Review article summarizing and critically evaluating results from numerous toxicological studies on nanomaterials

Subject of investigation

The significance of toxicology studies of artificially produced nanoparticles

Core statement

A large majority of nanotoxicological studies does not, methodologically speaking, meet the high qualitative requirements placed on toxicological studies.

The substance

Industrially produced nanomaterials have low diameters and large surface-to-volume ratios. In principle, therefore, they could act differently in organisms or the environment than larger particles of the same chemical composition.

Results in detail

• Up to the year 2000, only a few hundred toxicological studies had appeared on the impacts of nanomaterials on health or the environment. Since 2001 the number of such studies has increased explosively, rising to more than 10,000 in just 15 years. But quality does not always go hand in hand with quantity here. Many of the studies do not provide any clear information on the safety of nanomaterials. Many are even self-contradictory or arrive at totally false conclusions. This is often because the properties of the nanomaterials investigated in the studies have not been sufficiently well characterized.
• 1000 studies have now been more accurately analyzed; these look at the three exposure routes of lungs, gastrointestinal tract, and skin, and at the importance of instillation versus inhalation for investigation of lung exposure. The results are as follows:
  1) There is no doubt that nanoparticles can find their way into the lungs and gastrointestinal tract. However, only a very small proportion of the dose administered reaches as far as the bloodstream, which could distribute the nanoparticles to additional organs. In fact, the large majority of the nanoparticles administered are removed by the immune defense cells or excreted in feces. In the few studies citing systemic [RB2] [DC3] effects, there was no link with the nano properties of the particles—either because the studies had shortcomings or because the conclusions were uncertain.
  2) In studies where the nanoparticles were administered by instillation or inhalation, temporary inflammation was observed, regardless of the chemical composition of the nanoparticles. This indicates that the results of ingesting the particles are non-specific. All in all, the studies give no indication of “nanospecific” effects in the lungs.
  3) The studies repeatedly ignored the fact that nanoparticles can dissolve in body fluids. So the issue here is not the toxicology of nanoparticles but rather the toxicology of chemical elements or compounds, which has been investigated over a very long period.
  4) Due to the large number of different methods used in the nanotoxicological studies, the findings cannot be compared with one another. This is undoubtedly one explanation for the conflicting results.
  5) In the majority of studies, the properties of the nanoparticles were not characterized. This considerably undermines the significance of the findings, and some of the studies are therefore entirely meaningless. Internationally uniform standards are urgently needed for the methods applied in toxicological studies on nanoparticles.

Type of study

A systematic overview of the methodology and results published in nanotoxicological studies over 15 years.

About the author

Harald F. Krug, former professor at the University of Bern, headed international research collaboration at Empa, Switzerland, at the time the study was published. He was also a member of the steering committee of the DECHEMA workgroup for responsible handling and production of nanomaterials.

Original publication:

Harald F. Krug, Angew. Chem. Int. Ed. (2014), DOI 10.1002/anie.20140