Dose-Response Relationships For Blood Cobalt Concentrations and Health Effects: A Review of the Literature and Application of a Biokinetic Model

Abstract

Cobalt (Co) is an essential component of vitamin B₁₂. As with all metals, at sufficiently high doses, Co may exert detrimental effects on different organ systems, and adverse responses have been observed in animals, patients undergoing Co therapy, and workers exposed to respirable Co particulates. Although blood Co concentrations are postulated to be the most accurate indicator of ongoing Co exposure, little is known regarding the dose-response relationships between blood Co concentrations and adverse health effects in various organ systems. In this analysis, the animal toxicology and epidemiology literature were evaluated to identify blood Co concentrations at which effects have, and have not, been reported. Where necessary, a biokinetic model was used to convert oral doses to blood Co concentrations. Our results indicated that blood Co concentrations of 300 μg/L and less have not been associated with adverse responses of any type in humans. Concentrations of 300 μg/L and higher were associated with certain hematological and reversible endocrine responses, including polycythemia and reduced iodide uptake. Blood Co concentrations of 700–800 μg Co/L and higher may pose a risk of more serious neurological, reproductive, or cardiac effects. These blood concentrations should be useful to clinicians and toxicologists who are attempting to interpret blood Co concentrations in exposed individuals.

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Corrigendum

Acknowledgments

All of the authors are employed by ChemRisk, a consulting firm that provides scientific advice to the government, corporations, law firms, and various scientific/professional organizations. ChemRisk has been engaged by DePuy Orthopaedics, Inc., a manufacturer of prosthetic devices some of which contain cobalt. This article was prepared and written exclusively by the authors without review or comment by employees or counsel for DePuy. It is likely that this work will be relied upon in medical research, nutrition research, and litigation. Some of the authors may be called upon to serve as expert witnesses. Funding for the paper was primarily provided by DePuy.

Notes

*All calculations used to estimate blood Co concentrations are provided in the online supplementary materials.