Justification of the hygienic standard for the content of the pharmaceutical substance clindamycin hydrochloride in the air of the working area, taking into account its toxic properties, confirmed in a chronic inhalation experiment

Introduction. The growth in the production of antibacterial remedies, in particular clindamycin hydrochloride (CH), and the increase in the number of workers in contact with them have determined the relevance of experimental research to substantiate the maximum permissible concentration of CH in the air of the working area (MPC).

Material and methods. Using a complex of physiological, behavioral, hematological, biochemical and histological methods, the severity of toxic manifestations in white rats was studied depending on 3 successively threefold decreasing concentrations of CH inhaled over 4 months.

Results. Chronic inhalation exposure to CH at a concentration of 13.5 mg/m³ led to the development of significant shifts in a number of hematological (increase in the number of leukocytes due to a significant increase in the number of monocytes) and biochemical parameters of blood serum (increase in the levels of urea, total bilirubin and decrease in the concentration of direct bilirubin and cholesterol) and pronounced pathomorphological changes in the lung tissue, liver, kidneys, myocardium and spleen in the bodies of experimental animals. Exposure to CH at a concentration of 4.4 mg/m³ was accompanied by less pronounced and widespread toxic effects (an increase in total bilirubin and a decrease in the levels of direct bilirubin and cholesterol in the blood serum, mainly weak structural changes in the bronchi, lung parenchyma and spleen of experimental white rats). In experimental animals after chronic exposure to CH at a concentration of 1.6 mg/m³, the values of all studied morphofunctional parameters and histological characteristics of internal organs did not differ significantly from those in control ones.

Limitations. The research is limited to studying the toxic effect of the pharmaceutical substance CH in a chronic experiment with inhalation exposure. The results of the study are applicable for the justification of MPC of the studied substance in the air of the working area.

Conclusion. Based on the results of the inhalation experiment, the concentration of CH at the level of 4.4 mg/m³ was accepted as the threshold for chronic toxic effect, which was more than 3 times lower than the previously established threshold concentrations of subchronic specific dysbiotic and allergic effects, which determined the leading harmful general toxic effect on the body as a criterion for hygienic standardization of CH. Taking into account the calculated safety factor (11) to the threshold concentration of chronic toxic effects, MPC limit in the air of the working area for clindamycin hydrochloride aerosol was justified at the level of 0.4 mg/m³, hazard class II.

Compliance with ethical standards. The studies were carried out in accordance with the principles of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, March 18, 1986), the Directive of the European Parliament and the European Union on the protection of animals used in experiments 2010/63/EU and approved by the Bioethics Commission of the Scientific Practical Centre of Hygiene, dated March 29, 2022, No. 2.

Authors’ contribution:
Zemtsova V.O. – collection and processing of the material, statistical analysis, writing a text;
Bogdanov R.V. – concept and design of the study, editing;
Rjabceva S.N. – collection and processing of the material, statistical analysis;
Shevlyakov V.V. – writing a text, editing;
Sychik S.I. – concept and design of the study, editing;
Chernyshova E.V. – collection and processing of the material.
All co-authors are responsible for approving the final version of the article and ensuring the integrity of all its parts.

Conflict of interests. The authors declare no apparent and potential conflicts of interest in relation to the publication of this article.

Funding. The work was carried out as part of the implementation of task 03.10 of the State Scientific and Technical Program “Scientific and Technical Support for the Quality and Availability of Medical Services” for 2021–2025 and was financed from the republican budget.

Received: March 19, 2025 / Revised: June 6, 2025 / Accepted: November 25, 2025 / Published: January 15, 2026

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