Document ID: EPA-HQ-OPP-2016-0641-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2017-02-07T05:00Z

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

EPA Biopesticides and Pollution Prevention Division contact: [Ann Sibold
703 305-6502]

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: Email the completed template to: sibold.ann@epa.gov.

TEMPLATE:

[Bee Vectoring Technology Inc. 

[6F8508]

	EPA has received a pesticide petition ([6F8508]) from [Amy Plato
Roberts, Technology Sciences Group, Inc., 1150 18th Street., NW Suite
1000, Washington, DC 20036, Agent for Bee Vectoring Technology Inc.],
[4160 Sladeview Crescent #7, Mississauga, ON L5L 0A1 Canada] requesting,
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 
[Clonostachys rosea strain CR-7].

	

Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, [Amy Plato
Roberts, Technology Sciences Group, Inc., Agent for Bee Vectoring
Technology Inc.,] has submitted the following summary of information,
data, and arguments in support of their pesticide petition. This summary
was prepared by [Amy Plato Roberts, Technology Sciences Group, Inc.,
Agent for Bee Vectoring Technology 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.

I. [Bee Vectoring Technology Inc.] Petition Summary

	[6F8508]

Product Name and Proposed Use Practices

[Product Names:	CR-7 Technical (50% active ingredient (ai)); Technical
Grade Active Ingredient (TGAI) – EPA File Symbol 90641-R.

Vectorite with CR-7 (5% ai; End Use Product (EP)) – EPA File Symbol
90641-E.

Proposed Use Practices: CR-7 Technical is a 50% ai (TGAI) of
Clonostachys rosea strain CR-7 and is proposed for manufacturing use
only, for further formulation into registered end-use products.

Vectorite with CR-7 is a 5% ai formulated EP for application via bee
vectoring (using commercial honey bees or bumble bees) during the bloom
period of certain growing plants for the purposes of disease control and
prevention.  Application by bee vectoring is a very efficient method of
application that directly delivers a low dose of the active ingredient. 
Bees walk through a tray of the light, powdered EP on the way out of the
hive and deliver the product to the crop flowers, a common portal of
pathogen entry into the plant.]

	

B. Product Identity/Chemistry

	1. Identity of the pesticide and corresponding residues. [Clonostachys
rosea strain CR-7 (CAS No. Not applicable).  Clonostachys rosea is
ubiquitous in the environment and has been identified in tissue from a
variety of terrestrial plants, aquatic plants and all types of soils
(MRID No. 499492-10).  Information regarding the name, identity and
composition has been submitted to EPA (MRID No. 499492-01).

Clonostachys rosea is a beneficial endophyte that is used to control and
prevent spore production of Botrytis sp. and other similar plant
diseases in plant tissues and is used to enhance the plant’s natural
resistance (induced systemic resistance (ISR)).  Hyphae have been found
to coil around, penetrate and grow inside the hyphae and conidia of
Botrytis sp. (MRID No. 499492-01).]

	2. Magnitude of residues at the time of harvest and method used to
determine the residue. [NA--Remove]

	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, Clonostachys rosea strain CR-7, would not result in
residues that are of toxicological concern.]

C. Mammalian Toxicological Profile

[Studies to evaluate the safety of the active ingredient to mammals were
conducted and are summarized as follows:

Acute Pulmonary Toxicity/Pathogenicity Study in Rats (OCSPP 885.3150): 
A Pulmonary Toxicity / Pathogenicity study conducted to evaluate the
potential effects of a single high dose pulmonary exposure to pure
Clonostachys rosea strain CR-7 indicated the test material is low in
toxicity following acute exposure to the respiratory system (MRID No.
499492-02).  In this study, 36 male and 36 female rats were separated
into 4 groups: Group I, untreated, housed in a separate room (6/sex),
Group II, shelf controls, housed with Group IV (4/sex), Group III,
inactive test material (8/sex), and Group IV, test material, treated
(18/sex).  Treated rats received by tracheal injection, a single dose of
0.3 ml Clonostachys rosea strain CR-7 with counts of 3.1 x 108 colony
forming units per milliliter (CFU /ml), or 9.3 x 107 CFU/rat.  Rats were
observed often on the day of dosing and once daily thereafter for 21
days.  Interim sacrifices of treated rats were conducted on days 0, 3,
7, 14, and 21, and blood and tissue samples were collected from these
subjects at each sacrifice and cultured to quantify the clearance
pattern of the microbe.   There were no abnormal health observations and
no abnormalities identified during necropsy.  The test organism was not
detected in any tissues at any time point, and was considered cleared
from all tissues and blood by day 21.  The test substance Clonostachys
rosea strain CR-7 was determined to be non-toxic following tracheal
injection exposure in a single dose of 9.3 x 107 CFU/rat.  

Acute Oral Toxicity (OCSPP 870.1100):  An acute oral toxicity study
conducted to evaluate the potential effects of a limit dose of CR-7
Technical (50% ai) indicated the test material is low in acute toxicity
following oral exposure (MRID No. 499492-03).  Female albino rats
received a dose of 5,000 mg/kg CR-7 Technical by oral gavage and were
monitored for effects for two weeks.  No mortality occurred during the
study and the rats exhibited no clinical signs of toxicity.  All animals
gained weight each week.  The acute oral LD50 for CR-7 Technical (50%
ai) was identified as > 5,000 mg/kg in female albino rats (Toxicity
Category IV).  

An acute oral toxicity study conducted to evaluate the potential effects
of a limit dose of the formulated end-use product Vectorite with CR-7
(5% ai) indicated the test material is low in acute toxicity following
oral exposure (MRID No. 499493-02).  Female albino rats received a dose
of 5,000 mg/kg Vectorite with CR-7 by oral gavage and were monitored for
effects for two weeks.  No mortality occurred during the study and the
rats exhibited no clinical signs of toxicity.  All animals gained weight
each week.  The acute oral LD50 for Vectorite with CR-7 (5% ai) was
identified as > 5,000 mg/kg in female albino rats (Toxicity Category
IV).  

Acute Dermal Toxicity (OCSPP 870.1200): An acute dermal toxicity study
conducted to evaluate the potential effects of a limit dose of CR-7
Technical (50% ai) indicated the test material is low in acute toxicity
following dermal exposure (MRID No. 499492-04).  Male and female albino
rats received a single dose of 5,050 mg/kg CR-7 Technical, moistened
with deionized water and applied to intact skin. No mortality occurred
during the study and the rats exhibited no clinical signs of toxicity or
signs of dermal irritation at any time throughout the study.  All
animals gained weight each week.  The acute oral LD50 for CR-7 Technical
(50% ai) was identified as > 5,050 mg/kg in female albino rats (Toxicity
Category IV).  

An acute dermal toxicity study conducted to evaluate the potential
effects of a limit dose of the formulated end-use product Vectorite with
CR-7 (5% ai) indicated the test material is low in acute toxicity
following dermal exposure (MRID No. 499493-03).  Male and female albino
rats received a single dose of 5,050 mg/kg Vectorite with CR-7,
moistened with deionized water and applied to intact skin. No mortality
occurred during the study and the rats exhibited no clinical signs of
toxicity or signs of dermal irritation at any time throughout the study.
 All animals gained weight each week.  The acute oral LD50 for Vectorite
with CR-7 (5% ai) was identified as > 5,050 mg/kg in female albino rats
(Toxicity Category IV).

Acute Inhalation Toxicity Study in Rats (OCSPP 870.1300):  An acute
inhalation toxicity study was to be conducted to evaluate the potential
effects of a limit dose of the formulated end-use product Vectorite with
CR-7 (5% ai); however, the test facility was not able to obtain a
respirable particle size and the study was terminated (MRID No.
499493-04).  It was concluded that Vectorite with CR-7 cannot be
aerosolized to obtain an appropriate particle size to determine the
acute toxicity potential in rats.  Regardless, based on the results of
the Acute Pulmonary Toxicity / Pathogenicity Study in Rats (MRID No.
499492-02) and the fact that there is no association between
Clonostachys rosea and inhalation toxicity in literature search (MRID
No. 499492-10), it is expected that neither the active ingredient nor
the formulated end-use product would be toxic via the inhalation route
of exposure.

Primary Eye Irritation (OCSPP 870.2400):  A primary eye irritation study
on rabbits with CR-7 Technical (50% ai) indicated the test material is
minimally irritating based on a 48-hour exposure (MRID No. 499492-05). 
Two male and one female albino rabbits received a dose of 100 mg of CR-7
Technical placed into the conjunctival sac of the right eye of each
animal.  All treated eyes were washed with room temperature deionized
water for one minute after recording the 24-hour observation.  There
were no positive effects exhibited in any eyes at 48 hours after
treatment.  CR-7 Technical (50% ai) is rated as minimally irritating
(Toxicity Category III).  

A primary eye irritation study on rabbits with the formulated end-use
product Vectorite with CR-7 (5% ai) indicated the test material is
minimally irritating based on a 24-hour exposure (MRID No. 499493-05). 
Two male and one female albino rabbits received a dose of 100 mg of
Vectorite with CR-7 placed into the conjunctival sac of the right eye of
each animal.  All treated eyes were washed with room temperature
deionized water for one minute after recording the 24-hour observation. 
There were no positive effects exhibited in any eyes at 24 hours after
treatment.  Vectorite with CR-7 (5% ai) is rated as minimally irritating
(Toxicity Category IV).

   

Primary Dermal Irritation (OCSPP 870.2500):  A primary dermal irritation
study on rabbits with CR-7 Technical (50% ai) indicated the test
material is not irritating based on a 72-hour exposure (MRID No.
499492-06).  One male and two female albino rabbits received a dose of
500 mg of Vectorite with CR-7 moistened with deionized water and covered
with semi-permeable dressing.  The test substance was in contact with
skin for 4 hours.  There were no observations of dermal irritation at 1,
24, 48 and 72 hours after unwrapping.  CR-7 Technical (50% ai) is rated
as non-irritating (Toxicity Category IV).  

A primary dermal irritation study on rabbits with the formulated end-use
product Vectorite with CR-7 (5% ai) indicated the test material is not
irritating based on a 72-hour exposure (MRID No. 499493-06).  Two male
and one female albino rabbits received a dose of 500 mg of Vectorite
with CR-7 moistened with deionized water and covered with semi-permeable
dressing.  The test substance was in contact with skin for 4 hours. 
There were no observations of dermal irritation at 1, 24, 48 and 72
hours after unwrapping.  Vectorite with CR-7 (5% ai) is rated as
non-irritating (Toxicity Category IV).

7.	Hypersensitivity Incidents (OCSPP 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) (MRID No. 499492-10).

Literature searches have demonstrated that there are no reports of
ecological or human health hazards caused by Clonostachys rosea strains.
It does not produce recognized toxins, enzymes, or virulence factors
normally associated with mammalian invasiveness or toxicity.   The
results of toxicity testing show there is no risk to human health from
the active ingredient.  Clonostachys rosea strain CR-7 is not toxic,
pathogenic, infective or irritating to mammals.]

D. Aggregate Exposure

	1. Dietary exposure. 

	i. Food. [Dietary exposure from use of Clonostachys rosea strain CR-7,
as proposed, is minimal.  The intended use of Clonostachys rosea strain
CR-7 is application via bee vectoring (using commercial honey bees or
bumble bees) during the bloom period of certain growing plants for the
purposes of disease control and prevention.  Formulated end-use products
with this active ingredient are applied at very low use rates which
would not be expected to increase levels of the microbe above natural
levels (MRID No. 499492-10).  

The results of toxicity testing indicate there is no risk to human
health or the environment from Clonostachys rosea strain CR-7. There are
no reports of ecological or human health hazards caused by this
microorganism. 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
Clonostachys rosea strain CR-7 in consumed drinking water would be
unlikely.  Potential exposure to surface water would be negligible and
exposure to drinking water (well or ground water) would be impossible to
measure.   Clonostachys rosea is ubiquitous in the environment and has
been identified in tissue from a variety of terrestrial plants, aquatic
plants and all types of soils (MRID No. 499492-10).  

The intended use of Clonostachys rosea strain CR-7 is application via
bee vectoring (using commercial honey bees or bumble bees) during the
bloom period of certain growing plants for the purposes of disease
control and prevention.  Formulated end-use products with this active
ingredient are applied at very low use rates which would not be expected
to increase levels of the microbe above natural levels (MRID No.
499492-10).  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 Clonostachys rosea strain CR-7. There are
no reports of ecological or human health hazards caused by this
microorganism. 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 intended use of Clonostachys rosea strain
CR-7 is application via bee vectoring (using commercial honey bees or
bumble bees) during the bloom period of certain growing plants for the
purposes of disease control and prevention.  Formulated end-use products
with this active ingredient are applied at very low use rates which
would not be expected to increase levels of the microbe above natural
levels (MRID No. 499492-10).  The results of toxicity testing indicate
there is no risk to human health or the environment from Clonostachys
rosea strain CR-7. There are no reports of ecological or human health
hazards caused by this microorganism. 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, Clonostachys rosea
strain CR-7 would result in residues that are of toxicological concern.
The intended use of Clonostachys rosea strain CR-7 is application via
bee vectoring (using commercial honey bees or bumble bees) during the
bloom period of certain growing plants for the purposes of disease
control and prevention.  Formulated end-use products with this active
ingredient are applied at very low use rates which would not be expected
to increase levels of the microbe above natural levels (MRID No.
499492-10).  The results of toxicity testing indicate there is no risk
to human health or the environment from Clonostachys rosea strain CR-7.
There are no reports of ecological or human health hazards caused by
this microorganism. 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
Clonostachys rosea strain CR-7 is not toxic, pathogenic, infective or
irritating to mammals.  The intended use of Clonostachys rosea strain
CR-7 is application via bee vectoring (using commercial honey bees or
bumble bees) during the bloom period of certain growing plants for the
purposes of disease control and prevention.  Formulated end-use products
with this active ingredient are applied at very low use rates which
would not be expected to increase levels of the microbe above natural
levels (MRID No. 499492-10).  The results of toxicity testing indicate
there is no risk to human health or the environment from Clonostachys
rosea strain CR-7. There are no reports of ecological or human health
hazards caused by this microorganism. 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, Clonostachys rosea strain CR-7 would result in
residues that are of toxicological concern. There is a reasonable
certainty of no harm for infants and children from exposure to
Clonostachys rosea strain CR-7 from the proposed uses.]

G. Effects on the Immune and Endocrine Systems

	[To date there is no evidence to suggest that Clonostachys rosea strain
CR-7 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 or tolerance exemption for Clonostachys
rosea strain CR-7.]

I. International Tolerances

[A Codex Alimentarium Commission Maximum Residue Level (MRL) is not
established for Clonostachys rosea strain CR-7.]

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