*>EPA

UnilGu OLalcS
Environmental Protection
Agency
www.epa.gov/comptox
Computational Toxicology
Research Program
Fast, Automated
Chemical Screening for
Assessing Exposure, Hazard and Risk
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.
CompTox
Methods and Tools
ACToR and ToxRefDB
(Aggregated Computational
Toxicology Resource and
Toxicity Reference Database)
These publically available databases
enable scientists and the interested
public to search and download
thousands of toxicity testing results
on hundreds of chemicals. ACToR
aggregates data from more than
500 public sources on over 500,000
chemicals, and ToxRefDB captures
more than 30 years and $2 billion worth
of animal testing results. ACToR is the
umbrella data warehouse that provides
linkages to all available CompTox
chemical toxicity databases including
ToxRefDB, Distributed Structure-
Searchable Database (DSSTox) and the
ToxCast Database (ToxCastDB).
Too Little Data (%)
Too Many Chemicals
9912
10000/1

Cancer B Gentox
Repro Tox
CH-
DSSTox
(Distributed Structure-
Searchable Toxicity Database)
The website	ch
provides a	3
public forum )jq
for publishing
downloadable,
structure-
searchable,
standardized chemical structure files
associated with toxicity data.
ToxCast™
(Toxicity Forecaster)
Chemical Type ToxCast Phase I ToxCast Phase II Tox21
0
Pesticides/
Environmental
Manufactured/
Industrial
Highly Toxic
Pharmaceuticals
Consumer Products/
Food additives
42
73
0
230
150
100
2200
2800
500
2500
1500
Total unique
10000
ToxCast
PHASE I
ToxCast
PHASE II
| Tox21 |
300 1000	. .	10,0
Chemicals
EPA's Need for Toxicity Data
Office of Research and Development

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Computational Toxicology Research Program
A multiyear, multimillion dollar effort
that uses advanced science tools
to help understand how human
biology is impacted by exposure to
chemicals and to determine which
exposures are the most likely to lead
to adverse health effects. ToxCast™
currently includes over 500 fast,
automated chemical screening
tests that are assessing more than
1000 environmental chemicals.
All available ToxCast chemical
screening data can be queried
and downloaded from the ToxCast
database (ToxCastDB). ToxCastDB
provides all ToxCast data with
links to chemicals, assays, genes,
pathways and endpoints.
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),
the National Toxicology Program/
National institute of Environmental
Health Sciences and the National
Institutes of Health (NIH) Chemical
Genomics Center.
ToxPi
(Toxicological Priority Index)
Exposure Data: ExpoCast
Exposure Science for Prioritization and Toxicity Testing
Environment
Human
In vitro assays
[ToxCast)
Chemical
Pathways
Properties
(endocrine)
(descriptors)
A flexible prioritization support
software tool that incorporates
profiles, inferred toxicity pathways,
dose estimates and chemical
structural descriptors to calculate a
potential toxicity score.
ExpoCast
(Exposure Forecaster)
Works with ToxCast™ to determine
priority chemicals that may need
further screening and develops
novel approaches for evaluating
chemicals based on potential
1
HI
¦
I

Exposure
Mechanistic Informatics
Knowledge
Network
Exposbme 1
Database
Models Approaches
Systems
Models
for biologically relevant human
exposure.
Virtual Tissues
This research includes advanced
v - L I V E R
VIRTUAL LIVER PROJECT
computer models of the liver and
embryo that will be used to predict
the effects of chemicals in humans.
Virtual Liver (v-Liver™) will use fast,
automated chemical screening
data from ToxCast™ and other data
to simulate how chemicals could
cause liver disease and cancer in
people. Virtual Embryo (v-Embryo™)
will use ToxCast™ data to develop
predictions for what chemical
interactions will most likely lead to
toxicity and birth defects.
v-Embryo"'
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.
More information at:
www.epa.gov/comptox
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
Recycled/Recyclable
Printed on paper that contains a minimum
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processed chlorine free

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