v>EPA
United States
Environmental Protection
Agency
www.epa.gov/comptox
Virtual Tissues Research Project
ADVANCED COMPUTER SIMULATED MODELS OF LIVER & EMBRYO
USED TO PREDICT CHEMICAL TOXICITY
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.
It is difficult to conduct research to
predict how human health will be
impacted long-term by exposure to
chemicals. EPA's Virtual Liver and
Embryo projects are researching
how to use advanced computer
. models to simulate
how chemicals
may affect
these systems.
The traditional
method of exploring
how chemicals affect
humans is done using
controlled tests on
pregnant laboratory
animals. While these
practices provide
valuable information, they
can be both costly and
slow. Reliance on them
is one reason the pace
of testing has not kept
up with the development
of commercial chemicals, leaving
significant data gaps.
Since the liver frequently shows
the earliest signs of injury, the
Virtual Liver (v-Liver™) project is
researching how to simulate liver
function that can be used to help
predict the effects of chemicals in
humans. The idea is to have a cell-
based model that works to simulate
chemical actions in the liver in
order to estimate how much of a
chemical it takes to lead to health-
related effects, such as liver disease
and cancer.
Currently, v-Liver is using a selection
of every day chemical contaminants
with known human health effects to
		
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VIRTUAL LIVER PROJECT
develop proof that it can be used to
predict the potential for chemicals
to cause diseases. It organizes
evidence about biological networks
to clarify the toxic effects of new
chemicals (mechanism of action).
v-Liver plans to use fast, automated
chemical screening data from EPA's
Toxicity Forecaster (ToxCast™) and
other chemical data to simulate how
chemicals could cause liver toxicity.
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™ currently includes 500
fast, automated chemical screens
called high-throughput assays that
are assessing 1,000 chemicals.
Other computer simulated models
being developed are the Virtual
Embryo (v-Embryo™) models.
v-Embryo models will provide

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insights into how pregnant mother's
exposures to chemicals in the
environment might affect prenatal
development. The development
of an embryo, from conception to
birth, includes a highly coordinated
sequence of cellular behaviors and
interactions. While that process
goes perfectly the vast majority
of the time, at least three percent
of babies are born each year with
some observable malformation or
developmental condition that may
permanently shape the life of the
child.
The Virtual Tissues team includes
an interdisciplinary team of
toxicologists, computer engineers,
programmers, bioinformaticians,
biologists, mathematicians, and
other experts. The team aims to use
a selection of everyday chemicals
with known health effects in animals
to develop methods to use vast
collections of data, biological
knowledgebases and high-tech
computer modeling to build
computer-based virtual models.
The Virtual Tissue research
project works with EPA scientists
and outside partners, including
contractors, academia, industry, and
other governmental agencies.
Office of Research and Development

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Virtual Tissues Research Project
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,
ACTor, ToxRefDB and ToxPi.
For more information:
Virtual Liver:
www.epa.gov/ncct/virtual_liver
Virtual Embryo:
www.epa.gov/ncct/v-Embryo
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
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processed chlorine free
Office of Research and Development

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