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首页> 外文期刊>Environmental toxicology and chemistry >Adverse Outcome Pathway Network–Based Assessment of the Interactive Effects of an Androgen Receptor Agonist and an Aromatase Inhibitor on Fish Endocrine Function
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Adverse Outcome Pathway Network–Based Assessment of the Interactive Effects of an Androgen Receptor Agonist and an Aromatase Inhibitor on Fish Endocrine Function

机译：基于不良结果通路网络的雄激素受体激动剂和芳香酶抑制剂对鱼类内分泌功能相互作用的评估

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摘要

Predictive approaches to assessing the toxicity of contaminant mixtures have been largely limited to chemicals that exert effects through the same biological molecular initiating event. However, by understanding specific pathways through which chemicals exert effects, it may be possible to identify shared "downstream" nodes as the basis for forecasting interactive effects of chemicals with different molecular initiating events. Adverse outcome pathway (AOP) networks conceptually support this type of analysis. We assessed the utility of a simple AOP network for predicting the effects of mixtures of an aromatase inhibitor (fadrozole) and an androgen receptor agonist (17 beta-trenbolone) on aspects of reproductive endocrine function in female fathead minnows. The fish were exposed to multiple concentrations of fadrozole and 17 beta-trenbolone individually or in combination for 48 or 96 h. Effects on 2 shared nodes in the AOP network, plasma 17 beta-estradiol (E2) concentration and vitellogenin (VTG) production (measured as hepatic vtg transcripts) responded as anticipated to fadrozole alone but were minimally impacted by 17 beta-trenbolone alone. Overall, there were indications that 17 beta-trenbolone enhanced decreases in E2 and vtg in fadrozole-exposed fish, as anticipated, but the results often were not statistically significant. Failure to consistently observe hypothesized interactions between fadrozole and 17 beta-trenbolone could be due to several factors, including lack of impact of 17 beta-trenbolone, inherent biological variability in the endpoints assessed, and/or an incomplete understanding of interactions (including feedback) between different pathways within the hypothalamic-pituitary-gonadal axis. Environ Toxicol Chem 2020;00:1-10. (c) 2020 SETAC
机译：评估污染物混合物毒性的预测方法主要限于通过相同的生物分子引发事件发挥作用的化学物质。但是，通过了解化学物质发挥作用的特定途径，有可能将共享的“下游”节点识别为预测具有不同分子引发事件的化学物质相互作用影响的基础。不良结果途径（AOP）网络从概念上支持这种类型的分析。我们评估了一个简单的AOP网络在预测雌性黑头min生殖内分泌功能方面对芳香化酶抑制剂（fadrozole）和雄激素受体激动剂（17β-群勃龙）混合物的影响。将这些鱼单独或联合暴露于多种浓度的法卓唑和17β-群勃龙中，持续48或96 h。对AOP网络中2个共享节点的影响，血浆17β-雌二醇（E2）浓度和卵黄蛋白原（VTG）产生（以肝vtg成绩单衡量）对单独的fadrozole产生了预期的反应，但仅受到17β-群勃龙的影响最小。总体而言，有迹象表明，正如预期的那样，有17种β-群勃龙可增强暴露于法卓唑的鱼体内E2和vtg的降低，但结果通常没有统计学意义。无法持续观察到fadrozole和17β-群勃龙之间的假设相互作用可能是由于多种因素造成的，包括缺乏17β-群勃龙的影响，所评估终点的内在生物学变异性和/或对相互作用的不完全理解（包括反馈）在下丘脑-垂体-性腺轴内的不同路径之间。环境毒性化学2020; 00：1-10。 （c）2020年SETAC

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  • 来源
    《Environmental toxicology and chemistry》 |2020年第4期|913-922|共10页
  • 作者

  • 作者单位

    US EPA Great Lakes Toxicol & Ecol Div Duluth MN 55804 USA;

    Badger Tech Serv Great Lakes Toxicol & Ecol Div Duluth MN USA;

    CNR Great Lakes Toxicol & Ecol Div Duluth MN USA;

    Student Serv Contract Great Lakes Toxicol & Ecol Div Duluth MN USA;

    Oak Ridge Inst Sci & Educ Great Lakes Toxicol & Ecol Div Duluth MN USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Fish; Endocrine; Toxicity; Mechanism; Adverse outcome pathway;

    机译：鱼;内分泌;毒性;机制;不良后果途径;

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