Critical Choices in Predicting Stone Wool Biodurability: Lysosomal Fluid Compositions and Binder Effects

Chem Res Toxicol. 2021 Mar 15;34(3):780-792. doi: 10.1021/acs.chemrestox.0c00401. Epub 2021 Jan 19.

Abstract

The hazard potential, including carcinogenicity, of inhaled man-made vitreous fibers (MMVFs) is correlated with their biodurability in the lung, as prerequisite for biopersistence. Abiotic dissolution testing serves to predict biodurability. We re-analyzed the International Agency for Research on Cancer Monograph on MMVFs and found that the correlation between in vivo biopersistence and abiotic dissolution presented therein confounded different simulant fluids and further confounded evaluation of leaching vs structural elements. These are critical choices for abiotic dissolution testing, as are binder removal and the rate of the flow that removes ions during testing. Therefore, we experimentally demonstrated how fluid composition and binder affect abiotic dissolution of a representative stone wool MMVF. We compared six simulant fluids (all pH 4.5, reflecting the environment of alveolar macrophage lysosomes) that differed in organic acids, which have a critical role in their ability to modulate the formation of Si-rich gels on the fiber surfaces. Removing the binder accelerates the average dissolution rate by +104% (max. + 273%) across the fluids by suppression of gel formation. Apart from the high-citrate fluid that predicted a 10-fold faster dissolution than is observed in vivo, none of the five other fluids resulted in dissolution rates above 400 ng/cm2/h, the limit associated with the exoneration from classification for carcinogenicity in the literature. These findings were confirmed with and without binder. For corroboration, five more stone wool MMVFs were assessed with and without binder in one specific fluid. Again, the presence of the binder caused gel formation and reduced dissolution rates. To enhance the reliability and robustness of abiotic predictions of biodurability, we recommend replacing the critically influential citric acid in pH 4.5 fluids with other organic acids. Also, future studies should consider structural transformations of the fibers, including changes in fiber length, fiber composition, and reprecipitation of gel layers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Fluids / chemistry
  • Body Fluids / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Lysosomes / chemistry
  • Lysosomes / metabolism
  • Macrophages, Alveolar / chemistry
  • Macrophages, Alveolar / metabolism*
  • Mineral Fibers / analysis*

Substances

  • Mineral Fibers