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首页> 外文期刊>Environmental Science & Technology >Development of an in Vitro-Based Risk Assessment Framework for Predicting Ambient Particulate Matter-Bound Polycyclic Aromatic Hydrocarbon-Activated Toxicity Pathways
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Development of an in Vitro-Based Risk Assessment Framework for Predicting Ambient Particulate Matter-Bound Polycyclic Aromatic Hydrocarbon-Activated Toxicity Pathways

机译：基于体外的风险评估框架的开发，用于预测环境颗粒物约束的多环芳烃活化的毒性途径

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摘要

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed throughout the atmosphere as mixtures attached to ambient particulate matter (PM). PAHs usually elicit similar toxicological pathways but do so with varying levels of efficacy. In this study, we utilized high-throughput screening (HTS) in vitro data of PAHs to predict health risks associated with coarse and fine PM. PM samples with 22 PAH compounds obtained from residential areas close to industrial parks in central Taiwan were analyzed. On the basis of the PM-bound PAH concentrations and their activities reported in HTS assays, we developed a probabilistic model for estimating cumulative exposure of humans to PAHs. Activity-to-exposure ratio (AER) values were calculated to compare relative risks of activating the aryl hydrocarbon receptor (AhR), nuclear factor erythroid 2-related factor 2 (Nrf2), and tumor suppressor gene (p53) when children or adults were exposed to fine or coarse PM in different seasons. On the basis of AER values, the risk of fine PM exposure was relatively higher than the risk of exposure to coarse PM in pathway activation. Children as a susceptible population had a risk of the activating AhR pathway greater than that of adults. Particularly higher risks were observed in winter than in summer. Among three pathways, AhR was the most sensitive one activated by exposure to PAHs. In addition, the activation of the AhR, Nrf2, and p53 pathways was compared by in vitro reporter assays with and without the pre-extraction of PAHs from PM. Our proposed novel approach accounts for mixture toxicities in characterizing in vitro pathway-based risks via inhalation exposure to ambient PAHs.
机译：多环芳烃（PAHs）以附着在周围颗粒物（PM）上的混合物的形式广泛分布在整个大气中。多环芳烃通常会引起相似的毒理学途径，但其功效水平却有所不同。在这项研究中，我们利用PAHs的高通量筛选（HTS）体外数据来预测与粗颗粒和细颗粒PM相关的健康风险。分析了来自台湾中部工业园区附近居民区的22种PAH化合物的PM样品。根据在HTS分析中报告的PM结合的PAH浓度及其活性，我们开发了一个概率模型来估计人类对PAHs的累积暴露。计算活动暴露比（AER）的值，以比较在儿童或成人时激活芳基烃受体（AhR），核因子类红细胞2相关因子2（Nrf2）和抑癌基因（p53）的相对风险。在不同的季节暴露于细颗粒或粗颗粒PM基于AER值，细微PM暴露的风险相对于通路激活中粗PM暴露的风险相对较高。儿童作为易感人群的激活AhR途径的风险大于成人。与冬季相比，冬季的风险尤其高。在三种途径中，AhR是通过暴露于PAHs激活的最敏感的途径。此外，在有和没有从PM中预提取PAH的情况下，通过体外报告基因分析比较了AhR，Nrf2和p53途径的激活。我们提出的新方法通过吸入暴露于环境PAHs来表征混合物在基于体外​​途径的风险中的毒性。

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  • 来源
    《Environmental Science & Technology》 |2017年第24期|14262-14272|共11页
  • 作者

    Chou Wei-Chun; Hsu Chin-Yu; Ho Chia-Chi; Hsieh Jui-Hua; Chiang Hung-Che; Tsou Tsui-Chun; Chen Yu-Cheng; Lin Pinpin;

  • 作者单位

    Natl Hlth Res Inst, Natl Inst Environm Hlth Sci, Zhunan 35053, Taiwan;

    Natl Hlth Res Inst, Natl Inst Environm Hlth Sci, Zhunan 35053, Taiwan;

    Natl Hlth Res Inst, Natl Inst Environm Hlth Sci, Zhunan 35053, Taiwan;

    Kelly Govt Solut, Res Triangle Pk, NC 27709 USA;

    Natl Hlth Res Inst, Natl Inst Environm Hlth Sci, Zhunan 35053, Taiwan;

    Natl Hlth Res Inst, Natl Inst Environm Hlth Sci, Zhunan 35053, Taiwan;

    Natl Hlth Res Inst, Natl Inst Environm Hlth Sci, Zhunan 35053, Taiwan;

    Natl Hlth Res Inst, Natl Inst Environm Hlth Sci, Zhunan 35053, Taiwan;

  • 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);
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