Here - Stiftung Forschung 3R

Update on EPA’s
ToxCast Programme
Providing High-Throughput Decision Support
Tools for Chemical Risk Management
Robert Kavlock
National Center for Computational Toxicology
Office of Research and Development
US Environmental Protection Agency
Research Triangle Park, NC 27711, USA
kavlock.robert@epa.gov
Website: epa.gov/ncct/toxcast
The US EPA’s ToxCast research programme was launched in 2007 with the goal of
evaluating the use of high-throughput bioassays to detect key biological targets and
pathways that could be potential targets for chemicals and as a consequence of the
interaction cause diseases such as cancer, reproductive toxicity or birth defects (Dix et
al., 2007). As noted by the NRC in its vision for a new paradigm in toxicity testing (NRC,
2007), the traditional approach to toxicology uses expensive and time consuming animalbased
testing approach and is inadequate to cover the large numbers of chemicals in
commerce. In addition, since it does not provide mechanistic information on how the
chemicals exert toxicity, there remain large uncertainties in extrapolating data across
dose, species and life stages. ToxCast addresses many of the issues raised in the NRC
report. It is a multi-year, multi-million dollar effort to comprehensively apply batteries
of in vitro tests against chemicals with known toxicological phenotypes derived from
traditional guideline studies for cancer, reproductive impairment and developmental
disorders (see Martin et al., 2009a,b; Knudsen et al., 2009 for description and analyses
of the traditional legacy databases). With a commitment to transparency and public
release of all data (see epa.gov/actor for access), it is the most strategic and coordinated
public sector effort to transform toxicology. The goal is to acquire sufficient
information on a range of chemicals so that ‘bioactivity signatures’ can be discerned
that identify distinctive patterns of toxic effects, or phenotypes, observed in traditional
animal toxicity testing. The ToxCast predictive bioactivity signatures are based upon
physico-chemical properties, biochemical properties from high-throughput screening
(HTS) assays, cell-based phenotypic assays, genomic analyses of cells in vitro, and
responses in non-mammalian model organisms.
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AXLR8-2 WORKSHOP REPORT
Progress Report 2011 & AXLR8-2 Workshop Report