Evaluation of the peculiarity of the combined action of a number of chemicals based on the analysis of parameterized cause-effect relationships of marketers of exposure and negative effects and quantitative evaluation of additional health risk

Introduction. Assessing the type of combined action of chemicals is a complex and pressing problem of hygiene and preventive medicine.

The purpose of the work is to expand methodological approaches to assessing the characteristics of the combined interaction of a number of chemical substances based on the analysis of parameterized cause-and-effect relationships of exposure and negative effects and quantitative assessment of additional health risks.

Materials and methods. There was applied basic multiple logistic regression model, which is an assessment of the probability of developing a negative effect simultaneously with the isolated and combined effects of substances. The model was implemented for three components, the exposure of which was confirmed by exposure to biomarkers. Expert assessment of the type of combined action, carried out taking into account the regression coefficients of the adopted models. Quantitative assessment of the additional risk of negative effects from isolated and combined exposure to substances is carried out according to the parameters of cause-and-effect relationships of exposure to biomarkers and effects. Approbation of the methodological method provided for conditions of exposure to short-term aerogenic exposure to benzo(a)pyrene, significantly exceeding the reference concentrations (15.4 Rfc), with combustion oxide and hydrofluoride at the level of reference indicators (0.2–0.8 Rfc). The results of a study of cause-and-effect relationships based on previously conducted (in 2021–2022) medical examinations of four hundred fifty four exposed and unexposed 4-7 years children were used as biomarker effects.

Results. Depending on the binary combination of three chemical substances and the choice of biomarker of the negative effect (8 indicators), various options for the combined action were identified (24 options in total). For 10 of them, an increase in the adverse effect was established. The predominant nature of the action is the synergistic nature, which causes, in addition to the isolated one, the risk of developing negative effects on the part of the immune, bone and nervous systems, exceeding up to 56.8 times the acceptable level.

Limitations. During the combination effect, there was measured the substance in a binary combination of substances, taking into account the adverse effect and the direction of biomarkers.

Conclusion. In the practice of hygienic assessments, it is necessary to take into account the additional risk of developing negative effects with more complex types of combined action (synergism, antagonism) than simple summation, which will increase the objectivity of the hygienic assessment of the risk to the health of the exposed population.

Compliance with ethical standards. The study was approved by the local ethical committee of the Federal Scientific Center for Medical and Reservative Technologies for Risk Management of the Population of the Rospotrebnadzor (meeting protocol No. 2 dated 11.02.2021), and the Gelsinki Helsinki Declaration of the World Medical Association (as amended 2013) was carried out.

Contribution:
Zaitseva N.V. — editing;
Zemlyanova M.A. — the concept and design of the study, editing;
Koldibekova Yu.V. — the concept and design of the study, collection and processing of material, writing text;
Kiryanov D.A. — study concept and design, editing;
Chigvintsev V.M. — collection and processing of material, statistical processing.
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.

Acknowledgement. The study had no sponsorship.

Received: August 21, 2023 / Accepted: September 26, 2023 / Published: November 20, 2023