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ToxSci Advance Access published online on November 20, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn245
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Particokinetics and extrapulmonary translocation of intratracheally instilled ferric oxide nanoparticles in rats and the potential health risk assessment

Mo-Tao Zhu{dagger},{ddagger}, Wei-Yue Feng{dagger}, Yun Wang{dagger},{ddagger}, Bing Wang{dagger}, Meng Wang{dagger}, Hong Ouyang{dagger}, Yu-Liang Zhao{dagger} and Zhi-Fang Chai{dagger}

{dagger} Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China {ddagger} Graduate School of Chinese Academy of Sciences, Beijing 100049, China

Corresponding author: Wei-Yue Feng, P.O. Box 918, Beijing 100049, China. fengwy{at}mail.ihep.ac.cn, Tel: +8610 88233209; Fax: +8610 88235294.

Received September 5, 2008; revision received October 29, 2008; accepted November 7, 2008


  Abstract

Exposure to nanoparticles has presented potential risks to human cardiorespiratory systems. Pulmonary retention and extrapulmonary redistribution of inhaled nanoparticles have been considered to be important contributing factors of cardiorespiratory diseases. In the present work, 22 nm 59Fe2O3 nanoparticles (radioactive isotope 59Fe-labeled ferric oxide nanoparticles) were intratracheally instilled into the male Sprague Dawley rats at a dose of 4 mg/rat. Extrapulmonary distribution of 59Fe2O3 in organs and its metabolism in lung, blood, urine and feces were measured for 50 days of exposure. Phagocytosis and clearance of agglomerated nano-Fe2O3 by monocytes/macrophages were observed by histopathology and ICP-MS examination. Our results showed intratracheal-instilled nano-59Fe2O3 could pass through the alveolar-capillary barrier into systemic circulation within 10 min that consisted with one-compartment kinetic model. The nano-59Fe2O3 in the lung was distributed to organs rich in mononuclear phagocytes, including liver, spleen, kidney and testicle. The plasma elimination half-life of nano-59Fe2O3 was 22.8 day and the lung clearance rate was 3.06 µg/day, indicating the systemic accumulation and lung retention had occurred. The deposited nano-Fe2O3 in interstitial lung was probably contributed by the particles escaping from alveolar macrophages phagocytosis and macrophages clearance function overloading. Our results suggest that the effect of Fe2O3 nanoparticles exposure, even at low concentration, should be assessed because of the potential lung and systemic cumulative toxicity of the nanoparticles.

Key Words: ferric oxide nanoparticle; extrapulmonary translocation; particokinetics; lung retention; health risk assessment.


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