The analysis of theoretical and applied aspects of the application of alternative methods of toxicity research in the implementation of hygienic regulation of chemical production factors and the prospects of their use in Ukraine showed that scientific developments on the replacement of vertebrates in experiments on the study of chemical toxicity in both European countries and other countries great attention is paid to and significant support from state regulators. Validated alternative toxicity research methods are available in publicly available databases and cover virtually all types of toxic effects. In Ukraine, insufficient attention is being paid to this issue at the state level. The European vector of development of Ukraine obliges the state and scientists to actively introduce alternative methods of research in the field of industrial toxicology.

Received: 17.12.2019

Keywords: industrial toxicology, animals, alternative methods, European and Ukrainian legislative framework

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1. 1. Trakhtenberh IM, Kovalenko VM, Kokshareva NV, Zhminko PH, Chumak VT, Baula OP. Alternative methods and test systems. K.: VD Avitsena; 2008. 268 s.
2. 2. Kundiiev YuI, Cherniuk VI. Institute of Occupational Health of NAMS of Ukraine. Achievements and development prospects (up to the 85th anniversary of the Institute's foundation). Ukrainskyi zhurnal z problem medytsyny pratsi; 2013;(4):3-10).
3. 3. Klestova ZS, Holovko AM. Application of alternative invitro research methods. Problemy zooinzhenerii ta veterynarnoi medytsyny. 2014;29(2):142-5).
4. 4. Guidance Document on Good In Vitro Method Practices (GIVIMP) [Internet]; 2018, OECD Series on Testing and Assessment, No. 286, OECD Publishing, Paris [сited 2020 Jan 10].
5. 5. Michael Balls Robert, Combes Andrew Worth editors. The history of alternative test methods in toxicology. Academic Press; 2018: 352. doi.org/10.1016/B978-0-12-813697-3.00003-2
6. 6. Ward S. The 10th world congress: where have we been and where are we going? [Internet]; 2017 April 23: AltTox [сited 2020 Jan 10].
7. 7. EURL ECVAM Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches [Internet]. Zuang V. & Dura A. 2018; [сited 2020 Jan 10]. Available from:
8. 8. Trakhtenberh IM. Preventive toxicology and medical ecology Selected lectures for scientists and students. Kyiv: VD Avitsena; 2011. 317 s.
9. 9. Council Directive 89/391/EEC of 12 June 1989 on the introduction of measures to encourage improvements in the safety and health of workers at work. European Communities [Internet]; 1989 [сited 2020 Jan 10].
10. 10. Law of Ukraine «On Occupational Safety» [Internet]; 2695-XII vid 14.10.92 [сited 2020 Jan 10]. Vidomosti Verkhovnoi Rady Ukrainy.
11. 11. Law of Ukraine «On ensuring sanitary and epidemiological well-being of the population»[Internet]; 4005-XII vid 24.02.94. Vidomosti Verkhovnoi Rady Ukrainy) [сited 2020 Jan 10].
12. 12. Korshun MN., Krasnokutskaia LM. The principle of «three R» and the ways of its implementation in toxicological and hygienic studies. Ukrainskyi zhurnal z problem medytsyny pratsi. 2005; 3-4: 66-73). doi.org/10.33573/ujoh2005.03.066
13. 13. Russell WMS., Burch RL. The Principles of Humane Experimental Technique. London: Methuen & Co. Ltd.; 1959. 238 p.
14. 14. Tцrnqvist E., Annas A., Granath B., Jalkesten E., Cotgreave I., Цberg M. Strategic Focus on 3R Principles Reveals Major Reductions in the Use of Animals in Pharmaceutical Toxicity Testing. Plos one. 2014;9(7). doi.org/10.1371/journal.pone.0101638
15. 15. European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes. Strasbourg [Internet]; 18.III.1986. 11 [сited 2020 Jan 10].
16. 16. Directive 2010/63/EU of the European parliament and of the council of 22 September 2010 on the protection of animals used for scientific purposes [Internet]; [сited 2020 Jan 10].
17. 17. The Animal Welfare Act [Internet]. Public Law 89-544 Act of August 24, 1966 [сited 2020 Jan 10].
18. 18. Methodology for derivation of occupational exposure limitsof chemical agents The General Decision-Making Framework of the Scientific Committee on Occupational Exposure Limits (SCOEL) [Internet]; 2017; European Commission. B-1049. Brussels, 91 [сited 2020 Jan 10].
19. 19. Kim TW, Che JH, Jeong-Hwan, Yun JW. Use of stemcellsas alternative methods to animal experimentation in predictive toxicology. Regulatory toxicology and pharmacology. 2019; 105: 15-29. doi.org/10.1016/j.yrtph.2019.03.016
20. 20. Guerreiro DD, Mbemya GT, Bruno JB, Faustino LR,de Figueiredo JR, Rodrigues, APR. Invitro culture systems as an alternative for female reproductive toxicology studies. ZYGOTE. 2019;27(2):55-63. doi.org/10.1017/S0967199419000042
21. 21. Hartung T., Bruner L., Curren R., Eskes C., Goldberg A., McNamee P. et al. First Alternative Method Validated by a Retrospective Weight-of-Evidence Approach to Replace the Draize Eye Test for the Identification of Non-Irritant Substances for a Defined Applicability Domain. Altex. 2009;1(10):43-51. doi.org/10.14573/altex.2010.1.43
22. 22. Fukuda T, Gouko R, Eitsuka T, Suzuki R, Takahashi K, Nakagawa K et al. Human- Derived Corneal Epithelial Cells Expressing Cell Cycle Regulators as a New Resource for in vitro Ocular Toxicity Testing. Frontiers in genetics. 2019;10:578. doi.org/10.3389/fgene.2019.00587
23. 23. Asturiol D, Casati S, Worth A. Consensus of classification trees for skin sensitisation hazard prediction. 2016. Toxicology in Vitro; 36: 197-209. doi.org/10.1016/j.tiv.2016.07.014
24. 24. Bal-Price AK., Sunol C., G Weiss D., Vliet E., Westerink RHS, Costa LG. Application of in vitro neurotoxicity testing for regulatory purposes: Symposium III summary and research needs. NeuroToxicology. 2008;29:520-531. doi.org/10.1016/j.neuro.2008.02.008
25. 25. Hamm J., Sullivan K., Clippinger AJ., Strickland J., Bell S., Bhhataraid B. et al. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing. Toxicology in Vitro. 2017;41:245-59. doi.org/10.1016/j.tiv.2017.01.004
26. 26. Linval R De Pass. Alternative approaches in median lethality (LD50) and acute toxicity testing. Toxicology Letters. 1989; 49 (2-3): 159-70. doi.org/10.1016/0378-4274(89)90030-1
27. 27. Ekwall B. Correlation between cytotoxicity in vitro and LD50 values. Acta Pharmacologies et Toxicologica. 1983; 52: 80-99.doi.org/10.1111/j.1600-0773.1983.tb02685.x
28. 28. Clippinger AJ., Allen D., Behrsing H., KA Bëru Bë, Bolger MB. et al. Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity. Toxicology in Vitro. 2018;52:131-45. doi.org/10.1016/j.tiv.2018.06.009
29. 29. Validation of Alternative In Vitro Methods to Animal Testing: Concepts, Challenges, Processes and Tools. Griesinger C., Desprez B., Coecke S., Casey W, Zuang V. Adv Exp Med Biol. 2016;856:65-132. doi.org/10.1007/978-3-319-33826-2_4
30. 30. Law of Ukraine «On the protection of animals from ill-treatment» [Internet]; 3447-IV vid 21.02.2006 [сited 2020 Jan 10]. Available from: https://zakon.rada.gov.ua/laws/show/3447-15.
31. 31. The procedure for conducting scientific experiments, experiments on animals: nakaz MON Ukrainy vid 01.03.2012 No 249. Ofitsiinyi visnyk Ukrainy. 2012;24:82.
32. 32. Pro zatverdzhennia utochnenoho pereliku naukovykh doslidzhen i rozrobok, shcho vykonuvatymutsia u 2019 rotsi [Internet]. Nakaz MOZ Ukrainy vid 26.06.2019 No 1459 [сited 2020 Jan 11]. Available from: https://moz.gov.ua/article/ministry-mandates/ nakaz-moz-ukraini-vid-26062019--1459-pro-zatverdzhennja-utochnenogo-pereliku-naukovih- doslidzhen-i-rozrobok-scho-vikonuvatimutsja-u-2019-roci.
33. 33. Trakhtenberh YM, Kovalenko VN (Alternative methods in preclinical toxicological studies of drugs (soobshchenye 1). Visnyk farmakolohii ta farmatsii. 2006;6:23-31.
34. 34. Trakhtenberh YM, Kovalenko VN. Alternative methods in preclinical toxicological studies of drugs (soobshchenye 2). Visnyk farmakolohii ta farmatsii. 2006;7:19-29.
35. 35. Korshun MN. Theoretical and applied aspects of the use of second-order biological models in toxicological and hygiene studies (based on the materials of the VIII International Scientific and Practical Conference «Actual Problems of Toxicology. Safety of Human Life»). Sovremennыe problemы toksykolohy. 2007;3:66-7.
36. 36. Kuzminov OB. Evaluation of the cytotoxic effects of antihistamines - loratadine and desloratadine using a test object - bull sperm. Visnyk Dnipropetrovskoho universytetu. Biolohiia. Medytsyna. 2014;5(1):3-6. doi.org/10.15421/021401
37. 37. Kuzminov BP, Ostapiv DD, Zazuliak TS, Turkina VA, Mykitchak TI, Hrushka OI. Investigation of the toxicity of L-lysine of escinate in alternative test objects. 2014;3-4:85-9.
38. 38. Kovalenko VN. Alternative methods in the preclinical study of drug toxicity. Suchasni problemy toksykolohii. 2002; 4 [сited 2020 Jan 11].
39. 39. Trakhtenberh IM, Dmytrukha NM. Industrial toxicology: main directions, results and prospects of scientific activity. Ukrainian journal of occupational health. 2019;15(2):87- 101 doi.org/10.33573/ujoh2019.02.087
40. 40. Luhovskyi SP, Demetska OV, Tsapko VH. Modern approaches to testing and regulation of nanomaterials. Ukrainskyi zhurnal z problem medytsyny pratsi. 2019;15(4):263-70).doi.org/10.33573/ujoh2019.04.263
41. 41. Trakhtenberh IM, Marchenko ML, Bezdieniezhnykh NO, Kudriavets YuI. The advantages of the method of studying the toxic effect of heavy metal compounds in human cell culture in vitro compared to the traditional in vivo method in animals as more reliable and adequate. Suchasni problemy toksykolohii. 2010;(2-3):69-76.
42. 42. Trakhtenberh IM, Kudriavets YuI, Marchenko ML, Bezdieniezhnykh NO, An advanced model of a multi-organ toxicity system of xenobiotics based on in vitro coculture of human cells. Suchasni problemy toksykolohii. 2011;(1-2):60-4.
43. 43. Marchenko ML, Bezdieniezhnykh NO, Kudriavets YuI. Comparative characterization of the cytotoxic effect of heavy metal compounds on human cells cultured in vitro. Ukrainskyi zhurnal z problem medytsyny pratsi. 2008;3(15):27-34).
44. 44. Dmytrukha NM, Korolenko TK, Marchenko ML. Application of cell culture method in toxicological experiment. Suchasni problemy bioetyky. K.: Akademperiodyka. 2009:166-71.
45. 45. Dmytrukha NM, Lahutina OS. The use of alternative models to evaluate the toxicity of heavy metal compounds in vitro. Aktualni problemy profilaktychnoi medytsyny. 2019;2(18):18-30.
46. 46. Chekhun VF. Priority results of the Institute of Experimental Pathology, Oncology and Radiobiology. RE. Kavetsky NAS of Ukraine. Nauka ta naukoznavstvo. 2014;1:46-57.