[Federal Register Volume 63, Number 99 (Friday, May 22, 1998)]
[Rules and Regulations]
[Pages 28258-28261]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-13604]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300659; FRL-5790-3]
RIN 2070-AB78
Bacillus Thuringiensis Subspecies tolworthi Cry9C Protein and the
Genetic Material Necessary for its Production in Corn; Exemption from
the Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule amends an exemption from the requirement of a
tolerance for resid ues of the insecticide, Bacillus thuringiensis
subspecies tolworthi Cry9C protein and the genetic material necessary
for its production in corn for feed use only; as well as in meat,
poultry, milk, or eggs resulting from animals fed such feed. Plant
Genetic Systems (America), Inc. submitted a petition to the EPA under
the Federal Food, Drug and Cosmetic Act (FFDCA) as amended by the Food
Quality Protection Act (FQPA) of 1996 requesting the exemption from the
requirement of a tolerance. This regulation eliminates the need to
establish a maximum permissible level for residues of this plant-
pesticide in or on corn used for feed; as well as in meat, poultry,
milk, or eggs resulting from animals fed such feed.
EFFECTIVE DATE: This regulation is effective May 22, 1998. Objections
and requests for hearings must be received by EPA on or before July 21,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number [OPP-300659], must be submitted to: Hearing Clerk
(1900), Environmental Protection Agency, Rm. M3708, 401 M St., SW.,
Washington, DC 20460. Fees accompanying objections and hearing requests
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 identified by the docket control
number, [OPP-300659], must also be submitted to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticide Programs, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. In person, bring a copy of
objections and hearing requests to Rm. 119, CM #2, 1921 Jefferson Davis
Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may be submitted electronically by sending electronic mail (e-
mail) to: opp-docket@epamail.epa.gov. Copies of electronic objections
and hearing requests must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Copies of
electronic objections and hearing requests will also be accepted on
disks in WordPerfect 5.1/6.1 or ASCII file format. All copies of
electronic objections and hearing requests must be identified by the
docket number [OPP-300659]. No Confidential Business Information (CBI)
should be submitted through e-mail. Copies of electronic objections and
hearing requests on this rule may be filed online at many Federal
Depository Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Mike Mendelsohn, Regulatory
Action Leader, Biopesticides and Pollution Prevention Division (7511W),
Office of Pesticide Programs, Environmental Protection Agency, 401 M
St., SW., Washington, DC 20460, Office location, telephone number, and
e-mail: Room CS15-W29, 2800 Jefferson Davis Highway, Arlington, VA,
703-308-8715, e-mail: mendelsohn.mike@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: Plant Genetic Systems (America), Inc., 7200
Hickman Road, Suite 202, Des Moines, IA 50322 has requested in
pesticide petition (PP 7F4826) the establishment of an exemption from
the requirement of a tolerance for residues of the insecticide Bacillus
thuringiensis subspecies tolworthi Cry9C protein and the genetic
material necessary for its production in corn in or on all raw
agricultural commodities. A notice of filing (FRL-5739-9) was published
in the Federal Register (62 FR 49224, September 19, 1997), and the
notice announced that the comment period would end on October 20, 1997;
no comments were received. Plant Genetic Systems (America), Inc.
submitted an amendment to their petition on April 24, 1998 to request
the establishment of an exemption from the requirement of a tolerance
for residues of the insecticide Bacillus thuringiensis subspecies
tolworthi Cry9C protein and the genetic material necessary for its
production in corn only in corn used for feed; as well as in meat,
poultry, milk, or eggs resulting from animals fed such feed. This
exemption from the requirement of a tolerance will permit the marketing
of feed corn containing the plant-pesticide; as well as meat, poultry,
milk, or eggs resulting from animals fed such feed. The data submitted
in the petition and all other relevant material have been evaluated.
Following is a summary of EPA's findings regarding this petition as
required by section 408(d) of the Federal Food, Drug and Cosmetic Act
(FFDCA), 21 U.S.C. 346a, as recently amended by the Food Quality
Protection Act (FQPA), Pub. L. 104-170.
[[Page 28259]]
I. Risk Assessment and Statutory Findings
A. Product Identity/Chemistry
The Cry9C gene was originally isolated from a Bacillus
thuringiensis subsp. tolworthi strain. The gene was then synthesized
with plant preferred codons before it was stably inserted into corn
plants to produce a truncated and modified Cry9C protein. The tryptic
core of the microbially produced Cry9C delta-endotoxin is similar to
the Cry9C protein found in event CBH351 save for a single amino acid
substitution in the internal sequence and the addition of two amino
acids to the N-terminus. The Cry9C protein was produced and purified
from a bacterial host to utilize in the mammalian toxicity studies due
to the bacterium's greater production potential. Product analysis that
compared the Cry9C protein from the two sources included: SDS-PAGE,
Western blots, N-terminal amino acid sequencing, glycosylation tests
(for possible post- translational modifications) and insect bioassays.
No analytical method was included since this petition requests an
exemption from the requirement of a tolerance.
B. Mammalian Toxicological Profile
Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the
available scientific data and other relevant information in support of
this action and considered its validity, completeness and reliability
and the relationship of this information to human risk. EPA has also
considered available information concerning the variability of the
sensitivities of major identifiable subgroups of consumers, including
infants and children. Additionally, section 408(b)(2)(D)(v) requires
that, when considering whether to establish, modify, or revoke a
tolerance, the Agency consider ``available information'' concerning the
cumulative effects of a particular pesticide's residues and ``other
substances that have a common mechanism of toxicity.'' A high-dose
acute oral toxicity study (3,760 mg/kg body weight) showed no
mortalities. Transient weight losses were seen in three female treated
animals, with one not recovering her pre-dosing, pre-fast weight at 14
days after dose administration. The treated males showed no weight
losses. Transient weight loss has been observed in similar studies
conducted on other purified Cry proteins as well as microbial
pesticides containing Cry proteins and is not considered a significant
adverse effect. The in vitro digestibility study showed the Cry9C
protein to be stable to pepsin digestion at pH 2.0 for 4 hours. The
Cry9C protein is also heat stable, not being affected by incubation at
90 deg. C for 10 minutes. The Cry9C protein in corn is the trypsin
resistant core and is therefore stable to tryptic digest. A search for
amino acid homology did not reveal any significant homology with known
toxins or allergens. The genetic material necessary for the production
of the plant-pesticide active ingredient is the nucleic acids (DNA)
which comprise genetic material encoding the Cry9C protein and its
regulatory regions. Regulatory regions are the genetic material that
control the expression of the genetic material encoding the proteins,
such as promoters, terminators, and enhancers. DNA is common to all
forms of plant and animal life and the Agency knows of no instance
where these nucleic acids have been associated with toxic effects
related to their consumption as a component of food. These ubiquitous
nucleic acids as they appear in the subject plant-pesticide have been
adequately characterized by the applicant and supports EPA's conclusion
that no mammalian toxicity is anticipated from dietary exposure to the
genetic material necessary for the production of the Cry9C protein.
C. Aggregate Exposure
The available information on the aggregate exposure levels of
consumers (and major identifiable subgroups of consumers) to the Cry9C
protein residue include dietary exposure and exposure from non-
occupational sources. Exposure via the skin or inhalation is not likely
since the Cry9C plant-pesticide is contained within plant cells
essentially eliminating these exposure routes or reducing these
exposure routes to negligible. Drinking water is unlikely to be
significantly contaminated with Cry9C protein due to the low expression
of the protein in corn tissue, degradation of plant materials in the
soil and low leaching potential of a protein from a soil matrix.
Minimal to non-existent oral exposure could occur from ingestion of
meat, poultry, eggs or milk from animals fed corn containing the plant-
pesticide and from drinking water. While unlikely, meat, eggs or milk
from animals fed corn containing the plant-pesticide could contain
negligible but finite residues. This is viewed as a remote possibility
due to the low Cry9C expression level in corn tissue (3 to 250
g/gm dry weight), the anticipated degradation and elimination
of the Cry9C protein by the animal or the lack of uptake of such a
large protein by the animal's intestinal tract. It is not possible to
establish with certainty whether finite residues will be incurred, but
there is no reasonable expectation of finite residues. However, the
best available information on the uptake of intact proteins from the
diet would indicate that the intact Cry9C protein would not be
available in products from animals fed corn products containing Cry9C
protein.
D. Cumulative Effects
The Agency has considered available information on the cumulative
effects of such residues and other substances that have a common
mechanism of toxicity. These considerations included the cumulative
effects on adults as well as on infants and children of such residues
and other substances with a common mechanism of toxicity. Since there
is no indication of mammalian toxicity to the Cry9C protein from the
studies submitted, there is no reason to believe there would be
cumulative toxic effects.
E. Safety Determination
The tolerance exemption is limited to residues of the Cry9C protein
resulting from feed use only. The basis of safety for this tolerance
exemption includes both the results of the acute oral study at high
doses indicating no toxicity and the anticipated minimal to nonexistent
human dietary exposure of the Cry9C protein via animal feed use. Bt
microbial pesticides, containing Cry proteins other than Cry9C, have
been applied for more than 30 years to food and feed crops consumed by
the U.S. population. There have been no human safety problems
attributed to the specific Cry proteins. An oral dose of the tryptic
core Cry9C protein of at least 3,760 mg/kg was administered to 10
animals without mortality demonstrating a high degree of safety for the
protein. Transient weight loss in three female rodents was observed,
but not in any males. Transient weight loss has been observed in
similar studies conducted on other purified Cry proteins as well as
microbial pesticides and this is not considered a significant adverse
effect.
A comparison of the amino acid sequence of the Cry9C protein with
those found in the PIR, Swiss-Prot and HIV AA data bases did not reveal
any significant homology with known toxins or allergens. The in vitro
digestibility study showed the Cry9C protein to be stable to pepsin at
pH 2.0. The Cry9C protein was shown to be stable to heat at 90 deg. C
for 10 minutes and the Cry9C protein in corn is the trypsin resistant
core and is therefore stable to tryptic digest. The best available
information to date would indicate that edible products derived from
animals such as meat, milk
[[Page 28260]]
and eggs, intended for human consumption, have not been shown to be
altered in their allergenicity due to changes in the feed stock
utilized. This information would include no transfer of allergenic
factors from cattle fed soybeans to the derived meat or milk eaten by
individuals with food sensitivity to soybeans.
F. Infants and Children
FFDCA section 408(b)(2)(C) provides that EPA shall assess the
available information about consumption patterns among infants and
children, special susceptibility of infants and children to pesticide
chemical residues and the cumulative effects on infants and children of
the residues and other substances with a common mechanism of toxicity.
In addition, FFDCA section 408 provides that EPA shall apply an
additional tenfold margin of exposure (safety) for infants and children
in the case of threshold effects to account for pre- and post-natal
toxicity and the completeness of the database unless EPA determines
that a different margin of exposure (safety) will be safe for infants
and children. In this instance, based on all the available information,
the Agency concludes that infants and children will consume only
minimal, if any, residues of this plant-pesticide and that there is a
finding of no toxicity. Thus, there are no threshold effects of concern
and, as a result the provision requiring an additional margin of safety
does not apply. Further, the provisions of consumption patterns,
special susceptibility, and cumulative effects do not apply.
G. Other Considerations
1. Analytical method. The Agency is establishing an exemption from
the requirement of a tolerance without any numerical limitation;
therefore, the agency has concluded that an analytical method is not
required for enforcement purposes for this plant-pesticide.
2. Effects on the endocrine systems. EPA does not have any
information regarding endocrine effects for these kinds of pesticides
at this time. The Agency is not requiring information on the endocrine
effects of these plant-pesticides at this time; and Congress allowed 3
years after August 3, 1996, for the Agency to implement a screening and
testing program with respect to endocrine effects.
H. Existing Tolerances
A temporary exemption from the requirement of a tolerance for
residues of Bacillus thuringiensis subsp. tolworthi Cry9C and the
genetic material necessary for the production of this protein in corn,
only in corn used for feed; as well as in meat, poultry, milk, or eggs
resulting from animals fed such feed was established on April 10, 1998
under 40 CFR 180.1192 [63 FR 69]. The exemption from the requirement of
a tolerance in this rule makes permanent the temporary tolerance
exemption of 40 CFR 180.1192.
II. Conclusion
Based on the toxicology data cited and the limited exposure
expected with animal feed use, there is reasonable certainty that no
harm will result from aggregate exposure to the U.S. population,
including infants and children, to residues of Bacillus thuringiensis
subspecies tolworthi Cry9C protein and the genetic material necessary
for its production in corn. This includes all anticipated dietary
exposures and all other exposures for which there is reliable
information. The Agency has arrived at this conclusion because, as
discussed above, the temporary tolerance exemption is limited to feed
use only. The conclusion of safety is supported by the lack of toxicity
after administration of a high oral dose (3,760 mg/kg), the lack of
homology to known toxins or allergens, and the minimal to nonexistent
exposure via dietary and non-dietary routes. This exemption from the
requirement of a tolerance will be revoked if any experience with or
scientific data on this pesticide indicate that the tolerance is not
safe.
III. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``object'' to a tolerance exemption regulation issued by
EPA under new section 408(e) as was provided in the old section 408.
However, the period for filing objections is 60 days, rather than 30
days. EPA currently has procedural regulations which govern the
submission of objections and hearing requests. These regulations will
require some modification to reflect the new law. However, until those
modifications can be made, EPA will continue to use those procedural
regulations with appropriate adjustments to reflect the new law.
Any person adversely affected by this regulation may by June 22,
1998, 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
rulemaking. 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, and a summary of
any evidence relied upon by the objector (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 a 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). Information submitted in connection with an objection or
hearing request may be claimed confidential by marking any part or all
of that information as CBI. Information so marked will not be disclosed
except in accordance with procedures set forth in 40 CFR Part 2. A copy
of the information that does not contain CBI must be submitted for
inclusion in the public record. Information not marked confidential may
be disclosed publicly by EPA without prior notice.
IV. Public Record and Electronic Submissions
EPA has established a record for this rulemaking under docket
control number [OPP-300659] (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 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Room 119 of the Public Information and Records
Integrity Branch, Information Resources and Services, Division (7502C),
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
[[Page 28261]]
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 Virginia address in ``ADDRESSES'' at the
beginning of this document.
V. Regulatory Assessment Requirements
This final rule establishes an exemption from the tolerance
requirement under FFDCA section 408(d) in response to a petition
submitted to the Agency. The Office of Management and Budget (OMB) has
exempted these types of actions from review under Executive Order
12866, entitled Regulatory Planning and Review (58 FR 51735, October 4,
1993). This final rule does not contain any information collections
subject to OMB approval under the Paperwork Reduction Act (PRA), 44
U.S.C. 3501 et seq., or impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (Pub. L. 104-4). Nor does it require any
prior consultation as specified by Executive Order 12875, entitled
Enhancing the Intergovernmental Partnership (58 FR 58093, October 28,
1993), or special considerations as required by Executive Order 12898,
entitled Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations (59 FR 7629, February 16, 1994),
or require OMB review in accordance with Executive Order 13045,
entitled Protection of Children from Environmental Health Risks and
Safety Risks (62 FR 19885, April 23, 1997).
In addition, since tolerances and exemptions that are established
on the basis of a petition under FFDCA section 408(d), such as the
exemption in this final rule, do not require the issuance of a proposed
rule, the requirements of the Regulatory Flexibility Act (RFA) (5
U.S.C. 601 et seq.) do not apply. Nevertheless, the Agency previously
assessed whether establishing tolerances, exemptions from tolerances,
raising tolerance levels or expanding exemptions might adversely impact
small entities and concluded, as a generic matter, that there is no
adverse economic impact. The factual basis for the Agency's generic
certification for tolerance actions published on May 4, 1981 (46 FR
24950), and was provided to the Chief Counsel for Advocacy of the Small
Business Administration.
VI. Submission to Congress and the General Accounting Office
Under 5 U.S.C. 801(a)(1)(A), as added by the Small Business
Regulatory Enforcement Fairness Act of 1996, the Agency has 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 this rule in
today's Federal Register. This is not a ``major rule'' as defined by 5
U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: May 11, 1998.
Marcia E. Mulkey,
Director, Office of Pesticide Programs.
Therefore, 40 CFR chapter I 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. Section 180.1192 is revised to read as follows:
Sec. 180.1192 Bacillus thuringiensis subspecies tolworthi Cry9C
protein and the genetic material necessary for its production in corn;
exemption from the requirement of a tolerance.
The plant-pesticide Bacillus thuringiensis subspecies tolworthi
Cry9C protein and the genetic material necessary for its production in
corn is exempted from the requirement of a tolerance for residues, only
in corn used for feed; as well as in meat, poultry, milk, or eggs
resulting from animals fed such feed.
[FR Doc. 98-13604 Filed 5-21-98; 8:45 am]
BILLING CODE 6560-50-F
