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Erice statement on endocrine disrupters (inc. dioxin)
The following scientific consensus statement was released to the press
yesterday:
STATEMENT FROM THE WORK SESSION ON
ENVIRONMENTAL ENDOCRINE DISRUPTING CHEMICALS:
NEURAL, ENDOCRINE, AND BEHAVIORAL EFFECTS
THE PROBLEM
A multidisciplinary group of international experts gathered for a work
session on "Environmental Endocrine-Disrupting Chemicals: Neural,
Endocrine and Behavioral Effects" under the auspices of the International
School of Ethology at the Ettore Majorana Centre for Scientific Culture in
Erice, Sicily, November 5-10, 1995. The need for this work session grew
out of evidence accumulated since the first consensus statement on
endocrine disrupting chemicals was released in October, 1991. This first
statement was framed as a product of a work session on "Chemically-Induced
Alterations in Sexual and Functional Development: The Wildlife/Human
Connection". Research since 1991 has reinforced concerns over the scope of
the problems posed to human health and ecological systems by
endocrine-disrupting chemicals. New evidence is especially worrisome
because it underscores the exquisite sensitivity of the developing nervous
system to chemical perturbations that result in functional abnormalities.
Moreover, the consequences of these perturbations depend upon the stage of
development during which exposure occurs and are expressed in different
ways at different times in life, from birth through to advanced age. This
work session was convened because of the growing concern that failure to
confront the problem could have major economic and societal implications.
Those in attendance agreed that as scientists we seek only the truth; we
value diversity; we believe global problems require global solutions; and
our goal should be "science without borders and laboratories without walls"
(adapted from: Paul Dirac, Piotr Kapitza, and Antonio Zichichi, Erice
Statement, 1982).
The meeting was convened specifically to:
1. come to agreement in principle concerning the magnitude
and geographic scope of the impact of endocrine disruptors on brain
development and behavior;
2. review available technologies for ascertaining biologic
markers of exposure to and effects on the nervous system by endocrine
disruptors;
3. provide strategies for increasing communications and
collaboration among disciplines to optimize resources for future research;
and
4. suggest methods for translating the findings of this
work session into information that is useful for decision makers and the
public.
CONSENSUS STATEMENT
The following consensus was reached by participants at the worshop.
1. We are certain of the following:
* Endocrine-disrupting chemicals can undermine
neurological and behavioral development and subsequent potential of
individuals exposed in the womb or, in fish, amphibians, reptiles, and
birds, the egg. This loss of potential in humans and wildlife is expressed
as behavioral and physical abnormalities. It may be expressed as reduced
intellectual capacity and social adaptability, as impaired responsiveness
to environmental demands, or in a variety of other functional guises.
Widespread loss of this in nature can change the character of human
societies or destabilize wildlife populations. Because of profound
economic and social consequences emerge from small shifts in functional
potential at the population level, it is imperative to monitor levels of
contaminants in humans, animals, and the environment that are associated
with disruption of the nervous and endocrine systems and reduce their
production and release.
* Because the endocrine system is sensitive to
perturbation, it is a likely target for disturbance. In contrast to
natural hormones found in animals and plants, some of the components and
by-products of many manufactured organic compounds that interfere with the
endocrine system are persistent and undergo biomagnification in the food
web, which makes them of greater concern as endocrine disruptors.
* Man-made endocrine-disrupting chemicals range across
all continents and oceans. They are found in native populations from the
Arctic to the tropics, and, because of their persistence in the body, can
be passed from generation to generation. The seriousness of the problems
is exacerbated by the extremely low levels of hormones produced naturally
by the endocrine system which are needed to modulate and induce appropriate
responses. In contrast, many endocrine disrupting contaminants, even if
less potent than the natural products, are presented in living tissue at
concentrations millions of times higher that the natural hormones,.
Wildlife, laboratory animals, and humans exhibit adverse health effects at
contemporary environmental concentrations of man-made chemicals that act as
endocrine disruptors. New technology has revealed that some man-made
chemicals are present in tissue at concentrations previously not possible
to measure with conventional analytical methods, but at concentrations
which are biologically active.
* Gestational exposure to persistent man-made chemicals
reflects the lifetime of exposure of females before they become pregnant.
Hence, the transfer of contaminants to the developing embryo and fetus
during pregnancy and to the newborn during lactation is not simply a
function of recent maternal exposure. For some egg laying species, the
body-burden of the females just prior to ovulation is the most critical
period. For mammals, exposure to endocrine disruptors occurs during all of
prenatal and early postnatal development because they are stored in the
mother.
* The developing brain exhibits specific and often narrow
windows during which exposure to endocrine disruptors can produce permanent
changes in its structure and function. The timing of exposure is crucial
during early developmental stages, particularly during fetal development
when a fixed sequence of structural change is occurring and before
protective mechanisms have developed,. A variety of chemical challenges in
humans and animals early in life can lead to profound and irreversible
abnornmalities in brain development at exposure levels that do not produce
permanent effects in adults.
* Thyroid hormones are essential for normal brain
functions throughout life. Interference with thyroid hormone function
during development leads to abnormalities in brain and behavioral
development. The eventual results of moderate to severe alterations of
thyroid hormone concentrations, particularly during fetal life, are motor
dysfunction of varying severity including cerebral palsy, mental
retardation, learning disability, attention deficit hyperactivity disorder,
hydrocephalus, seizures and other permanent neurological abnormalities.
Similarly, exposure to man-made chemicals during early development can
impair motor function, spatial perception, learning, memory, auditory
development, fine motor coordination, balance, and attentional processes;
in severe cases, mental retardation may result.
* Sexual development of the brain is under the influence
of estrogenic (female) and androgenic (male) hormones. Not all endocrine
disruptors are estrogenic or anti-estrogenic. For example, new date reveal
that DDE, a breakdown product of DDT, found in almost all living tissue, is
an anti-androgen in mammals. Man-made chemicals that interfere with sex
hormone shave the potential to disturb normal brain sexual development.
Wildlife studies of gulls, terns, fishes, whales porpoises, alligators and
turtles link environmental contaminants with disturbances in sex hormone
production and/or action. These effects have been associated with exposure
to sewage and industrial effluents, pesticides, ambient ocean and
freshwater contamination, and the aquatic food web.
* Commonalties across species in the hormonal mechanisms
controlling brain development and function mean that adverse effects
observed in wildlife and in laboratory animals may also occur in humans,
although specific effects may differ from species to species. Most
important, the same man-made chemicals that have shown these effects in
mechanistic studies in laboratory animals also have a high exposure
potential for humans.
* The full range of substances interfering with natural
endocrine modulation of neural and behavioral development cannot be
entirely defined at present. However, compounds shown to have endocrine
effects include dioxins, PCBs, phenolics, phthalates, and many pesticides.
Any compounds mimicking or antagonizing actions of, or altering levels of,
neurotransmitters, hormones, and growth factors in the developing brain are
potentially in this group.
2. We estimate with confidence that:
* Every pregnant woman in the world has endocrine
disruptors in her body that are transferred to the fetus. She also has
measurable concentrations of endocrine disruptors in her milk that are
transferred to the infant.
* There may not be definable thresholds for responses to
endocrine disruptors. In addition, for naturally occurring hormones, too
much can be as severe a problem as too little. Consequently, simple
(monotonic) dose-response curves for toxicity do not necessarily apply to
the effects of endocrine disruptors.
* Because certain PCBs and dioxins are known to impair
normal thyroid function, we suspect that they contribute to learning
disabilities, including attention deficit hyperactivity disorder and
perhaps other neurological abnormalities. In addition, many pesticides
affect thyroid function and, therefore, may have similar consequences.
* Some endocrine disruptors or their breakdown products
are nearly equipotent to natural hormones. Even weak endocrine disruptors
may exert potent effects because they can bypass the natural protection of
blood binding proteins for endogenous hormones. Some disruptors also have
a substantially longer biological half-life than naturally produced
hormones because they are not readily metabolized, and as a result are
stored in the body and accumulate to concentrations of concern. Some
man-made chemicals that appear non-toxic are converted by the liver to more
toxic compounds. Also, compounds that are not toxic in the mother may be
toxic to her developing embryo, fetus or newborn. The exquisite
vulnerability of the fetal brain to methylmercury and lead are prime
examples of this principle.
* Functional deficits are not as easily measured as
physical anomalies or clinical disease, in part because they are typically
expressed as continuous measures, such as IQ, rather than the number of
cases in a population. Consequently, conventional population surveys may
overlook the extent of such deficits. Moreover, because such surveys tend
to express their findings as shifts in mean values even when they are based
on appropriate measures, they tend to obscure influences on the more
susceptible members of the population.
* Large amounts of man-made chemicals capable of
disrupting the endocrine and nervous systems are sold to, or produced and
used in, third world countries that lack the resources or technology to
properly monitor and control exposure levels. Insufficient and improper
training in handling chemicals and ignorance of concerning health effects
and monitoring strategies leads to the likelihood of very high levels of
exposure.
3. There are many uncertainties in our understanding
because:
* No one is exposure-free, thus confounding studies to
determine what is normal. Everyone is exposed at any single time and
throughout life to large numbers of manmade chemicals. Relatively few of
the manmade chemicals found in human tissue have been identified. Lack of
funding has seriously constrained testing these chemicals for their
potential to disrupt natural systems.
* Sensitive parameters, including neurological
abnormalities, behavioral and neuropsychiatric disorders, and
neuroanatomical, neurochemical, and neurophysiologic endpoints need to be
investigated. Most important, criteria at the population level need to
include the social and economic costs of impairment because the true costs
to society of such problems can be significant, e.g., the costs of a 5
point IQ loss across a population. Investigation of potential toxicity
typically includes laboratory, population and field studies, clinical
reports, and accident reports. However, developmental neurotoxicants
produce a spectrum of effects that are not typically evaluated. such as the
progression and latency of behavioral and neurological changes. In
addition, alternation of other systems can produce subsequent cognitive,
behavioral, and neurological dysfunction; i.e. diseases of other organ
systems that influence the brain; non-CNS drugs; other foreign substances
such as air pollutants; and immune system involvements that alter behavior.
* Trade secret laws afford industry confidentiality,
depriving the consumer and public health authorities of the right to know
the components of commercial products so they can be tested.
4. Our judgment is that:
* The benefits of reduced health care costs could be
substantial if exposure to endocrine-disrupting chemicals were reduced.
* A trivial amount of governmental resources is devoted
to monitoring environmental chemicals and health effects. The public is
unaware of this and believes that they are adequately protected. The
message that endocrine disruptors are present in the environment and have
the potential to affect many people over a lifespan has not effectively
reached the general public, the scientific community, regulators, or policy
makers. Although this message is difficult to reduce to simple statements
without over- or understating the problem, the potential risks to human
health are so widespread and far-reaching that any policy based on
continued ignorance of the facts would be unconscionable.
* The outcome of exposure is inadequately addressed when
based just on population averages. Instead, risk should be based on the
range of responses within a population -- that is, the total distribution.
The magnitude of the problem can be better determined by knowing the
distribution of responses to endocrine disruptors by individuals within
subsets of the population most at risk, such as pregnant women, developing
embryos, fetuses, and newborns, teens, the aged, the ill or those with
pre-existing endocrine disorders. The magnitude of the risks also depends
upon the endpoint under consideration. For example, a variety of motor,
sensory, behavioral, and cognitive functions, endpoints which are more
sensitive than cancer, must be considered when assessing neurological
function. This holds for wildlife and domestic animals, as well as human
populations.
* Wildlife have been effective models for understanding
endocrine disruption at the molecular, cellular, individual, population,
and ecosystem levels. Future research to examine diverse wildlife species
at all levels of biological organization must be broadened and adequately
supported.
* Those responsible for producing man-made chemicals must
assure product safety beyond a reasonable doubt. Manufacturers should be
required to release the names of all chemicals used in their products with
the appropriate evidence that the products pose no developmental health
hazard.
* Current panels of scientists who determine the
distribution of public research funds often have a narrow scope of
expertise and are thus ill-equipped to review the kind of interdisciplinary
research that is necessary in this field. Funding institutions should be
encouraged to increase the scope of representation on review panels and to
develop more appropriate mechanisms for interdisciplinary reviews.
Governmental agencies should also increase funding for multidisciplinary
extramural projects for surveillance of wildlife and human populations
where neurological damage is suspected and follow any leads with laboratory
research. In addition, populations of animals consuming the contaminated
foods also eaten by humans should be studied for developmental health
effects. It is important to observe a variety of vertebrate species
through multigenerational studies.
* Strategies for increasing interdisciplinary
communication and collaborations to optimize resources and future research
are needed. Studies should be designed more economically to include the
sharing of material among many collaborators. Interdisciplinary teams
should explore neurological and other types of damage at all levels of
biological organization from molecular through biochemical, physiological,
and behavioral.
* A concerted effort should be undertaken to deliver this
consensus statement to the public, key decision makers, and the media. In
addition, specially designed messages should be developed for family
physicians and others responsible for public health who are often unaware
of the possible role of occupational and environmental chemical pollutants
as agents underlying or constituting risk factors for "primary" human
diseases. Physicians must be trained in medical school about often latent
effects of pollutants on human development and health. This training is
currently inadequate. A coordinated speakers bureau and on-line systems
such as a site on the World Wide Web for endocrine-disruptors should be
established.
The scientists listed below signed the statement. They were all
participants in the meeting in Erice in November 1995 when and where the
statement was written.
Dr. Enrico Alleva
Head Section of Behavioral Pathophysiology
Institute of Neurobiology
Rome, Italy
Dr. John Brock
Chief - PCBs and Pesticides Laboratory
Center for Environmental Health
Centers for Disease Control
Atlanta, GA
Dr. Abraham Brouwer
Associate Professor and Toxicology and Research Coordinator
Department of Toxicology
Agricultural University
Wageningen, The Netherlands
Dr. Theo Colborn
Senior Program Scientist
Wildlife and Contaminants Project
WWF
WDC
Dr. M. Cristina Fossi
Professor
Department of Environmental Biology
University of Siena
Siena, Italy
Dr. Earl Gray
Section Chief
Developmental and Reproductive Toxicology Section
US EPA
Research Triangle Park, NC
Dr. Louis Guillette
Professor
Department of Zoology
University of Florida
Gainesville, FL
Peter Hauser, MD
Chief of Psychiatry Service (116A)
Baltimore VAMC
10 North Greene Street
Baltimore, MD
Dr. John Leatherland
Professor, Chair
Department of Biomedical Sciences
Ontario Veterinary College
University of Guelph
Ontario, Canada
Dr. Neil MacLusky
Professor
Director Basic Research
Div of Reproductive Science
Toronto Hospital
Ontario, Canada
Dr. Antonio Mutti
Professor
Laboratory of Industrial Toxicology
University of Parma Medical School
Parma, Italy
Dr. Paola Palanza
Researcher
Department of Biology and Physiology
University of Parma
Parma, Italy
Dr. Susan Porterfield
Associate Professor and Associate Dean of Curriculum
Medical College of Georgia
Augusta, GA
Dr. Risto Santti
Associate Professor
Department of Anatomy
Institute of Biomedicine
University of Turku
Turku, Finland
Dr. Stuart A. Stein
Associate Professor or Neurology, Medicine, Pediatrics, OB-GYN, and
Molecular and Cellular Pharmacology
University of Miami School of Medicine
Miami, FL
and
Chief of Neurology
Children's Hospital of Orange County,
Orange, CA
Dr. Frederick vom Saal
Professor
Division of Biological Sciences
University of MO
Columbia, MO
Dr. Bernard Weiss
Professor
Department of Environmental Medicine
University of Rochester
School of Medicine and Dentistry
Rochester, NY
Jackie Hunt Christensen
Institute for Agriculture and Trade Policy
1313 5th St. SE #303
Minneapolis, MN 55414
phone: 612-379-5980; fax: 612-379-5982
e-mail: <jchristensen@igc.apc.org>