A tiered approach to investigate the inhalation toxicity of cobalt substances. Tier 1: Bioaccessibility testing

Regul Toxicol Pharmacol. 2022 Mar:129:105124. doi: 10.1016/j.yrtph.2022.105124. Epub 2022 Jan 29.

Abstract

Bioelution tests measure in vitro the release of metal ion in surrogate physiological conditions (termed "bioaccessibility") and estimate the potential bioavailability relative to that of a known reference metal substance. Bioaccessibility of cobalt ion from twelve cobalt substances was tested in three artificial lung fluids (interstitial, alveolar and lysosomal) to gather information about the substances' fate and potential bioavailability in the respiratory tract after inhalation. The results can be used as one line of evidence to support grouping and read-across for substances lacking in vivo data, and where in vivo testing is not readily justifiable. Strong differences were observed in the dissolution behaviour of the substances in the different fluids, with the cobalt substances generally being less soluble in neutral pH fluids and more soluble in the acidic pH fluid. The resulting database, presented with its strengths and limitations, was used to support the formulation of an initial grouping of these cobalt substances into three categories.

Keywords: Bioelution; Lung; Metal compounds; Metals; Solubility.

MeSH terms

  • Administration, Inhalation
  • Cobalt / adverse effects*
  • Cobalt / chemistry*
  • Cobalt / pharmacokinetics
  • In Vitro Techniques / methods*
  • Lung / drug effects*
  • Particle Size

Substances

  • Cobalt