Document ID: EPA-HQ-OPP-2007-0947-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-10-03T04:00Z

EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY NOTICE OF
FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 
(1/1/2007)

EPA Biopesticides and Pollution Prevention Division contact: [insert
name and telephone number with area code]

 

INSTRUCTIONS:  Please utilize this outline in preparing the pesticide
petition.  In cases where the outline element does not apply, please
insert “NA-Remove” and maintain the outline. Please do not change
the margins, font, or format in your pesticide petition. Simply replace
the instructions that appear in green and brackets, i.e., “[insert
company name],” with the information specific to your action.

SUBMISSION: E-mail the completed template to: duggard.mari@epa.gov.

TEMPLATE:

AgriVir, LLC

To Be Assigned by EPA

	EPA has received a pesticide petition (To Be Assigned by EPA) from
AgriVir, LLC, 7700 Leesburg Pike, Suite 208, Falls Church, VA 22043
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.

(3)

	1. by establishing a tolerance for residues of

	2. to establish an exemption from the requirement of a tolerance for

	

	3. to establish an amendment/expansion of an existing tolerance
exemption for the

(1)

	1. microbial pesticide  Indian meal moth granulosis virus

	2. biochemical pesticide [insert name of active ingredient]

	

	3. plant-pesticide [insert name of active ingredient] in or on [insert
commodity].

	Pursuant to section 408(d)(2)(A)(i) of  FFDCA, as amended, AgriVir, LLC
has submitted the following summary of information, data, and arguments
in support of their pesticide petition. This summary was prepared by
AgriVir, LLC 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.

I. AgriVir, LLC  Petition Summary

	[To Be Assigned by EPA]

A. Product Name and Proposed Use Practices

	Indian Meal Moth Granulosis Virus (trade names: BioGuard-V, NutGuard-V,
FruitGuard-V) used for control of Indian meal moth on shelled and
inshell nuts, dried fruits, cereal grains, and other agricultural
commodities susceptible to infestation by Indian meal moth. The U.S.
Environmental Protection Agency has previously registered AgriVir's
microbial pest control product under EPA Reg. No. 733176-1. This is a
biological insecticide intended to control Indian meal moth, a serious
pest of various stored commodities. 

The Indian meal moth (or "IMM"), is a serious cosmopolitan pest of many
stored agricultural commodities and processed fractions. Infestation can
occur at any time from harvest to eventual consumption of the commodity.
 IMM is estimated to be responsible, for example, for approximately 90%
of the damage done to dried fruits and nuts in storage.  In facilities
where susceptible commodities are handled, fragments and other debris
from the commodities gets into cracks, crevices, and other places and
IMM propagates on this material. This establishes a general infestation
and reservoir for the Indian meal moth in such facilities.  

Control of Indian meal moth by this MPCA is by means of producing an
infection of the insect larvae with Indian meal moth granulosis virus
(IMMGV) such that the larvae stop eating and expire and do not progress
into mature, breeding adults Indian meal moths. The effect of the MPCA
occurs at a point soon after the hatch of Indian meal moth eggs on an
infested commodity such that damage to the commodity (by larvae feeding
on the commodity) is substantially reduced and the larvae generally do
not progress to a point of development where they are readily visible to
the untrained observer.  The IMMGV component of this MPCA is a naturally
occurring isolate of the Indian Meal Moth Granulosis Virus.  It has not
been genetically modified.

IMMGV has no hosts other than larvae of the Indian meal moth and acts by
making the Indian meal moth larvae sick, rather than by a toxic
mechanism (i.e., IMMGV does not produce any specific toxin which kills
the larvae).  Indian meal moth larvae succumb to granulosis disease due
to serious damage to one of their major organs for storage of nutrients.

The MPCA is prepared without isolation of IMMGV and, as such, the MPCA
which is the subject of the present petition consists, therefore, of a
homogenate of IMMGV occlusion bodies ("viral particles"), infected
Indian meal moth larval parts, heat sterilized wheat bran, brewer's
yeast, and vitamins and antioxidants (these latter two less than 0.6%
total of the product). 

The maximum label rate for the MPCA is 5 ozs. / ton of commodity (142 g
MPCA / 1087 Kg commodity).

The purpose of the present petition is to clarify the nature of the MPCA
under the existing Tolerance Exemption at 40 CFR 180.1218.  This
currently reads:

An exemption from the requirement of a tolerance is established for
residues of the microbial pesticide Indian Meal Moth Granulosis Virus
when used in or on all food commodities.

The present petition seeks to amend the above, existing Tolerance
Exemption so as to read as follows:

An exemption from the requirement of a tolerance is established for
residues of the microbial pesticide Indian Meal Moth Granulosis Virus
(Indian meal moth Granulosis virus infected Indian meal moth larval
parts homogenized with heat treated wheat bran and brewer’s yeast
by-products) when used in or on all food commodities.

This proposed amended description of the MPCA is believed to be more
accurate as it correctly represents all significant components of the
residues which may result from use of Indian meal moth granulosis virus
product on food commodities.

 

B. Product Identity/Chemistry

	1. Identity of the pesticide and corresponding residues. The pesticide
which is the subject of this petition is Indian meal moth granulosis
virus which is prepared as below summarized: 

Indian meal moth eggs are seeded onto a solid diet mixture composed of
heat treated (sterilized) wheat bran, brewers yeast, and trace amounts
of vitamins required for proper larval growth. 

The eggs are allowed to hatch and develop into Indian meal moth larva.

These larvae are infected with Indian meal moth Granulosis virus
(sourced from a prior batch) and the infection is allowed to propagate
to fullness. 

Water to form a slurry and this is homogenized.

The homogenized slurry is dried to yield dry solids.

The dried solids are cold milled to produce a final MPCA product which
is a fine, wettable powder. 

As can be understood from the production process the final MPCA is an
inseparable homogenate of infected insect larval parts, heat treated
wheat bran, and broken yeast cells and yeast byproducts. There are no
intentionally added inert ingredients in the MPCA.   The residues
present on treated food commodities will be residues of this homogenized
powdered MPCA.

	2. Magnitude of residues at the time of harvest and method used to
determine the residue. 

The maximum label rate for the MPCA is 5 ozs. / ton of commodity (142 g
MPCA / 1087 Kg commodity).  If no residues of the MPCA are lost by
further processing or handling of the treated commodity the worst case
theoretical residues of MPCA are:

0.142 Kg / 1087 Kg  =   0.00013 Kg/Kg   =   0.013 %  =  130 ppm

Because the maximum theoretical residues are very low and the MPCA has
no significant toxicological effects potential (see below for mammalian
toxicology profile) no method for residue analysis is used or proposed.
This is consistent with use of this MPCA under a Tolerance Exemption.

	3. A statement of why an analytical method of detecting and measuring
the levels of the pesticide residue are not needed. This product already
has an existing Tolerance Exemption (at 40 CFR 180.1218) for use on all
food commodities. Because the maximum theoretical residues are very low
and the MPCA has no significant toxicological effects potential (see
below for mammalian toxicology profile) no method for residue analysis
is used or proposed. This is consistent with use of this MPCA under a
Tolerance Exemption.

 

C. Mammalian Toxicological Profile

	The mode of action for IMMGV in its host, the larval stage of P.
interpunctella, is pathogenic in nature.  IMMGV produces granulosis
disease in the larvae of P. interpunctella.  "Granulosis" disease is so
named because cells in infected tissue sections, when observed under
light microscopy, are full of minute, refractile bodies termed
"granules".  The initial signs of granulosis disease occur several days
after larval ingestion of the viral occlusion bodies and consist of
sluggishness and loss of appetite.  These initial signs are followed by
a change in the appearance of the larvae.  They are normally light brown
and semilucent but when infected become opaque and white. This change is
the result of the massive accumulation of viral occlusion bodies in the
fat body of the infected larva. The fat body is the site of intermediary
metabolism in these larvae and it is in the fat body that fat, protein,
and glycogen are primarily stored. The pathogenicity of IMMGV to the
larva results from the mode of viral release from cells of the fat body.
 As discussed above, this occurs by rupture of the cells of the fat
body, thereby leading to degeneration and necrosis of the fat body and,
ultimately, death of the infected larva. 

The above-cited mode of action is distinct from a toxicity based mode of
action. That is, unlike some microbial pest control agents which produce
endo- or exo-toxins which act to kill the target pest, IMMGV produces no
toxins as part of its mode of action. 

Hazard Potential to Mammals:

IMMGV poses no hazard potential to mammals via ingestion, dermal
contact, or inhalation. There is no baculovirus (the type of virus which
IMMGV is) known to infect or replicate in any vertebrate host. Among
invertebrates, IMMGV itself has no known host other than larvae of P.
interpunctella and has been shown not to cross-infect lepidopteran or
other insects other than P. interpunctella.

A number of studies on the toxicity of baculoviruses, inclusive of
granulosis viruses, to animals have shown that these agents are
non-toxic by the oral, dermal, inhalation and injection routes of
exposure and that no effects on overall health, gross or micro
pathology, hematology, clinical chemistry, and antibody stimulation
occur in test animals. These studies have been published in the open
literature and were submitted as part of AgriVir, LLC's original
application for registration of this MPCA. 

Cell culture studies (submitted by AgriVir as part of its original
registration submission) have shown that IMMGV which is actively
infective and pathogenic to IMM larva does not produce cytotoxicity nor
does it replicate in or produce pathogenicity in the following mammalian
cell lines:

WI-38 (ATTC CCL 75: human lung [embryonic])  

WS1 (ATTC CRL 1502: human endothelium [embryonic skin])

CV-1 (ATTC CCL 70: African green monkey,  renal)

These cell culture studies further support the already established fact
that IMMGV poses no hazard to mammals.

	Due to the physical properties of the final product (a fine, dry
powder) the technical MPCA does have a mild to moderate, reversible eye
irritation potential. 

Hazard Potential to the Environment:

The only potential environmental effect of IMMGV is on the population of
Indian meal moths. This is because, as discussed above, IMMGV has no
hosts other than larvae of the Indian meal moth and acts by a
pathogenicity mechanism rather than a toxicity mechanism (i.e., IMMGV
does produce any specific toxin).  Since IMMGV is a naturally occurring
virus which has naturally infected Indian meal moth larvae for at least
decades and probably longer, its use on Indian meal moth larvae which
may infest dried fruits and nuts and other stored commodities cannot
reasonably be expected to endanger the Indian meal moth population as a
whole. 

Therefore, there are no reasonably anticipated or likely environmental
effects of use of IMMGV for protection of agricultural commodities from
Indian meal moth damage. 

Hazard Potential to Non-Target Species:

There is no hazard potential to non-target species. As above-noted,
there is no baculovirus known to infect or replicate in any vertebrate
host. Among invertebrates, IMMGV itself has no known host other than
larvae of P. interpunctella and has been shown not to cross-infect
lepidopteran or other insects other than P. interpunctella.

D. Aggregate Exposure

	1. Dietary exposure. [Insert text.]

	i. Food. -- The levels of residues in treated commodities will be very
low. The application rates for this MPCA are from 1 to 5 ounces of  MPCA
per ton of commodity to be treated.  The theoretical maximum residue
would be 130 ppm. Therefore, dietary exposure is insignificant.

	ii. Drinking water. The proposed use patterns for this MPCA are for
Indoor Food and Non-Food uses. Therefore, there is no potential for
drinking water exposure associated with the approval of this petition. 

	2. Non-dietary exposure. This MPCA  only has any pest control utility
in the treatment of various commodities for control of Indian meal moth.
Therefore, the only potential for non-dietary exposure is to applicators
and to mixer/loaders who will use this MPCA. These non-dietary exposures
are not covered within FQPA and they are expected to be low. Information
already in EPA's data bases which has been previously cited by AgriVir,
LLC indicates that workers involved with baculovirus production and use
do not experience adverse effects as a result of these exposures.

E. Cumulative Effects

	Due to its mechanism of action and extremely limited host specificity,
it can be reliably stated that this MPCA does not share a common
mechanism of action with any other conventional, biochemical, or
microbial pesticide.

F. Safety Determination

	1. U.S. population. Available information reliably supports that the
IMMGV in this MPCA will not produce adverse effects in humans of any age
as a result of exposure by ingestion, dermal contact, or inhalation and
– indeed – that IMMGV appears to be biologically inactive in other
than its natural host. This MPCA does contain heat treated wheat bran
which is derived from its use as a component of the larval diet for
preparing the MPCA. Wheat bran may contain wheat gluten and some
individuals are intolerant to wheat gluten (a condition known as
“celiac disease”). In such individuals the consumption of sufficient
amounts of gluten causes gastro-intestinal symptoms which are
uncomfortable and may be intensely so. Persons with celiac disease are
normally advised to avoid foods containing gluten in any significant
quantity.  Food labeling regulations in most of the world provide for a
standard as to what constitutes foods which can be labeled “gluten
free” such that persons with gluten intolerance can identify and
select such foods. Consumption of “gluten free” foods prevents onset
of the symptoms of gluten intolerance in persons who are gluten
intolerant.  In the United States, the Food and Drug Administration has
proposed that “gluten free” foods contain less than 20 ppm gluten
derived from components in such foods which may originally carry some
gluten and have been treated / processed to reduce or remove gluten. The
wheat bran used in preparation of the this IMMGV-containing MPCA is heat
sterilized prior to its use in MPCA production.  This destroys
micro-organisms which might otherwise contaminate the larval culture and
also denatures gluten which may be present in the wheat bran (wheat bran
being a fraction of wheat which is normally quite low in gluten anyway).
 Tests for gluten in the heat sterilized wheat bran show no detectable
gluten by method IS-1009-1979 (LOD 40 ppm) and the test report is
provided in the present petition to amend this tolerance exemption.  As
calculated in the present petition the theoretical maximum level of
gluten possible present in treated commodities and foods would be 0.005
ppm (5 ppb). This is calculated on the assumption that gluten is present
in the heat sterilized wheat bran at the 40 ppm limit of detection and
that the MPCA is applied at the maximum label rate.  This theoretical
maximum gluten residue is 4,000-times lower than the Food and Drug
Administration’s limit for gluten free foods of 20 ppm.  AgriVir, LLC
concludes therefore, that there is a reasonable certainty that no harm
to sensitive persons, including persons intolerant to gluten, will
result from dietary exposure to residues which could occur as a result
of approval of this petition.

Since the available information reliably supports that the IMMGV in this
MPCA will not produce adverse effects in humans of any age as a result
of exposure by ingestion, dermal contact, or inhalation and that the
other major components of this MPCA are themselves food substances and
dietary supplements, AgriVir, LLC concludes that there is a reasonable
certainty that no harm to the general adult population will result from
dietary exposure to residues which could occur as a result of approval
of this petition. 

 

	2. Infants and children. The available information reliably supports
that this MPCA will not produce adverse effects in humans of any age,
including infants and children and that the other major components of
this MPCA are themselves food substances and dietary supplements. The
potential for adverse effects on persons, including infants and
children, who are sensitive to gluten was discussed above and it is
clear that use of Indian meal moth granulosis product on food
commodities will meet presently proposed FDA standards for gluten free
foods.  These conclusions apply for exposure to this product by
ingestion, dermal contact, or inhalation,  Accordingly, AgriVir, LLC
concludes that there is a reasonable certainty that no harm to infants
and children will result from dietary exposure to residues which could
occur as a result of approval of this petition.

G. Effects on the Immune and Endocrine Systems

	There is no reliable information to indicate that IMMGV has a potential
to produce endocrine effects.  The available studies suggest that IMMGV
is essentially biologically inactive in any organism other than its
natural host, the larva of the Indian meal moth.

H. Existing Tolerances

§ 180.1218 Indian Meal Moth Granulosis Virus; exemption from

the requirement of a tolerance.

An exemption from the requirement of a tolerance is established for
residues of the microbial pesticide Indian Meal Moth Granulosis Virus
when used in or on all food commodities.

I. International Tolerances

	There are no Codex maximum residue levels [MRLsl established for
residues of IMMGV or of this whole MPCA. IMMGV containing products are
presently not registered for pest control outside of the U.S.. 

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