BfR | Annual Report 2013
78
Toxicological
in-vitro
test methods for
nanomaterials
Nanotechnology is considered worldwide to be a tech-
nology with huge potential. However, the safety of engi-
neered nanomaterials has not been sufficiently proven for
many applications. This new technology can only be suc-
cessful in the long term if nanomaterials do not pose a
risk both to human health and the environment. This also
involves the detection of genotoxic or mutagenic effects.
To identify such risks, screenings are first of all carried
out on bacteria and cell cultures in addition to tests on
mice and rats. The initial findings of these so called geno-
toxicity-test-batteries require verification using more de-
veloped and more complex model organisms, since cell
systems sometimes produce irrelevant results for mam-
malian organisms (“false-positives”). As a consequence,
many research projects focus on improving, optimising
and developing novel
in vitro
tests in order to identify
(geno-)toxic effects. The BfR has gained a longstand-
ing expertise in the field of alternatives to animal testing.
This know-how was applied to establish “animal-free” test
systems for nanomaterials, as in the EU-funded Nano
genotox project.
At the BfR, the department Experimental Toxicology and ZEBET develops and evaluates various alternatives
and complementary methods to animal experiments that are based on the 3R concept. It draws up new toxi-
cological assessment strategies and looks into innovative online-based technologies with the aim of identifying
and assessing internationally developed alternatives and complementary methods to animal experiments. The
department also develops new concepts to reduce the overall number of animals used in experiments. The new
German Animal Welfare Act places the BfR under obligation to address the goal of reducing the pain and suffer-
ing of laboratory animals. The department therefore also houses the experimental animal management section,
which can draw on high-level expertise in the field of laboratory animal science.
Alternatives to Animal Experiments
From April 2010 to March 2013, 16 laboratories and in-
stitutions from eleven European countries took part in a
wide-ranging European joint action coordinated by French
food authority ANSES. The objective of the Nanogenotox
project was to develop operating procedures to assess
the genotoxic and mutagenic potential of manufactured
nanomaterials which are relevant to the current market.
After the suitability of the methods was confirmed, they
were applied to a selected subset of nanomaterials. The
extensive project plan consisted of two phases: phase
one encompassed the physiochemical characterisation
of the material followed by the determination of the geno-
toxic potential employing a variety of cell-based assays.
Due to their sensitivity in detecting genotoxic properties
of nanomaterials
in vitro
systems mimicking the intestine
and the lung were used in inter-laboratory studies which
formed phase two of the project.
The BfR contributed to the Nanogenotox work packag-
es on two levels. First, the BfR led the “evaluation” work
package, assessing all of the consortium's work and re-
sults. In support of this the BfR organised an international
meeting of evaluators to establish the relevance of the
findings for regulatory acceptance. The BfR also devel-
oped
in vitro
methods for testing the genotoxicity of nano-
materials using human lung cells and three-dimensionally
reconstructed human skin models. In both test systems,
