Endocrine disrupting chemicals (EDCs) are broadly defined
as chemicals that can interfere with hormone action. These
chemicals are designed, produced, and marketed largely
for specific industrial purposes (e.g., plasticizers, pesticides,
etc). They are also found in some natural foods and may
become further concentrated as foods are processed or
can even contaminate foods during processing or storage.
Public interest in possible health threats posed by EDCs
is on the rise, leading to development of federal and
state policies designed to regulate or mediate perceived
EDC health risk. However, there is no comprehensive,
coordinated approach to regulating EDCs in the United States.
The Endocrine Society — the premier professional
organization for basic and clinical endocrine research and
the treatment of endocrine disorders — is concerned that
policy governing EDCs does not consider the full body of
research into EDCs. To address this issue scientifically, the
Society created a Task Force charged with summarizing
current knowledge about EDCs, including possible
mechanisms of action and potential health risks, and
with recommending actions the Society could take to
promote EDC research. The Task Force’s work resulted in
a comprehensive scientific document that is published in
Endocrine Reviews as the Society’s first Scientific Statement.1
The Scientific Statement presents a review of the EDC
literature, focused on the effects of low-dose exposure to
EDCs on endocrine systems, and clearly elaborates a strong
basis for concern about EDC health risks. Policies that fail
to adequately consider these low-dose effects, many of
which were identified through NIH-funded studies, could
lead to regulatory decisions that inappropriately define safe
levels for some EDCs. Furthermore, for many chemicals
in use today, no data exist on their EDC activity due to
a scarcity of rigorous scientific testing. Therefore, to be
comprehensive and relevant to public health, EDC policy
must be based on analysis of both low- and high-dose actions, as well as both short- and long-term exposures
and simultaneous exposure to multiple common EDCs.
Moreover, research efforts to illuminate endocrine disrupting
effects of all chemicals that enter the food chain or otherwise
lead to human exposure should be expanded. Finally, it
is critical that regulatory agencies understand that the
consequences of EDC exposures will depend upon the timing
of exposure. This is of particular concern when we consider
the increased sensitivity and vulnerability of developing
fetuses and infants to natural or artificial hormones.
The understanding that environmental chemicals can interfere
with hormone action has developed slowly over the past
50 years. Congress formally recognized EDCs as a public
health concern in 1996 when it passed the Food Quality
Protection Act and amendments to the Safe Drinking Water
Act. These laws included a mandate to the US Environmental
Protection Agency (EPA) to develop a program to identify
EDCs to which the human population may be exposed.
In response to the mandate, the EPA has worked for
more than 10 years to develop a formal system of
screens and tests that would be used to identify potential
EDCs in the environment. This Endocrine Disruptors
Screening Program (EDSP) has yet to be finalized, but
recent basic and clinical research into EDCs has provided
significant new information about the mechanisms of
EDCs on human health that could require modifications
to the plan. Thus, there is concern that this plan, if
implemented in its current form, will already be outdated.
New Information on EDC Actions Has Emerged.
Endocrinological research into EDCs over the past
decade has revealed important issues that have not
yet been incorporated into the EDSP or into risk
assessment paradigms employed by various government
agencies, which concentrate on steroid and thyroid
hormone receptor-based mechanisms. For example,
it is now clear that other hormone receptor types and
functions, including those involved in metabolism,
obesity, and brain signaling, can be targets of EDCs.
EDCs may also act beyond the exposed individual. For
example, exposures of pregnant women to EDCs can
result in exposure of the fetus through placental transfer,
and exposure can continue in the newborn through breastfeeding.
The CDC has collected biomonitoring data indicating
that several dozen industrial chemicals, including some EDCs, are routinely found in amniotic fluid.2 Thus, nearly all
babies born in the United States are exposed to industrial
chemicals and are potentially at risk of EDC actions.
Recent reports show multi-generational effects of some EDCs
(that is, the consequences of exposure are passed to future
generations) through modification of DNA and other heritable
mechanisms. Therefore, the endocrine disrupting potential
of a compound extends far beyond actions at hormone
receptors. It is therefore evident that EDCs need not bind to
a hormone receptor in order to disrupt endocrine signaling
in the exposed individual, her offspring, and subsequent
generations, facets of EDC exposure that have not yet been
incorporated into the EDSP or public policy in general.
EDC Effects Are Seen at Low Levels of Exposure.
Current EDC policy relies largely on data produced from
toxicological studies examining the effects of high doses
of chemicals. A substance must show adverse effects that
increase proportionally with dose in order to be considered
dangerous by classical toxicological standards. However,
many EDC effects occur at low doses even when high
dose effects are not apparent. In fact, increasing amounts
of hormone or hormone mimic can squelch a measured
adverse effect by overwhelming or down-regulating the
endocrine system’s ability to respond. In this circumstance,
an effect seen at low levels of exposure would not be
observed at high levels of exposure. By excluding lowdose
studies from policy considerations, the regulatory
community may not be accounting for harmful EDC
actions that exhibit hormone-like dose-response profiles.
Basic Research Predicts Human Disease.
EDC effects may not be detectable until years after the initial
exposure occurs and may affect the offspring of the exposed
individual. This was first demonstrated for diethylstilbestrol
(DES), which was given to pregnant women in the mid-
20th century with the intention of preventing miscarriage.
In early adulthood, the daughters of these women were
observed to develop a rare cancer at a higher rate than
women who had not been exposed to DES before birth.
The observation led to basic research studies in animal
models that confirmed the causal relationship of prenatal
DES exposure to the development of cancer later in life. The
confirmation of DES’ effects illustrates in reverse the power
of research in appropriate animal models. However, current
screening and testing guidelines often overlook delayed effects such as those caused by DES or fail to incorporate
complex endpoints of EDC actions to reveal adverse effects.
Scientific Controversy of EDCs Still Exists.
While the effects of DES have been confirmed, controversy
remains over the effects of other EDCs such as bisphenol
A (BPA). In 2007 a group of 38 independent NIH-funded
investigators determined that “…human exposure to BPA is
within the range that is predicted to be biologically active in
over 95% of people sampled.”3 In support of this position the
Center for the Evaluation of Risks to Human Reproduction
(CERHR) concluded in 2008 that there is “…some concern
for effects on the brain, behavior, and prostate gland in
fetuses, infants, and children at current human exposures
to bisphenol A.”4 This concern is further supported by the
recent demonstration that urinary BPA concentrations are
significantly associated with diagnoses of type 2 diabetes
and cardiovascular disease in humans.5 Despite these
opinions and scientific findings, the FDA ruled in 2008 that
BPA is safe even for infants.6 Similar controversies exist
over other EDCs, such as perchlorate and phthalates.
Also controversial is the effect of fetal exposure to
EDCs on the male reproductive system. Some studies
have suggested poor semen quality and certain types
of testicular cancer may be the result of fetal or early
exposure to certain EDCs, but scientific interpretation of
the studies varies, and conclusive data do not yet exist.
There are likely to be a number of explanations to
account for the broadly divergent conclusions by
different groups of scientists on these issues, but the
reliance primarily on toxicological studies, including
high-dose, short-term exposures, for public health risk
assessment contributes to these uncertainties.
The scientific controversy over EDCs influences relevant
policy decisions. The Endocrine Society encourages
further research to resolve the scientific discrepancies and
uncertainty and recommends that policymakers consider
taking a precautionary approach when developing policy
about chemicals that may be harmful to the public.
When conclusive evidence is lacking, but sound scientific
studies indicate a strong possibility for adverse health
effects, it is the responsibility of the federal government
to develop policies that protect people from the risk of
exposure, or at the very least inform them of this risk.
Furthermore, while some chemicals have been shown
to have endocrine-disrupting activity, there are no data
on the vast majority of the thousands of compounds in
use and in the environment today. Thus, policies must
be developed to consistently and comprehensively
examine all chemicals for potential EDC activity.
Identifying direct links between EDC exposure and childhood
or adult disease is difficult for many reasons, including the
challenges of accurately assessing a lifetime of exposure
to a complex mixture of potentially harmful agents.
Furthermore, direct clinical investigations would be difficult
and even unethical in many circumstances. It is therefore
important that policy considerations include development
and validation of animal model systems that, combined
with detailed laboratory analyses of EDC mechanisms, will
accurately predict and quantify potential effects in humans.
As more information about endocrine disruptor
effects and mechanisms becomes available, it will be
increasingly important to carefully quantify the extent
of human exposure to EDCs and assess the inherent
risk in that exposure. Additionally, it will become
increasingly necessary to provide research funding so
that scientists can further examine EDC effects.
Endocrine research is needed to elucidate the mechanisms
whereby EDCs interfere with endocrine systems necessary
for normal development and physiology. Toxicologic
research is needed to understand the dose-response
relationship between general endpoints of toxicity and
chemical exposures that typically involve doses higher
than those which alter endocrine systems. Epidemiologic
research is needed to identify and quantify levels of
human exposure that correlate with disease development.
Environmental science is needed to identify sources
of exposure. All disciplines must work together with
policymakers in order to ensure that a comprehensive
examination of EDC exposure and its effects on human
health is used as the basis for federal policy decisions.
The Endocrine Society is concerned that the public
may be placed at risk because critical information about
potential health effects of endocrine disrupting chemicals
to which Americans are exposed is being overlooked in
the development of federal guidelines and regulations.
Endocrinologists, toxicologists, epidemiologists, and
environmental scientists must work together with federal
agencies and legislators to develop comprehensive screening
programs for all chemicals and regulations governing EDCs in
manufactured products, the food supply, or the environment.
Therefore, The Endocrine Society
supports the following positions:
Regulatory oversight of endocrine disrupting chemicals
should be centralized such that regulations pass
through a single office to ensure coordination among
agencies. Coordination is required for comprehensive
and consistent regulations among all relevant federal
agencies setting guidelines for acceptable exposure,
manufacturing, sale, and human use of EDCs.
Policy should be based on comprehensive data covering
both low-level and high-level exposures. Furthermore,
tests and screens used to determine EDC activity of
chemicals should be balanced between those that
examine simple mechanisms and others that instead
measure integrated biological outcomes, thereby
encompassing substances that have effects through
several mechanisms, whether known or unknown.
Policy should be developed and revised under
the direction of a collaborative group comprising
endocrinologists, toxicologists, epidemiologists,
and policymakers. The same group should
identify knowledge gaps and recommend
research directions to fill those gaps.
Until such time as conclusive scientific evidence
exists to either prove or disprove harmful effects
of substances, a precautionary approach should
be taken in the formulation of EDC policy.
The federal government should develop a public
awareness campaign to inform the public of the
risks and potential risks related to the presence of
EDCs in the environment and in the food supply.
The federal government should support further research
into EDCs, including the development of high-throughput
assays that would allow the testing of many chemicals
for EDC activity at a full range of concentrations.
This position statement has been endorsed
by the American Thyroid Association
Diamanti-Kandarakis E. et al. 2009. Endocrine-Disrupting Chemicals:
An Endocrine Society Scientific Statement. Endo Rev 30(4):293-342
Barr D.B., Bishop A., Needham L.L. (2007) Concentrations of xenobiotic
chemicals in the maternal-fetal unit. Reprod Toxicol. 23:260-266
vom Saal et al, Reprod Toxicol. 2007 Aug-Sep;24(2):131-8. Epub 2007 Jul 27
Chapin et al, Birth Defects Res B Dev Reprod Toxicol. 2008 Jun;83(3):157-395
Lang et al, JAMA 2008; 300:1303-10
Tanne, BMJ. 2008 Aug 26;337:a1429. doi: 10.1136/bmj.a1429