Refined biokinetic model for humans exposed to cobalt dietary supplements and other sources of systemic cobalt exposure

Chem Biol Interact. 2014 Jun 5;216:53-74. doi: 10.1016/j.cbi.2014.04.001. Epub 2014 Apr 13.

Abstract

An updated biokinetic model for human exposures to cobalt (Co) was developed based on a comprehensive set of human pharmacokinetics data collected from five male and five female volunteers who ingested ∼1 mg Co/day of a Co supplement for 3 months. Three key experimental observations from the human dosing studies were incorporated into the model: (1) an increase in the measured fraction of large molecular serum protein bound Co from 95% during dosing to 99% after dosing; (2) a linear decrease in Co red blood cell concentration after dosing; and (3) Co renal clearance consistent with estimated glomerular filtration rates and free Co²⁺ concentration. The model was refined by adding compartments accounting for (1) albumin bound Co in intravascular fluid (serum); (2) albumin bound Co in extravascular fluid with physiologic exchange rates of albumin bound Co between extravascular and intravascular fluid; and (3) a novel sequential cascade of compartments representing red blood cell ages between 1 and 120 days. Reasonable agreement between the modeled and measured urine, serum, and whole blood concentrations were observed (r>0.84, slope=0.79-1.0) with gastrointestinal absorption rates between 9% and 66%. In addition, model predictions agreed well with data from several external studies representing healthy human volunteers, dialysis patients, anephric patients, a Co-poisoning incident and whole body retention studies. Our revised model considerably improves the state of knowledge on human Co kinetics, and should be helpful for evaluating elevated blood Co concentrations in currently exposed populations, such as metal-on-metal (MoM) hip implant patients.

Keywords: Albumin binding; Cobalt; Red blood cell kinetics; Renal excretion; Renal reabsorption; Toxicokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albumins
  • Cobalt / blood
  • Cobalt / pharmacokinetics*
  • Cobalt / urine
  • Computer Simulation*
  • Dietary Supplements
  • Female
  • Humans
  • Male
  • Models, Biological*
  • Protein Binding
  • Reproducibility of Results

Substances

  • Albumins
  • Cobalt