Concentration-dependent systemic response after inhalation of nano-sized zinc oxide particles in human volunteers

Monsé, Christian; Hagemeyer, Olaf; Raulf, Monika; Jettkant, Birger; Kampen, V. van; Kendzia, Benjamin; Gering, Vitali; Kappert, Günther; Weiß, Tobias; Ulrich, Nadin; Marek, É. M.; Bünger, Jürgen; Brüning, Thomas; Merget, R.

doi:10.1186/s12989-018-0246-4

Cited by 96 publications

(86 citation statements)

References 33 publications

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“…Increased blood levels of acutephase response protein SAA was observed at 1 and 2 mg/m 3 and increased CRP already at 0.5 mg/m 3 (Mons e et al 2018). Notably, these effects were observed at doses that are below the occupational exposure limit for ZnO in many countries (Mons e et al 2018;Vogel and Cassee 2018). In a separate study, acute exposure of healthy human adults to 0.5 mg/m 3 mass concentration of ZnO (<0.1 mm in diameter) for 2 h did not result in acute-phase response or inflammation (Beckett et al 2005).…”

Section: Introductionmentioning

confidence: 90%

“…Based on these calculations and the results obtained, humans may activate acute phase response more readily following exposure to ZnO compared to the C57BL/6 mice used in the current study. In these mice, the lowest-observed-adverseeffect level (LOAEL) for induction of SAA3 in lung tissue was 100 mg/kg bw for the uncoated ZnO and 33 mg/kg bw for the coated ZnO, whereas the LOAEL for SAA in blood is calculated as 20 mg/kg bw for the human volunteers (Mons e et al 2018). Several studies have demonstrated induction of localized acute phase response in lungs following inhalation exposure to nanomaterials and combustion particles (Halappanavar et al 2011;Saber et al 2013Saber et al , 2014Poulsen et al 2017).…”

Section: Effects On the Acute-phase Responsementioning

confidence: 95%

“…Human inhalation of ZnO nanoparticles induces ZnO dose-dependent increases in body temperature and, neutrophilia at 1 and 2 mg/m 3 . Increased blood levels of acutephase response protein SAA was observed at 1 and 2 mg/m 3 and increased CRP already at 0.5 mg/m 3 (Mons e et al 2018). Notably, these effects were observed at doses that are below the occupational exposure limit for ZnO in many countries (Mons e et al 2018;Vogel and Cassee 2018).…”

Section: Introductionmentioning

confidence: 95%

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Acute phase response and inflammation following pulmonary exposure to low doses of zinc oxide nanoparticles in mice

et al. 2019

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Inhalation of nanosized zinc oxide (ZnO) induces metal fume fever and systemic acute phase response in humans. Acute phase response activation is a cardiovascular risk factor; we investigated whether pulmonary exposure of mice can be used to assess ZnO-induced acute phase response as well as inflammation and genotoxicity. Uncoated (NM-110) and triethoxycaprylylsilane-coated (NM-111) ZnO nanoparticles were intratracheally instilled once at 0.2, 0.7 or 2 mg/ mouse (11, 33 and 100 mg/kg body weight). Serum amyloid A3 mRNA level in lung tissue, bronchoalveolar lavage (BAL) fluid cellularity, and levels of DNA strand breaks in BAL fluid cells, lung and liver tissue were assessed 1, 3 and 28 days post-exposure. Global transcription patterns were assessed in lung tissue using microarrays. The acute-phase response serum amyloid A3 mRNA levels were increased on day 1; for uncoated ZnO nanoparticles at the highest dose and for coated ZnO nanoparticles at medium and highest dose. Neutrophils were increased in BAL fluid only after exposure to coated ZnO nanoparticles. Genotoxicity was observed only in single dose groups, with no dose-response relationship. Most changes in global transcriptional response were observed after exposure to uncoated ZnO nanoparticles and involved cell cycle G2 to M phase DNA damage checkpoint regulation. Although, uncoated and coated ZnO nanoparticles qualitatively exerted similar effects, observed differences are likely explained by differences in solubility kinetics. The finding of serum amyloid A3 induction at low exposure suggests that mouse models can be used to assess the nanoparticle-mediated induction of acute phase responses in humans.

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Section: Introductionmentioning

confidence: 90%

Section: Effects On the Acute-phase Responsementioning

confidence: 95%

Section: Introductionmentioning

confidence: 95%

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Acute phase response and inflammation following pulmonary exposure to low doses of zinc oxide nanoparticles in mice

et al. 2019

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“…However, studies have shown that, in MS welders, respiratory symptoms clearly increase during working days, although the exposure was not extreme compared to the current exposure limit [173]. More recently, Monse et al [174] reported a concentration-response relationship with nano-sized ZnO particles in a low concentration range was, with systemic inflammatory effects of inhaled nano-sized ZnO particles, observed at concentrations well below the occupational exposure limit for ZnO. These observations clearly indicate that the current occupational exposure limit (OEL) may not be sufficient to fully prevent harm in welders.…”

Section: Occupational Exposure Limitsmentioning

confidence: 98%

Welding Fumes, a Risk Factor for Lung Diseases

Riccelli

Goldoni

Poli

et al. 2020

IJERPH

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(1) Background: Welding fumes (WFs) are composed of fine and ultrafine particles, which may reach the distal airways and represent a risk factor for respiratory diseases. (2) Methods: In vitro and in vivo studies to understand WFs pathogenesis were selected. Epidemiological studies, original articles, review, and meta-analysis to examine solely respiratory disease in welders were included. A systematic literature search, using PubMed, National Institute for Occupational Safety and Health Technical Information Center (NIOSHTIC), and Web of Science databases, was performed. (3) Results: Dose, time of exposure, and composition of WFs affect lung injury. Inflammation, lung defense suppression, oxidative stress, DNA damage, and genotoxic effects were observed after exposure both to mild and stainless steel WFs. (4) Conclusions: The detection of lung diseases associated with specific occupational exposure is crucial as complete avoidance or reduction of the exposure is difficult to achieve. Further studies in the area of particle research may aid the understanding of mechanisms involved in welding-related lung disease and to expand knowledge in welding-related cardiovascular diseases.

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“…In a rat experiment, cardiac inflammation and the development of fibrosis 7 days after exposure to ZnO nanoparticles was observed [5]. Recently, we reported flu-like symptoms, fever and an increase of inflammatory markers in blood after exposure to inhaled ZnO nanoparticles at or above 1 mg/m 3 [6].…”

Section: Introductionmentioning

confidence: 98%

Heart rate variability and cardiac repolarization after exposure to zinc oxide nanoparticles in healthy adults

Aweimer

Jettkant

Monsé

et al. 2020

J Occup Med Toxicol

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Background: Exposure to airborne zinc oxide (ZnO) particles occurs in many industrial processes, especially in galvanizing and welding. Systemic inflammation after experimental inhalation of ZnO particles has been demonstrated previously, but little is known about the impact on the cardiovascular system, particularly on the autonomic cardiac system and the risk of arrhythmias. In this study we investigated the short-term effects of ZnO nanoparticles on heart rate variability (HRV) and repolarization in healthy adults in a concentration-dependent manner at rest and during exercise in a controlled experimental setup. Methods: Sixteen healthy subjects were exposed to filtered air and ZnO particles (0.5, 1.0 and 2.0 mg/m 3) for 4 h, including 2 h of cycling at low workloads. Parameters were assessed before, during, immediately after, and about 24 h after each exposure. For each subject, a total number of 46 10-min-sections from electrocardiographic records were analyzed. Various parameters of HRV and QT interval were measured. Results: Overall, no statistically significant effects of controlled ZnO inhalation on HRV parameters and QT interval were observed. Additionally, a concentration-response was absent. Conclusion: Inhalation of ZnO nanoparticles up to 2.0 mg/m 3 for 4 h does not affect HRV and cardiac repolarization in healthy adults at the chosen time points. This study supports the view that cardiac endpoints are insensitive for the assessment of adverse effects after short-term inhalation of ZnO nanoparticles.

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Concentration-dependent systemic response after inhalation of nano-sized zinc oxide particles in human volunteers

Cited by 96 publications

References 33 publications

Acute phase response and inflammation following pulmonary exposure to low doses of zinc oxide nanoparticles in mice

Acute phase response and inflammation following pulmonary exposure to low doses of zinc oxide nanoparticles in mice

Welding Fumes, a Risk Factor for Lung Diseases

Heart rate variability and cardiac repolarization after exposure to zinc oxide nanoparticles in healthy adults

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