[Federal Register Volume 86, Number 88 (Monday, May 10, 2021)]
[Notices]
[Pages 24909-24911]
[FR Doc No: 2021-09775]

=======================================================================
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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-91769; File No. SR-NYSE-2021-08]

Self-Regulatory Organizations; New York Stock Exchange LLC; Order
Granting Approval of a Proposed Rule Change of New Rules Providing for
the Registration and Obligations of Non-DMM Market Makers

May 4, 2021.

I. Introduction

    On March 12, 2021, New York Stock Exchange, Inc. (``NYSE'' or
``Exchange'')

filed with the Securities and Exchange Commission (``Commission'')
pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934
(``Act'') \1\ and Rule 19b-4 thereunder,\2\ proposed new rules
providing for the registration and obligations of Non-DMM Market
Makers. The proposed rule change was published for comment in the
Federal Register on March 25, 2021.\3\ The Commission has received no
comments on the proposed rule change. The Commission is approving the
proposed rule change.
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    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
    \3\ See Securities Exchange Act Release No. 91377 (March 19,
2021), 86 FR 15974 (March 25, 2021) (``Notice'').
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II. Description of the Proposed Rule Change

    The Exchange proposes rules governing Non-DMM Market Makers who
would be electronic, off-floor market makers.\4\ Non-DMM Market Makers
would comprise a new category of market participants on the Exchange
and would have responsibilities different than those of Designated
Market Makers (``DMMs'') and Supplemental Liquidity Providers
(``SLPs'').
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    \4\ A ``Non-DMM Market Maker'' would be defined as a member
organization that acts as a Non-DMM Market Maker pursuant to Rule
7P. See Notice, id. at 15974.
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    Non-DMM Market Makers are not intended to replace DMMs or SLPs on
the Exchange and would not assume any of the responsibilities already
assigned to DMMs or SLPs pursuant to Exchange Rules (for example, Non-
DMM Market Makers would not perform any trading floor functions such as
those assigned to DMMs). Instead, under the proposed rules, for all
securities that trade on the Exchange, a member organization may
register as a Non-DMM Market Maker and be subject to obligations
similar to those of Market Makers on NYSE Arca, Inc. (``NYSE Arca'')
and NYSE American LLC (``NYSE American'') to, among other things,
maintain continuous, two-sided trading interest in the securities in
which they are registered as a Non-DMM Market Maker (``Two-Sided
Obligation'') and adhere to certain pricing obligations.
    The Exchange proposes the following rules, based on NYSE Arca and
NYSE American rules of the same number with non-substantive changes, to
govern the registration and obligations of Non-DMM Market Makers on the
NYSE:
     Proposed Rule 1.1(p) (definition of Market Maker
Authorized Trader);
     Proposed Rule 1.1(t) (definition of Non-DMM Market Maker);
     Proposed Rule 7.20 (Registration of Non-DMM Market
Makers);
     Proposed Rule 7.21 (Obligations of Market Maker Authorized
Traders);
     Proposed Rule 7.22 (Registration of Non-DMM Market Makers
in a Security); and
     Proposed Rule 7.23 (Obligations of Non-DMM Market Makers).
    These proposed rules would be applicable only to Non-DMM Market
Makers. They would not apply to DMMs or SLPs, who would continue to be
governed by existing Exchange rules applicable to those market
participants.\5\
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    \5\ See, e.g., NYSE Rules 98, 103, 103B, 104, and 107B.
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Proposed Rule Changes

Rule 1.1
    Rule 1.1 sets forth definitions of terms that are used throughout
the Exchange rules. The Exchange proposes to add the following
definitions to the rule:
     The Exchange proposes to amend current Rule 1.1(p) to set
forth the definition of ``Market Maker Authorized Trader'' or ``MMAT.''
A ``Market Maker Authorized Trader'' or ``MMAT'' would be defined as an
Authorized Trader (as defined in Rule 1.1(a)) who performs market
making activities pursuant to Rule 7P on behalf of a Non-DMM Market
Maker.
     The Exchange proposes to amend current Rule 1.1(t) to set
forth the definition of ``Non-DMM Market Maker.'' A ``Non-DMM Market
Maker'' would be defined as a member organization that acts as a Non-
DMM Market Maker pursuant to Rule 7P. Accordingly, for purposes of
Exchange rules, the term ``Non-DMM Market Maker'' does not include DMMs
or SLPs.
Rule 7P, Section 2
    The Exchange proposes to amend Section 2 under Rule 7P, which is
currently designated as ``Reserved,'' and rename it ``Non-DMM Market
Makers.'' The Exchange proposes that the rules set forth in this
section would apply only to the proposed new group of Non-DMM Market
Makers and would not be applicable to DMMs or SLPs.
Rule 7.20
    The Exchange proposes to add Rule 7.20 and title it ``Registration
of Non-DMM Market Makers.'' Proposed Rule 7.20 would set forth the
requirements for member organizations to apply for registration as Non-
DMM Market Makers. The Exchange proposes that its Non-DMM Market Makers
have the same registration requirements as Market Makers on NYSE Arca
and NYSE American. The Exchange proposes to require member
organizations interested in acting as Non-DMM Market Makers to submit
an application to the Exchange. Proposed Rule 7.20 would also set forth
the criteria the Exchange may consider in determining whether to
approve or disapprove a prospective Non-DMM Market Maker's application
and specify how a Non-DMM Market Maker's registration may be suspended,
terminated, or withdrawn.
Rule 7.21
    The Exchange proposes to add Rule 7.21 and title it ``Obligations
of Market Maker Authorized Traders.'' Proposed Rule 7.21 would provide
that Market Maker Authorized Traders (``MMATs'') are permitted to enter
orders only for the account of the Non-DMM Market Maker for which they
are registered. In addition, the proposed rule would specify the
registration requirements for MMATs and the procedures for suspension
and withdrawal of registration of MMATs. Specifically, the proposed
rule would provide that a Non-DMM Market Maker must submit an
application to the Exchange to register an associated person as an
MMAT. An MMAT must meet certain requirements, and a Non-DMM Market
Maker must ensure that its MMATs are qualified to perform market making
activities. Proposed Rule 7.21 also provides that the Exchange may
suspend or withdraw an MMAT's registration.
Rule 7.22
    The Exchange proposes to add Rule 7.22 and title it ``Registration
of Non-DMM Market Makers in a Security.'' Proposed Rule 7.22 would set
forth the process for Non-DMM Market Makers to become registered in a
security and the factors the Exchange may consider in approving such
registration. Non-DMM Market Makers may submit a request to the
Exchange to be registered in a security, and the Exchange will evaluate
whether to approve such registration, taking into consideration factors
including the Non-DMM Market Maker's financial resources, experience in
making markets, operational capability, and the character of the market
for the security. Non-DMM Market Makers will generally be permitted to
register in securities in which a DMM and/or SLP is also registered,
subject to the Exchange's evaluation of the character of the market

for a given security.\6\ Finally, the proposed rule would also describe
both termination of a Non-DMM Market Maker's registration in a security
by the Exchange and voluntary termination by a Non-DMM Market Maker.
---------------------------------------------------------------------------

    \6\ Orders entered by Non-DMM Market Makers will be allocated in
accordance with Rules 7.36 and 7.37 and be treated as a Book
Participant. Non-DMM Market Makers will not be eligible to
participate in the allocation process as a DMM Participant.
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Rule 7.23
    The Exchange proposes to add Rule 7.23 and title it ``Obligations
of Non-DMM Market Makers.'' Proposed Rule 7.23 would set forth the
obligation of Non-DMM Market Makers to engage in a course of dealings
for their own account to assist in the maintenance, insofar as
reasonably practicable, of fair and orderly markets on the Exchange.
The proposed rule would delineate the specific responsibilities and
duties of Non-DMM Market Makers, including the Two-Sided Obligation
applicable to securities in which the Non-DMM Market Maker is
registered and the requirement that the interest satisfying the Two-
Sided Obligation be not more than the Designated Percentage (as defined
in Proposed Rule 7.23) away from the National Best Bid or Offer
(``NBBO''). Proposed Rule 7.23 also provides that Non-DMM Market Makers
will be subject to certain minimum capital requirements and sets forth
the circumstances under which a Non-DMM Market Maker could be subject
to disciplinary action or suspension or revocation of registration by
the Exchange for failure to comply with the course of dealings
obligations set forth in this proposed rule.
    Specifically, with respect to the Two-Sided Obligation, proposed
Rule 7.23(a)(1)(A) provides that Non-DMM Market Makers would be
required to maintain displayed interest identified as interest meeting
the Two-Sided Obligation on a continuous basis during Core Trading
Hours for those securities in which the Non-DMM Market Maker is
registered. Proposed Rule 7.23(a)(1)(B) provides that interest
satisfying a Non-DMM Market Maker's Two-Sided Obligation must not be
more than the Designated Percentage away from the then current NBBO, or
if there is no NBBO, not more than the Designated Percentage away from
the last reported sale for that security. With respect to minimum
capital requirements, proposed Rule 7.23(a)(2) provides that Non-DMM
Market Makers would be required to maintain adequate minimum capital in
accordance with Rule 15c3-1 under the Act.

III. Discussion and Commission Findings

    After careful consideration, the Commission finds that the
Exchange's proposed rule change is consistent with the requirements of
the Act and the rules and regulations thereunder applicable to national
securities exchanges. In particular, the Commission finds that the
Exchange's proposed rule change is consistent with Section 6(b)(5) of
the Act,\7\ which requires that the rules of an exchange be designed,
among other things, 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, and to remove impediments to and perfect
the mechanism of a free and open market and a national market
system.\8\
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    \7\ 17 U.S.C. 78f(b)(5).
    \8\ In approving this proposed rule change, the Commission has
considered the proposed rule's impact on efficiency, competition,
and capital formation. See 15 U.S.C. 78c(f).
---------------------------------------------------------------------------

    As described above, the Exchange proposes to adopt rules for the
registration and obligations of Non-DMM Market Makers that are
substantially comparable to NYSE Arca and NYSE American rules. The
Exchange stated that the proposed rules are designed to enable market
makers that are registered on the Exchange's affiliated markets to
become registered on the Exchange as Non-DMM Market Makers by meeting
the same registration requirements and by agreeing to be subject to the
same obligations.\9\ The Exchange represented that the proposed Non-DMM
Market Makers are not intended to supplant existing DMMs or SLPs or
their roles on the Exchange and Non-DMM Market Makers would not assume
any of the responsibilities already assigned to DMMs or SLPs pursuant
to Exchange Rules.\10\ According to the Exchange, the proposed rules
are intended to provide for a new category of market maker that the
Exchange believes will promote competition on the Exchange by enhancing
the range and diversity of market making activity on the Exchange.
Further, the Exchange stated that the proposal would promote
competition by encouraging additional displayed liquidity. The Exchange
also stated that the proposal would facilitate price discovery and
promote market quality on the Exchange.\11\
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    \9\ See Notice, supra note 3 at 15976.
    \10\ While the proposed obligations for Non-DMM Market Makers
are less stringent than those for DMMs and SLPs, the proposed rules
would not affect the existing roles or obligations of DMMs and SLPs.
    \11\ See id.
---------------------------------------------------------------------------

    The Commission believes that introducing a new category of market
maker--Non-DMM Market Makers--could promote competition on the
Exchange. Further the Commission believes that the introduction of Non-
DMM Market Makers on the Exchange and their obligations to the market
as required under NYSE Rule 7.23 could provide additional, supplemental
liquidity to the market and could enhance price discovery.
    Based on the foregoing, the Commission therefore finds that the
proposed rule change is consistent with the Act.

IV. Conclusion

    It is therefore ordered, pursuant to Section 19(b)(2) of the
Act,\12\ that the proposed rule change (SR-NYSE-2021-08) be, and hereby
is, approved.
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    \12\ 15 U.S.C. 78s(b)(2).

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\13\
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    \13\ 17 CFR 200.30-3(a)(12).
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J. Matthew DeLesDernier,
Assistant Secretary.
[FR Doc. 2021-09775 Filed 5-7-21; 8:45 am]
BILLING CODE 8011-01-P


Mike Mattheisen/DC/USEPA/US

02/27/2008 08:13 AM

	To

<EMAIL_ADDRESS>
	cc

	Joseph Nash/DC/USEPA/US@EPA

	Subject

	Fw: TSCA Health and Safety Data Reporting

Ms. Nottoli, below are the answers that EPA recently gave to four
questions that were submitted by another correspondent on the same
subject as your question.  These answers provide additional
clarification and guidance, and address your question.  Feel free to
contact me should you have any other questions.

Persons who must submit include importers of lead and lead compounds
that are in, or part of, articles that are consumer products intended
for use by children.  The phrase “intended for use by children” is
defined in 40 CFR 710.43.

Health and safety studies concerning the lead and lead compounds in
articles that are consumer products intended for use by children are
among those studies that must be submitted. The types of studies that
are reportable are described at 40 CFR 716.21(a)(8)(i).  The phrase
“intended for use by children” is defined in 40 CFR 710.43

As a general matter, all known health and safety studies of the types
described at 40 CFR 716.21(a)(8)(i) must be reported, regardless of
their date.  However, analyzed aggregations of monitoring data are not
subject to reporting under this rule if they were based on monitoring
data acquired more than 5 years before a substance was listed under 40
CFR 716.120. 40 CFR 716.20(a)(7).  In addition, 40 CFR 716.25 provides
that persons subject to this rule are not required to search their
records for reportable information dated before January 1, 1977, unless
specifically required to do so in a rule.  Health and safety studies
dated before January 1, 1977, must nevertheless be reported if they are
known.

The rule only requires the reporting of unpublished health and safety
studies (defined in 40 CFR 716.3) that relate to any measurable lead
content in, or that assess children’s exposure (including
bioavailability) to lead from, consumer products intended for use by
children (except for children’s metal jewelry as described by the
Consumer Product Safety Commission in 72 FR 920 (Jan. 9, 2007)).  That
is, the amendment at 716.21(a)(8) is intended to limit reporting to only
two subsets of all possible unpublished health and safety studies.
Whether or not “product content” data constituted a health and
safety study would depend on the extent to which the information met the
considerations in 716.3.  For example, a simple, isolated list of
ingredients or an isolated analysis of product content would not likely
be considered a health and safety study, whereas an analysis of product
ingredients coupled with an evaluation of hazard or human or
environmental exposure or risks would likely be considered a health and
safety study.  Regulations governing studies to be reported and studies
not subject to reporting are found at 40 CFR 716.10 and 40 CFR 716.20,
respectively.

Mike Mattheisen

Acting Branch Chief

Chemical Information and Testing Branch

Chemical Control Division

US EPA Office of Pollution Prevention and Toxics

202-564-3077

----- Forwarded by Joseph Nash/DC/USEPA/US on 02/13/2008 04:26 PM -----

"Nottoli, Eileen"<EMAIL_ADDRESS>
02/13/2008 04:24 PM

	To

	Joseph Nash/DC/USEPA/US@EPA

	cc

	Subject

	TSCA Health and Safety Data Reporting

Mr. Nash:

I have read the Final Rule on Health & Safety Data Reporting published
in the Federal Register on January 29, 2008.  I would like clarification
on whether  EPA intends to have manufacturers/importers submit all
analytical data showing lead content of materials used to make products
intended for children?  In reading the preamble at 5112, it appears that
EPA seeks all "studies showing any measurable lead content".

Eileen M. Nottoli

Allen Matkins Leck Gamble Mallory & Natsis LLP /

Three Embarcadero Center, 12th Floor, San Francisco, CA 94111 /

Phone:<PHONE_NUMBER> / Fax:<PHONE_NUMBER>

-


[Federal Register Volume 84, Number 71 (Friday, April 12, 2019)]
[Notices]
[Pages 15025-15027]
[FR Doc No: 2019-07327]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-85554; File No. SR-LCH SA-2019-001]

Self-Regulatory Organizations; LCH SA; Notice of Filing and
Immediate Effectiveness of Proposed Rule Change To Amend the CDS and
Options Fee Grid for CDSClear Clearing Members Effective Retroactively
From January 1st, 2019

April 8, 2019.
    Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934
(``Act''),\1\ and Rule 19b-4 thereunder,\2\ notice is hereby given that
on March 25, 2019, Banque Centrale de Compensation, which conducts
business under the name LCH SA (``LCH SA''), filed with the Securities
and Exchange Commission (``Commission'') the proposed rule change
described in Items I and II below, which Items have been prepared
primarily by LCH SA. LCH SA filed the proposal pursuant to Section
19(b)(3)(A) of the Act,\3\ and Rule 19b-4(f)(2) \4\ thereunder, so that
the proposal was effective upon filing with the Commission. The
Commission is publishing this notice to solicit comments on the
proposed rule change from interested persons.
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    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
    \3\ 15 U.S.C. 78s(b)(3)(A).
    \4\ 17 CFR 240.19b-4(f)(2).
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I. Clearing Agency's Statement of the Terms of Substance of the
Proposed Rule Change

    The proposed rule change will modify both CDS and Options fee grid
for CDSClear activities applicable from January 1st, 2019.

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

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

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

1. Purpose
    The purpose of this proposed rule change is for LCH SA to (1)
modify the annual fixed fee that covers all Index and Single Name CDS
self-clearing activity for a General Clearing Member and its affiliates
under the Unlimited Tariff, and (2) establish a new Unlimited Tariff to
cover all Options self-clearing activity for Clearing Members as well
as slightly increase the cap in the existing fee grid for the options
clearing service.
    The proposed CDSClear fee changes will be retroactive from January
1st, 2019.
    The need to apply the fees retroactively results from the long year
end 2018 shutdown of the U.S. federal government (the ``Shutdown'') and
the subsequent closure of the Securities and Exchange Commission
(``SEC'') past December 26th. As a result of the Shutdown, beginning on
December 27, 2018, the SEC was closed and SEC employees were out of the
office until an appropriation was enacted and the SEC reopened on
January 28, 2019. Because the SEC was closed, any filing submitted to
the SEC during the Shutdown was not considered ``received'' (i.e.,
legally filed) until the SEC reopened in January 2019. Accordingly,
when filing no. LCH SA-2018-006 was formally submitted to the SEC on
December 27th, 2018 through the Electronic Form 19b-4 Filing System
(``EFFS'') operated by the SEC, the filing was not considered as duly
``received,'' and therefore did not receive an official ``filing date''
until the SEC reopened end of January 2019, at which point the filing
was rejected on technical grounds because the year indicated in the
file number was no longer accurate.
    As discussed and agreed with its clearing members and because LCH
SA had also intended the fee change to become effective from January
1st, 2019, LCH SA's national competent authorities had been duly
advised of the proposed fee change that was also rule certified with
the Commodity Futures Trading Commission (``CFTC'') on December 20,
2018 \5\ in a manner that would have permitted the fee change to take
effect early January 2019.
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    \5\ See https://www.lch.com/system/files/media_root/Fee%20grid%20changes__20%20Dec%202018.pdf.
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    Given the termination on December 31st, 2018 of the previous
CDSClear annual fixed fee amount applicable to General members under
the Unlimited Tariff and any other alternative solution, the absence of
the retroactive application of the new proposed and agreed fee grid
would cause a potential harm to the LCH SA CDSClear business because
CDSClear would have been without a regulatory approved fee grid
including the new annual clearing fixed fee amount under the General
Member Unlimited Tariff and would thus not have been in a position to
collect the relevant revenues throughout its entire fee grid. Further,
as described below, the annual fixed fee for the CDS Unlimited Tariff
for General Members is supposed to decrease and no change has been made
to the General Member Introductory Tariff and the Select Member Tariff
so that none of them would be caught unaware if retroactive approval is
granted.
(1) Annual Clearing Fixed Fee (General Member Unlimited Tariff)
    Until December 31st, 2018, CDSClear was offering an all you can eat
type of tariff called the ``CDS Unlimited Tariff'' for General Members
that covers all self-clearing CDS Index and Single Name activity for a
Clearing Member (``CM'') and its affiliates for an annual fixed fee of
[euro]2,000,000 (no variable fee).The proposed change will modify the
annual fixed fee of the CDS Unlimited Tariff for General Members from
[euro]2,000,000 per year to [euro]1,700,000 per year from January 1st,
2019. This fixed fee will cover all clearing fees for Index and Single
Name CDS house activity excluding Sovereign CDS for all affiliates of a
given CM group.
(2) Options Clearing Service Fee Grid
    In addition, LCH SA is proposing to modify the CDSClear fee grid
set up for the Options clearing service. Currently, Clearing Members
and Clients that participate in the CDSClear Options clearing service
are charged the clearing fees as follows:

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

------------------------------------------------------------------------
General Member:
    Onboarding Fees............       [euro]30k  one-off fee per Legal
                                                  Entity waived until 31-
                                                  Mar-18.
    Clearing Fees..............             $15  per million of option
                                       [euro]15   notional on U.S.
                                                  Indices.*
                                                 per million of option
                                                  notional on European
                                                  Indices.
        Floor on clearing fees.      [euro]150k  Per calendar year (no
                                                  pro-rating).
        Cap on Clearing fees...      [euro]500k  Per calendar year (no
                                                  pro-rating).
Select Member:

    Onboarding Fees............       [euro]30k  one-off fee per Legal
                                                  Entity waived until 31-
                                                  Mar-18.
    Clearing Fees..............             $18  per million of option
                                       [euro]18   notional on U.S.
                                                  Indices.*
                                                 per million of option
                                                  notional on European
                                                  Indices.
        Cap on Clearing fees...      [euro]500k  Per calendar year (no
                                                  pro-rating).
Client:
    Clearing Fees..............             $20  per million of option
                                       [euro]20   notional on U.S.
                                                  Indices.
                                                 per million of option
                                                  notional on European
                                                  Indices.
Clearing fee holiday from launch until 31-Dec-2017 for all Members and
 Clients.
------------------------------------------------------------------------
* Subject to regulatory approval.

    As specified in the new LCH CDSClear options fee grid attached
below under Exhibit 5, effective from 1st January 2019, it is proposed
to:
    (a) Rename the current Options clearing service tariff the Options
Introductory Tariff;
    (b) Increase the annual cap in the Options Introductory Tariff from
[euro]500k to [euro]600k for both General Members and Select Members;
    (c) Introduce a new tariff called the Options Unlimited Tariff
available to both General Members and Select Members and in which
Members would pay an annual fixed fee to cover all the self-clearing
fees for Credit Index Options of all affiliated entities of a given
Clearing Member Group. The level of this annual fixed fee (no pro-
rating) would be set to:

[rtarr8] [euro]375k for General Members
[rtarr8] [euro]400k for Select Members
    (d) Maintain the one-off onboarding fee of [euro]30k to the Options
clearing service under the following terms and conditions:
    (i) The onboarding fee will be waived for all General and Select
Members until 31-Mar-2019;
    (ii) Under the Options Introductory Tariff, an onboarding fee will
be charged for each legal entity (even if of the same Group) onboarding
the service; and
    (iii) Under the Options Unlimited Tariff, only one single
onboarding fee will be charged for all affiliated entities of a given
Clearing Member Group onboarding the service.
2. Statutory Basis
    Section 17A(b)(3)(D) of the Act requires that the rules of a
clearing agency provide for the equitable allocation of reasonable
dues, fees, and other charges.\6\
---------------------------------------------------------------------------

    \6\ 15 U.S.C. 78q-1(b)(3)(D).
---------------------------------------------------------------------------

    With respect to the change of the CDS Unlimited Tariff, LCH SA has
determined in consultation with its clearing members that the reduction
in the annual fixed fee for General Members covering their Index and
Single Name CDS self-clearing activity is reasonable and appropriate
given the costs and expenses to LCH SA in providing the CDSClear
service as well as the fact that the business is now reaching a more
mature stage in its development and therefore requires less investment
in the future.
    As explained above and as agreed with the clearing members,
applying the fees retroactively is also reasonable. Absent the Shutdown
and subsequent closure of the Commission, as duly expected by the
CDSClear members pursuant to the consultation process, the proposed fee
changes including the new annual fixed fee amount for the General
Members would have been immediately applicable from January 1st, 2019
pursuant to Section 19(b)(3)(A) \7\ of the Act and Rule 19b-4(f)(2).\8\
---------------------------------------------------------------------------

    \7\ 15 U.S.C. 78s(b)(3)(A).
    \8\ 17 CFR 240.19b-4(f)(2).
---------------------------------------------------------------------------

    The proposed changes to the Options clearing service fee grid in
consultation with CDSClear members aim at:

--Offer CDSClear Clearing Members a true ``all you can eat'' tariff
that covers all their self-clearing activities across the whole scope
of products eligible at CDSClear
--Incentivize additional clearing members to onboard and use the
Options clearing service by providing a more attractive tariff in which
the marginal cost of clearing options reduces as more volumes are
cleared.
--Building enough interdealer liquidity on the Options clearing service
such that buy-side clients can also get comfortable with clearing
credit index options at LCH SA CDSClear service, which is key for the
market participants to get the full benefits of clearing options from a
multilateral netting and the associated operational risk decrease
perspective.

    The proposed fee grid will apply equally to all General Members,
Select Members and clients that will voluntary join this CDSClear
offering and LCH SA believes that it is reasonable and appropriate.
    LCH SA believes that imposing such clearing fees is consistent with
the requirements of Section 17A of the Act \9\ and the regulations
thereunder applicable to it, and in particular provides for the
equitable allocation of reasonable fees, dues, and other charges among
clearing members and market participants by ensuring that Members pay
reasonable fees and dues for the services provided by LCH SA, within
the meaning of Section 17A(b)(3)(D) of the Act.
---------------------------------------------------------------------------

    \9\ 15 U.S.C. 78q-1.
---------------------------------------------------------------------------

B. Clearing Agency's Statement on Burden on Competition

    Section 17A(b)(3)(I) of the Act requires that the rules of a
clearing agency not impose any burden on competition not necessary or
appropriate in furtherance of the purposes of the Act.\10\ LCH SA does
not believe that the proposed rule change would impose any burden on
competition.
---------------------------------------------------------------------------

    \10\ 15 U.S.C. 78q-1(b)(3)(I).
---------------------------------------------------------------------------

    As noted above, LCH SA believes that the fees and any related
discount have been set up at an appropriate level given the costs and
expenses to LCH SA in offering and maintaining the relevant CDSClear
services.
    Additionally, the fees and related discounts will apply equally to
all Clearing Members of CDSClear.
    Further, LCH SA does not believe that the proposed rule change
would have a burden on competition because it does not adversely affect
the ability of such Clearing Members or other market participants
generally to engage in cleared transactions or to access clearing
services.

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

    Written comments relating to the proposed rule change have not been
solicited or received. LCH SA will notify the Commission of any written
comments received by LCH SA.

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

    (a) The foregoing rule change has become effective pursuant to
Section 19(b)(3)(A) of the Act \11\ and paragraph (f) of Rule 19b-4
\12\ 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.
---------------------------------------------------------------------------

    \11\ 15 U.S.C. 78s(b)(3)(A).
    \12\ 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 Number SR-LCH SA-2019-001 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 Number SR-LCH SA-2019-001. 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 such filings will also be available for inspection
and copying at the principal office of LCH SA and on LCH SA's website
at https://www.lch.com/resources/rules-and-regulations/proposed-rule-changes-0. All comments received will be posted without change. Persons
submitting comments are cautioned that we do not redact or edit
personal identifying information from comment submissions. You should
submit only information that you wish to make available publicly. All
submissions should refer to File Number SR-LCH SA-2019-001 and should
be submitted on or before May 3,2019.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\13\
---------------------------------------------------------------------------

    \13\ 17 CFR 200.30-3(a)(12).
---------------------------------------------------------------------------

Jill M. Peterson,
Assistant Secretary.
[FR Doc. 2019-07327 Filed 4-11-19; 8:45 am]
BILLING CODE 8011-01-P


US ENVIRONMENTAL PROTECTION AGENCY

		WASHINGTON, D.C.  20460

OFFICE OF PREVENTION,

PESTICIDES AND

TOXIC SUBSTANCES

DATE: August 10, 2006

MEMORANDUM

SUBJECT:	Didecyl Dimethyl Ammonium Chloride (DDAC) - Report of the
Antimicrobials Division Toxicity Endpoint Committee (ADTC) and the
Hazard Identification Assessment Review Committee (HIARC).

FROM:	Timothy F. McMahon, Ph.D.; Chair, ADTC

Michelle Centra, Pharmacologist;  Executive Secretary, ADTC

Antimicrobials Division (7510C)

TO:	Steve Malish, Ph.D., Toxicologist

Kathryn Montague, Team Leader	Risk Assessment and Science Support Branch
(RASSB)

Antimicrobials Division (7510C)

and

Tracy Lantz, Chemical Review Manager

Velma Noble, Team Leader

Regulatory Management Branch I

Antimicrobials Division (7510C)

PC Code: 069149

On  February 10, 2000, the Health Effects Division (HED)  HIARC
reviewed the recommendations of the toxicology reviewer for didecyl
dimethyl ammonium chloride (DDAC) with regard to the acute and chronic
Reference Doses (RfDs) and the toxicological endpoint selection for
occupational/residential exposure risk assessments.  The potential for
increased susceptibility of infants and children from exposure to DDAC
was also evaluated as required by the Food Quality Protection Act (FQPA)
of 1996.  In November of 2005, members of the ADTC met with the HED
Hazard Science Policy Council to discuss revision of the dermal
endpoints.  The conclusions drawn at this meeting are presented in this
report.

Committee Members in Attendance

HIARC members present: Willam Burnam, Vicki Dellarco, Elizabeth Doyle,
Pamela Hurley, Tina Levine, Elizabeth Mendez, David Nixon, Nicole
Paquette, Jess Rowland, and Brenda Tarplee.

Also in attendance were:  Winston Dang (AD), Tim McMahon (AD)

HIARC Data Evaluation/Report Presentation:
_______________________________

Jonathan Chen, Ph.D.

ADTC members: Michelle Centra,  Jonathan Chen, Ph.D., Stephen Dapson,
Ph.D.,  Roger Gardner,  Karen Hamernik, Ph.D., Timothy Leighton, Tim
McMahon, Ph.D., Melba Morrow, D.V.M., John Redden, Najm Shamim, Ph.D.,
Sanyvette Williams-Foy, D.V.M.

ADTC Data Evaluation/Report Presentation:
___________________________________

Tim McMahon, Ph.D., Chair

COMMITTEE MEMBERS  (Signature indicates concurrence unless otherwise
stated)

Stephen Dapson 			_________________________________________

Jonathan Chen			_________________________________________

Roger Gardner			_________________________________________

Karen Hamernik			_________________________________________

Tim McMahon (Chair)		_________________________________________

Melba Morrow			_________________________________________

John Redden			_________________________________________

SanYvette Williams		_________________________________________

Michelle Centra

(Executive Secretary)		 _________________________________________

Najm Shamim			_________________________________________

Timothy Leighton		    ________________________________________
INTRODUCTION

On February 10, 2000, the Health Effects Division (HED) Hazard
Identification Assessment Review Committee (HIARC) reviewed the
recommendations of the toxicology reviewer for didecyl dimethyl ammonium
chloride (DDAC) with regard to the acute and chronic Reference Doses
(RfDs) and the toxicological endpoint selection for
occupational/residential exposure risk assessments. The potential for
increased susceptibility of infants and children from exposure to DDAC
was also evaluated as required by the Food Quality Protection Act (FQPA)
of 1996. In December of 2005, the Antimicrobials Division(s ADTC updated
the dermal endpoints for DDAC  based on the recently adopted use of
dermal irritation as an endpoint for short-term dermal risk assessments.

HAZARD IDENTIFICATION

Acute Reference Dose (RfD)				Subpopulation Females 13+

Study Selected:   Developmental Toxicology - Rat, OPPTS 870.3700;  (
83-3

MRID No.: 	41886701

Executive Summary: In a prenatal developmental toxicity study (MRID
41886701), twenty five bred female CD( (Sprague-Dawley) rats per group
were administered DDAC (80.8% a.i.) in deionized water orally by gavage
at doses of 0, 1, 10, or 20 mg/kg/day on gestation days (GD) 6-15,
inclusive.  On GD 21, dams were sacrificed, subjected to gross necropsy,
and all fetuses examined externally, viscerally, and skeletally for
malformations/variations.   Maternal toxicity was observed at the mid
and high dose group in the form of audible respiration with the high
dose presenting with other observations.  Further, a treatment related
decrease in body weight gain was noted during the dosing period
(gestation day(s 6-15), the dosing period plus post dosing period
(gestation days 6-21) and for the corrected body weight gains for the
high dose.  There was also low food efficiency compared with controls
during the dosing period for the mid and high dose group.  The maternal
LOAEL is 10 mg/kg/day, based on reductions in body weight gain and
clinical signs of toxicity (audible respiration).  The maternal NOAEL is
1 mg/kg/day.   Developmental toxicity was noted at the high dose in the
form of increased incidences of skeletal variations.  Therefore, the
developmental toxicity LOAEL is 20 mg/kg/day based on an increased
incidence of skeletal variations, and the developmental toxicity NOAEL
is 10 mg/kg/day.

Dose and Endpoint for Establishing RfD: Developmental NOAEL of 10
mg/kg/day based on  increased incidences of skeletal variations at 20
mg/kg/day.

Uncertainty Factor (UF): 100X (10X for intraspecies extrapolation; and
10X for interspecies extrapolation)

Acute RfD (females 13+) =        10 mg/kg/day (NOAEL)    =     0.1
mg/kg/day

                                                               100 (UF)

Comments about Study/Endpoint/Uncertainty Factor:  The developmental
endpoint is presumed to occur after a single exposure.  Since the effect
developed from in utero exposure, they are applicable for risk
assessment for female 13-50 subpopulation group only.

Acute Reference Dose (RfD)		General Population Including Infants and
Children+

Since the developmental endpoint selected is only applicable to Females
13+, another endpoint was considered for the general population
including infants and children.  However, an appropriate endpoint was
not identified for this population subgroup.  The maternal toxicity
(decreases in body weight gains) observed in maternal animals in the rat
and rabbit studies are NOT appropriate since the effects are not
attributable to a single exposure (dose).  Other oral studies did not
indicate endpoints that are appropriate for this exposure period.

Study Selected:     	None

MRID No.: 	None

Executive Summary: 	None

Dose and Endpoint for Establishing RfD:	None

Uncertainty Factor (UF):	 None

Comments about Study/Endpoint/Uncertainty Factor:	This risk assessment
is NOT required for this subpopulation.

Chronic Reference Dose (RfD)

Study Selected:  Chronic Oral Toxicity Study - Dog, OPPTS 870.4100; (
83-1b)

MRID No.: 	41970401

Executive Summary: In a chronic one year oral toxicity study (MRID
41970401), male and female beagle dogs were given test compound at
dosages of 0, 3, 10, or 20/30 mg/kg/day (dosage at 30 mg/kg/day was not
tolerated well and was discontinued on day 31, dosing was resumed on day
36 at 20 mg/kg/day).  No treatment-related deaths occurred during the
study.  The treatment-related clinical signs (soft/mucoid feces, emesis)
were observed frequently in high-dose animals.  Hematology or urinalysis
results were normal.  Total cholesterol levels were significantly
decreased in the high-dose females.  Gross and histopathological
findings did not reveal any treatment-related effects. The LOAEL is 20
mg/kg/day based on increase incidence of clinical observations (emesis
and soft/mucoid feces) in males and females and decreased total
cholesterol levels in females.  The  NOAEL is 10 mg/kg/day.

Dose and Endpoint for Establishing RfD:   NOAEL of 10mg/kg/day based on
increased incidence of clinical observations (emesis and soft/mucoid
feces) in males and females and decreased total cholesterol levels in
females at 20 mg/kg/day (LOAEL)

Uncertainty Factor(s):	100X (10X for intraspecies extrapolation; and 10X
for interspecies extrapolation)

Comments about Study/Endpoint/Uncertainty Factor: The lowest NOAEL in
the most sensitive species following chronic exposure and is appropriate
for chronic dietary risk assessment.

Occupational/Residential Exposure

Dermal Absorption

The dermal absorption factor is not required since route-specific
studies are available to assess the need for endpoints.

Dermal  Exposure

NOTE: studies are available for both the technical grade active
ingredient (80% a.i.) and two formulated products of DDAC (0.13% and 4%
a.i.).  Use of dermal irritation as an endpoint has recently been
adopted as a working policy measure for the Health Effects Division and
the Antimicrobials Division (meeting of the HED Hazard Science Policy
Council, November 30, 2005).  Therefore, endpoints for the technical and
formulated product are determined separately as needed.

2.4.3	Short-term Incidental Oral Exposure   (1-30 days)

Study Selected:   Developmental Toxicology - Rat, OPPTS 870.3700;  (
83-3

MRID No.: 	41886701

Executive Summary: See summary under Acute RfD endpoint above.

Endpoint selected: Developmental NOAEL of 10 mg/kg/day based on
increased incidences of skeletal variations at 20 mg/kg/day.

Uncertainty Factor (UF): 100X (10X for intraspecies extrapolation; and
10X for interspecies extrapolation)

2.4.4	Intermediate-term Incidental Oral Exposure   (30 days- 6 months)

Study Selected:  Chronic Oral Toxicity Study - Dog, OPPTS 870.4100; (
83-1b)

MRID No.: 	41970401

Executive Summary: See summary under Chronic RfD endpoint above.

Endpoint selected:   NOAEL of 10mg/kg/day based on decreased total
cholesterol levels in females at 20 mg/kg/day (LOAEL)

Uncertainty Factor(s):	100X (10X for intraspecies extrapolation; and 10X
for interspecies extrapolation)

2.4.5	Short-term Dermal Exposure, technical grade a.i.  (1-30 days)

Study Selected: 90-Day Dermal Toxicity Study - Rat, 870.3250; ( 82-3

MRID No.: 	41305901

Executive Summary: In a subchronic dermal toxicity study (MRID
41305901), fifteen Sprague-Dawley rats per sex per group received
repeated dermal dosing of test compound at 0, 2, 6, or 12 mg/kg/day
(concentrations of 0.1, 0.3, and 0.6%) for 6 hours/day, 5 days/week for
13 weeks.  No treatment-related effects were noticed in mortality,
weight gain, food consumption, or systemic toxicity.  Toxicity was
limited to treated skin of mid-dose females and high-dose males and
females.  The clinical and gross findings (erythema, edema, exfoliation,
excoriation and ulceration) were confirmed by histopathological
examination, where increased incidence of hyperkertosis, acanthosis,
epidermitis, dermatitis and ulceration were noted beginning after 5 days
of exposure.  The systemic NOAEL is grater than 12 mg/kg/day (highest
dose tested).  The dermal LOAEL for dermal toxicity is 6 mg/kg/day.  The
dermal NOAEL is 2 mg/kg/day.

Dose and Endpoint for Risk Assessment:   Dermal toxicity  NOAEL of 2
mg/kg/day based on increased clinical and gross findings at 6 mg/kg/day
(LOAEL).

Comments about Study/Endpoint:. The HIARC and ADTC selected irritation
as the short-term endpoint based on the policy adopted for use of dermal
irritation as a short-term endpoint. It is noted from the 90-day dermal
toxicity study that no systemic toxicity was seen at the highest dose
tested but dermal irritation was present after 5 days of exposure.  It
is further noted that a second dermal toxicity study is available (MRID
40565301 and 41105801) in which a dilution of a product containing 6%
DDAC and 4% ADBAC was studied for 21 daysin guinea pigs. However,  the
rat study was chosen for the short-term endpoint because between these
two studies, the concentration evoking the irritation response was lower
in the rat study (8 µg/cm2) than in the guinea pig study (500 µg/cm2)
and occurred within the same time frame (rat response observed after 5
days, guinea pig response observed after approximately 10 days).

Short-term Dermal Exposure- formulated product, 0.13% a.i.

Study Selected: none

Comments about Study/Endpoint: There is an available 21-day dermal
toxicity study for a formulation of DDAC at 0.13% (MRID 45656601).  This
study shows no dermal irritancy or systemic effects up to and including
a limit dose of 1000 mg/kg.  Thus, an endpoint for short-term dermal
exposure to 0.13% a.i. is not required.

2.4.6	Intermediate (30 days-6 months) and Long-Term (> 6 months) Dermal
( Exposure

Study Selected: none

Comments about Study/Endpoint:  The available data show no appropriate
endpoint for intermediate- and long-term dermal risk.  Use of irritation
as an endpoint for the short-term is protective of any dermal or
systemic effects from longer term exposures.

 2.4.7   Inhalation Exposure (All Durations)

When DDAC is applied with a spraying system (e.g. sprayer), inhalation
may be a potential exposure route. Since no inhalation studies are
available, committee selected the oral NOAEL for this risk assessment.
Since the dose identified for inhalation risk assessments are from oral
studies, route-to-route extrapolation should be as follows:

Step I:		The inhalation exposure component (i.e., μg a.i./day) using a
100% (default) absorption rate and application rate should be converted
to an equivalent oral dose (mg/kg/day)

Step II:		To calculate the MOE(s , the equivalent oral dose converted
from Step I should then be compared to the oral NOAEL of 10 mg/kg/day
for short term exposure study (MRID 418867-01), and  the oral NOAEL of
10 mg/kg/day for intermediate and chronic oral exposure based on chronic
dog study (MRID 419704-01).

3.0    Margins of Exposure for Occupational/Residential Risk Assessments

For acute and chronic dietary exposures, the standard UF of 100 is
applied. The special hazard-based FQPA safety factor is reduced to 1x.

For incidental oral and dermal assessments, the MOE of 100 is applied
and for inhalation assessments, an MOE of 100 is applied.  An additional
database UF of 10x is applied for route-to-route extrapolation from an
oral endpoint.

4	CLASSIFICATION OF CARCINOGENIC POTENTIAL

4.1	Combined Chronic Toxicity/Carcinogenicity Study in Rats

MRID No.	41965101

Discussion of Tumor Data: In a chronic/carcinogenicity study (MRID
41965101), 60 Sprague-Dawley CD rats per sex per group were fed diets
containing DDAC (Batch # B-1889,  80.8% a.i.)  At 0,300,750 or 1500 ppm
(mg/kg/day equivalents:0,13,32,or 64 for males and 0, 16, 41, or 83 for
females) for two years.  High-dose animals showed significant, but
slight (<10%) decreases in mean body weight during the study.  Treatment
related effects consisted of increased incidence of sinusoidal blood,
hemosiderosis and histiocytosis in the mesenteric lymph nodes of high
dose animals.  In addition, a treatment-related increase in the
incidence of interstitial cell adenomas in testes was reported.  In this
study, the incidences of this tumor for control and treated animals are
: Control 1 (5%, 3/60); Control 2 (5% 3/60), 300ppm (12.5%, 1/8), 750ppm
(17.9%, 5/28), and 1500ppm (11.7%, 6/60).   However, because the
incidence was within  historical incidence range, this chemical is not
considered carcinogenic in this study.  (See Table 1)

Adequacy of the Dose Levels Tested:The high dose tested (HDT)  in the
study is appropriate for carcinogenicity testing based on slight but
statistically significant decrease in mean body weight (<10%) and some
histopathological changes.

Table 1:	Incidence of Testicular Interstitial Adenomas in Male
Sprague-Dawley Rats for the Studies conducted at Bushy Run Research
Center since 1987 1,2

Study

Dates of In-Life Phase

Group3

C1

C2

L

M

H

DDAC

06/13/88 to 06/19/90

3/60

3/60

1/18

5/28

7/60

Historical Control #1

03/22/88 to 03/27/90

3/59

1/60

-

-

-

Historical Control #2

03/08/89 to 03/13/91

4/59

7/60

-

-

-

Historical Control #3

04/29/91 to 05/04/93

1/60

6/60

-

-

-

 	             1. 	Data provided by Bushy Run Research Center (1995,
MRID 436138-01).

                         2. 	All rats were from Charles River Breeding
Laboratories, Portage MI.

                         3.  	C1 - Control Group 1; C2 - Control Group
2; L - Low-dose Group;

M - Mid -dose Group; and H- High-dose group.

4.2	Carcinogenicity Study in Mice

MRID No.	41802301

Discussion of Tumor Data: In a carcinogenicity study (MRID 41802301), 60
CD-1 mice per sex per group were fed diets containing DDAC (Batch #
B-1889,  80.8% a.i.) at levels of 0,100, 500 or 1000 ppm (mg/kg/day
equivalents:0, 15.0, 76.3, or 155.5 for males and 0, 18.6, 93.1,  or
193.1 for females) for 78 weeks. No treatment-related effects were noted
in the incidence of clinical signs, deaths, gross and histopathological
observations.  Hematological values were comparable among all study
groups.  The NOAEL for both male and females is 500 ppm (76.3 mg/kg/day
for males and 93.1 mg/kg/day for females), and the LOAEL is1500ppm
(155.5 mg/kg/day for males; 193.1 mg/kg/day for females).  The LOAEL is
based on decreases in mean body weights and body weight gains.  At the
level tested, the chemical is not carcinogenic.

Adequacy of the Dose Levels Tested: The HDT induce statistically
significant decreases ((10%) in mean body weight).

4.3  Mutagenicity

  SEQ CHAPTER \h \r 1 In an Ames test, with or without  microsomal
activation (S-9 fraction), DDAC was not mutagenic to Salmonella
typhimurium tester strains (MRID 40282201 and supplemental information
MRID 44005801).

In  forward gene mutation assays (MRID 93014008, reformat of 40895202)
DDAC was negative for induction of gene mutations in CHO cells at the
HGPRT locus, with levels of DDAC ranging from 1-10 μg/ml without S9
induction and 1-26 μg/ml with S9 induction.  Severe toxicity was
demonstrated at doses of ≥10 μg/ml (-S9) and ≥ 25 μg/ml (+S9).

In an in vitro chromosome aberration test (MRID 41252601), DDAC failed
to induce chromosome aberrations in Chinese hamster ovary (CHO) cells
harvested 26 hours after exposure to DDAC at concentrations of 1-8
μg/ml without microsomal fraction (S9) induction or DDAC at
concentrations of 2-8 μg/ml with S9 induction.  Cytotoxic effects were
observed at DDAC concentrations 16 μg/ml (with or without S9).

In an in vitro mutagenicity test (MRID 93014007, reformat of 40895201),
DDAC did not induce unscheduled DNA Synthesis (UDS) in primary rat
hepatocytes treated with DDAC at doses up to 2.00 μg/ml.  Higher
concentrations (4.0 μg/mL) of DDAC were severely cytotoxic.

4.4	Classification of Carcinogenic Potential

The HIARC classified DDAC as not likely to be a human carcinogen based
on the lack of evidences of carcinogenicity in mice or rats.

FQPA CONSIDERATIONS

5.1	Adequacy of the Data Base

-- Acute delayed neurotoxicity study in hen (if applicable)?	No

-- Acute and subchronic neurotoxicity studies (if applicable)? No

-- Developmental toxicity studies in Rat & Rabbits	Yes

- Two-Generation Reproduction Study	Yes

-Developmental neurotoxicity study (if applicable)	No

5.2	Neurotoxicity

Based on the available data, the committee concluded  that there is no
evidence DDAC will induce neurotoxic effects.

	5.3	Developmental Toxicity

In a developmental toxicity study in rabbits (MRID #: 410187-01), 16
female New Zealand White Rabbits per dose were administered  dose levels
of 0,1,3 or 10 mg/kg/day of DDAC (81% a.i.) by gavage on gestation days
6 - 18 inclusive.  The maternal toxicity NOAEL = 1 mg/kg/day; LOAEL = 3
mg/kg/day based on increased clinical signs (hypoactivity, labored
and/or audible respiration) and decreased body weight gain during the
dosing period.  The developmental toxicity NOAEL = 3  mg/kg/day; LOAEL =
10 mg/kg/day based on decreased fetal body weight and an increased
number of dead fetuses were reported.

In a developmental toxicity study in rats (MRID #: 418867-01), 25 female
 Sprague-Dawley  CD Rats were administered dose levels of 0,1,10 and 20
mg/kg/day DDAC (80.8% a.i.) by gavage on gestation days 6 - 15
inclusive.  The maternal toxicity NOAEL = 1 mg/kg/day; LOAEL = 10
mg/kg/day based on decreased body weight/weight gain.  The developmental
toxicity NOAEL = 10  mg/kg/day; LOAEL = 20 mg/kg/day based on skeletal
variations observed (split anterior archof the atlas, poorly ossified
thoracic centrum, bilobed thoracic centrum, unilateral short rib, poorly
ossified parietal, and poorly ossified sternebrae).

5.4	Reproductive Toxicity

In a two generation reproductive toxicity study in rats (MRID #:
418045-01), 28/sex/dose ( both F0 and F1) Sprague-Dawley  CD Rats were
fed a diet containing DDAC (80.8% a.i.) at dosage levels of 0, 300, 750,
or 1500ppm (during premating,  for both sexes = 22, 56, and 113
mg/kg/day;  for males  = 20, 50, or 103 mg/kg/day and for females =  24,
61, or 122 mg/kg/day).  Reproductive Toxicity NOAEL = 750ppm (56
mg/kg/day); LOAEL = 1500ppm (113 mg/kg/day) based on decreased pup body
weight/weight gain and food consumption were reported.

5.5	Determination of Susceptibility

There was no quantitative or qualitative evidence of increased
susceptibility to rat or rabbit fetus following in utero exposure in the
prenatal developmental toxicity studies or in the offspring when exposed
to adults in the two generation reproductive study.

5.6	Recommendation for a Developmental Neurotoxicity Study

There was no evidence in the available database to support the need for
a Developmental Neurotoxicity study for DDAC.

HAZARD CHARACTERIZATION

 DDAC was assigned Toxicity Category II in two acute oral toxicity
studies in rats, MRIDs 41394404 [65% a.i.; LD50 = 262 mg/kg (combined)]
and 42296101 [80% a.i.; LD50 = 238 mg/kg (combined)].  DDAC was assigned
Toxicity Category III in two acute dermal toxicity studies in rabbits,
MRIDs 42053801 [65% a.i.; LD50 = 2930 mg/kg (combined)] and 00071158
[50% a.i.; LD50 = 4350 mg/kg (combined)].  For acute inhalation toxicity
(MRID 00145074; TRID 455201010), the LC50 of DDAC (purity not reported)
was reported as 0.07 mg/L; Toxicity Category II was assigned.  For
primary eye irritation, DDAC was found to be corrosive (Toxicity
Category I) in two primary eye irritation studies in rabbits, MRIDs
41394404 [65% a.i.] and 42161602 [80% a.i].  For primary dermal
irritation, DDAC (80% a.i.) was found to be corrosive (Toxicity Category
I) in a primary dermal irritation study in rabbits (MRID 42161601).   A
dermal sensitization study in guinea pigs using BARDAC 2280 80% a.i.
(MRID 46367601) showed that DDAC is not a dermal sensitizer.

For subchronic toxicity, the database includes a 90-day oral toxicity
test in rats (MRID 40966302), a 90-day oral study in dogs (MRID
40262901), two 21-day dermal toxicity studies with  product
formulations (MRIDs 41105801 and 45656601), and a 90-day dermal toxicity
study in rats using the technical grade (MRID 41305901).  In the 90-day
rat oral feeding study (MRID 40966302), incidence of gross pathological
observations and non-neoplastic lesions, including a higher incidence of
glycogen depletion in the liver and contracted spleens were observed.
In the 21-day dermal toxicity study in guinea pigs, MRIDs 40565301 and
41105801, a 1:5 dilution of HS sanitizing solution (containing 6% DDAC
and 4% alkyl dimethyl benzyl ammonium chloride) at the high dose (1000
mg/kg/day) resulted in skin irritation was observed in week 2 of the
study, body weights decreased in week 3 of the study, and a slight
elevation of basophils and eosinophils as well as a slight elevation of
SGPT and SGOT.  In a 21-day dermal toxicity study in rats using
SS0853-01 ( 0.13% a.i., MRID 45656601), no toxicity  was observed at any
dose level tested .  In the 90-day dog feeding study (MRID 40269201), no
treatment-related clinical chemistry, hematology, urinalysis, or
pathological findings were observed.

In the 90-day dermal toxicity test in rats (MRID 41305901), systemic
toxicity was not observed and clinical and gross findings (erythema,
edema, exfoliation, excoriation and ulceration) were limited to the
treated skins.

For developmental toxicity, the data from two developmental toxicity
studies, one in the rat (MRID 41886701, range-finder MRID 42746901) and
another in the rabbit (MRID 41018701), do not indicate   SEQ CHAPTER \h
\r 1 increased susceptibility in rats or rabbits from in utero and
postnatal exposure to DDAC.  In the rat developmental toxicity study
(MRID 41886701), developmental toxicity (skeleton variations) was
observed only at treatment levels which also resulted in maternal
toxicity (audible respiration).  In the rabbit developmental toxicity
study, developmental toxicity (decreased fetal body weight and increased
number of dead fetuses) occurred at levels which also resulted in
maternal toxicity (hypo activity, audible respiration, and decreased
body weight gain).

For reproductive toxicity, the toxicity database for DDAC includes a
2-generational reproductive toxicity study in rats (MRID 41804501).  In
this study, 28/sex/dose (both F0 and F1) Sprague-Dawley CD rats were fed
a diet containing DDAC (80.8% a.i.) at dosage levels of 0, 300, 750, or
1500 ppm (during premating, for both sexes = 22, 56, and 133 mg/kg/day).
 The effects in offspring (decreased pup body weight/weight gain)
occurred at the same dose level as maternal effects (decreased maternal
body weight/weight gain and food consumption), 1500 ppm.  The NOAEL for
this study is 750 ppm (56 mg/kg/day) and the LOAEL for this study is
1500 ppm (113 mg/kg/day).

In a 1-year dog feeding study (MRID 41970401), beagle dogs were given
doses of 0, 3, 10, or 20/30 mg/kg/day in the diet.  Treatment-related
clinical signs (soft/mucoid feces, emesis) were observed frequently in
high-dose animals, and total cholesterol levels were significantly
decreased in high-dose females.

DDAC was not carcinogenic when administered in the diet in 2-year
chronic/ carcinogenicity studies in rats (MRID 41965101) and mice (MRID
41802301).  In the rat study, an increase in incidence of interstitial
cell adenomas in the tested were reported, but the incidence was with in
the range of historical controls.  In the mouse study, no
treatment-related effects were noted in the incidence of clinical signs,
deaths, and gross and histopathological observations.

For mutagenicity, DDAC was negative in a battery of tests.  In the Ames
test (MRID 40282201, supplemental information MRID 44005801), DDAC was
not mutagenic with or without metabolic activation.  In a forward gene
mutation test (MRID 93014008, reformat of 40895202), DDAC was negative
for induction of gene mutations in CHO cells at the HGPRT locus with and
without metabolic activation.  In an in vitro chromosome aberration test
(MRID 41252601),   SEQ CHAPTER \h \r 1 DDAC did not induce chromosome
aberration in the Chinese hamster ovary (CHO) cells with or without
metabolic activation.  In an unscheduled DNA synthesis (UDS) assay (MRID
93014007, reformat of 40895201), DDAC did not cause UDS in primary rat
hepatocytes.

Although there are no neurotoxicity studies available in the database,
the available toxicity for DDAC show no evidence for neurotoxic effects.

  SEQ CHAPTER \h \r 1 In a rat pharmacokinetics/ metabolism study (MRID
41617101 and addendum MRID 41385101), single oral doses of 14C-DDAC (5
or 50 mg/kg) or repeated dose (34 ppm of DDAC in the diet for 14 days
and then one single dose of 5 mg/kg of 14C-DDAC) were given to both male
and female rats.  DDAC was mostly excreted in the feces within 3 days
principally as parent compound and metabolites.  The elimination pattern
and metabolic profile was not substantially altered by the dose or
exposure duration.  Male and female rats showed similar elimination
patterns, but females metabolized DDAC more extensively than males.
Four major metabolites were identified as oxidation products with
oxidation confined to the decyl side chains.

ACUTE TOXICITY of DDAC:

Table 2.  Acute Toxicity Profile for DDAC

Guideline Number	Study Type/ Test substance (% a.i.)	MRID Number/
Citation	Results	Toxicity Category

870.1100

(§81-1)	Acute oral, rat

(Purity 65%)	MRID 41394404	  SEQ CHAPTER \h \r 1 LD50 =262 mg/kg
(combined)

  SEQ CHAPTER \h \r 1 LD50 =331 mg/kg (males)

  SEQ CHAPTER \h \r 1 LD50 =238 mg/kg (females)	II

870.1100

(§81-1)	Acute oral, rat

(Purity 80%)	MRID 42296101	  SEQ CHAPTER \h \r 1 LD50 =238 mg/kg
(combined)	II

870.1200

(§81-2)	Acute dermal, rabbit

(Purity 65%)	MRID 42053801	  SEQ CHAPTER \h \r 1 LD50 =2930 mg/kg
(combined)

  SEQ CHAPTER \h \r 1 LD50 =3140 mg/kg (males)

  SEQ CHAPTER \h \r 1 LD50 =2730 mg/kg (females)	III

870.1300

(§81-3)	Acute inhalation, rat

 (Purity not reported)	MRID 00145074

TRID 455201010	  SEQ CHAPTER \h \r 1 LC50 (combined) = 0.07 mg/L	II

870.2400

(§81-4)	Primary eye irritation, rabbit

(Purity 65% a.i.)	MRID 41394404	  SEQ CHAPTER \h \r 1 Corrosive.	I

870.2400

(§81-4)	Primary eye irritation, rabbit

(Purity 80% a.i.)	MRID 42161602	  SEQ CHAPTER \h \r 1 Corrosive.	I

870.2500

(§81-5)	Primary dermal irritation, rabbit

(Purity 80%)	MRID 42161601	Corrosive.	I

870.2600

(§81-6)	Dermal sensitization, guinea pigs

(Purity 80%)	MRID 46367601	Not a sensitizer.	NA

SUMMARY OF TOXICOLOGY ENDPOINT SELECTION-DDAC

The doses and toxicological endpoints selected for DDAC are summarized
below.

Exposure

Scenario

Dose Used in Risk Assessment

(mg/kg/day)

Target MOE/UF,

Special FQPA SF

for Risk Assessment

Study and Toxicological Effects

Acute Dietary

(Females 13+)

NOAEL(developmental) = 10 mg/kg/day

FQPA SF = 1

UF = 100 (10x inter-species extrapolation, 10x intra-species variation)

Prenatal Developmental Toxicity - Rat

MRID 41886701

LOAEL = 20 mg/kg/day based on increased incidence of skeletal
variations.

Acute RfD = 0.1 mg/kg/day (Females age 13+)

Acute dietary

(general pop.)

an acute dietary endpoint for the general population was not identified
in the database for DDAC.

Chronic Dietary

(general population)

NOAEL = 10

mg/kg/day

FQPA SF = 1

UF = 100 (10x inter-species extrapolation, 10x intra-species variation

Chronic Toxicity Study - Dog

MRID 41970401

LOAEL = 20 mg/kg/day based on increased incidence of clinical signs in
male and females and decreased total cholesterol levels in females.

Chronic RfD = 0.1 mg/kg/day

Dermal, Short-Term (technical a.i.)

NOAEL = 2

UF = 100Based on increased dermal clinical and gross findings

Rat 90-day Dermal Study

MRID 413059-01

Non-Dietary Exposures

Incidental Oral

Short-Term

NOAEL(developmental) = 10 mg/kg/day

Target MOE = 100 (10x inter-species extrapolation, 10x intra-species
variation)

FQPA SF = 1

Prenatal Developmental Toxicity - Rat

MRID 41886701

LOAEL = 20 mg/kg/day based on increased incidence of skeletal
variations.

Incidental Oral

Intermediate-Term

NOAEL  = 10 mg/kg/day

Target MOE = 100 (10x inter-species extrapolation, 10x intra-species
variation)

FQPA SF = 1

Chronic Toxicity Study - Dog

MRID 41970401

LOAEL = 20 mg/kg/day based on decreased total cholesterol levels in
females.

Dermal, Short-term (formulated product, 0.13% a.i.)

No endpoint identified.  No dermal or systemic effects identified in the
21-day dermal toxicity study (MRID 45656601) up to and including the
limit dose of 1000 mg/kg/day

Dermal, Short-term (TGAI 80% diluted to 0.1%)

NOAEL(dermal) = 2 mg/kg/day

(8 µg/cm2)c

Target MOE = 10 (3x inter-species extrapolation, 3x intra-species
variation)

90-day Dermal Toxicity - Rat

MRID 41305901

LOAEL = 6 mg/kg/day based on increased clinical and gross findings
(erythema, edema, exfoliation, excoriation, and ulceration) beginning on
day 4-5 of treatment.

Dermal, Intermediate- and Long-term (formulated product)

No appropriate endpoint identified.

Inhalation, Short-Term

NOAEL   = 10 mg/kg/daya

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DB UF- an additional 10x is necessary for route extrapolation.  If risk
estimates are below an MOE of 1000, a confirmatory inhalation toxicity
study may be required.

Prenatal Developmental Toxicity - Rat

MRID 41886701

LOAEL = 20 mg/kg/day based on increased incidence of skeletal
variations.

 Inhalation, Intermediate- and Long-Term

NOAEL  = 10

mg/kg/daya

 Target MOE = 100 (10x inter-species extrapolation, 10x intra-species
variation, 10x route-extrapolation)

DB UF- an additional 10x is necessary for route extrapolation.  If risk
estimates are below an MOE of 1000, a confirmatory inhalation toxicity
study may be required.

Chronic Toxicity Study - Dog

MRID 41970401

LOAEL = 20 mg/kg/day based on decreased total cholesterol levels in
females.

     UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no
observed adverse effect level, LOAEL = lowest observed adverse effect
level, RfD = reference dose, MOE = margin of exposure, LOC = Level of
concern, NA = Not Applicable.

  SEQ CHAPTER \h \r 1 aAn additional uncertainty factor of 10x is
applied for use of an oral endpoint for route-to-route extrapolation to
determine if a confirmatory inhalation toxicity study is warranted.

c  TGAI-based dermal endpoint = (2 mg/kg rat x 0.2 kg rat x 1000 ug/mg)
/ 50cm2  area of rat dosed = 8 µg/cm2  .

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