Particokinetics and Extrapulmonary Translocation of Intratracheally Instilled Ferric Oxide Nanoparticles in Rats and the Potential Health Risk Assessment

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 (59)Fe(2)O(3) nanoparticles (radioactive isotope (59)Fe-labeled ferric oxide nanoparticles) were intratracheally instilled into the male Sprague-Dawley rats at a dose of 4 mg/rat. Extrapulmonary distribution of (59)Fe(2)O(3) in organs and its metabolism in lung, blood, urine, and feces were measured for 50 days of exposure. Phagocytosis and clearance of agglomerated nano-Fe(2)O(3) by monocytes/macrophages were observed by histopathology and inductively coupled plasma-mass spectrometry examination. Our results showed intratracheal-instilled nano-(59)Fe(2)O(3) could pass through the alveolar-capillary barrier into systemic circulation within 10 min that consisted with one-compartment kinetic model. The nano-(59)Fe(2)O(3) in the lung was distributed to organs rich in mononuclear phagocytes, including liver, spleen, kidney and testicle. The plasma elimination half-life of nano-(59)Fe(2)O(3) was 22.8 days and the lung clearance rate was 3.06 microg/day, indicating the systemic accumulation and lung retention had occurred. The deposited nano-Fe(2)O(3) 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 Fe(2)O(3) nanoparticles exposure, even at low concentration, should be assessed because of the potential lung and systemic cumulative toxicity of the nanoparticles.

Physicochemical Characterization of Nebulized Superparamagnetic Iron Oxide Nanoparticles (SPIONs)

“…In other words, TEM provides a mean diameter number measurement of primary particles, whereas PCS and NTA provide a hydrodynamic diameter measurement of primary aggregates. (18) The zeta potential of the Rienso nanoparticles was measured before and after nebulization at each concentration and demonstrated an insignificant change overall. Rienso nanopartices in the initial solution demonstrated -38 -6 mV, -40 -3 mV, -42 -1 mV, and -40 -1 mV at 0.05 mg/mL, 0.1 mg/mL, 0.2 mg/mL, and 0.4 mg/mL, respectively.…”

“…(17) Nevertheless, it should duly be noted that despite clinical approval of selected SPION formulations for IV and oral administration, certain animal studies have questioned the biocompatibility of SPIONs and their lack of cytotoxicity following inhalation, specifically noting potential toxic effects due to macrophage clearance function overloading. (18) To the authors' knowledge, no controlled human inhalation studies have been carried out with aerosolized SPIONs, and as such, increased research is necessary to ascertain the biocompatibility of these nanoparticles before their application for human pulmonary use.…”

Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma

“…Once inhaled and deposited, nanoparticles appear to translocate to extra pulmonary sites and reach other target organs by different transfer routes and induce toxicological effects [4,19]. The generation of smoke at the workplace when the PS board is heated and dried may indicate the formation of a condensation aerosol (containing nanoparticles) from volatilised material.…”

Engineered nanomaterial uptake and tissue distribution: from cell to organism

“…ENMs taken up as agglomerate tend to be less easily degraded by the host as they can be detected in macrophages for several months, thus bearing a risk of long-term toxicity. 51,52 Pinocytosis Small particles ranging from a few nanometers to several hundred nanometers are generally taken up by pinocytosis (ie, fluid-phase uptake) occurring in almost all cell types ( Figure 2). There are four modes of pinocytosis, ie, macropinocytosis, adsorptive and receptor-mediated endocytosis, and alternative routes of uptake.…”