[Federal Register Volume 61, Number 150 (Friday, August 2, 1996)]
[Rules and Regulations]
[Pages 40340-40343]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-19811]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 5F4473/R2270; FRL-5391-3]
RIN 2070-AB78
Bacillus Thuringiensis CryIA(b) Delta-Endotoxin and the Genetic
Material Necessary for Its Production in All Plants; Exemption from
Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
[[Page 40341]]
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This rule establishes an exemption from the requirement of a
tolerance for residues of the plant pesticide active ingredients
Bacillus thuringiensis CryIA(b) delta-endotoxin and the genetic
material necessary for its production in all plants. A request for an
exemption from the requirement of a tolerance was submitted by Monsanto
Company. This regulation eliminates the need to establish a maximum
permissible level for residues of these plant pesticides in all plant
raw agricultural commodities.
EFFECTIVE DATE: Effective on August 2, 1996.
ADDRESSES: Written objections and hearing requests, identified by the
docket number [PP 5F4473/R2270] may be submitted to: Hearing Clerk
(1900), Environmental Protection Agency, Rm. M3708, 401 M St., SW.,
Washington, DC. 20460. A copy of any objections and hearing requests
filed with the Hearing Clerk should be identified by the docket 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 Highway, Arlington, VA. 22202. 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.
Comments and data may also be submitted electronically by sending
electronic mail (e-mail) to: opp-docket@epamail.epa.gov. Electronic
comments must be submitted as an ASCII file avoiding the use of special
characters and any form of encryption. Comments and data will also be
accepted on disks in WordPerfect 5.1 file format or ASCII file format.
All comments and data in electronic form must be identified by the
docket number [PP 5F4473/R2270]. No Confidential Business Information
(CBI) should be submitted through e-mail. Electronic comments on this
proposed 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: Michael L. Mendelsohn,
Biopesticides and Pollution Prevention Division (7501W), Office of
Pesticide Programs, U. S. Environmental Protection Agency, 401 M St.,
SW., Washington, DC 20460. Office location and telephone number: 5th
Floor CS, 2800 Crystal Drive, Arlington, VA 22202, Telephone No. 703-
308-8715), e-mail: mendelsohn.michael@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: Monsanto has genetically modified corn
plants to produce a truncated version of the pesticidal CryIA(b) delta-
endotoxin protein (derived from the soil microbe Bacillus
thuringiensis). EPA issued a notice, published in the Federal Register
of October 25, 1995 (60 FR 54689)(FRL-4982-4), which announced that the
Monsanto Company, 700 Chesterfield Parkway North, St. Louis, MO 63198
had submitted a pesticide petition (PP) 5F4473 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 the Bacillus
thuringiensis subsp. kurstaki Insect Control Protein (CryIA(b)) as
produced in plant cells. EPA has described the active ingredients
covered by this description as Bacillus thuringiensis CryIA(b) delta-
endotoxin and the genetic material necessary for its production in all
plants. ``Genetic material necessary for its production'' means the
genetic material which comprise (1) genetic material encoding the
CryIA(b) delta-endotoxin and (2) its regulatory regions. ``Regulatory
regions'' are the genetic material that control the expression of the
genetic material encoding the CryIA(b) delta-endotoxin, such as
promoters, terminators, and enhancers.
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 5F4473.
Product Analysis
Data was presented which showed that the truncated CryIA(b) toxin
can be extracted from corn leaf tissue and this purified material
displays characters and activities similar to that produced in E. coli
which has been transformed to produce CryIA(b). The similarities are
shown for the tryptic core proteins in molecular weight after SDS-PAGE,
immunorecognition in Western blots and ELISA, partial amino acid
sequence analysis, lack of glycosylation and bioactivity against either
European corn borer or corn earworm. This analysis justifies the use of
the microbially produced toxin as an analogue for the plant produced
protein in mammalian toxicity testing.
Toxicology Assessment
Toxicity
The toxicology data provided are sufficient to demonstrate that
there are no foreseeable human health hazards likely to arise from the
use of Bacillus thuringiensis CryIA(b) delta-endotoxin and the genetic
material necessary for its production in all plants.
The data submitted regarding potential health effects include
information on the characterization of the expressed CryIA(b) delta-
endotoxin in corn, the acute oral toxicity, and in vitro digestibility
of the delta-endotoxin. In an acute oral toxicity test of bacterially-
derived CryIA(b) protein, no test substance related deaths occurred at
a dose of 4,000 mg/kg.
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 and are readily degraded
in an in vitro digestibility assay would have little likelihood for
displaying oral toxicity, as demonstrated.
The data submitted by Monsanto support the prediction that the
CryIA(b) protein would be non-toxic 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(b) delta-endotoxin is not considered acutely toxic. Adequate
information was submitted to show that the test material derived from
microbial cultures were biochemically and insecticidally similar to the
delta-endotoxin as produced by the plant-pesticide in corn. Production
of microbially produced CryIA(b) delta-endotoxin was chosen in order to
obtain sufficient material for testing. In addition, the in vitro
digestibility studies indicate the delta-endotoxin would be rapidly
degraded following ingestion.
The genetic material necessary for the production of the Bacillus
thuringiensis CryIA(b) delta-endotoxin are the nucleic acids (DNA)
which comprise (1) genetic material encoding the CryIA(b) delta-
endotoxin and (2) its regulatory regions. ``Regulatory regions'' are
the genetic material that control the expression of the genetic
material encoding the CryIA(b) delta-endotoxin, such as promoters,
terminators, and enhancers. DNA is common to all forms of plant and
animal life and the Agency knows
[[Page 40342]]
of no instance where these nucleic acids have been associated with
toxic effects related to their consumption. These ubiquitous nucleic
acids as they appear in the subject active ingredient have been
adequately characterized by the applicant. Therefore, no mammalian
toxicity is anticipated from dietary exposure to the genetic material
necessary for the production of the Bacillus thuringiensis CryIA(b)
delta-endotoxin in any plants.
Allergenicity
Current scientific knowledge suggests that common food allergens
tend to be resistant to degradation by heat, acid, and proteases, are
glycosylated and present at high concentrations in the food. Monsanto
has submitted data demonstrating that the CryIA(b) delta-endotoxin is
rapidly degraded by gastric fluid in vitro and is non-glycosylated.
Studies submitted to EPA done in laboratory animals also have not
indicated any potential for allergic reactions to Bacillus
thuringiensis or its components, including the delta-endotoxin in the
crystal protein. Recent in vitro studies also confirm that the delta-
endotoxin would be readily digestible in vivo, unlike known food
allergens that tend to be resistant to degradation.
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
claiming allergic reactions. However, the Agency determined these
reactions were not 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 CryIA(b) delta-endotoxin was shown to have an
LD50 greater than 4,000 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 CryIA(b) delta-
endotoxin is not considered acutely. 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 and III) and residue data are triggered
by significant acute effects in studies such as the mouse oral toxicity
study.
The genetic material necessary for the production of the Bacillus
thuringiensis CryIA(b) delta-endotoxin are the nucleic acids (DNA)
which comprise: (1) Genetic material encoding the CryIA(b) delta-
endotoxin and (2) its regulatory regions. ``Regulatory regions'' are
the genetic material that control the expression of the genetic
material encoding the CryIA(b) delta-endotoxin, such as promoters,
terminators, and enhancers. As stated above, no mammalian toxicity is
anticipated from dietary exposure to the genetic material necessary for
the production of the Bacillus thuringiensis CryIA(b) delta-endotoxin
in any plant. Therefore, no residue data are required in order to grant
an exemption from the requirements of a tolerance for the plant
pesticides, Bacillus thuringiensis CryIA(b) delta-endotoxin and the
genetic material necessary for its production in plants.
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 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 or 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).
EPA has established a record for this rulemaking under docket
number [PP 5F4473/R2270] (including any comments and data submitted
electronically). 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.
Electronic comments may be sent directly to EPA at:
opp-docket@epamail.epa.gov.
Electronic comments 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 copies of 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 comments 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), this
action is not a ``significant regulatory action'' and, since this
action does not impose any information collection requirements as
defined by the Paperwork Reduction Act, 44 U.S.C. 3501 et seq., it is
not subject to review by the Office of Management and Budget. In
addition, this action does not impose any enforceable duty or contain
any
[[Page 40343]]
unfunded mandate as described in the Unfunded Mandates Reform Act of
1995 (Pub. L. 104-4), or require prior consultation with State
officials as specified by Executive Order 12875 (58 FR 58093, October
28, 1993), or special considerations as required by Executive Order
12898 (59 FR 7629, February 16, 1994).
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).
Under 5 U.S.C. 801(a)(1)(A) of the Administrative Procedure Act
(APA) as amended by the Small Business Regulatory Enforcement Fairness
Act of 1996 (Title II of Pub. L. 104-121, 110 Stat. 847), EPA submitted
a report containing this rule and other required information to the
U.S. Senate, the U.S. House of Representatives and the Comptroller
General of the General Accounting Office prior to publication of the
rule in today's Federal Register. This rule is not a ``major rule'' as
defined by 5 U.S.C. 804(2) of the APA as amended.
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and record
keeping requirements.
Dated: July 30, 1996.
Daniel M. Barolo,
Director, Office of Pesticide Programs.
Therefore, 40 CFR Part 180 is amended as follows:
PART 180--[AMENDED]
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. 180.1173, to read as follows:
Sec. 180.1173 Bacillus thuringiensis CryIA(b) delta-endotoxin and
the genetic material necessary for its production in all plants.
Bacillus thuringiensis CryIA(b) delta-endotoxin and the genetic
material necessary for its production in all plants are exempt from the
requirement of a tolerance when used as plant pesticides in all plant
raw agricultural commodities. ``Genetic material necessary for its
production'' means the genetic material which comprise genetic material
encoding the CryIA(b) delta-endotoxin and its regulatory regions.
``Regulatory regions'' are the genetic material that control the
expression of the genetic material encoding the CryIA(b) delta-
endotoxin, such as promoters, terminators, and enhancers.
[FR Doc. 96-19811 Filed 8-1-96; 8:45 am]
BILLING CODE 6560-50-F
