Biological effects of exposure to copper nanoparticles: markers of exposure

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Abstract

Introduction. Aerosol nanoparticles at operating metallurgical plants are potent of the significant risk factor that needs to be studied.

The purpose of the work was to study biological effects of exposure to copper nanoparticles compared to microparticles and identify potential markers of the exposure.

Materials and methods. Two experimental groups of rats, twelve animals each, were subchronically exposed to copper-containing nanoparticles and microparticles injected intraperitoneally. Changes in their biochemical parameters, tissues, and organs were then compared to those in the control rats administered with deionized water. During periodic medical examinations of workers occupationally exposed to copper-containing aerosols with different particle size distribution, additional laboratory and instrumental methods of testing were used to identify possible exposure effects to health manifested by changes in biochemical parameters.

Results. The experimental study showed that in liver, the exposure to copper nanoparticles, compared to microparticles, induced a more significant inhibition of replication of hepatocytes in regeneration, as demonstrated by the number of binuclear cells, and an increase in the number of Kupffer cells (tissue macrophages), while in kidney, it caused a more pronounced convoluted tubule brush border loss. The exposure to both micro- and nano-sized copper particles was found to induce pathological changes in neurons of the ganglionic layer of the cortex and basal nuclei. Test results showed a significant increase in the blood concentration of ceruloplasmin in the core personnel of the metallurgical plant following the exposure to copper aerosols rich in nanoparticles.

Limitations. The assessment of the results of the impact of copper nanoparticles in the composition of the aerosol on the health of 224 employees of the enterprise and the results of the experiment obtained on 36 animals corresponded to the current social and ethical standards and norms.

Conclusion. Specifics of the exposure to nanoparticles require a revision of approaches to regulating aerosols with account for particle size distribution.

Compliance with ethical standards. The study was approved by the Local Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers and conducted in compliance with the World Medical Association Declaration of Helsinki, Recommendations Guiding Physicians Involved in Biomedical Research Involving Human Subjects (National Standard of the Russian Federation GOST R 52379-2005, Good Clinical Practice (GCP), approved by Order Vo. 232-st of the Federal Agency for Technical Regulation and Metrology on September 27, 2005; Industry Standard OST 42-511-99, Rules for Conducting High-Quality Clinical Trials in the Russian Federation, dated December 29, 1998); the European Convention for the Protection of Vertebrate Animals used for Experimental or other Scientific Purposes (ETS No. 123), Directive 2010/63/EU of the European Parliament and of the Council of the European Union of September 22, 2010 on the Protection of Animals Used for Scientific Purposes, and other legal documents regulating the conduct of biomedical research involving human and animals.

Acknowledgements. The author would like to express his sincere gratitude to Prof. Boris A. Katsnelson; Marina P. Sutunkova, DSci. (Med.), Director of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Vladimir B. Gurvich, Dr. Sci. (Med.), Scientific Director of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Nadezhda V. Loginova, Researcher, Department of Toxicology and Bioprophylaxis; Ilzira A. Minigalieva, Dr. Sci. (Biol.), Head of the Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Dr. Vladimir Ya. Shur, Dr. Sci. (Phys.-Math.), Director of the Ural Center for Shared Use “Modern Nanotechnologies”, and Svetlana V. Grebenkina, Head of the Quality Control Department, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers.

Conflict of interest. The author declares no conflict of interest. 

Financing. The study had no sponsorship.

Received: February 6, 2022 / Accepted: March 24, 2023 / Published: April 20, 2023

About the authors

Vadim O. Ruzakov

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers of the Federal Service for Surveillance in the Sphere of Consumer Protection and Human Welfare

Author for correspondence.
Email: ruzakov@ymrc.ru
ORCID iD: 0000-0002-8902-0416

Assistant Director, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers of the Federal Service for Surveillance in the Sphere of Consumer Protection and Human Welfare, Yekaterinburg, 620014, Russian Federation.

e-mail: ruzakov@ymrc.ru 

Russian Federation

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