Determining the effect of drug "Warfarin sodium" on toxicity indicators in an acute experiment

Authors

  • D.O. Hlavachek State Institution “O.M. Marzіeiev Institute for Public Health of the National Academy of Medical Sciences of Ukraine”, Popudrenka str., 50, Kyiv, 02094, Ukraine https://orcid.org/0000-0002-0512-6927
  • O.Ye. Kondratenko State Institution “O.M. Marzіeiev Institute for Public Health of the National Academy of Medical Sciences of Ukraine”, Popudrenka str., 50, Kyiv, 02094, Ukraine https://orcid.org/0000-0002-9504-7228

DOI:

https://doi.org/10.26641/2307-0404.2023.3.288925

Keywords:

warfarin sodium, anticoagulants, DL50, intragastric administration, toxicological indicator

Abstract

The drug "Warfarin sodium" refers to anticoagulants of indirect action. It contains only one substance - warfarin sodium, the toxicological indicator of which have been studied in many countries. Therefore, the range of indicators for DL50 of warfarin sodium is very large. However, warfarin sodium has not yet been studied in Ukraine, its maximum permissible concentration in the air of the work area has not been established. Significant volumes of production and use of the drug “Warfarin sodium” on the territory of Ukraine necessitate the clarification of its main toxicological indicators and the establishment of the maximum allowable concentration in the air of the working area, which includes several stages. The first of them is the purpose of this work, namely: to establish DL50 upon intragastric administration of the drug "Warfarin sodium" to two species of animals in the conditions of an acute experiment. Experimental animals (60 non-linear white rats and 70 non-linear white mice) were divided into 9 groups. Six groups were injected with the drug "Warfarin sodium" in different doses: the first group (female rats) – 58 mg/kg per animal, the second (also female rats) – 29 mg/kg, the third (male rats) – 323 mg/kg, the fourth (also male rats) – 161.5 mg/kg, the fifth (mice of both sexes) – 374 mg/kg, the sixth (also mice of both sexes) – 187 mg/kg. Three control groups (the first – 6 male rats, the second – 6 female rats, the third – 14 mice) received distilled water. As a result, the mortality rates of experimental animals were obtained, on the basis of which, using the probit analysis method, the toxicity indicator of DL50 was determined: for female rats – 15.85 mg/kg, male rats – 398.11 mg/kg and mice –645.65 mg/kg. The established DL50 for male rats after intragastric administration of the drug "Warfarin sodium" may indicate an increase in their resistance to the drug, and this determines the expediency of periodic repeated acute experiments in order to verify the relevance of previously established DL50 of sodium warfarin. According to DL50 upon intragastric administration to female rats, which are the most sensitive species of animals to it, warfarin sodium belongs to highly hazardous substances.

References

Elango K, Javaid A, Khetarpal BK, et al. The Ef-fects of Warfarin and Direct Oral Anticoagulants on Systemic Vascular Calcification: A Review. Cells. 2021;10(4):773. doi: https://doi.org/10.3390/cells10040773

Gulati S, Gulati A. Anticoagulant rodenticide poisoning. Indian J Med Spec. 2018;9(3):150-3. doi: https://doi.org/10.1016/j.injms.2018.04.010

Assessment report Warfarin product type 14 (rodenticides). Directive 98/8/EC concerning the placing biocidal product on the market. Inclusion of active substances in annex I or IA to Directive 98/8/EC. European Chemicals Agency, Ireland; 2009. 61 p. Available from: https://circabc.europa.eu/sd/a/5bcfe8f9-228c-4bff-a347-556018a9af30/2009-09-16%20BPD%20Warfarin%20AR.pdf

PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004. PubChem Compound Summary for CID 16204922, Warfarin Sodium; [cited 2023 Apr 01]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Warfarin-Sodium

Warfarin sodium. Certificate of quality control department. Cadila Healthcare Limited [Internet]. 2018 [cited 2023 Jun 21]. Available from: https://www.zyduscadila.com/

[On approval of guidelines "Justification of the maximum permissible concentrations of drugs in the air of the working area and the atmospheric air of populated areas". Order of the MH of Ukraine dated 2005 Oct 21 No. 544] [Internet]. 2005 [cited 2023 Jun 21]. Ukrainian. Available from: https://zakon.rada.gov.ua/rada/show/v0544282-05#Text

[On the approval of methods for conducting research on the specific activity, safety, quality (efficacy) of disinfectants and their testing in practice. Order of the MH of Ukraine dated 2020 Sept 03 No. 2024] [Internet]. 2020 [cited 2023 Jun 21]. Ukrainian. Available from: https://moz.gov.ua/article/ministry-mandates/nakaz-moz-ukraini-vid-03092020--2024-pro-zatverdzhennja-metodiv-provedennja-doslidzhen-specifichnoi-aktivnosti-bezpechnosti-jakosti-efektivnosti-dezinfekcijnih-zasobiv-ta-ih-viprobuvannja-na-praktici

[On approval of hygienic regulations for the permissible content of chemical and biological substances in the air of the working area. Order of the MH of Ukraine dated 2020 Jul 14 No. 1596] [Internet]. 2020 [cited 2023 Jun 21]. Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/z0741-20#Text

Smith AJ. Guidelines for planning and conducting high-quality research and testing on animals. Lab Anim Res. 2020;21. doi: https://doi.org/10.1186/s42826-020-00054-0

Erhirhie EO, Ihekwereme CP, Ilodigwe EE. Advances in acute toxicity testing: strengths, weaknesses and regulatory acceptance. Interdiscip Toxicol. 2018;11(1):5-12. doi: https://doi.org/10.2478/intox-2018-0001

Halmi MI, Rahim MB, Othman AR. Estimation of LC50 and its Confidence Interval for the Effect of Ferrous Sulphate on Catla catla. JEMAT. 2018;6(1):21-3. doi: https://doi.org/10.54987/jemat.v6i1.402

[On the approval of the Methodological Guidelines "Justification of the permissible exposure limits (PELs) of chemical substances in the atmospheric air of populated areas". Order of the MH of Ukraine dated 2004 Oct 07 No. 485]. [Internet]. 2004 [cited 2023 Jun 21]. Ukrainian. Available from: https://zakon.rada.gov.ua/rada/show/v0485282-04#Text

Dutta S, Sharma PK, Misra AK, et al. A Case Report on Warfarin Induced Skin Necrosis: Drug-drug Interaction or Inappropriate Therapy. J Pharm Sci Therap. 2018;4(1):230-3. doi: https://doi.org/10.18314/jpt.v4i1.1445

Nsaful J, Adjei YO, Dedey F, et al. Warfarin-induced skin necrosis: a rare condition. Ghana Med J. 2020;54(4):269-73. doi: https://doi.org/10.4314/gmj.v54i4.10

Dearden JC, Hewitt M. Prediction of Human Lethal Doses and Concentrations of MEIC Chemicals from Rodent LD50 Values: An Attempt to Make Some Reparation. Altern Lab Anim. 2021;49(1-2):10-21. doi: https://doi.org/10.1177/0261192921994754

Published

2023-09-29

How to Cite

1.
Hlavachek D, Kondratenko O. Determining the effect of drug "Warfarin sodium" on toxicity indicators in an acute experiment. Med. perspekt. [Internet]. 2023Sep.29 [cited 2024Mar.3];28(3):12-8. Available from: https://journals.uran.ua/index.php/2307-0404/article/view/288925

Issue

Section

THEORETICAL MEDICINE