### BIOPESTICIDES REGISTRATION ACTION DOCUMENT



## Trichoderma asperelloides strain JM41R ( originally Trichoderma fertile strain JM41R)

Pesticide Chemical (PC) Code: 119000

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

May 20 , 2015Trichoderma asperelloides strain JM41R Page 2 of 29 Biopesticides Registration Action Document



### TABLE OF CONTENTS

I. EXECUTIVE SUMMARY

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

II. ACTIVE INGREDIENT OV ERVIEW

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

III. REGULATORY BACKGROUN D

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

A. Application s for Pesticide Product Registration

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

B. Food Tolerance Exemption

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

IV. RISK ASSESSMENT

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

A. Pr oduct Analysis Assessment (40 CFR § 158.2120)

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

B. Hu man Health Assessment (40 CFR § 158.2140)

................................ ................................ .......... 9

C. Environmen tal Assessment (40 CFR § 158.2150)

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

V. ENVIRONMENTAL JUSTIC E

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

VI. RISK MANAGEMENT DECI SION

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

VII. ACTIONS REQUIRED OF THE REGISTRANT

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

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

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

IX. BIBLIOGRAPHY

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

A. Studies Submitted to Support the T richoderma asperelloides strain JM41R

Pesticide Product Registratio n s

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

B. Environmental Protection Agency Risk Assessment Memoranda

................................ ............. 21

C. Other References

................................ ................................ ................................ ............................ 21

APPENDIX A. MICROBI AL PESTICIDES DATA R EQUIREMENTS

................................ ........................ 23

APPENDIX B. PESTICI DE PRODUCTS

................................ ................................ ................................ ........... 29Trichoderma asperelloides strain JM41R Page 3 of 29 Biopesticides Registration Action Document



### BIOPESTICIDES REGISTRATI ON ACTION DOCUMENT TEAM

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

Microbial Pesticides Branch

Science Reviews

Shannon Borges Environmental Effects Joel V. Gagliardi , Ph.D. Pro duct Analysis and Human Health

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

In

- Soon You, Ph.D. Environmental Effects

Regulatory

ShaRon Carlisle Associ ate Chief

Jeannine Kausch Regulatory Action Leader Kimberly Nesci Ch iefTrichoderma asperelloides strain JM41R Page 4 of 29 Biopesticides Registration Action Document

I. EXECUTIVE SUMMARY

Background

In October 2012

, Becker Underwood , Inc. (now BASF Corporation ) submitted registration application s for a manufacturing

- use pesticide product (MP) ( Trichoderma fertile strain JM41R Technical, EPA File Symbol: 71840

- RL) and an end

- use pesticide product (EP) ( Tricho Plus

, EPA File Symbol : 71840

- RU )

to the U .S. Environmental Protection Agen cy (EPA) under section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)

. Concurrently with these applications, Becker Underwood, Inc. (now BASF Corporation) filed a petition for a tolerance exemption

. At that time, the pesticide product s contain ed and the tolerance exemption involved the new active ingredient Trichoderma fertile strain

JM41R. Subsequently, BASF Corpo ration provided additional data on the identity o f the active ingredient in the pesticide products to the EPA. After reviewing these data, the EPA concluded that the correct identity of t he active ingredient was Trichoderma asperelloides strain JM41R and not Trichoderma fertile strain JM41R. In conjunction with the active ingredient clarification, BASF Corporation adjusted the names of the pesticide products to Trichoderma asperelloides st rain JM41R Technical (EPA File Symbol: 71840

- RL) and TRICHO PLUS TM Biofungicide (EPA File Symbol: 71840

- RU) and updated its tolerance exemption petition

.

Fungi of the genus Trichoderma are abundant in nature, especially in soil and close to plant roots ( Druzhinina et al ., 2006; Harman et al ., 2004). Since 1989, several Trichoderma species (e.g., Trichoderma polysporum and Trichoderma viride ) have been used in pesticide products

— notably without reported incidents

— to control various fungal plant pathogens s uch as Pythium species, Phytophthora species, Heterobasidion annosum , and Chondrostereum purpureum . In conjunction with the registration of some of these pesticide products, the EPA established the following tolerance exemptions:

(1) Gliocladium virens isolat e GL

- 21 (now recognized as Trichoderma virens isolate GL

- 21) ( 40

CFR 180.1100 )

– see the Federal Register of September 20, 1995 ( 60 FR 48657 ) and October 5, 1995 ( 60 FR 52248 ). (2) Trichoderma harzianum Rifai strain T

- 22 ( 40 CFR 180.1102 )

– see the Federal Register of April 7, 1999 ( 64 FR 16856 ). (3) Tr ichoderma harzianum strain T

- 39 ( 40 CFR 180.1201 )

– see the Federal Register of June 22, 2000 ( 65 FR 38753 ). (4) Trichoderma gamsii strain ICC 080 ( 40 CFR 180.1293 )

– see the Federal Register of F ebruary 25, 2010 ( 75 FR 8504 ). (5) Trichoderma asperellum strain ICC 012 ( 40 CFR 180.1294 )

– see the Federal Register of March 3, 2010 ( 75 FR 9527 ). (6) Trichoderma hamatum isolate 382 ( 40 CFR 180.1298 )

– see the Federal Register of July 23, 2010 ( 75 FR 43072 ). (7) Trichoderma virens strain G

- 41 ( 40 CFR 180.1310 )

– see the Federal Register of February 1, 2012 ( 77 FR 4903 ).

In 2003, a University of Pretoria student isolated Trichoderma asperelloides strain JM41R in South Africa. This particular fungus colonizes root surfaces close to inoculated plants, parasitizing and competitively displacing invasive fungi (e.g., Rhizoctonia species and Fusarium species) and mineralizing insoluble phosphate to create a form of this substance that is available to plants. In light of Trichoderma asperelloides strain JM41R’s fungicidal capabilities, BASF Corporation proposed toTrichoderma asperelloides strain JM41R Page 5 of 29 Biopesticides Registration Action Document

register a MP and an EP; both pesticide products contain Trichoderma asperelloides strain JM41R as an active ingredient, and the EP is to be applied to soil and growing media in commercial greenhouses to manage soilborne diseases caused by organisms such as Rhizoctonia species and Fusarium species.

The EPA ’s s cientists reviewed product analysis, toxicology, and nontarget organism data and information ( 40 CFR §§ 158.2120, 158.2140, and 158.2150, respectively) submitted to support the registration of the Tr ichoderma asperelloides strain JM41R pesticide product s

. Overall, such data and

information are adequate for risk assessment purposes , fulfill most of the current microbial pesticide data requirements

, and support registration of the pesticide product s und er FIFRA section 3(c)(5)

.

Product Analysis BASF Corporation fulfilled most of the product analysis data requirements for Trichoderma asperelloides strain JM41R , including product chemistry and composition, analysis of samples, and physical and chemical ch aracteristics, by submitting acceptable guideline studies. Although a one

- year storage stability and corrosion characteristics study is outstanding, the EPA is requiring these data as

term s of registration.

Toxicology BASF Corporation submitted a dequate m amm alian toxicology information to support the Trichoderma asperelloides strain JM41R pesticide product s

. An acute toxicity/pathogenicity study showed that, at a single high dose, Trichoderma asperelloides strain JM41R is not toxic, infective, or pathogeni c via the pulmonary route of exposure. The EPA waived acute oral toxicity/pathogenicity and acute injection toxicity/pathogenicity testing for this active ingredient, based on BASF Corporation’s scientific

rationale. The rationale cited to the results of o ther toxicological data done with Trichoderma asperelloides strain JM41R, a literature search that yielded no human pathogenicity concerns, and data describing a lack of active ingredient growth at 35°C or above. Moreover, BASF Corporation reported

that , t o date, no hypersensitivity incidents have occurred during research, development, and testing of Trichoderma asperelloides strain JM41R

. In l ight of the adequacy of the toxicological data, scientific

rationale

, and literature provided by BASF Corporation a nd the absence of hypersensitivity incidents, the EPA is not requiring testing at higher tiers (i.e., Tiers II and III)

.

Tolerance Exemption

The 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 asperelloides strain

JM41R. The EPA does not expect dietary (food and drinking water) or other non

- occupational risks

from use of Trichoderma asperelloides strain JM41R as an active i ngredient in the pesticide product s

. Although exposure to Trichoderma asperelloides strain JM41R through consumed food and drinking water may be possible, the EPA anticipates these types of exposures to be negligible because, among other things, applicatio ns of the EP will be made to soil and growing media within commercial greenhouses

, and typical food commodity processing procedures (e.g., peeling, washing, and/or additions of sugar, salt, and other preservatives) tend to remove microbes or render them no nviable (U.S.

EPA

, 1996). Furthermore, since applications of Trichoderma asperelloides strain JM41R are limited to commercial greenhouses , increased exposures of the active ingredient to the general population in residential settings are not expected. Shou ld Trichoderma asperelloides strain JM41R be present in food or drinking water or in residential settings

, supporting toxicological information indicate s that human
exposure to t his fung us would not result in adverse effects.Trichoderma asperelloides strain JM41R Page 6 of 29 Biopesticides Registration Action Document

Occupational Exposure Despite the low toxicological profile of Trichoderma asperelloides strain JM41R

, the EPA is requiring

baseline protective clothing for individuals who, due to their occupation, may be exposed to the active ingredient for prolonged periods and/ or multiple times

. A t a minimum, i ndividuals working with Trichoderma asperelloides strain JM41R to manage certain soilborne diseases are directed to wear a long

- sleeved shirt, long pants, socks, shoes, protective eyewear

, and a dust/mist filtering respirator meeting National Institute for Occupational Safety and Health (NIOSH) standards of at least N

- 95, R

- 95,

or P

- 95.

Nontarget Organisms

The EPA found that scientific rationale and a honey bee study submitted by BASF Corporation are sufficient to fulfill the nontarget organ ism data requirements and for risk assessment purposes. Further testing of nontarget organisms at higher tier levels (i.e., Tiers II, III, and IV) is not required. The EPA performed an environmental risk assessment based on inf ormation provided by BASF Cor poration and

has determined that unreasonable adverse effects to nontarget organisms are not expected from the proposed pesticidal uses of Trichoderma asperelloides strain JM41R

. Moreover, the EPA made a “no

e ffect” determination for direct and indi rect ef fects to endangered and threatened species and their

habitats from the proposed uses of Trichoderma asperelloides strain JM41R, as labeled

.

Public Participation

On Octob er 1, 2009, the EPA announced a policy to provide a more meaningful opportunity for t he public to participate in major registration decisions before they occur. According to this policy, the EPA provides a public comment period prior to making a registration decision for the following types of applications: new active ingredients; first fo od uses; first outdoor uses; first residential uses; or any other registration actions for which the EPA believes there may be significant public interest.

Consistent with the policy of making registration actions more transparent, the proposed pe sticid e product s containing Trichoderma asperelloides strain JM41R, a new active ingredient, and allowing for this active ingredient’s first food use were subject to a 15

- day comment period. During this comment period, the EPA received no comments on its prelimi nary decision to register the Trichoderma asperelloides strain JM41R pesticide products. Therefore, the EPA maintains that, based upon the risk assessment and information submitted in support of Trichoderma asperelloides s train JM41R Technical

and TRICHO P LUS TM Biofungicide, it is appropriate to issue these registrations. The basis for this

decision can be found in the risk assessment for Trichoderma asperelloides strain JM41R, which is characterized throughout this Biopesticides Registration Action Document (BRAD).Trichoderma asperelloides strain JM41R Page 7 of 29 Biopesticides Registration Action Document

II. ACTIVE INGREDIENT OVERVIEW

Biological Name: Trichoderma asperelloides strain JM41R

Culture Deposit: Agricultural Research Service Culture Collection (also known as the Northern Regional Research Laboratory Collection) i n Peoria,

Illinois under Accession Number NRRL

- 50759

OPP Chemical Code: 119000

Type of Pesticide: Microbial Pesticide

– Fungicide

See Appendix B for specific information (e.g.,

use site ( s ) , application rate ( s ) , method ( s ) of application, formulation type , and target pest (s) ) regarding

the p esticide product s containing this active ingredient.

III. REGULATORY BACKGROUND

A. Application s for Pesticide Product Registration

In October 2012

, Becker Underwood, Inc. (now BASF Corporation) submitted application s to register a
MP ( Trichoderma fertile strain JM41R Technical, EPA File Symbol: 71840

- RL) and an EP (Tricho Plus

, EPA File Symbol: 71840

- RU ) under FIFRA section 3. On January 1 6 , 201 3 ( 7 8 FR 3 422 )

, the EPA

announ ced receipt of these application s to register pesticide product s containing a new active ingredient and opened a 3 0

- day public comment period pursuant to the provi sions of FIFRA section 3(c)(4). The EPA received no comments on this publication.

Subsequently, BASF Corporation provided addi tional data (i.e., deoxyribonucleic acid ( DNA ) sequence information based on newly published taxonomies) on the identity of the active ingredient in these pesticide products to the EPA. After reviewing these data, the EPA concluded that the correct identity of the active ingredient was Trichoderma asperelloides strain JM41R and not Trichoderma fertile strain JM41R. In order to give the pu blic an opportunity to comment on this new information, the EPA republished its receipt of these applications with an updated and accurate description in th e Federal Register of January 21 , 2015 ( 80 FR 2929 )

. The EPA received no comments on this publication.

B. Food Tolerance Exemption

Concurrent with its registration application s and under Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(d), Becker Underwood, In c. (now BASF Corporation) s ubmitted a petition to establish an exemption from the requirement of a tolerance for Trichoderma fertile strain JM41R ( PP 2F8102 ). In the Federal Register of February 21, 2014 ( 79 FR 9870 )

, the EPA announced that BASF Corporation proposed to establish an exemption from the requirement of a tolerance for residues of the fungicide Trichoderma fertile strain JM41R in or on all food commodities and opened a 30

- day comment period.

The EPA received no comments on this publication.Trichoderma asperelloides strain JM41R Page 8 of 29 Biopesticides Registration Action Document

Subsequently, BASF Corporation provided additional data (i.e., DNA sequence information based on newly published taxonomies) on the identity of the pesticide to the EPA. After rev iewing these data, the EPA concluded that the correct identity of the pesticide was Trichoderma asperelloides strain JM41R

and not Trichoderma fertile strain JM41R. In order to give the public an opportunity to comment on this new information, the EPA repu blished its receipt of this tolerance exemption petition filing with an updated and accurate description in the Federal Register of January 28, 2015 ( 80 FR 4525 ) and placed a

rev ised petition from BASF Corporation into the docket. The EPA received no comments on this publication.

On May 18, 2015, the EPA established an exemption from the requirement of a tolerance for residues of Trichoderma asperelloides strain JM41R in or on al l food commodities when used in accordance with label directions and good agricultural practices ( 40 CFR § 180.1331 ; 80 FR 28201 ).

IV. RISK ASSESSMENT

In the Federal Register s of October 26, 2007 ( 72 FR 60988 )

, and August 30, 2012 ( 77 FR 52610 )

, the

EPA issued Final Rule s on the data requirements to support registration of microbial pesticides and updated the definition for microbial pesticides. The data and information evaluated for this BRAD were considered in light of these requirements.

The classifications that are found for each data submission are assigned by the EPA ’s science reviewers

and are an indication of the usefulness of the informa tion contained in the documents for risk assessment. A rating of “ acceptable ” indicates a study is scientifically sound and is useful for risk

assessment. A “ supplemental ” rating indicates the data provide some information that can be u seful for

risk asses sment. S tudies may have certain aspects determined not to be scientifically acceptable (“ supplemental : upgradeable ”). If a study is rated as “supplemental: upgradeable ,” the EPA always provides an indication of what is lacking or what can be provided to ch ange 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 appropr iate. An “unacceptable ” rating indicates 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 information submitted to the EPA in support of a pesticide registration. The active ingredient or particular product is classified into Toxicity Category I, II, III, or IV, where Toxicity Category I indicates the highest toxicity and Toxicity Category IV indicates the lowest toxicity (see section II .B

. of U.S. EPA ( 201 4 ) )

.

A. Product Analysis Assessment ( 40 CFR § 158.2120 )

With the exception of a one

- year storage stability and corrosion characteristics study, which the EPA is requiring as term s of registration, BASF Corporation fulfilled a ll product analysis data requirements for Trichoderma asperelloides strain JM41R. Refer to Tables 1 and 2 in Ap pendix A for a summary of the

data requirements, including both generic and product

- specific information.Trichoderma asperelloides strain JM41R Page 9 of 29 Biopesticides Registration Action Document

B. Human Health Assessment ( 40 CFR § 158.2140 )

1. Toxicity

B ASF Corporation fulfilled a ll toxicology data requirements for Trichoderma asperelloides strain

JM41R

. Acceptable or supplemental Tier I mammalian toxicology studies and sci entific rationale
support registration of the Trichoderma asperelloides strain JM41R pesticide product s

. The EPA is not requiring Tier II and Tier III studies for Trichoderma asperelloides strain JM41R, based on the adequacy

of the data and information provided by BASF Corporation for Tier I

.

Fo r a summary of the generic toxicology data requirements described in sections IV(B)(1)(a) and IV(B)(1)(b) of this document , as well as additional product

- specific data submitted to support the individual registration s , refer to Table s 3 and 4 in Appendix A

.

a. Acute Toxicity/Pathogenicity

– Tier I

Acute Oral Toxicity/Pathogenicity (Harmonized Guideline 885.3050; Master Record Identification Number (MRID No.) 489476

- 09) : Upon consideration of BASF Corporation’s scientific r ationale that cited to results of other toxicological data and public literature, the EPA waived acute oral toxicity/pathogenicity testing for Trichoderma asperelloides strain JM41R. An acute oral toxicity study conducted on female rats (MRID No. 489476

- 03 ) demonstrated that Trichoderma asperelloides strain JM41R is not toxic, while an acute pulmonary toxicity/pathogenicity study conducted on rats (MRID

No. 489476

- 02) showed that Trichoderma asperelloides strain JM41R is not toxic, pathogenic, or

infective. Further, Trichoderma asperelloides strain JM41R does not grow at or above 35°C (normal human body temperature is 37°C). Finally, although a literature search yielded two reports of infections

in humans from Trichoderma species, the fungi involved were Tri choderma longibranchiatum or Trichoderma harzianum and not Trichoderma asperelloides , and the infections were likely due to immune system dysfunction, invasive procedures involved with therapy for the overlying disease, and/or immunosuppressive drugs. The EPA believes these data and information, when taken together, indicate that this fungus would not be toxic, pathogenic, or infective through the oral route of exposure and that further testing is not necessary.

Acute Pulmonary Toxicity/Pathogenicity

– Rat ( Harmonized Gui deline 885.3150; MRID No . 489476

- 0 2 ) : In an acute pulmonary toxicity and pathogenicity study, groups of approximately 7

- to 8

- week

- old Sprague Dawley rats (15 per sex) were exposed by the intratracheal route to Trichoderma asperelloides

str ain JM41R. The test substance label claimed viability and lack of laboratory confirmation of the test substance viability resulted in animals receiving a dose of 4.7 x 10 7 colony

- forming units (CFU) per rat instead of the guideline dose of 10 8 CFU per rat. The animals were observed frequently on the day of dosing for mortality and signs of pharmacologic and/or toxic effects and once daily thereafter for 21 days. A control group (untreated) was observed concurrently. Tissue and blood samples taken at interim sacrifices from the group receiving the active test substance were cultured on days 0, 3, and 7. There were no abnormal general health observations. There were no observed abnormalities during necropsies through day 21. The test substance was confirmed do sed to all animal lungs at day 0 where counts of approximately 5 x 10 5 colony

- forming units per gram (CFU/g) were noted in all animal lung tissues. The study author concluded that the test substance cleared from all tissues by day 7 and a value of 0 was

re ported for most tissue samples, though the limit of detection based on dilution and sample sizes was not described and the report should have instead listed a value less than the detection limit. Also, a singleTrichoderma asperelloides strain JM41R Page 10 of 29 Biopesticides Registration Action Document

male at day 7 had a reported <100 CFU/g in th e lungs, while all other animals had 0 CFU/g detected; thus, clearance was apparently not established by day 7, and further sampling did not occur at interim and terminal sacrifices on days 14 and 21.

Trichoderma asperelloides strain JM41R is not toxic, p athogenic, or infective when administered by intratracheal instillation in a single dose of 4.7 x 10 7 colony

- forming units (CFU) per animal. The EPA rated this study supplemental because clearance was not definitively established and the 4.7 x 10 7 CFU

per animal dose used was below the acceptable guideline dose of 10 8 CFU per animal. Even with these deficiencies, however, the EPA still concluded that Trichoderma asperelloides strain JM41R showed a general pattern of clearance from lung tissues and considere d these data useful for risk assessment

purposes.

Acute Injection Toxicity/Pathogenicity (Harmonized Guideline 885.3200 ; MRID No. 489476

- 09 ) : Upon consideration of BASF Corporation’s scientific rationale that cited to results of other toxicological da ta and public literature, the EPA waived acute injection toxicity/pathogenicity testing for Trichoderma asperelloides strain JM41R. An acute oral toxicity study conducted on female rats (MRID No. 489476

- 03) and an acute inhalation toxicity study conducted on male and female rats (MRID No. 489476

- 05)

demonstrated that Trichoderma asperelloides strain JM41R is not toxic, while an acute pulmonary toxicity/pathogenicity study conducted on rats (MRID No. 489476

- 02) showed that Trichoderma asperelloides strain JM 41R is not toxic, pathogenic, or infective. Further, Trichoderma asperelloides strain JM41R does not grow at or above 35°C (normal human body temperature is 37°C). Finally, although a literature search yielded two reports of infections in humans from Trich oderma species, the fungi involved were Trichoderma longibranchiatum or Trichoderma harzianum and not Trichoderma asperelloides , and the infections were likely due to immune system dysfunction, invasive procedures involved with therapy for the overlying di sease, and/or immunosuppressive drugs. The EPA believes these data and information, when taken together, indicate that this fungus would not be toxic, pathogenic, or infective through the injection route of exposure (when the skin is bypassed as a barrier) and that further testing is not necessary

.

Hypersensitivity Incidents ( Harmonized Guideline 885.3400 ; MRID No

. 489476

- 0 9 ) : BASF Corporation reported that, to date, no hypersensitivity incidents, including immediate

- type or delayed

- type reactions

of human s and domestic animals, have occurred during research, development, or testing of Trichoderma asperelloides strain JM41R . Any future hypersensitivity incidents must be reported to the EPA (refer to test note #3 of 40 CFR § 158.2140(d))

.

Cell Culture ( Harm onized Guideline 885.3500 ; MRID No. 489476

- 0 9 ) : Not required because Trichoderma asperelloides strain JM41R is not a virus (refer to test note #4 of 40 CFR § 158.2140(d)).

b. Acute Toxicology and Subchronic Toxicity/Pathogenicity

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

– Tier III

The EPA is not requiring Tier II and Tier III studies for Trichoderma asperelloides strain JM41R, based on the adequacy of the data and inf ormation provided by BASF Corporation for Tier I.Trichoderma asperelloides strain JM41R Page 11 of 29 Biopesticides Registration Action Document

c. Endocrine Disruptors

As required by the Administrator under FFDCA section 408(p), the EPA has developed the Endocrine

Disru ptor Screening Program (EDSP) and has begun to implement the screening program that is to be used to test all pesticides in order to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect pr oduced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.”

FFDCA section 408(p)(4) authorizes the Administrator, by order, to exempt from the requirements of the Estrogenic Substances Screening Program a biologic substance or other substance if a determination is made that the substance is not anticipated to produce any effect in humans similar to an effect produced by a naturally occurring estrogenic substance.

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

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013, 1 and includes som e pesticides scheduled for registration revie w and chemicals found in water. Trichoderma asperelloides strain

JM41R is not among the group of pesticide active ingredients on the list s to be screened under the

EDSP.

The EPA believes that Trichoderma asper elloides strain JM41R

, the active ingredient described in this document, is a substance that would not likely produce any effect in humans similar to an effect produced by a naturally occurring estrogenic substance. As such, pursuant to Section 408(p)(4), the EPA

will determine in t he future whether it can exempt Trichoderma asperelloides strain JM41R from the requirements of the Section 408(p) EDSP. In the event the EPA does determine to exempt this substance from the EDSP, an order will be issued.

For fu rther information on the status of the EDSP, the policies and procedures, the list of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our websit e at http://www.epa.gov/end o/

.

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

Section 408(c)(2)(A)(i) of FFDCA allows the EPA to establish an exemption from the requirement for a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if the 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 d ietary exposures and all other exposures for which there is reliable information.” This includes exposure through drinking water and in residential settings but does not include occupational exposure. Pursuant to FFDCA section 408( c )(2)(B), in establishing or maintaining in effect an exemption from the requirement of a tolerance, the EPA must take into account the factors set forth in FFDCA section 408(b)(2)(C), which require the EPA to give special consideration to exposure of infants and children to the p esticide chemical residue in establishing a tolerance or tolerance exemption, and to “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to th e pesticide chemical residue . . . . ” Additional ly, FFDCA section 408(b)(2)(D) requires that the EPA consider “available information concerning the cumulative eff ects of

1 See http://www.gpo.gov/fdsys/pkg/FR

- 2013

- 06

- 14/pdf/2013

- 14232.pdf for the second list of chemicals.Trichoderma asperelloides strain JM41R Page 12 of 29 Biopesticides Registration Action Document

[a particular pesticide’ s] . . . residues and other substances that have a common mechanism of toxicity.”

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

Consistent with FFDCA section 408(b)(2)(D), the EPA reviewed the available scientific data and other

relevant information on Trichoderma asperelloides strain JM41R , and considered its validity, completeness, and reliability, as well as the relationship of this information to human risk. The EPA also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children.

Base d on the acute toxicity/pathogenicity information discussed previously and presented in Table 3 in Appendix A , t he data required for a FFDCA risk assessment for Trichoderma asperelloides strain

JM41R have been fulfilled.

a. Aggregate Exposure

In examining aggregate exposure, FFDCA section 408 directs the EPA to consider available information concerning exposures from the pesticide residue in food and all other non

- occupational exposures, including drinking water from grou nd water or surface water and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses).

Food Exposure and Risk Characterization : Exposure to residues of Trichoderma species , fungi commonly found in agricultural se ttings (i.e., soils and plant roots) and on fresh produce ( Druzhinina et
al ., 2006; Harman et al ., 2004; U.S. EPA, 2015a and 2015b ), in consumed food is possible. For optimal management of the target pests (i.e., soilborne diseases caused by organisms such as Rhizoctonia species

and Fusarium species), Trichoderma asperelloides strain JM41R needs to be applied to soil and growing media in commercial greenhouses in a manner that facilitates the fungus’ movement into the root zones of plants. This requires tha t end users take certain actions, depending on the treatment type, that would inevitably minimize the amount of Trichoderma asperelloides strain JM41R residues on above

- ground commodities. That is, although Trichoderma asperelloides strain JM41R can be app lied to soil, pesticide applications made to the soil include enough water or are followed immediately by irrigation to properly incorporate Trichoderma asperelloides strain JM41R into the soil. As Trichoderma asperelloides strain

JM41R colonizes the soil or growing media in close proximity to plant roots or the root surfaces of plants, it is possible that food commodities that develop underground (e.g., root and tuber vegetables) or adjacent to the soil/ground (e.g., cucumber) could be directly exposed to Trichoderma asperelloides strain JM41R. Although residues from use of pesticides containing Trichoderma asperelloides strain JM41R may be present on certain food commodities, processing procedures (e.g., peeling and washing) may reduce such residu es (U.S. EPA, 1996 ). Finally, since Trichoderma species can be endophytes (i.e., organisms that live within plants) ( Chaverri et al ., 2011 ), it is conceivable that Trichoderma asperelloides strain JM41R could be present within food commodities. Should Trichoderma

a sperelloides strain JM41R be present in or on food, supporting toxicological data and information indicate that no toxicity, pathogenicity, or infectivity is likely to occur with this type of exposure resulting from the use of this microbial pesticide when applied in accordance with label directions and good agricultural practices (see section IV(B)(1)(a) of this document and Table 3 in Appendix A ).Trichoderma asperelloides strain JM41R Page 13 of 29 Biopesticides Registration Action Document

Drinking Water Exposure and Risk Characterization : Trichoderma asperelloides s train JM41R is to be applied to soil or growing media in commercial greenhouses and is not intended for use in drinking water. Once applied, the risk of Trichoderma asperelloides strain JM41R passing through the soil to ground water is minimal to unlikely because the growing organism forms a cottony web that is stationary, and the spores are not the type (i.e., chlamydospores) that are able to survive unfavorable conditions such as water (Chaverri et al ., 2003). If Trichoderma asperelloides strain JM41R wer e to be transferred to surface or ground waters, it likely would not survive the conditions water is subjected to in wastewater treatment systems and drinking facilities (e.g., pH adjustments and chlorination) (Centers for Disease Control and Prevention, 2 015; U.S. EPA, 2004). Should Trichoderma asperelloides strain JM41R be present in drinking water, supporting toxicological data and information indicate that no toxicity, pathogenicity, or infectivity is likely to occur with this type of exposure resulting from the use

of this microbial pesticide when applied in accordance with label directions and good agricultural practices (see section IV(B)(1)(a) of this document and Table 3 in Appendix A ).

Non

- occupational, Residential R isk Characterization : Dermal or inhalation exposure to the general population due to use of Trichoderma asperelloides strain JM41R is not likely to occur, based on product labeling that limits the use site to commercial greenhouses. Even if additional non

- occupational exposures were to occur (e.g., through eventual expansion of use sites), no adverse effects attributed to Trichoderma asperelloides strain JM41R are anticipated, particularly in light of testing that indicates that this fungus is not toxic (ac ute inhalation toxicity, acute dermal toxicity, and acute pulmonary toxicity/pathogenicity tests), is only mildly irritating (primary dermal irritation test), and is not pathogenic or infective (acute pulmonary toxicity/pathogenicity test) at high doses ( s ee section IV(B)(1)(a) of this document and Table 3 in Appendix A ).

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

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to es tablish, modify, or revoke a tolerance, the EPA consider “available information concerning the cumulative effects of [a particular pesticide’s] . . . residues and other substances that have a common mechanism of toxicity.”

Trichoderma asperelloides strain JM41R is not toxic via the oral, dermal, or inhalation routes of

ex posure. Thus, f or the purposes of the tolerance action

, the EPA has concluded that Trichoderma asperelloides strain JM41R does not have a common mechanism of toxicity with other substances

. Following from this, therefore, the EPA concludes that there are no cumulative effects associated with Trichoderma asperelloides strain JM41R that need to be considered.

For information regarding the EPA’s efforts to determine chemicals that have a com mon mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the EPA’s website at http://www.epa.gov/pesticides/cumulative

.

c. Determination of Safety for the U.S. Popu lation, Infants and Children

U.S. Population : For all of the reasons discussed previously, there is reasonable certainty that no harm will result to the U.S. population, including infants and children, from aggregate exposure to residues of

Trichoderma as perelloides strain JM41R. This includes all anticipated dietary exposures and all other exposures for which there is reliable information.Trichoderma asperelloides strain JM41R Page 14 of 29 Biopesticides Registration Action Document

Infants and Children : FFDCA section 408(b)(2)(C) provides that the EPA shall apply an additional tenfold (10X) margi n of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure, unless the EPA determines based on reliable data 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, the EPA either retains the default value of 10X or uses a

different additio nal safety factor when reliable data available to the EPA support the choice of a different factor. Humans, including infants and children, have likely been exposed and continue to be exposed to Trichoderma asperelloides through soil and fresh produce, whe re it is commonly found, with no known or reported adverse effects. As discussed above, the EPA has concluded that Trichoderma asperelloides strain JM41R is not toxic, pathogenic, or infective to mammals, including infants and children. Because

there are n o threshold levels of concern to infants, children, and adults when Trichoderma asperelloides strain JM41R is used according to label directions and good agricultural practices, the EPA concludes that no additional margin of safety is necessary to protect infants and children.

3 . Occupational Exposure and Risk Characterization

Worker exposure to Trichoderma asperelloides strain JM41R is not e xpected to pose any undue risk. Regardless, the EPA is requiring appropriate protective clothing and precautionary statements on the pesticide product label to mitigate any potential risks to pesticide handlers and applicators due to prolonged and/ or multiple exposures. At a minimum, i ndividuals working with Trichoderma asperelloides strain JM41R to manage certain soi lborne diseases are directed to wear a long

- sleeved shirt, long pants, socks, shoes, protective eyewear , and a dust/mist filtering respirator meeting NIOSH

standards of at least N

- 95, R

- 95, or P

- 95.

4 . Human Health Risk Characterization

The EPA consider ed human exposure to Trichoderma asperelloides strain JM41R in light of the standard for registration in FIFRA and the re levant safety factors in FFDCA. When the Trichoderma asperelloides strain JM41R pesticide product s are applied /used in ac cordance with labeling approved by

the EPA , the EPA has determined that no unreasonable adverse effects to human health are expected and that there is a reasonable certainty that no harm will result to the U.S. population, including i nf ants and

children.

C. Environmen tal Assessment ( 40 CFR § 158.2150 )

1. Introduction

BASF Corporation submitted an application to register two pesticide products co ntaining Trichoderma asperelloides strain JM41R as their active ingredient (a.i.). The two products include a MP

, Trichoderma asperelloides strain JM41R Technical (EPA File Symbol : 71840

- RL), and an EP

, TRICHO

PLUS TM Biofungicide (EPA File Symbol : 71840

- RU)

. Trichoderma spp. are widely found in soil, and typically are understood to be saprotrophic, parasites of other fungi, and/or endophytes. Trichoderma asperelloides is an inhabitant of soil and used for biocontrol of plant diseases (Chaverri and Samuels,

2 013; Druzhinina et al

. , 2011). It can become established within the plant rhizosphere, where it may stimulate plant growth and defenses against disease (Druzhinina et al

. , 2011).Trichoderma asperelloides strain JM41R Page 15 of 29 Biopesticides Registration Action Document

TRICHO PLUS TM Biofungicide is intended for use in greenhouses to control soi lborne diseases caused by microorganisms such as Pythium

, Rhizoctonia

, Fusarium

, Sclerotinia , and Phytophthora

. Applications are to be soil directed and made through coarse spray, soil drench, or chemigation. The

label ing directs the user to apply TRICHO P LUS TM Biofungicide at a rate of 0.8 fluid ounces per 10,000 square feet and to reapply at 21

- to 28

- day intervals through out the growing season. While the EP is for use in greenhouses and can be applied to the soil or growing media of all plants grown in gr eenhouses

, the product label ing does not specify whether applications are restrict ed to enclosed greenhouses only

.

2

. Ecological Effects Data

BASF Corporation conducted a dietary exposure study on honey bee ( Apis mellifera ) and submitted

rationale to a ddress other data requirements for the FIFRA s ection 3 registration of products containi ng the new active ingredient. Details of the honey bee study and scientific rationale are discussed below. The information provided is sufficient to satisfy the nontarg et organism data requirements for ecological risk assessment for the a.i., Trichoderma asperelloides strain JM41R. Further testing of nontarget organisms at higher tiers is not required.

a

. Scientific Rationale (Harmonized Guidelines 885.4050, 885.4100 , 885.4150, 885.4200,

885.4240 , 885.4280, 885.4300, and 885.4340; MRID No. 489476

- 09)

Scientific rationale was provided to address the hazard of Trichoderma asperelloides strain JM41R to birds, wild mammals, freshwater and marine/estuarine fish and invert ebrates, nontarget plants

, and nontarget insects (MRID No. 489476

- 09). The rationale was written assuming that the active ingredient

was Trichoderma fertile ; however, BASF Corporation determined the curren t identity with better analysis . The rationale was based on knowledge of the natural occurrence of Trichoderma species, the

low conce ntration of the a.i. in the EP , its limited application to soil of potted plants in greenhouses, and lack of evidence of adverse effects to nontargets. Except for information that was specific to Trichoderma fertile (e.g., optimum growth temperature for this species), the rationale was applicable to Trichoderma asperelloides . Additionally, a literature search was performed using “ Trichoderma asperelloides ” as the search term, and no reports of adverse effects to nontarget organisms were found.

Based on the well

- characterized nature of Trichoderma species of fungi, adverse effects to nontarget organisms are unlikely as a result of the proposed applications of the EP as labeled. The rationale was determined to be acceptable.

b

. Honey Bee Toxicity/Pathogenicity (Harmonized Guideline 885.4380, MRID No. 493849

- 01)

A 17

- day oral toxicity and pathogenicity study was conducted with adult honey bees ( Apis mellifera ;
MRID No. 4938 49

- 01). Bees were exposed to a sucrose solution containing the active or inactive test substance, a sucrose solution only (untreated control), or dimethoate at 100 parts per million (positive

control ) . There were no significant differences in the active or inactive test substance groups for mortality or food consumption when compared to the control group bees. All the bees in the positive

control dimethoate group were dead by d ay 4. The study ended on d ay 17 when mortality in the untreated control group exc eeded 20%. Based on the results of this study, the test substance, Trichoderma asperelloides strain JM41R, was determined to be non

- toxic to the honey bee when

administered at 8.1 x 10 3 colony

- forming units per milliliter ( CFU/mL ) . The study was classified as supplemental because the level of exposure was below the expected environmental exposureTrichoderma asperelloides strain JM41R Page 16 of 29 Biopesticides Registration Action Document

concentration, which was determined to be 1.2 x 10 5 CFU /mL based on the proposed TRICHO PLUS TM Biofungicide label ing . It is possible that this study may be useful f or applications of Trichoderma asperelloides strain JM41R at lower rates; however, this study is not useful to the current risk assessment, and risk was determined based on other information.

3

. Risk Characterization and Description

Exposure of nontarg et organisms to Trichoderma asperelloides strain JM41R is expected to be minimal

, based on the proposed uses as labeled. Applications are to occur only in greenhouses, which will limit environmental exposure. The label ing does not specify that greenhouses in w hich TRICHO PLUS TM Biofungicide will be used must be enclosed; therefore, it is possible that greenhouses may be open on the sides at certain or at all times during the year. Some exposure to nontarget organisms that would e nter the greenhouse may occur ; h owever, applications are to be directed to soil or planting media in containers within the greenhouse. Therefore, the potential for any significant exposure to any nontarget organisms is expected to be very limited.

Information on bee hazard was inconc lusive based on the submitted study; however, exposure to bees as a result of the labeled uses is expected to be very low. Applications are directed to media or soil within containers in greenhouses, so they are not made to foliage and will not result in e xposure to bees intentionally introduced for pollination or incidentally visiting greenhouses. Native species of bees that live in soil are also unlikely to make use of the soil in the treated containers. Therefore, exposure to bees as a result of the prop osed labeled uses are not expected.

As described above, adverse effects that might result from exposure are also unlikely. Trichoderma asperelloides is widespread within soil and is saprotrophic on plant matter (Chaverri and Samuels

, 2013). Since it is as sociated with growth within the plant rhizosphere, its likely mode of action is stimulation of normal plant defenses (Druzhinina et al

. , 2011) and competition for resources (a common

mode of action for Trichoderma spp.). Therefore, its effects are expected to be limited to plant disease causing microorganisms for which it is labeled.

Based on limited exposure and very low likelihood of adverse effects, risk to nontarget organisms resulting from the proposed labeled applications of Trichoderma asperelloides strain JM41R is expected

to be minimal.

4

. Threatened and Endangered Species Assessment

The EPA has determined that adverse effects to nontarget organism are not expected as a result of the proposed applications of Trichoderma asperelloides strain JM4 1R. Therefore, the EPA makes a “no effect” determination for direct and indirect effects to endangered and threatened species and their habitats from the proposed uses of Trichoderma asperelloides strain JM41R, as labeled.

V. ENVIRONMENTAL JUSTICE

Th e EPA seeks to achieve environmental justice

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

— with respect to the development, implementation, and enforcement of environmental laws, regulatio ns, and policies. Fair treatment meansTrichoderma asperelloides strain JM41R Page 17 of 29 Biopesticides Registration Action Document

that no group of people, including racial, ethnic, or socioeconomic groups, should bear a disproportionate share of the negative environmental consequences resulting from industrial, municipal, and commercial operatio ns or the execution of federal, state, local, and tribal environmental programs and policies. Meaningful involvement means that (1) potentially affected community residents have an appropriate opportunity to participate in decisions about a proposed activi ty that will affect their environment and/or health; (2) the public’s contribution can influence the regulatory agency’s decision; (3) the concerns of all participants involved will be considered in the decision

- making process; and (4)

the decision

- makers seek out and facilitate the involvement of those potentially affected. The EPA has this goal for all communities and persons across the U.S

.

To help address potential environmental justice issues, during the 15

- day public participation comment period, th e EPA sought information on any groups or segments of the population who, as a result their location, cultural practices, or other factors, may have atypical, unusually high exposure to Trichoderma asperelloides strain JM41R , compared to the general popula tion. The EPA received no public comments on this particular matter.

For additional information regarding environmental justice issues, please visit the 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 warr ant the proposed claims for it; (2) Its labeling and other material required to be submitted comply with the requirements of FIFRA; (3) It will perform its intended function without unreasonable adverse effects on the environment; AND (4) W hen used in accordance with widespread and commonly recognized practice, it will not generally cause unreasonable adverse effects on the

environment.

To satisfy criterion 1, the EPA understands that Trichoderma asperelloides strain JM41R is well known

to ha ve fungicid al capabili ties

. The EPA has no knowledge that would contradict the claims made on the Trichoderma asperelloides strain JM41R Technical and TRICHO PLUS TM Biofungicide label s , and such pesticide products are not expected to cause u nreasonable adverse effects on the environment when used according to their respective label instructions. Criterion 2 is satisfied by the current product labels, as well as the data and information presented in this document. It is believed that the Trich oderma asperelloides strain JM41R pesticide products will not cause any unreasonable adverse effects on the environment, and TRICHO PLUS TM Biofungicide (end

- use pesticide product), in particular, is likely to manage certain soilborne diseases caused by orga nisms such as Pythium

, Rhizoctonia

, Fusarium

, Sclerotinia , and Phytophthora as claimed, satisfying criterion 3. Criterion 4 is satisfied in that the Trichoderma asperelloides strain JM41R pesticide products are not expected to cause unreasonable

adverse ef fects when used according to label instructions. Therefore, EPA believes Trichoderma asperelloides strain JM41R Technical and TRICHO PLUS TM Biofungicide, containing TrichodermaTrichoderma asperelloides strain JM41R Page 18 of 29 Biopesticides Registration Action Document

asperelloides strain JM41R as a new active ingredient, are eligible for registra tion 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 asperelloides strain JM41R for shipmen t, the registrant must provide a ppropriate final printed labeling to the EPA.

B. Terms of Registration

As terms of the Trichoderma asperelloides strain JM41R Technical and TRICHO PLUS TM Biofungicide registrations, the registrant must submit the results of a one

- year storage stability ( Harmonized Guideline 830.6317) and corrosion characteristics (Harmonized Guideline 830.6320) study for each pesticide product within 18 months of registration.

C. Reporting of Adverse Effects and Hypersensitivity Incidents

Notwithstanding the informatio n stated in the previous sections, it should be clearly understood that

certain specific data are required to be reported to the EPA as a requirement for maintaining the federal registration for a pesticide product. A brief summary of these types of data a re described below.

Reports of all incidents of adverse effects to the environment must be submitted to the EPA under the provisions stated in FIFRA section 6(a)(2). Additionally, all incidents of hypersensitivity (including both suspected and confirmed i ncidents) must be reported to the EPA under the provisions of 40 CFR § 158.2140(d).Trichoderma asperelloides strain JM41R Page 19 of 29 Biopesticides Registration Action Document

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

a.i. active ingredient

BRAD Biopesticides Registration Action Document

CFR Code of Federal Regulations

CFU colony

- forming unit s CFU/g colony

- forming units per gram

CFU/mL colony

- forming units per milliliter

DNA deoxyribonucleic acid

EDSP Endocrine Disruptor Screening Program

EP end

- use pesticide product

EPA United States Envi ronmental Protection Agency

FFDCA Federal Food, Drug, and Cosmetic Act

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FR Federal Register

lb/cu ft pounds per cubic foot

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

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

- use pesticide product

MRID No. Master Record Identification Number

NIOSH National Institute for Occupational Safety and Health

NRRL Northern Regional Research Laboratory

OPP Office of Pesticide Programs

PC Code Pesticide Chemical Code

PP Pesticide Petition

ppm parts per million

TGAI technical grade of the active ingredient

U.S. United StatesTrichoderma asperelloides strain JM41R Page 20 of 29 Biopesticides Registration Action Document

IX. BIBLIOGRAPHY

A. Studies Submitted to Support the T richoderma asperelloides strain JM41R Pesticide Product Registration s

MRID No. Study Information

489476

- 01 Sargent G. 2012

. Product Chemistry for Trichoderma fertile S train JM41R Technical

. Un published study prepared by Becker Underwood

, Inc., 132 pages.

489476

- 02 Doig A. 2012

. Trichoderma fertile S train JM41R: Acute Pulmonary Toxicity and Pathogenicity Study in Rats

. Project Number: 16704/12/OCR. Un published study prepared by Stillmeadow

, Inc., 37 pages.

489476

- 03 Kuhn J. 2011

. Trichoderma fertile S train JM41R: Acute Oral Toxicity Study (UDP) in

Rats

– Final Report

. Proj ect Number: 15357/11/OCR . Un published study prepared by

Stillmeadow

, Inc., 11 pages.

489476

- 04 Kuhn J. 2011

. Trichoderma fertile S train JM41R: Acute Dermal Toxicity in Rats

– Final Report

. Project Number: 15358/11/OCR. Unpublished study pr epared by Stillmeadow, Inc., 1 4 pages.

489476

- 05 Doig A. 2011

. Trichoderma fertile S train JM41R: Acute Inhalation Toxicity Study in Rats

– Final Report. Project Number: 15359/11/OCR . Un published study prepared by Stillmeadow, Inc., 18 pages.

489476

- 0 6 Kuhn J . 20 11

. Trichoderma fertile S train JM41R: Acute Eye Irritation Study in Rabbits

– Final Report

. Project Number: 15360/11/OCR

. Unpublished study prepared by

Stillmeadow

, Inc., 17 pages.

489476

- 07 Kuhn J. 2011

. Trichoderma fertile S train JM41R: Acute Dermal Ir ritation Study in

Rabbits

– Final Report . Pro ject Number: 15361/11/OCR . Un published study prepared by

Stillmeadow

, Inc., 11 pages.

489476

- 08 Younger C. 2012

. Trichoderma fertile S train JM41R: Honey Bee Testing ( Apis mellifera ),

Non

- target Insect Microbia l Testing

. Project Number: 16382/12/OCR . Unpublished study

prepar ed by Stillmeadow, Inc., 14 pages.

489476

- 09 Mileson B. 2012

. Response to Tier 1 Microbial Pesticide Data Requirements for Trichoderma fertile S train JM41R Technical. Unpublished study prep ared by Technology Sciences Group

, Inc., 75 pages.

489477

- 01 Sargent G. 2012

. Product Chemistry for Tricho Plus . Un published study prepared by

Becker Underwood

, Inc., 70 pages.Trichoderma asperelloides strain JM41R Page 21 of 29 Biopesticides Registration Action Document

MRID No. Study Information

489477

- 02 Mileson B. 2012

. Response to Tier 1 Microbial Pesticide Data Requ irements for Tricho

Plus . Unpubli shed study prepared by Becker Underwood , Inc., 27 pages.

492477

- 01 Sargent G . 2013. Addendum to Volume 2: Product Chemistry for Tricho Plus (MRID No.

489477

- 01). Un published study prepared by BASF Corporation, 74 pages.

492496

- 01 Sargent G. 2013

. Volume 2: Product Chemistry for Trichoderma fertile Strain JM41R

Technical

– Final Report

. Unpublished study prepared by BASF Corporation, 84 pages.

493849

- 01 Younger C . 2014

. Trichoderma fertile Strain JM41R: Honey Bee Testin g ( Apis mellifera ),

Non

- target Insect Microbial Testing. Project Number: 16382/12 . Unpublished study prepared by Stillmeadow

, Inc., 25 pages.

494690

- 01 Sargent G. 2014. Product Chemistry for Trichoderma asperelloides Strain JM41R Technical. Project Numbe r: 2014/7002837. Unpublished study prepared by BASF Corporation, 168 pages.

494691

- 01 Sargent G. 2014. Pr oduct Chemistry for Tricho Plus TM Biofungicide. Project Number: 2014/7002851. Unpublished study prepared by BASF Corporation, 87 pages.

B. Environme ntal Protection Agency Risk Assessment Memoranda

U.S. EPA. 201 5a

. Trichoderma asperelloides strain JM41R

. Memorandum from J.V. Gagliardi, Ph.D. through J.L. Kough, Ph.D. to J. Kausch, dated January 21

, 2015

.

U.S. EPA. 2015 b. Environmental risk assessme nt of Trichoderma asperelloides strain JM41R for a FIFRA section 3 registration for use in greenhouses

. Memorandum from S . Borges to J. Kausch,

dated February 18

, 2015

.

C. Other References

Centers for Disease Control and Prevention. 2015. Drinking W ater

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

.

Chaverri P, Samuels GJ. 2013. Evolution of habitat preferen ce and nutrition mode in a cosmopolitan fungal genus with evidence of interkingdom host jumps and major shifts in ecology. Evolution 67:

2823

– 2837. Available from https://psla.umd.edu/sites/default/files/_images/uploaded/Research/Chaverri_Lab/PDFs/evolution.p df

.

Chaverri P, Gazis RO, Samuels GJ. 2011. Trichoderma amazonicum , a new endophytic species on

Hevea brasiliensis and H

. guianensis fro m the Amazon basin. Mycologia 103(1):139

– 151. Available

from http://www.mycologia.org/content/103/1/139.full

.Trichoderma asperelloides strain JM41R Page 22 of 29 Biopesticides Registration Action Document

Chaverri P, Castlebury LA, Overton BE, Samuels GJ. 2003. Hypocrea / Trichoderma : species with conidiophore elongations and green conidia. Mycologia 95(6):1100

– 1140. Available from http://www.mycologia.org/content/95/6/1100.full

.

Druzhinina IS, Seidl

- Seiboth V, Herrera

- E strella A, Horwitz BA, Kenerley CM, Monte E, Mukherjee

PK , Zei linger S, Grigoriev IV, Kubicek CP. 2011. Trichoderma : the genomics of opportunistic

success. Nature Reviews Microbiology 9:749

– 759.

Druzhinina IS, Kopchinskiy AG, Kubicek CP. 2006. The first 1 00 Trichoderma species characterized by

molecular data. Mycoscience 47:55

– 64. Available from http://isth.info/library/pdf/61/isth_library_61.pdf

.

Harman GE, Howell CR, Viterbo A, Chet I, Lorito M. 2004. Trichoderma species

– opportunistic, avirulent plant symbionts. Nature Reviews Microbiology 2:43

– 56. Available from http://naldc.nal.usda.gov/download/25508/PDF

.

U.S. EPA. 2 014 . Chapter 7 of the Label Review Manual (Precautionary Statements) (Revised July 2014) . Available from http://www2.epa.gov/sites/production/files /2014

- 07/documents/chapter7_revised_final_0714.pdf

.

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

.

U.S. EPA. 1996. Microbial Pesticide Test Guidelines

– Background for Residue Analysis of Microbial Pest Control Agents (OPPTS 885.2000) (Dated February 1996). Available from http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series885.htm

.Trichoderma asperelloides strain JM41R Page 23 of 29 Biopesticides Registration Action Document

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

– SUBPART V )

TABLE 1. Product Analysis Data Requirements for Trichoderma asperelloides strain JM41R (Technical Grade of the Active Ingredient, TGAI), Trichoderma asperelloides strain JM41R Technical (Manufacturing

- use Pesticide Product, MP), and TRICHO PLUS TM Biofungicide ( End

- use Pesticide Product
, E P) (40 CFR § 158.2 120 ) 1

Har monized

Guideline

Number Data Requirement Results MRID No. TGAI MP EP

885.1100 Product Identity N/A Submitted data fulfill the requirement for product identity. Trichoderma asperelloides strain JM41R Technical contains 100.0% by weight Trichoderma asperelloides strain JM41R (contains a

minimum of 2.0 x 10 10 colony

- forming units (CFU) per gram). Submitted data fulfill the requirement for product identity.

TRICHO PLUS TM Biofungicide contains 5.5% by weight Trichoderma asperelloides strain JM41R (contai ns a minimum of 2.0 x

10 9 colony

- forming units (CFU) per gram). 494690

- 01 2 (replaces 489476

- 01

and 492496

- 01)

494691

- 01 3 (replaces 489477

- 01

and 492477

- 01)

885.1200 Manufacturing

Process Submitted data fulfill the requirement for manufacturing process.

885.1250 Deposition of a Sample in a Nationally Recognized Culture

Collection Trichoderma asperelloides strain

JM41R is on deposit with the Agricultural Research Service Culture Collection (also known as the Northern Regional Research Laboratory Collect ion) in Peoria,

Illinois und er Accession Number

NRRL 50759

. N/A 494690

- 01 (replaces 489476

- 01

and 492496

- 01)

885.1300 Discussion of

Formation of

Unintentional

Ingredients Submitted data fulfill the requirement for discussion of formation of unintentional ingredients. 494690

- 01 2 (replaces 489476

- 01

and 492496

- 01)

494691

- 01 3 (replaces 489477

- 01

and 492477

- 01) 885.1400 Analysis of Samples Submitted data fulfill the requirement for analysis of samples.

885.1500 Certification of

Limits N/A Limits listed on the confidential statement s of formula are adequate/acceptable.

1 In this case, the TGAI is equivalent to the MP.

2 Data package associated with t he TGAI/ MP.

3 Data package associated with the EP.Trichoderma asperelloides strain JM41R Page 24 of 29 Biopesticides Registration Action Document

TABLE 2. Physical and Chemical Characteristics f or Trichoderma asperelloides strain JM41R (Technical Grade of the Active Ingredient, TGAI), Trichoderma asperelloides strain JM41R Technical (Manufacturing

- use Pesticide Product, MP), and TRICHO PLUS TM Biofungicide (End

- use Pesticide Product, EP) (40 CFR § 158.2120) 1

Harmonized

Guideline

Number Data Requirement Results

MRID No. TGAI MP EP

830.6302 Color Dark green

N/A 494690

- 01 (replaces 489476

- 01

and 492496

- 01) 830.6303 Physical State Fine dry powder

830.6304 Odor Musty

830.6313 Stability to N ormal and Elevated Temperatures,

Metals and Metal Ions Stable 60 days above 24°C

830.6317 Storage Stability As term s of the Trichoderma asperelloides strain JM41R Technical and TRICHO PLUS TM Biofungicide registrations
, the EP A is requiring BASF Corporati on to submit the results of a one
- year storage stability st udy for each product within 18 months of registration. N/A

830.6319 Miscibility

N/A Not required because the pesticide products are not emulsifiable liquids (refer to test note #3 of 40 CFR § 158. 2120(d)). 494690

- 01 2 (replaces 489476

- 01

and 492496

- 01)

494691

- 01 3 (replaces 489477

- 01

and 492477

- 01)

830.6320 Corrosion Characteristics As terms of the Trichoderma asperelloides strain JM41R Technical

and TRICHO PLUS TM Biofungicide registrations, the EP A is requiring BASF Corporation to submit the results of a corrosion characteristics study for each product within 18 months of registration. N/A

830.7000 pH 6.0 (1% aqueous solution) N/A 5.0 (1% aqueous solution) 4 494690

- 01 2 (replaces 489476

- 01

and 4924 96

- 01)

494691

- 01 3 (replaces 489477

- 01

and 492477

- 01) 830.7100 Viscosity N/A Not required because the pesticide products are not liquids (refer to test note #5 of 40 CFR § 158.2120(d)).

830.7300 Density/Relative Density/Bulk Density

(Specific Gravity) 1 6.2 lb/cu f t N/A 44 lb/cu f t 4

1 In this case, the TGAI is equivalent to the MP.

2 Data package associated with t he TGAI/ MP.

3 Data package associated with the EP.

4 According to 40 CFR § 158.2120, these data ar e only required for the TGAI . Since BASF Corporation included this information with its application for TRICHO PLUS TM

Biofungicide, it is summarized appropriately in this table.Trichoderma asperelloides strain JM41R Page 25 of 29 Biopesticides Registration Action Document

T ABLE 3

. Toxicology Data Requirements for Trichoderma asperelloides strain JM41R (Technical Grade of the Active Ingredient, TGAI) and Trichoderma asperelloides strain JM41R Technical (Manufacturing

- use Pesticide Product, MP) (40 CFR § 158.2140) 1

Harmonized

Guideline

N umber Data Requirement Results MRID N o. TGAI MP

Tier I

885.3050 Acute Oral Toxicity/Pathogen icity Testing waived based on BASF Corporation’s scientific rationale, which cited to MRID No. 489476

- 03 (acute oral toxicity study conducted with the TGAI/MP) and MRID No.

489476

- 02 (acute pulmonary toxicity/pathogenicity study

conducted with the TGAI/MP) ; included a literature search that yielded no human pathogenicity concerns ; and provided data describing no growth of Trichoderma asperelloides

strain JM41R at 35°C or above. Classification: Acceptable

N/A 489476

- 09

885.3150 Acute Pulmonary Toxicity/Pa thogenicity Not toxic, infective, or pathogenic to rats when administered by intratracheal instillation in a single dose of 4.7 x 10 7 CFU per animal. Classification: Supplemental because clearance was not established and the dose used was below the guidel ine of

10 8 CFU per animal. 489476

- 02

885.3200 Acute Injection Toxicity/Pathogenicity Testing waived based on BASF Corporation’s scientific rationale, which cited to MRID No. 489476

- 03 (acute oral toxicity study conducted with the TGAI/MP) , MRID No.

48947 6

- 05 (acute inhalation toxicity st udy conducted with the TGAI/MP) and MRID No. 489476

- 02 (acute pulmonary toxicity/pathogenicity st udy conducted with the TGAI/MP);

included a literature search that yielded no human pathogenicity concerns ; and provided data describing no growth of Trichoderma asperelloides strain JM41R at 35°C

or above. Classification: Acceptable 489476

- 09

885.3400 Hypersensitivity

Incidents BASF Corporation reported that, to date, no hypersensitivity incidents, including immediate

- type or delayed

- type reactions of humans and domestic animals, have occurred during research, development, and testing of the TGAI/MP. Any future hypersensitivity incidents must be reported to the EPA (refer to test note #3 of 40 CFR § 158.2140(d)).

885.3500 Cell Culture Not required because Trichoderma asperelloides strain JM41R is not a virus (refer to test note #4 of 40 CFR § 158.2140(d)). N/ATrichoderma asperelloides strain JM41R Page 26 of 29 Biopesticides Registration Action Document

T ABLE 3

. Toxicology Data Requirements for Trichoderma asperelloides strain JM41R (Technical Grade of the Active Ingredient, TGAI) and Trichoderma asperelloides strain JM41R Technical (Manufacturing

- use Pesticide Product, MP) (40 CFR § 158.2140) 1

Harmonized

Guideline

N umber Data Requirement Results MRID N o. TGAI MP

870.1100 Acute Oral Toxicity N/A Oral LD 50 (female rats) > 5,000 mg/kg Classification: Acceptable

TOXICITY CATEG ORY IV 489476

- 03

870.1200 Acute Dermal Toxicity

N/A Dermal LD 50 (male and female rats combined) > 5,050 mg/kg Classification: Acceptable

TOXICITY CATEGORY IV 489476

- 04

870.1300 Acute Inhalation Toxicity Inhalation LC 50 (male and female rats combined) > 2.34 mg/L Classification: Supplemental because the particle

size (6.5 μm) was above the guideline standard.

TOXICITY CATEGORY IV 489476

- 05

870.2400 Acute Eye Irritation Trichoderma asperelloides strain JM41R is mildly irritating to the eyes of rabbits. Conjunctiva l irritation (e.g., redness) was noted on all rabbits at 24 hours after

test material instillation with resolution by 72 hours. Classification: Acceptable

TOXICITY CATEGORY III 489476

- 06

870.2500 Primary Dermal Irritation Trichoderma asperelloides strain JM41R is mildly irritating to the skin of rabbits. All animals were free of

slight dermal erythema without edema by 48 hours. Classification: Acceptable

TOXICITY CATEGORY IV 489476

- 07

Tiers II and III Toxicological testing at higher tiers is not require d for Trichoderma asperelloides strain JM41R.

1 In this case, the TGAI is equivalent to the MP.Tr ichoderma asperelloides strain JM41R Page 27 of 29 Biopesticides Registration Action Document

TABLE 4 . Toxicology Data Requirements for TRICHO PLUS TM Biofungicide (End

- use Pesticide Product, EP) (40 CFR § 158.2140)

Harmonized

Guideline

Numbe r Data Requirement Results MRID No.

885.3050 Acute Oral Toxicity/Pathogenicity

N/A N/A 885.3150 Acute Pulmonary Toxicity/Pathogenicity

885.3200 Acute Injection Toxicity/Pathogenicity

885.3400 Hypersensitivity

Incidents BASF Corporation reported tha t, to date, no hypersensitivity incidents, including immediate

- type or delayed

- type reactions of humans and domestic animals, have occurred during research, development, and testing of the EP. Any future hypersensitivity incidents must be reported to the E PA (refer to test note #3 of 40 CFR § 158.2140(d)). 489476

- 09

885.3500 Cell Culture N/A N/A

870.1100 Acute Oral Toxicity Testing waived based on BASF Corporation ’s scientific rationale, which cited to the results of MRID No. 489476

- 03 (acute oral

toxicit y study conducted with the TGAI/ MP , see Table 3 ), and because this formulation contains an inert ingredient that is not expected to be of toxicological concern (refer to test note #5 of 40 CFR § 158.2140(d)). Classification: Acceptable

TOXICITY CATEGORY IV

489477

- 02 870.1200 Acute Dermal Toxicity Testing waived based on BASF Corporation ’s scientific rationale, which cited to the res ults of MRID No. 489476

- 04 (acute dermal toxicity study conducted with the TGAI/ MP , see Table 3 ), and because this formulation contains an inert ingredient that is not expected to be of toxicological concern (refer to test note #5 of 40 CFR § 158.2140(d)). Classification: Acceptable

TOXICITY CATEGORY IV

870.1300 Acute Inhalation Toxicity Testing waived based on BASF Corporation ’s scientific rationale, which cited t o the results of MRID No. 489476

- 05 (acute inhalation toxicity study conducted with the TGAI/ MP, see Ta ble 3 )

, and because this formulation contains an inert ingredient

that is not expected to be of toxicological conce rn (refer to test note #5 of 40 CFR § 158.2140(d)). Classification: Acceptable

TOXICITY CATEGORY IV

870.2400 Acute Eye Irritation Testing waived based on BASF Corporation ’s scientific rationale, which cited to the results of MRID No. 489476

- 06 (acute eye irritation study conducted with the TGAI/MP, see Table 3 ), and because this formulation contains an inert ingredient that is not expected to be of toxicological concern (refer to test note #5 of 40 CFR § 158.2140(d)). Classification: Acceptable

TOXICITY C ATEGORY I II

870.2500 Primary Dermal

Irritation Testing waived based on BASF Corporation ’s scientific rationale, which cited to the results of MRID No. 489476

- 07 (primary dermal irritation study conducted with the TGAI/MP, see Table 3 ), and because this f ormulation contains an inert ingredient that

is not expected to be of toxicological concern (refer to test note #5 of 40 CFR § 158.2140(d)). Classification: Acceptable

TOXICITY CATEGORY IVTr ichoderma asperelloides strain JM41R Page 28 of 29 Biopesticides Registration Action Document

TABLE 5 . Nontarget Organism Toxicity and Environmental Fate Dat a Requirements for Trichoderma asperelloides strain JM41R (Technical Grade of the Active Ingredient, TGAI) (40 CFR § 158.2150)

Harmonized Guideline

Number Data Requirement Results MRID No.

Tier I

885.4050 Avian Oral Toxicity

Scientific rationale provide s sufficient information to determine that toxicity/pathogenicity is not expected. Classification: Acceptable 489476

- 09 885.4100 Avian Inhalation Toxicity/Pathogenicity

885.4150 Wild Mammal Toxicity/Pathogenicity

885.4200 Freshwater Fish Toxicity/Pa thogenicity

885.4240 Freshwater Invertebrate Toxicity/Pathogenicity

885.4280 Estuarine/Marine Fish and Invertebrate Testing

885.4300 Nontarget Plant Testing

885.4340 Nontarget Insect Testing

885.4380 Honey Bee Testing A 17

- day toxicity/patho genicity laboratory study showed that Trichoderma asperelloides strain JM41R is not toxic or pathogenic to honey bees at 8.1 x 10 3 CFU/mL. Classification: Supplemental because the test was done at a rate below the estimated

environmental concentration. 49 3849

- 01 (replaces 489476

- 08)

Tiers II, III, and IV Environmental testing at higher tiers is not required for Trichoderma asperelloides strain JM41R.Tr ichoderma asperelloides strain JM41R Page 29 of 29 Biopesticides Registration Action Document

APPENDIX B. PESTICIDE PRODUCTS

EPA Registration

Number Registration

Name Percentage

Activ e Ingredient Formulation Type Use Site(s) Method(s) of Application Application Rate(s) Target Pest

71840

- 14 TRICHO PLUS TM Biofungicide 5 .5 % End Use

– Wettable

Powder Soil or growing

media used

within

commercial greenhouses Coarse spray, soil drench, or co mmon irrigation application
systems 0.8 ounce of TRICHO

PLUS TM Biofungicide per 10,000 square feet of soil or growing media Soilborne diseases caused by organisms such as Pythium

, Rhizoctonia

, Fusarium

, Sclerotinia , and Phytophthora

71840

- 15 Trichoderma

as

perelloides

strain JM41R

Technical 100.0% Technical N/A