Toxicology testing of nanomaterials, particles and fibers

For over 20 years, we have conducted inhalation studies in rodents and thus are experienced also in complex studies. Thanks to our cutting-edge equipment, not only standard fiber and (nano-)particle aerosols can be generated, but also sophisticated exposure atmospheres, such as occupationally relevant bitumen aerosols. We study above all poorly soluble particles in environmentally relevant atmospheres and in occupational exposure scenarios, but also the toxicokinetics of retained particles in the lung and the mechanisms of toxic effects. Over the past years, the focus of interest in toxicology has expanded and is no longer on fine particulate matter only, but because of their wide range of applications now also includes engineered nanoparticles (< 0.1 µm). This is why cross-departmental pilot projects have been initiated at the institute, aimed at establishing robust, validated screening assays that allow the toxic potential of this type of particles to be evaluated. Substance categories currently under investigation are carbon nanotubes (CNT) and graphenes.

Nano-expertise for ongoing research projects

Research on particles and fibers has a long tradition at Fraunhofer ITEM. For the past ten years, this has also included nanomaterials, which have meanwhile become a focus of our research.

This trend was encouraged, among others, by the large number of new nanoscale substances that require toxicological safety testing, before they can get marketing approval. In addition to the multiplicity of metals, metal oxides, and carbon blacks, new synthetic nanomaterials such as carbon nanotubes and graphenes popped up and got into the focus of research. Fraunhofer ITEM scientists have been enrolled in various national and European research projects exemplarily addressing the combined use of in-vitro (screening) and in-vivo tests (physiological validation). The investigation pattern used includes gene expression analyses to look for early responses indicating a potential link to inflammatory, proliferative, genotoxic, or carcinogenic outcomes.

Among these projects are:

  • CarboTox
  • CaNTser
  • InhalT90
  • PLATOX
  • ICONS
© Fraunhofer ITEM

Assessment of nanomaterials requires their comprehensive characterization

Before experimental work can start, nanoparticle samples require comprehensive physicochemical characterization including the specific surface, zeta potential (indicating the surface charge of particles), endotoxin status as well as agglomeration and sedimentation behavior in liquid and air. In addition, chemical surface modifications with functional groups serving technical purposes play a pivotal role when it comes to characterizing the toxic potential.

© Fraunhofer ITEM

Saving time and resources through the combined use of in-vitro and in-vivo tests

In view of the plethora of new nanomaterials the competent authorities realized early the need for new well-accepted in-vitro assay packages. The focus was on high-throughput screening tools (cytotoxicity and genotoxicity) followed by very limited in-vivo testing to ensure validity of the in-vitro data. This method allows the time-consuming and highly expensive full testing to be restricted to identified top representatives of a category or group of similar substances.

Harmonization of testing criteria

The main objective of organizations such as OECD, ECHA and EPA has been to harmonize the initial characterization requirements for nanomaterials and to specify criteria how to narrow down the huge number of nanomaterials before entering into experimental testing. This process within the regulatory bodies is going on and, tendentiously, an expansion of existing testing guidelines is preferred to the adoption of separate pure “nano” guidelines.  The additional parameters recommended for nanomaterials address mainly their dissolution behavior and systemic translocation potential to remote locations after deposition in the target organ.

Overview of our services

  • Nose-only and whole-body exposure of rodents
  • Toxicokinetics of inhaled particles
  • Deposition and retention
  • Particle clearance by using radiolabeled tracers
  • Biopersistence of fibers
  • Bioavailability of metals from solid material particles
  • Inflammatory reactions in the lung
  • Enzymes and cytokines in bronchoalveolar lavage fluid
  • Oxidative damage parameters
  • Investigation of cell proliferation in the lung
  • Histopathology