Concept of assessing nanoparticle hazards considering nanoparticle dosemetric and chemical/biological response metrics.
Concept of assessing nanoparticle hazards considering nanoparticle dosemetric and chemical/biological response metrics.
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DOI：
10.1080/15287390903489422
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Oberdörster G
中科院分区：
文献类型：
--
作者：
Rushton EK;Jiang J;Leonard SS;Eberly S;Castranova V;Biswas P;Elder A;Han X;Gelein R;Finkelstein J;Oberdörster G
工程纳米颗粒（NPs）正在开发中，并被纳入许多商业产品，提高了在制造、使用和处置过程中人类接触的可能性。虽然已经报道了一些NPs潜在毒性的数据，但缺乏有效的简单测定方法来预测其体内毒性。评估基于NPs化学和生物活性的新反应指标，用于筛选可用于预测NPs体内毒性的试验。评估了两种无细胞和两种基于细胞的测定方法在预测八种具有广泛不同物理化学特征的不同颗粒类型的体内毒性方面的能力。无细胞系统包括基于荧光和电子自旋共振的氧化活性测定。基于细胞的系统还使用电子自旋共振和荧光素酶报告活性来对不同颗粒类型进行排序，并与低活性和高活性的基准颗粒进行比较。体内实验评估了大鼠的急性肺部炎症反应。所有试验的终点都与氧化应激有关，反应以单位NP表面积表示，以比较不同试验的结果。结果表明，NPs能够产生反应性物质，在生物系统中可导致氧化应激。铜NPs的活性最高，而TiO2和金NPs的活性最低。当基于测量的反应进行比较时，发现不同测定法之间NP活性排序的差异。然而，表达每单位颗粒表面积的化学（无细胞）和生物（细胞；体内）活性表明，所有体外检测结果与体内结果显著相关（R>0.81），其中细胞检测结果相关性最好（R>0.87）。本研究的数据表明，通过使用基于NP表面面积的剂量和反应指标，可以通过无细胞和细胞分析来预测NP的急性体内炎症潜力，但需要细胞成分来实现更高程度的预测能力。
Engineered nanoparticles (NPs) are being developed and incorporated in a number of commercial products raising the potential of human exposure during manufacture, use and disposal. Although data about the potential toxicity of some NPs have been reported, validated simple assays are lacking for predicting their in vivo toxicity. To evaluate new response-metrics based on chemical and biological activity of NPs for screening assays that can be used to predict NP toxicity in vivo. Two cell-free and two cell-based assays were evaluated for their power in predicting in vivo toxicity of eight distinct particle types with widely differing physico-chemical characteristics. The cell-free systems comprised fluorescence- and electron spin resonance-based assays of oxidant activity. The cell-based systems also used electron spin resonance as well as luciferase reporter activity to rank the different particle types in comparison to benchmark particles of low and high activity. In vivo experiments evaluated acute pulmonary inflammatory responses in rats. Endpoints in all assays were related to oxidative stress and responses were expressed per unit NP surface area to compare the results of the different assays. Results indicate that NPs are capable of producing reactive species, which in biological systems can lead to oxidative stress. Copper NPs had the greatest activity in all assays, while TiO2 and gold NPs generally were the least reactive. Differences in the ranking of NP activity among the assays were found when comparisons were based on measured responses. However, expressing the chemical (cell-free) and biological (cells; in vivo) activity per unit particle surface area showed that all in vitro assays correlated significantly with in vivo results (R>0.81), with the cellular assays correlating best (R>0.87). Data from this study indicate that it is possible to predict acute in vivo inflammatory potential of NPs with cell-free and cellular assays by using NP surface area-based dose and response metrics, but that a cellular component is required to achieve a higher degree of predictive power.
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DOI：
10.1089/089426802320282310
发表时间：
2002-06-01
期刊：
JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG
影响因子：
--
作者：
Ibald-Mulli, A;Wichmann, HE;Peters, A
通讯作者：
Peters, A
影响因子：
2.1
作者：
Dick, CAJ;Brown, DM;Stone, V
通讯作者：
Stone, V
影响因子：
3.8
作者：
Barrett, EG;Johnston, C;Finkelstein, JN
通讯作者：
Finkelstein, JN
影响因子：
3.8
作者：
McNeilly, JD;Heal, MR;Donaldson, K
通讯作者：
Donaldson, K
影响因子：
--
作者：
Maynard, Andrew D.
通讯作者：
Maynard, Andrew D.