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Bacillus thuringiensis CryIA(b) Delta-Endotoxin - Tolerance Requirement Exemption 8/95

[Federal Register: September 13, 1995 (Volume 60, Number 177)]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 4F4389/R2163; FRL-4973-3]
RIN 2070-AB78
CryIA(c) and CryIC Derived Delta Endotoxins of Bacillus Thuringiensis
    Encapsulated in Killed Pseudomonas Fluorescens; Exemption From the
    Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule establishes an exemption from the requirement of a
tolerance for residues of CryIA(c) and CryIC derived Pseudomonas
fluorescens (MATTCH Biosecticide) in or on all raw agricultural
commodities. Mycogen Corp. submitted a request for an exemption from
the requirement of a tolerance. This regulation eliminates the need to
establish a maximum permissible level for residues of this pesticide in
or on all raw agricultural commodities.

EFFECTIVE DATE: Effective on September 13, 1995.

ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP 4F4389/R2163], may be submitted to:
Hearing Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M
St. SW., Washington, DC 20460. Fees accompanying objections shall be
labeled "Tolerance Petition Fees" and forwarded to: EPA Headquarters
Accounting Operations Branch, OPP (tolerance fees) P.O. Box 360277M,
Pittsburgh, PA 15251. A copy of any objections and hearing requests
filed with the Hearing Clerk should be identified by the document
control number and submitted to: Public Response and Program Resources
Branch, Field Operations Division (7506C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St. SW., Washington,
DC 20460. In person, bring copy of objections and hearing requests to:
Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202.
    A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: opp-docket@epamail.epa.gov. Copies of objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect in 5.1
file format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket number [PP
4F4389/R2163]. No Confidential Business Information (CBI) should be submitted
through e-mail. Electronic copies of objections and hearing requests on
this rule may be filed online at many Federal Depository Libraries.
Additional information on electronic submissions can be found below in
this document.

FOR FURTHER INFORMATION CONTACT: By mail: Willie H. Nelson,
Biopesticides and Pollution Prevention Division, Office of Pesticide
Programs, Environmental Protection Agency, 401 M St. SW., Washington,
DC 20460. Office location and telephone number: 5th Floor, CS #1, 2800
Crystal Drive, Arlington, VA 22202, 703-308-8715; e-mail: nelson.willie
@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: In the Federal Register of January 17, 1995,
EPA issued a notice that Mycogen Corp., 4980 Carroll Canyon Rd., San
Diego, CA 92121, had submitted a pesticide petition (PP 4F4389) to EPA
requesting that the Administrator, pursuant to section 408(d) of the
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d),
establish an exemption from the requirement of a tolerance for a blend
of CryIA(c) and CryIC derived delta-endotoxins of pesticide Bacillus
thuringiensis encapsulated in killed Pseudomonas fluorescens for all
raw agricultural commodities (RAC's) when used in accordance with good
agricultural practices.
    There were no adverse comments or requests for referral to an
advisory committee received in response to the notice of filing of the
pesticide petition, PP 4F4389.

Product Analysis

    Mycogen Corp. submitted information which adequately described its
product (MATTCH). This product consists of a maxture of two
lepidopteran active toxins derived from naturally occurring delta
endotoxins as found in Bacillus thuringiensis. Delta endotoxins active
against lepidopteran species are formed as protoxins that are activated
in the alkaline gut environment of the insect. The active toxins in
this product are referred to by Mycogen Corp. as CryIA(c) and CryIC due
to their amino acid sequence similarity to these toxins. The protoxin
portion of these derived toxins comes from another CryI protein. These
are produced in Pseudomonas fluorescens.
    The data submitted in the petition and all other relevant material
have been evaluated. The toxicological data considered in support of
the exemption from the requirement of a tolerance include the
following: an acute oral toxicity/pathogenicity study, an in-vitro
digestibility study, and abridged data from Mycogen's previously
registered MVP product.

Toxicology Assessment

    The toxicology data provided are sufficient to demonstrate that
there are no foreseeable human health hazards likely to arise from the
use of CryIA(c) and CryIC derived delta-endotoxins of Bacillus
thuringiensis encapsulated in killed Pseudomonas fluorescens.
    Mycogen's data on potential health effects include information on
the characterization of the expressed CryIA(c) and CryIC derived delta-
endotoxin, the acute oral toxicity, and the in vitro digestibility of
the delta-endotoxin. No potential health effects are expected from the
use of this product.

Toxicity

    The Agency expects that proteins with no significant amino acid
homology to known mammalian protein toxins and which are readily
inactivated by heat or mild acidic conditions would also be readily
degraded in an in vitro digestibility assay and have little likelihood
of displaying oral toxicity in laboratory rodents.
    Mycogen's data support the prediction that the CryIA(c) and CryIC
proteins would be nontoxic to humans. When proteins are toxic, they are
known to act via acute mechanisms and at very low dose levels [Sjobald,
Roy D., et al. "Toxicological Considerations for Protein Components of
Biological Pesticide Products," Regulatory Toxicology and
Pharmacology, 15, 3-9 (1992)]. Therefore, since no significant acute
effects were observed, even at relatively high dose levels, the
CryIA(c) and CryIC delta-endotoxins are not considered acutely or
chronically toxic. In addition, the in vitro digestibility studies
indicate the delta-endotoxin would be rapidly degraded following
ingestion.
    Despite decades of widespread use of Bacillus thuringiensis as a
pesticide (it has been registered since 1961), there have been no
confirmed reports of immediate or delayed allergic reactions to the
delta-endotoxin itself despite significant oral, dermal, and inhalation
exposure to the microbial product. Several reports under FIFRA section
6(a)2 have been made for various Bacillus thuringiensis products with
allergic reactions being reported. However, these reactions were
determined not to be due to Bacillus thuringiensis itself or any of the
Cry toxins.

Residue Chemistry Data

    Residue chemistry data were not required because of the lack of
mammalian toxicity of this active ingredient. In the acute mouse oral
toxicity study, the CryIC delta-endotoxin was shown to have an
LD50 greater than 5,050 mg/kg. When proteins are toxic they are
known to act via acute mechanisms and at very low dose levels [Sjobald,
Roy D., et al. "Toxicological Considerations for Protein Components of
Biological Pesticide Products," Regulatory Toxicology and
Pharmacology, 15, 3-9 (1992)]. Therefore, since no significant acute
effects were observed, even at relatively high dose levels, the CryIC
delta-endotoxin is not considered acutely or chronically toxic. This is
similar to the Agency position regarding toxicity and the requirement
of residue data for the microbial Bacillus thuringiensis products from
which this plant pesticide was derived. (See 40 CFR 158.740(b)). For
microbial products, further toxicity testing to verify the observed
effects and clarify the source of the effects (Tiers II, III) and
residue data are triggered by significant acute effects in studies such
as the mouse oral toxicity study.

Conclusions

    Based on the information considered, the Agency concludes that
establishment of a tolerance is not necessary to protect the public
health. Therefore, the exemption from the requirement of a tolerance is
established as set forth below.
    Any person adversely affected by this regulation may, within 30
days after publication of this document in the Federal Register, file
written objections to the regulation and may also request a hearing on
those objections. Objections and hearing requests must be filed with
the Hearing Clerk, at the address given above (40 CFR 178.20). A copy
of the objections and/or hearing requests filed with the Hearing Clerk
should be submitted to the OPP docket for this rule making. The
objections submitted must specify the provisions of the regulation
deemed objectionable and the grounds for the objections (40 CFR
178.25). Each objection must be accompanied by the fee prescribed by 40
CFR 180.33(i). If a hearing is requested, the objections must include a
statement of the factual issue(s) on which a hearing is requested, the
requestor's contentions on such issues, a summary of any evidence
relied upon by the objector as well as the other materials required by
40 CFR 178.27. A request for a hearing will be granted if
the Administrator determines that the material submitted shows the
following: There is genuine and substantial issue of fact; there is
reasonable possibility that available evidence identified by the
requestor would, if established, resolve one or more of such issues in
favor of the requestor, taking into account uncontested claims of facts
to the contrary; and resolution of the factual issue(s) in the manner
sought by the requestor would be adequate to justify the action
requested (40 CFR 178.32).
     A record has been established for this rulemaking under docket
number [PP 4F4389/R2163] (including objections and hearing requests
submitted electronically as described below). A public version of this
record, including printed, paper versions of electronic comments, which
does not include any information claimed as CBI, is available for
inspection from 8 a.m. to 4:30 p.m., Monday through Friday, excluding
legal holidays. The public record is located in Room 1132 of the Public
Response and Program Resources Branch, Field Operations Division
(7506C), Office of Pesticide Programs, Environmental Protection Agency,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Written objections and hearing requests, identified by the document
control number [PP 4F4389/R2163], may be submitted to the Hearing Clerk
(1900), Environmental Protection Agency, Rm. 3708, 401 M St., SW.,
Washington, DC 20460.
    A copy of electronic objections and hearing requests filed with the
Hearing Clerk can be sent directly to EPA at:
                 opp-Docket@epamail.epa.gov

    A copy of electronic objections and hearing requests filed with the
Hearing Clerk must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption.
    The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer any objections and hearing requests received
electronically into printed, paper form as they are received and will
place the paper copies in the official rulemaking record which will
also include all objections and hearing requests submitted directly in
writing. The official rulemaking record is the paper record maintained
at the address in ADDRESSES at the beginning of this document.
    Under Executive Order 12866 (58 FR 51735, October 4, 1993), the
Agency must determine whether the regulatory action is "significant"
and therefore subject to all the requirements of the Executive Order
(i.e., Regulatory Impact Analysis, review by the Office of Management
and Budget (OMB)). Under section 3(f), the order defines
"significant" as those actions likely to lead to a rule (1) having an
annual effect on the economy of $100 million or more, or adversely and
materially affecting a sector of the economy, productivity,
competition, jobs, the environment, public health or safety, or State,
local or tribal governments or communities (also known as
"economically significant"); (2) creating serious inconsistency or
otherwise interfering with an action taken or planned by another
agency; (3) materially altering the budgetary impacts of entitlement,
grants, user fees, or loan programs; or (4) raising novel legal or
policy issues arising out of legal mandates, the President's
priorities, or the principles set forth in this Executive Order.
    Pursuant to the terms of this Executive Order, EPA has determined
that this rule is not "significant" and is therefore not subject to
OMB review.
    Pursuant to the requirements of the Regulatory Flexibility Act
(Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator
has determined that regulations establishing new tolerances or raising
tolerance levels or establishing exemptions from tolerance requirements
do not have a significant economic impact on a substantial number of
small entities. A certification statement to this effect was published
in the Federal Register of May 4, 1981 (46 FR 24950).

List of Subjects in 40 CFR Part 180

    Environmental Protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.

    Dated: August 31, 1995.

Daniel M. Barolo,
Director, Office of Pesticide Programs.

PART 180--[AMENDED]

    Therefore, 40 CFR part 180 is amended as follows:

    1. The authority citation for part 180 continues to read as follows:

       Authority: 21 U.S.C. 346a and 371.

    2. In subpart D, by adding new Sec. 180.1154, to read as follows:

Sec. 180.1154   CryIA(c) and CryIC derived Delta-Endotoxins of Bacillus
thuringiensis var. kurstaki Encapsulated in killed Pseudomonas
fluorescens, and the expression plasmid and cloning vector genetic
constructs.

    CryIA(c) and CryIC derived delta-endotoxins of Bacillus
thuringiensis var. kurstaki encapsulated in killed Pseudomonas
fluorescens and the expression plasmid and cloning vector genetic
constructs are exempt from the requirement of a tolerance when used in
or on all raw agricultural commodities.