Document ID: EPA-HQ-OPP-2008-0760-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-11-14T05:00Z

<EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY NOTICE OF
FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

(7/1/2007)>

<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, i.e., “[insert company
name],” with the information specific to your action.>

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

<TEMPLATE:>

<[Botry-Zen Limited]>

<[Insert petition number]>

<	EPA has received a pesticide petition ([insert petition number]) from
[Botry-Zen Limited], [21 Willis Street, PO Box 564, Dunedin, New
Zealand] 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
the microbial pesticide  [Ulocladium oudemansii (U3 Strain).]>

	Pursuant to section 408(d)(2)(A)(i) of  FFDCA, as amended, [Botry-Zen
Limited] has submitted the following summary of information, data, and
arguments in support of their pesticide petition. This summary was
prepared by [Botry-Zen Limited] 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. [Botry-Zen Limited]  Petition Summary>

<	[Insert petition number]>

<A. Product Name and Proposed Use Practices>

<	[The product names are Ulocladium oudemansii Technical (tgai; for
manufacturing use only) and BOTRY-Zen® (ep; for agricultural use). 
BOTRY-Zen(, the formulated end-use product containing Ulocladium
oudemansii (U3 Strain), is proposed  for the control of Botrytis cinerea
and Sclerotinia sclerotiorum in fruit and vegetable crops, and in
ornamental plants.  BOTRY-Zen( aggressively occupies the same physical
space and out competes Botrytis spp. and Sclerotinia spp. for the
nutrients in the dead and senescing plant tissue; it is a true
antagonist. BOTRY-Zen( is non-invasive and causes no damage to live
plant tissue.]>

<B. Product Identity/Chemistry>

<	1. Identity of the pesticide and corresponding residues. [Ulocladium
oudemansii is a naturally occurring soil saprophyte that is found in
soils worldwide.  Strains of this organism are generally not regarded as
human or animal pathogens.  The Ulocladium spp. isolate, coded as U3,
was originally isolated from kiwifruit leaf litter debris from a
kiwifruit research block at Massey University, Palmerston North in 1995.
 	The active ingredient is the asexual spore of the soil saprophytic
fungus Ulocladium oudemansii.  The organism acts as a biological control
agent by competing for the same ecological niche as Botrytis cinerea and
Sclerotinia sclerotiorum on fruit and vegetable crops and on ornamental
plants

	When spores of Ulocladium oudemansii (U3 Strain) are deposited on the
dead and senescent plant debris, and the right environmental conditions
exist, they germinate and colonize. The developed mycelium will proceed
to colonize the dead tissue and, if conditions are suitable, additional
sporulation can occur and these new spores are then available to
colonize remaining debris.  Ulocladium oudemansii (U3 Strain)
aggressively occupies the same physical space and out competes Botrytis
spp. and Sclerotinia spp. for the nutrients in the dead and senescing
plant tissue; it is a true antagonist. Ulocladium oudemansii (U3 Strain)
is non-invasive and causes no damage to live plant tissue. It is
expected that, when used as proposed, Ulocladium oudemansii (U3 Strain)
would not result in residues that are of toxicological concern.  
Ulocladium oudemansii (U3 Strain) will not be found actively growing on
living plant material and will only be found in the soil in association
with decomposing plant material.  If dead vegetative tissue is not
available, the fungus can not survive.]>

<	2. Magnitude of residues at the time of harvest and method used to
determine the residue. [Not applicable.]>

<	3. A statement of why an analytical method of detecting and measuring
the levels of the pesticide residue are not needed. [An analytical
method for residues is not applicable.  It is expected that, when used
as proposed, Ulocladium oudemansii (U3 Strain) would not result in
residues that are of toxicological concern.   Ulocladium oudemansii (U3
Strain) will not be found actively growing on living plant material and
will only be found in the soil in association with decomposing plant
material.  If dead vegetative tissue is not available, the fungus can
not survive.]>

<C. Mammalian Toxicological Profile>

<	[Studies to evaluate the safety to mammals were conducted on the
technical grade active ingredient (tgai) and are summarized as follows:>

1.	Acute Oral Toxicity/Pathogenicity (OPPTS 885.3050 and 870.1100):  In
an acute oral toxicity/pathogenicity study on rats (12 male/12 female)
using a dose of 0.5 mL/animal (equivalent to 108 cfu/animal)
administered via oral gavage, there were no adverse effects,
mortalities, clinical signs or abnormal macroscopic findings at
post-mortem.  No viable Ulocladium oudemansii (U3 Strain) was recovered
from the organs or blood of the treated animals during the study, and
the test material was rated as non-toxic and non-pathogenic.  

2.	Acute Dermal Toxicity/Pathogenicity (OPPTS 885.3100 and 870.1200): In
an acute dermal toxicity/pathogenicity study on rats (12 male/12 female)
using a dose of 0.5 mL/animal (equivalent to 108 cfu/animal)
administered via semi-occluded dermal application, there were no adverse
effects, mortalities, clinical signs or abnormal macroscopic findings at
post-mortem.  Animals were also observed for overt signs of toxicity at
the 0, 1, 2 and 4 hours after dosing, and subsequently once daily for up
to 21 days.  No viable Ulocladium oudemansii (U3 Strain) was recovered
from the organs or blood of the treated animals during the study, and
the test material was rated as non-toxic and non-pathogenic.

3.	Acute Pulmonary Toxicity/Pathogenicity (OPPTS 885.3150 and 870.1300):
 Due to the large size of the test organism particles and the rapid
sedimentation of them in solution, it was impossible to does test
animals.  The test facility was not able to effectively homogenize the
test material into suspension without destroying the Ulocladium
oudemansii (U3 Strain) in the test material.  The aerodynamic diameter
of the particles would not allow administration via the inhalation
route.

	

4.	Acute IP Injection Toxicity/Pathogenicity Study in Rats (OPPTS
885.3200):  In an acute IP injection toxicity / pathogenicity study on
rats (17 male/17 female) using a single high does of 0.1mL/animal (107
cfu/animal) there were no mortalities and there was no toxicity,
infectivity or pathogenicity observed.  Adhesions were formed at the
site where the test material was administered; however, the animal’s
immune systems overcame the issue over time.    No viable Ulocladium
oudemansii (U3 Strain) was recovered from the organs or blood of the
treated animals during the study, and the test material was rated as
non-toxic and non-pathogenic.

5.	Primary Eye Irritation (OPPTS 870.2400):  In a primary eye irritation
study on rabbits (3 female) using a dose of 0.1 ml per eye administered
topically, there was minimal irritation at one hour post dosing, but all
effects cleared by 24 hours.  No corneal opacity or iridal effects were
observed.  Ulocladium oudemansii (U3 Strain) was rated “minimally
irritating” to eyes. Infectivity was also evaluated in this study.  No
viable Ulocladium oudemansii (U3 Strain) was recovered from the organs
or blood of the treated animals during the study, and the test material
was rated as non-toxic and non-pathogenic.

6.	Primary Dermal Irritation (OPPTS 870.2500):  In a primary dermal
irritation study on rabbits (3 female) using a dose of 0.5 mL applied
via semi-occluded dermal application, there was very slight irritation
at on hour post dosing, but all effects cleared by 24 hours.  No
corrosive effects were observed.  Ulocladium oudemansii (U3 Strain) was
rated as a non-irritant.

7.	Dermal Sensitization (OPPTS 870.2600):  In a dermal sensitization
study performed on guinea pigs (10 animals) following the Magnusson and
Kligman Maximization Method, no sensitization was observed.  Under the
conditions of the test, Ulocladium oudemansii (U3 Strain) produced a 0%
sensitization rate and was rated as a non-sensitizer to guinea pig skin.

8. 	Hypersensitivity Incidents (OPPTS 885.3400):   The registrant has
noted that no incidents of hypersensitivity or any other adverse effects
have occurred through the research, development or testing of the active
ingredient and its related end-use product.  Should any incidents occur,
they will be reported per FIFRA Section 6(a)(2).

9.	Reverse Mutation Assay (“Ames Test”) (OPPTS 885.5000):  The
suspension and the extract of the test material were considered to be
non-mutagenic under the conditions of this test.  

In addition, growth temperature analysis has shown that Ulocladium
oudemansii (U3 Strain) does not grow above 30(C, which would indicate
that the active ingredient would be unlikely to infect humans or other
mammals with normal body temperatures above 37(C.  Further, in-house
testing has shown that Ulocladium oudemansii (U3 Strain) does not grow
in human serum or blood.  There are no known mycotoxins associated with
Ulocladium oudemansii (U3 Strain) or other Ulocladium species.  Finally,
literature searches have demonstrated that there are no reports of
ecological or human health hazards caused Ulocladium oudemansii (U3
Strain). It does not produce recognized toxins, enzymes, or virulence
factors normally associated with mammalian invasiveness or toxicity.   

The results of toxicity testing and the known growth temperature of the
organism show there is no risk to human health from the active
ingredient.  Ulocladium oudemansii (U3 Strain) is not toxic, pathogenic,
infective or irritating to mammals.]

<D. Aggregate Exposure>

<	1. Dietary exposure. >

<	i. Food. [Dietary exposure from use of Ulocladium oudemansii (U3
Strain), as proposed, is minimal.  The intended use of Ulocladium
oudemansii (U3 Strain) is to growing agricultural crops for the purposes
of disease control.  Ulocladium oudemansii (U3 Strain) has limited
survivability once its carrier nutrient source is exhausted. 

	The results of toxicity testing indicate there is no risk to human
health or the environment from Ulocladium oudemansii (U3 Strain). There
are no reports of ecological or human health hazards caused Ulocladium
oudemansii (U3 Strain). It does not produce recognized toxins, enzymes,
or virulence factors normally associated with mammalian invasiveness or
toxicity.  The absence of acute toxicity or pathogenicity in laboratory
animals demonstrates the benign nature of this strain.]>

<	ii. Drinking water. [Similarly, exposure to humans from residues of
Ulocladium oudemansii (U3 Strain)in consumed drinking water would be
unlikely.  Ulocladium oudemansii (U3 Strain) is not known to grow or
thrive in aquatic environments.  Potential exposure to surface water
would be negligible and exposure to drinking water (well or ground
water) would be impossible to measure. The intended use of Ulocladium
oudemansii (U3 Strain) is to growing agricultural crops for the purposes
of disease control.  Ulocladium oudemansii (U3 Strain) has limited
survivability once its carrier nutrient source is exhausted.  The risk
of the microorganism passing through the soil to ground water is minimal
to unlikely.  Additionally the fungus would not tolerate the conditions
water is subjected to in a drinking -water facility (including: 
chlorination, pH adjustments, high temperatures and/or anaerobic
conditions).  

	

		The results of toxicity testing indicate there is no risk to human
health or the environment from Ulocladium oudemansii (U3 Strain). There
are no reports of ecological or human health hazards caused by
Ulocladium oudemansii (U3 Strain). It does not produce recognized
toxins, enzymes, or virulence factors normally associated with mammalian
invasiveness or toxicity.  The absence of acute toxicity or
pathogenicity in laboratory animals demonstrates the benign nature of
this strain.]>

<	2. Non-dietary exposure. [The potential for non-dietary exposure to
the general population, including infants and children, is unlikely as
the proposed use sites are agricultural.  The intended use of Ulocladium
oudemansii (U3 Strain) is to agricultural crops for the purposes of
disease control.  Ulocladium oudemansii (U3 Strain) has limited
survivability once its carrier nutrient source is exhausted. Personal
Protective Equipment (PPE) mitigates the potential for exposure to
applicators and handlers of the proposed products, when used in
agricultural settings.

		The results of toxicity testing indicate there is no risk to human
health or the environment from Ulocladium oudemansii (U3 Strain). There
are no reports of ecological or human health hazards caused by
Ulocladium oudemansii (U3 Strain). It does not produce recognized
toxins, enzymes, or virulence factors normally associated with mammalian
invasiveness or toxicity.  The absence of acute toxicity or
pathogenicity in laboratory animals demonstrates the benign nature of
this strain.  Non-dietary exposures would not be expected to pose any
quantifiable risk due to a lack of residues of toxicological concern.]>

<E. Cumulative Effects>

<	[It is not expected that, when used as proposed, Ulocladium oudemansii
(U3 Strain) would result in residues that are of toxicological concern.
The intended use of Ulocladium oudemansii (U3 Strain) is to agricultural
crops for the purposes of disease control.  Ulocladium oudemansii (U3
Strain) has limited survivability once its carrier nutrient source is
exhausted. The results of toxicity testing indicate there is no risk to
human health or the environment from Ulocladium oudemansii (U3 Strain).
There are no reports of ecological or human health hazards caused by
Ulocladium oudemansii (U3 Strain). It does not produce recognized
toxins, enzymes, or virulence factors normally associated with mammalian
invasiveness or toxicity.  The absence of acute toxicity or
pathogenicity in laboratory animals demonstrates the benign nature of
this strain.]>

<F. Safety Determination>

<	1. U.S. population. [Acute toxicity studies have shown that Ulocladium
oudemansii (U3 Strain)is not toxic, pathogenic, infective or irritating
to mammals.  The intended use of Ulocladium oudemansii (U3 Strain) is to
agricultural crops for the purposes of disease control.  Ulocladium
oudemansii (U3 Strain) has limited survivability once its carrier
nutrient source is exhausted. The results of toxicity testing indicate
there is no risk to human health or the environment from Ulocladium
oudemansii (U3 Strain). There are no reports of ecological or human
health hazards caused by Ulocladium oudemansii (U3 Strain). It does not
produce recognized toxins, enzymes, or virulence factors normally
associated with mammalian invasiveness or toxicity.  The absence of
acute toxicity or pathogenicity in laboratory animals demonstrates the
benign nature of this strain.  There is a reasonable certainty of no
harm to the general US population from exposure to this active
ingredient.]>

<	2. Infants and children. [As mentioned above, it is not expected that,
when used as proposed, Ulocladium oudemansii (U3 Strain) would result in
residues that are of toxicological concern. There is a reasonable
certainty of no harm for infants and children from exposure to
Ulocladium oudemansii (U3 Strain) from the proposed uses.]>

<G. Effects on the Immune and Endocrine Systems>

<	[To date there is no evidence to suggest that Ulocladium oudemansii
(U3 Strain) functions in a manner similar to any known hormone, or that
it acts as an endocrine disrupter.]>

<H. Existing Tolerances>

<	[There is no US. EPA Tolerance for Ulocladium oudemansii (U3
Strain).]>

<I. International Tolerances>

<	[A Codex Alimentarium Commission Maximum Residue Level (MRL) is not
required for Ulocladium oudemansii (U3 Strain).]>

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