Urinary Cobalt Concentrations Research Articles

Coordination chemistry applied to anti-doping analysis: Cobalt quantification as its diethyldithiocarbamate complex by liquid chromatography coupled to high resolution tandem mass spectrometry.

Cobalt was included on the World Anti-Doping Agency Prohibited List in 2015 due to its effect on stimulus of erythropoiesis via stabilization of hypoxia-inducible factor. Although it has proven benefits for performance enhancement, the unavailability of inductively coupled plasma-mass spectrometry on routine of the accredited laboratories is a factor that reduces its applicability in anti-doping analysis. Therefore, an analytical method for quantification of urinary cobalt as its diethyldithiocarbamate complex by liquid chromatography coupled with high-resolution tandem mass spectrometry was developed and validated. Palladium was proposed as internal standard and rhodium as a complexation control. A microwave-assisted acid digestion of the urine samples was essential, not only to eliminate the matrix effect but mainly to avoid the non-specific bond of cobalt to endogenous molecules. A linear method was obtained over the studied range from a negative urine control to a spiked concentration of 25 ng/mL, with an estimated limit of quantification of 2.5ng/mL, and an adequate combined standard uncertainty of 11.4%. Considering that all reagents are commercially available, the proposed strategy is feasible to be included on routine sample preparation. Monitoring urinary cobalt concentrations globally opens the perspective to support the anti-doping system to define a suitable threshold value and to understand its potential misuse by athletes seeking for performance improvement.

Dose-response relationships between urinary cobalt concentrations and obesity, insulin resistance, and metabolic-related disorders in the general population.

Excessive cobalt exposure has been shown to induce various adverse health effects in animal and human toxicity studies. However, the relationships between cobalt exposure and obesity, insulin resistance, and metabolic-related disorders are rarely studied in epidemiological studies. This study aimed to explore the dose-response relationships between urinary cobalt concentrations and obesity, insulin resistance, and metabolic-related disorders. Adult participants (≥20 years) from the 2005 to 2018 National Health and Nutrition Examination Survey were included. Restricted cubic splines and the log-binomial regression were adopted. Multivariate adjusted prevalence ratios (95% confidence intervals) comparing extreme quartiles of urinary cobalt concentrations were 1.43 (1.29-1.57) for obesity, 1.43 (1.10-1.86) for insulin resistance, 1.21 (1.09-1.34) for metabolic syndrome, 1.16 (1.10-1.23) for elevated waist circumference, 1.20 (1.09-1.33) for elevated triglycerides, 1.14 (1.01-1.29) for reduced high-density lipoprotein cholesterol (HDL-C), 1.06 (0.98-1.15) for elevated blood pressure, and 0.91 (0.79-1.06) for elevated fasting glucose, respectively. Results from the restricted cubic splines showed that an initial steep increase in risk was followed by a weaker increase in risk or a platform beyond 1.0 µg/L for obesity (prevalence ratio (95% confidence interval): 1.41 (1.29-1.55)), insulin resistance (1.33 (1.07-1.65)), metabolic syndrome (1.18 (1.11-1.31)), elevated waist circumference (1.18 (1.11-1.25)), elevated triglycerides (1.21 (1.11-1.33)), and reduced HDL-C (1.15 (1.01-1.30)), respectively. In conclusion, the prevalence of obesity, insulin resistance, metabolic syndrome, elevated waist circumference, elevated triglycerides, and reduced HDL-C progressively increased with increasing urinary cobalt concentrations. The above associations are non-linear and there is not a "safe threshold" below which there are no toxic effects of cobalt.

Interdependence between urinary cobalt concentrations and hemoglobin levels in pregnant women

Cobalt is an essential trace element but may cause toxic effects upon occupational or environmental exposure. Women accumulate more cobalt than men at similar exposure levels which may be related to higher metabolic iron loss. During pregnancy these losses are much stronger but their influence on cobalt intake has not been studied. We have studied the associations between changes in hemoglobin and cobalt urinary excretion during pregnancy. 391 pairs of urine and blood samples from pregnant women were collected during the 12th and 32nd weeks of pregnancy and were analyzed for cobalt and hemoglobin. Mean concentrations of urinary cobalt were 0.73 and 1.6µg/g creatinine during the first and third trimesters, respectively (p<0.001). 84% of pregnant women had higher levels of cobalt in the third than in the first trimester. Cobalt concentrations were negatively associated to hemoglobin levels in the third trimester (p<0.05). Women with higher iron decreases between both trimesters had significant cobalt increases between these two periods. This correspondence involved a statistically significant difference in third trimester mean cobalt concentrations of anemic and non-anemic women, 1.8 and 1.5µg/g creatinine, respectively (p<0.05). No significant differences between these two groups were found during the first trimester. These results were used to construct generalized additive models both in normal and anemic women. The strong association between the changes of both iron status and cobalt urine levels found in pregnant women may be related to higher intestinal absorption of cobalt at iron depletion such as in the last pregnancy period when iron body demands are high. Possible toxicity effects of these cobalt increases along pregnancy should be considered in cases of populations occupationally or environmentally exposed to this metal.

Quantifying cobalt in doping control urine samples--a pilot study.

Since first reports on the impact of metals such as manganese and cobalt on erythropoiesis were published in the late 1920s, cobaltous chloride became a viable though not widespread means for the treatment of anaemic conditions. Today, its use is de facto eliminated from clinical practice; however, its (mis)use in human as well as animal sport as an erythropoiesis-stimulating agent has been discussed frequently. In order to assess possible analytical options and to provide relevant information on the prevalence of cobalt use/misuse among athletes, urinary cobalt concentrations were determined by inductively coupled plasma-mass spectrometry (ICP-MS) from four groups of subjects. The cohorts consisted of (1) a reference population with specimens of 100 non-elite athletes (not being part of the doping control system), (2) a total of 96 doping control samples from endurance sport athletes, (3) elimination study urine samples collected from six individuals having ingested cobaltous chloride (500 µg/day) through dietary supplements, and (4) samples from people supplementing vitamin B12 (cobalamin) at 500 µg/day, accounting for approximately 22 µg of cobalt. The obtained results demonstrated that urinary cobalt concentrations of the reference population as well as the group of elite athletes were within normal ranges (0.1-2.2 ng/mL). A modest but significant difference between these two groups was observed (Wilcoxon rank sum test, p < 0.01) with the athletes' samples presenting slightly higher urinary cobalt levels. The elimination study urine specimens yielded cobalt concentrations between 40 and 318 ng/mL during the first 6 h post-administration, and levels remained elevated (>22 ng/mL) up to 33 h. Oral supplementation of 500 µg of cobalamin did not result in urinary cobalt concentrations > 2 ng/mL. Based on these pilot study data it is concluded that measuring the urinary concentration of cobalt can provide information indicating the use of cobaltous chloride by athletes. Additional studies are however required to elucidate further factors potentially influencing urinary cobalt levels.

Occupational Exposure to Cobalt: A Population Toxicokinetic Modeling Approach Validated by Field Results Challenges the Biological Exposure Index for Urinary Cobalt

This study modeled the urinary toxicokinetics of cobalt exposure based on 507 urine samples from 16 workers, followed up for 1 week, and 108 related atmospheric cobalt measurements to determine an optimal urinary cobalt sampling strategy at work and a corresponding urinary exposure threshold (UET). These data have been used to calibrate a population toxicokinetic model, taking into account both the measurement uncertainty and intra- and interindividual variability. Using the calibrated model, urinary sampling sensitivity and specificity performance in detecting exposure above the 20 μg/m3 threshold limit value – time-weighted average (TLV-TWA) has been applied to identify an optimal urine sampling time. The UET value is obtained by minimizing misclassification rates in workplace exposures below or above the TLV. Total atmospheric cobalt concentrations are in the 5–144 μg/m3 range, and total urinary cobalt concentrations are 0.5–88 μg/g creatinine. A two-compartment toxicokinetic model best described urinary elimination. Terminal elimination half-time from the central compartment is 10.0 hr (95% confidence interval [8.3–12.3]). The optimal urinary sampling time has been identified as 3 hr before the end of shift at the end of workweek. If we assume that misclassification errors are of equal cost, the UET associated with the TLV of 20 μg/m3 is 5 μg/L, which is lower than the ACGIH-recommended biological exposure index of 15 μg/L. [Supplemental materials are available for this article. Go to the publisher's online edition of the Journal of Occupational and Environmental Hygiene for the following free supplemental resource: an appendix with discussion of the toxicokinetic model, priors, model checking, cross validation, and comparison of ROC curves for various urinary sampling strategy.]

Exposure assessment in the hard metal manufacturing industry with special regard to tungsten and its compounds

OBJECTIVESTo assess the exposure to tungsten, cobalt, and nickel in a plant producing hard metals. The main components of hard metals are tungsten carbide and cobalt metal. According to recent...

Urinary cobalt as a measure of exposure in the wet sharpening of hard metal and stellite blades.

The measurement of urinary cobalt as an estimator of exposure to airborne cobalt was evaluated during the wet sharpening of hard metal and stellite blades. The following possible confounding factors were also studied: smoking habits, personal hygiene, cobalt absorption through the skin, beer drinking, and vitamin B12 consumption. The study was conducted in 16 different workplaces manufacturing or maintaining blades and in laboratory experiments. Cobalt contamination and its removal from workers' hands were studied with different hand-washing methods, and cobalt from used gloves was also analyzed. The Finnish biomonitoring action level of 600 nmol/l (35.4 micrograms/l) was exceeded in 4 of the 16 workplaces, and the mean concentration of urinary cobalt was 241 (8-2705) nmol/l [14.2 (0.5-160) micrograms/l]. The coefficient of correlation between the cobalt concentrations in the air and in the workers' urine was 0.753. The urinary cobalt concentration corresponding to the Finnish occupational exposure limit for airborne cobalt (0.05 mg/m3) was 686 nmol/l (40.5 micrograms/l). The level of personal hygiene affected the urinary cobalt concentrations, and cobalt was absorbed through the skin. Beer and vitamin B12 consumption did not have any effect on the urinary levels of cobalt. The workers who smoked had higher urinary concentrations of cobalt than the nonsmoking workers. High concentrations of cobalt in coolants contaminated the workers' skin, and hand-washing did not remove cobalt very effectively. The results indicate that urinary cobalt can be used reliably to assess workers' exposure to airborne cobalt when wet-tip grinding processes are used. The results also show that workers' exposure to cobalt can be reduced by improving skin protection and personal hygiene in workplaces.

Exposure to cobalt in the welding process with satellite

In some small factories producing moulds for ceramic tiles using a cobalt alloy (stellite), environmental and biological (CoU) monitoring was conducted for eight workers employed in gas-shielded arc (MAG) and oxy-acetylene welding processes. During oxy-acetylene braze-welding, the exposure to cobalt is very low as are urinary cobalt concentrations. On the other hand, during the MAG welding process, the exposure levels can be excedd the TLV-TWA levels and correlated well with CoU at the end of a working shift. Two MAG welders followed for two consecutive wees, showed different patterns of urinary cobalt excretion: under the same environmental conditions, the higher CoU was found in the worker with greater past exposure. This aspect needs further evaluation before adopting CoU as a current indicator of occupational exposure to the metal.

Cobalt excretion in urine: results of a study on workers producing diamond grinding tools and on a control group

A study was carried out on cobalt (Co) excretion in the urine of 12 workers exposed to known cobalt concentrations in the stone cutting diamond wheel production and in six volunteers: four of these were exposed in the same work environment for a whole workshift and the other two were exposed to cobalt in a cabin under experimental conditions. The kinetics of the urinary excretion was multiphase: (i) a first stage of rapid elimination ( T 1 2 = 43.9 h. ); (ii) a second phase of slower elimination ( T 1 2 ″ = 10 days ); (iii) a longer period of retention, of the order of years, in subjects with higher exposure. In the control group (4 subjects), the excretion proved to be much faster in the first stage ( T 1 2 ′ = 20 h). The different behaviour of the two groups could be related to the different body burden, of cobalt and/or to the possibility of different kinetics induced by continuous exposure to the metal. Moreover, 3 weeks after the removal of the workers from exposure the urinary cobalt concentrations were not within the normal limits of CoU for the general population, (even for workers exposed to cobalt levels of the same order as the TLV). The increase of CoU concentrations in the first 3 h after the end of exposure, stresses the problem of when urine samples for biological monitoring of the workers should be collected. The present study confirms the utility of CoU in discriminating between exposed and non-exposed subjects as well as in assessing high and low level exposure.