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.
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
and
OMB [not the agency] will … independently assess any collection of information
to the extent that the agency exercises discretion in its implementation.
23
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: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2007-1081-0046
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: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2007-1081-0042
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.