Toxicology testing of nanomaterials, particles and fibers

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.

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.

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.