Endocrine disruptor

Endocrine disruptors are exogenous substances that act like hormones in the endocrine system and disrupt the physiologic function of endogenous hormones. Studies have linked endocrine disruptors to adverse biological effects in animals, giving rise to concerns that low-level exposure might cause similar effects in human beings.

Background

Since the publication of Rachel Carson’s Silent Spring (Carson, 1962), there has been increasing awareness that chemicals in the environment can exert profound and deleterious effects on wildlife populations and that human health is inextricably linked to the health of the environment. The last two decades, in particular, have witnessed a growing scientific concern, public debate, and media attention over the possible deleterious effects in humans and wildlife that may result from exposure to chemicals that have the potential to interfere with the endocrine system.

Endocrine disrupting compounds encompass a variety of chemical classes, including natural and synthetic hormones, plant constituents, pesticides, compounds used in the plastics industry and in consumer products, and other industrial by-products and pollutants. They are often pervasive and widely dispersed in the environment. Some are persistent, can be transported long distances across national boundaries, and have been found in virtually all regions of the world. Others are rapidly degraded in the environment or human body or may be present for only short periods of time but at critical periods of development.

One example of the devastating consequences of the exposure of developing animals, including humans, to endocrine disruptors is the case of the potent drug diethylstilbestrol (DES), a synthetic estrogen. Prior to its ban in the early 1970's, doctors mistakenly prescribed DES to as many as five million pregnant women to block spontaneous abortion and promote fetal growth. It was discovered after the children went through puberty that DES affected the development of the reproductive system and caused vaginal cancer.

The endocrine system

Main article: Endocrine system

Endocrine systems are found in most varieties of animal life. The endocrine system is made up of glands, which secrete hormones, and receptors which detect and react to the hormones.

Hormones are released by glands and travel throughout the body, acting as chemical messengers. Hormones interface with cells that contain matching receptors in or on their surfaces. The hormone binds with the receptor, much like a key would fit into a lock.

Endocrine disruptors

Disruption of the endocrine system can occur in various ways. Some chemicals mimic endogenous hormones, perhaps at inappropriate times. Other endocrine disruptors block the effects of a hormone from certain receptors by blocking the receptors on a cell. Still others directly stimulate or inhibit the endocrine system and cause overproduction or underproduction of hormones. Medical interventions may manipulate the endocrine system for the betterment of a patient, and unwanted effects of such therapy can be interpreted as due to endocrine disruption, but the term usually refers to disruption by environmental contaminants. Substances in question are also known as Endocrine Disrupting Chemicals (EDCs) or Hormone Disrupting Chemicals (HDCs), and belong to the group of xenobiotics, foreign chemicals that affect a biological system.

Some of the most well-known examples of EDCs are 17-alpha ethinylestradiol (the contraceptive pill), Dioxins, PCBs, PAHs, furans, phenols and several pesticides (most prominent DDT and its derivatives). Substances with estrogenic side effects include the xenoestrogens. There is a long list of substances which may disrupt the endocrine system but have not yet been scientifically proven to do so.

In recent years, some scientists have proposed that chemicals might inadvertently be disrupting the endocrine system of humans and wildlife. A variety of chemicals have been found to disrupt the endocrine systems of animals in laboratory studies, including naturally occurring substances, and there is strong evidence that chemical exposure has been associated with adverse developmental and reproductive effects on fish and wildlife in particular locations.

Recognition of the concept

Although there is some skepticism surrounding the concept, especially amongst those associated with the chemical industry, beginning in the late 1990's there began an increasing acceptance of the validity of the questions being posed by the theory.

A list of some of the important gatherings of researchers demonstrates the seriousness with which the concept was taken in the period:

1992 World Wildlife Fund Examination of the commonalities of adverse effects in wildlife, experimental animals and humans. Produced the “Wingspread Consensus Statement”

1994 National Institute of Environmental Health Sciences. Review of cellular biology, developmental effects, sources, and global health implications of environmental estrogens.

1995 German Federal Environmental Agency. Discussion about the occurrence and impact of endocrine disruptors and the potential risks that may arise to humans and the environment.

1995 Ministry of Environment and Energy, Denmark. Evaluation of the effects of estrogens on male reproductive development and function.

1995 US EPA Workshop on research needs for the Risk Assessment of health and environmental effects of endocrine disruptors.

1995 Chemical Manufacturer’s Association; World Wildlife Fund; US EPA. Workshop on screening methods for chemicals that alter thyroid hormone homeostasis, action, and function.

1995 UK Medical Research Council Institute for Environment & Health. Assessment on Environmental Estrogens: Consequences to Human Health and Wildlife.

1996 European Commission European workshop on the impact of endocrine disruptors on human health and wildlife.

1996 ECETOC Compendium of test methods for environmental estrogens.

1996 SETAC Workshop on principles and processes for evaluating endocrine disruption in wildlife.

1996 US Committee on the Environment and Natural Resources. Development of a national planning framework for endocrine disruptor research analysis of the existing federally funded research projects to help identify information gaps

1996 US EPA Workshop on the development of a risk strategy for assessing the ecological risk of endocrine disruption

1997 Federal Environment Agency, Germany Workshop on effects of endocrine disruptors on neuronal development and behavior.

1997 US EPA Special report on environmental endocrine disruption: an effects assessment and analysis.

1997 Health Council of the Netherlands. Evaluation of the effects of endocrine disruptors on human reproduction and development

1997 International Life Sciences Institute; Scientific evaluation of the potential for substances in the diet to influence the human endocrine system

1997 Japan Chemical Industry Association Evaluation of status and research needs of endocrine disrupting compounds in Japan

1998 Swedish Environmental Protection Agency. Endocrine disrupting substances-impairment of reproduction and development

1998 International Union of Pharmacology. Natural and anthropogenic environmental estrogens.

1998 Society of Environmental Toxicology and Chemistry. Workshop on endocrine disruption in invertebrates.

1999 National Research Council Hormonally active agents in the environment.

1999 European Commission. Scientific committee on toxicity, ecotoxicity, and the environment opinion on human and wildlife health effects of endocrine disruptors.

2000 Health and Environment Canada Workshop on endocrine disrupting substances in the Canadian environment

2000 US National Toxicology Program. Report of the endocrine disruptors low-dose peer review.

2000 Finnish Environment Institute Research for Management of Environmental Risks from Endocrine Disruptors

2001 Federal Environment Agency, Germany Second status seminar on endocrine disruptors.

Legal approach

The Congress of the United States has improved the evaluation and regulation process of drugs and other chemicals. The Food Quality Protection Act of 1996 and the Safe Drinking Water Act of 1996 simultaneously provided the first legislative direction requiring the EPA to address endocrine disruption through establishment of a program for screening and testing of chemical substances.

In 1998 the EPA began the endocrine disruptor screening and testing program by establishment of a framework for priority setting, screening and testing more than 85,000 chemicals in commerce. As of this writing ((2006)) the EPA is continuing to validate test methods for this program and has issued a notice of intent to begin the initial priority setting process. The basic concept behind the program is that prioritization will be based on existing information about chemical uses, production volume, structure-activity and toxicity. Screening is done by use of in vitro test systems (by examining, for instance, if an agent interacts with the estrogen receptor or the androgen receptor) and via the use of in animal models, such as development of tadpoles and uterine growth in prepubertal rodents. Full scale testing will examine effects not only in mammals (rats) but also in a number of other species (frogs, fish, birds and invertebrates).

The multitude of possible endocrine disruptors are technically regulated in the United States by many laws, including: the Toxic Substances Control Act, the Federal Insecticide, Fungicide, and Rodenticide Act, the Food, Drug and Cosmetic Act, the Clean Water, the Safe Drinking Water Act, and the Clean Air Act.

See also

• Endocrine system
• Hormone
• Xenoestrogen
• Theo Colborn
• Precautionary principle

External links

• List of suspected or possible endocrine disruptors
• Global assessment of the state-of-the-science of endocrine disruptors published in 2002 by the World Health Organisation (WHO).
  • Scientific Facts on Endocrine Disruptors, a peer-reviewed summary of the above WHO assessment, by GreenFacts.
• The NSF sponsored Environmental Signaling Network's website
• The EU strategy on EDCs
• The US EPA (strategy) on EDCs
• Synopses of new scientific findings about endocrine disruption
• Journalist's report on endocrine disruptors (OnEarth Magazine, Winter 2006)
• PBS Frontline Interview of Dr. Theo Colborn by Doug Hamilton, 1998.
• Hormonal Chaos: The Scientific and Social Origins of the Environmental Endocrine Hypothesis by Sheldon Krimsky
• "Sex-change chemicals in Potomac", BBC News, last updated 18 January 2007.

References

Colborn, Theo; Dianne Dumanoski; and John Peterson Myers. Our stolen future : are we threatening our fertility, intelligence, and survival? : a scientific detective story. New York : Dutton, 1996. 306 p. ISBN 0452274141