65246 Federal Register / Vol. 65, No. 211 / Tuesday, October 31, 2000 / Notices

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.

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

Federal Register / Vol. 65, No. 211 / Tuesday, October 31, 2000 / Notices 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 nondigestible proteins expressed as plantpesticides (64 FR 74152, December 21,

1999) (FRL–6098–2). The evaluation of

potential human allergenicity of nondigestible proteins expressed as plantpesticides 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

65248 Federal Register / Vol. 65, No. 211 / Tuesday, October 31, 2000 / Notices

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 PlantPesticides 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 wellrecognized 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 onfarm 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

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

65250 Federal Register / Vol. 65, No. 211 / Tuesday, October 31, 2000 / Notices

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)

Process Commodity

Crude Protein (All

Types) in Matrix

(%)a

% Cry9C in Crude Protein

Transgenic

Unsprayedb

Transgenic

Sprayedc

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 NAd 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. bUnsprayed = Not treated with Liberty Herbicide cSprayed = Post emergent treatment with Liberty Herbicide dNA - 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

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