[Federal Register: February 20, 2008 (Volume 73, Number 34)]
[Proposed Rules]
[Page 9239-9241]
[DOCID:fr20fe08-26]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 39

[Docket No. FAA-2007-0177; Directorate Identifier 2007-CE-093-AD]
RIN 2120-AA64

Airworthiness Directives; Taylorcraft Models A, B, and F Series
Airplanes

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

ACTION: Notice of proposed rulemaking (NPRM).

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SUMMARY: We propose to adopt a new airworthiness directive (AD) for
certain Taylorcraft Models A, B, and F series airplanes. This proposed
AD would require inspection of the wing strut attach fittings for
corrosion or cracks and would require repair or replacement if
corrosion or cracks are found. This proposed AD results from data
collected from an accident involving a Taylorcraft Model BF12-65
airplane. The wing separated from the airplane after the wing strut
attach fitting failed due to corrosion. We are proposing this AD to
detect and correct corrosion or cracks in the wing strut attach
fittings. This condition, if not corrected, could result in failure of
the wing strut attach fittings and lead to wing separation and loss of
control.

DATES: We must receive comments on this proposed AD by March 21, 2008.

ADDRESSES: Use one of the following addresses to comment on this
proposed AD:
     Federal eRulemaking Portal: Go to http://www.regulations.gov.
 Follow the instructions for submitting comments.

     Fax:<PHONE_NUMBER>.
     Mail: U.S. Department of Transportation, Docket
Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New
Jersey Avenue, SE., Washington, DC 20590.
     Hand Delivery: U.S. Department of Transportation, Docket
Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New
Jersey Avenue, SE., Washington, DC 20590, between 9 a.m. and 5 p.m.,
Monday through Friday, except Federal holidays.
    For service information identified in this proposed AD, contact
Taylorcraft Aviation, LLC, 2124 North Central Avenue, Brownsville,
Texas 78521; telephone:<PHONE_NUMBER>.

FOR FURTHER INFORMATION CONTACT: Andy McAnaul, Aerospace Engineer,
10100 Reunion Place, San Antonio, Texas 78216; telephone: (210) 308-
3365; fax:<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

Comments Invited

    We invite you to send any written relevant data, views, or
arguments regarding this proposed AD. Send your comments to an address
listed under the

ADDRESSES section. Include the docket number, ``FAA-2007-0177;
Directorate Identifier 2007-CE-093-AD'' at the beginning of your
comments. We specifically invite comments on the overall regulatory,
economic, environmental, and energy aspects of the proposed AD. We will
consider all comments received by the closing date and may amend the
proposed AD in light of those comments.
    We will post all comments we receive, without change, to http://www.regulations.gov
, including any personal information you provide. We

will also post a report summarizing each substantive verbal contact we
receive concerning this proposed AD.

Discussion

    This proposed AD results from data collected after a double
fatality accident involving a Taylorcraft Model BF12-65 airplane near
Oregon City, Oregon in July 2007. The fitting was corroded
approximately 70 percent through the fracture surface. The airplane's
fabric was wrapped around the lugs of the wing strut attach fitting
with the ends of the fabric stuffed into the fitting itself. The fabric
plugged the drain hole on the bottom of the fitting and prevented water
from draining out the front and back ends of the fitting. The fabric
also did not allow for easy visual inspection of the exterior and
interior of the fitting. In addition to fabric, the drain hole was
blocked by other foreign debris as well.
    The corrosion or cracking is most likely to occur in the section
between where the front and rear lift strut attach fittings are bolted
to the fuselage fitting. This condition, if not corrected, could result
in failure of the wing strut attach fittings and lead to wing
separation and loss of control.

Relevant Service Information

    We have reviewed Taylorcraft Aviation, LLC Service Bulletin No.
2007-002, dated November 8, 2007.
    The service information describes procedures for inspecting the
wing strut attach fitting part number A-A11 for cracks or corrosion and
procedures for any required repair or replacement.

FAA's Determination and Requirements of the Proposed AD

    We are proposing this AD because we evaluated all information and
determined the unsafe condition described previously is likely to exist
or develop on other products of the same type design. This proposed AD
would require inspection of the wing strut attach fitting for cracks
and corrosion and repair or replacement if cracks or corrosion are
found.

Costs of Compliance

    We estimate that this proposed AD would affect 3,119 airplanes in
the U.S. registry.
    We estimate the following costs to do the proposed inspection:

----------------------------------------------------------------------------------------------------------------
                                                                               Total cost per     Total cost on
                        Labor cost                             Parts cost         airplane       U.S.  operators
----------------------------------------------------------------------------------------------------------------
2 work-hours x $80 per hour = $160........................                $0              $160          $499,040
----------------------------------------------------------------------------------------------------------------

    We estimate the following costs to do any necessary replacements
that would be required based on the results of the proposed inspection.
We have no way of determining the number of airplanes that may need
this replacement:

------------------------------------------------------------------------
                                                         Total cost per
       Labor cost per fitting          Parts cost per    airplane  (for
                                           fitting        two fittings)
------------------------------------------------------------------------
30 work-hours x $80 per hour =                    $200            $5,200
 $2,400.............................
------------------------------------------------------------------------

    We have no way of determining the number of airplanes that may
require repair as a result of the proposed inspection or the extent of
repair that may be required.

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.

Regulatory Findings

    We have determined that this proposed AD would not have federalism
implications under Executive Order 13132. This proposed AD would 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 that the proposed
regulation:
    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); and
    3. 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.
    We prepared a regulatory evaluation of the estimated costs to
comply with this proposed AD and placed it in the AD docket.

Examining the AD Docket

    You may examine the AD docket that contains the proposed AD, the
regulatory evaluation, any comments received, and other information on
the Internet at http://www.regulations.gov; or in person at the Docket

Management Facility between 9 a.m. and 5 p.m., Monday through Friday,
except Federal holidays. The Docket Office (telephone<PHONE_NUMBER>)
is located at the street address stated 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, Safety.

The Proposed Amendment

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

PART 39--AIRWORTHINESS DIRECTIVES

    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]

    2. The FAA amends Sec.  39.13 by adding the following new AD:

Taylorcraft: Docket No. FAA-2007-0177; Directorate Identifier 2007-
CE-093-AD.

Comments Due Date

    (a) We must receive comments on this airworthiness directive
(AD) action by March 21, 2008.

Affected ADs

    (b) None.

Applicability

    (c) This AD applies to all serial numbers of Taylorcraft Models
A, BC, BCS12-D, BCS, BC12-D1, BC-65, BCS12-D1, BCS-65, BC12D-85,
BC12-65 (Army L-2H), BCS12D-85, BCS12-65, BC12D-4-85, BC12-D,
BCS12D-4-85, (Army L-2G) BF, BFS, BF-60, BFS-60, BF-65, BFS-65,
(Army L-2K) BF 12-65, BFS-65, BL, BLS, (Army L-2F) BL-65, BLS-65,
(Army L-2J) BL12-65, BLS12-65, 19, F19, F21, F21A, F21B, F22, F22A,
F22B, and F22C airplanes that are certificated in any category.

    Note: This AD applies to all Taylorcraft models listed above,
including those models not listed in Taylorcraft Aviation, LLC
Service Bulletin No. 2007-002, dated November 8, 2007. If there are
any other differences between this AD and the above service
bulletin, this AD takes precedence.

Unsafe Condition

    (d) This AD results from data collected from an accident
involving a Taylorcraft Model BF12-65 airplane. The wing separated
from the airplane after the wing strut attach fitting failed due to
corrosion. We are proposing this AD to detect and correct corrosion
or cracks in the wing strut attach fittings. This condition, if not
corrected, could result in failure of the wing strut attach fittings
and lead to wing separation and loss of control.

Compliance

    (e) To address this problem, you must do the following, unless
already done:
    (1) Initially inspect the left and right wing lift strut attach
fittings, part number (P/N) A-A11, for corrosion or cracking
following Taylorcraft Aviation, LLC Service Bulletin No. 2007-002,
dated November 8, 2007, using the following compliance times:
    (i) For airplanes that have never been equipped with floats or
snow skis: Within the next 90 days after the effective date of this
AD.
    (ii) For airplanes equipped with or that have ever been equipped
with floats or snow skis: Within the next 30 days after the
effective date of this AD.
    (2) If the airplane is equipped with floats or snow skis at the
time of the initial inspection required by paragraph (e)(1) of this
AD or at any time after the initial inspection required by paragraph
(e)(1) of this AD, you must repeat the inspection required in
paragraph (e)(1) of this AD as follows:

------------------------------------------------------------------------
        If the following exists:                      Then:
------------------------------------------------------------------------
(i) The airplane is equipped with        Inspect no later than 48 months
 floats or snow skis at the time of the   following the initial
 initial inspection required by           inspection and repetitively
 paragraph (e)(1) of this AD.             inspect thereafter at
                                          intervals not to exceed 48
                                          months. Continue these
                                          repetitive inspections until
                                          removal of floats or snow
                                          skis, at which time you must
                                          follow paragraph (e)(2)(ii) of
                                          this AD.
(ii) You remove floats or snow skis at   Inspect no later than 48 months
 any time following the initial           following the last inspection.
 inspection required by paragraph         After the inspection following
 (e)(1) of this AD.                       removal of floats or snow
                                          skis, no further inspections
                                          are required unless floats or
                                          snow skis are re-installed at
                                          a later date, at which time
                                          you must follow paragraph
                                          (e)(2)(iii) of this AD.
(iii) You install floats or snow skis    Inspect no later than 48 months
 at any time since the initial            following the last inspection
 inspection required by paragraph         or before further flight after
 (e)(1) of this AD.                       installation of floats or snow
                                          skis, whichever occurs later,
                                          and repetitively inspect
                                          thereafter at intervals not to
                                          exceed 48 months. Continue
                                          these repetitive inspections
                                          until removal of floats or
                                          snow skis, at which time you
                                          must follow paragraph
                                          (e)(2)(ii) of this AD.
------------------------------------------------------------------------

    (3) If you find cracking or material loss due to corrosion
during any of the inspections required in paragraph (e)(1) or (e)(2)
of this AD, before further flight, do the following:
    (i) Contact Taylorcraft Aviation, LLC at 2124 North Central
Avenue, Brownsville, Texas 78521; telephone:<PHONE_NUMBER> to obtain
an FAA-approved repair scheme or replacement procedure; and
    (ii) Repair following the FAA-approved repair scheme or replace
the left and/or right wing lift strut attach fitting(s), P/N A-A11,
following the replacement procedure.

Alternative Methods of Compliance (AMOCs)

    (f) The Manager, Fort Worth Airplane Certification Office, 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: Andy
McAnaul, Aerospace Engineer, 10100 Reunion Place, San Antonio, Texas
78216; telephone:<PHONE_NUMBER>; fax:<PHONE_NUMBER>. 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.

Related Information

    (g) To get copies of the service information referenced in this
AD, contact Taylorcraft Aviation, LLC, 2124 North Central Avenue,
Brownsville, Texas 78521; telephone:<PHONE_NUMBER>. To view the AD
docket, go to U.S. Department of Transportation, Docket Operations,
M-30, West Building Ground Floor, Room W12-140, 1200 New Jersey
Avenue, SE., Washington, DC 20590, or on the Internet at http://www.regulations.gov
.

    Issued in Kansas City, Missouri, on February 12, 2008.
David R. Showers,
Acting Manager, Small Airplane Directorate, Aircraft Certification
Service.
 [FR Doc. E8-2995 Filed 2-19-08; 8:45 am]

BILLING CODE 4910-13-P


[Federal Register Volume 83, Number 31 (Wednesday, February 14, 2018)]
[Notices]
[Pages 6650-6651]
[FR Doc No: 2018-02980]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-82665; File No. SR-C2-2018-003]

Self-Regulatory Organizations; Cboe C2 Exchange, Inc.; Notice of
Filing and Immediate Effectiveness of a Proposed Rule Change Relating
to the Options Regulatory Fee

February 8, 2018.
    Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934
(the ``Act''),\1\ and Rule 19b-4 thereunder,\2\ notice is hereby given
that on January 31, 2018, Cboe C2 Exchange, Inc. (the ``Exchange'' or
``C2 Options'') filed with the Securities and Exchange Commission (the
``Commission'') the 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 seeks to amend its Fees Schedule. The text of the
proposed rule change is available on the Exchange's website (http://www.c2exchange.com/Legal/), at the Exchange's Office of the Secretary,
and at the Commission's Public Reference Room.

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

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

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

1. Purpose
    The Exchange proposes to decrease the Options Regulatory Fee
(``ORF'') from $.0015 per contract to $.0014 per contract in order to
help ensure that revenue collected from the ORF, in combination with
other regulatory fees and fines, meets the Exchange's total regulatory
costs. The proposed fee change will be operative on February 1, 2018.
    The ORF is assessed by C2 Options to each Trading Permit Holder
(``TPH'') for options transactions cleared by the TPH that are cleared
by the Options Clearing Corporation (OCC) in the customer range,
regardless of the exchange on which the transaction occurs.\3\ In other
words, the Exchange imposes the ORF on all customer-range transactions
cleared by a TPH, even if the transactions do not take place on the
Exchange. The ORF is collected by OCC on behalf of the Exchange from
the Clearing Trading Permit Holder (``CTPH'') or non-CTPH that
ultimately clears the transaction. With respect to linkage
transactions, C2 Options reimburses its routing broker providing
Routing Services pursuant to C2 Options Rule 6.36 for options
regulatory fees it incurs in connection with the Routing Services it
provides.
---------------------------------------------------------------------------

    \3\ The ORF also applies to customer-range transactions executed
during Extended Trading Hours.
---------------------------------------------------------------------------

    Revenue generated from ORF, when combined with all of the
Exchange's other regulatory fees and fines, is designed to recover a
material portion of the regulatory costs to the Exchange of the
supervision and regulation of TPH customer options business. Regulatory
costs include direct regulatory expenses and certain indirect expenses
for work allocated in support of the regulatory function. The direct
expenses include in-house and third party service provider costs to
support the day to day regulatory work such as surveillances,
investigations and examinations. The indirect expenses include support
from such areas as human resources, legal, information technology and
accounting. These indirect expenses are estimated to be approximately
6% of C2 Options' total regulatory costs for 2018. Thus, direct
expenses are estimated to be approximately 94% of total regulatory
costs for 2018. In addition, it is C2 Options' practice that revenue
generated from ORF not exceed more than 75% of total annual regulatory
costs. These expectations are estimated, preliminary and may change.
These expectations are estimated, preliminary and may change. [sic]
There can be no assurance that our final costs for 2018 will not differ
materially from these expectations and prior practice; however, the
Exchange believes that revenue generated from the ORF, when combined
with all of the Exchange's other regulatory fees and fines, will cover
a material portion, but not all, of the Exchange's regulatory costs.
    The Exchange also notes that its regulatory responsibilities with
respect to TPH compliance with options sales practice rules have
largely been allocated to FINRA under a 17d-2 agreement.\4\ The ORF is
not designed to cover the cost of that options sales practice
regulation.
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    \4\ See Securities Exchange Act Release No. 76309 (October 29,
2015), 80 FR 68361 (November 4, 2015).
---------------------------------------------------------------------------

    The Exchange will continue to monitor the amount of revenue
collected from the ORF to ensure that it, in combination with its other
regulatory fees and fines, does not exceed the Exchange's total
regulatory costs. The Exchange monitors its regulatory costs and
revenues at a minimum on a semi-annual basis. If the Exchange
determines regulatory revenues exceed or are insufficient to cover a
material portion of its regulatory costs, the Exchange will adjust the
ORF by submitting a fee change filing to the Commission. The Exchange
notifies TPHs of adjustments to the ORF via regulatory circular. The
Exchange endeavors to provide TPHs with such notice at least 30
calendar days prior to the effective date of the change.
2. Statutory Basis
    The Exchange believes the proposed rule change is consistent with
the Securities Exchange Act of 1934 (the ``Act'') and the rules and
regulations thereunder applicable to the Exchange and, in particular,
the requirements of Section 6(b) of the Act.\5\ Specifically, the
Exchange believes the proposed rule change is consistent with Section
6(b)(4) of the Act,\6\ which provides that Exchange rules may provide
for the equitable allocation of reasonable dues, fees, and other
charges among its TPHs and other persons using its facilities.
Additionally, the Exchange believes the proposed rule change is
consistent with the Section 6(b)(5) \7\ requirement that the rules of
an exchange not be designed

to permit unfair discrimination between customers, issuers, brokers, or
dealers.
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    \5\ 15 U.S.C. 78f(b).
    \6\ 15 U.S.C. 78f(b)(4).
    \7\ 15 U.S.C. 78f(b)(5).
---------------------------------------------------------------------------

    The Exchange believes the proposed fee change is reasonable because
it would help ensure that revenue collected from the ORF, in
combination with other regulatory fees and fines, does not exceed the
Exchange's total regulatory costs. Moreover, the Exchange believes the
ORF ensures fairness by assessing higher fees to those TPHs that
require more Exchange regulatory services based on the amount of
customer options business they conduct. Regulating customer trading
activity is much more labor intensive and requires greater expenditure
of human and technical resources than regulating non-customer trading
activity, which tends to be more automated and less labor-intensive. As
a result, the costs associated with administering the customer
component of the Exchange's overall regulatory program are materially
higher than the costs associated with administering the non-customer
component (e.g., TPH proprietary transactions) of its regulatory
program.\8\ The Exchange believes the proposed fee change is equitable
and not unfairly discriminatory in that it is charged to all TPHs on
all their transactions that clear in the customer range at the OCC.
---------------------------------------------------------------------------

    \8\ If the Exchange changes its method of funding regulation or
if circumstances otherwise change in the future, the Exchange may
decide to modify the ORF or assess a separate regulatory fee on TPH
proprietary transactions if the Exchange deems it advisable.
---------------------------------------------------------------------------

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

    C2 Options does not believe that the proposed rule change will
impose any burden on competition that is not necessary or appropriate
in furtherance of the purposes of the Act, because it applies to all
TPHs. The proposed ORF is comparable to fees charged by other options
exchanges for the same or similar service. The Exchange believes any
burden on competition imposed by the proposed rule change is outweighed
by the need to help the Exchange adequately fund its regulatory
activities to ensure compliance with the Exchange Act.

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

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

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

    The foregoing rule change has become effective pursuant to Section
19(b)(3)(A) of the Act \9\ and paragraph (f) of Rule 19b-4 \10\
thereunder. 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 will institute proceedings to
determine whether the proposed rule change should be approved or
disapproved.
---------------------------------------------------------------------------

    \9\ 15 U.S.C. 78s(b)(3)(A).
    \10\ 17 CFR 240.19b-4(f).
---------------------------------------------------------------------------

IV. Solicitation of Comments

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

Electronic Comments

     Use the Commission's internet comment form (http://www.sec.gov/rules/sro.shtml); or
     Send an email to [email protected]. Please include
File No. SR-C2-2018-003 on the subject line.

Paper Comments

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

All submissions should refer to File No. SR-C2-2018-003. This file
number should be included on the subject line if email is used. To help
the Commission process and review your comments more efficiently,
please use only one method. The Commission will post all comments on
the Commission's internet website (http://www.sec.gov/rules/sro.shtml).
Copies of the submission, all subsequent amendments, all written
statements with respect to the proposed rule change that are filed with
the Commission, and all written communications relating to the proposed
rule change between the Commission and any person, other than those
that may be withheld from the public in accordance with the provisions
of 5 U.S.C. 552, will be available for website viewing and printing in
the Commission's Public Reference Room, 100 F Street NE, Washington, DC
20549, on official business days between the hours of 10:00 a.m. and
3:00 p.m. Copies of the filing also will be available for inspection
and copying at the principal office of the Exchange. All comments
received will be posted without change. Persons submitting comments are
cautioned that we do not redact or edit personal identifying
information from comment submissions. You should submit only
information that you wish to make available publicly. All submissions
should refer to File No. SR-C2-2018-003, and should be submitted on or
before March 7, 2018.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\11\
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    \11\ 17 CFR 200.30-3(a)(12).
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Eduardo A. Aleman,
Assistant Secretary.
[FR Doc. 2018-02980 Filed 2-13-18; 8:45 am]
BILLING CODE 8011-01-P


United States Environmental Protection Agency
     Chemical Safety and Pollution Prevention
     (7101)
                                                        EPA 712-[insert number]
                                                                  DRAFT 6-29-11

Product Performance
Test Guidelines

OCSPP 810.2700:

Products with Prion-Related Claims

                                     NOTICE

  This guideline is one of a series of test guidelines established by the Office of Prevention, Pesticides and Toxic Substances (OPPTS), United States Environmental Protection Agency for use in testing pesticides and chemical substances to develop data for submission to the Agency under the Toxic Substances Control Act (TSCA) (15 U.S.C. 2601, et seq.), the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7 U.S.C. 136, et seq.), and section 408 of the Federal Food, Drug and Cosmetic (FFDCA) (21 U.S.C. 346a).

  The OPPTS test guidelines serve as a compendium of accepted scientific methodologies and protocols that are intended to provide data to inform regulatory decisions under TSCA, FIFRA and/or FFDCA.  This document provides guidance for conducting the test, and is also used by EPA, the public and the companies that are subject to data submission requirements under TSCA, FIFRA and/or the FFDCA.  As a guidance document, these guidelines are not binding on either EPA or any outside parties, and the EPA may depart from the guidelines where circumstances warrant and without prior notice.  At places in this guidance, the Agency uses the word "should."    In this guidance, use of "should" with regard to an action means that the action is recommended rather than mandatory.   The procedures contained in this guideline are strongly recommended for generating the data that are the subject of the guideline, but EPA recognizes that departures may be appropriate in specific situations. You may propose alternatives to the recommendations described in these guidelines, and the Agency will assess them for appropriateness on a case-by-case basis.

  For additional information about OPPTS harmonized test guidelines and to access the guidelines electronically, please go to http://www.epa.gov/oppts and select "Test Methods & Guidelines" on the left side navigation menu.  You may also access the guidelines in http://www.regulations.gov grouped by Series under Docket ID #s: EPA-HQ-OPPT-2009-0150 through EPA-HQ-OPPT-2009-0159, and EPA-HQ-OPPT-2009-0576.

  DRAFT DOCUMENT DISCLAIMER:  This draft document is distributed solely for the purpose of external review.  It has not been formally disseminated by the EPA and should not be construed to represent any Agency determination or policy.  The information correction process under the Agency's Information Quality Guidelines does not apply until this document is formally disseminated by the EPA in its final form.  This draft document should only be cited or quoted in the context of providing comments.

OPPTS 810.2400: Products with Prion-Related Claims.

(a) Scope --

   (1)    Applicability. This guideline describes test methods that EPA believes will generally satisfy certain testing requirements of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) (7 U.S.C. 136, et seq.), and the Federal Food, Drug, and Cosmetic Act (FFDCA) (21 U.S.C., 301 et seq.).

   (2)    Background. Prion ("proteinaceous infectious particle") is a term often used to designate an infectious agent that causes progressive degenerative diseases of the central nervous system, which are collectively called the transmissible spongiform encephalopathies (TSEs or prion diseases), including scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), and various forms of Creutzfeldt-Jakob disease (CJD), etc.  These infectious particles, which accumulate in brain tissue during the incubation periods of TSEs, are comprised of abnormal folding conformations of a normal, ubiquitous protein called the "cellular" prion protein (PrP[C]).  This normal cellular prion protein is synthesized and eventually degraded through normal metabolic processes.  In certain instances, however, protein molecules may become misfolded.  When prion proteins misfold (hereafter called "prions"), the resultant shape change serves as a template to induce the misfolding of the normal cellular prion protein to produce more infectious prions and, thereby, propagate an infection.  These abnormal prions resist proteosomal degradation and slowly accumulate in the brain and infect brain tissue.

      The first described prion disease was scrapie, and so such infectious proteins are often designated collectively as PrPSc in all TSEs.  Some scientists prefer to use other terms such as PrPres, PrPd, PrPTSE, PrPCWD, and PrPCJD to designate the specific, abnormal forms of PrP associated with specific prion diseases.

      For purposes of this guidance, the terms "prions" and "TSE agents" are synonymous.  These abnormal prion proteins, although somewhat variable, share properties that distinguish them from normal PrP[C]: they are usually insoluble in non-denaturing detergent-salt solutions and relatively resistant to digestion with the enzyme proteinase K.  These properties are attributed to misfolding of PrP[C] to yield isoforms that are enriched in beta-sheet secondary structure.  Many scientific experts have concluded that the abnormal prion proteins themselves are the self-replicating infectious agents causing TSEs (Prusiner 1982, 2004); however, there remain notable reservations, as outlined by Manuelidis (2007a, b).

            1.  Manuelidis L.  2007a. A 25 nm virion is the likely cause of transmissible spongiform encephalopathies.  Journal of cellular biochemistry; 100(4):897-915.
            2.  Manuelidis L, Yu ZX, Barquero N, Mullins B. 2007b.  Cells infected with scrapie and Creutzfeldt-Jakob disease agents produce intracellular 25-nm virus-like particles.  Proceedings of the National Academy of Sciences of the United States of America; 104(6):1965-70.
            3.  Prusiner SB.  1982.  Novel proteinaceous infectious particles cause scrapie.  Science; 216:136-44.
            4.  Prusiner SB.  2004.  Detecting mad cow disease.  Scientific American; 291(1):86-93.

(b) Purpose.  This guideline provides pesticide applicants and registrants guidance on test systems and performance standards that apply to pesticide products intended to reduce the infectivity of prions on inanimate, environmental surfaces (hereafter called "prion-related products").  EPA encourages pesticide applicants and registrants to follow this guidance and submit a draft test protocol to EPA for review prior to conducting any studies.  EPA may revise this guidance over time, as needed, to reflect advances in available test methods and scientific knowledge pertaining to prions.  Studies conducted under this guideline are to be completed under EPA's Good Laboratory Practice regulations (40 CFR Part 160).

(c) Guidance --

   (1) Labeling Claims.  Testing conducted according to currently available test methods are adequate for measuring reduction in prion infectivity, but not for demonstrating complete destruction or inactivation of prions.  Accordingly, claims such as "inactivates," "destroys," "denatures" and "eliminates" are not supported by currently available test methods.  Further, a prion-related claim should include the type of prion against which the product has been successfully tested.  Assuming acceptable data were available, the following is the general format for a claim that EPA may consider accepting :

          "Has been demonstrated to reduce infectivity of prions (TSE agents) by (X) logs (insert log reduction number supported by data) based on a bioassay of the (insert prion type) in (insert type of organism in which the prions were tested)."

      An example of a claim that EPA could find to be acceptable depending on supporting data would be:

          "Has been demonstrated to reduce infectivity of prions (TSE agents) by six (6) logs based on a bioassay of the scrapie prion in transgenic mice."

   (2) Selecting a Test System.  The test system should be appropriate to the uses that appear on the proposed label.

      a. Carrier-based Method.  If the intended uses of a product are for reducing the infectivity of prions on inanimate surfaces, then a carrier-based, animal bioassay should be used to measure the amount of prion infectivity reduction that is achieved by the product when used according to label directions.  Examples of published, carrier-based test methods include:

            1.  Lemmer K, Mielke M, Kratzel C, Joncic M, Oezel M, Pauli G, Beekes M.  Decontamination of surgical instruments from prions. II. In vivo findings with a model system for testing the removal of scrapie infectivity from steel surfaces.  J Gen Virol. 2008 Jan;89(Pt 1):348-58.

            2.  Peretz D, Supattapone S, Giles K, Vergara J, Freyman Y, Lessard P, Safar JG, Glidden DV, McCulloch C, Nguyen H-OB, Scott M, DeArmond SJ, and Prusiner SB.  2006.  Inactivation of prions by sodium dodecyl sulfate.  J. Virol. 80:322-331.

            3.  Weissmann C, Enari M, Klohn PC, Rossi P, Flechsig E.  2002.  Transmission of prions. J Infect Dis 186 Suppl 2:S157-65.

            4.  Zobeley E, Flechsig E, Cozzio A, Enari M, and Weissman C.  1999.  Infectivity of scrapie prions bound to a stainless steel surface.  Molecular Medicine 5:240-243.

      b. Suspension-based Test Method.  If the intended use of a product includes only treating liquids (e.g., liquid wastes), then a suspension-based, animal bioassay should be used to measure the amount of prion infectivity reduction that is achieved by the product when used according to label directions.  An example of a published, suspension-based test method is:

            1.  Peretz D, Supattapone S, Giles K, Vergara J, Freyman Y, Lessard P, Safar JG, Glidden DV, McCulloch C, Nguyen H-OB, Scott M, DeArmond SJ, and Prusiner SB.  2006.  Inactivation of prions by sodium dodecyl sulfate.  J. Virol. 80:322-331.

   (3) Methods of Estimating the Reduction of Prion Infectivity.  Prion diseases are generally characterized by a long asymptomatic incubation period, followed by the rapid onset of symptoms, followed by death.  The length of the incubation period is reproducible upon repeated passages of a given prion and is inversely proportional to the log of the infectious dose of that prion, although at both very high and very low concentrations of infectivity the relationship is no longer linear.  Two methods of estimating the reduction of prion infectivity have been employed:  endpoint titration and incubation time interval assay.  The former method may be best suited to analyze suspension-based testing and the latter may be best suited for carrier-based testing.  Further, incubation time interval assays are generally not quite as accurate as endpoint titration assays (0.5 log difference), and may be less reliable for quantifying very low levels of infectivity.

      a. End-point Titration.  An end-point titration is a classical method of determining the titer of a sample (i.e., the concentration of the pathogen).  To begin with, a sample is serially diluted by a factor of 10 until less than 1 ID50 (the infectious dose which kills 50% of the pathogen) remains in the final dilution.  The resulting set of serial dilutions is used to inoculate a corresponding set of experimental animals, typically at least four animals per 10-fold dilution.  The experimental animals are observed for the appearance of symptoms, and the symptoms are scored.  The animals are observed for a predetermined period, usually 450 days for hamsters or 500 days for mice.  At the end of the predetermined period, any surviving animals would be humanely euthanized before they would die of the prion disease and given a thorough neuropathological examination that looks for signs of prion disease as described in section (4) below.  The titer may be determined by several statistical methods (see references below).   The titers of subsequent samples are determined in the same fashion.

      The following are examples of end-point titration methods:

                  1.  Andersen J, Barrett T, Scott GR.  1996.  Appendix 3.  Fifty percent effective dose (ED50): Spearman-Kärber method.  In Manual of the Diagnosis of Rinderpest.  (FAO Animal Health Manual  -  1)  Food and Agriculture Organization of the United Nations. Rome.  Available on-line: http://www.fao.org/docrep/w0049e/w0049e07.htm#appendix%203.%20fifty%20percent%20effective%20dose%20(ed50):%20spearman%20kärber%20method

                  2.  Reed LJ and Muench H.  A simple method for estimating fifty percent endpoints. Amer J Hyg 1938;27:493-7.

                  3.  Bliss CI.  The method of probits. Science. 1934 Jan 12;79(2037):38-39.

      b. Incubation Time Interval Assay.  An incubation time interval assay exploits the relationship between the length of the incubation period and the titer of the pathogen in an inoculum.  An endpoint titration of a starting brain homogenate is used to establish an empirical relationship between prion titer and length of incubation period.  Once the relationship is established, the titer of any subsequent sample is determined by observing the incubation period of an inoculated animal group (usually at least four) and using this value to predict a corresponding titer based on the empirically determined relationship.  The initial endpoint titration should not be greatly, if at all, separated in time from the experimental assay.  If the initial endpoint titration is to be replaced with historical animal model data, then sufficient control animals should be included to ensure that the historical animal model data are relevant to the experimental assay.

      The following are examples of incubation time interval assay methods:

                  1.  Prusiner SB, Cochran SP, Groth DF, Downey DE, Bowman KA, Martinez HM.  1982.  Measurement of the scrapie agent using an incubation time interval assay.  Ann. Neurol. April;11(4):353-8.

                  2.  Prusiner SB, Cochran SP, Downey DE, Groth DF.  1981.  Determination of scrapie agent titer from incubation period measurements in hamsters.  Adv Exp Med Biol. 134:385-99.

      The endpoint titration and incubation time interval assays yield similar results; however, the endpoint titration requires many more animals.  As a result, the incubation time interval assay is the more widely used assay method for prions since it is faster, uses fewer animals, and provides results that are negligibly different (+- 0.5 log) compared to the endpoint titration.  However, an endpoint titration assay may be more useful than an incubation time assay if the difference between the titer of the prions in the starting inoculum and the treated carrier is very high or very low, or if one wants to directly compare two samples with similar titers.  A comparison of the number of animals required for these assays is listed in Appendix 1.  The  263K strain of hamster-adapted scrapie is being provided as an example.  The endpoint titration requires between two and four times the animals as the incubation time interval assay.

      c. Other Relevant Tests.  EPA welcomes data from screening tests (such as Western blot, ELISA, Protein Misfolding Cyclic Amplification (PMCA), or cell culture assays), but such tests are not a substitute for the suspension-based or carrier-based tests.

   (4) Other important aspects of the test system include the following:

      Titer of prions:  Depending on the test method and type of prion used, the titer of the prions in the initial inoculum may range from 10[4] to 10[11] ID50 units/g of brain homogenate, based on currently available studies.  After dilution and drying of the inoculum on the carrier or in a suspension, the titer of the prions may be further reduced by 1-2 logs.  The study should have a reliable method for determining the concentration of prions in the initial inoculum and the concentration of prions dried on the carrier or mixed in a suspension.  The dynamic range of the test method's ability to measure reduction in infectivity should be well established.  In order for the test to be able to measure at least a six (6) log reduction in infectivity [see section (5) Evaluation of Success below], the titer of the prions on the carrier or in a suspension (i.e., the titer to which test animals will be exposed) should be at least 10[7] ID50 units/g brain homogenate (or about 10[9] ID50 units/g brain homogenate in the initial inoculum).  Finally, the protocol should address and balance such issues as the preparation of the initial inoculum, the order in which animals are inoculated, and how the animals are housed (see Animal Housing below).

      Prion type:  Several types of prions are available for use in infectivity tests, such as scrapie prions (hamster adapted 263K), BSE prions (mouse adapted 301V, 310C and 6BP1), and sCJD prions (human).  An animal-related prion (e.g., scrapie, CWD) should be selected for testing if the proposed use sites are animal-related (e.g., farm premises, farm equipment, veterinary clinics).  A human-related prion (e.g., sCJD) should be selected if the proposed use sites are related to humans (e.g., surgical instruments, hospital rooms, laboratories).  [Note:  Prospective registrants should consult with the U.S. Food and Drug Administration (FDA) for uses that are also under its jurisdiction (e.g., medical devices or adjuncts to medical devices).  The FDA considers claims of activity against prions (TSE agents) to be unique and unclassified, and recommends that product manufacturers seeking a product claim of reducing the infectivity of prions (TSE agents) for any healthcare use meet with FDA to learn the FDA's recommendations for seeking product approval.]  Human-derived TSE materials of a known titer currently are available at only a few research laboratories.

      Age of test animals at beginning of study:  Animals should be old enough to tolerate intracerebral inoculation without excessive mortality, i.e., in the following age ranges: mice, 6-10 weeks old; hamsters, 5-8 weeks old; and guinea pigs, 5-7 weeks old.  The study should continue up to the end of the animals' normal life span (the point at which normal mortality begins to increase significantly).  Historical mortality data on the selected strain of test animals should be provided to substantiate the selection of these critical lifespan points.

      Number of animals:  The numbers of animals in the treatment and control groups should be sized based on statistical validity, and the calculations supporting the proposed animal group sizes should be included.  The number of animals typically used is between 4 and 24.

      Types/Species of animals:  The type/species of animal is determined by the test method selected.  The test animals are either genetically homogeneous mice or hamsters, or transgenic (genetically altered to express the prion protein -- PrP --  of the host animal) mice or hamsters.  If the animals are transgenic, the test protocol should identify the source of the transgenic gene material and available information that characterizes it.  Native species of prions may also be tested in relevant animal species.

      Animal housing and environmental conditions:  The number of animals per cage should be kept to a minimum and the cages should be compatible with the animals.  Other animal housing issues should be addressed to avoid influencing the test results; for example, such as which groups may be housed next to each other, and rotating cages to balance exposure to heat, light, noise, etc.  Transgenic or wild-type mice can be housed 5-8 per cage, depending on the size of the cage, and hamsters are generally housed two per cage.  The temperature in the experimental animal room should be 22°C (+- 3°C).  The relative humidity should be at least 30% and preferably not exceed 70% other than during room cleaning.  Lighting should be artificial, the sequence being 12 hours light and 12 hours dark.

      Length of study:   The study should be extended as long as possible, taking into account the historical mortality data for the particular animal type/species used.  Transgenic or wild-type mice should be kept for 500 days.  Hamsters should be kept for 450 days.

      Examination of animals at end of study or when animals die prematurely:  When animals reach the defined age limit or die prematurely, tests should be performed on all members of both the treated and control groups, in order to ascertain whether they are infected with prions.  Such tests should include at least one of the following: Western blot, immunological histochemistry or "blind passage."  The method for dealing with premature deaths and how to place them into the statistical calculations should also be addressed in the statistical evaluation plan for the study.

      Evaluation of Success:  The target criterion for success is no less than six (6) logs of reduction of infectivity in the treated versus untreated (control) groups.

   	Submission of Draft Protocol:  Due to the wide variety of available animal bioassays for measuring reduction of prion infectivity by a prion-related product on environmental surfaces, the Agency strongly recommends that the registrant submit a draft test protocol to EPA for review prior to conducting such a study.  The Agency also recommends that the registrant request a pre-registration conference to discuss registration data and labeling requirements for a prion-related product.

Appendix 1.  Animals used in an endpoint titration versus an incubation time interval assay under different sets of assumptions

Assuming:

   * Initial brain titer of 10[10] ID50/g
   * 10 treatments are evaluated.
   * 6 animals are used per log dilution.
   * Each treatment reduces infectivity by 10[4].

  Endpoint titration:

   Initial titration (10 log dilutions)			    			10 x 6 =  60
   10 x Titration of each treatment (7 log dilutions)			     10 x 7 x 6 = 420
   Total										 480

  Incubation time interval assay:

   Titration/calibration curve (10 log dilutions)	    			10 x 6 =  60
   10 x 1 group per treatment					    	10 x 6 =  60
   Total										 120

Same assumptions except:

   * Each treatment reduces infectivity by 10[6].

  Endpoint titration:

   Initial titration (10 log dilutions)			    			10 x 6 =  60
   10 x Titration of each treatment (5 log dilutions)			     10 x 5 x 6 = 300
   Total										 360

  Incubation time interval assay:

   Titration/calibration curve (10 log dilutions)	    			10 x 6 =  60
   10 x 1 group per treatment					    	10 x 6 =  60
   Total										 120

Same assumptions except:

   * Each treatment reduces infectivity by 10[8].

  Endpoint titration:

   Initial titration (10 log dilutions)			    			10 x 6 =  60
   10 x Titration of each treatment (3 log dilutions)			     10 x 3 x 6 = 180
   Total										 240

  Incubation time interval assay:

   Titration/calibration curve (10 log dilutions)	    			10 x 6 =  60
   10 x 1 group per treatment					    	10 x 6 =  60
   Total										 120