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Yarış Atlarında Yasaklı Madde Olarak Kobalt

Year 2022, Volume: 33 Issue: 2, 85 - 91, 23.12.2022
https://doi.org/10.35864/evmd.1117325

Abstract

Kobalt mikro besin olmasının yanında, eritropoetik bir ajan olarak kabul edilmektedir. Uluslararası At Yarışları Federasyonu (IFHA), Uluslararası Binicilik Federasyonu (FEI), Dünya Anti-Doping Ajansı (WADA) gibi yarış otoriteleri, kobaltın eritropoetik etkisinin bilimsel çalışmalarda gösterilmiş olması sebebiyle kullanımını yasaklamış ancak vücutta doğal olarak bir miktar bulunması sebebiyle plazma ve idrar örnekleri için eşik limit belirlemiştir. IFHA paydaşları tarafından da eşik limit belirlemek amacıyla çeşitli çalışmalar yürütülmüş ve idrar için 100 ng/ml, plazma için 25 ng/ml eşik limit belirlenmiştir. Eşik limitin belirlendiği 2015 yılından bu yana yarışlarda kobalt ihlallerin çoğalması, konu ile ilgili yaptırımların artmasına neden olmuştur. Bu ihlaller Dünyada olduğu gibi, Türkiye'de de önemli sorun teşkil etmektedir. Kobalt ihlaline yol açabilecek uygulamaları araştırmak amacıyla kobaltın oral ve parenteral uygulamalarına dair bilimsel araştırmalar yürütülmüş, muhtemel riskler ortaya konulmaya çalışılmıştır. Bunun yanı sıra, kobaltın eritropoezis üzerine etkileri gösterilmiş ve geçmişte anemi tedavisinde kullanılmış olsa da belirli doz ve sıklıkta uygulandığında istenmeyen etkilerin meydana gelmesi nedeniyle kullanımından vazgeçilmiştir. Ayrıca, insan ve deney hayvanlarında yapılan çalışmalarda görülen eritropoetik etkiler, atlarda yapılan çalışmalarda net olarak ortaya konulmamış, performans üzerine etkileri bildirilmemiştir. Kobaltın farmakolojik özellikleri, toksik etkileri, atlarda kobalt gereksinimleri, kobalt eşik limitlerinin belirlenmesi ve kobalt ihlallerine yol açabilecek uygulamalar bu çalışmada sunulmaya çalışılmıştır.

References

  • Afohiuddin SM, Roy P, Chenard J. (1970). Experimental cobalt cardiomyopat.;(4):532
  • Alexander CS. (1972). Cobalt-beer cardiomyopathy. A clinical and pathologic study of twenty-eight cases. Am J Med.;53(4):395–417.
  • Anonim. (2022). Article 6 A (Racing) - Prohibited Substances. https://www.ifhaonline.org/resources/ifAgreement.pdf.Erişim tarihi: 24.02.2022.
  • Anonim. (2022a) .Cobalt Threshold Values – Advisory Document. https://www.ifhaonline.org/Default.asp?section=IABRW&area=12 Erişim tarihi: 24.02.2022.
  • Belaidi E, Beguin PC, Levy P, Ribuot C, Godin-Ribuot D. (2012 ). Delayed myocardial preconditioning induced by cobalt chloride in the rat: HIF-1α and iNOS involvement. Fundam Clin Pharmacol;26(4):454–62.
  • Burns TA, Dembek KA, Kamr A, Dooley SB, Dunbar LK, Aarnes TK, vd. (2017). Effect of Intravenous Administration of Cobalt Chloride to Horses on Clinical and Hemodynamic Variables. J Vet Intern Med.;32(1):441–9.
  • Davis JE, Fields JP. (1958). Experimental production of polycythemia in humans by administration of cobalt chloride. Proc Soc Exp Biol Med.;99(2):493–5.
  • EFSA. (2009). Scientific Opinion on the use of cobalt compounds as additives in animal nutrition. EFSA J.;7(12):1–45.
  • EFSA. (2012). Scientific Opinion on safety and efficacy of cobalt compounds (E3) as feed additives for all animal species: Cobaltous acetate tetrahydrate, basic cobaltous carbonate monohydrate and cobaltous sulphate heptahydrate, based on a dossier submitted by TREAC E. EFSA J.;10(7).
  • Elbetieha, A., AL-Thani, A.S., AL-Thani, R.K., Darmani, H., Owais W, Elbetieha A, Al-Thani AS, Al-Thani RK, Darmani H, Owais W. (2008). Effects of Chronic Exposure to Cobalt Chloride on the Fertility and Testes in Mice. J Appl Biol Sci;2(1):01–6
  • Elliott S. (2008).Erythropoiesis-stimulating agents and other methods to enhance oxygen transport. Br J Pharmacol.;154(3):529–41.
  • Gardner FH. (1953). The use of cobaltous chloride in the anemia associated with chronic renal disease. J Lab Clin Med.;41(1):56–64.
  • Hillyer LL, Ridd Z, Fenwick S, Hincks P, Paine SW. (2018). Pharmacokinetics of inorganic cobalt and a vitamin B12 supplement in the Thoroughbred horse: Differentiating cobalt abuse from supplementation. Equine Vet J. ;50(3):343–9. doi.10.1111/evj.12774
  • Ho ENM, Chan GHM, Wan TSM, Curl P, Riggs CM, Hurley MJ. (2015).Controlling the misuse of cobalt in horses. Drug Test Anal.;7(1):21–30.
  • Holly RG. (1955). Studies on iron and cobalt metabolism. J Am Med Assoc [Internet].;158(15):1349–52.
  • ICRP. (1993). Annals of the ICRP. C. 23, The International Commision on Radiologival Protection.
  • Jelkmann W. (2012).The Disparate Roles of Cobalt in Erythropoiesis, and Doping Relevance. Open J Hematol.;3(Ii):1–3.
  • Kabil E, Turhan E, Güneş E, Göktaş E., Pekkaya S, Dirikolu L. (2018).The Analysis Of Arsenic and Cobalt In Horseracing In Turkey. Içinde. s. 52–5. Available at: https://www.researchgate.net/publication/330727606_The_Analysis_Of_Arsenic_and_Cobalt_In_Horseracing_In_Turkey
  • Kinobe RT. (2016). Towards the elimination of excessive cobalt supplementation in racing horses: A pharmacological review. Res Vet Sci.;104:106–12. doi.org/10.1016/j.rvsc.2015.12.007
  • Knych HK, Arthur RM, Mitchell MM, Holser I, Poppenga R, Smith LL, vd. (2015). Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses. Drug Test Anal.;7(7):619–25.
  • Kriss JP, Carnes WH, Gross RT. (1955). Hypothyroidism and thyroid hyperplasia in patients treated with cobalt. J Am Med Assoc.;157(2):117–21.
  • Kwak YB, Yu J, Im EJ, Jeong BS, Yoo HH. (2021). Study of cobalt doping control via various routes in thoroughbred horses. Drug Test Anal.; Available at: https://pubmed.ncbi.nlm.nih.gov/34750992/
  • Leggett RW. (2008). The biokinetics of inorganic cobalt in the human body. Sci Total Environ.;389(2–3):259–69.
  • Liang R, Ghaffari S. (2016).Advances in understanding the mechanisms of erythropoiesis in homeostasis and disease. Br J Haematol.;174(5):661–73. doi/full/10.1111/bjh.14194
  • Lippi G, Franchini M, Guidi GC. (2005).Cobalt chloride administration in athletes: A new perspective in blood doping? Br J Sports Med.;39(11):872–3.
  • Lippi G, Franchini M, Guidi GC. (2006). Blood doping by cobalt. Should we measure cobalt in athletes? J Occup Med Toxicol.;1(1):2–4.
  • Manthe, Brette N., and Curtis R. Youngs. “An Overview of Vitamin Requirements of the Domestic Horse.” Natural Sciences Education, vol. 42, no. 1, John Wiley and Sons Inc, Dec. 2013, pp. 179–84, doi:10.4195/NSE.2012.00002.
  • National Research Council. Nutrient Requirements of Horses. (2007): Sixth Revised Edition [Internet]. [kaynak 20 Şubat 2022]. 360 s. Available at: http://www.nap.edu/catalog/11653/nutrient-requirements-of-horses-sixth-revised-edition
  • Palit S, Sharma A, Talukder G. (1994).Effects of cobalt on plants. Bot Rev.;60(2):149–81.
  • Popot MA, Ho ENM, Stojiljkovic N, Bagilet F, Remy P, Maciejewski P, vd. (2017).Interlaboratory trial for the measurement of total cobalt in equine urine and plasma by ICP-MS. Drug Test Anal.;9(9):1400–6.
  • Rodríguez-Jiménez FJ, Moreno-Manzano V. (2012).Modulation of hypoxia-inducible factors (HIF) from an integrative pharmacological perspective. Cell Mol Life Sci.;69(4):519–34.
  • Seven T, Can B, Darende Bn, Ocak S.(2018). Hava ve Toprakta Ağır Metal Kirliliği. Ulus Çevre Bilim Araştırma Derg [Internet].;1(2):91–103. https://dergipark.org.tr/en/pub/ucbad/issue/38487/447131
  • Shrivastava K, Bansal A, Singh B, Sairam M, Ilavazhagan G. (2010). Sub-chronic oral toxicity study in Sprague-Dawley rats with hypoxia mimetic cobalt chloride towards the development of promising neutraceutical for oxygen deprivation. Exp
  • Toxicol Pathol;62(5):489–96..doi.org/10.1016/j.etp.2009.06.012
  • Wenzel R, Major D, Hesp K, Doble P. (2018).Determination of vitamin B12 in equine urine by liquid chromatography – inductively coupled plasma – mass spectrometry. J Trace Elem Med Biol.;50(May):634–9.
  • WHO.(2006). Concise International Chemical Assessment Document 69: Cobalt and Inorganic Cobalt Compounds. World Heal Organ.1–93. Available at: http://www.who.int/ipcs/publications/cicad/cicad70.pdf
  • Wolf J, Levy IJ. (1954). Treatment of sickle-cell anemia with cobalt chloride. AMA Arch Intern Med.;93(3):387–96.

Cobalt as a Banned Substance in Racehorses

Year 2022, Volume: 33 Issue: 2, 85 - 91, 23.12.2022
https://doi.org/10.35864/evmd.1117325

Abstract

Besides being a micronutrient, cobalt is considered an erythropoietic agent. Racing authorities such as the International Federation of Horse Racing (IFHA), the International Equestrian Federation (FEI), and the World Anti-Doping Agency (WADA) have banned the use of cobalt because its erythropoietic effect has been demonstrated in scientific studies. However, a threshold limit has been set for plasma and urine samples due to the fact that there is some amount naturally in the body. Various studies have also been carried out by IFHA stakeholders to determine threshold limits. And a threshold limit of 100 ng/ml for urine and 25 ng/ml for plasma was determined. Since the threshold limit was determined in 2015, the increase in cobalt violations in races has led to an increase in the related sanctions. These violations pose an important problem in Turkey as well as in the world. Scientific researches on oral and parenteral applications of cobalt have been carried out in order to investigate the applications that may lead to cobalt violation, and possible risks have been tried to be revealed. In addition, the effects of cobalt on erythropoiesis have been shown and although it was used in the treatment of anemia in the past, its use was abandoned due to the occurrence of undesirable effects when applied at a certain dose and frequency. Furthermore, the erythropoietic effects seen in studies in humans and experimental animals have not been clearly demonstrated in studies performed in horses, and their effects on performance have not been reported. In this study, the pharmacological properties of cobalt, its toxic effects, cobalt requirements in horses, determination of cobalt threshold limits and applications that may lead to violations has been presented in this study.

References

  • Afohiuddin SM, Roy P, Chenard J. (1970). Experimental cobalt cardiomyopat.;(4):532
  • Alexander CS. (1972). Cobalt-beer cardiomyopathy. A clinical and pathologic study of twenty-eight cases. Am J Med.;53(4):395–417.
  • Anonim. (2022). Article 6 A (Racing) - Prohibited Substances. https://www.ifhaonline.org/resources/ifAgreement.pdf.Erişim tarihi: 24.02.2022.
  • Anonim. (2022a) .Cobalt Threshold Values – Advisory Document. https://www.ifhaonline.org/Default.asp?section=IABRW&area=12 Erişim tarihi: 24.02.2022.
  • Belaidi E, Beguin PC, Levy P, Ribuot C, Godin-Ribuot D. (2012 ). Delayed myocardial preconditioning induced by cobalt chloride in the rat: HIF-1α and iNOS involvement. Fundam Clin Pharmacol;26(4):454–62.
  • Burns TA, Dembek KA, Kamr A, Dooley SB, Dunbar LK, Aarnes TK, vd. (2017). Effect of Intravenous Administration of Cobalt Chloride to Horses on Clinical and Hemodynamic Variables. J Vet Intern Med.;32(1):441–9.
  • Davis JE, Fields JP. (1958). Experimental production of polycythemia in humans by administration of cobalt chloride. Proc Soc Exp Biol Med.;99(2):493–5.
  • EFSA. (2009). Scientific Opinion on the use of cobalt compounds as additives in animal nutrition. EFSA J.;7(12):1–45.
  • EFSA. (2012). Scientific Opinion on safety and efficacy of cobalt compounds (E3) as feed additives for all animal species: Cobaltous acetate tetrahydrate, basic cobaltous carbonate monohydrate and cobaltous sulphate heptahydrate, based on a dossier submitted by TREAC E. EFSA J.;10(7).
  • Elbetieha, A., AL-Thani, A.S., AL-Thani, R.K., Darmani, H., Owais W, Elbetieha A, Al-Thani AS, Al-Thani RK, Darmani H, Owais W. (2008). Effects of Chronic Exposure to Cobalt Chloride on the Fertility and Testes in Mice. J Appl Biol Sci;2(1):01–6
  • Elliott S. (2008).Erythropoiesis-stimulating agents and other methods to enhance oxygen transport. Br J Pharmacol.;154(3):529–41.
  • Gardner FH. (1953). The use of cobaltous chloride in the anemia associated with chronic renal disease. J Lab Clin Med.;41(1):56–64.
  • Hillyer LL, Ridd Z, Fenwick S, Hincks P, Paine SW. (2018). Pharmacokinetics of inorganic cobalt and a vitamin B12 supplement in the Thoroughbred horse: Differentiating cobalt abuse from supplementation. Equine Vet J. ;50(3):343–9. doi.10.1111/evj.12774
  • Ho ENM, Chan GHM, Wan TSM, Curl P, Riggs CM, Hurley MJ. (2015).Controlling the misuse of cobalt in horses. Drug Test Anal.;7(1):21–30.
  • Holly RG. (1955). Studies on iron and cobalt metabolism. J Am Med Assoc [Internet].;158(15):1349–52.
  • ICRP. (1993). Annals of the ICRP. C. 23, The International Commision on Radiologival Protection.
  • Jelkmann W. (2012).The Disparate Roles of Cobalt in Erythropoiesis, and Doping Relevance. Open J Hematol.;3(Ii):1–3.
  • Kabil E, Turhan E, Güneş E, Göktaş E., Pekkaya S, Dirikolu L. (2018).The Analysis Of Arsenic and Cobalt In Horseracing In Turkey. Içinde. s. 52–5. Available at: https://www.researchgate.net/publication/330727606_The_Analysis_Of_Arsenic_and_Cobalt_In_Horseracing_In_Turkey
  • Kinobe RT. (2016). Towards the elimination of excessive cobalt supplementation in racing horses: A pharmacological review. Res Vet Sci.;104:106–12. doi.org/10.1016/j.rvsc.2015.12.007
  • Knych HK, Arthur RM, Mitchell MM, Holser I, Poppenga R, Smith LL, vd. (2015). Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses. Drug Test Anal.;7(7):619–25.
  • Kriss JP, Carnes WH, Gross RT. (1955). Hypothyroidism and thyroid hyperplasia in patients treated with cobalt. J Am Med Assoc.;157(2):117–21.
  • Kwak YB, Yu J, Im EJ, Jeong BS, Yoo HH. (2021). Study of cobalt doping control via various routes in thoroughbred horses. Drug Test Anal.; Available at: https://pubmed.ncbi.nlm.nih.gov/34750992/
  • Leggett RW. (2008). The biokinetics of inorganic cobalt in the human body. Sci Total Environ.;389(2–3):259–69.
  • Liang R, Ghaffari S. (2016).Advances in understanding the mechanisms of erythropoiesis in homeostasis and disease. Br J Haematol.;174(5):661–73. doi/full/10.1111/bjh.14194
  • Lippi G, Franchini M, Guidi GC. (2005).Cobalt chloride administration in athletes: A new perspective in blood doping? Br J Sports Med.;39(11):872–3.
  • Lippi G, Franchini M, Guidi GC. (2006). Blood doping by cobalt. Should we measure cobalt in athletes? J Occup Med Toxicol.;1(1):2–4.
  • Manthe, Brette N., and Curtis R. Youngs. “An Overview of Vitamin Requirements of the Domestic Horse.” Natural Sciences Education, vol. 42, no. 1, John Wiley and Sons Inc, Dec. 2013, pp. 179–84, doi:10.4195/NSE.2012.00002.
  • National Research Council. Nutrient Requirements of Horses. (2007): Sixth Revised Edition [Internet]. [kaynak 20 Şubat 2022]. 360 s. Available at: http://www.nap.edu/catalog/11653/nutrient-requirements-of-horses-sixth-revised-edition
  • Palit S, Sharma A, Talukder G. (1994).Effects of cobalt on plants. Bot Rev.;60(2):149–81.
  • Popot MA, Ho ENM, Stojiljkovic N, Bagilet F, Remy P, Maciejewski P, vd. (2017).Interlaboratory trial for the measurement of total cobalt in equine urine and plasma by ICP-MS. Drug Test Anal.;9(9):1400–6.
  • Rodríguez-Jiménez FJ, Moreno-Manzano V. (2012).Modulation of hypoxia-inducible factors (HIF) from an integrative pharmacological perspective. Cell Mol Life Sci.;69(4):519–34.
  • Seven T, Can B, Darende Bn, Ocak S.(2018). Hava ve Toprakta Ağır Metal Kirliliği. Ulus Çevre Bilim Araştırma Derg [Internet].;1(2):91–103. https://dergipark.org.tr/en/pub/ucbad/issue/38487/447131
  • Shrivastava K, Bansal A, Singh B, Sairam M, Ilavazhagan G. (2010). Sub-chronic oral toxicity study in Sprague-Dawley rats with hypoxia mimetic cobalt chloride towards the development of promising neutraceutical for oxygen deprivation. Exp
  • Toxicol Pathol;62(5):489–96..doi.org/10.1016/j.etp.2009.06.012
  • Wenzel R, Major D, Hesp K, Doble P. (2018).Determination of vitamin B12 in equine urine by liquid chromatography – inductively coupled plasma – mass spectrometry. J Trace Elem Med Biol.;50(May):634–9.
  • WHO.(2006). Concise International Chemical Assessment Document 69: Cobalt and Inorganic Cobalt Compounds. World Heal Organ.1–93. Available at: http://www.who.int/ipcs/publications/cicad/cicad70.pdf
  • Wolf J, Levy IJ. (1954). Treatment of sickle-cell anemia with cobalt chloride. AMA Arch Intern Med.;93(3):387–96.
There are 37 citations in total.

Details

Primary Language Turkish
Subjects Veterinary Surgery
Journal Section Review
Authors

Ertuğrul Güneş 0000-0001-9872-1882

Murat Yıldırım 0000-0003-1902-3205

Publication Date December 23, 2022
Submission Date May 16, 2022
Published in Issue Year 2022 Volume: 33 Issue: 2

Cite

APA Güneş, E., & Yıldırım, M. (2022). Yarış Atlarında Yasaklı Madde Olarak Kobalt. Etlik Veteriner Mikrobiyoloji Dergisi, 33(2), 85-91. https://doi.org/10.35864/evmd.1117325

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