From:    Karen Claxon 
Subject: Better toxicological models needed

Date: June 1, 2000
Contacts: Bill Kearney, Media Relations Associate
Megan O'Neill, Media Relations Assistant
(202) 334-2138; e-mail 

Full report
http://books.nap.edu/catalog/9871.html

Press release:

Major Advances in Biology Should Be Used to Assess
Birth Defects From Toxic Chemicals

WASHINGTON -- New discoveries in developmental biology and genetics shoul=
d
be used when scientists analyze chemicals for their potential to cause
birth defects, says a new report from the National Research Council of th=
e
National Academies. Given recent advances in understanding how the proces=
s
of normal development occurs, methods can now be devised to determine how
chemicals disrupt it in humans.

Approximately half of all pregnancies in the United States result in
prenatal or postnatal death or an otherwise less than healthy baby. And
major developmental defects, such as neural tube and heart deformities,
occur in approximately 120,000 of the 4 million infants born here each
year. Exposure to toxic chemicals, both manufactured and natural, cause
about 3 percent of all developmental defects, and at least 25 percent mig=
ht
be the result of a combination of genetic and environmental factors.

"Many manufactured chemicals, as well as chemicals that occur in nature,
have not been adequately evaluated for developmental toxicity," said Elai=
ne
Faustman, chair of the committee that wrote the report and professor of
environmental health and director of the Institute for Risk Analysis and
Risk Communication, University of Washington, Seattle. "Our report provid=
es
a blueprint for using new findings about the dynamic processes involved i=
n
normal development to further our understanding of how human development
may be affected by potentially toxic chemicals. Collaboration among
scientists from many disciplines will be key in this endeavor, as will th=
e
integration of information from various databases."

New approaches to developmental toxicology are needed that emphasize
simultaneous research on several fronts by experts from multiple scientif=
ic
disciplines, the report says. It urges scientists to take advantage of ne=
w
knowledge about the human genome when studying how genes and the
environment interact to cause developmental defects. The report also call=
s
for an intensified effort to expand the understanding of how even the
smallest, simplest laboratory animals can serve as toxicological models f=
or
human biological systems, given recent advances in this area.

In most animals -- including those commonly used in laboratories, such as
the fruit fly, roundworm, zebrafish, and mouse -- scientists recently hav=
e
discovered how specific cells communicate with each other, ultimately
activating proteins that turn particular genes on and off, thus regulatin=
g
development. These "signaling pathways" are used repeatedly in various
combinations at different times and locations in the embryo and fetus.
Chemical disruption of these pathways could lead to abnormal development.
Strikingly similar pathways are found in a wide range of animal species,
including humans, and have changed very little over the course of time,
which means that studying the effects of chemicals on signaling pathways =
in
animal models could help facilitate understanding of abnormal development
in humans, the report says.

Relatively simple assessments using animal models, such as the roundworm
and fruit fly, could be used more effectively to provide clues about whic=
h
developmental pathways are most affected by specific chemicals, the
committee said. Based on findings from these tests or general concern abo=
ut
a chemical's prevalence in the environment, more extensive studies could =
be
conducted on animals whose biological systems more closely resemble those
of humans.

In addition, major new advances in genetics will help researchers gain
insight into how chemicals affect human development, the report says.
Mapping the human genome will increase understanding of gene function and
expression, and help researchers identify unique alterations in genes,
known as polymorphisms. Recent research has shown that individuals with
certain polymorphisms, who are also exposed to certain chemicals in utero=
,
have a higher occurrence of specific developmental defects than the gener=
al
population. New information on genetic variability in humans, especially
polymorphisms, is seen as key to understanding how the relationship betwe=
en
genes and the environment leads to developmental defects.

The committee emphasized that all stages of human development -- from
conception to puberty -- should be examined in toxicity studies, since al=
l
developmental periods are potentially susceptible to toxic agents. In
addition, there is a need to look at all adverse developmental outcomes,
including growth retardation, behavioral effects, and death.

The vast amounts of data that could be generated by testing thousands of
chemicals for potential developmental toxicity will require new databases
capable of organizing this information in a way that is useful for risk
assessment, the committee said. The databases should include information
from industry, academia, and government researchers, and be linked with
existing databases of developmental biology and genomics, as well as thos=
e
describing how drugs and chemicals are metabolized by the body. A separat=
e
relational database should be set up for chemicals that are found to
interact with particular signaling pathways. This would help researchers
study whether different chemicals that affect the same pathway are acting
in a similar manner.

The lack of opportunities for collaboration among scientists from differe=
nt
fields has impeded the application of new information to improve
developmental toxicology and risk assessment, the committee said. To
overcome this, educational programs and professional workshops should be
organized to facilitate interaction among researchers in developmental
toxicology, developmental biology, genomics, medical genetics,
epidemiology, and biostatistics.

The study was sponsored by the American Industrial Health Council, Center=
s
for Disease Control and Prevention, U.S. Department of Defense, U.S.
Environmental Protection Agency, U.S. Department of Veterans Affairs,
National Center for Toxicological Research, National Institute of
Environmental Health Sciences, National Institute of Child Health and Hum=
an
Development, and National Institute for Occupational Safety and Health. T=
he
National Research Council is the principal operating arm of the National
Academy of Sciences and the National Academy of Engineering. It is a
private, nonprofit organization that provides advice on science and
technology under a congressional charter. A committee roster follows.

Copies of Scientific Frontiers in Developmental Toxicology and Risk
Assessment will be available next month from the National Academy Press a=
t
the mailing address in the letterhead; tel. (202) 334-3313 or
1-800-624-6242. Reporters may obtain a prepublication copy from the Offic=
e
of News and Public Information at the letterhead address (contacts listed
above).

NATIONAL RESEARCH COUNCIL
Commission on Life Sciences
Board on Environmental Studies and Toxicology
Toxicology and Risk Assessment Program

Committee on Developmental Toxicology

Elaine M. Faustman, Ph.D. (chair)
Professor, Department of Environmental Health, and
Director, Institute for Risk Analysis and Risk Communication
University of Washington
Seattle

John C. Gerhart, Ph.D. (vice chair)*
Professor, Department of Molecular and Cell Biology
University of California
Berkeley

Nigel A. Brown, Ph.D.
Professor of Developmental Biology
Department of Anatomy and Developmental Biology
St. George's Hospital Medical School
London

George P. Daston, Ph.D.
Toxicologist
Miami Valley Laboratories
Procter & Gamble Co.
Cincinnati

Mark C. Fishman, M.D.
Chief of Cardiology; Director, Cardiovascular Research Center, and
Chief, Developmental Biology Laboratory
Massachusetts General Hospital, and
Professor of Medicine
Harvard Medical School
Boston

Joseph F. Holson, Ph.D.
President and Director
WIL Research Laboratories Inc.
Ashland, Ohio

Herman B.W.M. Ko=EBter, Ph.D.
Principal Administrator
Environmental Health and Safety Division
Organization for Economic Cooperation and Development
Paris

Anthony P. Mahowald, Ph.D. *
Louis Block Professor and Chair
Department of Molecular Genetics and Cell Biology
University of Chicago
Chicago

Jeanne M. Manson, Ph.D.
Fellow, Center for Clinical Epidemiology and Biostatistics
University of Pennsylvania
Philadelphia

Richard K. Miller, Ph.D.
Professor and Associate Chair of Obstetrics and Gynecology, and
Professor of Environmental Medicine
University of Rochester School of Medicine and Dentistry
Rochester, N.Y.

Philip E. Mirkes, Ph.D.
Research Professor, Department of Pediatrics
University of Washington
Seattle

Daniel W. Nebert, M.D.
Professor, Department of Environmental Health
University of Cincinnati Medical
Center, and
Professor, Department of Pediatrics
Division of Human Genetics
Children's Hospital Medical Center
Cincinnati

Drew M. Noden, Ph.D.
Professor of Embryology
Department of Biomedical Sciences
College of Veterinary Medicine
Cornell University
Ithaca, N.Y.

Virginia E. Papaioannou, Ph.D.
Professor of Genetics and Development
College of Physicians and Surgeons
Columbia University
New York City

Gary C. Schoenwolf, Ph.D.
Professor of Neurobiology and Anatomy, and
Member, Huntsman Cancer Institute
School of Medicine
University of Utah
Salt Lake City

Frank Welsch, D.V.M.
Senior Scientist and Head, Teratology Laboratory
Chemical Industry Institute of Toxicology
Research Triangle Park, N.C.

William B. Wood, Ph.D. *
Professor, Department of Molecular, Cellular, and Developmental Biology
University of Colorado, Boulder, and
Member, Cancer Institute
University of Colorado Health Sciences Center
Denver

RESEARCH COUNCIL STAFF

Carol A. Maczka, Ph.D.
Director, Toxicology and Risk
Assessment Program

Abigail E. Stack, Ph.D.
Project Director

* Member, National Academy of Sciences