[Federal Register Volume 65, Number 211 (Tuesday, October 31, 2000)]
[Notices]
[Pages 65246-65251]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-28076]



[[Page 65245]]

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Part VI





Environmental Protection Agency





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

Federal Register / Vol. 65, No. 211 / Tuesday, October 31, 2000 / 
Notices

[[Page 65246]]


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ENVIRONMENTAL PROTECTION AGENCY

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


Assessment of Scientific Information Concerning 
StarLink<Register> 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<Register> 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: 
<a href="/cdn-cgi/l/email-protection#bdd5c8c9c9d2d393cdd5d4d1fdd8cddc93dad2cb"><span class="__cf_email__" data-cfemail="eb839e9f9f8485c59b838287ab8e9b8ac58c849d">[email protected]</span></a>.

 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: <a href="/cdn-cgi/l/email-protection#563926267b3239353d33221633263778313920"><span class="__cf_email__" data-cfemail="ddb2adadf0b9b2beb6b8a99db8adbcf3bab2ab">[email protected]</span></a>, 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<Register> 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<Register> 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<Register> 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<Register> 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<Register> 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<Register> 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<Register> 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<Register> 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<Register> 
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<Register> 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<Register> 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<Register> corn is the 
potential allergenicity of Cry9C protein and the associated level of 
potential risk.
     In regard to the use of StarLink<Register> 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<Register> 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<Register> 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<Register> 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<Register> 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<Register> Herbicide
\c\Sprayed = Post emergent treatment with Liberty<Register> 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<Register> 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


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