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#499 - Chemicals And The Brain, Part 1, 19-Jun-1996

An international group of scientists and physicians --including U.S.
government scientists --issued a consensus statement May 30, 1996,
expressing great concern about the effects of hormone-disrupting
chemicals on the brain and central nervous system. The new statement
resulted from a workshop Nov. 5-10, 1995 at Erice, Italy. Therefore, we
will refer to this as the Erice Statement.[1]

Hormones are chemical messengers that travel in the blood stream,
turning on and off critical bodily functions to maintain health and
well being. Hormones control growth, development, and behavior in
birds, fish, reptiles, amphibians, and mammals, including humans. In
humans, 100 different hormones have been identified. Taken together,
the tissues and organs that produce, and respond to, hormones are
called the endocrine system. In 1991, an international group of 23
scientists issued a consensus statement, expressing great concern that
many synthetic (human-created) industrial chemicals can interfere with
hormones in wildlife and humans. (See REHW #263, #264). The 1991
statement focused on the ability of industrial chemicals to interfere
with sexual development and behavior in wildlife and humans. The Erice
Statement issued last month focuses attention on industrial chemicals
that can interfere with the development of the brain and other parts of
the central nervous system. The statement is not easy reading, but it
is important, so we present it verbatim.

The Erice Statement begins with a paragraph labeled "background," which
says, in part:

Research since 1991 has reinforced concerns over the scope of the
problems posed to human health and ecological systems by endocrine-
disrupting [hormone-disrupting] chemicals. New evidence is especially
worrisome because it underscores the exquisite sensitivity of the
developing nervous system to chemical perturbations [disturbances] 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.

CONSENSUS STATEMENT

The following consensus was reached by participants at the [Erice]
workshop.

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 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 [change] and
induce [cause] 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 than 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. [Gestation
is the period of development, from conception through birth; in the
case of eggs, it is the incubation period.] 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 [egg production] 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 [exposures] in humans and animals early in life can lead to
profound and irreversible abnormalities 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 [ability to move], spatial perception, learning,
memory, auditory development, fine motor coordination [for example,
coordinating movement of the hands and eyes], 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 data 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
hormones have 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.

[The Erice Statement continues; we will present the remainder in a
future issue of REHW.]

--Peter Montague (National Writers Union, UAW Local 1981/AFL-CIO)

=====

[1] The Erice Statement was signed by: 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, Georgia);
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; World Wildlife Fund;
Washington, D.C.;) Dr. M. Cristina Fossi (Professor, Department of
Environmental Biology; University of Siena; Siena, Italy); Dr. Earl
Gray (Section Chief; Developmental and Reproductive Toxicology Section;
U.S. Environmental Protection Agency [EPA] Research Triangle Park,
North Carolina); Dr. Louis Guillette (Professor; Department of Zoology;
University of Florida; Gainesville, Florida); Peter Hauser, M.D. (Chief
of Psychiatry Service [116A]; Baltimore Veterans Administration Medical
Center; 10 North Greene Street; Baltimore, Maryland); Dr. John
Leatherland (Professor, Chair; Department of Biomedical Sciences;
Ontario Veterinary College; University of Guelph; Guelph, Ontario,
Canada); Dr. Neil MacLusky (Professor; Director of Basic Research;
Division of Reproductive Science; Toronto Hospital; Toronto, 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, Georgia); Dr. Risto Santti (Associate Professor; Department of
Anatomy; Institute of Biomedicine; University of Turku; Turku,
Finland); Dr. Stuart A. Stein (Associate Professor of Neurology,
Medicine, Pediatrics, OB-GYN, and Molecular and Cellular Pharmacology;
University of Miami School of Medicine; Miami, Florida; and Chief of
Neurology Children's Hospital of Orange County, Orange, California);
Dr. Frederick vom Saal (Professor; Division of Biological Sciences,
University of Missouri; Columbia, Missouri); Dr. Bernard Weiss
(Professor, Department of Environmental Medicine; University of
Rochester School of Medicine and Dentistry; Rochester, New York).

Descriptor terms: hormones; endocrine disrupters; brain; central
nervous system; erice statement; wildlife; human health; thyroid;
cerebral palsy; mental retardation; learning disability; attention
deficit hyperactivity disorder; hydrocephalus; seizures; sexual
development; estrogen; androgen; sewage; pesticides; pcbs; phenolics;
phthalates;