[Federal Register Volume 65, Number 86 (Wednesday, May 3, 2000)]
[Notices]
[Pages 25717-25721]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-11033]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-935; FRL-6553-2]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
for Certain Pesticide Chemicals in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.

DATES: Comments, identified by docket control number PF-935, must be 
received on or before June 2, 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.C. of the ``SUPPLEMENTARY INFORMATION.'' To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-935 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Linda Hollis, EPA 
Biopesticides and Pollution Prevention Division (7505C), Office of 
Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg., 
1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: 
(703) 308-8733; e-mail address: <a href="/cdn-cgi/l/email-protection#89e1e6e5e5e0faa7e5e0e7ede8c9ecf9e8a7eee6ff"><span class="__cf_email__" data-cfemail="365e595a5a5f45185a5f5852577653465718515940">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

 
------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
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 Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'' 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 record for 
this action under docket control number PF-935. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, 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 Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal

[[Page 25718]]

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-935 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, Ariel Rios Bldg., 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 Highway, 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#026d72722f666d61696776426772632c656d74"><span class="__cf_email__" data-cfemail="bad5caca97ded5d9d1dfcefadfcadb94ddd5cc">[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-935. 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 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 identified 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. Make sure to submit your comments by the deadline in this 
notice.
    7. 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. What Action is the Agency Taking?

    EPA has received a pesticide petitions as follows proposing the 
establishment and/or amendment of regulations for residues of certain 
pesticide chemicals in or on various food commodities under section 408 
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that these petitions contain data or information 
regarding the elements set forth in section 408(d)(2); however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data support granting of the petitions. Additional data 
may be needed before EPA rules on the petitions.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: April 21, 2000.
Kathleen D. Knox,
Acting Director, Biopesticides and Pollution Prevention Division, 
Office of Pesticide Programs.

Summaries of Petitions

    The petitioner summaries of the pesticide petitions are printed 
below as required by section 408(d)(3) of the FFDCA. The summaries of 
the petitions were prepared by the petitioners and represent the view 
of the petitioners. The petition summaries announce the availability of 
a description of the analytical methods available to EPA for the 
detection and measurement of the pesticide chemical residues or an 
explanation of why no such method is needed.

I. AgriPhi, Inc.

OF6111

    EPA has received pesticide petition 0F6111 from AgriPhi, Inc., P.O. 
Box 4296, Logan, UT 84323-4296, proposing pursuant to section 408(d) of 
the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to 
amend 40 CFR part 180 by establishing a tolerance for residues of the 
microbial pesticide bacteriophages.
    Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended, 
AgriPhi, Inc. has submitted the following summary of information, data, 
and arguments in support of their pesticide petition. This summary was 
prepared by AgriPhi, Inc. and EPA has not fully evaluated the merits of 
the pesticide petition. The summary may have been edited by EPA if the 
terminology used was unclear, the summary contained extraneous 
material, or the summary unintentionally made the reader conclude that 
the findings reflected EPA's position and not the position of the 
petitioner.

A. Product Name and Proposed Use Practices

    AgriPHAGE is for the treatment of bacterial plant diseases, for 
example, bacterial spot in tomato and pepper and bacterial speck in 
tomato.

B. Product Identity/Chemistry

    1. Identity of the pesticide and corresponding residues. The major 
component of AgriPHAGE is water (>96%). Active ingredient, 
bacteriophages (phages), isolated from plant debris or soil is less 
than 2%. Remaining culture media ingredients are food grade such as 
peptone and brewer's yeast. Phages are inactivated within 24-48 hours 
after application to plants or soil. Inactivated phages are 
biodegradable and broken down by hydrolases secreted from soil flora or 
animals including humans. End products are recycled as nutrients for 
soil inhabitants, both animals and plants. No residue remains in the 
environment or on harvested fruit.
    2. Magnitude of residue at the time of harvest and method used to 
determine

[[Page 25719]]

the residue. Remaining culture media ingredients are food grade such as 
peptone and brewer's yeasts. Phages are inactivated within 24-48 hours 
after application to plants or soil.
    3. Analytical method. Phages are inactivated within 24-48 hours 
after application to plants or soil. Inactivated phages are 
biodegradable and broken down by hydrolases secreted from soil flora or 
animals to include humans. End products are recycled as nutrients for 
soil inhabitants, both animals and plants. No residue in the 
environment or on harvested fruit.

C. Mammalian Toxicological Profile

    Phages are ubiquitous, naturally-occurring entities found in soil, 
water, and in association with animals, including humans, and plants. 
The specific mode of action of the active component of AgriPHAGE 
mixtures is such that these bactericides are effective only against the 
bacterial pathogens which is target. Phages are species-specific, and 
do not attack other beneficial soil bacteria. There is no evidence for 
non-selective infection. Thus, non-target organisms, such as fish and 
wildlife are not affected.

D. Aggregate Exposure

    1. Dietary exposure--i. Food. Humans and other animals consume 
phages when they eat food. For example, humans ingest phages when they 
eat raw produce. For example, 1,000 (10<SUP>3</SUP>) to 5 x 
10<SUP>5</SUP> phages can be isolated routinely per gram (g) of high 
quality cheese. Pathogenic microorganisms are often found in foods; 
therefore, it is not surprising that E. coli and coliphages have been 
found in 11 of 12 foods purchased at retail markets. Ten purchases of 
each of the 12 foods were made. All 10 of fresh ground beef purchases 
were contaminated with E. coli, and all 10 contained coliphages. In 
addition to ground beef, E. coli and coliphages were found in fresh 
chicken, fresh pork, fresh oyster, fresh mushrooms, lettuce, chicken 
pot pie, biscuit dough, deli loaf, deli roasted turkey and package 
roasted chicken. Another example of phages in food has been 
Propionibacterium freundenreichii phage found in a concentration as 
high as 1.4 x 10<SUP>6</SUP>/gm of swiss cheese.
    ii. Drinking water. Animals are exposed daily to phages in water. 
Up to 2.5 x 10<SUP>8</SUP> phages/mL have been found in a natural 
unpolluted Norwegian lake. Investigators estimated that as much as one-
third of bacterial population could experience a phage attack each day. 
Without viruses to keep some microbial growth under control, microbes 
could have devastating effects on the environment.
    2. Non-dietary exposure. 4.0 x 10<SUP>7</SUP> infectious phage PFU/
gm of soil using Bacillus stearothermophilus as a host have been 
reported.

E. Cumulative Exposure

    Since phages are ubiquitous, naturally-occurring entities found in 
soil, water and in association with animals, including humans and 
plants and the fact that phages are inactived within 24-48 hours after 
application and the inactivated phages are biodegradable, no cumulative 
exposure with other compounds is expected.

F. Safety Determination

    1. U.S. population. Phages have been used as therapuetic agents and 
are active against bacteria of many human diseases such as anthrax, 
bronchitis, diarrhea, scarlet fever, typhus, cholera, diphtheria, 
gonorrhea, paratyphus, bubonic plague, and osteomyelitis.
    Hundreds of millions of persons have received live virus vaccines 
contaminated with phages. Contamination was found in polio, measles, 
mumps, and rubella vaccines. Recipients of contaminated vaccines showed 
no evidence of adverse reactions to phages. Because of concern about 
safety of phage contaminated vaccines, isolated phages from a vaccine, 
cultured to high titers and injected into 6-8 week old monkeys showed 
no adverse effects. Therefore, it is concluded that phage contaminating 
vaccines for humans posed no real threat to public health.
    2. Infants and children. Phages have been used as therapuetic 
agents and are active against bacteria of many human diseases such as 
anthrax, bronchitis, diarrhea, scarlet fever, typhus, cholera, 
diptheria, gonorrhea, paratyphus, bubonic plague, and osteomyelitis.
    Hundreds of millions of persons have received live virus vaccines 
contaminated with phages. Contamination was found in polio, measles, 
mumps, and rubella vaccines. Recipients of contaminated vaccines showed 
no evidence of adverse reactions to phages. Because of concern about 
safety of phage contaminated vaccines, isolated phages from a vaccine, 
cultured to high titers and injected into 6-8 week old monkeys showed 
no adverse effects. Therefore, it is concluded that phage contaminating 
vaccines for humans posed no real threat to public health.

G. Effects on the Immune and Endocrine Systems

    Phages have been used as therapuetic agents and are active against 
bacteria of many human diseases such as anthrax, bronchitis, diarrhea, 
scarlet fever, typhus, cholera, diptheria, gonorrhea, paratyphus, 
bubonic plague, and osteomyelitis.
    Hundreds of millions of persons have received live virus vaccines 
contaminated with phages. Contamination was found in polio, measles, 
mumps, and rubella vaccines. Recipients of contaminated vaccines showed 
no evidence of adverse reactions to phages. Because of concern about 
safety of phage contaminated vaccines, isolated phages from a vaccine, 
cultured to high titers and injected into 6-8 week old monkeys showed 
no adverse effects. Therefore, it is concluded that phage contaminating 
vaccines for humans posed no real threat to public health.

H. Existing Tolerances

    There are no existing tolerances for bacteriophages.

I. International Tolerances

    There are no known International Tolerances for bacteriophages.

II. Monsanto Company

PP 0E6066

    EPA has received a pesticide petition PP 0E6066 from Monsanto 
Company, 700 Chesterfield Parkway North, St. Louis, MO 63198, proposing 
pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 
CFR part 180 to establish an exemption from the requirement of a 
tolerance for the plant pesticide <greek-b>-D-glucuronidase (GUS) as a 
plant-incorporated protectant formulation inert ingredient, as 
expressed in plants in or on all raw agricultural commodities.
    Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended, 
Monsanto Company has submitted the following summary of information, 
data, and arguments in support of their pesticide petition. This 
summary was prepared by Monsanto Company and EPA has not fully 
evaluated the merits of the pesticide petition. The summary may have 
been edited by EPA if the terminology used was unclear, the summary 
contained extraneous material, or the summary unintentionally made the 
reader conclude that the findings reflected EPA's position and not the 
position of the petitioner.

[[Page 25720]]

A. Product Name and Proposed Use Practices

    <greek-b>-D-glucuronidase (GUS) is proposed for use as a plant-
incorporated protectant formulation inert ingredient. The GUS protein 
belongs to Family 2 of glycosyl hydrolases and catalyzes the hydrolysis 
of a range of glycosides, including p-nitrophenyl-<greek-b>-D-
glucuronide, a chemical which is not naturally occurring. When added to 
the plant, hydrolysis of this chromogenic compound releases a blue dye 
that functions as a visible scorable marker in plant transformation 
processes. The glucuronide conjugation activity of this protein has 
been thoroughly studied and the protein is widely prevalent in plants 
and microbes. GUS has no pesticidal activity.

B. Product Identity/Chemistry

    1. Identity of the pesticide and corresponding residues. The 
<greek-b>-D-glucuronidase gene, uidA, also known as gus or gusA gene, 
is derived from Escherichia coli strain K12. This gene encodes for the 
protein <greek-b>-D-glucuronidase (GUS). The E. coli-derived GUS 
protein expressed by genetically modified plants is 99.8% homologous 
and functionally equivalent to the native E. coli GUS protein. This 
change does not negatively affect the enzymatic activity of the 
protein. The plant-produced GUS protein is essentially equivalent to 
the native GUS protein, as determined by comparable molecular weights, 
immunoreactivity, amino acid sequences enzymatic activity. The GUS 
protein was originally isolated from E. coli present in mammals. E. 
coli is ubiquitous in the digestive systems of vertebrates, including 
humans, where primary glucuronidation functions in the liver. GUS is 
present in beef and in a number of invertebrate species, including 
nematodes, molluscs, snails, and insects. GUS activity has also been 
detected in over 50 plant species and in various tissues including 
embryo, fruit, seed coat and endosperm. These species include a number 
of human food sources, including potato, apple, almond, rye, rhubarb, 
and sugar beet.
    2. Magnitude of residue at the time of harvest and method used to 
determine the residue. A validated enzyme-linked immunosorbent Assay 
(ELISA) was performed to estimate the GUS protein levels in cotton leaf 
and seed tissue samples. Samples were collected from eight field 
locations in the United States during 1998 field trials. These field 
sites provided a variety of environmental conditions representative of 
regions where cotton is grown commercially. Mean cottonseed tissue 
levels of GUS protein in the two events ranged from 58.78 <greek-m>/g 
to 137.57 <greek-m>/g.
    3. Analytical method. Monsanto is requesting an exemption from the 
requirement of a tolerance and has also requested that the requirements 
for residue data be waived for GUS protein in all raw agricultural 
products. Analytical methods for the detection and measurement of the 
GUS protein are therefore not necessary.

C. Mammalian Toxicological Profile

    The mammalian health and safety of the GUS protein is based on a 
history of safe consumption by mammals, animal toxicity testing of the 
native GUS protein, and results of in vitro and in vivo studies of the 
protein expressed in plants. The history of safe use of the GUS protein 
is extensive. Exposure of humans to the GUS protein is commonplace 
through intestinal epithelial cells and intestinal microflora, 
bacterial exposure and in numerous foods containing the GUS protein 
with no known harmful effects. Previous feeding studies in humans and 
animals with large doses of E. coli strain K12 have also demonstrated 
the safety of the GUS protein, since no adverse effects were observed. 
In vitro and in vivo studies of the GUS protein derived from plants 
were conducted to confirm the safety of the protein; these studies 
included digestion in simulated gastric and intestinal fluids, an acute 
oral mouse toxicity study, and sequence homology studies on the GUS 
protein relative to proteins of toxicologic or allergenic concern. The 
GUS protein degraded rapidly when added to simulated gastric and 
intestinal fluids (SGF and SIF), which simulate human digestion, as 
assessed by both western blot analysis and enzymatic activity assays. 
Within 15 seconds of exposure to SGF, GUS protein was not detectable by 
western blot or enzymatic activity. After 2 hours in SIF, the protein 
had lost approximately 91% of its original enzymatic activity. Based on 
these results, it is concluded that the GUS protein, if ingested by 
humans, will readily degrade in the digestive tract where GUS protein 
is naturally present.
    Acute administration was considered appropriate to assess the 
safety of GUS, since proteins that are toxic typically act via acute 
mechanisms. The GUS protein used in this evaluation was over-produced 
and purified from Escherichia coli, characterized and administered by 
gavage to mice in an acute toxicity test at doses of 0, 0.69, 6.9, and 
69 mg/kg body weight. There were no treatment-related adverse effects 
in mice administered GUS protein by oral gavage at the highest dose 
tested. These results demonstrated that the GUS protein is non-toxic to 
mice. Previous feeding studies with large doses of Escherichia coli 
strain K12 containing GUS in humans and animals have also demonstrated 
the safety of the GUS protein since no adverse effects were observed.
    Although large quantities of a variety of proteins are consumed by 
humans each day, rarely do any of these tens of thousands of proteins 
elicit an allergenic response. Although there are no predictive assays 
available to assess the allergenic potential of proteins, the 
physicochemical profile of the protein provides a basis for assessing 
the allergenicity by comparing them to known protein allergens. A key 
parameter contributing to the allergenicity of food allergens appears 
to be stability to gastrointestinal digestion, especially stability to 
acid proteases like pepsin found in the stomach. Protein allergens must 
be stable to the peptic digestion and the acid conditions of the 
stomach system if they are to reach and pass through the intestinal 
mucosa where an immune response can be initiated. GUS is rapidly 
digested in SGF/SIF. Another significant factor contributing to the 
allergenicity of proteins is their high concentrations in foods that 
elicit an allergenic response. The uidA gene was not obtained from a 
source known to be allergenic or toxic. To confirm the lack of any 
allergenic or toxic effects of the GUS protein as shown by the history 
of safe consumption, the GUS protein sequence was compared to the 
sequences of proteins relevant to mammalian safety. Data bases of 
protein sequences associated with allergy, coeliac disease and toxicity 
were assembled from publicly available genetic data bases (Genbank, 
EMBL, PIR and SwissProt). The amino acid sequence of the GUS protein 
was compared using the FASTA sequence alignment tool. The GUS protein 
showed no structural homology to proteins relevant to human health.
    Therefore, the GUS protein has been demonstrated to be safe for 
consumption by both humans and animals by the natural occurrence of the 
GUS protein in the human gut and other organisms, including foods; 
mammalian safety as determined in toxicity studies of E. coli; rapid 
digestion in simulated gastric and intestinal fluids; lack of acute 
toxicity in mice; lack of allergenic potential and lack of homology 
with any known protein toxins.
    The genetic material necessary for the production of GUS as an 
inert ingredient are the nucleic acids (DNA) which comprise genetic 
material

[[Page 25721]]

encoding this protein and its regulatory regions. ``Regulatory 
regions'' are the genetic material that control the expression of the 
genetic material encoding the protein, such as promoters, terminators 
and enhancers. DNA is common to all forms of plant and animal life and 
the Agency has previously stated that they are not aware of an instance 
where these nucleic acids have been associated with toxic effects 
related to their consumption as a component of food. These ubiquitous 
nucleic acids, as they appear in the subject inert ingredient, have 
been adequately characterized. Therefore, no mammalian toxicity is 
anticipated from dietary exposure to the genetic material necessary for 
the production of the subject inert plant pesticidal ingredient.

D. Aggregate Exposure

    1. Dietary exposure--i. Food. The functional activity of the GUS 
protein has been thoroughly studied and the protein is present in a 
number of animals, plants and microbes. Considering that GUS is already 
present in both the environment and food, the presence of the GUS 
protein in transgenic plants is unlikely to pose additional health 
concerns for humans or animals. Additionally, the in vitro digestive 
fate data demonstrate that the protein is likely degraded by stomach 
digestion prior to passage to the intestinal tract. Finally, the GUS 
protein is degraded upon heating and looses its functional activity.
    ii. Drinking water. Transfer of the GUS protein to drinking water 
from genetically modified crops is highly unlikely given containment of 
the protein in plant cells and natural degradation upon plant 
senescence. However, if it were to occur, the levels would be 
insignificant compared to the levels of GUS protein produced by 
bacteria known to inhabit natural waters.
    2. Non-dietary exposure. Occupational exposure is anticipated to be 
minimal during handling, storage, transportation or disposal of 
transgenic plants containing the GUS protein, since the protein is 
contained within the cells of the plant. This containment also results 
in a lack of volatilization or movement.

E. Cumulative Exposure

    GUS belongs to a category of non-toxic proteinaceous substances 
that are not known to produce toxicological effects. The presence of 
the GUS protein in animals, plants and bacteria demonstrated a history 
of safe consumption of the protein in human food and animal feed 
supplies. Because there is no indication of mammalian toxicity caused 
by the GUS protein, there are no cumulative effects expected.

F. Safety Determination

    1. U.S. population. The toxicity profile for the GUS protein 
indicates essentially no risk from exposure to the overall U.S. 
population. Therefore, there is a reasonable certainty that no harm 
will result from aggregate exposure of the U.S. population, including 
infants and children, to the GUS protein and the genetic material 
necessary for its production. This includes all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.
    2. Infants and children. The functional activity of this protein 
has been thoroughly studied and the protein is present in plants, 
animals and microbes. Considering the widespread exposure to GUS, 
additional food sources containing the GUS protein are unlikely to pose 
health concerns for humans or animals, including infants and children. 
This is supported by a history of safe consumption of the GUS protein 
naturally occurring in food and confirmed by the lack of toxic effects 
in an acute mouse gavage study.

G. Effects on the Immune and Endocrine Systems

    No instances are known or reported of adverse reproductive or 
developmental effects to humans, domestic animals or wildlife as a 
result of exposure to the GUS protein or the microbial source of the 
uidA gene, Escherichia coli. The functional activity of this protein 
has been thoroughly studied and there is no known toxicological 
activity associated with this protein. Enzyme proteins are not known to 
interact or bind directly with the estrogen receptor, which would be 
necessary to produce endocrine effects. Further, there is little 
opportunity for systematic absorption of the GUS protein due to 
degradation upon heating and by digestive enzymes.

H. Existing Tolerances

    The registrant is not aware of any tolerances established for 
residues of GUS in raw agricultural commodities and or processed food/
feed.

I. International Tolerances

    The registrant is not aware of any Maximum Residue Levels (MRLs) 
established for GUS by the Codex Alimentarius Commission (CODEX).

[FR Doc. 00-11033 Filed 5-2-00; 8:45 am]
BILLING CODE 6560-50-F


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