title: 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.
authors.affiliation: GSF-National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg/Munich, Germany. Kreyling@gsf.de
authors.forename: W G
authors.initials: WG
authors.lastname: Kreyling
authors.forename: M
authors.initials: M
authors.lastname: Semmler
authors.forename: F
authors.initials: F
authors.lastname: Erbe
authors.forename: P
authors.initials: P
authors.lastname: Mayer
authors.forename: S
authors.initials: S
authors.lastname: Takenaka
authors.forename: H
authors.initials: H
authors.lastname: Schulz
authors.forename: G
authors.initials: G
authors.lastname: Oberdörster
authors.forename: A
authors.initials: A
authors.lastname: Ziesenis
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D007495:Iridium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010316:Particle Size; D051381:Rats; D011921:Rats, Inbred WKY; D013051:Spectrometry, Gamma; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D016482:Urinalysis
chemical_list: D000336:Aerosols; D007495:Iridium