BIOPESTICIDES REGISTRATION ACTION DOCUMENT



## Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

Pesticide Chemical (PC) Code: 01645 6

U.S. Environmental Protection Agency

Office of Pesticide P rograms Biopesticides and Pollution Prevention Division

July 26 , 2012Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 2 of 33 Biopesticides Registration Action Document

TABLE OF CONTENTS

I. EXECUTIVE SUMMARY

................................ ................................ ................................ ........................... 4

II. ACTIVE ING REDIENT OVERVIEW

................................ ................................ ................................ ........ 6

III. REGULATORY BACKGROUN D

................................ ................................ ................................ .............. 7

A. Applications for Pesticide Product Registration

................................ ................................ ............ 7

B

. Food Tolerance Exemption

................................ ................................ ................................ .............. 7

IV. RISK ASSESSMENT

................................ ................................ ................................ ................................ .... 7

A. Product Analysis Assess ment (40 CFR § 158.2120)

................................ ................................ ....... 8

B. Human Health Assessment (40 CFR § 158.2140)

................................ ................................ ........... 8

C. Environmental Assessment (40 CFR § 158.21 50)

................................ ................................ ......... 14

V. ENVIRONMENTAL JUSTIC E

................................ ................................ ................................ ................. 17

VI. RISK MANAGEMENT DECI SION

................................ ................................ ................................ .......... 17

VII. ACTIONS REQUIRED OF THE REGISTRANT

................................ ................................ .................... 18

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

................................ ................................ ...... 19

IX. BIBLIOGRAPHY

................................ ................................ ................................ ................................ ....... 20

A. Studies Submitted to Support the Pasteuria spp. ( Rotylenchulus reniformis nemtaode)

– Pr3 Pesticide Product Registrations

........................... 20

B. Environmental Protection Agency Risk Assessme nt Memoranda

................................ ............. 23

C. Other Refe rences

................................ ................................ ................................ ............................ 23

APPENDIX A. MICROBI AL PESTICIDES DATA R EQUIREMENTS

................................ ............................ 26

APPENDIX B. PESTICI DE PRODUCTS

................................ ................................ ................................ .............. 33Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 3 of 33 Biopesticides Registration Action Document

BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

Office of Pesticide Programs (OPP) Biopesticides and Pollution Prevention Division

Microbial Pesticides Branch

Science Reviews

Joel V. Gagliardi , Ph.D. Product Analysis, Human Health

John L. Kough, Ph.D. Product Analysis, Human Health Shannon Borges Environmental Effects

Regulations

Sheryl K. Reilly, Ph.D. Chief, Microbial Pesticides Branch

Jeannine Kausch Regulatory Action LeaderPasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 4 of 33 Biopesticides Registration Action Document

I. EXECUTIVE SUMMARY

In July and August 2010

, Pasteuria Bioscience, Inc. submitted application s for a manufacturing

use p esticide product, NAVIVA Tech (EPA File Symbol 85004

- U ), and two end

- use pesticide product s
, NAVIVA ST (EPA File Symbol 85004

- L ) and NAVIVA LF (EPA File Symbol 85004

- I ), to the United States Environmental Protection Agen cy (EPA) under section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)

. Concurrently with these applications, Pasteuria Bioscience, Inc. filed a petition for a toleran ce exemption for residues of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , the new active ingredient contained in all three proposed pesticide produc ts

. Backgro und

Pasteuria , a genus of bacteria, includes several species that have shown potential in con trolling plant

- parasitic nematodes that attack and cause significant damage to many valuable agricultural

crops (see, e.g., the Federal Register of December 28, 1994 ( 59 Federal R egister (FR) 66740 ), June 30, 2010 ( 75 FR 37734 ), and February 15, 2012 ( 77 FR 8736 ) for Final Rul es that established tolerance exemptions for residues of the nematicides, Pasteuria penetrans (40 Code of Federal Regulations (CFR) 180.1135), Pasteuria usgae (40 CFR 180.1290), and Pasteuria
nishizawae

– Pn1 (40 CFR 180.1311), respectively). These gram

- po sitive, mycelial, endospore

forming bacteria are obligate parasites (i.e., organisms that depend on particular hosts to complete their own life cycle) of nematodes and water fleas. 1 Pasteuria species are ubiquitous in

most environments and are found in nem atodes in at least 80 countries on 5 continents, as well as on islands in the Atlantic, Pacific, and Indian Oceans (Chen and Dickson 1998; Ciancio et al

. 1994; Sturhan 1988)

. H igher population densities often occur in areas where there is an ample supply o f nematode hosts (e.g., where crops susceptible to nematodes are cultivated) ( Centitas and Dickson 2004; Noel 2008; Tain et al . 2007 ). Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 was specifically isolated from soil samples collected in the sou theastern United States (U.S.)

.

Endospores of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 attach to Rotylenchulus

spp. at all life stages, except eggs. After an endospore attaches to the cuticle of a nematode host

, a germ tube penetrates the cuticle , and growth and sporogenesis begin in the pseudocoelom of the nematode. The nematode is eventually filled with cells, mycelial hyphae, and sporangia, which

lead s to its death. In light of the demonstrated nematicidal capabilities and host specific ity of

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , Pasteuria Bioscience , Inc. proposed to register pesticide products intended for use on several food and nonfood crops, primarily as seed or soil treatments, to control the reniform nematode ( Rotylenchulus reniformis )

.

EPA s cientists reviewed product analysis, toxicology, and nontarget organism data and information ( 40 CFR §§ 158.2120, 158.2140, and 158.2150, respectively) submitted to support

the registration of the t hree proposed Pasteuria s pp. ( Rotylenchulus reniformis nematode)

– Pr3 pesticide products. Overall, such data and information are adequate for risk assessment purposes

, fulfill the current microbial pesticide data requirements

, and support registration of the proposed products und er FIFRA section 3(c)(5)

.

1 Pasteuria ramosa is the only Pasteuria species that is known to parasitize water fleas; it is not an active ingredient in any pe sticides.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 5 of 33 Biopesticides Registration Action Document

For the purposes of FIFRA section 3(c)(5) registration, t he p roduct analysis data requirements for

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , including product chemistry and composition, analysis o f samples, and physical and chemical characteri stics, were fulfilled by acceptable guideline studies. Product Analysis

Adequate mamm alian toxicology data and information were submitted to support the Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 pest icide products. A cute oral, pulmonary, and injection toxicity/pathogenicity studies showed t hat, at a single high dose, Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 is not toxic and/o r p athogenic via these route s of

exposure

. Moreover, the appl icant reported that no hypersensitivity incidents occurred during

rese arch, development, or testing of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3.

In l ight of the results of the acute toxicity/pathogenicity data and the absence of hypersensit ivity incidents, testing at higher tiers (i.e., Tiers II and III) was not required. Toxicology

EPA concludes that there is a reasonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate expo sure to residues of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 . No dietary risks are expected from use of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 as an active ingredient in pesticide products. Significant exposure to Pasteuri a spp. ( Rotylenchulus reniformis nematode)

– Pr3 through food

and drinking water is not anticipated due to : (1) the proposed application methods of the end

- use pesticide products (soil directed, soil incorporated , and/or seed directed ; no aquatic applicati ons ) ; (2) the filtering effect of many particulate soil types; and (3 ) the conditions (e.g., filtration and pH adjustments) water is subjected to in wastewater treatment systems and drinking water

facilities

. Should Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 be present on food or in drinking water, its specificity for Rotylenchulus spp. and supporting acute oral toxicity and pathogenicity d ata indicate that human exposure to this bacterium would not result in

unreasonable adverse effects

. Tolerance Exemption

Despite the low toxicological profile of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , baseline personal protective equipment (PPE) is required for handlers that may be exposed to the active ingredient, due to their occupatio n, for prolonged periods or numerous times

. Handlers working with Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 in agricultural settings are directed to wear a long

- sleeved shirt, long pants, waterproof gloves, socks, shoes, and

a dust/mist filt ering respirator meeting National Institute for Occupational Safety and Health (NIOSH) standards of at least N

- 95, R

- 95, or P

- 95. For future products, EPA may require

additional PPE (e.g., protective eyewear) , other than the standard described above, on a product

specific basis. Occ upational Exposure

Data and other i nformation (e.g., scientific literature) submitted by the applicant to support requests to waive nontarget organism testing for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 are suff icient to fulfill the relevant microbial pesticide data requirements and for risk assessment purposes. Further testing of nontarget organisms at higher tier levels (i.e., Tiers II, III, and IV) is not required. EPA performed an environment al risk assessmen t based on data Nontarget OrganismsPasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 6 of 33 Biopesticides Registration Action Document

and other information provided by the ap plicant

, and determined that adverse effects to nontarget organisms are not anticipated from the proposed pesticidal uses of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 . Moreover, EPA mad e a “No Effect” determination for direct and indirect effects to listed species and their d esignated critical habitats resulting from these same proposed pesticidal uses.

On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunity for the public to participate i n major registration decisions before they occur. According to this policy, EPA intends to provide a public comment period prior to making a registration decision for, at minimum, the following ty pes of appli cations: new active ingredients; first food uses; first outdoor uses; first residential use s; or any other registration actions for which EPA believes there may be significant public interest

. Public Participation

Consistent with the policy of making registratio n actions more transparent, the proposed pesticide products containing Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3, a new active ingredient, and allowing for this active ingredient’s first outdoor and food uses were subject to a 30

- day comment period. During this comment period, no comments were received on EPA’s preliminary decision to register the Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 pesticide products, NAVIVA Tech, NAVIVA ST, and NAVIVA LF. Therefore, EPA maintained that, based upon the risk assessment and information submitted in support of registration of such pesticide products, it was appropriate to issue the NAVIVA Tech, NAVIVA ST, and NAVIVA LF registrations under FIFRA section 3(c)(5). The basis for this decision ca n be found in the risk assessment for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3, which is characterized throughout this Biopesticides Registration Action Document (BRAD).

II. ACTIVE INGREDIENT OVERVIEW

Biological Name: Pasteuria spp . ( Rotylenchulus reniformis nematode)

– Pr3

Culture Deposit: American Type Culture Collection in Manassas

, Virginia

under Accession N umber SD

- 583 4

OPP Chemical Code: 01645 6

Type of Pesticide: Microbial Pesticide

– Nematicide

See Appendix B for specific information (e.g., use sites, application rate s , methods of application, formulation type s , and target pests) regarding

the registered pesticide products containing this active ingredient.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 7 of 33 Biopesticides Registration Action Document

III. REGULATORY BACKGROUND

A. Applications for Pesticide Product Registration

In July and August 2010

, MacIntosh and Associates , Inc. (address: 1203 Hartford Avenue; Saint Paul, Minnesota 55116

- 1622 ) , on behalf of Pasteuria Bioscience , Inc. (address: 12085 Research Drive, Suite 185; Alachua, Florida 32615 ), submitted application s to register a manufacturing

use pesticide product, NAVIVA Tech (EPA File Symbol 85004

- U )

, and two end

- use pesticide product s
, NAVIVA ST (EPA File Symbol 85004

- L ) and NAVIVA LF (EPA File Symbol 85004

- I ), under FIFRA section 3. On November 24 , 2010 ( 75 FR 71697 ) and February 2, 2011 ( 76 FR

5805 )

, EPA announced receipt of these application s to register pesticide product s containing a new active ingredient and opened a 3 0

- day public comment period pursuant to the provisions of FIFRA section 3(c)(4). No comme nts were received followin g these publication s

.

B . Food Tolerance Exemption

Concurrent with its registration application s and under Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(d), MacIntosh and Associates , Inc. , on behalf of Pasteuria Bioscience , Inc.

, submitted a petition to establish an exemption from the requirement of a tolerance for Pasteuria reniformis

– Pr3 (now Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3) (Pesticide Petition (PP) 0F774 5 )

. In the Federal Register of February 4, 2011 ( 76 FR 6465 ), EPA

announced that Pasteuria Bioscience , Inc. proposed to establish an exemption from the requirement of a tolerance for residues of the microbial pesticide

, Pasteuria reniformi s

– Pr3

, in

or on all raw agricultural crops and opened a 30

- day comment period. Two comments were received following this publication and are addressed in the preamble to the Final R ule

.

On July 9, 2012, EPA established an exemption from the requiremen t of a tolerance for residues

of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 in or on all food commodities when applied as a nematicide and used in accordance with label directions and good agricultural practices (40 CFR § 180.1316; 77 FR 40271 ).

IV. RISK ASSESSMENT

In the Federal Register of October 26, 2007, EPA issued a Final Rule on the data requirements to support registration of microbial pesticides and upda ted the definition for microbial pesticides ( 72 FR 61002 )

. The rule became effective on December 26, 2007. The data and information evaluated for this BRAD were considered in ligh t of these requirements.

The classifications that are found for each data submission are assigned by EPA science

reviewers and are an indication of the usefulness of the information contained in the documents for risk assessment. A rating of “ acceptable ” indicates the study is scientifically sound and is

useful for risk assessment. A “ supplemental ” rating indicates the data provide some information that can be useful for risk assessment. The studies may have certain aspects determined not to be

scientifica lly acceptable (“ supplemental : upgradeable ”). If a study is rated as “supplemental: upgradeable ,” EPA 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 reviewer will

often state that t he study is not required by 40 C FR P art 158. Both “ acceptable” andPasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 8 of 33 Biopesticides Registration Action Document

“supplemental ” studies may be used in the risk assessment process as appropriate. An “unacceptable ” rating indicates that new data must be submitted.

F or the acu te toxicity data requirements, Toxicity C ategories are assigned based on the hazard(s) identified from studies and/or other infor mation submitted to EPA in support of a pesticide registration. The active ingredient or particular product is class ified into Toxicity Category I, II, III, or IV, where Toxicity Category I indicates the highest toxicity and Toxicity Category IV indicates the lowest toxicity (see 40 CFR § 156.62 )

.

A. Product Analysis Assessment ( 40 CFR § 158.2120 )

For purposes of registration under FIFRA section 3(c)(5), a ll product analysis data requirements

for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 have been fulfilled. Refer to Tables 1, 2, 3, and 4 in Appendix A for a summary of the data requirements, including both generic and product

- specific information.

B. Human Health Assessment ( 40 CFR § 158.2140 )

1. Toxicity

All toxicology data requirements for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

have been fulfilled

. Acceptable Tier I mammalian to xicology data and information support registration of the Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 pesticide products

. Furthermore, Tier II and Tier III studies were not required for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

, based on the lack of acute toxicity/pathogenicity in the Tier I

studies.

For a summary of the generic toxicology data requirements described in sections IV(B)(1)(a) and IV(B)(1)(b) (see pages 8

– 9 ) , as well as additional product

- specific data submitted to support the individual registrations, refer to Tables 5 and 6 in Appendix A

.

a. Acute Toxicity/Pathogenicity

– Tier I

Acute Oral Toxicity/Pathogenicity

– Rat ( Harmonized Guideline 885.3050; Master Record Identification Nu mber (MRID No.) 481 460

- 09 ) : Groups of fasted, 45

- to 48

- day

- old CD ® rats (3

per sex per group ) were given a single oral dose of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 at approximately 1.5 x 10 9 spores per animal. The animals were observed for a period of up to 21 days, with interim scheduled sacrifices on Days 7 and 14. Three males and

three females were treated with autoclaved Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 as controls, three males and three females were untreate d shelf controls, and another three

males and three females were untreated naïve controls. Based on the results of this study,

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 does not appear to be toxic and/or pathogenic in rats when dosed at appr oximately 1.5 x 10 9 spores per animal. Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 showed no clinical signs or major tissue abnormalities and no evidence of toxicity or pathogenicity to rats following a single oral

administration of 1.5 x 10 9 spores per rat. This study was rated supplemental

.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 9 of 33 Biopesticides Registration Action Document

Acute Pulmonary Toxicity/Pathogenicity

– Rat ( Harmonized Gui deline 885.3150; MRID No.

481 460

- 10 ) : Groups of fasted, 45

- to 48

- day

- old CD ® rats (3 per sex per group) were exposed by

the intratracheal rou te to Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 at a dose of approximately 1.5 x 10 8 spores per animal. The animals were then observed for up to 21 days.

Three males and three females were treated with autoclaved Pasteuria spp. ( Rotylenchulu s reniformis nematode)

– Pr3 as controls, while three males and three females were not treated and

served as naïve controls. Based on the results of this study, Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 does not appear to be toxic and/or pat hogenic in rats when dosed at approximately 1.5 x 10 8 spores per animal. Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 showed no clinical signs or major active ingredient

- related tissue abnormalities and no evidence of toxicity or pathogenicity to rats following a single intratracheal instillation of 1.5 x

10 8 spores per rat. This study was rated supplemental

.

Acute Injection Toxicity/Pathogenicity (Intra venous )

– Rat (Harmonized Guideline 885.3200;

MRID No . 481 460

- 1 1 ) : Groups of fasted, 45

- to 48

- day

- old CD ® rats (3 per sex per group) were exposed by the intravenous route to Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 at a dose of approximately 1 x 10 7 spores per animal. The animals were then observed for up to 21 days. Three males and three females were treated with autoclaved Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 as controls, while three males and three females were not treated and

served as naïve controls. Based on the results of this study, Pasteuria spp. ( Rot ylenchulus reniformis nematode)

– Pr3 does not appear to be toxic and/or pathogenic in rats when dosed at approximately 1 x 10 7 spores per animal. Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 showed no active ingredient

- related clinical signs o r major tissue abnormalities and no evidence of toxicity or pathogenicity to rats following a single intravenous injection of 1 x 10 7

spores per rat. This study was rated supplemental

.

Hypersensitivity Incidents ( Harmonized Guideline 885.3400; MRID No. 4 81 460

- 12 ) : The applicant reported that n o hypersensitivity incidents, including immediate

- type or delayed

- type
reactions of humans and domestic animals

, occurred during research, development, or testing of

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 . Any future hypersensitivity incidents must be reported to EPA (refer to test note #3 of 40 CFR § 158.2140(d))

.

Cell Culture ( Harmonized Guideline 885.3500) : This study is not required because Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr 3 is not a virus (refer to test note #4 of 40 CFR § 158.2140(d)).

b. Acute Toxicology and Subchronic Toxicity/Pathogenicity

– Tier II; Reproductive Fertility Effects, Carcinogenicity, Immunotoxicity, and Infectivity/Pathogenicity Analysis

– Ti er III

Tier II and Tier III studies were not required for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

, based on the lack of acute toxicity/pathogenicity in the Tier I studies.

c. Endocrine Disruptors

As required by the Administrator under FFDCA section 408(p), EPA has developed the Endocrine Disrup tor Screening Program (EDSP) and has begun to implement the screening program that is to be used to test all pesticides in order to determine whether certain substancesPasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 10 of 33 Biopesticides Registration Action Document

(including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.”

FFDCA se ction 408(p)(4) authorizes the Administrator, by order, to exempt from the requirements of the Estrogenic Substances Screening Program a biologic substance or other substance if a determination is made that the substance is not anticipated to produce any e ffect in humans similar to an effect produced by a naturally occurring estrogenic substance.

Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients a nd 9 inert ingredients. Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP.

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 is like ly a substance that would not produce any effect in humans similar to an effect produced by a naturally occurring estrogenic substance. As such, pursuant to FFDCA section 408(p)(4), EPA will determine in the future whether it can exempt Pasteuria spp. ( Rot ylenchulus reniformis nematode)

– Pr3 from the requirements of the Section 408(p) EDSP. In the event EPA does determine to exempt this substance from the EDSP, an order will be issued.

For further information on the status of the EDSP, the policies and pr ocedures, the list of 67 chemicals, future lists, the test guidelines

, and the Tier 1 screening battery, please visit our

website: http://www.epa.gov/endo/

.

2

. Federal Food, Drug, and Cosmetic Act (FFDCA ) Conside rations

Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an exemption from the requirement for a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the exemption is “safe.” Section 408(c)(2)(A) (ii) of FFDCA defines “safe” 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 exposures and all other exposures for

which there is reliable i nformation.” This includes exposure through drinking water and in

resi dential 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

t olerance, EPA must take into account the factors set forth in section 408(b)(2)(C) of FFDCA, which require EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance exemption

, 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

EPA consider “available information conc erning the cumulative effects of [a particular pesticide's]

. . . residues and other substances that have a common mechanism of toxicity.”

EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide residues. First, EPA de termines the toxicity of a pesticide . Second, EPA examines exposure to the pesticide through food, drinking water, and through other exposures that occur as a result of pesticide use in residential settings.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 11 of 33 Biopesticides Registration Action Document

Consistent with section 408(b)(2)(D) of FFDCA, E PA has reviewed the available scientific data and other relevant information, and considered its validity, completeness, and reliability and the relationship of this information to human risk. EPA has also considered available information concerning the va riability of the sensitivities of major identifiable subgroups of consumers, including infants and children.

Based on the acute toxicity/pathogenicity data and information discussed previously and presented in Table s 5 and 6 in Appendix A , t he data required for a FFDCA risk assessment for

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 have been fulfilled

.

a. Aggregate Exposure

In examining aggregate exposure, section 408 of FFDCA directs EPA to consider

availabl e information concerning exposures from the pesticide residue in food and all other non

occupational exposures, including drinking water from ground water or surface water and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses).

Food Exposure and Risk Characterization : Dietary exposure to Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

, a naturally occurring soil bacterium, is anticipated to be negligible

. For o ptimal control of the target pest

, renif orm nematode ( Rotylenchulus reniformis ), Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 is appli ed in a manner that facilitates spore

movement into or spore placement near th e root zone of potentially affected plants . This requires

that end users take certain actions , depending on the treatment type, that would inevitably

minimize the amount of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 residues on

above ground food commodities. That is, although Pasteuria spp. ( Rotylenchulus reniform is nematode)

– Pr3 can be applied to soil , plants, or seeds, some s e eds are incorporated into the soil immediately after treatment ( at

- planting, hopper box, planter box, or slurry box seed treatment s )

, and pesticide applications made to plants or the soil are always followed by irrigation to incorporate Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 into the soil

. In instances where food commodities develop underground or where treated seed is diverted for food or feed
purposes or to process into oil , exposure to Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 residues is a more likely scenario. Regardless of the situation, however, s hould residues of

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 result in or on food when used as a pesticide in accordance with label directions and good agricultural practices, its lack of toxicity

and pathogenicity (as demonstrated in available data) indicate that no adverse effects are likely to occur with respect to any exposures to such residu es (see section IV(B)(1)(a) on pages 8

– 9 and

Table s 5 and 6 in Appendix A ).

Drinking Water Exposure and Risk Characterization : Exposure to residues of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 in consumed drink ing water is possible but not likely. The proposed use patterns for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 are soil

directed

, soil incorporated , and/or seed directed , thereby limiting contact with surface water by

drift and runoff

. Furthe rmore, ground water is not expected to have significant exposure to

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , given that this microbial pesticide would likely be filtered out by the particulate nature of many soil types as are other

microor ganisms (Aislabie et al . 2001; DeFelice et al . 1993; Pang et al . 2008)

. I f Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 were to be transferred to surface or ground water s (e.g., through spray drift or runoff) that are intended for eventual huma n consumption andPasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 12 of 33 Biopesticides Registration Action Document

directed to wastewater treatment systems or drinking water facilities

, it may not survive some of

the cond itions water is subjected to in such systems or facilities , including chlor ination, pH adjustments, and filtration (Center s for Dise ase Control and Prevention 2009; U.S. EPA 2004)

. In the remote likelihood that Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 is present in drinking water (e.g., water not subject to certain conditions in treatment systems or facilities),

its lac k of toxicity and pathogenicity demonstrated by the available data indicate that no toxicity, pathogenicity, and/or infectivity is likely to occur with respect to any exposures to residues of

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 in drin king water that might result from pesticide applications made in accordance with label directions and good agricultural practices (see section IV(B)(1)(a) on pages 8

– 9 and Table s 5 and 6 in Appendix A )

.

Non

- occupational, Res idential Risk Characterization : Given Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 ’ s natural occurrence in soil, non

- occupational exposure to the

bacterium almost certainly is already occurring

. Additional non

- occupational exposure to

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 due to pesticidal applications is not expected because all proposed pesticide end

- use products are labeled for use in distinct agricultural settings. Even if additional non

- occupational exposures were to occu r (e.g., eventual expansion of use sites)

, the lack of toxicity, pathogenicity, and irritation demonstrated in the available data indicate that no adverse effects are likely to occur with respect to any exposures to such residues that might result from pes ticide applications made in accordance with label directions and good agricultural practices (see section IV(B)(1)(a) on pages 8

– 9 and Table s 5 and

6 in Appendix A ).

b. Cumulative Effects from Substances with a Common Mech anism of Toxicity

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance exemption, EPA consider “available information concerning the cumulative effects of [a particular pesticide’s]

. . . res idues and other substances that have a common mechanism of toxicity.”

No mechanism of toxicity in mammals has been identified for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , and Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 does

no t appear to produce a toxic metabolite against the target pest

. For the purposes of the tolerance action, therefore, EPA has assumed that Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 does not have a common mechanism of toxicity with other subst ances. For information regarding EPA ’s efforts to determine chemicals that have a common mechanism of toxicity and

to evaluate the cumulative effects o f such chemicals, see EPA ’s website at http://ww w.epa.gov/pesticides/cumulative

.

c. Determination of Safety for the United States Population, Infants and Children

FFDCA section 408(b)(2)(C) provides that, i n considering the establishment of a tolerance or tolerance exemption for a pesticide chemica l residue, EPA shall assess the available information about consumption patterns among infants and children, special susceptibility of infants and children to pesticide chemical residues, and the cumulative effects on infants and children of the

residues a nd other substances with a common mechanism of toxicity. In addition, FFDCA section 408(b)(2)(C) provides that EPA shall apply an additional tenfold (10X) margin of exposure ( safety ) for infants and children in the case of threshold effects to account for prenatalPasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 13 of 33 Biopesticides Registration Action Document

and postnatal toxicity and the completeness of the database on toxicity and exposure

, unless EPA determines that a different margin of exposure ( safety ) will be safe for infants and children. This additional margin of exposure ( safety ) is commonly referred to as the Food Quality Protection Act Safety Factor. In applying this provision, EPA either retains the default value of 10X

, or uses a different additional or no safety factor when reliable data are available to support a different

additional or no safety factor.

Based on the acute toxicity an d pathogenicity data /information discussed in section IV(B)(1)(a) (see pages 8

– 9) and Tables 5 and 6 in Appendix A

, as well as Pasteuria spp. ( Rotylenchulus reniformis nematod e)

– Pr3 ’s host specificit y for Rotylenchulus spp. nematode s , EPA concludes that there are no threshold effects of concern to infants, children, or adults when Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 is used as labeled in accordance with g ood agricultural practices. As a result, EPA concludes that no additional margin of exposure (safety) is necessary.

Moreover, based on the same data and EPA analysis as presented directly above, the Agency is

able to conclude that there is a reasonable ce rtainty that no harm will result to the U.S. population, including infants and children, from aggregate exposure to the residues of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 when it is used as labeled and in accordance

w ith good agricultural practices as a nematicide . Such exposure includes all anticipated dietary exposures and all other exposures for which there is reliable information. EPA has arrived at this conclusion because, considered collectively, the data and information available on Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 do not demons trate toxic

, pathogenic , and/or

infective potential to mammals, including infants and children.

3. Occupational Exposure and Risk Characterization

Handler exposure to Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 is not expected to pose any undue risk. Regardless, appropriate personal protective equipment and precautionary statements are required on pesticide product labels to mitigate any potential risks to pesticide

hand lers due to prolonged or numerous exposures. Handlers applying Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 end

- use pesticide products in agricultural settings must wear a long

- sleeved shirt, long pants, waterproof gloves, socks, shoes, and a d ust/mist filtering respirator meeting NIOSH standards of at least N

- 95, R

- 95, or P

- 95. For future products,

a dditional PPE (e.g., protective eyewear) , other than the standard described above, may be required on a product

- specific basis.

4. Human Health R isk Characterization

EPA considered human exposure to Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 in light of the standard for registration in FIFRA and the relevant safety factors in FFDCA. A

determination has been made that no unreason able a dverse effects to the U.S. population in general, and to infants and children in particu lar, will result when Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 pesticide products are used in accordance with EPA

- approved labeling.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 14 of 33 Biopesticides Registration Action Document

C. Environmenta l Assessment ( 40 CFR § 158.2150 )

Data and other i nformation (e.g., scientific literature) submi tted by the applicant to support requests to waive nontarget organism testing for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 are sufficient to fulfill the relevant microbial pesticide data requirements and for risk assessment purposes. Furthe r testing of nontarget organisms at higher tier levels (i.e., Tiers

I I, III, and IV) is not required . EPA performed an environmental risk assessment based on data

and other information provided by the ap plicant

, and determined that adverse effects to nonta rget organisms are not anticipated from the proposed pesticidal uses of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

. Moreover, EPA has made a “No Effect” determination for direct and indirect effects to listed species and their designated crit ical habitats resulting from these same proposed pesticidal uses.

For a summary of the generic data requirements described in sections IV(C)(1) (see pages 14

– 17) , refer to Table 7 in Appendix A

.

1. Ecological Exposure a nd Risk Characterization

a. Terrestrial Animals and Plants

Birds ( Harmonized Guideline 885.4050)

, Wild Mammals (Harmonized Guideline 885.4150)

, Nontarget Plants (Harmonized Guideline 885.4300), Nontarget Insects ( Harmonized Guideline 885.4340)

, and Honey Bees (Harmonized Guideline 885.4380) (MRID No. 481 460

- 17 ) : The proposed end

- use pesticide products are for use on several crops, including food and ornamental

crops

. The liquid formulation end

- use pesticide product may be applied by soil

- directed spr ay or chemigation, including both soil

- directed and foliage

- directed (e.g., ov erhead sprinkler) chemigation. Applications are to be followed with a sufficient amount of water to move the

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 spores into the root zone. Therefore, both formulations will primarily deposit Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 into the soil. While this type of application reduces the potential for exposure to many nontarget species, exposure to nontarget sp ecies consuming, contacting, or living in the soil will not necessarily be eliminated.

Data and other i nformation submitted by Pasteuria Bioscience, Inc. to support its waiver requests provides sufficient information to conclude that adverse effects are n ot expected in birds,

non target insects, and honey bees as a result of exposure to Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

. Pasteuria spp. are widespread in their distribution throughout t he

world (Chen and Dickson 1998; Ciancio et al . 199 4; Sayre and Starr 1985; Sturhan 1988) . They are known only as parasites of plant

- parasitic nematodes, with the exception of Pasteuria ramosa that is known only to parasitize Daphnia spp. (Atibalentja et al

. 2004 ; Chen and Dickson 1998; Sayre et al . 1991). Therefore, Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 is not expected to be toxic or pathogenic to birds, nontarget insects

, or honey bees if they are exposed

as a result of the proposed pesticidal applications.

An acute oral toxicity/patho genicity study with laboratory rats (MRID No. 481 460

- 09) and an acute oral toxicity study (MRID No. 481 460

- 13) are available to evaluate the potential effects of

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 on wild mammals. T he acute oral

toxic ity/pathogenicity study is summarized in section IV(B)(1)(a) on page 8 . No signs of toxic orPasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 15 of 33 Biopesticides Registration Action Document

pathogenic effects were observed in that study. The study was determined to be supplemental because clearance and infectivity were not observed. The acute oral tox icity study showed no evidence of toxicity in rats dosed with 5

, 000 milligrams per kilogram bodyweight , and this study was determined to be acceptable. These studies show that toxicity/pathogenicity of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– P r3 to laboratory rats is not expected. There is no reason that the test animals in these studies would not be adequate models with which to determine potential effects to wild mammals, so adverse effects to wild mammals are not expected as a result of the proposed pesticidal applications of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

.

Non target plant testing is not required because Pasteuria species are not related to any known plant pathogen. Adverse effects on plants are not expected to resu lt from the proposed pesticidal applications of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

.

Additionally, there are no reports of toxicity or pathogenicity of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 to nontarget terrestrial animals or plants. To support its data waiver rationale, the applicant performed a search within the Agricola and PubMed databases, along with several biological journals (i.e., Journal of Bacteriology, Applied and Environmental Microbiology, FEMS Microbio logy Ecology, Soil Biology and Bioch emistry) for the period of

1980

– 2010. The search was conducted using “ Pasteuria ” as the search word, and returned no reports of acute toxicity data on birds , freshwater fish, freshwater invertebrates, nontarget insects, and honey bees . The Biopesticides and Pollution Prevention Division also conducted a search

within the Environmental Information Database that is available to EPA. This database simultaneously searches the Agricola, Biosis Previews, CAB Abstracts, Energy S cience and Technology, General Science Abstracts, and the National Technical Information Service literature search databases. The search was performed with the term “ Pasteuria ” coupled with

each of the search terms of “ bird, ” “mammal,” “invertebrate,” “art hrop od,” “insect,” “honey bee,” “plant pathogen, ” and “phytopathogen” for all of the years available (1926

– present) . No unanticipated reports of adverse effects of Pasteuria species in nontarget organisms were found in any of these searches. 2 Any reports o f effects to nontarget organisms related to Pasteuria species that are found in the future may trigger the need for testing; however, given the specificity of these bacteria for their hosts as is currently understood, such reports are not expected.

Based on the information above and available data, adverse effects are not expected to occur to terrestrial animals or plants as a result of the proposed pesticidal applications of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

.

b. Aquatic Animals and Plants

Freshwater Fish ( Harmonized Guideline 885.4200) , Freshwater Invertebrates ( Harmonized Guideline 885.4240)

, Estuarine/Marine Fish and Inverte brates (Harmonized Guideline 885.4280) , and Nontarget Plants (Harmoniz ed Guideline 885.4300) (MRID No

. 4 81 460

- 17 )

2 Pasteuria ramosa is already recognized as parasitizing water fleas and is not considered an “unanticipated” report

. : Since the proposed applications are intended to deposit Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 in the soil, some runoff of the active ingredient to freshwater andPasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 16 of 33 Biopesticides Registration Action Document

marine/estua rine environments is expected. A pplications of the l iquid formulation and seed

treatment , however, are intended primarily to put Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 in the root zone of the treated plants, so these amounts are not likely to be significant. Pasteuria sp ecies are naturally found in soil, so some natural presence of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 in surface waters is expected. To date, no information is available on the size of naturally occurring populations of Pasteuria species

.

Scientific ratio nale was submitted to fulfill data requirements for and support effects conclusions

f

or freshwater aquatic organisms . The rationale provides sufficient information to conclude that adverse effects are not expected in freshwater fish or freshwater invertebr ates as a result of
exposure to Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 . The rationale was similar to that presented for terrestrial organisms in that Pasteuria species are found in soils worldwide.

Pasteuria ramosa is a closely related sp ecies that parasitizes Daphnia magna and other Daphnia species (Ebert et al . 1996); however, it is widely understood that all other known Pasteuria

sp ecies are obligate parasites of soil

- dwelling nematodes (Atibalentja et al

. 2004; Chen and Dickson 1998; S ayre et al . 1991).

There are no available reports in the literature documenting pathogenicity or toxicity to freshwater fish or invertebrates as a result of exposure to Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

. A search

, si milar to the o ne described for terrestrial animals and plants, was performed for aquatic animals and plants. In addition to the s earch terms used for terrestrial animals and plants , the terms “fish,” “aquatic,” “freshwater,” “estuarine,” and “marine”

were also searched. No unanticipated reports of adverse effects of Pasteuria species in nontarget organisms were found in any of these searches. 3 As noted above, reports of adverse effects that may be found in the future may trigger the need for testing; however, none are an ticipated due to the specificity of Pasteuria species for their nematode hosts.

B ased on the information submitted, adverse effects to freshwater and marine/estuarine fish, invertebrates, and plants are not expected as a result of exposure to proposed pes ticidal applications of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3

.

2. Environmental Fate Data

As t he data and information provided are sufficient to fulfill the Tier I nontarget organism data requirements and allow for nontarget organi sm risk asse ssment for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , f urther testing at higher tier levels (i.e., Tiers II, III, and IV) is not required.

3

. Threatened and Endangered Species Assessment

Since EPA has determined that no effe cts are ant icipated for any non target species exposed to

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 as a result of the proposed applications, effects to federally listed threatened and endangered species and their designated

critical ha bitats are also not expected. Therefore, a “No Effect” determination is made for direct and indirect effects to listed species and their designated critical habitats resulting from the

3 Pasteuria ramosa is already recognized as parasitizing water fleas and is not considered an “unanticipated” report

.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 17 of 33 Biopesticides Registration Action Document

proposed pesticidal uses of Pasteuria spp. ( Rotylenchulus reniformis nematode )

– Pr3 , as labeled.

V. ENVIRONMENTAL JUSTICE

EPA seeks to achieve environmental justice

— the fair treatment and meaningful involvement of all people regardless of race, color, national origin, or income

— with respect to the development, implementation, 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 fro m industrial, municipal, and commercial operations or the execution of federal, state, local, and tribal environmental programs and policies. Meaningful involvement means that (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 decis ion

- making process; and (4) the decision

- makers seek out and facilitate the involvement of those potentially affected. EPA has this goal for all communities and persons

across the United States.

To help address potential environmental justice issues, dur ing the 30

- day public participation comment period, EPA sought information on any groups or segments of the population who, as a result their location, cultural practices, or other factors, may have atypical, unusually high
exposure to Pasteuria spp. ( Roty lenchulus reniformis nematode)

– Pr3 , compared to the general population. No public comments were received on this particular matter.

For additional information regarding environmental justice issues, please visit EPA’s web site at http://www.epa.gov/compliance/environmentaljustice/index.html

.

V I

. RISK MANAGEMENT DECISION

Section 3(c)(5) of FIFRA permits for the registration of a pesticide provided that all the following det erminations are made:

(1) Its composition is such as to warrant the proposed claims for it; (2) Its labeling and other material required to be submitted comply with the requirements of FIFRA; (3) It will perform its intended function without unr easonable adverse effects on the environment; AND (4) When used in accordance with widespread and commonly recognized practice, it will not generally cause unreasonable adverse effects on the

environment.

To satisfy criterion 1, the P asteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 pesticide products have well

- known properties. EPA has no knowledge that would contradict the claims

made on the NAVIVA Tech, NAVIVA ST, and NAVIVA LF label s, and such pesticide products

are not expec ted to cause unreasonable adverse effects on the environment when used accordingPasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 18 of 33 Biopesticides Registration Action Document

to the ir respective label instructions. Criterion 2 is satisfied by the current product label s, as well

as the data and information presented in this document. It is believed that the Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 pesticide products will not cause any unreasonable

adverse effects on the environment, and NAVIVA ST and NAVIVA LF ( end

- use pesticide product s ) , in particular, are likel y to p rovide protecti on against reniform nematode as claimed, satisfying criterion 3. Criterion 4 is satisfied in that the Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 pesticide products are not expected to cause unreasonable adverse effects when used according to label instructions. Therefore, NAVIVA Tech

, NAVIVA ST , an d NAVIVA LF

, containing Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 as a new active ingredient,

are eligible for registration under FIFRA section 3(c)(5) for the labeled uses.

V I I

. A CTIONS REQUIRED OF THE REGISTRANT

A. Final Printed Labeling

Before releasing pesticide products containing Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 for shipment, the registrant is required to provide appropriate final printed labeling to EPA

.

B. Terms of Registration

As terms of the NAVIVA Tech, NAVIVA ST, and NAVIVA LF registrations, Pasteuria Bioscience, Inc. must submit additional information (confirmatory) on the discussion of unintentional ingredients (Harmonized Guideline 885.130 0) within six months of registration.

Additionally, as a term of the NAVIVA LF registration, Pasteuria Bioscience, Inc. must submit an analysis of samples (Harmonized Guideline 885.1400) for four additional batches.

C. Reporting of Adverse Effects and H ypersensitivity Incidents

Notwithstanding the information stated in the previous sections, it should be clearly understood

that certain specific data are required to be reported to EPA as a requirement for maintaining the federal registration for a pestic ide 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 EPA under the provisions stated in FIFRA section 6(a)(2). Additionally, all incidents of hypersens itivity (including both suspected and confirmed incidents) must be reported to EPA under the provisions of 40 CFR § 158.2140(d).Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 19 of 33 Biopesticides Registration Action Document

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

BRAD Biopesticides Registration Action Document

CFR Code of Federal Regul ations

cSt centistokes

EDSP Endocrine Disruptor Screening Program

EP end

- use pesticide product

EPA United States Environmental Protection Agency (the “Agency”)

FFDCA Federal Food, Drug, and Cosmetic Act

FIFRA Federal Insecticide, Fungicide, and Rodenticid e Act

FR Federal Register g/mL grams per milliliter lb/gal pounds per gallon

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

MP manufacturing

- use pesticide product

MRID No. Master Record Identification Number

NIOSH National Institute for Occupat ional Safety and Health

OPP Office of Pesticide Programs

PC Code Pesticide Chemical Code

PP Pesticide Petition

PPE personal protective equipment

TGAI technical grade of the active ingredient

U.S. United StatesPasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 20 of 33 Biopesticides Registration Action Document

I X. BIBLIOGRAPHY

A. Studies Submitted to Support the Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Pesticide Product Registrations

MRID No. Study Information

48 1 460

- 01 MacIntosh S, Smith K . 2010. Product Id entity: Pasteuria reniformis

– PR3

. Project Number: PBI/2010/008 . Unpublished study prepared by MacIntosh & Associates, Inc. an d Pasteuria Bioscience, Inc., 51 pages.

481460

- 02 Smith K. 2010. Manufacturing Process for Pasteuria reniformis

– PR3 . Project

Number: PBI/2010/009 . Unpublished study prepared by Pasteuria Bioscience, Inc., 36 pages.

481460

- 03 MacIntosh S. 2010. Discussion of the Formation of Unintentional Ingredients:

Pasteuria reniformis

– PR3. Project Number: 14059 /10 . Unpublished study prepared by MacIntosh & Associates, Inc., 29 pages.

481460

- 04 Smith K. 2010. Analysis of Samples/Enforcement Methods for Pasteuria reniformis

– PR3 . Unpublished study prepared b y Pasteuria Bioscience, Inc., 69

pages.

4 81460

- 05 Smith K. 2010. Certification of Limits for Pasteuria reniformis

– PR3 . Project

Number: PBI/2010/010 . Unpublished study prepared by Pasteuria Bioscience, Inc., 8 pages.

481460

- 06 Kaminsky M. 2010. Pasteuria reniformis

– PR3 Product Che mistry: Final Report. Project Number: 13888 /10. Unpublished study prepared by Stillmeadow, Inc., 16

pages.

481460

- 07 Smith K. 2010. Product Stability to Elevated Temperatures: Pasteuria reniformis

– PR3 . Project Number: PBI/115/53 . Unpubli shed study prepared by Pasteuria Bioscience, Inc., 8 pages.

481460

- 08 Smith K. 2010. Storage Stability & Corrosion Characteristics for Pasteuria reniformis

– PR3. Project Number: 13884/10, PBI/2010/001 . Unpublished study prepared by Pasteu ria Bioscience, Inc., 16 pages.

481460

- 09 Gingras B. 2010. Toxicity/Pathogenicity Testing of Pasteuria reniformis

– PR3 Following Acute Oral Challenge in Rats (Final Report) . Project Number: 2262/SN1, 2262

. Unpublished study prepar ed by IIT Res earch Institute, 59 pages.

481460

- 10 Gingras B. 2010. Toxicity/Pathogenicity Testing of Pasteuria reniformis

– PR3 Following Acute Intratracheal Chall enge in Rats ( Final Report ) . Project Number: 2262/SN2, 2262 . Unpublished study prepar ed by IIT Research Institute, 55 pages.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 21 of 33 Biopesticides Registration Action Document

MRID No. Study Information

481460

- 11 Gingras B. 2010. Toxicity/Pathogenicity Testing of Pasteuria reniformis

– PR3 Following Acute Injection Challenge i n Rats. Project Num ber: 2262/SN3, 2262

. Unpublished study prepar ed by IIT Research Institute, 57 pages.

481460

- 12 MacIntosh S. 2010. Hypersensitivity Incidents: Pasteuria reniformis

– PR3

. Project Number: PBI/2010/013 . Unpublished study prepared by MacIntosh & Associates, Inc., 6 pages.

481460

- 13 Sullivan D. 2010. Acute Oral Toxicity Study of Pasteuria reniformis

– PR3 in Rats. Project Number: 2262, 2262/SN7 . Unpublished study prepared by IIT

Research Institute, 28 pages.

481460

- 14 Sullivan D. 2 010. Acute Dermal Toxicity Study of Pasteuria reniformis

– PR3 in Rabbits. Project Number: 2262, 2262/SN8 . Unpublished study prepared by IIT Research Institute, 30 pages.

481460

- 15 Sullivan D. 2010. Acute Eye Irritation Study of Pasteuria renif ormis

– PR3 in

Rabbits. P roject Number: 2262, 2262/SN9 . Unpublished study prepared by IIT Research Institute, 25 pages.

481460

- 16 Sullivan D. 2010. Acute Dermal Irritation Study of Pasteuria reniformis

– PR3 in Rabbits. Project Number: 226 2, 2262/SN10 . Unpublished study prepared by IIT Research Institute, 25 pages.

481460

- 17 MacIntosh S, Smith K, Hewlett T. 2010. Request for Waiver from the Requirement to Conduct Guideline Studies (Avian Oral Toxicity, Freshwater Fish

Toxic ity/Pathogenicity, Freshwater Invertebrate Toxicity/Pathogenicity, Non

Target Insect Testing, and Honey Bee Testing) for Pasteuria reniformis

– PR3

. Project Number: PBI/2010/012 . Unpublished study prepared by Pasteuria

Bioscience , Inc., 29 p ages.

482061

- 01 MacIntosh S, Smith K. 2010. Product Identity and Manufacturing Process:

Pasteuria reniformis

– PR3 (Liquid Formulation; End Product). Project Number:

PBI/2010/ 015 . Unpublished study prepared by Pasteuria Bioscience, Inc. and MacIntosh & Associates, Inc., 17 pages.

482061

- 02 MacIntosh S. 2010. Discussion of Formation of Unintentional Ingredients:

Pasteuria reniformis

– PR3 (Liquid Formulation; End Product). Unpublished study prepared by MacIntosh & Associates, In c., 6 pages.

482061

- 03 Smith K. 2010. Analysis of Samples/Enforcement Methods for Pasteuria reniformis

– PR3 (Liquid Formulation; End Product). Unpublished study prepared by Pasteuria Bioscience, Inc., 20 pages.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 22 of 33 Biopesticides Registration Action Document

MRID No. Study Information

482061

- 04 Smith K. 2010. Certification of Limits for Pasteuria reniformis

– PR3 (Liquid Formulation; End Product). Project Number: PBI/201 0/017 . Unpublished study prepared by Pasteuria Bioscience, Inc. , 8 pages.

482061

- 05 Kaminsky M. 2010. Pasteuria reniformis

– Liquid Formulation: Product Chemistry

– Fin al Report. Project Number: 14078 /10. Unpublished study prepared by Stil lmeadow, Inc., 9 pages.

482061

- 06 Smith K. 2010. Storage Stability : Interim Report Pasteuria reniformis

– PR3 (Liquid Formulation; End Produc t). Project Number: PBI/2010/018 . Unpublished study prepared by Pasteuria Bioscience, Inc., 8 pages.

4 82061

- 07 Smith K. 2010. Corrosion Characteristics for Pasteuria ren iformis

– PR3 (Liquid Formulation; End Product). Project Number: 13884/10 . Unpublished study prepared by Stillmeadow , Inc., 11 pages.

482061

- 08 MacIntosh S. 2010. Hypersensitivity Incidents: Pasteuria reniformis

– PR3 (Liquid Formulation; End Produc t). Project Number: PBI/2010/019 . Unpublished study prepared by MacIntosh & Associates, Inc., 6 pages.

482061

- 09 Sullivan D. 2010. Acute Oral Toxicity Study of Pasteuria reniformis

– PR3 (End Product) in Rats. Project Number: 2262/SN1 5. Unpublished study prepared by IIT Research Institute, 28 pages.

482061

- 10 Sullivan D. 2010. Acute Dermal Toxicity Study of Pasteuria reniformis

– PR3 (End Product) in Ra bbits. Project Number: 2262/SN16, 2262, 16 . Unpublished

s tudy prepa red by IIT Research Institute, 28 pages.

482061

- 11 Sullivan D. 2010. Acute Eye Irritation Study of Pasteuria reniformis

– PR3 (End Product) in Rabbits. Project Number: 2262, 17, 2262/SN17 . Unpublished study prepared by IIT Research Institute, 2 2 pages.

482061

- 12 Sullivan D. 2010. Acute Dermal Irritation Study of Pasteuria reniformis

– PR3 (End Product) in Rabbits. Project Number: 2262, 18, 2262/SN17 . Unpublished

s tudy prepared by IIT Research Institute, 22 pages.

482744

- 01 Kaminsky M. 2010. Pasteuria reniformis

– Pr3 and Pasteuria reniformis

– Seed Treatment: Product Chemistry

– Fin al Report. Project Number: 14450 /10. Unpublished study prepared by Stillmeadow, Inc., 10 pages.

482744

- 03 MacIntosh S. 2010. Request for Waiv ers from the Requirement to Conduct Toxicology Guideline Study: Acute Inhalation Toxicity for Pasteuria reniformis

– Pr3 & Pasteuria reniformis

– Seed Treatme nt. Project Number: PBI/2010/025

. Unpublished study prepared by MacIntosh & Associa tes, Inc., 7 pages.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 23 of 33 Biopesticides Registration Action Document

MRID No. Study Information

482744

- 04 MacIntosh S. 2010. Request for Waivers from the Requirement to Conduct Toxicology Guideline Study: Acute Inhalation Toxicity for Pasteuria renifo rmis

– Liquid Formulati on. Project Number: PBI/2010/026 . Unpublished study prepared by MacIntosh & Associates, Inc., 7 pages.

485990

- 01 MacIntosh S, Smith K. 2011. Product Identity

– Pasteuria spp. ( Rotylenchulus reniformis nematode)(Su pplement to MRID No. 481460

- 01). Unpublished study prepared by Pasteuria Bioscience, Inc. and MacIntosh & Associates, Inc., 2 0

pages.

486056

- 01 Smith K. 2011. Storage Stability Pasteuria spp. ( Rotylenchulus reniformis ) : Supplement to MRID No. 481460

- 08

– Final Report. Project Number:

P BI/2010/001 . Unpublished study prepared by Pasteuria Bioscience, Inc., 8 pages.

486056

- 02 Kaminsky M

. 2011. Pasteuria reniformis

– PR3 Corrosion Characteristics : Final Report. Project Number: 13889 /10. Unpublished study prepared by Stillmeadow

, Inc., 10 pages.

486057

- 01 Smith K. 2011. Storage Stability Pasteuria spp. ( Rotylenchulus reniformis )(Liquid Formulation; EP): Supplement to MRID No. 482061

- 06

– Final Report. Project Number: PBI/2010/018. Unpublished study prepared by Pasteuria Bioscience, Inc., 8 pages.

486057

- 02 Kaminsky M. 2011. Pasteuria reniformis

– Liquid Formulation Corrosion Characteristics: Final Report. Project Number: 13884/10. Unpublished study

pre pared by Stillmeadow, Inc., 11 pages.

B. Environmental Protection Agency Risk Assessment Memoranda

U.S. EPA. 2011a. Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 . Memorandum from J.V. Gagliardi , Ph.D. and J.L. Kough, Ph.D. to J. Kausch dated March 2 , 201 2

.

U.S. EPA. 2011b. Environmental Risk Assessment of Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 (PC 016456 ) for a Section 3 Registration of the Technical Product (EPA File Symbol 85004

- U ) and Two End Use Pr oducts (EPA File Symbol s 85004

- L and

85004

- I) for Control of the Reniform Nematode . Memorandum from S. Borges to J. Kausch dated March 26, 2012

.

C. Other References

Aislabie J, Smith JJ, Fraser R, McLeod M. 2001. Leaching of bacterial indicators of faecal

contamination thr ough four New Zealand soils. Australian Journal of Soil Research

39:1397

– 1406.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 24 of 33 Biopesticides Registration Action Document

Atibalentja N, Jakstys BP, Noel GR. 2004. Life cycle, ultrastructure, and host specificity of the

North American isolate of Pasteuria that parasitizes the soybean cyst ne matode, Heterodera glycines

. Journal of Nematology 36:171

– 180.

Centers for Disease Control and Prevention. 2009. Drinking Water

- Water Treatment. Available

from http:// www.cdc.gov/healthywater/drinking/public/water_treatment.html

.

Cetintas R, Dickson DW. 2004. Persistence and suppressiveness of Pasteuria penetrans to Meloidogyne arenaria Race 1. Journal of Nematology 36:540

– 549.

Chen ZX, Dickson DW. 1998. Review of P asteuria penetrans : biology, ecology, and biological control potential. Journal of Nematology 30:313

– 340.

Ciancio A, Bonsignore R, Vovlas N, Lamberti F. 1994. Host records and spore morphometrics of Pasteuria penetrans group parasites of nematodes. Jour nal of Invertebrate Pathology

63:260

– 267.

DeFelice K, Wollenhaupt N, Buchholz D. 1993. Aquifers and Soil Filter Effect. Available from http://extension.missouri.edu/p/WQ24

.

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 serie s B . 351:1689

– 1701.

Noel GR . 2008. IPM of soybean cyst nematode in the USA. In : Integrated Management and Biocontrol of Vegetable and Grain Crops Nematodes. Eds. A. Cianio and K.G. Mukerji. Springer. Pages 119

– 126.

Pang L, M cLeod M, Aislabie J, Šim ůnek J, Close M, Hector R. 2008. Modeling transport of microbes in ten undisturbed soils under effluent irrigation. Vadose Zone Journal 7:97

– 111.

Sayre RM, Wergin WP, Schmidt JM, Starr MP. 1991. Pasteuria nishizawae sp. nov., a mycelial and endospore

- form ing bacterium parasitic on cyst nematodes of genera Heterodera and

Globodera

. Research in Microbiology 14:551

– 564.

Sayre RM, Starr MP. 1985. Pasteuria penetrans (ex Thorne, 1940) nom. rev., comb. n., sp. n., a mycelial and endospore

- forming bacterium p arasitic in plant

- parasitic nematodes. Proceedings of the Helminthological Society of Washington 52:149

– 165.

Sturhan D. 1988. New host and geographical records of nematode

- parasitic bacteria of the Pasteuria penetrans group. Nematologica 34:350

– 356.

T ain B, Yang J, Zhang K

- Q. 2007. Bacteria used in the biological control of plant

- parasitic nematodes: populations, mechanisms of action, and future prospects. FEMS Microbiology Ecology 61:197

– 213.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 25 of 33 Biopesticides Registration Action Document

U.S. EPA. 2004. Primer for Municipal Wastewater Treatmen t Systems. EPA 832

- R

- 04

- 001.

Available from http://www.epa.gov/npdes/pubs/primer.pdf

.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 26 of 33 Biopesticides Registration Action Document

A PPENDIX A. MICROBIAL PESTICIDES DATA REQUIREMENTS (40 CFR PA RT 158

– SUBPART V )

TABLE 1. Product Analysis Data Requirements for the Technical Grade of the Active Ingredient (TGAI)
, Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , and the Manufacturing

- Use Pesticide Product ( MP )
, NAVIVA Tech (40 CFR § 15 8.2 120 )

Harmonized

G uideline

N umber Data Requirement Results

MRID No. Pasteuria spp. ( Rotylenchulus

reniformis nematode)

– Pr3 NAVIVA Tech

885.1100 Product Identity N/A Submitt ed data fulfill the requirement for product identity. NAVIVA Tech

conta ins 99.88 % by weight Pasteuri a spp. ( Rotylenchulus reniformis nematode)

– Pr3 (contains at least 1 x

10 8 spores per gram). 481460

- 01

485990

- 01

885.1200 Manufacturing

Process Submitted data fulfill the requiremen t for manufacturing process

. 481460

- 02

N /A Deposition of a Sample in a Nationally Recognized Culture

Collection Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 is on deposit with the American Type Culture Collection in Manassas, Virginia under Accession Number

SD

- 5834

. N/A 481460

- 01

485 990

- 01

885.1300 Discussion of

Formation of

Unintentional

Ingredients Submitted data fulfill the requiremen t for discussion of formation of unintentional ingredients for purposes of FIFRA section 3(c)(5) registration

. As a term of the NAVIVA Tech registrat ion, EPA is requiring additional information (confirmatory) on this data requirement. 481460

- 03

885.1400 Analysis of S amples Submitted data fulfill the requirement for analysis of samples. 481460

- 04

8 85 .1 50 0 Certification of

L imits N/A Limits listed o n t he confidential

statement of formula are adequate/a cceptable. 481460

- 05Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 27 of 33 Biopesticides Registration Action Document

TABLE 2

. Product Analysis Data Requirements for the End

- Use Pesticide Product ( E P s ), NAVIVA ST and NAVIVA LF (40 CFR § 158.2120)

Harmonized

Guideline

Number Data Requirement Results MRID No.

NAVIVA ST * NAVIVA LF **

885.1100 Product Identity Submitted data fulfill the requirement for product identity. NAVIVA ST

contains 99.88 % by weight

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 (contains at

least 1 x 10 8 spores per gram). Submitted data fulfill the requirement for product identity. NAVIVA LF contains

33.29 00 % by weight Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 ( contains at

least 1.3 x 10 7 spores per gram)

. 481460

- 01*

485990

- 01*

48 2061

- 01**

885.1200 Manufacturing Process Submitted data fulfill the requirement for manufacturing

process. 481460

- 02*

482061

- 01**

N/A Deposition of a Sample in a Nationally Recognized

Culture Collection N/A N/A

885.1300 Discussion of Formation of

Unint entional Ingredients Submitted data fulfill the requiremen t for discussion of formation of unintentional ingredients for purposes of FIFRA section 3(c)(5) registration

. As a terms of the NAVIVA ST and NAVIVA LF registrations, EPA is requiring additional

in formation (confirmatory) on this data requirement. 481460

- 03*

482061

- 02**

885.1400 Analysis of Samples Submitted data fulfill the requirement for analysis of samples

. Submitted data fulfill the requirement for analysis of samples for purposes of

FIFRA sec tion 3(c)(5) registration. As a term of the NAVIVA LF registration, EPA is requiring submission of analysis of samples for

four additional batches. 481460

- 04*

482061

- 03**

885.1500 Certification of Limits Limits listed on the confidential statement of form ula are adequate/acceptable. 481460

- 05 *

482061

- 04**Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 28 of 33 Biopesticides Registration Action Document

TABLE 3

. Physical and Chemical Characteristics for the Technical Grade of the Active Ingredient (TGAI), Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , and the Manufacturing

- Use Pesticide Pro duct (MP), NAVIVA Tech ( 40 CFR § 158.2120)

Harmonized

G uideline N umber Data Requirement Results MRID No.

Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 NAVIVA Tech

830.6302 1 Color Caramel brown, light beige, brownish

- yellow, brown

481460

- 06 830.6303 1 Physical State Liquid

830.6304 1 Odor Like wet dog or dog food

830.6313 1 Stability to Normal and

E levated Temperatures, Metals,

and Metal I ons After 14 days at 54°C, viability was reduced by 25%. 481460

- 07

830.6317 Storage Stability St abl e at least 12 months when stored at 4°C

. 481460

- 08

48 6056

- 0 1

830.6319 Miscibility N/A Not required because

NAVIVA Tech is not an

e mulsifiable liquid form of a microbial pesticide (refer to test note #2 of 40 CFR § 158.2120(d)). N/A

830.6320 Corrosion

Ch aracteristics N/A Stable at least one year at 20°C in packaging. 481 460

- 08

486056

- 0 2

830.7000 1 pH 5.03

– 5. 14 481460

- 06

830.7100 Viscosity N/A 1.48 cSt (20°C)

1.02 cSt (40°C) 482744

- 0 1

830.7300 1 Density/Relative Density/Bulk Density

(Specific Gravity) 1.0 4 g/ mL 481 460

- 06

1 According to 40 CFR § 158.2120, these data are only required for the technical grade of the active ingredient. Since Pasteuria

Bioscience

, Inc. included this informati on with its application for NAVIVA Tech , it is summarized appropri ately in this table.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 29 of 33 Biopesticides Registration Action Document

TABLE 4. Physical and Chemical Characteristics for the End

- Use Pesticide Product s (EP s ), NAVIVA ST and NAVIVA LF (40 CFR § 158.2120)

Harmonized

Guideline Number Data Requirement Results MRID No.

NAVIVA ST * NAVIVA LF **

830.6302 1 Color Caramel brown, light beige, brownish

- yellow,

brown N/A 481460

- 06

830.6303 1 Physical State Liquid 481460

- 06*

482061

- 05**

830.6304 1 Odor Like wet dog or dog food N/A 481 460

- 06

830.6313 1 Stability to Normal and Elevated Temper atures, Metals, and Metal Ions After 14 days at 54°C, viability was reduced by

25%. N/A 481460

- 07

830.6317 Storage Stability St able at least 12 months when stored at 4°C. 481460

- 08*

486056

- 01*

482061

- 06**

486057

- 01**

830.6319 Miscibility Not required bec ause the end

- use pesticide products,

NAVIVA ST and NAVIVA LF , are not emulsifiable liquid forms of microbial pesticides (refer to test note #2 of 40 CFR § 158.2120(d)). N/A

830.6320 Corrosion Characteristics Stable at least one year at 20°C in packaging. Stable at least one year at 4°C in packaging. 481460

- 08*

486056

- 02*

482061

- 07**

486057

- 02**

830.7000 pH 5.03

– 5.14 1 3.5

– 4.5 2 481 460

- 06 *

830.7100 Viscosity 1.48 cSt (20°C) 1.02 cSt (40°C) 363.88 cSt (20°C) 253.62 cSt (40°C) 482744

- 01*

482061

- 05**

830.7300 Density/Relative Density/Bulk Density

(Specific Gravity) 1.04 g/mL 1 8.5 lb/gal 2 481 460

- 06 *

1 According to 40 CFR § 158.2120, these data are only required for the technical grade of the active ingredient. Since Pasteuri a

Bioscience, Inc. included this information with its applications for NAVIVA ST and/or NAVIVA LF , it is summarized appropriately in this table.

2 Obtained from the confidential statement of formula for the end

- use pesticide product.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 30 of 33 Biopesticides Registration Action Document

T ABLE 5

. Toxicology Data Requirements for the Techn ical Grade of the Active Ingredient (TGAI)
, Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , and the Manufacturing

- Use Pesticide Product (MP)
, NAVIVA Tech (40 CFR § 158.2140)

Harmonized

Guideline

N umber Data Requirement Results MRID N o.

Pasteu ria spp. ( Rotylenchulus

reniformis nematode)

– Pr3 NAVIVA Tech

Tier I

885.3050 Acute Oral Toxicity/Pathogenicity Not toxic and/or pathogenic to rats
when administered by oral gavage in a single dose of 1.5 x 10 9 spores per animal.

Classification: Suppl emental N/A 481 460

- 09

885.3150 Acute Pulmonary Toxicity/Pathogenicity Not toxic and/or pathogenic to rats when administered by intratracheal instillation in a single dose of 1.5 x 10 8
spores per animal.

Classification: Supplemental N/A 481 460

- 10

885.3200 Acute Injection Toxicity/Pathogenicity (Intra venous ) N ot toxic and/or pathogenic to rats
when administered intravenously in a single dose of 1.0 x 10 7 spores per animal

. Classification: Supplemental N/A 481 460

- 11

885.3400 Hypersensitivity

Incidents The applicant reported that n o hypersensitivity incidents, including

immediate

- type or delayed

- type reactions of humans and domestic animals

, occurred durin g research, development, or testing of the TGAI or MP

. Any future hypersensitivity incidents must be rep orted to EPA (refer to test note #3 of 40 CFR § 158.2140(d))

. 481 460

- 12

885.3500 Cell Culture Not required because Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 is not a virus (refer to test note #4 of 40 CFR § 158.2140(d)). N/A N/A

870.1100 Acute Oral Toxicity N/A Oral LD 50 combined (male and female rats) > 5,000 mg/kg Classification: Acceptable

TOXICITY CATEGORY I V 481 460

- 13

870.1200 Acute Dermal Toxicity N/A Dermal LD 50 combined (male and female rabbits) > 2,000 mg/kg

Classification: Accep table

TOXICITY CATEGORY I II 481 460

- 14

870.1300 Acute Inhalation Toxicity N/A Waived based on the results of

MRID No

. 481460

- 10 and

because this formulation contains inert ingredients that are not expected to be of toxicological

conce rn (refer to test note #5 of 40 CFR § 158.2140(d)). Classification: Acceptable

TOXICITY CATEGORY III 482744

- 0 3

870.2400 Acute Eye Irritation N/A NAVIVA Tech was practically

non

- irritating to the eyes of

rabbits. Classification: Acceptable

TOXICITY CATEGORY I II 481 460

- 15

870.2 500 Primary Dermal

Irritation N/A NAVIVA Tech was essentially

non

- irritating to the skin of

rabbits. Classification: Acceptable

TOXICITY CATEGORY I V 481460

- 16Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 31 of 33 Biopesticides Registration Action Document

T ABLE 5

. Toxicology Data Requirements for the Techn ical Grade of the Active Ingredient (TGAI)
, Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 , and the Manufacturing

- Use Pesticide Product (MP)
, NAVIVA Tech (40 CFR § 158.2140)

Harmonized

Guideline

N umber Data Requirement Results MRID N o.

Pasteu ria spp. ( Rotylenchulus

reniformis nematode)

– Pr3 NAVIVA Tech

Tiers II and III Not required for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3, bas ed on the lack of acute toxicity/pathogenicity in the Tier I

studies.

TABLE 6

. Toxicology Data Requirements for the End

- Use Pesticide Product s (EPs)
, NAVIVA ST and NAVIVA LF (40 CFR § 158.2140)

Harmonized

Guideline

Number Data Requirement Results MRI D No.

NAVIVA ST * NAVIVA LF **

885.3050 Acute Oral Toxicity/Pathogenicity N/A N/A

885.3150 Acute Pulmonary Toxicity/Pathogenicity N/A N/A

885.3200 Acute Injection Toxicity/Pathogenicity N/A N/A

885.3400 Hypersensitivity

Incidents The applicant report ed than n o hypersensitivity incidents, including

immediate

- type or delayed

- type reactions of humans and domestic animals

, occurred during research, development, or testing of the EP s

. Any future hypersensitivity incidents must be reported to EPA (refer to test note #3 of 40 CFR § 158.2140(d)). 481460

- 12 *

482 061

- 08**

885.3500 Cell Culture N/A N/A

870.1100 Acute Oral Toxicity Oral LD 50 combined (male and female rats) > 5,000 mg/kg Classification: Acceptable

TOXICITY CATEGORY I V 481460

- 13 *

482 061

- 09**

870.1 200 Acute Dermal Toxicity Dermal LD 50 combined (male and female rabbits) > 2,000 mg/kg Classification: Acceptable

TOXICITY CATEGORY I II 481 460

- 14*

482061

- 10**

870.1300 Acute Inhalation Toxicity Waived based on the results of MRID No

. 481460

- 10 and because this formulation contains inert ingredients that are not expected to be of toxicological conce rn (refer to test note #5 of 40 CFR § 158.2140(d)). Classification: Acceptable

TOXICITY CATEGORY III 482744

- 03 *

482744

- 04 **

870.2400 Acute Eye Irritation NAVIVA ST was practically non

irritating to the eyes of rabbits.

Classification: Acceptable

TOXICITY CATEGORY I II NAVIVA LF was essentially non

irritating to the eyes of rabbits.

Classification: Acceptable

TOXICITY CATEGORY IV 481460

- 15*

482061

- 11**

870.2500 Pr imary Dermal

Irritation The EP test substances were essentially non

- irritating to the skin of rabbits. Classification: Acceptable

TOXICITY CATEGORY I V 481 460

- 16*

482061

- 12**Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 32 of 33 Biopesticides Registration Action Document

TABLE 7

. Nontarget Organism Toxicity and Environmental Fate Data Requir ements for the Technical Grade of the Active Ingredient (TGAI), Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 (40 CFR § 158.2150)

Harmonized Guideline

Number Data Requirement Results MRID No.

Tier I

885.4050 Avian Oral Toxicity Data and other information provide sufficient

information to determine that toxicity/pathogenicity to avian wildlife is not expected as a result of the proposed pesticidal

uses. Classification: Acceptable 481460

- 17

885.4100 Avian Inhalation Toxicity/Pathogenicity Not r equired 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)). N/A

885.4150 Wild Mammal Toxicity/Pathogenicity Tests required by 40 CFR § 158.2140 are adequate and appropriate for assessment of

hazards to wild mammals. Studies submitted with laboratory rats indicate no adverse effects due to oral exposure. Classification: Acceptable for wild mammal

risk assessment N/A

885.4200 F reshwater Fish Toxicity/Pathogenicity Data and other information provide sufficient

information to determine that toxicity/pathogenicity to freshwater fish and invertebrates is not expected as a result of the proposed pesticidal uses. Classification: Accep table 481460

- 17

885.4240 Freshwater Invertebrate Toxicity/Pathogenicity

885.4280 Estuarine/Marine Fish and Invertebrate Testing Not required as the microbial pesticide will not be applied directly to water and is not expected to

enter marine/estuarine environments in amounts that would result in significant concentrations (refer to test note #6 of 40 CFR § 158.2150(e)). N/A

885.4300 Nontarget Plant Testing Not required as the microbial pesticide is not taxonomically related to any known plant pathogens (refer to test note #7 of 40 CFR § 158.2150(e)). N/A

885.4340 Nontarget Insect Testing Data and other information provide sufficient

information to determine that toxicity/pathogenicity to honey bees and nontarget insects is not expected as a result of t he proposed pesticidal uses. Classification: Acceptable 481460

- 17

885.4380 Honey Bee Testing

Tiers II, III, and IV Not required for Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3, based on the acceptability of the data and other information provided for Tier I

.Pasteuria spp. ( Rotylenchulus reniformis nematode)

– Pr3 Page 33 of 33 Biopesticides Registration Action Document

APPENDIX B. PESTICIDE PRODUCTS

EPA Registration

Number Registration

Name Percentage

Active Ingredient Formulatio n Type Use Site(s) Method(s) of Application Application Rate (s) Target Pest

85004

- 4 NAVIVA

Tech 99.88% Technic al N/A N/A N/A N/A

85004

- 5 NAVIVA

ST 99.88%

End Use

– Liquid Various

food and

nonfood

crops Seed Treatment (Preplant or Commercial) 2.4

– 243 fluid ounces of NAVIVA ST per 100 pounds of seed

Reniform nematode ( Rotylenchulus

reniformis )

85004

- 8 NAVIVA

LF 3 3.29 00 % Ground application equipment or chemigation 0.13

– 6.4 fluid ounces of NAVIVA LF per 100 square feet of crop area