BIOPESTICIDES REGISTRATION ACTION DOCUMENT



## Trichoderma virens strain G

- 41

Pesticide Chemical (PC) Code: 176604

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

February 6 , 2012Trichoderma virens strain G

- 41 Page 2 of 34 Biopesticides Registration Action Document

TABLE OF CONTENTS

I. EXECUTIVE SUMMARY

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

II. ACTIVE INGREDIENT OV ERVIEW

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

III. REGULATORY BACKG ROUND

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

A. Applications for Pesticide Product Registration

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

B. North American Free Trade Agreement Joint Review

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

C. Food Tolerance Exemption

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

IV. RISK ASSESSMENT

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

A. Product Analysis Assessment (40 CFR § 158.2120)

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

B. Human Health Assessment (40 CFR § 158.2140)

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

C. Environmental Assessment (40 CFR § 158.2150)

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

V. E NVIRONMENTAL JUSTICE

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

VI. RISK MANAGEMENT DECI SION

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

VII. ACTIONS REQUIRED OF THE REGISTRANT

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

A. Final Printed Labeling

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

B. Terms of Registration

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

C. Reporting of Adverse Effects and Hypersensitivity Incidents

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

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

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

IX. BIBLIOGRAPHY

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

A. Studies Submitted or Cited to S upport the Trichoderma virens strain G

- 41 Pesticide Product Regi strations

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

B. Environmental Protection Agency Risk Assessment Memoranda

................................ ............. 22

C. Other References

................................ ................................ ................................ ............................ 22

APPENDIX A. MICROBI AL PESTICIDES DATA R EQUIREMENTS

................................ ............................ 24

APPENDIX B. PESTICI DE PRODUCTS

................................ ................................ ................................ .............. 33Trichoderma virens strain G

- 41 Page 3 of 34 Biopesticides Registration Action Document

BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

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

Science Reviews

Ibrahim S. Barsoum , Ph.D. Product Analysis, Human Health United States Environmental Protection Agency

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

Leila Heikkila Human Heal th Health Canada Pest Management Regulatory Agency

James Elwin Product Analysis, Environmental Effects

Regulations

Sheryl K. Reilly, Ph.D. Chief, Microbial Pesticides Branch United States Environmental Protection Agency

Jeannine Kausch Regulatory Action LeaderTrichoderma virens strain G

- 41 Page 4 of 34 Biopesticides Registration Action Document

I. EXECUTIVE SUMMARY

In September 2009, BioWorks, Inc. submitted application s for a manufacturing

- use pesticide product, G

- 41 Technical (EPA File Symbol 68539

- I), and an end

- use pesticide product, BW240 WP Biological Fungicide (EPA File Symbol 68539

- O), to both the United States Environmental Protection Agency (EPA) and the Health Canada Pest Management Regulatory Agency (PMRA) and requested a North American Free Trade Agreement (NAFTA) Joint Review of these application s

. Background

1 Concurrently with these applications, BioWor ks, Inc. submitted an application for another end

- use pesticide product, BW240 G Biological Fungicide (EPA File Symbol 68539

- RN), and filed a petition for a tolerance exemption for residues of Trichoderma virens strain G

41, the new active ingredient conta ined in all three proposed pesticide products, with EPA only.

Trichoderma virens

, including strain G

- 41

, is a naturally occ urring fungus that is native to the United States and is widely distributed throughout the world, inhabiting forest, agricultural

, and orchard soils, as well as plant litter (Samuels 1996). Trichoderma virens strain G

- 41 was isolated from soil samples taken from Aphan o myces

- suppressive fields in Livingston County, New York. Much like other Trichoderma species, Trichoderma virens strai n G

- 41 inhibits or kills certain plant

- pathogenic fungi (e.g., Rhizoctonia species and Fusarium species ) through several mechanisms: (1) competition for food and space, (2) mycoparasitism, (3) antibiosis, and (4 ) induction of plant defense responses (Kener ley 2010, Samuels 1996) . Given the fungicidal capabilities of Trichoderma virens strain G

- 41, BioWorks

, Inc. proposed to register these pestici de products to control soilborne plant pathogens and plant root diseases that ad versely affect agricultural, gree nhouse , and nursery crops , as well as plants in residential settings (e.g., vegetables, fruit, and ornamentals).

EPA and /or PMRA scientists reviewed product analysis, toxicology, and nontarget organism data and information (40 Code of Federal Reg ulations (CFR) §§ 158.2120, 158.2140, and 158.2150, respectively) submitted to support the registration of the t hree proposed Trichoderma virens strain G

- 41 pesticide products. Overall, such data and information are adequate for risk assessment purposes , f ulfill the current microbial pesticide data requirements

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

.

Most of the p roduct analysis data requirements for Trichoderma virens strain G

- 41 , including product chemistry and composition, analysis of samples, and physical and chemical characteri stics, were fulfilled by acceptable guideline studies. Although a one

- year storage stability and corrosion characteristics study is ou tstanding, EPA reviewed a n interim report of a storage stability and corrosion characteristics study and , as a term of registration, is requiring the final report of this study be submitted approximately one year from the date of registration

. Product Analysis

Adequate mamm alian toxicology data were submitted or cited to support the Trichoderma virens strain G

- 41 pesticide products. An acute injection toxicity/pathogenicity study showed t hat, at a single high dose, Trichoderma virens strain G

- 41 is not toxic , in fective, and/o r pathogenic via the Toxicology

1 See http://www.epa.gov/oppfead1/internatio nal/naftatwg/guidance/jointreview

- biope.pdf

.Trichoderma virens strain G

- 41 Page 5 of 34 Biopesticides Registration Action Document

intraperitoneal route of exposure , while two acute o ral toxicity/pathogenicity studies (one conducted with Trichoderma virens strain G

- 41 and the other conducted with functionally similar Trichoderma virens strain GL

- 21 ( formerly known as Gliocladium virens strain GL

- 21) ) indicate that, at a single high dose, Trichoderma virens strain G

- 41 is not toxic and/or pathogenic via the oral route of exposure. 2 A cute p ulmonary toxicity/patho genicity test ing demonstrated that Tricho derma virens strain GL

- 21, a functionally similar strain to Trichoderma virens strain G

- 41, was not toxic to, infective in, or pathogenic for rats when given a single intratracheal dose. Given the functional similarity of these two strains, EPA concluded t hat Trichoderma virens strain G

- 41 is also not likely to be toxic, infective, and/or pathogenic through the inhalation route. Moreover, no hypersensitivity incidents, occurring during rese arch, development, or testing of Trichoderma virens strain G

- 41 , wer e reported by the applicant . In light of the results of the injection

, pulmonary, and oral toxicity/pathogenicity data

, as well as the absence of hypersensitivity incidents, testing at higher tiers (i.e., Tiers II and III) was not required.

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 residues of Trichoderma virens strain G

- 41 . No dietary risks are expected from use of Trich oderma virens strain G

- 41 as an active ingredient in pesticide products. Significant exposure to Trichoderma virens strain G

- 41

— through food and drinking water and exceeding already present background levels

— is not anticipated due to : (1) the proposed appl ication methods of the end

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

. Should this microbial pesticide be present on food or in drinking water, the acute oral toxicity an d pathogenicity data available for Trichoderma virens strain G

- 41 and functionally similar Trich oderma virens strain GL

- 21 demonstrated that no toxicity, infectivity, and/or pathogenicity is likely to oc cur with any exposure level of Trichoderma virens strain G

- 41 resulting from application in accordance with good agricultural practices

. Tolerance Exem ption

Despite the low toxicological profile of Trichoderma virens strain G

- 41 , baseline personal protective equipment (PPE) is required for handlers that may be exposed to the active ingredient, due to their occupation, for prolonged periods or numero us times . Handlers working with Trichoderma virens strain G

- 41 in agricultural settings are directed to wear a long

- sleeved shirt, long pants, socks, shoes, protective eyewear, and a dust/mist filtering respirator meeting National Institute for Occupationa l Safety and Health (NIOSH) standards of at least N

- 95, R

- 95, or P

- 95. EPA may require different PPE, other than the standard described above, on a product

- specific basis. Occupationa l Exposure

Data and other i nformation (e.g., scientific literature) subm itted by the applicant to support Nontarget Organisms

2 With its pesticide product applications, BioWorks, Inc. cited to toxicological data done with a similar

, previously registered strain of Trichoderma virens , GL

- 21 (Kenerley 2010). Although GL

- 21 and G

- 41 are not identical, the two strains share many characteristics typical of Trichoderma virens (e.g., particular morphological features and weak growth at the temperature of the human body (37°C)) , and thus are considered to be functionally similar. Based on thes e similarities, EPA concluded that data on Trichoderma virens strain GL

- 21 would be representative of the toxicological nature of Trichoderma virens strain G

- 41.Trichoderma virens strain G

- 41 Page 6 of 34 Biopesticides Registration Action Document

requests to waive nontarget organism testing for Trichoderma virens strain G

- 41 are sufficient to fulfill the relevant microbial pesticide data requirements and for risk assessment purposes. Further testing of nontarget or ganisms at higher tier levels (i.e., Tiers II, III, and IV) is not required. EPA performed an environment al risk assessment based on data and other information provided by the ap plicant

, and determined that adverse effects to nontarget organisms are not

an ticipated from the proposed pesticidal uses of Trichoderma virens strain G

- 41. Moreover, EPA has made a “No Effect” determination for direct and indirect effects to listed species and their designated critical habitats resulting from these same proposed pe sticidal uses.

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

. Public Participation

Consistent with the policy of making registration actions more transparent, the proposed
pe sticide products containing Trichoderma virens strain G

- 41

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

- day comment period. During this comment period, no comments were received on EPA’s preliminary decision to register the Trichoderma virens strain G

- 41 pesticide products, G

- 41 Tec hnical, BW240 WP Biological Fungicide, and BW240 G Biological Fungicide. Therefore, EPA maintained that, based upon the risk assessment and information submitted in support of registration of such pesticide products, it was appropriate to issue the G

- 41 Te chnical, BW240 WP Biological Fungicide, and BW240 G Biological Fungicide registrations under FIFRA section 3(c)(5)

. The basis for this decision can be found in the risk assessment for Trichoderma virens strain G

- 41, which is characterized throughout this B iopesticides Registration Action Document ( BRAD )

.

II. ACTIVE INGREDIENT OVERVIEW

Biological Name: Trichoderma virens strain G

- 41

Culture Deposit: American Type Culture Collection in Manassas

, Virginia under Accession N umber ATCC 20906

OPP Chemical Code: 176604

Type of Pesticide: Microbial Pesticide

– Fungicide

See Appendix B for specific information (e.g., use sites, application rate s , methods of application, formulation type s , and target pe sts) regarding the registered pesticide products containing this active ingredient.Trichoderma virens strain G

- 41 Page 7 of 34 Biopesticides Registration Action Document

III. REGULATORY BACKGROUND

A. Applications for Pesticide Product Registration

On September 18, 2009

, T echnology Sciences Group, Inc. (address: 1150 18 th Street NW, Su ite 1000; Washington

, District of Columbia 20036 ) , on behalf of BioW orks, Inc. (address: 100 Rawson Road, Suite 205; Victor, New York 14564), submitted application s to register a manufacturing

- use pesticide product, G

- 41 Technical (EPA File Symbol 68539

- I )

, and two end

use pesticide product s , BW240 WP Biological Fungicide (EPA File Symbol 68539

- O ) and BW240 G Biological Fungicide (EPA File Symbol 68539

- RN), under FIFRA section 3. On M arch 10, 2010

, EPA announced receipt of these application s to register pes ticide product s containing a new active ingredient ( 75 Federal Register (FR) 11175 ) and opened a 3 0

- day public comment period pursuant to the provisions of FIFRA section 3(c)(4). No comments were received following this publication.

B. North American Free Trade Agreement Joint Review

Trichoderma virens strain G

- 41 was the subject of a NAFTA Joint Review conducted by EPA and PMRA.

C . Food Tolerance Exemption

Concurrent wit h its registration application s and under Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(d), Technology Sciences Group, Inc. , on behalf of BioWorks, Inc.

, submitted a petition to establish an exemption from the requirement of a tolerance for Tric hoderma virens strain G

- 41 (Pesticide Petition (PP) 9F7 618 )

. In the Federal Register of March 10, 2010 ( 75 FR 11171 ), EPA announced that Technology Sciences Group, Inc., on behal f of BioWorks, Inc., proposed to establish an exemption from the requirement of a tolerance for residues of the fungicide

, Trichoderma virens strain G

- 41

, in or on all food commodities and opened a 30

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

On February 1 , 2012, EPA established an exemption from the requirement of a tolerance for residues of Trichoderma virens strain G

- 41, in or on all food commodities, when applied as a fungicide and used in accordance with good agricultu ral practices (40 CFR § 180.1310; 77 FR 4903 ).

IV. RISK ASSESSMENT

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

. The rule became effective on December 26, 2007. The data and information eval uated for this BRAD were considered in light of these requirements.

The classifications that are found for each data submission are assigned by EPA science reviewers and are an indication of the usefulness of the information contained in the documents for risk assessment. A rating of “ acceptable ” indicates the study is scientifically sound and is useful for risk assessment. A “ supplemental ” rating indicates the data provide some information that can be useful for risk assessment. The studies may have certa in aspects determined not to beTrichoderma virens strain G

- 41 Page 8 of 34 Biopesticides Registration Action Document

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 will often 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 assessment process as appropriate. An “unacceptable ” rating in dicates that new data must 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 submitted to EPA in support of a pesticide registration. The activ e ingredient or particular product is classified into Toxicity Category I, II, III, or IV, where Toxicity Category I indicates the highest toxicity and Toxicity Category IV indicates the lowest toxicity (see 40 CFR § 156.62 )

.
A. Product Analysis Assessment ( 40 CFR § 158.2120 )

With the exception of a one

- year storage stability and corrosion characteristic s study, which EPA will require as a term of registration, a ll product analysis data requirements for Trichoderma virens strain G

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

- specific i nformation.

B. Human Health Assessment ( 40 CFR § 158.2140 )

1. Toxicity

All toxicology data requirements for Trichoderma virens strain G

- 41 have been fulfilled

. Acceptable Tier I mammalian toxicology data and information support registration of the Trichoderma virens strain G

- 41 pesticide products

. Furthermore, Tier II and Tier III studies were not required for Trichoderma virens strain G

- 41

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

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

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

.
a. Acute Toxicity/Pathogenicity

– Tier I

Acute Oral Toxicity/Pathogenicity

– Rat ( Harmonized Guideline 885.3050; Master Record Identification Number (MRID No.) 4 83438

- 01 ) : In an acute oral toxicity study, groups of young Sprague

- Dawley albino rats (12 per sex) were given a single oral dose of G

- 41 technical grade of the active ingredient (TGAI) (1.5 x 10 9 c olony

- for ming units per milliliter (cfu/mL)) in Phosphate Buffered Saline at doses of 1.5 x 10 8 colony

- forming units (cfu) per animal. The animals were then observed for a period of up to 21 days with interim scheduled sacrifices on Days 3, 7, and 14. A group of an imals (5 per sex) were also dosed with inactivated test substance. A group of control (untreated) animals (5 per sex) and a group of shelf contro l animals (2 per sex) were concurrently conducted. There were no treatment

- related clinical signs, and no

necro psy findings other than an empty digestive system in one animal from the test substance group. There were no changes in body weight, other than in one animal from the test substance group who lost weight on Day 3. The test substance had cleared from all ti ssu es and organs byTrichoderma virens strain G

- 41 Page 9 of 34 Biopesticides Registration Action Document

Day 7; however, the sensitivity of detection indicated low recovery of the microbial pest control agent (MPCA) fr om tissues and fluids (0.5

– 9%). C learance of the MPCA by Day 7 is uncertain

. Trichoderma virens strain G

- 41 is not toxic to rats when administered by oral gavage in a single dose of 1.5 x 10 8 cfu per animal. This study was rated acceptable.

Acute Oral Toxicity/Pathogenicity

– Rat (Harmonized Guideline 885.3050; MRID No. 407198

- 04) : In a 14

- day acute oral tox ic ity/pathogen i ci ty study in Sprague

- Dawley rats (13 per sex) with Trichoderma virens strain GL

- 21, there were no mortalities, and no signs of infectivity/pathogenicity were observed following oral administration at 10 8 cfu in 2.0%

c arb oxy methyl cellulose per animal in a m aximum dosing volume o f 5 milliliters . General signs of toxicity (lethargy, r apid breathing) were observed 1 hour post treatment, but all signs had resolved by Day 1. There were no observable abnormalities upon necropsy, and all animals gained weight throu ghout the study. Interim sacrifices (Day s 1, 7 and 14) were carried out to analyze for the presence of the microbe in kidney, lungs, liver, brain, spleen, mesenteric lymph nodes

, and blood as a clearance assessment of the test organism. The test organism w as detected in the feces on Day 1 and in low levels in the lungs (one animal) on Day 7 only; the test organism had cleared from all organs/tissue by Day 14. Trichoderma virens strain GL

- 21 is not toxic to, infective in, or pathogenic for rats when administ ered in a single oral dose at 10 8 cfu per animal. This study was originally rated acceptable but is supplemental in this situation (test organism is not the active ingredient proposed for registration)

.
Acute Pulmonary Toxicity/Pathogenicity ( Harmonized G ui deline 885.3150; MRID No s

. 407198

- 04 and 408640

- 02 ) : In a 21

- day acute pulmonary toxi ci ty/pathogen i city study in rats with Trichoderma virens strain GL

- 21

, no mortality, toxicity

, or pathogenicity was observed following intratracheal administration at 10 8 cfu per animal. General signs of toxicity (poor weight gain; lethargy; rapid breathing; rough hair coat) were observed after dosing, but all signs had resolved by Day 4. Interim sacrifices (Days 1, 7 and 14) were carried out to analyze for the presence o f the microbe in kidney, lungs, liver, brain, spleen, mesenteric lymph nodes

, and blood as a clearance assessment of the test organism. The test organism was steadily cleared from the lungs of test animals after 2

– 3 weeks. For other organs/tissues, the tes t organism was detected on Day 1 in low numbers in the liver, blood, mesenteric lymph nodes, spleen, kidney

, and brain. The test organism had cleared in all organs/tissues by Da y 7, except for one animal that had low levels of the organism in the spleen on Day 14. Upon necropsy, treated animals appeared normal except for the appearance of grey spots in the lungs at each interim sacrifice. The peritracheal lymph nodes of dosed animals often appeared enlarged and pale. This can most likely be attributed to th e admin istration of the test substance and probably represents the test material itself. Trichoderma virens strain GL

- 21 is not toxic to, infective in, or pathogenic for rats when administered in a single intratracheal dose at 10 8 cfu per animal. This stud y was originally rated acceptable but is supplemental in this situation (test organism is not the active ingredient proposed for registration)

.
Acute Injection Toxicity/Pathogenicity (Intra peritoneal)

– Rat (Harmonized Guideline 885.3200; MRID No s

. 478651

- 02 and 482368

- 01 ) : In an acute intraperitoneal infectivity study, young adult Wistar rats were injected with approximately 10 7 cfu of the G

- 41 TGAI in distilled water by intraperitoneal route (3 per sex; 1 milliliter per animal). A vehicle control group, which received sterile, distilled water, was also included. The animals were observed once daily for 21 days. The observation included changes in the skin and fur, eyes and mucous membrane, respiratory system, circulatory system, autonomic and central nerv ous system, somatomotor activity, andTrichoderma virens strain G

- 41 Page 10 of 34 Biopesticides Registration Action Document

behavior pattern. Particular attention was directed to observations of tremors, convulsions, diarrhea, lethargy, salivation, sleep and coma; all observed toxic signs were recorded. Clearance, however, was not unequivoc ally assessed as it is not specified as a requirement for infectivity testing by intraperitoneal injection. There were no mortalities, no toxic signs in any of the animals, no abnormal findings upon necropsy, and body weight gain was not affected. While cl earance was not directly assessed in this study, the lack of clinical findings upon necropsy, in combination with the lack of mortality and signs of toxicity in the animals, strongly suggests that Trichoderma virens strain G

- 41 is also not pathogenic by in traperitoneal injection. Trichoderma virens strain G

- 41 is not toxic , infective, and/or pathogenic to rats when administered intraperitoneally in a single dose of 10 7 cfu per animal. This study was rated acceptable.

Hypersensitivity Incidents ( Harmoniz ed Guideline 885.3400; MRID No. 482526

- 01 ) : No hypersensitivity incidents, including immediate

- type or delayed

- type reactions of humans and domestic animals that occurred during research, development, or testing of Trichoderma virens strain G

- 41

, were repo rted by the applicant . Any future hypersensitivity incidents must be reported to EPA (refer to test note #3 of 40 CFR § 158.2140(d))

.
Cell Culture ( Harmonized Guideline 885.3500) : This study is not required because Trichoderma virens strain G

- 41 is not a virus (refer to test note #4 of 40 CFR § 158.2140(d)).

b. Acute Toxicology and Subchronic Toxicity/Pathogenicity

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

– Tier III

Tie r II and Tier III studies were not required for Trichoderma virens strain G

- 41

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

c. Endocrine Disruptors

As required under FFDCA sectio n 408(p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally o ccurring 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 potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a quantitative rela tionship between the dose and the E, A, or T effect.

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

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of che micals 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 endocrine disru ptors.Trichoderma virens strain G

- 41 Page 11 of 34 Biopesticides Registration Action Document

Trichoderma virens strain G

- 41 is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Under FFDCA section 408(p), EPA must screen all pesticide chemicals. Accordingly, EPA anticipates issuing fu ture EDSP orders/data call

- ins for all pesticide active ingredients.

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

.

2

. Federal Food, Drug, and Cosmetic Act (FFDCA ) Considerations

Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an exemption from the requirement for a tolerance (the legal lim it for a pesticide chemical residue in or on a food) only if EPA determines that the exemption is “safe.” Section 408(c)(2)(A)(ii) of FFDCA defines “safe” to mean that “there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.” This includes exposure through drinking water and in resi dential settings

, but does not include occupational exposure . Pursuant to section 408(c)(2)(B) of FFDCA, in establishing or maintaining in effect an exemption from the requirement of a tolerance, EPA must take into account the factors set forth in section 408(b)(2)(C) of FFDCA, which require EPA to give special con sideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance exemption

, and to “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pest icide chemical residue....” Additionally, section 408(b)(2)(D) of FFDCA requires that EPA consider “available information concerning the cumulative effects of [a particular pesticide's]

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

EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide residues. First, EPA determines the toxicity of pesticides. Second, EPA examines exposure to the pesticide through food, drinking water, and through othe r exposures that occur as a result of pesticide use in residential settings.

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

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

- 41 have been fulfilled

.
a. Aggregat e Exposure

In examining aggregate exposure, section 408 of FFDCA directs EPA to consider available information concerning exposures from the pesticide residue in food and all other nonoccupational exposures, including drinking water from ground water or surface water and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses).Trichoderma virens strain G

- 41 Page 12 of 34 Biopesticides Registration Action Document

Food Exposure and Risk Characterization : A ll p roposed Trichoderma virens strain G

- 41 applications are soi l directed or soil incorporated because of the targeted soilborne pests (e.g., Rhizoctonia spp. and Fusarium spp. ). Based on calculations made in EPA’s environmental risk assessment, t hese applications are not expected to significantly increase the populations of this fungus above natura l levels in the soil . No reports were available in the literature describing natural concentrations of Trichoderma virens ; however, Trichoderma species have been reported in various types of soils at concentrations of 10 4 to 10 6 colony

- forming units per gr am ( cfu/g ) (Leandro et al . 2007, Liu et al . 2008). Based on the maximum application rate of the proposed end

- use pesticide products containing Trichoderma virens strain G

- 41

, the estimated amount of Trichoderma virens applied to the soil surface is approxi mately 6.7 x 10 3 colony

- forming units per square centimeter ( cfu/cm 2 ). Assuming a bulk density of 1 to 2 grams per cubic centimeter ( g/cm 3 ), the maximum application rate will not result in soil concentrations that are substantially greater than concentrati ons of Trichoderma virens naturally found in the soil, and overall increased exposure to Trichoderma virens in the terrestrial environment , including on above

g round plant parts such as food commodities

, is not expected. Work by Jackson et al . (1991)
suppo rts this conclusion given that, after Trichoderma virens and three other Trichoderma isolates were incorporated into soil, fungal numbers either transiently increased, rem ained stable, or declined. Should this microbial pesticide be present on food, the ac ute oral toxicity and pathogenicity data available for Trichoderma virens strain G

- 41 and functionally similar Trichoderma virens strain GL

- 21 demonstrated no toxicity, infectivity, and/or pathogenicity is likely to occur with any exposure level of Trichod erma virens strain G

- 41 resulting from application in accordance with good agricultural practices (see section IV(B)(1)(a) and Table 5 in Appendix A ).

Drinking Water Exposure and Risk Characterization : Exposure to residues o f Trichoderma virens strain G

- 41 in consumed drinking water is unlikely. The proposed use patterns for Trichoderma virens strain G

- 41 are soil directed and soil incorporated , thereby limiting contact with surface water by drift and runoff

. Furthermore, gro und water is not expected to have significant exposure to Trichoderma virens strain G

- 41 since , like other Trichoderma species

, this fungus would likely be filtered out by the particulate nature of many soil types

, and be concentrated in upper soil horizon s (Longa et al . 2009, Sariah et al . 2005) near plant roots (USPTO 2010)

. I f Trichoderma virens strain G

- 41 were to be transferred to surface or ground

water s (e.g., through spray drift or runoff) that are intended for eventual human consumption and directe d to wastewater treatment systems or drinking water facilities

, it likely w ould not survive the cond itions water is subjected to in such systems or facilities , including chlorination, pH adjustments, filtration , and occasionally high temperatures (Center s for Dise ase Control and Prevention 2009, U.S. EPA 2004)

. For instance, Trichoderma virens strain G

- 41 does not grow well at 37°C (Kenerley 2010, Lumsden et al . 1996)

, and test data has shown it to be unstable at elevated temperatures; there fore, any heat t reatment applied to water containing Trichoderma virens strain G

- 41 would probably render the fungus non

- viable. In the remote likelihood that this microbial pesticide is present in drinking water (e.g., water not subject to treatment systems or facilities ), the acute oral toxicity and pathogenicity data available for Trichoderma virens strain G

- 41 and functionally similar Trichoderma virens strain GL

- 21 demonstrated no toxicity, infectivity, and/or pathogenicity is likely to occur with any exposure level o f Trichoderma virens strain G

- 41 resulting from application in accordance with good agricultural practice s (see section IV(B)(1)(a) and Table 5 in Appendix A )

.Trichoderma virens strain G

- 41 Page 13 of 34 Biopesticides Registration Action Document

Non

- occupational, Residential Risk Characterization : Given Trich oderma virens ’ natural occurrence in soil (Samuels 1996)

, non

- occupational exposure to the fungus is likely already occurring

. E ven with the proposed pesticide applications of Trichoderma virens strain G

- 41, it is not likely that there will be a significan t increase in these exposures due to the relative stability of typical background levels in the soil (see calculations and information presented in the food exposure section above). I f significant non

- occupational exposures were to occur, such exposures

wo uld not exceed EPA’s level of concern in light of test results that indicated Trichoderma virens strain G

- 41 is not toxic ( acute pulmonary toxicity/pathogenicity, acute inhalation toxicity, and acute dermal toxicity), is non

- irritating (primary dermal irri tation), and is not pathogen ic or infective (acute pulmonary toxicity/pathogenicity) (see section IV(B)(1)(a) and Table s 5 and 6 in Appendix A ).

b. Cumulative Effects from Substances with a Common Mechanism of Toxicity

Se ction 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 subst ances that have a common mechanism of toxicity.”

There are several Trichoderma species used as active ingredient s in registered pesticide products. While these different microbial pest control agents may produce similar metabolites, the likelihood of adver se cumulative effects via a common mechanism of toxicity is not anticipated

, based on the lack of toxicity/pathogenicity potential of the active ingredients used on food and/or labeled for residential uses (U.S. EPA 2008 , 2010a, 2010b, and 2010c )

. For info rmation regarding EPA ’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects o f such chemicals, see EPA ’s website at http://www.epa.gov/pest icides/cumulative

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

FFDCA section 408(b)(2)(C) provides that, in considering the establishment of a tolerance or tolerance exemption for a pesticide chemical residue, EP A 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 subs tances with a common mechanism of toxicity. In addition, FFDCA section 408(b)(2)(C) provides that EPA shall apply an additional tenfold (10X) margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal

t oxicity and the completeness of the database on toxicity and exposure unless EPA determines that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly referred to as the Food Quality Protection Act Safety Factor. In applying this provision, EPA either retains the default value of 10X or uses a different additional safety factor when reliable data available to EPA support the choice of a different factor.

Based on the acute toxicity and pathogenicity data / information summarized in section IV(B)(1)(a) and Table s 5 and 6 in Appendix A

, as well as use of Trichoderma pesticide products since 1989 without reported adverse effects to humans, EPA concludes that there are no thr eshold effects of concern to infants, children, or adults when Trichoderma virens strain G

- 41 is used as labeled in accordance with good agricultural practices. As a result, EPA concludes thatTrichoderma virens strain G

- 41 Page 14 of 34 Biopesticides Registration Action Document

no additional margin of exposure (safety) is necessary to prote ct infants and children and that not adding any additional margin of exposure (safety) will be safe for infants and children.

Moreover, based on the same data and EPA analysis as presented directly above, the Agency is able to conclude that there is a rea sonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate exposure to the residues of Trichoderma virens strain G

- 41 when it is used as labeled and in accordance with good agricultural practices as a fungicide . Such exposure includes all anticipated dietary exposures and all other exposures for which there is reliable information. EPA has arrived at this conclusion because, considered collectively, the data and information available on Trichoderma vire ns strain G

- 41, as well as data available on functionally similar Trichoderma virens strain GL

- 21, do not demonstrate toxic, pathogenic, and/or infective potential to mammals, including infants and children.

3. Occupational Exposure and Risk Characteriz ation

Handler exposure to Trichoderma virens strain G

- 41 is not expected to pose any undue risk. Regardless, appropriate personal protective equipment and precautionary statements are required on pesticide product labels to mitigate any potential risks to pesticide handlers due to prolonged or numerous exposures. Handlers applying Trichoderma virens strain G

- 41 end

- use pesticide products in agricultural settings must wear a long

- sleeved shirt, long pants, socks, shoes, protective eyewear, and a dust/mist f iltering respirator meeting NIOSH standards of at least N

95, R

- 95, or P

- 95. EPA may require different PPE, other than the standard described above, on a product

- specific basis.

4. Human Health Risk Characterization

EPA considered human exposure to Tri choderma virens strain G

- 41 in light of the standard for registration in FIFRA and the relevant safety factors in FFDCA. A determination has been made that no unreason able adverse effects to the United States population in general, and to infants and child ren in particu lar, will result when Trichoderma virens strain G

- 41 pesticide products are used in accordance with EPA

- approved labeling.

C. Environmental Assessment ( 40 CFR § 158.2150 )

Data and other i nformation (e.g., scientific literature) submitted by the applicant to support requests to waive nontarget organism testing for Trichoderma virens s train G

- 41 are sufficient to fulfill the relevant microbial pesticide data requirements and for risk assessment purposes. Further testing of nontarget organisms at higher tier levels (i.e., Tiers I I, III, and IV) is not required . EPA performed an environme ntal risk assessment based on data and other information provided by the ap plicant

, and has determined that adverse effects to nontarget organisms are not anticipated from the proposed pesticidal uses of Trichoderma virens strain G

- 41. Moreover, EPA has ma de a “No Effect” determination for direct and indirect effects to listed species and their designated critical habitats resulting from these same proposed pesticidal uses.

For a summary of the generic data requirements described in sections IV(C)(1), r efer to Table 7 in Appendix A

.Trichoderma virens strain G

- 41 Page 15 of 34 Biopesticides Registration Action Document

1. Ecological Exposure and Risk Characterization

a. Terrestrial Animals and Plants

Birds ( Harmonized Guideline 885.4050) and Wild Mammals (Harmonized Guideline 885.4150) (MRID Nos. 4786 51

- 03 and 482526

- 01) : Data and other i nformation submitted by BioWorks, Inc. to support its waiver requests showed that Trichoderma virens strain G

- 41 is not expected to be toxic or pathogenic to birds or mammals because ( 1) birds and mammals are commonly exposed to this fungus; ( 2) Trichoderma virens strain G

- 41 does not grow at mammalian or avian body temperatures; and ( 3) Trichoderma virens strain G

- 41 is similar to Trichoderma virens strain GL

- 21, which was previously determined to present minimal risk to birds and mammals

. Trichoderma virens is a ubiquitous fung us in terrestrial environments, inhabiting soil of all types and plant litter (Samuels 1996). Therefore, wild mammals and birds are commonly exposed to this fungus. Trichoderma virens strain G

- 41 also do es not grow at 3 9 oC or above (Kenerley 2010 ). Kenerley (2010) also provides data to show that Trichoderma virens strain G

- 41 is biologically similar to Trichoderma virens strain GL

- 21 and is expected to have a similar toxicity/pathogenicity profile

. Trichoderma virens strain G

- 41 is not expected to adverse ly affect wild mammals, since no toxicity or pathogenicity was shown in laboratory rats exposed to G

- 41 Technical by injection at 10 7 units of MPCA per animal (submitted in MRID Nos. 478651

- 02 and 482 368

- 01). Based on this information, adverse effects to wild mammals and birds are not anticipated to result from the proposed labeled uses of Trichoderma virens strain G

- 41.

Nontarget Insects ( Harmonized Guideline 885.4340) and Honey Bees (Harmonized Guideline 885.4380) (MRID Nos.478651

- 03 and 482526

- 01) : BioWorks, Inc. presented s imilar data and information to support waiver requests and a conclusion of minimal exposure and risk to nontarget insects and honey bees. Trichoderma virens strain G

- 41 is no t expected to be toxic or pathogenic to honey bees and other insects

, because it is a naturally occurring fungus that is not an insect pathogen, and it also has not been known to produce insect epizootics (i.e., widespread outbreaks of disease that spread quickly) . It is also native to the United States and is widely distributed throughout the world, inhabiting forest, agricultural and orchard soils as well as plant litter (Samuels 1996). The end

- use pesticide products are proposed for use in greenhouses,

n urseries, and soil treatments, which will reduce exposure to honey bees and many other insects. Since Trichoderma virens is naturally found in soils and plant litter, soil

- and ground

- dwelling insects are commonly exposed to this fungus. As discussed below (see “nontarget plants” summary) , the proposed applications of T richoderma virens strain G

- 41 are not expected to increase the concentrations of this fungus above naturally occurring levels. Based on these lines of evidence, the proposed pesticidal uses o f Trichoderma virens strain G

- 41 are not expected to result in adverse effects to honey bees and other nontarget insects.

Nontarget Plants ( Harmonized Guideline 885.4300 ; MRID Nos. 478651

- 03 and 482526

- 01 ) : BioWorks, Inc. presented data and other informa tion to support waiver requests and show that Trichoderma virens strain G

- 41 will not cause adverse effects in nontarget plants

. Trichoderma virens is a naturally occurring fungus that is native to the United States and is widely distributed throughout the world, inhabiting forest, agricultural and orchard soils

, as well as plant litter (Samue ls 1996). Therefore, nontarget terrestrial plants are commonly exposed to Trichoderma virens . The proposed applications are also not expected to significantly increase the populations of this fungus in soil above natural levels. No reports were available in the literature describing natural concentrations of T richoderma virens ; however, Trichoderma spp. have been reported inTrichoderma virens strain G

- 41 Page 16 of 34 Biopesticides Registration Action Document

various types of soils at concentrations of 1 0 4 to 10 6 cfu/g (Leandro et al . 2007, Liu et al . 2008). Based on the maxi mum application rate of the end

- use pesticide products containing
T

richoderma virens strain G

- 41

, and its report ed minimum viability in the end

- use pesticide product s (5 x 10 6 cfu/g), the estimated amount of Trichoderma virens applied to the soil surface is approximately 6.7 x 10 3 cfu/cm 2

. Assuming a soil bulk density of 1 to 2 g/cm 3

, the maximum application rate will not result in soil concentrations that are substantially greater tha n concentrations of Trichoderma virens naturally found in the soil , and increased exposure to Trichoderma virens in the terrestria l environment is not expected. Trichoderma virens is also not related to known plant pathogens. The refore, based on the data a nd information presented, adverse effects to terrestrial nontarget plants resulting from the proposed pesticidal applications of Trichoderma virens strain G

- 41 are not expected.

b. Aquatic Animals and Plants

Freshwater Fish ( Harmonized Guideline 8 85.4200) , Freshwater Invertebrates ( Harmonized Guideline 885.4240)

, Estuarine/Marine Fish and Inverte brates (Harmonized Guideline 885.4280) , and Nontarget Plants (Harmonized Guideline 885.4300) (MRID Nos. 478651

- 03 and 482526

- 01) : BioWorks, Inc. presented s imilar data and information to support waiver requests and show that adverse effects to freshwater and marine/estuarine fish and invertebrates will not occur as a result of the proposed applications of Trichoderma virens strain G

- 41. Similar data and info rmation was als o provided for aquatic plants. Trichoderma virens is native to the United States and is widely distributed

, inhabiting forest, agricultural and orchard soils

, as well a s plant litter (Samuels 1996). Given the ubiquitous distribution of Trich oderma virens in soil, this microbe is very likely washed into freshwater and marine/estuarine systems in nature, and fish, invertebrates, and aquatic plants are commonly exposed to this fungus

. As discussed above (see “nontarget plants” summary) , the maxi mum proposed application rate is not expected to raise the concentration of Trichoderma virens in the soil above naturally occurring levels, so runoff from treated areas is expected to contain similar amounts of Trichoderma virens as would be expected in r unoff from natural areas. Trichoderma virens is also not known to proliferate in water, so Trichoderma virens deposited in water from runoff would not become established in aquatic environments. Based on this data and information, the proposed pesticidal a pplications of Trichoderma virens strain G

- 41 are not expected to result in significant exposure of nontarget aquatic organisms to levels above those that occur naturally, and adverse effects to freshwater and marine/estuarine fish, invertebrates, and plan ts are not expected.

2. Environmental Fate Data

As t he data and information provided are sufficient to fulfill the Tier I nontarget organism data requirements and allow for nontarget organism risk asse ssment for Trichoderma virens strain G

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

3

. Threatened and Endangered Species Assessment

Since EPA has determined that no effects are ant icipated for any non target species exposed to Trichoderma virens strain G

- 41 a s a result of the proposed applications, effects to threatened and endangered species and their designated critical ha bitats are also not expected. Therefore, a “No Effect” determination is made for direct and indirect effects to listed species and their d esignated critical habitats resulting from the proposed pesticidal uses of Trichoderma virens strain G

- 41 , asTrichoderma virens strain G

- 41 Page 17 of 34 Biopesticides Registration Action Document

labeled.

V. ENVIRONMENTAL JUSTICE

EPA seeks to achieve environmental justice

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

— with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. Fair treatment means that no group of people, including racial, ethnic, or socioeconomic gro ups, should bear a disproportionate share of the negative environmental consequences resulting from industrial, municipal, and commercial operations or the execution of federal, state, local, and tribal environmental programs and policies. Meaningful invol vement means that (1) potentially affected community residents have an appropriate opportunity to participate in decisions about a proposed activity that will affect their environment and/or health; (2) the public’s contribution can influence the regulator y 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 a nd persons across the United States.

To help address potential environmental justice issues, during the 30

- day public participation comment period, EPA sought information on any groups or segments of the population who, as a result their location, cultur al practices, or other factors, may have atypical, unusually high exposure to Trichoderma virens strain G

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

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

.

V I

. RISK MANAGEMENT DECISION

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

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

To satisfy criterion 1, the Trichoderma virens strain G

- 41 pesticide products have well

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

- 41 Technical, BW240 WP Biological Fungi cide, and BW240 G Biological Fungicide label s, and such pesticide products are not expected to cause unreasonable adverse effects on the environment when used according to the ir respective label instructions. Criterion 2 is satisfied by the current productTrichoderma virens strain G

- 41 Page 18 of 34 Biopesticides Registration Action Document

label s, as well as the data and information presented in this document. It is believed that the Trichoderma virens strain G

- 41 pesticide products will not cause any unreasonable adverse effects on the environment, and BW240 WP Biological Fungicide and BW2 40 G Biological Fungicide (end

- use pesticide product s ) , in particular, are likel y to provide protection against fungal pests as claimed, satisfying criterion 3. Criterion 4 is satisfied in that the Trichoderma virens strain G

- 41 pesticide products are not expected to cause unreasonable adverse effects when used according to label instructions. Therefore, G

- 41 Technical, BW240 WP Biological Fungicide, and BW240 G Biological Fungicide

, containing Trichoderma virens strain G

- 41 as a new active ingredient, are eligible for registration under FIFRA section 3(c)(5) for the labeled

uses.

V I I

. ACTIONS REQUIRED OF THE REGISTRANT

A. Final Printed Labeling

Before releasing pesticide products containing Trichoderma virens strain G

- 41 for shipment, the registrant is required to provide appropriate final printed labeling to EPA

.

B. Terms of Registration

As terms of the G

- 41 Technical, BW240 WP Biological Fungicide, and BW240 G Biological Fungicide registrations, BioWorks, Inc. must submit the results of a one

- yea r s torage s tability (Harmonized Guideline 830.6317) and c orrosion c haracteristics (Harmonized Guideline 830.6320) study within one year of registration

.
Additionally, as a term of the BW240 G Biological Fungicide registration, BioWorks, Inc. must submit a dditional information (confirmatory) on the d iscussion of fo rmation of u nintentional i ngredients (Harmonized Guideline 885.1300) and a nalysis of s amples (Harmonized Guideline 885.1400) data requirements within six months of registration.

C. Reporting of Adverse Effects and Hypersensitivity Incidents

Notwithstanding the information stated in the previous sections, it should be clearly understood that certain specific data are required to be reported to EPA as a requirement for maintaining the federal reg istration 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).Trichoderma virens strain G

- 41 Page 19 of 34 Biopesticides Registration Action Document

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

BRAD Biopesticides Registration Action Document CFR Code of Federal Regulations

c fu colony

- forming unit (s) cfu/cm 2 colony

- forming units per square centimeter cfu/g colony

- forming units per gram cfu/mL colony

- forming unit s per milliliter EDSP Endocrine Disruptor Screening Program EP end

- use pesticide produc t EPA United States Environmental Protection Agency (the “Agency”) FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FR Federal Register
g gram g/cm 3 grams per cubic centimeter LC 50 median lethal concentra tion. 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 me dian 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 a nimal (e.g., mg/kg). mg/kg milligram s per kilogram mg/L milligram s per liter MP manufacturing

- use pesticide product MPCA microbial pest control agent MRID No. Master Record Identification Number NAFTA North American Free Trade Agreement NIOSH National Ins titute for Occupational Safety and Health OPP Office of Pesticide Programs PC Code Pesticide Chemical Code PMRA Health Canada Pest Management Regulatory Agency PP Pesticide Petition PPE personal protective equipment
ppm parts per million TGAI technical g rade of the active ingredient U.S. United States USPTO United States Patent and Trademark OfficeTrichoderma virens strain G

- 41 Page 20 of 34 Biopesticides Registration Action Document

I X. BIBLIOGRAPHY

A. Studies Submitted or Cited to Support the Trichoderma virens strain G

- 41 Pesticide Product Registrations

MRID No

. Study Information

407198

- 04 David R. 1988. Acute Oral Toxicity/Pathogenicity Study of Alginate Prill of Strain GL21 in Rats

– Final Report. Study Number: G

- 7131.222. Unpublished study prepared by Microbiologi cal Associates, Inc., 22 pages.

407198

- 05 David R. 1988. Acute Pulmonary Toxicity/Pathogenicity Study of Spores of Strain GL21 in Rats

– Interim Report. Study Number: G

- 7131.225. Unpublished study prepared by Microbiological Associates, Inc., 20 pages.

4 07198

- 06 David R. 1981. Acute Intravenous Toxicity/Pathogenicity Study of Mycelia of Strain GL21 in Rats

– Interim Report. Study Number: G

- 7131.224. Unpublished study prepared by Microbiological Associates, Inc., 21 pages.

408640

- 01 David R. 1988. Acute I ntravenous Toxicity/Pathogenicity Study of Mycelia of Strain GL21 in Rats

– Final Report. MBA Study Number: G

- 7131.224. Unpublished study prepared by Microbiological Associates, Inc., 23 pages.

408640

- 02 David R. 1988. Acute Pulmonary Toxicity/Pathogenici ty Study of Spores of Strain GL21 in Rats

– Final Report. MBA Study Number: G

- 7131.225. Unpublished study prepared by Microbiological Associates, Inc., 23 pages.

478649

- 01 Brookman D. 2009. Product Chemistry of BW240 Granules. Project Number: BW240G/001. Unpublished study prepared by Technology Sciences Group, Inc., 57 pages.

478650

- 01 Brookman D. 2009. Product Chemistry of BW240 WP. Project Number: BW240/001. Unpublished study prepared by Technology Sciences Group, Inc., 79
pages.

478650

- 02 Kuhn J. 2009 . BW240 WP: Acute Oral Toxicity Study (UDP) in Rats

– Final Report. Project Number: 12982/09. Unpublished study prepared by Stillmeadow, Inc., 11 pages.

478650

- 03 Kuhn J. 2009. BW240 WP: Acute Dermal Toxicity Study in Rats

– Final Report. Project Number: 12983/09. Unpublished study prepared by Stillmeadow, Inc., 12
pages.

478650

- 04 Younger C. 2009. BW240 WP: Acute Inhalation Toxicity Study in Rats

– Final Report. Project Number: 12984/09. Unpublished study prepared by Stillmeadow, Inc., 18 pages.Trichoderma virens strain G

- 41 Page 21 of 34 Biopesticides Registration Action Document

MRID N o. Study Information

478650

- 05 Kuhn J. 2009. BW240 WP: Acute Eye Irritation Study in Rabbits

– Final Report. Project Number: 12985/09. Unpublished study prepared by Stillmeadow, Inc., 17
pages.

478650

- 06 Kuhn J. 2009. BW240 WP: Acute Dermal Irritation Study in Rabbits

– Final Report. Project Number: 12986/09. Unpublished study prepared by Stillmeadow, Inc., 12 pages.

478651

- 01 Brookman D. 2009. Product Chemistry of G

- 41 Technical. Project Number: BWG41/001, G6 690/PHYCHEM, G6690. Unpublished study prepared by Technology Sciences Group, Inc., 95 pages.

478651

- 02 Prakash P. 2009. G41 Technical Grade Active Ingredient: Acute Injection Toxicity/Pathogenicity Study in Wistar Rats. Project Number: G6692/AP/R, G6692. Unpublished study prepared by Advinus Therapeutics Private Ltd., 28
pages.

478651

- 03 Mileson B. 2009. Response to Tier I Microbial Pesticide Data Requirements for G

- 41 Technical. Unpublished study prepared by Technology Sciences Group, Inc., 47 pages.

4 78708

- 01 Even M. 2009. Response to Tier I Microbial Pesticide Data Requirements for G

- 41 Technical. Unpublished study prepared by Technology Sciences Group. Inc., 32 pages.

481964

- 02 Even M. 2010. Response to Tier I Microbial Pesticide Data Requirements for BW240 G. Unpublished study prepared by Technology Sciences Group, Inc., 4
pages.

482104

- 01 Brookman D. 2010. Supplemental Product Chemistry of BW240 WP. Project Number: BW240WP/002. Unpublished study prepared by Technology Sciences Group, Inc., 22 pag es.

482104

- 02 Even M. 2010. Response to Tier I Microbial Pesticide Data Requirements for BW240 WP. Unpublished study prepared by Technology Sciences Group, Inc., 4
pages.

482120

- 01 Brookman D, Bjornson H. 2010. Supplemental Product Chemistry of G

- 41 Tech nical. Project Number: BWG41/002. Unpublished study prepared by Technology Sciences Group, Inc., 57 pages.

482368

- 01 Prakash P. 2009. G41 Technical Grade Active Ingredient: Acute Injection Toxicity/Pathogenicity Study in Wistar Rats

– Final Report. Projec t Number: G6692. Unpublished study prepared by Advinus Therapeutics Private Ltd., 7
pages.Trichoderma virens strain G

- 41 Page 22 of 34 Biopesticides Registration Action Document

MRID No. Study Information

482526

- 01 Mileson B, Even M. 2010. Response to Tier I Microbial Pesticide Data Requirements for G

- 41 Technical. Unpublished study prepared by BioWorks, Inc., 220 pages.

483438

- 01 Monds K. 2010. G41 TGAI: Acute Oral Toxicity/Pathogenicity Study in Rats

– Final Report. Project Number: 14392/10. Unpublished study prepared by Stillmeadow , Inc., 28 pages.

B. Environmental Protection Agency Risk Assessment Memoranda

U.S. EPA. 2011a. Review of Product Chemistry, Manufacturing Process, Discussion of Formation of Unintentional Ingredients, Analysis of Samples, Certification of Limits, and P hysical and Chemical Characteristics for Section 3 Registration of an End Use Product BW240 G (EPA Reg. No. 68539

- RN). Memorandum from I.S. Barsoum, Ph.D. and J.L. Kough, Ph.D. to J. Kausch dated July 7, 2011.

U.S. EPA. 20 11 b

. Environmental Risk Assessmen t of the FIFRA Section 3 registration of Trichoderma virens strain G

- 41 (PC Code 176604 ; EPA File Symbols 68539

- I,

- O,

- RN). Memorandum from S. Borges to J. Kausch dated November 14, 2011.

U.S. EPA. 2011c. Review of Product Chemistry, Manufacturing Pr ocess, Discussion of Formation of Unintentional Ingredients, Analysis of Samples, Certification of Limits, Physical and Chemical Characteristics, and Acute Toxicity Studies for Section 3 Registration of an MUP G

- 41 Technical (EPA Reg. No. 68539

- I) and an E P BW240 WP (EPA Reg. No. 68539

- O). Memorandum from I.S. Barsoum, Ph.D. and J.L. Kough, Ph.D. to J. Kausch dated December 20, 2011.

C. Other References

Bjornsen HR. 2009. Cover Letter Accompanying Application for Pesticide Registration (re: Applicatio n to Register BW240 G). Letter from H.R. Bjornsen to S. Reilly dated September 18, 2009.

Brookman D. 2010. Supplement Product Chemistry of BW240 Granules. Unpublished study prepared by Technology Sciences Group, Inc., 16 pages (No MRID No.).

Cente rs for Disease Control and Prevention. 2009. Drinking Water

- Water Treatment. Available from http://www.cdc.gov/healthywater/drinking/public/water_treatment.html

.

Jacks on AM, Whipps JM, Lynch JM. 1991. Production, delivery systems, and survival in soil of four fungi with biocontrol potential. Enzyme Microb

. Tech . 13:636

– 642.

Kenerley CM. 2010. Report on studies comparing two strains of Trichoderma virens ; GL21 and G41. Texas A&M University, Department of Plant Pathology and Microbiology. Unpublished report.Trichoderma virens strain G

- 41 Page 23 of 34 Biopesticides Registration Action Document

Leandro LFS, Guzman T, Ferguson LM, Fernandez GE, Louws FJ. 2007. Population dynamics of Trichoderma in fumigated and compost

- amended soil and on strawb erry roots. Appl

. Soil Ecol . 35:237

– 246.

Liu B, Glenn D, Buckley K. 2008. Trichoderma communities in soils from organic, sustainable, and conventional farms, and their relation with Southern blight of tomato. Soil Biol

. Biochem . 40:1124

– 1136.

Lo nga CMO, Savazzini F, Tosi S, Elad Y, Pertot I. 2009. Evaluating the survival and environmental fate of the Biocontrol agent Trichoderma atroviride SC1 in vineyards in northern Italy. J. Appl

. Microbiol . 106:1549

– 1557.

Lumsden RD, Walter JF, Baker C P. 1996. Development of Gliocladium virens for damping

- off disease control. Can

. J

. Plant Pathol . 18:463

– 468.

Samuels GJ. 1996. Trichoderma : A review of biology and systematics of the genus. Mycol

. Res

. 100:923

– 935.

Sariah M, Choo CW, Zakaria H, N orihan MS. 2005. Quantification and characterization of Trichoderma spp. from different ecosystems. Mycopathologia 159:113

– 117.

U.S. EPA. 2010a. Trichoderma asperellum strain ICC 012 Biopesticides Registration Action Document dated March 4, 2010 (a vailable as “Supporting & Related Material” within docket ID number EPA

- HQ

- OPP

- 2009

- 1004 at http://www.regulations.gov ).

U.S. EPA. 2010b. Trichoderma gamsii strain ICC 080 Biopesticides Registration Action Document dated March 4, 2010 (available as “Supporting & Related Material” within docket ID number EPA

- HQ

- OPP

- 2009

- 1003 at http://www.regulations.gov ).

U.S. EPA. 2010c. Trichoderma hamatum isolate 382 Biopes ticides Registration Action Document dated July 13, 2010 (available as “Supporting & Related Material” within docket ID number EPA

- HQ

- OPP

- 2010

- 0489 at http://www.regulations.gov ).

U.S. EPA. 2008. Trichoder ma Species Final Registration Review Decision (signed September 11, 2008). Available from http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

OPP

- 2006

- 0245

- 0008;oldLink=false

.
U.S. EPA. 2004. Primer for Municipal Wastewater Treatment Systems. EPA 832

- R

- 04

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

.

USPTO. 2010. Contro l of Plant Diseases and Enhancing Plant Growth Using a Combination of a Trichoderma virens Species and a Rhizosphere Competent Trichoderma harzianum Species (United States Patent Application

– US 2010/0028303 A1). Available from http://www.freepatentsonline.com/20100028303.pdf

.Trichoderma virens strain G

- 41 Page 24 of 34 Biopesticides Registration Action Document

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

– SUBPART V )

TABLE 1. Product Analysis Data Requirements for the Technical Grade o f the Active Ingredient (TGAI) , Trichoderma virens strain G

- 41, and the Manufacturing

- Use Pesticide Product ( MP ) , G

- 41 Technical (40 CFR § 158.2 120 )
Harmonized

G uideline N umber Data Requirement Results MRID No. Trichoderma virens strain G

- 41 G

- 41 Tech nical

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

- 41 Technical contains 12.10% by weight Trichoderma virens strain G

- 41.

478651

- 01 482120

- 01 885.1200 Manufacturing Process Submitted data fulfill the r equiremen t for manufacturing process

.

Not applicable Deposition of a Sample in a Nationally Recognized Culture Collection Trichoderma virens strain G

- 41 is on deposit with the American Type Culture Collection in Manassas, Virginia under Accession Number ATCC 20906. N/A

885.1300 Discussion of Formation of Unintentional

Ingredients Submitted data fulfill the requiremen t for discussion of formation of unintentional ingredients

.

885.1400 Analysis of S amples Submitted data fulfill the requirement for analy sis of samples. 478651

- 01

8 85 .1 50 0 Certification of L imits N/A Limits listed o n the confidential statement of formula are

adequate/a cceptable. 478651

- 01 482120

- 01Trichoderma virens strain G

- 41 Page 25 of 34 Biopesticides Registration Action Document

TABLE 2. Product Analysis Data Requirements for the End

- Use Pestic ide Product ( E P s ), BW240 WP Biological Fungicide and BW240 G Biological Fungicide (40 CFR § 158.2120)
Harmonized

Guideline Number Data Requirement Results MRID No. BW240 WP* BW240 G**

885.1100 Product Identity Submitted data fulfill the requirement f or product identity. BW240 WP contains 1.15% by weight Trichoderma harzianum Rifai strain T

- 22 and 0.61% by weight Trichoderma virens strain G

- 41. Submitted data fulfill the requirement for product identity. BW240 G contains 1.15% by weight Trichoderma har zianum Rifai strain T

- 22 and 0.61% by weight Trichoderma virens strain G

- 41. 478649

- 01* * Brookman (2010)* * 478650

- 01* 482104

- 01*

885.1200 Manufacturing Process Submitted data fulfill the requirement for manufacturing
process. 478649

- 01** 478650

- 01* 482104

- 01*

N/A Deposition of a Sample in a Nationally Recognized

Culture Collection N/A N/A

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

formation of unintentional ingredients. Submitted data fulfill the requirement for discussion of formation of unintentional ingredients for purposes of FIFRA section 3(c)(5) registration. As a term of the BW240 G registration, EPA is requiring additional information (confirmatory) on this data requiremen t. 478649

- 01** 478650

- 01*

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

. Submitted data fulfill the requirement for discussion of formation of unintentional ingredients for purposes of FIFRA section 3(c)(5)

re gistration. As a term of the BW240 G registration, EPA is requiring additional information (confirmatory) on this data requirement. 478649

- 01** 478650

- 01*

885.1500 Certification of Limits Limits listed on the confidential statement of formula are adequate /acceptable. 478649

- 01** Brookman (2010)** 478650

- 01* 482104

- 01*Trichoderma virens strain G

- 41 Page 26 of 34 Biopesticides Registration Action Document

TABLE 3

. Physical and Chemical Characteristics for the Technical Grade of the Active Ingredient (TGAI), Trichoderma virens strain G

- 41, and the Manufacturing

- Use Pesticide Product (MP), G

- 41 Technical (40 CFR § 158.2120)

Harmonized G uideline N umber Data Requirement Results MRID No. Trichoderma virens strain G

- 41 G

- 41 Technical

830.6302 1 Color Gray

- green

478651

- 01 830.6303 1 Physical State Solid 830.6304 1 Odor Slight musty odor

830.6313 1 Stability to Normal and E levated Temperatures, Metals, and Metal I ons Unstable at elevated temperatures; stable to metals or metal ions (iron metal, aluminum metal, iron acetate, and aluminum acetate).

830.6317 Storage Stability Stable at 4°C a nd 21°C for 6 months. As a term of the G

- 41 Technical registration, EPA is requiring the results of a

one - year storage stability and corrosion characteristics study be submitted within one year of registration

.

830.6319 Miscibility N/A Not required becau se G

- 41 Technical is not an

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

830.6320 Corrosion Characteristics Not corrosive to polyethylene bag in a six

- month study. As a term of the G

- 41 Technical registration, EPA is requiring the results of a one

- year storage stability and corrosion characteristics study be submitted within one year of registration

. 478651

- 01

830.7000 1 pH 5.6 (1% solution)

830.7100 Viscosity N/A Not required because G

- 41 Techni cal is not a liquid form of a microbial pesticide (refer to test note #4 of 40 CFR § 158.2120(d)). N/A

830.7300 1 Density/Relative Density/Bulk Density

(Specific Gravity) 0.178 g/cm 3 478651

- 01

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

Inc. included this information with its application for G

- 41 Technical , it is summarized appropriately in this table.Trichoderma virens strain G

- 41 Page 27 of 34 Biopesticides Registration Action Document

TABLE 4. Physical and Chemical Characteristics fo r the End

- Use Pesticide Product s (EP s ), BW240 WP Biological Fungicide and BW240 G Biological Fungicide (40 CFR § 158.2120)
Harmonized Guideline Number Data Requirement Results MRID No. BW240 WP* BW240 G** 830.6302 Color N/A N/A 830.6303 Physical Sta te N/A N/A 830.6304 Odor N/A N/A

830.6313 Stability to Normal and Elevated Temperatures, Metals, and Metal Ions N/A N/A

830.6317 Storage Stability Stable at 4°C and 21°C for 6 months

. As terms of the BW240 WP and BW240 G registration s , EPA is requiring the results of a one - year storage stability and corrosion characteristics study be submitted within one year of registration

. 478649

- 01** 478650

- 01*

830.6319 Miscibility Not required because the end

- use pesticide products, BW240 WP and BW240 G, are not em ulsifiable liquid forms of microbial pesticides (refer to test note #2 of 40 CFR § 158.2120(d)). N/A

830.6320 Corrosion Characteristics Not corrosive to polyethylene bag in a six

- month study

. As term s of the BW240 WP and BW240 G registration s , EPA is requ iring the results of a one year storage stability and corrosion characteristics study be submitted within one year of registration

. 478649

- 01** 478650

- 01*

830.7000 1 pH 4.35 (1% solution) N/A 482104

- 01*

830.7100 Viscosity Not required because the end

- use pesticide products, BW240 WP and BW240 G, are not liquid forms of microbial pesticides (refer to test note #4 of 40 CFR § 158.2120(d)). N/A

830.7300 1 Density/Relative Density/Bulk Density

(Specific Gravity) 0.147 g/cm 3 N/A 2

1 According to 40 CFR § 158.2 120, these data are only required for the technical grade of the active ingredient. Since BioWorks,

Inc. included this information with its application for BW240 WP and/or BW240 G

, it is summarized appropriately in this table

. 2 Obtained from the confid ential statements of formula for the end

- use pesticide products.Trichoderma virens strain G

- 41 Page 28 of 34 Biopesticides Registration Action Document

T ABLE 5

. Toxicology Data Requirements for the Technical Grade of the Active Ingredient (TGAI) , Trichoderma virens strain G

- 41, and the Manufacturing

- Use Pesticide Product (MP) , G

- 41 Technic al (40 CFR § 158.2140) Harmonized

Guideline N umber Data Requirement Results MRID N o. Trichoderma virens strain G

- 41 G

- 41 Technical
Tier I

885.3050 Acute Oral Toxicity/Pathogenicity Not toxic to rats when administered by oral gavage in a single dose of 1.5 x 10 8 cfu per animal. Although a pattern of pathogenicity was established, pathogenicity was not unequivocally assessed given a sensitivity of detection that demonstrated low recovery of the MPCA from tissues and fluid (0.5

– 9%). Classification: Acc eptable TOXICITY CATEGORY IV N/A 483438

- 01

885.3150 Acute Pulmonary Toxicity/Pathogenicity Fulfilled based on the results of MRID Nos. 407198

- 05 and 408640

- 02 (acute pulmo nary toxicity/pathogenicity study ) and MRID No. 478650

- 04 (acute inhalation toxicity study)

. N/A 478708

- 01 482526

- 01

885.3200 Acute Injection Toxicity/Pathogenicity (Intra peritoneal ) N ot toxic, infective, and/or pathogenic

to rats when administered intraperitoneally in a single dose of 10 7 cfu per animal

. Classification: Acceptable N/A 478651

- 02 482368

- 01

885.3400 Hypersensitivity Incidents No hypersensitivity incidents, including immediate

- type or delayed

- type reactions of humans and domestic animals that occurred durin g research, development, or testing of the TGAI or MP , were report ed by the applicant. Any future hypersensitivity incidents must be reported to EPA (refer to test note #3 of 40 CFR § 158.2140(d))

. 482526

- 01

885.3500 Cell Culture Not required because Trichoderma virens strain G

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

870.1100 Acute Oral Toxicity N/A Waived based on the results of MRID No. 4 83438

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

conce rn. Classification: Acceptable T OXICITY CATEGORY III 478651

- 03

870.1200 Acute Dermal Toxicity N/A Waived because this formulation contains inert ingredients that are not expected to be of toxicological conce rn. Classification: Acceptable TOXICITY CATEGORY III 478651

- 03Trichoderma virens strain G

- 41 Page 29 of 34 Biopesticides Registration Action Document

T ABLE 5

. Toxicology Data Requirements for the Technical Grade of the Active Ingredient (TGAI) , Trichoderma virens strain G

- 41, and the Manufacturing

- Use Pesticide Product (MP) , G

- 41 Technic al (40 CFR § 158.2140) Harmonized

Guideline N umber Data Requirement Results MRID N o. Trichoderma virens strain G

- 41 G

- 41 Technical

870.1300 Acute I nhalation Toxicity N/A Waived based on the results of MRID No s

. 478650

- 04, 407198

- 05, and 408640

- 02 and because this formulation contains inert ingredients that are not expected to be of toxicological conce rn. Classification: Acceptable TOXICITY CATEGORY I II 478651

- 03

870.2400 Acute Eye Irritation N/A Waived because this formulation contains inert ingredients that are not expected to be of toxicological conce rn. Classification: Acceptable TOXICITY CATEGORY III 478651

- 03

870.2500 Primary Dermal Irritation N/A Waived because this formulation contains inert ingredients that are not expected to be of toxicological conce rn. Classification: Acceptable TOXICITY CATEGORY III 478651

- 03

Tiers II and III Not required for Trichoderma virens strain G

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

Additional Studies

885.3050 Acute Oral Toxicity/Pathogenicity Not toxic to, infective in, or pathogenic for rats when given a single oral dose of 10 8 cfu/animal ( Trichoderma virens strain GL

- 21). Classification: Acceptable but supplemental in this situation (test organism is not the MPCA proposed for registration). N/A 407198

- 04

885.3150 Acute Pulmonary Toxicity/Pathogenicity Not toxic to, infective in, or pathogenic for rats when given a sin gle intratracheal dose of 10 8 cfu/animal ( Trichoderma virens strain GL

- 21). Classification: Acceptable but supplemental in this situation (test organism is not the MPCA proposed for registration). N/A 407198

- 05 408640

- 02Trichoderma virens strain G

- 41 Page 30 of 34 Biopesticides Registration Action Document

T ABLE 5

. Toxicology Data Requirements for the Technical Grade of the Active Ingredient (TGAI) , Trichoderma virens strain G

- 41, and the Manufacturing

- Use Pesticide Product (MP) , G

- 41 Technic al (40 CFR § 158.2140) Harmonized

Guideline N umber Data Requirement Results MRID N o. Trichoderma virens strain G

- 41 G

- 41 Technical

885.3200 Acute Injection Toxicity/ Pathogenicity (Intravenous) Not infective in or pathogenic for rats when given a single intravenous dose of 0.1 gram (g)/animal ( Trichoderma virens strain GL

- 21). The data supports the conclusion, however, that the test material is acutely toxic and lethal for test animals via mechanical clogging of capillaries. Classification: Acceptable but supplemental in this situation (test organism is not the MPCA proposed for registration). N/A 407198

- 06 408640

- 01

TABLE 6

. Toxicology Data Requirements for the End

- Use Pesticide Product s (EPs) , BW240 WP Biological Fungicide and BW240 G Biological Fungicide (40 CFR § 158.2140)
Harmonized

Guideline Number Data Requirement Results MRID No. BW240 WP * BW240 G **

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

88 5.3150 Acute Pulmonary Toxicity/Pathogenicity N/A N/A

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

885.3400 Hypersensitivity Incidents No hypersensitivity incidents, including immediate

- type or delayed

- type reactions of humans and domestic ani mals that occurred during research, development, or testing of the EP s , were reported by the applicant. Any future hypersensitivity incidents must be reported to EPA (refer to test note #3 of 40 CFR § 158.2140(d)). 482104

- 02* 481964

- 02 **

885.3500 Cell Cul ture N/A N/A

870.1100 Acute Oral Toxicity Oral LD 50 female rats > 5,000 mg/kg Classification: Acceptable TOXICITY CATEGORY I V Waived based on the results of MRID No. 478650

- 02, which evaluated a substance with identical active ingredients (1.15% Trichoder ma harzianum Rifai strain T

- 22 and 0.61% Trichoderma virens strain G

- 41) and nearly identical inert ingredients to BW240 G. Classification: Acceptable TOXICITY CATEGORY I V 478650

- 02 * Bjornsen (2009)**

870.1200 Acute Dermal Toxicity Dermal LD 50 combined (m ale and female) rats > 5,050 mg/kg Classification: Acceptable TOXICITY CATEGORY I V Waived based on the results of MRID No. 478650

- 03, which evaluated a substance with identical active ingredients (1.15% Trichoderma harzianum Rifai strain T

- 22 and 0.61% Tri choderma virens strain G

- 41) and nearly identical inert ingredients to BW240 G. Classification: Acceptable TOXICITY CATEGORY I V 478650

- 03* Bjornsen (2009)**Trichoderma virens strain G

- 41 Page 31 of 34 Biopesticides Registration Action Document

TABLE 6

. Toxicology Data Requirements for the End

- Use Pesticide Product s (EPs) , BW240 WP Biological Fungicide and BW240 G Biological Fungicide (40 CFR § 158.2140)
Harmonized

Guideline Number Data Requirement Results MRID No. BW240 WP * BW240 G **

870.1300 Acute Inhalation Toxicity 4

- Hour Inhalation LC 50 combined (male and female) rats > 5.14 m g/L Classification: Acceptable TOXICITY CATEGORY I V Waived based on the results of MRID No. 478650

- 04, which evaluated a substance with identical active ingredients (1.15% Trichoderma harzianum Rifai strain T

- 22 and 0.61% Trichoderma virens strain G

- 41) an d nearly identical inert ingredients to BW240 G. Classification: Acceptable TOXICITY CATEGORY I V 478650

- 04* Bjornsen (2009)**

870.2400 Acute Eye Irritation BW240 WP was minimally irritating to the eye of rabbits based on the maximum irritation score of 18 obtained 24 hours after

treatment. P ositive effects cleared by Day 4

. Classification: Acceptable TOXICITY CATEGORY I II Waived based on the results of MRID No. 478650

- 0 5 , which evaluated a substance with identical active ingredients (1.15% Trichoderma harz ianum Rifai strain T

- 22 and 0.61% Trichoderma virens strain G

- 41) and nearly identical inert ingredients to BW240 G. Classification: Acceptable TOXICITY CATEGORY I II 478650

- 05* Bjornsen (2009)**

870.2500 Primary Dermal Irritation BW240 WP was non

- irritati ng to the skin of rabbits. Classification: Acceptable TOXICITY CATEGORY I V Waived based on the results of MRID No. 478650

- 0 6 , which evaluated a substance with identical active ingredients (1.15% Trichoderma harzianum Rifai strain T

- 22 and 0.61% Trichoderma virens strain G

- 41) and nearly identical inert ingredients to BW240 G. Classification: Acceptable TOXICITY CATEGORY IV 478650

- 06* Bjornsen (2009)**Trichoderma virens strain G

- 41 Page 32 of 34 Biopesticides Registration Action Document

TABLE 7

. Nontarget Organism Toxicity and Environmental Fate Data Requirements for the T echnical Grade of the Active Ingredient (TGAI), Trichoderma virens strain G

- 41 (40 CFR § 158.2150)
Harmonized Guideline Number Data Requirement Results MRID No.

Tier I

885.4050 Avian Oral Toxicity Data and other information provide sufficient informatio n to determine that toxicity/pathogenicity to avian wildlife is not expected as a result of the proposed pesticidal

uses. Classification: Acceptable 478651

- 03 482526

- 01

885.4100 Avian Inhalation Toxicity/Pathogenicity Not required as the nature of the mic robial pesticide does not indicate potential pathogenicity to birds or relatedness to any known bird pathogens (refer to test note #3 of 40 CFR § 158.2150(e)). N/A

885.4150 Wild Mammal Toxicity/Pathogenicity

Data and other information provide sufficient i nformation to determine that toxicity/pathogenicity to wild mammals, freshwater and marine/estuarine fish and invertebrates, honey bees, nontarget insects, and nontarget plants is not expected as a result of the proposed pesticidal uses. Classification: Ac ceptable 478651

- 03 482526

- 01 885.4200 Freshwater Fish Toxicity/Pathogenicity

885.4240 Freshwater Invertebrate Toxicity/Pathogenicity

885.4280 Estuarine/Marine Fish and Invertebrate Testing

885.4300 Nontarget Plant Testing

885.4340 Nontarget In sect Testing

885.4380 Honey Bee Testing
Tiers II, III, and IV Not required for Trichoderma virens strain G

- 41 based on the acceptability of the data and other information provided for Tier I

.Trichoderma virens strain G

- 41 Page 33 of 34 Biopesticides Registration Action Document

APPENDIX B. PESTICIDE PRODUCTS

EP A Reg. Number Registration Name Percentage Active Ingredient Formulation Type Use Site(s) Method(s) of Application Application Rate (s) Target Pest

68539

- 8 G

- 41 Technical 12.10% 3 Technical N/A N/A N/A N/A

68539

- 9 BW240 WP Biological Fungicide 1.15% 2
0.61% 3 End Use

– Wettable Powder Various agricultural

, greenhouse , and
nursery crops , as well

as residential plants

(e.g., vegetables, ornamentals, and fruit) Chemigation (agricultural and

commercial applications) 1

– 32 ounces BW240 WP per 100 gallons of water

Various fungal pests Cutting or bare

- root ed transplant dip (agricultural and

commercial applications) (1) 0.25

– 5 pounds of BW240 WP per 20 gallons of water

(2) Direct dip into BW240 WP powder

Soil drench (agricultural and

commercial applica tions) (1) Shallow beds or pots (up to 4

- inch depth)

– 50

– 100 gallons of prepared mixture 1 per 800 square feet of beds or pots

(2) Deep beds or pots (greater than 4

- inch depth)

– 100 gallons of prepared mixture 1 per 400 square feet of beds or pots, 1⁄2 cup of prepared mixture 1 per 3

- inch diameter pot , or 1 cup of prepared mixture 1 per 6

- inch diameter pot

In

- furrow spray or transplant starter solution (agricultural and

commercial applications) 1

– 32 ounces of BW240 WP per acre of soil

Bulb, tube r, or cut potato seed piece

treatment (agricultural and

commercial applications) (1) 0.03

– 3 pounds of BW240 WP p er 100 pounds of bulbs or cut potato seed pieces

(2) Dip bulbs, tubers, or cut potato seed pieces into suspension of 0.25

– 5 pounds of BW240 WP per 20 gallons of water

Seed drench (residential applications) Prepared mixture (1

– 3 tablespoons of BW240 WP per gallon of water) to 25 feet of planting furrow

Transplants or potted

plants (residential

applications) 1/2

– 1 cup of prepared mix ture 1 per transplant or per 4

– 8 inch diameter pot
New and established plant beds (residential applications) 1 gallon of prepared mixture 1 per 25 square feet of plant bedTrichoderma virens strain G

- 41 Page 34 of 34 Biopesticides Registration Action Document

EP A Reg. Number Registration Name Percentage Active Ingredient Formulation Type Use Site(s) Method(s) of Application Application Rate (s) Target Pest

68539

- 10 BW240 G Biological Fungicide 1.15% 2
0.61% 3 End Use

– Granular Vario us agricultural

, g reenhouse , and
nursery crops (e.g., vegetables, ornamentals, and fruit) In

- furrow soil

treatment 2.5

– 6 pounds of BW240 G
per 1⁄2 acre of soil

Various fungal pests Planting mix amendment (greenhouse and nursery applications) 1

– 3 poun ds of BW240 G per cubic yard of planting mix

Bed incorporation (nursery applications) 0.5

– 7.5 pounds of BW240 G per 1,000 square feet of bed

Transplant 0.2

– 8 ounces of BW240 G per planting hole

Broadcast (turf only) (1) New turf seed i ngs

– 1

– 4 pounds of BW240 G per 1,000 square feet of turf

(2) Established turf (early spring)

– 1

– 4 pounds of BW240 G per 1,000 square feet of turf

(3) Established turf (late summer/early fall)

- 1

– 2 pounds of BW240 G per 1,000 square feet of turf

1 Prepared mixture = BW240 WP + water

2 Trichoderma harzianum Rifai strain T

- 22

3 Trichoderma virens strain G

- 41