31-DAY STUDY OF COBALT(II) CHLORIDE INGESTION IN HUMANS: PHARMACOKINETICS AND CLINICAL EFFECTS

The United Kingdom Expert Group on Vitamins and Minerals concluded that ingesting cobalt (Co)-containing supplements up to 1400 g 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 g Co/d (10-19 g 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 g/L) than in males (16/21 g/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 g/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.