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Biological functions of cobalt and its toxicology and detection in anti-doping control

https://doi.org/10.32362/2410-6593-2021-16-4-318-336

Full Text:

Abstract

Objectives. Over the last decade, hematopoietic stimulants have grown increasingly popular in elite sports. This is supported by the growing number of high-profile doping scandals linked to their use. A group of these stimulants includes cobalt salts, which cause an increase in the oxygen capacity of the blood as well as a powerful stimulation of metabolic processes, resulting innoticeable competitive advantages. The use of cobalt salts is regulated according to the Prohibited List of the World Anti-Doping Agency (WADA). Currently, only a few works have been dedicated to solving the problem of detecting the abuse of cobalt salts in anti-doping control. Only a few laboratories have included cobalt salt determination in their methodological bases. The purpose of this review is to attract the attention of the scientific community to the toxicity of cobalt compounds, consequences of their intake, and pharmacokinetics, as well as the problems in their detection methods due to their widespread availability in the modern market and the growing number of abuse cases.
Results. The main biological functions of cobalt, cellular levels of exposure, toxicity, and symptoms of cobalt salt poisoning are presented in detail in this review article. The data from the literature on the main methods for detecting cobalt as a doping agent have been generalized and systematized. There is a major focus on the amount of cobalt in dietary supplements that could cause an athlete to test positive for cobalt when they are consumed.
Conclusions. After analyzing promising cobalt detection approaches and methods, it was determined that high-performance liquid chromatography in combination with inductively coupled plasma mass spectrometry has an undeniable advantage for detecting cobalt as a doping agent. The lack of explicit WADA requirements for detection methods and the lack of its obligation to determine cobalt make it tempting for unscrupulous athletes to use its salts. Therefore, antidoping laboratories must implement the abovementioned method as soon as possible.

About the Authors

I. V. Pronina
National Anti-Doping Laboratory (Institute), Lomonosov Moscow State University; Institute of General Pathology and Pathophysiology
Russian Federation

Irina V. Pronina, Cand. Sci. (Chem.), Main Specialist, Doping Control Department; Senior Researcher, Pathogenomics and Transcriptomics Laboratory

10-1, Elizavetinskii per., Moscow, 105005

8, ul. Baltiiskaya, Moscow, 125315

Scopus Author ID 8161867200

ResearcherID G-3951-2014


Competing Interests:

The authors declare no conflicts of interest.



E. S. Mochalova
National Anti-Doping Laboratory (Institute), Lomonosov Moscow State University
Russian Federation

Elena S. Mochalova, Acting Director

(Institute)

10-1, Elizavetinskii per., Moscow, 105005


Competing Interests:

The authors declare no conflicts of interest.



Yu. A. Efimova
MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)
Russian Federation

Yuliya A. Efimova, Cand. Sci. (Chem.), Assistant Professor, I.P. Alimarin Department of Analitical Chemistry

86, Vernadskogo pr., Moscow, 119571


Competing Interests:

The authors declare no conflicts of interest.



P. V. Postnikov
National Anti-Doping Laboratory (Institute), Lomonosov Moscow State University
Russian Federation

Pavel V. Postnikov, Cand. Sci. (Chem.), Head of the Doping Control Department

10-1, Elizavetinskii per., Moscow, 105005


Competing Interests:

The authors declare no conflicts of interest.



References

1. Nieboer E., Sanford W.E. Essential, toxic and therapeutic functions of metals (including determinant of reactivity). In: Rev. Biochem. Toxicol. New York: Elsevier; 1985;7:205–245

2. Salnikow K., Donald S.P., Bruick R.K., Zhitkovich A., Phang J.M., Kasprzak K.S. Depletion of intracellular ascorbate by the carcinogenic metals nickel and cobalt results in the induction of hypoxic stress. J. Biol. Chem. 2004;279(39):40337–40344. https://doi.org/10.1074/jbc.m4030572003

3. Lippi G., Franchini M., Guidi G.C. Cobalt chloride administration in athletes: a new perspective in blood doping? Br. J. Sports Med. 2005;39(11):872–873. https://doi.org/10.1136/bjsm.2005.019232

4. Jelkmann W. Erythropoiesis stimulating agents and techniques: a challenge for doping analysts. Curr. Med. Chem. 2009;16(10):1236–1247. https://doi.org/10.2174/092986709787846668

5. Lippi G., Franchini M., Guidi G.C. Blood doping by cobalt. Should we measure cobalt in athletes? J. Occup. Med. Toxicol. 2006;1:18. https://doi.org/10.1186/1745-6673-1-18

6. Lippi G., Montagnana M., Guidi G.C. Albumin cobalt binding and ischemia modified albumin generation: an endogenous response to ischemia? Int. J. Cardiol. 2006;108(3):410–411. https://doi.org/10.1016/j.ijcard.2005.03.040

7. Davis J.E., Fields J.P. Experimental production of polycythemia in humans by administration of cobalt chloride. Proc. Soc. Exp. Biol. Med. 1958;99(2):493–495. https://doi.org/10.3181/00379727-99-24395

8. Morgulis I.I., Khlebopros R.G. Biologicheskaya rol’ kobal’ta (The biological role of cobalt). Krasnoyarsk: Krasnoyarskii nauchnyi tsentr Sib. Otd. Ros. Akad. Nauk; 2005. 24 p. URL: http://modernproblems.org.ru/ecology/25-hlebopos10.html (accessed May 12, 2021) (in Russ.).

9. Kudrin A.V. Metals and proteolytic enzymes. Vopr. biol., med. i farm. khimii = Probl. of Biol., Med. and Pharm. Chemistry. 1999;(3):19–24 (in Russ.)

10. Taylor A., Marks V. Cobalt: a review. J. Hum. Nutr. 1978;32(3):165–177. https://doi.org/10.3109/09637487809144525

11. Ueno M., Seferynska J., Beckman B., Brookins J., Nakashima J., Fisher J. W. Enhanced erythropoietin secretion in hepatoblastoma cells in response to hypoxia. Am. J. Physiol. 1989;257:(4Pt. 1):C743–C749. https://doi.org/10.1152/ajpcell.1989.257.4.c743

12. Kaliman P.A., Belovetskaya I.V. Effect of cobalt chloride on the activity of key enzymes of heme metabolism in rat liver. Biokhimiya = Biochemistry. 1986;51(8):1307–1308 (in Russ.).

13. Osinskii S., Levitin I., Bubnovskaya L. Selectivity of the action of redox-active complexes of cobalt(III) on tumor tissue. Eksperimental’naya onkologiya = Experimental Oncology. 2004;26(2):18–24 (in Russ.).

14. Izom G.E., Way J.L. Cyanide intoxication: protection with cobaltous chloride. Toxicol. Appl. Pharmacol. 1973;24(3):449–456. https://doi.org/10.1016/0041-008x(73)90051-3

15. Gardner F.H. The use of cobaltous chloride in the anemia associated with chronic renal disease. J. Lab. Clin. Med. 1953;41(1):56–64.

16. Wintrobe M.M., Grinstein M., Dubash J.J., Humphreys S.R., Ashenbrucker H., Worth W. The anemia of infection, VI. The influence of cobalt on the anemia associated with inflammation. Blood. 1947;2(4):323–331. https://doi.org/10.1182/blood.v2.4.323.323

17. Christensen J.M., Poulsen O.M., Thomsen M. A short-term cross-over study on oral administration of soluble and insoluble cobalt compounds: sex differences in biological levels. Int. Arch. Occup. Environ. Health. 1993;65(4):233. https://doi.org/10.1007/bf00381196

18. Edel J., Pozzi G., Sabbioni E., Pietra R., Devos S. Metabolic and toxicological studies on cobalt. Sci. Total Environ. 1994;150(1–3):233–244. https://doi.org/10.1016/0048-9697(94)90159-7

19. Young R.S. Cobalt. In: Frieden E. (Ed.). Biochemistry of the Essential Ultratrace Elements. UK: Springer; 1985;3:133–147. URL: https://link.springer.com/chapter/10.1007/978-1-4684-4775-0_6

20. Taylor A. Detection and monitoring of disorders of essential trace elements. Ann. Clin. Biochem. 1996;33(Pt 6):486–510. https://doi.org/10.1177/000456329603300603

21. Barceloux D.G. Cobalt. J. Toxicol. Clin. Toxicol. 1999;37(2):201–206. https://doi.org/10.1081/clt100102420

22. Cobalt in Hard Metals and Cobalt Sulfate, Gallium Arsenide, Indium Phosphide and Vanadium Pentoxide. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, France: 2006. V. 86. 353 p. URL: http://monographs.iarc.fr/ENG/Monographs/vol86/mono86.pdf (accessed May 12, 2021).

23. Beuck S., Schänzer W., Thevis M. Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesisstimulating agents in current and preventive doping analysis. Drug Test. Analysis. 2012;4(11):830–845. https://doi.org/10.1002/dta.390

24. Ebert B, Jelkmann W. Intolerability of cobalt salt as erythropoietic agent. Drug Test Anal. 2014;6(3):185–189. https://doi.org/10.1002/dta.1528

25. Jelkmann W. The disparate roles of cobalt in erythropoiesis, and doping relevance. Open J. Hematol. 2012;3(1):1–9.

26. Zang Q., Yan Q., Yang H., Wei W. Oxygen sensing and adaptability won the 2019 Nobel Prize in Physiology or medicine. Genes & Diseases. 2019;6(4):328–332. https://doi.org/10.1016/j.gendis.2019.10.006

27. Stolze I.P., Mole D.R., Ratcliffe P.J. Regulation of HIF: prolyl hydroxylases. Novartis Found. Symp. 2006;272:15–25. https://doi.org/10.1002/9780470035009.ch3

28. Epstein A.C., Gleadle J.M., McNeill L.A., Hewitson K.S., O’Rourke J., Mole D.R., Mukherji M., Metzen E., Wilson M.I., Dhanda A., Tian Y.M., Masson N., Hamilton D.L., Jaakkola P., Barstead R., Hodgkin J., Maxwell P.H., Pugh C.W., Schofield C.J., Ratcliffe P.J. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell. 2001;107(1):43–54. https://doi.org/10.1016/s0092-8674(01)00507-4

29. Kolomeitsev A.V., Tararina L.I., Morgulis I.I. The effect of cobalt chloride on hematopoiesis in mice early after exposure. Vestnik KrasGAU = The Bulletin of KrasGAU. 2003;2:101–103 (in Russ.).

30. Goncharevskaya O.A., Monin Yu.G., Natochin Yu.V. Regulation of the rate of proximal and distal reabsorption with intratubular administration of cobalt. Fiziologicheskii zhurnal SSSR = J. Physiology USSR. 1985;71(10):1287–1292 (in Russ.).

31. Yamagami K., Nishimura S., Sorimachi M. Cd2+ and Co2+ at micromolar concentrations mobilize intracellular Ca2+ via the generation of inositol 1,4,5-triphosphate in bovine chromaffin cells. Brain Res. 1998;798(1–2):316–319. https://doi.org/10.1016/s0006-8993(98)00445-4

32. Comhaire S., Blust R., Van Ginneken L., Vanderborght, O.L.J. Branchial cobalt uptake in the carp, Cyprinus carpio: effect of calcium channel blockers and calcium injection. Fish Physiol. Biochem. 1998;18(1):1–13. https://doi.org/10.1023/A:1007746117932

33. Goldberg M.A., Imagawa S., Dunning S.P., Bunn H.F. Oxygen sensing and erythropoietin gene regulation. In: Baldamus C.A., Koch K.M., Scigalla P., Wieczorek L. (Eds.). Erythropoietin: From Molecular Structure to Clinical Application; Contrib. Nephrol. Basel: Karger; 1989;76:39–56. https://doi.org/10.1159/000417880

34. Bruick R.K. Oxygen sensing in the hypoxic response pathway: regulation of the hypoxia-inducible transcription factor. Genes Dev. 2003;17(21):2614–2623. https://doi.org/10.1101/gad.1145503

35. Malard V., Berenguer F., Pratt O., Ruat S., Steinmerz G., Quemeneur E. Global gene expression profiling in human lung cells exposed to cobalt. BMS Genomics. 2007;8:147–164. https://doi.org/10.1186/1471-2164-8-147

36. Romanova T.A., Kravchenko O.V., Morgulis I.I., Kuzubov A.A., Krasnov P.O., Avramov P.V. Hypothesis of hemoprotein sensor confirmed by ab initio quantum-chemical method. Russ. J. Coord. Chem. 2004;30(6):403–406. https://doi.org/10.1023/B:RUCO.0000030160.11788.20

37. Mucklow E.S., Griffin S.J., Delves H.T., Suchak B. Cobalt poisoning in a 6-year-old. Lancet. 1990;335(8695):981. https://doi.org/10.1016/0140-6736(90)91053-d

38. Simonsen L.O., Harbak H., Bennekou P. Cobalt metabolism and toxicology–a brief update. Sci. Total Environ. 2012;432:210–215. https://doi.org/10.1016/j.scitotenv.2012.06.009

39. Bradberry S., Sabatta M., Vale J. Cobalt Chloride. UKPID Monograph. URL: www.inchem.org/documents/ukpids/ukpids/ukpid50.htm (accessed May 12, 2021).

40. Finley B.L., Monnot A.D., Paustenbach D.J., Gaffney S.H. Derivation of a chronic oral reference dose for cobalt. Regul. Toxicol. Pharm. 2012;64(3):491–503. https://doi.org/10.1016/j.yrtph.2012.08.022

41. Linna A., Oksa P., Groundstroem K., Halkosaari M., Palmroos P., Huikko S., Uitti J. Exposure to cobalt in the production of cobalt and cobalt compounds and its effect on the heart. Occup. Environ. Med. 2004;61(11):877–885. https://doi.org/10.1136/oem.2003.009605

42. Yuan Y., Hilliard G., Ferguson T., Millhorn D.E. Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel-Lindau protein by direct binding to hypoxia-inducible factor-alpha. J. Biol. Chem. 2003;278(18):15911–15916. https://doi.org/10.1074/jbc.m300463200

43. Simonsen L.O., Brown A.M., Harbak H., Kristensen B.I., Bennekou P. Cobalt uptake and binding in human red blood cells. Blood Cell Mol. Dis. 2011;46(4):266–276. https://doi.org/10.1016/j.bcmd.2011.02.009

44. Unice K.M., Monnot A.D., Gaffney S.H., Tvermoes B.E., Thuett K.A., Paustenbach D.J., Finley B.L. Inorganic cobalt supplementation: Prediction of cobalt levels in whole blood and urine using a biokinetic model. Food Chem. Toxicol. 2012;50(7):2456–2461. https://doi.org/10.1016/j.fct.2012.04.00

45. Gray M.J., Zhang J., Ellis L.M., Semenza G.L., Evans D.B., Watowich S.S., Gallick G.E. HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas. Oncogene. 2005;24(19):3110–3120. https://doi.org/10.1038/sj.onc.1208513

46. Singh N.K., Chhabra R., Datta K. Nonenzymatic synthesis of delta-aminolevulinate (ALA) by cobalt (Co++). Biochem. Biophys. Res. Commun. 1987;143(2):439–446. https://doi.org/10.1016/0006-291x(87)91373-8

47. Chai Y.C., Mendes L.F., van Gastel N., Carmeliet G., Luyten F.P. Fine-tuning pro-angiogenic effects of cobalt for simultaneous enhancement of vascular endothelial growth factor secretion and implant neovascularization. Acta Biomater. 2018;72:447–460. https://doi.org/10.1016/j.actbio.2018.03.048

48. Peters K., Schmidt H., Unger R.E., Kamp G., Pröls F., Berger B.G., Kirkpatrick C.J. Paradoxical effects of hypoxiamimicking divalent cobalt ions in human endothelial cells in vitro. Mol. Cell. Biochem. 2005;270(1–2):157–166. https://doi.org/10.1007/s11010-005-4504-z

49. De Laia A.G.S., Valverde T.M., Barrioni B.R., da Silva Cunha P., de Goes A.M., de Miranda M.C., Gomes D.A., Gueiros-Junior C.M., de Sa M.A., de Magalhães Pereira M. Cobalt-containing bioactive glass mimics vascular endothelial growth factor A and hypoxia inducible factor 1 function. J. Biomed. Mater. Res. A. 2021;109(7):1051–1064. https://doi.org/10.1002/jbm.a.37095

50. Okamoto S., Eltis L.D. The biological occurrence and trafficking of cobalt. Metallomics. 2011;3(10):963–970. https://doi.org/10.1039/c1mt00056j

51. Gluhcheva Y., Pavlova E., Petrova E., Tinkov A.A., Ajsuvakova O.P., Skalnaya M.G., Vladov I., Skalny A.V. The Impact of Perinatal Cobalt Chloride Exposure on Extramedullary Erythropoiesis, Tissue Iron Levels, and Transferrin Receptor Expression in Mice. Biol. Trace Elem. Res. 2020;194(2):423–431. https://doi.org/10.1007/s12011-019-01790-8

52. Xu X., Liu T., Wu J., Wang Y., Hong Y., Zhou H. Transferrin receptor-involved HIF-1 signaling pathway in cervical cancer. Cancer Gene Ther. 2019;26(11–12):356–365. https://doi.org/10.1038/s41417-019-0078-x

53. De Boeck M., Kirsch-Volders M., Lison D. Cobalt and antimony: genotoxicity and carcinogenicity. Mutat. Res. 2003;533(1–2):135–152. https://doi.org/10.1016/j.mrfmmm.2003.07.012

54. Shukla D., Saxena S., Purushothaman J., Shrivastava K., Singh M., Shukla S., Malhotra V.K., Mustoori S., Bansal A. Hypoxic preconditioning with cobalt ameliorates hypobaric hypoxia induced pulmonary edema in rat. Eur. J. Pharmacol. 2011;656(1–3):101–109. https://doi.org/10.1016/j.ejphar.2011.01.038

55. Saxena S., Shukla D., Bansal A. Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride. Toxicol. Appl. Pharmacol. 2012;264(3):324–334. https://doi.org/10.1016/j.taap.2012.08.033

56. Suzuki J. Time-course changes in VEGF expression and capillarity in the early stage of exercise training with Co treatment in rat skeletal muscles. Acta Physiol. Scand. 2004;181(2):225–232. https://doi.org/10.1111/j.1365-201x.2004.01279.x

57. Hoffmeister T., Schwenke D., Krug O., Wachsmuth N., Geyer H., Thevis M., Byrnes W.C., Schmidt W.F.J. Effects of 3 Weeks of Oral Low-Dose Cobalt on Hemoglobin Mass and Aerobic Performance. Front. Physiol. 2018;9:1289. https://doi.org/10.3389/fphys.2018.01289

58. da Justa Neves D.B., Caldas E.D. Dietary supplements: International legal framework and adulteration profiles, and characteristics of products on the Brazilian clandestine market. Regul. Toxicol. Pharmacol. 2015;73(1):93–104. https://doi.org/10.1016/j.yrtph.2015.06.013

59. Krug O., Thomas A., Walpurgis K., Piper T., Sigmund G., Schänzer W., Laussmann T., Thevis M. Identification of black market products and potential doping agents in Germany 2010–2013. Eur. J. Clin. Pharmacol. 2014;70(11):1303–1311. https://doi.org/10.1007/s00228-014-1743-5

60. Thevis M., Krug O., Piper T., Geyer H., Schänzer W. Solutions Advertised as Erythropoiesis-stimulating Products were Found to Contain Undeclared Cobalt and Nickel Species. Int. J. Sports Med. 2015;37(1):82–84. https://doi.org/10.1055/s-0035-1569350

61. Geyer H., Braun H., Burke L.M., Stear S.J., Castell L.M. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance-Part 22. Br. J. Sports Med. 2011;45(9):752–754. https://doi.org/10.1136/bjsports-2011-090180

62. Geyer H., Parr M.K., Koehler K., Mareck U., Schänzer W., Thevis M. Nutritional supplements cross-contaminated and faked with doping substances. J. Mass Spectrom. 2008;43(7):892–902. https://doi.org/10.1002/jms.1452

63. Ho E.N.M., Chan G.H.M., Wan T.S.M., Curl P., Riggs C.M., Hurley M.J., Sykes D. Controlling the misuse of cobalt in horses. Drug Test. Anal. 2015;7(1):21–30. https://doi.org/10.1002/dta.1719

64. Hillyer L.L., Ridd Z., Fenwick S., Hincks P., Paine S.W. Pharmacokinetics of inorganic cobalt and a vitamin B12 supplement in the Thoroughbred horse: Differentiating cobalt abuse from supplementation. Equine Vet. J. 2018;50(3):343–349. https://doi.org/10.1111/evj.12774

65. Calbet J.A., Lundby C., Koskolou M., Boushel R. Importance of hemoglobin concentration to exercise: acute manipulations. Respir. Physiol. Neurobiol. 2006;151(2–3):132–140. https://doi.org/10.1016/j.resp.2006.01.014

66. Reichel C., Gmeiner G. Erythropoietin and analogs. In: Thieme D., Hemmersbach P. (Eds.). Doping in Sports: Biochemical Principles, Effects and Analysis. Handbook of Experimental Pharmacology. Berlin, Heidelberg: Springer; 2010;195:251–294. https://doi.org/10.1007/978-3-540-79088-4_12

67. Okano M., Sato M., Kaneko E., Kageyama S. Doping control of biosimilar epoetin kappa and other recombinant erythropoietins after intravenous application. Drug Test. Anal. 2011;3(11–12):798–805. https://doi.org/10.1002/dta.369

68. Rodriguez-Jimenez F.J., Moreno-Manzano V. Modulation of hypoxia-inducible factors (HIF) from an integrative pharmacological perspective. Cell. Mol. Life Sci. 2012;69(4):519–534. https://doi.org/10.1007/s00018-011-0813-4

69. Jelkmann W. Efficacy of recombinant erythropoietins: is there unity of international units? Nephrol. Dial. Transpl. 2009;24(5):1366–1368. https://doi.org/10.1093/ndt/gfp058

70. Jefferson J.A., Escudero E., Hurtado M.E., Pando J., Tapia R., Swenson E. R., Prchal J., Schreiner G.F., Schoene R.B., Hurtado A., Johnson R.J. Excessive erythrocytosis, chronic mountain sickness, and serum cobalt levels. Lancet. 2002;359(9304):407–408. https://doi.org/10.1016/s0140-6736(02)07594-3

71. Jansen H.M., Knollema S., van der Duin L.V., Willemsen A.T., Wiersma A., Franssen E.J., Russel F.G., Korf J., Paans A.M. Pharmacokinetics and dosimetry of cobalt-55 and cobalt-57. J. Nucl. Med. 1996;37(12):2082–2086.

72. Ebert B., Jelkmann W. Intolerability of cobalt salt as erythropoietic agent. Drug Test Anal. 2014;6(3):185–189. https://doi.org/10.1002/dta.1528

73. Weißbecker L. Die Kobalttherapie. Deutsch. Med. Wochenschr. 1950;75:116–118.

74. Weissbecker L. Neue Möglichkeiten der Kobalttherapie. Klin.Wochenschr. 1951;29:80–82. https://doi.org/10.1007/BF01480495

75. Curtis J.R., Goode G.C., Herrington J., Urdaneta L.E. Possible cobalt toxicity in maintenance hemodialysis patients after treatment with cobaltous chloride: a study of blood and tissue cobalt concentrations in normal subjects and patients with terminal and renal failure. Clin. Nephrol. 1976;5(2):61–65.

76. Schirrmacher U.O. Case of cobalt poisoning. Brit. Med. J. 1967;1(5539):544–545. https://doi.org/10.1136/bmj.1.5539.544

77. Licht A., Oliver M., Rachmilewitz E.A. Optic atrophy following treatment with cobalt chloride in a patient with pancytopenia and hypercellular marrow. Isr. J. Med. Sci. 1972;8(1):61–66.

78. Kriss J. P., Carnes W. H., Gross R. T. Hypothyroidism and thyroid hyperplasia in patients treated with cobalt. J. Am. Med. Assoc. 1955;157(2):117–121. https://doi.org/10.1001/jama.1955.02950190017004

79. Jacobziner H., Raybin H.W. Poison control... accidental cobalt poisoning. Arch. Pediatr. 1961;78:200–205.

80. Lison D., De Boeck M., Verougstraete V., KirschVolders M. Update on the genotoxicity and carcinogenicity of cobalt compounds. Occup Environ Med. 2001;58(10):619–625. https://doi.org/10.1136/oem.58.10.619

81. Pulido M.D., Parrish A.R. Metal-induced apoptosis: mechanisms. Mutat Res. 2003;533(1–2):227–241. https://doi.org/10.1016/j.mrfmmm.2003.07.015

82. Aggarwal S.K., Kinter M., Herold D.A. Determination of cobalt in urine by gas chromatography-mass spectrometry employing nickel as an internal standard. J. Chromatogr. B. 1992;576(2):297–304. https://doi.org/10.1016/0378-4347(92)80203-3

83. Minakata K., Suzuki M., Suzuki O. Application of electrospray ionization tandem mass spectrometry for the rapid and sensitive determination of cobalt in urine. Anal. Chim. Acta 2008;614(2):161–164. https://doi.org/10.1016/j.aca.2008.03.043

84. Todorovska N., Karadjova I., Arpadjan S., Stafilov T. Electrothermal atomic absorption spectrometric-determination of cobalt in human serum and urine. Acta Pharm. 2003;53(2):83–90.

85. Sarmiento-Gonzalez A., Marchante-Gayon J.M., Tejerina-Lobo J.M., Paz-Jimenez J., Sanz-Medel A. Highresolution ICP-MS determination of Ti, V, Cr, Co, Ni, and Mo in human blood and urine of patients implanted with a hip or knee prosthesis. Anal. Bioanal. Chem. 2008;391(1):2583–2589. https://doi.org/10.1007/s00216-008-2188-4

86. Popot M.-A., Ho E.N.M., Stojiljkovic N., Bagilet F., Remy P., Maciejewski P., Loup B., Chan G.H.M., Hargrave S., Arthur R.M., Russo C., White J., Hincks P., Pearce C., Ganio G., Zahra P., Batty D, Jarrett M., Brooks L., Prescott L.-A., BaillyChouriberry L., Bonnaire Y. and Wan T.S.M. Interlaboratory trial for the measurement of total cobalt in equine urine and plasma by ICP-MS. Drug Test Anal. 2017;9(9):1400–1406. https://doi.org/10.1002/dta.2191

87. Knoop A., Planitz P., Wüst B., Thevis M. Analysis of cobalt for human sports drug testing purposes using ICPand LC-ICP-MS. Drug Test Anal. 2020;12(11–12):1666–1672. https://doi.org/10.1002/dta.2962

88. Galay E.Ph., Dorogin R.V., Temerdashev A.Z. Quantification of cobalt and nickel in urine using inductively coupled plasma atomic emission spectroscopy. Heliyon. 2021;7(1):e06046. https://doi.org/10.1016/j.heliyon.2021.e06046


Supplementary files

1. The effect of HIF at normal partial pressure of oxygen is normoxia in the cell and at oxygen deficiency is hypoxia (similar to the effect of cobalt preparations)
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2. This is to certify that the paper titled Biological functions of cobalt and its toxicology and detection in anti-doping control commissioned to us by Irina V. Pronina, Elena S. Mochalova, Yuliya A. Efimova, Pavel V. Postnikov has been edited for English language and spelling by Enago, an editing brand of Crimson Interactive Inc.
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  • For the first time, a literature review on the use of cobalt salts as blood-forming stimulants and doping agents is presented. They are included in the WADA Prohibited List.
  • Only a few anti-doping control laboratories introduce regulated approaches fordefining this type of doping agent into their methodological base.
  • The main methods for detecting cobalt as a doping agent are generalized and systematized.
  • The conclusion is made regarding the undeniable advantage of the HPLC–ICP–MS method, which is its ability to distinguish endogenous cobalt, which is a component of cyanocobalamin (vitamin B12), from the prohibited inorganic cobalt.

For citation:


Pronina I.V., Mochalova E.S., Efimova Yu.A., Postnikov P.V. Biological functions of cobalt and its toxicology and detection in anti-doping control. Fine Chemical Technologies. 2021;16(4):318-336. https://doi.org/10.32362/2410-6593-2021-16-4-318-336

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ISSN 2410-6593 (Print)
ISSN 2686-7575 (Online)