Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats.

Abstract

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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Systemic Vascular Disease in Male B6C3F1 Mice Exposed to Particulate Matter by Inhalation: Studies Conducted by the National Toxicology Program

“…A primary function of the lung is to provide an extensive capillary network for the uptake and distribution of inhaled substances directly into the bloodstream. Recently, Takenaka et al reported that inhalation of low concentrations of ultrafine (15 nm) elemental silver particles by rats over a 7-day period appeared rapidly in the blood at day 0 and decreased rapidly thereafter (27). Low concentrations of silver were subsequently found in the liver, kidney, spleen, brain, and heart.…”

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“…Many studies have investigated the impact of these inhaled particles on the body. Takenaka et al [75] exposed rats to 50 µg fine silver particles through intratracheal instillation for a few hours.…”

“…After inhalation, particles accumulate in the different organs, especially in the liver [75][76][77]. In a study conducted on healthy mice, Khandoga et al [76] reported that ultrafine carbon particles, when translocated after inhalation, went through the microcirculation of extrapulmonary organs, leading especially to platelet accumulation in the hepatic microvasculature.…”