Time-response relationship of nano and micro particle induced lung inflammation. Quartz as reference compound

Research output: Contribution to journalJournal articleResearchpeer-review

Martin Roursgaard, Steen Seier Poulsen, Lars K. Poulsen, Maria Hammer, Keld A. Jensen, Satoshi Utsunomiya, Rodney C. Ewing, Tonci Balic Zunic, Gunnar D. Nielsen, Søren T. Larsen

An increasing number of engineered particles, including nanoparticles, are being manufactured, increasing the need for simple low-dose toxicological screening methods. This study aimed to investigate the kinetics of biomarkers related to acute and sub-chronic particle-induced lung inflammation of quartz. Mice were intratracheal instilled with 50 µg of microsized or nanosized quartz. Acute inflammation was assessed 1, 2, 4, 8, 16 or 48 hours post exposure, whereas sub-chronic inflammation was investigated 3 months after exposure. Markers of acute inflammation in the bronchoalveolar lavage fluid (BALF) were neutrophils (PMN), tumor necrosis factor-alpha (TNF-a), interleukin (IL)-1ß, macrophage inflammatory protein-2 (MIP-2), keratinocyte derived chemokine (KC) and total protein, which were all close to maximum 16 hours post instillation. No major differences were seen in the time-response profiles of nano- and micro-sized particles. The potency of the two samples cannot be compared; during the milling process, a substantial part of the quartz was converted to amorphous silica and contaminated with corundum. For screening, BALF PMN, either TNF-a or IL-1ß at 16 hours post instillation may be useful. At 3 months post instillation, KC, PMN and macrophages were elevated. Histology showed no interstitial inflammation three months post instillation. For screening of sub-chronic effects, KC, PMN, macrophages and histopathology is considered sufficient.
Original languageEnglish
JournalHuman & Experimental Toxicology
Volume29
Issue number11
Pages (from-to)915-933
Number of pages19
ISSN0960-3271
DOIs
Publication statusPublished - 2010

    Research areas

  • Animals, Bronchoalveolar Lavage Fluid, Cytokines, Dose-Response Relationship, Drug, Female, Inhalation Exposure, Mice, Mice, Inbred BALB C, Microscopy, Electron, Transmission, Nanoparticles, Neutrophils, Particle Size, Pneumonia, Powder Diffraction, Quartz, Surface Properties, Time Factors, Toxicity Tests, X-Ray Diffraction

ID: 33717947