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Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties.
Particle and Fibre Toxicology ( IF 7.2 ) Pub Date : 2020-08-08 , DOI: 10.1186/s12989-020-00369-9
Katja Maria Bendtsen 1 , Louise Gren 2, 3 , Vilhelm Berg Malmborg 2, 3 , Pravesh Chandra Shukla 4 , Martin Tunér 4 , Yona J Essig 5 , Annette M Krais 5 , Per Axel Clausen 1 , Trine Berthing 1 , Katrin Loeschner 6 , Nicklas Raun Jacobsen 1 , Henrik Wolff 7 , Joakim Pagels 2, 3 , Ulla Birgitte Vogel 1, 8
Affiliation  

Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28, and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black. Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15–22 nm, specific surface area: 152–222 m2/g, and count median mobility diameter: 55–103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12–0.60), polycyclic aromatic hydrocarbon content (1–27 μg/mg) and acid-extractable metal content (0.9–16 μg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28 post-exposure, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in lung on day 28 and in liver on day 90 correlated with acellular particle-induced ROS. We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights specific surface area, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.

中文翻译:

滴注五种设计用于理化性质不同的柴油机排气颗粒后,C57BL / 6小鼠的颗粒表征和毒性。

柴油机废气具有致癌性,暴露于柴油机颗粒会危害健康。我们调查了旨在具有不同理化特性的柴油机废气颗粒的毒性,以便将健康影响归因于特定的颗粒特征。在发动机进气氧浓度为13%的情况下比较了三种燃料的颗粒:MK1超低硫柴油(DEP13)和两种加氢处理的植物油(HVO13)和菜籽甲酯(RME13)的可再生柴油燃料。此外,MK1超低硫柴油的柴油颗粒产生的进气O2浓度为9.7%(DEP9.7)和17%(DEP17)。与参考柴油颗粒和炭黑相比,我们在小鼠单次气管内滴注后第1、28和90天评估了理化性质以及组织病理学,炎症和遗传毒性反应。五个颗粒的物理性质存在中等变化:一次粒径:15–22 nm,比表面积:152–222 m2 / g,计数中值迁移度直径:55–103 nm。在化学成分上发现更大的差异:有机碳/总碳之比(0.12-0.60),多环芳烃含量(1-27μg/ mg)和可酸萃取的金属含量(0.9-16μg/ mg)。气管内暴露于所有五个颗粒会引起相似的毒理学反应,但效力不同。暴露后第28天,在暴露于DEP13和HVO13的小鼠中观察到肺部颗粒保留,而其他燃料类型的保留较少。RME暴露引起有限的反应,而其余颗粒在第1天引起剂量依赖性炎症和急性期反应。DEP13在第28天诱导了急性期反应,在第90天引起了炎症。与媒介物相比,DNA链断裂水平没有增加,但与空白滤膜提取物对照相比,在肺和肝脏中DNA断裂的水平增加了。第一天的中性粒细胞流入与估计的沉积表面积最相关,但也与元素碳,有机碳和PAHs相关。第28天,肺中和90天时,肝脏中的DNA链断裂水平与脱细胞颗粒诱导的ROS相关。我们研究了旨在改变其理化特性的柴油机尾气颗粒。我们的研究突出了比表面积,元素碳含量,多环芳烃和产生ROS的潜力,作为柴油颗粒毒性的物理化学预测指标。但与空白滤器抽取对照相比,肺和肝中的这些元素增加。第一天的中性粒细胞流入与估计的沉积表面积最相关,但也与元素碳,有机碳和PAHs相关。第28天,肺中和90天时,肝中的DNA链断裂水平与脱细胞颗粒诱导的ROS相关。我们研究了旨在改变其理化特性的柴油机尾气颗粒。我们的研究突出了比表面积,元素碳含量,多环芳烃和产生ROS的潜力,作为柴油颗粒毒性的物理化学预测指标。但与空白滤器抽取对照相比,肺和肝中的这些元素增加了。第一天的中性粒细胞流入与估计的沉积表面积最相关,但也与元素碳,有机碳和PAHs相关。第28天,肺中和90天时,肝脏中的DNA链断裂水平与脱细胞颗粒诱导的ROS相关。我们研究了旨在改变其理化特性的柴油机尾气颗粒。我们的研究突出了比表面积,元素碳含量,多环芳烃和产生ROS的潜力,作为柴油颗粒毒性的物理化学指标。我们研究了旨在改变其理化特性的柴油机尾气颗粒。我们的研究突出了比表面积,元素碳含量,多环芳烃和产生ROS的潜力,作为柴油颗粒毒性的物理化学指标。我们研究了旨在改变其理化特性的柴油机尾气颗粒。我们的研究突出了比表面积,元素碳含量,多环芳烃和产生ROS的潜力,作为柴油颗粒毒性的物理化学指标。
更新日期:2020-08-08
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