Critical evaluation of a previous animal feeding study with SAS

Subject of investigation

Statement from a Dutch study of 2014: At that time, a scientific team under the leadership of the University of Wageningen claimed that two synthetic amorphous silicas investigated in animal trials are damaging to health.

Core statement

The publication of the Dutch scientists has serious methodological shortcomings. Their conclusions about health hazards from synthetic amorphous silica are questionable, to say the least.

The substance

Two commercially available synthetic amorphous silicas were investigated, one from Wacker Chemie and the other from Evonik.

Results in detail:

  • In 2014 the findings of a study were published, in which rats were administered feed partly loaded with a high dose of synthetic amorphous silica for up to 84 days. The result was claimed that both of the investigated substances increase the risk of liver fibrosis and alter parts of the small intestinal mucosa; in addition, the synthetic amorphous silica administered was said to accumulate in milk and kidneys.
  • The 2017 publication identifies a number of methodological shortcomings in the 2014 paper and, by statistical analysis of the results, comes to entirely different conclusions. The authors therefore recommend that the tissue samples of the original trials be reevaluated by an expert pathologist or an independent pathology workgroup, using a reliable definition for liver fibrosis. They also recommend that the results be reanalyzed using an appropriate statistical method.
  • Specifically, the authors of the new study point to the following faults:
    • The definition of the size of nanoparticles used in the 2014 paper differs from that of the ISO Technical Committee 229: Nanotechnologies, with no explanation for the deviation.
    • The spectra of the substances investigated differ significantly from those recorded by the producers for quality assurance purposes several years earlier. This, and an abnormally high carbon content for both substances, indicates either incorrect measurement by the Dutch team or a change in the synthetic amorphous silicas during storage or handling.
    • Current OECD guidelines for animal testing of this kind prescribe a certain period for oral ingestion and a defined number of test animals and groups. The Dutch team did not observe either requirement: The number of test animals, for example, was significantly lower. The 2014 paper did not offer any explanation for this.
    • The above-mentioned OECD guidelines also prescribe the maximum daily dose to be administered to the test animals. For one of the two synthetic amorphous silicas investigated, however, the researchers chose a daily dose that was higher by a factor of 2.5.
    • Various schemata exist for classifying the severity of a liver fibrosis. The Dutch team did not, however, disclose the definition of the schema it used, which makes it difficult to categorize the results.
    • Several inconsistencies exist in the analysis of published liver-tissue samples, so that neither an inflammation nor some other change in liver tissue can be proven with certainty on the basis of the published data for the present samples. The photos published of the tissue samples of the intestinal mucosa suggest that the choice of section plane itself leads to artefacts and so to false results. The Dutch team gave no details on the preparation of the tissue samples.
    • The information on accumulation of synthetic amorphous silica in milk and kidney is difficult to assess on the basis of the published data, due mainly to the absence of various control measurements and analyses.
    • The 2014 publication does not indicate the degree of experience of the pathologists who examined the tissue samples. Such samples can be reliably assessed only by qualified experts.
    • The authors of the 2017 paper have attempted statistical analysis of the published Dutch data. They did not succeed in verifying the results of the original publication. Either the data are faulty, or they have been wrongly reproduced in the publication. Moreover, the statistical approach selected is wrong in this particular case because the Dutch scientists consider all the tissue samples as being independent, even when they come from the same animal.

Type of study

Detailed analysis and reassessment of the 2014 publication of Van der Zande et al.

About the authors

At the time of publication, two of the authors (Peter Morfeld, Nils Krueger) were employees of Evonik and two (Axel Bosch, Mario Heinemann) of Wacker Chemie. At the time of publication of the study Klaus Weber was toxicologic pathologist and managing director of AnaPath GmbH, a Swiss company specializing in histopathological laboratory services.

Original publications


Nils Krueger et al., EC Pharmacology and Toxicology 3.2 (2017), 49-61;

Publication criticized:

Meike van der Zande et al., Particle and Fibre Toxicology 11 (2014), 8;