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

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

doi:10.1007/s00204-020-02923-y

Christian Monsé, Vera Van Kampen + Show 11 more

Open Access

https://doi.org/10.1007/s00204-020-02923-y

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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.

Highlights

Employees exposed to zinc-containing fumes may suffer from metal fume fever after inhalation, especially during handling of hot-dip galvanized sheet metal or when welding
While a number of older experimental inhalation studies reported adverse health effects after high exposures to zinc oxide (ZnO) (Gordon et al 1992; Fine et al 1997), no effects were detected in 12 subjects after inhalation of 0.5 mg/m3 ZnO for 2 h at rest (Beckett et al 2005)
The evaluation of parts of the questionnaires relevant for this study did not demonstrate an increase of the effect ratings after micro- and nano-sized ZnO exposure compared to sham

Summary

Introduction

Human experimental inhalation studies using ZnO particles are sparse— with different particle sizes. While a number of older experimental inhalation studies reported adverse health effects after high exposures to zinc oxide (ZnO) (Gordon et al 1992; Fine et al 1997), no effects were detected in 12 subjects after inhalation of 0.5 mg/m3 ZnO for 2 h at rest (Beckett et al 2005). Several recent studies focused on exposures of zinc-containing welding fumes in various settings (different concentrations and inhalation times, repetitive inhalations). The key aspect of these studies was a simulation of exposure conditions close to the workplace, but the particle size was not experimentally modified (Brand et al 2014, 2019; Krabbe et al 2019)

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