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首页> 外文期刊>Environmental toxicology and chemistry >Case Study in 21st Century Ecotoxicology: Using In Vitro Aromatase Inhibition Data to Predict Short‐Term In Vivo Responses in Adult Female Fish
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Case Study in 21st Century Ecotoxicology: Using In Vitro Aromatase Inhibition Data to Predict Short‐Term In Vivo Responses in Adult Female Fish

机译：21世纪生态毒理学的案例研究：使用体外芳香酶抑制数据预测成年女性鱼类的体内反应中的短期

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The present study evaluated whether in vitro measures of aromatase inhibition as inputs into a quantitative adverse outcome pathway (qAOP) construct could effectively predict in vivo effects on 17 beta-estradiol (E2) and vitellogenin (VTG) concentrations in female fathead minnows. Five chemicals identified as aromatase inhibitors in mammalian-based ToxCast assays were screened for their ability to inhibit fathead minnow aromatase in vitro. Female fathead minnows were then exposed to 3 of those chemicals: letrozole, epoxiconazole, and imazalil in concentration-response (5 concentrations plus control) for 24 h. Consistent with AOP-based expectations, all 3 chemicals caused significant reductions in plasma E2 and hepatic VTG transcription. Characteristic compensatory upregulation of aromatase and follicle-stimulating hormone receptor (fshr) transcripts in the ovary were observed for letrozole but not for the other 2 compounds. Considering the overall patterns of concentration-response and temporal concordance among endpoints, data from the in vivo experiments strengthen confidence in the qualitative relationships outlined by the AOP. Quantitatively, the qAOP model provided predictions that fell within the standard error of measured data for letrozole but not for imazalil and epoxiconazole. However, the inclusion of measured plasma concentrations of the test chemicals as inputs improved model predictions, with all predictions falling within the range of measured values. Results highlight both the utility and limitations of the qAOP and its potential use in 21st century ecotoxicology. Environ Toxicol Chem 2021;00:1-16. (c) 2020 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
机译：本研究评估了芳族酶抑制的体外测量是否作为分量不良结果途径（QAOP）构建体的输入可以有效地预测雌性Fathead MinNows中的17β-雌二醇（E2）和Vitellogen（VTG）浓度的体内效应。筛选了五种鉴定为哺乳动物的毒性酶抑制剂的化学物质，筛选其在体外抑制Fathead Minnow芳香酸酶的能力。然后将雌性Fathead MinNows暴露于其中3种化学品：Letrozole，环氧喹唑和咪唑酮浓度 - 反应（5浓度加对照）24小时。符合AOP的预期，所有3种化学品均导致血浆E2和肝VTG转录中的显着降低。对卵巢中的芳香酶和卵泡刺激激素受体（FSHR）转录物的特征补偿性上调（FSHR）转录物用于Letrozole，但不适用于其他2个化合物。考虑到端点之间的集中响应和时间相应的整体模式，来自体内实验的数据加强了对AOP概述的定性关系的信心。定量地，QAOP模型提供了在Letrozole的测量数据的标准误差内下降的预测，但不适用于咪唑唑和环氧喹唑唑。然而，将测试化学品的测量血浆浓度包含为输入改进的模型预测，所有预测落在测量值范围内。结果突出了QAOP的实用性和局限性及其在21世纪生态毒理学的潜在用途。环境毒素化学2021; 00：1-16。 （c）2020 setac。本文已被美国政府员工捐款，他们的工作是美国的公共领域。

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