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defined and published in the form of a
position paper (Van der Burg et al., 2011).
The work in WP1 started with the
establishment and selection of in silico
pre-screening methods to categorise
chemicals, using (quantitative) structureactivity
relationships (Q)SARs. This will be
done for major classes of toxicity prioritised
in REACH (carcinogenesis, mutagenesis
and reproductive (CMR) toxicity and
persistent, (very) bioaccumulative toxic
(PBT/vPvB) compounds). With this we
prioritise further in silico/in vitro toxicity
testing. As a starting point, we are using
a unique database which comprises
abbreviated predictions from more than 70
(Q)SAR models on endpoints for physicochemical
properties, fate, eco-toxicity,
absorption, metabolism and toxicity. A
methodology that alerts for potential
reproductive toxicity will be developed
and integrated all into one module, a
fast and efficient toxicity screening tool
will be generated based on available in
silico techniques, mostly QSARs that can
identify toxicological profiles that will drive
the risk assessment of the chemical, e.g.,
mutagenic, genotoxic carcinogenic, or
endocrine-active properties.
WP2 focussed on expansion of two different
databases, which contain information
relevant to reproductive toxicity; RepDose
(repeated dose) and FeDTex (fertility and
developmental toxicity). First reproductive
toxicity studies were identified from peerreviewed
publications, as well as other
databases provided by other partners.
Available studies on reproductive toxicity
were selected for data entry. In particular,
the amount of chemicals in FeDTex will
be more than doubled in the course of
ChemScreen, mounting up to over 300. A
significant overlap with RepDose is created
to allow comparison of in vivo data with
the same chemical and evaluate possible
predictivity of repeated dose toxicity for
reproductive toxicity.
WP2 scientists started a unique
collaboration with WP3 and the NCCT on
the identification of critical endpoints of
reproductive toxicity using combined, in
depth analysis of databases present at
three different locations (i.e., Fraunhofer
Institute, RIVM and NCCT). These results
will become available in the next period,
and will be extended to ecotoxicological
endpoints using the EDUKON database
present at the University of Konstanz (see
WP5).
The aim of WP3 is the design of a
‘minimal essential’ reproductive toxicity
screen, consisting of a number of in
vitro assays that are representative of
those parameters in reproductive toxicity
that are crucial for reproductive hazard
assessment. A literature survey of past
experience will result in a prioritised list
of parameters that need to be addressed
in hazard assessment. This part of the
work is ongoing. Meanwhile, progress
was obtained with the optimisation and
amendment to higher-throughput of two
tests that are very likely to be included
in the final battery, namely a genomicsbased
improved embryonic stem cell test,
and steroidogenesis assays. In addition,
zebrafish early life stage tests and oocyte
maturation/fertilisation tests are being
66 PROGRESS REPORTS FROM EU-FUNDED PROJECTS
Progress Report 2011 & AXLR8-2 Workshop Report