[Federal Register: April 16, 2008 (Volume 73, Number 74)]
[Notices]
[Page 20632-20634]
[DOCID:fr16ap08-50]

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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OPP-2008-0046; FRL-8359-1]

Notice of Filing of Pesticide Petitions for Residues of Pesticide
Chemicals in or on Various Commodities

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment or modification of regulations
for residues of pesticide chemicals in or on various commodities.

DATES: Comments must be received on or before May 16, 2008.

ADDRESSES: Submit your comments, identified by docket identification
(ID) number EPA-HQ-OPP-2008-0046 and the pesticide petition number (PP)
of interest, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
     Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
     Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket's normal hours of operation (8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays). Special
arrangements should be made for deliveries of boxed information. The
Docket Facility telephone number is<PHONE_NUMBER>.
    Instructions: Direct your comments to EPA-HQ-OPP-2008-0046 the
assigned docket ID number and the pesticide petition number of
interest. EPA's policy is that all comments received will be included
in the docket without change and may be made available on-line at
http://www.regulations.gov, including any personal information
provided, unless the comment includes information claimed to be
Confidential Business Information (CBI) or other information whose
disclosure is restricted by statute. Do not submit information that you
consider to be CBI or otherwise protected through regulations.gov or e-
mail. The regulations.gov website is an ``anonymous access'' system,
which means EPA will not know your identity or contact information
unless you provide it in the body of your comment. If you send an e-
mail comment directly to EPA without going through regulations.gov,
your e-mail address will be automatically captured and included as part
of the comment that is placed in the docket and made available on the
Internet. If you submit an electronic comment, EPA recommends that you
include your name and other contact information in the body of your
comment and with any disk or CD-ROM you submit. If EPA cannot read your
comment due to technical difficulties and cannot contact you for
clarification, EPA may not be able to consider your comment. Electronic
files should avoid the use of special characters, any form of
encryption, and be free of any defects or viruses.
    Docket: All documents in the docket are listed in the docket index
available in regulations.gov. To access the electronic docket, go to
http://www.regulations.gov, select ``Advanced Search,'' then ``Docket
Search.'' Insert the docket ID number where indicated and select the
``Submit'' button. Follow the instructions on the regulations.gov
website to view the docket index or access available documents.
Although listed in the index, some information is not publicly
available, e.g., CBI or other information whose disclosure is
restricted by statute. Certain other material, such as copyrighted
material, is not placed on the Internet and will be publicly available
only in hard copy. Publicly available docket materials are available
electronically at http://www.regulations.gov, or, if only available in
hard copy, at the OPP Regulatory Public Docket in Rm. S-4400, One
Potomac Yard (South Bldg.),

2777 S. Crystal Dr., Arlington, VA. The hours of operation of this
Docket Facility are from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.

FOR FURTHER INFORMATION CONTACT: The person listed at the end of the
pesticide petition summary of interest.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).
    This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed at the end of the pesticide petition
summary of interest.

B. What Should I Consider as I Prepare My Comments for EPA?

    1. Submitting CBI. Do not submit this information to EPA through
regulations.gov or e-mail. Clearly mark the part or all of the
information that you claim to be CBI. For CBI information in a disk or
CD-ROM that you mail to EPA, mark the outside of the disk or CD-ROM as
CBI and then identify electronically within the disk or CD-ROM the
specific information that is claimed as CBI. In addition to one
complete version of the comment that includes information claimed as
CBI, a copy of the comment that does not contain the information
claimed as CBI must be submitted for inclusion in the public docket.
Information so marked will not be disclosed except in accordance with
procedures set forth in 40 CFR part 2.
    2. Tips for preparing your comments. When submitting comments,
remember to:
    i. Identify the document by docket ID number and other identifying
information (subject heading, Federal Register date and page number).
    ii. Follow directions. The Agency may ask you to respond to
specific questions or organize comments by referencing a Code of
Federal Regulations (CFR) part or section number.
    iii. Explain why you agree or disagree; suggest alternatives and
substitute language for your requested changes.
    iv. Describe any assumptions and provide any technical information
and/or data that you used.
    v. If you estimate potential costs or burdens, explain how you
arrived at your estimate in sufficient detail to allow for it to be
reproduced.
    vi. Provide specific examples to illustrate your concerns and
suggest alternatives.
    vii. Explain your views as clearly as possible, avoiding the use of
profanity or personal threats.
    viii. Make sure to submit your comments by the comment period
deadline identified.

II. Docket ID Numbers

    When submitting comments, please use the docket ID number and the
pesticide petition number of interest, as shown in the table.

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                 PP Number                        Docket ID Number
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PP 3F4188                                   EPA-HQ-OPP-2008-0173
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PP 7F7248                                   EPA-HQ-OPP-2008-0173
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PP 3H5662                                   EPA-HQ-OPP-2008-0173
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PP 7F7208                                   EPA-HQ-OPP-2008-0132
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PP 7F7260                                   EPA-HQ-OPP-2008-0168
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PP 7F7293                                   EPA-HQ-OPP-2008-0167
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PP 8F7328                                   EPA-HQ-OPP-2008-0217
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III. What Action is the Agency Taking?

    EPA is printing notice of the filing of pesticide petitions
received under section 408 of the Federal Food, Drug, and Cosmetic Act
(FFDCA), 21 U.S.C. 346a, proposing the establishment or modification of
regulations in 40 CFR part 180 for residues of pesticide chemicals in
or on various food commodities. EPA has determined that the pesticide
petitions described in this notice contain data or information
regarding the elements set forth in FFDCA section 408(d)(2); however,
EPA has not fully evaluated the sufficiency of the submitted data at
this time or whether the data support granting of the pesticide
petitions. Additional data may be needed before EPA rules on these
pesticide petitions.
    Pursuant to 40 CFR 180.7(f), a summary of each of the petitions
included in this notice, prepared by the petitioner, is included in a
docket EPA has created for each rulemaking. The docket for each of the
petitions is available on-line at http://www.regulations.gov.

New Tolerances

    1-3. PPs 3F4188, 7F7248, and 3H5662. (EPA-HQ-OPP-2008-0173). Dow
Agro Sciences LLC, 9330 Zionsville Road, Indianapolis, IN-46268,
proposes to establish a tolerance for residues of the insecticide
chlorpyrifos in or on food commodities grass, forage (Crop group 17) at
11 parts per million (ppm); grass, hay (Crop group 17) at 30 ppm;
barley, grain at 0.5 ppm; barley, straw at 2 ppm; barley, hay at 3 ppm;
barley, milled feed fractions at 1 ppm; barley, grain at 0.5 ppm;
barley, grain at 0.5 ppm; barley, grain at 0.5 ppm; barley, grain at
0.5 ppm; barley, grain at 0.5 ppm; barley, grain at 0.5 ppm; barley,
grain at 0.5 ppm; barley, grain at 0.5 ppm; barley, grain at 0.5 ppm;
barley, grain at 0.5 ppm; barley, grain at 0.5 ppm; barley, grain at
0.5 ppm; barley, grain at 0.5 ppm; barley, grain at 0.5 ppm; barley,
grain at 0.5 ppm; and barley, grain at 0.5 ppm. Adequate enforcement
methods are available for determination of chlorpyrifos residues in
plant and animal commodities. The available Analytical Enforcement
Methodology was previously reviewed in the June 20, 2000, Chlorpyrifos.
Revised Product and Residue Chapters of the Health Effects Division
(HED) Chapter of Reregistration Eligibility Decision (RED). Contact:
Akiva Abramovitch,<PHONE_NUMBER><EMAIL_ADDRESS>    4. PP 7F7208. (EPA-HQ-OPP-2008-0132). Bayer CropScience, 2 T.W.
Alexander Drive, Research Triangle Park, NC 27709, proposes to
establish a tolerance for residues of the herbicide thiencarbazone-
methyl (BYH 18636 - parent) as methyl 4-[(4,5-dihydro-3-methoxy-4-
methyl-5-oxo-1H-1,2,4-triazol-1-yl) carboxamidosulfonyl-5
methylthiophene-3-carboxylate (IUPAC nomenclature) in or on the food
commodities field corn grain at 0.01 ppm; sweet corn kernels at 0.01
ppm; wheat grain at 0.01 ppm; and soybean seed at 0.01 ppm.
Thiencarbazone-methyl (BYH 18636 parent and metabolites) as methyl 4-
[(4,5-dihydro-3-methoxy-4-methyl-5-oxo-1H-1,2,4-triazol-1-yl)
carboxamidosulfonyl]-5-methylthiophene-3-carboxylate (IUPAC
nomenclature) and metabolites BYH 18636-N-desmethyl, and BYH 18636-MMT-
glucoside determined

individually and expressed in thiencarbazone-methyl equivalents in or
on the food commodities field corn forage at 0.03 ppm; sweet corn
forage at 0.15 ppm; field corn stover at 0.04 ppm; sweet corn stover at
0.04 ppm; pop corn stover at 0.04 ppm; sweet corn (k+cwhr) at 0.01 ppm;
wheat,hay at 0.02 ppm; wheat,straw at 0.02 ppm; wheat,forage at 0.09
ppm; soybean,forage at 0.04 ppm; soybean,hay at 0.15 ppm; and cotton
gin by-products at 0.15 ppm. Thiencarbazone-methyl (BYH 18636 parent
and metabolites) as methyl 4-[(4,5-dihydro-3-methoxy-4-methyl-5-oxo-1H-
1,2,4-triazol-1-yl) carboxamidosulfonyl]-5-methylthiophene-3-
carboxylate (IUPAC nomenclature), and metabolite BYH 18636-MMT
(expressed in thiencarbazone-methyl equivalents) are proposed based on
the tissue to feed ratio as determined from the lactating dairy cow
feeding study applied to a new diet calculated from the above proposed
tolerances in or on the food commodities milk at 0.01 ppm; cattle, meat
at 0.01 ppm; cattle, fat at 0.01 ppm; cattle, liver at 0.05 ppm;
cattle, kidney at 0.02 ppm; goat, meat at 0.01 ppm; goat, fat at 0.01
ppm; goat, liver at 0.05 ppm; goat, kidney at 0.02 ppm; hog, meat at
0.01 ppm; hog, fat at 0.01 ppm; hog, liver at0.05 ppm; hog, kidney at
0.02 ppm; horse, meat at 0.01 ppm; horse, fat at 0.01 ppm; horse, liver
at 0.05 ppm; horse, kidney at 0.02 ppm; sheep, meat at 0.01 ppm; sheep,
fat at 0.01 ppm; sheep, liver at 0.05 ppm; and sheep, kidney at 0.02
ppm. A high pressure liquid chromatography/triple stage quadrupole mass
spectrometry (HPLC/MS/MS) method that employs the use of internal
standards has been developed and validated for quantification of BYH
18636 analyte residues in plant matrices. The analytical method was
developed for the determination of the residues of BYH18636 (parent),
and its metabolites BYH18636-MMT-glucoside and -N-desmethyl in/on plant
materials. The calculated limit of detection (LOD) ranges from 0.001 to
0.003 ppm. The limit of quantitation (LOQ) for this method is 0.01 ppm
for each analyte in plant matrices. Contact: Hope A. Johnson, (703)
305-5410<EMAIL_ADDRESS>    5. PP 7F7260. (EPA-HQ-OPP-2008-0168). BASF Corporation, P.O. Box
13528, Research Triangle Park, NC 27709, proposes to establish a
tolerance for residues of the insecticide metaflumizone in or on food
commodities grape at 0.01 ppm; citrus fruits group (crop group 10) at
0.01 ppm; and tree nuts group (crop group 14) at 0.01 ppm. BASF
Analytical Method No. 531/0 was developed to determine residues of
metaflumizone and its metabolites M320I04 and M320I23, the residues of
concern in plants, and in crop matrices. In this method, residues of
metaflumizone are extracted from plant matrices with methanol/water
(70:30; v/v) and then partitioned into dichloromethane. For oily
matrices, the residues are extracted with a mixture of isohexane/
acetonitrile (1:1; v/v). The final determination of metaflumizone and
its metabolites is performed by liquid chromatography/mass spectrometry
(LC/MS/MS). Contact: Julie Chao,<PHONE_NUMBER><EMAIL_ADDRESS>    6. PP 7F7293. (EPA-HQ-OPP-2008-0167). Syngenta Crop Protection
Inc., P.O. Box 18300, Greensboro, NC 27419-8300, proposes to establish
a tolerance for residues of insecticide thiamethoxam {3-[(2-chloro-5-
thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-oxadiazin-4-
imine{time} (CAS Reg. No. 153719-23-4) and its metabolite [N-(2-chloro-
thiazol-5-ylmethyl)-N'-methyl-N'-nitro-guanidine] in or on food
commodities fruit, citrus (Crop Group 10) at 0.3 ppm; and nut, tree
(Crop Group 14) including pistachio at 0.3 ppm. Syngenta Crop
Protection, Inc. has submitted practical analytical methodology for
detecting and measuring levels of thiamethoxam in or on raw
agricultural commodities. This method is based on crop specific cleanup
procedures and determination by liquid chromatography with either
ultraviolet (UV) or mass spectrometry (MS) detections. The limit of
detection (LOD) for each analyte of this method is 1.25 ng injected for
samples analyzed by UV and 0.25 ng injected for samples analyzed by MS,
and the limit of quantification (LOQ) is 0.005 ppm for milk and juices,
and 0.01 ppm for all other substrates. Contact: Julie Chao, (703) 308-
8735<EMAIL_ADDRESS>    7. PP 8F7328. (EPA-HQ-OPP-2008-0217). Bayer CropScience, 2 T.W.
Alexander Drive, Research Triangle Park, NC 27709, proposes to
establish a tolerance for residues of the herbicide isoxaflutole 5-
cyclopropyl-4-(2-methylsulfonyl-4-trifluoromethylbenzoyl) isoxazole and
its metabolite 1-(2-methylsulphonyl-4-trifluoromethylphenyl)-2-cyano-3-
cyclopropyl propane-1,3-dione (RPA 202248), calculated as the parent
compound in or on food commodities corn, field, grain corn at 0.02 ppm;
corn, field, forage at 0.02 ppm; and corn, field, stover at 0.02 ppm. A
practical analytical method has been developed for detecting and
quantifying levels of Isoxaflutole and RPA 202248 in or on raw
agricultural commodities obtained from field corn. This method allows
monitoring of these commodities with residues at or above the levels
proposed in this petition. Quantitation of analytes as individual
components is performed by daughter-ion detection using liquid
chromatography/mass spectroscopy (LC/MS/MS). The limit of quantitation
(LOQ) for all analytes is 0.01 ppm. The proposed analytical enforcement
method to determine isoxaflutole-derived residues in plants has been
validated by an independent laboratory. Contact: Erik Kraft, (703) 308-
9358<EMAIL_ADDRESS>
Amendment to Existing Tolerance

    PPs 3F4188, 7F7248, and 3H5662. (EPA-HQ-OPP-2008-0173). Dow Agro
Sciences LLC, 9330 Zionsville Road, Indianapolis, IN, 46268, proposes
to amend the tolerances in 40 CFR 180.342 for residues of the
insecticide chlorpyrifos in or on the food commodities cattle, fat at
0.6 ppm; goat, fat at 0.4 ppm; horse, fat at 0.5 ppm; hog, fat at 0.4
ppm; and sheep, fat at 0.4 ppm. Adequate enforcement methods are
available for determination of chlorpyrifos residues in plant and
animal commodities. The available Analytical Enforcement Methodology
was previously reviewed in the June 20, 2000, Chlorpyrifos. Revised
Product and Residue Chapters of the Health Effects Division (HED)
Chapter of Reregistration Eligibility Decision (RED). Contact: Akiva
Abramovitch,<PHONE_NUMBER><EMAIL_ADDRESS>
List of Subjects

    Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.

    Dated: March 31, 2008.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
[FR Doc. E8-8003 Filed 4-15-08; 8:45 am]

BILLING CODE 6560-50-S


[Federal Register: June 12, 2006 (Volume 71, Number 112)]
[Notices]
[Page 33735]
[DOCID:fr12jn06-60]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. RP04-360-005]

Maritimes & Northeast Pipeline, L.L.C.; Notice of Compliance
Filing

June 6, 2006.
    Take notice that on June 1, 2006, Maritimes & Northeast Pipeline,
L.L.C. (Maritimes) submitted for filing as part of its FERC Gas Tariff,
First Revised Volume No. 1, First Revised Sheet No. 10, proposed to be
effective on January 1, 2005.
    Maritimes states that it is supplementing its May 24 compliance
filing in the captioned docket with the revised tariff sheet because it
was inadvertently left out of the filing. Maritimes states that the
supplemental sheet reflects the reduced settlement rates under Rate
Schedule MNPAL.
    Maritimes states that copies of its filing have been mailed to all
affected customers of Maritimes and interested State commissions.
    Any person desiring to protest this filing must file in accordance
with Rule 211 of the Commission's Rules of Practice and Procedure (18
CFR 385.211). Protests to this filing will be considered by the
Commission in determining the appropriate action to be taken, but will
not serve to make protestants parties to the proceeding. Such protests
must be filed in accordance with the provisions of section 154.210 of
the Commission's regulations (18 CFR 154.210). Anyone filing a protest
must serve a copy of that document on all the parties to the
proceeding.
    The Commission encourages electronic submission of protests in lieu
of paper using the ``eFiling'' link at http://www.ferc.gov. Persons

unable to file electronically should submit an original and 14 copies
of the protest to the Federal Energy Regulatory Commission, 888 First
Street, NE., Washington, DC 20426.
    This filing is accessible on-line at http://www.ferc.gov, using the

``eLibrary'' link and is available for review in the Commission's
Public Reference Room in Washington, DC. There is an ``eSubscription''
link on the Web site that enables subscribers to receive e-mail
notification when a document is added to a subscribed docket(s). For
assistance with any FERC Online service, please e-mail
<EMAIL_ADDRESS>or call<PHONE_NUMBER> (toll free). For

TTY, call<PHONE_NUMBER>.

Magalie R. Salas,
Secretary.
[FR Doc. E6-9104 Filed 6-9-06; 8:45 am]

BILLING CODE 6717-01-P


[Federal Register Volume 79, Number 207 (Monday, October 27, 2014)]
[Notices]
[Pages 63979-63981]
[FR Doc No: 2014-25431]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-73395; File No. SR-MIAX-2014-53]

Self-Regulatory Organizations; Miami International Securities
Exchange LLC; Notice of Filing and Immediate Effectiveness of a
Proposed Rule Change To Amend the MIAX Top of Market (``ToM'') and AIS
Data Feeds

October 21, 2014.
    Pursuant to the provisions of 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 October 6, 2014, Miami International Securities
Exchange LLC (``MIAX'' or ``Exchange'') filed with the Securities and
Exchange Commission (``Commission'') a proposed rule change as
described in Items I, II, and III below, which Items have been prepared
by the Exchange. 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.
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I. Self-Regulatory Organization's Statement of the Terms of Substance
of the Proposed Rule Change

    The Exchange is filing a proposal to amend the MIAX Top of Market
(``ToM'') and AIS data feeds.

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 aspects of such
statements.

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

1. Purpose
    The Exchange proposes to amend the MIAX Top of Market (``ToM'')
market data feed, the MIAX Express Interface (``MEI'') connectivity
service,\3\ and Administrative Information Subscriber (``AIS'') market
data feed. Specifically, the Exchange proposes removing messages
related to administrative information and Liquidity Seeking Events
(``LSE'') from ToM and the MEI Port connection, while also adding the
information to the AIS data feed to the extent that it is not already
included with AIS.
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    \3\ MIAX Express Interface is a connection to MIAX systems that
enables Market Makers to submit electronic quotes to MIAX.
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    ToM provides market participants with a direct data feed that
includes the Exchange's best bid and offer, with aggregate size, and
last sale information, based on displayable order and quoting interest
on the Exchange. The ToM data feed includes data that is identical to
the data sent to the processor for the Options Price Regulatory
Authority (``OPRA''). The ToM and OPRA data leave the MIAX system at
the same time, as required under Section 5.2(c)(iii)(B) of the Limited
Liability Company Agreement of the Options Price Reporting Authority
LLC (the ``OPRA Plan''), which prohibits the dissemination of
proprietary information on any more timely basis than the same
information is furnished to the OPRA System for inclusion in OPRA's
consolidated dissemination of options information. In addition to
MIAX's best bid and offer, with aggregate size and last sale
information, subscribers that currently subscribe to ToM also receive:
opening imbalance condition information; opening routing information;
Expanded
    Quote Range \4\ information, as provided in MIAX Rule 503(f)(5);
Post-Halt Notification,\5\ as provided in MIAX Rule 504(d), and
Liquidity Refresh,\6\ condition information, as provided in MIAX Rule
515(c)(2). This additional information (the ``administrative
information'') is included in the ToM feed as secondary information.
The administrative information is also currently available to non-
Market Makers through the AIS data feed and MIAX Market Makers via
connectivity with the MIAX Express Interface (``MEI''),\7\ for which
they are assessed connectivity fees.
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    \4\ Where there is an imbalance at the price at which the
maximum number of contracts can trade that is also at or within the
highest valid width quote bid and lowest valid width quote offer,
the System will calculate an Expanded Quote Range (``EQR''). The EQR
will be recalculated any time a Route Timer or Imbalance Timer
expires if material conditions of the market (imbalance size, ABBO
price or size, liquidity price or size, etc.) have changed during
the timer. Once calculated, the EQR will represent the limits of the
range in which transactions may occur during the opening process.
See Exchange Rule 503(f)(5).
    \5\ After the Exchange has determined to end a trading system
halt, the System will broadcast to subscribers of the Exchange's
data feeds, a Post-Halt Notification. See Exchange Rule 504(d).
    \6\ If a Market Maker quote was all or part of the MIAX Best Bid
or Offer (``MBBO'') and the Market Maker's quote was exhausted by
the partial execution of the initiating order, the System will pause
the market for a time period not to exceed one second to allow
additional orders or quotes refreshing the liquidity at the MBBO to
be received (``liquidity refresh pause''). See Exchange Rule
515(c)(2).
    \7\ MIAX Express Interface is a connection to MIAX systems that
enables Market Makers to submit electronic quotes to MIAX.
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    The Exchange proposes to remove all the secondary administrative
information including LSE related information from the ToM data feed
and from the MEI Port connectivity service, with the exception of the
Post-Halt Notification. The secondary administrative information and

Liquidity Seeking Event data being removed from ToM and the MEI Port
includes: (i) Opening imbalance condition information; (ii) opening
routing information; (iii) Expanded Quote Range information, as
provided in MIAX Rule 503(f)(5); (iv) Liquidity Refresh messages, as
provided in MIAX Rule 514(c)(2); (v) Route Timer information, as
provided in MIAX Rule 529; (vi) PRIME related auction messages, as
provided in MIAX Rule 515A; and (vii) any other similar timer or
auction related messages. ToM subscribers will continue to receive the
direct data that includes the Exchange's best bid and offer, with
aggregate size, and last sale information based on displayable order
and quoting interest on the Exchange, and the Post-Halt Notification.
The ToM data feed includes data that is identical to the data sent to
the processor for the Options Price Regulatory Authority (``OPRA'').
Both Full Service and Limited Service MEI Ports will continue to
provide Market Makers with the ability to send quotes and purge
messages in the same manner as they do currently. The Exchange also
proposes to amend the AIS data feed to specifically include all the
secondary administrative information and LSE related information that
is being removed from ToM and the MEI Port connection. The Exchange
notes that most of this administrative information is already included
in the AIS data feed, as described above. In order to receive the
secondary administrative information and LSE related messages, the ToM
subscribers and users of the MEI Port connectivity service will have to
connect to the Exchange with an AIS data feed. The Exchange notes that
ToM subscribers may receive the AIS data feed at no additional cost.\8\
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    \8\ See SR-MIAX-2014-51.
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    Because of the technology changes associated with this rule
proposal, the Exchange will announce the implementation date of the
proposal in a Regulatory Circular to be published no later than 90 days
after the publication of the approval order in the Federal Register.
The implementation date will be no later than 90 days following
publication of the Regulatory Circular announcing publication of the
approval order in the Federal Register.
2. Statutory Basis
    The Exchange believes that its proposed rule change is consistent
with Section 6(b) \9\ of the Act in general, and furthers the
objectives of Section 6(b)(5) \10\ of the Act in particular, in that it
is designed to prevent fraudulent and manipulative acts and practices,
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
mechanisms of a free and open market and a national market system and,
in general, to protect investors and the public interest.
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    \9\ 15 U.S.C. 78f(b).
    \10\ 15 U.S.C. 78f(b)(5).
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    The proposed changes to the market data products are designed to
increase the efficient use of connectivity bandwidth between market
participants and the Exchange in a manner that promotes just and
equitable principles of trade, fosters cooperation and coordination
with persons engaged in facilitating transactions in securities,
removes impediments to and perfect the mechanisms of a free and open
market and a national market system. The Exchange believes that the
changes will enhance the quality and usefulness of ToM, the MEI Ports,
and AIS market data product to the benefit of all market participants
that subscribe to such products.
    The ToM market data product is designed to promote just and
equitable principles of trade by providing all subscribers with top of
market data that should enable them to make informed decisions on
trading in MIAX options by using the ToM data to assess current market
conditions that directly affect such decisions. The market data
provided by ToM and AIS, and the connectivity of MEI, removes
impediments to, and is designed to further perfect, the mechanisms of a
free and open market and a national market system by making the MIAX
market more transparent and accessible to market participants making
routing decisions concerning their options orders. The ToM market data
product is also designed to protect investors and the public interest
by providing data to subscribers that is already currently available on
other exchanges and will enable MIAX to compete with such other
exchanges, thereby offering market participants with additional data in
order to seek the market center with the best price and the most
liquidity on which to execute their transactions, all to the benefit of
investors and the public interest, and to the marketplace as a whole.

B. Self-Regulatory Organization's Statement on Burden on Competition

    The Exchange does not believe that the proposed rule change will
impose any burden on competition not necessary or appropriate in
furtherance of the purposes of the Act. On the contrary, the Exchange
believes that the changes to the market data products will enhance
competition in the U.S. options markets by enhancing the quality and
usefulness of a market data product that is similar to that which is
currently provided on other options exchanges.\11\
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    \11\ The Exchange notes that the ToM market data product
competes with similar products offered by other markets such as
NASDAQ OMX PHLX, LLC (``PHLX'') and the International Stock Exchange
LLC (``ISE''). For example, PHLX and ISE offer market data products
that are similar to ToM: data feeds that show the top of the market
entitled Top of PHLX Options (``TOPO'') and the ISE TOP Quote Feed.
See e.g., Securities Exchange Act Release No. 60459 (August 7,
2009), 74 FR 41466 (August 17, 2009) (SR-Phlx-2009-54) (Order
Approving a Proposed Rule Change to Establish Fees for the Top of
PHLX Options Direct Data Feed Product).
---------------------------------------------------------------------------

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

    Written comments were neither solicited nor received.

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

    Because the foregoing 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 after the date of the filing, or such
shorter time as the Commission may designate, it has become effective
pursuant to 19(b)(3)(A) of the Act \12\ and Rule 19b-4(f)(6) \13\
thereunder.
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    \12\ 15 U.S.C. 78s(b)(3)(A).
    \13\ 17 CFR 240.19b-4(f)(6). In addition, Rule 19b-4(f)(6)
requires a self-regulatory organization to give the Commission
written notice of its intent to file 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.
The Exchange has satisfied this requirement.
---------------------------------------------------------------------------

    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 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 Number SR-MIAX-2014-53 on the subject line.

Paper Comments

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

All submissions should refer to File Number SR-MIAX-2014-53. 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 Number SR-MIAX-2014-53 and should be
submitted on or before November 17, 2014.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\14\
---------------------------------------------------------------------------

    \14\ 17 CFR 200.30-3(a)(12).
---------------------------------------------------------------------------

Kevin M. O'Neill,
Deputy Secretary.
[FR Doc. 2014-25431 Filed 10-24-14; 8:45 am]
BILLING CODE 8011-01-P


[Federal Register Volume 82, Number 184 (Monday, September 25, 2017)]
[Rules and Regulations]
[Pages 44502-44504]
[FR Doc No: 2017-20047]

=======================================================================
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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 39

[Docket No. FAA-2017-0639; Product Identifier 2017-CE-016-AD; Amendment
39-19052; AD 2017-19-22]
RIN 2120-AA64

Airworthiness Directives; British Aerospace Regional Aircraft
Airplanes

AGENCY: Federal Aviation Administration (FAA), Department of
Transportation (DOT).

ACTION: Final rule.

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SUMMARY: We are superseding Airworthiness Directive (AD) 2014-07-09 for
British Aerospace Regional Aircraft Jetstream Series 3101 and Jetstream
Model 3201 airplanes. This AD results from mandatory continuing
airworthiness information (MCAI) originated by an aviation authority of
another country to identify and correct an unsafe condition on an
aviation product. The MCAI describes the unsafe condition as both the
need for newly added inspections for corrosion, which includes the door
hinges/supporting structure and attachment bolts for the main spar
joint and engine support, and inadequate existing instructions for
inspection for corrosion for several areas including the rudder hinge
location on the vertical stabilizer. We are issuing this AD to require
actions to address the unsafe condition on these products.

DATES: This AD is effective October 30, 2017.
    The Director of the Federal Register approved the incorporation by
reference of certain publications listed in the AD as of October 30,
2017.

ADDRESSES: You may examine the AD docket on the Internet at http://www.regulations.gov by searching for and locating Docket No. FAA-2017-
0395; or in person at Document Management Facility, U.S. Department of
Transportation, Docket Operations, M-30, West Building Ground Floor,
Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590.
    For service information identified in this AD, contact BAE Systems
(Operations) Limited, Customer Information Department, Prestwick
International Airport, Ayrshire, KA9 2RW, Scotland, United Kingdom;
telephone: +44 1292 675207; fax: +44 1292 675704; email:
<EMAIL_ADDRESS>Internet: http://www.baesystems.com/Businesses/RegionalAircraft/. You may view this referenced service
information at the FAA, Policy and Innovation Division, 901 Locust,
Kansas City, Missouri 64106. For information on the availability of
this material at the FAA, call<PHONE_NUMBER>. It is also available on
the Internet at http://www.regulations.gov by searching for Docket No.
FAA-2017-0639.

FOR FURTHER INFORMATION CONTACT: Doug Rudolph, Aerospace Engineer, FAA,
Small Airplane Standards Branch, 901 Locust, Room 301, Kansas City,
Missouri 64106; telephone:<PHONE_NUMBER>; fax:<PHONE_NUMBER>; email:
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

Discussion

    We issued AD 2014-07-09, Amendment 39-17823 (79 FR 22367; April 22,
2014) (``AD 2014-07-09''). That AD required actions intended to address
an unsafe condition on British Aerospace Regional Aircraft Model
Jetstream Series 3101 and Jetstream Model 3201 airplanes and was based
on mandatory continuing airworthiness information (MCAI) originated by
an aviation authority of another country.
    Since we issued AD 2014-07-09, more extensive reports of corrosion
have been received, resulting in the need to inspect additional areas.
    We issued a notice of proposed rulemaking (NPRM) (82 FR 28592; June
23, 2017) to amend 14 CFR part 39 by adding an AD that would apply to
British Aerospace Regional Aircraft Model Jetstream Series 3101 and
Jetstream Model 3201 airplanes and supersede AD 2014-07-09.
    The European Aviation Safety Agency (EASA), which is the Technical
Agent for the Member States of the European Community, has issued EASA
AD No.: 2017-0073, dated April 27, 2017 (referred to after this as
``the MCAI''), to correct an unsafe condition for the specified
products. The MCAI states:

    Maintenance instructions for BAE Jetstream 3100 and 3200
aeroplanes, which are approved by EASA, are currently defined and
published in the BAE Systems (Operations) Ltd Jetstream Series 3100
& 3200 Corrosion Prevention and Control Programme (CPCP) document,
JS/CPCP/01. These instructions have been identified as mandatory for
continued airworthiness.
    Failure to accomplish these instructions could result in an
unsafe condition.
    EASA issued AD 2012-0036 to require operators to comply with the
inspection instructions as contained in the CPCP at Revision 6.
    Since that AD was issued, reports have been received of finding
extensive corrosion. While affected areas are covered by an existing
zonal inspection, it has been determined that this inspection is
inadequate to identify the corrosion in those areas. Consequently,
new inspection items 52-11-002 C1, 200/EX/01 C2, 500/IN/02 C1, 600/
IN/04 C1 and 700/IN/04 C1 have been added to the CPCP at Revision 8.
    For the reason described above, this [EASA] AD retains the
requirements of EASA AD 2012-0036, which is superseded, and requires
accomplishment of the actions specified in BAE Systems (Operations)
Ltd Jetstream Series 3100 & 3200 CPCP, JS/CPCP/01, Revision 8
(hereafter referred to as `the CPCP' in this AD).

The MCAI can be found in the AD docket on the Internet at: https://www.regulations.gov/document?D=FAA-2017-0639-0002.

Comments

    We gave the public the opportunity to participate in developing
this AD. The following presents the comment received on the NPRM and
the FAA's response to the comment.

Summary Clarification

    Kenneth MacKinnon of BAE Systems Regional Aircraft stated that the
Summary and Reason, paragraph (e) of this AD, both list corrosion
issues that were introduced at Revision 6, which he assumes was
mandated by AD 2014-07-09. He assumes this is an error and that both
sections should summarize the changes introduced at Revisions 7 and 8,
as detailed in the BAE SYSTEMS Certification Plans AWR/768/J3I and AWR/
815/J31 respectively. BAE wants the summary to better reflect the
changes since FAA AD 2014-07-09.
    We partially agree with this comment. The Summary and Reason,
paragraph (e)

of this AD, could contain language to better clarify the unsafe
condition. We disagree with including all of the details in this AD
because we matched the intent of the EASA AD, and the details provided
are included in the service documents. We have added language to the
Summary and Reason, paragraph (e) of this AD, to clarify the unsafe
condition.

Conclusion

    We reviewed the relevant data, considered the comments received,
and determined that air safety and the public interest require adopting
this AD with the change described previously. We have determined that
these minor changes:
     Are consistent with the intent that was proposed in the
NPRM for correcting the unsafe condition; and
     Do not add any additional burden upon the public than was
already proposed in the NPRM.
    We also determined that these changes will not increase the
economic burden on any operator or increase the scope of this AD.

Related Service Information Under 1 CFR Part 51

    We reviewed British Aerospace Jetstream Series 3100 & 3200
Corrosion Prevention and Control Programme, Manual Ref: JS/CPCP/01,
Revision 8, dated October 15, 2016. The service information describes
procedures for a comprehensive corrosion prevention and control
program. This service information is reasonably available because the
interested parties have access to it through their normal course of
business or by the means identified in the ADDRESSES section of this
document.

Costs of Compliance

    We estimate that this AD will affect 42 products of U.S. registry.
We also estimate that it would take about 100 work-hours per product to
comply with the basic requirements of this AD. The average labor rate
is $85 per work-hour.
    Based on these figures, we estimate the cost of this AD on U.S.
operators to be $357,000, or $8,500 per product.
    The scope of damage found in the required inspection could vary
significantly from airplane to airplane. We have no way of determining
how much damage may be found on each airplane or the cost to repair
damaged parts on each airplane or the number of airplanes that may
require repair.

Authority for This Rulemaking

    Title 49 of the United States Code specifies the FAA's authority to
issue rules on aviation safety. Subtitle I, section 106, describes the
authority of the FAA Administrator. ``Subtitle VII: Aviation
Programs,'' describes in more detail the scope of the Agency's
authority.
    We are issuing this rulemaking under the authority described in
``Subtitle VII, Part A, Subpart III, Section 44701: General
requirements.'' Under that section, Congress charges the FAA with
promoting safe flight of civil aircraft in air commerce by prescribing
regulations for practices, methods, and procedures the Administrator
finds necessary for safety in air commerce. This regulation is within
the scope of that authority because it addresses an unsafe condition
that is likely to exist or develop on products identified in this
rulemaking action.
    This AD is issued in accordance with authority delegated by the
Executive Director, Aircraft Certification Service, as authorized by
FAA Order 8000.51C. In accordance with that order, issuance of ADs is
normally a function of the Compliance and Airworthiness Division, but
during this transition period, the Executive Director has delegated the
authority to issue ADs applicable to small airplanes and domestic
business jet transport airplanes to the Director of the Policy and
Innovation Division.

Regulatory Findings

    We determined that this AD will not have federalism implications
under Executive Order 13132. This AD will not have a substantial direct
effect on the States, on the relationship between the national
government and the States, or on the distribution of power and
responsibilities among the various levels of government.
    For the reasons discussed above, I certify this AD:
    (1) Is not a ``significant regulatory action'' under Executive
Order 12866,
    (2) Is not a ``significant rule'' under the DOT Regulatory Policies
and Procedures (44 FR 11034, February 26, 1979),
    (3) Will not affect intrastate aviation in Alaska, and
    (4) Will not have a significant economic impact, positive or
negative, on a substantial number of small entities under the criteria
of the Regulatory Flexibility Act.

Examining the AD Docket

    You may examine the AD docket on the Internet at http://www.regulations.gov by searching for and locating Docket No. FAA-2017-
0639; or in person at the Docket Management Facility between 9 a.m. and
5 p.m., Monday through Friday, except Federal holidays. The AD docket
contains the NPRM, the regulatory evaluation, any comments received,
and other information. The street address for the Docket Office
(telephone<PHONE_NUMBER>) is in the ADDRESSES section. Comments will
be available in the AD docket shortly after receipt.

List of Subjects in 14 CFR Part 39

    Air transportation, Aircraft, Aviation safety, Incorporation by
reference, Safety.

Adoption of the Amendment

    Accordingly, under the authority delegated to me by the
Administrator, the FAA amends 14 CFR part 39 as follows:

PART 39--AIRWORTHINESS DIRECTIVES

0
1. The authority citation for part 39 continues to read as follows:

    Authority:  49 U.S.C. 106(g), 40113, 44701.

Sec.  39.13   [Amended]

0
2. The FAA amends Sec.  39.13 by removing Amendment 39-17823 (79 FR
22367; April 22, 2014), and adding the following new AD:

2017-19-22 British Aerospace Regional Aircraft: Amendment 39-19052;
Docket No. FAA-2017-0639; Product Identifier 2017-CE-016-AD.

(a) Effective Date

    This airworthiness directive (AD) becomes effective October 30,
2017.

(b) Affected ADs

    This AD replaces AD 2014-07-09, Amendment 39-17823 (79 FR 22367;
April 22, 2014) (``2014-07-09'').

(c) Applicability

    This AD applies to British Aerospace Regional Aircraft Jetstream
Series 3101 and Jetstream Model 3201 airplanes, all serial numbers,
certificated in any category.

(d) Subject

    Air Transport Association of America (ATA) Code 5: Time Limits.

(e) Reason

    This AD was prompted by mandatory continuing airworthiness
information (MCAI) originated by an aviation authority of another
country to identify and correct an unsafe condition on an aviation
product. The MCAI describes the unsafe condition as both the need
for newly added inspections for corrosion, which includes the door
hinges/supporting structure and attachment bolts for the main spar
joint and engine support, and inadequate existing instructions for
inspection for corrosion for several areas including the rudder
hinge location on the vertical stabilizer. We are issuing this AD to
require actions to address the unsafe

condition on these products as a result of possible corrosion on the
rudder upper hinge bracket and internal wing, areas of the
passenger/crew door hinges and supporting structure, the main spar
joint, and the engine support attachment bolts, which could lead to
reduced structural integrity with consequent loss of control.

(f) Actions and Compliance

    Comply with paragraphs (f)(1) through (3) of this AD within the
compliance times specified, unless already done:
    (1) Before further flight after October 30, 2017 (the effective
date of this AD), incorporate BAE Systems (Operations) Limited
Jetstream Series 3100 & 3200 Corrosion Prevention and Control
Programme, Manual Ref. JS/CPCP/01, Revision 8, dated October 15,
2016, into the Limitations of your FAA-approved maintenance program
(instructions for continued airworthiness) on the basis of which the
operator or the owner ensures the continuing airworthiness of each
operated airplane, as applicable to the airplane model.
    (2) Do all tasks in the BAE Systems (Operations) Limited
Jetstream Series 3100 & 3200 Corrosion Prevention and Control
Programme, Manual Ref. JS/CPCP/01, Revision 8, dated October 15,
2016, at the compliance times specified in the manual, or within the
next 12 months after October 30, 2017 (the effective date of this
AD), whichever occurs later; except for the following tasks, which
must be done within 12 months after October 30, 2017 (the effective
date of this AD): 52-11-002 C1, 200/EX/01 C2, 500/IN/02 C1, 600/IN/
04 C1, and 700/IN/04 C1.
    (3) If any discrepancy, particularly corrosion, is found during
any inspections or tasks required by paragraphs (f)(1) or (2) of
this AD, within the compliance time specified, repair or replace, as
applicable, all damaged structural parts and components and do the
maintenance procedures for corrective action following BAE Systems
(Operations) Limited Jetstream Series 3100 & 3200 Corrosion
Prevention and Control Programme, Manual Ref. JS/CPCP/01, Revision
8, dated October 15, 2016. If no compliance time is defined, do the
applicable corrective action before further flight.

(g) Other FAA AD Provisions

    The following provisions also apply to this AD:
    (1) Alternative Methods of Compliance (AMOCs): The Manager,
Small Airplane Standards Branch, FAA, has the authority to approve
AMOCs for this AD, if requested using the procedures found in 14 CFR
39.19. Send information to ATTN: Doug Rudolph, Aerospace Engineer,
FAA, Small Airplane Standards Branch, 901 Locust, Room 301, Kansas
City, Missouri 64106; telephone:<PHONE_NUMBER>; fax: (816) 329-
4090; email<EMAIL_ADDRESS>Before using any approved AMOC on
any airplane to which the AMOC applies, notify your appropriate
principal inspector (PI) in the FAA Flight Standards District Office
(FSDO), or lacking a PI, your local FSDO.
    (2) Contacting the Manufacturer: For any requirement in this AD
to obtain corrective actions from a manufacturer, the action must be
accomplished using a method approved by the Manager, Small Airplane
Standards Branch; or the European Aviation Safety Agency (EASA), or
BAE Systems (Operations) Limited's EASA DOA. If approved by the DOA,
the approval must include the DOA-authorized signature.
    (3) Reporting Requirements: For any reporting requirement in
this AD, a federal agency may not conduct or sponsor, and a person
is not required to respond to, nor shall a person be subject to a
penalty for failure to comply with a collection of information
subject to the requirements of the Paperwork Reduction Act unless
that collection of information displays a current valid OMB Control
Number. The OMB Control Number for this information collection is
2120-0056. Public reporting for this collection of information is
estimated to be approximately 5 minutes per response, including the
time for reviewing instructions, completing and reviewing the
collection of information. All responses to this collection of
information are mandatory. Comments concerning the accuracy of this
burden and suggestions for reducing the burden should be directed to
the FAA at: 800 Independence Ave. SW., Washington, DC 20591, Attn:
Information Collection Clearance Officer, AES-200.

(h) Related Information

    Refer to MCAI European Aviation Safety Agency 2017-0073, dated
April 27, 2017. The MCAI can be found in the AD docket on the
Internet at: https://www.regulations.gov/document?D=FAA-2017-0639-0002.

(i) Material Incorporated by Reference

    (1) The Director of the Federal Register approved the
incorporation by reference (IBR) of the service information listed
in this paragraph under 5 U.S.C. 552(a) and 1 CFR part 51.
    (2) You must use this service information as applicable to do
the actions required by this AD, unless the AD specifies otherwise.
    (i) BAE Systems (Operations) Limited Jetstream Series 3100 &
3200 Corrosion Prevention and Control Programme, Manual Ref. JS/
CPCP/01, Revision 8, dated October 15, 2016.
    (ii) Reserved.
    (3) For British Aerospace Jetstream Series 3100 and 3200 service
information related to this AD, contact BAE Systems (Operations)
Limited, Customer Information Department, Prestwick International
Airport, Ayrshire, KA9 2RW, Scotland, United Kingdom; telephone: +44
1292 675207; fax: +44 1292 675704; email:
<EMAIL_ADDRESS>Internet: http://www.baesystems.com/Businesses/RegionalAircraft/.
    (4) You may review copies of the referenced service information
at the FAA, Policy and Innovation Division, 901 Locust, Kansas City,
Missouri 64106. For information on the availability of this material
at the FAA, call<PHONE_NUMBER>. In addition, you can access this
service information on the Internet at http://www.regulations.gov by
searching for and locating Docket No. FAA-2017-0639.
    (5) You may view this service information that is incorporated
by reference at the National Archives and Records Administration
(NARA). For information on the availability of this material at
NARA, call<PHONE_NUMBER>, or go to: http://www.archives.gov/federal-register/cfr/ibr-locations.html.

    Issued in Kansas City, Missouri, on September 14, 2017.
Pat Mullen,
Acting Deputy Director, Policy & Innovation Division, Aircraft
Certification Service.
[FR Doc. 2017-20047 Filed 9-22-17; 8:45 am]
BILLING CODE 4910-13-P


Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 1 of 13 Reviewer: John Doherty ReRegistration Branch III, HED ( 7509C) Secondary Reviewer: Jess Rowland Science Information Management Branch, HED ( 7509C)

TXR # 0050236 DER for a Special Non Guideline Study with Human Volunteers Study Type: Special Non Guideline Cholinesterase Study with Human Volunteers.

DP Barcode No.: D277372 PC Code: 058001 Submission No.: S602411 Test Material: Azinphos methyl ( purity: 89.2 to 91.6%, batch number 703 0139).

Citation: P. McFarlane and S. Freestone, " A Randomized Double Blind Placebo Controlled Study with Azinphos Methyl to Determine the No Effect Level on Plasma and RBC Cholinesterase Activity After Repeated Doses." Inveresk Research, Study No.: ICR 013580, April 15, 1999. MRID No.: 45476101 Sponsor: Bayer Corporation, 17745 South Metcalf, Stilwell, KS 66085 9104.

In Life Phase: March 2, 1999 to April 15, 1999.

Executive Summary: In this special 28 day dosing study ( MRID No.: 45476101) with human subjects ( males only), a group of 4 volunteers were dosed as placebo ( lactose) and a group of 8 volunteers were dosed with 0.25 mg/ kg/ day of azinphos methyl ( 89.1% to 91.6% purity) for 28 consecutive days. Dosing was orally by capsule and the subjects were housed in a clinic throughout the dosing period. The subjects were monitored for reactions and samples of their blood were taken at predose ( 8 times) and daily throughout the dosing period. On some days, a blood sample was taken both prior to administering the dose and 4 hours after. The blood was separated and assessed for both plasma cholinesterase ( ChE) and red blood cell acetylcholinesterase ( RBC AChE). In addition, hematology, clinical chemistry and urinalysis were evaluated as well as blood pressure and ECG. Systemic Effects. There were no reactions to treatment and blood pressure and ECG parameters were not affected. Eight of the 12 volunteers were noted to have symptoms of a viral infection and some were treated with paracetamol. This was not considered to affect the interpretation of the study. Cholinesterase assessments. The plasma ChE in IU/ mL for the baseline ( mean " the standard deviation) was 6965" 1327 ( 19%) for the placebo group ( 4 subjects) and 5307" 1048 ( 20%) for the azinphos methyl treated group ( 8 subjects) meaning that the azinphos methyl group Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 2 of 13 was already 24% less prior to test material administration. The RBC AChE in IU/ mL for the baseline was 10933" 255 (" 2.3%) for the placebo group and 11049" 478 ( 4.3%) for the azinphos methyl treated group prior to dosing. The mean values and variance are as would be expected for assessment of plasma ChE and RBC AChE from human subjects. The postdosing group mean data were compared three ways in an effort to see if azinphos methyl caused inhibition of either plasma ChE or RBC AChE. Neither comparison of the group mean for the dosed group with i. the placebo group at each time interval or ii. the dosed groups baseline mean ( the most appropriate method) indicated inhibition of either plasma ChE or RBC AChE. In particular, the maximum decrease in plasma ChE was only 6% and the maximum decrease for RBC AChE was 9% ( which occurred only on one day) when compared to the baseline mean. Also, samples taken 4 hours after dosing on several occasions did not indicate inhibition. In conclusion, a dose of 0.25 mg/ kg/ day of azinphos methyl for 28 days did not result in either clinical symptomology or inhibition of either plasma ChE or RBC AChE in human males. The NOAEL is 0.25 mg/ kg/ day.

Classification: Classification of this study is RESERVED pending establishment of an Agency policy for classification of studies using human subjects.

Compliance: A Combined Good Clinical Practice ( CPMP/ ICH/ 135/ 95) for treatment of human subjects and a OECD Good Laboratory Practice statement was provided ( dated August 3, 1999). A Statement of Data Confidentiality ( no claim) was also provided ( dated August 13, 1999). Information on the volunteer consent form and other aspects of the ethical treatment of the subjects such as the study being conducted in accordance with the Declaration of Helsinki, as amended in 1975, 1983, 1989 and 1996 were provided.

A. Study Constants and Materials 1. Test Material: Chemical: Azinphos methyl Chemical name: S( 3,4 dihydro 4 oxobenzo[ d] 1,2,3) triazin 3 ylmethyl) O, O dimethyl phosphordithioate Batch: 703 0139 Purity: 89.2% to 91.6% Structure: No electronic structure available. CAS Number: 86 50 0. Description: Granulated powder. Supplier: Bayer Corporation 2. Vehicle of Placebo: Chemical: Lactose Purity: No information provided. Standard stock preparation. Supplier: J M Loverage, Company Batch 28811 Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 3 of 13 3. Test Subjects: Species: Human volunteers all males Race: All Caucasian Age: Criteria for inclusion in the study was to be between 18 and 50 years of age. The mean age " the standard deviation of the placebo group was 35.3" 9.5 years and was 29.3" 9.6 years for the group dosed with azinphos methyl. Body Weight: 61.8 to 90.4 kg. Housing: From the day before the first dose until 24 hours after receiving the last dose the subjects resided in the clinic and remained under constant medical and nursing supervision and received a standardized diet.

Pages 19 to 22 of the study report describe many details for the criteria that must be met to be included in this study. Each subject was given a screening examination to assure that there were no medical reasons for exclusion. In general, only individuals in good health and not on drugs ( prescription or otherwise), non smokers and capable of communicating with the medical staff were selected. Objections from the subjects personal physician also was cause to preclude a persons participation in the study. Agricultural workers and pesticide applicators or persons exposed to an anti cholinesterase within a month of the dosing were not eligible. During the study, no alcohol or caffeine or other medications were allowed. Note: During the study several of the subjects received paracetamol to control headache and viral symptoms, also, one subject received antibiotics. HED does not consider that either treatment with paracetamol or the antibiotics would compromise the study.

4. Study Protocol: Table 1 illustrates the study protocol.

Group Number of Subjects Assessments Placebo 4 males 0.25 mg azinphos methyl 8 males  General clinical exam ( self reporting of any possible symptoms).  Systolic and diastolic blood pressure just prior to each dose.  Electrocardiogram ( 12 lead), Hematology and Clinical Chemistry and Urinalysis: prior to dosing and on days 1, 7, 14, 21 and 28.  Plasma ChE and RBC AChE assessments  on screening days  14,  12,  10,  8,  6,  4 and  1; and then daily after dosing with special assessments on days on days 1, 2, 3, 4, 5, 7, 10, 14, 17, 21, 24 and 28 when two blood samples were taken to include sampling before each dose and 4 hours after the dosing 5. Rationale for Dose Level Selection. The dose level of 0.25 mg/ kg/ day was selected based on the results of animal studies and an earlier study with human subjects that indicated that this would be a NOAEL. for inhibition of plasma and RBC cholinesterase.

6. Dosing. Each subject was dosed by capsule containing either the placebo ( lactose) or azinphos methyl approximately 5 minutes after breakfast. Table 3 ( page 38 of the study report, copy attached) shows the amount in mg of placebo or azinphos methyl actually given to each subject on each day.

7. Statistics: The data were analyzed by the SAS ( v6.07) program. This system produced all summary Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 4 of 13 tables and data listings. The study report ( page 31) discusses the use of Retrospective Power Calculation to detect clinically relevant differences if the study was repeated.

The repeated measures ANOVA model was used for analysis of percentage change from baseline plasma and RBC cholinesterases using the pooled baseline values as covariate. This was done by comparing the goodness of fit statistics ( Akaike's Information Criterion and Schwart'z Bayestan Criterion) for both models including and excluding the pooled baseline value. Table M1.1.1 ( pages 491 to 501) presents the results of the statistical tests.

Specific Methods and Results 1. Assessment for clinical reactions.

All subjects remained on the study for the scheduled time. Comments on the general health and adverse events or reactions that may possibly be related to treatment for each subject are illustrated in Table 2. Note: During the dosing period the investigators were blind to whether or not the subject actually received azinphos methyl and they made their determination regarding possibly treatment related effects based on the symptoms only.

Table 2. Individual subject analysis for adverse effects. .

# General Condition and Possible Reactions HED Conclusion Placebos 1 4 adverse events. Viral illness on day 27. Headache on day 27 ( attributed to the environment), myalgia on day 19 and mouth dryness on day 27. . Subject did not receive azinphos methyl.

5 13 adverse events. Viral illness. Chest pain on days 7 and 9, rhinitis day 17 ), rash on day 11 and pruritus on day 11, elevated ALT from day  14 to day 28, headache on day 14, 16, 18, 24, 26, The headache and other symptoms were treated with paracetamol and attributed to the ward environment or virus. Subject did not receive azinphos methyl.

8 0 adverse events.

12 0 adverse events.

Azinphos Methyl Treated 2 14 adverse events. Both pre and post dose headaches ( on days  2, 3, 8, 21, 23, 27 and 28). Treated with paracetamol and attributed to the environment and a viral illness. Not related to treatment.

3 2 adverse events. Headache ( treated with paracetamol) on day 1 and rhinitis on day 14 and thought to be related to a viral illness. Not related to treatment. Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 5 of 13 # General Condition and Possible Reactions HED Conclusion 4 4 adverse events. Nausea thought to be related to the diet. Headache ( day 11) rhinitis and coughing thought to be related to viral illness. Not related to treatment.

6 1 1 adverse events. Dietary related gastrointestinal symptoms and headache ( intermittent) treated with paracetamol. Not related to treatment.

7 5 adverse events. Viral illness related to mouth dryness and coughing treated with paracetamol. Raised ALT and GGT Not related to treatment.

9 8 adverse events. Diet related indigestion, back pain and raised AST. Not related to treatment.

10 7 adverse events. Viral illness related to rhinitis and coughing and headache ( also attributed to the ward conditions). Mouth ulcer and facial pain treated with ibuprofen and amoxycillin. Not related to treatment.

11 2 adverse events. Viral illness thought to be related to lymphadenopathy and rhinitis treated with paracetamol. Not related to treatment.

Overall Comment on treated subjects. Much the same symptoms that were reported in the placebo group without indications of increased intensity were also reported in the group dosed with azinphos methyl.

Not all aliments that a subject reported are mentioned above since some were very obviously not recognized as being response to treatment with an organophosphate. For example, skin lesions are not mentioned.

It is concluded that none of the subjects dosed with azinphos methyl developed symptoms indicative of organophosphate poisoning. Most of the subjects ( i. e. 8 of the 12 on the study) were reported to have developed a viral illness with some subjects apparently having more viral related symptoms than others. It should also be noted that there was no increase in the severity of the symptoms in the subjects when compared with the controls and the severity was graded as 1 or 2 ( low degree).

Another apparent cause of adverse events was discomfort related to being confined in the clinic. This is understandable.

2. Specific tests Blood pressure and heart rate. There were no changes in blood pressure or heart rate in response to azinphos methyl administration.

ECG. There were no clinically significant effects on the ECG patterns of the subjects on this study.

3. Clinical Chemistry Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 6 of 13 Hematology. Appendix K ( pages K1 to K24 in Volume 2) indicates that hemoglobin, red blood cells, hematocrit. mean cell hemoglobin concentration, mean cell volume, white blood cells count ( including neutrophils, lymphocytes, monocytes. eosinophils. basophils, LUC ( large unclassified cells), and platelets were assessed.

There were no meaningful effects of azinphos methyl on these parameters.

Clinical Chemistry. Appendix L ( pages L1 to L23 in Volume 2) indicates that urea, glucose. AST ( aspartate aminotransferase), ALT ( alanine aminotransferase), LDH ( lactate dehydrogenase), sodium, potassium, chloride, TP ( total protein), albumin, T. Bi ( total bilirubin), GGT ( gamma glutamyl transferase) and creatinine were assessed.

There were some increases in AST and ALT that resolved themselves and were not considered to be related to treatment. For example they were transient ( self resolving) and considered to be within normal variation.

4. Cholinesterase Assessment.

General Preparation and Separation and Basic Assay.

Blood samples ( 4.5 mL) were taken by venipuncture each day at screening, on days  14,  12,  10,  8,  6,  4,  2, and  1 ( before dosing) and on days 1, 2, 3, 4, 5, 6, 7, 10, 14, 17, 21, 24 and 28 postdosing. Page 26 of the study report states that on postdosing days samples were taken prior to dosing and 4 hours postdosing. However, the individual subject data tables in Appendix M of the study report present data to indicate that blood cholinesterase was measured every day of the study. The samples were collected in tubes containing EDTA and centrifuged to separate the plasma from the RBCs. These were shipped to IR laboratory at Elphinstone Research Centre on wet ice and assayed the same day. The actual time between sample collection and assay time was not stated and may have been different for each day and there may have been different interval times for each subject. . Plasma ChE and RBC AChE was assessed following the SOP/ CLC/ 043 using an Hitachi Analyzer. This analyzer utilizes acetylthiocholine as the substrate and is a modification of Ellman's original method.

Plasma ChE and RBC AChE baseline values and variability of the data.

A general summary of the plasma ChE and RBC AChE for the baseline data is presented in Table 3.

Table 3. Mean baseline plasma ChE and RBC AChE data. Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 7 of 13 Plasma ChE ( IU/ L) Placebo Group AZM Group RBC AChE ( IU/ L) Placebo Group AZM Group 6965" 1327 (" 19%) 5307" 1048 (" 20%) ( range 5722 to 8757) ( range 3366 to 6840) 10933" 255 (" 2.3%) 11049" 478 (" 4.3%) ( range 10663 to 11196) ( range 10394 to 11854) Baseline Values Note: There is a 24% difference between the placebo and treated group before the start of AZM dosing. This is likely due to the subjects with the two highest plasma ChE values are in the placebo group and the subject with the lowest is in the AZM group.

The 19% and 20% standard deviation shows poor precision. The placebo and treated group are very comparable prior to dosing.

There is good precision since the standard deviations are small ( 2.3% and 4.3%)

5739" 1071 (" 19%) 5256" 1325 (" 25%) 6285" 1199(" 19%) 6402" 1129(" 18%) 5715" 757 (" 13%) 11595" 1323(" 11%) 12810" 1013(" 8%) 12712" 961 (" 8%) 11524" 1296 (" 11%) 11387" 1280 (" 11%) Comparison of the baseline values with the acute study ( a)

Similarly large standard deviations were obtained in both studies. The standard deviations for the subchronic study are smaller than for the acute study meaning that there was better precision in the acute study.

( a). Refer to MRID No.: 44786901 for the acute study with humans and azinphos methyl. The acute study had four dose levels for males and the baseline is presented for each dose group. There were 12 subjects in the placebo group for the acute study and 7 subjects in each group dosed with AZM. This compares with only 4 subjects in the placebo groups and 8 subjects in the dosed group for the 28 day study.

Table 3 shows that the standard deviation is 19 to 20% of the mean for the plasma ChE data ( based on 4 subjects). This compares with a 13 25% obtained in the previous acute study with azinphos methyl in human subjects. The standard deviation for RBC AChE was only 2.3 to 4.3% for the baseline values which indicates good precision. However, throughout the course of the study the standard deviations for RBC AChE means were as high as 15%. ( i. e see day 1for the placebo group at 4 hours after dosing in Appendix M, Table M2.2 also shown in Table 4 below).

There is much variation between the subject with the lowest ( 3366" 100 IU/ L) baseline plasma ChE and the highest ( 8757" 442 IU/ L) but these recordings are within the normal range for human plasma ChE.

Assessment for Inhibition of Plasma ChE and RBC AChE Based on Group Mean Data.

Table 4 illustrates group mean data for plasma ChE and RBC AChE assessments at selected time intervals. The potential for azinphos methyl to inhibit both plasma ChE or RBC AChE was assessed three ways.

i. by comparison of the day to day value for the azinphos methyl treated group with the same day value for the placebo group. Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 8 of 13 Since plasma ChE for the group that was to receive the azinphos methyl was already 24% less than the placebo before the start of dosing, all values were remained about 17 to 24% less than the placebo throughout dosing. Thus, there was no inhibition. The lowest decease for RBC AChE was only 3% but many values were higher for the dosed group relative to the placebo group.

ii. by comparison of the same day predosing cholinesterase data with the cholinesterase data obtained 4 hours after dosing.

The maximum difference was 9% decrease for the 10 hour sample but his was not sustained and the 4 hour sample was low for the placebo ( 5%, i. e. 10346/ 10933 = 0.946 or 5%) group also indicating an experimental variation and not true inhibition.

iii. by comparison of the azinphos methyl group data obtained each day with the predosing baseline value.

Table 4 shows that at day 10 the 4 hour postdosing sample was 7% lower than the predosing assessment. However, the placebo group was also 8% lower after 4 hours. Thus, the 7% decrease is not considered inhibition.

Neither of these three methods resulted in an indication that azinphos methyl inhibited either plasma ChE or RBC AChE at any time interval.

Assessment of plasma ChE and RBC AChE inhibition based on analysis of individual subjects.

Table 5 illustrates the plasma ChE and RBC AChE data for each subject on the study.

Plasma ChE. Table 5 shows that in the placebo group plasma ChE can be reduced to 86% and elevated to 110% above the baseline obtained by repeated samplings both before and during the dosing period. Table 5 also shows that for the subjects dosed with azinphos methyl their predosing baseline can be as low as 84% ( subject # 11) of his baseline mean. During the dosing period, one subject (# 9) in the azinphos methyl group was reduced to as much as 83% of his baseline mean. Thus, there is no indication of inhibition of plasma ChE when the individual subject data are evaluated. Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 9 of 13 Table 4. Comparison of Plasma ChE and RBC AChE in the Placebo and Azinphos Methyl Dosed Groups Based on Group Mean Data.

Day ( a) Plasma ChE ( IU/ L) Placebo 0.25 AZM % Diff. ( b) % Diff.( c) RBC AChE ( IU/ L) Placebo 0.25 AZM % Diff. ( b) % Diff ( c)

Baseline( e) 6965" 1327 5307" 1048  24%  10933" 225 11409" 478 + 4%

1 6532" 1153 4980" 965  24%  6% 6465" 1170 4985" 988  24%  6% (~) ( d) (~) 10738" 699 11220" 811 + 5% ~ 11681" 1723 11683" 803 ~ + 2% (+ 9%) (+ 4%)

4 6669" 1258 5219" 959  22% ~ 6420" 1502 5139" 957  20%  3% ( 4%) (~) 9543" 956 11256" 791 + 18% ~ 10742" 812 11170" 928 + 4%  2% (+ 13%) (~)

8 6440" 1363 5098" 989  21%  4% 10706" 539 11151" 610 + 4%  2%

10 6768" 1546 5323" 960  17% ~ 6733" 1286 5250" 970  22% ~ (~) (~) 11263" 643 11233" 1139 ~ ~ 10346" 1323 10399" 733 ~  9% ( 8%) ( 7%)

12 6452" 1288 5095" 1080  21%  4% 11770" 1499 11393" 1163  3% ~

16 6545" 1195 5208" 1010  20%  2% 10953" 539 10992" 515 ~  4%

21 7013" 1425 5437" 1010  22% + 2% 6791" 1179 5432" 998  20% + 2% ( 3%) (~) 10587" 224 10909" 728 + 3%  4% 10383" 339 11552" 1363 + 11% ~ ( 2%) (+ 6%)

24 7172" 1617 5477" 931  24% + 3% 6989" 1224 5637" 1079  19% + 6% ( 3%) (+ 3%) 11555" 1297 11425" 898 ~ ~ 11620" 1715 11391" 675  2% ~ (~) (~)

28 6819" 1537 5512" 964  19% + 4% 6752" 1418 5560" 888  18% + 5% (~) (~) 11381" 1043 11488" 694 ~ ~ 11428" 525 11326" 895 ~ ~ (~) (~)

Data are from Appendix M Tables M2.1( plasma ChE) and M2.2 ( RBC AChE) pages M45 to M56. ( a) Days " baseline", 1, 4, 8, 10, 12, 16, 21, 24 and 28 were selected for inclusion in this table to show representative values. Days 1, 4, 10, 21, 24 and 28 also were days on which blood samples were taken before the azinphos methyl was administered and 4 hours after administration. ( b) The percent difference between the mean for the azinphos methyl dosed group and the mean for the placebo is calculated for each day. ( c) The percent difference between the mean for the azinphos methyl dosed group at each day is calculated based on the mean baseline value for the azinphos methyl group. ( d) The value for plasma ChE or RBC AChE obtained prior to dosing is compared with the value obtained 4 hours after dosing. ( e). The baseline is the mean " the standard deviation for the value of the cholinesterase made on days  14,  12. 10,  8,  6,  4,  2 and  1. Each days predosing value is presented in Tables M2.1 and M2.2. ~ indicates that the value was essentially the same as the baseline. Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 10 of 13 Table 5. Individual subject analysis. The baseline mean " the standard deviation is presented together with the lowest and the highest reading over the course of the 28 day dosing period.

Su bje ct Nu mb er Plasma ChE ( IU/ L) Baseline Data Dosing Data RBC AChE ( IU/ L) Baseline Data Dosing Data Placebos 1 Mean: 6258" 264 Low: 5827 ( 93%) Low: 5590 ( 89%) High: 6692 ( 107%) High: 6813 ( 109%) Mean: 10867" 1141 Low: 9455 ( 87%) Low: 9104 ( 84%) High: 12789 ( 118%) High: 12606 ( 116%)

5 Mean: 8757" 442 Low: 8215 ( 94%) Low: 7670 ( 88%) High: 9390 ( 107%) High: 9666 ( 110%) Mean: 11004" 1502 Low: 9144 ( 83%) Low: 8696 ( 79%) High: 13699 ( 125%) High: 12914 ( 117%)

8 Mean: 5722 Low: 5384 ( 94%) Low: 4927 ( 86%) High: 6092 ( 106%) High: 6099 ( 107%) Mean 10663 Low: 9663 ( 91%) Low: 9074 ( 85%) High: 12794 ( 120%) High: 13719 ( 129%)

12 Mean: 7121 Low: 6930 ( 97%) Low: 6195 ( 87%) High : 7501 ( 105%) High: 7612 ( 107%) Mean: 11196 Low: 10096 ( 90%) Low: 8672 ( 77%) High: 11855 ( 106%) High: 13570 ( 121%)

Overall comment on placebos. Plasma may be as low as 86% and as high as 110% of baseline, RBC may be as low 77% and as high as 129% of baseline.

Azinphos Methyl Treated 2 Mean: 5684 Day 11: 5589 ( 98%) Low: 5348 ( 94%) Low: 5140 ( 90%) High: 6093 ( 107%) High: 6625 ( 117%) Mean: 10394 Day 11: 10111 ( 97%) Low: 9189 ( 88%) Low: 9228 ( 89%) High: 11162 ( 107%) High: 11815 ( 114%) Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 11 of 13 Su bje ct Nu mb er Plasma ChE ( IU/ L) Baseline Data Dosing Data RBC AChE ( IU/ L) Baseline Data Dosing Data 3 Mean: 4807 Day 11: 4979 (+ 104%) Low: 4625 ( 96%) Low: 4101 ( 85%)

High: 5779 ( 120%) Mean: 11079 Day 11: 10247 ( 92%) Low: 10009 ( 90%) Low: 9017 ( 81%)

High: 11242 ( 101%)

4 Mean: 3366" 100 Day 11: 3744 (+ 112%) Low: 3185 ( 95%) Low: 3141 ( 93%)

High: 6014 ( 177%) Mean: 11361" 2291 Day 11: 11494 (~) Low: 9051 ( 80%) Low: 9290 ( 82%)

High: 11996 ( 106%)

6 Mean: 5639 Day 11: 6003 ( 107%) Low: 5434 ( 96%) Low: 5411 ( 96%)

High: 6840 ( 121%) Mean: 11215 Day 11: 10781 ( 96%) Low: 9573 ( 85%) Low: 9054 ( 81%)

High: 13071 ( 117%)

7 Mean: 6209 Day 11: 6662 ( 107%) Low: 5972 ( 96%) Low: 5726 ( 92%)

High: 6759 ( 109%) Mean: 10811 Day 11: 10444 ( 97%) Low: 9276 ( 86%) Low: 9436 ( 87%)

High: 11998 ( 111%)

9 Mean: 4914 Day 11: 4691 ( 95%) Low: 4682 ( 95%) Low: 4078 ( 83%)

High: 5092 ( 104%) Mean: 11194 Day 11: 10425 ( 93%) Low: 9265 ( 83%) Low: 8533 ( 76%)

High: 13385 ( 120%)

10 Mean: 6840 Day 11: 6610 ( 97%) Low: 6358 ( 93%) Low: 5891 ( 86%)

High: 6947 ( 102%) Mean: 10483 Day 11: 10852 ( 104%) Low: 9269 ( 88%) Low: 9668 ( 92%)

High: 13895 ( 133%)

11 Mean: 4998" 365 Day 11: 4794 ( 96%) Low: 4214 ( 84%) Low: 4362 ( 87%) Mean: 11854" 1269 Day 11: 11789 (~) Low: 10341 ( 87%) Low: 9436 ( 80%) Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 12 of 13 Su bje ct Nu mb er Plasma ChE ( IU/ L) Baseline Data Dosing Data RBC AChE ( IU/ L) Baseline Data Dosing Data High: 5602 ( 112%) High: 13881 ( 117%)

Overall Comment on treated subjects. There was no indication of inhibition of either plasma ChE or RBC AChE. The absolute value of the lowest value is below the mean is about the same as the absolute value as the higher value is above the mean.

Data are from Tables M3 in Appendix M. The first entry: is the mean of the 8 baseline assessments " the standard deviation. The standard deviation was calculated by the reviewer. Not all baseline entries are accompanied by the standard deviation. The high and low values are those that occurred following dosing. The percentage in () is the change relative to the baseline for that individual.

RBC AChE. Table 5 shows that in the placebo group, RBC ACHE can be reduced to 77% ( subject # 12) of the baseline mean whereas the maximum decrease in the treated group was 76% ( subject # 9' s baseline mean. There were many values that were higher than the mean during the course of the study. For example, subject # 9 which had the largest decrease of 23% on day 14 also had a value that was 20% higher than the baseline mean. The graphs of this individuals cholinesterase data are appended. Thus, there is no indication that there was inhibition of RBC AChE based on individual subject data.

Analysis at day 11. Based on the review of a similar study with one other organophosphate ( diazinon, MRID No.: 45184301), the inhibition of plasma ChE plateaued at approximately day 11. Thus, data from day 11 are presented in Table 5 since if there was inhibition it would be expected to have been evident on this day. The eight subjects had plasma ChE of 98%, 104%, 112%, 107%, 107%, 95%, 97% and 96% mean and RBC AChE of 97%, 92%, ~ 100%, 96%, 97%, 93%, 104% and ~ 100% of the predose mean. There was also no pattern of inhibition at later days that would indicate that the time to plateau for azinphos methyl was longer than for diazinon. Thus, there is no indication of biologically meaningful inhibition in any of the subjects.

Discussion and Conclusions.

1. Study Author's Conclusion.

The study author ( page 56 of the study report) concluded that there were no adverse effects of azinphos methyl and that there was no clinically relevant reductions in plasma or RBC cholinesterase at a dose level of 0.25 mg/ kg/ day for 28 days.

2. Discussion and Conclusion. Azinphos Methyl/ 1998 Special 28 day study in humans.

Page 13 of 13 The reviewer concurs with the study author that there was no biologically meaningful inhibition of either plasma ChE or RBC AChE in the human subjects dosed daily for 28 days with 0.25 mg/ kg of azinphos methyl by oral capsule. There were also no indications that the subjects experienced adverse reactions to daily administration of azinphos methyl for 28 days.

3. Classification and Study Deficiencies.

The classification of this study is being reserved until the Agency formulates a policy for classifying studies with human subjects.

There were no study deficiencies that would compromise the interpretation of the study. There were some reporting problems in that some critical information on methods and procedures were scattered in Appendixes of the study and not in the study methods and materials section. Also, Table 3 of the study report was found to be misleading in that it does not specifically state that the placebo group was dosed with lactose since only a weight of material administered was given.


[Federal Register Volume 80, Number 176 (Friday, September 11, 2015)]
[Notices]
[Pages 54794-54795]
[FR Doc No: 2015-22949]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-3156]

Drug Interactions With Hormonal Contraceptives: Public Health and
Drug Development Implications; Public Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public meeting; request for comments.

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

SUMMARY: The Food and Drug Administration (FDA) is announcing a public
meeting entitled ``Drug Interactions with Hormonal Contraceptives:
Public Health and Drug Development Implications'' and an opportunity
for public comment on the topic of drug interactions with hormonal
contraceptives (HCs). The goal of this public meeting is to provide an
opportunity for FDA to seek input from experts on the public health
concerns associated with use of HCs and interacting drugs that might
affect efficacy and safety, pharmacokinetic (PK)/pharmacodynamic (PD)
considerations in designing drug interaction studies with HCs during
drug development, and approaches to translating the results of drug
interaction information into informative labeling and communication.
The input received may be used to refine FDA's thinking on HC drug
interaction study design and interpretation, and labeling communication
on drug interaction risk.

DATES: The public meeting will be held on November 9, 2015, from 8:30
a.m. to 4:30 p.m. Individuals who wish to attend the meeting in person
or via Web cast must register by October 9, 2015. Please submit either
electronic or written comments by December 15, 2015, to receive
consideration. See the SUPPLEMENTARY INFORMATION section for
information on how to register for the meeting and submit electronic or
written comments.

ADDRESSES: The meeting will be held at the FDA White Oak Campus, 10903
New Hampshire Ave., Bldg. 31 Conference Center, Section A of the Great
Room (Rm. 1503), Silver Spring, MD 20993. Entrance for the public

meeting participants (non-FDA employees) is through Building 1, where
routine security check procedures will be performed. For more
information on parking and security procedures, please refer to http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    Submit electronic comments to http://www.regulations.gov. Submit
written comments to the Division of Dockets Management (HFA-305), Food
and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD
20852. All comments should be identified with the docket number found
in brackets in the heading of this document.
    FDA will post the agenda approximately 5 days before the meeting
at: http://www.fda.gov/Drugs/NewsEvents/ucm459342.htm.

FOR FURTHER INFORMATION CONTACT: Christine Le, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 3196, Silver Spring, MD 20993, 301-796-
2398, email<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. Background

    In general, HCs are highly effective in preventing pregnancy when
used correctly. However, concomitant use of other drugs may affect the
safety and/or efficacy of HCs due to drug interactions affecting either
blood levels (PK) and/or physiologic effects (PD) of HC components
(e.g., estrogen and progestins). Understanding drug interaction
potential of HCs and other drugs is important when investigating HC-
related issues, and in the design and conduct of clinical trials.
Evolving knowledge on drug interaction mechanisms has led to new
insights and increased interest in the clinical investigation of drug
interactions with HCs.
    Historically, most drug interaction studies conducted during drug
development with HCs have not had a clearly stated rationale for the
choice of HCs being studied. Questions remain as to whether the study
results of specific contraceptive steroids can be extrapolated to other
progestins or estrogens or other dose strengths. The choice of HC is
important because different progestins may have different metabolic
and/or transporter pathways and safety profiles. Without a mechanistic
understanding of the underlying drug-drug interaction (DDI) mechanism,
it is difficult to interpret and extrapolate study results from one HC
to another.

II. Discussion Topics for the Meeting and for Public Comments

    The public meeting on November 9, 2015, will include a discussion
of the following topics on which FDA is also seeking public comment:
     Public health concerns associated with use of HCs and
interacting drugs that might affect efficacy and safety.
     PK and PD considerations in designing drug interaction
studies with HCs during drug development. Key elements in designing a
study include a mechanistic understanding of potential DDI mechanisms,
the choice of contraceptive products and their dose, study population/
duration, and proper selection of a PK alone or PK-PD-based drug
interaction study approach.
     Drug interaction study result interpretation and its
potential impact on guidance of HC use in women of childbearing
potential who are enrolled in clinical trials for other therapeutic
agents during drug development.
     The current approach of translating the results from drug
interaction studies into labeling recommendations and opportunities to
improve the communication to healthcare providers.
     Research opportunities and tools for investigating the
safe use of HCs in the presence of other drugs.
    The input received may be used to refine FDA's thinking on the drug
interaction study design with HCs and labeling communication of drug
interaction risks with HCs.

III. Meeting Attendance and Participation

    If you wish to attend these meetings, register online at https://www.surveymonkey.com/r/HC-DDIMeeting. Please register by October 9,
2015. Those who are unable to attend the meetings in person can
register to view a live Web cast of the meetings. You will be asked to
indicate in your registration whether you plan to attend in person or
via the Web cast. Your registration should also contain your complete
contact information, including name, title, affiliation, address, email
address, and phone number.
    Seating will be limited, so early registration is recommended.
Registration is free and will be on a first-come, first-served basis.
However, FDA may limit the number of participants from each
organization based on space limitations. Registrants will receive
confirmation once they have been accepted. Onsite registration on the
day of the meetings will be based on space availability. If you need
special accommodations because of disability, please contact Christine
Le (see FOR FURTHER INFORMATION CONTACT) at least 7 days before the
meeting.
    FDA will hold an open public comment period during the November 9,
2015, public meeting to give the public an opportunity to comment.
Registration for open public comment will occur at the registration
desk on the day of the meeting on a first-come, first-served basis.

IV. Comments

    Regardless of whether you attend this meeting, you can submit
electronic or written comments, including responses to the public
docket (see ADDRESS above), by December 15, 2015. Received comments may
be seen in the Division of Dockets Management between 9 a.m. and 4
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

V. Transcripts

    Transcripts for the November 9, 2015, meeting will be posted, when
available, at http://www.fda.gov/Drugs/NewsEvents/ucm459342.htm.

    Dated: September 4, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-22949 Filed 9-10-15; 8:45 am]
 BILLING CODE 4164-01-P


Comment Info: =================

General Comment:May 12, 2014

Dear Mr. Zeller:

I am writing as an individual consumer to request an extension of the comment period for the Food and Drug Administration's ("FDA") Proposed Rule Deeming Tobacco Products to be Subject to the Federal Food, Drug, and Cosmetic Act, as amended by the Family Smoking and Prevention and Tobacco Control Act (the "Proposed Rule") published at 79 Fed. Reg. 23,142 and Federal Register No. 2014-09491. On behalf of myself, I am requesting that the comment period for the Proposed Rule be extended by the FDA for an additional 105 days, from its current 75-day period, to 180 days.

The Proposed Rule raises a number of significant issues and questions that are important and relevant to me, as a consumer of products that are proposed for regulation under the Proposed Rule. The Proposed Rule asks about a hundred different questions I might want to respond to. I want to provide my thoughts and comments on many of these issues, but my time to devote to researching and providing thoughtful comments on these important questions is limited. I have already spent many hours researching and dissecting these issues, but they take time. I know that the FDA took many years to even come up with the Proposed Rule, so I do not think it is at all unreasonable to allow the public a mere six months to comment on it. This is our only opportunity, as consumers, to provide our feedback.

I feel very strongly about e-cigarettes as an alternative to combustible cigarettes. I have smoked for over forty years trying all the options available without success until I started using a vaporizer.  After 3 months I have reduced my nicotine level to 6mg/mL and am on my way to 0mg soon.  Vaping has been my only option that worked and I am so very grateful!  I breath so much easier and the daily cough I had is completely gone.  Quite simply, I firmly believe that they saved my life.  I don’t want to go back to tobacco cigarettes, but am certain I will if the e-cigarette is banned or the juices not readily available.  I enjoy the juices as they provide a flavor other than tobacco.   I wish to provide you with my personal story, as well as science- and evidence-based responses to your questions so that you can take my comment into account. I realize that the FDA has the authority under 21 CFR 10.40 to extend this time frame and that the FDA has exercised this authority on numerous occasions in the past. I would therefore ask that you do so here, so that all stakeholders have the opportunity to provide their comments on this proposed regulation.

I appreciate your consideration of my request and am happy to discuss this issue with you further.

Barbara L Browder Age 60 928-239-9294 Sedona, Arizona