Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats
Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats
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DOI：
10.1080/00984100290071658
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发表时间：
2002-10-01
期刊：
影响因子：
--
通讯作者：
Cox, C
中科院分区：
文献类型：
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作者：
Oberdörster, G;Sharp, Z;Cox, C
对静脉注射超细颗粒的研究表明，肝脏是其从血液循环中摄取的主要器官。通过血液腔室测量吸入的超细颗粒向肺外器官的转移受到方法学困难（即标记可能脱落、部分溶解）和分析限制（极少量的测量）的阻碍。我们的初步研究目的是确定大鼠吸入单颗粒超细元素碳颗粒后，这些颗粒是否会转移到肝脏和其他肺外器官。我们使用氩气中C - 13石墨电极的电火花放电产生了计数中值直径（CMDs）为20 - 29纳米（几何标准偏差1.7）的超细C - 13颗粒作为气溶胶。9只费希尔344大鼠在全身吸入室中暴露于这些颗粒6小时，浓度分别为180和80微克/立方米；在暴露后0.5、18和24小时各处死3只动物。6只未暴露的大鼠作为对照。切除肺叶、肝脏、心脏、大脑、嗅球和肾脏，匀浆并冷冻干燥，以便通过同位素比率质谱法分析添加的C - 13。在C - 13颗粒中未检测到有机C - 13。暴露后0.5小时在肺中保留的C - 13比超细颗粒的大鼠沉积模型预测值少约70%，并且在暴露后24小时内没有显著变化。以暴露浓度归一化，暴露后期间每克肺平均添加的C - 13约为9纳克/克器官/微克/立方米。仅在高暴露浓度下，吸入后0.5小时肝脏中就积累了大量的C - 13，而在暴露后18和24小时，所有暴露大鼠肝脏中的C - 13量比肺中保留的C - 13负荷大约高五倍。在检查的其他器官中未检测到C - 13的显著增加。这些结果表明，在吸入暴露1天后，超细元素碳颗粒有效地转移到肝脏。转移途径包括从沉积在整个呼吸道的超细碳颗粒直接进入血液腔室。然而，由于预测性颗粒沉积模型表明，仅呼吸道沉积可能无法完全解释肝脏的C - 13负荷，因此也需要考虑胃肠道中存在的超细颗粒的输入。超细碳颗粒和其他不溶性（金属）超细颗粒向血液和肺外组织的这种转移可能有很大差异。
Studies with intravenously injected ultrafine particles have shown that the liver is the major organ of their uptake from the blood circulation. Measuring translocation of inhaled ultrafine particles to extrapulmonary organs via the blood compartment is hampered by methodological difficulties (i.e., label may come off, partial solubilization) and analytical limitations (measurement of very small amounts). The objective of our pilot study was to determine whether ultrafine elemental carbon particles translocate to the liver and other extrapulmonary organs following inhalation as singlet particles by rats. We generated ultrafine C-13 particles as an aerosol with count median diameters (CMDs) of 20-29 nm (GSD 1.7) using electric spark discharge of C-13 graphite electrodes in argon. Nine Fischer 344 rats were exposed to these particles for 6 h. in whole-body inhalation chambers at concentrations of 180 and 80 mug/m(3); 3 animals each were killed at 0.5, 18, and 24 h postexposure. Six unexposed rats served as controls. Lung lobes, liver, heart, brain, olfactory bulb, and kidney were excised, homogenized, and freeze-dried for analysis of the added C-13 by isotope ratio mass spectrometry. Organic C-13 was not detected in the C-13 particles. The C-13 retained in the lung at 0.5 h postexposure was about 70% less than predicted by rat deposition models for ultrafine particles, and did not change significantly during the 24-h postexposure period. Normalized to exposure concentration, the added C-13 per gram of lung on average in the postexposure period was similar to9 ng/g organ/mug/m(3). Significant amounts of C-13 had accumulated in the liver by 0.5 h postinhalation only at the high exposure concentration, whereas by 18 and 24 h postexposure the C-13 amount of the livers of all exposed rats was about fivefold greater than the C-13 burden retained in the lung. No significant increase in C-13 was detected in the other organs which were examined. These results demonstrate effective translocation of ultrafine elemental carbon particles to the liver by 1 d after inhalation exposure. Translocation pathways include direct input into the blood compartment from ultrafine carbon particles deposited throughout the respiratory tract. However, since predictive particle deposition models indicate that respiratory tract deposits alone may not fully account for the hepatic C-13 burden, input from ultrafine particles present in the GI tract needs to be considered as well. Such translocation to blood and extrapulmonary tissues may well be different between ultrafine carbon and other insoluble (metal) ultrafine particles.