Radiation Dosimetry of Internal Contamination by Inorganic Compounds of Cobalt

Hollins, J.G.; McCullough, Roger S.

doi:10.1097/00004032-197108000-00010

Cited by 17 publications

(9 citation statements)

References 2 publications

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“…Hollins and McCullough [16] reported that at 10 72 h post intraperitoneal administration of radiolabelled cobalt chloride, the liver, skeleton and muscle contained 20 25% of total body activity with 7 8% accumulating in the kidney. Hollins and McCullough [16] reported that at 10 72 h post intraperitoneal administration of radiolabelled cobalt chloride, the liver, skeleton and muscle contained 20 25% of total body activity with 7 8% accumulating in the kidney.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses

Knych

Arthur

Mitchell

et al. 2014

Drug Testing and Analysis

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Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were administered a single intravenous dose of cobalt chloride or cobalt gluconate and serum and urine samples collected for up to 10 days post administration. Cobalt concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) and pharmacokinetic parameters determined. Additional blood samples were collected for measurement of equine EPO concentrations as well as to assess any effects on red blood cell parameters. Horses were observed for adverse effects and heart rate monitored for the first 4 h post administration. Cobalt was characterized by a large volume of distribution (0.939 L/kg) and a prolonged gamma half-life (156.4 h). Cobalt serum concentrations were still above baseline values at 10 days post administration. A single administration of cobalt had no effect on EPO concentrations, red blood cell parameters or heart rate in any of the horses studied and no adverse effects were noted. Based on the prolonged gamma half-life and prolonged residence time, regulators should be able to detect administration of a single dose of cobalt to horses.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses

Knych

Arthur

Mitchell

et al. 2014

Drug Testing and Analysis

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“…Following the intravenous administration of 1 mg Co(II)/kg as cobaltous chloride to rats, 4.7% of the dose was secreted in the bile by 2 h (Gregus & Klaassen, 1986). Following the injection of the same dose of Co(II) to rats, 72.6% of the dose was excreted in the urine by 4 d. Cobalt was distributed to the largest extent to the liver, kidneys, and heart following the oral or parental administration of soluble cobalt to the rat (Hollins & McCullough, 1971;Stenberg, 1983;Alexanderson, 1988) or following the oral or intravenous administration of cobaltous chloride to rabbits, swine, and calves (Gregus & Klaassen, 1986). These results suggested that there was no species variability.…”

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confidence: 99%

“…Therefore, there may be a longer component to the blood concentration curve that was not determined in this study. Hollins and McCullough (1971) were able to describe cobalt whole-body retention in rats by a sum of five exponential terms over a period of 400 d. They used radioactive cobalt and probably observed cobalt exchange into endogenous compounds that have a very slow turnover. Because the amounts of cobalt in the extra two exponential terms were so small, they probably have little toxicological significance.…”

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confidence: 99%

Disposition, Toxicity, and Intestinal Absorption of Cobaltous Chloride in Male Fischer 344 Rats

Ayala-Fierro¹,

Firriolo²,

Carter³

1999

Journal of Toxicology and Environmental Health

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The absorption and disposition of inorganic cobalt salts after oral administration have not been well characterized. The objectives of this study were to compare in vivo results with cobalt transport through the in vitro everted small intestine and to relate the disposition results to a biochemical indicator of cobalt toxicity. Cobalt chloride was given to male Fischer 344 rats orally at 33.3 mg Co(II)/kg or intravenously at 4.16 mg Co(II)/kg. By 36 h, 74.5% of the oral dose was eliminated in the feces. The liver, kidney, and heart accumulated cobalt to the greatest extent. Following the single oral dose, the blood cobalt concentration-time curve was triphasic, peaked at 3.2 h, and had an absorptive half-life of 0.9 h, an elimination phase half-life of 3.9 h, and a terminal elimination half-life of 22.9 h. Following intravenous administration, 10.1% of the dose was excreted in the feces, indicating that cobalt can be secreted in the bile. Following a single intravenous injection, the concentration-time curve displayed three segments. The first segment, which occurred during the first 4 h, had a rapid half-life of 1.3 h. The second phase, from 4 to 12 h, demonstrated a slower clearance rate with a half-life of 4.3 h. The final and slowest phase, from 12 to 36 h, had a half-life of 19 h. Intestinal jejunal ring experiments indicated that cobalt transport has both active and passive components; however, cobalt transport through the in vitro rat everted duodenum indicated that cobalt transport had almost exclusively passive components with facilitated diffusion. The finding that uptake was saturable may explain the small extent of absorption following oral dosing. Heme oxygenase studies following subcutaneous and intravenous administration resulted in an increase in activity (twofold) over controls, while oral administration did not. We concluded that the extent of cobalt absorption across the gastrointestinal tract is incomplete, and that the concentration administered and the route of exposure may determine its systemic toxicity.

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“…Testes data in the literature were sparse. Based on our assumed interpretation of the data of Hollins and McCullough (1971) and that of Gregus and Klaassen (1986), approximately 0.2% ID remained in testes at 2 hr and 0.4% ID of the activity remaining in the carcass remained in testes at 10 d. No literature values could be found for 60 Co in ovaries.…”

Section: Resultsmentioning

confidence: 82%

Biokinetics of Systemically Distributed 60Co in the Rat

Weber

Doyle-Eisele²,

Seilkop³

et al. 2012

Health Physics

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LBERI, a member of the Medical Countermeasures to Radiologic Threats (MCART) consortium funded by NIAID, was tasked to develop biokinetic models for the distribution of radionuclide threats using the most likely routes of incorporation in both small and large animals. In the present paper, the biokinetics of systemically administered soluble cobalt-60 (60Co) have been examined. Male and female jugular-vein-catheterized (JVC) F344 rats received intravenous (IV) doses of 11.2 kBq of 60CoCl2. The distribution of the radiocobalt was followed for 28 d, with tissue sampling done at 1 and 4 h, and at 1, 2, 4, 8, 16, and 28 d. Urine and feces were collected daily. Tissues and excreta were analyzed by gamma pulse height analysis. Within 8d, 93% of the cobalt was eliminated from the body primarily though urine. The highest tissue burdens were found in liver, gastrointestinal (GI) tract, and muscle shortly after administration. These tissues cleared quickly so that by the conclusion of the 28-d study, less than 3% of the recovered dose remained in the body. The results are comparable to published literature values for tissue content of 60Co and for excretion patterns up to 30 d after injection. These results will provide the data needed to construct a biokinetic model for the unperturbed biokinetics of 60Co in rats, which will subsequently be used to evaluate the impact of administered decorporating agents on organ radiation doses. The animal model described in this paper is representative of that used for other routes of radionuclide administration such as inhalation, ingestion and wound contamination that have been studied at LBERI in support of the MCART and NIAID programs.

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Radiation Dosimetry of Internal Contamination by Inorganic Compounds of Cobalt

Cited by 17 publications

References 2 publications

Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses

Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses

Disposition, Toxicity, and Intestinal Absorption of Cobaltous Chloride in Male Fischer 344 Rats

Biokinetics of Systemically Distributed 60Co in the Rat

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