vyEPA
United States
Environmental Protection
Agency
www.epa.gov/comptox

Toxicity Forecaster (ToxCast M)
SCREENING
CHEMICALS TO PREDICT TOXICITY
FASTER AND BETTER
ToxCast Chemical Screening
Tens of thousands of chemicals
are currently in commerce, and
hundreds more are introduced every
year. Because current chemical
testing is expensive and time
consuming, only a small fraction
of chemicals have been assessed
adequately for potential risk.
The U.S. Environmental Protection
Agency is working to change the
current approach to chemical
toxicity risk assessment through its
Computational Toxicology Research
Program (CompTox). The program
uses innovative research that
integrates advances in molecular
biology, chemistry, and computer
science to more effectively and
efficiently rank chemicals based
on potential risks. Using CompTox
methods and tools, a large number
of chemicals can be screened
effectively for risks at a small cost in
a very short amount of time.
One developed chemical screening
tool is the Toxicity Forecaster
(ToxCast™). ToxCast™ is a multi-year
effort that was launched in 2007 to
develop a cost-effective approach
for prioritizing the thousands
of chemicals that need toxicity
testing. ToxCast uses advanced
science tools to help understand
how human body processes are
impacted by exposure to chemicals
and to determine which exposures
are most likely to lead to adverse
health effects. ToxCast is being
developed in phases. The first
phase appropriately called "Proof
of Concept" was completed in 2009
and it profiled over 300 researched
chemicals (primarily pesticides) in
over 500 state-of-the-art tests called
high-throughput screening assays.
The chemicals screened in phase
one already had extensive toxicity
testing results from traditional
chemical tests, mostly animal
tests. Having both the ToxCast and
animal testing results allows EPA
to compare results and determine
if both screening processes make
similar predictions. Phase two is
screening 700 additional chemicals
from a broad range of sources
including drugs, "green" chemicals,
chemicals in cosmetics and other
consumer products.
A large contributor to ToxCast™
is the Tox21 collaboration. Tox21
pools chemical research, data
and screening tools from multiple
federal agencies including the Food
and Drug Administration (FDA),
National Toxicology Program/
National Institute of Environmental
Health Science and National
Human Genome Research Institute/
NIH Chemical Genomics Center
to provide additional chemical
safety information.
As ToxCast screens more chemicals,
EPA will be able to determine which
combinations of high-throughput
assays are best used as indicators
for different types of potential
toxicity that can lead to health
effects such as chronic diseases or
reproductive problems.
Using EPA's online Aggregated
Computational Toxicology data
warehouse, scientists and others
who are interested can search and
find all available toxicity testing
data including results from ToxCast
which can be found in the ToxCast
database (ToxCastDB).
ACToR aggregates chemical
research data from over 500 public
sources on over 500,000 chemicals
and links to ToxRefDB which stores
the thousands of animal toxicity
studies on hundreds of chemicals.
ToxCastDB allows users to search
and download data for all ToxCast
chemicals, assays, genes, pathways
and endpoints. It allows for
associations and biologically driven
data mining.
Chemical
fl
S i Pathway

Cell Population
Assay Target Biology
(e.g., Estrogen Receptor)
Exposure
Office of Research and Development

-------
Toxicity Forecaster (ToxCast™)
Collaboration
Opportunities
The CompTox Research Program
partners and collaborates with
EPA regions and program
offices, industry, academia, trade
associations, other federal agencies,
state and local government agencies
and non-governmental organizations
with an interest in revolutionizing
the current approach to assessing
chemical toxicity risk to humans
and the environment. Collaboration
opportunities include a Communities
of Practice group and different
types of agreements that facilitate
the sharing of research data
and studies.
The CompTox program goal is to
provide fast, automated tests for
screening and assessing chemical
exposure, hazard and risk. Housed
within EPA's Office of Research
and Development, CompTox is
composed of three main elements.
The largest component is the
National Center for Computational
Toxicology (NCCT), which was
established in 2005 to coordinate
research on chemical screening
and prioritization, informatics and
systems modeling.
The second element consists of
research in EPA's National Health
and Environmental Effects Research
Laboratory (NHEERL) and National
Exposure Research Laboratory
(NERL). The final components are
the academic centers working on
various aspects of computational
toxicology funded by EPA's Science
to Achieve Results (STAR) program.
Other CompTox tools and research
projects include DSSTox, ExpoCast,
Virtual Liver, Virtual Embryo,
and ToxPi.
For more information:
ToxCast:
htt p ://e pa .g ov/ n cct/toxcast/
ToxCastDB:
http://actor.epa.gov/actor/faces/
ToxMiner/Home.jsp
ACToR:
http://actor.epa.gov/actor
ToxRefDB:
http://actor.epa.gov/toxrefdb
Contact:
National Center for
Computational Toxicology
Robert Kavlock
Director
kavlock.robert@epa.gov
David Dix
Deputy Director
dix.david@epa.gov
Monica Linnenbrink
Public Affairs Specialist
linnenbrink.monica@epa.gov
Main Office: 919-541-4219
www.epa.gov/comptox
109 T.W. Alexander Drive (B-205-01)
Research Triangle Park, NC 27711
Office of Research and Development

-------