Bacillus pumilus strain GHA 180 Page 1 of 27 Biopesticides Registration Action Document

BIOPESTICIDES REGISTRATION ACTION DOCUMENT



### Bacillus pumilus strain GHA 180 Pesticide Chemical (PC) Code: 016485

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

March 12, 2012Bacillus pumilus strain GHA180 Page 2 of 27 Biopesticides Regis tration Action Document

TABLE OF CONTENTS

I. EXECUTIVE SUMMAR Y

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

II. ACTIVE INGREDIEN T OVERVIEW

................................ ................................ ................. 5

III. REGULATORY BACKGROUN D

................................ ................................ ....................... 5

A. Applications for Pesticide Registration

................................ ................................ ................................ ................ 5

B. Food Tolerance Exemption

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

IV. RISK ASSESSMENT

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

A. Product Analysis Assessment (40 CFR § 158.2120)

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

B. Human Health Assessment (40 CFR § 158.2140)

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

C. Environmental Assessment (40 CFR § 158.2150)

................................ ................................ .............................. 12

V. ENVIRONMENTAL JU STICE

................................ ................................ .......................... 12

VI. RISK MANAGEMENT DECISION

................................ ................................ .................. 13

VII. ACTIONS REQUIR ED BY THE REGISTRANT

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

VIII. GLOSSARY OF A CRONYMS AND ABBREVIA TIONS

................................ ........... 15

A. Studies Submitted to Support the Bacillus pumilus GHA180 Pesticide Product Re gistrations

.................. 16

B. Environmental Protection Agency Risk Assessment Memoranda

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

C. Other References

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

APPENDIX A. MICROBI AL PESTICIDES DATA R EQUIREMENTS

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

APPENDIX B. PESTICI DE PRODUCTS

................................ ................................ ............... 27Bacillus pumilus strain GHA180 Page 3 of 27 Biopesticides Regis tration Action Document

BIOPESTICIDES REGISTRATIO N ACTION DOCUMENT TEAM

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

Microbial Pesticides Branch

Science Reviews

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

John L. Kough, Ph.D. Product Analysis, Human Health

Gail Tomimatsu , Ph.D. Environmental Effects

Regulations

Sheryl K. Reilly, Ph.D. Chief, Microbial Pesticides Branch Alan Reynolds Team Leader, Microbial Pesticides Branch

Susanne Cerrelli Regulatory Action LeaderBacillus pumilus strain GHA180 Page 4 of 27 Biopesticides Regis tration Action Document

I. EXECUTIVE SUMMARY

Bacillus pumilus strain GHA180 is a new microbial active ingredient discovered in an apple tree rhizosphere in Mexico. This active ingredient is a bacteri um that produces metabolites that suppress the fungal plant pathogens Pythi um ultimum, Fusarium oxysporum, Rhizoctonia solani

and Alternaria spp

. This bacterium colonizes plant roots, forming a biofilm.

Premier Horticulture Ltd. h as proposed to register t hree end

- use pesticide product s (EPs) :

**•** GHA 180 Biological Fungicide

, an a queous suspension, to incorporate into peat moss or growing media or as a soil drench in greenhouses and enclosed nurseries to suppress plant pathogens that attack root systems

. ( Contain s 0.37 % Bacillus pumilus strain
GHA180, a minimum of 1 x 10 9 viable s pores/ml)

**•** Pro

- Mix GHA180 and Pro

- Mix Tandem. B o th Pro

- Mix products are a series of growing media formulations that contain Bacillus pumilus strain GHA180 to suppress plant pathogens that attack root systems. (Both Pro

- Mix products contain Bacillus pumilu s strain GHA180 at 0.001%, with a minimum of 5 x 10 4 viable spores per a gram

of media

. )

P ro

- M ix GHA180 and Pro

- Mix Tandem are each formulated into eight different custom blended growing mixes: BX, HP, TA, FPX, MPX, PGX, VFT and BRK Blends . There are 16 di fferent blended growing mixes in total

.

Environmental Protection Agency (EPA) scientists have reviewed product analysis, toxicology, and nontarget organism data and information (40 Code of Federal Regulations (CFR) §§ 158.2120, 158.2140, and 158.2150, re spectively) submitted to support the registration of th e three proposed Bacillus pumilus strain GHA 180 products

. Overall, these data and information are adequate for risk assessment purposes , fulfill current data requirements

, and allow for registration u nder Section 3(c)(5) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)

.

Acceptable guideline studies to support the proposed use of these products fulfilled p roduct analysis data requirements for Bacillus pumilus strain GHA 180 , including product chemistry and composition, analysis of samples, and physical and chemical characteri stics

.

Adequate mamm alian toxicology data and information were submitted to support Bacillus pumilus strain GHA 180 pesticide products.

EPA has concluded 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 Bacillus pumilus strain GHA 180. No dietary risks are expected from use of Bacillus pumilus str ain GHA

180 as an active ingredient in pesticide products.

The proposed use sites for Bacillus pumilus strain GHA180 are limited to greenhouse and

contained nurseries . I t was determined that the use sites for Bacillus pumilus strain GHA180 on the proposed labels would not result in significant nontarget species exposure and did not trigger the nontarget and environmental fate date requirements under 40 CFR § 158.2150

.Bacillus pumilus strain GHA180 Page 5 of 27 Biopesticides Regis tration Action Document

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. Under this polic y, EPA provide s a public comment period prior to making a registration decision for 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 be lieves there may be significant public interest.

Consistent with the policy of making registration actions more transparent, the proposed

re gistration and first food use of pe sticide products containing the new active ingredient

, Bacillus pumilus strain GHA 180, were subject to a 30

- day comment period. During this comment period, no comments w ere received

. T he registration s of this new active ingredient includes the

first food use for Bacillus pumilus strain GHA 180. The Agency’s risk assessments and

c onclusions that the standards for registration under FIFRA section 3(c)(5) have been met for the proposed active ingredient, Bacillus pumilus strain GHA 180 and are provided in this

B iopesticide Registration Action Document ( BRAD)

.

II. ACTIVE INGREDIEN T OVERVIEW

Biological Name: Bacillus pumilus strain GHA 180

Culture Deposit: International Depository Authority of Canada, under the reference

number IDAC No. 260707

- 01

OPP Chemical Code: 016485

Type of Pesticide: Microbial Pesticide

– Fungi cide

See Appendix B for specific information (e.g., use sites, application rate s , methods of application, formulation type s , and target pests) regarding the registered pesticid e products containing this active ingredient.

III. REGULATORY BACKGROUND

A. Applications for Pesticide Registration

On February 14, 2010 , Premier Horticulture , (address: 1, avenue Premier, Rivie`re

- du

- Loup, Quebec, Canada G5R6C1 ) submitted applications to register three end

- use products, GHA 18 0 Biological Fungicide (EPA File Symbol 74267

– E), Pro

- Mix GHA 180 (EPA File Symbol 74267

– G) and Pro

- Mix Tandem (EPA File Symbol 74267

– U) under FIFRA section 3

. At that time

Premier Horticulture applied to register GHA 180 Biological Fungicide (EPA File Sym bol

74267

– E) also as a manufacturing product. On November 24, 2010

, EPA announced receipt of

these application s to register pesticide product s containing a new active ingredient ( 75 Fede ral Register (FR) 71698 ) 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

.Bacillus pumilus strain GHA180 Page 6 of 27 Biopesticides Regis tration Action Document

B. Food Tolerance Exemption

Concurrent with its registration application s and u nder Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(d), Premier Horticultur e submitted a petition to establish an exemption from the requirement of a tolerance for Bacillus pumilus GHA180 (Pesticide Petition (PP)
0F7698)

. In the Federal Register of September 30, 2010 ( 75 FR 60452 ), EPA announced that

Premier Horticulture proposed to establish an exemption from the requirement of a tolerance for

residues of the fungicide, Bacill us pumilus GHA180 in or on all agricultural commodities and water systems when applied as described in the draft label and opened a 30

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

IV. RISK ASSESSMENT

In the Federal Registe r 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 6100 2 )

. 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 for each data submission are assigned by EPA science reviewers and i ndicat e the usefu lness 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 what can be provided to change the rating to

“ acceptable .” If there is simply a “ supplemental ” rating, the reviewer often will state that t he study is not required by 40 C FR P art 158. Both “ acceptable” and “supplemental ” studies may be

used in the risk assessm ent process as appropriate. An “unacceptable ” rating indicates that new

data need to be submitted.

For the acu te toxicity data requirements, Toxicity C ategories are assigned based on the hazard(s) identified from studies and/or other infor mation submitte d to EPA in support of a pesticide registration. The active ingredient or particular product is classified as Toxicity Category I, II, III, or IV, where Toxicity Category I indicates the highest toxicity and Toxicity Category IV indicates the lowest toxici ty.

A. Product Analysis Assessment ( 40 CFR § 158.2120 )

Bacillus pumilus strain GHA180 is a new microbial active ingredient discovered in an apple tree rhizosphere in Mexico. This bacteri um produces metabol i tes that suppress the fungal plant pathogens Pythium ultimum, Fusarium oxysporum, Rhizoctonia solani and Alternaria spp. and colonizes plant root s, forming a biofilm

. A ll product analysis data requirements for Bacillus pumilus strain GHA180 were fulfilled to support current use sites . Refer to Tables 1 , 2, 3, 4 , 5,

and 6 in Appendix A for a brief summary of the data requ irements, including both generic and product

- specific information.

B. Human Health Assessment ( 40 CFR § 158.2140 )Bacillus pumilus strain GHA180 Page 7 of 27 Biopesticides Regis tration Action Document

1. Toxicity

All toxicology data requirements for Bacillus pumilus strain GHA180 were fulfilled

. Acceptable Tier I mammalian toxicology data and information support registration of the Bacillus pumilus

strain GHA180 pesticide products

. Furthermore, Tier II and Tier III studies were not required for Bacillus pumilus strain GHA180 b ecause of the lack of acute toxicity/pathogenicity in the Tier I

studies.

For a compr ehensive summary of the generic toxicology data requirements described in sections IV(B)(1)(a) and IV(B)(1)(b), as well as additional product

- specific data submitted to support the individual registrations, refer to Table 7 in Appendix A

.

a. Acute Toxicity/Pathogenicity

– Tier I

Acute Oral Toxicity/ Pathogenicity ( Office of Chemical Safety and Pollution Prevention (OCSPP)
Guideline 885.3050; and Acute Pulmonary Toxicity/Pathogenicity (OCSPP Guideline
885.3150; Master Record Identification Number (MRID No 48005019

. W aiver rationale for a cute o ral and pulmonary toxicity/pathogenicity data requirements w ere submitted by Premier Horticulture Ltd , b ased on the acute injection toxicity and pathogenicity

stud y and the oral, dermal and inhalation acute toxicity study results discussed below

. All of

those tes ts show ed no evidence of infectivity, pathogenicity

, toxicity , or other adverse effects.

EPA determined that in light of these results, adverse effects from exposure to Bacillus pumilus

GHA180 are not expected, and waived the ac ute oral toxicity/pathogenic ity and acute pulmonary

t oxicity/pathogenicity data requirements for this active ingredient. ) :

Thirty young adult rats (15/ sex) were injected intravenously with Bacillus pu milus GHA180 TGAI (1.4×10 10

– 6.0×10 10 CFU/mL) at a dose of 6.8×10 7 CFU/animal . Two control groups (5/sex/treatment) were treated with inactivated Bacillus pumilus GHA180 TGAI

, and saline.The

animals were observed for up to 21 days. Bacterial cell counts w ere made on the blood, liver, kidney, spleen, lungs, mandibular lymph node, brain, and cecum contents of the rats given live

bacteria on study d ays 0, 7, 14 and 21, and on d ay 21 for the control groups. All animals gained weight and a ppeared normal during the study, and n o visible ab nor malities were noted at necropsy. The test organism completely cleared from the blood, kidneys, mandibular lymph nodes and cecum contents of the animals by day 14, and it showed a pattern of clearance but had not completely cleared from the liver and spleen by day 21. No Bacillus pumilus GHA180 was detected in the tissues/ organs of the animals treated with the inactivated test material or the untreated control group. Bacillus pumilus GHA180 was not toxic, infective or pathog enic to rats

when dosed intravenously at 6.8 × 10 7 CFU/animal. This study was classified as Acceptable. Acute Injection Toxicity/Pathogenicity (OCSPP Guideline 885.3200; MRID No. 48005025 ) :

No hypersensitivity incidents, including immediate

- type or delayed

- type reactions of humans

and d omestic animals during research, development, or testing of Bacillus pumilus GHA180 were reported by the applicant . Any future hypersensitivity incidents must be reported per

OCSPP Guideline 885.3400. Hypersensitivity Incidents (OCSPP Guideline 885.3400 ) :

Cell Culture (OCSPP Guideline 885.3500) This study w as not required because Bacillus pumilus strain GHA180 is not a virus (refer to test note #4 of 40 CFR § 158.2140(d)). :Bacillus pumilus strain GHA180 Page 8 of 27 Biopesticides Regis tration Action Document

Acute Oral Toxicity (OCSPP Guideline 870.1100 ; MRID No. 48005020 ) : Using the up and down method, 3 fasted young adult female rats were given a single oral gavage dose of Bacillus pumilus GHA180 TGAI ( 1.4×10 10

– 6.0×10 10 CFU/mL ) at a concentration of 5000 mg/kg body weight (bw), and observed for 14 days. All animals gained weight and appeared normal throughout the study. No visible abnorma lities were found at necropsy. The

LD 50 > 5000 mg/kg bw

. This study was classified as Acceptable; EPA Toxicity Category IV.

Ten young adult rats (5/sex) were exposed to 5050 mg/kg of Bacill us pumilus GHA180 TGAI (1.4×10 10

– 6.0×10 10 CFU/mL ) for 24 hours on a clipped area of skin ( ~10% of the body surface area ), and observed for 14 days. One female died on day 1 ; at necropsy, mottled lungs and a def ormed liver were noted but

not attributed to the test substance. All other animals gained weight and appeared normal during the study. No dermal irritation resulted from exposure to the test material, and observable abnormalities were not found at necropsy

. The LD 50 was > 5050 mg/kg bw. This study was classified as Acceptable; EPA Toxicity Category IV. Acute Dermal Toxicity (OCSPP Guideline 870.1200 ; MRID 48005021 ) :

Groups of young adult rats (5/sex/group) were exposed nose

- only to Bacillus pumilus GHA180 TGAI (1.4×10 10

– 6.0×10 10 CFU/mL ) aero sol for 4 hours at a concentration of 2.18 mg/L, then observed for 14 days. All animals gained weight and appeared normal throughout the study. No abnormalities were

observed at necropsy. The LC 50 > 2.18 mg/L. This study was classified as Acceptable; EPA T oxicity Category IV. Acute Inhalation Toxicity (OCSPP Guideline 870.1300 ; MRID 48005022 ) :

Acute Eye Irritation (OCSPP Guideline 870.2400; MRID 48005023 ) : Three New Zealand White rabbits (2 male, 1 female) were exposed to 0.1 mL of undiluted Bacillus pumilus GHA180 TGAI (1.4x10 10

– 6.0x10 10 CFU/mL ; instilled into the conju nctival sac of the right eye ) and observed for eye irritation at 1, 24, 48, and 72 hours after exposure

. Corneal opacitiy was observed in 1 male at 1 hour post exposure, which cleared by 48 hours. No iritis or conjunctival irritation was noted in any anima l throughout the study. The maximum average score was 17.3 at 1 hour after exposure

. Bacillus pumilus GHA180 TGAI was mildly irritating to the eye

. This study was classified as Acceptable; EPA Toxicity Category I II.

The skin of 3 rabbits (1 male , 2 female ) were exposed to 0.5 mL (under a patch) of Bacillus pumilus GHA180 TGAI (1.4×10 10

– 6.0×10 10 CFU/mL) for 4 hours on an approximately 2.5 × 2.5 cm area of the body surface. The animals w ere observed at 1, 24, 48, and 72 hours after patch removal. Very slight erythema was noted on 1 animal at 1 hour after patch removal ; this cleared by 24 hours. No other rabbit exhibited skin irritation during the study . The primary irritation

index was 0. 1. This study was classified as Acceptable; EPA Toxicity Category IV. Primary Dermal Irritation (OCSPP Guide line 870.2500 ; MRID 480050

- 24 ) :

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 Bacillus pumilus GHA 180 based on the lack of acute toxicity/pathogenicity in the Tier I studies.Bacillus pumilus strain GHA180 Page 9 of 27 Biopesticides Regis tration Action Document

c. Endocrine Disruptors

As required under FFD CA 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 “na turally occurring estrogen, 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 p otential 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 EDSP wh ere 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 quantita tive relationship between the dose and the E, A, or T effect.

Between October 2009 a nd 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 li st of chemicals was selected 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 endocr ine disruptors.

Bacillus pumilus GHA 180 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 pesti cide chemicals. Accordingly, 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 websi te: http://www.epa.gov/endo/

.

2

. Federal Food, Drug, and Cosmetic Act (F FDCA ) Considerations

Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an exemption from the requirement for a tolerance (the legal lim it for a pesticide chemical resi due 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) 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 cons ideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide

chemic al 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 mechanism of toxicity.”

EPA perfo rms a number of analyses to determine the risks from aggregate exposure t o pesticideBacillus pumilus strain GHA180 Page 10 of 27 Biopesticides Regis tration Action Document

residues. First, EPA determines the tox icity of pesticides. Second, EPA examines exposure to the pesticide through food, drinking water, and through other exposures that o ccur as a result of pesticide use in residential settings.

Consistent with s ection 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

rela tionship of thi s 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/pathogenicit y data and information discussed previously and presented in Table 7 in Appendix A , t he data required for a FQPA risk assessment for Bacillus pumilus strain GHA 180 have been fulfilled

. Hence, EPA determined that the exemption is

“safe”.

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 wate r from ground water or surface water and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses).

Dietary Exposure and Risk Characterization : Bacillus spp. including Bacillus pumilus are commonly found in agricu ltural settings (i.e. soils) and are present on fresh produce of all kinds

with no known adverse effects. The Manual of Clinical Microbiology (9 th edition) mentions that dried food such as spices, milk powder and grains often contain large amounts of Bacil lus

spores. Bacillus pumilus has been described as a natural, halotolerant component of fermented

fish sauce and in cocoa bean fermentations (Doyle et. al, 1997)

. Bacillus pumilus strain GHA180 is not known to produce any mammalian toxins

, and no foodborne disease outbreaks associated

with Bacillus pumilus strain GHA180 or foodborne toxin production from Bacillus pumilus

strain GHA180 have been reported. Based on extensive testing of Bacillus pumilus strain

GHA180 TGAI , no toxicity, infectivity, pathogenici ty or other adverse effects from dietary

exposure to Bacillus pumilus strain GHA180 are expected. Even if oral exposure should occur by ingesting harvested fruit vegetables, and/ or tobacco

, EPA concludes that there is a reasonable certainty that no harm w ill result from exposure to such residues because of the lack of toxicity, infectivity, and or pathogenicity in the previously described toxicological studies (see section IV(B)(1)(a) and Table 7 in Appendix A ).

Drinking Water R isk Characterization : Since Bacillus pumilus is naturally present in soils,

exposure to Bacillus pumilus from surface and possibly groundwater can be expected. No adverse effects are expected or have been reported from exposure to Bacillus pumilus through drinking water

. According to the World Health Organization, Bacillus species are often detected in drinking water even after going through acceptable water treatment processes, largely because the spores are resistant to these disinfection processes ( World Health Organization, 2011)

. Should this microbial pesticide be present in drinking water , no adverse effects are expected from exposure to Bacillus pumilus GHA180 through drinking water, based on the results of toxicity studies described in section (B)(1 )(a) and Table 7 in Appendix A

.Bacillus pumilus strain GHA180 Page 11 of 27 Biopesticides Regis tration Action Document

Non

- occupational, Residential Risk Characterization : The use sites for these products include greenhouse and contained nurseries . As stated previously, Bacillus pumilus is naturally present in

man y habitats . B ased on the studies and other information submitted to satisfy data requirements for registration of the end

- use pesticide products containing the active ingredient Bacillus pumilus strain GHA180, no toxicity, infectivity, pathogenicity or o ther adverse effects from

non

- occupational exposure are expected (see section IV(B)(1)(a), above, and Table 7 in Appendix A ).

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

me chanism of toxicity.”

EPA has not found Bacillus pumilus strain GHA180 to share a common mechanism of toxicity with any other substance, and Bacillus pumilus strain GHA180 do es not appear to produce a toxic metabolite as its mode of action against target p est s

. Therefore, f or the purposes of this tolerance action, EPA has assumed that Bacillus pumilus strain GHA180 do es not have a common mechanism of toxicity with other substances. For information on EPA ’s efforts to

determine which chemicals have a common mechanism of toxicity and to evaluate the

cumulative ef fects o f such chemicals, see EPA ’s website at http://www.epa.gov/pesticides/cumulative

.

c. Determination of Safety for the U.S. Population, Inf ants and Children

FFDCA sectio n 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 sectio n 408(b)(2)(C) provides that EPA shall apply an additional tenfold (10X) margin of safety for

infants and children in the ca se of threshold effects to account for prenatal and postnatal toxicity and the complet eness 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 sa fety is commonly referred 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 toxicity and pathogenicity data summarized in section IV(B)(1)(a) and Table

7 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 Bacillus pumilus strain GHA180. This includes all anticipated dietary exposures and all other exposures for which there is reliable information. EPA has arrived at this conclusion because the

data and in formation available on Bacillus pumilus strain GHA180 do es not demonstrate toxic, pathogenic, and/ or infective potential to mammals. Because there are no threshold effects of concern, the provision requiring an additional margin of safety does not apply.Bacillus pumilus strain GHA180 Page 12 of 27 Biopesticides Regis tration Action Document

3. Occupational Exposure and Risk Characterization

Handler exposure to Bacillus pumilus strain GHA180 is not expected to pose any undue risk.

A ppropriate personal protective equipment and precautionary statements are required on pesticide product la bels to mitigate any potential risks to pesticide handlers due to prolonged or numerous exposures. Handlers applying Bacillus pumilus strain GHA180 liquid end

- use products in agricultural settings must wear a long

- sleeved shirt, long pants, socks, shoes,

w aterproof 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

EP A considered human exposure to Bacillus pumilus strain in light of the standard for registration in FIFRA and the relevant safety factors in FFDCA. A determination has been made

that no unreasonab le adverse effects to the U.S. population in general, and to infants and children in particu lar, will result when Bacillus pumilus strain GHA180 pesticide products are used in

accordance with EPA

- approved labeling.

C. Environmental Assessment ( 40 CFR § 158.2150 )

The Agency has performed a n environmental risk assessment for the proposed uses of Bacillus pumilus strain GHA180 . T he proposed use sites for Bacillu s pumilus strain GHA180 were

limited to greenhouse and contained nurseries

. EPA determined that these use sites for Bacillus pumilus strain GHA180 would not result in significant nontarget species exposure and d id not trigger the nontarget and environment al fate date requirements under 40 CFR § 158.2150

. Further testing of nontarget organisms at highe r tier levels (i.e., Tiers II, III, and IV) is not required for the current uses and application methods.

For a comprehensive summary of the generic data requirements described in sections IV(C)(1),

refer to Table 8 in Appendix A

.

1

. Threatened and Endangered Species Assessment

A “No Effect” determination is also made for direct and indirect effects to listed species and their designated critical habitats from proposed uses of Bacillus pumilus strain GHA180 as labeled.

The ex posure of nontarget organisms to Bacillus pumilus strain GHA180 is not expected to

increase the amount of Bacillus pumilus above levels that are found naturally in the environment because the use of products containing this active ingredient are limited to green house and

enclosed nurseries. Further testing of nontarget organisms at higher tier levels is not required.

B ased on the data, literature citations, and data waiver rationale provided by the applicant

, BPPD

has determined that adverse effects to non target organisms are not anticipated from the proposed

uses of Bacillus pumilus strain GHA180

.

V. ENVIRONMENTAL JUSTICE

EPA seeks to achieve environmental justice

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

— with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. FairBacillus pumilus strain GHA180 Page 13 of 27 Biopesticides Regis tration Action Document

treatment means that no group of people, including racial, ethnic, or socioeconomic groups, should bear a dispr oportionate 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) po tentially 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 seek out and facilitate the involvement of those potentially affected. EPA has this goal for all communities and persons

across the Un ited States.

EPA sought information on any groups or segments of the population who, as a result their location, cultural practices, or other factors, may have atypical, unusually high exposure to Bacillus pumilus strain GHA180 compared to the general po pulation. No public comments were received on this particular matter.

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

.

V I

. RISK MANAGEMENT DECISION

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

(1) Its composition is such as to warrant th e 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 us ed in accordance with widespread and commonly recognized practice, it will not generally cause unreasonable adverse effects on the

environment.

To satisfy criterion 1, the Bacillus pumilus strain GHA180 pesticide products have well

- known

pro perties. EPA has no knowledge that would contradict the claims made on the GHA 180 Biological Fungicide

, Pro

- Mix ‘ GHA180’, and Pro

- Mix Tandem EP label s . These products are not expected to cause unreasonable adverse effects on the environment when used acco rding to label instructions. Criterion 2 is satisfied by the current product label s, as well as the data and

information presented in this document. It is believed that the Bacillus pumilus strain GHA180 1 will not cause any unreasonable adverse effects on the environment, and the GHA 180 Biological Fungicide

, Pro

- Mix ‘ GHA180’, and Pro

- Mix Tandem EP s (end

- use product s ) , in particular, are likely to protect against fungal pests as claimed, thereby satisfying criterion 3.

Criterion 4 is satisfied in that the Bacillus pumilus strain GHA180 pesticide products are not expected to cause unreasonable adverse effects when used according to label instructions. Therefore, the GHA 180 Biological Fungicide, Pro

- Mix ‘ GHA180’, and Pro

- Mix Tandem (all containing Bacillus p umilus strain GHA180 as a new active ingredient ) are eligible for registration under FIFRA section 3(c)(5) for labeled uses. If the applicant proposes uses that are

more extensive in the future (e.g., outdoor or aquatic applications )

, EPA will likely requ ire that

additional data be submitted in conjunction with a registration amendment request

.Bacillus pumilus strain GHA180 Page 14 of 27 Biopesticides Regis tration Action Document

V I I

. ACTIONS REQUIRED BY THE REGISTRANT

A. Final Printed Labeling

Before releasing pesticide products containing Bacillus pumilus strain GHA180 for shipment, th e registrant is required to provide appropriate final printed labeling to EPA

.

B . 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 provisions stated in FIFRA section 6(a)(2). Additionally, all incidents of hypersensitivity (including both suspected and confirmed incidents) must be reported to EPA under the provisions of 40 CFR § 158.2140(d).Bacillus pumilus strain GHA180 Page 15 of 27 Biopesticides Regis tration Action Document

V III. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

ASAE American Society of Agricultural Engineers

BPPD Biopesticides and Pollution Prevention Division

BRAD Biopesticides Registration Action Document

bw body weight of animal

CFR Code of Federal Regulations

c fu colony

- forming unit (s) cfu/kg colony

- forming units per kilogram

cfu/mL colony

- forming unit s per milliliter

cP centipoise

DSMZ Deutsche Sammlung von Mikroorganismen und Zellkulturen (the German Strain Collection for Microorganisms)

EDSP Endocrine Disrupto r 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 p er milliliter

LC 50 median lethal concentration. A statistically derived concentration of a substance that can be expected to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume of water, air, or feed (e.g., mg/L, mg/kg, or ppm).

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

MP manufacturing

- use product

MRID No. Master Record Identification Number

NIOSH National Institute for Occupational Safety and Health

NR RL Northern Regional Research Laboratory

OCSPP Office of Chemical Safety and Pollution Prevention

OPP Office of Pesticide Programs

PC Code Pesticide Chemical Code

PP Pesticide Petition

PPE personal protective equipment

ppm parts per million

TGAI technica l grade of the active ingredient

ULV ultra low volumeBacillus pumilus strain GHA180 Page 16 of 27 Biopesticides Regis tration Action Document

I X. BIBLIOGRAPHY

A. Studies Submitted to Support the Bacillus pumilus GHA180 Pesticide Product Registrations

MRID Citation Reference

48005000 Premier Horticu lture (2010) Submission of Product Chemistry and Toxicity Data in Support of the Application for Registration of GHA 180, Pro

- Mix GHA 180,

and Pro

- Mix Tandem and the Petition for Tolerance of Bacillus pumilus GHA

180. Transmittal of 25 Studies.

48005001 Libman, G. (2009) Product Chemistry for ( Bacillus pumilus GHA 180). Unpublished study prepared by Premier Tech, Ltd. 33 p.

48005002 Libman, G. (2009) Product Chemistry for PRO

- MIX 'BX' Tandem. Project Number: PHL/LA/WI/137E3/USA. Unpublished study prepare d by Premier Tech, Ltd. 77 p.

48005003 Libman, G. (2010) Product Chemistry for Pro

- Mix GHA 180 'BX' Blend. Unpublished study prepared by Premier Tech, Ltd. 89 p.

48005004 Libman, G. (2010) Product Chemistry for Pro

- Mix GHA 180 'HP' Blend. Unpublished stu dy prepared by Premier Tech, Ltd. 80 p.

48005005 Libman, G. (2010) Product Chemistry for Pro

- Mix GHA 180 'TA' Blend. Unpublished study prepared by Premier Tech, Ltd. 92 p.

48005006 Libman, G. (2010) Product Chemistry for Pro

- Mix GHA 180 'FPX' Blend. Unpu blished study prepared by Premier Tech, Ltd. 90 p.

48005007 Libman, G. (2010) Product Chemistry for Pro

- Mix GHA 180 'MPX' Blend. Unpublished study prepared by Premier Tech, Ltd. 80 p.

48005008 Libman, G. (2010) Product Chemistry for Pro

- Mix GHA 180 'PGX' Blend. Unpublished study prepared by Premier Tech, Ltd. 92 p.

48005009 Libman, G. (2010) Product Chemistry for Pro

- Mix GHA 180 'VFT' Blend. Unpublished study prepared by Premier Tech, Ltd. 92 p.

48005010 Libman, G. (2010) Product Chemistry for Pro

- Mix G HA 180 'BRK' Blend. Unpublished study prepared by GNL Consultation Services and Premier Tech, Ltd. 80 p.

48005011 Libman, G. (2010) Product Chemistry for Pro

- Mix Tandem 'BX' Blend. Unpublished study prepared by Premier Tech, Ltd. 126 p.

48005012 Libman, G. (2010) Product Chemistry for Pro

- Mix Tandem 'HP' Blend. Unpublished study prepared by Premier Tech, Ltd. 118 p.

48005013 Libman, G. (2010) Product Chemistry for Pro

- Mix Tandem 'TA' Blend. Unpublished study prepared by Premier Tech, Ltd. 94 p.

48005014 Libman, G. (2010) Product Chemistry for Pro

- Mix Tandem 'FPX' Blend. Unpublished study prepared by Premier Tech, Ltd. 92 p.

48005015 Libman, G. (2010) Product Chemistry for Pro

- Mix Tandem 'MPX' Blend. Unpublished study prepared by Premier Tech, Ltd. 82 p.Bacillus pumilus strain GHA180 Page 17 of 27 Biopesticides Regis tration Action Document

48005016 Libman, G. (2010) Product Chemistry for Pro

- Mix Tandem 'PGX' Blend. Unpublished study prepared by Premier Tech, Ltd. 94 p.

48005017 Libman, G. (2010) Product Chemistry for Pro

- Mix Tandem 'VFT' Blend. Unpublished study prepared by Premier Tech, Ltd. 94 p.

48005018 Libman, G. (2010) Product Chemistry for Pro

- Mix Tandem 'BRK' Blend. Unpublished study prepared by Premier Tech, Ltd. 77 p.

48005019 Libman, G. (2010) Waiver Request for Microbial Pesticide Data Requirements: Bacillus pumilus GHA 180 a nd Formulated Products. Unpublished study prepared by Premier Horticulture. 35 p.

48005020 Kuhn, J. (2009) Acute Oral Toxicity Study (UDP) in Rats: Bacillus Pumilus

GHA

- 180 TGAI: Amended Final Report. Project Number: 11547/08. Unpublished study prepared b y Stillmeadow, Inc. 12 p.

48005021 Kuhn, J. (2010) Acute Dermal Toxicity Study in Rats: Bacillus pumilus GHA

- 180 TGAI: Amended Final Report. Project Number: 11548/08. Unpublished study prepared by Stillmeadow, Inc. 15 p.

48005022 Carter, L. (2009) Acute Inhalation Toxicity Study in Rats: Bacillus pumilus GHA

180 TGAI: Amended Final Report. Project Number: 11549/08. Unpublished study prepared by Stillmeadow, Inc. 19 p.

48005023 Kuhn, J. (2009) Acute Eye Irritation Study in Rabbits: Bacillus pumilus GHA

- 18 0 TGAI: Amended Final Report. Project Number: 11550/08. Unpublished study prepared by Stillmeadow, Inc. 18 p.

48005024 Kuhn, J. (2009) Acute Dermal Irritation Study in Rabbits: Bacillus pumilus GHA

180 TGAI: Amended Final Report. Project Number: 11551/08. Unpublished study prepared by Stillmeadow, Inc. 13 p.

48005025 Monds, K. (2009) Acute Intravenous Toxicity/Pathogenicity Study in Rats with a Microbial Pest Control Agent (MPCA): Bacillus pumilus GHA

- 180 TGAI: Amended Final Report. Project Number: 11552/ 08. Unpublished study prepared by Stillmeadow, Inc. 21 p.

48391500 Premier Horticulture, Inc. (2011) Submission of Product Chemistry Data in Support of the Applications for Registration of GHA 180 Biological Fungicide,

Pro

- Mix GHA 180 and Pro

- Mix Tandem. Transmittal of 1 Study.

48391501 Libman, G. (2011) Addendum to Product Process Bacillus pumilus GHA 180 and Formulated Products: Addendum to MRID 48005001. Unpublished study prepared by: GNL Consultation Services and Premier Horticulture, Inc. 12 p.

4853 7300 Premier Horticulture, Inc. (2011) Submission of Product Chemistry Data in Support of the Application for Registration of Pro

- Mix GHA 180, GHA 180 Biological Fungicide and Pro

- Mix Tandem. Transmittal of 2 Studies.

48537302 Libman, G. (2011) Clarificat ion about Storage Stability Data of Promix GHA 180 and Promix Tandem. Unpublished study prepared by Premier Horticulture, Ltd. 8 p.

. 48537303 Libman, G. (2011) Microbiological Analyses: Certificates of Analysis for GHA

-Bacillus pumilus strain GHA180 Page 18 of 27 Biopesticides Regis tration Action Document

180. Project Number: STIS/10109. Un published study prepared by Premier Horticulture, Ltd. 8 p.

48559501 Libman, G. (2011) 16S rRNA Gene Sequence and DNA Fingerprinting of the GHA 180 Bacterial Strain. Project Number: 1104081623E. Unpublished study prepared by GNL Consultation Services and Premier Horticulture, Inc. 32p.

48559502 Libman, G. (2011) Product Chemistry for (Bacillus pumilus GHA180). Project Number: PHL/LA/WI/128E2. Unpublished study prepared by GNL Consultation Services. 31p.

B. Environmental Protection Agency Risk Asse ssment Memoranda

U.S. EPA. 2011a

. Bacillus pumilus strain GHA180. Memorandum from Joel V. Gagliardi, Ph.D., and J. L. Kough, Ph.D., to S. Cerrelli dated March 22, 2011

U.S. EPA. 2011b. Bacillus pumilus strain GHA180. Review of deficiency responses.

Mem orandum from Joel V. Gagliardi, Ph.D., and J. L. Kough, Ph.D., to S. Cerrelli dated October
20, 2011.

C. Other References

Aunpad, R. and K. Na

- Bangchang . 2007. Pumilicin 4, a novel bacteriocin with anti

- MRSA and

anti

- VRE activity produced by newly isolated bacteria Bacillus pumilus strain WAPB4. Curr.

Microbiol. 55(4):308

- 13.

Babana, A.H., H. Bathily, F. Samaké, K. Maïga, D. Traoré and A. Dicko. 2011. Microbiological Control of Bacterial Soft Rot Caused by Bacillus pumilus Od23 on Potato. British Mic robiology Research Journal 1(3): 41

- 48.

Banerjee C ., C.I. Bustamante , R. Wharton , E. Talley and J.C. Wade . 1988. us Bacillus infections in patients with cancer. Arch. Intern. Med. 148(8):1769

- 74.

Bathily, H., A.H. Babana and F. Samaké. 2010. Bacillus pumilus, a new pathogen on potato tubers in storage in Mali. African Journal of Microbiology Research 4(20):2067

- 2071.

Bentur H.N

., A.M. Dalzell and F.A. Riordan . 2007. Central venous catheter infection with Bacillus pumilus in an immunocompetent child: a case report. Ann. Clin. Microbiol. Antimicrob. 6(1):12.

Bottone, E.J. and R.W. Peluso. 2003. Production by Bacillus pumilus (MSH) of an antifungal compound that is active against Mucoraceae and Aspergillus species: preliminary report. J. Med.

Microbiol. 52: 69

- 74

.

Doyle, M.P., L.R. Beuchat and T.J. Montville. 1997. Food Microbiology: Fundamentals and Frontiers. American Society for microbiology, Washington, D.C.

Farhat H ., E. Chachaty

, S. Antoun

, G. Nitenberg and J.R. Zahar . 2008. Two cases of BacillusBacillus pumilus strain GHA180 Page 19 of 27 Biopesticides Regis tration Action Document

infection and immunodepression. Med. Mal. Infect. 38(11):612

- 4.

Font, M.I., D.D.M. Bassimba, M.C. Cebrián, L.M. Molina and C. Jordá. 2009. First report

of Bacillus pumilus on Phaseolus vulgaris in Spain. New Disease Reports 19:54.

From, C

., V. Hormazabal and P.E. Granum . 2007. Food poisoning associated with pumilacidin

producing Bacillus pumilus in rice. Int. J. Food Microbiol. 115(3):319

- 24.

From C ., R. Pukall , P. Schumann , V. Hormazábal and P.E. Granum . 2005. Toxin

- producing ability

among Bacillus spp. outside the Bacillus cereus group. Appl. Environ. Microbiol. 71(3):1178

- 83.

Galal, A.A., A.A. El

- Bana and J. Janse. 2006. Bacillus pumilus, A New Pathogen on Mango Plants. Egyptian Journal of Phytopathology. 34(1):17

- 29.

Kramer, J.H. and R.J. Gilbert. 1989. Bacillus cereus and other Bacillus species, p. 21

- 70. In M.P. Doyle (ed.), Foodborne Pathogens. Marcel Dekker, Inc., New York.

Meyer, A. and O. Gottheil.1901. In: Gottheil, O. Botanische beschreibung einiger bodenbakterien.

Zentralbl. Bakteriol. Parasiten kd. Infektionskr. Hyg. Abt. II 7:680

- 691.

Murray, P.R, et al., Manual of Clinical Microbiology. Washington

, D. C. : ASM Press; 9th edition,

2007.

Naruse N ., O. Tenmyo , S. Kobaru , H. Kamei , T. Miyaki , M. Konishi and T. Oki . 1990. Pumilacidin, a complex of new antiviral antibiotics. Production, isolation, chemical properties, structure and biological activity. J. Antibiot. (Tokyo) 43(3):267

- 80.

Ozkocaman V ., T. Ozcelik , R. Ali , F. Ozkalemkas , A. Ozkan , C. Ozakin , H. Akalin , A. Ursavas , F.

Coskun , B. Ener and A. Tunali . 2007. Bacillus spp. among hospitalized patients with haematological malignancies: clinical features, epidemics and outcomes. Int. J. Food Microbiol. 115(3):319

- 24.

Saleh, O.I., P.

- I. Huang and J.

- S. Huang. 1997. Bacillus pumilus, the cause of bacterial blotch o f immature balady peach in Egypt. Journal of Phytopathology 145:44

Skerman, V.B.D., V. McGowan and P.H.A. Sneath (eds.). 1980. Approved lists of bacterial names. Int. J. Syst. Bacteriol. 30:225

- 420.

Tena D

., J.A. Martinez

- Torres

, M.T. Perez

- Pomata

, J.A. Sáez

- Nieto

, V. Rubio and J. Bisquert

. 2007. Cutaneous infection due to Bacillus pumilus : report of 3 cases. Clin. Infect. Dis. 44(4):40

- 2.

World Health Organization, Guidelines for Drinking

- water Quality.(2011) Fourth Edition

.Bacillus pumilus strain GHA180 Page 20 of 27 Biopesticides Regis tration Action Document

A PPENDIX A. MICROBIAL PESTICIDES DATA REQUIREMENTS (40 CFR PART 158

– SUBPART V )

TABLE 1. Produ ct Analysis Data Requirements for the Technical Grade of the Active Ingredient (TGAI) / GHA 180 (40 CFR § 158.2 120 )

OCSPP

G uideline

N umber Data Requirement Results MRID No. TGAI GHA 180 ( E P )

885.1100 Product Identity Submitted data fulfill the

req uirement for product identity. Submitted data fulfill the requirement for product identity. 48005001

48559501

885.1200 Manufacturing Process Submitted data fulfill the requirement for manufacturing

process. 48005001

48391501

Not a pplicable Depositio n of a Sample in a Nationally Recognized Culture

Collection Bacillus pumilus strain GHA180 is on deposit at the International Depository Authority of Canada, IDAC

No. 260707

- 01 Not applicable 48005001

885.1300 Discussion of Formation

of Unintentional Ing redients Submitted data fulfill the requirement for discussion of formation of unintentional ingredients 48005001

885.1400 Analysis of Samples Submitted data fulfill the requirement for analysis of samples 48005001

48537303

885.1500 Certification of Limi ts Not applicable Limits listed on the

confidential statement of

formula are adequate/acceptable CSFs dated July 12, 2011

Additional Studies

830 .1800 Enforcement Analytical

Method Not applicable Submitted data fulfill the requirement for an

enforcement analytical

method 48005001Bacillus pumilus strain GHA180 Page 21 of 27 Biopesticides Regis tration Action Document

TABLE 2 . Physical and Chemical Characteristics for the Technical Grade of the Active Ingredient ( (TGAI )/ GHA 180 Biological Fungicide (EP) (40 CFR § 158.2120)

OCSPP

G uideline

N umber Data Requirement Results MRID No.

TGA I GHA 180 Biological Fungicide

( E P )

830.6302 Color Amber 48005001

48559502

830.6303 Physical State Liquid 48005001

48559502

830.6304 Odor Musty 48005001

48559502

830.6313 Stability to Normal and

Elevated Temperatures, Metals,

and Metal Ions Vegetativ e cells expected to denature at >50 o C. 48005001

48559502

830.6317 Storage Stability Stable for at least one year; storage conditions not defined. 48005001

830.6319 Miscibility Not required per OCSPP 830.1000(e)(2), the product is not an emulsifiable liq uid

. 830.6320 Corrosion

Characteristics No corrosion observed during the storage stability testing 48005001

830.7000 pH 6

- 7. 48005001

48559502

830.7100 Viscosity Not applicable 2

- 5 mPa.s at 20 °C 48005001

830.7300 Density/Relative Density/Bulk D ensity

(Specific Gravity) 62.30 lbs/ft. 48005001

48559502Bacillus pumilus strain GHA180 Page 22 of 27 Biopesticides Regis tration Action Document

TABLE 3

. Product Analysis Data Requirements for the End

- Use Product ( E P), Pro

- Mix GHA 180 (40 CFR § 158.2120)

OCSPP Guideline

Number Data Requirement Results MRID No.

885.1100 Product Identi ty Submitt ed data fulfill the requirement for product identity

. 48005003

- 48005010

885.1200 Manufacturing Process Submitted data fulfill the requirement for manufacturing process. 48005003

- 48005010

48391501 Not applicable Deposition of a Sample in a

Natio nally Recognized

Culture Collection Not applicable Not applicable

885.1300 Discussion of Formation of Unintentional Ingredients Submitted data fulfill the requirement for

discussion of formation of unintentional ingredients for the current use sites.

. 4 8005003

- 48005010

885.1400 Analysis of Samples Submitted data fulfill the requirement for analysis of samples 48005003

- 48005010

885.1500 Certification of Limits Limits listed on the confidential statement of formula are adequate/acceptable 48005003

- 4800 5010

CSFs dated

1/7/11

Additional Studies

830.1800 Enforcement Analytical

Method An analytical method is not required for enforcement purposes since the Agency is establishing an exemption from the requirement of a tolerance without any numerical limitat ion. 48005003

- 48005010Bacillus pumilus strain GHA180 Page 23 of 27 Biopesticides Regis tration Action Document

TABLE 4 . Product Analysis Data Requirements for the End

- Use Product (EP), Pro

- Mix Tandem (40 CFR § 158.2120)

OCSPP Guideline

Number Data Requirement Results MRID No.

885.1100 Product Identity Submitted data fulfill the requi rement for product identity. 48005011

- 48005018

885.1200 Manufacturing Process Submitted data fulfill the requirement for manufacturing process. 48005011

- 48005018

48391501 Not applicable Deposition of a Sample in a Nationally Recognized

Culture Collectio n Not applicable Not applicable

885.1300 Discussion of Formation of Unintentional Ingredients Submitted data fulfill the requirement for

discussion of formation of unintentional ingredients for the current use sites. 48005011

- 48005018

885.1400 Analysis of Samples Storage stability was shown up to two years in peat growing mixes stored outdoors with temperature variations from

- 30 to +30 o C 48005011

- 48005018

885.1500 Certification of Limits Limits listed on the confidential statement of formula are adequ ate/acceptable 48005011

- 48005018

CSFs dated

1/7/11

830.1800 Enforcement Analytical

Method An analytical method is not required for enforcement purposes since the Agency is establishing an exemption from the requirement of a tolerance without any

numerica l limitation.

TABLE 5 . Physical and Chemical Characteristics for the End

- Use Product (EP), Pro

- Mix Tandem (40 CFR § 158.2120)

OCSPP Guideline

Number Data Requirement Results MRID No.

830.6317 Storage Stability Storage stability was sho wn up to two years in peat growing mixes stored outdoors with temperature variations

from

- 30 to +30 o C. 48005011

- 48005018

48537302

830.6319 Miscibility Not applicable, the product is not an emulsifiable liquid.

830.6320 Corrosion Characteristics Not Req uired

. The peat based soil mixes

were not considered corrosive material

830.7100 Viscosity Not applicable, the product is a solid

830.7300* Density/Relative Density/Bulk Density (Specific Gravity) 8

- 10 lbs/ft 3 CSFs dated

1/7/11Bacillus pumilus strain GHA180 Page 24 of 27 Biopesticides Regis tration Action Document

TABLE 6 . Physic al and Chemical Characteristics for the End

- Use Product (EP), Pro

- Mix GHA 180 (40 CFR § 158.2120)

OCSPP Guideline Number Data Requirement Results MRID No.

830.6317 Storage Stability Storage stability was shown up to two years in peat growing mixes stor ed outdoors with temperature variations

from

- 30 to +30 o C. 48005003

- 48005010

48537302

830.6319 Miscibility Not applicable, the product is not an emulsifiable liquid.

830.6320 Corrosion Characteristics Not Required

. The peat based soil mixes

were not co nsidered corrosive material

830.7100 Viscosity Not applicable, the product is a solid

830.7300* Density/Relative Density/Bulk Density (Specific Gravity) 8

- 10 lbs/ft 3 CSFs dated

1/7/11Bacillus pumilus strain GHA180 Page 25 of 27 Biopesticides Regis tration Action Document

TABLE 7 . Toxicology Data Requirements for the Techni cal Grade of the Active Ingredient (TGAI)/ and for the

End

- Use Products (EP), GHA 180 Biological Fungicide

, Pro

- Mix GHA 180 Pro

- Mix Tandem (40 CFR § 158.2140)

OCSPP

Guideline

Number Data Requirement TGAI GHA 180 Biological Fungicide (EP) Pro

- Mix

GHA 180 (EP) Pro

- Mix

GHA 180

Tandem (EP) MRID

No.

885.3050 Acute Oral Toxicity/ Pathogenicity No evidence of infectivity, pathogenicity or toxicity were noted in the Acute Injection study or in any of the submitted acute studies listed below. Exposures throug h the pulmonary or oral routes are not expected to produce adverse effects based on existing test and product

characterization information. Not applicable Not applicable Not applicable 48005019

885.3150 Acute Pulmonary Toxicity/ Pathogenicity Not applica ble Not applicable Not applicable

885.3200 Acute Injection Toxicity/ Pathogenicity 15 male and 15 female rats were injected with TGAI (1.4×10 10

– 6.0×10 10 CFU/mL) at a dose of 6.8×10 7
CFU/animal and observed up to 21 days. All animals survived, gained weight, and appeared normal during the study. No observable ab normalities were noted in any animal at necropsy. The test organism completely cl eared from the blood, kidneys, mandibular lymph nodes and cecum contents of the animals by day 14, and showed a pattern of clearance but had not completely cleared from the liver and spleen by day 21. No t est organism was

detected in the tissues/ organs of the animals treated with the inactivated test material or the untreated control group.

Classification: Acceptable

– not toxic, infective or pathogenic to rats when dosed by IV at 6.8 × 10 7 CFU/animal. Not applicable Not applicable Not applicable 48005025

885.3500 Cell Culture Not applicable Not applicable Not applicable Not applicable

870.1100 Acute Oral Toxicity Oral LD 50 was >5000 mg/kg bw.

Classification: Acceptable

TOXICITY CATEGORY IV Data on

TGAI supports these EPs 48005020

870.1200 Acute Dermal Toxicity The LD 50 was >5050 mg/kg bw.

Classification: Acceptable

TOXICITY CATEGORY IV Data on TGAI supports these EPs 48005021

870.1300 Acute

Inhalation Toxicity The LC

50 Combined was > 2.18mg/L.

Class ification: Acceptable

TOXICITY CATEGORY IV Data on TGAI supports these EPs 48005022

870.2400 Acute Eye

Irritation Two male and one female rabbits were treated with 0.1 mL

test material No iritis or positive conjunctival irritation was noted on any rabbit throughout the study. The maximum average score was 17.3 at one hour after test material

instillation

. Bacillus pumilus GHA180 TGAI was mildly irritating to the eye

. Classification: Acceptable

TOXICITY CATEGORY III Data on TGAI supports these EPs 480050 23

870.2500 Primary

Dermal

Irritation One male and two female rabbits were dermally exposed to 0 Bacillus pumilus GHA180 TGAI (1.4×10 10

– 6.0×10 10 CFU/mL) Very slight erythema was noted on one animal one hour after patch removal with

clearance by 24 hours. No dermal irritation was noted on any other rabbit during the study. The primary irritation

index was 0.1. CLASSIFICATION: Acceptable

TOXICITY CATEGORY IV Data on TGAI supports these EPs 48005024Bacillus pumilus strain GHA 180 Page 26 of 27 Biopesticides Registration Action Document

TABLE 8

. Nontarget Organism Toxicity and Environmental Fate Data Requirements for the Technical Grade of the Active Ingredient (TGAI), Bacillus pumilus train GHA180

. (40 CFR § 158.2150)

OCSPP Guideline

Number Data Requirement Results MRID

No.

Tier I

885.4050 Avian Oral Toxicity Not require d per 40 CFR § 158.2150

. T he current label use patterns for greenhouse and nursery use would not result in significant nontarget species

exposure. 48005019

885.4100 Avian Inhalation Toxicity/Pathogenicity

885.4150 Wild Mammal Toxicity/Pathogenicity

885.4200 Freshwater Fish Toxicity/Pathogenicity

885.4240 Freshwater InvertebrateToxicity/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 Bacillus pumilus strain GHA180 based on the current uses and application methods.Bacillus pumilus strain GHA 180 Page 27 of 27 Biopesticides Registration Action Document

APPENDIX B. PESTICIDE PRODUCTS

EPA File Symbol Registration

Name Growing

Medium

Blends Percentage

Active

In gredient Formulation Type Use Site(s) Method(s)

of Application Application

Rate Target Pest

74267

- E GHA 180 Biological Fungicide Not applicable 0.37% End

- use Product Greenhouses

And Enclosed

Nurseries Growing

media of

Ornamentals and vegetable

transpl ants Incorporatio

n Into Peat

Moss Or Growing

Media Soil

Drench As directed

on label Pythium

, Fusarium

and
Rhizoctonia

74267

- G Pro

- Mix

GHA 180 BX, HP, TA,
FPX, MPX, PGX, VFT

or BRK 0.001% End

- use Product Horticultural

and agricultural

plants

Tobacco germinating

seeds Plant in Growing

Medium Not applicable,

pre

- mixed potting mix Pythium,

Fusarium
Rhizoctonia

Alternaria Aspergillus

74267

- U Pro

- Mix

Tandem BX, HP, TA,
FPX, MPX, PGX, VFT

or BRK 0.001% End

- use Product Horticultural

and agricultur al

plants

Tobacco germinating

seeds Plant in Growing

Medium Not applicable,

pre

- mixed potting mix Pythium,

Fusarium
Rhizoctonia

Alternaria Aspergillus