**BIOPESTICIDES REGISTRATION ACTION DOCUMENT**

Bacteriophage of Clavibacter michiganensis subspecies michiganensis

Pesticide Chemical (PC) Code: 228983

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

September 29 , 2011Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 2 of 22

Biopesticides Registration Action Document **TABLE OF CONTENTS I**  **. EXECUTIVE SUMMARY**  **................................ ................................**  **................................ .**  **4 II.**  **ACTIVE INGREDIENT OV ERVIEW**  **................................ ................................**  **.............. 6**  **II I.**  **REGULATORY BACKGROUN D**  **................................ ................................**  **.................... 7**  **A .**  **Applications for Pesticide Registration ................................**  **................................ ................................**  **. 7**  **B .**  **Food Tolerance Exemption ................................**  **................................ ................................**  **..................... 7**  **IV. RISK ASSESSMENT**  **................................ ................................**  **................................ .........**  **7**

**A .**  **Product Analysis Assessment (40 CFR § 158.2120) ................................**  **................................ ............**  **8 B**  **. Hum**  **an Health Assessment (40 CFR § 158.2140) ................................**  **................................ ................**  **8 C**  **. Environmental**  **Assessment (40 CFR § 158.2150)**  **................................ ................................**  **............. 13**  **V .**  **ENVIRONMENTAL JUSTIC E**  **................................ ................................**  **....................... 14**  **VI .**  **RISK MANAGEMENT DECI SION**  **................................ ................................**  **................ 15**  **VII. ACTIONS REQUIRED BY**  **THE REGISTRANT ................................**  **......................... 15**  **A .**  **Final Printed Labeling ................................**  **................................ ................................**  **.......................... 15**  **B. Terms of Registration ................................**  **................................ ................................**  **............................ 15**  **C .**  **Repor ting of Adverse Effects and Hypersensitivity Incidents**  **................................ ...........................**  **16 VIII. GLOSSARY OF AC**  **RONYMS AND ABBREVIAT IONS**  **................................ ............**  **17 IX.**  **BIBLIOGRAPHY ................................**  **................................ ................................**  **.............. 18**  **A .**  **Studies Submitted to Support the AgriPhage CMM Pesticide Product Registration**  **..................... 18**  **B .**  **Environm ental Protection Agency and Pest Management Regulatory Agency Risk Assessment**  **Mem oranda**  **................................ ................................**  **................................ ................................**  **................. 18**  **APPENDIX A .**  **MICROBIAL PESTICIDES DATA REQUIREMENTS**  **............................. 20**  **APPENDIX B .**  **PESTICIDE PRODUCTS ................................**  **................................ ................**  **22**Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 3 of 22

Biopesticides Registration Action Document

**BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM**

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

**Microbial Pesticides Branch**
**Science Reviews** U.S. Environmental Protection Agency Joel V. Gagliardi , Ph.D. Product Anal ys is, Environmental Effects, Human Health Health Canada Pest Management Regulatory Ag ency Jonas Ptasinski Product Anal ys is, Environmental Effects , Human Health **Regulations** U.S. Environmental Protection Agency Sheryl K. Reill y, Ph.D. Chief, Microbial Pesticides Branch Denise Greenway Regulatory Action Leader Anna Gross Regulatory Action Leader Matthew Thompson Regulatory Action LeaderBacteriophage of Clavibacter michiganensis subsp. michiganensis Page 4 of 22

Biopesticides Registration Action Document **I .**  **EXECUTIVE SUMMARY** In March 2009 , OmniLy

tics, Inc . submitted an application for an end

-use pesticide product, AgriPhage CMM (EPA File Sy mbol 67986

- A) , to both the United States Environmental Protection Agency

(EPA) and the Health Canada Pest Management Regulatory Agency (PMRA) , and requested a North American Free Trade Agreement (NAFTA) Joint Review of its application. AgriPhage CMM contains a new active ingredient, bacteriophage active against Clavibacter michiganensis subsp. michiganensis (referred to hereafter in this document as bacteriophage of Clavibacter michiganensis subsp. michiganensis ) , and is proposed for use as a bactericide on tomato plants to control bacterial canker disease. AgriPhage CMM is composed of individually

derived mixtures of a library of bacteriophage with specific activity for l ys ing Clavibacter michiganensis subsp. michiganensis pathogenic to tomato es . Bacteriophage are viruses that only infect specif

ic bacteria. Clinical uses encompass all manner of administration from injection/intravenous and surgical wound applications , to topical and ingestible preparations . They are also used to test normal and variousl y impaired human immune system function s . Th ere have been no reports of adverse effects from such administrations of bacteriophage in the published literature or in scientifically controlled case studies. Literature cited by the applicant demonstrated that bacteriophage are present in high numbers in the environment , including non

-polluted waters up to 10 10 PFU/Land up to 10 5 PFU/L in treated drinking water. Bacteriophage presence has been reported in foods and feeds ranging from 10

- 10 5 PFU/100 g in meats and up to 10 7 PFU/100 g in cheese, without any known harmful effects after consumption. Bacteriophage are common and abundant in soils and in a wide range of plant materials. The main risk issue associated with the use of bacteriophage as a pesticide is whether the ho st bacterium produce toxins or pathogenicity factors. Peer

- reviewed literature , anal ys is of the host strain , and the bacteriophage properties submitted by the applicant show ed the host strains do not produce toxic or pathogenic factors

. H ost range testing verifie d that the bacteriophage cannot cross

infect bacteri a that may

carry toxins. EPA and PMRA scientists have reviewed product anal ys is, toxicology , and nontarget organism data and information submitted to support the registration of the bacteriophage of Clavibacter michiganensis subsp. michiganensis pesticide product. P roduct anal ys is data requirements for bacteriophage of Clavibacter michiganensis subsp. michiganensis , including product chemistry and composition, analysis of samples, and physical and chemical characteri stics, were fulfilled by acceptable guideline studies. The applicant included a thorough scientific literature review , and requested th at EPA waive the data requirements for mammalian and nontarget organism toxicology , pathogenicity, in fectivity and irritation testing for bacteriophage of Clavibacter michiganensis subsp. m ichiganensis , based upon their biological proper ties and narrow host

range. EPA found the scientific rationale s submitted by the applicant to satisfy the requirement s , since the literature demonstrated that bacteriophage are unable to infect eukaryotic cells , have a host range limited to the target bacterium, and l ys e rather than l ys ogenize (integrate into) host cells, thereb y limiting any ability to transfer genetic traits from bacterial hosts

. It is reasonable to expect that the se bacteriophage are not capable of infecting any eukaryotic organisms, including humans and nontarget animals and plant species , since no bacteriophage infections of eukaryotic organisms have been reported

.Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 5 of 22

Biopesticides Registration Action Document EPA concludes that there is a reasonable certainty that no harm will result to the United States population, including infants and children, from aggregate exposure to residues of bacteriophage of Clavibacter michiganensis subsp. michiganensis

. Based on the narrow host range of bacteriophage of Clavibacter michiganensis subsp. michiganensis to certain bacterial species and the inability of bacteriophage in general to infect eukaryotic cells, bacteriophage of Clavibacter michiganensis subsp. michiganensis are not expected to pose any singular or cumulative risks to humans, including infants and children, or to other mammals through exposure in the food su pply , from drinking or surface waters, or through other non

- dietary exposures. In addition , nonoccupational exposure is considered unlikely for bacteriophage of Clavibacter michiganensis subsp. michiganensis as all currently proposed uses occur in distinctly agricultural or commercial settings; there are no proposed uses for residential areas. Despite the low toxicological profile of bacteriophage of Clavibacter michiganensis subsp. michiganensis , baseline personal protective equipment (PPE) is required f or handlers that may

be exposed to the active ingredient. Handlers working with bacteriophage of Clavibacter michiganensis subsp. michiganensis in occupational and agricultural settings are directed to wear a long

- sleeved shirt, long pants, socks, shoes, and waterproof gloves; a dust/mist filtering respirator meeting National Institute for Occupational Safety and Health (NIOSH) standards of at least N

- 95, R
- 95, or P
- 95 is required for workers when repeated inhalation exposures occur. The submitted data and other information fulfill ed the current data requirements and were adequate f

or risk assessment purposes. EPA has concluded that the proposed use of bacteriophage of Clavibacter michiganensis subsp. m ichiganensis meets the safety standards for re gistration under Section 3(c)(5) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)

. On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunity for the public to participate in 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 types of applications: new active ingredients; first food uses; first outdoor uses; first residential uses; or any other registration actions for which EPA believes there may be significant public interest. Consistent with the policy of making registration actions more transparent, the proposed registration decision for the pe sticide product containing bacteriophage of Clavibacter michiganensis subsp. michiganensis , a new active ingredient, wa s subject to a 30

- day comment period. In addition to containing a new active ingredient, the registration of this product would result in both the first outdoor use and first food use for bacteriophage of Clavibacter michiganensis subsp. michiganensis

. The docket identification number , associated with these registration actions and accessed through either http://www.regulations.gov/ or http://www.epa.gov/pesticides/regulating/registration

- status.html , is EPA

- HQ
- OPP
- 20 09
- 0539
. The f ollowing documents were available for comment in EPA

- HQ
- OPP
- 2009
- 0539 : (1) proposed bacteriophage of Clavibacter michiganensis subsp. michiganensis Biopesticides Registration Action Document (BRAD) ; (2) environmental risk assessment for bacteriophage of Clavibacter michiganensis subsp. michiganensis ; and (3) proposed product label for the end

-use pesticide product, AgriPhage CMM (EPA File S ymbol 67986
- A). While a final decision on registration is contingent upon review and consideration of public comments , none were received , EPA believes that, based upon the risk assessment and information submitted in support of AgriPhage CMM , it is in the best interest of the public and the environment to issueBacteriophage of Clavibacter michiganensis subsp. michiganensis Page 6 of 22

Biopesticides Registration Action Document this registration

. The basis for this decision can be found in the risk assessment for bacteriophage of Clavibacter michiganensis subsp. michiganensis , which is characterized throughout this BRAD
. **II .**  **ACTIVE INGREDIENT OVERVIEW**  **Biological Name:** Bacteriophage of Clavibacter michiganensis subsp. michiganensis **OPP Chemical Code:** 228983 **Type of Pesticide:**  Microbial Pesticide

– Bactericide See Appendix B for specific information ( e.g., use sites, application rates, methods of application, formulation ty pes, and target pests) regarding the pesticide product containing this active ingredient.Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 7 of 22

Biopesticides Registration Action Document **III. REGULATORY BACKGROUND**  **A .**  **Application for Pesticide Registration** On March 23, 2009 , OmniLy tics, Inc. (address: 9100 South 500 West, Sandy , Utah 84070 ) submitted an application to register an end

-use pesticide product, AgriPhage CMM (EPA File Sy mbol 67986

- A) , under FIFRA section 3. On M arch 10, 2010 , EPA announced receipt of this application to register a pesticide product containing a new active ingredient ( 75 Federal Register (FR) 11175 ) and opened a 3 0
- day public comment period pursuant to the provisions of FIFRA section 3(c)(4). No comments were received following this publication

. **B .**  **North American Free Trade Agreement Joint Review** Bacteriophage of Clavibacter michiganensis subsp. michiganensis was the subject of a North American Free Trade Agreement joint registration review conducted b y the Environmental Protection Agency

Office of Pesticide Programs and the Health Canada Pest Management Regulatory

Agency (PMRA). **C. Food Tolerance Exemption**  Concurrent with its registration application and under Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(d), OmniLy tics, Inc. submitted a petition to establish an exemption from the re quirement of a tolerance for bacteriophage of Clavibacter michiganensis subsp. michiganensis (Pesticide Petition (PP) 9E7552 ). Inthe Federal Register of September 23, 2009 ( 7 4 FR 48556 ), EPA announced that Interregional Research Project Number 4 (IR

- 4), Rutgers University , on behalf of OmniLy tics, Inc., proposed to establish an exemption from the requirement of a tolerance for residues of the microbial pesticide , bacteriophage of Clavibacter michiganensis subsp. michiganensis , in or on tomato and opened a 30

- day comment period. No comments were received following this publication

. **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 updated 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 light of these requirements. The classifications that are found for each data submission are assigned b y EPA science reviewers and are an indication of the usef ulness 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 scientifically

acceptable (“ supplemental : upgradeable ”). If a study is rated as “ supplemental : upgradeable ,” EPA always provides an indication of what is lacking or wh at can be provided to change the rating to “ acceptable .” If there is simply a “ supplemental ” rating, the reviewer will often state that the study is not required b y 40 C FR P art 158. Both “ acceptable ” and
“ supplemental ” studies may be used in the risk asses sment process as appropriate. An
“unacceptable ” rating indicates that new data must be submitted.Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 8 of 22

Biopesticides Registration Action Document For the acute toxicity

data requirements, Toxicity C ategories are assigned based on the hazard(s) identified from studies and/or other information submitted to EPA in support of a pesticide registration. The active ingredient or particular product is classified into Toxicity Category I , II, III, or IV, where Toxicity Category Iindicates the highest toxicity and Toxicity

Category IV indicates the lowest toxicity (40 CFR § 156.62 )

. **A .**  **Product Analysis Assessment (** **40 CFR § 158.2120 )**  All product anal ys is data requirements for bacteriophage of Clavibacter michiganensis subsp. michiganensis have been fulfilled (Master Record Identification Numbers ( MRID Nos
. ) 477204
- 01, 480536
- 01 and 483831

- 01). Refer to Tables 1 and 2 in Appendix A for a brief summary of the data requirements. **B .**  **Human Health Assessment (** **40 CFR § 158.2140 )**  **1 .**  **Toxicity** All toxicology

data requirements for bacteriophage of Clavibacter michiganensis subsp. michiganensis have been fulfilled with submission of valid studies from public literature

. Acceptable Tier I mammalian toxicology information found therein support s registration of bacteriophage of Clavibac ter michiganensis subsp. michiganensis pesticide product

. Furthermore, Tier II and Tier III studies were not required for bacteriophage of Clavibacter michiganensis subsp. michiganensis based on the public literature provided for Tier I toxicity /pathogenicity studies. Refer to Table 3 in Appendix A for a brief summary of the data requirements. **a. Acute Toxicity/Pathogenicity** 

**– Tier I**  The applicant included a thorough literature review and set of rationale s adequate to satisfy requirements for toxicology , pathogenicity , infectivity, and irritation testing for bacteriophage of Clavibacter michiganensis subsp. michiganensis (MRID No
. 477204
- 02). The submitted literature established that bacteriophage have been used historically and through modern times in lieu of , or to assist the action of , antibiotics. Clinical uses encompass all manner of administration from injection/intravenous and surgical wound applications to topical and ingestible preparation s. They are also used to test normal and variousl y impaired human immune system function. There have been no reports of adverse effects from such administrations of bacteriophage in the published literature or in cases using controlled scientific studies. Also submitted were literature citations showing that bacteriophage are present in high numbers in the environment , including in non

-polluted waters up to 10 10 PFU/Land up to 10 5 PFU/L in treated drinking water

. EPA determined that the data requirements are met based on submitted literature

.Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 9 of 22

Biopesticides Registration Action Document **b. Acute Toxicology and Subchronic Toxicity/Pathogenicity** 

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

**– Tier III**  Tier II and Tier III studies were not required for bacteriophage of Clavibacter michiganensis subsp. michiganensis based on the lack of acute toxicity /pathogenicity demonstrated by the public literature submission that satisfied the Tier I data requirement s , and a Toxicity Category IVhas been determined for bacteriophage of Clavibacter michiganensis subsp. michiganensis product Agriphage

- CMM
. **c. Endocrine Disruptors**  As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally

occurring estro gen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two - tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the E DSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a quantitative relationship betwe en the dose and the E, A, or T effect. 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 and 9 inert ingredients. This list of chemicals was sel ected based on the potential for human exposure through pathways such as food and water, residential activity, and certain post

- application agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors. B acteriophage of Clavibacter michiganensis subsp. michiganensis is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Under FFDCA section 408(p), EPA must screen all pesticide chemicals. Accordingl y, EPA anticipates issuing future EDSP orders/data call

- ins for all pesticide active ingredients. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

. **2 .**  **F ederal Food, Drug, and Cosmetic Act**  **( FFDCA** **) Considerations** 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 information.” This includes exposure through drinking water and in residential settings but does not include occupational exposure. Pursuant to section 408(c)(2)(B)Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 10 of 22

Biopesticides Registration Action Document of FFDCA, in establishing or maintaining in effect an exemption from the requirement of a tolerance, 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 concerning the cumulative effects of [a particular pesticide's]

. . . residues and other substances that have a common me chanism of toxicity .” EPA performs a number of anal ys es to determine the risks from aggregate exposure to pesticide residues. First, EPA determines the toxicity of pesticides. 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. Consistent with section 408(b)(2)(D) of FFDCA, EPA 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 variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. Based on the acute toxicity /pathogenicity information discussed previously and presented in Table 3 in Appendix A , the data required for a FFDCA risk assessment for b acteriophage of Clavibacter michiganensis subsp. michiganensis have been fulfilled

. **a. Aggregate Exposure**  In examining aggregate exposure, section 408 of FFDCA directs EPA to consider available information concerning exposures from the pesticide residue in food and all other nonoccupational 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 : All bacteriophage , including those at issue in this action, are similar in nature in that they are host

- specific, attacking only bacteria

. Published scientific literature submitted by the registrant, and other publically available literature indicate that humans are exposed to bacteriophage dail y, and bacteriophage are commonly found in humans , with no known adverse effects

. Indeed, humans and other animals routinely consume bacteriophage when they eat food such as meat and cheese

. Several studies have suggested that 100% of the ground beef and chicken meat sold at retail contain various levels of various bacteriophage

. For example, bacteriophage were recovered from 100% of examined fresh chicken and pork sausage samples and from 33% of delicatessen meat samples anal yz ed

. The levels ranged from 3.3

- 4.4x10 10 PFU/100g of fresh chicken, up to 3.5x10 10 PFU/100g of fresh pork, and up to 2.7x10 10 PFU/100g of roast turkey samples

. Bacteriophage recovered were ty picall y in the range of 10 1

- 10 5 PFU/100 g in meats and up to 10 7 PFU/100 g in cheese

. Based on the above and the fact that bacteriophage are host

- specific ; these organisms are not known to pose any human health effects

. Throughout the literature cited by the registrant and other publically available literature, there have been no known adverse effects to humans from inges tion of bacteriophage in food or water

. Accordingl y , the Agency concludes that when Clavibacter michiganensis subsp. m ichiganensis specific bacteriophage are used according to the manner intended, there is a reasonable certainty that no harm will result to humans from allBacteriophage of Clavibacter michiganensis subsp. michiganensis Page 11 of 22

Biopesticides Registration Action Document anticipated dietary

exposures (through food) to any residues resulting from such use. Bacteriophage are ubiquitous in the environment ; therefore, humans and other mammals are regularl y exposed to bacteriophage with no adverse effects reported from ingestion of bacteriophage in the food or water suppl y in the published scientific literature. A literature review show ed bacteriophage are already commonly consumed b y humans via various foods. Bacteriophage may transmit genes for substances that may be toxic or associated with pathogenicity pathogenicity if they can infect a bacterium that contains these genes and they are incorporated into the bacteriophage, usuall y through l ys ogeny , however, bacteriophage are incapable of producin g toxins outside host bacteria and bacteriophage of Clavibacter michiganensis are tested to ensure they cannot infect pathogens that carry toxins or pathogencity factors, and that they

do not lysogenize target plant pathogenic bacteriam thereb y miniminzing any abil ity to acquire harmful genetic material or any sort
. Drinking W

ater Risk Characterization : Bacteriophage of Clavibacter michiganensis subsp. michiganensis are not intended for use in drinking water, nor are the approved uses likely to result in these bacteriophage reaching surface water or ground water that might be used as drinking water

. Furthermore, in the unlikely event that bacteriophage of Clavibacter michiganensis subsp. michiganensis do reach water consumed b y humans, for the many reasons enumerate d above, the Agency concludes that when bacteriophage of Clavibacter michiganensis subsp. michiganensis are used in the manner intended, there is a reasonable certainty that no harm will result to humans from all anticipated dietary exposures (through water) to any residues resulting from such use. . If oral exposure should occur through consumed drinking water, however, EPA concludes that there is a reasonable certainty that no harm will result from exposure to such residues because of the lack of toxicity, infectivity, and or pathogenicity demonstrated in the previously described toxicology submission (see section IV(B)(1)(a) and Table 3 in Appendix A)

. Nonoccupational, Residential Risk Characterization : Since bacteriophage of Clavibacter michiganensis subsp. michiganensis are host specific, the potential for nonoccupational, nondietary

exposures (i.e., dermal and inhalation exposures) to these bacteriophage by the general population, including infants and children, is highly unlikel y . Moreover, the general population, including infants and children, are exposed to bacteriophage daily in food and drinking water with no known adverse effects ever being reported

. Additionally, all proposed uses occur in distinctly

agricultural or c ommercial settings, and there are no proposed uses for residential areas

. The Agency concludes , therefore, that in the unlikely event there is nonoccupational, nondietary exposure to those specific bacteriophage , such exposures would pose no risks to the g eneral population, including infants and children. Nonoccupational exposure is not expected for bacteriophage of Clavibacter michiganensis subsp. michiganensis as all proposed uses occur in distinctly agricultural or commercial settings, and there are no proposed uses for residential areas. **b. Cumulative Effects from Substances with a Common Mechanism of Toxicity**  Section 408(b)(2)(D)(v) of FFDCA requires that , when considering whether to establish, modify , or revoke a tolerance exemption, EPA consider “available information concerning the cumulative effects of [a particular pesticide’s]

... residues and other substances that have a common mechanism of toxicity .”Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 12 of 22

Biopesticides Registration Action Document EPA has not found bacteriophage of Clavibacter michiganensis subsp. michiganensis to share a common mechanism of toxicity with any other substances, and each bacteriophage isolate added to the AgriPhage CMM library is tested for ability to infect closel y related bacteria. Inability to infect bacteria outside the genus Claviba c ter is important to prevent passage of toxic or pathogenic genes to other bacteria b y the bacteriophage

. The registrant has in place limitations for bacteriophage hosts, namely use of onl y non - toxigenic Clavibacter michiganensis subspecies michiganensis (an obligate plant associated bacterium infecting tomatoes) to produce phage, and use of only

l ytic (and not lysogenic) 1 bacteriophage, giving further assurance that toxin production would not even be carried as a trait by these bacteriophage. For the purposes of this tolerance action, therefore, EPA has assumed that bacteriophage Clavibacter michiganensis

_______________________________________________ 1 Lytic bacteriphages only multiply and kill the ir host bacterium by cell lysis at the end of their life cycle. Lysogenic bacteriophage can multiply via the lytic cycle, but usually enter a quiescent state in the host bacterium, and integrate their DNA into the host’s DNA. The host harboring the bacteriophage DNA is not affected by the presence of the bacteriophage’s DNA. When the infected bacterium undergoes normal cell division, t he bacteriophage genes are replicated along with the host’ s, and are passed on to the bacterial “daughter” cells. If the bacteriophage begins to replicate, and brings into its DNA any genes encoding toxins or pathogens, the lysogenic
-type bacteriophage can transmit those genes to other similar host bacteria that otherwise would not pro duce the toxins or pathogenic substances. subsp. michiganensis does not have a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity

and to evaluate the cumulative effects of such chemicals, see EPA’s website at http://www.epa.gov/pesticides/cumulative

. **c. Determination of Safety for the U.S. Population, Infants and Children** FFDCA section 408(b)(2)(C) provides that 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 and 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 safety for infants and children in the case of threshold effe cts to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly

ref erred to as the FQPA Safety Factor. In applying this provision, EPA either retains the default value of 10X or uses a different additional safety factor when reliable data available to EPA support the choice of a different factor. Based on the acute toxic ity and pathogenicity public literature submission summarized in section IV (B)(1)(a) and Table 3 in Appendix A , EPA concludes that there is a reasonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate exposure to the residues of bacteriophage of Clavibacter michiganensis subsp. michiganensis

. This includes all anticipated dietary exposures and all other exposures for which there is reliable information. EPA has arrived at this conclusion because the information available on bacteriophage of Clavibacter michiganensis subsp. michiganensis do es not demonstrate toxic, pathogenic, and/or infective potential to mammals. Thus, there are no threshold effects of concern and, as a result, the provision requiring an additional margin of safety does not apply

.Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 13 of 22

Biopesticides Registration Action Document **3 .**  **Occupational Exposure and Risk Characterization** Handler exposure to bacteri ophage of Clavibacter michiganensis subsp. michiganensis is not expected to pose any undue risk , but appropriate personal protective equipment and precautionary

statements are required on pesticide product labels to mitigate any potential risks to pesticide handlers due to prolonged or numerous exposures. Handlers applying bacteriophage of Clavibacter michiganensis subsp. michiganensis end

-use products in commercial and agricultural settings must wear a long

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

- 95, R
- 95, or P
- 95. Additional PPE, other than the standard described above, may be required on a product

- specific basis. **4 .**  **Human Health Risk Characterization** EPA considered human exposure to bacteriophage of Clavibacter michiganensis subsp. michiganensis in light of the standard for registration in FIFRA and the relevant safety factors in FFDCA. A determination has been made that no unreasonable adverse effects to the U.S. population in general, and to infants and children in particular, will result when bacteriophage of Clavibacter michiganensis subsp. michiganensis pesticide product i s used in accordance with EPA
- accepted labeling. **C .**  **Environmental Assessment (** **40 CFR § 158.2150**  **)** The public literature submitted by the applicant to support the pesticide products containing bacteriophage of Clavibacter michiganensis subsp. michiganensis , are sufficient to fulfill the Tier I nontarget organism data requirements and for risk assessment purposes. Further te sting of nontarget organisms at higher tier levels (i.e., Tiers II, III, and IV) is not required for the current uses and application methods. EPA has performed an environmental risk assessment based on the public literature provided by the applicant and h as determined that the proposed use of bacteriophage of Clavibacter michiganensis subsp. michiganensis does not pose significant risk to nontarget organisms when used according to label directions. For a comprehensive summary of the generic data requirem ents described in sections IV(C)(1), refer to Table 4 in Appendix A

. **1 .**  **Ecological Exposure and Risk Characterization** Since bacteriophage are not capable of infecting eukaryotic cells, it is reasonable to expect those bacteriophage are also not capable of causing infection in eukaryotic organisms. Nontarget bacteria are unlikely

to be adversel y affected , since individual bacteriophage ty pically have a limited host range. Additionally, the applicant has a testing program to ensure pesticidal bacteriophage do not have a broad host range. Bacteriophage are ubiquitous in the environment, and nontarget organisms are regularl y exposed directly to bacteriophage with no adverse effects reported in the published scientific literature. Bacteriophage may carry or transfer genes from bacteria they

infected for substances that may be toxic to nontarget organisms ; however, they are incapable of producing toxins outside of their host bacterium , since they consist solely

of genetic material encapsulated in a protein envelope and do not have the metabolic processes required for toxin production. The applicant has in place limitations for the bacterial hosts, namely use of only nontoxigenic Claviba cter michiganensis subsp. michiganensis to produce the bacteriophageBacteriophage of Clavibacter michiganensis subsp. michiganensis Page 14 of 22

Biopesticides Registration Action Document and use of onl y l ytic (and not lysogenic) bacteriophage, giving further assurance that toxin production would not even be carried as a trait by these bacteriophage. Based on the narrow ho st range of bacteriophage of Clavibacter michiganensis subsp. michiganensis to certain bacterial species , as well as the biological properties of bacteriophage in general, they are not expected to pose any hazard to nontarget terrestrial or aquatic organisms. **2 .**  **Environmental Fate Data** As the information provided for the current uses and application methods is sufficient to both satisfy the Tier I nontarget organism data requirements and for nontarget organism risk asse ssment for bacteriophage of Clavibacter michiganensis subsp. michiganensis , f urther testing at higher tier levels (i.e., Tiers II, III, and IV) is not required

. **3 .**  **Threatened and Endangered**  **Species Assessment** EPA has determined that adverse effects will not occur to nontarget organisms as a result of the proposed labeled applications of bacteriophage of Clavibacter michiganensis subsp. michiganensis

. Since EPA has determined that no effects are anticipated for any nontarget species exposed to bacteriophage of Clavibacter mich iganensis subsp. michiganensis as a result of the proposed labeled applications, effects to federally listed , threatened and endangered species and their designated critical habitats 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 proposed uses of bacteriophage of Clavibacter michiganensis subsp. michiganensis , 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 from 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 decision

- making process; and (4) the decision

- makers se ek 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, EPA seeks 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 bacteriophage of Clavibacter michiganensis subsp. michiganensis , 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.Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 15 of 22

Biopesticides Registration Action Document 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** Pursuant to Section 3(c)(5) of FIFRA, EPA may registered a pesticide provided that all the following determinations 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 unreasonable adverse effects on the environment; AND (4) When used in accordance with widespread and commonly recognized practice, it will not generall y cause unreasonable adverse effects on the environment. With respect to criterion 1, the proposed pesticide product containing bacteriophag e of Clavibacter michiganensis subsp. michiganensis has well

- known properties. EPA has no knowledge that would contradict the claims made on the AgriPhage CMM label , and the pesticide product is not expected to cause unreasonable adverse effects on the environment when used according to the label instructions. Regarding c riterion 2 , the current product label, as well as the data and information presented in this document , comply with the requirements of FIFRA

. It is believed that bacteriophage Clavibacter m ichiganensis subsp. michiganensis pesticide product will not cause any unreasonable adverse effects on the environment, and AgriPhage CMM is likely

to provide protection against bacterial canker disease on tomatoes as claimed, thus satisfying criterion 3. Criterion 4 is satisfied in that bacteriophage Clavibacter michiganensis subsp. michiganensis pesticide product is not expected to cause unreasonable adverse effects when used according to label instructions. AgriPhage CMM , containing bacteriophage of Clavibacter michiganensis subsp. michiganensis as a new active ingredient, is eligible for registration under FIFRA section 3(c)(5) for the labeled uses. **V I**  **I .**  **ACTIONS REQUIRED BY THE REGISTRANT**  **A .**  **Final Printed Labeling** Before releasing AgriPhage CMM for shipment, the registrant is required to provide appropriate final printed labeling to EPA
. **B .**  **Terms of Registration** EPA has determined the following terms must be met for the registration of bacteriophage of Clavibacter michiganensis subsp. michiganensis as a new microbial active ingredient. 1. A new Storage Stability Study (OCSPP 830.6317) of bacteriophage of Clavibacter michiganensis subsp. michiganensis must be submitted within one (1) year of registration to support the labeled viability claim of the product. The original storage stability study submitted was found to be ACCEPTABLE, but a substantial decline of PFU/mL occurred after the first 120 days o f the study. The new study will verify the viability claim of the product.Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 16 of 22

Biopesticides Registration Action Document
2. A new 5
-batch analysis (OCSPP 830.1400) to support a change in manufacturing site must be submitted within one (1) ye ar of registration to support the integrity of pesticide products produced at the new facility

. **C .**  **Reporting of Adverse Effects and Hypersensitivity 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 pesticide product. A brief summary of these types of data are described below. Reports of all incidents of adverse effects to the environment must be submitted to EPA under the provisi ons stated in FIFRA section 6(a)(2). Additionally, all incidents of hy persensitivity (including both suspected and confirmed incidents) must be reported to EPA under the provisions of 40 CFR § 158.2140(d).Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 17 of 22

Biopesticides Registration Action Document **VIII .**  **GLOSSARY OF ACRONYMS AND ABBREVIATIONS**  BPPD Biopesticides and Pollution Prevention Division BRAD Biopesticides Registration Action Document CFR Code of Federal Regulations cP centipoise EDSP Endocrine Disruptor Screening Program EP end

-use product EPA Environmental Protection Agency (the “Agency”) FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FR Federal Register g/mL gram per milliliter MP manufacturing

-use product MRID No. Master Record Identification Number NI OSH National Institute for Occupational Safety and Health OCSPP Office of Chemical Safety and Pollution Prevention OPP Office of Pesticide Programs PC Code Pesticide Chemical Code PFU Plaque Forming Unit PP Pesticide Petition PPE personal protective equipment TGAI technical grade of the active ingredientBacteriophage of Clavibacter michiganensis subsp. michiganensis Page 18 of 22

Biopesticides Registration Action Document **IX .**  **BIBLIOGRAPHY A**  **. Submitted**  **Studies** MRID No. Study

Title 47720400 Interregional Research Project No. 4 (2009) Submission of Product

Chemistry , Toxicity , and Residue Data in Support of the Application for Registration of Agriphage

- CMM, and the Petition for Tolerance of Bacteriophage of Clavibacter michiganensis subsp. michiganensis for Use on Tomatoes. Transmittal of 3 Studies. 47720401 Walbeck, A. (2009) Product Chemistry : Bacteriophage of Clavibacter

michiganensis subsp. michiganensis

– AgriPhage

- CMM. Project Number: 0430B. Unpublished study prepared by

OmniLy tics, Inc. 295 p. 47720402 Walbeck, A.; Braverman, M. (2009) Rationale for Waiver of Toxicity

and Residue Data Requirements: Bacteriophage of Clavibacter michiganensis subsp. michiganensis

- AgriPhage

- CMM. Project Number: 0430B. Unpublished study prepared by

OmniLy tics, Inc. 175 p. 47720403 Walbeck, A.; Braverman, M. (2009) Rationale for Waiver of Non Target

Organism Testing Requirements: Bacteriophage of Clavibacter michiganensis subsp. michiganensis

– AgriPhage

- CMM. Project Number: 0430B. Unpublished study prepared by

OmniLy tics, Inc. 169 p. 48053600 Omnily

tics, Inc. (2010) Submission of Product Chemistry D ata in Support of the Application for Registration of AgriPhage

- CMM. Transmittal of 1 Study

. 48053601 Blum , K. (2010) Product Anal ys is Test Guidelines: AgriPhage

- CMM.

Project Number: IR/4/PR/0430B. Unpublished study p repared by Omnily tics, Inc. 335 p. 48383100 OmniLy

tics, Inc. (2011) Submission of Product Chemistry D ata in Support of the Application for Regis tration of AgriPhage

- CMM. Transmittal of 1 Study

. 48383101 Blum, K. (2010) Product Anal ys is Test Guidelines: AgriPhage

- CMM.

Project Number: IR

/4/PR/430B. Unpublished study p repared by OmniLy tics, Inc. 327 p. **B .**  **Environmental Protection Agency and Pest Management Regulatory Agency**  **Risk Assessment Memoranda**  PMRA. 2011a. Avian Oral; Avian Pulmonary , Inhalation or Injection; Fish: Freshwater; Arthropods: Terrestrial; Arthropods: Aquatic; Non
- Arthropod invertebrates: Terrestrial; Non
- Arthropod invertebrates: Aquatic; Plants: Terrestrial; Plants: Aquatic ─ Waiver Request Sub. No
. 2009
- 1066/ OmniLy tics In c. [OMT] Lytic bacteriophage of Clavibacter michiganensis subsp. michiganensis [TOM]
. Data Evaluation Record from J. Ptasinski signed March 25, 2010 and J.V. Gagliardi signed June 2, 2011.Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 19 of 22

Biopesticides Registration Action Document
U.S. EPA. 20 11 b

. Bacteriophage of Clavibacter michiganensis subsp. michiganensis

– AgriPhage CMM
. Memorandum from J.V. Gagliardi , and J
. Ptasinski to A
. Gross dated May 25 , 2011
. U.S. EPA. 2011c
. Human Health and Environmental Risk Assessment of Bacteriophage of Clavibacter michiganensis subsp. michiganensis (PC Code: 228983 )

. Memorandum from J.V. Gagliardi to A. Gross dated Jun e 30 , 2011.Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 20 of 22

Biopesticides Registration Action Document

**A PPENDIX**  **A .**  **MICROBIAL PESTICIDES DATA REQUIREMENTS**

**(40 CFR PART 158** 

**– SUBPART**  **V )**  **TABLE 1 .**  **Product Analysis**  **Data Requirem ents for**  **Bacteriophage of**  **Clavibacter michiganensis subsp.**  **michiganensis ,**  **AgriPhage CMM (40 CFR § 158.2**  **120 )**  **OCSPP Guideline**  **Number Data Requirement**  **Results MRID No.**  885.1100 Product Identity Submitted data fulfill the requirement for product identity. 477204
- 01 480536
- 01 483831
- 01 885.1200 Manufacturing Process Submitted data fulfill the requirement for manufacturing process. 477204
- 01 480536
- 01 483831
- 01 Not applicable Deposition of a Sample

in a Nationally Recognized Culture Collection Not applicable

- Enforcement Analytical Method was

conducted in lieu of Depositing a Sam ple in a Nationally Recognized Culture Collection 885.1300 Discussion of Formation

of Unintentional Ingredients Submitted data fulfill the requirement for discussion of

formation of unintentional ingredients. 477204
- 01 480536
- 01 483831
- 01 885.1400 Analysis of Samples Submitted data fulfill the requirement for analysis of samples. 477204
- 01 480536
- 01 483831
- 01 885.1500 Certification of Limits Limits listed on the confidential statement of f ormula are adequate/acceptable. **Additional Studies** 830.1800 Enforcement Analytical Method Submitted data fulfill the requirement for an enforcement

analytical method. 477204
- 01 480536
- 01 483831
- 01 **TABLE 2**  **. Physical and Chemical Characteristics for**  **Bacteriophage of Clavibacter michiganensis**  **subsp. michiganensis**  **, AgriPhage CMM**  **(40 CFR § 158.2120) OCSPP**  **Guideline Number**  **Data Requirement Results**  **MRID No.** 830.6302 Color Golden Yellow 477204
- 01 830.6303 Physical State Liquid 477204
- 01 830.6304 Odor None to slight 477204
- 01 830.6313 Stability to Normal and Elevated Tem peratures, Metals, and Metal Ions Not applicable 477204
- 01

830.6317 Storage Stability At least one year at 4°C 477204
- 01 830.6319 Miscibility Com pletely miscible in water 477204
- 01 830.6320 Corrosion

Characteristics Not corrosive 477204
- 01 830.7000 pH 5.3
- 6.2 477204
- 01 830.7100 Viscosity 0.90 cP at 21°C 477204
- 01 830.7300 Density/Relative

Density/Bulk Density (Specific Gravity) 1.002
- 1.006 g/mL 477204
- 01Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 21 of 22

Biopesticides Registration Action Document

**T ABLE**  **3 .**  **Toxicology Data Requirements for AgriPhage CMM**  **(40 CFR § 158.2140) OCSPP Guideline**  **Number Data Requirement**  **Results MRID No.**  **Tier I** 885.3050 Ac ute Oral

Toxicity/Pathogenicity Fulfilled by public literature showing that bacteriophage are viruses that only infect specific bacteria. Bacteriophage are present in high numbers in the environment and non-polluted waters and there have been no reports of adverse effects from exposure. **Classification: Acceptable** 477204
- 02 885.3150 Ac ute Pulmonary

Toxicity/Pathogenicity 885.3200 Ac ute Injection

Toxicity/Pathogenicity (Intravenous) 885.3400 Hy

persensitivity Incidents No hypersensitivity incidents, including immediate

- ty pe or delayed

- ty

pe reactions of

humans and domestic animals that occurred during research, development, or testing of the AgriPhage CMM , were reported by the applicant. Any future hypersensitivity incidents must be reported per OCSPP Guideline 885.3400. 885.3500 Cell Culture Fulfilled by public literature showing that bacteriophage are viruses that only infect specific bacteria. Bacteriophage are present in high numbers in the environment and non-polluted waters and there have been no reports of adverse effects from exposure . **Classification: Acceptable** 477204
- 02 870.1100 Ac ute Oral Toxicity 870.1200 Ac ute Dermal Toxicity 870.1300 Ac ute Inhalation

Toxicity 870.2400 Ac ute Eye Irritation **Tiers II and III** Not required for bacteriophage of Clavibacter michiganensis subsp. michiganensis based on the lack o f acute toxicity/pathogenicity demonstrated in public literature that satisfied the Tier I requirements

.
**TABLE 4 .**  **Nontarget Organism Toxicity and Environmental Fate Data Requirem ents**  **for Bacteriophage of**  **Clavibacter**

**michiganensis subsp.**  **michiganensis ,**  **AgriPhage CMM (40 CFR § 158.2150)**  **OCSPP Guideline Number**  **Data Requirement Results**  **MRID No. Tier I**  885.4050 Avian Oral Toxicity Fulfilled by p ublic literature showing that that, since bacteriophage are not capable of infecting eukaryotic cells, it is reasonable to expect that bacteriophage are also not capable of causing infection in eukaryotic organisms. Nontarget bacteria are unlikely to be adversely affected since individual bacteriopha g e ty pical ly have a limited host range amongst bacteria and it is uncommon for a bacteriophage to be able to infect outside of a bacterial species. Additionally, the registrant has a testing program to ensure pesticidal bacteriophage do not have a broad host range. **Classification: Acceptable** 477204
- 03 885.4100 Avian Inhalation

Toxicity/Pathogenicity 885.4150 Wild Mammal

Toxicity/Pathogenicity 885.4200 Freshwater Fish

Toxicity/Pathogenicity 885.4240 Freshwater Invertebrate

Toxicity/Pathogenicity 885.4280 Estuarine/Marine Fish and

Invertebrate Testing 885.4300 Nontarget Plant Testing 885.4340 Nontarget Insect Testing 885.4380 Honey Bee Testing **Tiers II, III, and IV** Not required for bacteriophage of Clavibacter michiganensis subsp. michiganensis based on the current uses and application methods.Bacteriophage of Clavibacter michiganensis subsp. michiganensis Page 22 of 22

Biopesticides Registration Action Document

**APPENDIX B .**  **PESTICIDE PRODUCT**
**EPA File Sym** **bol Registration** 

**Name Percentage** 

**Active Ingredient**  **Formulation**

**Type Use Site(s)**  **Method(s) of Application**  **Application**

**Rate Target** 

**Pest** 67986
- A AgriPhage

CMM 0.0 00 5% End Use To mato Seedling Treatment (4 leaf stage) (Foliar Spray or Hydroponic) 1 pint of

AgriPhage

CMM/ 12
- 25 gallons of water per 9600 ft2 greenhouse space Bacterial

Canker Disease

Hydroponic Greenhouse Treatment 1/2 to 1 quart

of Agriphage

CMM/ 12
- 25 gallons of water per 9600 ft2 greenhouse space Field Treatment (Foliar Spray) 1
- 2 pints of

AgriPhage

CMM/ 50
- 100 gallons of water/acre for field applications