BIOPESTICIDES REGISTRATION ACTION DOCUMENT



## Trichoderma hamatum isolate 382

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

Version #1

June 1, 2010Trichoderma hamatum isolate 382 Page 2 of 22 Biopesticides Registra tion Action Document

TABLE OF CONTENTS

I. BACKGROUND ................................................................................................................ .. 4

II. ACTIVE INGRED IENT OVERVIEW.............................................................................. 4

III. REGULATORY BACKGROUND..................................................................................... 5

A. Applications for Pesticide Registration .................................................................................... 5

B. Food Tolerance Exemptions ................................................................................................... 5

IV. RISK ASSESSMENT .......................................................................................................... 5

A. Product Analysis Assessment (40 CFR § 158.2120) ................................................................... 6

B. Human Health Assessment (40 CFR § 158.2140) ....................................................................... 6

C. Environmental Assessment (40 CFR § 158.2150) ....................................................................... 9

V. ENVIRONMENTAL JUSTICE ....................................................................................... 11

VI. RISK MANAGEMENT DECISION................................................................................ 11

VII. TERMS AND CONDITIONS OF THE REGISTRATION(S)...................................... 11

VIII. GLOSSARY OF ACRONYM S AND ABBREVIATIONS ............................................ 12

IX. BIBLIOGRAPHY............................................................................................................. . 13

A. Studies Submitted to Support the Trichoderma hamatum isolate 382 Pesticide Product ............... 13

B. Environmental Protection Ag ency Risk Assessment Memoranda .............................................. 16

C. Other References ................................................................................................................ 17

APPENDIX A. MICROBIAL PESTICIDES DATA REQUIREMENTS ............................ 18Trichoderma hamatum isolate 382 Page 3 of 22 Biopesticides Registra tion Action Document

BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

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

Microbial Pesticides Branch

Science Reviews

Ibrahim Barsoum, Ph.D. Product Analysis, Human Health John Kough, Ph.D. Product Analysis, Human Health Shannon Borges Environmental Effects Zigfridas Vaituzis, Ph.D. Environmental Effects

Regulations

Sheryl Reilly, Ph.D. Chief, Microbial Pesticides Branch Ann Sibold Regulatory Action LeaderTrichoderma hamatum isolate 382 Page 4 of 22 Biopesticides Registra tion Action Document

I. BACKGROUND

Trichoderma hamatum isolate 382 is a naturally occurring fungus that is found widely in soils, potting media, corn grits, and flour, as well as on root surfaces of various plants, decaying bark, rotting wood, fruits, and vegetables. It is intended for use in compost and soilless growing media to suppress soil borne plant pathogens, including Pythium species, Phytophthora species,

Fusarium species, Rhizoctonia solani

, Sclerotium rolfsii , and Thielaviopsis basicola . The mode

of action for Trichoderma hamatum isolate 382 is primarily though colonization of compost or soilless growing media before disease-causing microorganisms, such as those mentioned previously, have an opportunity to do so.

On October 1, 2009, the Environmental Protection Agency (EPA or the Agency) announced a new policy to provide a more meaningful opportunity for the public to participate in major registration decisions before they occur. According to this new policy, the Agency intends to provide a public comment period prior to making a registration decision for, at minimum, the following types of applications: new active ingred ients; first food uses; first outdoor uses; first residential uses; and any registration decisions for which the Agency believes there may be substantial public interest.

Consistent with the new policy of making registration actions more transparent, Trichoderma

hamatum isolate 382 is subject to a 30-day comment period as a “new active ingredient” whose registration would result in a “first outdoor us e,” a “first food use,” and possibly a “first residential use.” While a final decision on registration is contingent upon review and consideration of public comments, the Agency presently believes that, based upon the preliminary risk assessment and information submitted in support of registration of Trichoderma

hamatum isolate 382, it is in the best interest of the public and the environment to issue the registration for Trichoderma hamatum isolate 382. The basis for this preliminary decision can be

found in the risk assessment for Trichoderma hamatum isolate 382, which is characterized throughout this Biopesticides Registration Ac tion Document (BRAD) and the associated reference documents written by Agency scientists.

II. ACTIVE INGREDIENT OVERVIEW

Biological Name: Trichoderma hamatum isolate 382

Culture Deposit: American Type Culture Collection in Manassas, Virginia under Accession Number 20765

OPP Chemical Code: 119205

Type of Pesticide: Microbial Pesticide/Biofungicide

III. REGULATORY BACKGROUNDTrichoderma hamatum isolate 382 Page 5 of 22 Biopesticides Registra tion Action Document

A. Applications for Pesticide Registration

On February 20, 2007, Interregional Research Project Number 4 (IR-4) of Rutgers University (address: 500 College Road, East, Suite 201W, Princeton, NJ 08540), acting as the authorized agent for Sellew and Associates, LLC (addr ess: 84 Shadybrook Lane, Carlisle, MA 01741), submitted an application to register Trichoderma hamatum isolate 382 (EPA File Symbol 74205- G) under section 3 of the Federal Insecticide, F ungicide, and Rodenticide Act (FIFRA). On July 22, 2009, the Agency announced receipt of this application to register a pesticide product containing a new active ingredient ( 74 Federal Register [FR] 36215 ) and opened a 30-day public comment period pursuant to the provisions of FIFRA section 3(c)(4). No comments were received following this publication.

B. Food Tolerance Exemptions

Concurrent with their registration application and under Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(d), IR-4 (on behalf of Se llew and Associates, LLC) submitted a petition to establish an exemption from the requirement of a tolerance for Trichoderma hamatum isolate 382 (Pesticide Petition [PP] 7E7188). In the Federal Register of July 22, 2009 ( 74 FR 36200 ), the Agency announced that IR-4 (on behalf of Sellew and Associates, LLC) proposed to establish an exemption from the requirement of a tolerance for residues of the microbial pesticide, Trichoderma hamatum isolate 382, in or on all food commodities and opened a 30-day comment period.

One comment, which specifically stated that the aforementioned petition should be rejected without full testing for 20 years, was received in response to the notice of filing. The Agency notes that neither the data requirements nor the data guidelines require 20 years of testing; the applicant has fulfilled all applicable data requirements to support the petition by providing acceptable toxicology studies. For the proposed uses described on the pesticide product label (soilless potting media, compost and soil), the Agency has made a preliminary conclusion that there is a reasonable certainty that no harm will result to the United States population, including infants and children, from aggregate exposure to the residues of Trichoderma hamatum isolate

382.

IV. RISK ASSESSMENT

On October 26, 2007, the Agency issued a Final Rule in the Federal Register on the data requirements to support registration of microbial pesticides and updated the definition for microbial pesticides ( 72 FR 61002 ). The rule became effective on December 26, 2007. The data and information evaluated for this BRAD were considered in light of these requirements.

The classifications that are found for each data submission are assigned by Agency 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 certain aspects determined not to be scientifically accep table (“SUPPLEMENTAL: UPGRADABLE”). If a study is rated as “SUPPLEMENTAL: UPGRADABLE,” the Agency always provides anTrichoderma hamatum isolate 382 Page 6 of 22 Biopesticides Registra tion Action Document

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 the study is not required by the current 40 Code of Federal Regulations (CFR) part 158. Both “ACCEPTABLE” and “SUPPLEMENTAL” studies may be used in the risk assessment process as appropriate. An “UNACCEPTABLE” rating indicates that new data need to be submitted.

For the acute toxicity data requirements, toxicity categories are assigned based on the hazard(s) identified from studies and/or other information submitted to the Agency in support of a pesticide registration. The active ingredient or particular product is classified into Toxicity Category I, II, III, or IV, where Toxicity Categor y I indicates the highest toxicity and Toxicity Category IV indicates the lowest toxicity.

A. Product Analysis Assessment ( 40 CFR § 158.2120 )

All product analysis data requirements for Trichoderma hamatum strain 382 have been satisfied

. Refer to Tables 1 and 2 in Appendix A for a brief summary of these data requirements, including both generic and product-specific information. Additionally, the comprehensive Agency risk assessments that evaluate these data are available as “Supporting & Related Materials” within Docket Number EPA-HQ-OPP-2010-0489 at http://www.regulations.gov (U.S. EPA 2009, 2010b).

B. Human Health Assessment ( 40 CFR § 158.2140 )

1. Toxicity

All toxicology data requirements for Trichoderma hamatum strain 382 have been satisfied. Acceptable Tier I mammalian toxicology data/information support the registration of

Trichoderma hamatum strain 382. Furthermore, Tier II and Tier III studies were not required for

Trichoderma hamatum strain 382 based on the lack of acute toxicity/pathogenicity in the Tier I

studies. Refer to Table 3 in Appendix A for a brief summary of these data requirements, including both generic and product-specific information. Additionally, the comprehensive Agency risk assessments that evaluate these data are available as “Supporting & Related Materials” within Docket Number EPA-HQ-OPP-2010-0489 at http://www.regulations.gov (U.S. EPA 2009, 2010b, 2010c).

2. Endocrine Disruptors

As required under FFDCA section 408(p), the Agen cy has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may have an effect in hum ans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the 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 pr oceed to the next stage of the EDSP where the Agency will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine-related effects caused by the substance, and establish a quantitative relationship between the dose and the E, A, or T effect.Trichoderma hamatum isolate 382 Page 7 of 22 Biopesticides Registra tion Action Document

Between October 2009 and February 2010, the Agency issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was 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 disruptors.

Trichoderma hamatum strain 382 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), the Agency must screen all pesticide chemicals. Accordingly, the Agency anticipates issuing future EDSP orders/data call-ins for all pesticide active ingredients.

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

.

3. Food Quality Protection Act (FQPA) Considerations

Section 408(c)(2)(A)(i) of the Federal Food, Drug, and Cosmetic Act allows the Agency 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 Agency determines that the exemption is “safe.” Section 408(c)(2)(A)(ii) of FFDCA defines “safe” to mean that “there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.” This includes exposure through drinking water and in residential settings, but does not include occupational exposure. Pursuant to section 408(c)(2)(B) of FFDCA, in establishing or maintaining in effect an exemption from the requirement of a tolerance, the Agency must take into account the factors set forth in section 408( b)(2)(C) of FFDCA, which require the Agency to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue....” Additionally, section 408(b)(2)(D) of FFDCA requi res that the Agency consider “available information concerning the cumulative effects of [a particular pesticide's] residues and other substances that have a common mechanism of toxicity.”

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

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

Based on the acute toxicity/pathogenicity data presented in Table 3 in Appendix A, the data required for a FQPA risk assessment for Trichoderma hamatum strain 382 have been satisfied

.Trichoderma hamatum isolate 382 Page 8 of 22 Biopesticides Registra tion Action Document

a. Aggregate Exposures

In examining aggregate exposure, section 408 of FFDCA directs the Agency 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).

Dietary Exposure and Risk Characterization : No harmful effects to humans are expected from eating treated food. Dietary exposure to the microbial pesticide is likely to occur, but the lack of acute oral toxicity, infectivity, and pathogenicity support the establishment of an exemption from the requirement of a tolerance for Trichoderma hamatum isolate 382.

Dietary exposure to the microbial active ingredient is expected to be minimal. The label directions specify that product is to be mixed into potting soil or applied to soil and will not likely result in residues on crops.. Moreover, Trichoderma hamatum isolate 382 lives in soils and is unlikely to live on the plants because any spores that do end up on the plant due to application would decrease over time due to weathering, desiccation, and ultraviolet radiation, which can kill even quiescent forms of the fungus. In the remote likelihood that the applied fungus grew on the edible portions of a treated crop, the results of the oral toxicity testing demonstrated that no toxicity or pathogenicity in treated animals occurred, even when dosed with the fungus at high levels by the oral route of exposure.

Drinking Water Risk Characterization : Drinking water exposure is expected to be negligible because the microbial fungicide will not be applied to water. Further, Trichoderma hamatum isolate 382 is a soil microorganism and would not proliferate in aquatic environments. Moreover, the Agency believes that Trichoderma hamatum isolate 382 within the soil will not likely percolate into water due both to the large size of the fungal spores and the fact that they adhere to soil particles. Even in the unlikely event that dietary exposure occurs through drinking water, the Agency concludes that there is a reasonable certainty that no harm will result because of the lack of acute oral toxicity/pathogenicity to mammals.

Nonoccupational, Residential Risk Characterization : Trichoderma hamatum isolate 382 is a naturally occurring microorganism and is ubiquitous in the environment. Trichoderma hamatum isolate 382 will be applied to soiless potting media, compost and/or soil primarily in greenhouses and nurseries. Although some applications to soilless potting media, compost and/or soil may be in residential areas, non-dietary exposure would be expected to be below the Agency’s level of concern because of its low toxicity classification, and because the lab results indicate

Trichoderma hamatum isolate 382 is not pathogenic to mammals.

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

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

The Agency has not found Trichoderma hamatum isolate 382 to share a common mechanism ofTrichoderma hamatum isolate 382 Page 9 of 22 Biopesticides Registra tion Action Document

toxicity with any other substances, and Trichoderma hamatum isolate 382 does not appear to produce a toxic metabolite as its mode of action against the target pest. For the purposes of this tolerance exemption action, therefore, the Agency has assumed that Trichoderma hamatum isolate 382 does not have a common mechanism of toxicity with other substances. For information regarding the Agency’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cu mulative effects of such chemicals, see the Agency’s website at http://www.epa.gov/pesticides/cumulative

.

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

FFDCA section 408(b)(2)(C) provides that the Agency shall assess the available information about consumption patterns among infants and children, special susceptibility of infants and children to pesticide chemical residues, and the cumulative effects on infants and children of the residues and other substances with a common mechanism of toxicity. In addition, FFDCA section 408(b)(2)(C) provides that the Agency shall apply an additional tenfold margin 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 unless the Agency determines that a different margin of safety will be safe for infants and children. Margins of exposure (safety), which are often referred to as uncertainty factors, are inco rporated into Agency risk assessments either directly or through the use of a margin of exposure analysis, or by using uncertainty (safety) factors in calculating a dose level that poses no appreciable risk.

Based on the acute toxicity and pathogenicity data summarized in Table 3 of Appendix, the Agency concludes that there is a reasonable certainty that no harm will result to the United States population, including infants and children, from aggregate exposure to the residues of

Trichoderma hamatum isolate 382. This includes all anticipated dietary exposures and all other exposures for which there is reliable information. The Agency has arrived at this conclusion

because the data available on Trichoderma hamatum isolate 382 do not demonstrate toxic, pathogenic, or infective potential to mammals. Thus, there are no threshold effects of concern and, as a result, the provision requiring an additional margin of safety does not apply.

3. Occupational Exposure and Risk Characterization

In light of the Tier I acute toxicity/pathogenic ity studies, which did not show any toxicity or pathogenicity via the oral, pulmonary, or intraper itoneal injection routes of exposure, handler

exposure to Trichoderma hamatum isolate 382 is not expected to pose any undue risk. Regardless, appropriate personal protective equipment and precautionary statements are required to be on the product label to mitigate any potential risks to pesticide handlers due to prolonged exposure. Handlers working with Trichoderma hamatum isolate 382 must wear a long-sleeved shirt, long pants, socks, shoes, waterproof gloves, and a dust/mist filtering respirator meeting National Institute for Occupational Safety and H ealth (NIOSH) standards of at least N-95, R-95, or P-95 when mixing, loading, or applying the product.

C. Environmental Assessment ( 40 CFR § 158.2150 )

1. Nontarget Organism ToxicologyTrichoderma hamatum isolate 382 Page 10 of 22 Biopesticides Registra tion Action Document

All nontarget toxicology data requirements for Trichoderma hamatum isolate 382 have been

satisfied . Acceptable Tier I nontarget toxicology data/information support the registration of

Trichoderma hamatum strain 382. Refer to Table 4 in Appendix A for a brief summary of these data requirements. Additionally, the comprehensive Agency risk assessment that evaluates thesedata is available as “Supporting & Related Materials” within Docket Number EPA-HQ-OPP2010-0489 at http://www.regulations.gov (U.S. EPA 2010a).

2. Environmental Fate and Ground Water Data

As the information provided is sufficient to both satisfy the Tier I nontarget organism data requirements and for nontarget organism risk assessment for Trichoderma hamatum isolate 382, further testing at higher tier levels (i.e., Tiers II, III, and IV) is not required.

3. Ecological Exposure and Risk Characterization

The Agency has performed an environmental risk assessment based on the literature citations and studies provided by the registrant and has determined that the proposed uses of Trichoderma

hamatum isolate 382 do not pose a hazard to wildlife. Trichoderma hamatum isolate 382 is a naturally occurring strain of Trichoderma hamatum . This and other Trichoderma species are ubiquitous and occur widely in soils, including agricultural soils in concentrations ranging up

to10 6 colony-forming units per gram (cfu/g) of dry soil. The concentrated technical product

contains at least 1 x 10 7 cfu/g. Trichoderma hamatum isolate 382 and is intended for application to soilless potting media, compost and soil primarily in nurseries and greenhouses, for the production of ornamentals and vegetable plants. Due to the nature of the application method, exposure to terrestrial nontarget organisms is expected to be low. The use of Trichoderma

hamatum isolate 382 as proposed is not expected to significantly increase the amount of

Trichoderma hamatum or other Trichoderma species beyond levels that are already present in container media or in soils. Post application s hould not produce effects not already seen from the

natural Trichoderma species concentration fluctuations.

The applicant has submitted data waiver rationales to satisfy data requirements for nontarget organism risk assessment with the technical grade of the active ingredient (TGAI). Submitted data, data waiver rationales, and a search by the Agency of several literature databases provides sufficient information to determine that toxicity /pathogenicity to wild mammals, avian wildlife, freshwater and marine/estuarine vertebrates and invertebrates, honey bees, nontarget insects, and terrestrial and aquatic plants is not expected from the proposed label uses. As a result, a “No

Effect” determination is also made for direct and indirect effects to listed species and their designated critical habitats resulting from the registered uses of Trichoderma hamatum isolate 382, as labeled.

The information provided is sufficient to both satisfy the Tier I nontarget organism data requirements and for nontarget organism risk assessment for the active ingredient. Further testing of nontarget organisms at higher tier levels is not required.

4. Threatened and Endangered Species Assessment

Since the Agency has determined that no effects are anticipated for any nontarget species exposed to Trichoderma hamatum isolate 382 as a result of the proposed labeled applications, effects to threatened and endangered species and their designated critical habitats are also notTrichoderma hamatum isolate 382 Page 11 of 22 Biopesticides Registra tion Action Document

expected. Therefore, a “No Effect” determination is made for direct and indirect effects to listed species and their designated critical habitats resulting from the registered uses of Trichoderma

hamatum isolate 382, as labeled.

V. ENVIRONMENTAL JUSTICE

The Agency seeks to achieve environmental justice—the fair treatment and meaningful involvement of all people regardless of race, color, national origin, or income—with respect to the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result their location, cultural practices, or other factors, may have atypical, unusually high exposure to Trichoderma hamatum isolate 382, compared to the general population. Please comment if you are aware of any subpopulations that may have atypical, unusually high exposure compared to the general population.

For additional information regarding environmental justice issues, please visit the Agency’s web

site at http://www.epa.gov/compliance/environmentaljustice/index.html

.

VI. RISK MANAGEMENT DECISION

Section 3(c)(5) of FIFRA provides for the registration of a new active ingredient if it is determined that (A) its composition is such as to warrant the proposed claims for it; (B) its labeling and other materials required to be submitted comply with the requirements of FIFRA; (C) it will perform its intended function w ithout unreasonable adverse effects on the environment; and (D) when used in accordance with widespread and commonly recognized practice, it will not generally cause unreasonable adverse effects on the environment.

The four criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied by the science assessments supporting the product containing Trichoderma hamatum isolate 382. This product is not expected to cause unreasonable adverse effects and is likely to provide protection as claimed when used according to label instructions. Therefore, the Agency believes

that Trichoderma hamatum isolate 382 is eligible for registration for the labeled uses.

VII. TERMS AND CONDITIONS OF THE REGISTRATION(S)

There are no terms and/or conditions associated with this registration.

VIII. GLOSSARY OF ACRONYMS AND ABBREVIATIONS

BRAD Biopesticides Registration Action Document CFR Code of Federal RegulationsTrichoderma hamatum isolate 382 Page 12 of 22 Biopesticides Registra tion Action Document

cfu colony-forming units cfu/g colony-forming units per gram °C degrees Celsius EDSP Endocrine Disruptor Screening Program EP end-use product EPA Environmental Protection Agency (the “Agency”) FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FR Federal Register g/mL grams per milliliter IR-4 Interregional Research Project Number 4 LLC limited liability company

MRID No. Master Record Identification Number NIOSH National Institute for Occupational Safety and Health OCSPP Office of Chemical Safety and Pollution Prevention OPP Office of Pesticide Programs

PP Pesticide Petition TGAI technical grade of the active ingredient

IX. BIBLIOGRAPHY

A. Studies Submitted to Support the Trichoderma hamatum isolate 382 Pesticide Product RegistrationTrichoderma hamatum isolate 382 Page 13 of 22 Biopesticides Registra tion Action Document

43543801 Hoitink, H.; Stoneman, W.; Bowman, L.; et al . (1995) Trichoderma hamatum isolate 382--Product Identity and Disclosure of Ingredients, Manufacturing Process, and Discussion on the Formation of Unintentional Ingredients: Lab Project Number: 49B. Unpublished study prepared by Ohio State University, CHR. Hansen's Biosystems, and Earthgro. 55 pages.

43543802 Stoneman, W.; Bowman, L.; Feldman, K. (1995) Trichoderma hamatum isolate 382--Analysis of Samples, Certification of Ingredient Limits, Analytical Method for Certified Limits, and Physical and Ch emical Properties: Lab Project Number: 49B. Unpublished study prepared by CHR. Hansen's Biosystems and Earthgro. 22 pages.

43543803 Hoitink, H.; Hartman, C.; Biehn, W. (1995) Trichoderma hamatum isolate 382 Safety Data in Support of Petition for Proposing a Temporary Exemption from the Requirements of a Tolerance for Thichoderma hematum (sic) for Use in Vegetable Bedding Plant Production: Lab Project Number: 49B. Unpublished study prepared by Ohio State University and IR-4. 157 pages.

43543804 Hoitink, H. (1995) Trichoderma hamatum isolate 382: Hypersensitivity Incidents with Microbial Pest Control Agents: Statement of Finding No Hypersensitivity: Lab Project Number: 49B. Unpublished study prepared by Ohio State University. 4 pages.

43543805 Hoitink, H. (1995) Trichoderma hamatum isolate 382: Plant Studies: Request for Waiver of the Requirements for Testing: Lab Project Number: 49B. Unpublished study prepared by Ohio State University. 72 pages.

43543806 Hoitink, H.; Hartman, C.; Biehn, W. (1995) Trichoderma hamatum isolate 382: Product Performance Data: Lab Project Number: 49B. Unpublished study prepared by Ohio State University and IR-4. 59 pages.

44420001 Cascino, J.; O'Leary, M. (1997) Trichoderma hamatum isolate 382-Product Identify (sic) and Disclosure of Ingredients, Manufacturing Process and Discussion on the Formation of Unintentional Ingredients: Amendment: Lab Project Number: 49B. Unpublished study prepared by Sylvan Bioproducts and Earthgro. 29 pages.

44420002 Stoneman, W.; Bowman, L.; O'Leary, M. et al . (1997) Trichoderma hamatum isolate 382-Analysis of Samples, Certifi cation of Ingredient Limits, Analytical Methods for Certified Limits Physical and Chemical Properties, Analysis of 5 Production Batches: Amendment: Lab Project Number: 49B. Unpublished study prepared by CHR. Hansen Biosystems, Earthgro Inc., and Sylvan Bioproducts. 24 pages.

44420003 Shelton, L. (1996) Acute Oral Toxicity /Pathogenicity Study in Rats: TH382: Lab Project Number: M96AW33.6G41: 18.6G41. Unpublished study prepared by Microbiological Associates, Inc. 88 pages.Trichoderma hamatum isolate 382 Page 14 of 22 Biopesticides Registra tion Action Document

44420004 Shelton, L. (1997) Acute Intraperitoneal Toxicity Study in Rats: FB299 and TH382: Lab Project Number: M96AW33.6P31: 18.6P31. Unpublished study prepared by Microbiological Associates, Inc. 65 pages.

44420005 O'Leary, M. (1997) Trichoderma hamatum strain 299 (sic)-Statement of Finding of No Adverse Effects to Users/Workers: Lab Project Number: 49B. Unpublished study prepared by Earthgro. 4 pages.

44422004 Shelton, L. (1997) Acute Intraperitoneal Toxicity Study in Rats: FB299 and TH382: Lab Project Number: M96AW33.6P31: 18.6P31. Unpublished study prepared by Microbiological Associates, Inc. 65 pages.

45583601 Cascino, J.; O'Leary, M. (2001) Trichoderma hamatum isolate 382--Analysis of Samples, Certification of Ingredient Li mits, Analytical Methods for Certified Limits, Physical and Chemical Properties, Analysis of 5 Production Batches: Lab Project Number: 49B. Unpublished study prepared by Sylvan Bioproducts. 52

pages.

45583602 Hoitink, H.; Biehn, W.; Hartman, C. (1995) Trichoderma hamatum isolate 382 Safety Data in Support of Petition Proposing a Temporary Exemption from the Requirement of a Tolerance for Trichoderma hamatum for Use in Vegetable Bedding Plant Production: Lab Project Number: 49B. Unpublished study prepared by Ohio State University. 57 pages.

45583603 Shelton, L. (1996) Acute Oral Toxic ity/Pathogenicity Study in Rats: TH382: Lab Project Number: M96AW33.6G41. Unpublished study prepared by Microbiological Associates, Inc. 88 pages.

45583604 Biehn, W. (2001) Trichoderma hamatum isolate 382 Hypersensitivity Incidents with Microbial Pest Control Agents: Statement of Finding of No Hypersensitivity: Lab Project Number: 49B. Unpublished study prepared by Ohio State University, OARDC. 4 pages.

45583605 Hoitink, H. (2001) Nontarget Plant St udies--Pathogenicity and Phytotoxicity Testing of Trichoderma hamatum isolate 382 on Conifers (1998-2000): Lab Project Number: 49B. Unpublished study prepared by Ohio State University, OARDC. 22 pages.

45583606 Hoitink, H. (2001) Nontarget Plant St udies--Pathogenicity and Phytotoxicity Testing of Trichoderma hamatum isolate 382 on Corn (1998-2000): Lab Project Number: 49B. Unpublished study prepared by Ohio State University, OARDC. 19 pages.

45583607 Hoitink, H.; Hartman, C.; Biehn, W. (1995) Trichoderma hamatum isolate 382 Product Performance Data: Lab Project Number: 49B. Unpublished study prepared by Ohio State University, OARDC. 59 pages.Trichoderma hamatum isolate 382 Page 15 of 22 Biopesticides Registra tion Action Document

46010601 Hoitink, H.; Cascino, J.; O'Leary, M. (2002) Trichoderma hamatum isolate 382 – Product Identity and Disclosure of Ingredients, Manufacturing Process and Discussion on the Formation of Unintentional Ingredients. Project Number: 49B, IR/4/PR/NO/49B. Unpublished study prepared by Ohio State University, Sylvan Bioproducts, and Sellew & Associates LLC. 276 pages.

46010602 O'Leary, A. (2000) Acute Pulmonary Toxicity/Pathogenicity Study in Rats with

Trichoderma hamatum , Strain TH 382. Project Number: 011695/1. Unpublished study prepared by Ricerca Biosciences, LLC. 30 pages.

46999701 O'Leary, A. (2000) Acute Pulmonary Toxicity/Pathogenicity Study in Rats with

Trichoderma hamatum , Strain TH382. Project Number: 011695-1. Unpublished study prepared by Ricerca, Inc. 29 pages.

47005702 Braverman, M. (2004) Trichoderma hamatum isolate 382: Rationale for Waivers. Project Number: 49B. Unpublished study prepared by Interregional Research Project No. 4. 46 pages.

47005703 Braverman, M. (2004) Trichoderma hamatum isolate 382 Safety Information Rationale for Waivers. Project Number: 49B. Unpublished study prepared by Interregional Research Project No. 4. 27 pages.

47015501 Hoitink, H.; Cascino, J.; O'Leary, M. (2004) Trichoderma hamatum isolate 382 Product Identity and Disclosure of Ingredients, Manufacturing Process and Discussion on the Formation of Unintentional Ingredients. Project Number: 49B, 20765. Unpublished study prepared by Ohio State University, Sellew & Associates LLC, and Ohio State University. 251 pages.

47068102 Braverman, M. (2007) Trichoderma hamatum isolate 382 - Rationale for Waivers-Non Target and Environmental Effects. Project Number: 49B. Unpublished study prepared by Interregional Research Project No. 4. 126 pages.

47598902 Baysal-Gurel, F.; Hoitink, H; Miller, S. (2008) Storage/Stability Characteristics for the Dry Product Formulation of Trichoderma hamatum 382. Unpublished study prepared by Ohio State University. 82 pages.

47598903 Stoneman, W. (2008) Five Batch Analysis/Chemistry for the Dry Product

Formulation of Trichoderma hamatum 382. Unpublished study prepared by Ohio State University and Sylvan Biosciences. 78 pages.

47598904 Braverman, M. (2008) Trichoderma hamatum isolate 3982 - Safety Information - Rationale for Waivers. Project Number: 49B. Unpublished study prepared by Interregional Research Project No. 4. 59 pages.

47598905 Durando, J. (2008) Trichoderma hamatum (TH382) - Primary Skin Irritation in Rabbits: Final Report. Project Number: 24091. Unpublished study prepared by Product Safety Laboratories. 21 pages.Trichoderma hamatum isolate 382 Page 16 of 22 Biopesticides Registra tion Action Document

47598906 Durando, J. (2008) Trichoderma hamatum (TH382) - Primary Eye Irritation in Rabbits. Project Number: 24090. Unpublished study prepared by Product Safety Laboratories. 24 pages.

47598907 Gingras, B. (2008) Sensitivity of Detection of Trichoderma hamatum TH382 for Toxicity/Pathogenicity Testing in Rats. Project Number: 2193/SN1. Unpublished study prepared by IIT Research Institute. 41 pages.

47598908 Gingras, B. (2008) Toxicity/Pathogenicity Testing of Trichoderma hamatum TH382 Following Acute Intraperitoneal Challenge in Rats. Project Number: 2193/SN2. Unpublished study prepared by IIT Research Institute. 89 pages.

47613701 Diehle, D. (2008) Manufacturing Protocol and Standard Operating Procedures for

Trichoderma hamatum 382. Unpublished study prepared by Sylvan Bioproducts Inc. 25 pages.

47747601 Braverman, M. (2009) Trichoderma hamatum isolate 382 Safety Information – Rationale for Waivers. Project Number: IR/4/PR/NO/49B. Unpublished study prepared by Interregional Research Project No. 4. 5 pages.

47980202 Braverman, M. (2010) Trichoderma hamatum isolate 382 - Primary Skin Irritation in Rabbits. Amendment Number 1 to MRID 47598905. Project Number: 0049B. Unpublished study prepared by Interregional Research Project No. 4. 4

pages.

47980203 Braverman, M. (2010) Trichoderma hamatum isolate 382 - Primary Eye Irritation in Rabbits: Amendment Number 1 to MRID 47598906. Project Number: 0049B. Unpublished study prepared by Interregional Research Project No. 4. 4 pages.

48050501 Stoneman, W. (2010) Manufacturing Proce ss, Certified Limits and Physical and Chemical Properties of the TGAI/EP of Trichoderma hamatum 382: Amendment Number One to MRID 47613701 and 47598903. Unpublished study prepared by Sylvan Bioproducts, Inc. 4 pages.

B. Environmental Protection Agency Risk Assessment Memoranda

U.S. EPA. 2009. Review of Product Chemistry, Manufacturing Process, and Acute Toxicity studies of the end use product (EP) Flora guard (EPA Reg. No. 74205-G) containing the active ingredient (AI) Trichoderma hamatum isolate 382 (0.9%). Memorandum from I. Barsoum, Ph.D. and J. Kough, Ph.D. to A. Sibold dated December 14, 2009.

U.S. EPA. 2010a. Environmental Risk Assessment of Trichoderma hamatum isolate 382 (PC 119205) for Use in Plant Growing Media; Decision No. 376203, DP Barcode No. 368013, MRIDs 477476-01, 470681-02, 455836-05, 455836-06. Memorandum from S. Borges and Z. Vaituzis, Ph.D. to A. Sibold dated January 5, 2010.

U.S. EPA. 2010b. Review of the Registrant’s Response to the Deficiencies Found by the Agency in its Review of Product Chemistry, Manufactur ing Process, and Acute Toxicity StudiesTrichoderma hamatum isolate 382 Page 17 of 22 Biopesticides Registra tion Action Document

of the Product Trichoderma hamatum isolate 382 (EPA Reg. No. 74205-G). Memorandum from I. Barsoum, Ph.D. and J. Kough, Ph.D. to A. Sibold dated April 27,

2010.

U.S. EPA. 2010c. Review of Information to Support a Food Tolerance Determination for

Trichoderma hamatum isolate 382 (ATCC# 20765), the Active Ingredient in Floraguard Related to Tolerance Petition (7E7188). Memorandum from J. Kough, Ph.D. to A. Sibold dated May 18, 2010.

C. Other References

Brewer, D. and A. Taylor. 1981. Trichoderma hamatum isolated from pasture soil. Mycopathologia 76:167–173.

Leandro, L. F. S., T. Guzman, L. M. Ferguson, G. E. Fernandez, and F. J. Louws. 2007. Population dynamics of Trichoderma in fumigated and compost-amended soil and on strawberry roots. Applied Soil Ecology 35:237–246.

Liu, B., D. Glenn, and K. Buckley. 2008. Trichoderma communities in soils from organic, sustainable, and conventional farms, and their relation with Southern blight of tomato. Soil Biology and Biochemistry 40:1124–1136.

Prinzinger, R., A. Pressmar, and E. Schleucher. 1991. Body temperature in birds. Comparative Biochemistry and Physiology 99A(4):499

– 506.

Appendix A. Microbial Pesticides Data Requirements (40 CFR Part 158 - Subpart V)Trichoderma hamatum isolate 382 Page 18 of 22 Biopesticides Registra tion Action Document

*NOTE: Master Record Identification Numbers listed in the following tables are representative of supporting data for the original registration of the product containing Trichoderma hamatum

isolate 382.

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

hamatum isolate 382, and Its Associated End- Use Product (EP) (40 CFR § 158.2120)

Results OCSPP

Guideline

Number Data Requirement TGAI EP MRID No.

885.1100 Product Identity Not applicable Submitted data satisfy the requirement for product identity. This product

contains 0.9% w/w

Trichoderma hamatum isolate 382 (not less than 1 x

10 7 cfu/g).

885.1200 Manufacturing Process

885.1300 Discussion of Formation

of Unintentional Ingredients Submitted data satisfy the requirements for manufacturing process and discussion of formation of unintentional ingredients. 47015501

47598902

47598903

47598904

47613701

45583601

Not applicable Deposition of a Sample in a Nationally Recognized Culture

Collection Trichoderma hamatum isolate 382 is on deposit with the American Type Culture Collection in Manassas, Virginia under Accession

Number 20765. Not applicable 47015501

47598902

47598903

47598904

47613701

45583601 885.1400 Analysis of Samples Submitted data sa tisfy the requirement for analysis of samples. 45583601

47598903

885.1500 Certification of Limits Not applicable Limits listed on the

confidential statement of

formula are adequate/acceptable. 45583601

Additional Studies 830.1800 Enforcement Analytical

Method Not applicable Acceptable 45583601Trichoderma hamatum isolate 382 Page 19 of 22 Biopesticides Registra tion Action Document

TABLE 2. Physical and Chemical Charact eristics for the End-Use Product (EP), Trichoderma hamatum isolate 382 (40 CFR § 158.2120)

OCSPP

Guideline

Number Data Requirement Results MRID

Number

830.6302 Color Light brown 47598903

830.6303 Physical State Solid, dry powder 47598903

830.6304 Odor Soil like 47598903 830.6313 Stability to Normal and

Elevated Temperatures, Metals,

and Metal Ions Not required for an EP Not applicable

830.6317 Storage Stability After 128 days of stor age at 4o and 25o C, the viability of

Trichoderma hamatum isolate 382 was 1.3 x 10 8 cfu/g in the

EP. 47598902

830.6319 Miscibility Not required because Trichoderma hamatum isolate 382 is not an emulsifiable form of microbial pesticide (refer to test note #2 of 40 CFR § 158.2120(d)). 47598903

830.6320 Corrosion

Characteristics The EP is not corrosive by composition or chemical structure. 47598903

830.7000 pH 7.2 CSF 830.7100 Viscosity Not required because Trichoderma hamatum isolate 382 is not a liquid form of microbial pesticide (refer to test note #4 of 40 CFR § 158.2120(d)). 47598903

830.7300 Density 0.197 grams per milliliter (g/mL) CSF

Additional Studies 830.6315 Flammability Not flammable 47598903

830.6314 Oxidation/Reduction; Chemical Incompatibility The oxidation/reduction potential of the EP is not relevant based on the fact that this is a granular material and that the EP is not a product of formulation of the active ingredient with the inert ingredients. The material is relatively dry (10% moisture) and shipped in bags in which the organism is grown, and the material will be added to the potting media or its components directly. The EP is a lower moisture

concentration than the media formulation 48050501

830.6316 Explodability Product is not potentially explosive. 47598903

830.6321 Dielectric Breakdown Voltage Product is not intended for use around electrical equipment. 47598903Trichoderma hamatum isolate 382 Page 20 of 22 Biopesticides Registra tion Action Document

TABLE 3. Toxicology Data Requirements for the Tec hnical Grade of the Active Ingredient (TGAI), Trichoderma

hamatum isolate 382, and Its Associated End-Use Product (EP) (40 CFR § 158.2140)

Results OCSPP Guideline

Number Data Requirement

TGAI EP MRID

Number

Tier I

885.3050 Acute Oral Toxicity/Pathogenicity Not toxic, infective, and/or pathogenic to rats when dosed

at 3.9 x 10 8 colony-forming units (cfu) per animal. Classification: Acceptable Not applicable 45583603

885.3150 Acute Pulmonary Toxicity/Pathogenicity Not toxic, infective, and/or pathogenic to rats when dosed

at 1.3 x 10 7 cfu per animal. Classification: Acceptable Not applicable 46999701

46010602

885.3200 Acute Injection Toxicity/Pathogenicity Not toxic, infective, and/or pathogenic to rats when dosed

at 4.0 x 10 7 cfu per animal. Classification: Acceptable Not applicable 47598908

885.3400 Hypersensitivity

Incidents No hypersensitivity incidents, including immediate-type or delayed-type reactions of humans and domestic animals occurring during the testing or production of the TGAI and EP, were observed by the applicant. Any future hypersensitivity incidents must be reported per OCSPP Guideline 885.3400. Not applicable

885.3500 Cell Culture Not required because

Trichoderma hamatum isolate 382 is not a virus (refer to test note #4 of 40 CFR § 158.2140(d)). Not applicable Not applicable

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity Not applicable Waived based on (1)

Trichoderma hamatum isolate 382’s ubiquitous presence in the environment; (2) the

absence of incidents of hypersensitivity, allergies, or other adverse effects, despite varying uses of

Trichoderma hamatum isolate 382 since 1986; and (3) all inert ingredients in the end-use product formulation being exempt from the requirement of a

tolerance. Classification: Acceptable 47598904

870.2400 Acute Eye Irritation Not applicable Trichoderma hamatum isolate 382 was mildly irritating to the eye based on the highest maximum mean total score of 7.3, recorded

1 hour after test material

instillation. Classification: Acceptable

TOXICITY CATEGORY

III 47598906Trichoderma hamatum isolate 382 Page 21 of 22 Biopesticides Registra tion Action Document

TABLE 3. Toxicology Data Requirements for the Tec hnical Grade of the Active Ingredient (TGAI), Trichoderma

hamatum isolate 382, and Its Associated End-Use Product (EP) (40 CFR § 158.2140)

Results OCSPP Guideline

Number Data Requirement

TGAI EP MRID

Number

870.2500 Primary Dermal Irritation Not applicable Trichoderma hamatum isolate 382 was slightly irritating to the skin. The Primary Irritation Index was

0.3. Classification: Acceptable

TOXICITY CATEGORY

IV 47598905

Tiers II and III Not required for Trichoderma hamatum isolate 382 based on the lack of acute toxi city/pathogenicity in the Tier I studies.

Additional Studies

Not applicable Sensitivity of Detection Intraperitoneal pathogenicity/toxicity testing could be performed usingpotato dextrose agar as a nonselective recovery medium

for rat tissue other than the stomach, cecum, and intestinal tract, while potato dextrose agar with gentamicin may be used as the

enumeration medium for determination of the presence

of Trichoderma hamatum

isolate 382 in the cecum. Classification: Acceptable Not applicable 47598907Trichoderma hamatum isolate 382 Page 22 of 22 Biopesticides Registra tion Action Document

TABLE 4. Nontarget Organism Toxicity and Environmental Fa te Data Requirements for the Technical Grade of the Active Ingredient (TGAI), Trichoderma hamatum isolate 382 (40 CFR § 158.2150)

OCSPP Guideline

Number Data Requirement Results MRID

Number 885.4050 Avian Oral Toxicity

885.4200 Freshwater Fish Toxicity/Pathogenicity

885.4240 Freshwater Invertebrate Toxicity/Pathogenicity

885.4280 Estuarine/Marine Fish and Invertebrate Testing 885.4300 Nontarget Plant Testing 885.4340 Nontarget Insect Testing 885.4380 Honey Bee Testing Data waiver rationales provide sufficient

information to determine that toxicity/pathogenicity to avian wildlife, 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 label uses. Classification: Acceptable 47068102

885.4100 Avian Inhalation Toxicity/Pathogenicity Data waiver rationales were submitted. However, this information was not required as the nature of the microbial 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)). 47747601

885.4150 Wild Mammal Toxicity/Pathogenicity Tests required by 40 CFR § 158.2140 are adequate and appropriate for assessment of hazards to wild mammals (refer to test note #4 of 40 CFR § 158.2150(e)). Testing indicates no adverse effects to laboratory rats at 3.9 x 10 8 cfu per animal when dosed orally. Data waiver rationales also support the conclusion that

adverse effects to wild mammals are not expected as a result of the proposed label uses. Classification: Acceptable for wild mammal

risk assessment 45583603

47068102

Tiers II, III, and IV Not required for Trichoderma hamatum isolate 382 based on the acceptability of the waiver rationales provided for Tier I.