Кобальта хлорид инструкция по применению для людей

7 Cobalt

In the early 1960s cobalt salts, chloride or sulfate, were added to some brands of beer in order to stabilize the foam; as a result of this intervention, heavy beer drinkers developed cardiomyopathy, which led to a high mortality rate (Morin et al., 1971). It is likely that poor nutrition and ethanol played a synergistic role with cobalt in the development of this disease (Lauwerys and Lison, 1994; Seghizzi et al., 1994). Cardiomyopathy was also described in two workers exposed to heavy dust concentrations from cobalt-containing ores for 2 months and 2 years, respectively (Jarvis et al., 1992). Cardiomyopathy was also reported after exposure to hard-metal dust in a man responsible for weighing and mixing tungsten carbide and cobalt powder (Kennedy et al., 1981).

The bioavailability of cobalt increases in the presence of tungsten carbide. Endotracheal instillation of tungsten carbide-cobalt mixture in rats causes severe alveolitis and fatal pulmonary edema, whereas the corresponding dose of cobalt powder alone causes a moderate inflammatory response (Lauwerys and Lison, 1994).

Mice exposed to 30 mg/m³ cobalt sulfate heptahydrate for 90 days developed arteritis in the main coronary artery (2/17 compared to controls 0/18). In a long-term inhalation study of exposure to 3.0 mg/m³ cobalt for 24 months, 2/48 animals developed arteritis in coronary arteries versus 0/46 in controls. The number of animals with arteritis in the renal arteries was 5/48 versus 1/46. Thus, there was a significantly increased risk when all groups were taken into account (Moyer et al., 2002).

In a cross-sectional study of 30 cemented tungsten carbide workers with a mean exposure duration of 9.9 years, a weak but significant inverse correlation was found between duration of exposure and resting left ventricular function. Nine workers with abnormal chest X-ray findings had relatively lower exercise right ventricular ejection fractions. Diminished right ventricular reserve was probably due to fibrotic lung disease and early cor pulmonale. The authors concluded that although overt left ventricular dysfunction was not present, prolonged exposure to industrial cobalt may have a weak cardiomyopathic effect (Horowitz et al., 1988).

No increased mortality risk of all circulatory disease or IHD were observed in the largest cohort of French hard-metal workers comprising totally 7459 men and women. The SMRs were 0.88 (95% CI 0.75-1.03) and 0.93 (95% CI 0.71-1.19), respectively (Moulin et al., 1998).

A cohort of 3163 male Swedish hard-metal workers was followed from 1951 to 1982. In the total cohort, the SMR for IHD was 0.99 (95% CI 0.80-1.21). In a subgroup with estimated high cobalt exposure and long-term (> 10 years) exposed workers, a higher SMR was observed (SMR 1.69, 95% CI 0.96-2.75) (Hogstedt and Alexandersson, 1990).

Thus, cardiomyopathy has been induced by the intake of cobalt-containing beer and after inhalation of high concentrations of dust from cobalt-containing ores. Signs of cor pulmonale have been observed as a result of fibrotic lung disease induced by inhalation of hard-metal dust. The majority of cohorts comprising cobalt-exposed hard-metal workers do not report an increased risk of IHD. However, one study suggests an excess in long-term exposed workers.

Reproductive and developmental toxicity

No studies were located regarding reproductive effects in humans after inhalation exposure to cobalt.

Both rats exposed to cobalt (as cobalt chloride) at 13.3–58.9 mg kg⁻¹ body weight per day for 2–3 months in drinking water or diet and mice exposed to cobalt (cobalt chloride) at 43.3 mg kg⁻¹ body weight per day for 13 weeks in drinking water exhibited testicular degeneration and atrophy.

Long-term exposure of cobalt-containing aerosols resulted in effects on reproductive end points. Testicular atrophy was reported in rats, but not in mice, exposure to 10 mg cobalt per m³ as cobalt sulfate over 16 days. Following exposure of mice to cobalt for 13 weeks, a decrease in sperm motility was found at 1.14 mg cobalt per m³, and testicular atrophy was found at 11.4 mg cobalt per m³ (Grimsely and Harris, 2012).

Cobalt

Cobalt is an essential component of vitamin B₁₂. In the past, cobalt chloride was used to treat the anemia of CKD [145]. Cobalt induces erythropoiesis, acting as an inducer of hypoxia-inducible factor (HIF) [146]. Because of its side effects, including cardiomyopathy and thyroid dysfunction, its use was discontinued [147]. There is a positive correlation between serum cobalt levels and atherosclerosis in MHD patients [112]. More rigorous studies are needed to examine the potential benefits and hazards of cobalt intake for chronic dialysis patients.

5.1.1.2 Digestive Absorption

Gastrointestinal absorption of cobalt depends on the type of compound given, dose, and nutritional status. Less than 0.5% of CoO given orally to hamsters at a dose of 5 mg is absorbed (Wehner and Craig, 1972), whereas gastrointestinal absorption of cobalt chloride given to rats is estimated to be about 30% (Comar and Davis, 1947; Carlberger, 1961; Taylor, 1962). Gastrointestinal absorption of radiolabeled cobalt chloride in rats was found to vary between 11 and 34%, inversely correlating with the administered dose (0.01-1000 μg/rat) (Taylor, 1962). Both amino acids and sulfhydryl groups complex with cobalt ions and reduce their absorption. Iron deficiency increases the absorption of cobalt and simultaneous administration of iron with cobalt reduces cobalt absorption (Schade, 1970). Some data also indicate that gastrointestinal absorption is more efficient in young rats (98 and 85% at days 1 and 20, respectively) (Naylor and Harrison, 1995). After oral administration of cobalt, the largest concentrations are found in the liver, kidney, and spleen (Domingo, 1989).

5.1.1.2 Digestive

Gastrointestinal absorption of cobalt depends on the type of compound given, dose, and nutritional status. Less than 0.5% of CoO given orally to hamsters at a dose of 5 mg is absorbed (Wehner and Craig, 1972), whereas gastrointestinal absorption of cobalt chloride given to rats is estimated to be approximately 30% (Carlberger, 1961; Comar and Davis, 1947; Taylor, 1962). the gastrointestinal absorption of radiolabeled cobalt chloride in rats was found to vary between 11 and 34%, depending inversely on the administered dose (0.01–1000 μg/rat) (Taylor, 1962). Both amino acids and sulfhydryl groups complex with cobalt ions and reduce absorption. Iron deficiency increases the absorption of cobalt, and simultaneous administration of iron and cobalt reduces cobalt absorption (Schade, 1970). Some data also indicate that the gastrointestinal absorption is more efficient in young rats (98 and 85% at days 1 and 20, respectively) (Taylor and Harrison, 1995). After oral administration, the largest concentrations are found in liver, kidney, and spleen (Domingo, 1989).

Cobalt [SED-15, 847; SEDA-31, 386; SEDA-32, 415; SEDA-33, 450]

Respiratory Between 1967 and 2003, 22 cases of asthma were diagnosed in a cobalt plant [48^c]. The incidence was highest in the departments with the highest cobalt exposures and all were in departments in which irritant gases were present in the ambient air in addition to cobalt.

Skin In 14 464 patients (68% women and 32% men) with suspected allergic dermatitis who underwent patch tests about 10% reacted positively to cobalt chloride [43^c]. Cobalt sensitization was associated with textile and leather work in women and with cleaning work in men.

In nail art three layers are applied, with decorations added between the layers. An allergic reaction to cobalt chloride in nail-art materials has been reported in a 37-year-old woman, who developed multiple, intensely itchy, eczematous periungual and palmar lesions on both hands; a patch test with cobalt was positive [49^A].

A 41-year-old man developed suspected occupational hand dermatitis, but had clinical features that were not typical of contact dermatitis, with discrete excoriated papules and some lichenified plaques on the dorsum of the hands and wrists; the palms were unaffected [50^A]. Punch biopsies from the backs of the hands suggested lichen simplex. However, patch testing was positive with various salts of cobalt. At work he had been exposed to cobalt in a viscous polyester resin, which he had sanded without gloves.

Immunologic Delayed-type IV cobalt hypersensitivity has been reported in a patient who had received a metal-on-metal bearing in a total hip arthroplasty several years before [51^A]. Such reactions, although rare, can cause arthroplasty failure [52^R].

3.16 Cobalt

In the mid-1960s, an acute and fulminant form of dilated cardiomyopathy with a 40% fatality rate was described in heavy beer drinkers in Quebec City, Canada, and in several American cities.^204,205 Epidemiologic investigations and animal studies implicated as the etiology cobalt chloride salt that was added to the beer to stabilize the foam. Autopsy demonstrated high levels of cobalt in endomyocardial tissue along with myocardial tissue degeneration, increased vacuolation, and interstitial edema^205,206; all chambers of the heart were affected, with an atrial predilection.^205,207 Concomitant polycythemia, pericardial effusion, hypothyroidism, lactic acidosis, gastrointestinal ulcerations, and elevated liver enzymes may distinguish cobalt-induced cardiomyopathy from other etiologies of dilated cardiomyopathy.^205–207

Although the addition of cobalt to beer was discontinued in the late 1960s, cobalt-induced dilated cardiomyopathy has been described following occupational exposures to this element^207,208 and in patients who have had a hip replacement with metal-on-metal acetabular surface joints.²⁰⁴

Hypoxic Preconditioning and Deferoxamine

Hypoxic preconditioning has been shown in both hippocampal cells and in the Rice-Vannucci neonatal rat model to activate protective mechanisms, possibly by triggering expression of gene products or deoxygenation of a heme moiety. Levels of a hypoxia-inducible transcription factor (HIF-1) are elevated in the penumbra in neonatal rats treated with hypoxia preconditioning (Bergeron et al, 2000). Pretreatment of animals with either cobalt chloride or DFO before injury was found to provide a 75% or 56% degree of protection, respectively. Other studies in the ischemic gerbil model (Patt et al, 1990), as well as in the neonatal rat, mouse, and lamb models, have shown decreased injury with use of DFO (Groenendaal et al, 2000; Kompala et al, 1986; Palmer et al, 1994; Sarco et al, 2000). DFO may act by iron chelation or by inducing HIF-1, or by other mechanisms. Although it has not been tested in human trials, it is a good candidate for clinical trials in neonates, as it has been studied extensively in clinical situations requiring iron chelation.

1.7 Cobalt

Finely divided cobalt metal powder, cobalt oxide, and cobalt sulfide have given rise to fibrosarcoma at sites of subcutaneous injection and to rhabdomyosarcoma following intramuscular injection in rats (Gilman, 1966). Researchers were able to produce such neoplasms with fine particles from surgical prostheses made from a cobalt-chromium alloy. Cobalt chloride has been shown to decrease the fidelity of DNA synthesis in vitro (Sirover and Loeb, 1976a), to induce morphological transformation, and to enhance the viral transformation of hamster embryo cells (Casto et al., 1979; DiPaolo and Casto, 1979).

There have been few reports of cancer in cobalt workers, despite previous heavy occupational exposure. In certain nickel extraction plants in the USSR, increased mortality from lung cancer was found in workers in the cobalt recovery shops, as well as those in nickel-processing departments (Saknyn and Shabynina, 1973). However, exposure to arsenic-containing dust was heavy and these workers may also have been exposed to nickel. There are no convincing reports of cancer having arisen in relation to surgical prostheses with cobalt-containing alloys, despite raised blood and urinary cobalt levels. The IARC (1991) consider cobalt and cobalt compounds to be possibly carcinogenic to humans (Group 2B) (IARC, 1991). The reader is again referred to chapters on the selected mechanisms of metal toxicity and carcinogenesis (Chapter 9) and the chapter on cobalt (Chapter 34) in this handbook for further information.