A review of the health hazards posed by cobalt

Abstract

Cobalt (Co) is an essential element with ubiquitous dietary exposure and possible incremental exposure due to dietary supplements, occupation and medical devices. Adverse health effects, such as cardiomyopathy and vision or hearing impairment, were reported at peak blood Co concentrations typically over 700 µg/L (8-40 weeks), while reversible hypothyroidism and polycythemia were reported in humans at ~300 µg/L and higher (≥2 weeks). Lung cancer risks associated with certain inhalation exposures have not been observed following Co ingestion and Co alloy implants. The mode of action for systemic toxicity relates directly to free Co(II) ion interactions with various receptors, ion channels and biomolecules resulting in generally reversible effects. Certain dose-response anomalies for Co toxicity likely relate to rare disease states known to reduce systemic Co(II)-ion binding to blood proteins. Based on the available information, most people with clearly elevated serum Co, like supplement users and hip implant patients, have >90% of Co as albumin-bound, with considerable excess binding capacity to sequester Co(II) ions. This paper reviews the scientific literature regarding the chemistry, pharmacokinetics and systemic toxicology of Co, and the likely role of free Co(II) ions to explain dose-response relationships. Based on currently available data, it might be useful to monitor implant patients for signs of hypothyroidism and polycythemia starting at blood or serum Co concentrations above 100 µg/L. This concentration is derived by applying an uncertainty factor of 3 to the 300 µg/L point of departure and this should adequately account for the fact that persons in the various studies were exposed for less than one year. A higher uncertainty factor could be warranted but Co has a relatively fast elimination, and many of the populations studied were of children and those with kidney problems. Closer follow-up of patients who also exhibit chronic disease states leading to clinically important hypoalbuminemia and/or severe ischemia modified albumin (IMA) elevations should be considered.

Evidence against implant-derived cobalt toxicity: Case report and retrospective study of serum cobalt concentrations in an orthopedic implant population

“…The majority of the affected subjects also had elevated hemoglobin, hematocrit, and ERY counts which were interpreted as a result of Costimulated erythropoiesis. Increased erythropoiesis is a well-known effect of Co exposure [11,22]. Stimulation of erythropoiesis by administration of Co salts has been reported as a successful treatment for anemia [23].…”

Regulatory risk assessments

“…The data set employed by Kroes et al 47 claimed to contain 730 'carcinogens', as noted above, was not included in the publication and seems to have been 'lost'. A presumably similar data set from an earlier publication (Cheeseman et al 55 ) is available however and contains 706 substances (709 claimed, 706 listed).…”

“…Although not explicitly stated in ICH M7 (but mentioned in the prior EMA 48 and FDA 49 guidance documents), the derivation of the default TTC relies on the methodology of Kroes et al 47 In note 5 of ICH M7, monofunctional alkyl chlorides are discussed as follows with reference to a publication by Brigo Not mentioned is the fact that Brigo and Müller employed methodology significantly different to that of Kroes et al 51 in that:…”

“…Model-free linear extrapolation of TD 50 values at a cancer risk level of 1 in 10 6 was applied by Cheeseman et al 51 and Kroes et al 47 to all compounds in the data set irrespective of their genotoxicity status. This approach is inappropriate for non-genotoxic carcinogens, for which the normal regulatory approach is to assume a threshold exists.…”

Review Article: Flow battery systems with solid electroactive materials

“…First, the environmental impacts of Co needs to be addressed. 260 Although the recycling of Co from a flow cell system should be easier than static laminated Li-ion batteries, the toxicity of Co means that recovery and recycling is important. Second, the cost of Co is relatively high because of its relatively low earth abundance; and high energy inputs are needed during processing and manufacturing LCO, further demonstrating the need for implementation of effective material recycling.…”