BfR
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Annual Report 2014
56
Omics methods in regulatory toxicology
In the life sciences, the term omics refers to a range of
bioanalytical methods which can be used to examine
complex molecular changes in biological samples. With
such methods, changes of biomolecules in celluar sys-
tems can be recorded as a whole. Genomics, for exam-
ple, are methods which simultaneously analyse genes of
a cell or tissue in a single experiment.
As foreign substances such as chemicals can already
have an effect on a molecular level, the application of
omics methods of toxicology creates new possibilities.
Such methods can therefore help to explain mechanisms
which have an underlying toxic effect, such as liver dam-
age caused by a particular substance. However, their
use for regulatory purposes, such as the authorisation
procedures for pesticides, is still in its early stages and is
currently subject to considerable uncertainty with regard
to reliability and the interpretation of the data.
To achieve progress in this area, the BfR conducts its
own research. For example, the Institute investigated
the combination effects and toxicity mechanisms of fun-
gicides in animal studies and cell culture experiments
using omics methods. The aim was to find out whether
changes in the cell culture observed with omics methods
were similar to those in animal studies and whether cell
culture experiments could replace animal testing in regu-
latory procedures in the medium term. In the BfR study,
rats received various test substances over 28 days, both
separately and in combination, as did the cell cultures.
Using a particular omics method (transcriptomics), the
institute then analysed how the individual substances
and their combinations influence the expression of cer-
tain genes. The focus of BfR´s investigation was one
main target organ of the substances: the liver and cor-
responding liver cell lines.
A result is shown schematically in the diagram on
page 57. The animal experiment showed that fungicide
mixtures influence more genes in total than the individual
substances. In mixture 1 there were 105 modified genes
compared to the 69 and 64 genes that were altered by
separate application of epoxiconazole and cyprocona-
zole. In addition, several genes were found that were
modified by all substances and combinations (30 in the
animal experiment, two in the cell culture experiment)
and could serve as markers for the toxicity of mixtures.
The gene expression patterns also allow the detection of
similarities and differences in the toxicity mechanism of
the various tested substances.
The working area of chemicals and pesticide safety affects many areas of consumer and user health
protection. The BfR is one of the central institutes for health-related substance assessments in Germany.
Multiple departments of the Institute, such as the Departments for Exposure, for Chemicals and Product
Safety and for Pesticide Safety, are concerned with this issue.
Chemicals Safety
>>
Omics methods analyse all
changes of biomolecules
in cellular systems at the
same time in a single
experiment.
