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

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

Chemico-biological interactions (2014-04-15)
Kenneth M Unice, Brent D Kerger, Dennis J Paustenbach, Brent L Finley, Brooke E Tvermoes
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cobalt, powder, <150 μm, ≥99.9% trace metals basis
Sigma-Aldrich
Cobalt, wire, diam. 1.0 mm, 99.995% trace metals basis
Sigma-Aldrich
Cobalt, powder, 2 μm particle size, 99.8% trace metals basis
Sigma-Aldrich
Cobalt, rod, diam. 5.0 mm, 99.95% trace metals basis
Sigma-Aldrich
Cobalt, foil, thickness 0.1 mm, ≥99.99%
Sigma-Aldrich
Cobalt, foil, thickness 1.0 mm, 99.95% trace metals basis
Sigma-Aldrich
Cobalt, foil, thickness 0.1 mm, 99.95% trace metals basis
Sigma-Aldrich
Cobalt, granular, 99.99% trace metals basis
Sigma-Aldrich
Cobalt, pieces, 99.5% trace metals basis
Sigma-Aldrich
Cobalt, Carbon coated magnetic, nanopowder, <50 nm particle size (TEM), ≥99%
Cobalt, foil, 15mm disks, thickness 0.125mm, as rolled, 99.99+%
Cobalt, foil, not light tested, 50x50mm, thickness 0.02mm, 99.9%
Cobalt, foil, light tested, 50x50mm, thickness 0.05mm, as rolled, 99.9%
Cobalt, foil, not light tested, 100x100mm, thickness 0.007mm, 99.9%
Cobalt, foil, 6mm disks, thickness 0.05mm, as rolled, 99.9%
Cobalt, foil, light tested, 25x25mm, thickness 0.01mm, 99.9%
Cobalt, foil, 8mm disks, thickness 0.125mm, as rolled, 99.99+%
Cobalt, foil, light tested, 25x25mm, thickness 0.05mm, as rolled, 99.9%
Cobalt, foil, not light tested, 25x25mm, thickness 0.01mm, 99.9%
Cobalt, foil, not light tested, 100x100mm, thickness 0.009mm, 99.9%
Cobalt, wire reel, 0.05m, diameter 1.0mm, hard, 99.99+%
Cobalt, foil, light tested, 25x25mm, thickness 0.025mm, 99.9%
Cobalt, foil, not light tested, 25x25mm, thickness 0.0025mm, temporary acrylic support, 99.9%
Cobalt, foil, light tested, 50x50mm, thickness 0.015mm, 99.9%
Cobalt, foil, 8mm disks, thickness 0.25mm, as rolled, 99.9%
Cobalt, foil, 8mm disks, thickness 0.0125mm, 99.9%
Cobalt, foil, not light tested, 100x100mm, thickness 0.02mm, 99.9%
Cobalt, foil, not light tested, 100x100mm, thickness 0.0125mm, 99.9%
Cobalt, wire reel, 0.05m, diameter 2.0mm, hard, 99.99+%
Cobalt, foil, not light tested, 25x25mm, thickness 0.002mm, temporary acrylic support, 99.9%