Document ID: EPA-HQ-OPP-2011-0669-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-09-07T04:00Z

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: Sheryl Reilly, Branch Chief, 703-308-8269 

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: hollis.linda@epa.gov.

TEMPLATE:

AgraQuest, Inc.

[1F7896]

	EPA has received a pesticide petition (insert petition number) from AgraQuest, Inc., 1540 Drew Avenue, Davis, CA 95618 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

(Options (pick one)
   
   	

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

(Options (pick one)
   
   	1. microbial pesticide  Bacillus subtilis strain QST 713 variant Soil

		
	

Pursuant to section 408(d)(2)(A)(i) of  FFDCA, as amended, AgraQuest, Inc. has submitted the following summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by AgraQuest, 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. AgraQuest, Inc. Petition Summary
   
   	[1F7896]
A. Product Name and Proposed Use Practices

	Bacillus subtilis strain QST 713 is the active ingredient in the formulated end-use product Serenade[(R)] ASO (EPA Reg. No. 69592-12), with uses as a foliar spray on many agricultural field and greenhouse crops, soil treatment for selected agricultural field corps, foliar and soil drench treatments for ornamentals including turf, in fields, greenhouses and nurseries.  Serenade ASO is also sold under an alternate brand name into the consumer home and garden market for use on a variety of crops for foliar applications.   

Bacillus subtilis strain QST 713 variant Soil is the active ingredient in the proposed formulated end-use product Serenade[(R)] Soil DPZ(TM).  The formulated product containing Bacillus subtilis strain QST 713 variant Soil is intended for use as a fungicide for the control or suppression of various soil diseases including Rhizoctonia spp., Pythium spp., Fusarium spp., Verticillium spp., and Phytophthora spp.  Treatment with Serenade Soil DPZ enhances plant growth and plant health.  The end-use product, Serenade Soil DPZ, consists of a 1.57% active ingredient aqueous suspension formulation that is mixed with water and applied as a soil drench or in-furrow spray with conventional application equipment.  It may also be shaked-in or injected into the soil prior to-, at-, or post-planting/transplanting of crops alone or with most types of liquid nutrients.  Serenade Soil DPZ can be mixed with chemical fungicides registered for soil applications.  It may be applied as a water-based slurry alone or with other registered seed treatment insecticides and fungicides through standard slurry or mist commercial seed treatment equipment.  The product would be applied at a maximum application rate of 6 quarts per acre for field applications. 

B. Product Identity/Chemistry

1. Identity of the pesticide and corresponding residues. Bacillus subtilis strain QST 713 variant Soil is a microbial pesticide active ingredient.  Serenade Soil DPZ's fermentation and formulation processes and inert ingredients are the same as for Serenade ASO (EPA Reg. No. 69592-12); therefore no new impurities are produced as the strains differ in a single point mutation which results in enhanced root colonization by Bacillus subtilis strain QST 713 variant Soil compared to the parent strain Bacillus subtilis strain QST 713.  Therefore, the active ingredient Bacillus subtilis strain QST 713 and Bacillus subtilis strain QST 713 variant Soil are substantially similar and data supporting the existing registration of Serenade ASO is supportive of the proposed product Serenade Soil DPZ.  
       
The parent strain Bacillus subtilis strain QST 713 is a EPA- registered microbial pesticide active ingredient and has an exemption from tolerance (40 CFR §180.1209).  Bacillus subtilis strain QST 713 variant Soil has the same active component and has been shown to have the same activity spectrum as Bacillus subtilis strain QST 713 with enhanced plant growth and promotion of plant health when applied in the soil prior to-, at-, or post-planting/transplanting of crops or as a seed treatment.

	2. Magnitude of residues at the time of harvest and method used to determine the residue. Since Bacillus subtilis is a ubiquitous organism, it is commonly recovered from soil, water and decomposing plant residue.  It is found at population levels of 10[6] to 10[7] per gram of soil (EPA Risk Assessment of Bacillus subtilis, February, 1997); therefore, any residues of Bacillus subtilis strain QST 713 variant Soil on crops at the time of harvest are not of concern due to the low toxicity and non-pathogenic nature of these strains, and the long history of human exposure to Bacillus subtilis spores including use of the strain as a probiotic.  In addition, common food handling practices would further reduce human exposure.  It would be difficult to routinely determine if any Bacillus subtilis strain QST 713 variant Soil residue on crops were from the natural environment or from applications of the microbial pest control agent.  Studies indicate that the MPCA concentration is elevated directly after foliar application to crops but then declines rapidly, though Bacillus spores may persist at low levels on the plant surfaces and in the soil community.  Environmental factors can reduce populations on plant surfaces due to UV radiation, excess moisture, and competition for nutrients from other microbes.  Bacillus subtilis strain QST 713 variant Soil applied to the soil would be expected to become part of the soil community and have no negative effect on the indigenous soil community.

	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 detecting Bacillus subtilis strain QST 713 variant Soil is not applicable.  It is expected that, when used as proposed, Bacillus subtilis strain QST 713 variant Soil would not result in residues that are of toxicological concern. 

C. Mammalian Toxicological Profile

	Bacillus subtilis strain QST 713 and Bacillus subtilis strain QST 713 variant Soil are produced under the same conditions; therefore, the resulting products are substantially similar.  It is not unreasonable to conclude, based on the similarity in product composition and production, measured physical/chemical, and pathogenicity / infectivity toxicity data that data generated for Bacillus subtilis strain QST 713 can be used to bridge any data gaps for which there are no corresponding Bacillus subtilis strain QST 713 variant Soil toxicity data.  (This concept was proposed to and accepted by BPPD at a December 14, 2010 pre-registration meeting with AgraQuest.)  At the request of the Agency a study to evaluate the safety to mammals and demonstrate equivalence of the strains has been conducted with the Bacillus subtilis strain QST 713 variant Soil and compared to the same study conducted Bacillus subtilis strain QST 713, and is summarized as follows: 
There was no mortality in any group during the study.  During observations for clinical signs, all animals appeared normal for the duration of the study.  The gross necropsy conducted at termination of the study revealed no observable abnormalities with the exception of two enlarged and/or discoloured spleens from the test group.  The test organism had cleared completely from treatment group blood and brains by Day 21 and showed a pattern of clearance for the lungs, liver, spleen, kidneys mesenteric lymph nodes and cecum contents. 

The test substance was determined to be non-toxic, non-infective and non-pathogenic to rats when injected intravenously at a dose of 6.6 x 108 cfu/rat. 

Due to the similarity of the results for both Intravenous Toxicity / Pathogenicity Study in Rats conducted with Bacillus subtilis strain QST 713 and Bacillus subtilis strain QST 713 variant Soil, it is not unreasonable to conclude, that data generated for Bacillus subtilis strain QST 713 can be used to bridge any data gaps for which there are no corresponding Bacillus subtilis strain QST 713 variant Soil data.  Therefore, the battery of OPPTS series 885 studies that were conducted on Bacillus subtilis strain QST 713 technical powder to determine the potential detrimental effects to humans by the strain are representative of the toxicological / pathogenicity profile of the strain Bacillus subtilis strain QST 713 variant Soil.  Results from studies on file with Agency are summarized below.

                    OPPTS Guideline Number     (OPP Number)
                                  Study Title
                                Test Substance
                                 Study Result
                                   Tox. Cat.
                                    MRID #
                                   885.3100
Acute Dermal Toxicity / Pathology Rabbits
QST 713 Technical Powder
LD50 >2000 mg/kg;
Doses: 2.3E +11  -  1.73E+11 cfu  /animal
no deaths occurred;
no signs of systemic  toxicity
                                      III
                                   44651907
                                   885.3200
Acute Intravenous (Injection) Toxicity / Pathogenicity  Rats 
QST 713 Technical Powder
LD50 >9.4E+06 cfu/animal 
not toxic or pathogenic; 
no mortality and no adverse clinical signs
                                      N/A
                                   44651908
                                   885.3150
Acute (Intratracheal) Pulmonary Toxicity / Pathogenicity
Rats
QST 713 Technical Powder
LD50 >1.2E+08 cfu/animal
in 0.1 ml
not toxic or pathogenic;
no mortality and no adverse effects 
                                      N/A
                                   44651909 
                                   885.3400
Hypersensitivity Incidents
QST 713 Technical Powder
none reported
                                      N/A
                                       
                               885.3050
(152-30)
Acute Oral Toxicity / Pathogenicity
Rats
QST 713 Technical Powder
LD50 >1.13E+08 cfu/animal
not toxic or pathogenic
                                      IV
                                   44651906 
                                   870.2400
Acute Eye Irritation Rabbits
QST 713 Technical Powder
mild or slight irritant
                                      III
                                   44664602 
                                   870.2500
Acute Dermal Irritation Rabbits
QST 713 Technical Powder
slight irritant
                                      IV
                                   44664601 
Toxicity Data on End-Use Product
Both Serenade ASO (EPA Reg. No. 69592-12), Serenade AS (EPA Reg. No. 695925-8) and Serenade Soil DPZ (EPA Reg. No. 69592-EI) contain the same amount of active ingredient, and based on the similarity in product composition and production, measured physical/chemical, and pathogenicity / infectivity toxicity data, it is not unreasonable to conclude that the end-use product toxicity data for Serenade AS, non-organic formulation and Serenade ASO, eligible for organic production under NOP regulations, support Serenade Soil DPZ acute toxicity Tier 1 870 series data requirements.  Results for the currently registered products to support Serenade Soil DPZ are as follows:
OPPTS Guideline Number
Study Title
Test Substance
Study Result
                               Toxicity Category
                                    MRID #
OPPTS 870.1100
Acute Oral Toxicity 
Serenade AS
LD50 >5000 mg/kg
                                      IV
                                   45385304
OPPTS 870.1200
Acute Dermal Toxicity
Serenade AS
LD50 >5000 mg/kg
                                      IV
                                   45385305
OPPTS 870.1300
Acute Inhalation Toxicity
Serenade AS
LC50 >1.45 mg/L
                                      III
                                   45385306
OPPTS 870.2400
Acute Eye Irritation
Serenade AS
nonirritant
                                      IV
                                   45385307
OPPTS 870.2500
Acute Dermal Irritation
Serenade AS
mild or slight irritant
                                      IV
                                   45385308
OPPTS 870.2600
Dermal Sensitization
Serenade AS
not a sensitizer
                                      N/A
                                   45385309

Serenade ASO contains the same certified limits of active ingredient as Serenade AS.  All of the inert ingredients in Serenade ASO are from EPA's Inert List, 4(a) or 4(b).  Under the USDA's National Organic Program the active ingredient also qualifies as an organic material, thus Serenade ASO is labeled in the USA for use in organic agriculture.  Serenade ASO should be considered even more toxicologically benign and environmentally sound than Serenade AS.  A comparison of the additives for the two products is located in MRID 46012201.  By extension the data generated on Serenade AS is supportive of Serenade Soil DPZ.

The results of toxicity testing with Bacillus subtilis strain QST 713 and Bacillus subtilis strain QST 713 variant Soil and information found in published literature, and EPA Bacillus subtilis Case 6012, Final Registration Review Decision (March 2010) on this strain and other strains of Bacillus subtilis indicate that no foreseeable risks to human health are to be expected by Bacillus subtilis strain QST 713 variant Soil.

D. Aggregate Exposure

	1. Dietary exposure. Due to the ubiquitous nature of the organism, the concentrations of Bacillus subtilis and other closely related Bacillus species that already exist in the environment, the likelihood of increased risk to humans or animals from the use of Serenade Soil DPZ is low.  EPA in its registration review decision concluded "the risk posed to adults, infants, and children is likely to be minimal because of the low acute oral toxicity/Pathogenicity potential of Bacillus subtilis strain QST 713."  Common food handling practices such as washing and peeling would also reduce any residues on crops.  It is not unreasonable to conclude, based on the similarity in product composition and production, measured physical/chemical, and pathogenicity / infectivity toxicity data, that the risk from any potential exposure to Bacillus subtilis strain QST 713 variant Soil in Serenade Soil DPZ would be minimal.

	i. Food. Due to the ubiquitous nature of the organism, the concentrations of Bacillus subtilis and other closely related Bacillus species that already exist in the environment, the likelihood of increased risk to humans or animals from the use of Serenade Soil DPZ is low.  EPA in its registration review decision concluded "the risk posed to adults, infants, and children is likely to be minimal because of the low acute oral toxicity/Pathogenicity potential of Bacillus subtilis strain QST 713."  It is not unreasonable to conclude, based on the similarity in product composition and production, measured physical/chemical, and pathogenicity / infectivity toxicity data, that the risk from any potential exposure to Bacillus subtilis strain QST 713 variant Soil in Serenade Soil DPZ would be minimal.

	ii. Drinking water.  As discussed in literature and EPA Bacillus subtilis Case 6012, Final Registration Review Decision (March 2010), intake of low levels of ubiquitous Bacillus subtilis in drinking water may occur but exposure would represent a minimal risk due to the low toxicity of the strain.  Similarly exposure to other strains of Bacillus subtilis would not represent a greater risk.  It is not unreasonable to conclude, based on the similarity in product composition and production, measured physical/chemical, pathogenicity / infectivity toxicity data, that the risk from any potential exposure to Bacillus subtilis strain QST 713 variant Soil in Serenade Soil DPZ would be minimal and equivalent to the risk from exposure to Bacillus subtilis strain QST 713.
	2. Non-dietary exposure. The use sites for Serenade Soil DPZ containing Bacillus subtilis strain QST 713 variant Soil include both agricultural and residential garden sites.  Based on the toxicity information on file with the Agency, aggregate exposure to Bacillus subtilis strain QST 713 variant Soil would be below the levels in the safety testing conducted on Bacillus subtilis strain QST 713 and would not represent an undue risk due to the lack of residues of toxicological concern and the low toxicity of the product and active ingredient.  Therefore, the non-dietary exposures to the general population, including infants and children would not be expected to pose any quantifiable risk due to a lack of residues of toxicological concern.  Serenade Soil DPZ in the manufacturing plant (fermentation facility) will be minimal due to rigorous Good Manufacturing Practices and quality controls put in place to minimize contamination, cross contamination, and exposure to the workers, and also due to protective equipment worn by manufacturing plant workers.  Therefore, inadvertent releases in the workplace would not be expected to increase the risk to workers, especially since high levels of the organism already exist in this environment.  The EPA Risk Assessment of Bacillus subtilis (February, 1997) concludes that ``human health and environmental hazards of Bacillus subtilis are low'' and ``the number of microorganisms released from the fermentation facility is low''.  Furthermore exposure to Bacillus subtilis strain QST 713 variant Soil would be minimized by use of required personal protection equipment by applicators, handlers and manufacturing workers.  It is not unreasonable to conclude, based on the similarity in product composition and production, measured physical/chemical, and pathogenicity / infectivity toxicity data, that the risk from any potential exposure to Bacillus subtilis strain QST 713 variant Soil in Serenade Soil DPZ would be minimal and equivalent to the risk from exposure to Bacillus subtilis strain QST 713 which has been fully assessed by the Agency.  

E. Cumulative Effects

	According the EPA Bacillus subtilis Case 6012, Final Registration Review Decision (March 2010), no toxic mechanism has been associated with the mode of action of Bacillus subtilis strain QST 713; therefore, no cumulative toxic effect would be expected for this strain or with other related strains of Bacillus subtilis.  Therefore, it is not unreasonable to conclude, based on the similarity in product composition and production, measured physical/chemical, and pathogenicity / infectivity toxicity data that no cumulative toxic effect would result from exposure to Bacillus subtilis strain QST 713 variant Soil in Serenade Soil DPZ.  Therefore, the likely hood of adverse dietary effects is expected to be minimal for the general population and to infants and children.

F. Safety Determination

	1. U.S. population. Bacillus subtilis strain QST 713 is not pathogenic or infective to mammals.  There have been no reports of toxins associated with the organism and acute toxicity/pathogenicity data demonstrate that Bacillus subtilis strain QST 713 is non-toxic, non-pathogenic, and non-irritating or slightly irritating to the skin and eyes depending on the formulation type.  Therefore, it is not unreasonable to conclude, based on the similarity in product composition and production, measured physical/chemical, and pathogenicity / infectivity toxicity data for Bacillus subtilis strain QST 713 and Bacillus subtilis strain QST 713 variant Soil that there is reasonable certainty of no harm to the general US population from exposure to residues of the substantially similar active ingredient Bacillus subtilis strain QST 713 variant Soil in Serenade Soil DPZ, when used as proposed.

	2. Infants and children. As stated above, it is not expected that, when used as proposed, Bacillus subtilis strain QST 713 variant Soil would result in residues of toxicological concern.  This conclusion is supported by the data on the substantially similar strain Bacillus subtilis strain QST 713, public literature and EPA's Bacillus subtilis Case 6012, Final Registration Review Decision (March 2010).  There is reasonable certainly of no harm to infants and children from exposure to Bacillus subtilis strain QST 713 variant Soil from the proposed uses.  

G. Effects on the Immune and Endocrine Systems

	Bacillus subtilis strain QST 713 and Bacillus subtilis strain QST 713 variant Soil are naturally occurring, non-pathogenic organisms.  There is no evidence to suggest that Bacillus subtilis strain QST 713 or the substantially similar Bacillus subtilis strain QST 713 variant Soil will compromise the immune or endocrine systems, or that it functions in a manner similar to any known hormone or endocrine disruptor. 

H. Existing Tolerances

	While there are no existing tolerances for Bacillus subtilis strain QST 713 variant Soil, there is an exemption from tolerance for the substantially similar Bacillus subtilis strain QST 713.  On July 5, 2000, EPA established an exemption from the requirement of a tolerance for residues of the Bacillus subtilis strain QST 713 in or on all raw agricultural commodities when applied/used according to label instructions in 40 CFR §180.1209 which reads as follows; 

An exemption from the requirement of a tolerance is established for residues of the microbial pesticide Bacillus subtilis strain QST 713 when used in or on all food commodities.

FR Doc. 00-16803 Filed 7-3-00; 8:45 am
BILLING CODE 6560-50-F.

I. International Tolerances

	There is no Codex alimentarius commission maximum residue level for Bacillus subtilis strain QST 713.   
EU - Maximum Residue Levels (Reg. (EC) No 396/2005) (MRLs) as amended by Commission Regulation (EC) No 839/2008 of 31 July 2008 to include in Annex IV Bacillus subtilis strain QST 713 as an active substance for which no maximum residue levels (MRLs) in or on food and feed of plant and animal origin are required.