Uncertainties in risk analysis and modern approaches to their reduction

View or download the full article: 
PDF icon health-risk-analysis-2024-1-18.pdf
UDC: 
614.78
DOI: 
10.21668/health.risk/2024.1.18.eng
Authors: 

E.A. Saltykova1,2, O.N. Savostikova1

Organization: 

1Centre for Strategic Planning and Management of Biomedical Health Risks, 10 Pogodinskaya St., bldg 1, Moscow, 119121, Russian Federation
2Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences, 19 Bolshoy Karetny pereulok, bldg 1, Moscow, 127051, Russian Federation

Abstract: 

The article analyzes the most common approaches to the risk assessment procedure and focuses on uncertainties at each stage of risk analysis. These uncertainties not only impede risk analysis but are also able to skew its results. The greatest impact on reliability of final risk assessments is caused by uncertainties associated with assessment of exposure, in particular, with establishing toxicological parameters in experiments and their extrapolation onto assessed population groups. An effect of a selected toxicant on a test animal sample is identified with an expected negative effect produced by it on a real human population. In addition, in laboratory experiments, in contrast to natural conditions, a population is affected only by controlled factors in small amounts.

Next, the article describes some uncertainties that arise at the stage of assessing the dose-effect relationship; in studies aimed at reducing uncertainties at this stage, it is almost impossible to detect a link between pollution and diseases not declared for research purposes. The problem of toxicological assessment of mixtures is described; the article highlights that at the moment there are no data on effects produced by most known mixtures on human health or any data on possible interactions between different chemicals either. The concept of exposome is described, which is an analysis of impacts of all environmental factors on an individual throughout his lifetime.

It is concluded that the existing concepts of risk assessment are applicable mainly for comparing hypothetical benefits and hypothetical damage at the population level. Given that, it seems quite relevant to develop such a concept of risk assessment that can be additionally used in planning preventive measures aimed at reducing morbidity and mortality and increasing life expectancy. At the same time, this concept should include a comprehensive assessment of mixtures affecting the body, considering the influence of natural and climatic conditions and non-specific reactions of the body.

Keywords: 
risk analysis, risk assessment, uncertainty, exposure, “dose – effect", influence of natural conditions, mixtures of chemicals, the exposome concept
Saltykova E.A., Savostikova O.N. Uncertainties in risk analysis and modern approaches to their reduction. Health Risk Analysis, 2024, no. 1, pp. 178–187. DOI: 10.21668/health.risk/2024.1.18.eng
References: 
  1. Panchenko S.V., Linge I.I., Vorob'eva L.M., Kapyrin I.V., Savkin M.N., Utkin S.S., Arakelyan A.A., Kryshev I.I. [et al.]. Prakticheskie rekomendatsii po voprosam otsenki radiatsionnogo vozdeistviya na cheloveka i biotu [Practical recommendations for assessing radiation effects on humans and biota]. Moscow, OOO Sam Poligrafist Publ., 2015, 265 p. (in Rus-sian).
  2. Kaptsov V.A., Zolotnikova G.P., Geger' E.V. Risk zdorov'yu naseleniya v usloviyakh tekhnogennogo zagryazneniya [Risk for public health caused by technogenic pollution]. Bryansk, Bryansk State University Publ., 2016, 160 p. (in Russian).
  3. Medvedeva S.A. Environmental risk. General concepts and assessment methods. XXI vek. Tekhnosfernaya bezopasnost', 2016, vol. 1, no. 1 (1), pp. 67–81 (in Russian).
  4. Sugak E.V., Kuznetsov E.V., Nazarov A.G. Information technologies of the estimation of ecological safety. Gornyi informatsionno-analiticheskii byulleten', 2009, no. S18, pp. 39–45 (in Russian).
  5. Zaitseva N.V., Zemlyanova M.A., May I.V., Alekseev V.B, Trusov P.V., Khrushcheva E.V., Savochkina A.A. Efficiency of health risk mitigation: complex assessment based on fuzzy sets theory and applied in planning activities aimed at ambient air protection. Health Risk Analysis, 2020, no. 1, pp. 25–37. DOI: 10.21668/health.risk/2020.1.03.eng
  6. Karelin A.O., Lomtev A.Yu., Volkodaeva M.V., Yeremin G.B. The improvement of approaches to the assessment of effects of the anthropogenic air pollution on the population in order to management the risk for health. Gigiena i sanitariya, 2019, vol. 98, no. 1, pp. 82–86. DOI: 10.18821/0016-9900-2019-98-1-82-86 (in Russian).
  7. Shur P.Z., Khasanova А.А., Tsinker М.Yu., Zaitseva N.V. Methodical approaches to assessing public health risks under combined exposure to climatic factors and chemical air pollution caused by them. Health Risk Analysis, 2023, no. 2, pp. 58–68. DOI: 10.21668/health.risk/2023.2.05.eng
  8. Zaitseva N.V., May I.V., Kleyn S.V., Kiryanov D.А., Andrishunas А.М., Sliusar N.N., Maksimova Е.V., Kamaltdinov М.R. On assessing impacts exerted by objects of accumulated envi-ronmental damage on human health and life expectancy. Health Risk Analysis, 2022, no. 1, pp. 4–16. DOI: 10.21668/health.risk/2022.1.01.eng
  9. Petrov S.B., Petrov B.A. Assessment of health risk of particulate matter components of at-mospheric emissions of multifuel power plants. Ekologiya cheloveka, 2019, no. 6, pp. 4–10. DOI: 10.33396/1728-0869-2019-6-4-10 (in Russian).
  10. Fabisiak J.P., Jackson E.M., Brink L.L., Presto A.A. A risk-based model to assess envi-ronmental justice and coronary heart disease burden from traffic-related air pollutants. Environ. Health, 2020, vol. 19, no. 1, pp. 34. DOI: 10.1186/s12940-020-00584-z
  11. Novikov S.M., Fokin M.V., Unguryanu T.N. Actual problem of methodology and development of evidence-based health risk assessment associated with chemical exposure. Gigiena i sanitariya, 2016, vol. 95, no. 8, pp. 711–716. DOI: 10.18821/0016-9900-2016-95-8-711-716 (in Russian).
  12. Pound P., Ritskes-Hoitinga M. Is it possible to overcome issues of external validity in pre-clinical animal research? Why most animal models are bound to fail. J. Transl. Med., 2018, vol. 16, no. 1, pp. 304. DOI: 10.1186/s12967-018-1678-1
  13. Shekunova E.V., Kovaleva M.A., Makarova M.N., Makarov V.G. Dose Selection in Preclinical Studies: Cross-Species Dose Conversion. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya. Regulyatornye issledovaniya i ekspertiza lekarstvennykh sredstv, 2020, vol. 10, no. 1, pp. 19–28. DOI: 10.30895/1991-2919-2020-10-1-19-28 (in Russian).
  14. Salomova H., Kosimov, H., Zhumaeva Z. Hygienic justification of the permissible safety standards for the insecticide “zaragen” in some environmental objects. Vestnik vracha, 2019, vol. 1, no. 4, pp. 105–109 (in Russian).
  15. Filonyuk V.A., Shevlyakov V.V., Dudchik N.V. Methodology of microbial preparations hygienic regulation and methods of measurements microorganisms content in the working zone air. Minsk, BelNIIT «Transtekhnika» Publ., 2018, 264 p. (in Russian).
  16. Khamidulina Kh.Kh., Tarasova E.V., Proskurina A.S., Egiazaryan A.R., Zamkova I.V., Dorofeeva E.V., Rinchindorzhieva E.A., Shvykina S.A., Petrova E.S. On the need for the development of hygienic standards (MACS) in the water and air of the working area for perfluorooctanoic acid in the Russian Federation. Toksikologicheskii vestnik, 2020, no. 5 (164), pp. 21–31. DOI: 10.36946/0869-7922-2020-5-21-31 (in Russian).
  17. Jumaeva A.A., Iskandarova G.T. Toxicological-hygienic parameters of seller insecticide application in agriculture. Effektivnost' primeneniya innovatsionnykh tekhnologii i tekhniki v sel'skom i vodnom khozyaistve: sbornik nauchnykh trudov mezhdunarodnoi nauchno-prakticheskoi onlain konferentsii, posvyashchennoi 10-letiyu obrazovaniya Bukharskogo filiala Tashkentskogo instituta inzhenerov irrigatsii i mekhanizatsii sel'skogo khozyaistva. Kursk, Izd-vo “Durdona”, 2020, pp. 437–439 (in Russian).
  18. Sauts A.V. Determination of MPC methane in the air of populated areas. Vestnik Severo-Vostochnogo federal'nogo universiteta im. M.K. Ammosova, 2018, no. 3 (65), pp. 17–23. DOI: 10.25587/SVFU.2018.65.14065 (in Russian).
  19. Guidance on information requirements and chemical safety assessment. Part E: Risk characterization. Helsinki, European Chemicals Agency, 2016, 49 p. Available at: https://echa.europa.eu/documents/10162/13632/infor-mation_requirements_p... (March 02, 2023).
  20. Guidance in a Nutshell on Chemical Safety Assessment. European Chemical Agency, 2009. Available at: https://echa.europa.eu/documents/10162/13632/nutshell_guidance_csa_en.pdf (March 02, 2023).
  21. Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterization of dose [concentration] – response for human health. Helsinki, European Chemi-cals Agency, 2012, 195 p. Available at: https://echa.europa.eu/documents/10162/17224/informa-tion_requirements_r... (March 02, 2023).
  22. Guidance on Assessment Factors to Derive a DNEL. Technical Report No. 110. Brussel, ECETOC, 2010, 211 p. Available at: https://www.ecetoc.org/wp-content/uploads/2021/10/ECETOC-TR-110-Guidance... (March 02, 2023).
  23. Committee on Toxicity Testing and Assessment of Environmental Agents. Toxicity Testing in the Twenty-First Century: A Vision and a Strategy. Washington, DS, National Academic Press, 2007.
  24. Keller D.A., Juberg D.R., Catlin N., Farland W.H., Hess F.G., Wolf D.C., Doerrer N.G. Identification and Characterization of Adverse Effects in 21st Century Toxicology. Toxicol. Sci., 2012, vol. 126, no. 2, pp. 291–297. DOI: 10.1093/toxsci/kfr350
  25. Münzel T., Hahad O., Sørensen M., Lelieveld J., Duerr G.D., Nieuwenhuijsen M., Daiber A. Environmental risk factors and cardiovascular diseases: a comprehensive expert review. Cardiovascular Research, 2022, vol. 118, no. 14, pp. 2880–2902. DOI: 10.1093/cvr/cvab316
  26. Yin J., Wu X., Li S., Li C., Guo Z. Impact of environmental factors on gastric cancer: A review of the scientific evidence, human prevention and adaptation. J. Environ. Sci. (China), 2020, vol. 89, pp. 65–79. DOI: 10.1016/j.jes.2019.09.025
  27. Dhimal M., Neupane T., Lamichhane Dhimal M. Understanding linkages between environmental risk factors and noncommunicable diseases – A review. FASEB Bioadv., 2021, vol. 3, no. 5, pp. 287–294. DOI: 10.1096/fba.2020-00119
  28. Petrov S.B., Zhernov Yu.V. Evaluation of the effectiveness of technological measures to manage the risk to public health when exposed to atmospheric emissions of multi-fuel combined heat and power plants. Ekologiya cheloveka, 2022, vol. 11, pp. 761–770. DOI: 10.17816/humeco110989 (in Russian).
  29. Zaitseva N.V., Zemlyanova M.A., Koldibekova Yu.V., Zhdanova-Zaplesvichko I.G., Pe-rezhogin A.N., Kleyn S.V. Evaluation of the aerogenic impact of priority chemical factors on the health of the child population in the zone of the exposure of aluminum enterprises. Gigiena i sanitariya, 2019, vol. 98, no. 1, pp. 68–75. DOI: 10.18821/0016-9900-2019-98-1-68-75 (in Rus-sian).
  30. GBD 2019 Risk Factors Collaborators. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet, 2020, vol. 396, no. 10258, pp. 1223–1249. DOI: 10.1016/S0140-6736(20)30752-2
  31. Murray C.J.L. The Global Burden of Disease Study at 30 years. Nat. Med., 2022, vol. 28, no. 10, pp. 2019–2026. DOI: 10.1038/s41591-022-01990-1
  32. Kienzler A., Bopp S.K., van der Linden S., Berggren E., Worth A. Regulatory assessment of chemical mixtures: Requirements, current approaches and future perspectives. Regul. Toxicol. Pharmacol., 2016, vol. 80, pp. 321–334. DOI: 10.1016/j.yrtph.2016.05.020
  33. McCarty L.S., Borgert C.J. Review of the toxicity of chemical mixtures: theory, policy, and regulatory practice. Regul. Toxicol. Pharmacol., 2006, vol. 45, no. 2, pp. 119–143. DOI: 10.1016/j.yrtph.2006.03.004
  34. Heys K., Shore R.F., Pereira M.G., Jones K.C., Martin F.L. Risk assessment of environmental mixture effects. RSC Adv., 2016, vol. 6, pp. 47844–47857. DOI: 10.1039/C6RA05406D
  35. Backhaus T., Karlsson M. Screening level mixture risk assessment of pharmaceuticals in STP effluents. Water Res., 2014, vol. 49, pp. 157–165. DOI: 10.1016/j.watres.2013.11.005
  36. Evans R.M., Scholze M., Kortenkamp A. Examining the feasibility of mixture risk assess-ment: a case study using a tiered approach with data of 67 pesticides from the Joint FAO/WHO Meeting on Pesticide Residues (JMPR). Food Chem. Toxicol., 2015, vol. 84, pp. 260–269. DOI: 10.1016/j.fct.2015.08.015
  37. Bopp S.K., Kienzler A., van der Linden S., Lamon L., Paini A., Parissis N., Richarz A.-N., Triebe J., Worth A. Review of case studies on the human and environmental risk assessment of chemical mixtures. Identification of priorities, methodologies, data gaps, future needs: JRC Technical Report. Luxembourg, Publications Office of the European Union, 2016, 89 p. DOI: 10.2788/272583
  38. Bopp S.K., Barouki R., Brack W., Dalla Costa S., Dorne J.-L.C.M., Drakvik P.E., Faust M., Karjalainen T.K. [et al.]. Current EU research activities on combined exposure to multiple chemicals. Environ. Int., 2018, vol. 120, pp. 544–562. DOI: 10.1016/j.envint.2018.07.037
  39. Bopp S.K., Kienzler A., Richarz A.-N., van der Linden S.C., Paini A., Parissis N., Worth A.P. Regulatory assessment and risk management of chemical mixtures: challenges and ways forward. Crit. Rev. Toxicol., 2019, vol. 49, no. 2, pp. 174–189. DOI: 10.1080/10408444.2019.1579169
  40. Binderup M.-L., Dalgaard M., Dragsted L.O., Hossaini A., Ladefoged O., Lam H.R., Larsen J.C., Madsen C. [et al.]. Combined Actions and Interactions of Chemicals in Mixtures: The Toxicological Effects of Exposure to Mixtures of Industrial and Environmental Chemicals. FødevareRapport, 2003, no. 12, 158 p.
  41. Kortenkamp A., Backhaus T., Faust M. State of the Art Report on Mixture Toxicity. Final Report, 2009.
  42. Ankley G.T., Edwards S.W. The Adverse Outcome Pathway: A Multifaceted Framework Supporting 21st Century Toxicology. Curr. Opin. Toxicol., 2018, vol. 9, pp. 1–7. DOI: 10.1016/ j.cotox.2018.03.004
  43. Ankley G.T., Bennett R.S., Erickson R.J., Hoff D.J., Hornung M.W., Johnson R.D., Mount D.R., Nichols J.W. [et al.]. Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment. Environ. Toxicol. Chem., 2010, vol. 29, no. 3, pp. 730–741. DOI: 10.1002/etc.34
  44. Perkins E., Garcia-Reyero N., Edwards S., Wittwehr C., Villeneuve D., Lyons D., Ankley G. The adverse outcome pathway: A conceptual framework to support toxicity testing in the twenty-first century. Computational Systems Toxicology. In: J. Hoeng, M.C. Peitsch eds. New York, NY, Humana Press, 2015, pp. 1–26. DOI: 10.1007/978-1-4939-2778-4_1
  45. Vinken M., Knapen D., Vergauwen L., Hengstler J.G., Angrish M., Whelan M. Adverse outcome pathways: a concise introduction for toxicologists. Arch. Toxicol., 2017, vol. 91, no. 11, pp. 3697–3707. DOI: 10.1007/s00204-017-2020-z
  46. Ramos R.G., Olden K. Gene-environment interactions in the development of complex disease phenotypes. Int. J. Environ. Res. Public Health, 2008, vol. 5, no. 1, pp. 4–11. DOI: 10.3390/ijerph5010004
  47. Wild C.P. Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol. Biomarkers Prev., 2005, vol. 14, no. 8, pp. 1847–1850. DOI: 10.1158/1055-9965.EPI-05-0456
  48. Rappaport S.M., Smith M.T. Environment and disease risks. Science, 2010, vol. 330, no. 6003, pp. 460–461. DOI: 10.2307/40931653
  49. Wild C.P. The exposome: from concept to utility. Int. J. Epidemiol., 2012, vol. 41, no. 1, pp. 24–32. DOI: 10.1093/ije/dyr236
  50. Riggs D.W., Yeager R.A., Bhatnagar A. Defining the Human Envirome: An Omics Ap-proach for Assessing the Environmental Risk of Cardiovascular Disease. Circulation Research, 2018, vol. 122, no. 9, pp. 1259–1275. DOI: 0.1161/CIRCRESAHA.117.311230
  51. Klyuev N.N., Yakovenko L.M. “Dirty” cities in Russia: factors determining air pollution. Vestnik Rossiiskogo universiteta druzhby narodov. Seriya: Ekologiya i bezopasnost' zhizned-eyatel'nosti, 2018, vol. 26, no. 2, pp. 237–250. DOI: 10.22363/2313-2310-2018-26-2-237-250 (in Russian).
  52. Surzhikov V.D., Surzhikov D. V., Ibragimov S.S., Panaiotti E.A. Air pollution as the factor of the influence on the life quality of the population. Byulleten' VSNTs SO RAMN, 2013, no. 3–2 (91), pp. 135–139 (in Russian).
  53. Tsimmerman V.I., Badmaeva S.E. The impact of the industry branches on the city air environment. Vestnik KrasGAU, 2015, no. 4 (103), pp. 3–6 (in Russian).
  54. Beelen R., Raaschou-Nielsen O., Stafoggia M., Andersen Z.J., Weinmayr G., Hoffmann B., Wolf K., Samoli E. [et al.]. Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project. Lancet, 2014, vol. 383, no. 9919, pp. 785–795. DOI: 10.1016/S0140-6736(13)62158-3
  55. Air pollution and child health: prescribing clean air. WHO, 2018. Available at: https://www.who.int/publications/i/item/WHO-CED-PHE-18-01 (March 11, 2023).
  56. Borchert F., Beronius A., Ågerstrand M. Characterisation and analysis of key studies used to restrict substances under REACH. Environ. Sci. Eur., 2022, vol. 34, pp. 83. DOI: 10.1186/s12302-022-00662-8
  57. Saltykova M.M., Balakaeva A.V., Shopina O.V., Bobrovnitsky I.P. Analysis of associations between air pollution and mortality from noncommunicable diseases across genders and age-groups. Ekologiya cheloveka, 2021, no. 12, pp. 14–22. DOI: 10.33396/1728-0869-2021-12-14-22 (in Russian).
  58. Borge R., Requia W.J., Yagüe C., Jhun I., Koutrakis P. Impact of weather changes on air quality and related mortality in Spain over a 25 year period [1993–2017]. Environ. Int., 2019, vol. 133, pt B, pp. 105272. DOI: 10.1016/j.envint.2019.105272
  59. Tsallagova R.B., Kopytenkova O.I., Makoeva F.K., Nanieva A.R. Cardiovascular risk assessment of the population under adverse weather conditions. Gigiena i sanitariya, 2020, vol. 99, no. 5, pp. 488–492. DOI: 10.47470/0016-9900-2020-99-5-488-492 (in Russian).
  60. Mistry M.N., Schneider R., Masselot P., Royé D., Armstrong B., Kyselý J., Orru H., Sera F. [et al.]. Comparison of weather station and climate reanalysis data for modelling temperature-related mortality. Sci. Rep., 2022, vol. 12, no. 1, pp. 5178. DOI: 10.1038/s41598-022-09049-4
Received: 
20.06.2023
Approved: 
10.10.2023
Accepted for publication: 
20.03.2024

You are here

Home