprod Contracep 2001; 21; 157-60)

Study on Testicular Toxicity of 2-Bromopropane, an Environmental Endocrine Disrupter

2-Bromopropane (2-BP) is considered as a kind of environmental endocrine disrupters (EDs). Its reproductive and hematopoietic toxicity has aroused the attention of international toxicologists during the past five years.In the present study, we aimed to determine experimentally the testicular toxicity of 2-BP in male rats. Materials & Methods Forty SD male rats were divided into four groups of 10 rats each. The rats were intra-abdominally administered 2-BP once per day for 5 days continuously at the doses of 1800 mg/kg, 600 mg/kg, 200 mg/kg and normal saline, respectively. The rats were dissected one week after the first administration. Results The body weight, absolute testes weight and relative testes weight of the rats in 1 800 mg/kg dose group decreased significantly with comparison to those of the con- trol group,while the weight of accessory gonads showed no significant change. With the increase of dosage, the seminiferous tubules damage rate aggravated while the ratio of spermatogonia in total germ cells fell with P<0. 05. The seminiferous tubule area of rats in 1800 mg/kg group also reduced significantly. Under light microscopic examination, the spermatogonia of administered rats showed degeneration and chro- matin condensation. The nucleus of spermatocytes appeared hyperchromatic and py- knotic.Obvious testicular damage could be found in rats of high dose group, including large amount of spermatogonia necrosis or loss and reduced spermatocyte number. The electron microscopic findings were similar to those of the light microscopy, except that typical morphological change was found in the middle dose group: the structure of spermatogonia was destroyed, mitochondrion and endoplasmic reticulum scattered outside, nucleus disintegrated; some of the spermatocytes' membrane became nuclear, chromatin condensed and cogulation necrosis appeared; the nuclear membrane of round spermatids also showed slight damage. Conclusion The results indicated that testis was the target organ of 2-BP's reproduc- tive toxicity. The testicular toxicity of 2-BP started from damaging spermatogonia and its damage on spermatogonia was most obvious among all germ cells.

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.

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.

Back-propagation network improved by conjugate gradient based on genetic algorithm in QSAR study on endocrine disrupting chemicals

Since the complexity and structural diversity of man-made compounds are considered, quantitative structure-activity relationships (QSARs)-based fast screening approaches are urgently needed for the assessment of the potential risk of endocrine disrupting chemicals (EDCs). The artificial neural net-works (ANN) are capable of recognizing highly nonlinear relationships, so it will have a bright applica-tion prospect in building high-quality QSAR models. As a popular supervised training algorithm in ANN, back-propagation (BP) converges slowly and immerses in vibration frequently. In this paper, a research strategy that BP neural network was improved by conjugate gradient (CG) algorithm with a variable selection method based on genetic algorithm was applied to investigate the QSAR of EDCs. This re-sulted in a robust and highly predictive ANN model with R2 of 0.845 for the training set, q2pred of 0.81 and root-mean-square error (RMSE) of 0.688 for the test set. The result shows that our method can provide a feasible and practical tool for the rapid screening of the estrogen activity of organic compounds.

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.

Genomic organization and transcriptional modulation in response to endocrine disrupting chemicals of three vitellogenin genes in the self-fertilizing fish Kryptolebias marmoratus

Vitellogenin（Vtg）is the precursor of egg yolk proteins,and its expression has been used as a reliable biomarker for estrogenic contamination in the aquatic environment.To examine the biomarker potential of the self-fertilizing killifish Kryptolebias marmoratus Vtgs（Km-Vtgs）,full genomic DNAs of Km-Vtgs-Aa,Km-Vtgs-Ab,and Km-Vtgs-C were cloned,sequenced,and characterized.Three Vtg genes in K.marmoratus are tandemly placed in a550 kb section of the same chromosome.In silico analysis of promoter regions revealed that both the Km-Vtgs-Aa and Km-Vtgs-Ab genes had an estrogen response element（ERE）,but the Km-Vtgs-C gene did not.However,all three Km-Vtgs genes had several ERE-half sites in their promoter regions.Phylogenetic analysis demonstrated that the three deduced amino acid residues were highly conserved with conventional Vtgs protein,forming distinctive clades within teleost Vtgs.Liver tissue showed the highest expression of Km-Vtg transcripts in all tested tissues（brain/pituitary,eye,gonad,intestine,skin,and muscle）in response to endocrine disrupting chemical（EDC）-exposed conditions.Km-Vtg transcripts were significantly increased in response to 17β-estradiol（E2）,tamoxifen（TMX）,4-n-nonylphenol（NP）,bisphenol A（BPA）,and octylphenol（OP）over 24 hr exposure.The Km-Vtg-A gene was highly expressed compared to the control in response to NP and OP.EDC-induced modulatory patterns of Km-Vtg gene expression were different depending on tissue,gender,and isoforms.

内分泌干扰物对良性前列腺增生的影响

前列腺增生是老年男性患者的常见病,发病率极高,病因机制复杂且受多种因素影响。内分泌干扰物是一类广泛存在的化合物,结构类似于激素,可对人体内分泌产生干扰。前列腺生长受到性激素调控,内分泌干扰物可以影响前列腺的生长进而导致前列腺增生的发生和进展。本文综合性分析了内分泌干扰物对前列腺增生影响的研究现状,重点分析了内分泌干扰物促进前列腺增生的作用机制,同时提出了减少内分泌干扰物暴露的预防措施,以期为临床医生和人民群众提高对内分泌干扰物和前列腺增生疾病之间联系的认识,减少内分泌干扰物的危害提供参考和借鉴。

核受体活性筛选在内分泌干扰物检测中的应用

内分泌干扰物是备受国内外关注的一类污染物,其种类繁多、分布范围广,在各类介质如水体、土壤、大气、生物体乃至人体中均有检出,对生态环境和人类健康具有潜在威胁。核受体途径是内分泌干扰物发挥作用的重要机制之一,一些内分泌干扰物可通过核受体介导途径调节靶基因的转录,从而产生内分泌干扰活性。常见的核受体响应的生物筛选方法采用离体细胞或无细胞测试,具有操作简便、速度快的特点。这些方法可用于化学纯品的内分泌干扰活性筛查,也可应用于实际复杂介质中内分泌干扰物的识别。该文综述了国内外内分泌干扰物筛选的标准方法及现状、基于核受体响应的内分泌干扰活性筛选方法以及核受体活性筛选在不同复杂介质内分泌干扰物检测中的应用,并对基于核受体活性筛选的内分泌干扰物检测的未来研究重点以及我国内分泌干扰物筛选方法的建立进行了展望,以期为我国新污染物筛查提供数据和技术参考。