80 FR 35350 - Use of High Throughput Assays and Computational Tools; Endocrine Disruptor Screening Program; Notice of Availability and Opportunity for Comment

ENVIRONMENTAL PROTECTION AGENCY

Federal Register Volume 80, Issue 118 (June 19, 2015)

Page Range		35350-35355
FR Document		2015-15182
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.
Federal Register, Volume 80 Issue 118 (Friday, June 19, 2015)
[Federal Register Volume 80, Number 118 (Friday, June 19, 2015)]
[Notices]
[Pages 35350-35355]
From the Federal Register Online  [www.thefederalregister.org]
[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: (202) 564-6625; email address: [email protected].
    For general information contact: The TSCA-Hotline, ABVI-Goodwill, 
422 South Clinton Ave., Rochester, NY 14620; telephone number: (202) 
554-1404; email address: [email protected].

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

[[Page 35351]]

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

[[Page 35352]]

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

[[Page 35353]]

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).

[[Page 35354]]

 
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/

[[Page 35355]]

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.thefederalregister.org/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
35350 Federal Register / Vol. 80, No. 118 / Friday, June 19, 2015 / Notices

may claim all or part of a response and approval pursuant to 5 CFR efficient screening using alternative test
confidential. EPA will disclose 1320.12. EPA will issue another Federal methods to some assays in the Tier 1
information that is covered by a claim Register document pursuant to 5 CFR battery to protect human health and the
of confidentiality only to the extent 1320.5(a)(1)(iv) to announce the environment.
permitted by, and in accordance with, submission of the ICR to OMB and the DATES: Comments must be received on
the procedures in TSCA section 14 and opportunity to submit additional or before August 18, 2015.
40 CFR part 2. comments to OMB. If you have any ADDRESSES: Submit your comments,
Burden statement: The annual public questions about this ICR or the approval identified by docket identification (ID)
reporting and recordkeeping burden for process, please contact the technical number EPA–HQ–OPPT–2015–0305, by
this collection of information is person listed under FOR FURTHER one of the following methods:
estimated to average 31.5 hours per INFORMATION CONTACT. • Federal eRulemaking Portal: http://
response. Burden is defined in 5 CFR Authority: 44 U.S.C. 3501 et seq. www.regulations.gov. Follow the online
1320.3(b). instructions for submitting comments.
The ICR, which is available in the Dated: June 10, 2015.
Do not submit electronically any
docket along with other related James Jones, information you consider to be
materials, provides a detailed Assistant Administrator, Office of Chemical Confidential Business Information (CBI)
explanation of the collection activities Safety and Pollution Prevention. or other information whose disclosure is
and the burden estimate that is only [FR Doc. 2015–14946 Filed 6–18–15; 8:45 am] restricted by statute.
briefly summarized here: BILLING CODE 6560–50–P • Mail: Document Control Office
Respondents/Affected Entities: (7407M), Office of Pollution Prevention
Entities potentially affected by this ICR and Toxics (OPPT), Environmental
are companies that manufacture, ENVIRONMENTAL PROTECTION Protection Agency, 1200 Pennsylvania
process or import chemical substances, AGENCY Ave. NW., Washington, DC 20460–0001.
mixtures or categories. [EPA–HQ–OPPT–2015–0305; FRL–9928–69] • Hand Delivery: To make special
Estimated total number of potential arrangements for hand delivery or
respondents: 1. Use of High Throughput Assays and delivery of boxed information, please
Frequency of response: On occasion. Computational Tools; Endocrine follow the instructions at http://
Estimated total average number of Disruptor Screening Program; Notice www.epa.gov/dockets/contacts.html.
responses for each respondent: 1. of Availability and Opportunity for Additional instructions on
Estimated total annual burden hours: Comment commenting or visiting the docket,
31.5 hours. along with more information about
Estimated total annual costs: $2,388. AGENCY: Environmental Protection dockets generally, is available at http://
This includes an estimated burden cost Agency (EPA). www.epa.gov/dockets.
of $2,388 and an estimated cost of $0 for ACTION: Notice. FOR FURTHER INFORMATION CONTACT: For
capital investment or maintenance and technical information contact: Jane
operational costs. SUMMARY: This document describes how
EPA is planning to incorporate an Robbins, Office of Science Coordination
III. Are There Changes in the Estimates alternative scientific approach to screen and Policy (OSCP), Office of Chemical
from the Last Approval? chemicals for their ability to interact Safety and Pollution Prevention,
with the endocrine system. This will Environmental Protection Agency, 1200
There is a decrease of 916 hours in the
improve the Agency’s ability to fulfill its Pennsylvania Ave. NW., Washington,
total estimated respondent burden
statutory mandate to screen pesticide DC 20460–0001; telephone number:
compared with that identified in the ICR
chemicals and other substances for their (202) 564–6625; email address:
currently approved by OMB. This
ability to cause adverse effects by their robbins.jane@epa.gov.
decrease reflects additional both For general information contact: The
adjustment changes from a reduction in interaction with the endocrine system.
The approach incorporates validated TSCA-Hotline, ABVI-Goodwill, 422
the assumed number of PAIR reports South Clinton Ave., Rochester, NY
filed annually, and program changes high throughput assays and a
computational model and, based on 14620; telephone number: (202) 554–
resulting from mandatory electronic 1404; email address: TSCA-Hotline@
submissions of PAIR reports. In recent current research, can serve as an
alternative for some of the current epa.gov.
years (FY 2011–FY 2014), EPA has
received no PAIR submissions and, for assays in the Endocrine Disruptor SUPPLEMENTARY INFORMATION:
the purposes of this analysis, EPA Screening Program (EDSP) Tier 1 I. General Information
assumes an annual rate of one battery. EPA has partial screening
submission per year. At the time OMB results for over 1800 chemicals that A. Does this action apply to me?
last renewed this ICR, EPA estimated an have been evaluated using high This action is directed to the public
average of 33 reports from 14.8 throughput assays and a computational in general, and may be of interest to a
submitters based on fiscal year 2006– model for the estrogen receptor wide range of stakeholders including
2010 data. The ICR supporting pathway. In the future, EPA anticipates those interested in endocrine testing of
statement provides a detailed analysis of that additional alternative methods will chemicals (including pesticides), and
the change in burden estimate. This be available for EDSP chemical the EDSP in general. Since others also
screening based on further
asabaliauskas on DSK5VPTVN1PROD with NOTICES

change is both an adjustment and a may be interested, the Agency has not
program change. advancements of high throughput assays attempted to describe all the specific
and computational models for other entities that may be affected by this
IV. What is the Next Step in the Process endocrine pathways. Use of these action.
for this ICR? alternative methods will accelerate the
EPA will consider the comments pace of screening, decrease costs, and B. What is the agency authority for
received and amend the ICR as reduce animal testing. In addition, this taking this action?
appropriate. The final ICR package will approach advances the goal of providing The EDSP is established under section
then be submitted to OMB for review sensitive, specific, quantitative, and 408(p) of the Federal Food, Drug and

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Cosmetic Act (FFDCA), 21 U.S.C. integration of 21st-century integrated protection and labor organizations,
346a(p). Section 408(p)(1) requires EPA assessment and testing approaches environmental and public health
‘‘to develop a screening program, using broadly, beyond EDSP, across a wide groups, and research scientists. EDSTAC
appropriate validated test systems and range of chemicals related to regulatory recommended that EPA’s program
other scientifically relevant information and non-regulatory decisions made in address both potential human and
to determine whether certain substances programs under the Agency’s purview wildlife effects; examine effects on
may have an effect in humans that is (Ref. 2). Much of the knowledge gained estrogen, androgen, and thyroid
similar to an effect produced by a in using these approaches for EDSP hormone-related processes; and include
naturally occurring estrogen, or such screening will be useful in applying non-pesticide chemicals, contaminants,
other effects as [EPA] may designate.’’ high throughput assays and and mixtures in addition to pesticide
[21 U.S.C. 346a(p)(1)]. Section 408(p)(2) computational models to thousands of chemicals (Ref. 2).
requires that the screening program be chemicals across many toxicological In 1998, based on the EDSTAC
implemented ‘‘after obtaining public endpoints and exposure scenarios. recommendations, EPA established the
comment and review . . . by the EDSP using a two-tiered approach (Ref.
scientific advisory panel established D. What should I consider as I prepare 4). The purpose of Tier 1 (referred to as
under section 25(d) of the Federal my Comments for EPA? ‘‘screening’’) is to identify substances
Insecticide, Fungicide, and Rodenticide 1. Submitting CBI. Do not submit this that have potential biological activity
Act. . .’’ [21 U.S.C. 346a(p)(2)]. information to EPA through (‘‘bioactivity’’) in the estrogen,
This document describes the new regulations.gov or email. Clearly mark androgen, or thyroid hormone pathways
scientific methods that are available as the part or all of the information that using a battery of assays. The purpose
alternatives to some of the current EDSP you claim to be CBI. For CBI of Tier 2 (referred to as ‘‘testing’’) is to
Tier 1 screening assays and solicits information in a disk or CD–ROM that identify and establish a dose-response
public comment on EPA’s plan to use you mail to EPA, mark the outside of the relationship for any adverse effects that
these alternative approaches to screen disk or CD–ROM as CBI and then might result from the endocrine
chemicals for their ability to interact identify electronically within the disk or bioactivity identified through the Tier 1
with the endocrine system. The CD–ROM the specific information that assays. The ultimate purpose of the
approach described in this document is is claimed as CBI. In addition to one EDSP is to provide information to the
not binding on either EPA or any complete version of the comment that Agency that will allow the Agency to
outside parties, and EPA may depart includes information claimed as CBI, a evaluate any possible endocrine effects
from the approach presented in this copy of the comment that does not associated with the use of a chemical
document where circumstances warrant contain the information claimed as CBI and take appropriate steps to mitigate
and without prior notice. must be submitted for inclusion in the any related risks to ensure protection of
public docket. Information so marked public health.
C. What action is the agency taking? In 2009, the Agency issued test orders
will not be disclosed except in
This document describes and solicits accordance with procedures set forth in requiring Tier 1 screening for 67
comments on how EPA is planning to 40 CFR part 2. chemicals (‘‘List 1’’) (Ref. 5). Between
incorporate scientific advancements and 2. Tips for preparing your comments. the time needed to review the
tools into the EDSP. The adoption of When preparing and submitting your substantial volume of ‘‘other
scientific advancements into the EDSP comments, see the commenting tips at scientifically relevant information’’
has been underway and part of the submitted by test order recipients to
http://www.epa.gov/dockets/
public dialogue about EDSP for several satisfy selected screening assays, the
comments.html.
years. As EPA has consistently time and resources of industry spent
indicated, the Agency intends to II. Background generating data, the time spent by the
continue to incorporate in the EDSP Agency reviewing the information, and
A. What is the Endocrine Disruptor
new methods involving high throughput the delays resulting from the limited
Screening Program (EDSP)?
assays and computational toxicology. laboratory capacity for conducting many
Also, EPA has identified a universe of The Food Quality Protection Act of the Tier 1 assays and corresponding
approximately 10,000 chemicals as (FQPA) of 1996 amended FFDCA to time extension requests, the review of
potential candidates for screening and require EPA ‘‘to develop a screening the initial List 1 chemicals has taken
testing under the EDSP (Ref. 1). This program, using appropriate validated over four years and has imposed
approach is expected to accelerate the test systems and other scientifically significant burdens on test order
pace of screening, add efficiencies, relevant information, to determine recipients and the agency. The Agency
decrease costs, and reduce animal whether certain substances may have an is still finalizing the data evaluation
testing. effect in humans that is similar to an records and determinations concerning
EPA is planning to incorporate the effect produced by a naturally occurring which of the List 1 chemicals need
partial screening results from validated estrogen, or such other effects as [EPA] further Tier 2 testing. More information
high throughput assays and may designate’’ (21 U.S.C. 346a(p)(1)). on the EDSP history and the status of
computational models as an alternative Also in 1996, the Agency chartered the current activities is available at http://
to data from some of the current assays Endocrine Disruptor Screening and www.epa.gov/endo.
in the EDSP Tier 1 screening battery. Testing Advisory Committee (EDSTAC),
Currently, EPA has partial screening under the provisions of the Federal B. What is meant by ‘‘high throughput
asabaliauskas on DSK5VPTVN1PROD with NOTICES

results for over 1800 chemicals that Advisory Committee Act (FACA) (5 assays and computational model’’?
have been evaluated using the high U.S.C. App. 2, section 9(c)), to provide High throughput assays are automated
throughput assays and computational advice on developing an endocrine methods that allow for a large number
model for the estrogen receptor disruptor screening program (Ref. 3). of chemicals to be rapidly evaluated for
pathway. The EDSTAC was comprised of a specific type of bioactivity at the
The use of high-throughput assays members representing the commercial molecular or cellular level. This
and computational models for EDSP chemical and pesticides industries, approach, which can help identify
screening is an initial step in EPA’s Federal and State agencies, worker compounds that may modulate specific

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other key events in the estrogen identifies those chemicals that are overall framework—i.e., the Tier 1
pathway. pesticide active ingredients, pesticide screening battery and Tier 2 testing
inert ingredients, and on EDSP Lists 1 approach focused on estrogen, androgen
III. Using High Throughput Assays and
or 2 (Ref. 10). This is a ‘‘living’’ database and thyroid pathways in humans and
Computational Models for Screening
that will continue to incorporate wildlife remains unaffected. Instead, as
A. How Will ToxCastTM data be used for bioactivity results for chemicals as they discussed above, EPA is planning to
screening in the EDSP? become available. This database is adopt sensitive, specific, quantitative,
The ability to screen chemicals available at http://www.epa.gov/endo and efficient screening methods that
rapidly for bioactivity in several and in the docket identified for this will rapidly screen many chemicals and
endocrine pathways, and reducing the document in a format that can be easily substantially decrease costs and animal
use of animals in testing, have been reviewed and manipulated use and may be used as an alternative
EDSP goals since 1998, when the electronically (Ref. 10). It is important, to some EDSP Tier 1 screening assays.
program was first adopted (Ref. 4). As however, not to equate a determination
Accordingly, EPA intends a future
previously noted, when the first Tier 1 of a chemical’s bioactivity from the ‘‘ER
recipient of an EDSP test order to be
orders (for List 1 chemicals) were issued Model’’ with a determination that a
able to satisfy the screening requirement
in 2009, EPA had not confirmed the chemical causes endocrine disruption.
for ER, ERTA, and uterotrophic in one
reliability and relevance of the The World Health Organization (WHO)/
International Programme on Chemical of three ways: (1) cite existing
ToxCastTM results so that they could be ToxCastTM ‘‘ER Model’’ for bioactivity
cited as ‘‘other scientifically relevant Safety (IPCS) defines endocrine
disruption as being caused by ‘‘an data as ‘‘other scientifically relevant
information’’ to satisfy the Tier 1 ER information’’ (where available); (2)
binding, ERTA, and uterotrophic assays exogenous substance or mixture that
alters function(s) of the endocrine generate new data relying on the 18 ER
(Ref. 13). However, since that time, EPA
system . . . and . . .consequently high throughput assays and the
has reached a critical juncture,
determining that the science has causes adverse health effects in an intact ToxCastTM ‘‘ER Model’’ for bioactivity;
progressed such that reevaluation of organism or its progeny, or or (3) generate their own data using the
EPA’s earlier position is warranted. (sub)populations’’ (Ref. 18). Bioactivity current Tier 1 ER binding, ERTA, and
Based on scientific advances, EPA is an indicator that a chemical has the uterotrophic assays.
intends to implement the use of high potential to alter endocrine function, B. How Does EPA intend to use high
throughput assays and computational but (1) whether the chemical actually
throughput assays and computational
models to evaluate, and to a significant alters endocrine function and (2)
models for the EDSP in the future?
extent, screen chemicals. The in vitro whether that altered function produces
high throughput and computational an adverse outcome in an intact animal EPA believes that ongoing adoption of
model alternatives provide an accurate cannot be determined without further alternative methods and technologies
quantitative measure of specific testing (i.e., Tier 2 testing). will continue to advance EDSP
endocrine pathway bioactivity and The EDSP has been developed over screening of chemicals for bioactivity in
mechanisms. The current Tier 1 battery the past 19 years, and has demonstrated the estrogen, androgen, and thyroid
includes animal-based assays that do that the current screening process may pathways. EPA is continuing research
not clearly identify or differentiate take upwards of 5 years before a Tier 1
on the ‘‘ER Model’’ to determine if
pathways and mechanisms. Specifically, decision is available or Tier 2 test orders
ToxCastTM assays can provide
the current Tier 1 ER binding, ERTA are issued. In light of recent advances in
comparable information as that of the
and uterotrophic assays do not provide high throughput assays and
Female Rat Pubertal and the Fish Short
both estrogen agonist and antagonist computational models, and advances
likely to come in the next two years, it Term Reproduction assays. In addition,
activity and animals are required to
is prudent for the Agency to consider research continues on the ToxCastTM
conduct the ER binding and
new, rapid screening methods. The ‘‘AR Model’’ for bioactivity which, if
uterotrophic assays.
EPA is planning to adopt in vitro high availability of additional alternative fully validated, may be considered as an
throughput assays and computational high throughput assays and alternative (alone or with the ‘‘ER
models for detecting and measuring ER computational models in the near term Model’’) for the following current Tier 1
agonist and antagonist bioactivity as an will allow EPA to screen more assays: AR binding, Male Rat Pubertal,
alternative for three current Tier 1 chemicals in less time, involve fewer Hershberger, and Fish Short Term
assays: 1) ER binding in vitro assay (Ref. animals, and cost less for everyone. Reproduction. Research is also
14); 2) ER transcriptional activation in Furthermore, reconsideration of the underway to develop steroidogenesis
vitro assay (ERTA) (Ref. 15); and 3) in EDSP List 2 chemicals may be ToxCastTM (STR) and thyroid (THY)
vivo uterotrophic assay (Refs. 16 and appropriate since ‘‘ER Model’’ data are bioactivity models. Over time, the
17). EPA is also planning to accept available for many List 2 and other Agency’s goal is to develop a set of
existing results for chemicals that have chemicals (Refs. 10 and 19). Ongoing ‘‘non-animal’’ high throughput assays
been evaluated using the ToxCastTM use of high throughput assays and and computational bioactivity models as
‘‘ER Model’’ for bioactivity. The computational models will address an alternative to all of the assays in the
accompanying database contains the ER thousands of chemicals in the future. current Tier 1 screening battery. The
agonist bioactivity and ER antagonist These advancements in the EDSP following table is intended to illustrate
asabaliauskas on DSK5VPTVN1PROD with NOTICES

bioactivity for over 1800 chemicals and screening program will not affect the the evolution of screening in the EDSP:

Alternative high throughput assays and computational model for EDSP
Current EDSP Tier 1 battery of assays Tier 1 battery

Estrogen Receptor (ER) Binding .............................................................. ER Model (alternative).
Estrogen Receptor Transactivation (ERTA) ............................................. ER Model (alternative).
Uterotrophic .............................................................................................. ER Model (alternative).
Female Rat Pubertal ................................................................................ ER, STR , and thyroid (THY) Models (Future).

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Federal Register / Vol. 80, No. 118 / Friday, June 19, 2015 / Notices 35355

9789264067417-en. superfund.docket@epa.gov, or by mail Abstract: This information collection
18. World Health Organization (WHO)/ to: EPA Docket Center, Environmental request pertains to trade secrecy claims
International Programme on Chemical Protection Agency, Mail Code 28221T, submitted under Section 322 of the
Safety (IPCS). Global Assessment of the 1200 Pennsylvania Ave. NW., Emergency Planning and Community
State-of-the-Science of Endocrine
Disruptors. WHO/IPCS/EDC/02.2. 2002.
Washington, DC 20460. Right-to-Know Act of 1986 (EPCRA).
Available at http://www.who.int/ipcs/ EPA’s policy is that all comments EPCRA contains provisions requiring
publications/new_issues/endocrine_ received will be included in the public facilities to report to State and local
disruptors/en. docket without change including any authorities, and EPA, the presence of
19. U.S. EPA. Endocrine Disruptor Screening personal information provided, unless extremely hazardous substances
Program; Final Second List of Chemicals the comment includes profanity, threats, (Section 302), inventory of hazardous
and Substances for Tier 1 Screening; information claimed to be Confidential chemicals (Sections 311 and 312) and
Notice. Federal Register (78 FR 35922, Business Information (CBI) or other manufacture, process and use of toxic
June 14, 2013) (FRL–9375–8). Available information whose disclosure is chemicals (Section 313).
at http://www.gpo.gov/fdsys/pkg/FR–
restricted by statute. Section 322 of EPCRA allows a
2013–06–14/pdf/2013–14232.pdf.
FOR FURTHER INFORMATION CONTACT: Sicy facility to withhold the specific
Authority: 21 U.S.C. 346a(p). Jacob, Office of Emergency chemical identity from these EPCRA
Dated: June 11, 2015. Management, Mail Code 5104A, reports if the facility asserts a claim of
James J. Jones, Environmental Protection Agency, 1200 trade secrecy for that chemical identity.
Assistant Administrator, Office of Chemical Pennsylvania Ave. NW., Washington, The provisions in Section 322 establish
Safety and Pollution Prevention. DC 20460; telephone number: (202) the requirements and procedures that
[FR Doc. 2015–15182 Filed 6–18–15; 8:45 am] 564–8019; fax number: (202) 564–2620; facilities must follow to request trade
BILLING CODE 6560–50–P email address: jacob.sicy@epa.gov. secrecy treatment of chemical identities,
SUPPLEMENTARY INFORMATION: as well as the procedures for submitting
Supporting documents which explain in public petitions to the Agency for
ENVIRONMENTAL PROTECTION detail the information that the EPA will review of the ‘‘sufficiency’’ of trade
AGENCY be collecting are available in the public secrecy claims.
docket for this ICR. The docket can be Trade secrecy protection is provided
[EPA–HQ–SFUND–2006–0361; FRL—9929–
32–OSWER] viewed online at www.regulations.gov for specific chemical identities
or in person at the EPA Docket Center, contained in reports submitted under
Proposed Information Collection WJC West, Room 3334, 1301 each of the following: (1) Section 303
Request; Comment Request; Trade Constitution Ave. NW., Washington, (d)(2)- Facility notification of changes
Secret Claim Submissions under the DC. The telephone number for the that have or are about to occur, (2)
Emergency Planning and Community Docket Center is 202–566–1744. For Section 303 (d)(3)—Local Emergency
Right-to-Know Act. additional information about EPA’s Planning Committee (LEPC) requests for
public docket, visit http://www.epa.gov/ facility information to develop or
AGENCY: Environmental Protection dockets. implement emergency plans, (3) Section
Agency (EPA). Pursuant to section 3506(c)(2)(A) of 311—Material Safety Data Sheets
ACTION: Notice. the PRA, EPA is soliciting comments (MSDSs) submitted by facilities, or lists
and information to enable it to: (i) of those chemicals submitted in place of
SUMMARY: The Environmental Protection evaluate whether the proposed the MSDSs, (4) Section 312—Emergency
Agency (EPA) is planning to submit an collection of information is necessary and hazardous chemical inventory
information collection request (ICR), for the proper performance of the forms (Tier I and Tier II), and (5) Section
‘‘Trade Secret Claims Submitted under functions of the Agency, including 313 Toxic chemical release inventory
the Emergency Planning and whether the information will have form.
Community Right-to-Know Act.’’ (EPA practical utility; (ii) evaluate the Form Number: EPA Form 9510–1.
ICR No. 1428.10, OMB Control No. accuracy of the Agency’s estimate of the Respondents/affected entities: Entities
2050–0078) to the Office of Management burden of the proposed collection of potentially affected by this action are
and Budget (OMB) for review and information, including the validity of manufacturers or non-manufacturers
approval in accordance with the the methodology and assumptions used; subject to reporting under Sections 303,
Paperwork Reduction Act. Before doing (iii) enhance the quality, utility, and 311/312 or 313 of the Emergency
so, EPA is soliciting public comments clarity of the information to be Planning and Community Right-to-
on specific aspects of the proposed collected; and (iv) minimize the burden Know Act (EPCRA).
information collection as described of the collection of information on those Respondent’s obligation to respond:
below. This is a proposed extension of who are to respond, including through Mandatory if the respondents would
the ICR, which is currently approved the use of appropriate automated like to claim the chemical identity for
through December 31, 2015. An Agency electronic, mechanical, or other any of the chemicals as trade secret in
may not conduct or sponsor and a technological collection techniques or any of the reports required to be
person is not required to respond to a other forms of information technology, submitted under EPCRA.
collection of information unless it e.g., permitting electronic submission of Estimated number of respondents:
displays a currently valid OMB control responses. EPA will consider the 332 (total).
asabaliauskas on DSK5VPTVN1PROD with NOTICES

number. comments received and amend the ICR Frequency of response: Annual for
DATES: Comments must be submitted on as appropriate. The final ICR package claims submitted under EPCRA Sections
or before August 18, 2015. will then be submitted to OMB for 312 and 313.
ADDRESSES: Submit your comments, review and approval. At that time, EPA Total estimated burden: 3,154 hours
referencing Docket ID No. EPA–HQ– will issue another Federal Register (per year). Burden is defined at 5 CFR
SFUND–2006–0361, online using notice to announce the submission of 1320.03(b).
www.regulations.gov (our preferred the ICR to OMB and the opportunity to Total estimated cost: $206,155 (per
method), by email to submit additional comments to OMB. year). No capital and operation and

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Document Created: 2018-02-22 11:10:06
Document Modified: 2018-02-22 11:10:06
Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice.
Dates		Comments must be received on or before August 18, 2015.
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;
FR Citation		80 FR 35350