Read Full Report

Date: Aug. 3, 1999
Contacts: Cheryl Greenhouse, Media Relations Consultant
Jennifer Cavendish, Media Relations Assistant
(202) 334-2138; e-mail <>


Research Needed to Reduce Scientific Uncertainty About Effects of Hormonally Active Agents in the Environment

WASHINGTON -- Although there is evidence of harmful health and ecological effects associated with exposure to high doses of chemicals known as hormonally active agents – or endocrine disrupters – little is understood about the harm posed by exposure to the substances at low concentrations, such as those that typically exist in the environment, says a new report from a National Research Council committee.

To gain more insight into the effects that these chemicals have on reproduction and development, the nervous system, the immune system, the incidence of cancer, and other aspects of the biology of humans and wildlife, new studies should be conducted that follow groups of at-risk subjects from conception through adulthood.

"Determining the risk to humans from contact with these chemicals in the environment is difficult because ordinary exposure to these agents has not been routinely monitored," said committee chair Ernst Knobil, the Ashbel Smith Professor and H. Wayne Hightower Professor in the Medical Sciences, Medical School, University of Texas, Houston. "Determining what these exposures actually are is therefore of primary importance."

Hormonally active agents (HAAs) include a wide variety of chemicals that mimic the actions of sex hormones and have been associated with adverse reproductive and developmental effects in wildlife. Exposure can occur from a variety of sources. For example, eating food that is contaminated with polychlorinated biphenyls (PCBs) or DDT, and using commercial products such as cleaners, pesticides, and food additives are ways in which people may come in contact with these chemicals.

Some researchers have concluded that these compounds may produce adverse health effects in humans and believe that exposure may increase the incidence of breast cancer. There are also concerns that the compounds may play a role in the reported declines in sperm counts, increased rates of testicular and prostate cancer, and other male reproductive disorders.

The specific mechanisms of action are not well-understood for most reported associations between HAAs and various biologic effects, the committee said. Furthermore, the majority of the evidence is based on studies done on wildlife and laboratory animals; very little is known about how the compounds affect humans.

Links to Cancer Uncertain

Although some HAAs have been associated with tumors of the thyroid, pituitary, and adrenal glands in lab animal experiments, an evaluation of the available data does not support an association between breast cancer and adult exposure to HAAs, the committee said. And although a recent study reported an association between the pesticide dieldrin and breast cancer, additional epidemiological and laboratory studies are needed to help confirm or refute this possible relationship.

The current literature does not support associations between HAAs in the environment and other hormonally sensitive cancers such as testicular, prostate, and endometrial cancer, the report says. However, few studies have measured the levels of HAAs in adult humans in relation to cancer risk, and no studies have been conducted to examine associations between the risk of cancer and exposure to HAAs during fetal development.

Appropriately designed, long-term studies are needed to document the presence or absence of links between HAAs and various cancers in humans, the committee said. These studies should address the latency period between exposure and disease, and the role of genetics and other factors that could affect a person's risk of developing cancer. In addition, chemical concentrations of HAAs in the blood should be measured to distinguish between groups experiencing different exposures.

Research on suitable animal models also is needed to examine the role that prenatal exposure to suspected chemicals plays in inducing cancer later in life or in subsequent generations, the committee said. These laboratory studies should focus initially on HAAs that have been shown to induce cancers of the thyroid, pituitary, and adrenal glands in laboratory animals.

Reproduction and Development

Adverse reproductive and developmental effects have appeared in wildlife and laboratory animals as a consequence of exposures to some HAAs. In humans, fetal exposure to pesticides and other pollutants from maternal consumption of contaminated fish or other food products can cause lower birth weights and premature births, and has been linked to lower IQs and memory deficits as well as delayed neuromuscular development.

Given the evidence to date, increases in the incidence of male reproductive disorders in humans, such as testicles that have not descended to the scrotum and testicular cancer, cannot be linked to exposures to HAAs found in the environment, the committee said.

Regional differences in sperm concentrations have been observed, and those differences should be studied to determine whether any variations seen could be associated with environmental or other factors, the committee said. Additionally, more research is needed to determine whether sperm concentrations are declining.

To better understand the effects that HAAs have on reproduction and development in humans and wildlife, the committee said, carefully designed studies should be conducted on wildlife species that have been exposed to HAAs and that exhibit population declines, abnormal sexual behavior, or deformities. Furthermore, long-term studies of human populations suspected of being affected by HAAs are needed. These studies should track groups of people at key developmental stages from conception through adulthood.

Neurologic and Immunologic Effects

Evidence already exists that links fetal exposure to high concentrations of PCBs from industrial accidents, and exposure to PCBs and some pesticides found in fish and other food products, with abnormalities in the developing nervous system. Similarly, monkeys exposed to HAAs while in the womb and during nursing have lapses in brain function when examined 14 months after exposure. Rats and mice exposed to the chemicals before birth suffer impaired movement and learning ability.

Several HAAs affect diverse elements of the immune system in laboratory animals. In addition, there is evidence that birds of the Great Lakes exhibited immune system dysfunction after exposure to the chemicals, as did captive seals that were fed contaminated fish from the Baltic Sea. Such immunosuppression is believed to be the reason for the increased incidences of bacterial and viral infections in seals in similarly contaminated waters.

In humans, data on the immunologic effects of HAAs are inadequate to support any definitive conclusions, the committee said. Studies are needed on the prevalence of autoimmune problems in groups of people suspected of being affected by HAAs, especially children whose mothers were exposed to the agents during pregnancy. Studies that include various life phases should use immunologic tests that are routinely conducted by physicians, to clarify the relationship between HAA exposure and human health. Laboratory studies also are needed to determine whether HAAs currently in pesticides, cleaning solutions, and skin care products have any affect on the immune system.

Ecological Effects

Environmental HAAs probably have contributed to declines in some wildlife populations -- including fish and birds of the Great Lakes and alligators of Lake Apopka in Florida -- and possibly to diseases and deformities in mink in the United States, river otters in Europe, and marine mammals in European waters, the committee said. Such contaminants, along with inbreeding, may have contributed to the low birth rate of the endangered Florida panther, and the increased incidence of embryonic death and deformities observed in snapping turtles of the Great Lakes. It is difficult, however, to determine a clear causal relationship between these changes and exposure to HAAs given all of the other environmental factors involved, the committee said.

Long-term studies of wildlife populations subjected to low-level HAA exposures are needed to assess the effects that these chemicals have in altering population size, life expectancy, and other ecological factors, the committee said. Such research should examine the links between chemical exposures and alterations in key developmental stages to understand how they affect populations in the long term.

The study was funded by the U.S. Environmental Protection Agency, the National Biological Service of the U.S. Department of the Interior, and the Centers for Disease Control and Prevention. 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 institution that provides independent advice on science and technology issues under a congressional charter. A committee roster follows.

Read the full text of Hormonally Active Agents in the Environmentfor 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).

Commission On Life Sciences
Board on Environmental Studies and Toxicology
Committee on Hormonally Active Agents in the Environment

Ernst Knobil1 (chair)
Ashbel Smith Professor and H. Wayne Hightower Professor in the Medical Sciences
Laboratory for Neuroendocrinology
University of Texas-Houston Medical School

Howard A. Bern1
Professor of Zoology
Department of Integrative Biology
University of California

Joanna Burger
Professor of Biology
Environmental and Occupational Health Sciences Institute
Rutgers University
Piscataway, N.J.

D. Michael Fry
Center for Avian Biology
University of California

John P. Giesy
Department of Zoology
Michigan State University
East Lansing

Jack Gorski1
Department of Biochemistry
University of Wisconsin

Charles J. Grossman
Administrative Officer and Research Investigator
Department of Veterans Affairs Medical Center, and
Xavier University
Cincinnati, Ohio

Louis J. Guillette Jr.
Department of Zoology
University of Florida

Barbara S. Hulka2
Kenan Professor
Department of Epidemiology
School of Public Health
University of North Carolina
Chapel Hill

James C. Lamb IV
Vice President
Scientific and Technical Services
Jellinek, Schwartz, & Connolly Inc.
Arlington, Va.

Leslie A. Real
Department of Biology
Emory University

Stephen H. Safe
Distinguished Professor
Department of Veterinary Physiology and Pharmacology
Texas A&M University
College Station

Ana M. Soto
Associate Professor
Department of Anatomy and Cellular Biology
Tufts University

John J. Stegeman
Senior Scientist
Department of Biology
Woods Hole Oceanographic Institution
Woods Hole, Mass.

Shanna Helen Swan
Research Professor
Department of Family and Community Medicine
University of Missouri

Frederick S. vom Saal
Division of Biological Sciences
University of Missouri


Carol Maczka
Director, Toxicology and Risk Assessment Program

David Policansky
Director, Ecology and Natural Resources Program

1 Member, National Academy of Sciences
2 Member, Institute of Medicine