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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