To substantiation of the list of hazardous highly toxic chemicals that are subject to special control regarding handling, storage, use and disposal. Part III (bipyridyl herbicides paraquat and diquat)

  • Authors: M.G. Prodanchuk, G.M. Balan, O.P. Kravchuk, P.G. Zhminko, I.M. Maksymchuk, N.P. Chermnykh
  • UDC: 631.348:661.162.2
  • DOI: 10.33273/2663-4570-2021-91-2-22-30
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M. Prodanchuk1, G. Balan1, O. Kravchuk1, P. Zhminko1, I. Maksymchuk2, N. Chermnykh1

1 LI Medved’s Research Centre of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine
2 National Police of Ukraine, Kyiv, Ukraine

ABSTRACT. The Aim of the Research. To identify a group of highly toxic chemicals which over the past decades are most often used in deliberate criminal and suicidal incidents, sabotage, and terrorist act; the handling, storage, use and disposal of which must be especially carefully monitored by law enforcement agencies. In this part of the article bipyridyl herbicides paraquat and diquat are considered.

Materials and Methods. An analytical review of scientific publications was carried out using the abstract databases of scientific libraries Pub Med, Medline and text databases of scientific publishing houses Elsevier, Pub Med, Central, BMJ group as well as other VIP databases. Methods of systemic, comparative, and content analysis were used.

Results and Conclusions. Analytical review of literature data and research carried out at the State Enterprise Scientific Centre of Preventive Toxicology, Food and Chemical Safety named after Academician L.I. Medved of the Ministry of Health of Ukraine, showed that highly toxic bipyridyl herbicides paraquat and diquat can pose a threat to human life and health. Recently, in particular for more than a quarter of a century, they have become a real weapon in the hands of criminals, delinquents, and terrorists all over the world.

Suicidal incidents, which also take place along with intentional criminal, terrorist, and sabotage acts, should not be concealed. Based on the analysis of the toxicity, clinical and morphological expression of intoxication when exposed to these chemicals, considering various routes of entry into the body, the need to include them in the List of hazardous highly toxic chemicals, the handling, storage, use, and disposal of which require stricter control of law enforcement agencies, is justified.

Key Words: bipyridyl herbicides, paraquat, diquat, health risk, acute poisoning.



1. Jeyaratnam J. Acute pesticide poisoning: a major global health problem. World Health Stat Q. 1990;43:139–44.

2. Eddleston M, Phsiisps MR, Self poisoning with pesticides. BMG. 2004;328:42–4.

3. Gunnell D, Eddleston M, Phillips MR, et al. The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health. 2007;7:357–9.

4. Dawson AH, Eddleston M, Senarathna L, et al. Acute human lethal toxicity of agricultural pesticides: a prospective cohort study. PloS Med. 2010;7:e1000357.

5. Yin Y, Guo X, Zhang SL, et al. Analysis of paraquat intoxication epidemic (2002–2011) within China. Biomed Environ Sci. 2013;26:509–12.

6. Patel V, Ramasundarahettige C, Vijayakumar L, et al. Suicide mortality in India: a nationally representative survey. Lancert. 2012;379:2343–51.

7. Chang SS, Lu TH, Eddleston M, et al. Factors associated with the decline in suicide by pesticide poisoning in Taiwan: a time trend analysis, 1987–2010. Clin Toxicol. 2012;50:471–80.

8. Gawarammana IB, Buckley NA. Medical management of paraquat ingestion. Br J Clin Pharmacol. 2011;72:745–57. DOI:10.1111/j.1365-2125.2011.04026.x.

9. Gawarammana IB, Buckley NA, Mohamed F, Nazer K, et al. High-dose immunosuppression to prevent death after paraquat self-poisoning – a randomized controlled trial. Clin Toxicol. 2017. DOI:org/10.1080/15563650.2017.1394465.

10. Senarathna l, Eddleston M, Wilks MF, et al. Prediction of outcome after paraquat poisoning by measurement of the plasma paraquat concentration. QJM. 2009;102:251–259.

11. Li LR, Sydenham E, Chaudhary B, et al. Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis. Cochrane Database Syst Rev. 2014;8:CD008084.

12. Wu WP, Lai MN, Lin CN, et al. Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study. PloS One. 2014;9:e87568.

13. Ghorbani A, Masoumi K, Forouzan A, et al. Effect of pulse therapy with glucocorticoids and cyclophosphamide in patients with paraquat poisoning. Hong Kong J Emerg Med. 2015;22:235–40.

14. Parakvat i dikvat. Gigiyenicheskiye kriterii sostoyaniya okruzhayushchey sredy. Sovmestnoye izdaniye Programmy OON po okruzhayushchey srede. Mezhdunarodnoy organizatsii truda i VOZ. Zheneva; 1989. 158 s.

15. Makovskiy VN. Toksikologo-gigiyenicheskoye issledovaniye dipiridilovykh gerbitsidov (dikvata i parakvata) [dissertatsiya] Kiyev; 1972.

16. Hutchinson G, Daisley H, Simeon D, Simmonds V, Shetty M, Lynn D. High rates of paraquat-induced suicide in southern Trinidad. Suicide Life Threat Behav. 1999;29:186–91.

17. Bourke T. Suicide in Samoa. Pac Health Dialog. 2001;8:213–9.

18. Dargan P, Shiew C, Gawarammana I, Jones A. Paraquat poisoning: caution in interpreting prognosis based on plasma paraquat concentration. Clin Toxicol. 2006;44:762.

19. Casey P, Vale JA. Deaths from pesticide poisoning in England and Wales: 1945-1989. Hum Exp Toxicol. 1994;13:95–101.

20. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2008 annual report of the American Association of Poison Control Centers National Poison Data System (NPDS): 26th annual report. Clin Toxicol. (Phila) 2009;47:911–1084.

21. Wilks MF, Tomenson JA, Fernando R, Ariyananda PL, Berry DJ, Buckley NA, et al. Formulation changes and time trends in outcome following paraquat ingestion in Sri Lanka. Clin Toxicol. (Phila) 2011;49:21–8.

22. Wanhalder R, Coraldyn J, De Reuck F. Diquat intoxication. Am J Med 1981;70:1267–71.

23. McCarthy LG, Speth CP. Diquat intoxication. Ann Emerg Med 1983;12:394–6.

24. Balan GM. Prodanchuk NG. Bubalo NN. Babich VA. Sostoyaniye i perspektivy antidotnoy terapii ostrykh otravleniy pestitsidami. Suchasnі problemi toksikologії. kharchovoї ta khіmіchnoї bezpeki. 2015;1–2:67–76.

25. Elenga N, Merlin C, Le Guern R, Kom-Tchamen R, et al. Clinical features and prognosis of paraquat poisoning in French Guiana. Med. 2018;97:15(e9621).

26. Yang W, Tiffany-Castiglioni E. The bipyridyl herbicide paraquat induces proteasome dysfunction in human neuroblastoma SH-SY5Y cells. J Toxicol. Environ Health A. 2007;70:1849–57.

27. Castello PR, Drechsel DA, Patel M. Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain. J Biol Chem. 2007;282:14186–93.

28. Bonneh-Barkay D, Reaney SH, Langston WJ, Di Monte DA. Redox cycling of the herbicide paraquat in microglial cultures. Brain Res Mol Brain Res 2005; 134:52–6.

29. Adam A, Smith LL, Cohen GM. An assessment of the role of redox cycling in mediating the toxicity of paraquat and nitrofurantoin. Environ Health Perspect. 1990;85:113–7.

30. Zhao F, Wang W, Wang C, et al. Mfn2 protects dopaminergic neurons exposed to paraquat both in vitro and in vivo. Biochim. et biophys. acta. Mol. Basis Disease. 2017;6:1359–1370.

31. Cai Z, Zheng F, Ding Y, et al. Nrf2 – regulated miR-380-3p blocks the translation of Sp3 protein and its mediation of paraquat – induced toxicity in mouse neuroblastoma N2a cells. Toxicol. Sci. 2019;171(2):515–529.

32. Cocheme HM, Murphy MP. Complex is the major site of mitochondrial superoxide production by paraquat. J Biol Chem. 2008;283:1786–89.

33. Costantini P, Petronilli V, Colonna R, Bernardi P. On the effects of paraquat on isolated mitochondria. Evidence that paraquat causes opening of the cyclosporin A-sensitive permeability transition pore synergistically with nitric oxide. Toxicology. 1995;99:77–88.

34. Tawara T, Fukushima T, Hojo N, Isobe A, Shiwaku K, Setogawa T, et al. Effects of paraquat on mitochondrial electron transport system and catecholamine contents in rat brain. Arch Toxicol 1996;70:585–9.

35. Bus JS, Aust SD, Gibson JE. Paraquat toxicity: proposed mechanism of action involving lipid peroxidation. Environ Health Perspect. 1976;16:139–46.

36. Yamada K, Fukushima T. Mechanism of cytotoxicity of paraquat. II. Organ specificity of paraquat-stimulated lipid peroxidation in the inner membrane of mitochondria. Exp Toxicol Pathol 1993;45:375–80.

37. Kurisaki E. Lipid peroxidation in human paraquat poisoning. J Toxicol Sci. 1985;10:29–33.

38. Sun Y, Zheng J, Xu Y, Zhang X. Paraquat-induce dinflammatory response of microglia through HSP60/TLR4 signaling. Hum. and Exp. Toxicol. 2018;37(11):1161–1168.

39. Xu G, Wang X, Yu H, Wang C, et al. Beclin 1, LC3 and p62 expression in paraquat-induced pulmonary fibrosis. Hum. and Exp. Toxicol. 2019;38(7):794–802.

40. Rasooli R, Pourgholamhosein F, Kamali Y. Combination Therapy With Pirfenidone plus Prednizolone Ameliorates Paraquat-Induced Pulmonary Fibrosis. Inflammation 2018;41(1):134–142.

41. Pourgholamhossein F, Rasooli R, Pournamdari M, et al. Pirfenidone protects against Paraquat-Induced lung injury and fibrosis in mice by modulation of Inflammation, oxidative stress, and gene expression. Food and Chem. Toxicol. 2018;112:39–46.

42. Fowler BA, Brooks RE. Effects of the herbicide paraquat on the ultrastructure of mouse kidney. Am J Pathol 1971;63:505–20.

43. Roberts DM, Wilks MF, Roberts MS, Swaminathan R, Mohamed F, Dawson AH, et al. Changes in the concentrations of creatinine, cystatin C and NGAL in patients with acute paraquat self-poisoning. Toxicol Lett 2011;202:69–74.

44. Matsumori H, Matsumoto T, Ishikawa H. Acute toxic effects of paraquat on ultrastructure of rat liver. Acta Pathol Jpn. 1984;34:507–18.

45. Gao x, Wang WZ, Xiao Qm, Qix N, et al. Correlation between neutrophil gelatinaseassociated lipocalin and soluble CD14 subtype on the prognosis evaluation of acute paraquat poisoning patients. Hum. and Exp. Toxicol. 2020;39(4):402–10.

46. Gao Y, Guo S, Wang Y, Yu S, et al. Lymphocyte and its CD4+ and CD8+ subgroup changes after paraquat poisoning. Hum. and Exp. Toxicol. 2019;38(9):1024–1030.

47. Li H, Zhu Q, Wang S, et al. Paraquat exposure delays stem progenitor leydig cell regeneration in the adult rat testis. Chemosphere 2019;231:60–71.

48. Moyano P, Sanjuan J, Garcia J, et al. Primary hippocampal estrogenic dysfunction induces synaptic proteins alteration and neuronal cell death after single and repeated paraquat exposure. Food and Chem. Toxicol. 2020;136:110–111.

49. Eddleston M, Phillips MR. Self poisoning with pesticides. BMG. 2020;328:42–4.


Received 04/26/2021