Kreyling W G, Cox C, Ferron G A, Oberdörster G
GSF-Forschungszentrum für Umwelt und Gesundheit, GmbH, Projekt Inhalation, Neuherberg, Germany.
Exp Lung Res. 1993 Jul-Aug;19(4):445-67. doi: 10.3109/01902149309064357.
Lung clearance of a well-defined uniform and respirable material was conducted to aid in the development of models used to relate inhalation of inorganic hazardous particles to organ doses and bioassay measurements, and in particular to aid in the extrapolation of animal data to humans. In the present study, lung clearance was investigated in Long-Evans rats using monodisperse, porous, 0.8- and 1.7-microns-diameter cobalt oxide (Co3O4) test particles. An advanced inhalation technique for rats using endotracheal intubation yielded exclusive particle deposition in the pulmonary region without external pelt contamination, thus allowing for clearance studies starting directly after inhalation. The kinetics of lung clearance was distinguished between the two dominant clearance mechanisms of mechanical particle transport to the larynx and translocation of dissolved particle material to blood. A particle fraction of about 40% was cleared by short-term particle transport to the larynx, both the long-term particle transport rate and the translocation rate of dissolved particle material given as fractional rates of the retained particle mass in the lungs were not constant with time. The former declined from 0.03 to 0.004 d-1 during 6 months after inhalation. The latter depended on the specific surface area of the porous particles and increased with time from 0.08 and 0.04 d-1 for 0.8- and 1.7-microns particles, respectively. The results obtained were compared to previously reported data obtained from Fischer-344 rats and HMT rats. These were part of a previously reported interspecies comparison of lung clearance followed in seven species, including humans, and using the same batches of Co3O4 test particles. Long-term lung retention was similar in Long-Evans rats and HMT rats but decreased faster for both particle sizes than in Fischer-344 rats, as a result of a significantly faster translocation of dissolved material from the test particles to blood. Mechanical particle transport to the larynx was comparable in all three species.
对一种明确界定的均匀且可吸入物质进行肺部清除研究，以协助开发用于将无机有害颗粒的吸入与器官剂量及生物测定测量相关联的模型，特别是协助将动物数据外推至人类。在本研究中，使用单分散、多孔、直径为0.8微米和1.7微米的氧化钴（Co3O4）测试颗粒，对Long-Evans大鼠的肺部清除情况进行了研究。一种使用气管插管的先进大鼠吸入技术可使颗粒仅沉积在肺部区域，而无外部皮毛污染，从而能够在吸入后直接开始清除研究。肺部清除的动力学在颗粒机械性转运至喉部和溶解颗粒物质转运至血液这两种主要清除机制之间有所区别。约40%的颗粒部分通过短期颗粒转运至喉部而被清除，长期颗粒转运速率和溶解颗粒物质的转运速率（均以肺部留存颗粒质量的分数速率表示）随时间并非恒定不变。前者在吸入后6个月内从0.03降至0.004 d⁻¹。后者取决于多孔颗粒的比表面积，对于0.8微米和1.7微米的颗粒，分别从0.08和0.04 d⁻¹随时间增加。将所得结果与先前从Fischer-344大鼠和HMT大鼠获得的报告数据进行了比较。这些数据是先前报告的七种物种（包括人类）肺部清除种间比较的一部分，且使用的是同一批次的Co3O4测试颗粒。Long-Evans大鼠和HMT大鼠的长期肺部留存情况相似，但两种颗粒尺寸的留存率下降速度均比Fischer-344大鼠快得多这是由于测试颗粒中溶解物质向血液的转运明显更快。在所有三个物种中，颗粒向喉部的机械性转运情况相当。
