[Federal Register Volume 87, Number 23 (Thursday, February 3, 2022)]
[Notices]
[Pages 6206-6211]
[FR Doc No: 2022-02182]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-94094; File No. SR-CboeBZX-2022-005]

Self-Regulatory Organizations; Cboe BZX Exchange, Inc.; Notice of
Filing and Immediate Effectiveness of Proposed Rule Change To List and
Trade Shares of the Goldman Sachs Physical Gold ETF Under BZX Rule
14.11(e)(4) (Commodity-Based Trust Shares)

January 28, 2022.
    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 January 25, 2022, Cboe BZX Exchange, Inc. filed with the Securities
and Exchange Commission (``Commission'') the proposed rule change as
described in Items I and II below, which Items have been substantially
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

    Cboe BZX Exchange, Inc. (the ``Exchange'' or ``BZX'') is filing
with the Securities and Exchange Commission (``Commission'' or the
``SEC'') a proposed rule change to list and trade shares of the Goldman
Sachs Physical Gold ETF (the ``Trust'') under BZX Rule 14.11(e)(4),
Commodity-Based Trust Shares.
    The text of the proposed rule change is also available on the
Exchange's website (http://markets.cboe.com/us/equities/regulation/rule_filings/bzx/), 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
Statutory Basis for, the Proposed Rule Change

1. Purpose
    The Exchange proposes to list and trade the Shares under BZX Rule
14.11(e)(4),\3\ which governs the listing and trading of Commodity-
Based Trust Shares on the Exchange.\4\ The Commission has previously
approved and noticed for immediate and effective proposals that are
substantively identical to this proposal that permit the listing and
trading of the Shares on NYSE Arca, Inc. (``Arca'').\5\ Further, the
Shares are currently listed and traded on Arca and as of December 14,
2021 and had net assets of $414.19 million.
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    \3\ The Commission approved BZX Rule 14.11(e)(4) in Securities
Exchange Act Release No. 65225 (August 30, 2011), 76 FR 55148
(September 6, 2011) (SR-BATS-2011-018).
    \4\ All statements and representations made in this filing
regarding (a) the description of the portfolio, (b) limitations on
portfolio holdings, or (c) the applicability of Exchange rules and
surveillance procedures shall constitute continued listing
requirements for listing the Shares on the Exchange.
    \5\ See Securities Exchange Act No. 82372 (December 21, 2017),
82 FR 61601 (December 28, 2017) (SR-NYSEArca-2017-140) (the
``Original Proposal''). See also Securities Exchange Act No. 82593
(January 26, 2018), 83 FR 4718 (February 1, 2018) (SR-NYSEArca-2017-
140) (Order Approving the Original Proposal). The order approving
the Original Proposal was later amended on November 20, 2020 to
reflect (i) a change in the sponsors and the custodian of the Perth
Mint Physical Gold ETF, which was renamed as the Goldman Sachs
Physical Gold ETF, (ii) the elimination of an investor's ability to
take delivery of Physical Gold, and (iii) in connection with the
change of custodian, the removal of the Government Guarantee, and to
amend certain other representations in the Proposal. See Securities
Exchange Act No. 90529 (November 30, 2020), 85 FR 78391 (December 4,
2020) (SR-NYSEArca-2020-100) (the ``Updated Proposal'').
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    Goldman Sachs Asset Management, L.P. is the sponsor of the Trust
(the ``Sponsor''). The Bank of New York Mellon is the trustee of the
Trust (the ``Trustee''). JPMorgan Chase Bank, N.A., London branch
serves as the custodian of the Trust's gold bullion (the ``Custodian'')
and is responsible for the safekeeping of the gold owned by the Trust.
The Shares are registered with the Commission by means of the Trust's
registration statement on Form S-3 (the ``Registration Statement'').\6\
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    \6\ On June 11, 2019 the Trust filed with the Commission a
registration statement on Form S-1 under the Securities Act of 1933
relating to the Trust (File No. 333-224389) (``S-1 Registration
Statement''). The S-1 Registration Statement was declared effective
by the SEC on June 20, 2019. On December 28, 2020, the Trust filed
with the Commission the Registration Statement on Form S-3 under the
Securities Act of 1933 relating to the Trust (File No. 333-251769).
The Registration Statement was declared effective by the SEC on
January 8, 2021.

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    The Trust will not be registered as an investment company under the
Investment Company Act of 1940, as amended,\7\ and is not required to
register under such act. The Trust is not a commodity pool for purposes
of the Commodity Exchange Act, as amended.\8\
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    \7\ 15 U.S.C. 80a-1.
    \8\ 17 U.S.C. 1.
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Goldman Sachs Physical Gold ETF
    The Trust's primary objective is for the Shares to reflect the
performance of the price of gold less the expenses of the Trust's
operations. Although the Shares are not the exact equivalent of an
investment in gold, they provide investors with an alternative that
allows a level of participation in the gold market through the
securities market.
Operation of the Gold Market
    The global trade in gold consists of over-the-counter (``OTC'')
transactions in spot, forwards, and options and other derivatives,
together with exchange-traded futures and options. The OTC market
trades on a continuous basis and accounts for most global gold trading.
Market makers and participants in the OTC market trade with each other
and their clients on a principal-to-principal basis. The main centers
of the OTC market are London, New York and Zurich. Most OTC market
trades are cleared through London. The London Bullion Market
Association (``LBMA'') plays an important role in setting OTC gold
trading industry standards.
Futures Exchanges
    Although the Trust will not invest in gold futures, information
about the gold futures market is relevant as such markets contribute
to, and provide evidence of, the liquidity of the overall market for
gold. The most significant gold futures exchange in the U.S. is COMEX,
operated by Commodities Exchange, Inc., a subsidiary of New York
Mercantile Exchange, Inc., and a subsidiary of the Chicago Mercantile
Exchange Group (the ``CME Group''). Other commodity exchanges include
the Tokyo Commodity Exchange (``TOCOM''), the Multi Commodity Exchange
Of India (``MCX''), the Shanghai Futures Exchange, ICE Futures US (the
``ICE''), and the Dubai Gold & Commodities Exchange.\9\
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    \9\ The CME Group and the ICE are members of the Intermarket
Surveillance Group (``ISG'').
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The London Bullion Market Association
    The LBMA is a trade association that, among other duties, maintains
and publishes ``Good Delivery'' lists that establish a set of criteria
that a refiner and its gold must satisfy before being accepted for
trading. Although the market for Physical Gold \10\ is distributed
globally, most OTC market trades are cleared through London. The LBMA
coordinates the market for gold and acts as the principal point of
contact between the market and its regulators. A primary function of
the LBMA is its involvement in the promotion of refining standards by
maintenance of the ``London Good Delivery Lists,'' which are the lists
of LBMA accredited melters and assayers of gold as well as the
specifications to which a bar/ingot must adhere. The LBMA also
coordinates market clearing and vaulting, and promotes good trading
practices. ``Good Delivery'' is a list of specifications a bar or ingot
must meet to trade on the London gold markets. The standards for gold
bars meeting the ``London Good Delivery Lists'' are published in LBMA's
``The Good Delivery Rules for Gold and Silver Bars''. Gold is usually
traded on the London market on a loco London basis. This means the gold
is physically held in vaults in London or is transferred into accounts
established in London. Payment upon settlement and delivery of a loco
London spot trade is usually in U.S. dollars, two business days after
the trade date. Delivery of the gold is either by physical delivery or
through the LBMA clearing system to an unallocated account.
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    \10\ ``Physical Gold'' means gold bullion that meets the London
Good Delivery Standards.
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Creation and Redemption of Shares by Authorized Participants
    According to the Registration Statement, authorized participants
may purchase (i.e., create) or redeem Shares only in blocks of 25,000
Shares (each such block, a ``Creation Unit'') in the Trust. Creation
Units are offered to authorized participants at the Trust's net asset
value (``NAV''). The size of a Creation Unit is subject to change. The
creation and redemption of Creation Units will only be made in exchange
for the delivery to the Trust or the distribution by the Trust of the
amount of gold represented by the Creation Units being created or
redeemed, the amount of which will be based on the combined Fine Ounces
\11\ represented by the number of Shares included in the Creation Units
being created or redeemed determined on the day the order to create or
redeem Creation Units is properly received.
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    \11\ ``Fine Ounce'' means an ounce of 100% pure gold, Fine
Ounces being determined, as to Physical Gold, by multiplying the
gross weight in ounces by the fineness, expressed as a fraction of
the fine metal content in parts per 1,000 in accordance with London
Good Delivery Standards and, as to gold held on an unallocated
basis, by the number of Fine Ounces credited to the applicable
unallocated account from time to time (such account being
denominated in Fine Ounces).
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    Orders to create and redeem Creation Units may be placed only by
authorized participants. An authorized participant must: (1) Be a
registered broker-dealer or other securities market participant, such
as a bank or other financial institution, which, but for an exclusion
from registration, would be required to register as a broker-dealer to
engage in securities transactions, (2) be a participant in the
Depository Trust Company (``DTC'') and (3) must have an agreement with
the Custodian establishing an account or have an existing account
meeting the standards described herein.
    Gold is delivered to the Trust and distributed by the Trust through
credits and debits between authorized participants' accounts, the trust
unallocated metal account and the trust allocated metal account. When
the Trustee requests creation of a basket at an authorized
participant's request, the authorized participant will then transfer
gold to the trust unallocated metal account. Once that gold is received
in the trust unallocated metal account, the Custodian will then
allocate the gold to the trust allocated metal account where it will be
stored for safekeeping. All gold represented by a credit to any
authorized participant's unallocated account represents a right to
receive Fine Ounces of gold. London Bars must further conform to London
Good Delivery Standards.
Creation Procedures--Authorized Participants
    On any business day, an authorized participant may place an order
with the Trustee to create one or more Creation Unit. For purposes of
processing both purchase and redemption orders, a ``business day''
means any day other than a day: (1) When the Exchange is closed for
regular trading; or (2) if the order or other transaction requires the
receipt or delivery, or the confirmation of receipt or delivery, of
gold in the United Kingdom, or in some other jurisdiction on a
particular day, (A) when banks are authorized to close in the United
Kingdom, or in such other jurisdiction or when the London gold market
is closed or (B) when banks in the United Kingdom, or in such other
jurisdiction are, or the London gold market is, not open for a full
business day and the order or other transaction requires the execution
or completion of procedures which cannot be executed or completed by
the close of the business day. Purchase orders must be placed

prior to the Order Cutoff Time \12\ on any business day.
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    \12\ ``Order Cutoff Time'' is defined, with respect to any
business day, as (i) 3:59:59 p.m. New York City time on such
business day or (ii) another time agreed to by the Sponsors and the
Trustee as to which the Sponsor has notified registered owners of
Shares and all existing authorized participants.
    \13\ ``Basket Gold Amount'' refers to the amount of gold that
must be deposited for issuance of one Creation Unit or that is
deliverable on surrender of one Creation Unit.
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Determination of Required Deposits
    The Trustee shall determine the Basket Gold Amount \13\ for each
business day, and each such determination thereof and the Trustee's
resolution of questions concerning the composition of the Basket Gold
Amount shall be final and binding on all persons interested in the
Trust. At the creation of the Trust, the initial Basket Gold Amount was
500 Fine Ounces of gold. After the initial deposit of gold into the
Trust, the Creation Unit Gold Amount for each business day shall be an
amount of gold equal to:
[GRAPHIC] [TIFF OMITTED] TN03FE22.044

Where:

(a) = the total number of Fine Ounces of gold held in the Trust as
of the opening of business on such business day

(b) = the number of Fine Ounces of gold equal in value to the
Trust's unpaid expense accrual as of the opening of business on such
business day

(c) = the total number of Shares outstanding as of the opening of
business on such business day

(d) = 25,000 (or other number of Shares in a Creation Unit for such
business day). Fractions of a Fine Ounce of gold included in the
Basket Gold Amount smaller than 0.001 Fine Ounces shall be
disregarded. The Sponsor shall publish, or shall designate another
person to publish, for each business day, the Basket Gold Amount
Delivery of Required Deposits
    An authorized participant who places a purchase order is
responsible for crediting the trust unallocated metal account with the
required gold deposit amount by 4:00 p.m. London time on the second
business day following the purchase order date. No Shares will be
issued unless and until the Custodian has informed the Trustee that it
has credited to the trust allocated metal account at the Custodian the
corresponding amount of gold. Upon transfer of the gold deposit amount
to the trust allocated metal account, the Trustee will direct DTC to
credit the number of Creation Units ordered to the authorized
participant's DTC account. The expense and risk of delivery, ownership
and safekeeping of gold, until such gold has been received by the
Custodian on behalf of the Trust, shall be borne solely by the
authorized participant.
Redemption Procedures--Authorized Participants
    The procedures by which an authorized participant can redeem one or
more Creation Unit will mirror the procedures for the creation of
Creation Units. On any business day, an authorized participant may
place an order with the Trustee to redeem one or more Creation Units.
Redemption orders must be placed prior to the Order Cutoff Time on each
business day the Exchange is open for regular trading (normally 9:30
a.m. Eastern Time). A redemption order so received is effective on the
date it is received in satisfactory form by the Trustee. The redemption
procedures allow only authorized participants to redeem Creation Units.
An investor may not redeem Creation Units other than through an
authorized participant. By placing a redemption order, an authorized
participant agrees to deliver the Creation Unit to be redeemed through
DTC's book-entry system to the Trust no later than the second business
day following the effective date of the redemption order. Prior to the
delivery of the redemption distribution for a redemption order, the
authorized participant must also have wired to the Trustee the non-
refundable transaction fee due for the redemption order. The redemption
distribution from the Trust consists of a credit to the redeeming
authorized participant's account representing the amount of the gold
held by the Trust evidenced by the Shares being redeemed as of the date
of the redemption order. A redeeming authorized participant is
responsible for any applicable tax, fees or other governmental charge
that may be due, as well as any charges or fees in connection with the
transfer of gold and the issuance and delivery of the Shares, and any
expense associated with the delivery of gold other than by credit to an
authorized participant's unallocated account with the Custodian or
another LBMA-member clearing bank.
Delivery of Redemption Distribution
    The redemption distribution due from the Trust is delivered to the
authorized participant on the second business day following the
redemption order date if, by 9:00 a.m. Eastern time on the second
business day following the redemption order date, the Trustee's DTC
account has been credited with the Creation Units to be redeemed. The
Custodian will arrange for the redemption amount in gold to be
transferred from the trust allocated metal account to the trust
unallocated metal account, and thereafter, as necessary, to the
redeeming authorized participant's account. With respect to a
redemption order provided in the ordinary course, the Custodian shall
deliver unallocated gold to the account indicated by the redeeming
authorized participant in its redemption order by 4:00 p.m. London Time
on the second business day following the order date.
Valuation of Gold and Computation of NAV
    On each business day that the Exchange is open for regular trading,
as promptly as practicable after 4:00 p.m., Eastern time, the Trustee
will value the gold held by the Trust and will determine the NAV of the
Trust, as described below. The NAV of the Trust is the aggregate value
of gold and other assets, if any, of the Trust (other than any amounts
credited to the Trust's reserve account, if any) including cash, if
any, less liabilities of the Trust, which include estimated accrued but
unpaid fees, expenses and other liabilities. All gold is valued based
on its Fine Ounce content, calculated by multiplying the weight of gold
by its purity; the same methodology is applied independent of the type
of gold held by the Trust. The Trustee values the gold held by the
Trust based on the afternoon LBMA Gold Price, or the morning LBMA Gold
Price, if such day's afternoon LBMA Gold Price is not available. If no
LBMA Gold Price is available for the day, the Trustee will value the
Trust's gold based on the most recently announced afternoon LBMA Gold
Price or morning LBMA Gold Price. If the Sponsor determines that such
price is inappropriate to use, it shall identify an alternate basis for
evaluation to be employed by the Trustee. The Sponsor may instruct the
Trustee to use a different price which is reasonably available to the
Trustee at no cost to the Trustee that the Sponsor determines to fairly
represent the commercial value of the Trust's gold. Once the value of
gold has been determined, the Trustee will subtract all estimated
accrued but unpaid fees, expenses and other liabilities of the Trust
from the total value of gold and any other assets of the Trust (other
than any amounts credited to the Trust's reserve account), including
cash, if any. The resulting figure is the NAV of the Trust. The Trustee
will also determine the NAV per share by dividing the NAV of the Trust
by the number of the Shares outstanding

as of the close of trading on the Exchange (which includes the net
number of any Shares deemed created or redeemed on such evaluation
day).\14\
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    \14\ The exchange of Shares to facilitate the delivery of
Physical Gold is subject to applicable product premiums and the
delivery fees associated with the transport of Physical Gold to
delivery applicants.
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Secondary Market Trading
    The Shares may trade in the secondary market on the Exchange at
prices that are lower or higher relative to their NAV per share. The
amount of the discount or premium in the trading price relative to the
NAV per share may be influenced by non-concurrent trading hours between
the Exchange and the COMEX, London and Zurich. While the Shares will
trade on the Exchange during all trading sessions, liquidity in the
global gold market may be reduced after the close of the major world
gold markets, including London, Zurich and COMEX, usually at 1:30 p.m.
Eastern Time. As a result, during this time, trading spreads and the
resulting premium or discount on the Shares may widen.
Availability of Information Regarding Gold
    Currently, the Consolidated Tape Plan does not provide for
dissemination of the spot price of a commodity such as gold over the
Consolidated Tape. However, there will be disseminated over the
Consolidated Tape the last sale price for the Shares, as is the case
for all equity securities traded on the Exchange (including exchange-
traded funds). In addition, there is a considerable amount of
information about gold and gold markets available on public websites
and through professional and subscription services. Investors may
obtain gold pricing information on a 24-hour basis based on the spot
price for an ounce of gold from various financial information service
providers, such as Reuters and Bloomberg. Reuters and Bloomberg, for
example, provide at no charge on their websites delayed information
regarding the spot price of Gold and last sale prices of Gold futures,
as well as information about news and developments in the gold market.
Reuters and Bloomberg also offer a professional service to subscribers
for a fee that provides information on Gold prices directly from market
participants.
    Complete real-time data for Gold futures and options prices traded
on the COMEX are available by subscription from Reuters and Bloomberg.
There are a variety of other public websites providing information on
gold, ranging from those specializing in precious metals to sites
maintained by major newspapers. In addition, the LBMA Gold Price is
publicly available at no charge at www.lbma.org.uk.
    Investors may obtain gold pricing information based on the spot
price for a Fine Ounce from various financial information service
providers. Current spot prices also are generally available with bid/
ask spreads from gold bullion dealers. In addition, the Trust's website
will provide pricing information for gold spot prices and the Shares.
Market prices for the Shares will be available from a variety of
sources including brokerage firms, information websites and other
information service providers. The NAV of the Trust will be published
by the Sponsor on each day that the Exchange is open for regular
trading and will be posted on the Trust's website.
Intraday Indicative Value (``IIV'')
    The IIV is an indicator of the value of the Trust's net assets at
the time the IIV is disseminated. The IIV is calculated and
disseminated every 15 seconds during Regular Trading Hours.\15\ The IIV
is generally calculated using the prior day's closing net assets of the
Trust as a base and updating throughout the trading day changes in the
value of the gold and cash held by the Trust.
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    \15\ Regular Trading Hours is the time between 9:30 a.m. and
4:00 p.m. Eastern Time.
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    The IIV will be disseminated by the Exchange or a major market data
vendor. In addition, the IIV is available through on-line information
services such as Bloomberg Finance L.P. and Reuters.
Availability of Information
    The Trust's website, Goldman Sachs Physical Gold ETF
(www.gsam.com), which is publicly accessible at no charge, contains the
following information: (a) The prior business day's NAV per Share, the
reported daily closing price and the reported daily trading volume; (b)
the Basket Gold Amount; (c) the midpoint of the bid-ask price as of the
time the NAV per Share is calculated (the ``Bid-Ask Price''); (d) the
calculation of the premium or discount of such price against such NAV
per Share; (e) data in chart form displaying the frequency distribution
of discounts or premiums of the bid-ask price against the NAV per
Share, within appropriate ranges for each of the four previous calendar
quarters; and (f) the current prospectus of the Trust.\16\ Finally, the
Trust's website will provide the last sale price of the Shares as
traded in the U.S. market. In addition, information regarding market
price and trading volume of the Shares will be continually available on
a real-time basis throughout the day on brokers' computer screens and
other electronic services. Information regarding the previous day's
closing price and trading volume information for the Shares will be
published daily in the financial section of newspapers.
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    \16\ See https://www.gsam.com/content/gsam/us/en/individual/products/etf-fund-finder/goldman-sachs-physical-gold-etf.html#activeTab=performance.
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Criteria for Initial and Continued Listing
    The Trust will be subject to the criteria in Rule 14.11(e)(4) for
initial and continued listing of the Shares. The Exchange will obtain a
representation that the Trust's NAV will be calculated daily and that
these values and information about the assets of the Trust will be made
available to all market participants at the same time. The Exchange
notes that, as defined in Rule 14.11(e)(4)(C)(i), the Shares will be:
(a) Issued by a trust that holds a specified commodity \17\ deposited
with the trust; (b) issued by such trust in a specified aggregate
minimum number in return for a deposit of a quantity of the underlying
commodity; and (c) when aggregated in the same specified minimum
number, may be redeemed at a holder's request by such trust which will
deliver to the redeeming holder the quantity of the underlying
commodity. Upon termination of the Trust, the Shares will be removed
from listing. The Trustee, Bank of New York Mellon, is a trust company
having substantial capital and surplus and the experience and
facilities for handling corporate trust business, as required under
Rule 14.11(e)(4)(E)(iv)(a) and that no change will be made to the
trustee without prior notice to and approval of the Exchange.
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    \17\ For purposes of Rule 14.11(e)(4), the term commodity takes
on the definition of the term as provided in the Commodity Exchange
Act.
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Trading Halts
    With respect to trading halts, the Exchange may consider all
relevant factors in exercising its discretion to halt or suspend
trading in the Shares. The Exchange will halt trading in the Shares
under the conditions specified in BZX Rule 11.18. Trading may be halted
because of market conditions or for reasons that, in the view of the
Exchange, make trading in the Shares inadvisable. These may include:
(1) The extent to which trading is not occurring in underlying gold
market; or (2) whether other unusual conditions or circumstances
detrimental to the maintenance of a fair and orderly market are
present. Trading in the

Shares also will be subject to Rule 14.11(e)(4)(E)(ii), which sets
forth circumstances under which trading in the Shares may be halted.
Trading Rules
    The Exchange deems the Shares to be equity securities, thus
rendering trading in the Shares subject to the Exchange's existing
rules governing the trading of equity securities. BZX will allow
trading in the Shares during all trading sessions on the Exchange. The
Exchange has appropriate rules to facilitate transactions in the Shares
during all trading sessions. As provided in BZX Rule 11.11(a), the
minimum price variation for quoting and entry of orders in securities
traded on the Exchange is $0.01 where the price is greater than $1.00
per share or $0.0001 where the price is less than $1.00 per share.
Surveillance
    The Exchange believes that its surveillance procedures are adequate
to properly monitor the trading of the Shares on the Exchange during
all trading sessions and to deter and detect violations of Exchange
rules and the applicable federal securities laws. Trading of the Shares
through the Exchange will be subject to the Exchange's surveillance
procedures for derivative products, including Commodity-Based Trust
Shares. The issuer has represented to the Exchange that it will advise
the Exchange of any failure by the Trust or the Shares to comply with
the continued listing requirements, and, pursuant to its obligations
under Section 19(g)(1) of the Act, the Exchange will surveil for
compliance with the continued listing requirements. If the Trust or the
Shares are not in compliance with the applicable listing requirements,
the Exchange will commence delisting procedures under Exchange Rule
14.12. The Exchange may obtain information regarding trading in the
Shares and Gold futures via ISG, from other exchanges who are members
or affiliates of the ISG, or with which the Exchange has entered into a
comprehensive surveillance sharing agreement.\18\
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    \18\ For a list of the current members and affiliate members of
ISG, see www.isgportal.com.
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Information Circular
    Prior to the commencement of trading, the Exchange will inform its
members in an Information Circular of the special characteristics and
risks associated with trading the Shares. Specifically, the Information
Circular will discuss the following: (i) The procedures for the
creation and redemption of Baskets (and that the Shares are not
individually redeemable); (ii) BZX Rule 3.7, which imposes suitability
obligations on Exchange members with respect to recommending
transactions in the Shares to customers; (iii) how information
regarding the IIV and the Trust's NAV are disseminated; (iv) the risks
involved in trading the Shares outside of Regular Trading Hours when an
updated IIV will not be calculated or publicly disseminated; (v) the
requirement that members deliver a prospectus to investors purchasing
newly issued Shares prior to or concurrently with the confirmation of a
transaction; and (vi) trading information. In addition, the Information
Circular will advise members, prior to the commencement of trading, of
the prospectus delivery requirements applicable to the Shares. Members
purchasing the Shares for resale to investors will deliver a prospectus
to such investors. The Information Circular will also discuss any
exemptive, no-action and interpretive relief granted by the Commission
from any rules under the Act.
2. Statutory Basis
    The Exchange believes that the proposal is consistent with Section
6(b) of the Act \19\ in general and Section 6(b)(5) of the Act \20\ in
particular in that it is designed to prevent fraudulent and
manipulative acts and practices, to promote just and equitable
principles of trade, to foster cooperation and coordination with
persons engaged in facilitating transactions in securities, to remove
impediments to and perfect the mechanism of a free and open market and
a national market system and, in general, to protect investors and the
public interest.
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    \19\ 15 U.S.C. 78f.
    \20\ 15 U.S.C. 78f(b)(5).
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    The Commission has approved numerous series of Trust Issued
Receipts, including Commodity-Based Trust Shares, to be listed on U.S.
national securities exchanges. In order for any proposed rule change
from an exchange to be approved, the Commission must determine that,
among other things, the proposal is consistent with the requirements of
Section 6(b)(5) of the Act, specifically including: (i) The requirement
that a national securities exchange's rules are designed to prevent
fraudulent and manipulative acts and practices; and (ii) the
requirement that an exchange proposal be designed, in general, to
protect investors and the public interest.
    The Exchange believes that the proposed rule change is designed to
prevent fraudulent and manipulative acts and practices in that the
Shares will be listed and traded on the Exchange pursuant to the
initial and continued listing criteria in Exchange Rule 14.11(e)(4).
The Exchange has in place surveillance procedures that are adequate to
properly monitor trading in the Shares in all trading sessions and to
deter and detect violations of Exchange rules and applicable federal
securities laws. The Exchange may obtain information via ISG from other
exchanges that are members of ISG or with which the Exchange has
entered into a comprehensive surveillance sharing agreement.
    The proposed rule change is designed to perfect the mechanism of a
free and open market and, in general, to protect investors and the
public interest in that it will facilitate the listing and trading of
an additional type of exchange-traded product that will enhance
competition among market participants, to the benefit of investors and
the marketplace. As noted above, the Exchange has in place surveillance
procedures relating to trading in the Shares and may obtain information
via ISG from other exchanges that are members of ISG or with which the
Exchange has entered into a comprehensive surveillance sharing
agreement.
    As noted above, the Commission has previously approved the Original
Proposal, which considered together with the Updated Proposal is
substantively identical to this proposal which permits the listing and
trading of the Shares.
    For the above reasons, the Exchange believes that the proposed rule
change is consistent with the requirements of Section 6(b)(5) of the
Act.

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

    The Exchange does not believe that the proposed rule change will
impose any burden on competition that is not necessary or appropriate
in furtherance of the purpose of the Act. The Exchange believes that
the proposed amendment will facilitate the listing of an additional
exchange-traded product on the Exchange, which will enhance competition
among listing venues, to the benefit of issuers, investors, and the
marketplace more broadly.

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

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

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

    Because the foregoing proposed rule change does not: (i)
Significantly affect the protection of investors or the public
interest; (ii) impose any significant burden on competition; and (iii)
become operative for 30 days from the date on which it was filed, or
such shorter time as the Commission may designate, it has become
effective pursuant to Section 19(b)(3)(A) of the Act \21\ and Rule 19b-
4(f)(6) \22\ thereunder.\23\
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    \21\ 15 U.S.C. 78s(b)(3)(A).
    \22\ 17 CFR 240.19b-4(f)(6).
    \23\ 17 CFR 240.19b-4(f)(6). In addition, Rule 19b-4(f)(6)(iii)
requires a self-regulatory organization to give the Commission
written notice of its intent to file the proposed rule change, along
with a brief description and text of the proposed rule change, at
least five business days prior to the date of filing of the proposed
rule change, or such shorter time as designated by the Commission.
The Exchange satisfied this requirement.
---------------------------------------------------------------------------

    A proposed rule change filed under Rule 19b-4(f)(6) \24\ normally
does not become operative prior to 30 days after the date of the
filing. However, pursuant to Rule 19b-4(f)(6)(iii),\25\ the Commission
may designate a shorter time if such action is consistent with the
protection of investors and the public interest. The Exchange has asked
the Commission to waive the 30-day operative delay so that the proposed
rule change may take effect upon filing and BZX may list the Shares as
soon as practicable. The Commission believes that waiver of the 30-day
operative delay is consistent with the protection of investors and the
public interest because the proposed rule change does not raise any new
or novel issues. Accordingly, the Commission waives the 30-day
operative delay and designates the proposal operative upon filing.\26\
---------------------------------------------------------------------------

    \24\ 17 CFR 240.19b-4(f)(6).
    \25\ 17 CFR 240.19b-4(f)(6)(iii).
    \26\ For purposes only of waiving the 30-day operative delay,
the Commission has considered the proposed rule's impact on
efficiency, competition, and capital formation. See 15 U.S.C.
78c(f).
---------------------------------------------------------------------------

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

IV. Solicitation of Comments

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

Electronic Comments

     Use the Commission's internet comment form (http://www.sec.gov/rules/sro.shtml); or
     Send an email to [email protected]. Please include
File Number SR-CboeBZX-2022-005 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-CboeBZX-2022-005. 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 Number SR-CboeBZX-2022-005 and should be submitted
on or before February 24, 2022.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\27\
---------------------------------------------------------------------------

    \27\ 17 CFR 200.30-3(a)(12).
---------------------------------------------------------------------------

J. Matthew DeLesDernier,
Assistant Secretary.
[FR Doc. 2022-02182 Filed 2-2-22; 8:45 am]
BILLING CODE 8011-01-P


UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON,  D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

MEMORANDUM

Date: 	2/12/2014

SUBJECT:	Aminopyralid.  Human Health Assessment Seeping  Document in Support of

Registration Review

PC Code: 005100

Decision  No.: 482282

Petition No.:  NA

Risk  Assessment Type:  NA TXRNo.: NA

MRIDNo.:  NA

DP Barcode: D414395

Registration No.:  62719-519

Regulatory Action: Registration Review

Case  No.:  7267

CAS No.:  150114-71-9

40 CFR:

FROM:

Douglas Dotson, Ph.D., Chemist

Jaime D'Agostino, Ph.D., Toxicologist  .- Zaida Figueroa, Industrial Hygienist

Risk Assessment  Branch II Health Effects Division (7509P) Office of Pesticide Programs

THROUGH: Christina Swartz, Branch Chief

Risk Assessment  Branch II

Jess Rowland, Acting Associate Director

Dana Vogel, Associate Director Health Effects Division (7509P) Offic

TO:	Veronica Dutch, Chemical Review Manager Pesticide Re-Evaluation  Division (7508P) Office of Pesticide Programs

Attached is the Health Effects Division's (HED) human health risk assessment seeping document for aminopyralid to support registration review.

Executive Summary

The Health Effects Division Aminopyralid Registration Review Team has evaluated the database and the most recent human health risk assessment for the herbicide aminopyralid.   HED performed this evaluation in order to determine the scope of work necessary to support the established tolerances and existing registrations during registration review.  The primary source

of information for this evaluation was the most recent human health risk assessment (D359088,

D. Dotson, et al, 10/22/2009).

Aminopyralid, 4-amino-3,6-dichloro-2-pyridinecarboxylic acid, is a systemic postemergence herbicide that belongs to the pyridine carboxylic acid class of herbicides.  It is currently registered for use in rangeland, permanent grass pastures, non-cropland areas, natural areas, grazed areas in and around these sites, as well as on wheat and com.  In addition, it is registered for use on wildlife habitat and industrial vegetation management areas, including right-of-way for roads, railroads, and utility lines.  Aminopyralid provides systemic postemergence  broad

The toxicology database for aminopyralid  is complete, and no additional toxicity studies are required.  HED's  Hazard and Science Policy Council (HASPOC) determined that a subchronic inhalation study in the rat is not required for aminopyralid.  The toxicology database for aminopyralid  includes studies with both the acid (XDE-750) and triisopropanolammonium (TIPA) salt (GF-871).

An immunotoxicity study was submitted subsequent to the last risk assessment and has been reviewed by HED.  The immunotoxicity study is considered to be acceptable and has no impact on the overall hazard characterization, including doses and endpoints selected (along with traditional uncertainty factors) for risk assessment.  The toxicology studies with aminopyralid indicate that the main target organs in the rat and dog were the stomach, ileum, and cecum following administration  in subchronic and chronic studies.  There is no evidence of neurotoxicity, carcinogenicity, or qualitative or quantitative susceptibility of the developing fetus or offspring, based on results from the developmental, reproductive, or carcinogenic toxicity studies.  Therefore, based on the completeness of the database, the lack of susceptibility, the lack of neurotoxicity, and the conservative nature ofthe exposure assessment, HED previously recommended that the required 1Ox Food Quality Protection Act (FQPA) Safety Factor be reduced to 1x.

The residue chemistry database is adequate to support current registration review requirements. Adequate metabolism (crops, livestock, and rotational crops), storage stability, magnitude of the residue, and processing data are available to support the registered uses.  Adequate methods are available for enforcement of the currently established tolerances.  The tolerance expression has been updated to include both coverage and compliance statements.

The dietary exposure database is adequate to support current registration requirements.  The last risk assessment provided chronic dietary exposure estimates that are not of concern for all population subgroups (D359088, D. Dotson, et al, 10/22/2009). The general U.S. population and all subgroups use less than 1% of the cPAD.  As part of registration review, HED anticipates performing revised dietary exposure analyses to reflect current Agency policy and potentially updated drinking water estimates.

The residential exposure database is complete.  During registration review, a revised residential exposure assessment that includes post-application incidental oral exposure to children (1 <2 years old) playing on treated recreational sites might be required.  This assessment should incorporate recently updated Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment.  The Agency might revisit the need for a quantitative post-application spray drift exposure assessment for aminopyralid during registration review.

There is sufficient information available to assess occupational exposure and risk from the registered uses.  The previous occupational handler assessment covered the relevant exposure scenarios and did not result in risk estimates of concern.  Revised occupational handler assessments might be required during registration review to include revised surrogate unit exposures for occupational handlers.  An occupational quantitative post-application assessment was not conducted previously because a dermal endpoint was not selected for aminopyralid. Therefore, a quantitative occupational post-application assessment will not be necessary during registration review.

Introduction

HED evaluated the most recent human health risk assessment for aminopyralid in association with updates to its toxicity, exposure, and usage databases to determine if sufficient data are available, and if further updates are needed, to support registration review.  The most recent human health risk assessment was performed in 2009 when HED evaluated a request for a new use on corn (D359088, D. Dotson, et al, 10/22/2009).

Tolerances for aminopyralid are established in 40 CFR

The structure, the chemical names, and other identifiers can be found in the chemical identity table in Attachment 1.

Hazard Identification/Toxicology

The herbicidal mode of action for aminopyralid is that of a plant growth regulator.  It disrupts normal growth by acting like a class of plant growth hormones known as auxins.  The chemical moves systemically throughout the plant and deregulates plant growth metabolic pathways affecting the growth process of the plant.  This disruption of plant growth processes results in

control and death of susceptible plant species.  The toxicological mode of action in mammals is unknown.

The toxicology database for aminopyralid is complete and no additional toxicity studies are required.  HED’s HASPOC determined that a subchronic inhalation study in the rat is not required for aminopyralid (J. VanAlstine, TXR#005100, 4/17/2013,). The toxicology database for aminopyralid includes studies with both the acid (XDE-750) and TIPA salt (GF-871).  Unless otherwise noted, the acid form was used in the studies discussed in this section.

An immunotoxicity study was recently submitted and has been reviewed by HED (MRID

48364401).  The study is acceptable, and the results show no evidence of immunotoxicity.  These results are consistent with the existing toxicological database which does not indicate that the chemical targets the immune system.  Given the above information, HED concludes that this new immunotoxicity study has no impact on the overall hazard characterization, including doses and endpoints selected (along with traditional uncertainty factors) for risk assessment.

The toxicology database for aminopyralid indicates that the stomach, ileum, and cecum are targets for this chemical.  In subchronic studies in rats and dogs, hyperplasia of the mucosal epithelium was observed.  In addition, hypertrophy of the mucosal epithelium was observed in the subchronic dog study.  Following chronic exposure of rats and dogs, hypertrophy (dog) and hyperplasia (dog and rat) of the mucosal epithelium was observed, as well as cecal enlargement (rat), thickening of the stomach mucosa (dog), slight lymphoid hyperplasia of the gastric mucosa (dog), and chronic mucosal inflammation (dog).  No adverse effects were observed when the TIPA salt was given to rats for 13 weeks.  No adverse effects were observed in subchronic or chronic feeding studies in mice exposed to the acid form.

Stomach effects were also observed in a developmental toxicity study in rabbits.  Ulcers and erosions were seen in the glandular mucosa of the stomach in maternal animals.  Other effects noted were decreased body weights and incoordinated gait.  No developmental effects were seen in fetuses.  In another developmental rabbit study with the TIPA salt, severe inanition (exhaustion from lack of food), body weight loss, decreased fecal output, and incoordinated gait were observed in maternal animals.  Decreased fetal body weights were observed at the next highest dose.  No effects were noted in developmental toxicity studies in rats with either the acid or TIPA salt, or a reproduction study in rats.  Therefore, there was no evidence of increased pre- and/or post-natal quantitative and qualitative susceptibility in the rat or rabbit.

No systemic toxic effects were observed in a 28-day dermal toxicity study in rats; however, dermal toxicity was indicated by slight epidermal hyperplasia in males.  In an acute neurotoxicity study in rats, fecal soiling in males and urine soiling in females were observed at the limit dose. No adverse effects were observed in a chronic neurotoxicity study at the highest dose tested.

Aminopyralid is classified as “not likely to be carcinogenic to humans.” No increases in any tumors were found in carcinogenicity studies in rats and mice.  Aminopyralid was negative in all mutagenicity studies, except for an in vitro chromosome aberration assay in Sprague Dawley rats.  In this assay, the acid form induced chromosome aberrations, but only at cytotoxic

concentrations.  Thus, the clastogenic response was induced secondary to toxicity.  An acceptable rat metabolism study for aminopyralid is available.

Both the acid and TIPA salt of aminopyralid have low acute toxicity (Toxicity Category IV) via oral, dermal, and inhalation routes of exposure.  Both forms are not irritating to the skin and are not skin sensitizers.  The acid form is severely irritating to the eye (Toxicity Category I) while the TIPA salt is not irritating to the eye (Toxicity Category IV).

In the most recent risk assessment, the required 10x FQPA Safety Factor was reduced to 1x based on: 1) the lack of increased pre- and post-natal susceptibility of rats and rabbits to in utero and/or post-natal exposure in the developmental and reproductive toxicity studies; 2) there is no evidence of neurotoxicity in the database; and 3) the risk assessment does not underestimate exposure because the dietary assessment is based on conservative assumptions such as tolerance- level residues in foods and upper-bound modeled estimates of residues in drinking water.

These conclusions are not expected to change during registration review.  The toxicological endpoints and doses used in the most recent human health risk assessment are summarized in Attachment 3.  The toxicity profile of aminopyralid is summarized in Attachment 4.

Conclusions for Hazard Identification/Toxicology

The toxicity database is complete for the purpose of registration review, and is appropriate for assessment of potential carcinogenic, mutagenic, developmental, and reproductive effects.  The FQPA Safety Factor was reduced to 1x based on a number of factors including the lack of susceptibility in developmental and reproduction studies in rats and rabbits, the lack of evidence for neurotoxicity, and the conservative assumptions used in the exposure assessments.  No new toxicity data are required.  Although the conclusions are not expected to change, HED will consider the appropriateness of the existing endpoints based on current policies and risk assessment methodologies during registration review.

Dietary Exposure

The residue chemistry database is adequate to support current registration review requirements (D360100, D. Dotson, 10/22/2009).  Adequate metabolism (crops, livestock, and rotational crops), storage stability, magnitude of the residue, and processing data are available to support the registered uses.  Adequate methods are available for enforcement of the currently established tolerances.  No residue chemistry data deficiencies were cited in the previous risk assessment for aminopyralid.  The previous risk assessment stated that the proposed label for corn should be modified to specify that spray or spot applications may not be made after the V6 growth stage, and that forage may not be harvested prior to the dent stage of growth.  The registrant added these restrictions to the label.

For the 2009 risk assessment, HED conducted a chronic dietary exposure assessment for all currently registered food uses (D369212, D. Dotson, 10/22/2009). The assessment was unrefined and, therefore, conservative.  It was based on the assumption that aminopyralid

residues are present at tolerance levels in all commodities for which tolerances have been established, and that 100% of those crops are treated.  DEEM™ Version 7.81 default processing factors were applied to all processed commodities for which they were available.  Drinking water was incorporated directly into the dietary assessment using the estimated drinking water concentration (EDWC) for surface water.  The EDWC is a modeled surface water residue estimate provided by the Environmental Fate and Effects Division (EFED; D361926, 7/24/2009, R. Baris).  It was generated by the Tier 1 FQPA Index Reservoir Screening Tool (FIRST) Model. The EDWC includes aminopyralid only.  It is the only residue of concern in drinking water for risk assessment.  The chronic dietary risk estimates were not of concern for the general U.S. population and all population subgroups.  All subgroups use less than 1% of the cPAD.  During registration review, HED will likely conduct a new dietary exposure and risk assessment if there are significant changes in the drinking water estimates.  If an assessment is needed, HED will use the most current dietary exposure model and food consumption survey.

Conclusions for Dietary Exposure

No new data are needed to assess potential dietary exposure and risk for aminopyralid. However, HED anticipates performing a new dietary exposure assessment during registration review.  The most current drinking water models will be used for this assessment.  In addition, the most current version of the dietary model will be used, along with any potential changes in endpoints and doses for risk assessment.

Residential Exposure

 Residential Handlers

Based on the current registered use pattern, aminopyralid is not applied by homeowners to residential or recreational settings; therefore, a residential handler exposure assessment will not be needed for registration review.

 Residential Post-Application

Aminopyralid is applied by commercial handlers to natural recreation areas (e.g., wildlife management areas, campgrounds, trailheads and trails) to control weeds.  As there is potential for short-term exposure of adults and children from entering areas previously treated with aminopyralid, residential post-application exposures associated with the use of aminopyralid to control weeds on residential and recreational sites were assessed in 2005 (M. Collantes, D305672).

Residential post-application dermal and inhalation exposure assessments were not required because: 1) no dermal endpoint was selected, and 2) inhalation exposure was expected to be negligible for outdoor uses associated with treated recreation areas.  Risks resulting from hand- to-mouth transfer, incidental ingestion of pesticide-treated turf grass and soil scenarios were assessed using the HED Draft Standard Operating Procedures (SOPs) for Residential Exposure Assessments (12/18/97), and the Revisions to the Standard Operating Procedures (SOPs) for

Residential Exposure Assessment (Science Advisory Council for Exposure Policy 12, Revised February 22, 2001).  The results of the post-application residential exposure assessment indicate no risks of concern, with MOEs >61,000 (LOC = 100).

A revised residential exposure assessment that includes post-application incidental oral exposure to children (1 <2 years old) playing on treated recreational sites might be required under registration review.  This assessment should incorporate recently updated procedures found in

the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide

Exposure Assessment.

In accordance with the updated Part 158 data requirements (2007), a turf transferrable residue (TTR) study is required for all residential or occupational turf uses (e.g., sod farms, golf courses, parks, and recreational areas).  However, a TTR study is not required for aminopyralid at this time because post-application incidental oral exposure calculated previously (D305672, M. Collantes, 05/24/2005) resulted in MOEs 10 times as high as the level of concern (e.g., an

MOE> 1,000 compared to the LOC of 100); therefore, using the default residue transfer values should provide an adequate margin of safety for any potentially higher residues seen in a chemical-specific TTR study.

 Spray Drift

The Agency has not considered residential post-application inhalation exposure for aminopyralid because there are no registered residential uses at this time.  However, residential exposures resulting from off-site transport (e.g., spray drift or volatilization) might occur as a result of applications of aminopyralid.  The Agency is in the process of evaluating these types of exposures and might, as appropriate, develop policies and procedures to identify the need for

and, subsequently, the way to incorporate these post-application exposures into the Agency’s risk assessments.  The Agency might conduct a spray drift assessment and examine the need for a volatilization assessment for aminopyralid during registration review.

Conclusions for Residential Exposure

The residential exposure database is complete.  Based on the current registered uses, a residential handler exposure assessment will not be conducted during registration review.  However, the Agency might conduct a revised residential post-application assessment that includes post- application incidental oral exposure of children (1 <2 years old) playing on treated recreational sites.  This assessment should incorporate recently updated procedures found in the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment.

Aggregate Risk Assessment

The most recent aggregate risk assessment was performed in conjunction with the 2009 risk assessment.  For aggregate assessment, exposure estimates resulting from food, drinking water, and residential uses are combined.  As no acute endpoint was identified and cancer risk is not a

concern for aminopyralid, acute and cancer aggregate risk assessments were not performed. There are residential uses for aminopyralid on recreational sites (e.g., campgrounds).  The non- dietary scenarios included in the aggregate assessment consisted of incidental oral exposures (e.g., hand-to-mouth transfer of residues, object-to-mouth, and ingestion of soil).  These

scenarios are short-term in duration and are applicable to children only.  There are no non-dietary scenarios for aminopyralid that are appropriate for assessing adults, therefore, the aggregate exposure estimates for adults are equivalent to the chronic dietary (food + water) estimates.  A short-term aggregate risk assessment was performed for various subgroups comprised of children less than 12 years old (i.e., all infants <1 year old, children 1-2, children 3-5, and children 6-12). The short-term aggregate risk estimates were not of concern.  Aggregate MOEs ranged from

25,000-33,000, whereas the LOC was 1,000.

Based on the registered and proposed uses, there are no residential scenarios that are likely to result in intermediate-term exposure (30-180 days, continuous).  Therefore, HED has not conducted an intermediate-term aggregate risk assessment for aminopyralid.  Dietary (food + water) consumption is the only source of exposure to aminopyralid that is expected to result in chronic exposure.  Therefore, the long-term aggregate exposure and risk estimates are equivalent to the chronic dietary exposure and risk estimates discussed above.  The chronic dietary risk estimates were not of concern for the general U.S. population and all population subgroups.  All subgroups use less than 1% of the cPAD.

Conclusions for Aggregate Exposure and Risk

Acute, intermediate-term, and cancer aggregate risk assessments were not performed for aminopyralid.  The short- and long-term aggregate risk estimates are not of concern to HED for any of the population subgroups for which risk estimates were generated.  At the time of registration review, HED will conduct a new aggregate risk assessment that will be based on residential exposures estimated using the updated residential SOPs, and will include any potential updates to points of departure or exposure estimates from food and drinking water.

Occupational Exposure

Aminopyralid is registered for use in a variety of non-cropland areas and grazed areas, as well as on wheat and corn.  It can be applied as a broadcast treatment by ground, aerial, and handheld equipment.  The Agency has determined that there is a potential for occupational handler and post-application exposures resulting from the registered uses of aminopyralid.

 Occupational Handlers

The previous exposure and risk assessments evaluated a number of occupational handler scenarios that represented the major aminopyralid short- and intermediate-term occupational exposures associated with application equipment and formulation type.  The risk assessments indicated that there are no risks of concern associated with occupational handler scenarios for workers wearing baseline clothing (i.e., long pants, long sleeve shirt, shoes plus socks).

HED will likely reevaluate the occupational handler assessment for aminopyralid to address updates to HED’s exposure policies, specifically, revisions to the Agency’s scenario-specific surrogate handler exposure data and assumptions for body weights.

 Occupational Post-application

The previous risk assessments evaluated a number of representative occupational post- application scenarios based on the registered uses.  HED has determined that there are potential dermal exposures of people entering treated sites (e.g., harvesters) after pesticide application is complete.  However, since no dermal endpoints were selected, a quantitative post-application exposure assessment for agricultural workers was not conducted.

In accordance with the updated Part 158 data requirements (2007), one or more dislodgeable foliar residue (DFR) studies are required when a pesticide has residential or occupational uses that could result in post-application dermal exposure.  However, a DFR study is not required for aminopyralid at this time because no dermal endpoints were selected, and therefore, a dermal post-application exposure assessment is not required.

After application of the product, agricultural workers could be exposed to residues from both the aminopyralid salt and the parent acid.  Therefore, the restricted entry interval (REI) for agricultural occupational exposure is based on the acute toxicity of both aminopyralid acid technical and the TIPA salt.  Aminopyralid acid is classified as Toxicity Category IV for acute dermal irritation and lethality following acute dermal exposure.  However, under the requirements for the Worker Protection Standard for Agricultural Pesticides (WPS), aminopyralid is classified as Toxicity Category I in an acute toxicity eye irritation study. According to WPS, a 48-hour REI is assigned to chemicals with acute Toxicity Category I classifications.  Furthermore, chemicals classified as Toxicity Category I for eye irritation

require the use of protective eyewear.  Therefore, HED recommends that during registration review the proper REI be included on all registered master labels and all the supplemental labels to ensure that the REIs are adequate to protect workers from post-application exposures to aminopyralid.

Based on the Agency’s current practices, a quantitative post-application inhalation exposure assessment was not performed for aminopyralid.  However, if new policies or procedures are put into place, the Agency might revisit the need for a quantitative occupational post-application inhalation exposure assessment for aminopyralid during registration review.

Conclusions for Occupational Exposure and Risks

Updated occupational handler exposure assessments will likely be required under registration review based upon revisions to the Agency’s scenario-specific surrogate handler exposure data and assumptions for body weights.  No occupational post-application dermal exposure assessment will be required under registration review; however, the Agency might revisit the need for a quantitative occupational post-application inhalation exposure assessment.  HED recommends that, during registration review, the proper REI be included on all registered master

labels and all the supplemental labels to ensure that the REIs are adequate to protect workers from post-application exposures to aminopyralid.

Public Health and Pesticide Epidemiology Data

For this evaluation, the Agency consulted both the OPP Incident Data System (IDS) and the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) databases for pesticide incident data on the active ingredient aminopyralid (Memo, D415939, S. Recore, 11/12/2013).  The purpose of the database search was to identify potential patterns in the frequency and severity of the health effects attributed to aminopyralid exposure. Aminopyralid is not included in the Agricultural Health Study (AHS); and therefore, that study does not provide information for this report.

For the Main IDS, from January 1, 2008 to September 11, 2013, there were 3 incidents reported for single chemical only in the database.  There were 11 additional incidents reported involving more than one chemical.  The incidents reported were classified as moderate severity.  Overall, there are few incidents involving aminopyralid reported to IDS.  In Aggregate IDS, from January

1, 2008 to September 11, 2013, there were 35 reported incidents involving aminopyralid.

The SENSOR-Pesticides database covers 11 states from 1998-2009, although reporting varies from state to state.  Cases of pesticide-related illnesses are ascertained from a variety of sources including reports from local Poison Control Centers, state Department of Labor workers’ compensation claims when reported by physicians, reports from State Departments of Agriculture, and physician reports to state Departments of Health.  A query of SENSOR- Pesticides from 1998 to 2009 revealed that two cases involving aminopyralid were reported. Both cases involved multiple active ingredients and were low in severity.

Based on the low frequency and severity of incident cases reported in both IDS and SENSOR- Pesticides, there does not appear to be a concern at this time that would warrant further investigation.  The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be included in the risk assessment.

Tolerance Assessment and International Harmonization

Tolerances for residues of aminopyralid in or on agricultural commodities are established in

40CFR the table below.  Compliance with the tolerance levels specified below is to be determined by measuring only free and conjugated aminopyralid.” For animal commodities, the tolerances are established as follows:  “Tolerances are established for residues of the herbicide aminopyralid, 4- amino-3,6-dichloro-2-pyridinecarboxylic acid, including its metabolites and degradates, in or on

the commodities in the table below.  Compliance with the tolerance levels specified below is to be determined by measuring only aminopyralid.”

The Codex Alimentarius Commission (Codex) has established maximum residue limits (MRLs) for aminopyralid on both plant and livestock commodities.  The Codex residue definition is the same for both types of commodities:  aminopyralid and its conjugates that can be hydrolyzed, expressed as aminopyralid.  In the cases where the U.S. and Codex have established MRLs for the same commodities, the MRLs are not harmonized.  Codex has established MRLs for commodities that do not have U.S. tolerances.  Canada has established MRLs for wheat grain, wheat bran, and several livestock commodities.  The Canadian residue definitions and MRLs are all harmonized with those of the U.S.  The harmonized tolerances include those for wheat grain, wheat bran, and livestock commodities.  Canada does not set MRLs in livestock feed items, so there is no issue with harmonization for these commodities.  The international residue limit

status sheet can be found in Attachment 6.

During registration review, HED will revisit the tolerances and harmonize them with the Codex MRLs, when possible.  The U.S. tolerances for some of the wheat and livestock commodities are slightly lower than the Codex MRLs for the same commodities.  The U.S. could potentially harmonize with Codex by making slight increases to the tolerances for wheat grain, hay, and straw.  The same is true for the meat and meat byproducts of cattle, goats, horses, and sheep.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in the human-health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations,”     HYPERLINK http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf )  (http://www.hss.ener    HYPERLINK http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf )  gy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf).  The OPP

typically considers the highest potential exposures from the legal use of a pesticide when conducting human-health risk assessments, including, but not limited to, people who obtain drinking water from sources near agricultural areas, the variability of diets within the U.S., and people who might be exposed when harvesting crops.  Should these highest exposures indicate potential risks of concern, OPP further refines the risk assessments to ensure that the risk estimates are based on the best available information.

Cumulative Risk Assessments

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to aminopyralid and any other substances, and aminopyralid does not appear to produce a toxic metabolite produced by other substances.  For the purposes of this action, therefore, EPA has not assumed that aminopyralid has a common mechanism of toxicity with other substances.  For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations

and procedures for cumulating effects from substances found to have a common mechanism on

EPA’s website at      HYPERLINK http://www.epa.gov/pesticides/cumulative/   http://www.epa.gov/pesticides/cumulative/.

Human Studies

The previous aminopyralid risk assessments relied in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical.  Studies such as the Pesticide Handlers Exposure Database, Outdoor Residential Exposure Task Force, and Agricultural Handler Exposure Task Force have been reviewed by the Agency and found, on the basis of available evidence, to have been neither fundamentally unethical nor significantly deficient relative to standards of ethical research conduct prevailing when they were conducted. There is no barrier in EPA’s “Protection of Human Subjects” Regulation to reliance on these studies.

Risk Assessment Updates, Data Deficiencies, and Label Revisions

No data deficiencies were identified for aminopyralid.

EPA anticipates conducting the following risk assessment updates during registration review: Toxicology:

?	HED will consider the appropriateness of the existing endpoints based on current policies and risk assessment methodologies.

Residue Chemistry:

?	None. Dietary Exposure:

?	Revised dietary exposure analyses might be required to reflect updated dietary exposure models and updated drinking water estimates.

Occupational/Residential Exposure:

?	HED anticipates conducting revised occupational exposure assessments to reflect the use of the most recent handler exposure data and updated body weights.

?	The Agency might conduct a revised residential post-application assessment that incorporates recently updated procedures found in the Health Effects Division’s 2012

Standard Operating Procedures for Residential Pesticide Exposure Assessment.

References

 Memoranda Relevant to Registration Review Author Barcode Date Title D. Dotson D359088 10/22/2009 Aminopyralid.  Human Health Risk Assessment for the Proposed

Use on Field Corn (PP#8F7455)J. VanAlstineNA4/7/2013Aminopyralid:  Summary of Hazard and Science Policy Council

(HASPOC) Meeting of March 28, 2013:  Recommendations on the

Requirement of a Subchronic Inhalation StudyD. DotsonD36010010/22/2009Aminopyralid and Aminopyralid Triisopropanolammonium (TIPA) Salt. Request to Add Uses on Field Corn to MilestoneWater) Exposure and Risk Assessment for the Section 3

Registration on Field CornM. CollantesD3056725/24/2005Occupational and Residential Exposure Risk Assessment for

Proposed Uses of AminopyralidZ. FigueroaD37049710/22/2009Aminopyralid Occupational Exposure Assessment for the

Registration of Milestone Herbicide for Use on CornR. BarisD3619267/24/2009Tier I Drinking Water Exposure Assessment for the Section 3 New

Use of Triisopropanolamine Salt of Aminopyralid on Field Corn and

Field Corn Grown for EnsilageS. RecoreD41593911/12/2013Aminopyralid: Tier I Review of Human Incidents

Attachments

Attachment 1.  Chemical Identity Table Attachment 2.  Toxicology Data Requirements Attachment 3.  Aminopyralid Endpoint Selection Table Attachment 4.  Toxicity Profile Table

Attachment 5.  Summary of Occupational Uses Based on Registered Labels for Aminopyralid

Attachment 6.  International Residue Limit Status

                                                                                Attachment 1.  Chemical Identity Table

 Aminopyralid Nomenclature. Chemical structure NH2

Cl

OH Cl	N

OCommon nameAminopyralidCompany experimental nameXDE-750IUPAC name4-amino-3,6-dichloropyridine-2-carboxylic acidCAS name4-amino-3,6-dichloro-2-pyridinecarboxylic acidCAS registry number150114-71-9Chemical structure

NH2	HO	CH3

Cl

H3C

.	N OH

Cl	N	OH	OH

O

CH3Common nameAminopyralid, triisopropanolammonium (TIPA) saltPC Code005209Company experimental nameXDE-750 TIPA saltIUPAC name4-amino-3,6-dichloropyridine-2-carboxylic acid - (2RS,2′?RS,2″?RS)-1,1′?,1″?- nitrilotripropan-2-ol (1:1)CAS name4-amino-3,6-dichloropyridine-2-carboxylic acid compound with 1,1′?,1″?- nitrilotris[2-propanol] (1:1)CAS registry number566191-89-7End-use product (EP)Milestone

Attachment 2.  Toxicology Data Requirements

The requirements (40 CFR 158.340) for aminopyralid residential and occupational use are shown below.  Use of the new guideline numbers does not imply that the new (1998) guideline

protocols were used.

 Test Technical

Required

Satisfied870.1100   Acute Oral Toxicity ........................................................

870.1200   Acute Dermal Toxicity ...................................................

870.1300   Acute Inhalation Toxicity...............................................

870.2400   Primary Eye Irritation.....................................................

870.2500   Primary Dermal Irritation ...............................................

870.2600   Dermal Sensitization ......................................................yes yes yes yes yes yesyes yes yes yes yes yes870.3100   Oral Subchronic (rodent) ................................................

870.3150   Oral Subchronic (nonrodent) ..........................................

870.3200   21/28-Day Dermal ..........................................................

870.3250   90-Day Dermal ...............................................................

870.3465   90-Day Inhalation...........................................................yes yes no yes noyes yes yes no1

---870.3700a Developmental Toxicity (rodent) ...................................

870.3700b Developmental Toxicity (nonrodent) .............................

870.3800   Reproduction ..................................................................yes yes yesyes yes yes870.4100a Chronic Toxicity (rodent) ...............................................

870.4100b Chronic Toxicity (nonrodent) .........................................

870.4200a Oncogenicity (rat)...........................................................

870.4200b Oncogenicity (mouse) ....................................................

870.4300   Chronic/Oncogenicity ....................................................yes no yes yes yesyes yes yes yes yes870.5100   Mutagenicity—Gene Mutation - bacterial ......................

870.5300   Mutagenicity—Gene Mutation - mammalian.................

870.5375   Mutagenicity—Structural Chromosomal Aberrations ....

870.5395   Mutagenicity—Mammalian Erythrocyte Micronucleus .

870.5550   Mutagenicity—Unscheduled DNA Synthesis ................

870.5915   Mutagenicity—In Vivo Sister Chromatid Exchangeyes yes yes no no noyes yes yes yes yes

--870.6100a Acute Delayed Neurotox. (hen)......................................

870.6100b 90-Day Neurotoxicity (hen) ...........................................

870.6200a Acute Neurotox. Screening Battery (rat) ........................

870.6200b 90 Day Neurotox. Screening Battery (rat) ......................

870.6300   Develop. Neuro ..............................................................no no yes yes no---

--- yes

no2870.7485   General Metabolism .......................................................

870.7600   Dermal Penetration .........................................................yes noyes yes870.7800   Immunotoxicity…………………………………………yesyes1 Requirement fulfilled by 21/28 day study.

2 Requirement fulfilled by chronic neurotoxicity study.

Attachment 3.  Endpoint Selection Tables

Summary of Toxicological Doses and Endpoints for Use in Human Risk Assessments

A

Point of Departure = A data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. N/A = not applicable. Ae = acid equivalent. XDE-750 = acid form of aminopyralid. GF-871 = triisopropanolammonium salt of aminopyralid.

 Summary of Toxicological Doses and Endpoints for Aminopyralid for Use in Occupational Human Health

Risk Assessments.

Exposure/ Scenario

Point of

Departure

Uncertainty/ FQPA Safety FactorsRfD, PAD,

Level of Concern for Risk Assessment

Study and Toxicological Effects

Dermal Short- Term (1-30 days) Intermediate- Term (1-6 months)

N/A

N/A

N/A

28-day dermal toxicity study in rats.

No systemic toxicity seen at the limit dose

(1,000 mg/kg/day) (XDE-750) Dermal risks are not of concern.

Inhalation Short- Term (1-30 days) Intermediate- Term (1-6 months)

NOAEL=104 mg ae/kg/day

UFA= 10x

UFH=10x

Occupational

LOC for MOE

= 100Developmental rabbit study (GF-871)

LOAEL=260 mg/kg/day

based on severe inanition (exhaustion resulting from lack of food) and body weight loss, decreased fecal output, and mild incoordinated gait.Cancer (oral,

dermal, inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant

tumor increases in two adequate rodent carcinogenicity studies.Point of Departure = A data point or an estimated point that is derived from observed dose-response data and  used

to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. ). FQPA SF = FQPA Safety Factor. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. Ae = acid equivalent. XDE-750 = acid form of aminopyralid. GF-871 = triisopropanolammonium salt of aminopyralid.

                                                                Attachment 4.  Toxicity Profiles

 Acute Toxicity Profile - Aminopyralid Technical (XDE-750). Guideline No. Study Type MRID(s) Results Toxicity

Category

870.1100

Acute oral-rat

46235603

LD50 = >5000 mg/kg/bw

(both sexes)

IV

870.1200

Acute dermal-rabbit

46235605

LD50 = >5000 mg/kg/bw

(both sexes)

IV

870.1300

Acute inhalation-rat

46235607

LC50 = >5.5 mg/L (both sexes)

IV

870.2400

Acute eye irritation-rabbit

46235609

Corneal opacity in 1/3 unresolved through day 35

I

870.2500

Acute dermal irritation-rabbit

46235611

non-irritant

IV

870.2600

Skin sensitization-guinea pig

46235613

Not a sensitizer

N/A

 Acute Toxicity Profile - Aminopyralid Triisopropanolammonium Salt (GF-871). Guideline No. Study Type MRID(s) Results Toxicity

Category

870.1100

Acute oral-rat

46235604

LD50 = >5000 mg/kg/bw

(both sexes)

IV

870.1200

Acute dermal-rabbit

46235606

LD50 = >5000 mg/kg/bw

(both sexes)

IV

870.1300

Acute inhalation-rat

46235608

LC50 = >5.79 mg/L (both sexes)

IV

870.2400

Acute eye irritation-rabbit

46235610

No positive signs of corneal opacity, iritis or conjunctivitis observed

IV

870.2500

Acute dermal irritation -rabbit

46235612

Slight erythema observed at 24 hours and 72 hours, resolving by study day 7

IV

870.2600

Skin sensitization-guinea pig

46235614

Not a sensitizer

N/A

Subchronic, Chronic, and Other Toxicity ProfileGDLNStudy TypeDose LevelsMRIDResults

870.3100

2001-13 WEEK FEEDING-RAT (XDE-

750) with 4 week recovery period

mg/kg/day =

0, 10, 100, 500, 1000

Acceptable/Guideline

46235621

NOAEL (mg/kg/day): M=500, F= 1000

LOAEL (mg/kg/day): M=1000 based on hyperplasia of the

mucosal epithelium of the ileum and cecum. F=not determined

870.3100

2004-13 WEEK FEEDING-RAT (GF-

871)‡

XDE-750 TIPA*

mg/kg/day=

0, 192, 500, 1000

mg ae/kg/day=

0, 100, 260, 520

Acceptable/Guideline

46235622

NOAEL (mg/kg/day):

520

LOAEL (mg/kg/day): not determined

870.3100

2001-13 WEEK FEEDING-MOUSE (XDE-750)

mg/kg/day =

0, 10, 100, 500, 1000

Acceptable/Guideline

46235618

NOAEL (mg/kg/day):

1000

LOAEL (mg/kg/day): not determined

870.3150

2002-13 WEEK FEEDING-DOG (XDE-

750)

%=0, 0.15, 0.75, 3.0

30000

mg/kg/day =

M: 0, 55, 282, 1070

F: 0, 53, 232, 929

Acceptable/Guideline

46235623

NOAEL (mg/kg/day): M=282, F= 232

LOAEL (mg/kg/day): M=1070, F=929 based on stomach

histopathology (slight diffuse hyperplasia and hypertrophy of the mucosal epithelium).

870.3200

2002-28 DAY DERMAL- RAT (XDE-750)

mg/kg/day =

0, 100, 500, 1000

Acceptable/Guideline

46235626

Systemic: NOAEL (mg/kg/day):

1000

LOAEL: (mg/kg/day) not determined

Dermal: NOAEL (mg/kg/day): M=100, F=1000

LOAEL (mg/kg/day): M=500, based on histopathological changes (slight epidermal hyperplasia).

F=not determined

870.3700

2001- DEVELOPMENTAL TOX-RAT

(XDE-750)

mg/kg/day =

0, 100, 300, 1000

Acceptable/Guideline

46235629

Maternal: NOAEL (mg/kg/day): 1000

LOAEL (mg/kg/day): not determined

Developmental: NOAEL (mg/kg/day): 1000

LOAEL (mg/kg/day): not determined

870.3700

2004- DEVELOPMENTAL TOX-RAT

(GF-871)‡

XDE-750 TIPA*

mg/kg/day=

0, 200, 500, 1000

mg ae/kg/day=

0, 104, 260, 520

Acceptable/Guideline

46235631

Maternal: NOAEL (mg/kg/day): 520

LOAEL (mg/kg/day): not determined

Developmental: NOAEL (mg/kg/day): 520

LOAEL (mg/kg/day): not determined

870.3700

2002- DEVELOPMENTAL

TOX-RABBIT (XDE-750)

mg/kg/day =

0, 25, 100, 250 (phase 1)

mg/kg/day =

0, 500, 750 (phase 2) Acceptable/Guideline

46235630

Maternal: NOAEL (mg/kg/day): 250

LOAEL (mg/kg/day): 500 based on decrease in body weight (GD 7-10), decreased food consumption,

incoordinated gait

(23/26), and ulcers and erosions of the stomach.

Developmental: NOAEL (mg/kg/day): 500

LOAEL (mg/kg/day): not determined

870.3700

2004- DEVELOPMENTAL TOX-RABBIT (GF-871)‡

XDE-750 TIPA*

mg/kg/day=

0, 200, 500, 1000

mg ae/kg/day=

0, 104, 260, 520

Acceptable/Guideline

46235632

Maternal: NOAEL (mg/kg/day): 104

LOAEL (mg/kg/day): 260 based on severe inanition and body weight loss, decreased fecal output, and mild incoordinated gait.

Developmental: NOAEL (mg/kg/day): 260

LOAEL (mg/kg/day): 520 based on decreased fetal body weights.

870.3800

2003-2-GENERATION REPRODUCTION-RAT (XDE-750)

mg/kg/day =

0, 50, 250, 1000

Acceptable/Guideline

46235635

Parental: NOAEL (mg/kg/day):

1000

LOAEL (mg/kg/day): not determined

Reproductive: NOAEL (mg/kg/day):

1000

LOAEL (mg/kg/day): not determined

Offspring: NOAEL (mg/kg/day):

1000

LOAEL (mg/kg/day): not determined

870.4100

2003-1 YEAR FEEDING- DOGS

(XDE-750)

% =0, 0.03, 0.30, 3.0

30000

mg/kg/day = M: 0, 10, 99, 967

F: 0, 9, 93, 1038

Acceptable/Guideline

46235627

NOAEL (mg/kg/day): M=99, F= 93

LOAEL (mg/kg/day): M=967, F=1038

based on thickening of stomach mucosa (females), and stomach histopathology in all animals (slight diffuse hyperplasia and

hypertrophy of the

mucosal epithelium, slight lymphoid hyperplasia of the gastric mucosa and very slight/slight chronic mucosal inflammation).

870.4200

2003-18 MONTH CARCINOGENICITY- MICE (XDE-750)

mg/kg/day =

0, 50, 250, 1000

Acceptable/Guideline

46235628

NOAEL (mg/kg/day): M=1000

LOAEL (mg/kg/day):

not determined.

870.4300

2004-2 YEAR TOXICITY/ CARCINOGENICITY- RAT

(XDE-750)

mg/kg/day =

0, 50, 500, 1000

Acceptable/Guideline

46235615

NOAEL (mg/kg/day):50

LOAEL (mg/kg/day): 500 based on cecal enlargement, slight mucosal hyperplasia (males) and slightly decreased body weights.

870.5100

2004-BACTERIAL REVERSE MUTATION ASSAY (XDE-750)

0, 100, 333, 1000, 3300 or 5000

Acceptable/Guideline

46235636

Negative

870.5100

2004-BACTERIAL REVERSE MUTATION ASSAY (GF-871)

XDE TIPA *

33, 100, 333, 1000, 3330,

5000

Acceptable/Guideline

46235637

Negative

870.5300

2004-IN VITRO MAMMALIAN CELL GENE MUTATION TEST

0, 31, 63, 125, 250, 500,

1000, 1500, 2070 1000, 2000, 4000

Acceptable/Guideline

46235801

Negative

870.5300

2004-IN VITRO MAMMALIAN CELL GENE MUTATION TEST (GF-871)

XDE TIPA *

250, 500, 1000, 2000,

4000

Acceptable/Guideline

46235804

Negative

870.5375

2002-IN VITRO MAMMALIAN CELL CHROMOSOME ABERRATION TEST (XDE-750)

0, 32, 65, 129, 259, 518,

1035, 2070 125, 250, 500, 750, 1000,

1400, 1700, 2070 μ?g/mL without metabolic activation and 0, 62.5,

125, 500, 1000 or 2070 μ?g/mL with metabolic activation (2nd assay);

400, 600, 800, 1000,

1200, 1400, 1600, 1700,

1800, 2070 μ?g/mL

without metabolic activation (3rd assay).

Acceptable/Guideline

46235802

XDE induced chromosome aberrations, but only at cytotoxic concentrations; the clastogenic response was induced secondary to toxicity.

870.5375

2004-IN VITRO MAMMALIAN CELL CHROMOSOME ABERRATION TEST (GF-871)

XDE TIPA *

1000, 2000, 4000

Acceptable/Guideline

46235803

Negative

870.5395

2002-MAMMALIAN ERYTHROCYTE MICRONUCLEUS TEST (XDE-750)

mg/kg/day = 0, 500,

1000 or 2000

Acceptable/Guideline

46235805

Negative

870.5395

2004-MAMMALIAN ERYTHROCYTE MICRONUCLEUS TEST (GF-871)

mg/kg/day = 0, 500,

1000, or 2000

Acceptable/Guideline

46235806

Negative

870.6200

2001-ACUTE NEUROTOXICITY-RAT (XDE-750)

mg/kg/day =

0, 500, 1000, 2000

Acceptable/Guideline

46235616

NOAEL (mg/kg/day):

1000

LOAEL (mg/kg/day):

2000

based on fecal soiling in males and urine soiling in females.

870.6200

2003-CHRONIC NEUROTOXICITY-RAT (XDE-750)

mg/kg/day =

0, 5, 50, 500, 1000

Acceptable/Guideline

46235617

NOAEL (mg/kg/day):

1000

LOAEL (mg/kg/day):

not determined

870.7485

2004-METABOLISM AND PHARMACOKINETICS- RAT (XDE-750)

mg/kg/day = Low dose: 50

High dose: 1000

Repeated low dose:

50 (unlabelled)

for 14 days, 50 (labelled)

on day 15

Acceptable/Guideline

46235807

Recovery after 168 hrs:

96% in low dose (urine-50%, feces-43%, tissues-0.1%, cage wash-

3%), 95% in high dose (urine-41%, feces-43%, tissues-1%, cage wash-

10%), and 95% in the repeated low dose (urine-

59%, feces-33%, tissues-

0.1%, cage wash-3%). XDE -750 represented

>96% of administered dose (AD) in urine and

100% AD in feces. Three unknown components (>

4%) found in urine were

also found in dose formulations.

870.7800

2010- IMMUNOTOXICITY- RAT (XDE-750)

mg/kg/day = 0 or 1038

Acceptable/Guideline

48364401

Systemic NOAEL (mg/kg/day):

Not determined

LOAEL (mg/kg/day):

1038 based on increased cecum size

Immunotoxicity NOAEL (mg/kg/day):

1038

LOAEL (mg/kg/day): Not determined

Non- Guideline

XDE-750, Triisopropanolammonium salt,

Dissociation and Metabolism in Male Fischer 344 Rats

mg/kg/day=

50 or 96

46235833

14C-XDE-750 and 14C- XDE-750-TIPA, when administered orally to rats, were bioequivalent in terms of absorption, distribution, metabolism, and excretion of the

amino-dichloro-picolinate portion of the molecule(s).

Attachment 5.  Summary of Occupational Uses Based on Registered Labels for

Aminopyralid

Summary of Occupational Uses Based on Registered Labels for Aminopyralid.

EPA Reg. No.

Registration NameFormulation

% ai or ae

Use site62718-518Aminopyralid TechnicalLiquid

95.3%Wheat (including durum), permanent

grass pastures, rangeland, fallow cropland, conservation reserve areas, industrial sites, rights-of-way, non- irrigation ditch banks,

wildlife/natural areas, grazed areas62719-519MilestoneEmulsifiable Concentrate

21.1%Wheat (including durum), corn,

rangeland, permanent grass pastures (including grasses grown for hay), conservation reserve areas, non- cropland industrial sites, rights-of- way, non-irrigation ditch banks, wildlife/natural areas, grazed areas62719-525CleanwaveEmulsifiable Concentrate

1.92%Wheat (including durum)62719-537Milestone VMEmulsifiable Concentrate

21.1%Non-cropland areas industrial sites,

rights-of-way, non-irrigation ditch banks, wildlife/natural areas, grazed areas62719-572Milestone VM Plus (alternate

name Capstone)Emulsifiable Concentrate

1.15%Rangeland, permanent grass pastures,

conservation reserve areas, forests, non-cropland areas industrial

sites, rights-of-way, fencerows, nonirrigation, ditch banks, wildlife/natural areas, grazed areasFL070003CleanwaveEmulsifiable Concentrate

1.92%Grass, forage, hay, pastures

Attachment 6.   International Residue Limit Status

Aminopyralid (005100; 11-8-2013)

 Summary of US and International Tolerances and Maximum Residue Limits. Residue Definition: US Canada Mexico1 Codex2 40 CFR 180.610 (a) (1)

Plants: Free and conjugated Aminopyralid (4-amino-3,6-dichloro-2- pyridinecarboxylic acid)Plants:4-amino-3,6-

dichloro-2- pyridinecarboxylic acid (free and conjugated)aminopyralid and its

conjugates that can be hydrolysed, expressed as aminopyralid.CommodityTolerance (ppm) /Maximum Residue Limit (mg/kg)USCanadaMexico1Codex2Corn, field, forage0.30Corn, field, grain0.20

Corn, field, stover

0.203 fodder (dry) of cereal

grains)Grain, aspirated fractions0.2Grass, forage25

Grass, hay

5070 hay or fodder (dry) of

grassesWheat, bran<IP_ADDRESS> wheat bran, unprocessedWheat, forage2.0Wheat, grain<IP_ADDRESS>

Wheat, hay

4.03 fodder (dry) of cereal

grains)Wheat, straw0.250.3 straw of cereal grainsUS [40 CFR 3,6-dichloro-2- pyridinecarboxylic acidSame as above

CommodityTolerance (ppm) /Maximum Residue Limit (mg/kg)USCanadaMexico1Codex2Cattle, fat0.020.02Cattle, kidney0.30.31

Cattle, meat

<IP_ADDRESS> meat (from mammals

other than marine mammals)Cattle, meat byproducts,

except kidney

<IP_ADDRESS> edible offal

mammalian (except kidney)Goat, fat0.020.02Goat, kidney0.30.31

Goat, meat

<IP_ADDRESS> meat (from mammals

other than marine mammals)

 Summary of US and International Tolerances and Maximum Residue Limits. Residue Definition: US Canada Mexico1 Codex2 Goat, meat byproducts, except kidney

<IP_ADDRESS> edible offal

mammalian (except kidney)Horse, fat0.020.02Horse, kidney0.30.3

Horse, meat

<IP_ADDRESS> meat (from mammals other than marine mammals)Horse, meat byproducts, except kidney

<IP_ADDRESS>edible offal mammalian

(except kidney)Milk0.030.03Sheep, fat0.020.02Sheep, kidney0.30.31

Sheep, meat

<IP_ADDRESS> meat (from mammals other than marine mammals)Sheep, meat byproducts, except kidney

<IP_ADDRESS> edible offal

mammalian (except kidney)MRLs With No US EquivalentBarley0.1Eggs0.01 (*)Kidney of pigs1Oats0.1Poultry meat0.01 (*)Poultry, edible offal of0.01 (*)Straw of cereal grains0.3Triticale0.1Completed: : M. Negussie; 08/29/131 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.