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首页> 外文学位 >Predicting the estrogenic and androgenic activity of environmental waters: A quantitative study on mixture interactions.
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Predicting the estrogenic and androgenic activity of environmental waters: A quantitative study on mixture interactions.

机译：预测环境水的雌激素和雄激素活性：混合物相互作用的定量研究。

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摘要

Steroid hormones confer biological activity to effluents of wastewater treatment plants (WWTPs). The occurrence of estrogen and androgen hormones in addition to their biological effects in the environment have been widely studied and there is a growing consensus that mixtures of steroid hormones; albeit at low ng L-1concentrations, lead to endocrine disruption in some aquatic organisms. These mixtures may also be influenced by the contributions of synthetic estrogens and androgens, which may display either additive or antagonistic activity.;Agreement between the chemically and biologically derived IEQs means that the major contributors to the biological effect have been successfully identified. However, the biological assays measure the contribution of additive, antagonistic and synergistic activity in the mixture; therefore, the biologically derived IEQs represent the net biological activity. Chemical methods are unable to predict these interactions and as such the result of the concentration addition (CA) approach (Equation 1) is often inconclusive and suggestive of interacting components. An interaction model that can estimate the net biological activity of a mixture from the concentrations of individual mixture constituents (chemical methods) is thus necessary.;The aRP can be calculated for any nth mixture constituent by measuring the degree to which the mixture components altered the activity of the standard and assessing those changes as a function of mixture ratios. The interaction method was validated using a mixture of testosterone, with two anti-androgens, di-n-butyl phthalate, and bisphenol A in the YAS. Mixtures of 17β-estradiol, estriol, 17&agr;-dihydroequilin and di-n-butyl phthalate were evaluated in the YES assay. Using Equation 3 the net estrogenic and androgenic activity of the mixtures was estimated. There was a significant improvement over the CA based approach in Equation 1. Overall, in 24 out of 32 mixtures tested there was no significant difference between the aRP and observed responses. Large percent errors were observed in the CA model, particularly when the proportion of antagonists was high as the CA model tended to over-predict the responses. On the contrary, only two aRP model predictions exceeded 50% error. Risk assessors should use the CA model with caution as it could over-predict biological responses and an alternative approach such as the aRP model could be used. In this regard, a database of aRP values for identified antagonistic/synergistic compounds could be assembled and estimations of biological activity could be made using these aRP values. The aRP interaction model could also be used to provide fundamental understanding to the behavior of the constituents in a complex mixture.;Although the interaction model presented may account for possible deviations from additivity in environmental mixtures, predictions of mixture effects may be complicated by matrix interferences. In this regard, a sensitive bioassay; such as the E-Screen, which is capable of detecting concentrations as low as 0.27 ng L-1 of 17β-estradiol equivalents is beneficial. However, one major drawback to the E-Screen assay is the 6-day analysis time. In order to maintain the sensitivity of the assay and reduce the analysis time, Fourier Transform Infra-red Imaging Spectroscopy (FT-IRIS) was used to probe the bio-molecular level events that occur in single cells prior to a detectable response in cellular proliferation. The investigation revealed that changes occur on the sub-cellular level at 48-hours after incubation which are comparable to the 6 day E-Screen responses (Pearson R = 0.978). The FT-IRIS response appears to be due to the increase in mucins which are known to play a role in cellular signaling and proliferation. The EC 50 values for the E-screen and FT-IRIS assay were 2.29 and 2.56 ppt respectively, indicating that the molecular changes, which are observed at the single cell level using FT-IRIS, are reflective of physiological changes that are observed as the cell population responds to 17β-estradiol. The study indicates that sophisticated imaging and microscopy techniques such as FT-IRIS may play a role in environmental bio-analytical methods. (Abstract shortened by UMI.).
机译：类固醇激素赋予废水处理厂（WWTP）废水以生物活性。雌激素和雄激素除了在环境中具有生物学作用外，还已广泛研究，并且越来越多的共识是类固醇激素的混合物。即使在低ng L-1浓度下，也会导致某些水生生物内分泌的破坏。这些混合物也可能受到合成雌激素和雄激素的贡献的影响，它们可能表现出加性或拮抗活性。化学和生物衍生的IEQ之间的协议意味着已经成功地确定了生物效应的主要贡献者。然而，生物学测定法测量混合物中添加剂，拮抗和协同活性的贡献。因此，生物衍生的IEQ代表净生物活性。化学方法无法预测这些相互作用，因此，浓度添加（CA）方法（等式1）的结果通常是不确定的，暗示了相互作用的成分。因此，需要一种相互作用模型，该模型可以根据单个混合物成分的浓度（化学方法）估算混合物的净生物活性。通过测量混合物成分改变混合物的程度，可以计算出第n种混合物成分的aRP。标准的活性，并根据混合比评估这些变化。在YAS中，使用睾丸激素与两种抗雄激素，邻苯二甲酸二正丁酯和双酚A的混合物验证了相互作用的方法。在YES测定中评估了17β-雌二醇，雌三醇，17α-二氢安息香和邻苯二甲酸二正丁酯的混合物。使用方程式3，估计混合物的净雌激素和雄激素活性。方程式1中基于CA的方法有了显着改进。总体而言，在测试的32种混合物中，有24种的aRP与观察到的响应之间没有显着差异。在CA模型中观察到较大的百分比误差，尤其是当拮抗剂的比例很高时，因为CA模型倾向于过度预测响应。相反，只有两个aRP模型预测超过了50％的误差。风险评估者应谨慎使用CA模型，因为它可能高估生物学反应，并且可以使用替代方法，例如aRP模型。在这方面，可以组装用于确定的拮抗/协同化合物的aRP值数据库，并可以使用这些aRP值进行生物活性估计。 aRP相互作用模型还可以用于提供对复杂混合物中成分行为的基本了解。;尽管所提供的相互作用模型可能解释了环境混合物中与可加性的可能偏差，但混合物干扰的预测可能会因基质干扰而变得复杂。在这方面，进行灵敏的生物测定；例如E-Screen，它能够检测到低至0.27 ng L-1的17β-雌二醇当量的浓度是有益的。但是，E-Screen分析的一个主要缺点是分析需要6天的时间。为了维持测定的灵敏度并减少分析时间，使用了傅里叶变换红外成像光谱（FT-IRIS）来探测在单个细胞中发生的生物分子水平事件，然后才能检测到细胞增殖的反应。研究表明，孵育后48小时，亚细胞水平发生了变化，这与6天E-Screen反应相当（Pearson R = 0.978）。 FT-IRIS反应似乎是由于粘蛋白增加而引起的，粘蛋白已知在细胞信号传导和增殖中起作用。 E-screen和FT-IRIS测定的EC 50值分别为2.29和2.56 ppt，表明使用FT-IRIS在单细胞水平观察到的分子变化反映了生理变化。细胞群对17β-雌二醇有反应。研究表明，诸如FT-IRIS之类的复杂成像和显微镜技术可能在环境生物分析方法中发挥作用。 （摘要由UMI缩短。）。

著录项

  • 作者

    Johnson, Candice M.;

  • 作者单位

    Temple University.;

  • 授予单位 Temple University.;
  • 学科 Biology General.;Health Sciences Toxicology.;Engineering Environmental.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 198 p.
  • 总页数 198
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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