FIFRA Scientific Advisory Panel Meeting CHARGE QUESTIONS

Scientific Issues Associated with Prioritizing the Universe of Endocrine Disruptor Screening Program (EDSP) Chemicals Using Computational Toxicology Tools

The agency intends to screen those chemicals which have the greatest potential to interact with the endocrine systems in humans and other species. To that end, EPA has proposed an approach to determine the order in which to screen certain classes of chemicals (

e.g., drinking water contaminants and pesticide inert ingredients, including fragrances) using the Tier 1 battery under EPA’s Endocrine Disruptor Screening Program (EDSP). This proposed chemical prioritization process uses existing information including physicochemical properties and exposure information together with information from computational toxicology methods, including in silico expert systems, effects-based chemical category and read-across concepts, and empirical in vitro

low throughput and high throughput (HTP) testing. Thus, a number of specific current and emerging technical methods are involved in the proposed chemical prioritization process to cover the large EDSP chemical inventory

See the attachment for complete text.

EPA Final Charge

3 comments. Leave a Reply

  1. CPDA

    Given the deficiencies in EPA’s original ICR, OMBs approval on its face would
    appear to violate the Paperwork Reduction Act. OMB has sole authority for interpreting
    the PRA’s provisions and applying them to the ICRs agencies submit, but it
    cannot defer to the judgment of EPA. OMB concurs, for in the Information Collection
    Rule OMB says:

    OMB [not the agency] shall determine whether the collection of information,
    as submitted by the agency, is necessary for the proper performance of the
    agency’s functions…22

    OMB [not the agency] will … independently assess any collection of information
    to the extent that the agency exercises discretion in its implementation.
    Similarly, it is OMB⎯ not EPA⎯that has the sole authority to determine “whether
    the burden of the collection of information is justified by its practical utility.”24

    Complete Statement:!documentDetail;D=EPA-HQ-OPPT-2007-1081-0046

  2. American Chemistry Council

    Subsequently, OMB approved the information collection activity of the Agency for
    EDSP List 1. However, OMB issued Terms of Clearance which included very specific
    conditions the Agency would need to meet prior to the Agency expanding the list of EDSP
    substances. The OMB Terms of Clearance3 state:

    This information collection is approved for the 67 chemicals published by EPA at
    74 Fed. Reg. 17579 (April 15, 2009). OMB appreciates the continuing dialog with
    respect to the practical utility of the Tier I battery of EDSP assays and the role
    that the results from these first 67 chemicals will play in ensuring practical utility
    for subsequent groups of chemicals. Nonetheless, under the principles of the PRA,
    EPA should promote and encourage test order recipients to submit Other
    Scientifically Relevant Information (OSRI) in lieu of performing all or some of
    the Tier I assays, and EPA should accept OSRI as sufficient to satisfy the test
    orders to the greatest extent possible. For this reason, and to further validate
    EPA’s burden estimates, OMB requests that EPA provide a report re-estimating
    the burden of this information collection based on responses to the Tier I test
    orders, including the use of cost-sharing and data compensation, the submission
    and acceptance of existing data and OSRI, and description of any instances in
    which submission of OSRI was deemed insufficient to satisfy the testing order.
    OMB requests this report prior to or at the time of submission of revision of this
    information collection to cover additional chemicals. In addition, in order to
    ensure that EPA has maximized the practical utility of the Tier I assays as the
    program moves forward, EPA should ensure sufficient opportunity prior to
    submission of any revision to this collection for public comment and peer review
    of the EPA tools to be developed to guide agency decisions on whether a
    chemical must proceed to Tier II, including the Weight of the Evidence Approach
    and Standard Evaluation Procedures.

    See complete comments:!documentDetail;D=EPA-HQ-OPPT-2007-1081-0042

  3. Johns Hopkins

    New OECD Test Guidelines Available for Endocrine Disruptor Testing

    The Organization for Economic Co-operation and Development (OECD) has
    officially adopted two test guidelines for test methods to identify
    substances with the potential to affect the function of the endocrine
    system. Both test guidelines describe in vitro methods that do not use
    animals, and the tests are appropriate for use in the U.S. Environmental
    Protection Agency (EPA) Endocrine Disruptor Screening Program.

    The new test guidelines are available on the ICCVAM website:
    OECD Test Guideline 457: BG1Luc Estrogen Receptor Transactivation Test
    Method for Identifying Estrogen Receptor Agonists and Antagonists is
    available at link. (PDF)

    OECD Test Guideline 455: Performance-Based Test Guideline for Stably
    Transfected Transactivation In Vitro Assays to Detect Estrogen Receptor
    Agonists is available at link. (PDF)

    Test Guideline 457 describes the BG1Luc estrogen receptor (ER)
    transactivation (TA) assays to detect ER agonist and antagonists and
    provides performance standards for each assay. The test guideline was
    based on data from an international validation study coordinated by the
    National Toxicology Program Interagency Center for the Evaluation
    ofAlternative Toxicological Methods (NICEATM). The validation study
    included laboratories in the United States, Japan, and Italy.

    NICEATM worked closely with the EPA to usher this method through the OECD
    nomination and adoption process. The adoption of Test Guideline 457 means
    that these methods may now be used in the 34 member countries of the
    OECD. In July 2012, the EPA announced its acceptance of the BG1 method
    as an alternative to the HeLa9903 TA assay in response to a
    recommendation by the Interagency Coordinating Committee on the
    Validation of Alternative Methods (ICCVAM).

    Test Guideline 455 has been updated to include both the BG1 and HeLa9903
    methods, and now describes general characteristics of stably transfected
    transactivation in vitro assays to detect ER agonists. This
    performance-based test guideline also provides standards for development
    of new test methods of this type. These standardsinclude a harmonized
    list of reference chemicals that should be tested during assay
    development, as well as performance standards that should be met by
    successful assays.

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