September 9-10, 2009 Lister Hill Auditorium NLM, National Institutes of Health Bethesda, Maryland

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

1Quill Law Group LLC

Welcome

Terry F. Quill

Quill Law Group LLC1667 K St, NW

Washington, DC 20006202-508-1075

[email protected]


Getting StartedAnnouncements

ReceptionBreaksMembership Opportunities

Thank youSponsorsEPASpeakers

Goals

Some Perspective

3Quill Law Group LLP

GoalsOpen an Industry/Agency and Inter-industry

Dialogue to:Facilitate EDSP Implementation

Better understand procedural stepsAddress Interpretation of Tier 1 Screening ResultsAddress 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


Some PerspectiveLets 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.


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.


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.


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. 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.


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?


Issues ContinuedWhat 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 2What data are generally available for pesticide

chemicals?10

Quill Law Group LLC

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.


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

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.


(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.


(3) Substances

In carrying out the screening program described in paragraph (1), the Administrator

(A) shall provide for the testing of all pesticide chemicals; and

(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.


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?


(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?


(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.


IssuesEPA shall issue testing orders to:

RegistrantsManufacturers 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. 18Quill Law Group LLC

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).


(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? 20Quill Law Group LLC

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.


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?


September 9-10, 2009 Lister Hill Auditorium NLM, National Institutes of Health Bethesda, Maryland

Documents

Transcript of September 9-10, 2009 Lister Hill Auditorium NLM, National Institutes of Health Bethesda, Maryland