Cobalt and its compounds: update on genotoxic and carcinogenic activities

Abstract

This article summarizes recent experimental and epidemiological data on the genotoxic and carcinogenic activities of cobalt compounds. Emphasis is on the respiratory system, but endogenous exposure from Co-containing alloys used in endoprostheses, and limited data on nanomaterials and oral exposures are also considered. Two groups of cobalt compounds are differentiated on the basis of their mechanisms of toxicity: (1) those essentially involving the solubilization of Co(II) ions, and (2) metallic materials for which both surface corrosion and release of Co(II) ions act in concert. For both groups, identified genotoxic and carcinogenic mechanisms are non-stochastic and thus expected to exhibit a threshold. Cobalt compounds should, therefore, be considered as genotoxic carcinogens with a practical threshold. Accumulating evidence indicates that chronic inhalation of cobalt compounds can induce respiratory tumors locally. No evidence of systemic carcinogenicity upon inhalation, oral or endogenous exposure is available. The scarce data available for Co-based nanosized materials does not allow deriving a specific mode of action or assessment for these species.

Keywords:

• Bioaccessibility
• tumors
• nanoparticles
• classification
• labeling
• DNA damage
• DNA repair
• topoisomerase
• humans
• occupational exposure
• implants
• hip prosthesis
• free radicals
• solubilization

Acknowledgements

The authors thank the reviewers for their thoughtful comments which contributed to improve the quality of the review.

Declaration of interest

In accordance with Taylor & Francis policy and his ethical obligation as a researcher, DL is reporting that he received funding from the Cobalt Development Institute (CDI, Guilford, UK) to conduct this review under the grant “CDI Study 80.” The CDI, now known as Cobalt Institute (CI) [cobaltinstitute.org], is a nonprofit trade association composed of producers, users, recyclers, and traders of cobalt. The present review paper is the exclusive professional work product of the authors and does not necessarily reflect the views of the financial sponsor. The CDI was not involved in determining the content of the review or in the writing of the manuscript. The CDI did not see the manuscript before the present submission. D. Lison, S. van den Brule, and G. Van Maele-Fabry did not appear in any regulatory or legal proceeding that used the contents of this manuscript. In the past five years, the authors did not receive other funding from the CDI.