Cobalt accumulation in horses following repeated administration of cobalt chloride.
Abstract: To monitor cobalt concentrations in urine, red blood cells and plasma after chronic parenteral administration of cobalt chloride evaluate these results against the current International Federation of Horseracing Authorities thresholds for detecting cobalt misuse. Methods: Eight mares were randomly assigned to four treatment groups, with two mares in each group: Group 1 - control group, Group 2 - 25 milligrams cobalt intravenously as CoCl weekly, Group 3 - 50 milligrams cobalt intravenously as CoCl weekly, and Group 4 - 25 milligrams cobalt intravenously mid-week and at the end of the week. Urine and blood samples were collected before each weekly administration so that trough levels were assessed. In the group receiving two doses per week, urine and blood were collected prior to the dose given at the end of each week. Samples were initially collected at time zero then weekly for 10 weeks. Three further collections of urine and blood were made at days 81, 106 and 127. Methods: Urine creatinine measurements to assess horse hydration status were performed by the Jaffe reaction method. Cobalt determinations in plasma, blood and urine were by inductively coupled plasma-mass spectrometry. Haematocrit concentrations, used to calculate red cell cobalt levels, were performed using a microhematocrit centrifuge. Statistical analyses were conducted in Genstat (v17, VSNi). Results: Marked cobalt accumulation was evident with increasing cobalt concentrations for all sample matrices in specimens collected immediately prior to cobalt administration. Correlation between the sample matrices improved when urine cobalt concentration was adjusted for creatinine level. Red cell cobalt levels remained elevated for at least 12 weeks after cessation of administration, consistent with the lifespan of the red cell. There was no significant change in haematocrit concentrations for the duration of the study. Conclusions: The current urine cobalt threshold was only effective at detecting acute cobalt exposure while the plasma cobalt threshold was able to consistently identify chronic high-level cobalt exposure and potential cobalt misuse. The threshold values legislated for urine cobalt do not correlate with those set for plasma. The acute nature of urinary cobalt excretion provides a relatively small window through which cobalt administration is detected. Plasma and red cell cobalt concentrations can provide a clearer picture of potential cobalt misuse.
© 2019 Australian Veterinary Association.
Publication Date: 2019-08-16 PubMed ID: 31418855DOI: 10.1111/avj.12872Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Veterinary
Summary
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This research investigates the accumulation of cobalt in horses following repetitive administration of cobalt chloride. It monitored cobalt levels in urine, red blood cells, and plasma in comparison to the International Federation of Horseracing Authorities standards for detecting cobalt misuse. The results showed a marked accumulation of cobalt in all tested samples. The study suggests that plasma and red cell cobalt concentrations give a better indication of cobalt misuse in horses.
Study Design and Methodology
- In the study, eight mares were randomly distributed across four groups, each group designed to represent different treatment conditions.
- Control Group 1 did not receive any treatment.
- Group 2 received 25 milligrams of cobalt chloride intravenously on a weekly basis.
- Group 3 received 50 milligrams of cobalt chloride intravenously on a weekly basis.
- Group 4 received 25 milligrams of cobalt chloride intravenously twice a week.
- Urine and blood samples were taken before each treatment administration; this is known as trough level assessment. The group receiving two doses per week had samples taken before the second weekly dose.
- Initially, samples were collected at time zero and then weekly for 10 weeks. Three further collections of urine and blood samples were made at days 81, 106, and 127.
- The research team used the Jaffe reaction method to assess horse hydration status with urine creatinine measurements. Cobalt concentrations in plasma, blood, and urine were determined by inductively coupled plasma-mass spectrometry.
- Microhematocrit centrifuge was used to test haematocrit concentrations and calculate red cell cobalt levels.
- Statistical analyses were conducted using the Genstat software tools (version 17, VSNi).
Results
- Results showed significant cobalt accumulation across all sample matrices tested. The accumulation increased with the escalating cobalt concentrations present in samples collected just before cobalt administration.
- Greater correlation across the sample matrices was found when urine cobalt concentration was adjusted for creatinine level.
- Red cell cobalt levels stayed elevated for at least 12 weeks after the administration was stopped, aligning with the lifespan of the red cell. There was no substantial change in haematocrit concentrations throughout the study duration.
Conclusions
- The study concluded that the currently-set urine cobalt threshold was only effective at pinpointing acute cobalt exposure.
- The plasma cobalt threshold was better at constantly detecting chronic high-level cobalt exposure and potential misuse.
- The threshold values for urine cobalt do not correlate with those set for plasma. The nature of urinary cobalt excretion is acute, providing a relatively small window for cobalt administration detection.
- The research suggests that cobalt concentrations in plasma and red cells can give a clearer picture and be a more effective way of identifying potential cobalt misuse in horses.
Cite This Article
APA
Wenzel RG, Major D, Hesp KF, Hall E, Doble P.
(2019).
Cobalt accumulation in horses following repeated administration of cobalt chloride.
Aust Vet J, 97(11), 465-472.
https://doi.org/10.1111/avj.12872 Publication
Researcher Affiliations
- NSW Health Pathology, Trace Elements Laboratory, Royal North Shore Hospital, Level 5, Acute Services Building, Pacific Highway, St Leonards, New South Wales, 2065, Australia.
- Centre for Forensic Science, University of Technology Sydney, Broadway, New South Wales, 2001, Australia.
- Derek Major Consulting Pty Ltd, Richmond, New South Wales, 2753, Australia.
- NSW Health Pathology, Trace Elements Laboratory, Royal North Shore Hospital, Level 5, Acute Services Building, Pacific Highway, St Leonards, New South Wales, 2065, Australia.
- Veterinary Biostatistics, University of Sydney, Camden, New South Wales, 2570, Australia.
- Centre for Forensic Science, University of Technology Sydney, Broadway, New South Wales, 2001, Australia.
MeSH Terms
- Animals
- Cobalt / administration & dosage
- Cobalt / blood
- Cobalt / standards
- Cobalt / urine
- Creatinine / urine
- Female
- Horses / urine
- New South Wales
- Plasma / chemistry
- Sports
References
This article includes 27 references
- Harris P, Coenen M, Frape D. Equine nutrition and metabolic diseases. In: The equine manual. Saunders Ltd., Philadelphia, Pennsylvania, 2006;72.
- Simonsen LO, Harbak H, Bennekou P. Cobalt metabolism and toxicology-a brief update. Sci Total Environ 2012;432:210-215.
- Tvermoes BE, Unice KM, Paustenbach DJ. Effects and blood concentrations of cobalt after ingestion of 1 mg/d by human volunteers for 90 d. Am J Clin Nutr 2014;99:632-646.
- Carter E, Valli V, McSherry B. The kinetics of hematopoiesis in the light horse I. The lifespan of peripheral blood cells in the normal horse. Can J Comp Med 1974;38:303.
- Kinobe RT. Towards the elimination of excessive cobalt supplementation in racing horses: a pharmacological review. Res Vet Sci 2016;104:106-112.
- Estey MP, Diamandis EP, Van Der Straeten C. Cobalt and chromium measurement in patients with metal hip prostheses. Clin Chem 2013;59:880-886.
- Daniel J, Ziaee H, Pradhan C. Blood and urine metal ion levels in young and active patients after Birmingham hip resurfacing arthroplasty: four-year results of a prospective longitudinal study. J Bone Joint Surg Br 2007;89:169-173.
- Krug O, Kutscher D, Piper T. Quantifying cobalt in doping control urine samples-a pilot study. Drug Test Anal 2014;6:1186-1190.
- International Federation of Horseracing Authorities. International agreement on breeding, racing and wagering. 2017.
- Ho EN, Chan GH, Wan TS. Controlling the misuse of cobalt in horses. Drug Test Anal 2015;7:21-30.
- Knych HK, Arthur RM, Mitchell MM. Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses. Drug Test Anal 2015;7:619-625.
- Flora SJ, Pachauri V. Chelation in metal intoxication. Int J Environ Res Public Health 2010;7:2745-2788.
- Llobet JM, Domingo JL, Corbella J. Comparison of the effectiveness of several chelators after single administration on the toxicity, excretion and distribution of cobalt. Arch Toxicol 1986;58:278-281.
- Apple FS, Quist HE, Otto AP. Release characteristics of cardiac biomarkers and ischemia-modified albumin as measured by the albumin cobalt-binding test after a marathon race. Clin Chem 2002;48:1097-1100.
- Lippi G, Montagnana M, Guidi GC. Albumin cobalt binding and ischemia modified albumin generation: an endogenous response to ischemia?. Int J Cardiol 2006;108:410-411.
- Yaqub LS, Mshelia WP, Ayo JO. Erythrocyte osmotic fragility and hematological responses of horses administered ascorbic acid and exposed to road transportation. J Equine Vet 2014;34:1324-1328.
- Hanzawa K, Watanabe S. Changes in osmotic fragility of erythrocytes during exercise in athletic horses. J Equine Sci 2000;11:51-61.
- WADA Laboratory Committee. Decision limits for the confirmatory quantification of threshold substances. 2014.
- Sauve JF, Levesque M, Huard M. Creatinine and specific gravity normalization in biological monitoring of occupational exposures. J Occup Environ Hyg 2015;12:123-129.
- Warrack BM, Hnatyshyn S, Ott KH. Normalization strategies for metabonomic analysis of urine samples. J Chromatogr B Analyt Technol Biomed Life Sci 2009;877:547-552.
- Boeniger MF, Lowry LK, Rosenberg J. Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review. Am Ind Hyg Assoc J 1993;54:615-627.
- Abbott Laboratories. Creatinine. 2006.
- International Organization for Standardization. ISO 15189:2012 medical laboratories - requirements for quality and competence. 2012.
- Burns T, Dembek K, Kamr A. Effect of intravenous administration of cobalt chloride to horses on clinical and hemodynamic variables. J Vet Intern Med 2018;32:441-449.
- Simonsen LO, Brown AM, Harbak H. Cobalt uptake and binding in human red blood cells. Blood Cells Mol Dis 2011;46:266-276.
- Mobasheri A, Proudman CJ. Cobalt chloride doping in racehorses: concerns over a potentially lethal practice. Vet J 2015;205:335-338.
- Finley BL, Monnot AD, Gaffney SH. Dose-response relationships for blood cobalt concentrations and health effects: a review of the literature and application of a biokinetic model. J Toxicol Environ Health B Crit Rev 2012;15:493-523.
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