The results of an experimental toxicological assessment of the pharmaceutical substance ambroxol hydrochloride, justification of the maximum permissible content in the air of the working area

Abstract

Introduction. Ambroxol hydrochloride is a biologically active substance used as a pharmaceutical substance in the manufacture of medicines for secretolytic therapy in the case of acute and chronic bronchopulmonary diseases. To date, there is no hygienic standard for the safe content of substances in the air of the working area in the republic.
 The study aims to substantiate and develop the maximum permissible concentrations and hazard class of the pharmaceutical substance ambroxol hydrochloride in the air of the working area.
 Materials and methods. The authors have conducted experimental toxicological studies of the pharmaceutical substance on animals (rats, mice, rabbits) in accordance with the requirements of technical regulatory legal acts and recommendations of methodological documents regulating the justification of hygienic standards.
 Results. Scientists have found that the pharmaceutical substance ambroxol hydrochloride, when injected into the stomach and inhaled, is classified as a low-hazard substance at an average lethal dose/concentration (according to GOST 12.1.007-76), has a mild irritant effect on the skin and moderate on the mucous membranes of the eyes, does not exhibit a skin-resorptive effect, is characterized by a weak cumulative effect and does not it has sensitizing activity. Under the conditions of inhalation of the substance into the body of laboratory animals (rats), the threshold values of acute and chronic harmful effects of this pharmaceutical substance were at the level of 90 mg/m3 (in terms of the effect on the functional state of the nervous activity of rats) and 30 mg/m3, respectively (in terms of changes in behavioral indicators, weight and mass coefficient spleen, blood glucose, alanine aminotransferases and urea) accordingly.
 Conclusion. Based on the experimental results of the toxicological assessment, the authors have justified the standard of permissible content of the pharmaceutical substance ambroxol hydrochloride in the air of the working area at the level of 4.0 mg/m3, they also have established the hazard class of the substance according to GOST 12.1.007-76 (class 3, medium-hazard substances).
 Ethics. The Bioethics Commission of the State Enterprise "SPCH” has approved the use of laboratory animals for experimental purposes (Protocol No. 1 dated 03/04/2020). The treatment of animals was in accordance with the provisions of 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.