AGENCY: Environmental Protection Agency (EPA).

Note: EPA no longer updates this information, but it may be useful as a reference or resource.

[Federal Register: October 31, 2000 (Volume 65, Number 211)]
[Notices]
[Page 65245-65251]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr31oc00-123]

[[Page 65245]]

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Part VI

Environmental Protection Agency

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Assessment of Scientific Information Concerning StarLink Corn
Cry9C Bt Corn Plant-Pesticide; Notice

[[Page 65246]]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-867B; FRL-6754-3]

Assessment of Scientific Information Concerning
StarLink Corn Cry9C Bt Corn Plant-Pesticide

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: On October 25, 2000, Aventis CropScience (Aventis) submitted
new information in support of its petition (PP 9F5050) for an exemption
from the requirement of a tolerance for the genetically engineered
``plant-pesticide'' materials in StarLink corn. These materials are the
Bacillus thuringiensis subsp. tolworthi Cry9C protein and the genetic
material (DNA) necessary for the production of this protein. While the
original petition requested an exemption covering both the Cry9C DNA
and Cry9C protein in all food commodities, this submission limits the
request only to foods made from StarLink corn. The Aventis submission
specifically addresses the potential allergenicity of the Cry9C protein
that may be present in human food made from StarLink corn, a
line of genetically modified corn developed by Aventis. This notice
provides information on Aventis' submission and outlines the U.S.
Environmental Protection Agency's process for seeking public comment on
and external scientific review of the new information.

DATES: Comments, identified by docket control number PF-867B, must be
received on or before November 27, 2000.

ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as
provided in Unit I. of the Supplementary Information. To ensure proper
receipt by EPA, it is imperative that you identify docket control
number PF-867B in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: Paul Lewis, Office of Science
Coordination and Policy (7101C), Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703)
305-5369; fax number: (703) 605-0656; e-mail address:
hutton.phil@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

This action is directed to the public in general. This action may,
however, be of interest to those persons who are technical experts in
human allergenicity, as well as those persons who produce or handle
corn grain or processed food made from corn grain. Since other entities
may also be interested, the Agency has not attempted to describe all
the specific entities that may be affected by this action. If you have
any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.

B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?

1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Biopesticide Internet Home Page at http://
www.epa.gov/pesticides/biopesticides. The EPA Biopesticide Internet
Home Page will, at a minimum, contain the body of Aventis' October 25,
2000, submission. To access this Notice on the Home Page, select ``Laws
and Regulations,'' ``Regulations and Proposed Rules,'' and then look up
the entry for this document under the ``Federal Register--Environmental
Documents.'' You can also go directly to the Federal Register listings
at http://www.epa.gov/fedrgstr/.
2. In person. The Agency has established an official docket in
connection with this Notice under docket control number PF-867B.
Associated public dockets exist for: (1) the initial Notice of Filing
for the food use Cry9C tolerance petition, 9F05050 (docket control
number PF-867); (2) the notice soliciting public comment on EPA data
evaluation records, questions within an EPA background document
regarding the use of amino acid homology, the Brown Norway Rat Model,
and other items regarding the assessment for potential allergenicity,
(docket control number PF-867A); and (3) the February 29, 2000 SAP
meeting, (docket control number OPP-00641). The official record for
EPA's review of the Aventis petition will include, in addition to the
documents in the dockets listed above, any materials submitted to EPA
in connection with this Federal Register Notice, including any
information claimed as Confidential Business Information (CBI). This
official record includes the documents that are physically located in
the docket, as well as the documents that are referenced in those
documents. The public version of the official record does not include
any information claimed as CBI. The public version of the official
record, which includes printed, paper versions of any electronic
comments submitted during an applicable comment period, is available
for inspection in the Public Information and Records Integrity Branch
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

You may submit comments through the mail, in person, or
electronically. To ensure proper receipt by EPA, it is imperative that
you identify docket control number PF-867B in the subject line on the
first page of your response.
1. By mail. Submit your comments to: Public Information and
Records Integrity Branch (PIRIB), Information Resources and Services
Division (7502C), Office of Pesticide Programs (OPP), Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA. The PIRIB is open from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB
telephone number is (703) 305-5805.
3. Electronically. You may submit your comments electronically by
e-mail to: opp-docket@epa.gov, or you can submit a computer disk as
described above. Do not submit any information electronically that you
consider to be CBI. Avoid the use of special characters and any form of
encryption. Electronic submissions will be accepted in WordPerfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-867B. Electronic comments may
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI that I Want to Submit to the Agency?

Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this

[[Page 65247]]

document as CBI 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. In addition to one complete
version of the comment that includes any information claimed as CBI, a
copy of the comment that does not contain the information claimed as
CBI must be submitted for inclusion in the public version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person listed under FOR FURTHER INFORMATION CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

You may find the following suggestions helpful for preparing your
comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide copies of any technical information and/or data you
used that support your views.
4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
5. Provide specific examples to illustrate your concerns.
6. Offer alternative ways to improve the notice or collection
activity.
7. Make sure to submit your comments by the deadline in this
notice.
8. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
Register citation.

II. Background

A. What Action is the Agency Taking?

Today, EPA is announcing the receipt and public availability of a
submission from Aventis concerning its pending petition to establish an
exemption from the requirement of a tolerance for the genetically
engineered ``plant-pesticide'' materials in StarLink corn. These
materials are the Bacillus thuringiensis subsp. tolworthi Cry9C protein
and the genetic material (DNA) necessary for the production of this
protein. The requested exemption would cover both the Cry9C DNA and
Cry9C protein in all food commodities. In addition, EPA is inviting
public comment on the submission as it relates to the petition.
Further, EPA is announcing its intention to hold a public meeting of an
independent, external scientific peer review group during the week of
November 27 - December 1, 2000, to consider the potential allergenicity
of Cry9C.
The following paragraphs provide background on the matters being
announced today.
1. Regulatory history. On April 7, 1999, EPA announced the receipt
of a pesticide petition (PP 9F5050) (64 FR 16965) (FRL-6069-8) from
AgrEvo USA Company; (Aventis has since succeeded to the interests of
AgrEvo USA Company; also, this petition superceded a petition for an
exemption that was submitted in 1997 by AgrEvo at the time AgrEvo
initially applied for registration.) The petition, 9F5050, proposed an
amendment to 40 CFR 180.1192 to expand the exemption from the
requirement of a tolerance for Bacillus thuringiensis subspecies
tolworthi Cry9C protein and the genetic material necessary for its
production in corn. At that time and currently, the existing exemption
covered these substances in corn, only when the corn was used for
animal feed, and in meat, poultry, milk, or eggs resulting from animals
fed such feed. The petition sought to extend the exemption for these
substances to all food commodities.
EPA completed its initial review of the data submitted in support
of this petition and solicited public comment on the data evaluation
records and on a list of questions regarding human allergenicity
assessment for non-digestible proteins expressed as plant-pesticides
(64 FR 74152, December 21, 1999) (FRL-6098-2). The evaluation of
potential human allergenicity of non-digestible proteins expressed as
plant-pesticides was also the subject of a February 29, 2000, FIFRA
Scientific Advisory Panel (SAP) meeting (65 FR 5636) (FRL-6490-6). The
SAP report was issued on June 29, 2000 and the SAP ``* * * agreed that
based on the available data, there is no evidence to indicate that
Cry9C is or is not a potential food allergen.''
In September of this year, the Cry9C DNA was first detected in
processed food made from corn, indicating that Star-Link corn had been
used directly in it's manufacture, contrary to the restrictions on the
Aventis registration for StarLink corn. Following confirmation of this
detection, the food product in which the Cry9C DNA had been detected
was recalled by the manufacturer. Additional detections and recalls
followed. On October 12, 2000, EPA announced that Aventis, in response
to the Agency's strong urging, had requested voluntary cancellation of
its registration for StarLink corn. Available information indicates
that some portion of the 1999 StarLink crop entered the human food
supply, but there is uncertainty about how much. Due to concerns that
StarLink corn from the 2000 growing season might also directly enter
the food supply, the U. S. Department of Agriculture took steps to
bring all available StarLinkTM corn under its control. While these
efforts continue, to date, USDA has successfully located and imposed
controls on at least 88% of the 2000 StarLink crop; the government is
confident that this portion of the 2000 StarLink corn crop is being
handled so that Cry9C DNA and protein will not enter the human food
supply. Nevertheless, there remains concern about the potential
presence of the Cry9C protein in human food.
2. Aventis submission concerning allergenicity. Aventis has
expressed its continuing interest in an exemption for the presence of
Cry9C (DNA and protein) in human food. Given the actions that assure no
future planting of StarLink corn, however, Aventis has narrowed the
scope of its original petition. While the original petition requested
an exemption covering both the Cry9C DNA and Cry9C protein in all food
commodities, this submission limits the request only to foods made from
StarLink corn. In addition, Aventis has asked that the exemption be
granted only for a limited time of 4 years, which time, Aventis
contends, is necessary to allow all processed foods potentially made
from StarLink corn grown in 1999 or 2000 to pass through the channels
of trade.
To support its contention that Cry9C is safe for human consumption
for this period, Aventis has submitted new information regarding the
potential allergenicity of the Cry9C protein that may be present in
StarLink corn. The Aventis submission contains an
``Introduction'' which appears to summarize the contents of the
remainder of the document. This Introduction, which does not reflect
the Agency's position, is reprinted below.

Introduction from Aventis Submission

A. Background

StarLink corn was registered in 1998 for use by the
U.S. Environmental Protection Agency (EPA) under the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) for use as
animal feed and for industrial uses (production of ethanol, for
example). In granting that registration, EPA concluded that Cry9C
protein and related DNA met the safety standard under the FQPA for
use in field corn for animal feed use. That is, EPA

[[Page 65248]]

concluded that ``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'' (U.S. EPA Bt
Plant-Pesticides Biopesticides Registration Action Document, page
IIB18, EPA Scientific Advisory Panel (SAP) website, October 2000
science assessment document). The EPA and the EPA's SAP were not
able to conclude that the Cry9C protein was or was not an allergen
(FIFRA SAP Report, Session I-A Set of Scientific Issues being
Considered by the Environmental Protection Agency Regarding: Food
Allergenicity of Cry9C Endotoxin and other Non-digestible Proteins,
page 8, June 2000) and, thus, registration for human food use has
not yet been granted.
StarLink corn is a variety of corn modified through
traditional and well-recognized techniques of genetic modification
to contain the plant-pesticide Bacillus thuringiensis (``Bt'')
subspecies toliworthi Cry9C protein and the genetic material
necessary for the production of the protein (DNA). Bt proteins have
insecticidal properties and have been used commercially for more
than 30 years. Among these products are microbial sprays (Agree,
XenTari) with the Cry9B protein, which is highly homologous with the
Cry9C protein. Corn plants with the Bt protein have been widely and
safely used for a number of years. These products thus have a long
history of safe use.
Pursuant to the registration, StarLink corn was
planted in 1998, 1999 and 2000. Approximately, 10,000 acres were
planted in 1998, 250,000 acres were planted in 1999, and 350,000
acres were planted in 2000 out of the approximately 80,000,000 acres
of corn planted in the United States in each of those years.
Although StarLink corn was not registered for use in human
food, it now appears that through means not well known, not all of
the corn has been kept within the scope of the registered uses
(animal feed and non-food industrial uses). The significance to
human health of the potential presence of the Cry9C protein and/or
the DNA in human food is the subject of this analysis. The analysis
relies on the best available data and information and conservative
assumptions to assess the potential risks to human health, if any.

B. Approach of the Analysis

Human health assessments typically involve an evaluation of the
potential hazard of the material in question and an evaluation of
the magnitude of potential exposure to the material. The analysis
set forth in this document follows that approach.
First, it identifies the material of potential concern. In the
case of StarLink corn, the only component of the corn that
presents any potential for human health concern is the Cry9C protein
and, only then, with regard to the potential for it to cause an
allergic reaction in sensitized individuals. The EPA stated that
there are no issues relative to the safety of food containing
StarLink other than the potential allergenicity issue.
Concerning the allergenicity question, this assessment provides
a comprehensive review of all available information and data and
concludes that Cry9C is not an allergen.
After addressing the data and information pertinent to
assessing the question of whether the Cry9C protein is likely to be
an allergen, the analysis then turns to an assessment of the
potential amount of the protein to which humans might be exposed.
This analysis takes into account available information about:
(1) The amount of StarLink corn planted in 1999 and
2000 and the known or probable disposition of that corn.
(2) Quantity of Cry9C protein in corn.
(3) The quantity of corn contained in different food products.
(4) The fate and disposition of Cry9C protein in food.
(5) Quantity of various foodstuffs which contain corn consumed
by various population subgroups.
(6) Other relevant data.
This assessment considers the risk of adverse allergic
responses as a result of a very low level and temporary dietary
exposure to Cry9C protein. The strongly supported conclusion is that
Cry9C is not an allergen. Furthermore, the assessment strongly
concludes that even if Cry9C protein were allergenic, the low level
and temporary exposures would neither sensitize individuals nor
elicit an allergic response in sensitized individuals. The full
basis for these conclusions is set forth below.

C. Context for the Assessment

In order to evaluate properly the potential human health
consequences of the presence of Cry9C protein in human food, one
must understand how corn is harvested and how it moves through
various steps in the distribution chain before it is ultimately used
in the production of food for human consumption. With that
information, it becomes apparent that there is substantial dilution
at each stage of the movement of corn from the farm to the table. To
put it differently, the corn from one field or farm is commingled at
each stage of the process with corn from other fields and farms.
This section sets forth a brief summary of that information. A
full explanation of whole corn handling and grain processing at dry
mills is contained in Appendix 1, Corn Handling and Grain Handling
Discussion prepared by the North American Millers Association and
the National Feed and Grain Association.
Whole corn handling operations from farm to elevator. Virtually
all farmers harvest corn with a combine equipped with a corn header
and transfer the harvested grain from the combine to a truck to
deliver either to on-farm storage, a feedlot, or a commercial grain
elevator. Farm trucks today typically hold 200 to 800 bushels with
the average size about 400 bushels.
When the grain is delivered to a local elevator, it is dumped
into a pit. From the pit, the grain is normally conveyed via a
bucket elevator to the top of grain storage bins where it is dropped
to the bottom of the bin, or onto other grain. Bin sizes at country
elevators generally range from 10,000 bushels to 1,000,000 bushels
with an average of 70,000 to 80,000 bushels.
Throughout this grain handling process, there is a continuous
blending and commingling of the corn from any one farm. The farm
truck often carries corn taken from different fields on the farm.
When the farm truck arrives at the elevator at harvest, it is
frequently one of many trucks in line to dump. In the binning of the
grain, the contents of each truck are dumped on top of each other in
continuous fashion.
As grain is dropped from the top of storage bins at the
elevator, the grain forms an inverted conical shape, as the grain
enters at the center and flows out to the sides of the bin. There is
a ``layering'' effect of the grain from each individual truck.
When the grain is drawn from the bottom of the bin, a different
flow pattern develops. The grain flowing out will form a ``core'' in
the center. The center portion of the grain bin flows out first,
then a cone develops, with the upper portions of the grain flowing
out toward the early part of the removal process. As the bin
empties, the grain at the sides of the bins starts to flow out of
the bottom.
All the truck deliveries used to fill the bin are commingled in
the storage/handling process. The degree of mixing of the grain will
depend in part on the point at which the truck was dumped.
Commingling further occurs as elevators often draw from multiple
bins in order to ``blend'' grain for loading into one transport
conveyance to meet quality specifications of different customers.
If an average farm truckload of 400 bushels of pure
StarLink corn were to be delivered to an elevator and
placed into even a small 10,000 bushel bin, a commingling/dilution
of that grain on the order of 3 to 5 times is a conservative
expectation, with 3 probably a ``worst case'' situation (Appendix 1,
Corn Handling and Grain Handling Discussion prepared by the North
American Millers Association and the National Grain and Feed
Association).
Grain processing at dry mills. Grain is delivered from
elevators to dry corn mills via trucks or rail cars. Trucks
typically haul 1,000 bushels with rail cars holding about 3,500
bushels. The initial receiving process is much like that at the
elevator, dumping into a pit and elevating grain into storage bins,
which hold the grain until it enters the processing stream.
Most dry corn mills are continuous process (rather than batch).
Because the grain in a milling operation is being continuously mixed
through tempering, milling, and handling, the degree of dilution at
any one stage is probably much greater than the factor of three,
considered to be the ``worst case'' at the elevator. Assuming
conservatively that there are only seven handling and processing
operations, each of which is assumed to dilute the grain by a factor
of three, suggests that one truckload of pure StarLink
corn would be diluted by several orders of magnitude, prior to
reaching the food processor or consumer.
Wet milling. Corn is received at wet milling plants via truck,
railcar, or barge. Corn is stored at wet mills in a manner similar
to dry mills or grain elevators.
The corn wet milling process separates corn into four basic
components: starch, germ, fiber and protein. There are five basic

[[Page 65249]]

steps to accomplish this process. All processes in corn wet milling
are continuous (rather than batch).
Incoming corn is inspected and cleaned. It is then steeped in a
dilute sulfurous acid solution for 30 to 40 hours. This results in
the breaking of the starch and protein bonds. The next step in the
process involves coarse grind, which separates the germ from the
rest of the kernel. Corn germ is subject to mechanical and solvent
extraction to remove oil, which is then refined through degumming,
alkali treatment, bleaching, winterization, and vacuum steam
stripping deoderization. The remaining slurry consisting of fiber,
starch and protein is finely ground and screened to separate the
fiber from the starch and protein. Fiber is combined with the water
from corn steeping to produce corn gluten feed. The remaining starch
and gluten are separated into hydrocyclones. The separated gluten is
dried to produce corn gluten meal. The remaining starch is
repeatedly washed in fresh water. Water from this washing step flows
back through the process countercurrently to the flow of corn. The
starch is then converted to sweetners or fermentation products or
dried and packaged as starch (Blanchard, 1992). Of the wet milled
corn, approximately 60 percent is directed toward sweetner
production, 25 percent toward alcohol production, and 15% toward
starch production. In the latter case 80 percent is directed toward
industrial purposes while the remaining 20 percent is used in food
starches (Personal communication, Corn Refiners Association).
As in the case of the dry milling discussion, commingling of
corn occurs. It is estimated that one truckload of pure
StarLink corn would be diluted by several orders of
magnitude, prior to reaching the food processor or consumer. This
extensive processing likely leads to, at least, degradation of
protein.

D. Safety of Cry9C DNA and DNA Generally

With respect to the safety of Cry9C DNA and DNA in general, EPA
has concluded that:
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
components of food. These ubiquitous nucleic acids as they appear in
the subject plant pesticide have been adequately characterized by
the applicant and supports (sic) EPA's conclusion that no mammalian
toxicity is anticipated from dietary exposure to the genetic
material necessary for the production of the Cry9C protein. (63 FR
28259, May 22, 1998).
There is an EPA proposed exemption from the requirement of a
tolerance for nucleic acids produced in plants as part of a plant-
pesticide (Plant Pesticides; Subject to the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug,
and Cosmetic Act (FFDCA): Proposed Rule, 59 FR 60505, November 23,
1994). This proposal states:
Residues of nucleic acids produced in living plants as part of
a plant-pesticide active or inert ingredient, including both
deoxyribonucleic acid and ribonucleic acids, are exempt from the
requirement of a tolerance.
More recently, EPA confirmed its views concerning the safety of
nucleic acid in its background materials from the October 18-20,
2000 SAP meeting; Biopesticides Registration Action Document: Bt
Plant-Pesticides (http://www.epa.gov/scipoly/sap/).
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.
In addition, the U.S. Food and Drug Administration (FDA) has
also concluded that DNA is generally recognized as safe (1992, FDA
Food Policy).
Based on these EPA and FDA statements, the presence of Cry9C
DNA in food is not relevant to the safety assessment of
StarLink corn because it is recognized as safe.

E. Assessment of Potential Toxicity of Cry9C Protein

Based on the history of the use of Bt microbial pesticides and
available toxicity data on Cry9C protein, it is reasonable to
conclude that, other than possible allergenicity, there are no
toxicity issues related to the food and feed use of Cry9C protein.
EPA concurs with that conclusion.
In the final rule establishing the exemption from the
requirement of a tolerance for Cry9C protein and genetic material in
feed EPA stated:
Bt microbial pesticides, containing Cry proteins other than
Cry9C, have been applied for more than 30 years in 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. (63 FR 28258, May 22, 1998).
The lack of acute oral toxicity of Cry9C protein is consistent
with the lack of toxicity and established safety of other Cry class
proteins previously approved for use by the Agency. Furthermore,
additional toxicity studies submitted to EPA support this conclusion
(MRID #44734302 and 44734303). Thus, general toxicity issues are not
considered further in this assessment.

F. Assessment of Potential Allergenicity of Cry9C Protein

Given that DNA is recognized as safe, and that there are no
general toxicity issues related to Cry9C protein, the only remaining
issue relative to the safety of StarLink corn is the
potential allergenicity of Cry9C protein and the associated level of
potential risk.
In regard to the use of StarLink corn in animal feed,
the EPA concluded that
The Cry9C protein would not likely cause an allergic reaction
to man when used in feed corn because; (1) it was not from
allergenic sources and (2) the best available information indicates
that edible products derived from animals such as meat, milk and
eggs intended for human consumption, have not been shown to be
altered in their allergenicity due to changes in the feed stock
utilized. (U.S. EPA Bt Plant-Pesticides Biopesticides Registration
Action Document, page IIB18, EPA Scientific Advisory Panel website,
October 2000 science assessment document.)

This document provides a brief background on food allergy and,
drawing on new information and analysis, provides a risk assessment
regarding the potential allergenicity for StarLink corn
expressing Cry9C protein in food. A discussion of the new
information relevant to the allergenic potential of the Cry9C
protein is also included. Based on a review of all available
information and data, this assessment concludes that there is a
reasonable certainty that Cry9C protein is not an allergen, and is
not likely to become an allergen even if there were long-term
consumption.
In an independent review by Dr. S.L. Hefle of the Food Allergy
Research and Resource Program, University of Nebraska, Dr. Hefle
concluded that ``the data shared by Aventis, taken in total, while
not conclusive provide evidence that (sic) of low probability of
allergenicity of Cry9C'' (Appendix 2). A written statement submitted
by Dr. S.L. Taylor of the same organization to EPA's SAP (October
20, 2000) supports this conclusion (Appendix

G. Food Allergens and the Use of the Peanut for Comparison Purposes

Food allergy affects 1-2% of adults and 6-8% of children in the
United States (Sampson, H.A. et al., 1996; Metcalfe, D.D. et al.,
1996). Protecting food allergic patients from unexpected exposure to
food allergens is a critical priority. Food allergy assessments
ensure that food allergic patients are protected from unexpected
exposure to the allergens that might cause them harm. In addition,
food allergy assessment evaluates the potential of any new protein
to become a new allergen, and to create a newly sensitized
population.
In his written submission to the SAP (October 20, 2000), Dr.
S.L. Taylor stated that sensitization to foods requires multiple
exposures over an extended time period and at a relatively high
percentage of total protein content (Appendix 3).
For StarLink corn, there is no history of significant
consumption, and hence no real potential for allergic sensitization.
Furthermore, based on available data and information, the amount of
Cry9C protein that could potentially be present in corn products
would be present at levels far below those required to cause
sensitization. Therefore, it is reasonable to conclude that there
are not now and will not be in the future any ``at risk'' consumers.
Furthermore, the EPA has previously concluded that after more than
30 years of commercial use of microbial products containing a
variety of Cry proteins, including proteins from the Cry9 class, no
allergy has been attributed to Cry proteins (McClintock et al.,
1995; EPA, 1999).
Most allergenic proteins are present in levels of 1 to 40% of
the total protein of the allergenic food (Metcalfe, D.D., et al.,
1996; Yunginger, J.W et al., 1997; Li-Chan, E. and Nakai, S., 1989;
Murphy, P.A. and Resurrection, A.P., 1984; Kalinski, A. et al.,
1990; Carpentier, B.A. and Lemmel, D.E., 1984; Goldberg, R.B. et
al., 1983; Burks, A.W.

[[Page 65250]]

et al., 1992; Lotan, R. et al., 1975; Crouch and Sussex, 1981). In
contrast, there is an extremely low percentage (0.0129%) of the
Cry9C protein in StarLink corn grain (Table 1) (MRID
#45025701).
Even lower levels of Cry9C protein might be expected in foods
containing corn as an ingredient since, following dry or wet
milling, the protein is redistributed into individual commodities.
Thereafter food processing exposes the protein to a range of
potential degradation procedures which in some instances could
completely destroy the protein. In taco shells, for example, no
protein was detected (Preliminary Study for Detection of Cry9C
Protein in Taco Shells, FIFRA 6(a)(2) report, submitted to EPA on
10/16/00; MRID #44384301 and Analysis of Taco Shells for Cry9C
Protein submitted to EPA on 10/24/00).

Table 1.--Quantities of Cry9C Protein in Processed Commodities of StarLink Corn (CBH351) Expressed as
Percent of Crude Protein (MRID #45025701)
----------------------------------------------------------------------------------------------------------------
% Cry9C in Crude Protein
Crude Protein --------------------------
Process Commodity (All Types) in Transgenic Transgenic
Matrix (%)\a\ Unsprayed\b\ Sprayed\c\
----------------------------------------------------------------------------------------------------------------
Whole corn 8.9 - 10 0.0116 0.0129
----------------------------------------------------------------------------------------------------------------
Dry Mill Composite Grits 7 - 10.3 0.00861 0.0111
------------------------------------------------------------------------
Hull Material 8 0.0130 0.0163
------------------------------------------------------------------------
Meal 7.5 - 9.0 0.00989 0.0118
------------------------------------------------------------------------
Flour 5.2 - 7.8 0.0149 0.0147
------------------------------------------------------------------------
Solvent Extract Germ 12-25 0.0345 0.0298
------------------------------------------------------------------------
Crude Oil 0 NA\d\ NA
------------------------------------------------------------------------
Refined Oil 0 NA NA
----------------------------------------------------------------------------------------------------------------
Wet Mill Steepwater Concentrate 41-62 0.000034 0.000078
------------------------------------------------------------------------
Hull Material 8 0.00719 0.0146
------------------------------------------------------------------------
Gluten 41-60 0.00015 0.00011
------------------------------------------------------------------------
Starch 0.6 NA NA
------------------------------------------------------------------------
Solvent Extracted Germ 22.6 0.00056 0.00063
------------------------------------------------------------------------
Crude Oil 0 NA NA
------------------------------------------------------------------------
Refined Oil 0 NA NA
----------------------------------------------------------------------------------------------------------------
\a\ Range of data from Wolff, I.A. 1982; Ensminger, M.E. et al., 1990; McGregor, C.A. 1994.
\b\Unsprayed = Not treated with Liberty Herbicide
\c\Sprayed = Post emergent treatment with Liberty Herbicide
\d\NA - concentration was below limit of quantitation (LOQ) for these samples.

Since allergy to Cry9C protein does not already exist, the
extremely low level of Cry9C protein estimated to be consumed using
a reasonable, worst case exposure assessment leads to the conclusion
that the Cry9C protein present in StarLink corn is very
unlikely to become an allergen.
Peanuts account for the majority of fatal and near-fatal, food-
induced, anaphylactic reactions in the United States (Yunginger JW,
et al., 1988; Li, X-M, et al., 2000). About 1.5 million Americans
(Li, X-M, et al., 2000) are allergic to peanuts. Given the severity,
prevalence, and frequently lifelong persistence of peanut allergy, a
comparison of the potential allergenicity of a new protein, such as
Cry9C protein, with peanuts, one of the most potent known human food
allergens, provides an extremely conservative and protective
assessment.
This concludes the quotation of the Introduction from the
Aventis submission of October 25, 2000.
3. EPA Review Process--Public and External Scientific Peer Review.
EPA intends that its decisions involving biotechnology and public
health be based on the best available scientific information and
expertise. Moreover, EPA is committed to conducting its regulatory
decision-making in a transparent and participatory manner. Therefore,
EPA has decided it would be prudent to seek independent scientific peer
review of the information submitted by Aventis in support of the
petition for a time-limited exemption for Cry9C in human food, as well
as other available and relevant information.
The Agency has not yet determined who will participate in the peer
review group, and therefore cannot set a specific date or location for
the public meeting of the peer review group. Pending determination of
the availability of experts and meeting space, EPA expects to hold a
one or two day meeting during the week of November 27 - December 1 (or
possibly earlier)at a location in the Washington, DC metropolitan area.
EPA also recognizes that new data may become available in the coming
weeks, and the date of the public meeting may need to be adjusted to
allow full consideration of all relevant information. As is its
practice, EPA will develop and provide to the peer reviewers a
``charge,'' that is a series of questions raising scientific issues on
which EPA will seek the members' advice. EPA will also provide to the
members various documents as background for the consideration of these
issues.
By November 3, 2000, EPA will make available on the web and public
docket (PF-867B) the Agency's initial evaluation of the new
information, as well as announce the actual peer review meeting date/
location and charge to the peer review group. The Aventis

[[Page 65251]]

submission is available on our website as of the publication of this
notice.
In addition, consistent with its practice and because of the
widespread public interest in these particular matters, EPA is
providing an opportunity for the public to comment on the Aventis
submission. EPA will accept comments submitted on or before November
27, 2000. In order for comments to be considered in the peer review
process, EPA does not anticipate granting any requests for an extension
of time to comment. As discussed above, during the comment period, EPA
also expects to make available additional information that it will be
providing to the scientific peer review group. The public is welcome to
comment on these materials as well. Finally, EPA will make any public
comments available to the members of the scientific peer review group.
In addition, anyone having information concerning any allegations
of adverse effects in humans from ingestion of food that may have
contained StarLink corn should submit such information for
consideration by the government. This information should be sent to:
Food and Drug Administration, Office of Field Programs, Division of
Enforcement Programs, Outbreak Coordinaiton Staff, HFS-605, 200 C St.,
SW., Washington, DC 20204. FDA will share this information with EPA as
soon as it is received.

B. What is the Agency's Authority for Taking this Action?

The Agency is soliciting input to aid in determining whether there
is a reasonable certainty of no harm for the proposed amendment of the
existing exemption from the requirement of a tolerance under the
Federal Food, Drug and Cosmetic Act (FFDCA). EPA is also acting under
the authority of the Federal Insecticide, Fungicide, and Rodenticide
Act (FIFRA).

List of Subjects

Environmental protection, Pesticides and Pests.

Dated: October 27, 2000.
Susan B. Hazen,
Acting Deputy Director, Office of Pesticide Programs.

[FR Doc. 00-28076 Filed 10-27-00; 4:39 p.m.]
BILLING CODE 6560-50-S

AGENCY: Environmental Protection Agency (EPA).

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