United States . • -
Environmental Protection,
Agency
Prevention, Pesticides
And Toxic Substances
(7506C)
October 1998
FOR YOUR INFORMATION
Screening and Testing Chemicals for
Endocrine Disrupting Properties
In recent years, some scientists have
proposed that chemicals might bq
disrupting'the hormone (endocrine)
systems of humans and wildlife, resulting in
reproductive disorders, birth defects, immune
dysfunction, and other harmful effects. A
variety of chemicals have been found to
disrupt the endocrine systems of animals in
laboratory studies, and compelling evidence
has accumulated that endocrine systems of
certain fish and wildlife have been altered by
chemicals that contaminate their habitats.
With few exceptions, however, such effects \
have not .been conclusively demonstrated in
human beings to date..
Because of the potentially serious •'. '
consequences of human exposure to endocrine
disrupting chemicals, Congress included a
, mandate to EPA in the Food Quality
Protection Act of 1996 and the 1996
amendments to the Safe Drinking Water Act to
develop an endocrine disrupter screening arid
testing program. We formed an advisory
committee, the Endocrine Disrupter Screening
and Testing Advisory Committee (EDSTAC),
to develop recommendations for such a
program, which were finalized in August
19S98. We then used EDSTAC's
recommendations to design our endocrine
disrupter screening and testing program. This
document summarizes some of the key
EDSTAC recommendations and the actions
we are taking. •
What is the endocrine system?
f I ^he endocrine system consists of glands
I and the hormones they produce that
A guide the development, growth,
reproduction, and behavior of human beings
and animals. Some of the endocrine glands
include the pituitary, thyroid, and adrenal
glands, the female ovaries and male testes.
Hormones are chemicals, produced by
endocrine glands, that travel through the
bloodstream and cause responses in other parts
of the body. An example is estrogen, which is
essential for female reproductive function.
Hormones can produce, both positive and
negative effects. For example, some types of
breast cancer are exacerbated by estrogen, but
studies also'indicate that estrogen has a
protective effect in combating heart disease
and osteoporosis- related fractures in older
women.
What are endocrine disrupters?
Chemicals that interfere with the normal
functioning of this complex system and
came harmful effects are known as
"endocrine disrupters." Disruption of the
endocrine system can occur in various ways.
For example, some chemicals may mimic a
natural hormone,"fooung" the body into over-
responding to the stimulus or responding at
inappropriate times. Other chemicals may
block the effects of a hormone in parts of the
body normally sensitive to it. Still others may
directly stimulate or inhibit the endocrine
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system, causing overproduction or
underproduction of hormones. Certain drugs
are used to intentionally cause some of these
effects, such as birth control pills.
Has EPA ever required endocrine
disrupter tests before now?
Ws currently screen new pesticides
and industrial chemicals prior to
their introduction into commerce
and seek to control any which may pose an
unreasonable risk to human health and the
environment. New pesticides are routinely
tested in animals for effects on reproduction,
fertility, and the developing fetus before they
are approved for use. Older pesticides are
tested as part of our ongoing re-registration
program, a comprehensive reevaluation of all
pesticides first approved before 1984. The
growth and development of offspring are also
evaluated, including an assessment of birth
defects or other abnormalities. Although these
tests are not specifically designed to identify
endocrine disruption, they can detect certain
reproductive and developmental effects which
may result from endocrine disruption.
Once re-registration is completed in 2002, we
will re-examine all pesticides every 15 years.
At the same time, we are also reassessing all
tolerances (maximum limits for pesticide
residues in food) and tolerance exemptions for
both active and inert pesticidal ingredients to
ensure they meet the new safety standards
established by the Food Quality Protection Act
(FQPA)ofl996. The FQPA tolerance
reassessment will be completed by 2006.
Wliat gives EPA legal authority to test
for endocrine disrupters?
A uthority for screening and testing
/\ endocrine disrupting chemicals is
JL Vjbased on the Food Quality Protection
Act and Safe Prinking Water Act
Amendments, both passed by the United States
Congress in August 1996, which require us to:
...develop a screening program, using
appropriate validated test systems and other
scientifically relevant information, to
determine whether certain substances may
have an effect in humans that is similar to an
effect produced by a naturally occurring
estrogen, or such other endocrine effect as the
Administrator may designate...
The law requires us to implement this program
by August 1999. In addition EPA has broad
general authority to require testing under the
Toxic Substances Control Act and the Federal
Insecticide, Fungicide and Rodenticide Act.
What was the EDSTAC?
f I ^he Endocrine Disrupter Screening and
I Testing Advisory Committee
-L (EDSTAC) was a federal
advisory committee formed in 1996 to make
recommendations on how to develop the
screening and testing program called for by
Congress. The EDSTAC was composed of
representatives from industry, government,
environmental and public health groups,
worker safety groups, and academia. These
committee, members were charged with
developing consensus-based
recommendations on a scientifically
defensible screening and testing program that
would provide us the necessary information
In addition to addressing human
health effects, the EDSTAC agreed
to broaden its scope to consider
effects on -wildlife. The committee
also agreed to consider not only
estrogenic effects, but those
related to the androgen and
thyroid hormones, as well. The
committee also recommended that
we consider common mixtures in
addition to pesticides and
industrial chemicals.
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about certain endocrine effects of chemicals to
make regulatory,, decisions about them.
In addition to addressing human health effects,
the EDSTAC agreed to broaden its scope to
consider effects on wildlife. The committee
also agreed to consider not only estrogenic
/effects, but those related to the androgen and
thyroid hormones, as well. The committee also
recommended that we consider common
mixtures in addition to pesticides arid.
industrial chemicals. ; .
Members thoroughly reviewed and discussed
scientific information and sought the opinion
of other experts and members of the public
during its two-year deliberations. The
EDSTAC presented its final report to us in
September 199S. "
What were EDSTAC's
recommendations? ,
f | ^he EDSTAC identified approximately
I 87,000 chemicals to be examined for
JL initial sorting and priority setting.
EDSTAC recognized that deciding which
chemicals to screen and test first would be the
first challenge.
Which Chemicals Should We Test First?
We will test the potentially riskiest chemicals
first. However, there are many chemicals for
which there is little endocrine-related data we.
can use to evaluate their endocrine-disrupting ,
potential.
In order to identify high-risk chemicals we
know little about, EDSTAC recommended that
,we, in partnership with industry, conduct
roboticized assembly-line chemical assays,
called "high throughput pre-screening," on
approximately 15,000 pesticides and industrial
chemicals to obtain information quickly on ,
whether these chemicals can interact in certain
ways with the endocrine system. This will .
enable us to prioritize them for further
screening and testing.
The high-throughput screen data will be
incorporated into other existing data in a
specialized data base that will help us identify
chemicals with the potential to disrupt the
. endocrine system. By comparing the
characteristics of known endocrine disrupters
with those of a chemical for which we have
little or no data, we will be able to identify
potential endocrine disrupters based on
characteristics like chemical structure and
other properties.
Based on existing information, we will sort
chemicals into four categories:
> Tier One Screening Group,
consisting of chemicals for which
. there is insufficient endocrine-related
. data. If the high-throughput screens ;
indicate endocrine disruption potential,
or other indicators exist, the Tier One
screening tests will provide more data
to show whether a chemical can
interact with the endocrine system and
if more in-depth testing is warranted;
*•' Tier Two Testing Group, consisting
". of chemicals for which enough data
exists to show the potential for
endocrine disrupting properties. These
. chemicals will proceed directly to
reproductive and developmental
testing. These tests will show us what
kind of effects the chemical can cause;
>••'•' Risk Assessment Group, consisting of
chemicals for which enough data
already exists to support a full risk
assessment; and
> Polymers, which will be' placed oh
"hold" status.. Because of their large .
molecular size, it is unlikely that they
• can be absorbed through membranes.
We will first test their building blocks
(monomers and oligomers)j which are
more likely to interact with an
organism's biochemical processes.
What will the screening process consist of?
Tier One Screening will consist of short-term
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tests in vitro (outside the living body and in an
artificial environment) and in vivo (in the
living body of an animal). .These tests are
designed to identify chemicals that may
interact with the endocrine system.
Wlmt will the testing process consist of?
Tier Two Testing will consist primarily of
longer-term, in vivo reproductive and
developmental tests that will determine
whether a chemical causes harmful endocrine-
mediated effects in humans and wildlife..
How will risk be evaluated?
A chemical can cause harmful effects at one
exposure level, and have little or no.effect at
another. Thus, we have to determine the
relationship between possible exposures to a
chemical and the resulting harmful effects. To
estimate exposure, we use data gathered from
agricultural field studies, industrial use
statistics, water and wildlife monitoring
studies, chemical production volumes, and
other relevant sources.
If humans or animals will not be exposed to
levels of a chemical that have been shown to
cause problems, we conclude that the
chemical is not likely to cause harm. On the
other hand, if exposure levels exceed or come
close to those suspected or known to produce
problems, we will expect the chemical to
cause harm. We will then take regulatory
action to reduce risk to acceptable levels. The
endocrine disrupter testing data will be
incorporated into our ongoing FQPA pesticide
tolerance reassessment process.
Will the public have any say in which
chemicals will be tested first?.
Yes. The EDSTAC recommended that
citizens concerned that adverse health effects
in their area might be linked to exposure to
endocrine disrupting chemicals be permitted to
nominate chemicals for top priority testing.
This will ensure that low-production chemicals
that affect small groups in localized areas, for
example, will not fall through the cracks of the
core priority setting process, which will focus
on high-production chemicals with national
impact.
How will EPA use EDSTAC's
recommendations?
We will use EDSTAC's recommendations to
design our comprehensive endocrine disrupter
screening and testing plan. In accordance with
the provisions of FQPA, we will solicit public
comment and scientific peer review by the
FIFRA Scientific Advisory Panel and the EPA
Science Advisory Board, two blue-ribbon
panels of external experts and scientists, by
March 1999; and we will report to Congress
on the program's progress by August 2000.
We will continue to work with other federal
agencies, state agencies, the private sector, and
non-governmental organizations to develop,
standardize, and validate screening and testing
methods as we fully establish the program.
Consistent with EDSTAC's recommendations
on communications and public outreach, we
will provide information to members of the
public and interested stakeholders on the
screening and testing program itself, screening
and testing results, and about the nominations
process.
Where Can I Go For More
Information?
For a free hard copy of the EDSTAC report,
call EPA's TSCA Hotline at (202) 554-1404.
All EDSTAC documents are available from
the EDSTAC web site at http://www.epa.gov/
opptintr/index.htm. Or contact us at:
Communication Services Branch, Office of
Pesticide Programs, U.S. EPA (7506C), 401 M
Street, SW,Washington, DC 20460,
(703) 305-5017
or visit our general web page at:
http://www.epa.gov/pesticides
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