[Federal Register Volume 88, Number 64 (Tuesday, April 4, 2023)]
[Notices]
[Pages 19952-19953]
[FR Doc No: 2023-06966]

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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OMS-2021-0325; FRL-10864-01-OMS]

Agency Information Collection Activities; Submission to the
Office of Management and Budget for Review and Approval; Comment
Request; Improving Customer Service

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: The Environmental Protection Agency (EPA) has submitted an
information collection request (ICR), Improving Customer Service (EPA
ICR Number 2687.01, OMB Control Number 2030-NEW) to the Office of
Management and Budget (OMB) for review and approval in accordance with
the Paperwork Reduction Act. This is a proposed new ICR. Public
comments were previously requested via the Federal Register on October
13, 2021, during a 60-day comment period. This notice allows for an
additional 30 days for public comments.

DATES: Comments may be submitted on or before May 4, 2023.

ADDRESSES: Submit your comments, referencing Docket ID Number EPA-HQ-
OMS-2021-0325, to EPA online using https://www.regulations.gov/ (our
preferred method) or by mail to EPA Docket Center, Environmental
Protection Agency, Mail Code 28221T, 1200 Pennsylvania Ave. NW,
Washington, DC 20460. The EPA's policy is that all comments received
will be included in the public docket without change including any
personal information provided, unless the comment includes profanity,
threats, information claimed to be Confidential Business Information
(CBI) or other information whose disclosure is restricted by statute.
    Submit written comments and recommendations to OMB for the proposed
information collection within 30 days of publication of this notice to
www.reginfo.gov/public/do/PRAMain. Find this particular information

collection by selecting ``Currently under 30-day Review--Open for
Public Comments'' or by using the search function.

FOR FURTHER INFORMATION CONTACT: Augusto Cangahuala, Office of Customer
Advocacy, Policy, and Portfolio Management, U.S. Environmental
Protection Agency, 1200 Pennsylvania Ave. NW, Washington, DC 20460;
telephone number:<PHONE_NUMBER>; email address:
[email protected].

SUPPLEMENTARY INFORMATION: This is a new ICR. An agency may not
conduct, or sponsor and a person is not required to respond to a
collection of information unless it displays a currently valid OMB
control number.
    Public comments were previously requested via the Federal Register
on October 13, 2021, during a 60-day comment period (86 FR 56932). This
notice allows for an additional 30 days for public comments. Supporting
documents, which explain in detail the information that the EPA will be
collecting, are available in the public docket for this ICR. The docket
can be viewed online at www.regulations.gov or in person at the EPA
Docket Center, WJC West, Room 3334, 1301 Constitution Ave. NW,
Washington, DC. The telephone number for the Docket Center is 202-566-
1744. For additional information about EPA's public docket, visit
http://www.epa.gov/dockets.
    Abstract: A modern, streamlined and responsive customer experience
means: raising government-wide customer experience to the average of
the private sector service industry; developing indicators for high-
impact Federal programs to monitor progress towards excellent customer
experience and mature digital services; and providing the structure
(including increasing transparency) and resources to ensure customer
experience is a focal point for agency leadership. This proposed
information collection activity provides a means to garner customer and
stakeholder feedback in an efficient, timely manner in accordance with
the Administration's commitment to improving customer service delivery
as discussed in Section 280 of OMB Circular A-11 at https://www.performance.gov/cx/a11-280.pdf. As discussed in OMB guidance,
agencies should identify their highest-impact customer journeys (using
customer volume, annual program cost, and/or knowledge of customer
priority as weighting factors) and select touchpoints/transactions
within those journeys to collect feedback. These results will be used
to improve the delivery of Federal services and programs. It will also
provide government-wide data on customer experience that can be
displayed on www.performance.gov to help build transparency and
accountability of Federal programs to the customers they serve. As a
general matter, these information collections will not result in any
new system of records containing privacy information and will not ask
questions of a sensitive nature, such as sexual behavior and attitudes,
religious beliefs, and other matters that are commonly considered
private.
    The Environmental Protection Agency will only submit collections if
they meet the following criteria.
     The collections are voluntary.
     The collections are low burden for respondents (based on
total burden hours or burden-hours per respondent) and are low cost for
respondents and the Federal Government.
     The collections are non-controversial and do not raise
issues of concern to Federal agencies.
     Any collection is targeted to the solicitation of opinions
from respondents who have experience with the program or may have
experience with the program in the near future.
     Personally identifiable information (PII) is collected to
the extent necessary and not retained.
     Information gathered is intended to be used for general
service improvement and program management purposes.
     Upon agreement between OMB and the agency all or a subset
of information may be released as part of A-11, Section 280
requirements only on performance.gov. Summaries of customer research
and user testing activities may be included in public-facing customer
journey maps or summaries.
     Additional release of data must be done coordinated with
OMB.
    These collections will allow for ongoing, collaborative and
actionable communications between the Agency, its customers and
stakeholders, and OMB as it monitors agency compliance on Section 280.
These responses will inform efforts to improve or maintain the quality
of service offered to the public. If this information is not collected,
vital feedback from customers and stakeholders on services will be
unavailable.
    Form Numbers: None.
    Respondents/affected entities: Individuals and entities who have
experience with the program or may have experience with the program in
the near future.
    Respondent's obligation to respond: Voluntary.
    Estimated number of respondents: 2,001,550 (total).
    Frequency of response: On occasion.
    Total estimated burden: 101,125 hours.
    Estimated annual cost: There are no annualized capital/startup or
operation & maintenance costs.
    Changes in estimates: This is a new collection.

Courtney Kerwin,
Director, Regulatory Support Division.
[FR Doc. 2023-06966 Filed 4-3-23; 8:45 am]
BILLING CODE 6560-50-P


[Federal Register Volume 78, Number 123 (Wednesday, June 26, 2013)]
[Notices]
[Page 38311]
[FR Doc No: 2013-15191]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Project No. 2880-011]

Broad River Electric Cooperative and Cherokee Falls Associates;
Aquenergy Systems, Inc.; Notice of Application for Transfer of License,
and Soliciting Comments and Motions To Intervene

    On June 18, 2013, Broad River Electric Cooperative and Cherokee
Falls Associates (transferors) and Aquenergy Systems, Inc. (transferee)
filed an application for transfer of license for the Cherokee Falls
Project, FERC No. 2880, located on the Broad River in Cherokee County,
South Carolina.
    Applicants seek Commission approval to transfer the license for the
Cherokee Falls Project from transferor to transferee.
    Applicants' Contact: Transferor: Mr. Douglass E. Wilson, President
& Chief Executive Officer, Broad River Electric Cooperative, Inc., P.O.
Box 2269, 811 Hamrick Street, Gaffney, SC 29342, telephone (864) 489-
5737 and Mr. Charles R. Zappala, Shareholder, Cherokee Falls
Associates, 625 Liberty Ave., Suite 3100, Pittsburgh, PA 15222.
Transferee: Mr. Steve Champagne, Executive Vice President and General
Counsel, Aquenergy Systems, Inc., c/o Enel Green Power North America,
Inc., One Tech Drive, Suite 220, Andover, MA 01810.
    FERC Contact: Patricia W. Gillis<PHONE_NUMBER>.
    Deadline for filing comments and motions to intervene: 30 days from
the issuance date of this notice by the Commission. Comments and
motions to intervene may be filed electronically via the Internet. See
18 CFR 385.2001(a)(1) and the instructions on the Commission's Web site
under http://www.ferc.gov/docs-filing/efiling.asp. Commenters can
submit brief comments up to 6,000 characters, without prior
registration, using the eComment system at http://www.ferc.gov/docs-filing/ecomment.asp. You must include your name and contact information
at the end of your comments. If unable to be filed electronically,
documents may be paper-filed. To paper-file, an original plus seven
copies should be mailed to: Kimberly D. Bose, Secretary, Federal Energy
Regulatory Commission, 888 First Street NE., Washington, DC 20426. More
information about this project can be viewed or printed on the eLibrary
link of Commission's Web site at http://www.ferc.gov/docs-filing/elibrary.asp. Enter the docket number (P-2880) in the docket number
field to access the document. For assistance, call toll-free 1-866-208-
3372.

    Dated: June 19, 2013.
Kimberly D. Bose,
Secretary.
[FR Doc. 2013-15191 Filed 6-25-13; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register Volume 81, Number 105 (Wednesday, June 1, 2016)]
[Notices]
[Pages 35099-35101]
[FR Doc No: 2016-12790]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-77905; File No. SR-BatsEDGX-2016-19]

Self-Regulatory Organizations; Bats EDGX Exchange, Inc.; Notice
of Filing and Immediate Effectiveness of a Proposed Rule Change to Rule
11.7, Opening Process

May 25, 2016.
    Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934
(the ``Act''),\1\ and Rule 19b-4 thereunder,\2\ notice is hereby given
that on May 13, 2016, Bats EDGX Exchange, Inc. (the ``Exchange'' or
``EDGX'') filed with the Securities and Exchange Commission
(``Commission'') the proposed rule change as described in Items I and
II below, which Items have been prepared by the Exchange. The Exchange
has designated this proposal as a ``non-controversial'' proposed rule
change pursuant to Section 19(b)(3)(A) of the Act \3\ and Rule 19b-
4(f)(6)(iii) thereunder,\4\ which renders it effective upon filing with
the Commission. The Commission is publishing this notice to solicit
comments on the proposed rule change from interested persons.
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    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
    \3\ 15 U.S.C. 78s(b)(3)(A).
    \4\ 17 CFR 240.19b-4(f)(6)(iii).
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I. Self-Regulatory Organization's Statement of the Terms of Substance
of the Proposed Rule Change

    The Exchange filed a proposal to amend Rule 11.7, Opening Process,
to await a two-sided quotation from the listing exchange prior to
opening a security for trading during Regular Trading Hours.\5\
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    \5\ See Exchange Rule 1.5(y).
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    The text of the proposed rule change is available at the Exchange's
Web site at www.batstrading.com, at the principal office of the
Exchange, and at the Commission's Public Reference Room.

II. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

    In its filing with the Commission, the Exchange included statements
concerning the purpose of and basis for the proposed rule change and
discussed any comments it received on the proposed rule change. The
text of these statements may be examined at the places specified in
Item IV below. The Exchange has prepared summaries, set forth in
Sections A, B, and C below, of the most significant parts of such
statements.

A. Self-Regulatory Organization's Statement of the Purpose of, and the
Statutory Basis for, the Proposed Rule Change

1. Purpose
    The Exchange proposes to amend Rule 11.7, Opening Process, to await
a two-sided quotation from the listing exchange prior to opening a
security for trading during Regular Trading Hours.
    Exchange Rule 11.7 describes the Exchange's current opening
process. Subparagraph (a) to Rule 11.7 states that prior to the
beginning of the Regular Session,\6\ Users \7\ who wish to participate
in the Opening Process may enter orders to buy or sell.\8\ Subparagraph
(a)(2) to Rule 11.7 provides that, with certain exceptions,\9\ all
orders with a time-in-force instruction of Regular Hours Only may
participate in the Opening Process. Subparagraph (b) to Rule 11.7
states that the Exchange will open by performing the Opening Process in
which the System will attempt to match buy and sell orders that are
executable at the midpoint of the National Best Bid and Offer
(``NBBO''). Subparagraph (c) to Exchange Rule 11.7 sets forth the
process by which the System sets the opening price of the Opening
Process. Currently, the System \10\ sets the price of the Opening
Process at the midpoint of the first NBBO after 9:30:00 a.m. Eastern
Time. However, for securities listed on either the New York Stock
Exchange, Inc. (``NYSE'') or NYSE MKT LLC (``NYSE MKT''), the System
currently sets the price of the Opening Process at the midpoint of the
first NBBO subsequent to the first reported trade on the listing
exchange after 9:30:00 a.m. Eastern Time. The Exchange may
alternatively set the price of the Opening Process for securities
listed on either the NYSE or NYSE MKT at the midpoint of the then
prevailing NBBO when the first two-sided quotation published by the
relevant listing exchange after 9:30:00 a.m. Eastern Time, but before
9:45:00 a.m. Eastern Time if no first trade is reported by the listing
exchange within one second of publication of the first two-sided
quotation by the listing exchange. The System waits to set the price at
the midpoint of the first NBBO as set forth above because securities
listed on the NYSE or NYSE MKT may not open at precisely 9:30:00 a.m.
Eastern Time.
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    \6\ See Exchange Rule 1.5(hh).
    \7\ See Exchange Rule 1.5(ee).
    \8\ Orders cancelled prior to the Opening Process will not
participate in the Opening Process.
    \9\ The following order types and instruction may not
participate in the opening process: (i) Limit Orders with a Post
Only instruction, (ii) the Discretionary Range of Limit Orders, and
(iv) Intermarket Sweep Orders (``ISOs'') not modified by Rule
11.7(a)(1), and (iii) orders with a Minimum Execution Quantity
instruction. See Exchange Rule 11.7(a)(2). Orders that are
designated for the Regular Session that cannot participate in the
Opening Process will not be accepted by the System until the Opening
Process is completed or a Contingent Opening. Id. Limit Orders with
a Reserve Quantity may participate to the full extent of their
displayed size and Reserve Quantity. Id. Limit Orders with a
Discretionary Range may participate up to their ranked limit price
for buy orders and down to their ranked limit price for sell orders.
Id. All Limit Orders with a Pegged instruction will be eligible for
execution in the Opening Process based on their pegged prices at the
time the Opening Process is conducted. Id.
    \10\ See Exchange Rule 1.5(cc).
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    Pursuant to subparagraph (b) of Rule 11.7, all orders executable at
the midpoint of the NBBO will continue to be processed in time
sequence, beginning with the order with the oldest time stamp and not
in accordance with Exchange Rule 11.9(a)(2)(B), which outlines priority
at the midpoint of the NBBO. Matches occur until there are no remaining
contra-side orders or there is an imbalance of orders. An imbalance of
orders may result in orders that cannot be executed in whole or in
part. Any unexecuted orders may then be placed by the System on the
EDGX Book,\11\ cancelled, executed, or routed to away Trading Centers
in accordance with the Users' instructions pursuant to Exchange Rule
11.11.
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    \11\ The term ``EDGX Book'' is defined as ``the System's
electronic file of orders.'' See Exchange Rule 1.5(d).
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    The Exchange proposes to amend subparagraph (c) to Rule 11.7 to now
await a two-sided quotation from the listing exchange prior to opening
a security for trading during Regular Trading Hours. As amended,
subparagraph (c)(2) to Rule 11.7 would state that the System would set
the price of the Opening Process at the midpoint of the first NBBO
subsequent to the first two-sided quotation published by the listing
exchange after 9:30:00 a.m. Eastern Time. For securities listed on
either the NYSE or NYSE MKT, subparagraph (c)(1)(i) to Rule 11.7 would
state that the System would set the price of the Opening Process at the
midpoint of the first NBBO subsequent to the first reported trade and
first reported quotation on the listing exchange after 9:30:00 a.m.
Eastern Time. Pursuant to subparagraph (c)(1)(i) to Rule 11.7, the
Exchange will utilize the existing NBBO to calculate each securities'
[sic] opening price once a trade and two-sided quotation are received
from the listing exchange, regardless of the order in which the

trade or quotation are received. The Exchange believes the proposed
rule change will enable the listing market's quotation to be
incorporated into the NBBO, which the Exchange would, in turn, utilize
in its calculation of the midpoint of the NBBO. The Exchange believes
doing so would result in an opening price that more closely reflect the
opening market prices and conditions for that security. Under
subparagraph (c)(1)(ii) to Rule 11.7, the Exchange will continue to
alternatively set the price of the Opening Process for securities
listed on either the NYSE or NYSE MKT at the midpoint of the then
prevailing NBBO when the first two-sided quotation published by the
relevant listing exchange after 9:30:00 a.m. Eastern Time, but before
9:45:00 a.m. Eastern Time if no first trade is reported by the listing
exchange within one second of publication of the first two-sided
quotation by the listing exchange.
2. Statutory Basis
    The Exchange believes that its proposal is consistent with Section
6(b) of the Act \12\ in general, and furthers the objectives of Section
6(b)(5) of the Act \13\ in particular, in that it is designed to
promote just and equitable principles of trade, to foster cooperation
and coordination with persons engaged in facilitating transactions in
securities, to remove impediments to and perfect the mechanism of a
free and open market and a national market system and, in general, to
protect investors and the public interest. The Exchange believes the
proposed rule change will promote just and equitable principles of
trade, removes impediments to, and perfect the mechanism of, a free and
open market and a national market system because it enables the System
to execute the Opening Process at a price that is objectively
established by the market for the security. The proposal would enable
the listing market's quotation to be incorporated into the NBBO, which
the Exchange would, in turn, utilize in its calculation of the midpoint
of the NBBO. The Exchange believes doing so would result in an opening
price that more closely reflect the opening market prices and
conditions for that security. Therefore, the Exchange believes the
proposed rule change promotes just and equitable principles of trade
because it ensures a midpoint price that the Exchange believes would
accurately reflect the market for the security.
---------------------------------------------------------------------------

    \12\ 15 U.S.C. 78f(b).
    \13\ 15 U.S.C. 78f(b)(5).
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B. Self-Regulatory Organization's Statement on Burden on Competition

    The Exchange does not believe that the proposal will impose any
burden on competition not necessary or appropriate in furtherance of
the purposes of the Act. The proposed rule change will enable the
Exchange to incorporate the listing market's quotation into its
calculation of the midpoint of the NBBO, resulting in an opening price
that would more closely reflect the opening market prices and
conditions for that security. Therefore, the Exchange believes the
proposed rule change will promote competition by enhancing the quality
of the Exchange's opening process.

C. Self-Regulatory Organization's Statement on Comments on the Proposed
Rule Change Received From Members, Participants, or Others

    The Exchange has neither solicited nor received written comments on
the proposed rule change.

III. Date of Effectiveness of the Proposed Rule Change and Timing for
Commission Action

    Because the proposed rule change does not (i) significantly affect
the protection of investors or the public interest; (ii) impose any
significant burden on competition; and (iii) become operative for 30
days from the date on which it was filed, or such shorter time as the
Commission may designate, it has become effective pursuant to Section
19(b)(3)(A) of the Act \14\ and Rule 19b-4(f)(6) thereunder.\15\
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    \14\ 15 U.S.C. 78s(b)(3)(A).
    \15\ 17 CFR 240.19b-4(f)(6). As required under Rule 19b-
4(f)(6)(iii), the Exchange provided the Commission with written
notice of its intent to file the proposed rule change, along with a
brief description and the text of the proposed rule change, at least
five business days prior to the date of filing of the proposed rule
change, or such shorter time as designated by the Commission.
---------------------------------------------------------------------------

    A proposed rule change filed pursuant to Rule 19b-4(f)(6) under the
Act \16\ normally does not become operative for 30 days after the date
of its filing. However, Rule 19b-4(f)(6)(iii) \17\ permits the
Commission to designate a shorter time if such action is consistent
with the protection of investors and the public interest. The Exchange
has asked the Commission to waive the 30-day operative delay so that
the proposal may become operative immediately upon filing. The Exchange
states that waiver of the 30-day operative delay would allow market
participants to immediately realize the benefits of what may be more
accurate opening prices. Based on the foregoing, the Commission
believes the waiver of the operative delay is consistent with the
protection of investors and the public interest. Therefore, the
Commission hereby waives the operative delay and designates the
proposal operative upon filing.\18\
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    \16\ 17 CFR 240.19b-4(f)(6).
    \17\ 17 CFR 240.19b-4(f)(6)(iii).
    \18\ For purposes only of waiving the 30-day operative delay,
the Commission has also considered the proposed rule's impact on
efficiency, competition, and capital formation. See 15 U.S.C.
78c(f).
---------------------------------------------------------------------------

    At any time within 60 days of the filing of the proposed rule
change, the Commission summarily may temporarily suspend such rule
change if it appears to the Commission that such action is necessary or
appropriate in the public interest, for the protection of investors, or
otherwise in furtherance of the purposes of the Act. If the Commission
takes such action, the Commission shall institute proceedings to
determine whether the proposed rule change should be approved or
disapproved.

IV. Solicitation of Comments

    Interested persons are invited to submit written data, views, and
arguments concerning the foregoing, including whether the proposed rule
change is consistent with the Act. Comments may be submitted by any of
the following methods:

Electronic Comments

     Use the Commission's Internet comment form (http://www.sec.gov/rules/sro.shtml); or
     Send an email to<EMAIL_ADDRESS>Please include
File No. SR-BatsEDGX-2016-19 on the subject line.

Paper Comments

     Send paper comments in triplicate to Secretary, Securities
and Exchange Commission, 100 F Street NE., Washington, DC 20549-1090.

All submissions should refer to File No. SR-BatsEDGX-2016-19. This file
number should be included on the subject line if email is used. To help
the Commission process and review your comments more efficiently,
please use only one method. The Commission will post all comments on
the Commission's Internet Web site (http://www.sec.gov/rules/sro.shtml). Copies of the submission, all subsequent amendments, all
written statements with respect to the proposed rule change that are
filed with the Commission, and all written communications relating to
the proposed rule change between the Commission and any person, other
than those that may be withheld from the

public in accordance with the provisions of 5 U.S.C. 552, 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. Copies of
the filing also will be available for inspection and copying at the
principal office of the Exchange. All comments received will be posted
without change; the Commission does not edit personal identifying
information from submissions. You should submit only information that
you wish to make available publicly. All submissions should refer to
File No. SR-BatsEDGX-2016-19, and should be submitted on or before June
22, 2016.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\19\
---------------------------------------------------------------------------

    \19\ 17 CFR 200.30-3(a)(12).
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Brent J. Fields,
Secretary.
[FR Doc. 2016-12790 Filed 5-31-16; 8:45 am]
 BILLING CODE 8011-01-P


[Federal Register Volume 88, Number 206 (Thursday, October 26, 2023)]
[Notices]
[Pages 73634-73635]
[FR Doc No: 2023-23635]

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DEPARTMENT OF TRANSPORTATION

Federal Railroad Administration

[Docket No. FRA-2010-0033]

New Jersey Transit's Request To Amend Its Positive Train Control
System

AGENCY: Federal Railroad Administration (FRA), Department of
Transportation (DOT).

ACTION: Notice of availability and request for comments.

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SUMMARY: This document provides the public with notice that, on October
16, 2023, New Jersey Transit (NJT) submitted a request for amendment
(RFA) to its FRA-certified positive train control (PTC) system. The RFA
notifies FRA of a planned PTC outage to its I-ETMS PTC System for
maintenance purposes. FRA is publishing this notice and inviting public
comment on the railroad's RFA to its PTC system.

DATES: FRA will consider comments received by November 13, 2023. FRA
may consider comments received after that date to the extent
practicable and without delaying implementation of valuable or
necessary modifications to a PTC system.

ADDRESSES:
    Comments: Comments may be submitted by going to https://www.regulations.gov and following the online instructions for
submitting comments.
    Instructions: All submissions must include the agency name and the
applicable docket number. The relevant PTC docket number for this host
railroad is Docket No. FRA-2010-0033. For convenience, all active PTC
dockets are hyperlinked on FRA's website at https://railroads.dot.gov/research-development/program-areas/train-control/ptc/railroads-ptc-dockets. All comments received will be posted without change to https://www.regulations.gov; this includes any personal information.

FOR FURTHER INFORMATION CONTACT: Gabe Neal, Staff Director, Signal,
Train Control, and Crossings Division, telephone:<PHONE_NUMBER>, email:
[email protected].

SUPPLEMENTARY INFORMATION: In general, Title 49 United States Code
(U.S.C.) section 20157(h) requires FRA to certify that a host
railroad's PTC system complies with Title 49 Code of Federal
Regulations (CFR) part 236, subpart I, before the technology may be
operated in revenue service. Before making certain changes to an FRA-
certified PTC system or the associated FRA-approved PTC Safety Plan
(PTCSP), a host railroad must submit, and obtain FRA's approval of, an
RFA to its PTC system or PTCSP under 49 CFR 236.1021.
    Under 49 CFR 236.1021(e), FRA's regulations provide that FRA will
publish a notice in the Federal Register and invite public comment in
accordance with 49 CFR part 211, if an RFA includes a request for
approval of a material modification of a signal or train control
system. Accordingly, this notice informs the public that, on October
16, 2023, NJT submitted an RFA to its PTCSP for its Interoperable
Electronic Train Management System (I-ETMS), which seeks FRA's approval
for an approximately two-hour but no greater that three-hour outage of
its PTC system to support NJT's PTC Back Office Subsystem upgrade to
improve the reliability and stability of NJT's I-ETMS PTC system. NJT'S
RFA states that the PTC system outage is necessary to perform the
upgrade to NJT's PTC Back Office System. The RFA is available in Docket
No. FRA-2010-0033. Interested parties are invited to comment on NJT's
RFA by submitting written comments or data. During FRA's review of this
railroad's RFA, FRA will consider any comments or data submitted within
the timeline specified in this notice and to the extent practicable,
without delaying implementation of valuable or necessary modifications
to a PTC system. See 49

CFR 236.1021; see also 49 CFR 236.1011(e). Under 49 CFR 236.1021, FRA
maintains the authority to approve, approve with conditions, or deny a
railroad's RFA at FRA's sole discretion.

Privacy Act Notice

    In accordance with 49 CFR 211.3, FRA solicits comments from the
public to better inform its decisions. DOT posts these comments,
without edit, including any personal information the commenter
provides, to https://www.regulations.gov, as described in the system of
records notice (DOT/ALL-14 FDMS), which can be reviewed at https://www.transportation.gov/privacy. See https://www.regulations.gov/privacy-notice for the privacy notice of regulations.gov. To facilitate
comment tracking, we encourage commenters to provide their name, or the
name of their organization; however, submission of names is completely
optional. If you wish to provide comments containing proprietary or
confidential information, please contact FRA for alternate submission
instructions.

    Issued in Washington, DC.
Carolyn R. Hayward-Williams,
Director, Office of Railroad Systems and Technology.
[FR Doc. 2023-23635 Filed 10-25-23; 8:45 am]
BILLING CODE 4910-06-P


EPA Reviewer: Robert P. Zendzian, Ph.D.			              Robert P. Zendzian

Toxicology Branch, HED

EPA Secondary Reviewer: Steven L. Malish, Ph.D. Toxicologist       _____________________

Team 1, RASSB/Antimicrobial Division

DATA EVALUATION REPORT

STUDY TYPE: Prenatal Developmental Toxicity Study - Rat; OPPTS 870.3700 [§83-3]; OECD 414.

PC CODE:  08802	DP BARCODE: D316702, D321264, D330028

REG:  2480-21972                                                 DECISION #: 341745

TEST MATERIAL (PURITY): Zinc pyridinethione; (98.3% a.i.)

SYNONYMS: ZPT, Zinc Pyrithione

CITATION:	Barnett, J. Jr. (2005). Percutaneous developmental toxicity study of zinc pyridinethione (ZPT) in rats. CR-DDS Argus Division (Horsham, Pennsylvania). Argus AEN00006, April 7, 2005. MRID 46534001. Unpublished.

SPONSOR:	Arch Chemicals, Inc., Cheshire, Connecticut

EXECUTIVE SUMMARY:  In a developmental toxicity study (MRID 46534001), zinc pyridinethione (98.3% a.i., batch/lot #<PHONE_NUMBER>) was dermally administered to 23-25 Crl:CD® (SD)IGS BR VAF/Plus® rats/dose at dose levels of 0, 10, 15, 30, or 60 mg/kg bw/day from day 0 through 20 of gestation.

Dermal administration of zinc pyridinethione resulted in maternal toxicity at 30 and 60 mg/kg/day.  Treatment-related effects at 60 mg/kg/day included clinical signs of toxicity (grade 1 erythema; grade 1 flaking; limited or no use of hindlimbs; shuffling gait; dehydration; low carriage; chromodacyorrhea; emaciation; chromorhinorrhea; hunched posture; decreased body weight and body weight gain, decreased uterine weight, decreased corrected body weight and corrected body weight gain, decreased absolute and relative feed consumption, and decreased muscle tone and mass.

At 30 mg/kg/day, there was an increase in the number of dams with limited use of hindlimbs, shuffling gait, decreased body weight and body weight gain, decreased corrected body weight and corrected body weight gain, and decreased absolute feed consumption.  There were no treatment-related maternal effects at 10 or 15 mg/kg/day.

The maternal LOAEL is 30 mg/kg bw/day, based on an increase in the number of dams with limited use of hindlimbs, shuffling gait, decreased body weight and body weight gain, decreased corrected body weight and corrected body weight gain, and decreased absolute feed consumption.  The maternal NOAEL is 15 mg/kg bw/day.

Developmental toxicity occurred at 60 mg/kg/day.  Treatment-related findings at 60 mg/kg/day included decreased fetal weight (total, male, and female), an increase in the percentage of litters and fetuses with incomplete ossification of the sternal centra, an increase in the percentage of fetuses with wavy ribs, and a decrease in the ossification site averages for the caudal vertebrae, forelimb phalanges and metacarpals, and hindlimb phalanges and metatarsals per fetus per litter.  There were no treatment-related developmental effects at 10, 15, or 30 mg/kg/day.

The developmental LOAEL is 60 mg/kg bw/day, based on decreased fetal weight (total, male, and female), an increase in the percentage of litters and fetuses with incomplete ossification of the sternal centra, an increase in the percentage of fetuses with wavy ribs, and a decrease in the ossification site averages for the caudal vertebrae, forelimb phalanges and metacarpals, and hindlimb phalanges and metatarsals per fetus per litter.  The developmental NOAEL is 30 mg/kg bw/day.

This developmental toxicity study in the rat is classified ACCEPTABLE-GUIDELINE and satisfies the guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in the rat.

COMPLIANCE:  Signed and dated GLP, Quality Assurance, Data Confidentiality, and Flagging Statements are provided.

I. MATERIALS AND METHODS

A. MATERIALS:

1. Test Material:

Zinc pyridinethione (ZPT)

Description:

Off-white to tan powder, which was refrigerated and protected from light

Lot/Batch #:

0108244691

Purity:

98.3% a.i.

Compound Stability:

Not provided

CAS #of TGAI:

13463-41-7

Structure:

2. Vehicle and/or positive control: Reverse osmosis membrane deionized water (R.O. deionized water); lot number and purity not provided

3. Test animals:

Species:

Female rats

Strain:

Crl:CD® (SD)IGS BR VAF/Plus®

Age/weight at study initiation:

Dams were approximately 62 days old and weighed 191-236 grams.

Source:

Charles River Laboratories, Inc., Raleigh, NC

Housing:

Dams were individually-housed in stainless steel, wire-bottom cages prior to mating.  During mating, each female was housed in the male rat's cage.  Dams were then individually-housed in nesting boxes after randomization.

Diet:

Certified Rodent Diet #5002 (provided by PMI Nutrition International, Inc., St. Louis, Missouri) was provided ad libitum; there were reportedly no contaminants at levels exceeding the maximum concentration limits for certified feed or deviations from expected nutritional requirements.

Water:

Local water that was processed by passage through a reverse osmosis membrane was provided ad libitum.  Water was analyzed twice annually for possible chemical contamination and monthly for possible bacterial contamination.  There were reportedly no contaminants found that interfered with the study results.

Environmental conditions:

Temperature:

Humidity:

Air changes:

Photoperiod:

Temperature was targeted at 18-26(C; the actual range was 20.8-22.1(C.

Humidity was targeted at 30-70%; the actual range was 38.5-64.6%.

10/hr

12-hours light/12-hours dark

Acclimation period:

Females were acclimatized for 5 days.  Dams also were acclimatized to Elizabethan collars for 3 days (for at least 30 minutes, two hours, and four hours, respectively) during the week prior to the start of treatment.

B. PROCEDURES AND STUDY DESIGN

1. In life dates:

Start:	December 14, 2004		End:	January 10-15, 2005

2. Mating:  After acclimation, female rats were placed with male rats at a 1:1 ratio.  The mating period lasted 6 days.  The day on which spermatozoa were present in the vaginal smear and/or a copulatory plug was observed in situ was considered to be gestation day (gd) 0.

3. Animal Assignment:  Animals were placed into dose groups using a computer-generated (weight-ordered) randomization procedure based on body weights recorded on gd 0 as indicated in Table 1.

TABLE 1.  Animal Assignment

Dose (mg/kg bw/day)

0

10

15

30

60

# Females

23

24

24

24

25

4. Dose Selection Rationale:  The dose levels were selected based on the results from a range-finding study (Argus AEN00005) where percutaneous administration of up to 400 mg/kg/day resulted in the following clinical signs at the top doses (400 and 200 mg/kg/day): flaking (grades 1 and 2), erythema (grade 1), scabbing at the administration site, dehydration, shuffling gait, limited use of hindlimbs, low carriage, emaciation, chromodacyorrhea, urine-stained abdominal fur, chormorhinorrhea, no use of hindlimbs, red perivaginal substance, lacrimation, and splayed limbs.  Additional observations that were noted only at the 200-mg/kg/day dose level were  hunched posture, mydriasis and scabbing on the right flank; at the 400-mg/kg/day dose level only, localized alopecia (limbs), ungroomed coat, red fur on the lower midline and hindlimbs, ptosis and scabbing on the right hindlimb were noted.  Animals at the top doses (400 and 200 mg/kg/day) also exhibited decreased body weight, reduced feed consumption, reduction in muscle tone, reduction in muscle mass, and increased resorptions.  Due to the toxic effects observed, dams administered the top doses were sacrificed after 11 to 14 daily dosages.

Clinical observations considered treatment-related in the remaining dose groups (100, 30, and 15 mg/kg/day) were flaking (grade 1), dehydration, shuffling gain and limited use of the hindlimbs.  Dams administered 30 or 100 mg/kg/day also exhibited erythema (grade 1), low carriage, emaciation, and hunched posture, while dams administered 100 mg/kg/day also exhibited chromodacyorrhea, urine stained abdominal fur, chromorhinorrhea, no use of the hindlimbs, red perivaginal substance, lacrimation, splayed hindlimbs, and mydriasis.  Additionally, dose-dependent reductions in body weight gain occurred at 100, 30, and 15 mg/kg/day for the entire dose period.  Decreased average gravid uterine weights (100 mg/kg/day), decreased absolute and relative feed consumption (30 and 100 mg/kg/day), decreased relative feed consumption values over the entire treatment period (100 mg/kg/day), reduced muscle tone (30 and 100 mg/kg/day), increased postimplantation loss (100 mg/kg/day), increased percentage of dams with resorptions and increased percentage of resorbed conceptuses per litter (100 mg/kg/day), decreased overall litter size and live fetuses (100 mg/kg/day), and decreased fetal weights (30 and 100 mg/kg/day) also were noted.

5. Dosage Preparation and Analysis:  Test formulations were prepared once and stored under refrigeration, protected from light.  Samples of the test formulations were analyzed for stability, homogeneity, and achieved concentration.

Stability was evaluated using samples prepared for 10- and 60-mg/mL dose formulation concentrations and stored under refrigeration protected from light.  The concentration at 7, 14, 21, and 28 days was compared to the concentration immediately after preparation, and stability was expressed as percent error.

All dose formulation concentration levels were evaluated for homogeneity.  Samples taken from the top, middle, and bottom were measured for mean concentration.  Relative standard deviation (RSD) was calculated based on the three mean values.

Samples from all dose concentration levels were obtained at the start and end of the study.  The actual and nominal concentrations were compared to determine the percent error.

Results	Homogeneity Analysis:  Initial analyses showed samples were not within the acceptable limits of (5% RSD.  The values were 7.5%, 7.1%, 6.1%, and 6.1% for the 10, 15, 30, and 60 mg/mL formulations, respectively.  The results from the backup homogeneity samples from the start of the study, however, were within the acceptable range, except for the 10 mg/mL concentration (14.5% RSD).

Stability Analysis:  Formulations were stable for up to 28 days when stored refrigerated and protected from light.

Concentration Analysis:  All concentration analyses from the start of the study were within the acceptable range (±10%), except for the 10-mg/mL concentration that was -15%; all concentration analyses from the end of the study were within the acceptable ranges, except for the 60-mg/mL concentration that was 10.9%.

The analytical data indicated that the mixing procedure was adequate and that the variance between nominal and actual dosage to the study animals was acceptable.

6. Dosage Administration:  All doses were administered dermally once daily on gd 0-20.  The duration of each exposure was at least 6 hours, and the same dosage site was used each day.  Dosing was based on the most recent body weight determination prior to administration.

The following method was used when dermally applying the test formulations.  A 3 cm x 4 cm site was demarcated with a permanent marker on the clipped area for the back.  The interior edges of a 3M Reston( Self-Adhering Foam Pad were then aligned to the markings on the back and secured.  The appropriate test formulation was applied to the pad and evenly distributed within the dosage site at the center of the rectangular area using a syringe with attached gavage needle.

Once the test formulation was applied, the 3M Reston( Self-Adhering Foam Pad was covered with Johnson & Johnson Nu Gauze( general-use gauze.  The general-use gauze did not touch the site of dosage administration.  On either side of the 3M Reston( Self-Adhering Foam Pad, 3M Micropore( tape and/or 3M Vetrap( bandaging tape was placed (without impairing the mobility of the rat) in order to secure the foam padding and gauze on the rat's back for the exposure period.  An Elizabethan collar was placed on the rat's neck, preventing access to the dosage site.

At the exposure period completion, the Elizabethan collars, 3M Reston( Self-Adhering Foam Pad, and Johnson & Johnson Nu Gauze( general-use gauze were removed from the back.  The back of each rat was then washed with soapy water and rinsed with warm water three times to ensure the removal of the test substance.  Bedding was changed, and the cage was wiped down with Zephiran® chloride solution (1:750) to remove any test formulation that may have been present in the cage.

C. OBSERVATIONS

1. Maternal Observations and Evaluations:  The animals were checked for morbidity at least twice a day.  General appearance was recorded daily before and after treatment.  Clinical observations, abortions, premature deliveries, and deaths were recorded 60±10 minutes after rinsing on gd 0-7, 9-11, 13-15, and 17-19.  A detailed post-treatment observation was performed on all animals on gd 8, 12, 16, and 20.

Prior to the first daily application, and at 24-hour intervals each day thereafter, each skin site was observed for signs of skin irritation and graded using the endpoints described by Draize and the National Research Council.  A hindlimb neurological evaluation was performed just prior to dosing on gd 8, 12, 16, and 20, in which dams were assessed for muscle tone and mass of the calf muscles.  Body weight data were recorded on gd 0 and daily during the treatment/post-treatment periods.  Feed consumption was recorded on gd 0, 3, 6, 9, 12, 15, 18, and 20, and feed left was recorded on the day of sacrifice.

All surviving dams were sacrificed on gd 21 via CO2 asphyxiation.  A caesarean section was performed, and a gross necropsy examination was conducted of the thoracic, abdominal, and pelvic viscera.  Gross lesions were retained in neutral buffered 10% formalin for possible future evaluation.

The number and distribution of the corpora lutea were recorded.  The uterus of each dam was removed, weighed, and examined for pregnancy, number and distribution of implantation sites, live and dead fetuses, and early (defined as a conceptus in which organogenesis was not grossly evident) and late (defined as one in which the occurrence of organogensis was grossly evident) resorptions.  Uteri of nonpregnant rats were stained with 10% ammonium sulfide to confirm the absence of implantation sites.  Nonresponding term fetuses were considered dead.  Dead fetuses and late resorptions were differentiated by the degree of autolysis present; marked to extreme autolysis indicated that the fetus was a late resorption.  Placentae were examined for size, color, and shape.

Dams that died prior to the schedule necropsy were examined for the cause of death on the day that mortality was observed.  These animals were examined for gross lesions, and the pregnancy status and uterine contents were recorded.  Concepti in utero were examined to the extent possible, using the same methods described for term fetuses.  Uteri of nonpregnant rats were stained with 10% ammonium sulfide to confirm the absence of implantation sites.

2. Fetal Evaluations:  After removal from the uterus, fetuses were placed in individual containers and individually identified with a tag noting the study number, litter number, uterine distribution, and fixative.  Fetuses were then weighed, examined for gross lesions, and sexed.  Live fetuses were sacrificed via an intraperitoneal injection of sodium pentobarbital.  Approximately half of the fetuses per litter were fixed in Bouin's solution and examined for visceral abnormalities by using a variation of the microdissection technique of Staples.  The heads subsequently were examined by free-hand sectioning, and the sections were stored in alcohol.  Decapitated carcasses were not retained.  A skeletal examination was performed on the remaining fetuses, which had been fixed in alcohol and stained with alizarin red S.  Skeletal preparations were retained in glycerin with thymol added as a preservative.  Representative photographs of alterations (gross, visceral, and skeletal) were taken.

Fetal abnormalities were classified as malformations (irreversible changes that occur at low incidences in this species or strain) or variations (common findings in this species and strain and reversible delays or accelerations in developments).

D. DATA ANALYSIS

1. Statistical Analyses: Clinical observations and other proportional data were analyzed using the Variance Test for Homogeneity of the Binomial Distribution.  The Bartlett's Test of Homogeneity of Variances was used to analyze continuous data (e.g., body weights, body weight changes, feed consumption values, litter averages for percent male fetuses, percent resorbed conceptuses, fetal body weights and fetal anomaly data).  If the Bartlett's Test of Homogeneity of Variances was not significant (p>0.001), Analysis of Variance (ANOVA) was used.  If the ANOVA was significant (p(0.05), a Dunnett's Test was used to identify the statistical significance of the individual group compared to the control.  If the Bartlett's Test was significant  (p(0.001), the Kruskal-Wallis Test was used when (75% of ties were present.  The Dunn's Method of Multiple Comparisons was used to identify the statistical significance of each individual group compared to the control where the Kruskal-Wallis Test was statistically significant (p(0.05).  If there were >75% ties, the Fisher's Exact Test was used.  Count data obtained at the caesarean-sectioning were evaluated using the procedures described above for the Kruskal-Wallis Test.

2. Indices: Index formulas were not reported in this study; pre- and post-implantation loss were calculated in this study by the reviewer.

3. Historical control data:  Historical control data are provided in Appendix H of the study to allow comparison with concurrent controls.  Summaries of reproductive indices, maternal necropsy observations, fetal gross external alterations, fetal soft tissue alterations, fetal skeletal alterations, and fetal ossification sites are provided.

II.  RESULTS

A. MATERNAL TOXICITY

1. Mortality and Clinical Observations:  There were no treatment-related mortalities.  One 15-mg/kg/day dam and one 60-mg/kg/day dam were found dead on gd 5.  There were no observed adverse clinical signs for either of these dams, and weight gain and feed consumption values were comparable to other rats in the respective dosage groups.  Additionally, all tissues for both dams appeared normal at necropsy.

Significant clinical observations are presented in Table 2.  There was a significant (p(0.01) increase in the number of 60-mg/kg/day dams exhibiting the following clinical signs: flaking (grade 1); limited use of hindlimbs; shuffling gait; dehydration; ungroomed coat; urine stained abdominal fur; low carriage; chromodacyorrhea; emaciation; chromorhinorrhea; and hunched posture.  Dams administered 60 mg/kg/day also exhibited erythema (grade 1) and no use of hindlimbs, which were considered treatment-related, although not statistically significant.  These clinical signs resulted in a significant (p(0.01) increase in the number of 60-mg/kg/day dams with abnormal detailed post-treatment clinical signs.  Dams administered 30 mg/kg/day also exhibited a slight but statistically nonsignificant increase in the incidence of limited use of hind limbs and shuffling gait.  There were no treatment-related clinical observations reported at 10 or 15 mg/kg/day.

TABLE 2.  Significant Clinical Observationsa

Observations

Dose (mg/kg bw/day)

0

10

15

30

60

Maximum possible incidence

506/23b

528/24

512/24

528/24

534/25

Mortality

0

0

1c

0

1d

Skin Reaction

Erythema (grade 1)

5/1e

0/0

0/0

0/0

2/2

Flaking (grade 1)

2/1

0/0

0/0

2/1

56/14**

Clinical Observations

Limited use of hindlimbs

0/0

0/0

0/0

3/2

133/24**

Shuffling gait

0/0

0/0

0/0

5/1

136/22**

Dehydration

0/0

0/0

0/0

2/1

198/21**

Ungroomed coat

0/0

0/0

0/0

0/0

161/19**

Urine-stained abdominal fur

0/0

0/0

0/0

0/0

83/12**

Low carriage

0/0

0/0

0/0

0/0

47/11**

Chormodacryorrhea

0/0

0/0

1/1

0/0

20/9**

Emaciation

0/0

0/0

0/0

0/0

37/7**

Chromorhinorrhea

0/0

0/0

2/1

0/0

19/8**

Hunched posture

0/0

0/0

0/0

0/0

6/4**

No use of hindlimbs

0/0

0/0

0/0

0/0

4/1

Detailed Post-treatment Observations

Appeared normal

89/23

94/24

91/23

92/24

31/21**

Were not normal

3/2

2/2

1/1

3/3

65/24**

a   Data obtained from page 38-39 in the study report.

b   Maximum possible incidence = (days x rats)/number of rats examined per group on gd 0-21.

c   Dam 2337 was found dead on gd 5.

d   Dam 2332 was found dead on day 5 of presumed gestation.

e   N/N = total number of observations/number of rats with observations

** Statistically different (p <0.01) from the control.

2. Body Weight: Body weights were significantly decreased in 30- and 60-mg/kg/day dams on gd 13-21 and gd 7-21, respectively.

Body weight gain data are summarized in Table 3.  Treatment-related, significant decreases in body weight gains occurred in both 30- and 60-mg/kg/day dams throughout the entire treatment period and the post-treatment period.  For the 30-mg/kg/day dams, significant (p(0.05 or p(0.01) decreases in body weight gains occurred during gd 12-15, 15-18,18-20, and 20-21.  For 60-mg/kg/day dams, significant (p(0.01) decreases in body weight gains occurred at all measured intervals except gd 3-6.  Body weight gains for 10- and 15-mg/kg/day dams were comparable to the control group throughout the treatment period.

Uterine weights were significantly (p(0.01) decreased in 60-mg/kg/day dams.  Corrected body weights were significantly decreased (p(0.01) at 30 and 60 mg/kg/day.  Corrected body weight gains were significantly reduced (p(0.01) at 30 mg/kg/day for gd 0-21 and at 60 mg/kg/day for gd 0-21 and 20-21.  Uterine weight, corrected body weight, and corrected body weight gains for 10- and 15-mg/kg/day dams were comparable to the control group.

TABLE 3.  Mean (±SD) Maternal Body Weight Gain (g)a

Interval

Dose in mg/kg bw/day (# of Dams)

0 (23)

10 (23)

15 (24b)

30 (24)

60 (23)

Treatment:

GD 0-3

18.5±5.7

17.7±5.3

14.7±6.5

14.8±6.1

12.3±7.0**

GD 3-6

7.7±9.9

6.2±8.4

9.2±3.4

6.9±7.2

14.1±7.3

GD 6-9

14.6±10.2

15.0±6.7

14.0±3.9

12.6±8.4

5.2±13.4**

GD 9-12

19.2±8.1

19.0±3.6

17.2±6.0

15.3±6.3

-4.1±19.0**

GD 12-15

20.6±5.1

19.4±7.9

19.7±5.2

12.4±6.8**

-8.0±11.7**

GD 15-18

35.8±8.4

35.3±6.4

32.3±7.4

29.2±7.8*

11.0±11.9**

GD 18-20

29.4±7.2

29.4±8.6

27.6±6.2

22.2±9.5**

21.2±9.0**

Post-treatment:

GD 20-21

16.8±6.0

15.3±6.6

17.4±5.2

12.3±5.5*

7.1±8.5**

Overall Body Weight Gain

GD 0-21

162.6±22.2

157.3±21.5

151.8±20.6

125.8±24.2**

48.8±28.5**

Uterine Weight

99.10±15.66

100.93±12.27

96.54±16.73

95.65±12.82

76.09±14.38**

Corrected BW Gain

GD  0-21

63.6±14.4

56.4±14.8

55.3±13.6

30.1±19.3**

-27.3±17.3**

GD 20-21

-82.3±16.6

-85.6±10.7

-79.1±15.5

-83.3±14.3

-69.0±12.9**

a   Data obtained from page 42-43 in the study report.

b   N=23 beginning on gd 3-6.  Calculations exclude values for dam 2337 because the dam was found dead on gd 5.

*   Statistically different (p <0.05) from the control.

** Statistically different (p <0.01) from the control.

3. Food Consumption:  Absolute and relative feed consumption data are summarized in Tables 4a and 4b.  Treatment-related, significant decreases in feed consumption (gd 0-21) occurred in both 30- and 60-mg/kg/day dams.  For the 30-mg/kg/day dams, significant (p(0.01) decreases in feed consumption values occurred during gd 18-20 and 20-21.  For 60-mg/kg/day dams, significant (p(0.01) decreases in absolute feed consumption values occurred during 6-9, 9-12, 12-15, 15-18, 18-20, and 20-21.  Absolute feed consumption values for 10- and 15-mg/kg/day dams were comparable to the control group throughout the treatment period.

Significant decreases (p(0.01) in relative feed consumption values occurred at 60 mg/kg/day for the overall treatment period (gd 0-21) and during gd 9-12, 12-15, and 15-18.  Relative feed consumption values for 10-, 15-, and 30-mg/kg/day dams were comparable to the control group throughout the treatment period.

TABLE 4a.  Mean (±SD) Absolute Maternal Feed Consumption (g/day)a

Interval

Dose in mg/kg bw/day (# of Dams)

0 (23)

10 (23)

15 (24b)

30 (24)

60 (23)

Treatment:

Days 0-3

18.8±2.1

18.4±1.7

18.2±2.1

18.2±2.0

17.9±2.3

Days 3-6

20.4±2.5

20.0±1.9

19.7±2.1

19.2±2.0

19.6±2.0

Days 6-9

22.6±2.7

22.0±1.9

21.9±2.0

21.2±1.9d

20.5±3.2**

Days 9-12

24.3±2.7

24.2±2.0

23.7±2.6

23.6±2.5

17.7±6.2**

Days 12-15

26.0±3.3

25.7±2.6

24.3±3.3c

23.7±2.9

16.6±5.8**

Days 15-18

28.4±3.6c

27.4±2.9

26.4±3.4c

26.1±3.3

17.2±5.0**

Days 18-20

29.0±4.0

27.6±3.3

27.5±2.5

25.4±3.3**

21.4±5.0**

Days 20-21

25.8±3.4

24.7±4.7c

25.6±3.8

20.8±3.9**

17.2±5.8**

Overall Feed Consumption

Days 0-21

24.0±2.4

23.5±1.7c

23.0±1.9

22.3±1.6**

18.5±2.5**

a   Data obtained from page 44 in the study report.

b   N=23 beginning on gd 3-6.  Calculations exclude values for dam 2337 because the dam was found dead on gd 5.

c   N=22 because values that appeared incorrectly recorded, as well as those that were associated with spillage or set/soiled feed, were excluded.

d   N=23 because values that appeared incorrectly recorded, as well as those that were associated with spillage or set/soiled feed, were excluded.

*   Statistically different (p <0.05) from the control.

** Statistically different (p <0.01) from the control.

TABLE 4b.  Mean (±SD) Relative Maternal Feed Consumption (g/kg/day)a

Interval

Dose in mg/kg bw/day (# of Dams)

0 (23)

10 (23)

15 (24b)

30 (24)

60 (23)

Treatment:

Days 0-3

78.7±6.6

77.1±5.7

76.6±7.2

77.0±6.8

75.4±8.4

Days 3-6

80.8±7.7

80.0±6.1

79.3±6.1

77.7±6.6

80.0±6.4

Days 6-9

86.0±7.3

84.4±6.0

84.5±5.7

82.7±5.5d

82.0±11.8

Days 9-12

86.8±7.1

87.0±4.8

86.0±7.1

87.2±7.6

69.1±21.5**

Days 12-15

86.9±7.8

86.5±6.7

83.0±9.9c

83.4±7.8

67.4±19.8**

Days 15-18

87.2±7.5c

85.0±7.6

83.4±9.4c

86.0±7.9

70.9±19.8**

Days 18-20

80.5±8.0

77.4±6.5

78.5±5.3

77.1±8.2

82.5±19.0

Days 20-21

67.5±8.1

65.0±10.0c

68.8±9.4

59.8±11.0

62.2±18.4

Overall Feed Consumption

Days 0-21

82.7±4.9

81.5±3.4c

80.7±4.4

80.4±3.0

74.3±5.3**

a   Data obtained from page 45 in the study report.

b   N=23 beginning on gd 3-6.  Calculations exclude values for dam 2337 because the dam was found dead on gd 5.

c   N=22 because values that appeared incorrectly recorded, as well as those that were associated with spillage or set/soiled feed, were excluded.

d   N=23 because values that appeared incorrectly recorded, as well as those that were associated with spillage or set/soiled feed, were excluded.

*   Statistically different (p <0.05) from the control.

** Statistically different (p <0.01) from the control.

4. Hindlimb Evaluation: Results from the hindlimb evaluation are presented in Tables 5a and 5b.  At 60 mg/kg/day, there was a significant (p(0.01) increase in the number of dams with low muscle tone, and a corresponding significant (p(0.01) decrease in the number of dams with moderate muscle tone on gd 12, 16, and 20.

Muscle mass was slightly decreased in one dam administered 60 mg/kg/day on gd 12.  There was a significant (p(0.01) increase in the number of 60-mg/kg/day dams that exhibited slightly reduced muscle mass, and a corresponding significant decrease (p(0.01) in the number of 60-mg/kg/day dams that exhibited normal muscle mass on gd 16 and 20.

At 30 mg/kg/day, low muscle tone was observed in 2 out of the 24 dams on gd 20.  This observation was not considered treatment-related because: 1) there was a low frequency of occurrence; 2) there was no corresponding loss of muscle mass; and 3) the measurement was not sufficient alone to demonstrate an adverse effect.  Muscle tone and muscle mass for 10- and  15-mg/kg/day dams were comparable to the control group throughout the treatment period.

TABLE 5a.  Muscle Tone (N)a

Dose in mg/kg bw/day (# of Dams)

0 (23)

10 (24)

15 (23b)

30 (24)

60 (24b)

GD 8 - Muscle Tone

None

0

0

0

0

0

Low

0

0

0

0

1

Moderate

23

24

23

24

23

High

0

0

0

0

0

GD 12 - Muscle Tone

None

0

0

0

0

1d

Low

0

0

0

0

15d**

Moderate

21c

22c

22d

23d

7d**

High

0

0

0

0

0

GD 16 - Muscle Tone

None

0

0

0

0

2

Low

0

0

0

0

21**

Moderate

23

24

23

24

1**

High

0

0

0

0

0

GD 20 - Muscle Tone

None

0

0

0

0

0

Low

0

0

0

2

21c**

Moderate

23

24

23

22

2c**

High

0

0

0

0

0

a   Data obtained from page 46-47 in the study report.

b  Excludes dams that were found dead on gd 5.

c  Excludes two rats in which evaluation was not performed.

d  Excludes one rat in which evaluation was not performed.

** Statistically different (p <0.01) from the control.

TABLE 5b.  Muscle Mass (N) a

Interval

Dose in mg/kg bw/day (# of Dams)

0 (23)

10 (24)

15 (23b)

30 (24)

60 (23)

GD 8 - Muscle Tone

Greatly reduced

0

0

0

0

0

Slightly reduced

0

0

0

0

0

Normal

23

24

23

24

24

GD 12 - Muscle Tone

Greatly reduced

0

0

0

0

0

Slightly reduced

0

0

0

0

1d

Normal

21c

22c

22d

23d

22d

GD 16 - Muscle Tone

Greatly reduced

0

0

0

0

0

Slightly reduced

0

0

0

0

6**

Normal

23

24

23

24

18**

GD 20 - Muscle Tone

Greatly reduced

0

0

0

0

0

Slightly reduced

0

0

0

0

12c**

Normal

23

24

23

24

11c**

a   Data obtained from page 46-47 in the study report.

b  Excludes dams that were found dead on gd 5.

c  Excludes two rats in which evaluation was not performed.

d  Excludes one rat in which evaluation was not performed.

** Statistically different (p <0.01) from the control.

5. Gross Pathology: There were no treatment-related gross pathology changes observed at any dose level.

6. Cesarean Section Data: Data are as summarized in Table 6.  There were no treatment-related changes in any of the following reproductive parameters at any dose level: corpora lutea, implantations, litter sizes, live fetuses, early and late resorptions, percentage of dead or resorbed conceptuses, and the percentage of live male fetuses.  At 60 mg/kg/day, there was a significant (p(0.01) decrease in fetal weight (total, male, and female).  Fetal weights recorded for 10-, 15-, and 30-mg/kg/day pups were comparable to the control group.  Pre- and post implantation losses (as calculated by our reviewers) appear to be comparable among groups, mainly due to the large standard deviations.

TABLE 6.  Cesarean Section Observations a

Observation

Dose (mg/kg bw/day)

0

10

15

30

60

# Animals Assigned (Mated)

23

24

24

24

25

# Animals Pregnant

23

23

24

24

23

  	Pregnancy Rate (%)

100.0

95.8

100.0

100.0

92.0

# Nonpregnant

0

1

0

0

2

Maternal Wastage

  	# Died

0

0

1

0

1

# Died Pregnant

0

0

1

0

0

# Died Nonpregnant

0

0

0

0

1

# Aborted

0

0

0

0

0

# Premature Delivery

0

0

0

0

0

Total # Corpora Lutea

Corpora Lutea/Dam

357

15.5±1.9

370

16.1± 2.0

348

15.1± 2.6

355

14.8± 2.3

361

15.7± 2.4

Total # Implantations

Implantations/Dam

334

14.5± 1.9

339

14.7±1.7

322

14.0±2.3

337

14.0±1.8

324

14.1±2.4

Total # Litters

23

23

24

24

23

Total # Live Fetuses

Live Fetuses/Dam

315

13.7±2.4

328

14.3±1.7

310

13.5±2.4

323

13.4±2.1

308

13.4±2.4

Total # Dead Fetuses

Dead Fetuses/Dam

0

0.0±0.0

0

0.0±0.0

0

0.0±0.0

0

0.0±0.0

0

0.0±0.0

Total # Resorptions

Total

19

11

12

14

16

Early

19

10

12

12

15

Late

0

1

0

2

1

Resorptions/Dam

Total

0.8±1.4

1.5±0.9

0.5±0.8

0.6±0.7

0.7±0.9

Early

0.8±1.4

0.4±0.8

0.5±0.8

0.5±0.7

0.6±0.9

Late

0.0±0.0

0.0±0.2

0.0±0.0

0.1±0.3

0.0±0.2

Litters with Total Resorptions

0

0

0

0

0

Mean Fetal Weight (g)

Total

5.35±0.26

5.25±0.45

5.28±0.29

5.31±0.44

4.31±0.47**

Males

5.52±0.29

5.41±0.46

5.44±0.27

5.44±0.45

4.39±0.49**

Females

5.15±0.30

5.07±0.44

5.10±0.31

5.17±0.44

4.23±0.48**

Sex Ratio (% Male)

51.9±16.7

52.2±13.8

52.1±12.7

47.6±15.3

47.5±14.9

Preimplantation Loss (%)

6.38±6.0

8.11±5.97

7.03±8.20

4.59±6.06

10.21±10.11

Postimplantation Loss (%)

5.79± 9.33

3.10±5.54

3.76±5.57

4.32±5.53

4.86±6.29

a   Data obtained from pages 48-49 in the study report.

b   Preimplantation loss ([(number of corpora lutea - number of implantations)]/number of corpora lutea) X 100) and postimplantation loss ([(number of implantations - number of live young)]/number of implantations) X 100) were calculated by our reviewers; no statistical analyses was conducted.

*   Statistically different (p <0.05) from the control.

** Statistically different (p <0.01) from the control.

B. DEVELOPMENTAL TOXICITY

1. External Examination:  There were no treatment-related gross external alterations (malformations or variations) at any dose level.

2. Visceral Examination:  There were no treatment-related visceral alterations (malformations or variations) at any dose level.

3. Skeletal Examination:  Significant skeletal findings are presented in Tables 7a and 7b.  There were no treatment-related skeletal malformations identified.  At 60 mg/kg/day, there was a significant (p(0.01) increase in the percentage of litters and fetuses with incomplete ossification of the sternal central.  There also was a significant increase in the percentage of fetuses (but not litters) with wavy ribs.  These increases were correlated to significant reductions in ossification site averages for the caudal vertebrae, forelimb phalanges and metacarpals, and hindlimb phalanges and metatarsals per fetus per litter at 60 mg/kg/day.  Skeletal alterations recorded for the 10-, 15-, and 30-mg/kg/day fetuses were comparable to the control group.

TABLE 7a.  Skeletal Examinationsa

Observationsb

Dose (mg/kg bw/day)

0

10

15

30

60

#Fetuses (litters) examined

164 (23)

171 (23)

161 (23)

168 (24)

160 (23)

#Fetuses (litters) affected

5 (4)

2 (1)

2 (2)

1 (1)

10 (6)

Wavy Ribs

Litter Percentage

Fetal Percentage

0 (0)c

0.0

0.0

0 (0)

0.0

0.0

0 (0)

0.0

0.0

0 (0

0.0

0.0

3 (2)

8.7

1.9**d,e

Incompletely Ossified Sternal Centra

Litter Percentage

Fetal Percentage

0 (0)

0.0

0.0

0 (0)

0.0

0.0

0 (0)

0.0

0.0

0 (0)

0.0

0.0

5 (3)

13.0**

3.1**e,f

a   Data obtained from pages 53-54 and 127-137 in the study report.

b   Some observations may be grouped together.

c   Fetal (litter) incidence

d   Fetus 2371-1 had other skeletal alterations.

e   Fetus 2399-13 had other skeletal alterations.

f    Fetus 2385-1 had other skeletal alteraions.

** Statistically different (p <0.01) from the control.

TABLE 7b.  Fetal Ossification Sites/Littera

Observation

Fetal Ossification Sites/Litter

------------------------------------------------------------------------ ---------

Dose in mg/kg bw/day

0

10

15

30

60

Vertebrae

Caudal

7.40±0.63

7.48±0.70

7.25±0.69

7.58±0.92

6.34±0.73**

Forelimbb

Metacarpals

4.00±0.00

4.00±0.00

4.00±0.00

4.00±0.00

3.97±0.08*

Phalanges

7.80±0.73

7.88±0.73

7.54±1.08

8.01±0.78

7.24±0.84*

Hindlimbsb

Metatarsals

4.72±0.26

4.78±0.25

4.72±0.25

4.77±0.29

4.22±0.26**

Phalanges

5.60±0.82

5.84±0.99

5.75±0.90

6.04±1.22

5.18±0.43*

a   Data obtained from pages 55 in the study report.

b  Calculated as average per limb.

*   Statistically different (p <0.05) from the control.

** Statistically different (p <0.01) from the control.

III. DISCUSSION and CONCLUSIONS

A. Maternal toxicity: Treatment related effects were seen at 30 and 60 mg/kg/day. Treatment-related effects at 60 mg/kg/day included clinical signs of toxicity (grade 1 erythema; grade 1 flaking, limited or no use of hindlimbs; shuffling gait; dehydration; ungroomed coat; urine stained abdominal fur; low carriage; chromodacryorrhea; emaciation; chromorhinorrhea; hunched posture; and no use of hindlimbs), decreased body weight and body weight gain, decreased uterine weight, decreased corrected body weight and corrected body weight gain, decreased absolute and relative feed consumption, and decreased muscle tone and mass.

At 30 mg/kg/day, there was an increase in the number of dams with limited use of hindlimbs, shuffling gait; decreased body weight and body weight gain, decreased corrected body weight and corrected body weight gain, and decreased absolute feed consumption.

The maternal LOAEL is 30 mg/kg bw/day, based on an increase in the number of dams with limited use of hindlimbs, shuffling gait, decreased body weight and body weight gain, decreased corrected body weight and corrected body weight gain, and decreased absolute feed consumption.  The maternal NOAEL is 15 mg/kg bw/day.

B. Developmental toxicity:

a. Deaths/Resorptions: There were no treatment-related effects on fetal deaths.

b. Altered Growth: At 60 mg/kg/day, there was a significant decrease in fetal weight (total, male, and female).

c. Developmental Variations: There were no treatment-related visceral variations.  At 60 mg/kg/day, there was an increase in the percentage of litters and fetuses with incomplete ossification of the sternal centra, an increase in the percentage of fetuses with wavy ribs, and a decrease in the ossification site averages for the caudal vertebrae, forelimb phalanges and metacarpals, and hindlimb phalanges and metatarsals per fetus per litter.

d. Malformations: There were no treatment-related external, visceral, or skeletal malformations.

The developmental LOAEL is 60 mg/kg bw/day, based on decreased fetal weight (total, male, and female), an increase in the percentage of litters and fetuses with incomplete ossification of the sternal centra, an increase in the percentage of fetuses with wavy ribs, and a decrease in the ossification site averages for the caudal vertebrae, forelimb phalanges and metacarpals, and hindlimb phalanges and metatarsals per fetus per litter.  The developmental NOAEL is 30 mg/kg bw/day.

IV. STUDY DEFICIENCIES:  Pre- and postimplantation losses were calculated; by the reviewer. There are no significant differences between the treatment and control groups, mainly due to the large standard deviations observed.

V. STUDY CLASSIFICATION: This study is classified as ACCEPTABLE-GUIDELINE and satisfies the guideline requirements for a developmental toxicity study (OPPTS 870.3700; OECD 414) in rats.

 Source: www.chemfinder.com

 Draize, J.H., Woodard, G., and Calvery, H.O. 1944. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J. Pharmacol. Exp. Ter. 82:377-390.

 National Research Council. 1977. Principles and Procedures for Evaluating the Toxicity of Household Substances. National Academy of Sciences: Washignton, DC. Pp. 30-31.

 Staples, R.E. 1974. Detection of visceral alteration in mammalian fetuses. Teratol. 9(3):A37-38.

 Salewski, E. 1964. Staining method for macroscopic demonstration of implantation sites in the rat uterus. Arch. Pathol. Exp. Pharmakol. 247:367.

 Snedcor, G.W. and Cochran, W.G. 1967. Variance Test for Homogeneity of the Binomial Distribution. In, Statistical Methods, 6th Edition. Iowa State University Press: Ames. Pp 240-241.

 Sokal, R.R., and Rohlf, F.J. 1969. Bartlett's Test of Homogeneity of Variances. In, Biometry. W.H. Freeman and Co.: San Francisco. Pp. 370-371.

 Snedcor, G.W. and Cochran, W.G. 1967. Analysis of Variance. In, Statistical Methods, 6th Edition. Iowa State University Press: Ames. Pp 258-298.

 Dunnett, C.W. 1955. A multiple comparison procedure for comparing several treatments with a control. J. Amer. Stat. Assoc. 50:1096-1121.

  Sokal, R.R., and Rohlf, F.J. 1969. Kruskal-Wallis Test. In, Biometry. W.H. Freeman and Co.: San Francisco. Pp. 370-371.

 Dunn, O.J. 1964. Multiple comparisons using rank sums. Technometrics 6(3):241-252.

 Siegal, S. 1956. The Fisher's Exact Probability Test. In, Nonparametric Statisticas for the Behavior Sciences. McGraw-Hill Co.: New York. Pp. 96-105.

Zinc Pyrithione	870.3700 Prenatal Developmental Toxicity Study/Rat

 PAGE

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	Prenatal Developmental Toxicity Study (rodents) (2005)  / Page  PAGE  21  of 18

[Zinc Pyrithione]	OPPTS 870.3700a/ OECD 414


[Federal Register Volume 87, Number 180 (Monday, September 19, 2022)]
[Notices]
[Page 57214]
[FR Doc No: 2022-20160]

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DEPARTMENT OF HOMELAND SECURITY

Federal Emergency Management Agency

[Docket ID FEMA-2022-0002; Internal Agency Docket No. FEMA-B-2018]

Proposed Flood Hazard Determinations for Winneshiek County, Iowa
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AGENCY: Federal Emergency Management Agency, Department of Homeland
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ACTION: Notice; withdrawal.

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SUMMARY: The Federal Emergency Management Agency (FEMA) is withdrawing
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