|NIH Collaborates with EPA to Improve the Safety
Testing of Chemicals|
New Strategy Aims to Reduce Reliance on Animal Testing
Testing the safety of chemicals ranging from pesticides to household
cleaners will benefit from new technologies and a plan for collaboration,
according to federal scientists from the National Institutes of
Health (NIH) and the U.S. Environmental Protection Agency (EPA),
who today announced a new toxicity testing agreement. The concept
behind this agreement is highlighted in the Feb. 15, 2008 issue
of the journal Science.
"I launched the NIH Roadmap for Medical Research five years
ago to create collaborations between institutes and centers on
big projects that none of them could do alone. But I never envisioned
a trans-agency collaboration testing for environmental toxins," said
NIH Director Elias A. Zerhouni, M.D. "This research collaboration
has the potential to make crucial discoveries that will protect
the public health by identifying and understanding chemical toxicants
to which people are exposed."
Two NIH institutes have formed a collaboration with the EPA to
use the NIH Chemical Genomics Center's (NCGC) high-speed, automated
screening robots to test suspected toxic compounds using cells
and isolated molecular targets instead of laboratory animals. This
new, trans-agency collaboration is anticipated to generate data
more relevant to humans; expand the number of chemicals that are
tested; and reduce the time, money and number of animals involved
in testing. Full implementation of the hoped-for paradigm shift
in toxicity testing will require validation of the new approaches,
a substantial effort that could consume many years.
This collaboration is being made possible through a newly signed
five-year Memorandum of Understanding (MOU), which leverages the
strengths of each organization. The MOU builds on the experimental
toxicology expertise at the National Toxicology Program (NTP),
headquartered at the National Institute of Environmental Health
Sciences (NIEHS), NIH; the high-throughput technology at NCGC,
managed by the National Human Genome Research Institute (NHGRI),
NIH; and the computational toxicology capabilities at the EPA's
recently formed National Center for Computational Toxicology (NCCT).
The MOU provides for sample and information sharing necessary
to more rapidly and effectively identify chemicals that might pose
possible risks to the health of humans and animals and to the environment.
It addresses opportunities for coordination in four basic areas
related to achieving the toxicant testing goals, including: identification
of toxicity pathways; selection of chemicals for testing; analysis
and interpretation of data; and outreach to the scientific and
regulatory communities. The collective budget is yet to be determined.
The MOU and the plans articulated in the Science article
provide a framework to implement the long-range vision outlined
in the 2007 National Research Council (NRC) report, Toxicity
Testing in the 21st Century: A Vision and a Strategy, which
calls for a collaborative effort across the toxicology community
to rely less on animal studies and more on in vitro tests
using human cells and cellular components to identify chemicals
with toxic effects. Importantly, the strategy calls for improvements
in dose-response research, which will help predict toxicity at
exposures that humans may encounter.
The collaborative research program is outlined in the jointly
authored Science paper.
The co-authors — Francis S. Collins, M.D., Ph.D., NHGRI
director; George M. Gray, Ph.D., assistant administrator for EPA's
Office of Research and Development which houses the NCCT; and John
R. Bucher, Ph.D., NTP associate director — describe the possibility
of shifting from reliance on animal testing to biochemical- and
cell-based assays, as well as those using lower organisms, such
as zebrafish and roundworms.
Data collection to determine chemical toxicity currently relies
heavily on whole-animal tests. The growing number of new chemicals,
high testing costs and public unease with animal testing led to
the search for alternate toxicology testing methods. Quantitative
high-throughput screening (qHTS), developed at NCGC, increases
the rate at which chemicals are tested, and profiles compounds
over a wide range of concentrations. These qualities make the new
qHTS technology ideal for toxicology testing, with the potential
for advancing the goal of more accurate and timely public health
"A central component of federal effort will explore the use of
high-throughput screening assays in toxicology," NHGRI's Dr.
Collins said. "Such assays allow for the testing of thousands to
hundreds of thousands of chemicals a day to determine their possible
toxic effect." NCGC is part of a larger
Molecular Libraries Imaging Program within the NIH Roadmap for
Medical Research. It was designed to advance research on molecules
from which most medicines marketed today are derived.
"We now are seeing tools newly available to us for chemical genomics
research deployed for greater refinement, speed and capacity in
chemical toxicity screening," Dr. Collins said.
"The experimental and computational expertise required to
transform toxicology is an enormous undertaking and too great for
any of our existing organizations to accomplish alone," said
NTP's Dr. Bucher. "This collaborative approach allows us to
draw on our individual strengths and establishes a long-term, multiple
U.S. federal agency commitment." NTP will contribute thousands
of compounds for testing. NTP's animal toxicology expertise will
be utilized, along with a large database of the chemicals' effects
on animals, with which the new cell-based data will be compared.
"As our detailed research strategy continues to develop,
we will welcome the participation of other federal partners, as
well as interested public and private sector organizations, to
make this vision of 21st century toxicology a reality" said
EPA's Dr. Gray. The EPA's engagement in this collaboration is part
of its ToxCast program—an initiative launched in 2007 to
revolutionize the agency's chemical toxicity evaluation procedures.
ToxCast use advances in computers, genomics and cellular biology
to speed up toxicity testing and enhance capacity to screen new
Follow this link for full-resolution b-roll clips from the NCGC
The Environmental Protection Agency's National Center for Computational
Toxicology (NCCT) is a part of EPA's Office of Research and Development
(ORD). Located in Research Triangle Park, N.C., NCCT coordinates
and implements EPA's research in the field of computational toxicology.
Computational toxicology is simply defined as the blending of modern
computer science with molecular biology. The Center's goal is to
improve the ability of the Agency to assess chemical hazard and
risk. The Center's goal is to make the process more effective and
efficient, while increasing the numbers of chemicals that can be
evaluated. For more information about NCCT and its programs, visit http://www.epa.gov/ncct/.
The National Human Genome Research Institute is part of the National
Institutes of Health. For more about NHGRI, visit www.genome.gov.
The National Institute of Environmental Health Sciences (NIEHS),
a component of the National Institutes of Health (NIH), supports
research to understand the effects of the environment on human
health. For more information on environmental health topics, please
visit our website at http://www.niehs.nih.gov/.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.