International Society of Regulatory Toxicology
and Pharmacology
2009 Endocrine Workshop
The Endocrine Disruptor Screening Program:
What Can Screening Results Tell Us About Potential Adverse
Endocrine Effects?
September 9-10, 2009
Lister Hill Auditorium NLM, National Institutes of Health
Bethesda, Maryland
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Welcome
Terry F. Quill
Quill Law Group LLC
1667 K St, NW
Washington, DC 20006
202-508-1075
terryquill54@comcast.net
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Getting Started
 Announcements
 Reception
 Breaks
 Membership Opportunities
 Thank you
 Sponsors
 EPA
 Speakers
 Goals
 Some Perspective
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Goals
 Open an Industry/Agency and Inter-industry Dialogue
to:
 Facilitate EDSP Implementation
 Better understand procedural steps
 Address Interpretation of Tier 1 Screening Results
 Address the issue of “Functional Equivalence”
 Express lingering industry concerns
 Open a dialogue with the scientific community and
among potential order recipients
 Tee up future EDSP issues
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Some Perspective
 Lets look at the EDSP and potential issues in light of
the Congressional mandate.
 Issues related to the endocrine screening provisions of:
 The Federal Food, Drug, and Cosmetic Act, 21 U.S.C.
346a(p) (FFDCA §408p); the Food Quality Protection Act
(FQPA); and
 The Safe Drinking Water Act, 42 U.S.C. §300j-17.
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Issues Related to FFDCA §408(p)
(1) Development
Not later than 2 years after August 3, 1996, the
Administrator shall in consultation with the Secretary of
Health and Human Services 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.
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Issues
 “Screening Program”
 EPA’s program likely exceeds Congressional intent.
 But more complete screening and testing will help to minimize
false positive results that would be seen with minimal screening
programs.
 Screens/tests must be validated.
 What constitutes validation?
 Deliberate and methodical validation effort over the last 10+
years.
 E.g., has the frog metamorphosis assay been “validated”?
 Human testing only?
 It may be possible to challenge wildlife testing to the extent it is
required pursuant to FQPA order authority.
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Issues Continued
“Estrogenic or other endocrine effect”
 What is an estrogenic or other endocrine effect?
 How will it be determined that a substance may have such an
effect?
 EPA is addressing estrogen, androgen and thyroid effects.
 Environmental community and Congress are moving toward
other effects such as metabolism and weight regulation.
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HR 2996 Committee Report
Theo Colborn
1996: Association  Causation
2009: Theory  Causation
EPA will come under greater pressure to expand the program to new
areas, include a greater number of substances, include new media
(drinking water), and speed up screening and testing.
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Issues Continued
 EPA relied on the advice of the EDSTAC to develop the
EDSP.
 EPA, not EDSTAC, must comply with the statutory
requirements.
 Two tiered program.
 What is the purpose of Tier 1 Screening?
 Ability to interact with the endocrine system.
 What does “interact” mean?
 What about dose?
 Doesn’t everything interact with the endocrine system in some way
at some dose?
 Trigger Tier 2 Testing.
 Do we need to know the Tier 2 assays first?
 What are the Tier 2 assays?
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Issues Continued
 What can the Tier 1 assays tell us? What can’t they tell us?
 HR 2996 Committee Report
 “Develop and publish criteria for evaluating the results of Tier I
screening and determining whether a chemical should undergo
Tier II analysis within one year of enactment.”
 ISRTP Workshop, Session 1
 What is “other scientifically relevant information”?
 Functionally equivalent data?
 EPA Criteria.
 EPA’s Approach for Considering Other Scientifically Relevant
Information (two page document)
 ISRTP Workshop Session 2
 What data are generally available for pesticide chemicals?
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Issues Continued
 Can screening results be used to conduct cumulative
risk assessments?
 Can risk assessments be conducted with tier 1 data?
 Can exposures to different chemicals be “added”?
 Workshop Session 3.
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Issues Continued
 Where do we go after initial screening?
 How will EPA use the data?
 Will new screening assays be developed?
 Will screening results influence Tier 2 Assay
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development?
Will further validation be necessary?
Can we address concerns of animal rights groups?
Will Congress and special interest groups change
the program?
What can be done to improve the screening battery?
ISRPT Workshop Session 4.
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(2) Implementation
Not later than 3 years after August 3, 1996, after obtaining
public comment and review of the screening program
described in paragraph (1) by the scientific advisory panel
established under section 25(d) of the Federal Insecticide,
Fungicide, and Rodenticide Act (7 U.S.C. 136w(d)) or the
science advisory board established by section 4365 of title
42, the Administrator shall implement the program.
 Implementation was an issue in the Deadline Lawsuits
(NRDC, et al. v. Whitman). EPA claimed that it implemented
the program with publication of its Policy Statement. 53
Fed. Reg. 71542 (Dec. 28, 1998).
 ISRTP Workshop, Session 5.
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(3) Substances
In carrying out the screening program described in
paragraph (1), the Administrator
(A) shall provide for the testing of all
chemicals; and
pesticide
(B) may provide for the testing of any other
substance that may have an effect that is
cumulative to an effect of a pesticide chemical
if the Administrator determines that a substantial
population may be
exposed to such substance.
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Issues
 Under FFDCA, “pesticide chemicals” includes inerts.
 Phase 1 consists of 58 active pesticide ingredients and 9 inerts.
 Phase 1 based on exposure potential of “pesticide chemicals.”
 Prevent product deselection.
 EPA could use FIFRA data call-ins to require testing of pesticide chemicals.
 What does “cumulative to an effect of a pesticide chemical” mean?
 What is a “substantial population”?
 Are mixtures “substances” under the Act?
 Ironically, pesticide chemicals may be the most data rich chemicals and may
generate the least concern for endocrine effects. Yet Congress focused on
those substances.
 DCI provisions obviate need for FQPA testing.
 Data rich substances may be best to validate EDSP battery.
 Are we validating screening assays on the backs of the pesticide industry and initial
order recipients?
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(4) Exemption
Notwithstanding paragraph (3), the Administrator may, by order,
exempt from the requirements of this section a biologic
substance or other substance if the Administrator determines
that the substance is anticipated not to produce any effect in
humans similar to an effect produced by a naturally occurring
estrogen.
 Will EPA provide for exemptions? It is not required to provide
exemptions.
 How is it “anticipated” that a substance does not produce an
effect?
 Are those substances with sufficient available data?
 Does this overlap with the requirement that EPA must minimize
duplicative testing?
 Does this apply only to screening/testing for human effects and
only to estrogenic effects?
 Did Congress intend to allow wildlife testing but allow exemptions
only for human effects?
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(5) Collection of information
(A) In general
The Administrator shall issue an order to a registrant of a
substance for which testing is required under this
subsection, or to a person who manufactures or imports a
substance for which testing is required under this
subsection, to conduct testing in accordance with the
screening program described in paragraph (1), and submit
information obtained from the testing to the Administrator,
within a reasonable time period that the Administrator
determines is sufficient for the generation of the information.
(B) Procedures
To the extent practicable the Administrator shall minimize
duplicative testing of the same substance for the same
endocrine effect, develop, as appropriate, procedures for fair
and equitable sharing of test costs, and develop, as
necessary, procedures for handling of confidential
business information.
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Issues
 EPA shall issue testing orders to:
 Registrants
 Manufacturers
 Importers
 What is a testing order; what are the procedures? Will there
be due process protections? For example, can a
manufacturer challenge a testing order?
 What is a “reasonable time period”?
 EPA must (to the extent practicable) :
 Minimize duplicative testing.
 Develop procedures for cost sharing. Will EPA recreate
the data compensation problems of FIFRA?
 Develop procedures for developing CBI.
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Noncompliance
(C) Failure of registrants to submit information
 Much like FIFRA procedures.
(D) Noncompliance by other persons
Any person (other than a registrant) who fails to comply with an
order under subparagraph (A) shall be liable for the same
penalties and sanctions as are provided under section 16 of the
Toxic Substances Control Act (15 U.S.C. 2615) in the case of a
violation referred to in that section. Such penalties and sanctions
shall be assessed and imposed in the same manner as provided in
such section 16.
 TSCA §16 provides for both civil ($32,500 per day) and criminal
(up to 1 year imprisonment and $32.5K/day).
 TSCA testing rules, unlike testing orders, result from rulemaking
prior to requiring testing. This provides sufficient notice and due
process (the rule could be challenged).
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(6) Agency action
 In the case of any substance that is found, as a result of
testing and evaluation under this section, to have an
endocrine effect on humans, the Administrator shall, as
appropriate, take action under such statutory authority as is
available to the Administrator, including consideration under
other sections of this chapter, as is necessary to ensure the
protection of public health.
 How will it be determined whether a substance has an
“endocrine effect on humans”?
 Can Tier 1 lead to action?
 Will Tier 2 allow for an evaluation of human effects?
 Did Congress intend to allow wildlife testing while not
allowing EPA to take action on testing results for wildlife?
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Issues and Comments Related to the Safe
Drinking Water Act
Sec. 300j-17. Estrogenic substances screening program
In addition to the substances referred to in section
346a(p)(3)(B) of title 21 the Administrator may provide for
testing under the screening program authorized by section
346a(p) of title 21, in accordance with the provisions of
section 346a(p) of title 21, of any other substance that may
be found in sources of drinking water if the Administrator
determines that a substantial population may be exposed
to such substance.
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Issues
 Note that this provision utilizes the procedures of FFDCA § 408p.
Therefore, EPA may issue testing orders under the SDWA.
 The SDWA only adds substances to the provisions of the FFDCA
endocrine screening program.
 It is unclear from the language of the SDWA what additional
substances may be added.
 “may be found in sources of drinking water”
 What is meant by “may be found”
 What are “sources of drinking water”?
 “that a substantial population may be exposed to . . .”
 What is a “substantial population”?
 What is meant by “may be exposed”
 HR 2996
 Will we see these substances added soon?
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