Experimental study of the mechanism of action and comparative assessment of the toxicity of zinc-containing nano- and microparticles under subacute inhalation exposure

Introduction. Zinc-containing nanoparticles in oxides, alloys with copper (brass), aluminum, magnesium, and other metals are produced in large volumes and applied in many spheres. This increases likelihood of exposure to them for the general population thereby creating elevated risks of new or more pronounced adverse effects in comparison with those produced by exposure to their micro-sized analogues.

The aim of this study. To analyze pathways specificity and comparatively assess toxicity of zinc-containing nanoparticles against micro-sized ones upon experimental sub-acute inhalation exposure exemplified by ZnO.

Materials and methods. We comparatively assessed chemical and physical properties of ZnO nanoparticles (NPs) and microsized particles (MPs), peculiarities of their biological distribution, accumulation, and toxic effects upon sub-acute inhalation exposure in the concentration equal to 0.5 mg/m³ in an experiment on rats.

Results. ZnO NPs and MPs have similar chemical composition but there is a huge difference (up to one million times) in physical properties. Due to it, NPs accumulate in a wider range of organs in higher concentrations (up to 1.3 times higher). NPs produce more pronounced (up to 2.5 times more against MPs) changes in biochemical and hematological indices of blood. We identified more pronounced pathomorphological changes in the brain, lungs, and the liver. The rats exposed to NPs tended to have change in behavioral response (1.5 times against those exposed to MPs).

Limitations. The study involved only sub-acute inhalation exposure simulated for female Wistar rats.

Conclusion. ZnO NPs and MPs have very different physical properties; NP peculiarities determine a wider range of organs for biodistribution and more intensive bioaccumulation. Exposure to NPs produces more pronounced adverse effects such as oxidative stress, cytolysis, inhibited thrombocytopoiesis, disrupted urea synthesis, imbalance of neuromediators, dysproteinemia; disrupted circulation in lung and brain tissues, inflammatory changes in liver parenchyma; developing stress reactions. Our findings allow developing more effective scientifically grounded preventive measures aimed at minimizing health risks upon airborne exposure to zinc-containing nanomaterials.

Compliance with ethical standards. The study was accomplished in conformity with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS No. 123) and requirements of the Ethics Committee of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies (the Meeting Protocol No. 3 dated February 14, 2023).

Contributions:
Zaitseva N.V. — study concept and design;
Zemlyanova М.А. — data analysis and editing the text;
Stepankov М.S. — data collection and analysis, writing the text;
Pustovalova О.V. — data collection and analysis;
Nikolaeva А.Е. — data collection and analysis.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version

Conflict of interest. The authors declare no conflict of interest.

Funding. The study was funded from the Federal Budget.

Received: July 22, 2025 / Revised: August 29, 2025 / Accepted: October 15, 2025 / Published: November 14, 2025

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