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Time course of lung retention and toxicity of inhaled particles: short-term exposure to nano-Ceria.

Keller J, Wohlleben W, Ma-Hock L, Strauss V, Gröters S, Küttler K, Wiench K, Herden C, Oberdörster G, van Ravenzwaay B, Landsiedel R - Arch. Toxicol. (2014)

Bottom Line: Inhaled Ceria is deposited in the lung and cleared with a half-time of 40 days; at aerosol concentrations higher than 0.5 mg/m(3), this clearance was impaired resulting in a half-time above 200 days (25 mg/m(3)).The progression toward the subsequent granulomatous reaction was driven by the duration and amount of the particles in the lung.The further progression of the biological response will be determined in the ongoing long-term study.

View Article: PubMed Central - PubMed

Affiliation: Experimental Toxicology and Ecology, BASF SE, 67056, Ludwigshafen am Rhein, Germany.

ABSTRACT
Two Ceria nanomaterials (NM-211 and NM-212) were tested for inhalation toxicity and organ burdens in order to design a chronic and carcinogenicity inhalation study (OECD TG No. 453). Rats inhaled aerosol concentrations of 0.5, 5, and 25 mg/m(3) by whole-body exposure for 6 h/day on 5 consecutive days for 1 or 4 weeks with a post-exposure period of 24 or 129 days, respectively. Lungs were examined by bronchoalveolar lavage and histopathology. Inhaled Ceria is deposited in the lung and cleared with a half-time of 40 days; at aerosol concentrations higher than 0.5 mg/m(3), this clearance was impaired resulting in a half-time above 200 days (25 mg/m(3)). After 5 days, Ceria (>0.5 mg/m(3)) induced an early inflammatory reaction by increases of neutrophils in the lung which decreased with time, with sustained exposure, and also after the exposure was terminated (during the post-exposure period). The neutrophil number observed in bronchoalveolar lavage fluid (BALF) was decreasing and supplemented by mononuclear cells, especially macrophages which were visible in histopathology but not in BALF. Further progression to granulomatous inflammation was observed 4 weeks post-exposure. The surface area of the particles provided a dose metrics with the best correlation of the two Ceria's inflammatory responses; hence, the inflammation appears to be directed by the particle surface rather than mass or volume in the lung. Observing the time course of lung burden and inflammation, it appears that the dose rate of particle deposition drove an initial inflammatory reaction by neutrophils. The later phase (after 4 weeks) was dominated by mononuclear cells, especially macrophages. The progression toward the subsequent granulomatous reaction was driven by the duration and amount of the particles in the lung. The further progression of the biological response will be determined in the ongoing long-term study.

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Structure of Ceria. Electron microscopy images of a representative ensemble of particles of Ceria NM-211 (a) and NM-212 (b) (see Table 1 for size characterization by complementary methods)
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Fig2: Structure of Ceria. Electron microscopy images of a representative ensemble of particles of Ceria NM-211 (a) and NM-212 (b) (see Table 1 for size characterization by complementary methods)

Mentions: Both Ceria were yellowish white powders that were produced by precipitation and were nominally uncoated. We completely re-characterized the Ceria NM-211 and NM-212 based on the nano-specific guidance on physical–chemical properties (Wohlleben et al. 2013). Table 1 indicates the techniques chosen for each end point (see “Materials and methods” section) and summarizes the results. The Ceria NM-212 material had an average primary particle diameter of 40 nm, in excellent accordance of electron microscopy with the crystallite size derived from the diffraction peak width and with the sphere-equivalent diameter derived from the BET-specific surface area of 27 m2/g (see Fig. 2). The Ceria NM-211 material consisted of considerably smaller primary particles with number-based median diameter of 8.2 nm (from TEM) and correspondingly larger specific surface (53 m2/g, from BET). Primary particles of both materials were crystalline with cubic lattice as it is the characteristic for cerianite and had irregular, but roughly globular shapes. In the as-produced powder, porosimetry by Hg intrusion indicated that these particles were aggregated and agglomerated to sizes that range from a few hundred nm to tens of µm.Table 1


Time course of lung retention and toxicity of inhaled particles: short-term exposure to nano-Ceria.

Keller J, Wohlleben W, Ma-Hock L, Strauss V, Gröters S, Küttler K, Wiench K, Herden C, Oberdörster G, van Ravenzwaay B, Landsiedel R - Arch. Toxicol. (2014)

Structure of Ceria. Electron microscopy images of a representative ensemble of particles of Ceria NM-211 (a) and NM-212 (b) (see Table 1 for size characterization by complementary methods)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4555363&req=5

Fig2: Structure of Ceria. Electron microscopy images of a representative ensemble of particles of Ceria NM-211 (a) and NM-212 (b) (see Table 1 for size characterization by complementary methods)
Mentions: Both Ceria were yellowish white powders that were produced by precipitation and were nominally uncoated. We completely re-characterized the Ceria NM-211 and NM-212 based on the nano-specific guidance on physical–chemical properties (Wohlleben et al. 2013). Table 1 indicates the techniques chosen for each end point (see “Materials and methods” section) and summarizes the results. The Ceria NM-212 material had an average primary particle diameter of 40 nm, in excellent accordance of electron microscopy with the crystallite size derived from the diffraction peak width and with the sphere-equivalent diameter derived from the BET-specific surface area of 27 m2/g (see Fig. 2). The Ceria NM-211 material consisted of considerably smaller primary particles with number-based median diameter of 8.2 nm (from TEM) and correspondingly larger specific surface (53 m2/g, from BET). Primary particles of both materials were crystalline with cubic lattice as it is the characteristic for cerianite and had irregular, but roughly globular shapes. In the as-produced powder, porosimetry by Hg intrusion indicated that these particles were aggregated and agglomerated to sizes that range from a few hundred nm to tens of µm.Table 1

Bottom Line: Inhaled Ceria is deposited in the lung and cleared with a half-time of 40 days; at aerosol concentrations higher than 0.5 mg/m(3), this clearance was impaired resulting in a half-time above 200 days (25 mg/m(3)).The progression toward the subsequent granulomatous reaction was driven by the duration and amount of the particles in the lung.The further progression of the biological response will be determined in the ongoing long-term study.

View Article: PubMed Central - PubMed

Affiliation: Experimental Toxicology and Ecology, BASF SE, 67056, Ludwigshafen am Rhein, Germany.

ABSTRACT
Two Ceria nanomaterials (NM-211 and NM-212) were tested for inhalation toxicity and organ burdens in order to design a chronic and carcinogenicity inhalation study (OECD TG No. 453). Rats inhaled aerosol concentrations of 0.5, 5, and 25 mg/m(3) by whole-body exposure for 6 h/day on 5 consecutive days for 1 or 4 weeks with a post-exposure period of 24 or 129 days, respectively. Lungs were examined by bronchoalveolar lavage and histopathology. Inhaled Ceria is deposited in the lung and cleared with a half-time of 40 days; at aerosol concentrations higher than 0.5 mg/m(3), this clearance was impaired resulting in a half-time above 200 days (25 mg/m(3)). After 5 days, Ceria (>0.5 mg/m(3)) induced an early inflammatory reaction by increases of neutrophils in the lung which decreased with time, with sustained exposure, and also after the exposure was terminated (during the post-exposure period). The neutrophil number observed in bronchoalveolar lavage fluid (BALF) was decreasing and supplemented by mononuclear cells, especially macrophages which were visible in histopathology but not in BALF. Further progression to granulomatous inflammation was observed 4 weeks post-exposure. The surface area of the particles provided a dose metrics with the best correlation of the two Ceria's inflammatory responses; hence, the inflammation appears to be directed by the particle surface rather than mass or volume in the lung. Observing the time course of lung burden and inflammation, it appears that the dose rate of particle deposition drove an initial inflammatory reaction by neutrophils. The later phase (after 4 weeks) was dominated by mononuclear cells, especially macrophages. The progression toward the subsequent granulomatous reaction was driven by the duration and amount of the particles in the lung. The further progression of the biological response will be determined in the ongoing long-term study.

Show MeSH
Related in: MedlinePlus