Toxicological study on the effect of long term inhalation of Synthetic Amorphous Silica (SAS)

Subject of investigation

Effects of months-long inhalation of synthetic amorphous silica.

Core statement

Aerosols of synthetic amorphous silica do not cause lung fibrosis, a pathological, often fatal, alteration of lung connective tissue.

The substances

The effects of three products based on synthetic amorphous silicon dioxide were studied: pyrogenic silica (AEROSIL® 200), surface-treated pyrogenic silica (AEROSIL® R 974), and wet-chemically produced silica (SIPERNAT® 22 S).

Results in detail

  • In 1991 a study1) was published in which for 13 weeks rats were made to inhale on the one hand synthetic amorphous silica and, on the other, quartz dust. The lung tissue was analyzed immediately after the inhalation phase and several times thereafter, up to 52 weeks after the end of the inhalation period. The result stated at the time was that whereas AEROSIL® R 974 and SIPERNAT® 22 S lead to only isolated and temporary changes in the lung, quartz dust causes long-term change. For AEROSIL® 200 the study concluded that inhalation leads to changes in lung tissue that are only partially reversible. In the study these changes were described as fibrosis. In a fibrosis there is proliferation of fibrous connective tissue in an organ, in this case the lung. This results in chronic inflammation of the tissue, leading in turn to stiffness in the lungs and breathing difficulties. Some of those affected develop lung cancer.
  • Using the tissue samples still available, the new study now answers the explicit question of whether silica triggers fibrosis and whether these pathological changes in the connective tissue of the lung can be fully reversed. To this end the tissue samples were examined directly after the 13-week exposure and the samples after the 13- and 52-week recovery phases.
  • For AEROSIL® 200, AEROSIL® R 974, and SIPERNAT® 22 S, no fibrosis was observed at any of these three points in time. After the 52-week recovery phase all the changes in the lung resulting from inhalation of silica had regressed, even for AEROSIL® 200. The original study of Reuzel et al. must therefore be revised in this particular. The silica concentrations to which the rats were exposed were 1.3 to 31 mg/m³ (AEROSIL® 200), 34.7 mg/m³ (AEROSIL® R 974), and 34.9 mg/m³ (SIPERNAT® 22 S).
  • In contrast, marked lung fibrosis was shown to be present in tissue samples of rats that had inhaled quartz sand, even after the 52-week recovery phase.

1) PG Reuzel et al., Food and Chemical Toxicology (1991), doi.: 10.1016/0278-6915(91)90205-L

Type of study

Histopathological analysis and assessment of tissue samples from the lungs of rats made to inhale synthetic amorphous silica and quartz dust.

About the authors

The authors are representatives of specialty chemicals companies, providers of specialist laboratory services, and the University of Rochester, and performed the assessments independently of one another. At the time of publication of the study, the main author, Klaus Weber, was toxicologic pathologist and managing director of AnaPath GmbH, a Swiss company specializing in histopathological laboratory services. The study was commissioned by Evonik.

Original publication:

Klaus Weber et al., Toxicology Research and Application (2018), DOI: 10.1177/2397847318805273