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The role of alveolar macrophages in the fate of ultrafine particles in the lung was investigated. Male Wistar-Kyoto rats were exposed to ultrafine gold particles, generated by a spark generator, for 6 h at a concentration of 88 μg/m 3 (4 × 10 6 /cm 3 , 16 nm modal mobility diameter). Up to 7 days, the animals were serially sacrificed, and lavaged cells and lung tissues were examined by transmission electron microscopy. The gold concentration/content in the lung, lavage fluid, and blood was estimated by inductively coupled plasma–mass spectrometry. Gold particles used were spherical and electron dense with diameters of 5–8 nm. The particles were individual or slightly agglomerated. By inductively coupled plasma–mass spectrometry analysis of the lung, 1945 ± 57 ng (mean ± SD) and 1512 ± 184 ng of gold were detected on day 0 and on day 7, respectively, indicating that a large portion of the deposited gold particles was retained in the lung tissue. In the lavage fluid, 573 ± 67 ng and 96 ± 29 ng were found on day 0 and day 7, respectively, which means that 29% and 6% of the retained gold particles were lavageable on these days. A low but significant increase of gold (0.03 to 0.06% of lung concentration) was found in the blood. Small vesicles containing gold particles were found in the cytoplasm of alveolar macrophages. In the alveolar septum, the gold particles were enclosed in vesicles observed in the cytoplasm of alveolar type I epithelial cells. These results indicate that inhaled ultrafine gold particles in alveolar macrophages and type I epithelial cells are processed by endocytotic pathways, though the uptake of the gold particles by alveolar macrophages is limited. To a low degree, systemic particle translocation took place. [ABSTRACT FROM AUTHOR]

Recently it was speculated that ultrafine particles (UFP) may translocate from deposition sites in the lungs to systemic circulation and whether long-term clearance differs between ultrafine and micrometer-sized particles. We have studied lung retention and clearance kinetics in 12 healthy male adult WKY rats up to 6 mo after an inhalation of 192r-radiolabeled, insoluble, ultrafine 15- to 20-nm iridium particles. Whole-body retention was followed by external gamma counting, and particle clearance kinetics were determined by excretion radioanalysis. Four rats each were sacrificed after 3 wk and 2 and 6 mo; all organs as well as tissues and the carcass were radioanalyzed to balance the entire deposited radioactivity of the particles. The most prominant fraction was retained in the lungs at each time point of sacrifice (26%, 15%, 6%, respectively), and clearance out of the body was solely via excretion. Extrapulmonary particle uptake did not continue to increase but decreased with time in liver, spleen, heart, and brain when compared to previous data obtained during the first 7 days after inhalation (Kreyling et al., 2002). UFP long-term lung retention derived from whole-body measurements was comparable to previously reported data using insoluble micrometer-sized particles (Bellmann et al., 1994; Lehnert et al., 1989). In addition, differential analysis including daily excretion data revealed a pattern of fractional particle clearance rate of the ultrafine iridium particles similar to that of micrometer- sized particles reported by Snipes et al. (1983) and Bailey et al. (1985). [ABSTRACT FROM AUTHOR]

Recently it was speculated that ultrafine particles may translocate from deposition sites in the lungs to systemic circulation. This could lead to accumulation and potentially adverse reactions in critical organs such as liver, heart, and even brain, consistent with the hypothesis that ultrafine insoluble particles may play a role in the onset of cardiovascular diseases, as growing evidence from epidemiological studies suggests. Ultrafine [sup 192]Ir radio-labeled iridium particles (15 and 80 nm count median diameter) generated by spark discharging were inhaled by young adult, healthy, male WKY rats ventilated for 1 h via an endotracheal tube. After exposure, excreta were collected quantitatively. At time points ranging from 6 h to 7 d, rats were sacrificed, and a complete balance of [sup 192]Ir activity retained in the body and cleared by excretion was determined gamma spectroscopically. Thoracic deposition fractions of inhaled 15- and 80-nm [sup 192]Ir particles were 0.49 and 0.28, respectively. Both batches of ultrafine iridium particles proved to be insoluble (<1% in 7 d). During wk 1 after inhalation particles were predominantly cleared via airways into the gastrointestinal tract and feces. This cleared fraction includes particles deposited in the alveolar region. Additionally, minute particle translocation of <1% of the deposited particles into secondary organs such as liver, spleen, heart, and brain was measured after systemic uptake from the lungs. The translocated fraction of the 80-nm particles was about an order of magnitude less than that of 15-nm particles. In additional studies, the biokinetics of ultrafine particles and soluble [sup 192]Ir was studied after administration by either gavage or intratracheal instillation or intravenous injection. They confirmed the low solubility of the particles and proved that (1) particles were neither dissolved nor absorbed from the gut, (2) systemically circulating particles were rapidly and quantitatively accumulated in the liver and spleen and retained there, and (3) soluble [sup 192]Ir instilled in the lungs was rapidly excreted via urine with little retention in the lungs and other organs. This study indicates that only a rather small fraction of ultrafine iridium particles has access from peripheral lungs to systemic circulation and extrapulmonary organs. Therefore, the hypothesis that systemic access of ultrafine insoluble particles may generally induce adverse reactions in the cardiovascular system and liver leading to the onset of cardiovascular diseases needs additional detailed and differentiated consideration. [ABSTRACT FROM AUTHOR]