Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 1 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA

**BIOPESTICIDES REGISTRATION ACTION DOCUMENT**



### PC Code 115002



## Isaria fumosorosea (formerly Paecilomyces fumosoroseus )

Apopka Strain 97

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

August 10 , 2011Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 2 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA **TABLE OF CONTENTS I.**  **BACKGROUND ................................**  **................................ ................................**  **.................. 4**  **II. ACTIVE INGREDIENT OV** **ERVIEW ................................**  **................................ ..............**  **4 III.**  **REGULATORY BACKGROUN D**  **................................ ................................**  **..................... 5**  **A .**  **Applications for Pesticide Registration ................................**  **................................ .....................**  **5 B**  **. Food Tolerance Exemptions**  **................................ ................................**  **................................ ....**  **6 IV.**  **RISK ASSESSMENT ................................**  **................................ ................................**  **.......... 6**  **A .**  **Product Analysis Assessment (40 CFR § 158.2120) ................................**  **................................ ....**  **7 B**  **. Hum**  **an Health Assessment (40 CFR § 158.2140) ................................**  **................................ .......**  **7 C**  **. Environmental Assessment (40 CFR §**  **158.2150) ................................**  **................................ ....**  **10 V.**  **ENVIRONMENTAL JUSTICE**  **................................ ................................**  **....................... 11**  **VI. RISK MANAGEMENT DECI**  **SION ................................**  **................................ ................**  **12 VII.**  **TERMS AND CONDITIONS OF THE REGISTRATION(**  **S) ................................**  **...... 12**  **VIII. GLOSSARY OF ACRONYMS**  **AND ABBREVIATIONS ................................**  **............ 13**  **IX. BIBLIOGRAPHY**  **................................ ................................**  **................................ ..............**  **14 A**  **. Studies Submitted to Support the**  **PFR -**  **97 Pesticide Product**  **................................ .....................**  **14 B**  **. Environm**  **ental Protection Agency Risk Assessment Mem oranda**  **................................ ..............**  **16 C**  **. Other References**  **................................ ................................**  **................................ .................**  **16 APPENDIX A**  **. MICROBIAL PESTICIDES**  **DATA REQUI REMENTS**  **............................. 18** Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 3 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA

**BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM**

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

**Microbial Pesticides Branch Science Reviews**  Ib rahim Barsoum, Ph.D. Product Anal ys is, Human Health John Kough, Ph.D. Product Anal ys is, Human Health Shannon Borges Environmental Effects Zi gfridas Vaituzis, Ph.D. Environmental Effects Gail Tomimatsu Environmental Effects **Regulations** Sheryl Reill y, Ph.D. Chief, Microbial Pesticides Branch Shanaz Bacchus Regulatory Action LeaderIsaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 4 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA **I .**  **BACKGROUND** The fungal active ingredient (ai) , Paecilomyces fumosoroseus Apopka strain 97, (PC Code 115002) has been reported to be originally isolated in 1986 from a meal y bug in a greenhouse in Apopka, FL . It was recentl y reclassified as Isaria fumosorosea (ARSEF 2011; Zimmermann , 2008) . In this and other Agency documents, i t is referred to as Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97, or as Paecilomyces fumosoroseus Apopka strain 97 or as P FR- 97. The pure culture was identified in 1988 and deposited at the American Ty pe Culture Collection (ATCC # 20874). This fungal strain is a pathogen of many orders of insects . Itoccurs naturally in populations of infected and dead insects and randomly in soils around the world . Itcan be grown readily on various culture media and exists in several morphological stages, depending upon the culture medium . On solid medium, conidiophores, co nidia , and mycelia are predominant , while submerged culture produces blastospores and mycelia. PFR - 97 TM MUP is the manufacturing use product (MUP) , registered under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) . It is formulated into the end - use product (EP), PFR- 97 TM 20% WDG that contains blastospores, mycelia and conidia . Under proper environmental conditions, spores of the fungus attach to and penetrate the cuticle of the target pest . The fungus grows inside the insect causing its de ath . The fungus then emerges from the dead insect to release more spores to infect other insects. The product identity data submitted by the registrant were sufficient in 199 8 to allow the proposed limited use patterns in greenhouses . The registrant submitted an amendment in 2009 to expand the uses to include food crops. 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 f ollowing types of applications: new active ingredients; first food uses; first outdoor uses; first residential uses; and any other registration decisions for which the Agency believes there may

be substantial public interest. Consistent with the new policy of making registration actions more transparent, Paecilomyces fum osoroseus Apopka strain 97 is now subject to a 30 - day comment period as a previousl y registered active ingredient whose registration amendment would result in a “first outdoor use,” a “first food use,” and possibly

a “first residential use.” The public comment period will conclude 30 days after the posting of these documents in the docket EPA - HQ - OPP - 2010 - 0088 . The risk assessment s for Paecilomyces fumosoroseus Apopka strain 97 are characterized throughout this Biopesticides Registration Action Document ( BRAD ) . **II .**  **ACTIVE INGREDIENT OVERVIEW**  **Biological Name:** Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 **Culture Deposit:** American T yp e Culture Collection in Manassas, Virginia under Accession Number 20874Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 5 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA **OPP Chemical Code:**  115002 **Type of Pesticide:** Microbial Pesticide/Biofungicide **III. REGULATORY BACKGROUND**  **A .**  **Applications for Pesticide Registration** On July 6, 1994, the Agency

received an application from W.R.Grace to register PFR- 97 TM MUP, a microbial insecticide, containing Paecilomyces fumosoroseus Apopka strain 97 as the active ingredient for manufacturing and end - use pesticide products. The registrant also requested the registration of two end - use p roducts (EPs), PFR - 97 TM 20% WDG and PFR - 97 TM WDG, containing 20 percent (%) and 12 % Paecilomyces fumosoroseus Apopka strain 97 , respectivel y . The proposed pesticidal use was for control of whiteflies, aphids, thrips and spider mites on ornamentals in green houses , as well as food crops outdoors . A notice of receipt of the application for registration under FIFRA of Paecilomyces fumosoroseus Apopka strain 97 as a new active ingredient was published in the Federal Register (FR) on November 2, 1994 ( 59 FR 54093 ). A pesticide petition for an exemption from tolerance (PP4F4372) was filed concurrently with the proposed Section 3 registration applications . The N otice of this Filing was published in the Federal Register simultaneousl y with the Notice above [ 59 FR 5409 2 , Number 211 (Wednesday , November 2, 1994)] . No comments were received in response to either of the FR Notices within the 30 - day comment period . On June 13, 1996, the pending products were transferred to Thermo Trilogy , which did not rep ropose the exemption from tolerance petition as required b y the Food Quality Protection Act (FQPA) of 1996. At that time, the Agency did not take any further action either on the request for the tolerance exemption or the pending food use registration application for PFR - 97 TM WDG. On April 22, 1998, the following PFR - 97 products were registered to Thermo Trilogy for non - food uses : (1) PFR- 97 TM MUP ( EPA Reg. No. 7 0051 - 17 ) , a manufacturing use product ; and (2) PFR- 97 TM 20% WDG ( EPA Reg. No. 70051 - 19 ), an end - use p roduct . The Agency

published the notices of registration for these product s in the FR on July 8, 1998 (63 FR 36899). Both products contain ed Paecilomyces fumosoroseus Apopka strain 97 as the active ingredient , and were intended for us e on ornamentals in greenhouses and in interiorscapes . The company was informed that additional data would be required for more extensive use patterns. On September 30, 1998, Thermo Trilogy formally withdrew the registration application for PFR - 97 TM WDG (12% ai), indicated that it would repropose the petition for food use as required b y the FQPA and requested six months for providing non - target organism data required for additional uses. The company did not follow through on these actions. In 2004, the product registrations were amended to remove the interiorscape use from the labels . Thermo Trilogy

has since changed its name to Certis USA , LLC (hereinafter referred to as “ Certis ” ) , currentl y located on 9145 Guilford Road, Suite 175, Columbia, MD 21046. On December 17, 2009 , Certis applied to amend the se pesticide registration s to include new uses on all food commodities . Th e Agency announce d receipt of the application in the FR on March 5, 2010 ( EPA HQ - OPP - 2010 - 0088; 75 FR 10259 ) , and opened a 30 - day public comment period pursuant to theIsaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 6 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA provisions of FIFRA section 3(c)(4). No comments were received in response to this publication. This docket has been reopened to provide the public 30 days to review and submit comments on the posted documents that informed the Agency ’s proposed decision regarding Certis’proposed amendment to allow food uses to the product registration s . **B .**  **Food Tolerance Exemptions**  A numeric tolerance or exemption from the requirement of a tolerance was not needed when the first products were registered in 199 8 , since they were not intended for use on food or animal feed commodities. Nevertheless, s afety factor s from the Food Quality Protection Act of 1996 (FQPA) were considered for potential secondary transfer of residues to drinking water during applications. In cluded w ith the December 17, 2009 , application to amend the product registrations was a petition to establish an exemption from the requirement of a tolerance on all food commodities for Paecilomyces fumosoroseus Apopka strain 97 (Pesticide Petition [PP] 9F7665) under the Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(d) . The Notice of Filing of the petition was published in the Federal Register of March 10, 2010 ( EPA HQ - OPP - 2010 - 0087, 7 5 FR 11171 ), and opened a 30 - day comment period. No comments were rece ived in response to the FR publication. 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. **IV. RISK**  **ASSESSMENT** The Agency

assessed the data submitted by Certis in 2009 for the proposed pesticide registration amendments. The classifications assigned b y Agency science reviewers to data that are submitted to support registration of a pesticide are an indication of the us efulness 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 acceptable (“Supplemental : Upgradable ”). If a study is rated as “Supplemental : Upgradable ,” the Agency always provides an indication of what is lacking or what can be provided to change the rating to “ Acceptable .” If there is simply a “Supplemental” rating, the reviewer will often state that the study is not required b y the current 40 Code of Federal Regulations (CFR) p art 158. Both “ Acceptable ” and “Sup plemental” studies may

be used in the risk assessment process as appropriate. An “ Unacceptable ” rating indicates that new data must be submitted. For the acute toxicity

data requirements, toxicity categories are assigned based on the hazard(s) identified from studies and/or other infor mation 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 Category Iindicates the highest toxicity and Toxicity

Category IV indicates the lowest toxicity . Refer to Tables 1 , 2 a, 2b , 3 and 4 in Appendix A for a brief summary of the data requirements, including both generic and product - specific information. Additionally, the comprehensive Agency riskIsaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 7 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA assessments that evaluate these data are available either in the Appendix of this BRAD a s summaries or as “Supporting & Related Materials” within Docket Number EPA - HQ - OPP - 2010 - 0088 at http://www.regulations.gov **A .**  **Product Analysis Assessment (** **40 CFR § 158.2120 )**  All product anal ys is data requirements for the proposed food uses of Isaria fumosorosea ( formerl y Paecilomyces fumosoroseus) Apopka strain 97 have been satisfied (Tables 1, 2a, 2b

– Appendix A) . A storage stability

study shows that the pesticide product has a shelf life of 1 year at 4 o C , but is less stable at 25 o C. The sample stored at 4 o C for 1 ye ar was still effec tive at c olonizing host insects, while that stored at 25 o C was not. The product label mu st bear appropriate storage statements and a corresponding expiration date. **B. Human Health Assessment**  **( 40 CFR § 158.2140**  **) 1**  **. Toxicity**  All toxicology

data requirements for Isaria fumosorosea ( formerly Pa ecilomyces fumosoroseus) Apopka strain 97 have been satisfied**.** Acceptable Tier I mammalian toxicology data/information support the registration of this fungal active pesticide ingredient . Furthermore, Tier II and Tier III studies were not required for PFR- 97 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 summaries of the Agency risk assessments that evaluate these data are available as “Supporting & Related Materials” within Docket Number EPA - HQ - OPP 2010 - 0088 at http://www.regulations.gov . **2 .**  **Endocrine Disruptors** As required under FFDCA section 408(p), the Agency has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may

h ave an effect in humans or wildlife similar to an effect produced by a “naturall y occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two - tiered approach to making the statutorily required determinati ons. 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 sy stems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP wh ere 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 b y the substance, and establish a quantitative relationship between the dose and the E, A, or T effect. 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 w ater, residential activity, and certain post - application agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors.Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 8 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA PFR - 97 is not among the group of 58 pesticide active ingredients on the initial list to b e screened under the EDSP. Under FFDCA section 408(p), the Agency must screen all pesti cide chemicals. Accordingl y, 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 .**  **F ood 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 resi due in or o n a food) onl y 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) o f 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 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 .” The Agency performs a number of analyses to determine the risks from aggregate exposure to pesticide residues. First, the Agency determines the tox icity 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 s ection 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 thi s 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 Isaria fumosorosea ( formerl y Paecilomyces fumosoroseus ) Apopka strain 97 have been satisfied. (See also, “Supporting & Related Materials” within Docket Number EPA - HQ OPP - 2010 - 0088 at http://www.regulations.gov .) **a .**  **Aggregate Exposure**  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).Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 9 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA Dietary Exposure : Dietary exposure to the microbial pesticide is unlikely to occur, but if humans were exposed to Isaria fumosorosea (

formerly Paecilomyces fumosoroseus ) Apopka strain 97 through the diet, no adverse effects would be expected, based upon the lack of acute oral toxicity, infectivity, and/or pathogenicity in laboratory

animals (results presented in Unit III.B. S ee additional discussion in Appendix A of th is BRAD, and “Supporting & Related Materials” within Docket Number EPA - HQ - OPP - 2010 - 0088 at http://www.regulations.gov). The following information is provided to demonstrate why residues of Isaria fumosorosea (

formerly Paecilomyces fumosoroseus ) Apopka strain 97 are not expected in food or feed commodities, or drinking water. 1. Food. Dietary

exposure to the microbial active ingredient is expected to be minimal to non existent . Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 is intended for directed ground and spray application , or soil application , to food and feed commodities . The active ingredient rapidl y degrades at room temperature, and as an insect pathogen, residues are not likely to accumulate on crops. 2. Drinking Wa ter : Drinking water exposure is expected to be negligible to non - existent, because the microbial fungicide will not be applied to water. Further, the insect pathogen Isaria fumosorosea ( formerl y Paecilomyces fumosoroseus ) Apopka strain 97 would not proli ferate in aquatic environments. The large fungal spores within the soil will not likely percolate into water due to the ir size and the fact that they readil y adhere to soil particles. 3. Other Nonoccupational Exposure : PFR- 97 is a naturally occurring microorganism and is ubiquitous in the environment. As a pesticidal active ingredient, PFR- 97 will be applied to agricultural crops in the field and to crops grown in greenhouses and nurseries that are not expected to be in close p roximity to residential areas . I f applications take place in residential areas, there is no evidence for inhalation or dermal toxicity at exposure levels even several orders of magnitude higher than expected for a typical residential end -product user (see Appendix A of the BRAD and “Supporting & Related Materials” within Docket Number EPA - HQ - OPP - 2010 - 0088 at http://www.regulations.gov) . Additionally , there have been no reports of adverse effects to humans from inhalation or dermal exposure to this widespread fungus , which has been in use in greenhouses as a pesticide for the past thirteen years . **b. Cumulative Effects from Substances with a Common Mechanism of Toxicity** Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to 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 .” Acute toxicity studies demonstrated that PFR- 97 , an insect pathogen, is practically non - toxic to mammals and no cumulative effects are anticipated. **c. Determination of Safety for the**  **U.S. Population, Infants, and Children** FFDCA sectio n 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 sectio n 408(b)(2)(C) providesIsaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 10 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA 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 complet eness 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 incorporated into Agency risk assessments , either directly , or through the use of a margin of exposure analy sis, or by using uncertainty (safety) factors in calculating a dose level that poses no appreciable risk. Based on the acute toxicity and pathogenicity data discussed in Table 3 in Appendix A of the BRAD and “Supporting & Related Materials” within Docket Number EPA - HQ - OPP - 2010 - 0088 at http://www.regulations.gov , EPA 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 PFR - 97 . 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 and information available on PFR - 97 do not demonstrate toxic, pathogenic, and/or infective potential to mammals. Thus, there are no threshold effects of concern and, as a result, an additional margin of safety is not necessary. **3 .**  **Occupational Exposure and Risk Characterization** In light of the Tier I acute toxicity /pathogenicity s tudies, which did not show any toxicity o r pathogenicity via the oral, pulmonary , or intraperitoneal injection routes of exposure, handler exposure to PFR - 97 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. H andlers working with PFR - 97 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 Health (NI OSH ) standards of at least N - 95, R- 95, or P - 95 when mixing, loading, or appl ying the product. **C .**  **Environmental Assessment (** **40 CFR § 1**  **58.2150 )**  **1 .**  **Nontarget Organism Toxicology** All nontarget toxicology

data requirements for the proposed uses of PFR- 97 have been satisfied. Acceptable Tier I nontarget toxicology data/information support the registration of PFR - 97 . Refer to Table 4 in Appendix A for a brief summary of these data requirements. Additionally, the summaries of the Agency

risk assessment s that evaluate Table 4 in Appendix A of this BRAD are available as “Supporting & Related Materials” within Dock et Number EPA - HQ - OPP - 2010 - 0088 at http://www.regulations.gov . **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 asse ssment for PFR - 97 , f urther 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 . PFR - 97 is a naturally occurring strain of Isaria fumosoroseaIsaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 11 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA (formerl y Paecilomyces fumosoroseus ). Isaria fumosorosea has been isolated from many species of insects, particularl y Lep idoptera, and has been collected from air, water, plants, other fungi, and often from soil. It is one of the most common entomopathogens known to affect ny mphs and adults of Bemisia species of whiteflies, and has caused epizootics in this species and in th e United S tates and other countries (Zimmerman, 2008). Data on natural concentrations of Paecilomyces fumosoroseus and persistence of this strain in the environment are not available. Exposure on the field is expected to occur at levels that would affect sensitive insects. Some offsite movement may occur with spray

drift, but exposure is expected to occur at lower levels outside of treated areas (US EPA memorandum dated July 21, 2011, from Shannon Borges to Shanaz Bacchus) The applicant has submitted data and rationale s to waiv e testing to satisfy data requirements for nontarget organism risk assessment with the technical grade of the active ingredient (TGAI). Submitted data, data waiver rationale s , and a search b y the Agency of several literature data bases provide d sufficient information to determine that toxicity /pathogenicity

to wild mammals, avian wildlife, freshwater and marine/estuarine vertebrates and invertebrates, and terrestrial and aquatic plants is not expected from the proposed label uses. There is uncertainty about the potential for adverse effects to certain non target insects and arachnids. While the honey bee study showed no toxicity to these beneficial insects, it was not of long enough duration to determine pathogenicity to them . Thus, the pesticide must not be applied while honey bees are activel y foraging . Further testing of nontarget organisms at higher tier levels is not required at this time , but may be required in the future (US EPA Borges, July

21, 2011 , Appendix A and “Supporting & Related Materials” within Docket Number EPA HQ - OPP - 2010 - 0088 at http://www.regulations.gov). **4 .**  **Threatened and Endangered**  **Species Assessment** A complete Endangered Species (ES) has not been completed for this registration amendment and will be conducted during the registration review process . As indicated in the Environmental Risk Assessment (US EPA, Borges , July

21, 2011) , included in this docket, EPA has determined that adverse effects to nontarget insects a s a result of the proposed new uses of Paecilomyces fumosoroseus Apopka strain 97 are possible . EPA has determined that risk of adverse effects is minimal to birds, wild mammals, freshwater fish and invertebrates, estuarine/marine fish and invertebrates, and nontarget terrestrial and aquatic plants . Therefore, EPA makes conclusions as follows regarding federally threatened and endangered (listed) species for the proposed new uses of Paecilomyces fumosoroseus Apopka 97.

 EPA makes “No Effect” determinations for direct effects to listed terrestrial vertebrates and plants and listed aquatic animals and plants for the proposed new uses .  EPA concludes that the proposed new uses of Paecilomyces fumosoroseus Apopka 97 have the potential to cause direct effects to listed terrestrial insects and arachnids, as well as indirect effects to listed species dependent on insects and arachnids (e.g., for food, pollination, habitat maintenance). Further analyses are needed to characterize the effects that may occur and the sp ecies potentiall y affected . Tier II environmental expression studies would allow for a more refined anal ys is and would likely reduce the number of species determined to be affected. **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 addressIsaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 12 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA 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 PFR - 97 , 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 i ssues, please visit the Agency ’s web site at http://www.epa.gov/compliance/environmentaljustice/index.html . **V I**  **. 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 perf orm its intended function without unreasonable adverse effects on the environment; and (D) when used in accordance with widespread and commonly recognized practice , it will not generall y cause unreasonable adverse effects on the environment. The four criteria of the Eligibility Determination for Pesticidal Active Ingredients are satisfied b y the science assessments supporting the product containing Isaria f umosorosea ( formerl y Paecilomyces fumosoroseus ) Apopka 97 . This product is not expected to cause unreasonable adverse effects and is likely to provide protection as claimed when used according to label instructions. The Agency believes , therefore , that Isaria f

umosorosea (formerly Paecilomyces fumosoroseus ) Apopka 97 is eligible for registration for the proposed uses . **V I**  **I .**  **TERMS AND CONDITIONS OF THE REGISTRATION(S)** As a term of registration, the registrant must submit analyses of unintentional ingredients in five production batches (40 CFR § 158.2120) .Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 13 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA **VIII .**  **GLOSSARY OF ACRONYMS AND ABBREVIATIONS** BRAD Biopesticides Registration Action Document CFR Code of Federal Regulations c fu 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 Interregio nal Research Project Number 4 LLC limited liability company MRID No. Master Record Identification Number NI OSH National Institute for Occupational Safety and Health OCSPP Office of Chemical Safety and Pollution Prevention OPP Office of Pesticide Program s PP Pesticide Petition TGAI technical grade of the active ingredientIsaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 14 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA **I X**  **. BIBLIOGRAPHY**  **A .**  **Studies Submitted to Support the** Paecilomyces fumosoroseus Apopka strain 97 **Pesticide Product Registration**  **Bibliography MRID**  **Citation Reference**  43139800 W.R. Grace & Co. (1994) Submittal of Product Chemistry , Toxicity / Pathogenicity , and Environmental Fate Data in Support of Registration of PFR- MUP. Transmittal of 4 studies. 43139801 Eyal, J. (1994) PFR - MUP Product Chemistry : Lab Project Number: 4775 - MUP CHEM. Unpublished study prepared by

W.R. Grace & Co. -- Conn. 128 p. 43139802 Jones, M. (1993) Acute Pulmonary Toxicity /Pathogenicity

Study of Paecilomyces fumosoroseus var. Apopka in Rats: Final Report: Lab Project Number: G - 7444.228.001. Unpublished study

prepared by

Microbiological Associates, Inc. 83 p. 43139803 Jones, M. (1993) Acute Intraperitoneal Toxicity /Pathogenicity

Study of Paecilomyces fumosoroseus var. Apopka in Rats: Final Report: Lab Project Number: G - 7444.226.001. Unpublished study

prepared by

Microbiological Associates, Inc. 65 p. 43139804 Eyal, J. (1994) PFT - MUP Environmental Fate Data: L ab Project Number: 4775 - MUP ENVFATE. Unpublished study prepared by W.R. Grace & Co. -- Comm. 19 p. 43139900 W.R. Grace & Co. (1994) Submittal of Product Chemistry Data in Support of Registration of PFR- 97 WDG. Transmittal of 1 study . 43139901 Eyal, J. (1994) PFR - 97 WDG Product Chemistry: L ab Project Number: 4775 - PFR - 97 -

CHEM. Unpublished study prepared by

W.R. Grace & Co. -- Conn. 89 p. 43146200 W. R. Grace & Co. - Conn. (1994) Submittal of Toxicity Data in Support of Registration of PFR- MUP and PFR - 97 WDG. Transmittal of 3 studies. 43146201 Wenk, M. (1994) Primary Eye Irritation Study

of Paecilomyces fumosoroseus var. Apopka in Rabbits: Final Report: L ab Project Number: G - 7473.230. Unpublished study prepared b y Microbiological Associates, Inc. 32 p. 43146202 Wenk, M. (1994) Primary Dermal Irritation Test of Paecilomyces fumosoroseus var. Apopka in Rabbits: Final Report: L ab Project Number: G - 7444.242. Unpublished study prepared b y Microbiological Associates, Inc. 29 p. 43146203 Wenk, M. (1994) Dermal Sensitization Test of Paecilomyces fumo soroseus var. Apopka

in Guinea Pigs: Final Report: L ab Project Number: G - 7444.245. Unpublished study prepared b y Microbiological Associates, Inc. 37 p. 43163900 W. R. Grace & Co. (1994) Submission of Toxicity Data for Paecilomyces fumosoroseus Apopka Strain 97 in Support of Registration. Transmittal of 1 study . 43163901 Jones, J. (1994) Acute Oral Toxicity /Pathogenicity Study

of Paecilomyces fumosoroseusIsaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 15 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA

var. Apopka in Rats: Final Report: Lab Project Number: G - 7444.222.006: 1602.222.006. Unpublished study

prepared by

Microbiological Associates Inc. 78 p. 43225500 W.R. Grace & Co. (1994) Submission of Toxicity Data for Paecilomyces fumosoroseus Apopka Strain 97 in Support of Registration. Transmittal of 1 study . 43225501 Wenk, M. (1994) Acute Dermal Toxicity Test of Paecilomyces fumosoroseus var. Apopka In Rabbits: Final Report: L ab Project Number: G - 7444.232. Unpublished study prepared b y Microbiological Associates, Inc. 36 p. 43292900 W.R. Grace & Co. - Conn. (1994) Subm ission of product chemistry data in support of registration for PFR- 97 20% WDG. Transmittal of 1 study . 43292901 Eyal, J. (1994) PFR - 97TM 20 (percent) WDG Product Chemistry : Lab Project Number:

4775/PFR/97/20/CHEM. Unpublished study prepared by

W. R. Gra ce & Co. Conn. 89 p. 43534800 W. R. Grace and Co. (1995) Submission of toxicology data in support of registration of PFR - MUP, PFR - 97, and PFR - 97 20% WDG. Transmittal of 3 studies. 43534801 Wenk, M. (1994) Repeat Primary Eye Irritation Study

of Paecilom

yces fumosoroseus var. Apopka in Rabbits: Final Report: L ab Project Number: G/7373/230R. Unpublished study prepared b y Microbiological Associates, Inc. 34 p. 43534802 Lawlor, T. (1994) Mutagenicity Test on Paecilomyces fumosoroseus Apopka Strain 97 in Salmonella/Mammalian - Microsome Reverse Mutation Assay (Ames Test) with a Confirmatory

Assay : Final Report: Lab Project Number: 16203/0/401R. Unpublished study prepared by

Hazleton Washington, Inc. 30 p. 43534803 Fre y, L.; Grimes, J.; Beavers, J. (1994) Pae cilomyces fumosoroseus Apopka Strain 97:

An Avian Oral Pathogenicity and Toxicity

Study in the Northern Bobwhite: L ab Project Number: 390/101. Unpublished study prepared by

Wildlife International Ltd. 25 p. 43664400 W. R. Grace & Co. -- Conn. (1995) Submission of Hazard to Non - Target Insects Data in

Support of Applications for Registration of PFR- 97 and PFR- 97 20% WDG. Transmittal of 1 Study . 43664401 Eyal, J. (1995) PFR - 97 20% WDG: Nontarget Insect Data: Effects on Beneficial Ins ects:

Lab Project Number: 4775 - 20WDG -NTI. Unpublished study prepared by

W. R. Grace & Co. -- Conn. 101 p. 47939500 Certis USA, LLC (2009) Submission of Product Chemistry and Toxicity

Data in Support of the Amended Registration of PFR- 97 20% WDG and the Petition for Tolerance of Paecilomyces fumosoroseus Apopka Strain 97. Transmittal of 9 Studies. 47939501 Simpson, A. (2009) Discussion of Formation of Unintentional Ingredients: PFR - 97 20%

WDG. Unpublished study prepared by

Certis USA, LLC. 38 p. 47939502 S impson, A. (2009) PRF - 97 20% WDG: Product Property Data Waivers: Phy sical and Chemical Characteristics. Unpublished study prepared by

Certis USA, LLC. 6 p. 47939503 DeVane, W. (2009) PRF - 97 20% WDG: Product Property Data Waivers: Storage Stability . Project Number: TTC0026/10. Unpublished study prepared by

Certis USA, LLC. 20 p.Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 16 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA 47939504 Dively , C. (2009) Paecilomyces fumosoroseus Apopka Strain 97: End Use Product: PFR 97 20%: Non - Target Plant Studies. Unpublished study prepared by

Certis USA, LLC. 2 5 p. 47939505 Dively , C. (2009) Paecilomyces fumosoroseus Apopka Strain 97: End Use Product: PFR 97 20%: Non - Target Insect Studies. Unpublished study prepared by

Certis USA, LLC. 45 p. 47939506 Dively , C. (2009) Paecilomyces fumosoroseus Apopka Strain 97: End Use Product: PFR 97 20%: Non - Target Freshwater Aquatic Invertebrate Testing, Tier I: Non - Target Freshwater Fish Testing, Tier I. Unpublished study prepared by

Certis USA, LLC. 23 p. 47939507 Dively , C. (2009) Paecilomyces fumosoroseus Apopka Strain 97: End Use Product: PFR 97 20%: Non - Target Wild Mammal Studies. Unpublished study prepared by

Certis USA, LLC. 16 p. 47939508 Dively , C. (2009) Paecilomyces fumosoroseus Apopka Strain 97: End Use Product: PFR 97 20%: Acute Toxicity

Studies/End Product (Alternative Formulation). Unpublished study prepared by

Certis USA, LLC. 10 p. 47939509 Nengel, S. (1998) PreFeRal WG: Acute Oral and Contact Toxicity to the Honey

Bee, Apis mellifera L. , in the Laboratory : Final Report. Project Number: 98338/01/BLEU. Unpublished study

prepared by

GAB Biotechnologie Gmbh. 23 p. **B .**  **Environmental Protection Agency Risk Assessment Memoranda** U.S. EPA. 1995 . Review of Product Chemistry , Manufacturing Process, and Acute Toxicity studies of the end use product (EP) PFR - 97 (EPA Reg. No s . 70051 - 17, 70051 - 19 ) containing the active ingredient (AI) Paecilomyces fumosoroseus Apopka strain 97 . Memorandum from Cindy Schaffer and Ro y Sjoblad, Ph.D. to Shanaz Bacchus dated September 8, 1995 . Reviews of Product chemistry - MRIDs 4329 2901, 43139901, 43139801, acute toxicology - MRIDs 431363901, 43225501, 43139802, 43139803, 43146201, 43146202, 43146203, 43534802. U.S. EPA. 2011. Review of Product Chemistry , Manufacturing Process, and Acute Toxicity studies of the end use product (EP) PFR - 97 (EPA Reg. No s . 70051 - 17, 70051 - 19) containing the active ingredient (AI) Paecilomyces fumosoroseus . Memorandum from I. Barsoum, Ph.D. and J. Kough, Ph.D. to Shanaz Bacchus, dated April 28, 2011 and July 20, 2011 . See Tables 1, 2a, 2b, 3. U.S. EPA. 2011. Environmental risk assessment for the FIFRA Section 3 new use registration of Paecilomyces fumosoroseus Apopka Strain 97 (EPA Reg. No. 70051 - 19) . Memorandum from Shannon Borges and Zigfridas Vaituzis to Shanaz Bacchus, dated July 21, 2011. **C .**  **Other References** ARS collection of Entompathogenic Fungal (ARSEF) Cultures. January 24, 2011. Isaria , plus Paecilomyces and Evlachovea USDA - ARS Biological Integrated Pest Management Research, Robert W. Holley

Center for Agriculture and Health. 538 Tow er Road, Ithaca, New York 14853 - 2901.Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 17 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA Zimmermann, G . 2008 . The entomopathogenic fungi Isaria farinosa (formerly Paecilmoyces farinosus ) and the Isaria fumosorosea species complex (formerly Paecilomyces fumosoroseus ): biology , ecology and use in biological control . Biocontrol Science and Technology 18: 865 - 901.Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 18 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA **Appendix A. Microbial Pesticides**  **Data Requirements (40 CFR Part 158 -**  **Subpart V** **)** *NOTE: Master Record Identification Numbers listed in the following tables are representative of supporting data for the original registration of the product containing Isaria fumosorosea (formerly Paecilomyces fumosoroseus ) Apopka strain 97 . **1 .**  **Product Identity and Mode of Action Product Identity**  The Agency

has classified Paecilomyces fumosoroseus Apopka strain 97 as an active ingredient for use in microbial pesticides . This fungal strain is an entomopathogenic fungus of many orders of insects . It occurs naturally

in populations of infected and dead insects and randomly in soils around the world . It can be cultured readily

on various culture media and exists in several morphological stages, depending upon the culture medium . On solid medium, conidiophores, conidia and mycelia are predominant while submerged culture produces blastospores and mycelia. PFR- 97 TM 20% WDG contains blastospores, mycelia and conidia. The genus Paecilomyces was created in 1907 b y Banier and was considered to be related to Penicillium . One taxonomic revision, done by Samson (1974) , redefined and monographed the genus as “those species with verticillate conidiophores bearing divergent whorls of branches and phialides” . The latest taxonomic revision is reported in ARS collection of Entompathogenic Fungal (ARSEF) Cultures in January 24, 2011 , which classifies the genus and species as Isaria fumosorosea. When PFR - 97 is grown on agar media or insects, the following observations have been noted. Colonies grow moderately fast on malt - agar , attaining a diameter of approximately 4 cm within 14 days at 25  C . These colonies consist of a basal felt with raised floccose overgrowth, powdery when freshl y isolated . In some isolates pink sy

nnemata occur which may be branched . They are white at first, remaining so or changing to pink shades, especiall y when sporulating abundantly . Reverse is uncolored or yellow . Odor is absent . Vegetative hyp hae are smooth - walled, hyaline, and 1.5 - 3.5 μm wide . Conidial structures are mostly complex , consisting of erect conidiophores arising from submerged or laterall y from aerial hy phae. Conidiophores are mono - or s ynnematous, up to 100μm in length, 1.5 - 2 μm wide, smooth walled, hyaline, consisting of verticillate branches bearing whorls of 4 to 6 phialides . Phialides are 5.7 - 8 x 1 - 2 μm, with a globose or ellipsoidal basal portion which tapers into a long distinct neck, about 0.5μm wide . PFR Apopka strain 97 in the MUP has verticillate branches bearing whorls of 6 phialides. Conidia are cylindrical to fusiform, smooth - walled, hyaline to slightly pink, 3 - 4 x 1 - 2 μm . Chlamydospores are absent. Growth on insects . On insects the fungus produces monomenatous conidiophores or distinct but loose sy nnemata . Sy

nnemata are erect, branched appearing pink and p owdery due to the conidia, and can grow up to 3 cm in length and 400μm in diameter . Conidiogenous elements are inflated . Condiophores are 2.5 - 4μm wide . Verticillate branches are more or less globose or broadl y c yl indrical, 4 - 9 x 3 - 4.5 μm . Phialides with a globose basal portion can be 2.3 - 3.5 μm wide. **Mode of Action:** Conidia of the fungus attach to, and penetrate the cuticle of the host insect , where they germinate andIsaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 19 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA grow . This leads to pathogenesis and eventual death of the diseased insect host. **Product Chemistry TABLE 1. Product**  **Analysis Data Requirements**  **for the**  **Manufacturing Use Product (** **MUP )**  **, Isaria fumosoro**  **s ea**  **(form erly**  **Paecilomyces fumosoroseus** **) Apopka strain 97**  **, a nd Its Associated End**  **- Use Product**  **(EP) (40 CFR § 158.2**  **120 )**  **OCSPP G** **uideline N**  **umber Data Requirement**  **Results MRID No.**  **MUP EP**  885.1100 Product Identity A sample of Paecilomyces fumosoroseus Apopka strain 97 is filed at American T ype Tissue Collection # 20874. (DER dated 09/08/1995, from Cindy Schaffer to Shanaz Bacchus, MRIDs 43139901 , 43139801) . Change in taxonomic identification in 2011 identifies fungus as Isaria fumosorosea (Zimmerman , 2008) Apopka strain 97. Acceptable . Submitted data satisfy the requirement for product identity. This product contains 20 % w/w of the MUP Paecilomyces fumosoroseus Apopka strain 97 (ranged from 1.5 x 10 9 to 3.26 x 10 9 cfu/g). (DER dated 09/08/1995 from Cindy Schaffer to Shanaz Bacchus, MRID † 43292901). Acceptable † 43292901 † 43139901 † 43139801

885.1200 Manufacturing

Process The MUP is manufactured as liquid

fermentation product at 10 8 cfu/ml onsite and is formulated into the End - use Product that is labeled at 10 9 cfu/gram (DER dated 09/08/95 from Cindy Schaffer to Shanaz Bacchus, MRID † 43139801, Supplementalrequired analysis of unintentional ingredients . Manufacturing process for PFR- 97 20% WDG was previously submitted in MRID 43292901. MSDS for the inert ingredients were provided in in MRID 47939508 **US EPA DER I. Barsoum to S. Bacchus, 04/28/11. Acceptable † 43292901 † 43139901 † 43139801 47939508 **

885.1300 Discussion of

Formation of Unintentional Ingredients ‘Beauveralides’ were detected as

secondary metabolites during the manufacturing process; s ignificance of this was not determined, but secondary metabolites not a human health concern for the non - food greenhouse uses. Supplemental . Levels of fungal and bacterial metabolites and MS - HPLC assay of negligible total beauverolides in broth acceptable ; calculated beauverolides in sediment. Confirmation required in five production batches. * **US EPA DER 05/20/11 from I. Barsoum to S. Bacchus, MRIDs 48383001, 48357702. Additional data provided for proposed food uses of the EP in 2011 are acceptable for detection and Quality Assurance and Qual ity control of fungal, bacterial and other potential metabolites. **US EPA DER 04/28/1 1 from I. Barsoum to S. Bacchus; MRID 47939501 , 47939508, dated 05/20 /11 ; ***US EPA DER dated 05/20/11 from I. Barsoum to S. Bacchus, MRIDs 48383001, 48357702 . Acceptable † 43292901 * † 43139901 * † 43139801 * 47939501 ** 47939501 ** 47939508 ** 48383001** * 483577 02 ** *

Not applicable Deposition of a

Sam ple in a Nationally Recognized Culture Collection Paecilomyces fumosoroseus Apopka

strain 97 is on deposit with ATCC Manassas, Virginia under Accession Number 20874 . Not required for EP Certis ’ MSDS.

885.1400 Analysis of S amples Submitted data satisfy the requirement for analysis of s am ples. The content of active ingredient ranged from 1.5 x † 43139801 † 43139901Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 20 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA **TABLE 1. Product Analysis**  **Data Requirements for**  **the Manufacturing Use Product**  **( MUP**  **) ,**  **Isaria fumosoro s**  **ea (form**  **erly Paecilomyces**  **fumosoroseus )**  **Apopka strain 97 , a**  **nd Its Associated End -**  **Use Product (EP)**  **(40 CFR § 158.2 120**  **) OCSPP**  **G uideline**  **N umber**  **Data Requirement Results**  **MRID No. MUP**  **EP**

10 9 to 3.26 x 10 9 cfu/g, which meets the label claim. DER 04/28/11 from I. Barsoum to S. Bacchus, MRID 47939501 . † 43292901 47939501

8 85 .1 50 0 Certification of

L imits Limits listed o n the Confidential Statement of Formula (CSF) are adequate/a cceptable. † 43139801 † 43139901 † 43292901 47939501 **Additional Studies** 830.1800 Enforcement Analytical

M ethod Not applicable Acceptable 47939501 † DER dated 09/08/95 from Cindy Schaffer to Shanaz Bacchus, MRIDs † 43139801 , † 43292901 *, † 43139901 *, † 43139801 * DER Hanna Daoud, CA Dept. Pesticide Registration, April 27, 1995; † 43139801 , † 43292901 *, † 43139901 *, † 43139801 For the initial registration of the active ingredient, US EPA evaluated the data submitted for this registration action in 19 95, but considered and utilized the CA data assessments in order to streamline the review process. ** US EPA DER s from I. Barsoum to S. Bacchus; MRID 47939501 ( 04/28/11 ) , 05/20/11 ; *** US EPA DER from I. Barsoum to S. Bacchus MRID 483577 02 , 48383001 , dated 05/20/11 . **TABLE 2**  **a . Physical and Chemical Characteristics for the Manufacturing**  **- Use Product**  **(M UP),**  **Isaria fumo so**  **rosea**

**( form**  **erly Paecilomyces fum**  **osoroseus ) Apopka strain 97 (40 CFR § 158.2120)**  **OCSPP G** **uideline N**  **umber Data Requirement**  **Results MRID**  **Number** 830.6302 Color Brown 43139801 830.6303 Phy sical State Solid and liquid (10% precipitate in broth) 830.6304 Odor Smoke flavor 830.6313 Stability to Normal and

E levated Tem peratures, Metals, and Metal I ons Stable at 4 o C up to 3 weeks; not stable at 25 o C . Stability to metals and metal ions not reported. 43139801 830.6317 Storage Stability Up to three weeks @ 4oC. (C . Schaffer , 1995 ) up to 6 months at 4  C (BRAD 050405 ) . 43139801 830.6319 Miscibility Not required because PFR 97 is not an emulsifiab le form of microbial pesticide [ refer to test note #2 of 40 CFR §

158.2120(d)] . N/A 830.6320 Corrosion

Characteristics Not corrosive in fermentation test vessels. 43139801 830.7000 pH 5.7 830.7100 Viscosity 6.4 Centipoise 830.7300 Density 1.06 830.6315 Flammability Not flammable N/A 830.6314 Oxidation/Reduction;

Chemical Incompatibility N/A 830.6316 Explodability N/A . 830.6321 Dielectric Breakdown Voltage N/A .Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 21 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA N/A = Not applicable **TABLE 2b**  **. Physical and Chemical Characteristics for the End**  **- Use Product**  **(EP), Isaria fumo**  **so rosea** 

**( form**  **erly Paecilomyces**  **fum osoroseus** **) Apopka strain 97 (40 CFR § 158.2120) Guideline Reference No./Property**  **Description of Result Methods**  830.6302 Color Yellow/Brown MRID 47939502 Certis’ MSDS 830.6303 Physical State Granular solid 830.6304 Odor Not required for EP 830.6313 Stability Not required for EP 830.6314 Oxidation/Reduction:

Chemical Incompatibility Not applicable, the product does not contain oxidizing or reducing agents . 830.6315 Flammability Not applicable, the product does not contain flammable ingredients. 830.6316 Explodability Not applicable, the product does not contain explosive ingredients. 830.6317 Storage Stability Stable in product packaging at 4° C for 12 months. Less stable in product packaging at 25°C after 12 mo nths. (Product label recommends storage at 4° to 6°C in a dry place . Sample stored at 4 o C for 1 year wa s still effective at colonizing host ins ects while

that stored at 25 o C was not). MRID 47939503 830.6319 Miscibility Not applicable, the product is not an emulsifiable liquid.

MRID 47939502 830.6320 Corrosion Characteristics Non - reactive to the product containers. 830.6321 Dielectric Breakdown Voltage Not applicable, the product is not for use around electrical equipment. 830.7000 pH 6.4 - 6.5 a 6.0 - 7.00b 830.7100 Viscosity Not applicable, the product is a solid. 830.7200 Melting Range Not required for EP 830.7220 Boiling Range Not applicable, the product is a solid. 830.7300 Density/Relative Density/Bulk

Density 0.60 - 0.65 g/mL a 600 g/Lb 830.7370 Dissociation Constant in Water Not required for EP 830.7550 Partition Coefficient Not required for EP 830.7840 Water Solubility Not required for EP 830.7950 Vapor Pressure Not required for EP aData from CSF for basic formulation . Basic formulation withdrawn 07/28 /11 (email from Chris Dively, Certis,USA, to Shanaz Bacchus, US EPA/OPP/BPPD) . b Data from CSF for alternate formulation . This is ne w basic formulation.Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 22 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA **T ABLE**  **3. Toxicology**  **Data Requirements for the Technical Grade of the Active Ingredient (TGAI),**  **Isaria fumo**  **so rosea (** 

**form erly**  **Paecilomyces fu m**  **osoroseus ) Apopka strain 97**  **(40 CFR § 158.2140) OCSPP**  **Guideline Number**  **Data Requirement Results**  **MRID Number**  **Tier I** 885.3050 Ac ute Oral

Toxicity/ Pathogenicity An oral dose of 1.7 x 10 6 cfu/animal in a conidia spore suspension did

not produce mortality or abnormal clinical effects. No signs of fungal contamination were reported for the brain, mesenteric lymph nodes, blood, kidney, spleen, liver, lung or cecum, and no infectivity or patho genicity was recorded. [DERs to Shanaz Bacchus from Cindy Schaffer (09/08/95)* and from Ibrahim Barsoum (04/28/11)**] Acceptable . Toxicity Category IV 43163901* 47939508**

885.3150 Ac ute Pulmonary

Toxicity/ Pathogenicity A single intratracheal dose (10 6 conidia spores/animal) resulted in no

deaths and there were no signs of toxicity in any animal. No signs of infection were seen and no colonization of the lungs was observed. Total clearance of the fungus was attained by day eight after treatment . Acceptable Toxicity Category IV 43139802

885.3200 Ac ute Injection

Toxicity/ Pathogenicity Single intraperitoneal doses of suspensions containing 1.6 x 10 7

conidia spores per animal had no toxic or pathogenic effects and the spores were cleared from the body within two days. 43139803

870.1200 Ac ute Dermal

Toxicity 2 grams of test substance applied to the skin of rabbits produced no

deaths and there was no evidence of systemic toxicity. Acceptable Toxicity Category III. 43225501 870.2500 Primary dermal

irritation In a four - hour exposure, the test substance (2 g/animal) was found to

be a slight dermal irritant. Acceptable Toxicity Category IV. 870.2400 Ac ute eye Irritation 0.1 mL of diluted test substance containing ≥10 7 cfu was instilled in the eye, which was examined at 1, 24, 48 and 72 hours, and at 4 and 7 days after treatment. The test substance produced slight irritation which was reversible by day 4 after treatment. The product was classified as Acceptable Toxicity Category IV. 43146201

Dermal Sensitization In guinea pig: The test substance (3.0 x 10 7

– 5.3 x 10 9 cfu) produced

no irritation or sensitization reaction in treated animals. The product wa s not a dermal sensitizer. Supplementa l. Not required for registration 43146202

885.3400 Hy

persensitivity Incidents Published literature pertaining to incidents involving other strains of

Paecilomyces have been evaluated and data submitted to demonstrate that those incidents do not involve PFR Apopka 97 strain . Incident data must be reported in a timely manner. None reported with regard to pesticide use during the time that the registered pesticide has been in use. 885.3500 Cell Culture Not required for a fungal active ingredient

– required for viruses. NA

Mutagenicity assay (Ames Assay): Sonicated blastospores and mycelium of Paecilomyces

fumosoroseus Apopka strain 97 (100

– 5000 μg/plate) yielded negative results in a reverse mutation assay in both the presence and absence of microsomal enzymes (S9). 43534802

**Tiers II and III** Not required for Paecilomyces fumosoroseus Apopka strain 97 based on the acceptability of the data and waiver rationales evaluated for Tier I.Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 23 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA **Subchronic, Chronic Toxicity and Oncogenicity** Tier II tests (Guidelines 152 - 40 through 152 - 49) involving acute oral, acute inhalation, subchronic oral, acute intraperitoneal, intracerebral, primary dermal, primary

eye, immune response, teratogenicity , virulence enhancement, and mammalian mutagenicity were (40 CFR 158.740(C)(2)(vi through xv) not required since survival, replication, infectivity , toxicity, or persistence of the microbial agent was not observed in the test animals treated in the Tier I acute oral infectivity test . Tier III tests (Guidelines 152 - 50 through 53) involving chronic testing, oncogenicity testing, mutagenicity , and teratogenicity were not required (40 CFR 158.740(C)(2)(xvi through xix) since Tier I I tests were not required. **Acute toxicity –**  **End -**  **use Product** For the End - use Product (EP) PFR - 97 20% WDG , the registrant requested that testing for data requirements be waived based on the results of the tests conducted on the TGAI and the nature of the inert ingredients **(**MRID 47939508 ). The rationales justifying these requests were acceptable to the Agency (US EPA DER dated 04/28/11 from I. Barsoum to Shanaz Bacchus) . Waiver Requests granted for EP : Acute Oral Toxicity

(OPPTS 870.1100) Acute Dermal Toxicity

(OPPTS 870.1200) : Acute Inhalation Toxicity (OPPTS 870.1300) Acute E ye Irritation (OPPTS 870.2400) Acute Dermal Irritation (OPPTS 870.2500) **Ecological and Environmental Effects** See US EPA Borges July 21, 2011, for Nontarget Organism Toxicity and Environmental Fate Data Requirements for the Technical Grade of the Active In gredient (TGAI), for Isaria fumosorosea ( formerl y Paecilomyces fumosoroseus ) Apopka strain 97 (40 CFR § 158.2150) in this docket for summaries of the data reviewed and presented in the table below . **Table 4**  . Summary

of data submitted to comply with nontarget organism data requirements published in 40 CFR § 158.2150 for support of the registration of Paecilomyces fumosoroseus Apopka strain 97. **Data Requirement OPPTS** 

**Guideline No. Results Summary and Classification**  **MRID No.** Avian oral toxicity/pathogenicity 885.4050 A study (supplemental) indicated that P. fumosoroseus Apopka Strain 97 is not toxic or pathogenic to birds . P. fumosoroseus Apopka Strain 97 does not grow at avian body temperatures and is not expected to pose a hazard to birds 43534803

Avian inhalation toxicity/pathogenicity 885.4100 Not required . P. fumosoroseus is not pathogenic to birds. N/A Wild mammal toxicity/pathogenicity 885.4150 Tests required by 40 CFR § 158.2140 are adequate/ appropriate for assessment of hazards to wild mammals . P. fumosoroseus Apopka Strain 97 was not toxic or pathogeni c to albino rats at 1.7 x 10 6 cfu/animal . Scientific rationale also support the conclusion that adverse effects to wild mammals are not expected. Acceptable 47939507

• Freshwater fish toxicity/pathogenicity • Freshwater 885.4200

885.4240 Data waiver rationale provides sufficient information to

determine that toxicity/pathogenicity to freshwater fish and invertebrates is not expected as a result of all applications 47939506Isaria fumosorosea ( formerly Paecilomyces fumosoroseus ) Apopka strain 97 DRAFT Aug 10 , 2011 Page 24 of 24 Biopesticides Registration Action Document

– EP A HQ - OPP - 2010 - 0088 FIFRA EP A HQ - OPP - 2010 - 0087 FFDCA **Data Requirement OPPTS** 

**Guideline No. Results Summary and Classification**  **MRID No.** invertebrate toxicity/pathogenicity except for aerial applications . Supplemental for aerial applications . Acceptable for all other applications Estuarine/marine fish and invertebrate testing 885.4280 Not required . P. fumosoroseus is not to be applied directly to water and is not expected to reach estuarine or marine environments in significant quantities . P. fumosoroseus was also shown to be nonpathogenic to two species of estuarine invertebrates. N/A Nontarget plant testing 885.4300 Scientific rationale was sufficient to conclude that no adverse effects are expected to nontarget plants . Paecilomyces fumosoroseus Apopka strain 97 is not related to any known plant pathogen and testing is not required. Acceptable 47939504 Nontarget insect testing 885.4340 Initial scientific rationale (MRID 47939505) was unac ceptable . Additional rationale provides sufficient information to conclude that Paecilomyces fumosoroseus Apopka strain 97 will be pathogenic to some nontarget species of insects Acceptable 47939505 48357703 Honey bee testing 885.4380 A honey bee study showed that Paecilomyces fumosoroseus Apopka strain 97 is not toxic to honey bees . Supplemental Additional rationale show that pathogenicity may not be likely, but a conclusion cannot be made without uncertainty. Acceptable 47939509 4 8357704