Experimental models of animal chronic pathology in assessing health risks for sensitive population groups

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[615.9+612.014.46]: 546.43
Authors: 

E.V. Drozdova1, S.I. Sychik1, V.A. Hrynchak1, S.N. Rjabceva2

Organization: 

1Scientific and Practical Center for Hygiene, 8 Akademicheskaya Str., Minsk, 220012, Republic of Belarus
2Institute of Physiology of the National Academy of Sciences of Belarus, 28 Akademicheskaya Str., Minsk, 220072, Republic of Belarus

Abstract: 

The methodology for health risk assessment and hygienic standardization of chemicals often neglects such a vulnerable population group as people with chronic non-communicable diseases. According to the data provided by the WHO, the prevalence of such pathologies is high in many European countries; therefore, when a disease burden in a certain population is unaccounted for, this may result in lower accuracy of accomplished assessments. On the other hand, introduction of too conservative safe factors when hygienic standards are being developed for chemicals in various media leads to high uncertainty and excessive limitations.

Our research goal was to provide scientific substantiation for a methodology for using experimental pathology models to improve reliability of hygienic standardization and accuracy of health risk assessments for sensitive population groups (people suffering from non-chronic communicable diseases) under exposure to naturally occurring chemicals. Another goal was to test this methodology by performing a case study on drinking water. The testing results indicate that a chronic 6-month exposure to model substances produced more apparent toxic effects on experimental animals with model pathologies (spontaneous hypertension and experimental histamine-induced nephropathy) in comparison with “healthy” animals.

This allowed us to recommend using experimental models of congenital and induced animal pathology bearing in mind target organs for toxic effects produced by the analyzed chemicals to substantiate hygienic standards, health risks taken into account. This should be done at the stage when dose-dependent reactions are identified (determination of no-effect and / or threshold levels) in addition to studies performed on “healthy” animals. It is most appropriate to use this approach when the following conditions are met: 1) a research object is naturally occurring chemicals that are widely spread in the environment due to its natural formation; 2) pathologies of organs (systems) that are targets for biological effects produced by the tested chemicals are widely spread in a population (circulatory diseases, diseases of the excretory system, etc.).

Keywords: 
experimental pathology models, nephropathy, spontaneously hypertensive rats, risk assessment, hygienic standardization, sensitive population groups, methodological approaches, barium, total mineralization
Drozdova E.V., Sychik S.I., Hrynchak V.A., Rjabceva S.N. Experimental models of animal chronic pathology in assessing health risks for sensitive population groups. Health Risk Analysis, 2022, no. 2, pp. 185–195. DOI: 10.21668/health.risk/2022.2.17.eng
References: 
  1. Uncertainty factors: Their use in human health risk assessment by UK Government. Leicester, Institute for Environment and Health Publ., 2003, 73 p.
  2. Shur P.Z., Khasanova A.A. Analytical review of approaches to providing safety when substantiating hygienic standards for chemicals contents in ambient air. Health Risk Analysis, 2021, no. 2, pp. 156–167. DOI: 10.21668/health.risk/2021.2.15.eng
  3. Calabrese E.J. Uncertainty factors and interindividual variation. Regul. Toxicol. Pharmacol., 1985, vol. 5, no. 2, pp. 190–196. DOI: 10.1016/0273-2300(85)90032-7
  4. Hattis D., Erdreich L., Ballew M. Human variability in susceptibility to toxic chemicals--a preliminary analysis of pharmacokinetic data from normal volunteers. Risk Anal., 1987, vol. 7, no. 4, pр. 415–426. DOI: 10.1111/j.1539-6924.1987.tb00479.x
  5. Dourson M.L., Felter S.P., Robinson D. Evolution of science-based uncertainty factors in noncancer risk assessment. Regul. Toxicol. Pharmacol., 1996, vol. 24, no. 2, pp. 108–120. DOI: 10.1006/rtph.1996.0116
  6. Scheuplein R., Charnley G., Dourson M.L. Differential sensitivity of children and adults to chemical toxicity: I. Biological basis. Reg. Toxicol. Pharmacol., 2002, vol. 35, no. 3, pp. 429–447. DOI: 10.1006/rtph.2002.1558
  7. Dourson M.L., Charnley G., Scheuplein R. Differential sensitivity of children and adults to chemical toxicity: II. Risk and regulation. Reg. Toxicol. Pharmacol., 2002, vol. 35, no. 3, pp. 448–467. DOI: 10.1006/rtph.2002.1559
  8. Hines R.N., Sargent D., Autrup H., Birnbaum L.S., Brent R.L., Doerrer N.G., Cohen Hubal E.A., Juberg D.R. [et al.]. Approaches for assessing risks to sensitive populations: lessons learned from evaluating risks in the pediatric population. Toxicol. Sci., 2010, vol. 113, no. 1, pp. 4–26. DOI: 10.1093/toxsci/kfp217
  9. Haber L.T., Maier A., Gentry P.R., Clewell H.J., Dourson M.L. Genetic polymorphisms in assessing interindividual variability in delivered dose. Regul. Toxicol. Pharmacol., 2002, vol. 35, no. 2 (pt 1), pp. 177–197. DOI: 10.1006/rtph.2001.1517
  10. Dourson M.L., Gadagbui B., Onyema C., McGinnis P.M., York R.G. Data derived extrapolation factors for developmental toxicity: A preliminary research case study with perfluorooctanoate (PFOA). Regul. Toxicol. Pharmacol., 2020, vol. 110, pp. 104502. DOI: 10.1016/j.yrtph.2019.104502
  11. Dourson M.L., Gadagbui B., Onyema C., McGinnis P.M., York R.G. Data derived Extrapolation Factors for developmental toxicity: A preliminary research case study with perfluorooctanoate (PFOA). Regul. Toxicol. Pharmacol., 2019, vol. 108, pp. 104446. DOI: 10.1016/j.yrtph.2019.104446
  12. Grynchak V.A., Sychik S.I. Peculiarities of the toxic effect of diisononyl phthalate plasticizer phthalate on experimental models. Gigiena i sanitariya, 2018, vol. 97, no. 5, pp. 474–477. DOI: 10.47470/0016-9900-2018-97-5-474-477 (in Russian).
  13. Dorne J.L.C.M. Human variability in hepatic and renal elimination: implications for risk assessment. Journal of Applied Toxicology, 2007, vol. 27, no. 5, pp. 411–420. DOI: 10.1002/jat.1255
  14. Burnett S.D., Karmakar M., Murphy W.J., Chiu W.A., Rusyn I. A new approach method for characterizing inter-species toxicodynamic variability. J. Toxicol. Environ. Health A, 2021, vol. 84, no. 24, pp. 1020–1039. DOI: 10.1080/15287394.2021.1966861
  15. Bhat V.S., Meek M.E.B., Valcke M., English C., Boobis A., Brown R. Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance. Crit. Rev. Toxicol., 2017, vol. 47, no. 9, pp. 729–749. DOI: 10.1080/10408444.2017.1303818
  16. Murray F.J., Schlekat C.E. Comparison of Risk Assessments of Boron: Alternate Approaches to Chemical-Specific Adjustment Factors. Human and Ecological Risk Assessment, 2004, vol. 10, no. 1, pp. 57–68. DOI: 10.1080/10807030490280954
  17. The public health impact of chemicals: knowns and unknowns. Geneva, World Health Organization, 2016. Available at: http://www.who.int/ipcs/publications/chemicals-public-health-impact/en/ (19.12.2021).
  18. Nakamoto H., Soeda Y., Seki T., Watanabe T., Satoh M. Possible involvement of descending serotonergic systems in antinociception by centrally administered elcatonin in mice. Biol. Pharm. Bull., 1999, vol. 22, no. 7, pp. 691–697. DOI: 10.1248/bpb.22.691
  19. Nakamoto H., Nemoto H., Sugahara S., Okada H., Suzuki H. Nifedipine and arotinolol in combination for accelerated-malignant hypertension: results of one year follow-up. Hypertens. Res., 1999, vol. 22, no. 2, pp. 75–80. DOI: 10.1291/hypres.22.75
  20. Nakamoto H., Hasegawa M. Targeted inactivation of the gene psaK encoding a subunit of photosystem I from the cyanobacterium Synechocystis sp. PCC 6803. Plant Cell Physiol., 1999, vol. 40, no. 1, pp. 9–16. DOI: 10.1093/oxfordjournals.pcp.a029479
  21. Zhuravlyov D.A. Hypertension models. Spontaneously hypertensive rats. Arterial’naya gi-pertenziya, 2009, vol. 15, no. 6, pp. 721–723. DOI: 10.18705/1607-419X-2009-15-6-721-723 (in Russian).
  22. Okamoto K., Aoki K. Development of a strain of spontaneously hypertensive rats. Jpn. Circ. J., 1963, vol. 27, pp. 282–293. DOI: 10.1253/jcj.27.282
  23. Plotnikov M.B., Aliev O.I., Anishchenko A.M., Sidekhmenova A.V., Shamanaev A.Yu., Fedorova E.P. Dynamics of blood pressure and quantity indices of erythrocytes in SHR in early period of arterial hypertension forming. Rossiiskii fiziologicheskii zhurnal im. I.M. Sechenova, 2015, vol. 101, no. 7, pp. 822–828 (in Russian).
  24. Sidekhmenova A.V., Aliev O.I., Anishchenko A.M., Shamanaev A.Yu., Fedorova E.P., Plotnikov M.B. Dynamics of indicators of platelets, white blood cells, and functional activity of the endothelium in young SHR rats. Sibirskii meditsinskii zhurnal (Tomsk), 2015, vol. 30, no. 3, pp. 61–65. DOI: 10.29001/2073-8552-2015-30-3-61-65 (in Russian).
  25. Kovaleva M.A., Makarova M.N., Selezneva A.I., Makarov V.G. Expediency of application of animals with the spontaneous hypertensia for modelling of the metabolic syndrome. Obzory po klinicheskoi farmakologii i lekarstvennoi terapii, 2012, vol. 10, no. 4, pp. 91–94 (in Russian).
  26. Cappelli-Bigazzi M., Rubattu S., Battaglia C., Russo R., Enea I., Ambrosio G., Chiariello M., Volpe M. Effects of high-cholesterol and atherogenic diets on vascular relaxation in spontaneously hypertensive rats. Am. J. Physiol., 1997, vol. 273, no. 2, pp. H647–H654. DOI: 10.1152/ajpheart.1997.273.2.H647
  27. Perez C.M., Hazari M.S., Ledbetter A.D., Haykal-Coates N., Carll A.P., Cascio W.E., Winsett D.W., Costa D.L., Farraj A.K. Acrolein inhalation alters arterial blood gases and triggers carotid body-mediated cardiovascular responses in hypertensive rats. Inhal. Toxicol., 2015, vol. 27, no. 1, pp. 54–63. DOI: 10.3109/08958378.2014.984881
  28. Abdel-Rahman A.A. Alcohol abolishes the hypotensive effect of clonidine in spontaneously hypertensive rats. Hypertension, 1994, vol. 24, no. 6, pp. 802–807. DOI: 10.1161/01.hyp.24.6.802
Received: 
03.02.2022
Approved: 
20.05.2022
Accepted for publication: 
21.06.2022

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