Translocation of Ultrafine Insoluble Iridium Particles From Lung Epithelium to Extrapulmonary Organs Is Size Dependent but Very Low

Abstract

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.

Does nanoparticle activity depend upon size and crystal phase?

“…Nanosized TiO 2 samples were prepared using several gas phase synthesis methods: a diffusion flame aerosol reactor (Jiang et al 2007), a premixed flame aerosol reactor (Thimsen and Biswas 2007), a furnace aerosol reactor (Namiki et al 2005;Okuyama et al 1986), and a spark aerosol reactor (Kreyling et al 2002). The diffusion flame aerosol reactor was used to synthesize TiO 2 nanoparticles with large size (≥ 30 nm) and different crystal structures (anatase; anatase and rutile mixtures).…”

“…The properties of TiO 2 nanoparticles were controlled by adjusting the reactant feed rates and the temperature-time history in these reactors. Amorphous TiO 2 nanoparticles with small sizes were produced using a spark aerosol generator as reported previously (Kreyling et al 2002). A titanium electrode was used and the spark was generated in an oxygen stream.…”

Nanoparticulate materials and regulatory policy in Europe: An analysis of stakeholder perspectives

“…However, it is important to note that this lung toxicity database has been limited to studies of three types of nanoparticles: titanium dioxide, carbon black and diesel particles (Warheit, 2004). NPM may also translocate within the body, for example from the nose and lungs to the central nerve system, the brain, into the systemic circulation and to organs like the liver (Nemmar et al, 2001;Takenaka et al, 2001;Kreyling et al, 2002;Oberdorster et al, 2002;Takenaka et al, 2004). The research covering the new types of NPM is limited and the number of studies of the environmental impacts of NPM are few.…”

Translocation Pathway of the Intratracheally Instilled Ultrafine Particles from the Lung into the Blood Circulation in the Mouse

“…Recent investigations provided evidence that the UFPs can be translocated from the lungs to the extrapulmonary organs (i.e., liver, heart, spleen, brain) via the blood circulation (Nemmar et al, 2001;Takenaka et al, 2001;Kreyling et al, 2002;Oberdörster et al, 2002). Indeed, Nemmar et al (2001Nemmar et al ( , 2002a have reported that intratracheally instilled UFPs in the form of ultrafine 99m Technetium-labelled carbon particles (100 nm) or albumin nanocolloid particles (diameter < 80 nm) are quickly translocated from the lung into the systemic circulation in hamsters and humans; radioactivity was detected in blood at 1 minute and 5 minutes, respectively.…”