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 (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 (192)Ir activity retained in the body and cleared by excretion was determined gamma spectroscopically. Thoracic deposition fractions of inhaled 15- and 80-nm (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 (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 (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#10; 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.

The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis. Rats were exposed for 6 hr at a concentration of 133 microg EAg m(3) (3 x 10(6) cm(3), 15 nm modal diameter) and were sacrificed on days 0, 1, 4, and 7. ICP-MS analysis showed that 1.7 microg Ag was found in the lungs immediately after the end of exposure. Amounts of Ag in the lungs decreased rapidly with time, and by day 7 only 4% of the initial burden remained. In the blood, significant amounts of Ag were detected on day 0 and thereafter decreased rapidly. In the liver, kidney, spleen, brain, and heart, low concentrations of Ag were observed. Nasal cavities, especially the posterior portion, and lung-associated lymph nodes showed relatively high concentrations of Ag. For comparison, rats received by intratracheal instillation either 150 microL aqueous solution of 7 microg silver nitrate (AgNO(3) (4.4 microg Ag) or 150 microL aqueous suspension of 50 microg agglomerated ultrafine EAg particles. A portion of the agglomerates remained undissolved in the alveolar macrophages and in the septum for at least 7 days. In contrast, rapid clearance of instilled water-soluble AgNO(3) from the lung was observed. These findings show that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well as after instillation of AgNO(3), and entered systemic pathways.

The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis. Rats were exposed for 6 hr at a concentration of 133 microg EAg m(3) (3 x 10(6) cm(3), 15 nm modal diameter) and were sacrificed on days 0, 1, 4, and 7. ICP-MS analysis showed that 1.7 microg Ag was found in the lungs immediately after the end of exposure. Amounts of Ag in the lungs decreased rapidly with time, and by day 7 only 4% of the initial burden remained. In the blood, significant amounts of Ag were detected on day 0 and thereafter decreased rapidly. In the liver, kidney, spleen, brain, and heart, low concentrations of Ag were observed. Nasal cavities, especially the posterior portion, and lung-associated lymph nodes showed relatively high concentrations of Ag. For comparison, rats received by intratracheal instillation either 150 microL aqueous solution of 7 microg silver nitrate (AgNO(3) (4.4 microg Ag) or 150 microL aqueous suspension of 50 microg agglomerated ultrafine EAg particles. A portion of the agglomerates remained undissolved in the alveolar macrophages and in the septum for at least 7 days. In contrast, rapid clearance of instilled water-soluble AgNO(3) from the lung was observed. These findings show that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well as after instillation of AgNO(3), and entered systemic pathways.

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The purpose of the present study was to determine the strain-specific phenotype variance of lung function parameters among common inbred laboratory mouse strains. In accordance with the "Mouse Phenome Project" run by The Jackson Laboratory (http://www.jax.org/phenome), lung volumes, lung mechanics, and diffusing capacity of 16 males and 16 females of the strains C3H/HeJ, BALB/cByJ, C57B1/6J, A/J, FVB/J, 129SV/ImJ, and SWR/J were determined in a standardized manner. The defined respiratory maneuvers for lung function testing were performed with a custom-made, computer-controlled servo-ventilator in anesthetized animals. Sex differences within the strains were found in most (83%) of the absolute lung function parameters. Usually, normalization to body or lung size completely compensates for the observed gender differences. There was great diversity between strains for all of the lung function parameters studied; for example, the total lung capacity as well as the pulmonary diffusing capacity for carbon monoxide varied by 50% and the static lung compliance by a factor of almost two among the strains. Little, but statistically significant variability was detectable for the dead space volume and the respiratory system resistance. There was no clear-cut evidence for any strain exhibiting either the smallest or the largest values for all parameters studied, suggesting that there were no simple allometric relationships of lung size between the strains. Well-established genealogical relationships among strains were not constantly reflected in phenotype similarities of pulmonary function. Therefore, these data strongly support heritable genetic traits for pulmonary function. Moreover, it constitutes a basis for further genetic lung function-related studies.