## T ABLE OF 

## C ONTENTS

I. PRELIMINARY WORK PLAN ..................................................................................................... .......... 4

A. Statutory and Regulatory Authority ........................................................................................ .......... 5

B. Background ................................................................................................................ ...................... 5

1. Regulatory History ........................................................................................................ ............... 6 2. Registered Products ....................................................................................................... ............. 6

3. Mode of Action ............................................................................................................ ................. 6

4. Use Profile ............................................................................................................... .................... 7

5. Tolerance Actions ......................................................................................................... ............... 7

C. Anticipated Data Needs and Risk Assessments .............................................................................. 7

1. Product Analysis: 40 CFR 158.2120......................................................................................... .. 7 2. Toxicology: 40 CFR 158.2140 .............................................................................................. ...... 8 3. Nontarget Organisms and Environmental Fate: 40 CFR 158.2150 ............................................ 9

D. Risk to Threatened and Endangered Species ............................................................................... 1 0

E. Endocrine Disruptor Screening Program ..................................................................................... .. 10

F. Literature Review ......................................................................................................... .................. 11

G. Incidents ................................................................................................................. ....................... 11

H. Summary of Anticipated Data Needs ............................................................................................. 11

I. Next Steps and Timeline ............................................................................................................... 12

II. BIBLIOGRAPHY ............................................................................................................. ................... 13

APPENDIX: Guidance for Commenters ................................................................................................ 18

Environmental Justice ......................................................................................................... .............. 18 Water Quality ................................................................................................................. ................... 18

Trade Irritants

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

Additional Information ........................................................................................................ ............... 18



### Tables

Table 1 Pesticide Product Containing the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato ................................................................................... 6

Table 2 Product Analysis Data Requirements and How They Are Met ................................................ 8

Table 3 Human Health Toxicology Data Re quirements and How They Are Met ................................ 9

Table 4 Ecological Toxicity Data Requirements and How They Are Met ............................................. 9

Table 5 Anticipated Data Needs for Cases 6509 and 6510— the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato ......................................................... 11

Table 6 EPA’s Estimated Timeline for Completing the Registration Review of the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato .............................. 12

## A CRONYMS AND 

## A BBREVIATIONS

BRAD Biopesticides Registration Action Document

CFR Code of Federal Regulations

DCI Data Call-in

EDSP Endocrine Disruptor Screening Program

EPA U.S. Environmental Protection Agency, or the Agency

ESA Endangered Species Assessment

EU European Union

EUP Experimental Use Permit

FFDCA Federal Food, Drug, and Cosmetic Act

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FQPA Food Quality Protection Act

FR Federal Register

FWP Final Work Plan

IDS Incident Data System

MRID Master Record Identification Number

MRL’s Maximum Residue Limits

NA Not applicable

OPP Office of Pesticide Programs

OPPIN Office of Pesticide Programs Information Network

P. Pseudomonas

PMRA Health Canada’s Pest Management Regulatory Agency

pv. pathovar

PWP Preliminary Work Plan

TMDL’s Total Maximum Daily Loads

X. XanthomonasI. PRELIMINARY WORK PLAN

This document concerns the Registration Review of two Cases: (1) Case 6509—Bacteriophage active against Xanthomonas campestris pv . vesicatoria (the bacterium that causes bacterial speck), and (2) Case 6510—Bacteriophage active against Pseudomonas syringae pv. tomato (the bacterium that causes bacterial spot). The U.S. Envir onmental Protection Agency (EPA or the Agency) is combining the Registration Review of these two Cases because they share a common tolerance exemption (40 CFR 180.1261) and, neither ingredient has its own EPA registration (the single EPA registration contains both active ingredients).

Case Name: Bacteriophage active against X. campestris pv. vesicatoria , and Bacteriophage active against P. syringae pv. tomato

Case No : 6509 and 6510 (respectively)

PC Codes: 006449 and 006521 (respectively)

EPA Reg. No : 67986-1

Docket: EPA-HQ-OPP-2015-0702

Registrant: OmniLyticsTM, Inc.

The docket for the bacteriophage active against X. campestris pv. vesicatoria and the bacteriophage active against P. syringae pv. tomato is now open, initiating the first public comment period for Registration Review Cases 6509 and 6510. This Preliminary Work Plan (PWP) document explains what EPA’s Office of Pesticide Program s (OPP) knows about the bacteriophage active against X. campestris pv. vesicatoria and the bacteriophage active against P. syringae pv. tomato , highlighting anticipated data and assessment needs, identifying types of information that would be especially useful to EPA in conducting the review, and providing an antic ipated timeline for completing review of these active ingredients.

The Registration Review process was designed to include a public participation component to solicit input from interested stakeholders. By shar ing this information in the docket, EPA intends to inform the public of what it knows about the bacteriophage active against X. campestris pv. vesicatoria and the bacteriophage active against P. syringae pv. tomato , and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on this active ingredient. EPA encourages all interested stakeholder s to review the PWP and to provide comments and additional information that will help EPA’s decision- making process for this pesticide. In addition to general areas on which persons may wish to comment, there are some areas identified in the PWP about which EPA specifically seeks comments and information. Interested stakeholders could include the following: environmental, nonprofit, or interest groups; pesticide manufacturers; agricultural labor or commodity groups; commercial, institutional, residential, and other users of pesticides; or the public-at-large.

The PWP begins by discussing the statutory and regulatory authority for Registration Review. Next, it provides background on the bacteriophage active against X. campestris pv. vesicatoria and the bacteriophage active against P. syringae pv. tomato including currently registered pesticide products; a description of the mode of action; application rates and methods; use sites; and tolerance exemption information. Then, it lists the anticipated data ne eds and risk assessments and a projected Registration Review timeline for the bacteriophage active against X. campestris pv. vesicatoria and the bacteriophage active against P. syringae pv. tomato . Finally, the PWP describes guidance for commenters; explains the next steps EPA will take for this Registration Review; summarizes background information for this Registration Re view; and lists supporting studies, risk assessment memoranda, and other documents.EPA-HQ-OPP-2015-0702 (Bacteriophages) www.regulations.gov

5 Further information about this case, including background and supporting documents, is available at http://www.regulations.gov (under “SEAR CH for: Rules, Comments, Adjudications or Supporting Documents,” enter the docket identification number, which is indicated above).

A. Statutory and Regulatory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a Registration Review program. All pesticides distributed or sold in the United States must generally be registered by EPA, based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on the product labeling. 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, EPA periodica lly reevaluates pesticides to make sure that, as change occurs, products in the marketplace can continue to be used safely. Information on this program is provided on EPA’s website.

EPA is implementing the Registration Review program pursuant to Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) section 3(g) and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing Registration Review begin at 40 CFR 155.40. EPA will consider benefits information and data as required by FIFRA. The public phase of Registration Review begins when the initial docket is opened for each case. The docket is EPA’ s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a Registration Review decision. After reviewing and responding to comments and data received in the docket during this initial comment period, EPA will develop a Final Work Plan (FWP) and anticipated schedule for the Registration Review for the bacteriophage active against X. campestris pv. vesicatoria and the bacteriophage active against P. syringae pv. tomato

.

B. Background

For ease-of-readabilty, the remainder of this document refers to the term “the bacteriophage active against Xanthomonas campestris pv. vesicatoria and the bacteriophage active against Pseudomonas syringae pv. tomato ” as “the bacteriophages active against X. campestris pv. vesicatoria

and P. syringae pv. tomato .”

A bacteriophage is a virus 1 that uses specific bacteria as its host cell (i.e., they are host-specific). Bacteriophages are ubiquitous in nature and are found in soil, food, and water. They are typically named based on the host bacteria and the pathovar (pv.), where the phrase, “the bacteriophage active against” precedes the name of the host bacteria and pathovar. The term “pv. (pathovar)” refers to a strain or set of strains with the same or similar characteristics...: however, unlike a strain, a pathovar is host-specific—it has a “distinctive pathogenicity to one or more plant hosts.” (ISPP 2001)

1 Viruses need a host cell to replicate, they cannot do it on their own. Viruses that use bacteria as its host are called bacter iophages.EPA-HQ-OPP-2015-0702 (Bacteriophages) www.regulations.gov

6 AgriPhageTM is manufactured by OmniLyticsTM, In c. Prior to 2005, the company referred to itself as AgriPhi or OmniLy ticsTM, two synonymous company nam es. By 2005, it had begun to use OmniLyticsTM as its sole company name (IR-4 2005) . AgriPhageTM is a pesticide product containing a mixture of the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato

. It is registered for use on peppers and tomatoes, against two bacterial diseases that are endemic to these crops—bacterial spot and bacterial speck (UW 2004). Bacterial spot is caused by X. campestris pv. vesicatoria while bacterial speck is caused by P. syringae pv. tomato (UW 2004).

1. Regulatory History

In 1994, AgriPhi Inc. first requested that the Agency issue it an experimental use permit (EUP) to investigate the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato (U.S. EPA 1994a). EPA granted the EUP on August 29, 1994 (U.S. EPA 1994b). On its own initiative, the Agency established a temporary exemption from the requirement of a tolerance; it was announced in a September 7, 1994, Federal Register Notice (59 FR 46247).

On December 9, 2005 (U.S. EPA 2005e), EPA registered AgriPhageTM, a pesticide end-use product containing the two active ingredients: the bacteriophage active against X. campestris pv. vesicatoria and the bacteriophage active against P. syringae pv. tomato

. A summary of the Agency’s registration decision is provided in the Biopesticides Registration Action Document (BRAD) (U.S. EPA 2005f). Because AgriPhageTM is applied to food, a rule establishing an exemption from the require ment of a tolerance was published in the Federal Register on December 28, 2005 (70 FR 76700).

2. Registered Products

OmniLyticsTM, Inc. is the only registrant for the pesticide product containing the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato as the active ingredients. The current pesticide registration is listed in Table 1; because the product is produced using an integrated process, there is no manufacturing-use product.

Table 1 Pesticide Product Containing the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato

EPA Reg. No Product Name Product Type % Active Ingredient First Registered

67986-1 AgriPhageTM end-use 0.046% December 9, 2005 (U.S. EPA 2005e)

3. Mode of Action

The mode of action for AgriPhageTM is through lysis, where the virus attacks the host cell and eventually causes its bacterial wall to break down and rupture, thus killing the bacteria. AgriPhageTM is host-specific, meaning that it will only attack the bacteria X. campestris pv. vesicatoria and P. syringae pv. tomato

.EPA-HQ-OPP-2015-0702 (Bacteriophages) www.regulations.gov

7 4. Use Profile

AgriPhageTM may be applied, at a maximum use rate of 0.00125 lb/A, to peppers and tomatoes that are grown commercially in the greenhouse or in the field. In the greenhouse, the product is applied as a foliar spray or by fogging. In the field, AgriPhageTM is applied via aerial application, conventional ground equipment, or conventional spray equipment (U.S. EPA 2011).

5. Tolerance Ac tions

As noted above under “Regulatory History,” a rule establishing an exemption from the requirement of tolerance was established on December 28, 2005 (70 FR 76700). Except for a 2009 Technical Amendment where the last three words of the 2005 exemption were changed from “tomatoes and peppers” to “pepper and tomato,” the language has not changed. The current tolerance exemption language reads:

§180.1261 Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae
pv. tomato specific Bacteriophages

. An exemption from the requirement of a tolerance is established for residues of Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. tomato specific bacteriophages in or on pepper and tomato.

[74 FR 26536, June 3, 2009]

The open literature tends to name a bacteriophage starting with the phrase “bacteriophage active against” followed by the name of the bacterial host. The active ingredients in this Registration Review are referred to as the bacteriophage active against X. campestris pv. vesicatoria and the bacteriophage active against P. syringae pv. tomato (or, the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato ). The current tolerance exemption language (above) describes the active ingredients using a different convention where the name of the bacteria is listed first. Nonetheless, this tolerance exemption pertains to the active ingredients covered in this PWP.

C. Anticipated Data Needs and Risk Assessments

Provided below are tables identifying the current data requirements for microbial pesticides as

s et forth in 40 CFR part 158, subpart V; they are arrayed by scientific discipline: Table 2--Product Analysis, Table 3--Human Health Toxicology, and Table 4 --Ec ot oxicity. Each table lists the respective data requirements and shows how the requirement has been met (or not met). The term “Guideline”

refers to the Agency test guidelines for microbial pesticides; these can be found under the 700 Series at: http://nepis.epa.gov/EPA/html/pubnumindex.html.

1. Product Analysis: 40 CFR 158.2120

EPA has identified two product analysis data gaps: Deposition of a sample in a nationally recognized culture collection (Guideline 885.1250) and Stability to normal and elevated temperatures, metals, and metal ions (Guideline 830.6313). All other data requirements have been fulfilled.EPA-HQ-OPP-2015-0702 (Bacteriophages) www.regulations.gov

8 Table 2 Product Analysis Data Requirements and How They Are Met

Guideline Data Requirement How the Requirement Is Met (MRID; Review)

P RODUCT C HEMISTRY AND C OMPOSITION

885.1100 Product identity 460938-01 (U.S. EPA 2004b) 461970-01 (U.S. EPA 2004b) 464624-01 (U.S. EPA 2005a) 465754-01 (U.S. EPA 2005c,d) 468873-01 (U.S, EPA 2010)

885.1200 Manufacturing process 460938-01 (U.S. EPA 2004b) 461970-01 (U.S. EPA 2004b) 464624-01 (U.S. EPA 2005a) 465754-01 (U.S. EPA 2005c,d)

885.1250 Deposition of a sample in a nationally recognized culture collection Data Gap

885.1300 Discussion of formation of unintentional ingredients 460938-01 (U.S. EPA 2004b) 461970-01 (U.S. EPA 2004b) 465754-01 (U.S. EPA 2005c,d)

A NALYSIS AND C ERTIFIED L IMITS

885.1400 Analysis of Samples: Preliminary Analysis 460938-01 (U.S. EPA 2004b) 465754-01 (U.S. EPA 2005c,d)

Five-Batch 460938-01 (U.S. EPA 2004b) 461970-01 (U.S. EPA 2004b) 480464-01 (U.S. EPA 2012) 492049-01 (U.S. EPA 2013)

885.1500 Certification of limits 460938-01 (U.S. EPA 2004b) 461970-01 (U.S. EPA 2004b) 465754-01 (U.S. EPA 2005c,d)

P HYSICAL AND C HEMICAL C HARACTERISTICS

830.6302 Color Self-Certification (OmniLyticsTM 2010)

830.6303 Physical state Self-Certification (OmniLyticsTM 2010)

830.6304 Odor Self-Certification (OmniLyticsTM 2010)

830.6313 Stability to normal and elevated temperatures, metals, and metal ions Data Gap

830.6317 Storage stability Self-Certification (OmniLyticsTM 2010)

830.6319 Miscibility Self-Certification (OmniLyticsTM 2010)

830.6320 Corrosion characteristics Self-C ertification (OmniLyticsTM 2010)

830.7000 pH Self-Certification (OmniLyticsTM 2010)

830.7100 Viscosity Self-Certification (OmniLyticsTM 2010)

30.7300 Density Self-Certification (OmniLyticsTM 2010)

2. Toxicology: 40 CFR 158.2140

EPA has waived most of the data requirem ents for human health toxicity, as described below. Generally, bacteriophages are ubiquitous in nature, consumed by humans through food, and host-specific. However, the Agency has identified one data gap: Cell Culture (Guideline 885.3500).EPA-HQ-OPP-2015-0702 (Bacteriophages) www.regulations.gov

9 Table 3 Human Health Toxicology Data Requirements and How They Are Met

Guideline Data Requirement How the Requirement Is Met (MRID; Review)

870.1100 Acute oral toxicity Waived. No adverse effects are expected via the oral route. The public literature demonstrates that humans and animals consume phages daily in their diets with no adverse effects.

465754-02, 465754-03 (U.S. EPA 2005c,d) 885.3050 Acute oral toxicity/pathogenicity

870.1200 Acute dermal toxicity Waived. Subm itted literature demonstrates that the bacteriophages active against X. campestris pv. vesicatoria

and P. syringae pv. tomato are nontoxic to humans.

465754-02, 465754-03 (U.S. EPA 2005c,d) 870.1300 Acute inhalation toxicity

870.2400 Acute eye irritation

870.2500 Primary dermal irritation

885.3150 Acute pulmonary toxicity/pathogenicity

885.3400 Hypersensitivity Incidents Waived. OmniLy ticsTM (2008) reported t hat hypersensitivity reactions have never been observed in any phase of bacteriophage production.

In the event, 40 CFR 158.2140(d)3 requires that the registrant must report hypersensitivity r eactions should they occur.

885.3500 Cell Culture Data Gap

3. Nontarget Organisms and Environmental Fate: 4 0 CFR 158.2150

EPA has waived all the ecologic al data requirements (U.S. EPA 2004a). Among the

factors listed in Table 4, OmniLyticsTM argued that bacteriophages are ubiquitous in the environment (they oc cur naturally in soil and water) and they are host-specific, meaning that they affect only one bacterial species and frequently, only a single strain.

Table 4 Ecological Toxicity Data Requirements and How They Are Met

Guideline Data Requirement How the Requirement Is Met (MRID; Review)

885.4050 Avian oral toxicity Waived. Hazard to avian species in not expected. 460938-02 (U.S. EPA 2004a); 465754-03 (U.S. EPA 2005c,d)

885.4100 Avian inhalation toxicity/pathogenicity Not Required. Under 40 CFR 158.2150(e)(3), these data are “required when the nature of the microbial pesticide and/or its toxins indicates potential pathogenicity to birds.” Because the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. t omato are host-specific, adverse effects to birds are not expected.

885.4150 Wild mammal toxicity/pathogenicity Waived. Based on conclusions pertai ning toxicity/pathogenicity to mammals. 460938-02 (U.S. EPA 2004a); 465754-03 (U.S. EPA 2005c,d)

885.4200 Freshwater fish toxicity/pathogenicity Waived. Exposure, hazard to freshwater fish is not expected. 460938-02 (U.S. EPA 2004a); 465754-03 (U.S. EPA 2005c,d)

885.4240 Freshwater invertebrate toxicity/pathogenicity Waived. Exposure, hazard to freshwater invertebrates is not expected. 460938-02 (U.S. EPA 2004a); 465754-03 (U.S. EPA 2005c,EPA-HQ-OPP-2015-0702 (Bacteriophages) www.regulations.gov

10 Table 4 Ecological Toxicity Data Requirements and How They Are Met

Guideline Data Requirement How the Requirement Is Met (MRID; Review)

885.4280 Estuarine/Marine fish testing

Estuarine and marine invertebrate testing NA. Under 40 CFR 258.2150(6), this testing is conditionally required, with the condition being: "if the product is intended for direct application into the estuarine or marine environment or expected to enter this environment in significant concentrations because of expected use or mobility pattern."

Use of the product is not intended for direct application to water. If it were to runoff because of heavy rain, for example, the concentration in estuarine waters is expected to be low.

885.4300 Nontarget plant testing Not Required. Under 40 CFR 158.2150(e)(7), these data are “required if the microbial pesticide is taxonomically related to a known plant pathogen. The pesticide is actually a virus that attacks the host cell (i.e., the bacteria

X. campestris pv. vesicatoria and P. syringae pv. tomato ), eventually causing the bacteria to rupture.

885.4340 Nontarget insect testing Waived. Hazard to nontarget species is not expected. 460938-02 (U.S. EPA 2004a); 465754-03 (U.S. EPA 2005c,d)

.4380 Honey bee testing Waived. Hazard to honeybees is not expected. 460938-02 (U.S. EPA 2004a); 465754-03 (U.S. EPA 2005c,d)

D. Risk to Threatened and Endangered Species

Based on the type and extent of use, and the low expected toxicity and exposure anticipated due to the nature of bacteriophages (they are host-specific and ubiquitous in the environment), the Agency believes that effects on the environment are not reasonably expected to occur from the registered use of the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv.

tomato . Therefore, the Agency anticipates making a “No Effect” determination under the Endangered Species Act (ESA) for direct and indirect effects to listed species and their habitats.

E. Endocrine Disruptor Screening Program

As required by the Administrator under the Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) and has begun to implement the screening program that is to be used to test all pesticides to determine whether certain substances (including pesticide active and ot her 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 section 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 effect 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 (DCI) for the first group of 67 chemicals, which contains 58 pesticide active ingredients and nine inert ingredients. A

second list of chemicals identified fo r EDSP screening was published on June 14, 2013 2 , and includes some pesticides scheduled for Registration Review and chemicals found in water. The bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato are not among the group of pesticide active ingredients on the lists to be screened under EDSP.

2 See http://www.regulations. gov/#!documentDetail;D=EPA-HQ -OPPT-2009-0477-0074 for the second list of chemicals.EPA-HQ-OPP-2015-0702 (Bacteriophages) www.regulations.gov

11 EPA, as part of this PWP believes that the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato are microbials that would not likely produce any effect in humans similar to an effect produced by a naturally occurring estrogenic substance. As such, pursuant to Section 408(p)(4), EPA will determine in the future whether it can exempt the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato from the requirements of EDSP section 408(p). 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 EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines, and the Tier 1 screening battery, please visit our website at http://www.epa.gov/endo/.

F. Literature Review

EPA searched several databases for the time period December 9, 2005 to present, looking for new information pertaining to the active ingredients pertaining to this Registration Review. None of the databases searched yielded any new information. Below are the databases considered.

1. The National Library of Medicine’s PubMed (NLM 2015);

2. Health Canada, which covers information concerni ng Health Canada’s Pest Managemen t Regulatory Agency (PMRA) (Cana da 2015);

3. The European Union (EU 2015) Pesticides data base;-

4. EPA’s ECOTOX databa se (U.S. EPA 2015a).

G. Incidents

Based on a search conducted on December 1, 2015 (U.S. EPA 2015b) covering the time period from1992 to present, no adverse human, domestic animal, or environmental incidents involving exposure to the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato as active ingredients in a pesticide formulation have been reported to OPP’s Incident Data System (IDS). The Agency will consider any incident data or comments submitted to this docket in response to

this PWP.

H. Summary of Anticipated Data Needs

The Agency has identified two Product Analysis data gaps and one for Toxicology; they are listed in Table 5. EPA expects to issue a DCI for these data.

Table 5 Anticipated Data Needs for Cases 6509 and 6510— the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato
Type of Data Requirement Guideline Requirement Timeframe (months from receipt of DCI)

Product Chemistry: 830.6313 Stability to normal and elevated temperatures, metals, and metal ions 8 months

885.1250 Deposition of a sample in a nationally recognized culture collection 6 months

Human Health

Toxicology: 885.3500 Cell Culture 18 monthsEPA-HQ-OPP-2015-0702 (Bacteriophages) www.regulations.gov

12 I. Next Steps and Timeline

After the 60-day comment period closes, EPA will review and respond to any comments received in a timely manner and then issue an FWP for Cases 6509 and 6510. Provided in Table 6 is the Agency’s estimated timeline for the Registration Review of the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv . tomato . Please note that this schedule is subject to revision should unforeseen issues arise during the Registration Review process. If an issue does arise (e.g., failure to acquire an EDSP exemption), an amended FWP may be issued at that time. That FWP will identify any newly anticipated data needs and set forth a new timeline.



### Table 6 EPA’s Estimated Timeline for Completing the Registration Review of the bacteriophages active against X. campestris pv. vesicatoria

and P. syringae pv. tomato

Activity Estimated Month

and Year

Docket Opening

Open Docket and 60-Day Public Comment Period for the bacteriophages active against X. campestris

pv. vesicatoria and P. syringae pv. tomato December 2015

Close Public Comment Period February 2016

Case Development

Issue Final Work Plan August 2016

Issue Data Call-in August 2017

Data Submission February 2019

Open 30-Day Public Comment

Period for Draft Risk Assessments August 2019

Close Public Comment Period September 2019

Registration Review Decision

Open 60-Day Public Comment Period for Proposed Registration Review Decision January 2020

Close Public Comment Period March 2020

Registration Review Final Decision and Begin Post-decision Follow-up March 2021

Estimated Total (years): ~6 years13 II. BIBLIOGRAPHY

A. Studies Supporting the Registration Review for the Bacteriophage active against Xanthomonas campestris pv. vesicatoria and the Bacteriophage active against Pseudomonas syringae pv . tomato

460938-00 AgriPhi. 2003a. Submission of Product Chemistry, Efficacy and Fate Data in Support of the Application for Registration of AgriPhage and the Experimental Use of AgriPhage. Prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. Transmittal of 2 Studies. October 10, 2003.

460938-01 AgriPhi. 2003b. Product Chemistry: Agri Phage. Unpublished study prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. 14 pp. October 10, 2003.

460938-02 AgriPhi. 2003c. Rationale for Waiver of Toxicology, Non-target Organism, and Residue Testing Requirements: AgriPhage. Unpublished study prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. 170 pp. October 10, 2003.

461970-00 AgriPhi. 2004a. Submission of Product Chemistry Data in Support of the Application for Registration of AgriPhage. Prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. Transmittal of 1 Study. February 6, 2004.

461970-01 AgriPhi. 2004b. Product Chemistry: AgriPhage: Addendum. Unpublished study prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. 53 pp. February 6, 2004.

463614-00 AgriPhi. 2004c. Submission of Product Chemistry Data in Support of the Application for Registration of AgriPhage. Prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. Transmittal of 1 Study. September 13, 2004.

463614-01 AgriPhi. 2004d. Product Chemistry: AgriPhage Comprehensive Resubmission. Unpublished study prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. 22 pp. September 13, 2004.

463940-00 AgriPhi. 2004e. Submission of Product Chemistry Data in Support of the Application for Registration of Xanthomonas campestris (A griPhage). Prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. Transmittal of 1 Study. November 1, 2004.

463940-01 AgriPhi. 2004f. Product Chemistry: AgriPhage Comprehensive Resubmission. Unpublished study prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. 23 pp. November 1, 2004.

464393-00 AgriPhi. 2004g. Submission of Product Chemistry Data in Support of the Application for Registration of AgriPhage and the Experimental Use of AgriPhage. Unpublished study prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. Transmittal of 1 Study. December 20, 2004.

464393-01 AgriPhi. 2004h. Product Chemistry: Agri Phage Resubmission to Address Quality Control Issues. Unpublished study prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. 24 pp. December 20, 2004.

464484-00 AgriPhi. 2005. Submission of Toxicity and Residue Data in Support of the Application for Registration for AgriPhage and the Experimental Use of AgriPhage. Prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. Transmittal of 1 Study. January 19, 2005.14 464484-01 AgriPhi. 2005b. Rationale for Waiver of Toxicity and Residue Data Requirements (Xanthomonas campestris). Unpublished study prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. 13 pp. January 19, 2005.

464624-00 AgriPhi. 2005c. Submission of Product Chemistry Data in Support of the Application for Registration of AgriPhage and the Experimental Use of AgriPhage. Prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. Transmittal of 1 Study. February 4, 2005.

464624-01 AgriPhi. 2005d. Product Chemistry: Supplement to Purification and Quality Control Procedures Discussion Submitted December 17, 2004. Unpublished study prepared by T. Jeffrey of Delta Analytical Corp., Agent for AgriPhi, Inc. 61 pp. February 4, 2005.

465754-00 OmniLyticsTM. 2005a. Submission of Produc t Chemistry, Toxicity, Residue, Exposure and Risk Data in Support of the Application for Registration of AgriPhage. Submitted by Michael Braverman, Ph.D. of the IR-4 Program and Agent for AgriPhi/OmniLyticsTM. Transmittal of 3 Studies. June 20, 2005.

465754-01 OmniLyticsTM. 2005b. Product Chemistr y: AgriPhage: Amendment of MRID 460938-01 and 461970-01. Project Number: 0372B. Unpublished study submitted by Michael Braverman, Ph.D. of the IR-4 Program and Agent for AgriPhi/OmniLyticsTM. 96 pp.
June 20, 2005.

465754-02 OmniLyticsTM. 2005c. AgriPhage: Rationale for Waiver of Toxicity and Residue Data Requirements. Project Number: 0372B. Unpublished study submitted by Michael Braverman, Ph.D. of the IR-4 Program and Agent for AgriPhi/OmniLyticsTM. 11 pp.
June 20, 2005.

465754-03 OmniLyticsTM. 2005d. AgriPhage: Rational e for Waiver of Toxicology, Non-Target Organisms, and Residue Testing Requirements. Project Number: 0372B. Unpublished study submitted by Michael Braverman, Ph.D. of the IR-4 Program and Agent for AgriPhi/OmniLyticsTM. 170 pp. June 20, 2005.

468873-00 OmniLyticsTM. 2006a. Submission of Product Chemistry Data in Support of the Amended Registration of AgriPhage. Submitted by Mi chael Braverman, Ph.D. of the IR-4 Program and Agent for AgriPhi/OmniLyticsTM. Transmittal of 1 Study. July 13, 2006.

468873-01 OmniLyticsTM. 2006b. Product Chemistry: AgriPhage. Project Number: 0372B. Unpublished study prepared by A. Walbeck of Om niLyticsTM, Inc. 60 pp. July 13, 2006.

480464-00 OmniLyticsTM. 2010a. Submission of Product Chemistry Data in Support of the Amended Registration of AgriPhage. Transmittal of 1 Study. March 30, 2010.

480464-01 OmniLyticsTM. 2010b. Product Chemistry: (AgriPhage): Bacteriophage for Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. Tomato. Unpublished study prepared by Kristine Blum of OmniLyticsTM, Inc. 56 pp. March 30, 2010.

481060-00 OmniLyticsTM, Inc. 2010c. Submission of Product Chemistry Data in Support of the Amended Registration of AgriPhage. Transmittal of 1 Study. May 21, 2010.

481060-01 OmniLyticsTM. 2010d. AgriPhage: Product Chemistry: Bacteriophage for Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. tomato. Project Number: 30/OP/00020/A. Unpublished study prepared by Kr istine Blum of OmniLyticsTM, Inc. 160 pp. (this study has been replaced by MRID 481135-01) May 21, 2010.15 481135-00 OmniLyticsTM. 2010e. Submission of Product Chemistry Data in Support of the Amended Registration of AgriPhage. Transmittal of 1 Study. May 28, 2010.

481135-01 OmniLyticsTM. 2010f. Product Chemistry: Bacteriophage for Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. Tom ato. Unpublished study prepared by Kristine Blum of OmniLyticsTM, Inc. 184 pp. May 28, 2010.

485354-00 OmniLyticsTM. 2011a. Submission of Product Chemistry Data in Support of the Amended Registration of AgriPhage. Transmittal of 1 Study. July 12, 2011.

485354-01 OmniLyticsTM. 2011b. Product Chemistry Bacteriophage for Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. to mato. Unpublished study prepared by Kristine Blum of OmniLyticsTM, Inc. 71 pp. July 12, 2011.

485982-00 OmniLyticsTM. 2011c. Submission of Exposure and Risk Data in Support of the Amended Registration of AgriPhage. Transmittal of 1 Study. August 8, 2011.

485982-01 OmniLyticsTM. 2011d. Justification for Zero Re-Entry Interval (REI) for Bacteriophage for Xanthomonas campestris pv. vesica toria and Pseudomonas syringae pv. tomato. Unpublished study prepared by OmniLyticsTM, Inc. 3p. August 8, 2011.

486369-00 OmniLyticsTM. 2011e. Submission of Product Chemistry Data in Support of the Registration of AgriPhage. Transmittal of 1 Study. October 6, 2011.

486369-01 OmniLyticsTM. 2011f. Product Analysis Test Guidelines: AgriPhage. Unpublished study prepared by Kristine Blum of OmniLyticsTM, In c. and submitted by Michael Braverman, Ph.D. of the IR-4 Program and Agent for OmniLyticsTM. 62p. October 6, 2011.

492049-00 OmniLyticsTM. 2013a. Submission of Product Chemistry Data in Support of the Amended Registration of AgriPhage. Transmittal of 1 Study. August 29, 2013.

492049-01 OmniLyticsTM. 2013b. Five Batch Analysis: Xcv: Xanthomonas campestris pv. vesicatoria. Unpublished study prepared by Tyler Homer of OmniLyticsTM, Inc. 10p. August 29, 2013.

B. U.S. Environmental Protection Agency

U.S. EPA. 1994a. Letter from the Agency to AgriPhi. Receipt of Application for a New Registration. U.S. Environmental Protection Agency Office of Pesticide Programs. March 31, 1994.

U.S. EPA. 1994b. Letter from Steve Robbins, EPA to Lee E. Jackson, AgriPhi. AgriPhage: Experimental Use Permit No. 67986-EUP-l. U.S. Envi ronmental Protection Agency Office of Pesticide Programs. August 29, 1994.

U.S. EPA. 2004a. Memorandum from Hillary Hill to Leonard Cole. Ecological Risk Assessment for Bacteriophage Active Against Xanthomonas campes tris pv. vesicatoria and Pseudomonas Syringae pv.

Tomato. MRID 460938-02. U.S. Environmental Protec tion Agency Office of Pesticide Programs. Data Review: MRID 460938-02. April 13, 2004. 6 pp.16 U.S. EPA. 2004b. Memorandum from Carl Etsitty to Leonard Cole: Review of Product Chemistry and Manufacturing Process Data Submitted by AgriPhi Inc., for the Registration of Agriphage, which

contains Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. tomato Specific Bacteriophages submitted on October 2003 by AgriPhi Inc., Baltimore, MD, (Submission No : S340771; PC Code 006431; DP Barcode: 300159; MRID No ‘s: 460938-01 and 461970-01). U.S. Environmental Protection Agency Office of Pesticide Programs. Data Review: MRID’s 460938-01 and 461970-01. May 21, 2004. 9 pp.

U.S. EPA. 2005a. Memorandum from Carl Etsitty to Leonard Cole. Review of Product Chemistry and Manufacturing Process Data Submitted by AgriPhi Inc., for the Registration of Agriphage, which

contains Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. tomato Specific Bacteriophages submitted by AgriPh i Inc., Baltimore, MD, (Submission No : S340771; PC Code 006431;
DP Barcode: 300159; MRID No 's: 46462401). U.S. Environmental Protection Agency Office of Pesticide Programs. Data Review: MRID 464624-01. March 14, 2005. 13 pp.

U.S. EPA 2005b. Letter from Janet Andersen, EPA to T. Jeffrey Jones, AgriPhi. Application for Registration. Bacteriophage to control Xanthomonas campestris . EPA Identifying Symbol 67986-R. U.S. Environmental Protection Agency. Office of Pesticide Programs. March 25, 2015.

U.S. EPA. 2005c. Memorandum from Carl Etsitty to Leonard Cole. Review of Product Chemistry and Manufacturing Process Data Submitted by AgriPhi Inc., for the Registration of Agriphage, which

contains Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. tomato Specific Bacteriophages submitted by AgriPhi Inc., (Submission No : S340771; PC Code 006431; DP Barcode:

300159: MRID No ‘s 465754-01, -02, -03. U.S. Environmental Protection Agency Office of Pesticide Programs. Data Reviews of MRID’s 465754-01, 465754-02, 465754-03. August 26, 2005.

U.S. EPA. 2005d. Memorandum from Carl Etsitty to Leonard Cole. Review of Product Chemistry and Manufacturing Process Data Submitted by AgriPhi lnc., for the Registration of Agriphage, which

contains Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. tomato Specific Bacteriophages submitted by AgriPhi Inc., (Submission S340771; PC Code: 006431; DP Barcode: 300159; MRID No 's: 465754-01, -02, -03). U.S. Environmental Protection Agency Office of Pesticide Programs. Data Review of MRID’s 465754-01, 465754-02, 465754-03. September 29, 2005

U.S. EPA. 2005e. Registration Notice and Stamped Label for AgriPhage. EPA Reg. No 67986-1. U.S. Environmental Protection Agency Office of Pesticide Programs. December 9, 2005.

U.S. EPA. 2005f. Biopesticides Registration Action Document. Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. tomato Specific Bacteriophages. U.S. Environmental Protection Agency. Office of Pesticide Programs. December 9, 2005.

U.S. EPA. 2010. Memorandum from Joel V. Gagliardi to Ann Sibold. Lytic bacteriophage isolated from and active against Xanthomonas campestr is pv. vesicatoria and Pseudomonas syringae pv. tomato. U.S. Environmental Protection Agency Office of Pesticide Programs. Data Review of MRID 468873-01. October 7, 2010.

U.S. EPA. 2011. Letter from Sheryl Reilly, EPA to Kristine Blum, OmniLyticsTM. Agriphage. EPA Reg. No. 67986-1. Submission dated May 28, 2010 and subsequent revisions. Decision No. 434829, and Submission dated June 6, 2006. Decision No. 369365. U.S. Environmental Protection Agency Office of Pesticide Programs. Letter Refers to MRID’s: 481135-01; 468873-01; a revised label is attached. October 17, 2011.17 U.S. EPA. 2012. Memorandum from Joel Gagliardi to Ann Sibold. Review of Product Chemistry Information provided by OmniLyticsTM, Inc. after an OECA Books and Records Inspection. U.S. Environmental Protection Agency Office of Pesticide Programs. Data Review of MRID 480464-01. January 10, 2012.

U.S. EPA. 2013. Memorandum from John Kough to Shanaz Bacchus. Review of OmniLyticsTM, Inc. Response to EPA letter April 8, 2013 after an OECA Books and Records Inspection. U.S. Environmental Protection Agency Office of Pesticide Programs. Data Review of MRID 492049-01.
November 26, 2013.

U.S. EPA. 2015a. Literature Search Using ECOTOX. U.S. Environmental Protection Agency. Office of Research and Development. National Health and Environmental Effects Research Laboratory. Search conducted on December 1, 2015. http://cfpub.epa.gov/ecotox/. Last database update: December 1, 2015.

U.S. EPA. 2015b. Email from Robert Miller to Kathleen Martin. Incidents for the Bacteriophage Active Against Xanthomonas campestris pv. vesicatoria and the Bacteriophage Active Against Pseudomonas syringae pv. tomato . U.S. Environmental Protection Agency Office of Pesticide Programs. December 1, 2015.

C. Other References

Canada. 2015. Search Engine for Health Canada (includes Health Canada’s Health Canada’s Pest Management Regulatory Agency). Health Canada. Search conducted on November 20, 2015. http://recherche-search.gc.ca/rGs/s_r?s t=s&langs=eng&st1rt=0&num=10&cdn=health

EU. 2015. The EU Pesticide Database. European Commission Department of Health and Food Safety. Search conducted on November 20, 2015. Last update: July 7, 2915. http://ec.europa.eu /food/plant/ pesticides/eu-pestici des-database/public/?ev ent=activesubstance.se lection&language=EN

IR-4. 2005. Letter from Michael Braverman, IR-4 to Janet Andersen, EPA. Product: AgriPhage 67986-R. IR-4 PR# 0372B. Response to Agency letter dated March 25, 2005. IR-4 Project. Rutgers University (note: this letter is MRID 465754-00). June 17, 2005.

ISPP. 2001. International Standard for Naming Pathovars of Phytopathogenic Bacteria International Society for Plant Pathology. Committee on the Taxonomy of Plant Pathogenic Bacteria. December 20, 2001. http://www.isppweb.org/about_tppb_naming.asp

NLM. 2015. Literature search using PubMed. U.S. National Library of Medicine. National Institutes of Health. Search conducted on November 20, 2015. Note: database updated frequently to include the latest publications). http ://www.ncbi.nlm.nih.gov/pubmed

OmniLyticsTM. 2008. Letter from Kristine Blum, OmniLyticsTM to the Agency. May 6, 2008.

OmniLyticsTM. 2010. Self-Certification Statement fo r the Physical/Chemical Properties for AgriPhage (EPA Reg. No 67986-1). Submitted (via EPA Form 8570-36) by Kristine Blum, Regulatory Director OmniLyticsTM, Inc. May 28, 2010.

UW. 2004. University of Wisconsin–Extension. Karen Delahaut and Walt Stevenson Tomato and Pepper Disorders: Bacterial Spot and Speck. R-05-04. http://learningstore.uwex. edu/assets/pdfs/A2604.pdfAppendix 

### Appendix : Guidance for Commenters

The public is invited to comment on the PWP and rationale. The areas below highlight topics of special interest to

EPA where comments, information submissions, or reference to sources of additional information could be of particular

use. EPA will consider all comments, as well as any additional information or data provided in a timely manner, prior to
issuing an FWP for this case.

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, in the development,
implementation, and enforcement of environmental laws, regulations, and policies. To help address potential

environmental justice issues, EPA seeks information on any groups or segments of the population who, as a result

of their location, cultural practices, or other factors, may have atypical, unusually high exposure to the
bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato compared to the general
population. Please comment if you are aware of any subpopulations that may have atypical, unusually high

exposure compared to the general population.

Water Quality. The bacteriophage active against X. campestris pv. vesicatoria and the bacteriophage active

against P. syringae pv. tomato are not identified as a cause of impairment for any water bodies listed as impaired

under section 303(d) of the Clean Water Act. In addition, EPA has not developed Total Maximum Daily Loads
(TMDL’s) for the bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato

. More

information on impaired water bodies and TMDL’s can be found at EPA’s website: http://water.epa.gov/lawsregs/lawsguidance/cwa/tmdl/. EPA invites submission of water quality data for this
pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the Office of

Pesticide Programs’ Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality

Data in OPP’s Registration Review Risk Assessment and Management Process to ensure they can be used
quantitatively or qualitatively in pesticide risk assessments.

Trade Irritants. Through the Registration Review process, EPA intends to solicit information on trade irritants and,

to the extent feasible, take steps toward facilitating irritant resolution. The Agency will work to harmonize

tolerance and international Maximum Residue Limits (MRL’s) and may modify tolerance levels to do so, when
possible. Growers and other stakeholders are asked to comment on any trade irritant issues resulting from lack

of MRL’s or disparities between U.S. tolerances and MRL’s in key export markets, providing as much specificity as possible regarding the nature of the concern.

Additional Information. Stakeholders also are asked to provide information and data that will assist the Agency in
refining the risk assessments. The Agency is interested in obtaining the following information on the
bacteriophages active against X. campestris pv. vesicatoria and P. syringae pv. tomato

.

 Confirmation on the following label information:

‐ Formulations

‐ Application sites

‐ Application methods and equipment

‐ Maximum application rates

‐ Frequency of application, application

intervals, and maximum number of
applications

‐ Geographic limitations on use

 Use or potential use distribution (e.g., acreage and

geographical distribution of relevant use sites)  Median and 90 th percentile reported use rates (lb active ingredient/1,000 square feet) from usage data—national, state, and county

 Application timing (date of first application and

application intervals)—national, state, and county

 Usage/use information for nonagricultural uses

 Typical application interval (days)

 State or local use restrictions

 Monitoring data