EPA-HQ-OPP-2011-0493 regulations.gov

page iiEPA-HQ-OPP-2011-0493 regulations.gov

page iii 

## T

ABLE 

## O F 

## C ONTENTS



### A. Intr oducti on .............................................................................................................. ..... 6 B. Background and Regula tory Informa tion ....................................................................... 6 1. Register ed Products ............................................................................................... 6 2. Exemption from the R equirement of Tolerance ...................................................... 8 C. Anticipated Data N eeds and Risk Asse ssment ............................................................. 8 1. Product Analysis (40 CFR 158. 2120) ..................................................................... 8 2. Human Health Toxici ty (40 CFR 158.2140) ............................................................ 9 3. Environmental Fate & Ecot oxicity (40 CFR 158.2150) ......................................... 10 4. Risk to Threatened and Endangered S pecies ....................................................... 11 5. Endocrine Disruptor Screening Pr ogram .............................................................. 12 6. Inci dents ............................................................................................................... 1 2 7. Summary of Data G aps ........................................................................................ 13 D. Timeline................................................................................................................... .... 13 E. Guidance fo r Comment ers .......................................................................................... 14 F. Environment al Justice .................................................................................................. 14 G. Water Qualit y ............................................................................................................. . 14 H. Trade Ir ritants ........................................................................................................... ... 14 I. Additional Information ................................................................................................... 15 J. Next Steps

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

BIBLIOGRAPHY ..................................................................................................................... 16

APPENDIX A: Federal Register Notices Related to the Toleranc e Exemption ....................... 20



## List of Tables

Table 1. Crosswalk of Original vs. Current Regist ration Num bers ............................................ 7 Table 2. Pesticide Products Containing Bacillus cereus strain BP01 ........................................ 7 Table 3. Summary of Product Analysis Data for Bacillus cereus strain BP01 ........................... 9 Table 4. Summary of Toxicology Data for Bacillus cereus strain BP01 ................................... 10 Table 5. Ecological Toxicity Data for Bacillus cereus strain BP01 ............................................ 11 Table 6. Summary of Data Gaps for Bacillus cereus strain BP01 ........................................... 13 Table 7. Projected Timeline for the Registration Review of Case 6053 .................................. 13EPA-HQ-OPP-2011-0493 regulations.gov

page iv 

## ACRONYMS Acronym Extension μg microgram a.i. Active ingredient ATTC American Type Tissue Collection
B. cereus Bacillus cereus CFR Code of Federal Regulations CFU Colony forming units DCI Data Call-in EDSP Endocrine Disruptor Screening Program EP End-use product EPA U.S. Environmental Protection Agency or, the Agency EPA Reg. No. EPA Registration Number: a two-part number assigned by EPA to identify each pesticide product registration. ETE Emetic Toxin FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act of 1996 FR Federal Register
g gram HBL Hemolytic enterotoxin IDS Incident Data System L liter
LD 50 Median Lethal Dose: a statistically-deriv ed single dose that can be expected to cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation). mg/kg bw Milligrams per kilogram of body weight mg/L Milligrams per liter (approximately equivalent to ppm)
mL Milliliter MP Manufacturing-use product MPCA Microbial pesticide control agent MRID Master Record IDentification (number): EPA's system of recording and tracking studies submitted to the Office of Pesticide Programs.
MRL Maximum residue limits Nhe Nonhemolytic enterotoxin NPIC National Pesticides Information Center OPP EPA’s Office of Pesticide Programs OPPTS Office of Prevention, Pesticides and Tox ic Substances; now the Office of Chemical Safety and Pollution Prevention (OCSPP) PC Code Pesticide Chemical Code: a six-di git number assigned by OPP to identify pesticide chemicals. TMDL Total maximum daily loadsEPA-HQ-OPP-2011-0493 regulations.gov

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## B ACILLUS CEREUS 

## R EGISTRATION 

## R EVIEW 

## T EAM



## Office of Pesticide Programs Biopesticides and Pollut ion Prevention Division Microbial Pesticides Branch

H UMAN 

## H EALTH 

### Primary Review : Kathleen Martin; MSES, MPA Secondary Review: John Kough, Ph.D.



## E NVIRONMENTAL 

## E FFECTS 

### Primary Review : Kathleen Martin Secondary Review : Shannon Borges



## R ISK 

## M ANAGEMENT 

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



## O FFICE OF 

## G ENERAL 

## C OUNCIL


### Philip Ross, Esq.Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

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## P RELIMINARY 

## W ORK 

## P LAN



### A. Introduction The Food Quality Protection Act (FQPA) of 1996 mandated the c ontinuous review of existing pesticides. All pesticides distributed or sold in the United States must generally be registered by the U.S. Envi ronmental Protection Agency (EPA or the Agency), based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on the product la beling. The Registra tion Review program is intended to make sure that, as the abili ty to assess risk evolves and as policies and practices change, all registered pesticides cont inue to meet the stat utory standard of no unreasonable adverse effects. Changes in science, public polic y, and pesticide use practices will occur over time. Through the Registrati on Review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can continue to be used safely. Informati on on this program is provided at: http://www.epa.gov/oppsrrd1/registration_review/.
The Agency has begun to implement the R egistration Review program pursuant to Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) sect ion 3(g) and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The Agency will cons ider benefits information and data as required by FIFRA. The public phase of Registration Re view begins when the initial docket is opened for each case. The docket is the Agency’s oppor tunity to state what it knows about the pesticide and what additional risk analyses and dat a or information it believes are needed to make a Registration Review decision. After reviewing and responding to comments and data received in the docket during this comment pe riod, the Agency will develop and commit to a final work plan and schedule for the Registration Review.
This Registration Review Summary Docum ent evaluates the microbial pest control agent (MPCA) Bacillus cereus strain BP01 (PC Code 129802; ATTC® Number: 55675). Further information about this case, includi ng background and supporting documents, is available at regulations.gov; under “Keywo rd” enter the docket number, which is EPA-HQ-OPP-2011-0493.

B. Background and Regulatory Information
1. Registered Products

Bacillus cereus (or B. cereus ) strain BP01 is a plant regul ator that is used mainly on cotton, but is also registered for use on a number of field and row crops including field corn, soybean, rice, peanut, cauliflower, and melons; it is applied aerially. EPA has registered seven products containing B. cereus strain BP01 as an active ingredient—one manufacturing-use product (MP) and six end-use products (EP). These products were first registered to MicroFlo Company; later, the registrations were transferred to Arysta Lifescience North America, LLC. Table 1 provides a crosswalk between the origin al and current EPA Registration Numbers (EPA Reg. No.).Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

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### Table 1 . Crosswalk of Original vs. Current Registration Numbers and Product Names

a The Registration Notice (EPA 1997g) for this pr oduct refers to it as “Mepichlor/BP01 4-2.”


### The first two products r egistered were the MP ( Bacillus cereus , strain BP01 Technical; EPA Reg. No. 66330-274) and an EP (Pix® Plus® Plant Regulator; EPA Reg. No. 66330-351). EPA registered (EPA 1997f) Bacillus Cereus BP01 Technical unconditionally but with a term that has been sa tisfied (SRA 1997b). Pix® Plus® Plant Regulator was also registered unconditiona lly (EPA 1997g; no terms); it contains mepiquat chloride (another plant growth regul ator) as a second active ingredient.
Between 1998 and 2010, the Agency regist ered five more pr oducts containing B. cereus strain BP01 as an active ingredient (EPA 1998b,c; 1999a; 2000b; 2010a). Three of these products (MepPlusTM Concen trate, MepPlusTM Pill, and ARY 0494-006; EPA Reg. Nos. 66330-280, -285, and -393, respectively) contain mepiquat chloride as a second active ingredient. 1 

### One product (BP01 1.7; EPA Reg. No. 66330-282) contains B. cereus strain BP01 as the single active ingredient and another product (PGRIV ® 

### /BP01 Foliar; EPA Reg. No. 66330-291) contai ns gibberellic acid as a second active ingredient. 2 

### Provided in Table 2 is a summary of the seven registered products; the table includes the percent B. cereus strain BP01 in each product and the products’ registered use sites.

Table 2 . Pesticide Products Containing Bacillus cereus strain BP01 as an Active Ingredient

EPA R EG

. N O P RODUCT N AME % A CTIVE I NGREDIENT (a..i.) R EGISTERED U SE S ITES R EGISTRATION N OTICE B. CEREUS 2 ND A

. I

. Products containing only B. cereus strain BP01

66330-274 Bacillus Cereus

, BP01 Technical 10.9 NA Manufacturing-use product EPA 1997f

66330-282 BP01 1.7 1.7 NA Cotton and soybean EPA 1998c

Products containing B. cereus strain BP01 and the active ingredient mepiquat chloride

66330-351 Pix ® Plus ® Plant Regulator 0.0058 4.2 Cotton EPA 1997g

66330-280 MepPlusTM Concentrate 0.032 23.5 Cotton EPA 1998b

66330-285 MepPlusTM Pill 0.11 95.8 Cotton EPA 1999a

1 MepPlusTM Concentrate was registered unconditionally (19 98b); MepPlusTM Pill and ARY 0494-006 were registered with conditions (1999a, 2010a).

2 EPA registered both unconditi onally (EPA 1998c, 2000b). EPA R EG

. N O

. P RODUCT N AME F IRST R EGISTERED Original Current

51036-282 66330-274 Bacillus Cereus , BP01 Technical 1997 51036-283 66330-351 Pix® Plus® Plant Regulator a 1997 51036-299 66330-280 MepPlusTM Concentrate 1998 51036-301 66330-282 BP01 1.7 1998 51036-306 66330-285 MepPlusTM Pill 1999 51036-325 66330-291 PGR-IV®/BP01 Foliar 2000 NA 66330-393 ARY 0494-006 2010Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

page 8 EPA R EG

. N O P RODUCT N AME % A CTIVE I NGREDIENT (a..i.) R EGISTERED U SE S ITES R EGISTRATION N OTICE B. CEREUS 2 ND A

. I

. 66330-393 ARY 0494-006 1.13 90 Cotton EPA 2010a

Products containing B. cereus strain BP01 and the active ingredient gibberellic acid

66330-291 PGR-IV ® /BP01 Foliar 0.1 0.225 Row and vegetable crops (these include: field corn, soybean, rice, peanut, cauliflower and melons) EPA 2000b



### 2. Exemption from the Requirement of Tolerance

Cotton is considered a food-use because cottonseed oil is used for cooking and cottonseed meal is used as animal feed. In a Final Rule published on August 4, 1997 (62 FR 41874), EPA established an exemption from the requirement of tolerance for residues of the microb ial plant regulator B. cereus strain BP01 in or on cottonseed ; it was codified at 40 CFR 180.1181. In 2001, the registrant sought to amend the tolerance exemption to include all raw agricul tural commodities, not just cotton. In a Final Rule (67 FR 70012; November 20, 2002), EPA expanded the original tolerance exemption to read: §180.1181 Bacillus cereus strain BP01; exemption from the requirement of a tolerance. An exemption from the requirement of a tolerance for residues of the Bacillus cereus strain BP01 in or on all raw agricultural commodities when applied/used in acco rdance with label directions.”
Appendix A provides a list of Federal Register notices regarding th e exemption from tolerance for residues of B. cereus strain BP01.

C. Anticipated Data Needs and Risk Assessment

Provided below are summaries and tables of the current data requirements for microbial pesticides. They are arrayed by scientific di scipline, and describe how the requirements have been satisfied, as well as any data gaps that have been identified.

1. Product Analysis (40 CFR 158.2120)

B. cereus is an aerobic and facultatively anaerobi c, spore-forming, gram-positive bacillus (LA DPH 2004) that causes two forms of foodborne illness. T he emetic form is characterized by nausea and vomiting and abdomin al cramps; it has a one- to six-hour incubation period. The diarrheal form manife sts as abdominal cramps and diarrhea (the diarrhea may be a small volume or profuse and watery); it has an eight- to sixteen-hour incubation period. The emet ic syndrome is caused by a preformed heat-stable emetic toxin (ETE). The diarrhea syndrome is caused by in vivo production of two heat-labile enterotoxins 3 

### —nonhemolytic enterotoxin (Nhe) and/or hemolytic enterotoxin (HBL). (Todar 2008). Because these toxins may caus e acute illness in humans, EPA intends to require an updated manufacturing process along with a new ‘discussion of formation of unintentional ingredient s.’ Provided in Table 3 is a summary of the Product Analysis requirements for B. cereus strain BP01 and how they have been met.

3 An enterotoxin is a substance t hat is released by a microorganism in to the intestine.Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

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### Table 3 . Summary of Product Analysis Data for Bacillus cereus strain BP01
40 CFR 158.2120 D ATA R EQUIREMENT (OPPTS G UIDELINE ) MRID H OW IT H AS B EEN A DDRESSED (EPA R EVIEW
, C ONCLUSIONS
, C OMMENTS )

Product Chemistry and Composition Product Identity (885.1100) 441773-01; 452680-01 EPA 1997a,c

Manufacturing process (885.1200) 441773-01 Because human health toxins endemic to B. cereus may contaminate production batches, EPA is requiring an updated manufacturing process.

D ATA G AP Deposition of a sample in a nationally recognized culture collection (885.1200) 441773-01 A sample of B. cereus strain BP01 was deposited in the American Type Tissue Collection as ATTC 55675. EPA 1997a

Discussion of formation of unintentional ingredients (885.1300) 441773-01 Because of concern regarding B. cereus toxins, EPA intends to require an updated discussion of unintentional ingredients.

D ATA G AP
Analysis and Certified Limits Analysis of samples (885.1400) 441773-02 All parts of this requirement have been satisfied. EPA 1997a,c; EPA 2002a
Certification of limits ( 885.1500) 441773-02 EPA 1997a
Physical and Chemical Characteristics Color (830.6302) 44177 3-03 light yellowish-brown. EPA 1997a Physical state (830.6303) 441773-03 powdery flakes. EPA 1997a Odor (830.6304) 441773-03 earthy, musty. EPA 1997a pH (830.7000) 441773-03 5.23 @ 21 ◦ C in a 5% aqueous suspension. EPA 1997a Bulk density (830.7300) 441773-03 0.224 g/mL. EPA 1997a
Corrosion characteristics (830.6320) 441773-04 In testing using a high density polyethylene (HDPE), study investigators demonstrated that B. cereus strain BP01 is not corro sive to this type of container. EPA 1997a Storage stability (830.6317) Waived (EPA 1997h) Stability to normal and elevated temperatures, metals and metal ions (830.6313) Waived (EPA 1997h)

Miscibility (830.6319) Only required for emulsifiable liquid forms of microbial pesticides. a B. cereus strain BP01 technical is a solid. Viscosity (830.7100) Only required for liquid forms of microbial pesticides. B. cereus strain BP01 technical is a solid. b

a 40 CFR 158.2120, test note 2.
b 40 CFR 158.2120, test note 4.



### 2. Human Health Toxicity (40 CFR 158.2140) EPA did not identify any gaps regarding human health toxicity. Table 4 provides brief summaries of the submitt ed data and shows the data gaps.Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

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### Table 4 . Summary of Toxicology Data for Bacillus cereus strain BP01

40 CFR 158.2120 D ATA R EQUIREMENT (OPPTS G UIDELINE ) MRID H OW IT H AS B EEN A DDRESSED (EPA R EVIEW
, C ONCLUSIONS
, C OMMENTS )

Acute oral toxicity/ pathogenicity (885.3050) 441773-06 B. cereus strain BP01 is not toxic, pathogenic or infective when a 1X 10 8
CFU a dose was administered orally. A distinct clearance pattern was observed throughout t he study. EPA 1997a,c

A CCEPTABLE S TUDY Acute pulmonary toxicity/ pathogenicity (885.3150) 441773-08 B. cereus BP01 was not toxic or pathogenic when a 7 to 9.33 X 10 7 CFU dose was administered intratracheally. A distinct clearance pattern was observed throughout t he study. EPA 1997a,c

A CCEPTABLE S TUDY Acute injection toxicity/ pathogenicity— intravenous (885.3200) 441773-09 B. cereus BP01 was not toxic when a 2 X 10 7 CFU dose was administered intravenously; however, clearance data wa s not submitted. Because the oral and intratracheal toxicity/pathogenici ty studies demonstrated distinct clearance patterns, EPA did not require that this study be repeated. EPA 1997a,c
S UPPLEMENTAL S TUDY Hypersensitivity incidents (885.3400) NOTE : Hypersensitivity incidents must be reported if they occur. b Such incidents include “immediate type and delayed-type reacti ons of humans or domestic animals....”

Cell culture (885.3500) NA. This study is only required for products whose active ingredient is a virus. c B. cereus is a bacterium. Acute oral toxicity (870.1100) 441773-05 In rats, LD 50 >5,000 mg/kg bw. EPA 1997a,c

A CCEPTABLE S TUDY Acute dermal toxicity (870.1200) 441773-07 A single, 2 g dose of B. cereus strain BP01 applied to the skin of rabbits. LD 50 >2,000 mg/kg bw. EPA 1997a,c

A CCEPTABLE S TUDY Acute inhalation toxicity (870.1300) Required when the product consists of, or under conditions of use would result in, an inhalable material (e.g., gas, volatile substa nces, or aerosol particulate). EPA does not expect that products containing B. cereus strain BP01 will result in an inhalable material. Acute eye irritation (870.2400) 441773-10 B. cereus strain BP01 was considered practically non-irritating when a 0.1g ocular dose was administered to rabbits; ocular irritation was no longer present by day 3. EPA 1997a,c

A CCEPTABLE S TUDY Primary dermal irritation (870.2500) 441773-07 A single, 2g dose of B. cereus strain BP01 applied to the skin of rabbits produced a produced a slight- to we ll-defined irritation at 72 hours post dosing. By day 14, all signs of signs of irritation resolved. EPA 1997a,c

A CCEPTABLE S TUDY

a CFU=colony forming unit
b 40 CFR 158.2140, test note 3.

c 40 CFR 158.2140, test note 6.



### 3. Environmental Fate & Ecotoxicity (40 CFR 158.2150) Table 5 (below) provides summaries of the ecotoxicity data and data gaps. EPA deemed the submitted avian oral toxicity st udy invalid/supplemental because the actual dose of test substance administered wa s unknown (EPA 1997b); however, based on the lack of toxicological findings, the re viewer was able to conclude that B. cereus strain BP01 was practically nontoxic to bobwhite qua il, adding that the st udy did not need to be repeated. EPA did not require that the study be repeated.Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

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### In 1997, when EPA assessed the ecological risks posed by products containing B. cereus strain BP01, use of such products was lim ited to cotton. In its 1997 ecological review (EPA 1997b), Agency scientists point ed out that for use sites beyond cotton, toxicity to freshwater fish and nontarget insects would need to be addressed, either through the submission of data or adequate waiv ers. In 2002, the tolerance exemption was expanded to include a number of crops including soybean, field corn, and melons (62 FR 41874). Because the Agency is conc erned about potential effects to freshwater fish and nontarget insects, we intend to require these data.

Table 5 . Ecological Toxicity Data for Bacillus cereus strain BP01
40 CFR 158.2120 D ATA R EQUIREMENT (OPPTS G UIDELINE ) MRID H OW IT H AS B EEN A DDRESSED (EPA R EVIEW
, C ONCLUSIONS
, C OMMENTS )

Avian oral toxicity (885.4050) 441773-12 Bobwhite Quail . When administered to bobwhite quail for five days at a dose of 4.44 X 10 7 CFU/g day, practically nontoxic to test animals. EPA 1997b.

S UPPLEMENTAL S TUDY Avian inhalation toxicity/ pathogenicity (885.4100) Data required when the nature of the microb ial pesticide and/or its toxins indicates potential pathogenicity to birds. a EPA does not expect B. cereus strain BP01 to be a potential avian pathogen. Wild mammal toxicity/ pathogenicity (885.4150) Required on a case -by-case basis.... b EPA expects that this study will not be needed.

Freshwater fish toxicity/ pathogenicity (885.4200) EPA expects to require these data (EPA 1997b).

D ATA G AP
Freshwater invertebrate toxicity/ pathogenicity (885.4240) 441773-14 Daphnia magna

. B. cereus strain BP01 was toxic to daphnids at concentrations ranging from 3.9 X 10 7 to 6.7 X 10 8 CFU/L. In addition, attenuated B. cereus strain BP01 and the sterile filtrate of B. cereus strain BP01 was toxic to daphnids at 50 mg/L. EPA 1997b

A CCEPTABLE S TUDY Estuarine/Marine fish testing
Estuarine & marine invertebrate testing (885.4280) EPA expects to require these data for pr oducts with aerial application.

D ATA G AP

Nontarget plant testing (885.4300) Required if the microbial pesticide is taxonomically related to a known plant pathogen. c

Nontarget insect testing (885.4340) EPA expects to require these data (EPA 1997b).

D ATA G AP Honey bee testing (885.4380) 453823-02 Honey bees were exposed to B. cereus strain BP01 (topical application) at doses ranging from 13 to 100 μg/bee. At the highest dose tested (i.e., 100 μg/bee) no significant adverse effects were seen. The acute LD50 is >100 μg/bee. EPA 2002b

A CCEPTABLE S TUDY

a 40 CFR 158.2150, test note 3.
b 40 CFR 158.2150, test note 4.

c 40 CFR 158.2150, test note 7.



### 4. Risk to Threatened and Endangered Species EPA has not conducted a risk assessment that supports a complete endangered species determination for B. cereus strain BP01. The ecological risk assessment planned during Registration Review will allo w the Agency to determine whether use ofBacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

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### B. cereus strain BP01 will have “no effect” 4 

### or “may affect” 4 

### federally-listed threatened or endangered species (listed spec ies) or their designated critical habitat. When an assessment concludes that a pesticide’s use “may affect” a listed species or its designated critical habitat, the Agency will co nsult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as appropriate.
Based on the specific use patterns and data gaps in ecological data, the Agency anticipates the need for new data. In addi tion, because this active ingredient has products that are registered for outdoor-use, the Agency is required to consider any effects on nontarget species, particularly those with endangered an d threatened status.

5. Endocrine Effects As required by the Administrator under the Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(p), EPA has devel oped the Endocrine Disruptor Screening Program (EDSP) and has begun to implement the screening program that is to be used to test all pesticides in order to determi ne whether certain substances (including pesticide active and other ingredients) may hav e an effect in humans or wildlife similar to an effect produced by a “naturally occurri ng estrogen, or other such endocrine effects as the Administrator may designate.”
FFDCA section 408(p)(4), authorizes the Ad ministrator, by order, to exempt from the requirements of the Estrogenic Substances Scr eening Program a biologic substance or other substance if a determinat ion is made that t he substance is not anticipated to produce any effect in humans sim ilar to an effect produced by a naturally occurring estrogenic substance.
Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chem icals, which contains 58 pesticide active ingredients and nine inert ingredients. B. cereus strain BP01, an MPCA that is endemic to soil, is not among the group of 58 pesticide active ingred ients on the initial list to be screened under the EDSP.
The Agency, as part of this final work plan, believes that B. cereus strain BP01, the active ingredient involved in this Registra tion Review case, likely is a substance that is anticipated not to produce any effect in humans similar to an effect produced by a naturally occurring estrogenic substance. As such, pursuant to Section 408(p)(4), EPA may exempt B. cereus strain BP01 from the requirement s of the Section 408(p) EDSP.

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

6. Incidents

The National Pesticides Informat ion Center (NPIC) database reported no incidents associated with products containing B. cereus strain BP01. The Office of

4 In assessing ecological risk EPA makes an “effects determi nation.” The effects determina tion may conclude that the pesticide’s use will have: “no effect" on a listed species, "may affect but is not likely to adversely affect" a listed specie s, or is "likely to adversely affect" a listed species. http://www.epa.gov/espp/ litstatus/eseffects.htmBacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

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### Pesticide Programs’ (OPP) Incident Data System (IDS) shows one report of adverse human, domestic animal, or environmental incidents for products containing B. cereus strain BP01. Using the classification syst em described at 40 CFR 159.184(c)(5), the incident is considered to be “H-C” and “D-B.” An incident classified as “H-C” is one where “the person alleged or exhibited symptoms more pr onounced, more prolonged or of a more systemic nature than minor sympt oms.” A “D-B” incident is one where an “animal exhibited or was alleged to have exhibited symptoms which may have been lifethreatening or resulted in re sidual disability.” The Agency will consider any incident data or comments submitted to this docket in response to this preliminary work plan.

7. Summary of Data Gaps Table 6 summarizes the data gaps for B. cereus strain BP01, case 6053.

Table 6. Summary of Data Gaps for Bacillus cereus strain BP01

P RODUCT A NALYSIS (40 CFR 158.2120) H UMAN H EALTH T OXICITY (40 CFR 158.2140) E COLOGICAL T OXICITY (40 CFR 158.2150)

Product Chemistry and Composition

 Manufacturing process; and

 Discussion of unintentional ingredients No Data Gaps Freshwater fish toxicity/pathogenicity
Estuarine/marine fish testing Estuarine & marine invertebrate testing
Nontarget insect testing



### D. Timeline The projected timeline for case 6053— Bacillus cereus strain BP01—Registration Review is listed in Table 7, below.

Table 7. Projected Timeline for the Registration Review of Case 6053

A CTIVITY E STIMATED M ONTH AND Y EAR

Phase 1 : Open the Public Docket Open Comment Period for Docket June 30, 2011 Close Comment Period August 30, 2011

Phase 2 : Case Development Develop Final Work Plan January 2012 Issue Data Call-in (DCI) January 2013 Data Submission January 2015 Open Public Comment Period for Preliminary Risk Assessments July 2016
Close Public Comment Period October 2016

Phase 3 : Registration Review Decision Open Comment Period for Proposed Registration Review Decision January 2017 Close Comment Period April 2017 Final Decision and Begin Post-Decision Followup 2017 

### Estimated Total (years) 6Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

page 14 

### E. Guidance for Commenters The public is invited to comment on EPA’ s preliminary Registration Review work plan and rationale. The Agency will consider all comm ents as well as any additional information or data provided in a timely manner prior to issuing a final work plan for the case.

F. Environmental Justice EPA seeks to achieve environmental just ice, the fair trea tment and meaningful involvement of all people, regar dless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potent ial environmental justice issues, the Agency seeks information on any groups or segments of th e population who, as a result of their location, cultural practices, or other fact ors, may have atypical, unusually high exposure to B. cereus strain BP01, compared to the general population. Pleas e comment if you are aware of any subpopulations that may have atypical, unusua lly high exposure compared to the general population.

G. Water Quality

B. cereus strain BP01 is not identified as a c ause of impairment for any water bodies listed as impaired under secti on 303(d) of the Clean Water Act. 5 

### In addition, no Total Maximum Daily Loads (TMDL) have been developed for B. cereus strain BP01. 6 

### More information on impaired water bodies and TMDL’s can be found at: http://www.epa.gov/owow/tmdl/. The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality st andards in Appendix A of the Offi ce of Pesticide Program’s (OPP) Standard Operating Procedure: Inclusi on of Impaired Water B ody and Other Water Quality Data in OPP’s Registration Re view Risk Assessment and Management Process 7 

### to ensure they can be used quantitatively or qua litatively in pesticide risk assessments.

H. Trade Irritants Through the Registration Review process, th e Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and other stakeholders ar e asked to comment on any trade irritant issues resulting from lack of Maximum Residue Limits (MRL’s) or disparities between Unit ed States tolerances and MRL’s in key export markets, providing as much specific ity as possible regarding the nature of the concern.

Residues of B. cereus strain BP01 are exem pt from the requireme nt of tolerance and there are no known MRL’s (FAO and WHO 2010). Therefore, the Agency does not anticipate that current uses of B. cereus strain BP01 will pose conc erns as trade irritants.

5 Based on information provided at: http://www.epa.gov/owow/tmdl/. 6 Based on information provided at: http://iaspub.e pa.gov/tmdl_waters10/text_search.tmdl_search_form.
7 This document can be found at: http://www.epa.gov/ oppsrrd1/registration_review/water_quality_sop.htm.Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

page 15 

### I. Additional Information Stakeholders are also specific ally asked to provide informat ion and data that will assist the Agency in refining the risk assessments, incl uding any species-specif ic ecological effects determinations. The Agency is interested in obt aining the following information regarding the use of B. cereus strain BP01:

 Confirmation on the following label information:

- Sites of application - Formulations - Application methods and equipment - Maximum application rates - Frequency of application, application intervals, and maximum number of

applications - Geographic limitations on use

 Use or potential use distribution

 Use history

 Usage/use information for nonagricultural uses (e.g., materials preservation)

 Typical application interval

 State or local use restrictions

 Monitoring data

J. Next Steps After the 60-day comment period closes, t he Agency will review and respond to any comments received in a timely manner and then issue a final work plan for case 6053: Bacillus cereus strain BP01.Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

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### BIBLIOGRAPHY

Submitted Studies
441773-00 Micro Flo Company. 1996. Submission of Product Chemistry and Toxicology Data in Support of the Application for Registration and Petition for Exemption from Tolerance Requirements for Bacillus cereus strain BP01. Transmittal of 17 Studies. December 11, 1996. 441773-01 Bowman, L. 1996. Product Identity and Disclosure of Ingredients, Manufacturing Process, Discussion of Formation of Impurities: ( Bacillus cereus Strain BP01). Unpublished study prepared by Chr Hansen BioSystems. 31 p. December 11, 1996. 441773-02 Bowman, L. 1996. Analysis of Samples, Ce rtification of Limits, and Analytical Methods: ( Bacillus cereus Strain BP01): Lab Project Number: AG 0205A: MC-004: MC-008. Unpublished study prepared by Chr Hansen BioSystems. 46 p. December 11, 1996. 441773-03 Stenzel, J.; Markley, B. 1996. Product Chemistry Testing of Bacillus cereus Strain BP01: Color, Physical State, Odor, Bulk Density, and pH: Amended (Final) Report: Lab Project Number: 147C-110: 147/092795/MUP-MPCA.FIFA/CHP104. Unpublished study prepared by Wildlife International Ltd. 34 p. December 11, 1996. 441773-04 Stenzel, J.; Markley, B. 1996. Product Chemistry Testing of Bacillus cereus Strain BP01: Corrosion Characteristics: Amended (Final) Report: Lab Project Number: 147C-109: 147/092795/MUP-MPCA.FIFB/CHP104. Unpublished study prepared by Wildlife International Ltd. 29 p. December 11, 1996. 441773-05 Johnson, W. 1996. Acute Oral Toxicity Study of Bacillus cereus Strain BP01 in Rats (Limit Test): Amended Final Report: Lab Project Number: L08594: L08594SN7. Unpublished study prepared by IIT Research Institute. 23 p. December 11, 1996. 441773-06 Sherwood, R. 1996. Toxicity/Pathogenicity Testing of Bacillus cereus Strain BP01 Following Acute Oral Challenge in Rats: Amended Final Report: Lab Project Number: L08594: L08594 SN2. Unpublished study prepared by IIT Research Institute. 73 p. December 11, 1996. 441773-07 Johnson, W. 1996. Acute Dermal Toxicity/Irritation Study of Bacillus cereus Strain BP01 in Rabbits: Amended Final Report: Lab Project Number: L08594: L08594SN5. Unpublished study prepared by IIT Research Institute. 28 p. December 11, 1996. 441773-08 Sherwood, R. 1996. Toxicity/Pathogenicity Testing of Bacillus cereus Strain BP01 Following Acute Intratracheal Challenge in Rats: Amended Final Report: Lab Project Number: L08594: L08594SN3. Unpublished study prepared by IIT Research Institute. 210 p. December 11, 1996. 441773-09 Sherwood, R. 1996. Toxicity Testing of Bacillus cereus Strain BP01 Following Acute Intravenous Challenge in Rats: Amended Final Report: Lab Project Number: L08594: L08594SN4. Unpublished study prepared by IIT Research Institute. 27 p. December 11, 1996. 441773-10 Johnson, W. 1996. Primary Eye Irritation Study of Bacillus cereus Strain BP01 in Rabbits: Amended Final Report: Lab Project Number: L08594: L08594SN6. Unpublished study prepared by IIT Research Institute. 25 p. December 11, 1996. 441773-11 Mega, W. 1996. Sensitivity of Detection of Bacillus cereus Strain BP01 for Toxicity/Pathogenicity Testing in Rats: Amended Final Report: Lab Project Number: L08594: L08594 SN1. Unpublished study prepared by IIT Research Institute. 36 p. December 11, 1996.Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

page 17 441773-12 Foster, J.; Beavers, J. 1996. Bacillus cereus Strain BP01: An Avian Oral Pathogenicity and Toxicity Study in the Northern Bobwhite: (Final Report): Lab Project Number: 378- 102. Unpublished study prepared by Wildlife International Ltd. 28 p. December 11, 1996. 441773-13 Drottar, K.; Swigert, J. 1996. Bacillus cereus Strain BP01: A 21-Day Life-Cycle Toxicity and Pathogenicity Test with the Cladoceran ( Daphnia magna ): Final Report: Lab Project Number: 378A-101A. Unpublished study prepared by Wildlife International Ltd. 38 p. December 11, 1996.
441773-14 Collins, M. 1996. Bacillus cereus Strain BP01—Toxicity to Daphnids ( Daphnia magna ) During a 21-Day Static-Renewal Test: Amended Final Report: Lab Project Number: 96-11-6760: 13633.1096.6100.264. Unpublished study prepared by Springborn Labs, Inc. 91 p. December 11, 1996. 441773-15 Crosby, K. 1996. Effect of Bacillus cereus Strain BP01 on Soybean Seedling Emergence, Plant Growth, and Phytotoxicity: (Amended Report): Lab Project Number: 6677-95-0282-BE-001: 6677-95-0282-BE-000. Unpublished study prepared by Ricerca, Inc. 51 p. December 11, 1996. 441773-16 Sherwood, R. 1996. Testing of Bacillus cereus Strain BP01 for Bacillus cereus Enterotoxin Production: Final Report: Lab Project Number: L08617: L08617 SN1. Unpublished study prepared by IIT Research Institute. 19 p. December 11, 1996. 441773-17 Geno, P.; Wall, C. 1996. Determination of Hemolysis Activity of BP01: Final Report: Lab Project Number: 01-6666-029. Unpublished study prepared by Southwest Research Institute. 5 p. December 11, 1996. 443318-01 Young, C.; Lethbridge, G.; Shaw, L.; et al. 1995. Survival of inoculated Bacillus cereus spores and vegetative cells in non-planted and rhizosphere soil. Soil Biol. Biochem. 27(8): 1017-1026. July 22, 1997. 443318-03 West, A.; Burges, H.; Dixon, T.; et al. 1985. Survival of bacillus thuringiensis and bacillus cereus spore inocula in soil: Effects of pH, moisture, nutrient availability, and indigenous microorganisms. Soil Biol. Biochem. 17(5): 657-665. July 22, 1997. 443318-04 West, A.; Burges, H. 1985. Persistence of bacillus thuringiensis and bacillus cereus in soil supplemented with grass or manure. Plant and Soil 83: 389-398. July 22, 1997. 443318-05 West, A.; Burges, H.; Dixon, T.; et al. 1985. Effect of incubation in non-sterilised and autoclaved arable soil on survival of bacillus thuringiensis and bacillus cereus spore inocula. New Zealand Journal of Agricultural Research 28: 559-566. July 22, 1997. 443318-06 Hagen, C.; Hawrylewicz, E.; Anderson, B. et al. 19??. Ability of Microorganisms to Establish Ecological Niches in Different Soils and Environments. Chapter 38 in Developments in Industrial Microbiology. July 22, 1997. 452680-00 Micro Flo Company. 2000. Submission of Product Chemistry Data in Support of the Registration of Bacillus Cereus Strain BP01 Technical. Transmittal of 1 Study. November 17, 2000. 452680-01 Smith, F. 2000. Product Identity and Composition, Description of Beginning Materials, and Description of Production Process: ( Bacillus cereus Strain BP01 Technical). Unpublished study prepared by Micro Flo Company. 98 p. (OPPTS 830.1550, 830.1600, 830.1620). November 17, 2000 453823-00 Micro Flo Company. 2001. Submission of Toxicity Data in Support of the Petition for Tolerance of Bacillus cereus strain BP01 in/on Cottonseed. Transmittal of 2 Studies. April 17, 2001.Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

page 18 453823-01 Gaskins, M. 1998. Determination of Emetic Toxin from Cultures of Bacillus cereus : MTT Assay for Cellular Cytotoxicity: Final Report: Lab Project Number: 980608. Unpublished study prepared by Micro Flo Company. 18 p. April 17, 2001. 453823-02 Hoxter, K.; Porch, J.; Krueger, H. 1999. Bacillus cereus BP01: An Acute Contact Toxicity Study with the Honey Bee: Lab Pr oject Number: 378-103A. Unpublished study prepared by Wildlife International Ltd. 22 p. (OPPTS 850.3020). April 17, 2001.



### EPA Reviews
U.S. EPA. 1997a. Memorandum from Cindy Schaffer, Microbiologist to James Boland, Regulatory Action Leader. BPPD Review of Data Submitted by Micro Flo Company for the Registration of Mepichlor/BP01 4-2; and the Applicability of a Tolerance Exemption for this chemical/microbial mixture (containing the active ingredients: Mepiquat chloride and Bacillus

cereus strain BP01).... U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. June 11, 1997. U.S. EPA. 1997b. Memorandum from Julie Fry Heminway to Phil Hutton. Review of non-target studies in support of registration of Bacillus cereus (BP01) technical (EPA File Symbol 51036- EIE) and the end-use product Mepichlor/BP014-2, (EPA File Symbol # 51036-EIG); DP BARCODE 0233600; ... ; MRID No's 44173-12,44173-13, 44173-14,44173-15,44173-16. U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. June 19, 1997. U.S. EPA. 1997c. Memorandum from Cindy Schaffer to James Boland. BPPD Review of Additional Data Submitted by Micro Flo Company for the Registration of Mepichlor/BP01 4-2 (containing the active ingredients: Mepiquat chloride and Bacillus cereus strain BP01) (Chemical No.: 119802). U.S. Environmental Protecti on Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. July 21, 1997. U.S. EPA. 1997h. Registration Eligibility Docum ent. Bacillus cereus strain BP01. U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. July 1997.

U.S. EPA. 2000a. Memorandum from Paul Zubkoff to Diana Horne. PGR-IV BP Foliar File Symbol 50136-GEL; MRID 449273-01. U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. April 4, 2000. U.S. EPA. 2002a. Memorandum from Carl Etsitty to Robyn Rose. BPPD Review the Emetic Toxin Absence Submitted by Micro Flo Company, lnc., for Bacillus cereus strain BP01 (Submission No.: S599536; DP Barcode: D277357; MRID 453823-01). U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. September 19, 2002. U.S. EPA. 2002b. Data Evaluation Report (DER ). Honey Bee Acute Contact Toxicity (OPPTS 850.3020). MRID 453823-02. Primary Review by Anthony Armstrong and Patricia Reno, Oak Ridge National Laboratory and Susanne Cerrelli, U.S. EPA. Secondary Review by Zigfridas Vaitusis, U.S. EPA. U.S. Environmental Protec tion Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. October 17, 2002.

Registration Notices U.S. EPA. 1997f. Notice of Pesticide Registration. Bacillus cereus BP01. EPA Reg. No. 51036-282. U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. July 30, 1997. NOTE: This is now EPA Reg. No. 66330-274.Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

page 19 U.S. EPA. 1997g. Notice of Pesticide Regist ration. Mepichlor/BP01 4-2. EPA Reg. No. 51036-283. U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. July 30, 1997. Note: This is now EPA Reg. No. 66330-351. U.S. EPA. 1998b. Notice of Pesticide Registration. MepPlusTM Concentrate. EPA Reg. No. 51036-299. U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. Ap ril 17, 1998. NOTE: This is now EPA Reg. No. 66330-280. U.S. EPA. 1998c. Notice of Pesticide Registration. Bacillus cereus BP01 1.7. EPA Reg. No. 51036-301. U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. May 12, 1998. NOTE: This is now EPA Reg. No. 66330-282. U.S. EPA. 1999a. Notice of Pesticide Registration. MepPlus Pill. EPA Reg. No. 51036-306. U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. January 20, 1999. NOTE: This is now EPA Reg. No. 66330-285. U.S. EPA. 2000b. Notice of Pesticide Registration. PGR-IV/BP Foliar. EPA Reg. No. 51036- 325. U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. October 5, 2000. NOTE: This is now EPA Reg. No. 66330-291. U.S. EPA. 2010a. Notice of Pesticide Registration. ARY 0494-006. EPA Reg. No. 66330-393. U.S. Environmental Protection Agency. Office of Pesticide Programs. Biopesticides and Pollution Prevention Division. March 18, 2010.



### Other Information
FAO and WHO. 2010. Codex Alimentarius. United Nations Food and Agriculture Organization & World Health Organization. Information retrieved on June 9, 2011. http://www.codexalimentarius.net/mrls/pestdes/jsp/pest_q-e.jsp

LA DPH. 2004. Infectious Disease Control Manual: Bacillus Cereus Toxi-Infection. Louisiana Department of Health and Hospitals. Louisiana Offi ce of Public Health. Infectious Disease Epidemiology Section. Information retrieved on June 15, 2011. http://www.dhh.louisiana.gov/offices/miscdo cs/docs-249/Manual/BacillusCereusManual.pdf SRA. 1997b. Letter from Frederick T. Smith, Regulatory Scientist SRA International, Inc. to James Boland, Regulatory Action Leader U.S. EPA Office of Pesticide Program. "Bacillus cereus BP01 Technical (Reg. No. 51036-282), September 19, 1997.
Todar, Kenneth. 2008. Todar’s Online Textbook of Bacteriology. University of Wisconsin. Information retrieved on June 8, 2011. http ://www.textbookofbacteriology.net/B.cereus.html.Bacillus cereus strain BP01 EPA-HQ-OPP-2011-0493 regulations.gov

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## APPENDIX A: Federal Register Notices Related to the Tolerance Exemption

Table A-1

. Federal Register Notices for Bacillus cereus strain Exemptions from the Requirement of Tolerance Federal Register Citation What Was Published

62 FR 12999 March 19, 1997 A Notice of Receipt to register two products containing the new active ingredient B. cereus strain BP01: Micro Flo Company’s 51036-EIE and -EIG.
Note: these were later transferred to Ar ysta Lifescience North America, with the registrations becoming 66330-274 and -351, respectively.
62 FR 34277 June 25, 1997 A Notice of Filing of Micro Flo Company ‘s pesticide petition (PP 7F4801) proposing the establishment of an exemption from the requirement of a tolerance for residues of B. cereus BP01.
62 FR 41874 August 4, 1997 The Final Rule establishing an exemption from tolerance for residues of the microbial plant regulator Bacillus cereus strain BP01 in or on cottonseed; it was codified at 40 CFR 180.1181 and read: “§180.1181 Bacillus cereus strain BP01;exemption from the requirement of a tolerance. An exemption from the require ment of a tolerance is established for residues of the microbial plant regulator Bacillus cereus strain BPO1 in or on cottonseed.”
66 FR 58481 November 21, 2001 A Notice of Filing regarding Micro Flo’s petition (PP 1F6324) to amend the tolerance exemption at 40 CFR 180.1181 to include all raw agricultural commodities, not just cotton.
67 FR 70012 November 20, 2002 The Final Rule expanding the original tolerance exemption; It reads: “§180.1181 Bacillus cereus strain BP01; exemption from the requirement of a tolerance. An exemption from the requirement of a tolerance for residues of the Bacillus cereus strain BP01 in or on all raw agricultural commodities when applied/used in accordance with label directions.”