BIOPESTICIDES REGISTRATION ACTION DOCUMENT

Pasteuria usgae

Pesticide Chemical (PC) Code: 006545

U.S. Environmental Protection Agency Office of Pesticide Programs Biopesticides and Pollution Prevention Division

Last Updated – May 3, 2010Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010



### Table of Contents

I. EXECUTIVE SUMMARY 4

II. ACTIVE INGREDIENT OVERVIEW 7

III. REGULATORY BACKGROUND 7 A. Applications for Pesticide Registration 7 B. Request for an Experimental Use Permit 8 C. Food Tolerance Exemptions 8

IV. RISK ASSESSMENT 9 A. Product Analysis Assessment 9 1. Product Chemistry and Composition 10 2. Analysis of Samples 11 3. Physical and Chemical Characteristics 11

B. Human Health Assessment 11 1. Toxicology 11 2. Food Quality Protection Act Considerations______________________ 14 3. Occupational Exposure and Risk Characterization 17
4. Human Health Risk Characterization 17
C. Environmental Assessment 17 1. Summary of Nontarget Organism Waiver Rationales 18
2. Environmental Effects Conclusions 20 3. Threatened and Endangered Species Assessment 21

V. ENVIRONMENTAL JUSTICE 21

VI. PUBLIC INTEREST FINDING 22

VII. RISK MANAGEMENT AND REGISTRATION DECISIONS 23

A. Determination of Eligibility 23

1. Pasteuria usgae – BL1 23
2. EconemTM and Pasteuria usgae – Liquid Formulation 23

B. Registration Review 24

C. Regulatory Decisions 24

1. Pasteuria usgae – BL1 24

2. EconemTM 25

3. Pasteuria usgae – Liquid Formulation 25

D. Labeling 26 VIII. ACTIONS REQUIRED BY THE REGISTRANT 26

A. Final Printed Labeling 26

B. Terms and Conditions of the Pasteuria usgae Pesticide Products 26

1. Pasteuria usgae – BL1 26

2. EconemTM 28

3. Pasteuria usgae – Liquid Formulation 28

C. Reporting of Adverse Effects and Hypersensitivity Incidents 29

IX. GLOSSARY OF ACRONYMS AND ABBREVIATIONS 30

X. BIBLIOGRAPHY 31

A. Studies Submitted to Support the Pasteuria usgae Pesticide Product Registrations 31

B. Environmental Protection Agency Risk Assessment Memoranda 36

C. Other References 36

APPENDIX A 38

APPENDIX B 48

2Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

Office of Pesticide Programs Biopesticides and Pollution Prevention Division
Microbial Pesticides Branch

Science Reviews

Stuart Schüssel Product Analysis, Human Health John Kough, Ph.D. Product Analysis, Human Health Shannon Borges Environmental Effects Zigfridas Vaituzis, Ph.D. Environmental Effects

Regulations

Sheryl Reilly, Ph.D. Chief, Microbial Pesticides Branch Jeannine Kausch Regulatory Action Leader

3Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

I. EXECUTIVE SUMMARY

Pasteuria species are gram-positive, mycelial, endospore-forming bacteria that are endoparasitic to nematodes and water fl eas. The microbial active ingredient, Pasteuria

usgae , is host-specific to the sting nematode ( Belonolaimus longicaudatus ), which can be damaging to a wide variety of crops such as turf and strawberry. The active agent of Pasteuria usgae is an endospore that attaches to a nd infects the host nematode during all life stages (except eggs ). These endospores are formed insi de the host, released into the soil when the infected nematode decomposes, and considered nonmotile and stable in the soil environment for several years.

Environmental Protection Agency (EPA or the Agency) scientists ha ve reviewed product analysis, toxicology, and nontarget organi sm/environmental fate data and other information (40 Code of Federal Regulations (CFR) §§ 158.2120, 158.2140, and 158.2150, respectively) submitted to support the registration of three Pasteuria usgae pesticide products. Previously, it was determ ined that the data and other information submitted adequately satisfied current guideline requirements for the purposes of particular time-limited, conditional registra tions under section 3(c )(7) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) fo r a manufacturing-use product ( Pasteuria usgae – BL1, EPA Registration Number 85004-1) and an end-use product (EconemTM, EPA Registration Number 85004-2) . The Agency is now proposing to conditionally register th e pending end-use product, Pasteuria usgae – Liquid Formulation (EPA File Symbol 85004-G), with this microbi al pesticide active i ngredient’s first food use and according to the provisions of FIFRA section 3(c)(7)(A). All pesticide products containing Pasteuria usgae are presumed to be in the public interest as they could serve as partial replacements for conventional nematic ides of continuing concern to the Agency (e.g., methyl bromide (ozone-depleting subs tance) and 1,3-dichloropropene (probable human carcinogen)).

For the purposes of conditional, time-limited registrations, product analysis data requirements for Pasteuria usgae (to include product chemistry and composition, analysis of samples, and physical and chem ical characteristics) were satisfied by acceptable guideline studies. Additional produc t analysis data that the Agency is requiring by specific dates include the following:

• A written description of quality control measures taken during the manufacturing process to screen for Pasteuria species that parasitize saprophytic nematodes. This information was submitted by the registrant in a timely manner and is currently being reviewed for acceptability.

• A new five-batch analysis with all batches from production level.

• Results from an ongoing twelve-month storage stability study. This information was submitted by the registrant in a timely manner and is currently being reviewed for acceptability.

4Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Lastly, documentation indicati ng official recognition of Pasteuria usgae as a species by
the Judicial Commission of the Internati onal Committee for Systematic Bacteriology must be submitted to the Agency when it becomes available.

Adequate mammalian toxicology data and other information were submitted to support

all of the Pasteuria usgae pesticide products. The Tier I microbial pesticide toxicological studies showed that, at a single high dose, Pasteuria usgae is not toxic and/or pathogenic via any examined route of exposure (i.e., or al, dermal, pulmonary, and injection). Since microbial enumeration was not performed in some of these tests because Pasteuria usgae would not grow on agar media, the infectivity was uncertain. However, because Pasteuria usgae spores are highly specific to the sti ng nematode, infectiv ity is unlikely to be a concern. Moreover, no hypersensitivity in cidents, occurring during the testing or production of Pasteuria usgae , were observed by the registra nt. Given the results of the Tier I toxicological studies a nd the absence of hypersensitivity incidents, testing at higher tiers was not required.

The Agency has made a preliminary conclusion that there is a reasonable certainty that no
harm will result to the Unite d States population, including in fants and children, from
aggregate exposure to the residues of Pasteuria usgae . No dietary risks are expected from

use of Pasteuria usgae as an active ingredient in pest icide products. Significant dietary exposure (through food and drinki ng water) is not expected given the established and proposed use patterns, use sites, and applic ation methods for the pesticide products, as well as standard practices for postharvest handling of food commodities (e.g., washing and cooking) and drinking water treatment (e .g., high temperatures and pH adjustments). In the unlikely event oral exposure should occur through food or drinking water, such
exposure to Pasteuria usgae is expected to be several orde rs of magnitude lower than the

dose used in the acute oral toxicity/pathogenicity test , during which no toxic or pathogenic effects were observe d in rats. Finally, nonoccupati onal exposure is considered unlikely for Pasteuria usgae as all currently approved or proposed uses occur in distinctly agricultural or commercial setti ngs, and there are no currently approved or proposed uses for residential areas.

Despite the low toxicological profile of Pasteuria usgae , baseline personal protective equipment (PPE) is required for handlers th at may be exposed to the active ingredient, due to their occupation, for prolonge d periods. Handlers working with Pasteuria usgae in manufacturing facilities or in occupational and agricultural settings are directed to wear a long-sleeved shirt, long pants, socks, shoes, waterproof gloves, and a dust/mist filtering respirator meeting National Institute for Occupational Safety and Health (NIOSH) standards of at least N-95, R-95, or P-95. Th e Agency may require additional PPE, other than the standard described above, on a pr oduct-specific basis. For example, protective eyewear is required for Econem TM, the registered granular Pasteuria usgae formulation.

Data waiver rationales were submitted in response to data requirements for avian, freshwater fish and invertebrate, insect, and honey bee nontarget organism testing requirements. The information provided is sufficient to satisfy the Tier I nontarget organism data requirements for the pesticide products containing Pasteuria usgae as an

5Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

active ingredient. Further tes ting of nontarget organisms at higher tier levels is not required. Based on the rationales submitted, adverse effects to terrestrial animals and plants or freshwater and marine /estuarine fish, invertebrates, and plants are not expected as a result of exposure to current a nd proposed labeled applications of Pasteuria usgae

. Furthermore, the Agency has made “No Eff ect” (NE) determinations for direct and indirect effects to listed speci es and their habitat as a resu lt of the current and proposed

uses of Pasteuria usgae

.

On October 1, 2009, the Agency announced a ne w policy to provide a more meaningful opportunity for the public to par ticipate in major regi stration decisions before they occur. According to this new policy, the Agency in tends to provide a public comment period prior to making a registration decision fo r, at minimum, the following types of applications: new active ingredients; first f ood uses; first outdoor uses; first residential uses; and any registration decisions for which the Agency believes there may be substantial public interest.

Consistent with the new policy of making re gistration actions more transparent, the proposed end-use product containing Pasteuria usgae as an active ingredient ( Pasteuria

usgae – Liquid Formulation, EPA File Symbol 85004-G) is subject to a 30-day comment period because the associated label allows for applications to strawberry, which is considered a “first food use” for this particul ar active ingredient. While a final decision on registration is contingent upon review and considerati on of public comments, the Agency presently believes that, based upon the preliminary risk assessment and information submitted in support of registration of Pasteuria usgae – Liquid Formulation, it is in the best interest of the public and th e environment to issue the registration for this pesticide product with a first food use. The basis for this preliminary decision can be

found in the risk assessment for Pasteuria usgae , which is character ized throughout this

BRAD.

6Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

II. ACTIVE INGREDIENT OVERVIEW

Biological Name: Pasteuria usgae

Culture Deposit: American Type Culture Collection in Manassas, Virginia under Accession Number SD-5835

Office of Pesticide Programs (OPP)
Chemical Code: 006545

Type of Pesticide: Microbial Pesticide – Nematicide

See Appendix B for specific information (e.g., use sites, application rates, methods of application, formulation types, and ta rget pests) regarding the registered and proposed pesticide products containing this active ingredient.

III. REGULATORY BACKGROUND

A. Applications for Pesticide Registration

On May 5, 2008, MacIntosh and Associates, Incorporated (address: 1203 Hartford Avenue, Saint Paul, Minnesota 55116-1622), acti ng as the authorized agent for Pasteuria Bioscience, Incorporated (a ddress: 12085 Research Drive, Suite 185, Alachua, Florida 32615), submitted an application to register Pasteuria usgae – BL1 (EPA File Symbol 85004-R) under FIFRA section 3. On August 13, 2008, the Agency announced receipt of this application to register a pesticide product containing a new active ingredient ( 73 Federal Register (FR) 47166 ) and opened a 60-day public comment period pursuant to the provisions of FIFRA sect ion 3(c)(4). No comments were received following this publication.

Pursuant to FIFRA section 3(c)(7)(C), a condi tional, time-limited registration was issued for the manufacturing-use product, Pasteuria usgae – BL1, on June 2, 2009 (EPA Registration Number 85004-1). The Agency announced the approval to conditionally register Pasteuria usgae – BL1, containing a new active ingredient, in the Federal Register of July 1, 2009 ( 74 FR 31426 ).

While the Agency was assessing the da ta submitted in connection with Pasteuria usgae

– BL1, MacIntosh and Associates, Incorporated (on behalf of Pasteuria Bioscience, Incorporated) submitted two additional applic ations for associated end-use products (Econem TM , EPA File Symbol 85004-E; Pasteuria usgae – Liquid Formulation, EPA File Symbol 85004-G). Pursuant to FIFRA secti on 3(c)(7)(A), a conditional, time-limited registration was issued for EconemTM, a granular end-use product to be applied to turf to

7Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

control sting nematode, on September 3, 2009 (EPA Registration Number 85004-2). The other end-use product is associated with a “n ew use” as one of the proposed use patterns (i.e., application to strawbe rry) requires the establishmen t of an exemption from the requirement of a tolerance under section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA) ( 40 CFR § 152.3 ). Pursuant to the provisions of FIFRA section 3(c)(4), on March 5, 2010, the Agency announced receipt of the application from MacIntosh and Associates, Incorporated (on be half of Pasteuria Bioscience , Incorporated) requesting to register a new use ( 75 FR 10259 ). No comments were received following this publication. A formal decision has not ye t been made on this application.

B. Request for an Experimental Use Permit

On January 14, 2009, receipt of an experiment al use permit application was announced in the Federal Register ( 74 FR 2070 ), and a 30-day public comment period was opened. No comments were received following this publi cation. After the asso ciated temporary exemption from the requirement for a tolerance was established for Pasteuria usgae (see section III(C) ), the experimental use permit was issued on August 12, 2009 (EPA Experimental Use Permit Number 85004-EUP-1) . This experimental use permit allowed the use of 59,675 pounds of formulated product (3,272.5 pounds of nematicidal active ingredient, Pasteuria usgae ) on 385 acres of strawberry and tu rf to evaluate control of the sting nematode under various methods of a pplication. The program was authorized only in the States of Alabama, Florida, Geor gia, Mississippi, and North Carolina and was effective from August 12, 2009 to August 31, 20 10. Issuance of this experimental use permit was announced in the Federal Register of August 27, 2009 ( 74 FR 43696 ).

C. Food Tolerance Exemptions

Concurrent with their experimental use permit application and under FFDCA section 408(d), MacIntosh and Associat es, Incorporated (on behalf of Pasteuria Bioscience, Incorporated) submitted a petition to esta blish a temporary exemption from the requirement of a tolerance for Pasteuria usgae (Pesticide Petition (PP) 8G7471). In the Federal Register of January 8, 2009 ( 74 FR 808 ), the Agency announced that MacIntosh and Associates, Incorporated (on behalf of Pasteuria Bioscience, Incorporated) proposed to establish a temporary exemption from the re quirement of a tolerance for residues of the microbial nematicide, Pasteuria usgae , in or on strawberries and opened a 30-day public comment period. No comments were r eceived following this publication.

On August 5, 2009, the Agency established a te mporary exemption from the requirement

of a tolerance for Pasteuria usgae when applied/used as a nematicide on strawberries in accordance with the terms of Experime ntal Use Permit 85004-EUP-1 (40 CFR § 180.1290; 74 FR 38970 ). This temporary exemption from the requirement of a tolerance expires and is revoked on December 31, 2010.

In addition to the petition associated with the temporary exemption that was submitted with the experimental use permit, MacIntosh and Associates, Incorpor ated (on behalf of Pasteuria Bioscience, Incorporated) also s ubmitted a separate petition, along with their

8Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

application for registration for Pasteuria usgae – Liquid Formulation (EPA File Symbol 85004-G), to establish a permanent exemption from the requirement of a tolerance for Pasteuria usgae (PP 9F7539). In the Federal Register of April 8, 2009 ( 74 FR 15969 ), the Agency announced that MacIntosh and Associat es, Incorporated (on behalf of Pasteuria Bioscience, Incorporated) proposed to es tablish a permanent exemption from the requirement of a tolerance for residues of the microbial nematicide, Pasteuria usgae , in or on all food commodities and opened a 30-da y public comment period. No substantive comments were received following this publicat ion. A formal decision has not yet been made on this petition.

IV. RISK ASSESSMENT

On October 26, 2007, the Agency issued a Final Rule in the Federal Register on the data requirements to support registra tion of biochemical and microbi al pesticides and updated

the definitions for biochemical and microbial pesticides ( 72 FR 61002 ). The rule became effective on December 26, 2007. The data and information evaluated for this Biopesticides Registration Action Document (B RAD) were considered in light of these requirements.

The classifications that are found for each data submission are assigned by Agency
science reviewers and are an indication of the usefulness of the information contained in

the documents for risk assessment. A rati ng of “ACCEPTABLE” indi cates the study is scientifically sound and is useful for ri sk assessment. A “SUPPLEMENTAL” rating indicates the data provide some information th at can be useful for risk assessment. The studies may have certain aspects determin ed not to be scientifically acceptable (“SUPPLEMENTAL: UPGRADABLE”). If a study is rated as “SUPPLEMENTAL: UPGRADABLE,” the Agency always provides an indication of what is lacking or what can be provided to change the rating to “ACCEPTABLE.” If there is simply a “SUPPLEMENTAL” rating, the revi ewer will often state that the study is not required by the current 40 CFR part 158. Both “ACCEPTABLE” and “SUPPLEMENTAL” studies may be used in the risk assessment pr ocess as appropriate. An “UNACCEPTABLE” rating indicates that new data need to be submitted.

For the acute toxicity data requirements, toxicity categories are assigned based on the hazard(s) identified from studies and/or info rmation submitted to the Agency. The active ingredient or particular product is classified into Toxicity Ca tegory I, II, III, or IV, where Toxicity Category I indicates the highest toxi city and Toxicity Cate gory IV indicates the lowest toxicity.

A. Product Analysis Assessment ( 40 CFR § 158.2 12 0 )

For purposes of conditional, time-limited registrations, all product analysis data requirements have been satisfied by accepta ble guideline studies. The Agency is requiring additional product analysis data on Pasteuria usgae by specific dates.

9Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

For a comprehensive guideline-by-guideline summary of the generic product analysis data requirements described in sections IV (A)(1), IV(A)(2), and IV(A)(3), as well as additional product-specific data submitted to support individual registrations, refer to

Tables 1 and 2 in Appendix A

.

1. Product Chemistry and Compositio n (Office of Chemical Safety and Pollution Prevention (OCSPP) Guidelines 885.1100, 885.1200, and 885.1300)

Pasteuria species are gram-positive, mycelial, endospore-forming bacteria that are endoparasitic to nematodes and water fleas. The endospores of Pasteuria species can be identified and counted microscopically, but it is difficult to distinguish between species unless high magnification electron microscopy is used so that size and shape of the spores
can be visualized and measur ed. Molecular techniques such as polymerase chain reaction (PCR) methods have been reported for Pasteuria penetrans but have not been developed for the other species. Therefore, host specificity assay, requiring the establishment of nematode cultures and a bioassay, is the most direct and reliable technique for species

identification.

Pasteuria usgae , a recently discovered strain, is host-specific to the sting nematode ( Belonolaimus longicaudatus ), which can be damaging to a variety of crops such as turf and strawberry. Currently, full recognition of Pasteuria usgae as a species is still pending
with the Judicial Commission of the International Committee for Systematic Bacteriology. Once Pasteuria usgae has been recognized and removed from the category
Candidatus , documentation indicating official re cognition must be provided to the Agency.

The active agent of Pasteuria usgae is an endospore that attach es to and infects the host nematode during all life stages (except eggs). Increased moisture, neutral pH, temperatures above 10°C, and sandy soil seem to provide the best environments for spore attachment to the host. In laboratory studies, Pasteuria species were able to attach to nematodes after exposure to high temperatur es and wide ranges of pH; however, at extremes, the number of attached spores pe r nematode was reduced and, in some cases,

no infection occurred after at tachment. After attachment of the endospore, a germ tube penetrates the nematode cuticle and my celial microcolonies are formed in the pseudocoelom, leading to eventual death of the host. The endospores formed inside the
host are released into the soil when the inf ected nematode decomposes. The spores are nonmotile and stable in the soil environment for several years.

Submitted data also adequately describe the production process and potential microbial contaminants, and these requirements have been satisfied for the purposes of conditional, time-limited registrations. The original manuf acturing process did not describe quality

control measures taken to confirm that Pasteuria usgae was the only Pasteuria species present in the master stock. A follow-up expl anation, which demonstrated that batches are screened for the presence of other microbe s and screened against sting nematodes to confirm the presence of Pasteuria usgae , still did not provide su fficient information to

10Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

indicate that screening for other Pasteuria species is conducted dur ing the manufacturing process. Other Pasteuria species, specifically those that parasitize saprophytic (non-plant pathogenic) nematodes, must be screened fo r during the manufacturing process. Pasteuria Bioscience, Incorporated must integrate quality control measures that screen for

Pasteuria species that parasitize sa prophytic nematodes, either immediately after freezing or after making seed stock, into their current manufacturing process and provide a written description of these measures to the Agen cy on or before October 1, 2009. Information submitted by Pasteuria Bioscience, Incor porated by October 1, 2009 (Master Record Identification Number (MRID No.) 478853-01) is currently being reviewed for acceptability.

2. Analysis of Sample s (OCSPP Guideline 885.1400)

Results of a preliminary five-batch analys is were provided and the requirement for analysis of samples has been satisfied for purposes of conditional, time-limited registrations. The preliminary analysis of samples provided to the Agency revealed a wide range of concentrations, with many re plicates containing 1–2 orders of magnitude
fewer Pasteuria usgae spores than the minimum specified on the Confidential Statement of Formula (CSF) and product label (i.e., 1 x 10 6 spores per milliliter). A follow-up explanation, attempting to address this va riability, mentioned several factors that

contributed to this inconsiste ncy and discussed how the concen tration of spores could be adjusted during the manufacturing process, if necessary. Despite this additional information, a new five-batch analysis, with all batches from production level, must be submitted to the Agency on or before May 1, 2011.

3. Physical and Chemical Char acteristics (OCSPP Guidelines 830.6302, 830.6303, 830.6304, 830.6313, 830.6317, 830.7000, and 830.7300)

Submitted data adequately describe the physical and chemical characteristics of Pasteuria

usgae ; however, a twelve-month storage stabil ity study was cited as ongoing with the original application. Therefore, the requirements for color, ph ysical state, odor, stability to normal and elevated temperatures, metals , and metal ions, pH, and density/relative density/bulk density (specific gravity) have been satisfied. When the storage stability study has been completed and the results have been compiled, these data must be submitted to the Agency on or before June 1, 2010. Information submitted by Pasteuria Bioscience, Incorporated by June 1, 2010 (MRID No. 479672-01) is currently being reviewed for acceptability.

B. Human Health Assessment

1. Toxicology

Adequate mammalian toxicology data and othe r information are available to support the registration of Pasteuria usgae pesticide products, includi ng the most recent end-use product ( Pasteuria usgae – Liquid Formulation, EPA File Symbol 85004-G) proposed for use on strawberry. All Tier I toxicology da ta requirements have been satisfied by

11Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

guideline studies. Furthermore, Tier II a nd Tier III studies were not required for Pasteuria usgae based on the lack of acute toxicity/p athogenicity in the Tier I studies.

For a comprehensive guideline-by-guideline summary of the generic toxicology data requirements described in sections IV(B)(1)(a ) and IV(B)(1)(b), as well as additional product-specific data submitted to support indivi dual registrations, refer to Tables 3 and 4

in Appendix A

.

a. Acute Toxicity/Pathogenicity – Tier I ( 40 CFR § 158.2140 )

Acute Oral Toxicity and Pathogenicity – Rat (OCSPP Guideline 885.3050; MRID No. 474267-09) : There were no treatment-related clini cal signs or necropsy findings in rats receiving a single oral dose of 1 x 10 8 Pasteuria usgae spores. Three males in the microbial pest control agent (MPCA)-treated group gained weight through day 14 but lost weight by day 21. All other animals gained weight prior to sc heduled sacrifice. Pasteuria

usgae does not appear to be t oxic and/or pathogenic in rats when dosed at 1 x 10 8
spores/animal. Since microbial enumeration wa s not performed because the test material would not grow on agar media, the infec tivity was uncertain. However, because the spores are highly specific to the sting nematode, infectivity is unlikely to be a concern. This study was rated “ACCEPTABLE,” and Pasteuria usgae was classified as

TOXICITY CATEGORY IV.

Acute Dermal Toxicity – Rat (OCSPP Guideline 885.3100; MRID No. 474267- 12 ) : There were no treatment-related significant ad verse effects seen in the dosed rats. Two males and one female had very slight erythema on day 1 with clearance by day 4. One male lost weight slightly during the second week and one male and two females lost weight during the first week, but all gained weight by the end of the study. All other animals gained weight throughout the st udy. Based on the results of this study, Pasteuria

usgae does not appear to be toxic in rats wh en treated with 2,000 milligrams /kilogram (mg/kg) at 10 8 spores/milliliter (mL). The acute dermal median lethal dose (LD 50 ) is greater than 2,000 mg/kg for 10 8 spores/mL in male and female rats. This study was rated “ACCEPTABLE,” and Pasteuria usgae was classified as TOXICITY CATEGORY IV.

Acute Pulmonary Toxicity and Pathogenicity – Rat (OCSPP Guideline 885.3150; MRID No. 474267-10) : In an acute pulmonary toxicity and pathogenicity assessment, there
were no test substance-related significant adverse effects seen in rats receiving a single dose of approximately 1–3 x 10 8 spores of Pasteuria usgae . One dosed female exhibited pale lungs. Additionally, one untreated control female lost weight by day 21 and another untreated control female lost weight by da y 14 but gained weight by day 21. One MPCAtreated male did not gain weight by day 7 but gained weight thereafter. All other animals gained weight throughout the study. Based on these results, Pasteuria usgae does not appear to be toxic and/or pathogenic in rats when dosed at approximately 1–3 x 10 8
spores/animal. Since microbial enumeration wa s not performed because the test material would not grow on agar media, the infec tivity was uncertain. However, because the spores are highly specific to the sting nematode, infectivity is unlikely to be a concern. This study was rated “ACCEPTABLE,” and Pasteuria usgae was classified as

12Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

TOXICITY CATEGORY IV.

Acute Injection Toxicity and Pathogenici ty – Rat (OCSPP Guideline 885.3200; MRID No. 474267-11) : There were no treatment-related signi ficant adverse effects seen in rats receiving a single intravenous dose of 10 8 Pasteuria usgae spores. One treated female lost weight by day 7 but gained we ight prior to sacrifice on da y 14. All other animals gained weight throughout the study. All animals survived and appeared normal during the study. No abnormalities were observed in any animal at necropsy or in harvested organs. No significant variations in orga n weight were found between different groups or sexes. The
acute intravenous LD 50 of Pasteuria usgae is greater than 1 x 10 8 spores/animal in male

and female rats. Pasteuria usgae does not appear to be toxic and/or pathogenic in rats
when dosed at 10 8 spores/animal. Since microbial enumeration was not performed
because the test material w ould not grow on agar media, the infectivity was uncertain. However, because the spores are highly spec ific to the sting nematode, infectivity is unlikely to be a concern. This study was rated “ACCEPTABLE.”

Hypersensitivity Incidents (OCSPP Guideline 885.3400; MRID No. 474350-02) : No hypersensitivity incidents, including immediate- type or delayed-type reactions of humans and domestic animals occurring duri ng the testing or production of Pasteuria usgae , were observed by Pasteuria Bioscien ce, Incorporated. Any future hypersensitivity incidents must be reported per OCSPP Guideline 885.3400.

Cell Culture (OCSPP Guideline 885.3500) : This study is not required because Pasteuria

usgae is not a virus (refer to test note #4 of 40 CFR § 158.2140(d)).

b. Acute Toxicology and Subchronic T oxicity/Pathogenicity – Tier II; Reproductive Fertility Effects, Carcinogenicity, Immunotoxicity, and Infectivity/Pathogeni city Analysis – Tier III ( 40 CFR § 158.2140 )

Tier II and Tier III studi es were not required for Pasteuria usgae based on the lack of acute toxicity/pathogenicity in the Tier I studies.

c. Endocrine Disruptors

As required under FFDCA section 408(p), th e Agency has developed the Endocrine Disruptor Screening Program (EDSP) to dete rmine whether certain substances (including pesticide active and other ingred ients) may have an effect in humans or wildlife similar to an effect produced by a “natur ally occurring estrogen, or othe r such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substa nce to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where the Agency will determine which, if any, of the Tier 2 tests are necessary based on the available data . Tier 2 testing is de signed to identify any

13Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

adverse endocrine-related eff ects caused by the substance, and establish a quantitative relationship between the dose a nd the E, A, or T effect.

Between October 2009 and February 2010, the Agen cy issued test orde rs/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active i ngredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pathways such as food and wa ter, residential activity, and certain postapplication agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors.

Pasteuria usgae is not among the group of 58 pesticid e active ingredients on the initial
list to be screened under the EDSP. Unde r FFDCA section 408(p), the Agency must screen all pesticide chemicals. Accordingly, the Agency anticipates issuing future EDSP orders/data call-ins for all pesticide active ingredients.

For further information on the status of the ED SP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, please visit our
website: http://www.epa.gov/endo/

.

2. Food Quality Protection Act (FQPA) Considerations

Section 408(c)(2)(A)(i) of the Federal Food, Drug, and Cosmetic Act allows the Agency to establish an exemption from the requireme nt for a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if the Agency determines that the exemption is “safe.” Section 408(c)(2)(A)(ii) of FFDCA defines “s afe” to mean that “there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary e xposures and all other exposures for which there is reliable in formation.” This includes exposure through drinking water and in resident ial settings, but does not include occupational exposure. Pursuant to section 408(c)(2)(B) of FFDCA, in establishing or maintaining in effect an exemption from the requirement of a toleran ce, the Agency must take into account the factors set forth in section 408(b)(2)(C) of FFDCA, which require the Agency to give special consideration to exposur e of infants and children to th e pesticide chemical residue in establishing a tolerance and to “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue....” Additionally, section 408(b)(2)(D ) of FFDCA requires that the Agency consider “available information concerning the cumulative effects of [a particular pesticide's] residues and other substances th at have a common mechanism of toxicity.”

The Agency performs a number of analyses to determine the risks from aggregate exposure to pesticide residues. First, the Agency determines the toxicity of pesticides. Second, the Agency examines exposure to the pesticide through food, drinking water, and through other exposures that occur as a result of pesticide use in residential settings.

Consistent with section 408(b )(2)(D) of FFDCA, the Agency has reviewed the available

scientific data and other rele vant information, and considered its validity, completeness, and reliability and the relationship of this information to human risk. The Agency has

14Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

also considered available information concer ning the variability of the sensitivities of major identifiable subgroups of consum ers, including infants and children.

Based on the acute toxicity/pat hogenicity data discussed previously and presented in
Table 3 in Appendix A , the data required for a FQPA risk assessment for Pasteuria usgae
have been satisfied.

a. Aggregate Exposures

In examining aggregate exposure, section 408 of FFDCA directs the Ag ency to consider available information concerning exposures fr om the pesticide residue in food and all other nonoccupational exposures, including drin king water from ground water or surface water and exposure through pestic ide use in gardens, lawns, or buildings (residential and other indoor uses).

Dietary Exposure and Risk Characterization : Dietary exposure to the naturally occurring soil bacterium, Pasteuria usgae , although a possibility, is anticipated to be negligible. For optimal control of sting nematode, Pasteuria usgae is applied in a manner that facilitates movement of spores into the root zone of th e affected crop. This requires that end users take two particular actions that w ould inevitably minimize the amount of Pasteuria usgae residues on aboveground food commodities—soil- directed applications and irrigation with a specified amount of water following any such applications. For food commodities that develop underground, exposure to Pasteuria usgae residues is a more likely scenario, although standard postharvest practices of wa shing, cooking, or processing would reduce residues below background levels, effectively le ssening dietary exposure. In general, any actual dietary exposure is expected to be seve ral orders of magnitude lower than the dose used in the acute oral toxicity/pathogenicity test referenced in section IV(B)(1)(a), during which no toxic or pathogenic effects we re observed in rats. Moreover, since Pasteuria

usgae is host-specific, no toxicity or pathogeni city in humans is likely to occur. The Agency concludes that there is a reasonable certainty that no harm will result from the
aggregate exposure to the residues of Pasteuria usgae in food.

Drinking Water Risk Characterization : Exposure of humans to residues of Pasteuria

usgae in consumed drinking water is unlikely. The currently approved and proposed use patterns, use sites, and application methods for Pasteuria usgae do not include direct application to aquatic environm ents. Furthermore, given that Pasteuria usgae spores attach specifically to the sting nematode, whic h is a plant-parasitic nematode that thrives only in sandy soil environments and is depende nt upon plant roots to sustain life, future proposals to add aquatic use si tes to pesticide products cont aining this bacterium are not expected. In the event that Pasteuria usgae is transferred to surface or ground water intended for eventual human consumpti on, the bacterium woul d not survive the conditions water is subjected to in a dri nking water treatment facility, including high temperatures, chlorination, pH adjustments, and/or filtration. Even if oral exposure should occur through consumed drinking water, the Agency concludes that there is a reasonable certainty that no harm will result from the exposure to the residues of Pasteuria usgae in all the anticipated drinking water exposures because of the lack of

15Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

acute oral toxicity/pathogenicity to ma mmals and the host-specific nature of the bacterium, as stated previously.

Nonoccupational, Residential Risk Characterization : Nonoccupational exposure is considered unlikely for Pasteuria usgae as all currently approved or proposed uses occur in distinctly agricultural or commercial se ttings, and there are no currently approved or proposed uses for residential areas.

The only other nonoccupational exposure is that which would normally be encountered as part of the natural environmen t (i.e., not as a result of pest icide use). As expected, since Pasteuria usgae is an obligate endoparasite of th e sting nematode, there have been no reports of adverse effects from human exposure to this bacterium that naturally occurs in sandy soils, particularly those of the sout heastern and midwestern United States.

b. Cumulative Effects from Substances with a Common Mechanism of Toxicity

Section 408(b)(2)(D)(v) of FFDCA requires that , when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available information concerning the cumulative effects of [a particular pesticide’ s] residues and other substances that have a common mechanism of toxicity.”

The Agency has not found Pasteuria usgae to share a common mechanism of toxicity with any other substances, and Pasteuria usgae does not appear to produce a toxic metabolite as its mode of action against the target pest. For the purposes of this tolerance action, therefore, the Agency has assumed that Pasteuria usgae does not have a common mechanism of toxicity with other substan ces. For information re garding the Agency’s efforts to determine which chemicals have a common mechanism of toxicity and to
evaluate the cumulative effects of such chemicals, see the Agency’s website at http://www.epa.gov/pesticides/cumulative

.

c. Determination of Safety for U. S. Population, Infants, and Children

FFDCA section 408(b)(2)(C) pr ovides that the Agency shall assess the available information about consumption patterns among infants and children, special susceptibility of infants and children to pest icide chemical residues, and the cumulative

effects on infants and children of the re sidues and other substa nces with a common mechanism of toxicity. In addition, FFDCA section 408(b)(2)(C) provides that the Agency shall apply an additional tenfold margin of safety for infants and children in the

case of threshold effects to account for prenatal and pos tnatal toxicity and the completeness of the database unless the Agency determines that a different margin of safety will be safe for infants and children. Margins of exposure (safety), which are often referred to as uncertainty factors, are incorp orated into Agency risk assessments either directly or through the use of a margin of exposure analysis, or by using uncertainty (safety) factors in calculating a dose level that poses no appreciable risk.

Based on the acute toxicity a nd pathogenicity data discusse d in section IV(B)(1)(a), the Agency concludes that there is a reasonable certainty that no harm will result to the

16Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

United States population, including infants a nd children, from aggregate exposure to the

residues of Pasteuria usgae . This includes all an ticipated dietary exposures and all other exposures for which there is reliable info rmation. The Agency has arrived at this
conclusion because the data available on Pasteuria usgae do not demonstrate toxic, pathogenic, or infective potential to mamma ls. Thus, there are no threshold effects of concern and, as a result, the provision requi ring an additional margin of safety does not apply. Further, the considerations of cons umption patterns, special susceptibility, and cumulative effects do not apply to pesticides without a demonstrated significant adverse

effect.

3. Occupational Exposure and Risk Characterization

In light of the Tier I acute toxicity/pathogenicity studies, which did not show any toxic and/or pathogenic effects to rats via oral, pulmonary, dermal, and intravenous routes of exposure (see section IV(B)(1)(a) ), handler exposure to Pasteuria usgae is not expected to pose any undue risk. Regardless, appropr iate personal protective equipment and precautionary statements are required on the pr oduct label to mitigate any potential risks to pesticide handlers due to prolong ed exposure. Handlers working with Pasteuria usgae in manufacturing facilities and applying th e end-use products in commercial and agricultural settings must wear a long-sleeved shirt, long pants, socks, shoes, waterproof gloves, and a dust/mist filteri ng respirator meeting NIOSH st andards of at least N-95, R95, or P-95. Additional PPE, other than the st andard described above, may be required on a product-specific basis (e.g., protective eyew ear for EconemTM, the registered granular Pasteuria usgae formulation).

4. Human Health Risk Characterization

The Agency considered human exposure to Pasteuria usgae in light of the standard for registration and safety factors in FIFR A and FFDCA, as amended by the FQPA. A

determination has been made that no unreasona ble adverse effects to the United States population in general, and to infants and children in particular, will result from the use of Pasteuria usgae when used in accordance with EPA-approved labeling.

C. Environmental Assessment

Exposure of nontarget organisms is possibl e with application of end-use products containing Pasteuria usgae to turf and strawberry. Pasteuria Bioscience, Incorporated has submitted data waiver rationales containing information cited in published literature to satisfy data requirements for nontarget organism testing with the te chnical grade of the active ingredient (TGAI). The following is a review of the rationa les submitted to support the registration of the manufacturing-use product and end-use products, as well as resulting conclusions regarding environmen tal risks based on the submitted waiver justifications.

For a comprehensive guideline-by-guideline summary of the nontarget toxicity data requirements, refer to Table 5 in Appendix A

.

17Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

1. Summary of Nontarget Organism Waiver Rationales ( 40 CFR §
158.2150 )

Data waiver rationales were submitted in response to data requirements for avian, freshwater fish and invertebrate, insect, and honey bee nontarget organism testing requirements. Justification for these waiver s is described in sections IV(C)(1)(a), IV(C)(1)(c), and IV(C)(1)(f). So me data requirements were not required based on the test notes described in 40 CFR § 158.2150(e), and e xplanations are prov ided in sections IV(C)(1)(b), IV(C)(1)(d), and IV (C)(1)(e). Overall, the information provided is sufficient to satisfy the Tier I nontarget organism data requirements for the manufacturing-use product and end-use products. Further testing of nontarget organisms at higher tier levels is not required.

a. Avian Oral Toxicity/Pathogenicity (OCSPP Guideline 885.4050)

The request to waive avian or al toxicity/pathogenicity tes ting is based on the rationale that exposure of birds to Pasteuria usgae as a result of its applications will be minimal,
and that no records are available in which toxicity or pathogenicity of Pasteuria usgae or other Pasteuria species to birds is reported. Pasteuria species are ubiquitous in soil environments where plant-parasitic nemat odes exist (Chen and Dickson 1998; Hewlett et al . 1994), and their population dynamics are strong ly linked to parasite -prey interactions with their nematode hosts (Ciancio and Queneherve 2000; Darban et al . 2005). Pasteuria

usgae is very specific to its host (Bekal et al . 2001; Giblin-Davis et al . 2001, 2003).

Extensive literature searches were performed within Agricola and PubMed databases, as well as several relevant journals, and no information was found relating exposure to naturally occurring Pasteuria usgae or other Pasteuria species to toxic or pathogenic

effects in birds. The searches also did not result in finding any reports of genotoxic, carcinogenic, allergenic, mutagenic, or teratogenic effects.

An argument could be made that the absence of a record of toxicity/pathogenicity to birds
is not evidence that such effects could not occur. However, since Pasteuria usgae is a naturally occurring and ubiquitous bacterium, there would likely have been reports in
these databases if it was toxic or pathogenic to birds. Based on this information, adverse
effects to avian wildlife resulting from exposure to Pasteuria usgae are not anticipated. Therefore, the rationale presented is acceptabl e and fulfills the data requirement for avian oral toxicity/pathoge nicity testing.

b. Avian Inhalation Toxicity/Patho genicity (OCSPP Guideline 885.4100)

These data are not required as the nature of the microbial pesticide does not indicate potential pathogenicity to bird s or relatedness to any known bi rd pathogens (refer to test note #3 of 40 CFR § 158.2150(e)).

18Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

c. Freshwater Fish Toxicity/Path ogenicity (OCSPP Guideline 885. 4200) and
Freshwater Inver tebrate Toxicity/Pathoge nicity (OCSPP Guideline 885.4240)

The requests to waive the data requirements fo r freshwater fish toxi city/pathogeni city and
freshwater invertebrate toxici ty/pathogenicity were combined. The rationale is similar to that for birds described above, wherein exposur e is expected to be limited and there are no reports of toxicity or pathogenicity of Pasteuria usgae to freshwater fish or invertebrates. Additionally, Pasteuria usgae and other Pasteuria species do not produce crystalline insect toxins like bacter ia that are toxic to insects (e.g., Bacillus thuringiensis ).

Pasteuria ramosa is a closely related species to Pasteuria usgae that is known to parasitize Daphnia magna and other Daphnia species. However, Pasteuria ramosa does not infect nematode hosts typical to other Pasteuria species (Ebert et al . 1996). Furthermore, neither Pasteuria usgae nor Pasteuria ramosa are included in published fish pathogen listings. Pasteuria usgae is unique in the ultrastructural characteristics of its spores, and this contributes to its specificity (Ebert et al . 1996; Giblin-Davis et al

. 2001).

Based on this information, adverse effects to freshwater fish or i nvertebrates resulting from labeled applications of Pasteuria usgae are not expected. The request to waive the data requirements for freshwater fish and invertebrate toxi city/pathogenicity testing is acceptable.

d. Estuarine/Marine Fish Testing and Estuarine/Marine Invertebrate Testing (OCSPP Guideline 885.4280)

These data are not required because Pasteuria usgae will not be applied to water and is not expected to enter marine/estuarine environments in amounts that are significantly higher than naturally occurri ng concentrations (refer to test note #6 of 40 CFR § 158.2150(e)).

e. Nontarget Plant Testing (OCSPP Guideline 885.4300)

These data are not required because Pasteuria usgae is not related to known plant pathogens, and adverse effects to plants are no t expected (refer to te st note #7 of 40 CFR § 158.2150(e)).

f. Nontarget Insect Testing (OCS PP Guideline 885.4340) and Honey Bee Testing (OCSPP Guideline 885.4380)

The requests to waive the data requirements for nontarget insect testing and honey bee testing were combined. The rationale is sim ilar to that given for other nontarget taxa above, wherein exposure to nontarget insects a nd honey bees is expected to be limited,

and neither Pasteuria usgae nor other Pasteuria species are included in published insect or honey bee pathogen listings. Pasteuria usgae and other Pasteuria species do not produce crystalline insect toxins as seen in other bacteria that ar e known to be toxic to

insects.

19Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Based on this information, adverse effects to nontarget insects or honey bees resulting from labeled applications of Pasteuria usgae are not expected, and the request to waiver these data requirements are acceptable.

2. Environmental Effects Conclusions

a. Terrestrial Animals and Plants

Data waiver rationales provide d sufficient information to conclude that adverse effects are not expected in birds, nontarget insects, and honey bees as a result of exposure to Pasteuria usgae (MRID No. 474267-13). These rationales addressed exposure via applications of gr anules containing Pasteuria usgae to turf; however, the rationales presented are also applicable to liquid applications to turf and strawberry. Pasteuria species are ubiquitous in soils worldwide, and Pasteuria usgae is highly host-specific to the plant-parasitic sting nematode ( Belonolaimus longicaudatus ). None of the uses are expected to increase the concentrations of Pasteuria usgae in the soil above naturally occurring levels. Soil app lications of granules to turf ar e expected to limit exposure in the environment. While liquid applications would result in exposure on fo liar surfaces of turf and strawberry plants, no reports of terrestr ial animal toxicity or pathogenicity from
exposure to Pasteuria usgae exist in the available scientific literature.

An acute oral toxicity and pathogenicity study with laboratory rats (MRID No. 474267- 09) is available with which to de termine the potential effects of Pasteuria usgae on wild mammals. Laboratory rats were dosed with 10 8 spores/mL and were observed for 21 days. No signs of toxic or pathogenic effects were observed throughout the test or at necropsy. This study demonstrates that toxici ty/pathogenicity to wild mammals is not expected from labeled applications of Pasteuria usgae

.

Nontarget plant testing is not required because Pasteuria usgae is not related to any known plant pathogen. Adverse effects on plants are not expected to result from labeled applications of Pasteuria usgae

.

Based on the above rationales, adverse effects are not expected to occur to terrestrial animals or plants as a result of labeled app lications of Pasteuria usgae . The request to waive these data requirements is acceptable.

b. Aquatic Animals and Plants

Data waiver rationales were submitted to fu lfill data requirements for and support effects conclusions for freshwater aquatic orga nisms (MRID No. 474267-13). These rationales addressed exposure via applica tions of granules containing Pasteuria usgae to turf; however, the rationales presented are also app licable to liquid applications to turf and strawberry. The rationales pr ovided sufficient information to conclude that adverse effects are not expected in freshwater fish or freshwater invertebrates as a result of
exposure to Pasteuria usgae . The rationales were similar to those presented for terrestrial

20Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

organisms in that Pasteuria species are ubiquitous in soils worldwide, and Pasteuria

usgae is highly host-specific to the plant-parasitic sting nematode ( Belonolaimus longicaudatus ). Soil applications in tu rf only are expected to li mit exposure in the aquatic environment, and runoff from both soil and liqui d applications is not expected to increase

the concentrations of Pasteuria usgae in freshwater environments above naturally occurring levels. There is no av ailable literature documenting reports of pathogenicity or toxicity to freshwater fish or inve rtebrates as a resu lt of exposure to Pasteuria usgae

. Pasteuria ramosa is a closely related species to Pasteuria usgae that does parasitize Daphnia magna and other Daphnia species. However, Pasteuria ramosa does not infect nematode hosts typical to other Pasteuria species, and Pasteuria usgae is very hostspecific and is not known to para sitize aquatic invertebrates.

Because the use of Pasteuria usgae is limited to applications to turf and strawberry and is not intended for application directly to water, exposure is not expected to be significant in aquatic environments, including marine or es tuarine systems. Therefore, testing with marine/estuarine animals and testing w ith aquatic plants is not necessary.

Based on the rationales submitted, adverse effects to freshwater and marine/estuarine fish, invertebrates, and plan ts are not expected as a re sult of exposure to labeled applications of Pasteuria usgae . The request to waive these data requirements is acceptable.

3. Threatened and Endangered Species Assessment

There are no listed endangered or threatened sp ecies related to the target pest. Since it is concluded that effects are not anticipat ed for nontarget species exposed to Pasteuria

usgae as a result of labeled applications, direct and indirect effects to listed species or their habitat are also not expected. Therefor e, the Agency has made “No Effect” (NE)

determinations for direct and i ndirect effects to listed specie s and their habitat as a result

of the uses of Pasteuria usgae

.

V. ENVIRONMENTAL JUSTICE

The Agency seeks to achieve environmental justice—the fair treatment and meaningful involvement of all people regardless of r ace, color, national origin, or income—with respect to the development, implementati on, and enforcement of environmental laws, regulations, and policies. Fair treatment means that no group of people, including racial, ethnic, or socioeconomic groups, should bear a disproportionate share of the negative environmental consequences resulting from industrial, municipal, and commercial operations or the execution of federal, state, local, and tribal environmental programs and policies. Meaningful involvement means th at (1) potentially affected community residents have an appropriate opportunity to participate in decisions about a proposed activity that will affect their environment and/or health; (2 ) the public’s contribution can influence the regulatory agency’s decision; (3) the concerns of all participants involved will be considered in the decision-making pro cess; and (4) the decision-makers seek out

21Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

and facilitate the involvement of those potentia lly affected. The Agency has this goal for all communities and persons across the United States.

To help address potential environmental just ice issues, the Agency seeks information on any groups or segments of the population who, as a result thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to Pasteuria

usgae , compared to the general population. Pl ease comment if you are aware of any subpopulations that may have atypical, unusua lly high exposure compared to the general population.

For additional information regarding envir onmental justice issues, please visit the Agency’s web site at http://www.epa.gov/compliance/en vironmentaljustice/index.html

.

VI. PUBLIC INTEREST FINDING

The Agency determines whether conditional re gistration of a pestic ide is in the public
interest in accordance with th e criteria set forth in the Fe deral Register of March 5, 1986 (58 FR 7268). There is a presumption that re gistration of a pestic ide is in the public interest if (1) the use is for a minor crop, (2 ) the use is a replacemen t for another pesticide that is of continuing concern to the Agenc y, (3) the use is one for which an emergency exemption under FIFRA section 18 has been gr anted (i.e., the basis for the exemption was lack of a registered alternative product), or (4) the use is against a pest of public health significance. Pasteuria usgae pesticide products could serve as partial replacements for conventional nematicides of continuing concern to the Agency (e.g., methyl bromide (ozone-depleting substance) and 1,3-dichloroprope ne (probable human carcinogen)). Based on this information, registration of Pasteuria usgae pesticide products are presumed to be in the public interest.

22Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

VII. RISK MANAGEMENT AND REGISTRATION DECISIONS

A. Determination of Eligibility

1. Pasteuria usgae – BL1 (EPA Registration Number 85004-1)

Section 3(c)(7)(C) of the Federal Insecticid e, Fungicide, and Rodenticide Act provides for the conditional registration of a pestic ide containing an active ingredient not contained in any currently re gistered pesticide for a peri od reasonably sufficient for the generation and submission of required da ta if the following are determined:

(1) Use of the pesticide during a defined period will not cause any
unreasonable adverse eff ect on the environment; (2) Use of the pesticide is in the public interest; AND (3) For data that are l acking, a reasonable period of time sufficient for generation of that data has not elap sed since the Agency first imposed the data requirements.

As discussed in this docume nt, use of products containing Pasteuria usgae is not likely to result in any unreasonable adverse effects on the environment, fulfilling criterion 1. Furthermore, as mentioned in section VI, the registration of Pasteuria usgae – BL1 is presumed to be in the public interest becau se it will be used to create end-use products that could serve as partial replacements fo r particular conventional nematicides of continuing concern to the Agency; thus, criteri on 2 has been satisfied. To satisfy criterion 3, insufficient time has elapsed since the in itial imposition of the data requirements outlined in section VIII(B)(1).

2. Econem TM (EPA Registration Number 85004-2) and Pasteuria usgae

– Liquid Formulation (EPA File Symbol 85004-G)

Section 3(c)(7)(A) of the Federal Insecticid e, Fungicide, and Rodenticide Act provides for the conditional registration of a pes ticide if the following are determined:

(1) The pesticide and proposed use are iden tical or substantially similar to any currently registered pe sticide and use thereof, or differ only in ways that would not significantl y increase the risk of unreasonable adverse effects on
the environment AND (2) Approving the registration in the manne r proposed by the applicant would not significantly increase the risk of any unreasonable adverse effect on the
environment.

Although these end-use pesticide products are not substantially similar to the manufacturing-use product, Pasteuria usgae – BL1 (EPA Registration Number 85004-1), use of these products to contro l sting nematode in commercial and agricultural settings is not likely to result in any unreasonable advers e on the environment, a conclusion that is

23Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

supported by the information presented througho ut this document. T hus, criterion 1, and by default, criterion 2 have both been satisfied.

B. Registration Review

The Federal Insecticide, Fungi cide, and Rodenticide Act, as amended by the FQPA of 1996, mandated the continuous review of existin g pesticides. All pest icides distributed and sold in the United States must genera lly be registered by the Agency, based on scientific data showing that they will not cause unreas onable risks to human health, workers, or the environment when used as directed in product la beling. The registration review program is intended to make sure that , as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory
standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluate s pesticides to make sure that as change occurs, products in the market place can be used safely. Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/

.

The Agency has implemented the registration review program pursuant to FIFRA section 3(g) and will review each re gistered pesticide every 15 ye ars to determine whether it

continues to meet the FIFRA standard for re gistration. A registrati on review decision is the Agency’s determination whether a pesticid e meets, or does not meet, the standard for registration in the Federal Insecticide, Fungicide, and Rodenticide Act. Pasteuria usgae will be included in the schedule for registration review at the end of the Fiscal Year when schedules are updated.

C. Regulatory Decisions

1. Pasteuria usgae – BL1 (EPA Registration Number 85004-1)

Based on the data submitted and under FIFRA section 3(c)(7)(C), the Agency granted a conditional, time-limited registration for the manufacturing-use product, Pasteuria usgae – BL1, containing Pasteuria usgae as a new active ingredient. Although the data were satisfactory, they were not sufficient to support an unconditional registration under FIFRA section 3(c)(5). Additional data, discu ssed in section VIII(B)(1), are necessary for a finding of registrability under FIFRA section 3(c)(5) and are still considered terms or conditions for the purposes of this registration.

Handler exposure to Pasteuria usgae is not expected to pose any undue risk given the Tier I acute toxicological studies, which showed that Pasteuria usgae is not toxic and/or pathogenic. Regardless, appropriate persona l protective equipmen t and precautionary statements are required on th e product label to mitigate any potential risks to pesticide handlers due to prolonged expos ure. Handlers working with Pasteuria usgae in manufacturing facilities must, at a minimum, w ear a long-sleeved shirt, long pants, socks, shoes, waterproof gloves, and a dust/mist filte ring respirator meeting NIOSH standards of at least N-95, R-95, or P-95.

24Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

2. EconemTM (EPA Registration Number 85004-2)

Based on the data submitted and under FIFRA section 3(c)(7)(A), the Agency granted a conditional, time-limited registration for the end-use product, EconemTM. Although the data were satisfactory to make the determina tions required by this se ction of FIFRA, they were not sufficient to support an unconditional registration under FIFRA section 3(c)(5). Additional data, discussed in section V III(B)(2), are necessary for a finding of registrability under FIFRA section 3(c)(5) a nd remain as terms or conditions for the purposes of this registration. Furthermore, the registrant must submit/cite all data required to support Pasteuria usgae – BL1 (as outlined in its associated registration notice) as this particular manufacturing-use product serv es as EconemTM’s source of active ingredient.

Handler exposure to Pasteuria usgae is not expected to pose any undue risk given the Tier I acute toxicological studies, which showed that Pasteuria usgae is not toxic and/or pathogenic. Regardless, appropriate persona l protective equipmen t and precautionary statements are required on th e product label to mitigate any potential risks to pesticide handlers due to prolonged expos ure. Handlers working with Pasteuria usgae in commercial and agricultural sett ings must, at a minimum, wear a long-sleeved shirt, long pants, socks, shoes, waterproof gloves, and a dust/mist filtering respirator meeting NIOSH standards of at least N-95, R-95, orP-95. In addition, because the productspecific data eye irritation data indicated that EconemTM most appropriately fit in Toxicity Category III, all handlers mu st also wear protective eyewear.

3. Pasteuria usgae – Liquid Formulation (EPA File Symbol 85004-G)

On October 1, 2009, the Agency announced a ne w policy to provide a more meaningful opportunity for the public to par ticipate in major regi stration decisions before they occur. According to this new policy, the Agency in tends to provide a public comment period prior to making a registration decision fo r, at minimum, the following types of applications: new active ingredients; first f ood uses; first outdoor uses; first residential uses; and any registration decisions for which the Agency believes there may be substantial public interest.

At this time, the Agency believes the data submitted fulfill the requirements of registration for the end-use product, Pasteuria usgae – Liquid Formulation, which

contains Pasteuria usgae as a nematicidal active ingredient and is labeled for this particular active ingredie nt’s first food use. Acut e toxicological data for Pasteuria usgae demonstrate that it is not toxic and/or pa thogenic via any examined route of exposure (i.e., oral, dermal, pulmonary, and injection). Moreover, because Pasteuria usgae spores are highly specific to the sting nematode, inf ectivity is unlikely to be a concern. Productspecific data and other information place this end-use product in either Toxicity Category III or IV. Finally, the Agency has no concerns for any nontarget organisms (to include threatened and endangered species) exposed to Pasteuria usgae in accordance with its currently approved or proposed uses as no toxic endpoints have been identified for

25Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

mammals, birds, plants, insects, honey bees , or aquatic organism s. Given the nontoxic

character of Pasteuria usgae and its associated end-use product, Pasteuria usgae

– Liquid Formulation, but also taking into c onsideration that certa in data are still outstanding for this pesticide product’s source of active ingredient (i.e., Pasteuria usgae – BL1, EPA Registration 85004-1), the Agency supports Pasteuria usgae – Liquid Formulation’s registration under Section 3(c)(7 )(A) of the Federal Insecticide, Fungicide,

and Rodenticide Act.

D. Labeling

The labels for the registered pesticide products containing the active ingredient, Pasteuria

usgae , are available at http://oaspub.epa.gov/pestlabl/ppls.home

.

VIII. ACTIONS REQUIRED BY THE REGISTRANT

A. Final Printed Labeling

Before releasing pestic ide products containing Pasteuria usgae for shipment, the registrant is required to pr ovide appropriate final printed labeling to the Agency.

B. Terms and Conditions of the Pasteuria usgae Pesticide Products

1. Pasteuria usgae – BL1 (EPA Registration Number 85004-1)

The Agency evaluated the data submitted in connection with the initial registration of the manufacturing-use product, Pasteuria usgae – BL1, containing Pasteuria usgae as a new active ingredient. Although it was determined that these data fulfilled current requirements for a conditional, time-limited FIFRA section 3(c)(7)(C) registration, the Agency required Pasteuria Bioscience, Inco rporated to submit the following additional
data and/or information in the time frames listed:

Study Type Required Data/Information Due Date

Analysis of Samples (OCSPP Guideline 885.1400) The preliminary analysis of samples provided to the Agency revealed a wide range of concentrations, with many replicates containing 1–2 orders of magnitude fewer Pasteuria usgae spores than the minimum specified on the Confidential Statement of Formula and product label (i.e., 1 x 10 6 spores per milliliter). A follow-up explanation, attempting to address this variability, mentioned several factors that contributed to this inconsistency and discussed how the concentration of spores could be adjusted during the manufacturing process, if necessary. Despite this additional information, a new five-batch analysis, with all batches from production level, must be submitted to the Agency. May 1, 2011

26Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Study Type Required Data/Information Due Date

Manufacturing Process

(OCSPP Guideline 885.1200) The original manufacturing process did not describe quality control

measures taken to confirm that Pasteuria usgae was the only Pasteuria species present in the master stoc k. A follow-up explanation, which demonstrated that batches are screened for the presence of other microbes and screened against sting nemat odes to confirm the presence of Pasteuria usgae , still did not provide sufficient information to indicate that screening for other Pasteuria species is conduct ed during the manufacturing process. Other Pasteuria species, specifically those that parasitize saprophytic (non-plant pathogenic) nematodes, must be screened for during the manufactur ing process. Pasteuria Bioscience, Incorporated must integrate quality control measures that screen for

Pasteuria species that parasitize saprophytic nematodes, either immediately after freezing or after maki ng seed stock, into their current manufacturing process and provide a written description of these measures to the Agency.

Information submitted by Pasteuri a Bioscience, Incorporated by October 1, 2009 (MRID No. 478853-01) is currently being reviewed for acceptability. October 1, 2009

Product Identity (OCSPP

Guideline 885.1100) Currently, full recognition of Pasteuria usgae as a species is still pending
with the Judicial Commission of the International Committee for Systematic Bacteriology. Once Pasteuria usgae has been recognized and removed from the category Candidatus , documentation indicating official recognition must be provided to the Agency. As soon as the specified

information becomes
available

Storage Stability (OCSPP Guideline 830.6317) The storage stability study for the technical grade of the active ingredient (TGAI)/manufacturing-use product (MP) has been cited as ongoing. When the study has been completed and the results have been compiled, these data must be submitted to the Agency. Within the discussion of these results, the test substance must be described to ensure that this data requirement has been fulfilled for both the TGAI and the MP (i.e., reference that the TGAI is equivalent to the MP for Pasteuria usgae

– BL1).

Information submitted by Pasteuri a Bioscience, Incorporated by June 1, 2010 (MRID No. 479672-01) is curren tly being reviewed for acceptability. June 1, 2010

27Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

2. Econem TM (EPA Registration Number 85004-2)

The Agency evaluated the data submitted in connection with the initial registration of the end-use product, Econem TM , containing Pasteuria usgae . Although it was determined that these data fulfill current requirements for a conditional, time-limited FIFRA section 3(c)(7)(A) registration, the Agency required Pa steuria Bioscience, In corporated to both submit/cite all data required to support Pasteuria usgae – BL1 (as outlined in its associated registration notice) and subm it the following additional data and/or

information in the time frames listed:

Study Type Required Data/Information Due Date

Analysis of Samples (OCSPP Guideline 885.1400) The preliminary analysis of samples provided to the Agency revealed a wide range of concentrations of Pasteuria usgae spores. A new fivebatch analysis, with all batches from production level, must be submitted to the Agency. August 1, 2011

Storage Stability (OCSPP Guideline 830.6317) The storage stability study for this end-use product has been cited as ongoing. When the study has been completed and the results have been compiled, these data must be submitted to the Agency.

Information submitted by Pasteuri a Bioscience, Incorporated by September 1, 2010 (MRID No. 480262-01) is currently being reviewed for acceptability. September 1, 2010

Corrosion Characteristics (OCSPP Guideline 830.6320) The corrosion characteristics study for this end-use product has been cited as ongoing. When the study has been completed and the results have been compiled, these data must be submitted to the Agency.

Information submitted by Pasteuri a Bioscience, Incorporated by September 1, 2010 (MRID No. 480262-02) is currently being reviewed for acceptability. September 1, 2010

3. Pasteuria usgae – Liquid Formulation (EPA File Symbol 85004-G)

The Agency has evaluated the data subm itted in connection with the proposed registration of the end-use product, Pasteuria usgae – Liquid Formulation, containing Pasteuria usgae . Although it has been determined that these data fulfill current requirements for a conditional, time-limited FIFRA section 3(c)(7)(A) registration, the Agency is proposing to require Pasteuria Bios cience, Incorporated to both submit/cite all data required to support Pasteuria usgae – BL1 (as outlined in its associated registration notice) and submit the following additional data and/or information in the time frames

listed:

Study Type Required Data/Information Due Date

Storage Stability (OCSPP Guideline 830.6317) The storage stability study for this end-use product has been cited as ongoing. When the study has been completed and the results have been compiled, these data must be submitted to the Agency. June 18, 2011

28Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Study Type Required Data/Information Due Date

Corrosion Characteristics (OCSPP Guideline 830.6320) The corrosion characteristics study for this end-use product has been cited as ongoing. When the study has been completed and the results have been compiled, these data must be submitted to the Agency. June 18, 2011

C. Reporting of Adverse Effects and Hypersensitivity Incidents

Notwithstanding the information stated in th e previous sections, it should be clearly understood that certain, specific data are required to be repo rted to the Agency as a requirement for maintaining the federal regi stration for a pesticide product. A brief summary of these types of data are described below.

Reports of all incidents of adverse effects to the environment must be submitted to the Agency under the provisions stated in FIFRA section 6(a)(2). Additionally, all incidents of hypersensitivity (including both suspected a nd confirmed incidents) must be reported to the Agency under the provisions of 40 CFR § 158.2140(d).

29Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

IX. GLOSSARY OF ACRO NYMS AND ABBREVIATIONS

BRAD Biopesticides Registration Action Document CFR Code of Federal Regulations
CSF Confidential Statement of Formula
cSt CentiStokes °C degrees Celsius EDSP Endocrine Disruptor Screening Program EPA Environmental Protection Agency (the “Agency”) FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FR Federal Register g/cm 3 grams per cubic centimeter

LD 50 median lethal dose. A statistically de rived single dose that can be expected
to cause death in 50% of the test an imals when administered by the route indicated (oral, dermal, or inhalation) . It is expressed as a weight of substance per unit weight of animal (e.g., mg/kg). mg/kg milligrams per kilogram

mL milliliter MP manufacturing-use product MPCA microbial pest control agent

MRID No. Master Record Identification Number

NE “No Effect” NIOSH National Institute for Occupational Safety and Health
OCSPP Office of Chemical Safe ty and Pollution Prevention OPP Office of Pesticide Programs
PC Code Pesticide Chemical Code PCR polymerase chain reaction

PP Pesticide Petition PPE personal protective equipment TGAI technical grade of the active ingredient

30Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

X. BIBLIOGRAPHY

A. Studies Submitted to Support the Pasteuria usgae Pesticide Product Registrations

474267-01 MacIntosh S, Smith K. 2008. Product Identity: Pasteuria usgae Spores- Liquid Suspension. Project Nu mber: PBI-2008-001. Unpublished report prepared by Pasteuria Bioscien ce, Incorporated and MacIntosh & Associates, Incorporated, 17 pages.

474267-02 Smith K. 2008. Manufacturing Process for Pasteuria usgae – Liquid Suspension. Project Number: PBI-2 008-003. Unpublished re port prepared by Pasteuria Bioscience , Incorporated, 17 pages.

474267-03 MacIntosh S. 2008. Discussion of Form ation of Unintentional Ingredients ( Pasteuria usgae ). Project Number: RES-32244301-0, 11467-07. Unpublished report prepared by Pa steuria Bioscience, Incorporated, 17 pages.

474267-04 Smith K. 2008. Analysis of Samples/Enforcement Methods for Pasteuria

usgae Spores – Liquid Suspension. U npublished report prepared by

Pasteuria Bioscience , Incorporated, 77 pages.

474267-05 Smith K. 2008. Certification of Limits for Pasteuria usgae – Liquid Suspension. Project Number: PBI-2 008-004. Unpublished report prepared by Pasteuria Bioscience , Incorporated, 13 pages.

474267-06 Kaminsky M. 2008. Pasteuria usgae Spores – Liquid Suspension (TGAI): Final Report. Project Number: 11565-08. Unpublished re port prepared by Stillmeadow, Incorporated, 17 pages.

474267-07 Smith K. 2008. Product Stability to Elevated Temperatures ( Pasteuria

usgae ). Project Number: PBI-2008-005. Unpublished report prepared by

Pasteuria Bioscience , Incorporated, 8 pages.

474267-08 Smith K. 2008. Interim Report: Storage Stability ( Pasteuria usgae ). Project Number: PBI-2008-006. Unpublis hed report prepar ed by Pasteuria Bioscience, Incorporated, 8 pages.

474267-09 Crutchfield V. 2008. Acut e Oral Toxicity/Pathogenicity Study in Rats (MPCA): Pasteuria usgae Spores – Liquid Suspension: Final Report. Project Number: 11463-07. Unpublishe d report prepared by Stillmeadow, Incorporated, 15 pages.

31Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

474267-10 Crutchfield V. 2008 Acute Pulmonary Toxicity/Pathogenicity Study in Rats (MPCA): Pasteuria usgae Spores – Liquid Susp ension: Final Report. Project Number: 11465-07. Unpublishe d report prepared by Stillmeadow, Incorporated, 15 pages.

474267-11 Crutchfield V. 2008. Acute Injection Toxicity/Pathogenicity Study in Rats (MPCA): Pasteuria usgae Spores – Liquid Suspension: Final Report. Project Number: 11466-07. Unpublishe d report prepared by Stillmeadow, Incorporated, 12 pages.

474267-12 Crutchfield V. 2008. Acute Dermal Toxicity/Pathogenicity Study in Rats (MPCA): Pasteuria usgae Spores – Liquid Suspension: Final Report. Project Number: 11464-07. Unpublishe d report prepared by Stillmeadow, Incorporated, 12 pages.

474267-13 MacIntosh S, Smith K, Hewlett T. 2008. Request for Waivers from the Requirement to Conduct Guideline Studies: Avian Oral Toxicity, Freshwater Fish Toxicity/Pathogenic ity, Freshwater Inve rtebrate Toxicity/ Pathogenicity, Non-Target Inse ct Testing, and Honey Bee Testing ( Pasteuria usgae ). Project Number: PBI- 2008-002. Unpublished report prepared by Pasteuria Bios cience, Incorporated, 29 pages.

474267-14 Pasteuria Bioscience, Incorpor ated. 2008. Copies of Publications ( Pasteuria usgae ). Unpublished report prepared by Pasteuria Bioscience, Incorporated, 334 pages.

474350-01 MacIntosh S. 2008. Request for Waivers from the Requirement to Conduct Physical and Chemical Characteristics Guideline Studies: Corrosion Characteristics – 830.6320 and Viscosity – 830.1700. Project Number: PBI-2008-008. Unpublished report prepared by MacIntosh & Associates, Incorporated, 43 pages.

474350-02 MacIntosh S. 2008. Hypersensiti vity Incidents – 885.3400. Project Number: PBI-2008-009. Unpublished report prepared by MacIntosh & Associates, Incorporated, 7 pages.

474350-03 MacIntosh S. 2008. Request for Waivers from the Requirement to Conduct Toxicology Guideline St udies: Acute Eye Irritation – 870.2400 and Primary Dermal Irritation – 870.2500. Project Number: PBI-2008-007. Unpublished report pr epared by Pasteuria Bioscience, Incorporated, 8 pages.

32Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

474979-01 MacIntosh S. 2008. Request for Waivers from the Requirement to Conduct Toxicology Guideline St udies: Acute Oral Toxicity – 870.1100, Acute Dermal Toxicity – 870.1200, and Acute Inhalation Toxicity – 870.1300. Project Number: PBI-2008- 012. Unpublished report prepared by MacIntosh & Associates, Incorporated, 9 pages.

475218-01 MacIntosh S, Smith K. 2008. Product Id entity and Manufacturing Process: Pasteuria usgae – Dry Granule. Project Number: PBI-2008-011. Unpublished report prepared by Past euria Bioscience, Incorporated and MacIntosh & Associates, Incorporated, 9 pages.

475218-02 MacIntosh S. 2008. Discussion of Forma tion of Unintentional Ingredients. Unpublished report prepared by MacI ntosh & Associates, Incorporated, 9 pages.

475218-04 Smith K. 2008. Certification of Limits for Pasteuria usgae – Clay Granule. Project Number: PBI- 2008-013. Unpublished report prepared by MacIntosh & Associates, Incorporated, 8 pages.

475218-05 Smith K. 2008. Interim Report (2): Storage Stability – Pasteuria usgae

. Project Number: PBI-2008-014. Unpublis hed report prepar ed by Pasteuria Bioscience, Incorporated, 8 pages.

475218-06 MacIntosh S. 2008. Interim Repor t: Corrosion Characteristics for Pasteuria usgae Spores – Clay Granule (E P). Project Number: 12008-08. Unpublished report prepared by Pa steuria Bioscience, Incorporated, 10 pages.

475218-07 MacIntosh S. 2008. Hypersensitivity Incidents: Pasteuria usgae . Project Number: PBI-2008-010. Unpublished report prepared by MacIntosh & Associates, Incorporated, 7 pages.

475218-08 Kuhn J. 2008. Acute Eye Irritation Study in Rabbits: Pasteuria usgae Spores – Clay Granule (End-Use Pr oduct): Final Report. Project Number: 12011-08. Unpublished report prepared by Stillmeadow, Incorporated, 16 pages.

475218-09 Kuhn J. 2008. Acute Dermal Irritation Study in Rabbits: Pasteuria usgae Spores – Clay Granule (End-Use Product): Final Report. Project Number: 12012-08. Unpublished report prepared by Stillmeadow, Incorporated, 11 pages.

33Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

475218-10 MacIntosh S. 2008. Request for Waivers from the Requirement to Conduct Toxicology Guideline Studi es: Acute Oral Toxicity, Acute Dermal Toxicity, and Acute Inhalation Toxicity for Pasteuria usgae Spores – Clay Granule (EP). Project Number: PB I-2008-015. Unpublished report prepared by MacIntosh & Associates, Incorporated, 9 pages.

475375-01 Smith K. 2008. Analysis of Samples/Enforcement Methods for Pasteuria

usgae Spores – Clay Granule. Unpublishe d report prepared by Pasteuria Bioscience, 20 pages.

475963-01 MacIntosh S, Smith K. 2008. Product Id entity and Manufacturing Process: Pasteuria usgae – Liquid Formulation. Pr oject Number: PBI-2008-017. Unpublished report prepared by Past euria Bioscience, Incorporated and MacIntosh & Associates, Incorporated, 17 pages.

475963-03 Smith K. 2008. Analysis of Samples/Enforcement Methods for Pasteuria

usgae – Liquid Formulation. Unpublished report prepared by Pasteuria Bioscience, Incorporated, 28 pages.

475963-04 Smith K. 2008. Certification of Limits for Pasteuria usgae – Liquid Formulation. Project Numb er: PBI-2008-020. Unpublished report prepared by Pasteuria Bios cience, Incorporated, 8 pages.

475963-05 MacIntosh S. 2008. Request for Waivers from the Requirement to Conduct Physical and Chemical Characterization Guideline Studies: Storage Stability – 830.6317, Corro sion Characteristics – 830.6320, and Viscosity – 830.7100 for Pasteuria usgae – Liquid Formulation (EP). Project Number: PBI-2008-021. Unpublished report prepared by

MacIntosh & Associates , Incorporated, 9 pages.

475963-06 MacIntosh S. 2008. Hypersen sitivity Incidents – 885.3400 for Pasteuria

usgae – Liquid Formulation. Project Number: PBI-2008-018. Unpublished report prepared by MacIntosh & Associates, Incorporated, 7 pages.

475963-07 MacIntosh S. 2008. Request for Waivers from the Requirement to Conduct Toxicology Guideline St udies: Acute Oral Toxicity – 870.1100, Acute Dermal Toxicity – 870.1200, and Acute Inhalation Toxicity –
870.1300 for Pasteuria usgae – Liquid Formulation (EP). Project Number: PBI-2008-019. Unpublished report prep ared by MacIntosh & Associates, Incorporated, 9 pages.

34Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

475963-08 MacIntosh S. 2008. Request for Waivers from the Requirement to Conduct Toxicology Guideline St udies: Acute Eye Irritation Study – 870.2400 and Primary Dermal Irritation Study – 870.2500 for Pasteuria

usgae – Liquid Formulation (EP). Project Number: PBI-2008-021. Unpublished report prepared by MacI ntosh & Associates, Incorporated, 8 pages.

476054-01 MacIntosh S. 2008. Discussion of Forma tion of Unintentional Ingredients: Pasteuria usgae – Liquid Formulation. Unpublished report prepared by MacIntosh & Associates, Incorporated, 8 pages.

476504-01 Harder J. 2009. Safety Study of Pasteuria usgae Liquid Formulation (EP) in Mice. Project Number: 2229- 001. Unpublished report prepared by IIT Research Institute, 32 pages.

476504-02 Kaminsky M. 2008. Pasteuria usgae Liquid Formulation: Product Chemistry – Final Report. Proj ect Number: 12492-08. Unpublished report prepared by Stillmeadow , Incorporated, 10 pages.

476504-03 Smith K. 2009. Storage Stability: Interim Report – Pasteuria usgae

– Liquid Formulation. Project Nu mber: PBI-2009-001. Unpublished report prepared by Pasteuria Bios cience, Incorporated, 9 pages.

476504-04 MacIntosh S. 2009. Interim Repor t: Corrosion Characteristics for Pasteuria usgae – Liquid Formulation (EP). Project Number: 12432-08. Unpublished report prepared by MacI ntosh & Associates, Incorporated, 10 pages.

476504-05 Harder J. 2009. Acute Eye Irritation Study of Pasteuria usgae Liquid Formulation (EP) in Rabbits . Project Number: 2229-001. Unpublished report prepared by IIT Research Institute, 27 pages.

476504-06 Harder J. 2009. Acute Dermal Irritation Study of Pasteuria usgae Liquid Formulation (EP) in Rabbits . Project Number: 2229-001. Unpublished report prepared by IIT Research Institute, 25 pages.

478853-01 Smith K. 2009. SOP for Manuf acturing Quality Control of Pasteuria

usgae – Liquid Suspension. Project Number: PBI-01-2009. Unpublished report prepared by Pasteuria Bioscience, Incorporated, 6 pages.

479672-01 Smith K. 2009. Storage Stability for Pasteuria usgae – Liquid Suspension (TGAI/MP): Final Report. Project Number: PBI-2008-006. Unpublished report prepared by Pasteuria Bioscience, Incorporated, 8 pages.

35Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

480262-01 Smith K. 2010. Storage Stability for Pasteuria usgae – Clay Granule (EP): Final Report. Project Number: PBI-2008-003. Unpublished report prepared by Pasteuria Bioscience, Incorporated, 8 pages.

480262-02 Kaminsky M. 2009. Pasteuria usgae Spores – Clay Granule (EP):
Corrosion Characteristics: Fi nal Report. Project Number: 12008-08. Unpublished report prepared by St illmeadow, Incorporated, 12 pages.

B. Environmental Protection Agency Risk Assessment Memoranda

U.S. EPA. 2009a. Environmental Risk Assessment of Pasteuria usgae (PC 006545) for Section 3 Registrations of the Technical Product ( Pasteuria usgae Spores – Liquid Suspension; EPA File Symbol 85004-R) and End-Use Products ( Pasteuria usgae Spores – Clay Granule, EPA File Symbol 85004-E; Pasteuria usgae – Liquid Formulation, EPA File Symbol 85004-G), for Control of Sting Nema todes in Turf and Strawberries. Memorandum from S. Borges and Z. Vaituzis, Ph.D. to J. Kausch dated April 8, 2009.

U.S. EPA. 2009b. Review of Product Ch emistry and Human Health Studies

for Pasteuria usgae (AF254387) – Liquid Suspension to Support the Registration of Technical Grade Active Ingred ient (EPA Reg. No. 85004-R). Memorandum from S. Schüssel and J.L. Kough, P h.D. to J. Kausch dated April 9, 2009.

U.S. EPA. 2009c. Review of Product Ch emistry and Human Health Studies for Pasteuria

usgae – Liquid Formulation and Clay Granule to Support Request for Experimental Use Permits (EPA Reg. N o. 85004-EUP-1) – Pasteuria Biosciences. Memorandum from S. Schüssel and J.L. Kough, Ph.D. to J. Kausch dated August 5, 2009.

U.S. EPA. 2009d. Review of Product Chem istry and Human Health Studies for Pasteuria

usgae – Clay Granule (EPA Reg. No. 85004- E) – Pasteuria Biosciences. Memorandum from S. Schüssel and J.L. Kough, Ph.D. to J. Kausch dated August 27, 2009.

U.S. EPA. 2010. Review of Additional Produc t Chemistry and Human Health Data for

Tolerance Petition for Pasteuria usgae – Liquid Formulation (EPA Reg. No. 85004-G) – Pasteuria Biosciences. Memorandum from S. Schüssel and J.L. Kough, Ph.D. to J. Kausch dated February 25, 2010.

C. Other References

Bekal S, Borneman J, Springer MS, Giblin -Davis RM, Becker JO. 2001. Phenotypic and molecular analysis of a Pasteuria strain parasitic to the sting nematode. Journal of Nematology 33:110–115.

36Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Chen ZX, Dickson DW. 1998. Review of Pasteuria penetrans : biology, ecology, and biological cont rol potential. Journal of Nematology 30:313–340.

Ciancio A, Queneherve P. 2000. Populations dynamics of Meloidogyne incognita and infestation levels by Pasteuria penetrans in a naturally infested field in Martinique. Nematropica 30:77–86.

Darban DA, Pathan MA, Bhatti AG, Maitelo SA. 2005. The effect of different initial densities of nematode ( Meloidogyne javanica ) on the build-up of Pasteuria

penetrans population. Journal of Zhejiang University 6B:113–118.

Ebert D, Rainey P, Embley TM, Scholz D. 1996. Development, life cycle, ultrastructure, and phylogenetic position of Pasteuria ramosa Metchnikoff 1888: rediscovery of an obligate endoparasite of Daphnia magna Straus. Philosophical Transactions of the Royal Society of London Series B 351:1689–1701.

Giblin-Davis RM, Williams DS, Wergin WP, Di ckson DW, Hewlett TE, Bekal S, Becker JO. 2001. Ultrastructure and development of Pasteuria sp. (S-1 strain), an obligate endoparasite of Belonolaimus longicaudatus (Nemata: Tyenchida). Journal of Nematology 33:227–238.

Giblin-Davis RM, Williams DS, Bekal S, Dick son DW, Brito JA, Becker JO, Preston JF.

2003. ‘ Candidatus Pasteuria usgae ’ sp. Nov., an obligate en doparasite of the phytoparasitic nematode, Belonolaimus longicaudatus

. International Journal of Systematic and Ev olutionary Microbiology 53:197–200.

Hewlett TE, Cox R, Dickson DW, Dunn RA. 1994. Occurrence of Pasteuria spp. in

Florida. Journal of Nematology 26:616–619.

37Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

APPENDIX A – MICROBIAL PESTICIDE DATA REQUIREMENTS

TABLE 1. Product Analysis Data Requirements for the Technical Grade of the Active Ingredient (TGAI)/ Manufacturing-Use Product (MP), Pasteuria usgae – BL1 (40 CFR § 158.2120)

Results Data Requirement (OCSPP Guideline) TGAI MP MRID
Number

Product Chemistry and Composition

Product Identity

(885.1100) Not applicable Pasteuria usgae is host-specific to the sting nematode ( Belonolaimus longicaudatus ), which can be damaging to a variety of crops such as turf and strawberry. The active agent of Pasteuria usgae is an endospore that attaches to and infects the host nematode during all life stages (except eggs). The endospores formed inside the host
are released into the soil when the infected nematode decomposes. The spores are nonmotile and
stable in the soil environment for several years. Classification: Acceptable. Currently, full recognition of Pasteuria usgae as a species is still pending with the Judicial
Commission of the International Committee for Systematic Bacteriology. Once Pasteuria

usgae has been recognized and removed from the category
Candidatus , documentation indicating official recognition must be provided to the Agency. 474267-01

Manufacturing Process (885.1200) Submitted data satisfied the requirement of manufacturing process for the TGAI/MP for the purposes of a conditional, time-limited FIFRA section 3(c)(7)(C) registration. Classification: Supplemental: Upgradeable. Pasteuria Bioscience, Incorporated mu st integrate quality control
measures that screen for Pasteuria species that parasitize saprophytic nematodes, either immediately after freezing or after making seed stock, into their current manufacturing process and provide a written des cription of these measures to the Agency on or before Octob er 1, 2009. This information has been provided to the Agency (MRID No. 478853-01) and is currently being reviewed for acceptability. 474267-02

Deposition of a Sample in a

Nationally Recognized

Culture Collection

(Not applicable) Pasteuria usgae is on deposit with the American Type Culture Collection in Manassas, Virginia under
Accession Number SD5835. Not applicable Not applicable

38Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Results Data Requirement (OCSPP Guideline) TGAI MP MRID

Number

Discussion of Formation of Unintentional Ingredients (885.1300) Submitted data satisfied the requirement of discussion of formation of unintentional ingredients for the TGAI/MP. Classification: Acceptable 474267-03

Analysis and Certified Limits

Analysis of Samples (885.1400) Submitted data satisfied the requirement of analysis of samples for the TGAI/MP for the purposes of a conditional, time-limited FIFRA section 3(c)(7)(C) registration. Classification: Unaccep table. A new five-batch analysis, with all batches from production level, must be submitted to the Agency on or before May 1, 2011. 474267-04

Certification of Limits (885.1500) Not applicable The certified limits for the active and inert ingredients fall
within the OCSPP Guideline 830.1750 specified ranges.
Classification : Acceptable 474267-05

Physical and Chemical Characteristics

Color (830.6302) Clear to very faint yellowbrown or cloudy at 24°C (5 batches) Not applicable 474267-06

Physical State

(830.6303) Liquid at 20°C Not applicable 474267-06

Odor (830.6304) No odor Not applicable 474267-06

Stability to Normal and Elevated Temperatures, Metals, and Metal Ions (830.6313) Stable after exposure to 54°C for 14 days. Not applicable 474267-07

Storage Stability (830.6317) Preliminary results indicate that af ter 1 month of storage at 4°C,
the TGAI/MP had a 5% loss of attachment and a 15% loss of infectivity. A twelve-month storage stability study is ongoing and results must be submitted to the Agency upon completion (on or before June 1, 2010). This information has been provided to the Agency (MRID No. 479672-01) and is currently being reviewed for acceptability. 474267-08

Miscibility (830.6319) Not applicable Not required because Pasteuria

usgae – BL1 is not an emulsifiable form of microbial pesticide (refer to test note #2 of 40 CFR § 158.2120(d)). Not applicable

Corrosion Characteristics (830.6320) Not applicable Waived because Pasteuria usgae

– BL1 will be packaged for very short time periods in plastic as it moves from the manufacturing facility to the formulation facility for end-use products. There will be no long-term exposure to the packaging. Classification: Acceptable 474350-01

pH (830.7000) 6.80–6.96 (5 batches)*

6–7.3** Not applicable 474267-06*

CSF**

39Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Results Data Requirement (OCSPP Guideline) TGAI MP MRID

Number

Viscosity (830.7100) Not applicable Waived because Pasteuria usgae

– BL1 is not viscous and will not be applied as a product. There will be no environmental exposure. Classification: Acceptable 474350-01

Density/Relative Density/Bulk

Density (Specific Gravity) (830.7300) Specific gravity = 1.006– 1.008 gram/cubic centimeter (g/cm 3 ) (5 batches)* Specific gravity = 1.0 g/cm 3 ** Not applicable 474267-06*

CSF**

TABLE 2. Product Analysis Data Requirements for the End-Us e Products, Econem TM and Pasteuria usgae

– Liquid Formulation (40 CFR § 158.2120)

Results Data Requirement (OCSPP Guideline) Econem TM * Pasteuria usgae – Liquid
Formulation** MRID
Number

Product Chemistry and Composition

Product Identity

(885.1100) Econem TM is an end-use product and a natural biological control for use on turf against sting nematodes. It
contains 0.0020% Pasteuria

usgae (at least 1 x 10 4 spores per gram or 4.5 x 10 6 spores per pound). Classification: Acceptable Pasteuria usgae – Liquid Formulation is proposed as an end-use product, which will be used to control sting nematodes in turf and strawberry. It
contains 0.0033% Pasteuria

usgae (at least 1.3 x 10 7 spores per gram or 5.8 x 10 9 spores per pound). Currently, Pasteuria

usgae has an exemption from the requirement of a tolerance for all food commodities pending with the Agency, while all inert ingredients in this formulation
are cleared for food use under 40 CFR part 180, subpart D (“Exemptions from Tolerances”). Classification: Acceptable 475218-01*
475963-01**

Manufacturing Process (885.1200) Submitted data satisfied the requirement of manufacturing process for this end-use product. Classification: Acceptable Submitted data satisfied the requirement of manufacturing process for this end-use product. Classification: Acceptable 475218-01*
475963-01**

Deposition of a Sample in a

Nationally Recognized

Culture Collection

(Not applicable) Not applicable Not applicable

40Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Results Data Requirement (OCSPP Guideline) Econem TM * Pasteuria usgae – Liquid
Formulation** MRID

Number

Discussion of Formation of Unintentional Ingredients (885.1300) Submitted data satisfied the requirement of discussion of

formation of unintentional ingredients for this end-use product. Classification: Acceptable Submitted data satisfied the requirement of discussion of

formation of unintentional ingredients for this end-use product. Classification: Acceptable 475218-02*
475963-01**

Analysis and Certified Limits

Analysis of Samples (885.1400) Submitted data satisfied the requirement of analysis of samples for this end-use product for the purposes of a conditional, time-limited FIFRA section 3(c)(7)(A) registration only.
Classification: Supplemental: Upgradeable. A new five-batch analysis,
with all batches from production level, must be submitted to the Agency on or before August 1, 2011. Submitted data satisfied the requirement of analysis of samples for this end-use product. Classification: Acceptable

475375-01*
475963-03**

Certification of Limits (885.1500) The certified limits for the active and inert ingredients
fall within the OCSPP Guideline 830.1750 specified

ranges. Classification: Acceptable The certified limits for the active and inert ingredients fall within
the OCSPP Guideline 830.1750 specified ranges. Classification: Acceptable 475218-04*
475963-04**

Physical and Chemical Characteristics

Color (830.6302) Not applicable Not applicable

Physical State

(830.6303) Not applicable Not applicable

Odor (830.6304) Not applicable Not applicable

Stability to Normal and Elevated Temperatures, Metals, and Metal Ions (830.6313) Not applicable Not applicable

Storage Stability (830.6317) A twelve-month storage stability study is ongoing

and results must be submitted to the Agency upon completion (on or before September 1, 2010).
This information has been provided to the Agency (MRID No. 480262-01) and is currently being reviewed for acceptability. A twelve-month storage stability study is ongoing, and the Agency is proposing to ask for the results of this study (to
be submitted on or before June 18, 2011) as one of the terms and conditions of registration for this end-use product. 475218-05*

476504-03**

41Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Results Data Requirement (OCSPP Guideline) Econem TM * Pasteuria usgae – Liquid
Formulation** MRID

Number

Miscibility (830.6319) Not required because

Econem TM is not an

emulsifiable form of microbial pesticide (refer to test note #2 of 40 CFR § 158.2120(d)). Not required because Pasteuria

usgae – Liquid Formulation is

not an emulsifiable form of microbial pesticide (refer to test note #2 of 40 CFR § 158.2120(d)). Not applicable

Corrosion Characteristics (830.6320) Testing is underway. The test material is being stored at
20oC. Evaluation of the container pieces, regarding
evidence of corrosion or other changes, will occur at months 0, 3, 6, 9, and 12. Results of the study must be submitted to the Agency upon completion (on or before September 1, 2010).
This information has been provided to the Agency (MRID No. 480262-02) and is currently being reviewed for acceptability. A 12-month corrosion characteristics study is ongoing, and the Agency is proposing to ask for the results of this study (to be submitted on or before June 18, 2011) as
one of the terms and conditions of registration for this end-use product. 475218-06*

476504-04**

pH (830.7000) Not applicable Not applicable

Viscosity (830.7100) Not required because

Econem TM is not a liquid form of microbial pesticide (refer to test note #4 of 40 CFR § 158.2120(d)). 15239.66 CentiStokes (cSt) at
20oC and 2591.34 cSt at 40oC 476504-02**

Density/Relative Density/Bulk

Density (Specific Gravity) (830.7300) Not applicable Not applicable

TABLE 3. Toxicology Data Requireme nts for the Technical Grade of the Active Ingredient (TGAI)/ Manufacturing-Use Product (MP), Pasteuria usgae – BL1 (40 CFR § 158.2140)

Results Data Requirement (OCSPP Guideline) TGAI MP MRID
Number

Tier I

Acute Oral Toxicity/Pathogenicity (885.3050) Not toxic and/or pathogenic to rats by oral dose of 1 x 10 8
spores/animal. Since microbial enumeration was not performed
because the test material would not grow on agar media, the infectivity was uncertain. However, because the spores are highly specific to the sting nematode, infectivity is unlikely

to be a concern. Classification: Acceptable
TOXICITY CATEGORY IV Not applicable 474267-09

42Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Results Data Requirement (OCSPP Guideline) TGAI MP MRID

Number
Acute Dermal Toxicity (885.3100) Not toxic to rats when treated with 2,000 mg/kg at 10 8
spores/mL. The acute dermal

LD 50 is greater than 2,000 mg/kg
for 10 8 spores/mL. Classification: Acceptable
TOXICITY CATEGORY IV Not applicable 474267-12

Acute Pulmonary Toxicity/Pathogenicity (885.3150) Not toxic and/or pathogenic to rats by pulmonary dose of 1–3 x

10 8 spores/animal. Since
microbial enumeration was not performed because the test material would not grow on agar media, the infectivity was uncertain. However, because the spores are highly specific to the sting nematode, infectivity is unlikely to be a concern. Classification: Acceptable
TOXICITY CATEGORY IV Not applicable 474267-10

Acute Injection Toxicity/Pathogenicity (885.3200) Not toxic and/or pathogenic to rats by intravenous dose of 1x

10 8 spores/animal. Since
microbial enumeration was not performed because the test material would not grow on agar media, the infectivity was uncertain. However, because the spores are highly specific to the sting nematode, infectivity is unlikely to be a concern. Classification: Acceptable Not applicable 474267-11

Hypersensitivity Incidents (885.3400) No hypersensitivity incidents, including immediate-type or delayed-type reactions of humans and domestic animals occurring during the testing or production of the TGAI/MP, were observed by the registrant. Any future hy persensitivity incidents must be reported per OCSPP Guideline 885.3400. 474350-02

Cell Culture (885.3500) Not required because Pasteuria

usgae is not a virus (refer to test note #4 of 40 CFR § 158.2140(d)). Not applicable Not applicable

Acute Oral Toxicity (870.1100) Not applicable Waived based on the results of
MRID Number 474267-09 and because the MP is equivalent
to the TGAI. Classification: Acceptable
TOXICITY CATEGORY

IV 474979-01

43Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Results Data Requirement (OCSPP Guideline) TGAI MP MRID

Number
Acute Dermal Toxicity (870.1200) Not applicable Waived based on the results of
MRID Number 474267-12 and because the MP is equivalent
to the TGAI. Classification: Acceptable
TOXICITY CATEGORY

IV 474979-01

Acute Inhalation Toxicity (870.1300) Not applicable Waived based on the results of
MRID Number 474267-10 and because the MP is equivalent
to the TGAI. Classification: Acceptable
TOXICITY CATEGORY

IV 474979-01

Acute Eye Irritation (870.2400) Not applicable Waived based on Pasteuria

usgae ’s lack of toxicity in the other toxicology studies and precautionary statements that mitigate potential for worker

exposure. Classification: Acceptable
TOXICITY CATEGORY

III 474350-03

Primary Dermal Irritation (870.2500) Not applicable Waived based on the results of
MRID Number 474267-12 and precautionary statements/personal protective equipment that mitigate potential for worker exposure. Classification: Acceptable
TOXICITY CATEGORY

III 474350-03

Tiers II and III Not required for Pasteuria usgae based on the lack of acute toxicity/p athogenicity in the Tier I studies.

TABLE 4. Toxicology Data Requirement s for the End-Use Products, Econem TM and Pasteuria usgae – Liquid Formulation (40 CFR § 158.2140)

Results Data Requirement (OCSPP Guideline) Econem TM * Pasteuria usgae – Liquid
Formulation** MRID

Number

Tier I

Acute Oral Toxicity/Pathogenicity (885.3050) Not applicable Not applicable

Acute Dermal Toxicity (885.3100) Not applicable Not applicable

Acute Pulmonary Toxicity/Pathogenicity (885.3150) Not applicable Not applicable

Acute Injection Toxicity/Pathogenicity (885.3200) Not applicable Not applicable

44Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Results Data Requirement (OCSPP Guideline) Econem TM * Pasteuria usgae – Liquid
Formulation** MRID

Number

Hypersensitivity Incidents (885.3400) No hypersensitivity incidents, including immediate-type or delayed-type reactions of humans and domestic animals occurring during the testing or production of these end-use products, were observed by the registrant. Any future hypersensitivity incidents must be reported per OCSPP Guideline 885.3400. 475218-07*
475963-06**

Cell Culture (885.3500) Not applicable Not applicable

Acute Oral Toxicity (870.1100) Waived based on the results of
MRID Number 474267-09 and

because this formulation contains inert ingredients, which

are not of toxico logical concern

and are cleared for food use. Classification: Acceptable
TOXICITY CATEGORY IV Waived based on the results of
MRID Number 474267-09 and

because this formulation contains inert ingredients, which are not of toxicological

concern and are cleared for
food use. Classification: Acceptable
TOXICITY CATEGORY

IV 475218-10*
475963-07**

Acute Dermal Toxicity (870.1200) Waived based on the results of
MRID Number 474267-12 and

because this formulation contains inert ingredients, which

are not of toxico logical concern

and are cleared for food use. Classification: Acceptable
TOXICITY CATEGORY III Waived based on the results of
MRID Number 474267-12 and

because this formulation contains inert ingredients, which are not of toxicological

concern and are cleared for

food use. Classification: Acceptable
TOXICITY CATEGORY

III 475218-10*
475963-07**

Acute Inhalation Toxicity (870.1300) Waived based on the results of
MRID Number 474267-10 and

because this formulation contains inert ingredients, which

are not of toxico logical concern

and are cleared for food use. Classification: Acceptable
TOXICITY CATEGORY III Waived based on the results of
MRID Number 474267-10 and

because this formulation contains inert ingredients, which are not of toxicological

concern and are cleared for
food use. Classification: Acceptable
TOXICITY CATEGORY

III 475218-10*
475963-07**

Acute Eye Irritation (870.2400) Econem TM was moderately irritating to the eye based on the highest maximum mean total score of 37.0, recorded 1 hour
after test material instillation. Classification: Acceptable
TOXICITY CATEGORY III Pasteuria usgae – Liquid Formulation was not irritating to the eye based on the highest

maximum mean total score of

0.0. Classification: Acceptable
TOXICITY CATEGORY

IV 475218-08*

476504-05**

Primary Dermal Irritation (870.2500) Econem TM was slightly irritating to the skin. The Primary
Irritation Index was 0.1. Classification: Acceptable
TOXICITY CATEGORY IV Pasteuria usgae – Liquid
Formulation was not a dermal irritant. The Primary Irritation
Index was 0.0. Classification: Acceptable
TOXICITY CATEGORY

IV 475218-09*

476504-06**

45Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Results Data Requirement (OCSPP Guideline) Econem TM * Pasteuria usgae – Liquid
Formulation** MRID

Number

Tiers II and III Not required for Pasteuria usgae based on the lack of acute toxicity/p athogenicity in the Tier I studies.

Additional Studies Subcutaneous Injection Toxicity (Not applicable) Not applicable None of the five lots of Pasteuria usgae – Liquid Formulation induced mortality or clinical signs of toxicity in mice when injected subcutaneously at a
concentration of 1.0 x 10 6 spores per animal. Classification: Acceptable 476504-01**

TABLE 5. Nontarget Organism and Environmental Fate Data Requirements for the Technical Grade of the Active Ingredient (TGAI), Pasteuria usgae (40 CFR § 158.2150)

Data Requirement (OCSPP Guideline) Results Toxicity Category/Description MRID

Number

Tier I Avian Oral Toxicity (885.4050) Data waiver rationale provides

sufficient information to determine that toxicity/pathogenicity to avian wildlife is not expected. Classification: Acceptable Not applicable 474267-13

Avian Inhalation Toxicity/Pathogenicity (885.4100) Not required as the nature of the microbial pesticide does not indicate potential pathogenicity to birds or relatedness to any known bird pathogens (refer to test note #3 of 40 CFR § 158.2150(e)). Not applicable Not applicable

Wild Mammal Toxicity/Pathogenicity (885.4150) Tests required by 40 CFR § 158.2140 are adequate and appropriate for
assessment of hazards to wild mammals (refer to test note #4 of 40 CFR § 158.2150(e)). Classification: Acceptable for wild
mammal risk assessment Testing indicates no
adverse effects to laboratory rats at 1 x

10 8 spores/mL when dosed orally. 474267-09

Freshwater Fish Toxicity/Pathogenicity (885.4200) Pasteuria usgae will not be applied directly to water and is not expected to
enter freshwater environments in amounts that are significantly higher than naturally occurring concentrations. Data waiver rationale provides

sufficient information to determine that toxicity/pathogenicity or substantial exposure to freshwater fish is not expected. Classification: Acceptable Not applicable 474267-13

46Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

Data Requirement (OCSPP Guideline) Results Toxicity Category/Description MRID

Number

Freshwater Invertebrate Toxicity/Pathogenicity (885.4240) Pasteuria usgae will not be applied directly to water and is not expected to
enter freshwater environments in amounts that are significantly higher than naturally occurring concentrations. Data waiver rationale provides

sufficient information to determine that toxicity/pathogenicity or substantial exposure to freshwater invertebrates is not expected. Classification: Acceptable Not applicable 474267-13

Estuarine/Marine Fish and Invertebrate Testing (885.4280) Not required because Pasteuria usgae will not be applied to water and is not expected to enter marine/estuarine
environments in amounts that are significantly higher than naturally occurring concentrations (refer to test note #6 of 40 CFR § 158.2150(e)). Not applicable Not applicable

Nontarget Plant Testing (885.4300) Not required because Pasteuria usgae is not related to known plant pathogens, and adverse effects to plants are not expected (refer to test note #7 of 40 CFR § 158.2150(e)). Not applicable Not applicable

Nontarget Insect Testing (885.4340) Data waiver rationale provides

sufficient information to determine that toxicity/pathogenicity to nontarget insects is not expected. Classification: Acceptable Not applicable 474267-13

Honey Bee Testing (885.4380) Data waiver rationale provides

sufficient information to determine that toxicity/pathogenicity to honey bees is not expected. Classification: Acceptable Not applicable 474267-13

Tiers II, III, and IV Not required for Pasteuria usgae based on the acceptability of the waiv er rationales provided for Tier I.

47Pasteuria usgae Biopesticides Registration Action Document (BRAD) May 2010

48 APPENDIX B – PASTEURIA USGAE MANUFACTURING-USE AND END-USE
PRODUCTS

EPA Registration

Number or

EPA File Symbol Registration

Name Percentage
Active Ingredient Formulation Type Use Site(s) Method(s) of Application Application

Rate Target

Pest

85004-1 Pasteuria

usgae – BL1 0.01% Technical N/A N/A N/A N/A

85004-2 Econem TM 0.0020% End Use –

Granular Turf Standard ground application equipment (e.g., drop spreader) 2–10 pounds of product per 1,000 square

feet of turf Sting

nematode

85004-G Pasteuria

usgae – Liquid

Formulation 0.0033% End Use – Liquid Turf and Strawberry Standard ground spray application equipment or chemigation 0.1–5 gallons of product per

100 square

feet of turf or

strawberry

bed Sting

nematode