Pure Appl. Chem.,
Vol. 70, No. 9, pp. v-vii 1998
Natural and anthropogenic environmental oestrogens:
the scientific basis for risk assessment
IUPAC, Executive Director
The title of this special issue of Pure and
Applied Chemistry is "Natural and Anthropogenic Environmental
Oestrogens: The Scientific Basis for Risk Assessment". The term
"oestrogen" as used here is to be interpreted broadly to include
both oestrogens and androgens and compounds that either mimic naturally
occurring hormones or affect the hormone system. This subject is known
by many names, "endocrine disrupters", "oestrogen mimics",
"hormone disrupters". Each of these names focuses on one aspect
of the subject.
The endocrine system in humans and animals has many
components. The major components are the endocrine glands, such as the pituitary,
thyroid and adrenal glands, the female ovaries and male testes. Hormones such
as oestrogen are the messengers of the system, turning certain functions on
or off. Hormones are transported in the blood in the free state or attached
to carrier proteins and bind to specific receptors at target organs. Chemicals
that are exogenous to the system can affect its operation at any of these
points. One can envisage chemicals that mimic the action of an endogenous
hormone, that compete for binding sites at the target organ, with no further
effect. Other modes of action possible are binding to hormones to inactivate
them, binding to the transport proteins or altering the synthesis or degradation
Effects from anthropogenic chemicals have been claimed
to cause reproductive and developmental problems in animals and humans. The
best known summary of the case for the existence of a problem is the book
"Our Stolen Future" by Theo Colborn, Dianne Dumanoski and John Peterson
Myers, Dutton, 1996. The history of environmental oestrogens as a public policy
issue includes statements from workshops such as the "Work Session on
Chemically-induced Alterations in the Developing Immune System: The Wild life/Human
Connection, Racine, Wisconsin, USA, February 1995" and "Statement
from the Work Session on Environmental Endocrine Disrupting Chemicals: Neural,
Endocrine and Behavioral Effects, Erice, Sicily, November 1995." The
US Environmental Protection Agency has issued a "Special Report on Environmental
Endocrine Disruption: An Effects Assessment and Analysis", EPA/630/R-96/012,
February 1997. The Organisation for Economic Co-operation and Development
(OECD) has adopted the following working definition for an endocrine disrupting
chemical (EDC) and a potential EDC as agreed upon by an European Union / World
Health Organization / OECD Workshop in Weybridge, UK in December 1996:
"An endocrine disrupting chemical (EDC) is an
exogenous substance that causes adverse health effects in an intact organism,
or its progeny, consequent to changes in endocrine function".
"A potential endocrine disrupting chemical (EDC)
is a substance that possesses properties that might be expected to lead
to endocrine disruption in an intact organism".
The actions taken by the OECD are representative of
those of governmental in this area. The OECD Test Guidelines Programme proposed
in September 1996 that new Test Guidelines should be developed and/or existing
Test Guidelines should be revised for the testing and hazard characterization
of endocrine disrupters. It was recognized that the existing OECD Test Guidelines
were probably insufficient as to endpoints addressing endocrine disruption
and that reliable (in vitro) screening methods for this purpose were
not yet available. They further proposed that a sound review of the area,
including current national policies and test requirements with respect to
endocrine disrupters was needed as a first step towards a global policy on
The OECD Endocrine Disrupters Project was launched in
November 1996. The major objectives of the project are to:
- co-ordinate current national and regional activities
on the risk assessment and management of endocrine disrupting chemicals
- develop internationally acceptable methods (OECD
Test Guidelines) for the hazard characterization of EDCs; and
- harmonize risk characterization approaches and regulatory
policies for EDCs among Member countries.
Dr. J. P. Myers, one of the authors of "Our Stolen Future" in a
speech at the Rio + 5 Forum Five years after the Earth Summit, UN Conference
on Environment and Development, 14 March 1997, makes the two best know points
from the book:
Let me challenge you with two simple facts.
1. First, Every one of you sitting here today is carrying at least 500
measurable chemicals in your body that were not part of human chemistry before
the 1920's. We are walking experiments, differing from all previous generations
of human ancestry in this regard.
2. And second, there is now incontrovertible scientific proof that a mother
shares some of these man-made chemicals with her baby while it is in her womb.
No baby has been born on the planet for at least two decades without some
exposure to novel chemicals in the womb. Some with little exposure. Some with
a lot. But none with none.
He goes on to say: In all likelihood, some, perhaps many of these compounds
will turn out to be benign, with no impact. But some we know already cause
It is this sentence, hidden away in Dr. Myers speech, that defines the technical
problem. Chemical compounds, new to the world or new to a particular environment,
are not part of our environment, they are our environment. We cannot return
to a pre-industrial condition and few would advocate that we do that. Our
task is thus to find those compounds, among Dr. Myers' 500, that are not benign.see
This series of reviews is a contribution to that task. The articles that
follow cover the full range of subjects that must be understood to begin answering
the questions that have been raised. The four articles in the Introduction
section provide an overview of the physiological structures and processes
that are involved in understanding the effects of environmental oestrogens.
In particular, the reviews of the "Comparative physiology of the reproductive
endocrine system in laboratory animals and humans" and "Comparative
reproductive physiology of non-mammalian species" provide insight into
how studies in one species can be applied to other species, especially man.
It is important to understand both the similarities and the differences in
order to draw appropriate conclusions from laboratory or field studies. The
next four articles discuss risk assessment and the interpretation of specific
types of epidemiological data.
This is followed by two articles discussing methods for assessing the risk
of compounds for which there is no epidemiological data. Structure activity/relations
and in vitro tests are often used as a guide to the potential risks
associated with new materials. Dodge and Ashby discuss how these techniques
can and cannot be used to evaluate environmental oestrogens. The next three
articles review metabolism and the sources and effects of dietary oestrogens,
especially naturally occurring materials. Given the large background levels
of naturally occurring oestrogens, it is important to understand how animals
and humans have, and have not, adapted to their presence. This understanding
helps in evaluating the possible effects of anthropogenic material. Will they
be neutralized by mechanisms that have evolved in response to natural materials
or are they qualitatively different? The article by Jobling reviews test methods
for endocrine disrupting chemicals. The limitations of test methods must be
understood if they are to be properly used as guides either to further research
or to policy. The article by Miyamoto and Klein addresses the key subjects
of environmental exposure, species differences and risk assessment. The concluding
articles discuss two specific case studies, nonylphenol and clover phyoestrogens.
These two case studies bring out what is known and what is not understood
about the effects of environmental oestrogens in humans and animals.
The Conclusions and Recommendations review the policy issues and how they
relate to the science. The authors point out that only high quality
science can answer the many remaining questions. This volume provides
the background information necessary for informed debate of the policy
issues. Science can provide quality controlled information, based on
reproducible, up-to-date, peer reviewed results and risk assessment.
In many cases, it cannot give the kinds of definitive answers the public
and policy makers would like. Policy makers, and ultimately the public,
will have to decide the level of risk they are willing to accept.
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