[Federal Register Volume 80, Number 118 (Friday, June 19, 2015)]
[Notices]
[Pages 35350-35355]
[FR Doc No: 2015-15182]

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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPPT-2015-0305; FRL-9928-69]

Use of High Throughput Assays and Computational Tools; Endocrine
Disruptor Screening Program; Notice of Availability and Opportunity for
Comment

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This document describes how EPA is planning to incorporate an
alternative scientific approach to screen chemicals for their ability
to interact with the endocrine system. This will improve the Agency's
ability to fulfill its statutory mandate to screen pesticide chemicals
and other substances for their ability to cause adverse effects by
their interaction with the endocrine system. The approach incorporates
validated high throughput assays and a computational model and, based
on current research, can serve as an alternative for some of the
current assays in the Endocrine Disruptor Screening Program (EDSP) Tier
1 battery. EPA has partial screening results for over 1800 chemicals
that have been evaluated using high throughput assays and a
computational model for the estrogen receptor pathway. In the future,
EPA anticipates that additional alternative methods will be available
for EDSP chemical screening based on further advancements of high
throughput assays and computational models for other endocrine
pathways. Use of these alternative methods will accelerate the pace of
screening, decrease costs, and reduce animal testing. In addition, this
approach advances the goal of providing sensitive, specific,
quantitative, and efficient screening using alternative test methods to
some assays in the Tier 1 battery to protect human health and the
environment.

DATES: Comments must be received on or before August 18, 2015.

ADDRESSES: Submit your comments, identified by docket identification
(ID) number EPA-HQ-OPPT-2015-0305, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider to be Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute.
     Mail: Document Control Office (7407M), Office of Pollution
Prevention and Toxics (OPPT), Environmental Protection Agency, 1200
Pennsylvania Ave. NW., Washington, DC 20460-0001.
     Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at http://www.epa.gov/dockets/contacts.html.
    Additional instructions on commenting or visiting the docket, along
with more information about dockets generally, is available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: For technical information contact:
Jane Robbins, Office of Science Coordination and Policy (OSCP), Office
of Chemical Safety and Pollution Prevention, Environmental Protection
Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001;
telephone number:<PHONE_NUMBER>; email address<EMAIL_ADDRESS>    For general information contact: The TSCA-Hotline, ABVI-Goodwill,
422 South Clinton Ave., Rochester, NY 14620; telephone number: (202)
554-1404; email address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    This action is directed to the public in general, and may be of
interest to a wide range of stakeholders including those interested in
endocrine testing of chemicals (including pesticides), and the EDSP in
general. Since others also may be interested, the Agency has not
attempted to describe all the specific entities that may be affected by
this action.

B. What is the agency authority for taking this action?

    The EDSP is established under section 408(p) of the Federal Food,
Drug and

Cosmetic Act (FFDCA), 21 U.S.C. 346a(p). Section 408(p)(1) requires EPA
``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
effects as [EPA] may designate.'' [21 U.S.C. 346a(p)(1)]. Section
408(p)(2) requires that the screening program be implemented ``after
obtaining public comment and review . . . by the scientific advisory
panel established under section 25(d) of the Federal Insecticide,
Fungicide, and Rodenticide Act. . .'' [21 U.S.C. 346a(p)(2)].
    This document describes the new scientific methods that are
available as alternatives to some of the current EDSP Tier 1 screening
assays and solicits public comment on EPA's plan to use these
alternative approaches to screen chemicals for their ability to
interact with the endocrine system. The approach described in this
document is not binding on either EPA or any outside parties, and EPA
may depart from the approach presented in this document where
circumstances warrant and without prior notice.

C. What action is the agency taking?

    This document describes and solicits comments on how EPA is
planning to incorporate scientific advancements and tools into the
EDSP. The adoption of scientific advancements into the EDSP has been
underway and part of the public dialogue about EDSP for several years.
As EPA has consistently indicated, the Agency intends to continue to
incorporate in the EDSP new methods involving high throughput assays
and computational toxicology. Also, EPA has identified a universe of
approximately 10,000 chemicals as potential candidates for screening
and testing under the EDSP (Ref. 1). This approach is expected to
accelerate the pace of screening, add efficiencies, decrease costs, and
reduce animal testing.
    EPA is planning to incorporate the partial screening results from
validated high throughput assays and computational models as an
alternative to data from some of the current assays in the EDSP Tier 1
screening battery. Currently, EPA has partial screening results for
over 1800 chemicals that have been evaluated using the high throughput
assays and computational model for the estrogen receptor pathway.
    The use of high-throughput assays and computational models for EDSP
screening is an initial step in EPA's integration of 21st-century
integrated assessment and testing approaches broadly, beyond EDSP,
across a wide range of chemicals related to regulatory and non-
regulatory decisions made in programs under the Agency's purview (Ref.
2). Much of the knowledge gained in using these approaches for EDSP
screening will be useful in applying high throughput assays and
computational models to thousands of chemicals across many
toxicological endpoints and exposure scenarios.

D. What should I consider as I prepare my Comments for EPA?

    1. Submitting CBI. Do not submit this information to EPA through
regulations.gov or email. Clearly mark the part or all of the
information that you claim to be CBI. For CBI information in a disk or
CD-ROM that you mail to EPA, mark the outside of the disk or CD-ROM as
CBI and then identify electronically within the disk or CD-ROM the
specific information that is claimed as CBI. In addition to one
complete version of the comment that includes information claimed as
CBI, a copy of the comment that does not contain the information
claimed as CBI must be submitted for inclusion in the public docket.
Information so marked will not be disclosed except in accordance with
procedures set forth in 40 CFR part 2.
    2. Tips for preparing your comments. When preparing and submitting
your comments, see the commenting tips at http://www.epa.gov/dockets/comments.html.

II. Background

A. What is the Endocrine Disruptor Screening Program (EDSP)?

    The Food Quality Protection Act (FQPA) of 1996 amended FFDCA to
require EPA ``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 effects as [EPA] may designate'' (21 U.S.C.
346a(p)(1)). Also in 1996, the Agency chartered the Endocrine Disruptor
Screening and Testing Advisory Committee (EDSTAC), under the provisions
of the Federal Advisory Committee Act (FACA) (5 U.S.C. App. 2, section
9(c)), to provide advice on developing an endocrine disruptor screening
program (Ref. 3). The EDSTAC was comprised of members representing the
commercial chemical and pesticides industries, Federal and State
agencies, worker protection and labor organizations, environmental and
public health groups, and research scientists. EDSTAC recommended that
EPA's program address both potential human and wildlife effects;
examine effects on estrogen, androgen, and thyroid hormone-related
processes; and include non-pesticide chemicals, contaminants, and
mixtures in addition to pesticide chemicals (Ref. 2).
    In 1998, based on the EDSTAC recommendations, EPA established the
EDSP using a two-tiered approach (Ref. 4). The purpose of Tier 1
(referred to as ``screening'') is to identify substances that have
potential biological activity (``bioactivity'') in the estrogen,
androgen, or thyroid hormone pathways using a battery of assays. The
purpose of Tier 2 (referred to as ``testing'') is to identify and
establish a dose-response relationship for any adverse effects that
might result from the endocrine bioactivity identified through the Tier
1 assays. The ultimate purpose of the EDSP is to provide information to
the Agency that will allow the Agency to evaluate any possible
endocrine effects associated with the use of a chemical and take
appropriate steps to mitigate any related risks to ensure protection of
public health.
    In 2009, the Agency issued test orders requiring Tier 1 screening
for 67 chemicals (``List 1'') (Ref. 5). Between the time needed to
review the substantial volume of ``other scientifically relevant
information'' submitted by test order recipients to satisfy selected
screening assays, the time and resources of industry spent generating
data, the time spent by the Agency reviewing the information, and the
delays resulting from the limited laboratory capacity for conducting
many of the Tier 1 assays and corresponding time extension requests,
the review of the initial List 1 chemicals has taken over four years
and has imposed significant burdens on test order recipients and the
agency. The Agency is still finalizing the data evaluation records and
determinations concerning which of the List 1 chemicals need further
Tier 2 testing. More information on the EDSP history and the status of
current activities is available at http://www.epa.gov/endo.

B. What is meant by ``high throughput assays and computational model''?

    High throughput assays are automated methods that allow for a large
number of chemicals to be rapidly evaluated for a specific type of
bioactivity at the molecular or cellular level. This approach, which
can help identify compounds that may modulate specific

biological pathways, was initially developed by pharmaceutical
companies for drug discovery. The results of these methods provide an
initial understanding of a biochemical interaction or possible role of
a chemical in a given biological process. In vitro high throughput
assays are usually conducted using a microtiter plate: a plate
containing a grid with a large number of small divots called ``wells.''
The wells contain chemical and/or biological substrate (e.g., living
cells or proteins). Depending on the nature of the experiment, changes
can be detected (e.g., color, fluorescence, etc.) when the chemical is
added to indicate whether there is bioactivity. High throughput
microtiter plates typically come in multiples of 96 wells (96, 384, or
1536), so that through the use of robotics, data processing and control
software, liquid handling devices, and sensitive detection methods, an
extremely large number of chemicals can be evaluated very efficiently.
    High throughput assays can be run for a range of test chemical
concentrations and produce concentration-response information
representing the relationship between chemical concentration and
bioactivity. The concentration-response data from multiple assays can
be mathematically integrated in a computational model of a biological
pathway, providing values representative of a chemical's bioactivity in
that pathway (e.g., estrogen receptor pathway). To reduce non-specific
results, the computational model can use results from multiple assays
and technologies to predict whether a chemical is truly bioactive in
the pathway being evaluated. The most prominent cause of non-specific
results (activity in an assay that is likely not due to bioactivity of
the chemical in the pathways) is cytotoxicity in cell-based assays. In
other cases, chemicals influence the assays through a manner dependent
on the physics and chemistry of the technology platform (i.e., ``assay
interference'').

C. What is ToxCast\TM\?

    To improve efficiencies in screening and testing chemicals, EPA
scientists are harnessing advances in molecular and systems biology,
chemistry, toxicology, mathematics, and computer technology. In doing
this, they are helping to revolutionize chemical screening and safety
testing based on advances in computational toxicology. A major part of
this effort is the Agency's Toxicity Forecaster, or ToxCast\TM\, which
uses automated, robotics-assisted high throughput assays to expose
living cells or proteins to chemicals and measure the results. The high
throughput assays produce concentration-response information
representing the relationship between chemical concentration and
bioactivity. These innovative methods have the potential to quickly and
efficiently screen large numbers of chemicals and other substances.
ToxCast\TM\ is part of EPA's contribution to a federal research
collaboration called ``Toxicity Testing in the 21st Century'', or
``Tox21,'' pooling resources and expertise from EPA, the National
Institutes of Health and the U.S. Food and Drug Administration to use
robotics for screening thousands of chemicals for potential bioactivity
(Ref. 6).
    As part of EPA's commitment to gather and share its chemical data
openly and clearly, all ToxCast\TM\ chemical data are publicly
available through user-friendly web applications called the interactive
Chemical Safety for Sustainability (iCSS) and EDSP21 dashboards (Refs.
7 and 8). The EDSP21 and iCSS dashboards provide accessible portals for
users to search and query the ToxCast\TM\ chemical data. Users can
review chemicals and data of interest, as well as export the
information. Making ToxCast\TM\ data available through the dashboards
creates an environment that encourages external stakeholder
interactions identifying potential issues, concerns, and suggesting
improvements.

D. What is meant by the ToxCast\TM\ ER Model for bioactivity?

    The ToxCast\TM\ ER Model for bioactivity (``ER Model'') includes
data from 18 estrogen receptor (ER) high throughput assays from
ToxCast\TM\ that detect multiple events in the receptor pathway. The ER
Model also includes a computational module that integrates the assay
data to produce a value for ER agonist and antagonist bioactivity for
each chemical (Ref. 9). An ER agonist binds and activates the receptor,
and an antagonist binds and blocks activation. These 18 high throughput
assays measure bioactivity at different sites along the ER pathway
including receptor binding, receptor dimerization, chromatin binding of
the mature transcription factor, gene transcription and changes in
estrogen-receptor growth kinetics. Bioactivity (i.e., response) is
measured using various detection methods (e.g., fluorescence, etc.)
across a range of concentrations to examine potential concentration-
response relationships, including no change across concentrations
indicating no bioactivity. Concentration-response relationships for
each assay are mathematically integrated in the ``ER Model'' to
quantify bioactivity from multiple assays. The computational model
integrates the results of each of the 18 ER assays as an area under the
curve (AUC) for ER agonist or antagonist bioactivity for each chemical.
The bioactivity values generally range from 0 to 1 for each chemical,
with 0 indicating no bioactivity and 1 approximating the positive
reference chemical (e.g., estradiol for ER agonism).
    In order to validate the ER Model, ToxCast\TM\ data have been
collected and reviewed on over 1800 chemicals, including ER reference
agonists and antagonists (Ref. 10). ER agonist and antagonist
bioactivity scores from the ``ER Model'' compare very well with
reported bioactivity of reference chemicals across a range of
structures and potencies. Of the over 1800 chemicals tested, over 1700
chemicals had very low or no detectable ER bioactivity (Ref. 10). The
``ER Model'' bioactivity scores were validated by comparing the scores
to 45 reference chemicals, equivalent to a performance-based approach
to validation. EPA also compared ``ER Model'' results to a database of
curated uterotrophic studies published in peer-reviewed literature. ER
agonist bioactivity scores accurately predicted in vivo ER agonist
activity for a large set (~150) of chemicals with uterotrophic data
(Refs. 9 and 11). The validation of the ``ER Model'' as an alternative
screening method for three current Tier 1 assays (ER binding, ER
transcriptional activation (ERTA), and uterotrophic) was peer reviewed
by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)
Scientific Advisory Panel (SAP) in December 2014 (Refs. 9 and 11). The
FIFRA SAP fully endorsed the use of these alternatives for the ER
binding and ERTA assays; however, there was not consensus among panel
members on the use of the ``ER Model'' as an alternative for the
uterotrophic assay (Ref. 11). In response to the concerns raised by the
FIFRA SAP, EPA has published a paper clarifying the relationship
between ``ER Model'' bioactivity and uterotrophic results, and
illustrating that a uterotrophic assay would provide no added value if
``ER Model'' data are available (Ref. 12). Based on these findings, EPA
concludes that ``ER Model'' data are sufficient to satisfy the Tier 1
ER binding, ERTA and uterotrophic assay requirements. The Agency
intends to build on the performance-based validation approach presented
at the December 2014 FIFRA SAP expanding this approach to include

other key events in the estrogen pathway.

III. Using High Throughput Assays and Computational Models for
Screening

A. How Will ToxCast\TM\ data be used for screening in the EDSP?

    The ability to screen chemicals rapidly for bioactivity in several
endocrine pathways, and reducing the use of animals in testing, have
been EDSP goals since 1998, when the program was first adopted (Ref.
4). As previously noted, when the first Tier 1 orders (for List 1
chemicals) were issued in 2009, EPA had not confirmed the reliability
and relevance of the ToxCast\TM\ results so that they could be cited as
``other scientifically relevant information'' to satisfy the Tier 1 ER
binding, ERTA, and uterotrophic assays (Ref. 13). However, since that
time, EPA has reached a critical juncture, determining that the science
has progressed such that reevaluation of EPA's earlier position is
warranted. Based on scientific advances, EPA intends to implement the
use of high throughput assays and computational models to evaluate, and
to a significant extent, screen chemicals. The in vitro high throughput
and computational model alternatives provide an accurate quantitative
measure of specific endocrine pathway bioactivity and mechanisms. The
current Tier 1 battery includes animal-based assays that do not clearly
identify or differentiate pathways and mechanisms. Specifically, the
current Tier 1 ER binding, ERTA and uterotrophic assays do not provide
both estrogen agonist and antagonist activity and animals are required
to conduct the ER binding and uterotrophic assays.
    EPA is planning to adopt in vitro high throughput assays and
computational models for detecting and measuring ER agonist and
antagonist bioactivity as an alternative for three current Tier 1
assays: 1) ER binding in vitro assay (Ref. 14); 2) ER transcriptional
activation in vitro assay (ERTA) (Ref. 15); and 3) in vivo uterotrophic
assay (Refs. 16 and 17). EPA is also planning to accept existing
results for chemicals that have been evaluated using the ToxCast\TM\
``ER Model'' for bioactivity. The accompanying database contains the ER
agonist bioactivity and ER antagonist bioactivity for over 1800
chemicals and identifies those chemicals that are pesticide active
ingredients, pesticide inert ingredients, and on EDSP Lists 1 or 2
(Ref. 10). This is a ``living'' database that will continue to
incorporate bioactivity results for chemicals as they become available.
This database is available at http://www.epa.gov/endo and in the docket
identified for this document in a format that can be easily reviewed
and manipulated electronically (Ref. 10). It is important, however, not
to equate a determination of a chemical's bioactivity from the ``ER
Model'' with a determination that a chemical causes endocrine
disruption. The World Health Organization (WHO)/International Programme
on Chemical Safety (IPCS) defines endocrine disruption as being caused
by ``an exogenous substance or mixture that alters function(s) of the
endocrine system . . . and . . .consequently causes adverse health
effects in an intact organism or its progeny, or (sub)populations''
(Ref. 18). Bioactivity is an indicator that a chemical has the
potential to alter endocrine function, but (1) whether the chemical
actually alters endocrine function and (2) whether that altered
function produces an adverse outcome in an intact animal cannot be
determined without further testing (i.e., Tier 2 testing).
    The EDSP has been developed over the past 19 years, and has
demonstrated that the current screening process may take upwards of 5
years before a Tier 1 decision is available or Tier 2 test orders are
issued. In light of recent advances in high throughput assays and
computational models, and advances likely to come in the next two
years, it is prudent for the Agency to consider new, rapid screening
methods. The availability of additional alternative high throughput
assays and computational models in the near term will allow EPA to
screen more chemicals in less time, involve fewer animals, and cost
less for everyone. Furthermore, reconsideration of the EDSP List 2
chemicals may be appropriate since ``ER Model'' data are available for
many List 2 and other chemicals (Refs. 10 and 19). Ongoing use of high
throughput assays and computational models will address thousands of
chemicals in the future.
    These advancements in the EDSP screening program will not affect
the overall framework--i.e., the Tier 1 screening battery and Tier 2
testing approach focused on estrogen, androgen and thyroid pathways in
humans and wildlife remains unaffected. Instead, as discussed above,
EPA is planning to adopt sensitive, specific, quantitative, and
efficient screening methods that will rapidly screen many chemicals and
substantially decrease costs and animal use and may be used as an
alternative to some EDSP Tier 1 screening assays. Accordingly, EPA
intends a future recipient of an EDSP test order to be able to satisfy
the screening requirement for ER, ERTA, and uterotrophic in one of
three ways: (1) cite existing ToxCast\TM\ ``ER Model'' for bioactivity
data as ``other scientifically relevant information'' (where
available); (2) generate new data relying on the 18 ER high throughput
assays and the ToxCast\TM\ ``ER Model'' for bioactivity; or (3)
generate their own data using the current Tier 1 ER binding, ERTA, and
uterotrophic assays.

B. How Does EPA intend to use high throughput assays and computational
models for the EDSP in the future?

    EPA believes that ongoing adoption of alternative methods and
technologies will continue to advance EDSP screening of chemicals for
bioactivity in the estrogen, androgen, and thyroid pathways. EPA is
continuing research on the ``ER Model'' to determine if ToxCast\TM\
assays can provide comparable information as that of the Female Rat
Pubertal and the Fish Short Term Reproduction assays. In addition,
research continues on the ToxCast\TM\ ``AR Model'' for bioactivity
which, if fully validated, may be considered as an alternative (alone
or with the ``ER Model'') for the following current Tier 1 assays: AR
binding, Male Rat Pubertal, Hershberger, and Fish Short Term
Reproduction. Research is also underway to develop steroidogenesis
ToxCast\TM\ (STR) and thyroid (THY) bioactivity models. Over time, the
Agency's goal is to develop a set of ``non-animal'' high throughput
assays and computational bioactivity models as an alternative to all of
the assays in the current Tier 1 screening battery. The following table
is intended to illustrate the evolution of screening in the EDSP:

------------------------------------------------------------------------
                                           Alternative high throughput
 Current EDSP Tier 1 battery of assays    assays and computational model
                                             for EDSP Tier 1 battery
------------------------------------------------------------------------
Estrogen Receptor (ER) Binding.........  ER Model (alternative).
Estrogen Receptor Transactivation        ER Model (alternative).
 (ERTA).
Uterotrophic...........................  ER Model (alternative).
Female Rat Pubertal....................  ER, STR , and thyroid (THY)
                                          Models (Future).

Male Rat Pubertal......................  AR, STR, and THY Models
                                          (Future).
Androgen Receptor (AR) Binding.........  AR Model (Future).
Hershberger............................  AR Model (Future).
Aromatase..............................  STR Model (Future).
Steroidogenesis (STR)..................  STR Model (Future).
Fish Short Term Reproduction...........  ER, AR, and STR Models
                                          (Future).
Amphibian Metamorphosis................  THY Model (Future).
------------------------------------------------------------------------

    The table indicates combinations of various alternative assays and
models that might overlap for evaluating potential endocrine
bioactivity of chemicals. The in vitro high throughput and
computational model alternatives provide a focused evaluation of the
mechanistic aspects of endocrine pathways, thereby providing specific
and quantitative measures of bioactivity. Several assays in the Tier 1
battery rely on intact animals and identify bioactivity in the multiple
biological pathways present. For this reason, the specificity of the in
vitro high throughput and computational model alternatives may be more
informative of specific endocrine pathway bioactivity.
    The annual EDSP Comprehensive Management Plan and future FIFRA SAP
meetings are opportunities for staying informed on EPA's scientific
progress on the evolution of Tier 1 screening in the EDSP. For
information, visit EPA's Web site (http://www.epa.gov/endo) or sign-up
to receive announcements go to (http://www.epa.gov/endo/pubs/assayvalidation/listserv.htm).

IV. Issues for Comment

    In connection with EPA's stated intention to use the scientific
tools discussed in this Notice as alternatives to some of the current
EDSP Tier 1 screening assays, EPA is specifically seeking public
comment on the following:
    1. The use of the ToxCast\TM\ ``ER Model'' for bioactivity as an
alternative method for the current ER binding and ERTA Tier 1 screening
assays.
    2. The use of the ToxCast\TM\ ``ER Model'' for bioactivity as an
alternative method for the current uterotrophic Tier 1 screening assay.
    3. The use of results from the ToxCast\TM\ ``ER Model'' for
bioactivity on over 1800 chemicals as partial screening for the
estrogen receptor pathway.

V. References

    The following is a listing of the documents that are specifically
referenced in this document. The docket includes these documents and
other information considered by EPA, including documents that are
referenced within the documents that are included in the docket, even
if the referenced document is not physically located in the docket. For
assistance in locating these other documents, please consult the
technical person listed under FOR FURTHER INFORMATION CONTACT.

1. U.S. EPA. Endocrine Disruptor Screening Program; Universe of
Chemicals and General Validation Principles. November 2012.
Available at http://www.epa.gov/endo/pubs/edsp_chemical_universe_and_general_validations_white_paper_11_12.pdf.

2. U.S. EPA. Endocrine Disruptor Screening Program for the 21st
Century: (EDSP21 Work Plan); The Incorporation of In Silico Models
and In Vitro High Throughput Assays in the Endocrine Disruptor
Screening Program (EDSP) for Prioritization and Screening; Summary
Overview. A Part of the EDSP Comprehensive Management Plan.
September 30, 2011. Available at http://www.epa.gov/endo/pubs/edsp21_work_plan_summary%20_overview_final.pdf.
3. U.S. EPA. Endocrine Disruptor Screening and Testing Advisory
Committee (EDSTAC); Final Report. August 1998. Available at http://www.epa.gov/endo/pubs/edspoverview/finalrpt.htm.
4. U.S. EPA. Endocrine Disruptor Screening Program; Proposed
Statement of Policy; Notice. Federal Register (63 FR 71542, December
28, 1998) (FRL-6052-9).
5. U.S. EPA. Endocrine Disruptor Screening Program; Tier 1 Screening
Order Issuance Announcement; Notice. Federal Register (74 FR 54422,
October 21, 2009) (FRL-8434-8).
6. U.S. EPA. Office of Research and Development (ORD); Description
of Computational Toxicology Research Program. Available at http://epa.gov/ncct.
7. U.S. EPA. Interactive Chemical Safety for Sustainability (iCSS)
Dashboard, Version 0.5. Available at http://actor.epa.gov/dashboard.
8. U.S. EPA. EDSP21 Dashboard. Available at http://actor.epa.gov/edsp21.
9. U.S. EPA. Integrated Bioactivity and Exposure Ranking: A
Computational Approach for the Prioritization and Screening of
Chemicals in the Endocrine Disruptor Screening Program. December
2014. Docket ID No. EPA-HQ-OPP-2014-0614-0003. Available at http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2014-0614-0003.
10. U.S. EPA. Endocrine Disruptor Screening Program (EDSP); Estrogen
Receptor Bioactivity Based on ToxCa \TM\ ``ER Model.'' June 1, 2015.
Available at http://www.epa.gov/endo.
11. U.S. EPA. FIFRA SAP Minutes No. 2015-01. FIFRA SAP Meeting on
the Integrated Bioactivity and Exposure-Based Prioritization and
Screening, held December 2-4, 2014. Docket ID No. EPA-HQ-OPP-2014-
0614-0029. March 2, 2015. Available at http://www.epa.gov/scipoly/sap/meetings/2014/december/120214minutes.pdf.
12. Browne, P., Judson, R.S., Casey, W., Kleinstreuer, N., Thomas,
R.S. Screening Chemicals For Estrogen Receptor Bioactivity Using A
Computational Model. Manuscript accepted for publication. Environ.
Sci. Technol. June 12, 2015. Available in the docket and
electronically at http://pubs.acs.org/journal/esthag.
13. U.S. EPA. Endocrine Disruptor Screening Program; Policies and
Procedures for Initial Screening; Notice. Federal Register (74 FR
17560, April 15, 2009) (FRL-8399-9). Note: the status and progress
of all List 1 Tier 1 orders are available at http://www.epa.gov/endo/pubs/toresources/index.htm.
14. U.S. EPA. Endocrine Disruptor Screening Program Test Guidelines;
OPPTS 890.1250: Estrogen Receptor Binding Assay Using Rat Uterine
Cytosol (ER-RUC). October 2009. EPA 740-C-09-005. Available at
http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series890.htm.
15.U.S.EPA. Endocrine Disruptor Screening Program Test Guidelines;
OPPTS 890.1300: Estrogen Receptor Transcriptional Activation (Human
Cell Line (HeLa-9903)). October 2009. EPA 740-C-09-006. Available at
http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series890.htm.
16.U.S.EPA. Endocrine Disruptor Screening Program Test Guidelines;
OPPTS 890.1600: Uterotrophic Assay. October 2009. EPA 740-C-09-0010.
Available at http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series890.htm.
17. Organization of Economic Co-operation and Development (OECD).
Test Guideline No. 440:Uterotrophic Bioassay in Rodents: A short-
term screening test for oestrogenic properties. OECD Guidelines for
the Testing of Chemicals, Section 4, OECD Publishing, Paris. DOI:
http://dx.doi.org/10.1787/

9789264067417-en.
18. World Health Organization (WHO)/International Programme on
Chemical Safety (IPCS). Global Assessment of the State-of-the-
Science of Endocrine Disruptors. WHO/IPCS/EDC/02.2. 2002. Available
at http://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en.
19. U.S. EPA. Endocrine Disruptor Screening Program; Final Second
List of Chemicals and Substances for Tier 1 Screening; Notice.
Federal Register (78 FR 35922, June 14, 2013) (FRL-9375-8).
Available at http://www.gpo.gov/fdsys/pkg/FR-2013-06-14/pdf/2013-14232.pdf.

    Authority:  21 U.S.C. 346a(p).

    Dated: June 11, 2015.
James J. Jones,
Assistant Administrator, Office of Chemical Safety and Pollution
Prevention.
[FR Doc. 2015-15182 Filed 6-18-15; 8:45 am]
BILLING CODE 6560-50-P


[Federal Register Volume 82, Number 80 (Thursday, April 27, 2017)]
[Notices]
[Pages 19413-19414]
[FR Doc No: 2017-08534]

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SECURITIES AND EXCHANGE COMMISSION

[Release Nos. 33-10350; 34-80512; File No. 265-27]

SEC Advisory Committee on Small and Emerging Companies

AGENCY: Securities and Exchange Commission.

ACTION: Notice of meeting.

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SUMMARY: The Securities and Exchange Commission Advisory Committee on
Small and Emerging Companies is providing notice that it will hold a
public meeting on Wednesday, May 10, 2017, in Multi-Purpose Room LL-006
at the Commission's headquarters, 100 F Street NE., Washington, DC. The
meeting will begin at 9:30 a.m. (EST) and will be open to the public.
The meeting will be webcast on the Commission's Web site at
www.sec.gov. Persons needing special accommodations to take part
because of a disability should notify the contact person listed below.
The public is invited to submit written statements to the Committee.
The agenda for the meeting includes matters relating to rules and
regulations affecting small and emerging companies under the federal
securities laws. Notice of this meeting is less than fifteen days prior
to the meeting due to an administrative delay.

DATES: The public meeting will be held on Wednesday, May 10, 2017.
Written statements should be received on or before May 8, 2017.

ADDRESSES: The meeting will be held at the Commission's headquarters,
100 F Street NE., Washington, DC. Written statements may be submitted
by any of the following methods:

Electronic Statements

     Use the Commission's Internet submission form (http://www.sec.gov/info/smallbus/acsec.shtml); or
     Send an email message to<EMAIL_ADDRESS>Please
include File Number 265-27 on the subject line; or

Paper Statements

     Send paper statements to Brent J. Fields, Federal Advisory
Committee Management Officer, Securities and Exchange Commission, 100 F
Street NE., Washington, DC 20549-1090.

All submissions should refer to File No. 265-27. This file number
should be included on the subject line if email is used. To help us
process and review your statement more efficiently, please use only one
method. The Commission will post all statements on the Advisory
Committee's Web site (https://

www.sec.gov/info/smallbus/acsec.shtml).
    Statements also will be available for Web site viewing and printing
in the Commission's Public Reference Room, 100 F Street NE.,
Washington, DC 20549, on official business days between the hours of
10:00 a.m. and 3:00 p.m. All statements received will be posted without
change; we do not edit personal identifying information from
submissions. You should submit only information that you wish to make
available publicly.

FOR FURTHER INFORMATION CONTACT: Julie Z. Davis, Senior Special
Counsel, at<PHONE_NUMBER>, Office of Small Business Policy, Division
of Corporation Finance, Securities and Exchange Commission, 100 F
Street NE., Washington, DC 20549-3628.

SUPPLEMENTARY INFORMATION: In accordance with Section 10(a) of the
Federal Advisory Committee Act, 5 U.S.C.-App. 1, and the regulations
thereunder, Elizabeth M. Murphy, responsible as Designated Federal
Officer of the Committee, has ordered publication of this notice.

    Dated: April 24, 2017.
Brent J. Fields,
Committee Management Officer.
[FR Doc. 2017-08534 Filed 4-26-17; 8:45 am]
 BILLING CODE 8011-01-P