Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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### Docket Number EPA - HQ - OPP - 2009 - 0509 

## Streptomyces Strain K61 Registration Review Final Decision

Case 6066 PC 129069 March 2011



## Approved by: ________________________ Keith A. Matthews, Director Biopesticides and Pollution Prevention Division Date: ______________________Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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## Table of Contents Streptom yces Strain K61 (Case 6066 ) I. INTRODUCTION ................................ ................................ ................................ .................... 4 A. Streptomyces Strain K61 General Background ................................ ................................ . 5 B. Streptomyces Strain K61 Registered Pesticide Products ................................ ................... 6 II. SCIENTIFIC ASSESSMENT ................................ ................................ ................................ 6 A. Product Analysis (40 CFR § 158.2120) ................................ ................................ ............... 6 B. Human Health ................................ ................................ ................................ ...................... 7 1. Acute Toxicity

– Tier I (40 CFR § 158.2140) ................................ ................................ .. 7 2. Subchronic Toxicity, Developmental Toxicity, Mutagenicity, and Immunotoxicity (Tier II); Chronic Testing (Tier III) ................................ ................................ .......................... 8 3. FQPA Assessment: Dietary Exposure and Risk Characterization ................................ . 8 4. Occupational Exposure and Risk Characterization ................................ ....................... 11 5. Endocrine Disruptors ................................ ................................ ................................ ...... 11 6. Human Health Risk Characterization ................................ ................................ ............. 12 C. Environmental Assessment ................................ ................................ ............................... 12 1. Effects on Nontarget Organisms

– Tier I (40 CFR § 158.2060) ................................ ..... 12 2. Environmental Fate, Ecological Exposure, and Environmental Expression

– Tiers II and III (40 CFR § 158.2060) ................................ ................................ ................................ 15 3. Endangered Species Assessment ................................ ................................ ..................... 15 4. Environmental Risk Characterization ................................ ................................ ............. 15 D. Product Performance (Efficacy) (40 CFR § 158.2070) ................................ ................... 16 E. Incidents ................................ ................................ ................................ .............................. 16 F. Public Comments ................................ ................................ ................................ ................ 16 G. Water Qual ity ................................ ................................ ................................ ..................... 17 H. Trade Irritants ................................ ................................ ................................ ................... 17 I. Environmental Justice ................................ ................................ ................................ ........ 17 III. FINAL REGISTRATION REVIEW DECISION ................................ ............................ 18 IV. BIBLIOGRAPHY ................................ ................................ ................................ ................ 18 V. GLOSSARY OF ACRONYMS AND ABBREVIATIONS ................................ ............... 22 VI. APPENDIX ................................ ................................ ................................ .......................... 24Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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### Streptom yces Strain K61 (Case 6066 ) Registration Review Team Human Health and Environmental Effects Joel Gagliardi (BPPD) Zi gfridas Vaituzis (BPPD) Risk Management Anna Gross (BPPD) Office of General Counsel Philip Ross, Esq.Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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4 I. INTRODUCTION This document is the Environmental Protection Agency ’s (EPA or the Agency) Final Registration Review Decision for Streptomyces Strain K61 and is being issued in accordance with 40 CFR §§ 155.57 and 155.58. A registration review decision is the Agency 's determination whether a pesticide meets, or does not meet, the standard for registration in the Federal Insecticide, Fungicide, and Rodentic ide Act (FIFRA). With regard to registered pesticides containing Streptomyces Strain K61, EPA determined that the FIFRA standard of registration has been met. For further information on Streptomyces Strain K61 , additional documents can be found in EPA’s public docket (EPA - HQ - OPP - 2009 - 0509 ) at www.regulations.gov . FIFRA, as amended b y the Food Quality Protection Act (FQPA) of 1996, mandated the continuous review of existing pesticides. All pesticides distributed or sold in the United States must generall y be registered b y EPA, based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy , and pesticide use practices will occur over time. Through the registration review program, the Agency periodically

reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safel y. Information on this program is provided at: http://www.epa.gov/oppsrrd1/registration_review/ . In 2006, the Agen cy

implemented the Registration Review program pursuant to FIFRA section 3(g) . EPA will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. In accordance with 40 CFR § 155.50, the Agency formally initiated registration review for Streptomyces Strain K61 (Case 6066 ). The following timeline highlights significant events that have occurred during the registration review of Streptomyces Strain K61 :  September 2009

– Publication o f the Streptomyces griseoviridis Strain K61 Summary Document in the docket (EPA - HQ - OPP - 2009 - 0509 ) for a 60 - day public comment period. The Summary Document also included the preliminary work plan (PWP). No comments were received.  October 2009

– A request by the registrant, Verdera Oy , to change the name of the a.i. to Streptomyces K61 was approved as part of a product formulation amendment . This change was made due to an inability to positively

identify this species as Streptomyces griseoviridis . 1 Both the label and C onfidential S tatement of F ormula (CSF) were updated 1 The species identification was under question during the initial registration of Streptomyces Strain K61, but the issue was resolved wi th help from a letter written by David Lambert (Associate Professor of Plant Pathology at the University of Maine) on May 19, 1993. In it, he argued that the lack of spiral spore chain morphology that was the basis for the determ ination that the strain was not Streptomyces griseoviridis was not a reliable enough characteristic for negative identification. This determination was supported by a May 26, 1993 memo from C. Schaffer to S. Lewis, in which it was recommended that BPPD accept the identification of the strain as Streptomyces grise oviridis . B ased on a February 2, 2005 letter from the German Collection of Microorganisms and Cell Cultures (DSM) ,Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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5 with the revised a.i. name. In order to harmonize both product registrations containing this a.i., Verdera Oy

will also be required , as part of the registration pro cess, to update the label and CSF for M yc ostop ® G Biofungicide (EPA Reg. No. 64137 - 9). This change affects only

the nomenclature of the a.i. It does not have an impact on any of the previously

completed risk assessments, which are still valid because all of the submitted studies were conducted using the same test material that is now registered as Streptomyces Strain K61.  January

2010

– Publication of the Streptomyces Strain K61 Final W ork Plan , which stated that the most recent exposure and risk assessments still supported the registration of the currently

registered pesticide products containing Streptomyces Strain K61 and that these products appeared to have met the requirement of registratio n review under 40 CFR § 155.50. The Final W

ork Plan also documented the modification of the active ingredient name designation from Streptomyces griseoviridis Strain K61 to Streptomyces Strain K61 .  July 2010

– Publication of the Streptomyces Strain K61 Proposed Decision for a 60 - day public comment period. No comments were received. The document proposed a final registration review decision affirming that the data on file continue to adequately support the registered pesticides containing Streptomyces Str ain K61 .  March 2011 - Publication of the Streptomyces Strain K61 Registration Review Final Decision, which formally determined that registered pesticides containing Streptomyces Strain K61 meet the current standards of registration under FIFRA. The infor mation evaluated to support Streptomyces Strain K61 , as published in the Summary Document , continues to support the active ingredient as summarized herein. The status of this and other registration review cases is available at: http://www.epa.gov/oppsrrd1/registration_review/reg_review_status.htm . Additional information on Streptomyces Strain K61 is available on the Biopesticides and Pollution Prevention D ivision’s website in the form of a succinct fact sheet ( http://www.epa.gov/oppbppd1/biopesticides/ingredients/factsheets/factsheet_129069.htm ). On October 26, 2007, the Agency issued a Final Rule in the Federal Register (FR) on the data requirements to support registration of biochemical and microbial pesticides and upd ated definitions for both biochemical and microbial pesticides (72 FR 61002). This rule became effective on December 26, 2007. The data and information summarized below were considered in light of these requirements. A. Streptomyces Strain K61 General Background Streptomyces Strain K61 is a naturall y occurring soil bacterium initially isolated from peat in Finland . It is believed to act against disease - causing fungi in at least two way s: by colonizing plant roots to deprive disease organisms of space and nourishment; and by producing antifungal compounds . It is closely related to the bacterial species that produ ces the antibiotic streptomycin. Streptomyces Strain K61 forms light colored colonies consisting of brown substrate mycelium, beige aerial mycelium, and long rectiflexible smooth spore chains. As a however, currently available data demonstrate that it is not possible that the strain in question is of the S . griseoviridis species, and th e a.i. has been re - classified as Streptomyces Strain K61.Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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6 microbial active ingredient, products containing Streptomyces Strain K61 are registered for control of seed, root and stem rot, and to prevent wilt of ornamentals, vegetables and tree and forest seedlings caused by Fusarium , Alternaria , and Phomopsis . Streptomyces Strain K61 also suppresses root rots of Pythium , Phytophthora and Rhizoctonia in greenhouse plants and is used as a seed treatment for seed or soil borne damping off and earl y root rot. Streptomyces Strain K61 is approved for use on all raw agricultural commodities and can be applied to seeds, soil, roots and transplants, or as a dip or spray . Based on data submitted to the Agency , Streptomyces Strain K61 is not expected to infect humans or to cause harmful effects if ingested. EPA determined, h owever, that users may experience mild eye and skin irritation as well as adverse effects on lungs. Current product labels specify

required personal pr otective equipment (PPE). A dverse human health or ecological risks are not expected as a result of exposure to this active ingredient when us ed as directed on product labels . Moreover, the assessment conducted in the course of this Registration Review and included in the docket indicates that all data requirements were adequatel y addressed in the course of Streptomyces Strain K61 registration . B. Streptomyces Strain K61 Registered Pesticide Products There are currently

two Streptomyces Strain K61 end use products (EPs) registered with EPA , both of which are listed in the table below. There are no registered manufacturing use products (MUPs) for Streptomyces Strain K61. EPA Reg. No. Registration Name Com pany Name Current Status % Streptomyces (a.i.) 64137 - 5 Mycostop ®

Biofungicide Verdera Oy Conditionally Registered (1993) 35% 2 64137 - 9 Mycostop ® G

Biofungicide Verdera Oy Registered (2002) 4% II. SCIENTIFIC ASSESSMENT A. Product Analysis (40 CFR § 158. 2120 ) The data and information submitted to support applications for registration for the active ingredient Streptomyces Strain K61 were reassessed and found sufficient to fulfill current product chemistry

data requirements (40 CFR § 158.2 120 ) for all the use patterns described above. Adequate product analy sis data for Streptomyces Strain K61 were found in th e submissions and reviews associated with the original registration of M ycostop ® (EPA Reg. No. 64137 - 5) in 1993 and in the reasse ssment d ocuments associated with this registration review. A list of supporting product chemistry studies (including MRIDs) can be found within the ‘ Studies Supporting Registration Review of Streptomyces Strain K61’ in the b ibliograph y . Mycostop ® G (EPA Reg. No. 64137 - 9) was determined to be substantially similar to Mycostop ®

. The 2 BPPD reviewed all applicable data and approved a product formulation amendment for Mycostop ® Biofungicide (EPA Reg. No. 64137 - 5) on October 30, 2009, w hich changed the concentration of a.i. from 30% to 35%. The label wa s updated to reflect the new concentration (associated MRIDs: 475768 - 01, 476780 - 01 and 477719 - 01).Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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7 manufacturer submitted new product chemistry data to support the product’s registration but relied on previousl y submitted Mycostop ® data to support all other data requirements. A summary of the the specific phy sical and chemical characteristics of Streptomyces Strain K61 is found in Table 1 of the Appendix. B. Human Health 1. Acute Toxicity

– Tier I (40 CFR § 158.2140 ) The acute toxicity

data submitted with the original registration of Mycostop ® (EPA Reg. No. 64137 - 5), as well as the justification to bridge to that data in support of the Mycostop ® G (EPA Reg. No. 64137 - 9) registration, were reassessed and found sufficient to address current acute toxicity data requirement s (40 CFR § 158. 2140 ). Acute toxicity results are discussed below. A summary

of the Streptomyces Strain K61 acute toxicity profile , categorized by guideline, is available in Table 2 of the Appendix. A complete list of the acute toxicity studies can be found in the Bibliography .  Acute Oral Toxicity/P athogenicity (Office of Chemical Safety and Pollution Prevention (OCSPP ) Guideline 885 .3050 )

– Rats (21 males, 21 females): MRID 418211 - 12. The data show no clinically

significant signs in rats. Streptomyces S train K61 was not detected in kidney , brain, liver, lungs, spleen, mesenteric ly mph nodes, or in blood or urine samples and cleared from the feces and cecum following day two . Necropsy

studies showed no significant signs of abnormalities. There w ere significant reductions in the weights of dosed males compared to controls at all study times and in the dosed females on day 8 and day

22. In the absence of p yro genic effec ts or an y sign of infectivity , however, the test organism was not toxic, infect ive or pathogenic to rats.

 Acute Injection Toxicity/Pathogenicity (OSCPP Guideline 885.3200) – Mice (38 males, 39 females): MRID 418211 - 15. An acute intraperitoneal injection of 5000 mg of the test article/Kg killed all males and females within 1 day of treatment. 1000 mg/Kg and 500 mg/Kg doses also caused some deaths within 2 day s of dosing. This indicates a toxic response to the test article rathe r than an infectious process, which was confirmed b y the mortality caused b y the heat - killed test art icle. The toxin appears to be heat stable. Adverse clinical si gns returned to normal by

day 5 in surviving mice except for one female with a distended abdomen and two with enlarged spleens. The spleens showed no sign of the test article. The LD 50 for intraperitoneal injection was estimated to be 1306 mg/Kg for males , 870 mg/Kg for females and 1042 mg/Kg for both sexes combined.

 Acute Pulmonary Toxicity/Pathogenicity (OCSPP Guideline 885.3150) – Rats (23 male, 23 female): MRID 418211 - 14. Gener ally , instillation of bacterial spores into rat lungs will result in a small number of deaths (which was seen in this study). Also, large numbers of spores are usually recovered from the lungs shortl y after dosing

– with successively lower numbers of spor es seen at later time intervals and concurrent increases in the spores iso lated from the caecal contents

– as a result of clearance from the lungs via the trachea and subsequent ingestion. The present study was not ty

pical in this regard. The authors rep orted that microscopic examination of the dosing preparation showed densel y packed inter - meshing mycelia in aggregations of 100 mm to 200 mm, whereas spores normall y have dimensions of 1Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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8 mm x 2 mm. They

concluded that the size of the mycelial masses would not penetrate into the peripheral lungs and would be rapidly cleared from the airway s by the pulmonary

mucociliary escalator s ys tem. Evidence regarding the infectivity /pathogenicit y of the test organ ism is, therefore, inconclusive since onl y small number s of viable organisms appeared to have reached the lower lungs. Since there was no proliferation of the organism by the end of the study

and because of the large particle size of the preparation, however, the authors concluded that Streptomyces Strain K61 would not present an infectious hazard under field conditions.

 Acute Pulmonary Toxicity/Pathogenicity (O CSPP Guideline 885 . 3150 )

– Rats (200 male, 200 female): MRIDs 424415 - 01, 424415 - 02. Streptomyces Strain K61 caused death in 54% of treated male an d 48% of treated female rats with 45% (male) and 40% (female) mortalit y occurring within the first 2 day s after intratracheal instillation. This high death rate may be due partially to the large size of the test organism; Streptomyces Strain K61 caused sufficient mortality to provoke concern about pulmonary exposure to significant amounts of the bacterium. Dosage was 0.1 mLof a 3.46 x 10 8 CFU/mL suspension.

 Acute Eye Irritation (O CSPP Guideline 870. 2400 )

– Rabbits (6 males): MRID 418211 - 16. Small numbers of spores of Streptomyces Strain K61 were found in the treated eyes of all 6 rabbits at 24 and 72 hours post - treatment, but none thereafter. Instillation of Streptomyces Strain K61 (>10 7 viable spores per eye) e licited transient, mild conjunctival irritation.

 Acute Dermal Toxicity/Pathogenicity (O CSPP Guideline 885 . 3100 )

– Rabbits (5 males. 5 females): MRIDs 418211 - 13, 422980 - 08. Streptomyces Strain K61 was not toxic to rabbits when a single 2 g/Kg dose was administered dermally . Rabbit body weights were not affected by an exposure of 2 g/Kg of Streptomyces Strain K61 .  Primary Dermal Irritation (OCSPP Guideline 870.2500) – Guinea Pigs (20 females): MRID 418211 - 17. Moderate reactivity (55% of responders) of guinea pig skin to Mycostop ® (EPA Reg. No. 64137 - 5) was recorded on day 2 following challenge of sensitized animals. While no determination was made of the amount of viable Streptomyces Strain K61 spores used in an y of the animal exposures and the dose formulations records are inconsistent, the basic conclusion that the end use product is a skin sensitizer is still valid. Mycostop ® is a moderate skin sensitizer. Dosage was 0.1 mLof a 3% w/v dilution of Mycostop ® in distilled water. 2. Subchronic Toxicity, Developmental Toxicity, Mutagenicity, and Immunotoxicity (Tier II); Chronic Testing (Tier III) Tier II and Tier III studies were not required for Streptomyces Strain K61 based on the lack of acute toxicity

observed in the Tier I studies for the EPs. 3. FQPA Assessment: Dietary Exposure and Risk Characterization Section 408(c)(2)(A)(i) of the Federal Food, Drug, and Cosmetic Act (FFDCA) allows 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 EPA determines that the exemption is “safe.” Section 408(c)(2)(A)(ii) of FFDCA defines “safe” to mean that “there is a reasonable certaintyStreptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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9 that no harm will resu lt 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 it d oes not include occupational exposure. Pursuant to section 408(c)(2)(B) of FFDCA, in establishing or maintaining in effect an exemption from the requirement of a tolerance, EPA must take into account the factors set forth in section 408(b)(2)(C) of FFDCA, which require EPA to give special 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 requires 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 .” EPA performs a number of anal ys es to determine the risks from aggregate exposure to pesticide residues. First, EPA determines the toxicity of pesticides. Second, EPA examines exposure to the pesticide through food, drinking water, and through other exposures that occur as a result of pesticide use in residential settings. Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the available scientific data and other relevant information, and considered its validity , completeness, and reliability and the relationship of this information to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. On the basis of acute toxicity data discussed above and summarized by guideline in Table 2 in the Appendix, the data requirements required for FQPA risk assessments for Streptomyces Strain K61 have been satisfied. a. Aggregate Exposures In examining aggregate exposure, section 408 of FFDCA directs EPA to consider available information concerning exposures from the pesticide residue in food and all other non occupational exposures, including drinking water from ground water or surface wat er and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses). i. Dietary Exposure and Risk Characterization Dietary exposure to Streptomyces Strain K61 is expected to be minimal. As the mode of action of Stre

ptomyces Strain K61 is through root colonization , the majority of applications are to seeds and soil. Certain foliar applications are permitted for the purposes of suppressing Botrytis infection and promoting growth ; however , d irect applications to crops are highl y diluted and residue s are not expected to persist. Regardless, any risk associated with dietary exposure is expected to be insignificant. Streptomyces Strain K61 is a naturall y occurring microbe found in soil s throughout the world , and there ar e no known reports of an y deleterious effects associated with its consumption . Additionally , the acute toxicity data on file with the Agency confirm its lack of acute toxicity

and support an exemption from the requirement of a tolerance (40 CFR § 180.11 20 ).Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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10 ii . Drinking Water Risk Characterization Exposure to Streptomyces Strain K61 via drinking water when the pesticide is used is not likely to be greater than curre nt/existing exposures. Although Streptomyces Strain K61 is found naturally , it does not thrive in aquatic environments. There are no aquatic use sites for the pesticide, so exposure in drinking water is not expected. In addition, there is no evidence of adverse effects from oral, dermal, or inhalation exposure to this microbial agent ( refer to the acute toxicity

summaries above and in Table 2 of the Appendix ). D ata on file with the Agency confirm the lack of oral toxicity /pathogenicit y of Streptomyces Strain K61 and continue to support its exemption from the requirement of a toleran ce. iii . Non - Occupational, Residential Risk Characterization There are no residential uses for Streptomyces Strain K61 . Non - occupational exposures are not expected; in the event of accidental exposure, no non - occup ational risks are anticipated. The acute toxicity

data on file with the Agency show a lack of acute toxicity for all routes of exposure. b. Cumulative Effects Section 408(b)(2)(D)(v) of the FFDCA requires the Agency to consider the cumulative effects of exposure to Streptomyces Strai n K61 and to other substances that have a common mechanism of toxicity . These considerations include the possible cumulative effects of such residues on infants and children. No mechanism of toxicity in mammals has been identified for Streptomyces Strain K61 ; therefore, no cumulative effect with other related compounds is anticipated. Because the data available demonstrate a low toxicity potential for Streptomyces Strain K61 , the likelihood of adverse dietary effects is expected to be minimal. c. Determination of Safety for U.S. Population, Infants, and Children FFDCA section 408(b)(2)(C) provides that EPA shall assess the available information about consumption patterns among infants and children, special susceptibility of infants and childr en 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) requires EPA to apply an additional ten - fold margin of safet y for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database , unless EPA determines that a different m argin of safet y will protect infants and children. Margins of exp osure (safet y), which are often referred to as uncertaint y factors, are incorporated into EPA ’s risk assessment either directly , through the use of a margin of exposure anal ys is, or by using uncertainty

(safet y) factors in calculating a dose level that pos es no appreciable risk. Based on the available acute toxicity data for Streptomyces Strain K61 , along with the expected exposure profile, EPA believes that there is reasonable certaint y that no harm will result from aggregate exposure to the United State s population, including infants and children, to the residues of Streptomyces Strain K61 . This includes all anticipated dietary exposures and allStreptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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11 other exposures for which there is reliable information. The Agency has arrived at this conclusion because the submitted data available on Streptomyces Strain K61 do not demonstrate significant toxic effect s on mammals. Thus, there are no threshold effec ts of concern and, as a result, the provision requiring an additional margin of safet y does not apply. Further, the considerations of consumption patterns, special susceptibility , and cumulative effects do not apply to pesticides without a demonstrated si gnificant adverse effect. d. Food Tolerance Exemptions On April 21, 1993, a Notice of Filing was published in the Federal Register for Streptomyces sp. strain K61: exemption from the requirement of a tolerance [50 FR 21403]. Under 40 CFR 180.1120, the biological pesticide Streptomyces sp. strain K61 is exempted from the requirement of a tolerance in or on all raw agricultural commodities when used as a fungicide for the treatment of seeds, cuttings, transplants, and plants of agricultural crops in ac cordance with good agricultural practices. 4. Occupational Exposure and Risk Characterization Due to the results of the acute pulmonary toxicity study , EPA is concerned about repeated exposure of workers, farm personnel or other agriculturists to Streptomyces Strain K6 1 . Though the primary

applications of Streptomyces Strain K61 are either soil - incorporated or seed treatments, fo liar applications are permitted , which increases the probability of repeated respiratory

exposure. Myco stop ® was als o found to be a moderate skin sensitizer. To mitigate the effects of occupational exposure to this a.i. , standard personal protective equipment (PPE) is required by

the label s for both Mycostop ® and My costop ® G, including lon g - sleeved shirt and long pants, waterproof gloves, and shoes plus socks. In addition, a dust/mist respirator or a NI OSH - approved respirator is required by the label s along with a four hour restricted - entry interval (REI) for both products . 5. Endocrine Disruptors As required by

FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively , these studies include acute, subchronic and chronic toxicity , including assessments of carcinogenicit y, neurotoxicity , developm ental, reproductive, and general or s ys temic toxicity . These studies include endpoints which may

be susceptible to endocrine influence, including effects on endocrine target organ histopathology , organ weights, estrus cyclicity , sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its registration decision , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required b y FFDCA section 408(p), Streptomyces Strain K61 is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced b y a “naturally occurring estrogen, or other such endocrine effects as theStreptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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12 Administrator may

designate.” The EDSP employ s a two - tiered approach to making the statutorily

required determinations. Tier 1 consists of a battery of 11 screening assay s to identify the potential of a chemical substance to interact with the estrogen, androgen, or thy roid (E, A, or T) hormonal s ys tems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal s ys tems will proceed to the next stage of the EDSP where EPA will determine which, if an y, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify an y adverse endocrine - related effects caused b y the substance, and establish a dose - response relationship between the dose and the E, A, or T effect. Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call - in s for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Streptomyces Strain K61 is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingl y, EPA will issue future EDSP orders/data call - ins, requiring the submission of EDSP screening assays for Streptomyces Strain K61. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/ . 6. Human Health Risk Characterization The human hazard and exposure assessments for Streptomyces Strain K61 indicate that the risks to human health are negligible to non - existent when products containing Streptomyces Strain K61 are used in accordance with their respective labels. These assessments are considered complete and current, and they satisfy the stand ards of registration review. All microbial pestici de toxicology

data requirements applicable to human health effects determinations for Streptomyces Strain K61 were considered and are fulfilled. C. Environmental Assessment 1. Effects on Nontarget Organisms

– Tier I (40 CFR § 158.2060) Based on data and information submitted to support applications for registration, as well as the associated assessments evaluating those data, all microbial pesticide nontarget organism and environmental fate data r equirements for the Streptomyces Strain K61 were considered and are fulfilled. Ecological data submitted for the registration of M ycostop ® and cited for the registration of M ycostop ® G are discussed below. (Additional testing on nontarget insects, marine / estarine animals, and nontarget plants was waived during registration beca use the conditions under which such tests are required were not met.) A summary of the Streptomyces Strain K61 ecological effects is available in Table 3 of the Appendix. A comple te list of the nontarget organism and environmental fate studies can be found in the b ibliography .  Avian Oral Toxicity/Pathogenicity (OCSPP Guideline 885.4050) – Mallard (50 birds in 10 treatment groups of 5 each) : MRID 418211 - 20. No mortalities occurred in any of the control groups (negative and sterile filtrate) or among the treated birds ( 2500 mg/Kg or approximately

2.45 x 10 9 cfu/Kg per day for five day s ). All birds were normal in appearance and behavior throughout the test period. There were no app arent effects on body weight orStreptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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13 feed consumption between the control and the treated groups. All birds were euthanized using carbon dioxide at the termination of the study and then subjected to gross necrops y. The results were not found to be remarkable except for two male birds in the control groups which had single plaques in their air sacs. In the treatment group, one male bird was small, with reduced muscle mass and feather loss on the rump. Two males and one female were found to have plaques on the ir air sacs, and a second female had plaques on and in the lungs and a somewhat pale spleen. The study is scientifically sound and demonstrated an LD 50 > 2,500 mg/Kg. This indicates that Streptomyces Strain K61 is not toxic or pathogenic to waterfowl . T he study fulfils EPA Guideline requirements for an avian oral pathogenicity

/toxicity test.

 Avian Oral Toxicity/Pathogenicity (OCSPP Guideline 885.4050) – Northern Bobwhite (50 birds in 10 treatment groups of 5 each): MRID 418211 - 19. No mortalities occurred in either of the control groups (negative or attenuated) and 2 occurred among the Streptomyces treated birds (2500 mg/Kg or approximately 2.45 x 10 9 cfu/Kg per day for five day s). Due to the nature of lesions obser

ved in the necrops y, neither death was considered to be treatment - related. All other birds were normal in appearance and behavior throughout the test period, except for one bird that exhibited limping, lethargy and a ruffled appearance. These conditions were not thought to be treatment - related. There were no apparent effects on body weight or feed consumption between the control and the treated groups. All birds were euthanized using carbon dioxide at the termination of the study

and then subjected to gross necrops y. The results were not found to be remarkable. The stud y was scientificall y sound and demonstrated an LD 50 > 2,500 mg/Kg. This indicates that Streptomyces Strain K61 is not toxic or pathogenic t o upland game birds. The study fulfilled EPA Guideline requirements for an avian oral pathogenicity /toxicity test.

 Freshwater Fish Toxicity/Pathogenicity (OCSPP Guideline 885.4200) – Rainbow trout (80 fish): MRID 418211 - 21. Five - gallon glass jars holding 15 liters of solution were used as th e exposure chambers. Groups of 10 fish were exposed to a control ( water) and five test concentrations, plus a killed - spore concentr ation equivalent to the high test level. One hundred percent mortality

occurred in the killed spore group (4.0 x 10 4 CFU/mL) at day 16, with 70% and 90% mortality

in the 2.0 x 10 4 CFU/mL group at day 25 and 26 respectively . Due to sporadic mortality , an LC 50 could not be calculated but was estimated to be greater than 40.8 mg/L (4.0 x 10 8 CFU/mL) at 7, 14, and 21 day s and gre ater than 10.2 mg/L at 30 day s . A NOAEC was determined to be 5.1 x 10 3 CFU/mL and there was no observed infectivity after 30 day s. The possibility

of toxicity

was indicated by

the killed spore and the 2.0 x 10 4 test concentration results, but a lack of toxicity at the 4.0 x 10 4 test concentration made thi s interpretation questionable. (P roblems with nonspecific toxicity when testing fungal preparations have been observed in the past and have been related to the autoclaving process used to kill the fungal spores for the killed spore control .) All trout were normal in appearance and behavior throughout the test period. The dissolved ox ygen ranged from 8.0 to 10.2 mg/L in the renewed solutions and 4.8 to 10.6 mg/L in the expired solutions, pH ranged from 7.6 to 8.4 in the renewed solutions and 7.1 to 8.3 in the in the expired solutions, and the temperature ranged from 11 to 13 ° C in both solutions. This study showed sporadic fish mortality and failed to demonstrate a definitive L C 50 value due to the absence of a dose - response trend with the observed mortalit y. The study results were not adequate for making a risk assessment.Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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14  Freshwater Fish Toxicity/Pathogenicity (OCSPP Guideline 885.4200) – Rainbow trout (70 fi sh): MRID 430903 - 01. The 30 - day static renewal toxicity

/pathogenicity

study of Mycostop ® (EPA Reg. No. 64137 - 5) to rainbow trout ( Oncorhynchus mykiss ) was conducted by Kemira Agro Oy . Single replicates of 10 fish each were exposed to Streptomyces Strain K61 concentrations of 0.25 x 10 5 , 0.50 x 10 5 , 1.0 x 10 5 , 2.0 x 10 5 , and 4.0 x 10 5 CFU/mL in dilution water , plus a dilution water control and a killed - spore treatment of 4.0 x 10 5 CFU/mL . The dietary

dose in the food offering was 10% of the water exposure concentration. Water chemistry measurements of dissolved oxygen, pH, and temperature indicated that overall, adequate water quality

was maintained throughout the term of the experiment. Gentle aeration was supplied to all test chambers to maintain the d issolved oxygen levels. The day 1, day 2, day 3, and day

4 LC 50 values were 2.8 x 10 5 , 1.6 x 10 5 , 1.2 x 10 5 , and 0.8 x 10 5 CFU/mL , respectivel y. The concentration - response line slopes for day s 1 - 4 were 15, 7.7, 7.7, and 7.7, respectivel y. The slope of the day 5 through day

30 concentration - response line was 15. The 30 - day NO A EC was 0.50 x 10 5 CFU/mL based on the lack of mortalit y, statistically significant growth effects, and sublethal/abnormal effects at this concentration. All surviving fish ate normally and showed an increase in length and weight on day 30 as compared to the representative group on day 0. No lesions or tissue discolorations were noted in any surviving fish at the end of the study.

 Freshwater Aquatic Invertebrate Toxicity/Pathogenicity (OCSPP Guideline 885.4240) – Daphnia (100 Daphnia magna in 5 treatment groups): MRID 418211 - 2 2. A 21 - day static renewal study

was conducted to determine th e toxicity and/or pathogen ic i ty

of Streptomyces Strain K61 spores to Daphnia magna . A control group was tested against four treatment groups, including a maximum nominal dose exposure of 1.0 x 10 6 CFU/mL and low and median doses of 10 4 and 10 5 CFU/mL , plus a dose of 1.0 x 10 6 CFU/mL of heat - killed spores. No significant differences (P>0.05) were found between the control and the exposure levels for reproduction and time to first brood. All of the offspring produced during the study appeared normal. Mean survival was 100% for control and low level concentration, 75% for the middle concentration, and 0% for the high concentration and killed spore treatment. Mortality

from killed spore treatments has been reported from previous studies and is thought to be caused by creating a toxic environment through the autoclaving process , which could have contributed to the effects observed in this test . A day 21 EC 50 was calculated to be approximately 190 mg/L (1.9 x 10 5 CFU/mL) . Daphnid growth was found to be significantly

affected at the middle concentration (1 x 10 5 CFU/mL ). The NO A EC was found to be 1.0 x 10 4 CFU/mL , the LOEC was 1.0 x 10 5 CFU/mL , and the MATC w as found to be 3 . 2 x 10 4 CFU/mL . The mean temperature s of the test solutions were 20.6 + 0.5 o C for the old and 20.5 + 0.5 oC for the new solutions. The pH values for the renewed solutions ranged from 7.8 to 8.5 (mean = 8.3 + 0.2) and for the expired solutions ranged from 4.8 to 8.8 (mean = 8.2 + 0.9). Dissolved oxygen concentrations in the renewed solutions ranged from 8.0 to 8.5 mg/L (94% to 100% saturation) at 21 o C (mean = 8.3 + 0.2 mg/L) and in the expired solutions ranged from 0.7 to 9.5 mg/L (8% to 112% saturation) at 21 o C (mean = 7.1 + 2.4 mg/L). The study

is scientifically

sound and demonstrated an EC 50 = 190 ppm (1.9 x 10 5 CFU/mL). This indicates that Streptomyces Strain K61 is not toxic or pathogenic to Daphnia magna . The study fulfils EPA Guideline requirements for an acute toxicity test for an aquatic invertebrate.Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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15  Toxicity/pathogenicity to Honey Bees (OCSPP Guideline 885.4380) – ( 25 bee pupae per treatment): MRID 418211 - 23. Three treatment levels, representing 240, 760 and 2400 ppm at a specific activity

of 9.8 x 10 8 cfu/g of diet , were tested along with an attenuated control and a negative control. Two replicates were tested at each concentration with 25 bees per replicate. Mortalities occurred in both of the control groups (negative and attenuated) and in all 3 of the treatment groups. The mortalities in the negative and attenuated control groups were 30% and 62%, respectivel y, while those in the 240, 760, and 2400 ppm concentrations averaged 20%, 26% and 28%, respectively . The pattern of mortalit y was not found to be dose responsive and did not appear to be treatment - related. The L C 50 was determined to be greater than 2400 ppm and the NOAEC was 2400 ppm , which was the highest concentration tested. Due to nonspecific mortality in the controls, however, the study is considered supplemental. The results were reliable enough to indicate that MYCOSTOP ® is not toxic or pathogenic to the honey

b ee. This study

also satisfie s the data requirements for nontarget insect testing (OCSPP Guideline 885.4340). 2. Environmental Fate, Ecological Exposure, and Environmental Ex pression

– Tiers II and III (40 CFR § 158.2060) Environmental fate data requirements (i.e., Tiers II, III, and IV) were not triggered for Streptomyces Strain K61 bec ause results of the nontarget toxicity /pathogenicity

Tier I studies did not demonstrate hazard to nontarget organisms . 3. Endangered Species Assessment Through a re - evaluation of the ecological effects data and EPA reviews of Streptomyces Strain K61, the Agency has determined that adverse effects will not occur to nontarget organisms as a result of the labeled applications of Streptomyces Strain K61 . In addition , Streptomyces Strain K61 is a naturall y occurring soil bacterium that suppresses the growth of plant pathogenic fungi. R eduction or loss of these fungi will not affect habitat or other resources required b y threatened and endangered species. Since EPA has determined that no effe cts are anticipated for an y nontarget species exposed to S

treptomyces Strain K61 as a result of the labeled applications, effects to federally listed threatened and endangered species and their designated critical habitats are also not expected. As a result of these anal ys es, the Agency has determined that registered uses of Streptomyces Strain K61 will have “no e ffect” on endangered or threatened terrestrial or aquatic species as listed b y the U.S. Fish and Wildlife Service (USFWS) and the National Marine Fisheries Services (NMFS) and will not destroy or adversel y modify

designated critical habitat. The ‘ Endangered Species Assessment for Streptomyces Strain K61’ can be found in the Registratio n Review docket EPA - HQ - OPP - 2009 - 0509 . 4. Environmental Risk Characterization Based on the reviews of the aforem entioned nontarget organism and environmental fate information , and the endangered species assessment, the Agency has determined that unre asonable adverse effects to nontarget organisms or the environment are not likely to result when products containing S treptomyces Strain K61 are used in accordance with their respectiveStreptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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16 labels. These assessments are considered complete and current, and they satisfy the standards of registration review. D. Product Perform ance (Efficacy) (40 CFR § 158.2070 ) Product performance data must be developed for all microbial pesticides to ensure efficacy when used in accordance with labeling directions and commonl y accepted pest control practices. The Agency waived all requirements to submit such efficacy data unles s the pesticide product bears a claim to control public health pests, although the Agency reserves the right to require, on a case - by - case basis, submission of efficacy data for any

pesticide product registered or proposed for registration. The Streptomyc es Strain K61 pesticide products are fungicides intended for agricultural use and do not have label ed uses for public health pests. The Agency has not requ ired submission of efficacy data to support any

of the claims on the current labels . E. Incide nts Two instance s of h yp ersensitivity were reported by Verdera Oy

prior to EPA registration. The first incident was reported in 1986, the details of which are included in MRID No. 418211 - 18. One part - time summer trainee at the Espoo Research Centre in Finland had sy mptoms of a mild alveolar reaction to Mycostop ® (EPA Reg. No. 64137 - 5). T he alveolar reaction could have been due to exposure to biological dust from M yc ostop ® , though there were indication s that the incident might have been avoided b y caref ul use of the safet y equipment that was recommended and provided. In 1991, a research associate in a lab in Fort Collins, CO , experienced dizziness, faintness, difficult y breathing and dilated pupils after treating seed with Mycostop ® . The individual had a history

of allergies and asthma and was not wearing the required face mask when exposed. The s ymptoms disappeared in approximately one hour , and no medical attention was sought. Th ese incident s do not have an y bearing on the hazard or risk assessed pe rtaining to the use of registered Streptomyces Strain K61 pesticide products in accordance with their product labels. Both individuals recovered completely , and no other employees working with M ycostop ® have reported an y problems. Lab el language on Strep tomyces Strain K61 products is appropriate and sufficient to protect users/handlers of these products. The Office of Pesticide Programs’ Incident Data System (IDS) indicates no other reports of adverse human, domestic animal, or environmental incidents for products containing Streptomyces Strain K61 . In addition, no incidents were reported in response to the Agency request for such information in the Streptomyces griseoviridis Preliminary Work Plan and Summary Document. F. Public Comments In accordance with 40 CFR § 155.50, the Agency formally in itiated registration review for Streptomyces Strain K61 in September 2009 , with the opening of a docket (Docket Number EPA - HQ - OPP - 2009 - 0 509 ) and the issuance of a Summary Document for a 60 - day public comment period. The Agency received no comments in resp onse to the Streptomyces griseoviridis Summary Document and the initial opening of the docket. A Federal Register (FR) Notice, published on July 28, 2010, announced the placement of the Streptomyces Strain K61 Proposed Decisio n document into the docket, and initiated a 60 - day public comment period toStreptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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17 allow for consideration of an y new information in advance of a Final Decision . EPA did not receive an y comments during the 60 - day public comment period for the Streptomyces Strain K61 registration review proposed d ecision. G. Water Quality Streptomyces Strain K61 has not been identified as a cause of impairment for an y water bodies listed as impaired under Section 303(d) of the Clean Water Act, based on information provided at : http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy .cause_detail_303d?p_cause_group_id=88 5 . In addition, no Total Maximum Daily L oads (TMDL s) have been developed for Streptomyces Strain K61 , based on information provided at: http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_i d=885&p_pollutant_group_name=PESTI CI DES . More information on impaired water bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/ . The Agency solicited comments when the Summary Document was published in September 2009 ; however, no comments, data, or information regarding the existence of an y water quality issues associated with Streptomy ces Strain K61 were received. H . Trade Irritants Trade irritants are not expected for Streptomyces Strain K61 . Through the registration review process, the Agency is soliciting information on trade irritants and, to the extent feasible, will take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any

trade irritant issues resulting from lack of Maximum Residue Levels (MRLs) or disparities between U.S. tolerances or exemptions from tolerance and MRL s or exemptions from MRL s in key

export markets, providing as much specificit y as possible regarding the nature of the concern. Trade irritants are not expected for Streptomyces Strain K61 because there are no U.S. tolerances for Streptomyces Strain K61 , nor are there Codex MRL’s. The Agency did not receive an y comments regarding the existence of any trade irritant issues associated with Streptomyces Strain K61 following issuance of the Summary Document . I . Environmental Justice EPA seeks to achieve environmental justice

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

—in the development, implementation, and enforcement of environmental laws, regulations, and polici es. To help address potential environmental justice issues, the Agency sought information, as explained in the Summary Document , on groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have at y pical, unusually

high exposure to registered pesticide products containing Streptomyces Strain K61 compared to the general population. The Agency

did not receive any

comments. At this time, EPA does not believe that use of the registered pesticide produc ts containing Streptomyces Strain K61 will cause harm to or a disproportionate impact on at - risk communities. For additional information regarding environmental justice issues, please visit EPA’s website at: http://www.epa.gov/compliance/environmentaljustice/index.html .Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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18 III. FINAL REGISTRATION REVIEW DECISION The Agency

has determined that no additional data are required at this time to support current registrations containing Streptomyces Strain K61 . The Agency has considered Streptomyces Strain K61 in light of the standard for registration and safety factors in FIFRA and FFDCA, as amended b y FQPA. EPA has found that there are not likel y to be an y unr easonable adverse effects to the U.S. population in general, and to infants and ch ildren in particular, or to nontarget organisms or the environment from the use of registered pesticide products containing Streptomyces Strain K61 when currentl y required la bel instructions are followed. In addition, EPA has made a “No Effect” determination for en dangered and threatened species, and their designated critical habitat, for Streptomyces Strain K61 . The Agency has found that it is not necessary to conduct a new risk assessment for this case and is , therefore , issuing a final decision in accordance with 40 CFR Section 155.53(c)(2) and 40 CFR Section 155.58. In accordance with 40 CFR §§ 155.57 and 155.58, the Agency ’s final registration review decision is th at the standards for Registration Review have been met and that the registrations of the two products containing Streptomyces Strain K61 be maintained. IV . BIBLIOGRAPHY A. Studies Supporting Registration Review of Streptomyces Strain K61 41821100 Kemira Oy

(1991) Submission of Chemistry and Toxicity Data in Support of Mycostop New A pplication Registration, and Petition for an Exemption from the Requirement of Tolerance. Transmittal of 23 studies. 41821101 Pulkkanen, H. (1990) Product Identity and Disclosure of Ingredi ents: Mycostop.

Unpublished study prepared by Kemira Oy. 10 p. 41821102 Bjorkqvist, B.; Leppanen, L. (1989) Determination of the Active Ingredient of

Streptomyces griseoviridis in Cucumber and Cabbage. Unpublished study prepared by Ke ira Oy. 10 p. 41821103 Bjorkqvist, B.; Leppanen, L.; Lahdenpera, M. (1990) Determination of Heptaenic

Antibiotic Residues in Cucumber Fruit and Dill after Mycostop Treatment. Unpublished study prepared by Kemira Oy. 12 p. 41821104 Raatikainen, N. (1990) Determination of the Antifungal Antibiotic Produced by Mycostop

in the Peat. Unpublished study prepared by University of Kuopio. 16 p. 41821105 Tuomisto, J. (1989) Summary Research Report. Unpublished study prepared by

University of Kuopio. 8 p. 41821106 Pulkkanen, H. (1990) Manufacturing Process: Mycostop. Unpublished study prepared by

Kemira Oy. 8 p. 41821107 Pulkkanen, H. (1990) Unintentional Ingredient Discussion: Mycostop. Unpublished study

prepared by Kemira Oy. 7 p. 41821108 Pulkkanen, H. (1991) Mycostop (Streptomyces Griseoviridis): Determination of Viability.

Unpublished study prepared by Kemira Oy. 6 p. 41821109 Pulkkanen, H. (1990) Certification of Limits: Mycostop. Unpub - lished study prepared byStreptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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19 Kemira Oy. 7 p. 41821110 Snelson, A. (1990) Determination of Color, Physical State, Odor, Density, and pH of

Mycostop: Lab Project Number: CO8074: 2. Un published study prepared by IIT Research Institute. 19 p. 41821111 Pulkkanen, H. (1991) Mycostop (Streptomyces Griseoviridis): Determination of Sto rage

Stability. Unpublished study prepared by Kemira Oy. 6 p. 41821112 Hossack, D.; Baker, M.; Denton, S. (1989) Acute Oral Toxicity and

Infectivity/Pathogenicity to Rats of Streptomyces griseoviridis (Mycostop): Lab Project Number: 89953D/RKY 114/0/AC. Unpub - lished study prepared by Huntingdon Research Centre Ltd. 28 p. 41821113 Liggett, M. (1989) Acute Dermal Toxicity to Rabbits of Streptomyces griseoviridis,

(Mycostop): Lab Project Number: 89892D/RKY 114/1/ AC. Unpublished study prepared by Huntingdon Research Centre Ltd. 12 p. 41821114 Hossack, D.; Baker, M.; Denton, S. (1989) Acute Pulmonary Toxicity and

Infectivity/Pathogenicity to Rats of Streptomyces Griseo - viridis (Mycostop): Lab Project Number: 89954D/RKY 114/0/AC. Unpublished study prepared b y Huntingdon Research Centre Ltd. 31 p. 41821115 Sherwood, R. (1990) Acute Intraperitoneal Toxicity Limit Testing of Streptomyces

griseoviridis, a Microbial Pesticide: Lab Project Number: LO8279. Unpublished study prepared by IIT Research Institute. 26 p. 41821116 Liggett, M.; Hossack, D.; Baker, M. (1989) Irritant Effects on the Rabbit Eye of

Streptomyces griseoviridis (Mycostop): Lab Project Number: 891076D/RKY 114/4/SE. Unpublished study prepared by Huntingdon Research Centre Ltd. 15 p. 41821117 Lacke nby, F. (1991) Skin Sensitization Study in the Guinea Pig (Magnusson - Kligman

Maximization Test): Lab Project Number: 5383 - 18R. Unpublished study prepared by Hazleton UK. 22 p. 41821118 Pulkkanen, H. (1990) Hypersensitivity Incident Reporting Mycostop. Un published study prepared by Kemira Oy. 4 p. 41821119 Beavers, J.; Smith, G. (1990) Mycostop (Streptomyces Griseoviridis) An Avian Oral

Pathogenicity and Toxicity Study in the Bobwhite: Lab Project Number: 293 - 102. Unpublished study prepared by Wildlife International Ltd. 20 p. 41821120 Beavers, J.; Smith, G. (1990) Mycostop (Streptomyces Griseoviridis) An Avian Oral

Pathogenicity and Toxicity Study in the Mallard: Lab Project Number: 293 - 103. Unpublished study prepared by Wildlife International Ltd. 20 p. 41821121 England, D. (1990) A 30 - Day Static Renewal Toxicity and Pathogeni - city Evaluation on the Effects of Streptomyces griseoviridis to Rainbow Trout (Oncorhynchus mykiss): Lab Project Number: 38678. Unpublished study prepared by Analytical Bio - Chemi stry Laboratories, Inc. 26 p. 41821122 England, D. (1990) A 21 - Day Static Renewal Toxicity and Pathogenicity Evaluation on the Effects of Streptomyces griseovirivis to Daphnia magna: Lab Project Number: 38679. Unpublished study prepared by Analytical Bio - Chemistry Laboratories, Inc. 23 p. 41821123 Hoxter, K.; Smith, G. (1990) A Dietary Pathogenicity and Toxicity Study with the Honey

Bee: Lab Project Number: 293 - 101. Unpublished study prepared by Wildlife International Ltd. 14 p. 42298000 E.R. Butts I ntl., Inc. (1992) Submission of product chemistry and toxicity data to support

the registration of the microbiocide Mycostop. Transmittal of 8 studies.Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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20 42298001 Mohammadi, O. (1992) Taxonomic Identification of Mycostop Biofungicide.

Unpublished study prep ared by Kemira Oy. 13 p. 42298002 American Cell T ype Culture Collection (1983) Culture Identification (Streptomyces

cultures): Lab Project Number: 564. Unpublished study. 11 p. 42298003 Franke, J. (1990) Streptomyces Characterization: Lab Project Number: SC 2344.

Unpublished study prepared by American Type Cell Culture Collection. 13 p. 42298004 Kroppenstedt, R. (1992) Identification of Your Isolates Strain SS6 (90 - 551), SS61 (90 -

552), SS12 (91 - 469), and SS31 (91 - 470). Unpublished study prepared by Deust che Sammlung von Mikroorganismen und Zellkuluten GmbH. 61 p. 42298005 Mohammadi, O. (1992) Antibiotic Sensitivity of Streptomyces griseoviridis Strain SS61.

Unpublished study prepared by Kemira Oy. 6 p. 42298006 Pulkannen, H. (1992) Manufacturing Process -- Mycostop: Supplement to MRID

41821106. Unpublished study prepared by Kemira Oy. 10 p. 42298007 Pulkannen, H. (1992) Mycostop (Streptomyces griseoviridis) Determination of Storage

Stability: Supplement to MRID 41821111. Unpublished study prepared by Kemira Oy. 7 p. 42298008 Liggert, M. (1989) Acute Dermal Toxicity to Rabbits of Streptomyces griseoviridis,

Mycostop: Supplement to MRID 41821113. Unpublished study prepared by Huntingdon Research Centre Ltd. 5 p. 42441500 Kemira Oy. (1992) Submission of toxicity data to support the registration of MYCOSTOP

biofungicide. Transmittal of 2 studies. 42441501 Mega, W. (1992) Sensitivity of Detection of Streptomyces griseoviridis for

Toxicity/Pathogenicity Testing of Rats: Final Report: Lab Project Number: L08363. Unpublished study prepared by IIT Research Institute. 21 p. 42441502 Mega, W. (1992) Pulmonary Toxicity/Pathogenicity Testing of Streptomyces

griseoviridis following Acute Intrachael Challenge in Rats: Final Report: Lab Project Number: L08363. Un

published study prepared by IIT Research Institute. 146 p. 43090300 Kemira Agro Oy (1994) Submittal of Pathogenicity Data in Support of Registration of

Mycostop Biofungicide. Transmittal of 1 study. 43090301 Bowman, J.; Sword, M. (1994) A 30 - Day Static Renewal Toxicity and Pathogenicity Evaluation on the Effects of Mycostop (Streptomyces griscoviridis) to Rainbow Trout (Oncorhynchus mykiss): Final Report: Lab Project Number: 41072. Unpublished study prepared by Analytical Bio - Chemistry Laboratories, Inc. 287 p. 45511400 Kemira Agro OY (2001) Submission of Product Chemistry Data in Support of the

Application for Registration of Mycostop G Biofungicide. Transmittal of 2 Studies. 45511401 Seiskari, P. (2001) Product Chemistry Data of Mycostop G Biofungicid e: Lab Project

Number: PCD MYCOSTOP G. Unpublished study prepared by Kemira Agro Oy. 27 p. 45511402 Klausner, K. (2001) Physical and Chemical Characteristics Data of Streptomyces K61 KF

Form ulation: Lab Project Number: 00 - 6000 - G1. Unpublished study prepar ed by Toxikon Corp. 21 p. 45623100 Kemira Agro Oy (2002) Submission of Product Chemistry Data in Support of the

Application for Registration of Mycostop G Biofungicide. Transmittal of 1 Study. 45623101 Seiskari, P. (2002) Product Chemistry Data (Addendum) of Mycostop G Biofungicide:

Lab Project Number: PCD MYCOSTOP G. Unpublished study prepared by Kemira Agro Oy . 13 p.Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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21 47576800 Verdera Oy (2008) Submission of Product Chemistry Data in Support of the Amended

Registration of Mycostop Biofungicide. Transmittal of 1 Study. 47576801 Seiskari, P. (2008) Updated Product Chemistry Data of Mycostop Biofungicide. Project

Number: REPORT/162/2. Unpublished study prepared by Verdera Oy. 17 p. 47678000 Verdera Oy (2009) Submission of Product Chemistry Data in Support of the Amended

Registration of Mycostop Biofungicide. Transmittal of 1 Study. 47678001 Korteniemi, M. (2009) Supplement to Updated Product Chemistry Data of Mycostop

Biofungicide: Streptomyces griseoviridis Strain K61 @ 35%. Project Number: 162/2 . Unpublished study prepared by Verdera Oy. 45 p. 47771900 Verdera Oy (2009) Submission of Product Chemistry Data in Support of the Amended

Registration of Mycostop Biofungicide. Transmittal of 1 Study. 47771901 Seiskari, P. (2009) Second Supplement to Updated Product Chemistry Data of Mycostop

Biofungicide. Project Number: 160/3. Unpublished study prepared by Verdera Oy. 14 p. B. Environmental Protection Agency Risk Assessment Memoranda Barsoum, I. 2002. Product Chemistry revie w of Mycostop G Biofungicide. U.S. EPA, Washington, D.C. Memorandum dated April 1, 2002. Barsoum, I. 2002. Review of follow - up data submitted by Verdera Oy for product Mycostop G. U.S. EPA, Washington, D.C. Memorandum dated October 10, 2002. Barsoum, I. 2008. Review of an updated product chemistry study of the product Mycostop Biofungicide. U.S. EPA, Washington, D.C. Memorandum dated December 16, 2008. Barsoum, I. 2009. Review of supplemental data submitted by the registrant in response to a deficiency letter sent by the Agency regarding the registration of the product Mycostop Biofungicide. U.S. EPA, Washington, D.C. Memorandum dated March 31, 2009. Schaffer, C. 1991. SACB Review of Data Submitted by Kemira Oy to Support the Registration of Mycostop. U.S. EPA, Washington, D.C. Memorandum dated September 28, 1991. Schaffer, C. 1992. SACB Review of Data Submitted by Kemira Oy to Support the Registration of Mycostop. U.S. EPA, Washington, D.C. Memorandum dated August 12, 1992. Schaffer, C. 1992. SAB Review of Acute Pulmonary Toxicity/Pathogenicity Data Resubmitted by Kemira Oy to Support the Registration of Mycostop. U.S. EPA, Washington, D.C. Memorandum dated September 17, 1992. Schaffer, C. 1992. SAB Review of Data Su bm itted by Kemira Oy to Support the Exemption from Tolerance for Mycostop. U.S. EPA, Washington, D.C. Memorandum dated November 3, 1992. Schaffer, C. 1992. SAB comment on the bridging of data from the resubmitted Acute Pulmonary Toxicity/Pathogenicity Dat a to the Acute Oral Toxicity/Pathogenicity study by Kemira Oy to Support the Registration of Mycostop. U.S. EPA, Washington, D.C. Memorandum dated November 10, 1992. Schaffer, C. 1993. SAB Review of Additional Information Regarding the Taxonomic Classific ation of Mycostop, Submitted for Registration by Kemira Oy. U.S. EPA, Washington, D.C. Memorandum dated May 26, 1993.Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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22 Schneider, W. 1990. OPP Scientific Assessment of the January 12, 1990, Kemira Oy Notification of a Small Scale Field Test of a Non - indi genous Strain of Streptomyces griseoviridis . U.S. EPA, Washington, D.C. Memorandum dated April 4, 1990. Sjoblod, R. 1988. Mammalian toxicology data requirements for registration of the microbial pesticide Mycostop. U.S. EPA, Washington, D.C. Memorandum dated December 16, 1988. Sjoblod, R. 1993. Mycostop Biofungicide: Company Response to Pulmonary Exposure/Toxicity Issues. U.S. EPA, Washington, D.C. Memorandum dated January 15, 1993. Vaituzis, Z. 1991. Kemira Oy Notification of a Small Scal e Field Test of a Non - indigenous Strain of Streptomyces griseoviridis . U.S. EPA, Washington, D.C. Memorandum dated May 31, 1991. Wozniak, C. 2002. Review of the Mammalian Toxicity, Pathogenicity, Hypersensitivity and Irritation Potential of Streptomyces griseoviridis relative to establishment of an appropriate restricted entry interval. U.S. EPA, Washington, D.C. Memorandum dated July 18, 2002. V . GLOSSARY OF ACRONYMS AND ABBREVIATIONS APHIS Animal and Plant Health Inspection Service BPPD Biopesticides and Pollution Prevention Division BRADs Biopesticides Registration Action Documents °C degrees Celsius CF R Code of Federal Regulations cfu colony - forming unit cm centimeter EC 50 half maximal effective concentration EDSP Endocrine Disruptor Screening Program EEC estimated environmental concentration. The estimated pesticide concentration in an

environment, such as a terrestrial ecosystem. EPA Environmental Protection Agency (the Agency) FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQ PA Food Quality Protection Act FR Federal Register g grams g/kg grams per kilogram kg kilograms L liter LC 50 median lethal concentration. A statistically derived concentration of a

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

death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It is expressed as a weight of substance per unit weight of animal (e.g., mg/kg). LO C level of concern LO EC lowest observable effect concentration mg milligrams mg/kg milligrams per kilogram mg/L milligrams per liter mL milliliterStreptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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23 mL/kg milliliters per kilogram MRID Nos. Master Record Identification Numbers NOAEC no observable adverse effect concentration NOEC no observable effe ct concentration OECD Organization for Economic Cooperation and Development OPP Office of Pesticide Programs OCSPP Office of Chemical Safety and Pollution Prevention PC Code Pesticide Chemical Code ppm parts per million PWP preliminary work plan SAR sy stemic acquired resistance TGAI technical grade of the active ingredient TMDLs Total Maximum Daily Loads TSA try

pticase soy

agar USDA United States Department of AgricultureStreptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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24 V I. APPENDI X TABLE 1. Product Analysis Data Requirements for Streptomyce s Strain K61 (40 CFR § 158.2120) Data Requirement (OCSPP Guideline) Results MRID Numbers Product Chemistry and Composition Product Identity (885.1100) Submitted data do not completely satisfy the requirement of product identity for

Streptomyces Strain K61 (Mycostop ® ) 418211 - 01 418211 - 02 418211 - 03 418211 - 04 418211 - 05 Product Identity (885.1100) Submitted data completely satisfy the requirement of product identity for

Streptomyces Strain K61 (Mycostop ® and Mycostop ® G). Mycostop ® : 422980 - 01 422980 - 02 422980 - 03 422980 - 04 422980 - 05 Mycostop ® G: 455114 - 01 Manufacturing Process (885.1200) Submitted data do not completely satisfy the requirement of manufacturing

process for Streptomyces Strain K61 (Mycostop ® ) 418211 - 06 Manufacturing Process (885.1200) Submitted data completely satisfy the requirement of manufacturing process for

Streptomyces Strain K61 (Mycostop ® and Mycostop ® G). Mycostop ® 422980 - 06 Mycostop ® G: 455114 - 01 Deposition of a Sample in a Nationally Recognized Culture Collection (Not applicable) A deposit of Streptomyces Strain K61 has been made in both the American Type

Culture Collection and at the German Collection of Microorganisms and Cell Cultures. 422980 - 02 422980 - 04 Discussion of Formation of Unintentional Ingredients (885.1300) Submitted data completely satisfy the requirement of discussion of formation of

unintentional ingredients for Streptomyces Strain K61 (Mycostop ® and Mycostop ® G). Mycostop ® 418211 - 07 Mycostop ® G: 455114 - 01 Analysis and Certified Limits Analysis of Samples (885.1400) Submitted data completely satisfy the requirement of analysis of samples for

Streptomyces Strain K61 (Mycostop ® and Mycostop ® G). Mycostop ® 418211 - 08 475768 - 01 476780 - 01 477719 - 01 Mycostop ® G: 455114 - 01 Certification of Limits (885.1500) Submitted data completely satisfy the requirement of certification of limits for

Streptomyces Strain K61 (Mycostop ® and Mycostop ® G). Mycostop ® 418211 - 00 475768 - 01 Mycostop ® G: 455114 - 01 Physical and Chemical Characteristics Color (830.6302) Mycostop ® : Hue: 2.5 Y, Value: 9, Chroma: 2

Mycostop ® G: Hue: 2.5 yr, Value: 8.5, Chroma: 4 418211 - 10 455114 - 02 Phy sical State (830.6303) Mycostop ® : Brow n - tan color, fine powdery solid. Not free - flowing. Mycostop ® G: Free - flowing powder. 418211 - 10 455114 - 02Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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25 Data Requirement (OCSPP Guideline) Results MRID Numbers Odor (830.6304) Mycostop ® : Sweaty, fishy, putrid, bitter

Mycostop ® G: Smells of mold 418211 - 10 455114 - 02 Stability to Normal and Elevated Temperatures, Metals, and Metal Ions (830.6313) The Agency has not required that these data be submitted for Streptomyces Strain

K61 . Not applicable Storage Stability (830.6317) Mycostop ® : below +8°C, viability over 10 8 CFU/g for 6 months Mycostop ® G: +4°C, viable > 12 months; +28°C, viable for 6 months 418211 - 11 422980 - 07 455114 - 02 Miscibility (830.6319) N/A Not applicable Corrosion Characteristics (830.6320) N/A Not applicable pH (830.7000) Mycostop ® (1%): 5.63

Mycostop ® G (1%): 7.68 418211 - 10 455114 - 02 Viscosity (830.7100) N/A Not applicable Density/Relative Density/Bulk Density (Specific Gravity) (830.7300) Mycostop ® : 28.68 lb/ft3

Mycostop ® G: 7.68 lb/ft3 418211 - 10 455114 - 02 TABLE 2. Toxicology Data Requirements for Streptomyces Strain K61 (40 CFR § 158.2140) Data Requirement (OCSPP Guideline) Results MRID Number Tier I Ac ute Oral Toxicity/Pathogenicity (885.3050) The data show no clinically significant signs in rats. Streptomyces Strain K61 was not detected in kidney, brain, liver, lungs, spleen, mesenteric lymph nodes, or in blood or urine samples, and cleared from the feces and cecum following day two. Necropsy studies show ed no significant signs of abnormalities. There were si gnificant reductions in the weights of dosed males compared to controls at all study times and in the dosed females on day 8 and day 22. In the absence of pyrogenic effects or any sign of infectivity, however, the test organism was not toxic, infective or pathogenic to rats. Classification: Acceptable 418211 - 12

Ac ute Pulmonary Toxicity/Pathogenicity (885.3150) Generally, instillation of bacterial spores into rat lungs will result in a small

number of deaths (which was seen in this study). Also, large numbers of spores are usually recovered from the lungs shortly after dosing

– with successively lower numbers of spores seen at later time intervals and concurrent increases in the spores isolated from the caecal contents

– as a result of clearance from the lungs via the trachea and subsequent ingestion. The present study was not typical in this regard. The author s reported that microscopic examination of the dosing preparation showed densely packed inter - me shing mycelia in aggregations of 100mm to 200 mm, whereas spores normally have dimensions of 1mm x 2 mm. They concluded that the size of the mycelial masses wo uld not penetrate into the peripheral lungs and would be rapidly cleared from the airways by the pulmonary mucociliary escalator system. Evidence regarding the infectivity/pathogenicity of the test organism is, therefore, inconclusive, since only small numbers of viable organisms appeared to have reached the lower lungs. Since there was no proliferation of the organism by the end of the study and because of the large 418211 - 14 418211 - 15Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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26 Data Requirement (OCSPP Guideline) Results MRID Number particle size of the preparation, however, the authors concluded that Streptomyces Strain K61 would not present an infectious hazard under field conditions. Classification: Uncceptable Ac ute Pulmonary Toxicity/Pathogenicity (885.3150) Streptomyces Strain K61 caused death in 54% of treated male and 48% of treated

female rats with 45% (male) and 40% (female) mortality occurring within the first 2 days after intratracheal instillation. This high death rate may partially be due to the large size of the test organism; Streptomyces Strain K61 caused sufficient mo rtality to prov oke concern about pulmonary exposure to significant amounts of the bacterium. Dosage was 0.1 mL of a 3.46 x 10 8 CFU/mL suspension. Classification: Acceptable 424415 - 01 424415 - 02

Ac ute Injection Toxicity/Pathogenicity (885.3200) An acute intraperitoneal injection of 5000 mg of the test article/Kg killed all males

and females within 1 day of treatment. 1000 mg/Kg and 500 mg/Kg doses also caused some deaths within 2 days of dosing. This indicates a toxic response to the test article rather than an infecti ous process, which was confirmed by the mortality caused by the heat - killed test article. The toxin appears to be heat stable. Adverse clinical signs returned to normal by day 5 in surviving mice except for one female with a distended abdomen and two with enlarged spleens. The spleens showed no sign of the test article. The LD 50 for intraperitoneal injection was estimated to be 1306 mg/Kg for males, 870 mg/Kg for females and 1042 mg/Kg for both sexes combined. Classification: Acceptable 418211 - 15

Hy pe rsensitivity Incidents (885.3400) Two instances of hypersensitivity were reported by Verdera Oy prior to EPA

registration. The first incident was reported in 1986, the details of which are included in MRID No. 418211 - 18. One part - time summer trainee at the Espoo Research Centre in Finland had symptoms of a mild alveolar reaction to Mycostop ® (EPA Reg. No. 64137 - 5). The alveolar reaction could have been due to exposure to biological dust from Mycostop ® , though there were indications that the incident might have been avoided by careful use of the safety equipment that wa s recommended and provided. In 1991, a research associate in a lab in Fort Collins, CO experienced dizziness, faintness, difficulty breathing and dilated pupils after treating seed with Mycostop ® . The individual had a history of allergies and asthma and was not wearing the required face mask when exposed. The symptoms disappeared in approximately one hour and no medical attention wa s sought. These incidents do not have any bearing on the hazard or risk assessed pertaining to the use of registered Streptomyces Strain K61 pesticide products in accordance with their product labels. Both individuals recovered completely and no other employees working with Mycostop ® have reported any problems . 418211 - 18

Cell Culture (885.3500) Not required because Streptomyces Strain K61 is not a virus (refer to test note #4

of 40 CFR § 158.2140(d)). Not applicable Ac ute Oral Toxicity (870.1100) Not applicable to the TGAI test substance. Not applicable Ac ute Dermal Toxicity (870.1200) Not applicable to the TGAI test substance. Not applicable Ac ute Inhalation Toxicity (870.1300) Not applicable to the TGAI test substance. Not applicable Ac ute Eye Irritation (870.2400) Not applicable to the TGAI test substance. Not applicable Primary Dermal Irritation (870.2500) Not applicable to the TGAI test substance. Not applicableStreptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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27 Data Requirement (OCSPP Guideline) Results MRID Number Tiers II and III Not required for Streptomyces Strain K61 based on the lack of acute toxicity/pathogenicity in the Tier I studies. Additional Studies Ac ute Dermal Toxicity * (870.1200) Streptomyces Strain K61 was not toxic to rabbits when a single 2 g/Kg dose was

administered dermally. Rabbit body weights were not affected by an exposure of 2 g/Kg of Streptomyces Strain K61. Class ification: Acceptable 418211 - 13 422980 - 08 Ac ute Eye Irritation * (870.2400) Small numbers of spores of Streptomyces Strain K61 were found in the treated

ey es of all 6 rabbits at 24 and 72 hours post - treatment, but none thereafter. Instillation of Streptomyces Strain K61 (>10 7 viable spores per eye) elicited transient, mild conjunctival irritation. Classification: Acceptable

– Toxicity Category IV. 418211 - 16 Primary Dermal Irritation * (870.2500) Moderate reactivity (55% of responders) of guinea pig skin to Mycostop ® (EPA

Reg. No. 64137 - 5) was recorded on day two following challenge of sensitized animals. While no determination was made of the amount of viable Streptomyces Strain K61 spores used in any of the animal exposures and the dose formulations records are inconsistent, the basic conclusion that the end use product is a skin sensitizer is still valid. Mycostop ® is a moderate skin sensitizer. Dosage was 0.1 mL of a 3% w/v dilution of Mycostop ® in distilled water. Classification: Acceptable 418211 - 17

* Not currently in the data requirements table in 40 CFR § 158.2140 for the TGAI test substance. TABLE 3. Nont arget Organism and Environmental Fate Data Requirements for Streptomyces Strain K61 (40 CFR § 158.2150) Data Requirement (OCSPP Guideline) Results MRID Number Tier I Avian Oral Toxicity (885.4050) The avian oral LD 50 wa s greater than 2,500 mg/kg body weight, based on results from

tests on both mallards and northern bobwhites. Classification: Acceptable 418211 - 20 418211 - 19 Avian Inhalation Toxicity/Pathogenicity (885.4100) Not required, as the nature of Streptomyces Strain K61 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)). Not applicable Wild Mammal Toxicity/Pathogenicity (885.4150) Not required for Streptomyces Strain K 61 because the results of the 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)). Not applicable Freshwater Fish Toxicity/Pathogenicity (885.4200) This study show ed sporadic fish mortality and failed to demonstrate a definitive LC 50

value due to the absence of a dose - response trend with the observed mortality. The study results were not adequate for making a risk assessment. Classification: Unaccept able 418211 - 21 Freshwater Fish Toxicity/Pathogenicity (885.4200) The 30 - day static renewal toxicity/pathogenicity study of Streptomyces Strain K61 to

rainbow trout ( Oncorhynchus mykiss ) was conducted by Kemira Agro Oy. Single replicates of 10 fish each were exposed to Streptomyces Strain K61 concentrations of 0.25x10 5 , 0.50x10 5 , 1.0x10 5 , 2.0x10 5 , and 4.0x10 5 CFU/mL in dilution water plus a dilution water control and a killed - spore treatment of 4.0x10 5 CFU/mL. The dietary dose in the food offering was 10% of the water exposure concentration. The 30 - day NOAEC was 0.50x10 5 CFU/mL based on the lack of mortality, statistically significant grow th effects, and sublethal/abnormal effects at th is concentration. All surviving fish ate normally and showed an increase in length and weight on day 30 as compared to the representative group on day 0. No lesions or tissue discolorations were noted in any 430903 - 01Streptomyces Strain K61 Case 6066 Docket Number EPA - HQ - OPP - 2009 - 0509 Registration Review Final Decision

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28 Data Requirement (OCSPP Guideline) Results MRID Number surviving fish at the end of the study. Classi fication: Acceptable Freshwater Invertebrate Toxicity/Pathogenicity (885.4240) A 21 - day static rene wal study was conducted to determine the toxicity and/or pathogenicity of Streptomyces Strain K61 spores to Daphnia magna . A control group wa s t ested against four treatment groups, including a maximum nominal dose exposure of 1.0 x 10 6 CFU/mL, low and median doses of 10 4 and 10 5 CFU/mL, plus a dose of 1.0 x 10 6 CFU/mL of heat - killed spores. No significant differences (P>0.05) were found between the control and the exposure levels for reproduction and time to first brood. All of the offspring produced during the study appeared normal. Mean survival was 100% for control and low level concentration, 75% for the middle concentration, and 0% for the high concentration and killed spore treatment. Mortality from killed spore treatments has been reported from previous studies, and is thought to be caused by creating a toxic environment through the autoclaving process. A day 21 EC 50 was calculated to be approximately 190 mg/L (1.9 x 10 5 CFU/mL). Daphnid grow th was found to be significantly affected at the middle concentration (1 x 10 5 CFU/mL). The NOAEC was found to be 1.0 x 10 4 CFU/mL, the LOAEC was 1.0 x 10 5 CFU/mL and the MATC was found to be 3.2 x 1 0 4 CFU/mL. This indicates that Streptomyces Strain K61 is practically non - toxic to Daphnia magna . The study fulfils EPA Guideline requirements for an acute toxicity test for an aquatic invertebrate. Classification: Acceptable 418211 - 22

Nontarget Plant Testing (885.4300) Not required for Streptomyces Strain K61 because the microbial pest control agent is

not taxonomically related to known plant pathogens (refer to test note #7 of 40 CFR § 158. 2150(e)). Not applicable Honey Bee Testing (885.4380) Nontarget Insect Testing (885.4340) Three treatment levels, representing 240, 760 and 2400 ppm at a specific activity of

9.8 x 10 8 cfu/g of diet, were tested along with an attenuated control and a negative control. T wo replicates were tested at each conce ntration with 25 bees per replicate. Mortalities occurred in both of the control groups (negative and attenuated) and in all 3 of the treatment groups. The mortalities in the negative and attenuated control groups were 30% and 62%, respectively, while th ose in the 240, 760, and 2400 ppm concentrations averaged 20%, 26% and 28%, respectively. The pattern of mortality wa s not found to be dose responsive and did not appear to be treatment related. The LC 50 was determined to be greater than 2400 ppm and the NOAEC was 2400 ppm, which was the highest concentration tested. Due to nonspecific mortality in the controls, however, the study is considered supplemental. The results were reliable enough to indicate that MYCOSTOP ® is not toxic or pathogenic to the ho ney bee. This study also satisfies the data requirements for nontarget insect testing (OCSPP Guideline 885.4340). Classification: Supplemental 418211 - 23

Tiers II, III, and IV Not required for Streptomyces Strain K61 based on the results of the nontarge t toxicity/pathogenicity Tier I studies, which did not demonstrate adverse hazards.