31-Day Study of Cobalt(II) Chloride Ingestion in Humans: Pharmacokinetics and Clinical Effects

Abstract

The United Kingdom Expert Group on Vitamins and Minerals concluded that ingesting cobalt (Co)-containing supplements up to 1400 μg Co/d is unlikely to produce adverse health effects. However, the associated blood Co concentrations and safety of Co-containing dietary supplements have not been fully characterized. Thus, blood Co kinetics and a toxicological assessment of hematological and biochemical parameters were evaluated following Co dietary supplementation in 5 male and 5 female volunteers who ingested approximately 1000 μg Co/d (10-19 μg Co/kg-d) as cobalt(II) chloride for a period of 31 d. Supplement intake was not associated with significant overt adverse events, alterations in clinical chemistries including blood counts and indicators of thyroid, cardiac, liver, or kidney functions, or metal sensitization. A non-clinically significant (<5%) increase in hemoglobin, hematocrit, and red blood cell (RBC) counts were observed in males but not females 1 wk after dose termination. Mean Co concentrations in whole blood/serum after 31 d of dosing were approximately two-fold higher in females (33/53 μg/L) than in males (16/21 μg/L). In general, steady-state concentrations of Co were achieved in whole blood and/or red blood cells (RBC) within 14–24 d. Temporal patterns of whole blood and serum Co concentrations indicated metal sequestration in RBC accompanied by slower whole blood clearance compared to serum. Data also indicated that peak whole blood Co concentrations up to 91.4 μg/L were not associated with clinically significant changes in clinical chemistries. In addition, Co blood concentrations and systemic uptake via ingestion were generally higher in females.

Acknowledgments

The authors thank Chris Ronk, Meghan Glynn, and Paul Scott for their assistance with the statistical analysis of the data.

All of the authors are employed or contracted by Cardno ChemRisk, a consulting firm providing scientific advice to the government, corporations, law firms, and various scientific/professional organizations. Cardno ChemRisk has been engaged by DePuy Orthopedics, 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. One of the authors (DP) has served as an expert witness for DePuy. Funding for the paper was provided by DePuy.