ReviewCobalt metabolism and toxicology—A brief update
Introduction
The toxic effects of cobalt are well known, and its absorption, distribution, metabolism and excretion have been thoroughly reviewed by e.g. Lauwerys and Lison (1994), Barceloux (1999) and Leggett (2008). For extensive and authoritative reviews see also ATSDR (2004) review and WHO (2006) summary. Recent studies have provided insight into the interference of cobalt (Co2 +) with the oxygen sensors in the hypoxia response pathway present in almost all animal cells, contributing to the understanding of the possible carcinogenic effects of cobalt. Moreover, insight has been provided into the membrane transport and accumulation of cobalt in human red blood cells. The results suggest that the transport pathway for cobalt (Co2 +) uptake is shared with calcium, with implications for cobalt biokinetics, and finally suggest that for biomonitoring long-term systemic cobalt exposure, occupationally or in patients e.g. following cobalt–chromium alloy metal-on-metal hip replacement, one should measure the cobalt content in red blood cells rather than the cobalt concentration in whole-blood or serum, to give an average value for the exposure over time. This would also apply to monitoring cases of potential misuse of cobalt salts to enhance aerobic performance. Moreover, the red cell cobalt content would reflect their exposure to ionized cobalt (Co2 +) that seems likely to be the primary toxic form. The present paper is a brief update of the biological functions of cobalt with special reference to its toxicity. Of note, the effects of cobalt are not only harmful, but may also be beneficial. Cobalt stimulates erythropoietin production and increases erythropoiesis, leading to increased oxygen-carrying capacity of the blood which is helpful under conditions of ischemia and tissue hypoxia. Moreover, preconditioning with cobalt salts akin to hypoxic preconditioning promotes tissue adaptation to hypoxia, improves hypoxic/ischemic tolerance and enhances physical endurance performance. It has even been proposed that cobalt preconditioning could possibly prevent high altitude-induced oxidative stress and ameliorate mountain sickness.
Section snippets
Cobalt toxicology. Adverse and putative beneficial effects of cobalt
The transition group metal cobalt is present in trace amounts in the human diet, primarily in vegetables and fish, and in drinking water. Cobalt is an essential micronutrient in the form of vitamin B12 (hydroxocobalamin), but inorganic cobalt as such is not required in human diets, and cobalt deficiency has never been described in humans (Taylor and Marks, 1978). A number of bacterial metalloenzymes (or metal-activated enzymes) have been identified that are dependent on cobalt in a form other
Metabolism of cobalt
For optimizing biomonitoring of systemic human exposure to toxic metals, and for valid interpretation of the results, it is essential to consider their metabolism and toxicokinetics (see, e.g. Christensen, 1995). The metabolism of cobalt (and its radioisotopes) has been studied both in man and in laboratory animals. Water-soluble cobalt salts are rapidly absorbed from the small intestine, though the bioavailability is incomplete and quite variable (see Leggett, 2008, and references therein).
Cobalt exposure. Biomonitoring of long-term systemic cobalt exposure
The occupational cobalt exposure in cobalt processing plants, hard-metal industry, diamond polishing and ceramic industry (e.g. the use of cobalt blue dyes) is well known and has been reviewed (see, e.g. Christensen, 1995). The occupational exposure has probably been somewhat reduced in more recent years due to improved work place hygiene. Of note, however, adverse reactions to heart and lung have recently been demonstrated following cobalt exposure near or slightly under the current
References (84)
- et al.
Cobalt deposition in rat erythrocytes and cardiac tissue as evidence for the biosynthesis of cobalt porphyrins
FEBS Lett
(1970) - et al.
Quantitative analysis of macrophage apoptosis vs. necrosis induced by cobalt and chromium ions in vitro
Biomaterials
(2005) Human exposure to toxic metals: factors influencing interpretation of biomonitoring results
Sci Total Environ
(1995)- et al.
Metabolic and toxicological studies on cobalt
Sci Total Environ
(1994) - et al.
C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation
Cell
(2001) - et al.
Molecular and immune toxicity of CoCr nanoparticles in MoM hip arthroplasty
Trends Mol Med
(2012) - et al.
Induction of apoptosis and necrosis by metal ions in vitro
J Arthroplasty
(2004) Allometric dependence of the life span of mammalian erythrocytes on thermal stability and sphingomyelin content of plasma membranes
Comp Biochem Physiol A Comp Physiol
(2007)- et al.
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway
Mol Cell
(2008) - et al.
Health risks associated with cobalt exposure—an overview
Sci Total Environ
(1994)
The biokinetics of inorganic cobalt in the human body
Sci Total Environ
Albumin cobalt binding and ischaemia modified albumin generation: an endogenous response to ischaemia?
Int J Cardiol
Erythropoietin improves place learning in fimbria-fornix-transected rats and modifies the search pattern of normal rats
Pharmacol Biochem Behav
Experimental cobalt cardiomyopathy
Am Heart J
Cobalt excretion in urine: results of a study on workers producing diamond grinding tools and on control group
Sci Total Environ
Induction of protein oxidation by cobalt and chromium ions in human U937 macrophages
Biomaterials
Cobalt cardiomyopathy. A critical review of literature
Sci Total Environ
Neuroprotective effect of cobalt chloride on hypobaric hypoxia-induced oxidative stress
Neurochem Int
Cobalt uptake and binding in human red blood cells
Blood Cells Mol Dis
Passive transport pathways for Ca2 + and Co2 + in human red blood cells. 57Co2 + as a tracer for Ca2 + influx
Blood Cells Mol Dis
Distribution of chromium and cobalt ions in various blood fractions after resurfacing hip arthroplasty
J Arthroplasty
Effect of chromium and cobalt ions on primary human lymphocytes in vitro
J Immunotoxicol
Blood and urinary concentrations as estimators of cobalt exposure
Arch Environ Health
Toxicological profile for cobalt
Disposition, toxicity, and intestinal absorption of cobaltous chloride in male Fisher 344 rats
J Toxicol Environ Health A
Cobalt
Clin Toxicol
Erythropoietic effect of cobalt in patients with or without anemia
N Engl J Med
Nanotoxicology of metal wear particles in total joint arthroplasty: a review of current concepts
J Appl Biomater Biomech
Soluble ions more than particulate cobalt–alloy implant debris induce monocyte costimulatory molecule expression and release of proinflammatory cytokines critical to metal-induced lymphocyte reactivity
J Biomed Mater Res
The clinical significance of metal ion release from cobalt–chromium metal-on-metal hip joint arthroplasty
J Eng Med
Comparative genotoxicity of cobalt nanoparticles and ions on human peripheral leucocytes in vitro
Mutagenesis
The validity of serum levels as a surrogate measure of systemic exposure to metal ions in hip replacement
J Bone Joint Surg Br
Experimental production of polycythemia in humans by administration of cobalt chloride
Proc Soc Exp Biol Med
The treatment of refractory anaemia of chronic renal failure with cobalt chloride
Q J Med
Improved cardiac contractile functions in hypoxia-reoxygenation in rats treated with low concentration Co2 +
Am J Physiol Heart Circ Physiol
Effects of testosterone, cobalt and hypoxia on erythropoietin production in the isolated perfused dog kidney
Ann N Y Acad Sci
Metal-on-metal bearings: the evidence so far
J Bone Joint Surg Br
Ionic channels of excitable membranes
Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles
PLoS One
Radiation dosimetry of internal contamination by inorganic compounds of cobalt: an analysis of cobalt metabolism in rats
Health Phys
Kinetic and mutational studies of the number of interacting divalent cations required by bacterial and human methionine aminopeptidases
Biochemistry
Cobalt in hard-metals and cobalt sulphate, gallium arsenide, indium phosphide and vanadium pentoxide
Monogr Eval Carcinog Risk Chem Hum
Cited by (445)
Microalgae potential to protect from heavy metals-induced carcinogenicity
2024, Algal ResearchRecent development of metal–organic frameworks in wound healing: Current status and applications
2024, Chemical Engineering JournalCross-talk between biometal ions and immune cells for bone repair
2024, Engineered RegenerationN, S co-doped carbon dots for fluorescent and colorimetric dual-mode detection of Co(II) in actual water
2024, Journal of Industrial and Engineering Chemistry