[Federal Register Volume 62, Number 122 (Wednesday, June 25, 1997)]
[Notices]
[Pages 34271-34276]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-16659]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-739; FRL-5721-7]


Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-739, must 
be received on or before July 25, 1997.
ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(7506C), Office of Pesticides Programs, Environmental Protection 
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments 
to: Rm. 1132, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically by following 
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential 
business information should be submitted through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). CBI should not be 
submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2. A copy of the comment that does not contain CBI must be submitted 
for inclusion in the public record. Information not marked confidential 
may be disclosed publicly by EPA without prior notice. All written 
comments will be available for public inspection in Rm. 1132 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: The regulatory action leaders listed 
in the table below:

------------------------------------------------------------------------
                                   Office location/                     
        Product Manager            telephone number          Address    
------------------------------------------------------------------------
Sheryl Reilly (PM 90).........  Rm. 5-W29, 5th Floor,   2800 Jefferson  
                                 CS-1, 703-308-8265 e-   Davis Hwy.,    
                                 mail:                   Arlington, VA  
                                 reilly.sheryl@epamail   22202          
                                 .epa.gov                               
Mike Mendelsohn (PM 90).......  Rm. 5-W44, 5th Floor,   Do.             
                                 CS-1, 703-308-8715 e-                  
                                 mail:                                  
                                 mendelsohn.mike@epama
il.epa.gov                             
Linda Hollis (PM 90)..........  Rm 5-J, 5th Floor, CS-  Do.             
                                 1, 703-308-8733 e-                     
                                 mail:                                  
                                 hollis.linda@epamail.
epa.gov                                
------------------------------------------------------------------------

SUPPLEMENTARY INFORMATION: EPA has received 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 supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-739] (including comments and data submitted 
electronically as described below). A public version of this record, 
including printed, paper versions of electronic comments, which does 
not include any information claimed as CBI, is available for inspection 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The official record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comment and data 
will also be accepted on disks in

[[Page 34272]]

Wordperfect 5.1 file format or ASCII file format. All comments and data 
in electronic form must be identified by the docket number (insert 
docket number) and appropriate petition number. Electronic comments on 
notice may be filed online at many Federal Depository Libraries.

List of Subjects

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

    Dated: June 12, 1997.

Janet L. Andersen,

Director, Biopesticides and Pollution Prevention Division, Office of 
Pesticide Programs.

Summaries of Petitions

    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 views of 
the petitioners. EPA is publishing the petition summaries verbatim 
without editing them in any way. The petition summary announces 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.

1. Kemira Agro Oy

PP 7F4137

A. Proposed Use Practices

    Registration of PRIMASTOP containing Gliocladium catenulatum Strain 
J1446 is being proposed for the following sites: Vegetables, herbs and 
spices, ornamentals, tree and shrub seedlings, turf, home and garden.
    PRIMASTOP is used for the control of damping-off, seed rot, root 
and stem rot, and wilt diseases caused by Rhizoctonia, Pythium, 
Phytophthora, Fusarium, Didymella, Botrytis, Verticillium, Alternaria, 
Cladosporium, Helminthosporium, Penicillium and Plicaria on vegetables, 
herbs, ornamentals and tree and forest seedlings grown in greenhouse or 
outdoors.
    PRIMASTOP can be incorporated in the growth substrate as a dry 
powder or as an aqueous suspension or applied by drenching, spraying or 
dipping.
    1. Incorporation into potting media.  The recommended rate for 
incorporation of PRIMASTOP in potting media is 5 to 30 oz/
yd3 (0.2 to 1 g/L) of growing media. If the incorporation is 
done with the aqueous suspension, mix 3.5 oz (100 g) of PRIMASTOP 
powder in 1.0 gallon (or 4 L) of water and carefully mix the suspension 
with the growth substrate (1.5-8.5 gal/yd3). Incorporation 
of PRIMASTOP can be followed with a drench application within 2 to 6 
weeks.
    2. Drench application. Drenching treatment can be done using a 0.2-
0.5% suspension. Seedling trays or beds can be drenched with PRIMASTOP 
at the recommended rate of 2 to 10 oz./100 ft2 (5-25 g/
m2). Drenching at sowing is recommended for vegetables 
(except for tomato and leek), herbs and ornamentals (except pansy) 
grown in peat or soil mixture. Drenching after emergence is recommended 
for tomato, leek, pansy and all seedlings grown in rockwool, such as 
cucumbers. Repeat treatment at transplanting.
    3. Foliar spray. PRIMASTOP can be sprayed or spread on the plant 
stems or foliar parts for control of Didymella or Botrytis with an 
aqueous suspension. Recommended concentration is up to 5%.
    4. Treatment of cuttings, bulbs or tubers. Cuttings, bulbs or 
tubers can be dipped in or sprayed with PRIMASTOP suspensionn before 
planting or storage. The product can also be incorporated in the 
storage mixture, such as sand or peat at a rate up to 1 g/L.

B. Product Identity/Chemistry

    1. Identity of pesticide and corresponding residues. The active 
ingredient in Primastop is Gliocladium catenulatum Strain J1446. The 
mechanism by which Gliocladium catenulatum Strain J1446 controls 
diseases appears to be enzymatic. Gliocladium catenulatum Strain J1446 
does not produce toxins or antibiotics. Further, Gliocladium 
catenulatum Strain J1446 is a naturally occurring microorganism. 
Gliocladium catenulatum is widespread in the environment.
    2. Magnitude of residue anticipated at the time of harvest and 
method used to determine the residue. No residues of Gliocladium 
catenulatum Strain J1446 are anticipated in treated crops at harvest. 
Subdivision M - Series 153A-3(a) indicates that ``if Tier I toxicology 
tests indicate no toxic or other harmful properties, then no residue 
data would be indicated.'' Studies with Gliocladium catenulatum Strain 
J1446 demonstrated low mammalian toxicity. No pathogenicity or 
infectivity was observed in any of the tests conducted with Gliocladium 
catenulatum Strain J1446. Further, Gliocladium catenulatum Strain J1446 
is a naturally occurring microorganism. Gliocladium catenulatum is 
widespread in the environment.
    3. Statement of why an analytical method for detecting and 
measuring the levels of the pesticide residue are not needed. 
Subdivision M - Series 153A-3(a) indicates that ``if Tier I toxicology 
tests indicate no toxic or other harmful properties , then no residue 
data would be indicated and thus a recommendation for an exemption from 
the requirement of a tolerance can be made.'' Studies with Gliocladium 
catenulatum Strain J1446 demonstrated low mammalian toxicity. No 
pathogenicity or infectivity was observed in any of the tests conducted 
with Gliocladium catenulatum Strain J1446. Further, Gliocladium 
catenulatum Strain J1446 is a naturally occurring microorganism. 
Gliocladium catenulatum is widespread in the environment.

C. Health and Safety

    Kemira Agro Oy conducted the required toxicology studies to support 
its petition for an exemption from the requirement of tolerance and 
associated registrations. The studies conducted indicate a low 
mammalian toxicity for Gliocladium catenulatum Strain J1446. No 
pathogenicity or infectivity was observed in any of the tests conducted 
with Gliocladium catenulatum Strain J1446. The mechanism by which 
Gliocladium catenulatum Strain J1446 controls diseases appears to be 
enzymatic. Gliocladium catenulatum Strain J1446 does not produce toxins 
or antibiotics.
    Toxicology data in support of the exemption from the requirement of 
a tolerance for Gliocladium catenulatum Strain J1446 included studies 
with the cell mass (technical) and with the formulated product as 
follows:
    1. Acute toxicity and/or pathogenicity.-- a. Gliocladium 
catenulatum Strain J1446 Cell Mass (Technical). i. Acute oral toxicity 
and pathogenicity in rats (acute oral LD50 > 4.04 to 5.86 
x  108 cfu/kg, clearance: < 3 days).
    ii. Acute pulmonary toxicity/pathogenicity in rats (acute pulmonary 
LC50 > 6.60 to 7.98  x  108 cfu/kg, clearance: < 7 days).
    iii. Acute intraperitoneal toxicity/pathogenicity in rats (acute 
intraperitoneal LD50 > 4.2  x  108 cfu/kg, clearance: < 7 
days).
    b. Gliocladium catenulatum Strain J1446 Formulation (Primastop). i. 
Acute oral LD50 toxicity in rats (> 2,000 mg/kg, EPA 
toxicity category III).
    ii. Acute dermal LD50 toxicity in rats (>2,000 mg/kg, 
EPA toxicity category III).

[[Page 34273]]

    iii. Acute dermal irritation in rabbits (minimal dermal irritant, 
EPA toxicity category IV).
    iv. Acute inhalation LC50 toxicity in rats (> 5.57 mg/L, 
EPA toxicity category V).
    v. Primary eye irritation (minimal eye irritant, EPA toxicity 
category IV).
    vi. Skin sensitization (sensitizer).
    vii. No hypersensitivity effects have been observed.
    c. The inert ingredients contained in the Gliocladium catenulatum 
Strain J1446 formulation, Primastop, are all minimal risk (List 4)(59 
FR 49400, September 28, 1994).
    2. Genotoxicity. Subdivision M Guidelines do not require the 
conduct of genotoxicity studies to support the registration of a 
microbial pest control agent, such as Gliocladium catenulatum Strain 
J1446.
    3. Reproductive and developmental toxicity. Subdivision M 
Guidelines do not require the conduct of reproductive and developmental 
toxicity studies to support the registration of a microbial pest 
control agent, such as Gliocladium catenulatum Strain J1446.
    4. Subchronic toxicity. Subdivision M Guidelines do not require the 
conduct of subchronic toxicity studies to support the registration of a 
microbial pest control agent, such as Gliocladium catenulatum Strain 
J1446.
    5. Chronic toxicity. Subdivision M Guidelines do not require the 
conduct of chronic toxicity studies to support the registration of a 
microbial pest control agent, such as Gliocladium catenulatum Strain 
J1446.
    Sufficient data exist to assess the hazards of Gliocladium 
catenulatum Strain J1446 and to make a determination on aggregate 
exposure, consistent with section 408(c)(2), for the exemptions from 
the requirement of a tolerance. The exposures, including dietary 
exposure, and risks associated with establishing the requested 
exemption from the requirement of a tolerance follows.

D. Threshold Effects

    Gliocladium catenulatum is a naturally occurring microorganism that 
is widespread in the environment. Both the cell mass (technical) and 
the formulation of Gliocladium catenulatum Strain J1446 demonstrated 
low toxicity. No pathogenicity or infectivity was observed in any of 
the tests conducted with Gliocladium catenulatum Strain J1446. No 
threshold effects were observed or are anticipated for Gliocladium 
catenulatum Strain J1446.

E. Non-threshold Effects

    Gliocladium catenulatum is a naturally occurring microorganism that 
is widespread in the environment. Both the cell mass (technical) and 
formulation of Gliocladium catenulatum Strain J1446 demonstrated low 
toxicity. No pathogenicity or infectivity was observed in any of the 
tests conducted with Gliocladium catenulatum Strain J1446. Non-
threshold effects were not observed nor are any anticipated for 
Gliocladium catenulatum Strain J1446.

F. Aggregate Exposure

    Gliocladium catenulatum is naturally occurring and widespread in 
the environment. The low toxicity and non-pathogenicity/infectivity of 
Gliocladium catenulatum Strain J1446 is demonstrated by the data 
summarized above. The product will be applied by incorporation into 
growing media and/or by drenching at seeding or in the early growing 
stages of the treated plants.
    1. Dietary exposure-- a. food. It is not anticipated that residues 
of Gliocladium catenulatum Strain J1446 will occur in treated raw 
agricultural commodities.
    b. Drinking water. It is not anticipated that residues of 
Gliocladium catenulatum Strain J1446 will occur in drinking water.
    2. Non-dietary exposure. The potential for non-occupational, non-
dietary exposure to the general population is not expected to be 
significant.

G. Cumulative Exposure

     There is no anticipated potential for cumulative effects of 
Gliocladium catenulatum Strain J1446 and other substances that have a 
common mechanism of toxicity. Clearance of Gliocladium catenulatum 
Strain J1446 from test species was < 3 days in two studies and < 7 days 
in a third study. Toxic effects produced by Gliocladium catenulatum 
Strain J1446 should not be cumulative with those of any other chemical 
compounds.

H. Determination of Safety for U.S. Population

    Gliocladium catenulatum Strain J1446 is a naturally occurring 
microorganism. Gliocladium catenulatum is widespread in the 
environment. The low toxicity of Gliocladium catenulatum Strain J1446 
is demonstrated by the data summarized above. Based on this 
information, the aggregate exposure to Gliocladium catenulatum Strain 
J1446 over a lifetime should not pose appreciable risks to human 
health. There is a reasonable certainty that no harm will result from 
aggregate exposure to Gliocladium catenulatum Strain J1446 residues. 
Exempting Gliocladium catenulatum Strain J1446 from the requirement of 
a tolerance should be considered safe and pose insignificant risk.

I. Determination of Safety for Infants and Children

    The toxicity and exposure data are sufficiently complete to 
adequately address the potential for additional sensitivity of infants 
and children to residues of Gliocladium catenulatum Strain J1446. There 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to Gliocladium catenulatum Strain 
J1446 residues.

J. Estrogenic Effects

    No specific tests have been conducted with Gliocladium catenulatum 
Strain J1446 to determine whether it may have an effect in humans that 
is similar to an effect produced by a naturally occurring estrogen or 
other endocrine effects. However, it is not likely that Gliocladium 
catenulatum strain J1446 would have estrogen or endocrine effects 
because:
    1. It is a naturally occurring microorganism. Gliocladium 
catenulatum is widespread in the environment.
    2. It has demonstrated low mammalian toxicity.
    3. No pathogenicity or infectivity was observed in any of the tests 
conducted with Gliocladium catenulatum Strain J1446.
    4. The mechanism by which Gliocladium catenulatum Strain J1446 
controls diseases appears to be enzymatic.
    5. Gliocladium catenulatum Strain J1446 does not produce toxins or 
antibiotics.

K. Existing Tolerances

    No tolerances or exemptions from the requirement of tolerance have 
been established or applied for domestically or internationally other 
that subject petition.

L. Environmental Fate

    Environmental fate data are not required to support the 
registration of a biopesticide unless results from Tier I studies 
indicate that risks would be expected from use of the product. 
Gliocladium catenulatum GStrain J1446 is a naturally occurring 
microorganism. Gliocladium catenulatum is widespread in the 
environment. Extensive literature searches revealed an absence of any 
ecological effects or environmental fate

[[Page 34274]]

data from Gliocladium catenulatum. (Sheryl Reilly)

2. Monsanto Company

PP 6E4657

A. Background Information and Use Profile

    The development of plant varieties containing useful new traits 
introduced by plant genetic engineering such as insect protection 
depends upon an effective means to select for the rare transformed 
plant cells containing the added gene. For example, a gene required for 
the production of an insecticidal protein in the plant tissue cannot be 
efficiently selected for several weeks after the transformation event 
as it does not, itself, provide a readily selectable property to the 
cell which carries it. Regenerating each cell from that transformation 
experiment to test for the presence of the gene would be both 
impractical and prohibitory, as the frequency that transformed cells 
are obtained is often as low as 1 in 10,000 or 1 in 100,000 of the 
cells treated (Fraley et al., 1984). Therefore, a selectable marker 
gene and a selective agent are used to identify the rare transformed 
cells for regeneration.
    A selectable marker gene allows a cell expressing that marker gene 
to grow in the presence of a selective agent by inactivating or 
neutralizing the agent which would otherwise inhibit the growth or kill 
the cell. The marker gene also permits tracking of linked traits that 
are difficult to identify at the cellular or whole plant level.
    For insect-protected corn plants, the gox gene was used as a 
selectable marker gene conferring tolerance to glyphosate. The 
glyphosate oxidoreductase (gox) gene from Achromobacter sp. strain LBAA 
(new genus Ochrobactrum anthropi) produces a protein (GOX) which 
degrades glyphosate. The GOX protein confers tolerance to glyphosate 
and provides a selectable marker used in initial laboratory stages of 
plant cell selection to identify plant cells containing agronomic genes 
of interest such as the cryIA(b) gene which imparts protection from 
certain lepidopteran insect pests.

B. Risk Assessment and Statutory Findings Toxicology Profile

    1. Data summary. Monsanto Company has requested an exemption from 
the requirement of a tolerance for glyphosate oxidoreductase (GOX) as a 
plant pesticide formulation inert ingredient. Included in the Monsanto 
submission to the EPA were several toxicology studies in support of the 
GOX protein as a pesticide formulation inert ingredient.
    The GOX protein used in these studies was produced in an E. coli 
over-expression system and partially purified. The GOX protein 
expressed in E. coli was characterized and shown to be substantially 
equivalent to the GOX expressed in insect-protected corn where it was 
utilized as a selectable marker protein.
    The following mammalian toxicity studies have been conducted to 
support this exemption from the requirement of a tolerance:
    a. A mouse acute oral gavage study was performed in which the No-
Observed-Effect-Level (NOEL) for toxicity of GOX protein administered 
as a single dose was considered to be 100 milligrams per kilogram (mg/
kg) (the highest tested target dose). The protein was administered by 
gavage to three groups of male and female mice at target dose levels of 
1, 10, and 100 mg/kg body weight. Appropriate hollow vector and vehicle 
controls were used. Mice were observed twice daily for signs of 
toxicity and food consumption was recorded daily. Food and water were 
provided ad libitum. All animals were sacrificed on post-dosing day 
seven and subjected to gross necropsy. Approximately 40 tissues were 
collected and saved for each animal in the test. There were no 
statistically significant differences in body weight, cumulative body 
weight or food consumption between the controls or GOX protein treated 
groups. No grossly observable pathologic changes were observed in mice 
at necropsy that were related to treatment.
    When proteins are toxic, they are known to act via acute mechanisms 
and at very low dose levels (Sjoblad, et al., 1992). The acute oral 
toxicity data submitted support the prediction that the GOX protein is 
non-toxic to humans.
    b. An in vitro digestive fate study of the GOX protein in simulated 
gastric and intestinal fluids demonstrated rapid protein degradation. 
In gastric fluid, the GOX protein degraded extremely rapidly; more than 
90% of the initially added GOX protein degraded after 15 seconds 
incubation as detected by western blot analysis. GOX enzymatic activity 
also dissipated readily; more than 96% of the added GOX activity 
dissipated after one minute incubation, the earliest time point 
measured.
    In intestinal fluid, GOX protein degraded rapidly; more than 90% of 
the initially added GOX protein degraded after 30 seconds incubation as 
detected by western blot analysis. GOX enzymatic activity also 
dissipated readily; more than 95% of the added GOX enzymatic activity 
dissipated after 60 minute incubation. The difference in dissipation of 
the enzymatic activity of GOX when compared to detection by western 
blot analysis suggests the antigenic sites on the GOX protein for the 
particular antibody used in this study were more sensitive to 
proteolytic degradation in simulated intestinal fluid under these 
conditions than is the functional active site of the GOX protein. The 
GOX protein degraded readily, though, as assessed by both western blot 
analysis and enzymatic activity.
    The results of this study established that the GOX protein and its 
associated functional activity will be efficiently degraded upon 
exposure to gastric and intestinal fluids in the mammalian digestive 
tract. Known protein allergens are often resistant to digestion.
    c. A homology assessment of the amino acid sequence of the GOX 
protein has been performed comparing this protein to known allergens or 
gliadin proteins. Monsanto has searched the amino acid sequences of the 
219 allergens present in public domain genetic databases (GenBank, 
EMBL, PIR, and SwissProt) for similarity to the amino acid sequences of 
the GOX protein using the FASTA computer program (Pearson and Lipman, 
1988). Monsanto concludes (i) that the gox gene introduced does not 
encode a known allergen, and (ii) that the introduced GOX protein does 
not share immunologically significant sequences with known allergens.
    The GOX protein is produced at low levels (ppm) by insect-protected 
corn plants and is contained within the cells of the corn plant. In 
documentation provided to the Agency, the range of GOX protein levels 
in insect-protected corn line samples as assessed using a validated 
ELISA specific to the GOX protein ranged from < 1.8 to 19.32 
g/g fresh weight (fwt) in leaf tissue, < 1.5 to 11.7 
g/g fwt in grain, and < 0.6 to 2.46 g/g fwt in whole 
plant tissue. Western blot analysis indicated that the GOX protein was 
not present in corn pollen.
    The genetic material encoding the GOX protein and the regulatory 
regions associated with the gene have been well characterized. Nucleic 
acids (DNA) is common to all forms of plant and animal life and there 
are no known instances of toxic effects related to their consumption. 
No mammalian toxicity is expected from dietary exposure to the genetic 
material necessary for the production of the GOX protein in corn.
    In summary, the safety of the GOX protein to mammals, including 
humans, was confirmed by demonstrating the rapid degradation of the GOX 
protein

[[Page 34275]]

under conditions which simulate mammalian digestion, by establishing 
the lack of toxicity to rodents in an acute gavage study and by 
establishing the lack of allergenic concerns.
    2. Acute toxicity. An acute mouse gavage study with GOX protein was 
performed to directly assess potential acute toxicity associated with 
this protein. No adverse effects were observed in mice dosed with GOX 
protein. Based on this study, in which the No-Observed-Effect-Level 
(NOEL) for toxicity of the protein administered as a single dose was 
considered to be 100 mg/kg (the highest tested target dose), no acute 
dietary risks are posed for infants, children or adults.
    3. Developmental/reproductive effects. No instances of reported 
adverse reproductive or developmental effects to humans, domestic 
animals or wildlife as a result of exposure to the GOX protein or the 
microbial source of the gox gene, Achromobacter, are known. Enzyme 
proteins have not been reported in literature to produce teratogenic 
effects or reproductive deficiency when fed to animals or man (Pareza 
and Foster, 1983).
    4. Chronic effects. In an in-vitro digestive fate study, the GOX 
protein was rapidly degraded in simulated gastric and intestinal fluid 
with more than 90% of the initially added GOX protein degraded after 15 
and 30 seconds incubation, respectively, as detected by western blot 
analysis. Consequently, no chronic effects are expected for infants, 
children or adults.
    5. Carcinogenicity. Protein enzymes are not considered to be 
carcinogenic (Pareza and Foster, 1983) and consequently, there is no 
carcinogenic risk associated with the GOX protein for infants, children 
or adults.
    6. Endocrine effects. Not applicable. Enzyme proteins are not known 
to interact or bind directly with the estrogen receptor to produce 
endocrine effects. Further, there is little opportunity for systematic 
absorption of the GOX protein due to rapid degradation by digestive 
enzymes. Therefore, no adverse effects to the endocrine system is 
known.

C. Aggregate Exposure

    1. Dietary exposure. Oral exposure to the GOX protein at very low 
levels may occur from ingestion of processed corn products; however, 
the lack of mammalian toxicity and the digestibility of the protein 
have been demonstrated as cited above.
    2. Drinking water exposure. Transfer of the GOX protein to drinking 
water is highly unlikely given containment of the protein in plant 
cells and natural degradation upon plant senescence. Western blot 
analysis has indicated that the GOX protein was not present in corn 
pollen.
    3. Non-occupational exposure. The GOX protein is produced at low 
levels as a selectable marker and is contained within the cells of the 
plant. Consequently, negligible exposure to the protein is expected 
from handling corn seed, leaf or other plant tissue at planting, during 
growth, or at harvest. In addition, negligible exposure to the GOX 
protein would be expected during storage, transportation, or disposal 
of insect-protected corn seed as the protein cannot drift or volatilize 
from the plant and its bioactivity is rapidly lost upon decomposition 
of the plant tissue.

D. Cumulative Risk

    The GOX enzyme was isolated from an Achromobacter species and 
catyalyzes the degradation of glyphosate to aminomethylphosphonic acid 
(AMPA) and glyoxylate. This conversion of glyphosate to AMPA and 
glyoxylate is the primary route for the degradation of glyphosate. This 
degradation inactivates the herbicide and allows the plant cell 
expressing the GOX protein to grow in the presence of glyphosate. This 
mechanism is not shared by other known selectable markers used in 
initial laboratory stages of plant cell selection. Consideration of a 
common mode of toxicity is not appropriate given that there is no 
indication of mammalian toxicity of the GOX protein and no information 
that indicates that toxic effects would be cumulative with any other 
compounds.

E. Safety Determinations

    1. U.S. general population. The toxicity profile for the GOX 
protein indicates no risk from exposure to the GOX protein by the 
overall U.S. population. Monsanto believes that the lack of acute 
toxicity, rapid digestibility of the GOX protein and lack of homology 
to known proteinaceous allergens or toxins provide evidence for the 
lack of toxicity and allergenicity and support an exemption from the 
requirement of a tolerance for the GOX protein.
    2. Infants and children. Monsanto considers the acute toxicity 
data, the rapid degradation of the GOX protein in the mammalian 
digestive system and the lack of homology to known proteinaceous 
allergens as evidence to support the safety of this protein to infants 
and children. Based upon this evidence, it is not expected that infants 
and children would be more more susceptible to this protein than is the 
adult population.

F. Residue Chemistry Data Summary

    As a plant pesticide formulation inert ingredient, the gox gene was 
used to produce the GOX protein which confers tolerance to glyphosate 
as the selectable marker. The GOX protein is produced in plant tissues 
including grain and forage at low levels as documented above. Mammalian 
safety of the protein has been demonstrated in acute oral toxicity test 
of the GOX protein. Analytical methods for the detection and 
measurement of the GOX protein are not needed as Monsanto is 
petitioning for an exemption from the requirement of a tolerance on the 
basis of mammalian safety. The GOX protein is not on the Food and Drug 
Administration's Generally Recognized as Safe (GRAS) list.

G. Environmental Fate Data Summary

    The GOX gene was cloned from an Achromobacter species, reported to 
be one of the most frequently occuring bacteria in the rhizosphere 
(Joos et al., 1988). The GOX protein is produced at low levels within 
the cells of the plant and expected to degrade at plant senescence and 
exposure to physical, chemical and microbial processes in the 
environment. (Mike Mendelsohn)

3. Seminis

PP 4E4310

A. Proposed Use Practices

     Recommended application method and rate(s), frequency of 
application, and timing of application. The inserted genes are under 
the control of a constitutive promoter. Therefore, the viral coat 
proteins will be produced within the tissues of the genetically 
engineered plant and will not be applied externally. In information 
provided to commercial growers, the resistance of the engineered plants 
to specific plant viruses will be described. However, Seminis states 
that no special instructions for use will be necessary. Appropriate 
cultural practices for growing seed with genetically engineered virus 
resistance will be determined by individual growers, as such practices 
are for all other plant varieties.

B. Product Identity/Chemistry

    1. Identity of the pesticide and corresponding residues. The 
pesticide consists of a pair of viral coat proteins that are produced 
by the genetically engineered plant. One protein consists of a fusion 
of 16 amino acids of the cucumber mosaic virus coat protein and 281 
amino acids of the watermelon mosaic virus 2 coat protein. The 
molecular weight of the chimeric coat

[[Page 34276]]

protein is approximately 33,203. The second protein consists of 279 
amino acids of the zucchini yellow mosaic virus coat protein with a 
molecular weight of approximately 31,458.
    2. Magnitude of residue anticipated at the time of harvest and 
method used to determine the residue. The viral coat proteins are 
expressed in plant tissues and, therefore, are not residues in the same 
manner as a pesticide applied externally to growing crop plants. 
Seminis believes that little concern exists for the presence of viral 
coat proteins remaining on or in genetically engineered plants as they 
are ubiquitous in nature, found in soil, water, terrestrial plants and 
raw produce.
    3. A statement of why an analytical method for detecting and 
measuring the levels of the pesticide residue are not needed. The 
Enzyme-Linked Immunoabsorbent Assay (ELISA) test can be used to 
determine expression levels of viral coat proteins in transformed 
plants, fruits and leaves. However, the available scientific literature 
indicates that viral coat proteins do not pose a threat to human health 
or the environment at any level. Therefore, Seminis states that an 
analytical method for detecting and measuring the level of engineered 
viral coat proteins is not needed.

C. Mammalian Toxicological Profile

    Viral coat proteins are substances that viruses produce during a 
plant infection to encapsulate and protect their genetic material. When 
the genetic material encoding the coat protein for a plant virus is 
introduced into a plant's genome, the plant is able to resist 
subsequent infections by that same virus as well as strains closely 
related to the donor virus. Virus-infected plants currently are and 
have been a part of both the human and domestic animal food supply, and 
Seminis agrees with EPA's finding that plant viruses are not known to 
be harmful to humans (59 FR 60519-60535, November 23, 1994)(FRL-4755-
3). All available data from the scientific literature indicates that 
plant viruses are not toxic to humans or other vertebrates. 
Additionally, plant viruses are unable to replicate in mammals or other 
vertebrates, eliminating the possibility of human infection. This has 
been shown by injections of purified whole virus into laboratory 
animals to develop antibodies for ELISA tests.
    More importantly, however, this tolerance exemption will apply to 
that portion of the viral genome coding for the whole coat protein and 
any sub-component of the coat protein expressed in the plant. This coat 
protein component alone is incapable of forming infectious particles. 
Because whole intact plant viruses are not known to cause deleterious 
human health effects, Seminis believes that it is reasonable to assume 
that a subunit of these viruses likewise will not cause adverse human 
health effects.

D. Aggregate Exposure

    1. Dietary exposure. a. Food. Seminis states that the use of viral 
coat protein-mediated resistance will not result in significant new 
dietary exposure to plant viruses. Entire infectious particles of 
zucchini yellow mosaic virus and watermelon mosaic virus, including the 
coat protein component, are already found in the fruit and tissues of 
many plants. Virus-infected food plants are and have been a part of the 
human and domestic animal food supply. Such food plants and food 
derived from them have been consumed, including by children and 
infants, with no detectable or observed adverse effects to human 
health.
    b. Drinking water. Seminis states that the use of viral coat 
protein-mediated resistance will not result in significant new levels 
of viral coat proteins from engineered plants in drinking water. Plant 
viruses are already present in soil and water. Viral coat proteins 
expressed in genetically engineered plants are limited to plant 
tissues. Upon plant senescence, viral coat proteins are believed to 
degrade in the soil in the same manner as other proteins. Consequently, 
Seminis believes that viral coat proteins produced as plant-pesticides 
would represent a negligible addition to those existing in drinking 
water.
    2. Non-dietary exposure (lawn care, topical insect repellents, 
etc.). The use of the genetically engineered viral coat proteins is for 
improved virus disease resistance in agricultural crops. Therefore, 
Seminis believes that non-dietary exposure to genetically engineered 
viral coat proteins will be minimal to non-existent.

E. Cumulative Exposure

     Exposure through other pesticides and substances with the common 
mode of toxicity as this pesticide. Seminis believes that due to the 
lack of toxicity associated with plant viruses and plant viral coat 
proteins, cumulative effects with other pesticides and substances will 
be non-existent.

F. Safety Determination

    1. U.S. population. There is no known toxicity associated with coat 
proteins from plant viruses. Consequently, a safety assessment is not 
needed for these proteins. Given the long history of mammalian 
consumption of the entire plant virus particle in foods, without any 
adverse human health effects, Seminis reasonably believes that 
consumption of a non-infectious component of the WMV plant virus is 
safe. There are no known data that indicate aggregate exposure to plant 
viral coat proteins under normal conditions will result in harm to any 
person.
    2. Infants and children. Viral coat proteins are ubiquitous in 
foods, including those foods consumed by infants and children. 
Moreover, there is not reason to believe that plant viral coat proteins 
are likely to occur in different amounts in foods consumed by children 
and infants. Further, there is no scientific evidence that viral coat 
proteins used as plant pesticides would have a different effect on 
children than on adults. Viral coat proteins are not toxic and, 
therefore, Seminis believes with reasonable certainty that no harm will 
result to Infants and Children from aggregate exposure to coat proteins 
from plant viruses.

G. Existing Tolerances

     An exemption from tolerance was granted for watermelon mosaic 
virus-2 and zucchini yellow mosaic virus coat proteins as expressed in 
Asgrow line ZW20 of Cucurbita pepo L. in November 1994 (59 FR 54824, 
November 2, 1994)(FRL-4908-1).

H. International Tolerance

     No known international tolerance or exemption from tolerance has 
been granted for watermelon mosaic virus-2 and zucchini yellow mosaic 
virus coat proteins. Seminis Vegetable Seeds, Inc. concludes that plant 
viruses, including watermelon mosaic virus-2 and zucchini yellow mosaic 
virus coat proteins, are not harmful to humans, and that there is a 
reasonable certainty that no harm will result from aggregate exposure 
to coat proteins of watermelon mosaic virus-2 and zucchini yellow 
mosaic virus, and the genetic material necessary for production, 
including all anticipated dietary exposures and all other non-
occupational exposures. Accordingly, Seminis believes that watermelon 
mosaic virus-2 and zucchini yellow mosaic virus coat proteins qualify 
for an exemption from the requirement of a tolerance in or on all raw 
agricultural commodities. (Linda Hollis)

[FR Doc. 97-16659 Filed 6-24-97; 8:45 am]
BILLING CODE 6560-50-F