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Comparative Study
. 2021 Jan;95(1):53-65.
doi: 10.1007/s00204-020-02923-y. Epub 2020 Oct 1.

Health effects after inhalation of micro- and nano-sized zinc oxide particles in human volunteers

Christian Monsé  1 , Monika Raulf  2 , Birger Jettkant  2 , Vera van Kampen  2 , Benjamin Kendzia  2 , Leonie Schürmeyer  2 , Christoph Edzard Seifert  2 , Eike-Maximilian Marek  2 , Götz Westphal  2 , Nina Rosenkranz  2 , Rolf Merget  2 , Thomas Brüning  2 , Jürgen Bünger  2
Affiliations
Comparative Study

Health effects after inhalation of micro- and nano-sized zinc oxide particles in human volunteers

Christian Monsé et al. Arch Toxicol. 2021 Jan.

Abstract

Inhalation of ZnO particles can cause inflammation of the airways and metal fume fever. It is unclear if different sizes of the particles alter these effects. However, various studies report higher biological activity of other nano-sized particles compared to microparticles. No effects at all were observed after inhalation of micro- and nano-sized zinc oxide (ZnO) particle concentrations of 0.5 mg/m3. Studies with different particle sizes of ZnO at higher exposures are not available. Accordingly, we hypothesized that inhalation of nano-sized ZnO particles induces stronger health effects than the inhalation of the same airborne mass concentration of micro-sized ZnO particles. 16 healthy volunteers (eight men, eight women) were exposed to filtered air and ZnO particles (2.0 mg/m3) for 2 h (one session with nano- and one with micro-sized ZnO) including 1 h of cycling at moderate workload. Effect parameters were symptoms, body temperature, inflammatory markers in blood and in induced sputum. Induced sputum was obtained at baseline examination, 22 h after exposure and at the end of the final test. The effects were assessed before, immediately after, about 22 h after, as well as two and three days after each exposure. Neutrophils, monocytes and acute-phase proteins in blood increased 22 h after micro- and nano-sized ZnO exposure. Effects were generally stronger with micro-sized ZnO particles. Parameters in induced sputum showed partial increases on the next day, but the effect strengths were not clearly attributable to particle sizes. The hypothesis that nano-sized ZnO particles induce stronger health effects than micro-sized ZnO particles was not supported by our data. The stronger systemic inflammatory responses after inhalation of micro-sized ZnO particles can be explained by the higher deposition efficiency of micro-sized ZnO particles in the respiratory tract and a substance-specific mode of action, most likely caused by the formation of zinc ions.

Keywords: Deposition efficiency; Human inhalation study; Micro-sized particles; Nanoparticles; Zinc oxide.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Averaged particle number and size distributions of airborne ZnO particles at 2.0 mg/m3. Left: micro-, right: nano-sized ZnO particles. In addition, the error bars of each individual size channel are shown
Fig. 2
Fig. 2
SEM (scanning electron microscopy) pictures of ZnO particles. Left: micro-, right: nano-sized ZnO particles at a magnification of 50,000 each
Fig. 3
Fig. 3
Time line of this study
Fig. 4
Fig. 4
Chemotaxis (migrated cells) of the dHL-60 cells in response to supernatants of NR8383 cells challenged with micro- and nano-sized ZnO particles. Results represent arithmetic means and standard deviations of three independent experiments. Commercially available silica nanoparticles served as positive control
Fig. 5
Fig. 5
Neutrophil numbers in blood after sham (0 mg/m3 ZnO) or inhalation of micro- and nano-sized ZnO particles at the different time points. Differences between ab, ac and bc were all p < 0.0001. All differences p < 0.05 are shown. Significance levels α = 0.0055 (for brackets) and 0.0166 (for a, b, c) after Bonferroni correction
Fig. 6
Fig. 6
Calculated lung deposition efficiency of ZnO particles in dependence of airway regions (a alveolar region, t tracheobronchial region, e extrathoracic region) and particle size. Sum: total deposition (sum of a, t and e), Intake: Total inhaled mass of ZnO particles
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