Hygienic regulation for jointly acting harmful factors and methodology of its experimental rationale

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Abstract

With the combined action of agents, the toxic effect depends not only on the time and effects levels of each of them but also on the combinations in which these levels are located. The main problems in the experimental substantiation of hygienic regulations for this type of action are the determination of this dependence, the establishment with its help of safe combinations of exposure levels and their description. In the work methods of their solution are offered.

This dependence is recommended to be obtained in the economical experiments proposed by the theory of mathematical planning. It is represented by a system of regression equations describing the dose dependencies observed at different moments after the onset of the impact (when indices are removed). In this case, the toxic effect is estimated by two indices, reflecting the degree of deviation of the state of the body of the experimental animals from the norm and the probability of this deviation.

Effective and ineffective combinations are determined by this system of equations when substituting in them the values of the toxic effect corresponding to its presence or absence. In turn, hygienically safe combinations are determined by a system describing ineffective combinations of exposure levels that include stock coefficients that are reasonable for each agent.

This system can be adopted as an experimentally valid hygiene regulation, which has the following advantages. It is determined by the results of the study of the joint rather than isolated action of agents, does not require the fulfillment of any conditions about the nature of this action (isoadditivity, etc.), and also takes into account not only the degree of deviation of the state of the organism of the experimental animals from the norm, but also the probability this deviation. In order to obtain the necessary information, we propose plans for experiments in which the number of groups of experimental animals is only one more than the number of cooperative agents.

An example of the proposed approach is given.

About the authors

Yury N. Katulskiy

Angarsk State Technical University

Author for correspondence.
Email: kagn47@mail.ru

MD, Ph.D., DSci., professor of the Department “Ecology and safety of human activity”, Angarsk State Technical University, Angarsk, 665835, Russia.

e-mail: kagn47@mail.ru

Russian Federation

References

  1. Avaliani S.L., Bezpal’ko L.E., Bobkova T.E., Mishina A.L. Prospective directions of development of the methodology of risk analysis in Russia. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 2013; 1: 33–5. (in Russian)
  2. Zholdakova Z.I., Kharchevnikova N.V., Mamonov R.A., Sinitsyna O.O. Methods for assessing the combined effect of substances. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 2012; 2: 86–9. (in Russian)
  3. Golubev A.A., Lyublina E.I., Tolokontsev N.A., Filov V.A. Quantitative Toxicology [Kolichestvennaya toksikologiya]. Leningrad: Meditsina; 1973. 287 p. (in Russian)
  4. Katsnel’son B.A., Novikov S.M. Methodical approaches to the study of combined action of industrial harmful substances. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 1986; 5: 59–62. (in Russian)
  5. Kustov V.V., Tiunov L.A., Vasil’ev G.A. Combined action of industrial poisons [Kombinirovannoye deystviye promyshlennykh yadov]. Moscow: Meditsina; 1975. 256 p. (in Russian)
  6. Methodological recommendations for planning and evaluating the effect of combined action of chemicals with repeated exposure. Kiev; 1977. (in Russian)
  7. Nagornyy P.A. Combined action of chemicals and methods of its hygienic study [Kombinirovannoye deystviye khimicheskikh veshchestv i metody yego gigiyenicheskogo izucheniya]. Moscow: Meditsina; 1984. 182 p. (in Russian)
  8. Sinitsyna O.O., Krasovskiy G.N., Zholdakova Z.I. Criteria for the threshold action of chemicals polluting different environmental objects. Vestnik RAMN. 2003; 3: 17–23. (in Russian)
  9. Establishment of experimental studies on the nature of the combined action of chemicals with a view to developing preventive measures: Methodological recommendations. Moscow; 1987. (in Russian)
  10. Birnbaum L., DeVito M. Use of toxic equivalency factors for risk assessment for dioxins and related. Toxicology. 1995; 105 (2–3): 391–401.
  11. Finney D.J. Probit analysis. 3rd ed. London: Cambridge University Press; 1971.
  12. Loeve S. Die quantitativen Problem der Pharmakologie. Ergebnisse der Physiologie. 1928; 27: 47–187.
  13. Supplementary quidance for conducting health risk assessment of chemical mixtures: Risk Assessment Forum, U.S. Environmental Protection Agency. Washington; 2001.
  14. Hygienic requirements for the protection of surface waters: SanPiN 2.1.5.980-00. Moscow; 2000. (in Russian)
  15. Maximum permissible concentration (MPC) of pollutants in the atmospheric air of urban and rural settlements: GN 2.1.6.3492-17. Moscow; 2017. (in Russian)
  16. Aver’yanov A.G. On the issue of assessing the air environment in the presence of several harmful components. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 1957; 8: 64–7. (in Russian)
  17. Maximum permissible concentration (MPC) of harmful substances in the air of the working area: GN 2.2.5.1313-03. Moscow; 2003. (in Russian)
  18. Korbakova A.I., Ivanov N.G., Kremneva S.N. The maximum permissible concentrations of mixtures of substances. In: Principles of maximum permissible concentrations [Printsipy predel’no dopustimykh kontsentratsiy]. A.A. Letavet, I.V. Sanotskiy, eds. Moscow: Meditsina; 1970: 20–129. (in Russian)
  19. Kustov V.V., Tiunov L.A. To the assessment of an air environment containing several harmful impurities. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 1960; 7: 92–3. (in Russian)
  20. Sanotskiy I.V. The current state of the issue of the combined action of gases, vapors and aerosols. In: Toxicology of New Industrial Chemical Substances [Toksikologiya novykh promyshlennykh khimicheskikh veshchestv]. A.A. Letavet, I.V. Sanotskiy, eds. Moscow: Meditsina; 1969: 6–13. (in Russian)
  21. Knizhnikov V.A., Dushutin K.K. Problems of hygienic regulation of the effects of combined and combined action. In: Methodological aspects of hygienic study of combined and combined effects [Metodologicheskiye aspekty gigiyenicheskogo issledovaniya sochetannykh i kombinirovannykh vozdeystviy]. L.A. Buldakov, Knizhnikov V.A., eds. Moscow; 1986: 12–9. (in Russian)
  22. Feron V.J., Groten J.P., Jonker D., Cassee F.R., Van Bladeren P.J. Toxicology of chemical mixtures: challenges for today and the future. Toxicology. 1995; 105 (2–3): 415–27.
  23. Katul’skiy Yu.N. Integral assessment of the animal organism in toxicological experiments. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 1986; 9: 47–9. (in Russian)
  24. Katul’skiy Yu.N. Methodical foundations of experimental study of the joint action of xenobiotics. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 1990; 4: 71–5. (in Russian)
  25. Katul’skiy Yu.N. About unification of indices of the possibility of disease occurrence in risk assessment methodology and the determination of the probability of non-carcinogenic effects in toxicological-hygienic, clinical and epidemiological studies and according to data about health-seeking behavior. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 2016; 10: 998–1002. (in Russian)
  26. Katul’skiy Yu.N. Risk assessment of the disease under the influence of systemic toxicants. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 2001; 6: 66–8. (in Russian)
  27. Katul’skiy Yu.N. Planning an experiment to study the dose-time dependence of the effect of the combined effect of harmful factors. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 2006; 4: 81–3.
  28. Katul’skiy Yu.N. Determination of ineffective levels of jointly acting harmful factors in the toxicological-hygienic experiment. In: Proceedings of the International Forum of the Scientific Council of the Russian Federation on Human Ecology and Environmental Hygiene [Materialy mezhdunarodnogo foruma Nauchnogo soveta RF po ekologii cheloveka i gigiyene okruzhayushchey sredy]. Moscow; 2016; V. 1: 289–92. (in Russian)
  29. Gorskiy V.G., Adler Yu.P., Brodskiy V.Z., Kuznetsov V.S. Linear Plans with Integer Levels. Zavodskaya laboratoriya. 1973; 5: 579–83. (in Russian)
  30. Katul’skiy Yu.N. On the dose-effect relationship in connection with the study of the joint action of chemical carcinogens. Voprosy onkologii. 1988; 3: 322–30.
  31. Katul’skiy Yu.N. Assessment of the effectiveness of harmful agents. Gigiena i sanitariya [Hygiene and Sanitation, Russian journal]. 2006; 6: 67–9. (in Russian)

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