Date: June 1, 2000
Contacts: Bill Kearney, Media Relations Associate
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Major Advances in Biology Should Be Used to Assess Birth Defects From Toxic Chemicals
WASHINGTON -- New discoveries in developmental biology and genetics should be used when scientists analyze chemicals for their potential to cause birth defects, says a new report
from the National Research Council of the National Academies. Given recent advances in understanding how the process 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 might 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 Elaine 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 provides a blueprint for using new findings about the dynamic processes involved in 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 the integration of information from various databases."
New approaches to developmental toxicology are needed that emphasize simultaneous research on several fronts by experts from multiple scientific disciplines, the report says. It urges scientists to take advantage of new knowledge about the human genome when studying how genes and the environment interact to cause developmental defects. The report also calls for an intensified effort to expand the understanding of how even the smallest, simplest laboratory animals can serve as toxicological models for 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 have discovered how specific cells communicate with each other, ultimately activating proteins that turn particular genes on and off, thus regulating 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 which developmental pathways are most affected by specific chemicals, the committee said. Based on findings from these tests or general concern about 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 general population. New information on genetic variability in humans, especially polymorphisms, is seen as key to understanding how the relationship between 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 all 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 those describing how drugs and chemicals are metabolized by the body. A separate 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 different 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, Centers 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 Human Development, and National Institute for Occupational Safety and Health. The 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.
Read the full text of Scientific Frontiers in Developmental Toxicology and Risk Assessment
for free on the Web, as well as more than 1,800 other publications from the National Academies. Printed copies are available for purchase from the National Academy Press Web site
or at the mailing address in the letterhead; tel. (202) 334-3313 or 1-800-624-6242. Reporters may obtain a pre-publication copy from the Office 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 ProgramCommittee on Developmental ToxicologyElaine M. Faustman, Ph.D. (chair)
Professor, Department of Environmental Health, and
Director, Institute for Risk Analysis and Risk Communication
University of Washington
SeattleJohn C. Gerhart, Ph.D. (vice chair)*
Professor, Department of Molecular and Cell Biology
University of California
BerkeleyNigel A. Brown, Ph.D.
Professor of Developmental Biology
Department of Anatomy and Developmental Biology
St. George's Hospital Medical School
LondonGeorge P. Daston, Ph.D.
Miami Valley Laboratories
Procter & Gamble Co.
CincinnatiMark 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
BostonJoseph F. Holson, Ph.D.
President and Director
WIL Research Laboratories Inc.
Ashland, OhioHerman B.W.M. Koëter, Ph.D.
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
ChicagoJeanne M. Manson, Ph.D.
Fellow, Center for Clinical Epidemiology and Biostatistics
University of Pennsylvania
PhiladelphiaRichard 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
SeattleDaniel W. Nebert, M.D.
Professor, Department of Environmental Health
University of Cincinnati Medical
Professor, Department of Pediatrics
Division of Human Genetics
Children's Hospital Medical Center
CincinnatiDrew M. Noden, Ph.D.
Professor of Embryology
Department of Biomedical Sciences
College of Veterinary Medicine
Ithaca, N.Y.Virginia E. Papaioannou, Ph.D.
Professor of Genetics and Development
College of Physicians and Surgeons
New York CityGary C. Schoenwolf, Ph.D.
Professor of Neurobiology and Anatomy, and
Member, Huntsman Cancer Institute
School of Medicine
University of Utah
Salt Lake CityFrank 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
RESEARCH COUNCIL STAFFCarol A. Maczka, Ph.D.
Director, Toxicology and Risk
Assessment ProgramAbigail E. Stack, Ph.D.
Member, National Academy of Sciences