SUPPORTING STATEMENT

ENVIRONMENTAL PROTECTION AGENCY

STANDARDS OF PERFORMANCE

NSPS SUBPART GGG

EQUIPMENT LEAKS OF VOC IN PETROLEUM REFINERIES

OCTOBER 2006

1.  Identification of the Information Collection

	1(a)  Title of the Information Collection

ICR for NSPS Subpart GGG - Equipment Leaks of VOC in Petroleum
Refineries

	1(b)  Short Characterization/Abstract

	The New Source Performance Standards (NSPS) for Equipment Leaks of VOC
(Volatile Organic Compound) in Petroleum Refineries were proposed on
January 4, 1983 and promulgated on May 30, 1984.  These standards apply
to the following facilities in petroleum refineries: compressors and the
group of all equipment (e.g., valves, pumps, flanges, etc.) within a
process unit in VOC service, commencing construction, modification or
reconstruction after the date of proposal.  This information is being
collected to assure compliance with 40 CFR part 60, subpart GGG.    SEQ
CHAPTER \h \r 1 The burden estimates presented in this ICR reflect
proposed amendments to the reporting and recordkeeping requirements in
Subpart GGG.

	Owners or operators of the affected facilities described must make
one-time-only notifications.  Owners or operators are also required to
maintain records of the occurrence and duration of any startup,
shutdown, or malfunction in the operation of an affected facility, or
any period during which the monitoring system is inoperative.
Monitoring requirements specific to Equipment Leaks of VOC in Petroleum
Refineries provide information on which components are leaking VOCs.
NSPS GGG references the compliance requirements of NSPS VV.  Owners or
operators are required to periodically (time period varies depending on
equipment type and leak history) record information identifying leaking
equipment, repair methods used to stop the leaks and dates of repair.
Semiannual reports are required to measure compliance with the standards
of NSPS Subpart VV as referenced by NSPS Subpart GGG.  These
notifications, reports, and records are essential in determining
compliance; and are required, in general, of all sources subject to
NSPS.  Any owner or operator subject to the provisions of this part
shall maintain a file of these measurements, and retain the file for at
least two years following the date of such measurements, maintenance
reports, and records.

	The Environmental Protection Agencies databases show that approximately
45 sources are currently subject to the standard, and it is estimated
that an additional 2 sources per year will become subject to the
standard in the next three years.  There have been no new refineries
built during the period of these regulations, and the increase is
expected to come solely from sources that meet the definition of
reconstruction or modification.  The labor hours are 8,317 per year and
the annual cost of this ICR will be $460,505.  All reports are sent to
the delegated State or Local authority.  In the event that there is no
such delegated authority, the reports are sent directly to the EPA
Regional Office.

2.   Need for and Use of the Collection

	2(a)  Need/Authority for the Collection

	The EPA is charged under Section 111 of the Clean Air Act, as amended,
to establish standards of performance for new stationary sources that
reflect:

. . . application of the best technological system of continuous
emissions reduction which (taking into consideration the cost of
achieving such emissions reduction, or any nonair quality health and
environmental impact and energy requirements) the Administrator
determines has been adequately demonstrated [Section 111(a)(l)].

	The Agency refers to this charge as selecting the best demonstrated
technology (BDT).  Section 111 also requires that the Administrator
review and, if appropriate, revise such standards every four years.  In
addition, Section 114(a) States that the Administrator may require any
owner or operator subject to any requirement of this Act to:

		(A) establish and maintain such records, (B) make such reports, (C)
install, use, and maintain such monitoring equipment and use such audit
procedures, or methods;  (D)  sample such emissions (in accordance with
such methods at such locations, at such intervals, during such periods,
and in such manner as the Administrator shall prescribe); (E) keep
records on control equipment parameters, production variables or other
indirect data when direct monitoring of emissions is impractical;  (F)
submit compliance certifications in accordance with Section 114(a)(3);
and (G) provide such other information as the Administrator may
reasonably require.

	In the Administrator's judgment, VOC emissions from Equipment Leaks of
VOC in Petroleum Refineries cause or contribute to air pollution that
may reasonably be anticipated to endanger public health or welfare.
Therefore, NSPS were promulgated for this source category at 40 CFR part
60, subpart GGG.

	2(b)  Practical Utility/Users of the Data

	The control of emissions of VOC from equipment leaks in petroleum
refineries requires not only the installation of properly designed
equipment, but also the operation and maintenance of that equipment.
Emissions of VOC from equipment leaks in petroleum refineries are the
result of operation of the compressors and the group of all equipment
(e.g., valves, pumps, flanges, etc.) within a process unit in VOC
service.  These standards rely on the prevention of VOC emissions by the
work practice of proper leak detection and timely repair.

The notifications required in these standards are used to inform the
Agency or delegated authority when a source becomes subject to these
standards.  The reviewing authority may then inspect the source to check
if the leaks are being detected and repaired and the standard is being
met.  Performance test reports are needed, as these are the Agency's
record of a source's initial capability to comply with the emission
standard and serve as a record of the operating conditions under which
compliance was achieved.  NSPS Subpart GGG references NSPS Subpart VV
for compliance.

Monthly monitoring of compressors and equipment in VOC service under
NSPS Subpart GGG shall take place as specified in NSPS Subpart VV
section 60.485(b).  For valves, if no leaks are detected for two
successive months, monitoring may be performed once per quarter (see
§60.482-7(c)).  If a leak is detected, the equipment shall be monitored
monthly until a leak is not detected for two successive months.  Also,
leak location shall be recorded in a log, and this information shall be
kept available for two years.  Leaks shall be repaired within 15 days
and the date of successful repair shall be recorded in the log.
Additionally, an owner or operator may use specified equipment
eliminating the need for monitoring, or seek approval of alternative
emission limitations under other various sections of 40 CFR subpart VV.
Semiannual reports shall be submitted itemizing the information for each
month.  Notifications are used to inform the Agency, or delegated
authority when a source becomes subject to a standard.  The reviewing
authority may then inspect the source to check if the standard is being
met.  The semiannual reports are used for problem identification, as a
check on source operations and maintenance, and for compliance
determinations.

The information generated by the monitoring, recordkeeping and reporting
requirements described in this ICR is used by the Agency to ensure that
facilities affected by the NSPS continue to identify and repair leaking
equipment and achieve compliance with the regulation.  Adequate
monitoring, recordkeeping, and reporting are necessary to ensure
compliance with these standards, as required by the Clean Air Act.  The
information collected from recordkeeping and reporting requirements is
also used for targeting inspections, and is of sufficient quality to be
used as evidence in court.

3.  Nonduplication, Consultations, and Other Collection Criteria

The recordkeeping and reporting requested is required under 40 CFR part
60, subpart GGG.

	3(a)  Nonduplication

	If the subject standards have not been delegated, the information is
sent to the appropriate EPA Regional Office.  Otherwise, the information
is sent directly to the delegated State or local agency.  If a State or
local agency has adopted their own similar standards to implement the
Federal standards, a copy of the report submitted to the State or local
agency can be sent to the Administrator in lieu of the report required
by the Federal standards.  Therefore, no duplication exists.

	3(b)  Public Notice Required Prior to ICR Submission to OMB

  SEQ CHAPTER \h \r 1 A public review and comment period will occur
following publication of the proposed amendments to the Standards of
Performance for Equipment Leaks of VOC in Petroleum Refineries (40 CFR
part 60, subpart GGG) in the Federal Register.

	3(c)  Consultations

  SEQ CHAPTER \h \r 1 	The EPA will provide a 60-day public comment
period after proposal of the amendments to the NSPS Subpart GGG.  All
affected parties will be given the opportunity to comment on the
proposed amendments during this period.  The EPA will consider all of
the comments received and may incorporate them in developing the final
amendments.

	During development of the proposed amendments, EPA held meetings and
conference calls with representatives of petroleum refining companies
and their trade associations (National Petroleum Refiners Association
and American Petroleum Institute); however, recordkeeping and reporting
requirements and related burden estimates were not discussed during
these meetings.

	3(d)  Effects of Less Frequent Collection

	  Less frequent information collection would decrease the margin of
assurance that facilities are continuing to meet the required standards.
 Requirements for information gathering and recordkeeping are useful
techniques to ensure that good operation and maintenance practices are
applied and emission limitations are met.  If the information required
by these standards was collected less frequently, the likelihood of
detecting poor operation and maintenance of control equipment and
noncompliance would decrease.

	3(e)  General Guidelines

	None of the reporting or recordkeeping requirements contained in 40 CFR
part 60, subpart GGG or otherwise pertinent to this request violate any
of the regulations established by OMB in 5 CFR 1320.6.

	3(f)  Confidentiality

	The required information consists of emissions data and other
information that have been determined not to be private.  However, any
information submitted to the Agency for which a claim of confidentiality
is made will be safeguarded according to the Agency policies set forth
in Title 40, Chapter 1, Part 2, Subpart B - Confidentiality of Business
Information (see 40 CFR 2; 41 FR 36902, September 1, 1976; amended by 43
FR 40000, September 8, 1978; 43 FR 42251, September 20, 1978; 44 FR
17674, March 23, 1979).

	3(g)  Sensitive Questions

	None of the reporting or recordkeeping requirements contained in 40 CFR
part 60, subpart GGG or otherwise pertinent to this request contain
sensitive questions.

4.  The Respondents and the Information Requested

	4(a)  Respondents/SIC Codes

	The respondents of the recordkeeping and reporting requirements are
petroleum refineries where the affected compressors or group of
equipment within a process unit commenced construction, modification, or
reconstruction after January 4, 1983.  The SIC code for the respondents
affected by the standards is SIC (U.S. Standard Industrial
Classification) Code 2911 which corresponds to the NAICS (North American
Industry Classification System) 324110 for petroleum refineries where
the affected compressors or group of equipment within a process unit
commenced construction, modification, or reconstruction after January 4,
1983.

	4(b)  Information Requested

.		(i)  Data Items

	All data in this ICR that is recorded and/or reported is required by 40
CFR part 60, subpart GGG.  Although monitoring of the various components
may be required on a weekly, monthly, quarterly, semi-annual or annual
basis, given the number of components that must be monitored at any
facility, monitoring overall is essentially occurring daily.  Therefore,
it is assumed that the average record keeping time for each day’s
worth of monitoring is 0.3 hours and that monitoring is done 365 days a
year.  An estimated 0.12 hours per day are needed to complete the tasks
required by the proposed amendments.

	A source must make the following reports:

Notifications for 40 CFR Part 60, Subpart GGG	Citation

Construction/reconstruction	60.7(a)(1)

Anticipated startup	60.7(a)(2)

Actual startup	60.7(a)(3)

Physical or operational change	60.7(a)(4)

Initial performance test	60.8(d)

Alternative standard selected	60.487(d)

Reports for 40 CFR Part 60, Subpart GGG

	Initial performance test results	60.8(a)

Comply with the provisions of 60.487	60.592(e)

Semiannual reports (this provision is proposed to be amended)	60.486,
60.487(a), 60.487(b), 60.487(c)

Performance test 	60.8, 60.487(e)

	A source must keep the following records:

Recordkeeping for 40 CFR Part 60, Subpart GGG	Citation

Startups, shutdowns, malfunctions	60.7(b)

All measurements, monitoring device, and performance testing
measurements	60.7(e)

Comply with the provisions of 60.486	60.592(e)

The date and instrument reading of each monitored component must be
recorded (this provision is proposed to be added)	60.486(a)

Each detected leak shall be recorded in a log and kept for 2 years (this
provision is proposed to be amended)	60.486(c)

Information pertaining to design requirements or closed vent systems and
control devices (this provision is proposed to be amended)	60.486(d)

Information pertaining to all equipment (this provision is proposed to
be amended)	60.486(e)

Information pertaining to all valves	60.486(f)

Information pertaining to valves complying with alternative compliance
requirements	60.486(g)

Design criteria and any changes	60.486(h)

Records for use in determining exemptions	60.486(i)

Information and data to demonstrate that a piece of equipment is not in
VOC service	60.486(j)

	Records are required to be retained for 2 years.

ii.  Respondent Activities

Respondent Activities

Read instructions

Perform initial performance test as per 40 CFR 60.485, Reference Method
21 and 22 tests, and repeat performance tests

Write the notifications and reports listed above

Enter information required to be recorded above

Submit the required reports developing, acquiring, installing, and
utilizing technology and systems for the purpose of collecting,
validating, and verifying information

Develop, acquire, install, and utilize technology and systems for the
purpose of processing and maintaining information

Develop, acquire, install, and utilize technology and systems for the
purpose of disclosing and providing information

Adjust the existing ways to comply with any previously applicable
instructions and requirements

Train personnel to be able to respond to a collection of information

Transmit or otherwise disclose the information

	As refiners replace/upgrade their monitoring equipment, they may choose
to use systems that automatically log the results of monitoring, which
can then be downloaded into a computer database.  This database can then
be used to develop the required reports.

5.  The Information Collected -- Agency Activities, Collection
Methodology, and Information Management

	5(a)  Agency Activities

	EPA conducts the following activities in connection with the
acquisition, analysis, storage, and distribution of the information
required under 40 CFR Part 60, Subpart GGG:

Agency Activities

Observe initial performance tests and repeat performance tests if
necessary

Review notifications and reports, including performance test reports,
and other reports, required to be submitted by industry

Audit facility records

Input, analyze, and maintain data in the Aerometric Information
Retrieval System (AIRS) database

	5(b)  Collection Methodology and Management

	Following notification of startup, the reviewing authority might
inspect the source to determine whether the pollution control devices
are properly installed and operated.  Performance test reports are used
by the Agency to discern a source’s initial capability to comply with
the emission standard.  Data and records maintained by the respondents
are tabulated and published for use in compliance and enforcement
programs.  The semiannual reports are used for problem identification,
as a check on source operation and maintenance, and for compliance
determinations.

	Information contained in the reports is entered into AIRS, which is
operated and maintained by EPA's Office of Air Quality Planning and
Standards.  AIRS is EPA’s database for the collection, maintenance,
and retrieval of compliance and annual emission inventory data for over
100,000 industrial and government-owned facilities.  EPA uses AIRS for
tracking air pollution compliance and enforcement by Local and State
regulatory agencies, and EPA Regional Offices and Headquarters.  EPA and
its delegated Authorities can edit, store, retrieve and analyze the
data.  The records required by this regulation must be retained by the
owner or operator for two years.

	5(c)  Small Entity Flexibility

	For this industry, there is a distribution of business sizes.  The
recordkeeping and reporting requirements were selected within the
context of this specific subpart and the specific process equipment and
pollutant.  A majority of the affected facilities are large businesses.
However, the impact on small businesses was taken into consideration
during development of the regulation.  Due to technical considerations
involving the process operations and leak detection and repair programs,
the recordkeeping and reporting requirements are the same for both small
and large businesses.  The Agency considers these requirements to be the
minimum needed to ensure compliance and, therefore, cannot reduce them
further for small businesses.  To the extent that larger businesses can
use economies of scale to reduce their burden, the overall burden will
be reduced.

	For sources that install “leakless” components, monitoring may not
be required for those components.  Monitoring (and therefore,
recordkeeping) may also be reduced for sources that maintain low
percentages of leaking components.  Additionally, alternative means of
emission limitation are allowed after proper demonstration of their
effectiveness to the Administrator.

	5(d)  Collection Schedule

	The specific frequency for each information collection activity within
this request is shown in Table 2: Annual burden of reporting and
recordkeeping requirements as a result of NSPS Subpart GGG.

6.  Estimating the Burden and Cost of the Collection

	Table 2 documents the computation of individual burdens for the
recordkeeping and reporting requirements applicable to the industry for
the Subpart included in this ICR.  The individual burdens are expressed
under standardized headings believed to be consistent with the concept
of burden under the Paperwork Reduction Act.  Where appropriate,
specific tasks and major assumptions have been identified.  The type of
industry costs associated with the information collection activity in
the standards are labor costs for using the VOC monitors.  Monitoring
equipment for leaks is standard in the industry for safety reasons.  To
the extent possible, the requirements of this standard are consistent
with industry practice.  Consequently, there are no capital costs
associated with this standard.  Responses to this information collection
are mandatory.  The 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.

	6(a)  Estimating Respondent Burden

	The average annual burden to industry over the next three years from
these recordkeeping and reporting requirements is estimated at 8,317
person-hours.  These hours are based on Agency studies and background
documents from the development of the standards or test methods, Agency
knowledge and experience with the NSPS program, the previously approved
ICR, and any comments received.

	6(b)  Estimating Respondent Costs

		(i)  Estimating Labor Costs

	This ICR uses labor rates of $55.34 per hour for technical (most
activities) and $78.54 per hour for managerial (assumed needed only for
performance tests).  These rates are from the United States Department
of Commerce Bureau of Labor Statistics, March 2000, “Table 10. Private
industry, by occupational and industry group.”  The rates are from
column 1, “Total compensation.”  The wage rates have been increased
by 110% to account for the benefit packages available to those employed
by private industry.

		(ii)  Estimating Capital and Operations and Maintenance Costs

	The only type of industry costs associated with the information
collection activity in the standards are labor costs.  There are no
capital/startup, or operation and maintenance costs.  The type of
industry costs associated with the information collection activity in
the standards are labor costs and maintenance costs for the VOC
monitors.  Monitoring equipment for leaks is standard in the industry
for safety reasons.  To the extent possible, the requirements of this
standard are consistent with industry practice.  Consequently, there are
no capital costs associated with this standard.

		(iii)  Capital/Start-up vs. Operating and Maintenance (O&M) Costs

	This is not applicable since this is a leak detection and repair
program with no continuous monitoring equipment, as stated in the
previous section.

	6(c)  Estimating Agency Burden and Cost

	The only costs to the Agency are those costs associated with analysis
of the reported information.  Publication and distribution of the
information are part of the AFS program.  Examination of records to be
maintained by the respondents will occur as part of the periodic
inspection of sources, which is part of EPA's overall compliance and
enforcement program.

	The average annual Agency cost during the 3 years of the ICR is
estimated to be $19,130 (from Table 1).  This cost is based on the
average hourly labor rate at a GS12 step 1 times a 1.6 benefits
multiplication factor to account for government overhead expenses for a
total of $36.98.  Details upon which this estimate is based appear in
Table 1: Average annual EPA resource requirements resulting from NSPS
Subpart GGG.

	6(d)  Estimating the Respondent Universe and Total Burden and Costs

Respondent Universe:

Regulation Citation:  40 CFR Part 60, Subpart GGG	(A)

No. of New Source/Year	(B)

No. of Initial Reports for New Sources	(C)

No. of Existing Sources	(D)

No. of Reports for Existing Sources	(E)

Total Annual Responses

(AxB)+(CxD)

First year after proposal	2	4	45	2	98

Second year after proposal	2	4	47	2	102

Third year after proposal	2	4	49	2	106

	The number of total respondents in the second year is 49.  This number
is the sum of Column A and Column C of the second row in the Respondent
Universe table above.  The number represents the number of existing
sources plus the number of new sources averaged over the three-year
period.  It is shown in block 9, Respondents, on Part II of the
Paperwork Reduction Act Submission Worksheet.

	The number of Total Annual Responses in the second year is 102.  This
is the number in Column E of the second row in the Respondent Universe
table.  It is shown in block 10, Annual Number of Responses, on Part II
of the Paperwork Reduction Act Submission Worksheet.  The total annual
labor costs are $460,505.  The number of burden hours on which this
estimate is based, 8,317, are shown on Part II of the Paperwork
Reduction Act Submission Worksheet on block 11, Hour and Cost Burden.
Details upon which this estimate is based appear in Table 2: Annual
burden of reporting and recordkeeping requirements as a result of NSPS
Subpart GGG.

	The total annual capital and O&M costs to the regulated entity are zero
dollars.  Capital and O&M costs are not applicable since this is a leak
detection and repair program with no continuous monitoring equipment
used.

	6(e)  Bottom Line Burden Hours and Cost Tables

	The bottom line burden hours and cost table for both the Agency and the
respondents appear below (Table 1 and Table 2).

	6(f)  Reasons for Change in Burden

	The increase in burden cost from the most recently approved ICR is due
to the proposal of amendments to the recordkeeping and reporting
requirements to NSPS Subpart VV and NSPS Subpart GGG.

	6(g)  Burden Statement

	The annual public reporting and recordkeeping burden for this
collection of information is estimated to average 804 hours per
response.  Burden means the total time, effort, or financial resources
expended by persons to generate, maintain, retain, or disclose or
provide information to or for a Federal agency.  This includes the time
needed to review instructions; develop, acquire, install, and utilize
technology and systems for the purposes of collecting, validating, and
verifying information, processing and maintaining information, and
disclosing and providing information; adjust the existing ways to comply
with any previously applicable instructions and requirements; train
personnel to be able to respond to a collection of information; search
data sources; complete and review the collection of information; and
transmit or otherwise disclose the information.  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.  The OMB control numbers for EPA's regulations are
listed in 40 CFR part 9 and 48 CFR chapter 15.

	To comment on the Agency's need for this information, the accuracy of
the provided burden estimates, and any suggested methods for minimizing
respondent burden, including the use of automated collection techniques,
EPA has established a public docket for this ICR under Docket ID Number
EPA-HQ-OAR-2006-0699, which is available for online viewing at
HYPERLINK "http://www.regulations.gov"  www.regulations.gov , or in
person viewing at the Air and Radiation Docket and Information Center in
the EPA Docket Center (EPA/DC), EPA West, Room 3334, 1301 Constitution
Avenue, NW, Washington, D.C.  The EPA Docket Center Public Reading Room
is open from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding
legal holidays.  The telephone number for the Reading Room is (202)
566-1744, and the telephone number for the Air and Radiation Docket and
Information Center is<PHONE_NUMBER>.  An electronic version of the
public docket is available at www.regulations.gov.  This site can be
used to submit or view public comments, access the index listing of the
contents of the public docket, and to access those documents in the
public docket that are available electronically.  When in the system,
select “search,” then key in the Docket ID Number identified above.
Also, you can send comments to the Office of Information and Regulatory
Affairs, Office of Management and Budget, 725 17th Street, NW,
Washington, D.C. 20503, Attention: Desk Officer for EPA.  Please include
the EPA Docket ID Number EPA-HQ-OAR-2006-0699 and OMB Control Number
2060-0067 in any correspondence.

Part B of the Supporting Statement

	This part is not applicable because no statistical methods were used in
collecting this information.

TABLE 1: AVERAGE ANNUAL EPA RESOURCE REQUIREMENTS RESULTING FROM NSPS
SUBPART GGG.

Activity	(A)  EPA Hours/ Occurrence	(B)  Occurrences/ Plant/ Year	(C)
EPA Hours/Plant Yeara	(D)  Plants/Year	(E)  EPA Hours/ Yearb

Initial Performance Tests (New Plants)	24	1	24	2	48

Repeat Performance Testsc (New Plants)	24	0.2	4.8	2	9.6

Report Review

	(New Plants)

Notification of construction	2	1	2	2	4

Notification of anticipated startup	0.5	1	0.5	2	1

Notification of actual startup	0.5	1	0.5	2	1

Notification of initial test	0.5	1.2	0.6	2	1.2

Review test results	8	1.2	9.6	2	19.2

(Existing Plants)

Emission Reports	4.2	2	8.4	49	412

Total Annual Hours

	496

Travel Expenses:

(1 person x 2 plants/year x 3 days/plant x $50 per diem) + ($250 round
trip/plant x 2 plants/year) = $800/year

Salary: d

(496 hours/year x $36.98/hour) = $18,330/year

Total Annual Cost = $800 + $18,330 = $19,130

a  A x B = C

b  C X D = E

c  Assume 20% of initial performance tests must be repeated due to
failure

d  Estimate an hourly wage of GS 12 Step 1 multiplied by a 1.6 benefits
multiplication factor to account for government overhead expenses for a
total of $36.98

TABLE 2: ANNUAL BURDEN OF REPORTING AND RECORDING REQUIREMENTS AS A
RESULT OF NSPS SUBPART GGGa

	(A)  Hours per Occurrence	(B)  Occurrences/ Respondent/Year	(C)  Hours/
Respondent/Year

(A x B)	(D)  Respondents/ Year	(E)  Hours/Year

(C x D)	(F)  Cost/Year

1. APPLICATIONS (Not Applicable)

2. SURVEY AND STUDIES (Not Applicable)

3. REPORT REQUIREMENTS

A. Read Instructions	1	1	1	2	2	111 c

B. Required Activities

Initial performance test	24	1	24	2	48	2,879 b

Repeat performance test	24	1	24	0.4 d	9.6	576 b

C. Create Information (Included in 3B)

D. Gather Existing Information (Included in 3E)

E. Write Report

Notification of construction or reconstruction	2	1	2	2	4	221 c

Notification of anticipated startup	2	1	2	2	4	221 c

Notification of actual startup	2	1	2	2	4	221 c

Notification of initial performance test	2	1	2	2	4	221 c

Report of performance test (Included in 3B)

Semiannual work practice reports	8.2	2	16.4	49 e	804	44,471 c

4. RECORDKEEPING REQUIREMENTS

A. Read Instructions (Included in 3A)

B. Plan Activities (Included in 3B)

C. Implement Activities (Included in 3B)

D. Develop Record System (Not Applicable)

E. Time to Enter Information

Records of operating parameters g	0.42	365 f	151.8	49 e	7,437	411,583 c

F. Train Personnel (Not Applicable)

G. Audits (Not Applicable)

5. TOTAL ANNUAL BURDEN

	8,317	$460,505

a  Estimating that there are approximately 6 plants (respondents) which
become subject over a 3-year period.  The number of new sources per year
equals 6/3 = 2.

b  Assume an average hourly wage of ($55.34 x 0.8E + $78.54 x 0.2E).
This amount was multiplied by the hours per year in Column E.

c  Assume 100% technical rate at $55.34/hour.

d  Assume 20% of initial performance tests must repeat due to failure.

e  Assume operation is 365 days per year as specified in the NSPS review
document.

f  Assume that average number of affected facilities over the next three
years is estimated by the number of affected facilities in the second
year (45 + 2 + 2 = 49).

g  Although monitoring of the various components may be required on a
weekly, monthly, quarterly, semi-annual or annual basis, given the
number of components that must be monitored at any facility, monitoring
overall is essentially occurring daily.  Therefore, it is assumed that
the average record keeping time for each day’s worth of monitoring is
0.3 hours and that monitoring is done 365 days per year.  An estimated
0.12 hours per day are needed to complete the tasks required by the
proposed amendments.


Borough and Homer City Borough). Pennsylvania did not provide MVEBs for
SO2, VOC, and NH3 because it concluded,
consistent with the presumptions regarding these precursors in the
Transportation Conformity Rule at 40 CFR 93.102(b)(2)(v), which
predated and were not disturbed by the litigation on the 1997
PM2.5 Implementation Rule, that emissions of these
precursors from motor vehicles are not significant contributors to the
Area's PM2.5 air quality problem. EPA issued conformity
regulations to implement the 1997 annual PM2.5 NAAQS in July
2004 and May 2005 (69 FR 40004, July 1, 2004 and 70 FR 24280, May 6,
2005). The D.C. Circuit Court's January 2013 decision does not affect
EPA's proposed approval of the MVEBs for the Area. The MVEBs are
presented in Table 8.

          Table 8--MVEBs for the Johnstown Area for the 1997 Annual and 2006 24-Hour PM2.5 NAAQS in TPY
----------------------------------------------------------------------------------------------------------------
                             County                                    Year            PM2.5            NOX
----------------------------------------------------------------------------------------------------------------
Cambria County..................................................            2017           62.79        1,707.03
                                                                            2025           46.71        1,077.46
Indiana County (Partial)........................................            2017            7.95          238.50
                                                                            2025            4.38          120.98
----------------------------------------------------------------------------------------------------------------

    EPA's substantive criteria for determining adequacy of MVEBs are
set out in 40 CFR 93.118(e)(4). Additionally, to approve the MVEBs, EPA
must complete a thorough review of the SIP, in this case the
PM2.5 maintenance plan, and conclude that with the projected
level of motor vehicle and all other emissions, the SIPs will achieve
its overall purpose, in this case providing for maintenance of the 1997
annual and 2006 24-hour PM2.5 NAAQS. EPA's process for
determining adequacy of a MVEB consists of three basic steps: (1)
Providing public notification of a SIP submission; (2) providing the
public the opportunity to comment on the MVEB during a public comment
period; and (3) EPA taking action on the MVEB.
    In this proposed rulemaking action, EPA is also initiating the
process for determining whether or not the MVEBs are adequate for
transportation conformity purposes. The publication of this proposed
rulemaking action starts a 30-day public comment period on the adequacy
of the submitted MVEBs. This comment period is concurrent with the
comment period on this proposed rulemaking action and comments should
be submitted to the docket for this rulemaking. EPA may choose to make
its determination on the adequacy of the budgets either in the final
rulemaking on this maintenance plan and redesignation request or by
informing Pennsylvania of the determination in writing, publishing a
notice in the Federal Register and posting a notice on EPA's adequacy
Web page (http://www.epa.gov/otaq/stateresources/transconf/adequacy.htm).\15\
---------------------------------------------------------------------------

    \15\ For additional information on the adequacy process, please
refer to 40 CFR 93.118(f) and the discussion of the adequacy process
in the preamble to the 2004 final transportation conformity rule.
See 69 FR at 40039-40043.
---------------------------------------------------------------------------

    EPA has reviewed the MVEBs and finds that the submitted MVEBs are
consistent with the maintenance plan and meet the criteria for adequacy
and approval in 40 CFR part 93, subpart A. Therefore, EPA is proposing
to approve the 2017 and 2025 PM2.5 and NOX MVEBs
for Cambria County and portions of Indiana County for transportation
conformity purposes. Additional information pertaining to the review of
the MVEBs can be found in the TSD dated February 12, 2015, ``Adequacy
Findings for the MVEBs in the 1997 and 2006 PM2.5 NAAQS
Maintenance Plan for the Johnstown, Pennsylvania 1997 and 2006
PM2.5 Nonattainment Areas,'' available on line at
www.regulations.gov, Docket ID No. EPA-R03-OAR-2014-0902.

VI. Proposed Actions

    EPA is proposing to approve Pennsylvania's request to redesignate
the Johnstown Area from nonattainment to attainment for the 1997 annual
and 2006 24-hour PM2.5 NAAQS. EPA has evaluated
Pennsylvania's redesignation request and determined that the Area meets
the redesignation criteria set forth in section 107(d)(3)(E) of the
CAA. The monitoring data demonstrates that the Johnstown Area attained
the 1997 annual and the 2006 24-hour PM2.5 NAAQS, as
determined by EPA in prior rulemaking actions and, for reasons
discussed herein, that it will continue to attain both NAAQS. Final
approval of this redesignation request would change the designation of
the Johnstown Area from nonattainment to attainment for the 1997 annual
and 2006 24-hour PM2.5 NAAQS. EPA is also proposing to
approve the associated maintenance plan for the Johnstown Area as a
revision to the Pennsylvania SIP for the 1997 annual and 2006 24-hour
PM2.5 NAAQS because it meets the requirements of section
175A of the CAA as described previously in this proposed rulemaking. In
addition, EPA is proposing to approve the 2007 emissions inventory as
meeting the requirement of section 172(c)(3) of the CAA for both NAAQS.
Furthermore, EPA is proposing to approve the 2017 and 2025
PM2.5 and NOX MVEBs for Cambria County and
portions of Indiana County for transportation conformity purposes. EPA
is soliciting public comments on the issues discussed in this document.
These comments will be considered before taking final action.

VII. Statutory and Executive Order Reviews

    Under the CAA, the Administrator is required to approve a SIP
submission that complies with the provisions of the CAA and applicable
Federal regulations. 42 U.S.C. 7410(k); 40 CFR 52.02(a). Thus, in
reviewing SIP submissions, EPA's role is to approve state choices,
provided that they meet the criteria of the CAA. Accordingly, this
action merely proposes to approve state law as meeting Federal
requirements and does not impose additional requirements beyond those
imposed by state law. For that reason, this proposed action:
     Is not a ``significant regulatory action'' subject to
review by the Office of Management and Budget under Executive Order
12866 (58 FR 51735, October 4, 1993);
     Does not impose an information collection burden under the
provisions of the Paperwork Reduction Act (44 U.S.C. 3501 et seq.);
     Is certified as not having a significant economic impact
on a substantial number of small entities under the Regulatory
Flexibility Act (5 U.S.C. 601 et seq.);
     Does not contain any unfunded mandate or significantly or
uniquely affect small governments, as described in the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4);
     Does not have Federalism implications as specified in
Executive Order 13132 (64 FR 43255, August 10, 1999);
     Is not an economically significant regulatory action based
on health or safety risks subject to Executive Order 13045 (62 FR
19885, April 23, 1997);
     Is not a significant regulatory action subject to
Executive Order 13211 (66 FR 28355, May 22, 2001);
     Is not subject to requirements of Section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (15 U.S.C. 272
note) because application of those requirements would be inconsistent
with the CAA; and
     Does not provide EPA with the discretionary authority to
address, as appropriate, disproportionate human health or environmental
effects, using practicable and legally permissible methods, under
Executive Order 12898 (59 FR 7629, February 16, 1994).
    In addition, this rule proposing to approve Pennsylvania's
redesignation request, maintenance plan, 2007 emissions inventory for
the 1997 annual and 2006 24-hour PM2.5 NAAQS, and MVEBs for
transportation conformity purposes for the Johnstown Area for both
NAAQS, does not have tribal implications as specified by Executive
Order 13175 (65 FR 67249, November 9, 2000), because the SIP is not
approved to apply in Indian country located in the state, and EPA notes
that it will not impose substantial direct costs on tribal governments
or preempt tribal law.

List of Subjects

40 CFR Part 52

    Environmental protection, Air pollution control, Incorporation by
reference, Nitrogen oxides, Particulate matter, Reporting and
recordkeeping requirements, Sulfur oxides, Volatile organic compounds.

40 CFR Part 81

    Air pollution control, National parks, Wilderness areas.

    Authority: 42 U.S.C. 7401 et seq.

    Dated: April 10, 2015.
William C. Early,
Acting Regional Administrator, Region III.
[FR Doc. 2015-09368 Filed 4-22-15; 8:45 am]
BILLING CODE 6560-50-P


[Federal Register Volume 83, Number 142 (Tuesday, July 24, 2018)]
[Notices]
[Pages 35041-35044]
[FR Doc No: 2018-15766]

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

SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-83666; File No. SR-NSCC-2018-004]

Self-Regulatory Organizations; National Securities Clearing
Corporation; Notice of Filing of a Proposed Rule Change To Terminate
the Commission Billing Service and the Commission Billing Limited
Membership

July 18, 2018.
    Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934
(``Act'') \1\ and Rule 19b-4 thereunder,\2\ notice is hereby given that
on July 13, 2018, National Securities Clearing Corporation (``NSCC'')
filed with the Securities and Exchange Commission (``Commission'') the
proposed rule change as described in Items I, II and III below, which
Items have been prepared by the clearing agency. The Commission is
publishing this notice to solicit comments on the proposed rule change
from interested persons.
---------------------------------------------------------------------------

    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
---------------------------------------------------------------------------

I. Clearing Agency's Statement of the Terms of Substance of the
Proposed Rule Change

    The proposed rule change consists of amendments to Rules and
Procedures of NSCC (``Rules'') in order to in order to terminate the
Commission Billing service and the Commission Billing type of limited
membership, as described in greater detail below.\3\
---------------------------------------------------------------------------

    \3\ Available at http://www.dtcc.com/legal/rules-and-procedures.
Capitalized terms used herein and not otherwise defined shall have
the meaning assigned to such terms in the Rules.
---------------------------------------------------------------------------

II. Clearing Agency's Statement of the Purpose of, and Statutory Basis
for, the Proposed Rule Change

    In its filing with the Commission, the clearing agency 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 clearing agency has prepared summaries,
set forth in sections A, B, and C below, of the most significant
aspects of such statements.

(A) Clearing Agency's Statement of the Purpose of, and Statutory Basis
for, the Proposed Rule Change

1. Purpose
    NSCC is proposing to revise its Rules in order to discontinue its
Commission Billing service and the Commission Billing type of limited
membership, for the reasons described below.
Overview of the Commission Billing Service
    As currently described in Rule 16, NSCC provides a service through
which it facilitates the payment of commissions on monthly basis
between its Members and Commission Billing Members.\4\ Brokers that use
this service to charge and collect commissions are Commission Billing
Members, which is a type of limited membership that allows these firms
to participate in NSCC solely for the collection of commissions.
---------------------------------------------------------------------------

    \4\ Id.
---------------------------------------------------------------------------

    Currently, Commission Billing Members are floor broker firms that
are members of the New York Stock Exchange (``NYSE'') and NYSE American
(formerly the American Stock Exchange), although historically the
service was available to floor broker firms on any U.S. exchange. As
provided for in Rule 2 of the Rules, Commission Billing Members
participate solely in the collection and payment of commissions as
provided for under Rule 16 of the Rules.\5\
---------------------------------------------------------------------------

    \5\ Id.
---------------------------------------------------------------------------

    Floor broker firms execute trades on behalf of their clients for a
commission. In order to process commission charges applied to clients
who are Members, floor broker firms that are Commission Billing Members
may submit these charges to NSCC. Commission charges are submitted to
NSCC in one of two ways. In most cases, where the Commission Billing
Member is a member of NYSE, NYSE may act as a payment-data aggregator
and creates and submits payment files to NSCC. Alternatively,
Commission Billing Members may submit payments directly to NSCC through
a web-based system. NSCC tabulates all payment records received on a
monthly basis, and either sends amounts to The Depository Trust Company
(``DTC'') for payment (for billed Members that are also Participants of
DTC) or processes

payments through Automated Clearing House, or ``ACH,'' payments.
    For many years, the Commission Billing service provided these
brokers and Members with an efficient way to submit and receive
commission payments when few alternative payment options existed in the
industry that would handle the large volume of transactions.
Rationale for Terminating the Commission Billing Service and Commission
Billing Limited Membership
    NSCC is proposing to terminate the Commission Billing service for a
number of reasons, as described below. Because the Commission Billing
type of limited membership exists only for the purposes of the use of
this service, NSCC would terminate the existing Commission Billing
memberships simultaneously with the termination of the service.
    Over the years, the volumes of trades handled by floor brokers
firms have decreased, leading to a significant decrease in commission
bill transactions and the use of this service. Between January 2017 and
June 2018, the Commission Billing service processed an average of
approximately 87 commission payments per month (averaging a total of
approximately $370,000 each month), compared to an average of
approximately 10,000 commission payments per month in the early 2000's.
The number of Commission Billing Members has also declined, with only
seven new firms joining over the last eight years. Commission Billing
Members have alternative methods to process commission payments. For
example, firms may process the charges and payments through their own
accounts payable systems, charging and collecting payments from their
clients directly. Due to the lower volumes of commission payments, this
is a more reasonable alternative to the Commission Billing Service than
it may have been when volumes of payments were higher. Therefore, the
industry's reliance on this service, which was built to provide an
efficient way to process large volumes of payments, has been
diminishing.
    Since the introduction of the service, NSCC has provided the
Commission Billing service as a utility service to the industry and its
Members; the service provided its Members and the industry with value,
but it was not designed to generate profit for NSCC. Over time, the
reduced volumes of transactions has caused this service to be provided
at a financial loss to NSCC. Costs of providing the service include
engaging an ACH settling bank and ongoing system operating costs.
    Additionally, due to the use of legacy systems that lack automation
and support features, the service continues to rely on manual processes
and requires personnel involvement. While errors in the operation of
the service are infrequent, the reliance on manual processes creates a
risk of such errors. Remediation of such errors, if they occur, could
distract support resources from higher priority tasks. NSCC would be
required to invest in enhancements to the systems that support the
Commission Billing service if it continued to offer the service.
    Therefore, due to the reduced reliance on this service by the
industry, the cost of providing this service, and the availability of
other methods for Members and brokers to process these payments, NSCC
is proposing to terminate the Commission Billing service.
    In order to terminate the Commission Billing service, NSCC would
amend the Rules to remove Rule 16 (Settlement of Commissions) and to
remove references to the Commission Billing type of limited membership
from Rule 1 (Definitions and Descriptions), Rule 2 (Members and Limited
Members), Rule 2A (Initial Membership Requirements), Rule 2B (Ongoing
Membership Requirements and Monitoring), Rule 18 (Procedures for When
the Corporation Declines or Ceases to Act), Rule 22 (Suspension of
Rules), Rule 24 (Charges for Services Rendered), Rule 26 (Bills
Rendered), Rule 34 (Insurance), Rule 37 (Hearing Procedures), Rule 46
(Restrictions on Access to Services), Rule 58 (Limitations on
Liability), Rule 64 (DTCC Shareholders Agreement), Addendum A (Fee
Structure), Addendum B (Qualifications and Standards of Financial
Responsibility, Operational Capability and Business History), Addendum
D (Statement of Policy Envelope Settlement Service, Mutual Fund
Services, Insurance and Retirement Processing Services, and Other
Services Offered by the Corporation), and Addendum P (Fine Schedule).
NSCC would also make necessary conforming changes to Addendum B
(Qualifications and Standards of Financial Responsibility, Operational
Capability and Business History) and Rule 1 (Definitions and
Descriptions). Finally, NSCC would add a legend to each of the above
listed Rules and Addenda that identifies the implementation date of the
proposed changes.
Implementation Timeframe
    Given that all current Commission Billing Members are floor broker
members of NYSE and NYSE American, NSCC will work closely with these
exchanges to provide these firms with notice of the proposed
termination of this service and their related limited memberships with
NSCC. NSCC also would provide these firms with time to transition to
alternative methods for the submission of charges and receipt of
commission payments. Subject to the approval of this proposed rule
change filing, NSCC would implement this proposed rule change and
terminate the Commission Billing service by no later than November 30,
2018.
2. Statutory Basis
    NSCC believes that the proposed changes are consistent with the
Section 17A(b)(3)(F) of the Act, which requires, in part, that the
rules of a registered clearing agency be designed to promote the prompt
and accurate clearance and settlement of securities transactions, for
the reasons described below.\6\ The proposed rule change would
terminate a service that takes up various resources (through its
reliance on manual operations and by operating at a financial loss) and
is no longer relied on by Members and the industry. Because NSCC would
no longer need to divert resources to an underutilized service, the
proposed rule change would afford NSCC the ability to employ those
resources in a manner that could better support and promote the prompt
and accurate clearance and settlement of securities transactions. In
that way, NSCC believes the proposed rule change is consistent with
Section 17A(b)(3)(F) of the Act.\7\
---------------------------------------------------------------------------

    \6\ 15 U.S.C. 78q-1(b)(3)(F).
    \7\ Id.
---------------------------------------------------------------------------

    Rule 17Ad-22(e)(21)(iv) under the Act requires, in part, that NSCC
be efficient and effective in meeting the requirements of its
participants and the markets it serves, and have the covered clearing
agency's management regularly review the efficiency and effectiveness
of its use of technology and communication procedures.\8\ As described
above, to continue providing the Commission Billing service, NSCC would
need to enhance the systems and technology used to operate the system
in order to implement more automation and support features. However,
given that the service currently operates at a financial loss and does
not provide the industry with the same value that it has in the past,
NSCC has determined that it would be more efficient and effective

in meeting the requirements of its Members to eliminate the service and
instead use its resources for higher priority services. Therefore, NSCC
believes the proposed rule change is consistent with Rule 17Ad-
22(e)(21)(iv).\9\
---------------------------------------------------------------------------

    \8\ 17 CFR 240.17Ad-22(e)(21)(iv).
    \9\ Id.
---------------------------------------------------------------------------

(B) Clearing Agency's Statement on Burden on Competition

    The proposed rule change could have an impact on competition
because Commission Billing Members that currently use the service to
process their commission bills, and firms that may apply to use the
service in the future, would no longer be able to do so. However, NSCC
does not believe that the impact of this proposed rule change on
competition would be significant. First, the proposal is unlikely to
have a significant impact because the use of the service has diminished
over time, as described above. NSCC has not onboarded a new Commission
Billing Member in over two years, and the number of active Commission
Billing Members has declined over time. Therefore, elimination of the
service is unlikely to impact many firms that may wish to join as
Commission Billing Members in the future. Second, while current
Commission Billing Members would need to use other methods to process
commission payments, alternatives currently exist, including using
their own accounts payable system. Given that volumes of commission
bills have trended lower over the past few years, these firms should
not incur a significant cost in processing commission bills and
collecting commission payments through their own internal billing
systems. Therefore, NSCC does not believe that the proposed rule change
would have a significant impact on competition.
    NSCC also believes that any impact the proposed rule change may
have on competition would be both necessary and appropriate in
furtherance of the purposes of the Act.
    The proposed rule change would afford NSCC the option to utilize
its resources for matters that better support and promote the prompt
and accurate clearance and settlement of securities transactions,
consistent with Section 17A(b)(3)(F) of the Act.\10\ The proposed rule
change would also allow NSCC to be more efficient and effective in
meeting the requirements of its Members by using its resources for
higher priority services, consistent with Rule 17Ad-22(e)(21)(iv) under
the Act.\11\ Therefore, by advancing NSCC's ability to meet the
requirements of both Section 17A(b)(3)(F) of the Act \12\ and Rule
17Ad-22(e)(21)(iv) under the Act,\13\ NSCC believes any impact the
proposed rule change may have on competition would be necessary in
furtherance of the purposes of the Act.
---------------------------------------------------------------------------

    \10\ 15 U.S.C. 78q-1(b)(3)(F).
    \11\ 17 CFR 240.17Ad-22(e)(21)(iv).
    \12\ 15 U.S.C. 78q-1(b)(3)(F).
    \13\ 17 CFR 240.17Ad-22(e)(21)(iv).
---------------------------------------------------------------------------

    Additionally, NSCC believes that the proposed rule change is a
reasonable method of advancing NSCC's ability to meet these
requirements. As noted above, Members' use of this service has reduced
over time, and the cost to NSCC of providing the service has outweighed
the benefit it provides to the industry. NSCC would provide Members and
Commission Billing Members with notice and time to transition to other
viable methods for processing these payments. Therefore, NSCC believes
the proposed rule change is a reasonable method of advancing NSCC's
ability to meet the requirements of both Section 17A(b)(3)(F) of the
Act \14\ and Rule 17Ad-22(e)(21)(iv) under the Act.\15\
---------------------------------------------------------------------------

    \14\ 15 U.S.C. 78q-1(b)(3)(F).
    \15\ 17 CFR 240.17Ad-22(e)(21)(iv).
---------------------------------------------------------------------------

    Therefore, NSCC does not believe that the proposed rule change
would have a significant impact on competition, and further believes
that any such impact would be both necessary and appropriate in
furtherance of the purposes of the Act.

(C) Clearing Agency's Statement on Comments on the Proposed Rule Change
Received From Members, Participants, or Others

    NSCC has not solicited or received any written comments relating to
this proposal. NSCC will notify the Commission of any written comments
that it receives.

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

    Within 45 days of the date of publication of this notice in the
Federal Register or within such longer period up to 90 days (i) as the
Commission may designate if it finds such longer period to be
appropriate and publishes its reasons for so finding or (ii) as to
which the self-regulatory organization consents, the Commission will:
    (A) By order approve or disapprove such proposed rule change, or
    (B) institute proceedings to determine whether the proposed rule
change should be 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 protected]. Please include
File Number SR-NSCC-2018-004 on the subject line.

Paper Comments

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

All submissions should refer to File Number SR-NSCC-2018-004. 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 website (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 website 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 NSCC and on DTCC's website
(http://dtcc.com/legal/sec-rule-filings.aspx). All comments received
will be posted without change. Persons submitting comments are
cautioned that we do not redact or edit personal identifying
information from comment submissions. You should submit only
information that you wish to make available publicly. All submissions
should refer to File Number SR-NSCC-2018-004 and should be submitted on
or before August 14, 2018.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\16\
---------------------------------------------------------------------------

    \16\ 17 CFR 200.30-3(a)(12).
---------------------------------------------------------------------------

Eduardo A. Aleman,
Assistant Secretary.
[FR Doc. 2018-15766 Filed 7-23-18; 8:45 am]
BILLING CODE 8011-01-P


 1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES DATE: February 28, 2001 MEMORANDUM SUBJECT: Oxadiazon: Assessment of Mode of Action on Liver Carcinogenicity FROM: Nancy McCarroll Toxicology Branch Health Effects Division ( 7509C)

THRU: Pauline Wagner, Co Chair Mechanism of Toxicity Assessment Review Committee ( MTARC) Health Effects Division ( 7509C)

and Karl Baetcke, Co Chair Mechanism of Toxicity Assessment Review Committee ( MTARC) Health Effects Division ( 7509C)

TO: William Burnham, Senior Scientist Advisor Chairman, Cancer Assessment Review Committee ( CARC) Immediate Office Health Effects Division ( 7509C)

cc: Anna Lowit, Executive Secretary, MTARC Veronique LaCapra, Chemical Review Manager, SRRD Branch Files Oxadiazon  2 PC Code: 109001 DP Barcode: D266361 Action: The Mechanism of Toxicity Assessment Review Committee ( MTARC) met on February 8, 2001 to evaluate the mechanistic and other relevant data to determine whether the available findings support peroxisome proliferation as a possible mechanism of action for liver tumors induction by Oxadiazon. The mechanistic data included one 14 day oral study in rats submitted by the Registrant ( MRID No. 42310001) and a journal article ( Richert et al., 1996).

Conclusions: Based on the weight of the evidence, there are sufficient data to classify Oxadiazon as a non genotoxic hepatocarcinogen. The available data also provide suggestive evidence of peroxisome proliferation. There are, however, weaknesses in the database that preclude acceptance of peroxisome proliferation as the mode of action for Oxadiazon induced liver tumors; these include:

( 1) No cell proliferation data were reported for rats or mice; hence, mitogenesis could not be mechanistically linked to proliferation of peroxisomes.

( 2) There was no convincing concordance between the dose response for peroxisomal enzymatic activity and tumor formation.

( 3) The role of decreased catalase activity, which generally increases in the presence of a proxisome proliferator, was not explained by the investigators of the submitted study.

The Committee concluded, therefore, that peroxisome proliferation may be a possible mode of action for Oxadiazon induced liver tumors in rats and mice. However, because of shortcomings in the database, the available information do not support this proposed non genotoxic mode of action for Oxadiazon at this time.  3 Committee Members in Attendance Members who were present and gave electronic concurrence to this report were: Karl Baetcke, Mike Ioannou, Anna Lowit, Alberto Protzel, and Pauline Wagner Data evaluation prepared by: Nancy McCarroll, Toxicology Branch Also in attendance were: Veronique LaCapra of SRRD and HaJung Sung of Rural Development Administration, Korea.  4 Proposed Mechanism of Action for Oxadiazon: Recommendations to the MTARC I. Background: The relevance of peroxisome proliferation ( PP) to hepatocarcinogenesis has been previously discussed ( see HED Memorandum: Lactofen: Assessment of Mode of Action on Liver Carcinogenicity from Robert F. Fricke to Christine Olinger, dated February 15, 2001). Within this document, criteria are presented that must be satisfied before a non genotoxic hepatocarcinogen can be classified as a PP. These criteria, which were established through the joint efforts of MTARC and CARC, are:

1. Changes in liver morphology indicating hepatomegaly as measured by increased relative liver weights and an increased number of peroxisomes as measured by morphometric analysis.

2. Evidence of cell proliferation as measured by increased relative liver weights and increased replicative DNA synthesis as measured by increased hepatocellular BrdU nuclear labeling in light microscopy.

3. Increased levels of enzymes involved in peroxisomal fatty acid metabolism, especially acyl or palmitoyl CoA oxidase.

II. Physical and Chemical Properties of Oxadiazon Oxadiazon, 2 tert butyl 4( 2,4 dichloro 5 isopropoxyphenyl) 1,3,4 oxadiazol 5 one, is a selective pre emergent and early post emergence herbicide that is effective primarily for the control of annual grasses and broadleaf weeds in turf. The trade name for Oxadiazon in the U. S. is Ronstar. Oxadiazon has no food or feed uses. Most of the usage is allocated to golf courses. However, the Registrant is now supporting use of Oxadiazon on golf courses, apartment/ condo lawns, athletic fields, parks, playgrounds, and cemeteries.

The mechanism of action is contact inhibition by affecting young shoots as they grow through the treated zone ( pre emergence) and complete coverage ( post emergence). Oxadiazon destroys cell membranes and inhibits photosynthesis, probably by generating oxidizing radicals in light and is a powerful inhibitor of plant, yeast and mouse protoporphyrinogen oxidase, an enzyme critical in the biosynthesis of chlorophyll and heme ( Matringe et al., 1989).

Oxadiazon has the following structure:

Empirical Formula: C 15 H 18 Cl 2 N 2 O 3 III. Classification of Carcinogenic Potential  5 According to the Cancer Assessment Review Committee ( CARC) report, dated August 27, 1987 ( HED Document No. 007798), the original peer review ( November 21, 1984, HED Document No. 004097) placed Oxadiazon into Group B2 ( probable human carcinogen) but there was a minority opinion that the agent should be placed in Group C ( possible human carcinogen). Review of the weight of theevidence on Oxadiazon by the Scientific Advisory Panel ( dated November 20, 1987) reiterated this minority view. Consequently, the current Agency decision on the carcinogenic potential of Oxadiazon concurs with the Scientific Advisory Panel's ( SAP) classification of Oxadiazon as a Group C carcinogen and the Q1* has been set at 1.4 x 10 1( mg/ kg/ day) 1 in human equivalents. The rationale for the original classification as group B2 was based on the increased incidence of malignant or combined malignant and benign liver tumors: a) in multiple species ( CD  1 mice and F344 rats of one or both sexes) and in multiple experiments ( liver tumors in two mouse studies and in one rat study). The decision to reclassify Oxadiazon as a Group C carcinogen was based on the rationale that liver tumors were produced in two of the three positive studies ( one mouse study and one rat study) at doses that exceeded the maximum tolerated dose ( MTD).

Since the time of the classification of the oncogenic potential of Oxadiazon as a Group C carcinogen, a new chronic/ oncogenicity study in rats ( MRID No. 40993401) and a new carcinogenicity study in mice ( MRID No. 40993301) have been submitted to the Agency. The Hazard Identification Assessment Review Committee ( HIARC) recommended that the Q1* be revisited and that the Cancer Assessment Review Committee ( CARC) reconvene to evaluate these more recent studies. The CARC is awaiting the outcome of the current MTARC deliberations before evaluating these more recent chronic studies.

IV. Mutagenicity Oxadiazon is neither mutagenic nor clastogenic but does cause neoplastic cell transformation in vitro. Acceptable bacterial assays with

97.49% Oxadiazon were negative for gene mutations in Salmonella typhimurium and Escherichia coli ( MRID Nos. 00069893 and 41871701). Similarly, neither 95.5% Oxadiazon nor recrystallized Oxadiazon ( 100%) were mutagenic or clastogenic in cultured mammalian cells and did not cause unscheduled DNA synthesis ( UDS) in primary rat hepatocytes. There is, however, evidence that both formulations induced neoplastic transformation in Syrian hamster kidney cells both in the presence and in the absence of S9 activation. The finding of positive cell transformation supports the evidence from mouse bioassays ( MRID Nos. 00444322, 00115733 and 40993301) and the rat long term studies ( MRID Nos. 00149003/ 00157780 and 40993401) of liver tumor induction.

V. Evaluation of the Toxicology Database for Peroxisome Proliferation as a Possible Mechanism of Action for Liver Tumors Induced by Oxadiazon Data submitted by the Registrant are from both guideline and one non guideline ( mechanistic) studies. In general, the database for Oxadiazon is complete and has been evaluated with respect to the potential of Oxadiazon to induce liver tumors via peroxisome proliferation. Results from submitted studies were selected to illustrate findings pertinent to peroxisome proliferation as the proposed mechanism of action of Oxadiazon and are summarized in Table 1. In addition, a published study conducted in rats, mice  6 and dogs ( Richert et al., 1996) has also been considered with pertinent results presented in Table 1. All data have been assessed relative to the peroxisome proliferation criteria presented earlier.

A. Criterion 1: Increased Liver Weights and Increased Peroxisome Proliferation As shown in Table 1, increased absolute and relative liver weights were seen in both sexes of several rat strains ( Sprague Dawley,

only examined, Fischer 344, CD, Wistar) in male and female mice ( CD 1 and ICR JCL) and Beagle dogs. The length of exposure ranged from 14 days to 2 years. Doses causing increased liver weights in rats ranged from

200 mg/ kg/ day ( 14 days), 51 mg/ kg/ day ( 6 months) to 6 mg/ kg/ day ( 24 months). In mice, the earliest time that liver weights were recorded in the Guideline studies was 52 weeks. At this interval, significant effects were seen at 113 mg/ kg/ day. By 104 weeks, liver weight increases were noted at doses

12 mg/ kg/ day. Similar results of significantly increased absolute and relative liver weights have been shown by Richert et al.( 1996) in Sprague Dawley rats (

200 mg/ kg/ day, 14 days) and CD 1 mice (

200 mg/ kg/ day, as early as 28 days post treatment) but not in Beagle dogs after 28 days of exposure. Regardless of the rodent species, hepatomegaly was generally more pronounced in males than in females. Hence, the data show convincing evidence pointing to hypertrophy as the cause of hepatomegaly in rats and mice. There is also evidence of hyperplasia in CD 1 mice but it was only seen in one of two studies conducted with this mouse strain and was not reported in strain ICRJCL

In the 14 day oral mechanism study ( MRID No. 42310001) with Sprague Dawley rats, electron micrographs showed an increase in peroxisomes at 500 mg/ kg/ day Oxadiazon. Livers from lower dose groups were not examined microscopically. However, electron microscopy of rat and mouse liver sections in the study of Richert et al. ( 1996), showed a qualitative and dosedependent increase in peroxisomes at 20 mg/ kg/ day ( minimal in 5 of 11 mice), 100 mg/ kg/ day ( moderate in 7 of 7 mice) and 200 mg/ kg/ day ( severe in 9 of 9 mice). Eight of 10 rats administered 500 mg/ kg/ day Oxadiazon also showed a " severe" increase in peroxisomes.

B. Criterion 2: Evidence of Cell Proliferation As stated above, there is ample evidence of increased relative liver weights; however, no study has been submitted on the effects, if any, of Oxadiazon on replicative DNA synthesis. It is of note that Oxadiazon was tested in two in vitro assays ( MRID Nos. 00115723 and  27) for UDS in primary rat hepatocytes. Both studies were negative for UDS, and cells undergoing DNA replication rather than DNA repair were reported to be evenly distributed among all groups.

C. Criterion 3: Evidence of Increased Enzymatic Activity Increased levels of enzymes associated with liver toxicity ( ALP, SGOT, SGPT and/ or LDH) were recorded in subchronic dietary studies lasting 90 days in rats as well as chronic studies lasting 1 2 years in rats, mice or dogs and can be seen in many of the studies listed in Table 1. In the 14 day oral mechanism study ( MRID No. 42310001) with Sprague Dawley rats, dose related increases in palmitoyl CoA oxidation ( PAO), palmitoyl carnitine transferase and acetyl carnitine  7 transferase ( ACT) were reported at 20, 200 and 500 mg/ kg/ day; effects at

200 mg/ kg/ day were significant. Catalase activity was, however, significantly reduced at 200 and 500 mg/ kg/ day. This decrease in catalase activity, which is generally increased in the presence of peroxisome proliferation, was not explained by the investigators.

In agreement with the peroxisomal enzyme activity results from the submitted 14 day study, Richert et al. ( 1996) found a significant ( p< 0.05) and dose related increase in rat ( PAO) and ACT at 200 and 500 mg/ kg/ day. In mice, the same investigators noted that increases in PAO were achieved at 100 ( 174% of control) and 200 mg/ kg ( p< 0.05). ACT was also significantly increased at these levels. No biochemical assays in dogs were performed. In vitro studies conducted as part of these investigations showed concentration dependent increases in both PAO and ACT at 2.5 10 x 10 5 M Oxadiazon in primary rat hepatocytes; no effect were seen in cultured human hepatocytes at comparable doses.

While increases in the activity of the two enzyme markers for peroxisome proliferation followed exposure to Oxadiazon, the concordance between the dose response for peroxisome enzymes and liver tumor induction is not strong. As shown in Table 2, a dose of 113 mg/ kg/ day induced significant ( p< 0.01) increases in adenomas (+ 23%) carcinomas (+ 41%) and adenomas/ carcinomas combined (+ 63%) in male mouse livers while a comparable dose ( 100 mg/ kg/ day) caused only a moderate increase in the number of peroxisomes and a less than 2 fold increase in PAO. At 10.6 mg/ kg/ day in the oncogenicity study, adenomas (+ 17%) carcinomas (+ 16%) and adenomas/ carcinomas combined (+ 33%) were also significantly increased. However, only a slight increase in the number of peroxisomes and no increased in PAO were seen.

Similar evidence of a weak response in peroxisome enzymes was note in male rats dosed with either 200 or 500 mg/ kg/ day Oxadiazon in the submitted mechanistic study or the published results of Richert et al., ( 1996). Increases in PAO only ranged from 1.4 to 2.1 fold over control while liver tumor induction was achieved at 3.5 mg/ kg/ day. ACT activity, which is distributed not only in the peroxisomes but also in endoplasmic reticulum and mitochondria, only reached a 6 fold increase in male rats at 500 mg/ kg/ day. Although temporal associations were considered, the Committee acknowledged , based on its experience with peroxisome proliferators that increased peroxisome enzyme activity generally occurs ( regardless of the time interval) at doses near the tumor doses. It concluded, therefore, that the findings with Oxadiazon indicate that tumorigenic doses were substantially lower than levels inducing peroxisome enzymes.

VI. Other Modes of Action As stated previously, Oxadiazon is not mutagenic, and with the exception of peroxisome proliferation, no other mode of action has been hypothesized for Oxadiazon. However, a possible alternative mode of action could be oxidative damage to DNA through the production of hydrogen peroxide by increased fatty acid oxidation. This is because of the decreased catalase activity noted in the 14 day submitted study. Theoretically, the reduction in catalase activity could lower the degradation rate of H 2 O 2 thus initiating increased levels of H 2 O 2. Cattley et al. ( 1998) have hypothesized that since catalase levels " are never increased more than twofold an imbalance between generation and degradation of H 2 O 2 within the peroxisome" would exist. The excess H 2 O 2, that would result from a loss of catalase  8 ( as demonstrated in the Oxadiazon study), could conceivably escape from the peroxisome, react with transition metals and form hydroxyl radicals. Cattley et al. note that if these radicals form in the proximity of macromolecules, oxidative damage may occur.

VII. Structural Activity Relationships ( SAR)

Oxadiazon is not known to be structurally related to other known herbicides that are also peroxisome proliferators ( Richert et al., 1996); however, a wide variety of chemical classes have been shown to have the potential to induce peroxisome proliferation.

VIII. Conclusions Based on the weight of the evidence, there are sufficient data to classify Oxadiazon as a nongenotoxic hepatocarcinogen. The available data also provide suggestive evidence of peroxisome proliferation. There are, however, weaknesses in the database that preclude acceptance of peroxisome proliferation as the mode of action for Oxadiazon induced liver tumors; these include:

( 1) No cell proliferation data were reported for rats or mice; hence, mitogenesis could not be mechanistically linked to proliferation of peroxisomes.

( 2) There was no convincing concordance between the dose response for peroxisomal enzymatic activity and tumor formation.

( 3) The role of decreased catalase activity, which generally increases in the presence of a proxisome proliferator, was not explained by the investigators of the submitted study.

The Committee concluded, therefore, that peroxisome proliferation may be a possible mode of action for Oxadiazon induced liver tumors in rats and mice. However, because of shortcomings in the data base, the available information do not support this proposed non genotoxic mode of action for Oxadiazon at this time.

REFERENCE Richert, L., Price, S., Chesne, C., Maita, K. Carmichael, N. ( 1996). Comparison of the induction of hepatic peroxisome proliferation by the herbicide oxadiazon in vivo in rats, mice, and dogs and in vitro in rat and human hepatocytes. Toxicol. Appl. Pharmacol 141: 35 43.

Cattley, R. C., DeLuca, J., Elcombe, C., Fenner Crisp, P., Lake, B. G., Marsman, D. S., Pastoor, T. A., Popp, J. A., Robinson, D. E., Schwetz, B., Tugwood, J., Wahli, W. ( 1998). Do peroxisome proliferating compounds pose a hepatocarcinogenic hazard to humans? Reg Toxicol and Pharm 27: 47 60.

Matringe, M., Camadro, J. M., Labbe, P., Scalla, R. ( 1989). Protoporphyrinogen oxidase inhibition by three peroxidizing herbicides: oxadiazon, LS 82 556 and M& B 39279. FEBS Letters 245, number 1, 2: 35 38.  9

Table 1 : Summary of Liver Effects with Oxadiazon Study ( MRID) Liver Weight Liver Enzymes Liver Histopathology ( Nonneoplastic) Liver histopathology ( Tumors)

14 Day Oral Peroxisome Proliferation

Rat ( Sprague Dawley)

( 42310001): 0, 20, 200,

500 mg/ kg/ day Abs & rel wt

( p< 0.05)

200 & 500 mg/ kg ( p< 0.05) and dose related at 200 & 500 mg/ kg  catalase,

PAO,

palmitoyl carnitine transferase,

ACT,  G 6 PO4ase at 500 mg/ kg At 500 mg/ kg:

peroxisome proliferation;

lipids;

sinusoidal dilation &

rough endoplasmic reticulum damage NA Oral Peroxisome Proliferation in

Rat ( Sprague Dawley): 0, 20,

200, 500 mg/ kg/ day 14 days ( 10/ group)

Mice ( CD 1): 0, 100,

200 mg/ kg/ day 28 days ( 12/ group)

Dogs ( Beagles): 0, 500 mg/ kg 28 days ( 3/ group)

( Richert et al., 1996) Abs & rel wt

( p< 0.05)

 200 mg/ kg/ day rats  100 mg/ kg/ day mice NS

500 mg/ kg/ day

dogs Dose related

PAO &

ACT; ( p< 0.05) at 200 &

500 mg/ kg/ day rats Dose related

PAO &

ACT; ( p< 0.05) at 200 ( PAO) & 200 & 500 mg/ kg/ day( ACT)  mice At 500 mg/ kg ( only dose tested):

peroxisome proliferation ( severe in 8/ 10  rats Dose related

peroxisome proliferation ( minimal at 20 5/ 11;

moderate at 100 7/ 7;

severe at 200 mg/ kg/ day 9/ 9  mice)

No effects dogs NA Abbreviations:

ALP = Alkaline phosphatase LDH = Lactate dehydrogenase SGOT = Serum glutamic oxaloacetic transaminase PAO = Palmitoyl CoA oxidase SGPT = Serum glutamic pyruvic transaminase ACT = Acetyl carnitine transferase  10

Study ( MRID) Liver Weight Liver Enzymes Liver Histopathology ( Nonneoplastic) Liver Histopathology ( Tumors)

90 Day Dietary

 Rat ( CD)

( 00111804): 0, 25, 100,

1000 mg/ kg/ day Abs & rel wt

( p< 0.05)

100 & 1000 mg/ kg (

 ) wks 4 & 13:

ALP (

100& 1000 mg/ kg;

 1000 mg/ kg), wk 13:

SGOT (

100& 1000 mg/ kg;  1000 mg/ kg),

wks 4 & 13:

SGPT(

100& 1000 mg/ kg;

 1000 mg/ kg) At 1000 mg/ kg (

 ) &

100 mg/ kg (

) : brown pig. Kupffer cells & bile canaliculi; marked variability in cell size and staining properties of hepatocytes &

necrotic hepatocytes ( Above findings generally seen in  90%

&  60%  ) NA Chronic/ Onco Rat ( Fischer 344)

( 00149003/ 00157780): 0,

10, 100, 1000, 3000 ppm (  0, 0.5, 4.8, 50.9, 163.1 mg/ kg/ day

; 0, 0.6, 5.9,

60.9, 192.7 mg/ kg/ day  ) Abs & rel wt

( p  0.05

0.001)

6 mo: 1000 (

) & 3000 ppm (

 ) ; 12 mo: 1000 & 3000 ppm (

 ) ; 24 mo: 100, 1000 & 3000 ppm (

) 6 mo: At  1000 ppm (

)

ALP, SGPT ( at 3000 ppm

)

SGOT ( at 3000 ppm  )

SGOT, SGPT,

LDH, ALP; 12 mo: ( at  1000 ppm

 )

ALP,

SGPT ; 24 mo: ( at 3000 ppm

)

ALP, LDH Progressive alterations from hypertrophy through fatty changes to necrosis (  1000 ppm

& 3000 ppm

) ( p< 0.05) pairwise and trend

adenomas &

carcinomas combined (  1000 ppm

) . No decrease in latency.

Benign & malignant tumors after prolonged exposure to hepatotoxic doses  11

Study ( MRID) Liver Weight Liver Enzymes Liver Histopathology ( Nonneoplastic) Liver histopathology ( Tumors)

Chronic/ Onco Rat ( Wistar) ( 40993401): 0,

0, 3, 10, 100, 1000 ppm (  0, 0.1, 0.4, 3.5, 39 mg/ kg/ day

; 0, 0.1, 0.4,

4.2, 44 mg/ kg/ day  ) Abs & rel wt

( p  0.05

0.001)

26 wk: 1000 ppm (

 ) ;

52 wk: 1000 ppm (

) ;

78 wk: 1000 ppm (

) ;

104 wk: 1000 ppm (

) wks 26:

LDH (

1000 mg/ kg & wk 52);

ALP (

1000 mg/ kg);

SGOT/ SGPT (

1000 mg/ kg). Wks 52, 78 &

104: No effects. At 1000 ppm ( p  0.01

0.001):

centrilobular hepato. swell.(

 ) ;

brown pigmentation in liver) (

 ) ;

foci of cell alteration (

) ;

bile duct proliferation)

(

) . At 100 ppm ( p< 0.05) ,

centrilobular hepato.

swell.(

) (

) S trend ( p< 0.01)

& S pairwise 100 &

1000 ppm ( p< 0.05

0.01) liver adenomas and/ or carcinomas combined. At 1000 ppm, S pairwise ( p< 0.05) carcinomas .

Onco Mice ( CD 1)

( 00044322): 0, 300,

1000, 2000 ppm (  0, 48,

153, 319 mg/ kg/ day

;

0, 62, 201, 417 mg/ kg/ day  ) Abs & rel wt

( p  0.05

0.01) at 104 wk:  300 ppm (

 ) wk 104: ( p  0.05

0.01)

ALP (  300 ppm  ,  1000 ppm

);

SGOT (  1000 ppm

 ) ;

SGPT (  300 ppm  ,  1000 ppm

)

centrilobular hypertrophy (  300 ppm

 ) ;

diffuse hepatocellular hyperplasia &

hypertrophy (  300 ppm

 ) ;

nodular hyperplasia &

hypertrophy (  300 ppm

 ) ;

focal necrosis ( 2000 ppm

 )  no stats p< 0.01

hepatocarcinomas (  1000 ppm

 ) . No decrease in latency.  12

Study ( MRID) Liver Weight Liver Enzymes Liver Histopathology ( Nonneoplastic) Liver histopathology ( Tumors)

Onco Mice ( CD 1)

( 00115733): 0, 100, 300,

1000, 2000 ppm (  0, 12,

37, 122, 254 mg/ kg/ day

; 0, 14, 44, 143, 296 mg/ kg/ day  ) Abs & rel wt

( p  0.05

0.001) at 105 wk:  100 ppm (

) ,  1000 ppm (  ) Not Done No detail; terminal sac:

lesions listed as masses ( all dose groups, both sexes), pale areas/ foci ( all dose groups, both sexes), raised areas ( all dose groups, females only) unscheduled deaths: pigmented Kupffer cells, hepatic single cell necrosis ( high dose males) p< 0.05 0.01

liver adenomas (  100 ppm

 ) ; p< 0.05

carcinomas (  100 ppm

1000 ppm  ) ;

p< 0.05 0.01

combined liver adenomas &

carcinomas (  100 ppm

 ) . p< 0.05 trend for carcinomas (

) , adenomas (  ) &

combined (

 )

Onco Mice ( ICR JCL)

( 40993301): 0, 3, 10,

100, 1000 ppm (  0, 0.3,

1, 11, 113 mg/ kg/ day

;

0, 0.3, 1, 9, 99 mg/ kg/ day  ) Abs & rel wt

( p  0.05

0.001) at 52 & 98 wk:

1000 ppm (

) , 98 wk:

1000 ppm (  ) wks 52:

ALP (

1000 mg/ kg & wk 98

 1000 ppm);

SGOT (

 100 ppm).

SGPT (

 100 ppm wk 52 & at wk 98;

 1000 mg/ kg at wk 52) At 1000 ppm ( p< 0.001):

centrilobular hepato.

swell.(  ) ;

diffuse hepatocellular swell.(

 ) ;

brown pigmentation (

 )

diffuse hepatocellular necrosis (

only) at 1000 ppm ( p< 0.05) but ( p< 0.001) at 100 ppm.

Also in

at 100 ppm:

( p< 0.001)

diffuse hepatocellular swell and

brown pigmentation (

only) p< 0.01

liver adenomas (  100 ppm

, 1000 ppm

) ;

p< 0.01

liver carcinomas (  100 ppm

, 1000 ppm

)

p< 0.01

liver adenomas/ carcinomas combined (  100 ppm

, 1000 ppm

) .

 : p< 0.05 0.01 trend for liver adenomas, carcinomas, and adenomas/ carcinomas combined.  13

Study ( MRID) Liver Weight Liver Enzymes Liver Histopathology ( Nonneoplastic) Liver histopathology ( Tumors)

1 Year Chronic Dog ( Beagles) ( 41326401)

0, 5, 20, 60, 200 mg/ kg/ day Abs & rel wt

( p  0.05

0.01) at necropsy:

: rel  60 mg/ kg/ day abs at  60 mg/ kg/ day also

but NS;  : abs  20 mg/ kg/ day rel also

but S only at 60 mg/ kg/ day wks 24 & 50:

SGOT (

60 mg/ kg ( p< 0.05)

periacinar apoptosis centriacinar hepatocytic vacuolation None 2 Generation Reproduction Rat ( CD)

( 41239801) 0, 20, 60,

200 ppm (  0, 1.5, 4.65,

15.5 mg/ kg/ day

; 0,

1.8, 5.6, 18.2 mg/ kg/ day  ) P adults: No effect F1 adults: Sli

rel wt 200 ppm  F1 and F2 offspring: Not measured Not measured P adults: No effects F1 adults: periacinar hepatocellular hypertrophy 200 ppm

F1 or F2 offspring: No effects None Abbreviations:

ALP = Alkaline phosphatase LDH = Lactate dehydrogenase SGOT = Serum glutamic oxaloacetic transaminase PAO = Palmitoyl CoA oxidase SGPT = Serum glutamic pyruvic transaminase ACT = Acetyl carnitine transferase a Data were extracted from Richert et al. ( 1996).

b Data were extracted from Richert et al. ( 1996).

c Data were from Mouse 23 month chronic toxicity and oncogenicity study ( MRID No. 40993301).

 14

Table 2. Summary of Peroxisomal Effects and Liver Tumor Induction in Male Mice Administered Oxadiazon Dose ( mg/ kg/ day) No. of Peroxisomesa Peroxisomal Enzyme Activitiesb Neoplasmsc Palmitoyl CoA oxidase (%

over control) Acetyl carnitine transferase (%

over control) Adenomas Carcinomas Adenomas/ Carcinomas Combined 0 0   2/ 69 3% 3/ 69 4% 5/ 69 7%

0.3    7/ 71 10% 1/ 71 1% 8/ 71 11%

1.1    2/ 71 3% 4/ 71 6% 6/ 71 8%

10.6    12/ 69**

17% 11/ 69*

16% 23/ 69**

33%

20 Slight ( 6/ 11) 106 113

100 Moderate ( 7/ 7) 174 389*

113    16/ 71**

23% 29/ 71**

41% 45/ 71**

63%

200 Severe ( 9/ 9) 259* 459.5*

* Significantly different than control ( p< 0.05)

** Significantly different than control ( p< 0.01)


[Federal Register Volume 85, Number 218 (Tuesday, November 10, 2020)]
[Notices]
[Pages 71659-71660]
[FR Doc No: 2020-24970]

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-1997-D-0444]

Special Considerations, Incentives, and Programs To Support the
Approval of New Animal Drugs for Minor Uses and for Minor Species;
Draft Guidance for Industry; Availability; Extension of Comment Period

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability; extension of comment period.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is
extending the comment period for the notice of availability that
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requested comments on draft guidance for industry (GFI) #61 entitled
``Special Considerations, Incentives, and Programs to Support the
Approval of New Animal Drugs for Minor Uses and for Minor Species.''
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    Dated: November 5, 2020.
Lauren K. Roth,
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[FR Doc. 2020-24970 Filed 11-9-20; 8:45 am]
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