Document ID: EPA-HQ-OPP-2008-0749-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-11-12T05:00Z

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:

Company Name: Isagro, S.p.A.

[Insert petition number] To Be Assigned by EPA

	EPA has received a pesticide petition [Insert petition number] (To Be
Assigned by EPA) from Isagro, S.p.A., Via Caldera 21, fabbricato D, la
3, 20153 Milano, Italy 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 to establish an exemption from the requirement of
a tolerance for microbial pesticide  Trichoderma gamsii strain ICC 080
(originally classified as Trichoderma viride)

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

	[To Be Assigned by EPA]

A. Product Name and Proposed Use Practices

	Trichoderma gamsii strain ICC 080 is a co-active ingredient with
Trichoderma asperellum strain ICC 012 in a microbial fungicide (trade
name: BiotenTM WG) used for control of main soil borne fungal plant
pathogens (i.e., Pythium spp., Phytophthora spp., Sclerotinia spp.,
Sclerotium spp., Thielaviopsis basicola, Rhizoctonia spp., Verticillum
spp.)  Bioten WP is mixed with planting soil or suspended in water and
applied to soil before and/or at transplanting or sowing.  The active
Trichoderma spp. ingredients act as pathogen antagonistics, colonizing
soil and roots to compete with plant pathogenic fungi for space and
nutrients.  Moreover, the antagonists also attack the cell walls of
pathogens with enzymes.

 Potted flowers and ornamentals (chrysanthemum, cyclamen, poinsettia,
primrose, etc):  

- In nursery, seeding and planting beds: 0.4 lb/yd3 of planting soil, by
mixing the product to soil or by suspending the product in the amount of
water which allows the complete wetting of the substrate immediately
after sowing or transplanting.

Vegetables (tomato, pepper, melon, fennel, artichoke, basil, celery,
bean, string bean, zucchini, egg plant, cucumber, aromatic herbs and
strawberries):

- In nursery: 0.4 lb/ yd3 of planting soil, by mixing the product to
soil or by suspending the product in the amount of water which allows
the complete wetting of the soil immediately after sowing or
transplanting.

- In glasshouse or in open field: spread 0.05 lb/1000 ft2 (2.2 lb/acre)
of the product uniformly onto the surface at tillage (5-7 days before
sowing).  Repeat the treatment at the same dosage rate at sowing or
transplanting.

	Lawns: 

- Apply from 0.05 to 0.1 lb/1000 ft2 (2.2 to 4.4 lb/acre) at sowing, at
restart of vegetative growth, and before the infection risk period, and
possibly follow the treatment with light irrigation.

B. Product Identity/Chemistry

  

	1. Identity of the pesticide and corresponding residues. The pesticide
which is the subject of this petition is Trichoderma gamsii strain ICC
080.  Since Trichoderma spp., including Trichoderma gamsii, are
ubiquitous in the environment, corresponding residues will be naturally
occurring.  

	2. Magnitude of residues at the time of harvest and method used to
determine the residue.  Since the pesticide is applied to soil before
and/or at sowing or transplanting the magnitude of residues is expected
to be at the same level as non-treated commodities.  No method for
residue analysis is proposed.     

	3. A statement of why an analytical method of detecting and measuring
the levels of the pesticide residue are not needed. Trichoderma spp.
products already have an existing Tolerance Exemption on all food/feed
commodities (40 CFR 180.1201).  The exemption from tolerance was
supported by the lack of acute oral toxicity/pathogenicity due to the
ubiquitous nature of the microbial and based on the acute oral
toxicology test in rats.   

 

C. Mammalian Toxicological Profile

The data submitted to support the initial registration of this active
ingredient include: acute toxicity/pathogenicity studies in rats to
demonstrate oral, pulmonary, and intraperitoneal effects.  Waivers have
been requested for MP testing of acute oral, dermal, and eye toxicity,
and primary dermal irritation based on the ubiquitous occurrence of
Trichoderma spp., results of TGAI testing for acute
toxicology/pathogenicity studies and results of EP testing of acute
oral, dermal, and eye toxicity, and primary dermal irritation. 
Technical product (MP) never leaves the plant since it is formulated
into EP at the same facility.  

1.  Acute oral toxicity/pathogenicity (OPPTS Gdln 885.3050): A single
oral administration of 2,000 mg Trichoderma gamsii strain ICC 080/kg bw
to rats revealed no toxic symptoms.  The animals gained the expected
weight throughout the whole study period.  

2.  Acute pulmonary toxicity/pathogenicity (OPPTS Gdln 855.3150): A
single intratracheal administration of 2.5 x 106 CFU Trichoderma gamsii
strain ICC 080/animal to rats revealed no toxic symptoms and no
mortality.  Body weight was not influenced by the treatment.  No
administration of fungal conidia from lung tissue into other organ
tissue or blood occurred.  Conidia were detected in the feces which can
be explained from swallowing of the applied suspension by the animals
during application.  The conidia density in the lung tissue and feces
decreased to zero within 21 days post application.

3.  Acute injection toxicity/pathogenicity (intraperitoneal) (OPPTS Gdln
855.3200): A single intraperitoneal administration of 1 x 107
Trichoderma gamsii strain ICC 080 per rat revealed slightly reduced
mortality, slight ataxia, slightly reduced muscle tone, slight dyspnoea,
mydriasis and writhing in all 6 animals.  All clinical signs had
completely recovered within 24 hours and no mortalities occurred.  The
animals gained the expected weight throughout the whole study period.

4.Hypersensitiviy incidents (OPPTS Gdln 885.3400): No incidents of
hypersensitivity have occurred during the development of this MPCA. 
Moreover, no incidents of hypersensitivity in humans have been reported
to the Agency regarding currently registered Trichoderma spp. products. 

Skin sensitization (EC Gdln B.6. and OECD Gdln 406) testing in guinea
pigs according to Magnusson and Kligman following exposure to 10% and
50% suspensions with a challenge of a 1% suspension of EP (Bioten WP
containing 2% Trichoderma gamsii and 2% Trichoderma asperellum) revealed
no sensitizing properties.

5. Cell culture (OPPTS Gdln 885.3500): This study is not required
because this MPCA is not a virus.  

  	

6. Acute oral toxicity (OPPTS Gdln 870.1100): The registrant has
requested exemption from this guideline requirement for testing MP for
the following reasons.

 (1) Acute oral toxicity/pathogenicity (OPPTS Gdln 885.3050) following
an administration of 2,000 mg TGAI/kg bw to rats revealed no toxic
symptoms. 

 (2) Acute oral toxicity (EC Gdln B.1, OECD Gdln 401 and OPPTS Gdln
885.3050) testing following an administration of 2,000 mg EP (Bioten WP
containing 2% Trichoderma gamsii and 2% Trichoderma asperellum)/kg bw to
rats revealed no toxic symptoms.

7. Acute dermal toxicity (Gdln 870.1200): The registrant has requested
exemption from this guideline requirement for testing MP for the
following reasons.

(1) Trichoderma spp. are ubiquitous in the environment and not known to
have dermal toxicity.

(2) No manufacture workers have shown evidence of dermal toxicity or
sensitivity to the MP.

(3) Acute dermal toxicity (EC Gdln B.3. and OECD Gdln 402) testing
following an administration of 2,000 mg EP (Bioten WP containing 2%
Trichoderma gamsii and 2% Trichoderma asperellum)/kg bw to rats revealed
no clinical signs of local or systemic toxicity.

8.  Acute inhalation toxicity (OPPTS Gdln 870.1300): The registrant has
requested exemption from this guideline requirement for testing MP for
the following reasons.

(1) The MP does not consist of, or under conditions of use would result
in, an inhalable material (e.g., gas, volatile substances, or aerosol
particulates).

(2) Acute inhalation toxicity (EC Gdln B.2. and OECD Gdln 402) testing
following an exposure of 5.2 mg EP (Bioten WP containing 2% Trichoderma
gamsii and 2% Trichoderma asperellum)/L air for 4 hours to rats by
inhalation revealed no signs of toxicity 

9. Acute eye irritation (OPPTS Gdln 870.2400): The registrant has
requested exemption from this guideline requirement for testing MP for
the following reason.

(1) Acute eye irritation (EC Gdln B.5. and OECD Gdln 405) testing
following a single application of 100 mg EP (Bioten WP containing 2%
Trichoderma gamsii and 2% Trichoderma asperellum) per animal into the
conjunctival sac of the right eye to three rabbits caused the following
effects: Conjunctival redness (grade 1) was observed in all animals 1
hour after instillation, but conjunctivae went back to normality (grade
0) afterwards; the cornea and the iris were not affected by instillation
of the test item; there were no systemic intolerance reactions.

10. Primary dermal irritation (OPPTS Gdln 87.2500): The registrant has
requested exemption from this guideline requirement for testing MP for
the following reason.

(1) Acute skin irritation patch test (EC Gdln B.4. and OECD Gdln 404)
testing following exposure to 500 mg EP (Bioten WP containing 2%
Trichoderma gamsii and 2% Trichoderma asperellum) to each of three
rabbits revealed the following effects: An erythema (grade 1) was
observed in all animals 24 hours to 5 days after patch removal; An
oedema (grade 1) was observed in one animal 72 hours and 4 days after
patch removal; there were no systemic intolerance reactions.

D. Aggregate Exposure

	1. Dietary exposure. 

		i. Food. Dietary exposure is expected to be negligible because the
microbial pesticide control agent (MPCA) is applied to soil before
and/or at sowing or transplanting.  Also there is no plant uptake of the
MCPA and populations of soil microbes are at normal levels at the time
of harvesting.

	ii. Drinking water. Drinking water exposure is expected to be
negligible because this MPCA is not applied to water.  Also both
percolation through soil and municipal treatment of drinking water would
greatly reduce the possibility of exposure to the MPCA.  Furthermore,
Trichoderma gamsii is a soil microorganism and is not expected to
proliferate in aquatic environments.

	2. Non-dietary exposure. This MPCA will be applied to agricultural
fields, turf, professional landscapes, and in home gardens.  Although
some applications may be near residential areas, non-dietary exposure
would be expected to be below the Agency’s level of concern because of
its low toxicity classification...

E. Cumulative Effects

	There are no other strains of Trichoderma gamsii registered at this
time.  Other species of the fungal genus Trichoderma are also registered
with a history of safe use.  There is no reason to believe that there is
any concern regarding the potential for cumulative effects of the
currently registers Trichoderma strains due to a common mechanism of
toxicity.  The toxicology studies performed on registered Trichoderma
spp. demonstrate a low toxicity potential for each fungal strain.

F. Safety Determination

	1. U.S. population. Considering the various routes of exposure
(dietary, drinking water, and exposure from non-occupational sources)
and low toxicological/pathogenicity potential, it can be concluded that
the proposed use of this MCPA will not pose significant risk to
populations including infants and children.

	2. Infants and children. FFDCA section 408 provides that EPA shall
apply an additional ten fold margin of exposure (safety) for infants and
children in case of threshold effects to account for pre- and post natal
toxicity and the completeness of the database unless EPA determines that
a different margin of exposure (safety) will be safe for infants and
children.  For current registered Trichoderma spp., The Agency believes
there is reliable data to conclude that there are no threshold effects
of concern to infants.  As a result, the provision requiring an
additional margin of exposure has not been applied for currently
registered Trichoderma spp.  The registrant believes the data presented
for this MCPA is as reliable to come to the same conclusion.  

G. Effects on the Immune and Endocrine Systems

	No additional data specifically on the endocrine effects of currently
registered Trichoderma spp. are required at this time by the Agency. 
This decision is partially based on the fact that there is no
information indicating that registered Trichoderma spp. produces a
metabolite that may be an endocrine disrupter.  Also, as expected for
non-pathogenic microorganisms, submitted toxicity/pathogenicity studies
in the rodent indicate that following several routes of exposure, the
immune system is still intact and able to process and clear the active
ingredient.  Therefore no adverse effects to the endocrine or immune
systems are known or expected.  The registrant believes the data
presented for this MCPA is as reliable to come to the same conclusions.

H. Existing Tolerances

            Trichoderma spp. products already have an existing Tolerance
Exemption on all food/feed commodities (40 CFR 180.1201).  

I. International Tolerances

	There are no Codex maximum residue levels [MRLs] established for
residues of Trichoderma spp.

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