雌二醇对生物体内分泌系统毒性作用机制的研究

雌二醇可扰乱生物体内激素的正常分泌,对生物体生殖发育、神经系统及免疫系统造成损伤。本文通过查阅大量文献,结合临床试验及动物试验,研究了雌二醇干扰生物体内分泌系统的作用机制,结果发现:持续大剂量的雌二醇可显著扰乱动物体的内分泌系统;脂溶性的雌二醇不易被降解,在人体内也没有特定的代谢途径,因此微量的雌二醇即可在体内蓄积进而对机体造成损伤。     

The Hourglass: A Conceptual Framework for the Transport of Biologically Active Compounds from Agricultural Landscapes

Recent research has suggested that the fate of biologically active compounds (BACs) originating from point sources such as wastewater treatment plants is fundamentally different from that of similar compounds released from nonpoint sources through runoff from agricultural landscapes. Downstream from wastewater treatment plants, BACs will degrade via a variety of mechanisms; however, their concentration in the water adjacent to the point of discharge may not decrease over time, as the compounds are continually released. In contrast, in agricultural systems, BACs are episodically introduced to surface water during snowmelt and rainstorm events, and under these circumstances, may be found in water for only hours or days after a storm event. Recent research in our laboratories as well as others, has suggested that sediments play an important role in the persistence of herbicides and steroids in watersheds after nonpoint source loading events. Conceptually, the sediment serves as both a sink and a source, equilibrating with BACs during storm events then slowly releasing them back into the water over time, long after the initial pulse of chemicals has moved downstream.     

Spatial and Temporal Patterns of Endocrine Active Chemicals in Small Streams Indicate Differential Exposure to Aquatic Organisms

Alkylphenolic chemicals (APCs) and hormones were measured six times from February through October 2007 in three Minnesota streams receiving wastewater to identify spatial and temporal patterns in concentrations and in estrogen equivalency. Fish were collected once during the study to evaluate endpoints indicative of endocrine disruption. The most commonly detected APCs were 4‐tert‐octylphenol and 4‐nonylphenol and the most commonly detected hormones were estrone and androstenedione. Chemical concentrations were greatest for nonylphenol ethoxycarboxylates (NPECs) (5,000‐140,000 ng/l), followed by 4‐nonlylphenol and 4‐nonylphenolethoxylates (50‐880 ng/l), 4‐tert‐octylphenol and 4‐tert‐octylphenolethoxylates with concentrations as great as 130 ng/l, and hormones (0.1‐54 ng/l). Patterns in chemicals and estrogen equivalency indicated that wastewater effluent is a pathway of APCs and hormones to downstream locations in this study. However, upstream contributions can be equally or more important indicating alternative sources. This study indicates that aquatic organisms experience both spatially and temporally variable exposures in the number of compounds, total concentrations, and estrogenicity. This variability was evident in fish collected from the three rivers as no clear upstream to downstream pattern of endocrine disruption endpoints emerged.     

Assessment of Endocrine‐Disrupting Chemicals Attenuation in a Coastal Plain Stream Prior to Wastewater Treatment Plant Closure

The U.S. Geological Survey is conducting a combined pre/post‐closure assessment at a long‐term wastewater treatment plant (WWTP) site at Fort Gordon near Augusta, Georgia. Here, we assess select endocrine‐active chemicals and benthic macroinvertebrate community structure prior to closure of the WWTP. Substantial downstream transport and limited instream attenuation of endocrine‐disrupting chemicals (EDCs) was observed in Spirit Creek over a 2.2‐km stream segment downstream of the WWTP outfall. A modest decline (less than 20% in all cases) in surface water detections was observed with increasing distance downstream of the WWTP and attributed to partitioning to the sediment. Estrogens detected in surface water in this study included estrone (E1), 17β‐estradiol (E2), and estriol (E3). The 5 ng/l and higher mean estrogen concentrations observed in downstream locations indicated that the potential for endocrine disruption was substantial. Concentrations of alkylphenol ethoxylate (APE) metabolite EDCs also remained statistically elevated above levels observed at the upstream control site. Wastewater‐derived pharmaceutical and APE metabolites were detected in the outflow of Spirit Lake, indicating the potential for EDC transport to aquatic ecosystems downstream of Fort Gordon. The results indicate substantial EDC occurrence, downstream transport, and persistence under continuous supply conditions and provide a baseline for a rare evaluation of ecosystem response to WWTP closure.     

Fathead Minnow and Bluegill Sunfish Life‐Stage Responses to 17β‐Estradiol Exposure in Outdoor Mesocosms

Developmental and reproductive effects of 17β‐estradiol (E2) exposure on two generations of fathead minnows and one generation of bluegill sunfish were assessed. Fish were exposed to E2 for six continuous weeks in outdoor mesocosms simulating natural lake environments. First generation fish were exposed while sexually mature. Second generation fathead minnows were exposed either during early development, sexual maturity, or both stages. Multiple endpoints were measured to assess effects of E2 exposure on fecundity and fish health and development. Plasma vitellogenin concentrations were highly variable in all fish. Differences in egg production timing for both species indicate differences in fecundity between females exposed to E2 and controls. First generation fathead minnows exposed to E2 had lower body condition factors and reduced secondary sexual characteristic expression by males. Only a difference in relative liver weight was observed in second generation fathead minnows. First generation bluegill males exposed to E2 had significantly smaller testes compared to controls. Although fish response was highly variable, results indicate that exposure to E2 at environmentally relevant concentrations affect fathead minnow and bluegill sunfish health and development, which may have implications for the health and sustainability of fish populations. Furthermore, exposure timing and environmental factors affect fish response to E2 exposure.     

罗时江中5种环境内分泌干扰物的分布特征

以典型的农业面源污染河流——大理洱海罗时江作为研究对象,采用固相萃取、超声萃取和气相色谱质谱联用技术,对河流水体和表层沉积物样品中5种EDCs〔环境内分泌干扰物,包括BPA(双酚A)、E1(雌酮)、E2(17β-雌二醇)、EE2(乙炔基雌二醇)和E3(雌三醇)〕进行分析测定.结果表明,罗时江水体中普遍存在EDCs,其中ρ(BPA)为1.01～43.64 ng/L,ρ(E1)为2.54～20.53 ng/L,ρ(E2)为nd～23.18 ng/L,ρ(EE2)为1.16～13.74 ng/L,ρ(E3)为nd～26.55 ng/L.各采样点EDCs污染通量结果显示,右所、邓川2个乡镇对EDCs污染贡献量最为显著,之后由于湿地截留以及河流的自净作用EDCs污染通量有所削减.罗时江对洱海的入湖EDCs贡献量为1.35～3.70μg/s.在城镇下游处沉积物中E1和E3的富集倍数均为各采样点中最高,这与河流水体中的污染通量变化趋势一致,进一步说明该处污染负荷的加剧,并且说明EDCs会在污染发生时于下游就近沉积.沉积物中w(E3)最高(1.48～28.44μg/kg),其次为w(E1)(0.36～2.95μg/kg),E2因迅速降解不易富集.      

太湖流域宜溧河酚类内分泌干扰物的空间分布及风险评价

以NP(nonylphenol,壬基酚)、4-t-OP(4-t-octylphenol,辛基酚)和BPA(bisphenol A,双酚A)为目标物质,研究酚类EDCs(内分泌干扰物)在太湖流域宜溧河地表水体和悬浮物中的空间分布特征及风险评价. 结果表明,太湖流域宜溧河地表水体中ρ(NP)、ρ(4-t-OP)和ρ(BPA)分别为156.2～434.0、11.8～19.4和89.8～353.8 ng/L,悬浮物中w(NP)、w(4-t-OP)和w(BPA)分别为520.0～9 818.2、52.0～454.5和39.0～2 454.5 ng/g. 流域内生活及工业污水排放可能是宜溧河流域水体中酚类EDCs的主要来源,ρ(NP)与ρ(NO₃-)呈显著正相关(R=0.860,P<0.01). 宜溧河水系中酚类EDCs在水相-悬浮物相的有机碳标准分配系数为4.14～6.41,表明悬浮颗粒物的吸附是水体中EDCs迁移的一个重要途径. 研究区域中NP、4-t-OP和BPA的入湖量分别为506、57.9和297 kg/a. 风险评价结果表明,该地区部分河段ρ(EDCs)具有潜在的生态风险.      

双酚A类似物雌激素干扰效应的定量结构-活性关系模型

由于双酚A(BPA)具有内分泌干扰等毒性效应,有些国家已经开始限制其在部分工业品生产中使用。一些双酚A类似物因用于替代BPA而被大量使用。因其与双酚A具有相似的分子结构,双酚A类似物是否也具有内分泌干扰等毒性效应受到越来越多的关注。采用逐步多元线性回归(MLR)方法,构建了可预测双酚A类似物雌激素效应的定量结构-活性关系模型。模型的决定系数R~2=0.899,去一法交叉验证系数Q_(LOO)~2=0.868,Bootstrapping验证系数Q_(BOOT)~2=0.755,均方根误差RMSE=0.339,表明模型具有较好的拟合优度、稳健性;验证集决定系数Q_(EXT)~2=0.921,外部验证系数Q_(EXT)~2=0.810,均方根误差RMSE=0.638,表明模型具有较好的预测能力。采用欧几里德距离方法和Wil iams图表征了模型应用域,依据分子描述符对模型进行了机理解释,并用所建模型,填补了22种其他双酚A类似物缺失的雌激素干扰效应数据。     

农药内分泌干扰效应研究进展

农药作为农业生产过程中的一类重要生产资料,主要用作杀虫剂、杀菌剂和除草剂等。由于农药的大量使用,目前在各类农产品及各种环境介质中都能被检测到,对饮食安全和环境健康带来潜在危害。研究发现,许多农药为内分泌干扰物,其能够干扰人类和其它生物体的内分泌系统正常功能。本文在总结国内外相关研究的基础上,对农药内分泌干扰效应的作用机理及筛选模型进行总结,对有机氯、有机磷和拟除虫菊酯等各类农药的内分泌干扰效应研究进展进行综述,并提出深入探究农药致毒作用机制和低剂量下多种农药联合毒性是本领域的重要研究方向。     

4-硝基酚对大鼠肝脏的毒性及氧化损伤

研究环境内分泌干扰物4-硝基酚(4-nitrophenol,PNP)对大鼠肝脏功能的毒性作用及其对核因子相关因子-2(Nrf2)通路的影响.20只SD雄性大鼠随机分成4个组,分别为对照组、1、10和100 mg·kg-1体重PNP处理组,连续皮下注射28d,检测肝脏的结构变化、氧化损伤和Nrf2及其相关基因的表达情况.结果表明,与对照组相比,100 mg·kg-1PNP处理组大鼠的血清肝功能主要指标ALT、AST、AKP活性和TBIL含量显著性升高p＜005);100 mg·kg-1组肝脏GSH-PX、CAT和SOD活性显著性降低p＜005);大鼠肝脏中Nrf2及其下游基因NQOI和HO-1 mRNA表达水平在1mg·kg-1组显著升高(p＜0.05),10、100 mg·kg-1组有升高趋势;100 mg ·kg-1组肝脏显微和超微结构都发现有不同程度的损伤.结果提示,皮下注射1 mg·kg-1 PNP引起了大鼠肝脏氧化损伤,机体可能通过提高Nrf2及其相关基因mRNA的表达水平来抵抗PNP引起的肝脏损伤;皮下注射100 mg·kg-1 PNP改变了肝脏的正常生理功能,造成肝细胞超微结构病理损伤,引起肝脏毒性.