Development of new methods for predicting hygienic standards for the content of medicines in the air of the working area on the example of non-steroidal anti-inflammatory drugs

Author:

Tonshin Anton A.1,Tkacheva Tatiana A.1,Kautina Svetlana V.1,Golubeva Margarita I.2

Affiliation:

1. Izmerov Research Institute of Occupational Health

2. All-Union Scientific Center for the Safety of Biologically Active Compound

Abstract

Introduction. Experts predict the hygienic standards of medicines in Russia in accordance with the methods common to all medicines (MG 1.1.726-98), developed more than 25 years ago on the basis of experimental materials obtained during the rationing of 66 medicines. By 2023, the content of more than 230 medicines of various pharmacological orientation has already been normalized in the air of the working area. Such an array of experimental materials makes it possible to study the relationship between the values of standard toxicological and pharmacological indicators and hygienic standards approved by law, already within the framework of individual pharmacological groups of drugs with the same mechanism of action, as well as to develop new forecasting approaches taking into account the specifics of pharmacological actions. The study aims to evaluate existing and develop new computational methods for predicting hygienic standards for the content of medicines in the air of the working area, taking into account the specifics of pharmacological action on the example of a group of nonsteroidal anti-inflammatory drugs. Materials and methods. Scientists studied the pharmacological group of nonsteroidal anti-inflammatory drugs. The main method of the study was a multiple correlation and regression analysis of the relationship between the values of hygienic standards and the values of toxicological and pharmacological parameters. As a mathematical model, the authors adopted a double logarithmic model. We evaluated the suitability of the mathematical model by Fisher's F-criterion, the statistical significance of the regression coefficients by the Student's t-criterion, the quality of approximation by the standard deviation, and the accuracy of the calculation by the average multiplicity of differences. Results. Experts have identified in a group of 15 non-steroidal anti-inflammatory substances normalized in the air of the working area, a reliable relationship between the values of toxicometry parameters and the values of therapeutic doses, on the one hand, and the values of hygiene standards, on the other. Scientists have developed and selected the most accurate and statistically significant formulas for calculating the safe concentrations of this group of drugs in the air of the working area. We found that the accuracy of the formulas developed by us, taking into account the specifics of the pharmacological action, is higher than that of the formulas from MG 1.1.726-98. From the formulas developed earlier, equations with greater accuracy for the hygienic rationing of nonsteroidal anti-inflammatory drugs have been identified. Conclusion. Taking into account the specifics of the pharmacological action of medicines when developing mathematical models for calculating the hygienic standard increases the accuracy of the forecast.

Publisher

FSBI Research Institute of Occupational Health RAMS

Subject

General Medicine

Reference17 articles.

1. Hygienic standards GN 1.1.701-98 Hygienic criteria for substantiating the need to develop MPC and SHEL (ODU) for harmful substances in the air of the working area, atmospheric air in populated areas, water in water bodies: Approved and put into effect by the Decree of the Chief State Sanitary Doctor of the Russian Federation of April 30, 1998 No. 15. Elektronnyy fond pravovoy i normativno-tekhnicheskoy dokumentatsii. https://docs.cntd.ru/document/1200011526 (Accessed: 22.11.2022) (in Russian).

2. Golubev A.A. The use of calculation methods in industrial toxicology to establish the approximate value of a number of constants and indicators. In: «Issues of general industrial toxicology». L., 1963: 23–31 (in Russian).

3. Zaeva G.N. On the application of calculation methods. In: «Toxicology of new industrial chemicals». M.; 1964: 150–164.

4. Ivanov N.G., Sidorov K.K., Maksimov G.G. Scientific foundations of accelerated methods for substantiating sanitary standards in the USSR. In: «Principles and methods for establishing MPCs for harmful substances». M., 1983: 25–29 (in Russian).

5. Ivanov N.G. Accelerated methods for establishing sanitary standards for industrial chemicals. In: «Preventive toxicology». Ed N.F. Izmerov. M. Tsentr mezhdunarodnykh proektov GKNT. 1984; 1: 138–151 (in Russian).

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