Cobalt excretion

In a series of studies conducted on human volunteers in the Division of Human Nutrition and Biology at the Institute of Nutrition of Central America and Panama, we employed the radiocobalt absorption test in the context of iron absorption tests. We used a modification of a 6-h cobalt excretion test to estimate absorption (44). Approximately 2.5 fiCi of cobalt-60 mixed with 4.74 mg (20 fimol) of cobalt chloride hexahy-drate was given in 100 mL of water after an overnight fast. The subjects remained fasting for 2 h postingestion and then consumed a standard breakfast. A liter or more of water was consumed during the final 4 h of the study. All urine produced during the 6 h was collected the excreted radioactivity was measured in a well-type y-counter. 

The amount of each element required in daily dietary intake varies with the individual bioavailabihty of the mineral nutrient. BioavailabiUty depends both on body need as deterrnined by absorption and excretion patterns of the element and by general solubiUty, and on the absence of substances that may cause formation of iasoluble products, eg, calcium phosphate, Ca2(P0 2- some cases, additional requirements exist either for transport of substances or for uptake or binding. For example, calcium-binding proteias are iavolved ia calcium transport an intrinsic factor is needed for vitamin cobalt,... 

Daabees, A.Y., N.A. El Domiaty, A.M. Hilmy, A.M. Awadallah, and E.M.A. Taleb. 1991. Mortality, distribution and excretion of cobalt and nickel administered subcutaneously to toads. Jour. Medical Res. Inst. (Egypt) 12 185-201. 

Cobalt is found in most natural foods. Although a necessary trace element, it is toxic to humans if ingested in large amounts. The human body does excrete in urine excessive amounts of cobalt compounds such as found in vitamin B ... 

Heavy metals stimulate or inhibit a wide variety of enzyme systems (16, 71, 72), sometimes for protracted periods (71, 73). These effects may be so sensitive as to precede overt toxicity as in the case of lead-induced inhibition of 8 ALA dehydrase activity with consequential interference of heme and porphyrin synthesis (15, 16). Urinary excretion of 8 ALA is also a sensitive indicator of lead absorption (74). Another erythrocytic enzyme, glucose-6-phosphatase, when present in abnormally low amounts, may increase susceptibility to lead intoxication (75), and for this reason, screens to detect such affected persons in lead-related injuries have been suggested (76). Biochemical bases for trace element toxicity have been described for the heavy metals (16), selenium (77), fluoride (78), and cobalt (79). Heavy metal metabolic injury, in addition to producing primary toxicity, can adversely alter drug detoxification mechanisms (80, 81), with possible secondary consequences for that portion of the population on medication. 

Factors which tend to decrease the availability of this vitamin include (1) cooking losses, since the vitamin is heat labile (2) cobalt deficiency in ruminants (3) intestinal malabsorption or parasites (4) lack of intrinsic factor (5) intestinal disease (6) aging (7) vegetarian diet (8) excretion... 

Cobalt must be supplied in the diet in its physiologically active form, vitamin B12. GI absorption of cobalt is about 25%, with wide individual variation excretion occurs mainly via the urine. The major part is excreted within days and the rest has a biological half-life of about two years. Originally, the therapy for pernicious anemia was to have patients eat large amounts of liver. The most reliable treatment now is monthly injections of cobalamin. 

Schilling s test assesses the oral absorption of vitamin B12 and is used to diagnose pernicious anaemia. The patient is injected intramuscularly with non-labelled vitamin B12, to saturate body stores. An oral dose of vitamin B12 labelled with cobalt-58 is administered, followed by a second dose labelled with cobalt-57 bound to intrinsic factor. Prior saturation of body stores ensures any absorbed radiolabelled vitamin B12 is rapidly excreted in the urine. Urinary excretion of orally administered vitamin B12 is low in patients with pernicious anaemia due to poor absorption. Absorption is increased when it is administered with intrinsic factor. The ratio of cobalt-57 to cobalt-58 is thus raised in patients with pernicious anaemia. Intrinsic factor antibody testing is now generally used to diagnose pernicious anaemia, though the Schilling s test may occasionally be used. 

Gregus and Klaassen carried out a comparative study of fecal and urinary excretion and tissue distribution of eighteen metals in rats after intravenous injection. Total (fecal + urinary) excretion was relatively rapid (over 50% of the dose in 4 days) for cobalt, silver and manganese between 50 and 20% for copper, thallium, bismuth, lead, cesium, gold, zinc, mercury, selenium and chromium and below 20% for arsenic, cadmium, iron, methylmercury and tin. Feces was the predominant route of excretion for silver, manganese, copper, thallium, lead, zinc, cadmium, iron and methylmercury whereas urine was the predominant route of excretion of cobalt, cesium, gold, selenium, arsenic and tin. Most of the metals reached the highest concentration in liver and kidney. However, there was no... 

Table III. Comparison of the 6-h Excretion of Cobalt-60 When Administered Alone or with 1000 mg of Ascorbic Acid in Normal Subjects...

Oral ingestion of cobalt salts results in ready absorption, probably in the jejunum. Although cobalt is readily absorbed, increased levels do not tend to cause significant accumulation. The majority (80%) of cobalt is excreted in the feces of rats and cattle. In contrast, in humans, 80% of absorbed cobalt is excreted via the urine and 15% is excreted in the feces by an enterohepatic pathway. Breast milk and sweat are secondary routes of excretion. The total body burden for the average person is estimated as 1.1 mg. Muscle contains the greatest mass of cobalt but the highest concentrations are found in fat. Cobalt present in the blood is associated with the red blood cells. 

The concentration of (EDTA) ", and thus the ability to complex metal ions, will depend upon the pH. A decrease in pH results in an increase in the deprotonation of EDTA and hence an increase in the concentration of the ED I A ion. The effect of this is that only metal ions with a very high affinity for EDTA will be able to form stable complexes. The stability constants for the EDTA and [diethylenetriaminepentaacetic acid] - (DTPA ) complexes with some important metal ions that are of particular interest for chelation therapy are listed in Table 7.3. It is important to note that the stability of the EDTA and DTPA complexes with toxic metals, such as lead, mercury, cadmium, or plutonium are quite similar to those with essential metals such as zinc, cobalt or copper however, the Ca complex is many orders of magnitude lower. This has important implications for chelation therapy. First, the mobilization and excretion of zinc and other essential metals are likely to be increased, along with that of the toxic metal during EDTA treatment and secondly, the chelation of the ionic calcium in the blood, that can cause tetany and even death, can be avoided by administering the chelator as the calcium salt. 

In vitro, cobalt(II) may replace zinc, magnesium, and manganese in a variety of enzymes, without affecting enzymatic activity (Lindskog 1970) this effect is due to the similar ionic sizes of these cations. Whether similar displacement reactions also occur in vivo is not known. Inhaled cobalt particles are rapidly cleared from the lung and excreted. 

Titanium has a tendency to accumulate in tissues. The concentrations can be very high, as indicated in Table 9.5. Titanium was not excreted in the urine of hamsters injected with metal salts (Merritt et al, 1992). Small concentrations were found in the serum, red blood cells and organs. Only 5.5% of the injected titanium was found in the kidneys, liver, lung and spleen tissues. The authors suggest that titanium accumulates at the injection site due to the high stability of the titanium dioxide that is formed at physiological conditions. In the same study nearly all the injected vanadium was recovered in the urine. This behaviour is similar to that of nickel and cobalt, and is related to the formation of highly soluble compounds. 

Experiments with metal salts and with stainless steel and Co-Cr-Mo electrodes corroded in vivo by applying anodic potentials showed that all the nickel and most of the cobalt were rapidly excreted (Brown et aL, 1988). Acceleration of corrosion by the use of anodic potentials obeys similar mechanisms both in vivo and in saline when a potential of 500 mV... 

Excretion of cobalt occurs in two phases a rapid phase, which takes place within a few days after ingestion, whereby 80-90% of the ingested Co is eliminated, and a second very slow phase, which concerns the residual 10% with a biological half-life of 2-15 years. 

Scansetti G, Botta GC, Spinelli P, Reviglione L, Ponzetti C (1994) Absorption and excretion of cobalt in the hard metal industry. Sci Total Environ 150 141-144... 

Although an excess of cobalt can be toxic to animals, there is a wide margin of safety between the nutritional requirement and the toxic level. Cobalt toxicosis is extremely unlikely to occur under practical farming conditions. Unlike copper, cobalt is poorly retained by the body tissues and an excess of the element is soon excreted. The toxic level of cobalt for cattle is 1 mg cobalt/kg body weight daily. Sheep are less susceptible to cobalt toxicosis than cattle and have been shown to tolerate levels up to 3.5 mg/kg. Excessive cobalt supplementation of ruminant diets can lead to the production of analogues of vitamin B12 and a reduction in the quantity of the true vitamin. Cobalt compounds pose a risk to human health as they cause cancer if inhaled and they irritate the skin for this reason, their use has been restricted in the... 

For methods of assay, see Swendslid ME, Halsted JA, Libby RL. Excretion of cobalt labeled vitamin B,2 after total gastrectomy. Proc Soc Exp Biol Med 83 226-228,... 

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