BIOPESTICIDES REGISTRATION 

ACTION DOCUMENT 

Paecilomyces fumosoroseus strain FE 9901

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF PESTICIDE PROGRAMS

BIOPESTICIDES AND POLLUTION PREVENTION DIVISION

May 8, 2011
P. fumosoroseus strain FE 9901 page ii 

Biopesticides Registration Action Document

TABLE OF CONTENTS

I. REGULATORY BACKGROUND ................................................................................ 1

A. Application for Pesticide Registration ................................................................... 1

B. Petition to Establish an Exemption from Tolerance .............................................. 1

C. Public Participation ............................................................................................... 1

D. North American Free Trade Agreement Joint Review .......................................... 2

II. BIOLOGICAL CONSIDERATIONS ........................................................................... 2

III. ACTIVE INGREDIENT CHARACTERIZATION ........................................................ 2

A. Analysis and Certified Limits ................................................................................ 3

B. Physical and Chemical Properties ........................................................................ 3

C. Identification and Characterization ....................................................................... 4

IV. HUMAN HEALTH RISK ASSESSMENT .................................................................. 4

A. Toxicity ................................................................................................................. 4

1. Acute Toxicity .................................................................................................. 4

2. Hypersensitivity Incidents ................................................................................ 5

3. Metabolites of Concern .................................................................................... 5

4. Effects on the Endocrine System ..................................................................... 5

B. Exposure .............................................................................................................. 6

1. Occupational Exposure ................................................................................... 6

2. Residential, School, and Day Care Exposure .................................................. 6

C. Risk Characterization ........................................................................................... 6

V. ENVIRONMENTAL ASSESSMENT .......................................................................... 7

A. Risk Characterization ........................................................................................... 7

B. Endangered Species Assessment ........................................................................ 7

VI. RISK MANAGEMENT .............................................................................................. 7

A. Decision ................................................................................................................ 7

B. Terms of the Registration ..................................................................................... 8

BIBLIOGRAPHY ............................................................................................................. 9

APPENDIX A: Data Requirements and How the Applicant Met Them........................ A-1

APPENDIX B: Biology and Taxonomy of P. fumosoroseus ........................................ B-1

APPENDIX C: Summary of Toxicity Studies .............................................................. C-1

Tables 

Table 1. Select Physical and Chemical Properties of P. fumosoroseus strain FE 9901 . 3

Table 2. Summary of Toxicology Data for P. fumosoroseus strain FE 9901 .................. 4

 
P. fumosoroseus strain FE 9901 page iii 

Biopesticides Registration Action Document

BIOPESTICIDES REGISTRATION ACTION DOCUMENT TEAM

Office of Pesticide Programs 

Biopesticides and Pollution Prevention Division 

Microbial Pesticides Branch 

SCIENCE REVIEW

Ibrahim Barsoum, Ph.D. Product Chemistry and Human Health Risk 

John Kough, Ph.D. Secondary Review of Product Chemistry and Human Health Risk

Gail Tomimatsu, Ph.D. Environmental and Ecological Risk 

REGULATORY

Kathleen Martin, M.S.E.S. Regulatory Action Leader 

Sheryl Reilly, Ph.D. Chief, Microbial Pesticides Branch 

 
P. fumosoroseus strain FE 9901 page iv 

Biopesticides Registration Action Document

ACRONYMS 

Acronym Extension 

ARS Agricultural Research Service

BRAD Biopesticides Registration Action Document

CFU Colony forming units

CFU/g Colony forming units per gram

DNA Deoxyribonucleic acid

EDSP Endocrine Disruptor Screening Program

EP End-use product

EPA U.S. Environmental Protection Agency or, the Agency

FFDCA Federal Food, Drug, and Cosmetic Act 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

g/cc Grams per cubic centimeter

LC50 Median Lethal Concentration

LD50 Median Lethal Dose

mg/kg bw Milligrams per kilogram of body weight

mg/L Milligrams per liter

MP Manufacturing-use product

MPCA Microbial pesticide control agent 

MRID Master Record IDentification (number)

NAFTA North American Free Trade Agreement 

NOF Notice of Filing

NOR Notice of Receipt

NR Not required

OECD Organization for Economic Cooperation and Development

OPP EPA’s Office of Pesticide Programs

OPPTS EPA's Office of Prevention, Pesticides and Toxic Substances; 

now the Office of Chemical Safety and Pollution Prevention

P. fumosoroseus Paecilomyces fumosoroseus

PMRA Health Canada’s Pest Management Regulatory Agency

RAPD-PCR Random Amplification of Polymorphic DNA-Polymerase Chain Reaction 

rDNA-ITS Ribosomal DNA-Internal Transcribed Spacer

TGAI Technical grade active ingredient

U.S. United States

UV Ultraviolet radiation

USDA U.S. Department of Agriculture

WP Wettable powder
P. fumosoroseus strain FE 9901 page 1 

Biopesticides Registration Action Document

 

 In May 2009, Natural Industries Inc. (represented by Technology Sciences Group, Inc.) applied 

to the U.S. Environmental Protection Agency (EPA or the Agency) for registration of two products 

containing the new mycoinsecticide Paecilomyces fumosoroseus strain FE 9901: 

Maunfacturing-Use End-Use

Product: NoFlyTM Technical NoFlyTM WP 

EPA Reg. No: 73314-7 73314-6 

% ai: 69.0% 18% 

Docket:1 EPA-HQ-OPP-2010-0093 

Proposed 

Uses:

Nonfood (e.g., ornamentals) greenhouse and nursery crops to control 

whiteflies, aphids, thrips, psyllids, mealybugs, leafhoppers, plant 

bugs, weevils, grasshoppers, Mormon crickets, locust, and beetles 

PC Code: 115003 

The applicant also petitioned for an exemption from the requirement of tolerance for any 

P.fumosoroseus strain FE 9901residues that may remain in or on food. 

I. REGULATORY BACKGROUND 

A. Application for Pesticide Registration 

 A Notice of Receipt (NOR), announcing EPA’s receipt of Natural Industries Incorporated’s 

applications to register P.fumosoroseus strain FE 9901, was published in the Federal Register on 

March 10, 2010 (75 FR 11175). You can find the NOR and supporting materials (e.g., draft label) at 

regulations.gov; the docket number is EPA-HQ-OPP-2010-0093. EPA received no comments in 

response to the NOR. 

B. Petition to Establish an Exemption from the Requirement of Tolerance 

 Under section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), the applicant 

petitioned the Agency (PP 9F7587) to establish an exemption from the requirement of a tolerance for 

residues of P.fumosoroseus strain FE 9901. A Notice of Filing (NOF) was published in the Federal 

Register on March 10, 2010 (75 FR 11171); it can be found at regulations.gov under docket number 

EPA-HQ-OPP-2010-0092. EPA received no comments in response to the NOF. In February 2011, 

Natural Industries Inc. (as represented by Technology Sciences Group, Inc.) withdrew their petition 

(TSG 2011). 

C. Public Participation 

 On October 1, 2009, EPA announced a new policy to provide a more meaningful opportunity for 

the public to participate in major registration decisions before they occur. According to this new policy, 

the Agency intends to provide a public comment period prior to making a registration decision for, at 

minimum, the following types of applications: new active 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. 

 

 

1

To access the public docket, go to www.regulations.gov; under “Enter Keyword or ID” enter the docket number, which is 

‘EPA-HQ-OPP-2010-0093.’ 
P. fumosoroseus strain FE 9901 page 2 

Biopesticides Registration Action Document

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

P. fumosoroseus strain FE 9901 was subject to a 30-day comment period as a “new active ingredient” 

whose registration would result in a “first food use.” The public comment period ran from 

October 6, 2010 to November 5, 2010; no comments were received. 

 D. North American Free Trade Agreement Joint Review 

 P. fumosoroseus strain FE 9901 was the subject of a North American Free Trade Agreement 

(NAFTA) joint registration review conducted by EPA’s Office of Pesticide Programs (OPP) and Health 

Canada’s Pest Management Regulatory Agency (PMRA). 

II. BIOLOGICAL CONSIDERATIONS (Altre and Vandenberg 2001; Bolckmans et aI.1995; Lacey 

et. al. 1999; Osborne et. al. 1990; Osborne and Landa1992; Smith 1993; MRID 477920-01) 

P. fumosoroseus is a naturally occurring fungus found in various soil types around the world, 

including Europe (Netherlands, Ireland, Spain); Asia (China, Japan, Pakistan, India); Africa (Ghana); 

and the United States. In the environment, P. fumosoroseus is dispersed as conidia, either by air or 

water movement or by other insects and/or mites. Conidia are spores and they are supported on 

specialized spore-producing “hyphae” (a filamentous stalk) known as conidiophores. As with other 

entomopathogenic2

 fungi, P. fumosoroseus infects its target by conidial attachment followed by 

germination, penetration into the host, vegetative growth within the organism, and then conidiogenesis 

(i.e., production of more conidia). 

 In laboratory testing, investigators determined that P. fumosoroseus strain FE 9901 grows best 

at (76.1o F; 24.5°C). At higher temperatures (79.7o F to 86.0o F; 26.5°C to 30°C), growth is significantly 

reduced and at temperatures greater than 95.0o F (35°C), the fungus will no longer grow. At 98.6oF 

(37oC), the organism is killed (P. fumosoroseus strain FE 9901 was unable to resume growth at room 

temperature after incubation at 98.6oF). 

 NoFlyTM WP’s target is the whitefly, and this microbial pesticide control agent (MPCA) is 

intended to control all stages of whitefly development (i.e., eggs, N1, N2, N3 and N4 larvae, and 

adults). The ability to infect whitefly eggs is unique among entomopathogenic fungi. The infection 

cycle of P. fumosoroseus strain FE 9901 is particularly rapid under optimal conditions. Initially, conidia 

attach to the cuticle or the dorsum of immature or adult whiteflies; the first symptoms of infection 

typically are apparent within one to two days after contact. Conidia and hyphae are present in the host 

hemocoel (body cavity) within one day. Fungal multiplication takes place through formation of hyphal 

bodies or blastospores. The mycelium (a branching network of hyphae) is present on the dorsum of the 

insect body within two days. Sporulation occurs within three days and reaches a maximum within five 

to seven days. 

P. fumosoroseus strain FE 9901 does not exhibit any atypical morphological, physiological, 

biochemical, pesticidal, or resistance characteristics. For more information on the biology and 

taxonomy, see Appendix B. 

III. ACTIVE INGREDIENT CHARACTERIZATION 

 Most of the data requirements under 40 CFR 158.2120 (Product Analysis) have been satisfied. 

A sample of P. fumosoroseus strain FE 9901 has been deposited in the U.S. Department of 

Agriculture’s Agricultural Research Service Collection of Entomopathogenic Fungal Cultures (USDA 

ARS) under the accession number ARSEF 4490. Described below are the studies that are not 

 

2

An entomopathogenic fungus is one that can act as a parasite of insects and kills or seriously disables them. 
P. fumosoroseus strain FE 9901 page 3 

Biopesticides Registration Action Document

acceptable or need further information, as terms of registration (see Section VI.B: Terms of the 

Registration, for a complete list). The physical and chemical properties of P. fumosoroseus strain FE 

9901 are provided in Table 1. 

A. Analysis and Certified Limits 

 Under Analysis of Samples, the registrant must submit a five-batch analysis of the EP (end-use 

product) and MP (manufacturing-use product), from the proposed manufacturing site, as a term of 

registration (OPPTS 885.1400). 

B. Physical and Chemical Properties 

 Three Physical and Chemical Characteristics (as discussed below) must be completed as terms 

of registration. Provided in Table 1 is a summary of the physical and chemical properties of NoFlyTM 

WP and NoFlyTM Technical. 

Stability to Normal and Elevated Temperatures, Metals and Metal Ions (OPPTS 830.6313) was 

satisfied for NoFlyTM Technical (MRID 480514-01); however, it has not been satisfied for 

NoFlyTM WP. 

Storage Stability (OPPTS 830.6317) must be addressed for both NoFlyTM Technical and 

NoFlyTM WP. For the Technical, Natural Industries Inc. has stated that they will conduct a 

combined storage stability/corrosion characteristic study as a term of registration (MRID 

480514-01). Regarding NoFlyTM WP, a study was submitted (MRID 477919-02); however, it is 

inadequate. First, the test guidelines for Storage Stability (OPPTS 830.6317; EPA 2002) 

recommend a test period of one year, at a minimum; the duration of the petitioner’s study was 

just six months. Further, one batch of the product was not produced at the proposed 

manufacturing site and the relative viability after six months was mediocre. The existing data 

support a three-month storage period, with the condition that a new study be conducted using 

the proposed formulation, manufactured at the proposed site. 

Corrosion Characteristics (OPPTS 830.6320) must be satisfied as a term of registration; Natural 

Industries Inc. has indicated that they intend to complete these studies (MRID 480514-01). 

Table 1. Select Physical and Chemical Properties of Paecilomyces fumosoroseus 

 strain FE 9901 (MRIDs 477919-01, 477920-01, and 480514-01) 

OPPTS 

Guideline 

Number 

Data 

Requirement 

VALUE

EP (NoFlyTM WP) MP (NoFlyTM Technical) 

830.6302 Color lilac (Pantone 435M/662C) lilac 

830.6303 Physical state powder slightly cohesive, dusty powder 

830.6304 Odor yeast-like yeast-like 

830.6313 Stability to normal and 

elevated temperatures, 

metals and metal ions 

Term of registration Above 104 ̊F (40 ̊C), this MPCA will 

not survive for any length of time; 

NoFlyTM Technical will not be 

exposed to metal or metal ions. 

830.6317 Storage stability Term of registration—submitted study 

is inadequate 

Term of registration 

830.6320 Corrosion characteristics Term of registration Term of registration; to be conducted 

with storage stability 

830.7000 pH (1% suspension 

in water) 

6.5 to 7.5 6.5 to 7.5 

830.7300 Bulk density 0.65 to 0.75 g/cc 0.6 to 0.7 g/cc 
P. fumosoroseus strain FE 9901 page 4 

Biopesticides Registration Action Document

 C. Identification and Characterization 

 Identification and characterization of P. fumosoroseus strain FE 9901 has been made using 

BioLog FF MicroPlateTM. Growth was observed on a variety of solid media agar formulations (e.g., 

Sabouraud dextrose, MacConkey, and chitin) over a wide range of pH values. Molecular fingerprints of 

P. fumosoroseus strain FE 9901 were compared with those of three other P. fumosoroseus isolates; 

two techniques were used: variable number tandem repeat, and inter-simple sequence repeat. Other 

technologies available to identify and characterize the microbe include rDNA-ITS (Ribosomal DNAInternal Transcribed Spacer) sequencing and RAPD-PCR (Random Amplification of Polymorphic DNA 

polymerase chain reaction). 

IV. HUMAN HEALTH RISK ASSESSMENT (EPA 2010b) 

 In assessing the risk of a pesticide to human health, EPA considers the toxicity of the pesticide 

in addition to exposure routes and levels. Provided in section A (below) is the toxicity of P. 

fumosoroseus strain FE 9901 and in section B, the exposure. The Risk Characterization is provided in 

section C. 

 A. Toxicity 

1. Acute Toxicity 

 With one exception (additional information is needed for the acute injection 

toxicity/pathogenicity study), all the data requirements under 40 CFR 158.2140 (Toxicology) 

have been met. A summary of the toxicity data for NoFlyTM WP and NoFlyTM Technical is 

provided in Table 2; for brief descriptions of the studies submitted, please see Appendix C. 

A complete listing of the terms of registration is provided in section VI.B. 

Table 2. Summary of Toxicology Data for Paecilomyces fumosoroseus strain FE 9901 

OPPTS 

Guideline 

Number 

Data 

Requirement 

TOXICITY AND CATEGORY1

EP (NoFlyTM WP) MP (NoFlyTM Technical) 

870.1100 Acute oral toxicity LD50 >5,000 mg/kg bw 

Category IV 

(MRID 477919-03) 

 LD50=600 mg/kg bw 

Category III 

870.1200 Acute dermal toxicity LD50>5,050 mg/kg bw 

Category III

(MRID 477919-04) 

Data waived 

(MRID 477920-06) 

870.1300 Acute inhalation toxicity LC50>2.18 mg/L 

Category III

(MRID 477919-05) 

Data waived 

(MRID 477920-06) 

870.2400 Acute eye irritation some redness 

Category IV

(MRID 477919-06) 

Data waived 

(MRID 477920-06) 

870.2500 Primary dermal irritation slightly irritating 

Category IV

(MRID 477919-07) 

Data waived 

(MRID 477920-06) 

885.3050 Acute oral toxicity/ 

pathogenicity 

TGAI2: Not infective or pathogenic to rats via the oral route. 

885.3150 Acute pulmonary 

toxicity/pathogenicity 

TGAI: Not infective or pathogenic to ferrets via the inhalation route. 

885.3200 Acute injection 

toxicity/pathogenicity 

(intraperitoneal) 

TGAI: Not infective or pathogenic to rats via injection, based on the 

available results (more information is needed).3

 (MRID 477920-05) 
P. fumosoroseus strain FE 9901 page 5 

Biopesticides Registration Action Document

1

Category I has the highest toxicity while Category IV has the lowest. For a description of the Toxicity Categories along with their 

limits, see 40 CFR 156.62. 

2

TGAI=technical grade active ingredient. 

3

Natural Industries Inc. must submit data showing microbial clearance from matrices other than blood (e.g., organs, body fluids)

(EPA 2010b). 

 2. Hypersensitivity Incidents (OPPTS 885.3400; MRID 480514-02) 

 The applicant reported that they have seen no incidents of hypersensitivity throughout 

the research, development, and testing of NoFlyTM Technical and WP; however, a literature 

search of the PubMed database (www.ncbi.nlm.nih.gov/pubmed) using the keywords 

“paecilomyces” and “allergy,” revealed 21 reports of hypersensitivity for this genus. In a 

supplemental study (MRID 477919-08), study investigators determined that NoFlyTM WP causes 

sensitization when applied to the skin of female guinea pigs. 

 Based on the assumption that most microorganisms contain substances that could elicit 

allergic reactions, EPA considers P. fumosoroseus strain FE 9901 to be a potential sensitizing 

agent. 

 3. Metabolites of Concern 

P. fumosoroseus strain FE 9901 may produce the metabolites Beauverolides M and I, 

and 2,6-pyridinedicarboxylic acid during the fermentation process. EPA does not expect these 

metabolites to be of concern because, overall, the acute toxicity of NoFlyTM Technical and WP is 

low (see Table 1). 

 4. Effects on the Endocrine System 

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

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar to an effect produced by 

a “naturally occurring estrogen, or other such endocrine effects as the Administrator may 

designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 

2 testing is designed to identify any adverse endocrine related effects caused by the substance, 

and establish a dose-response relationship between the dose and the E, A, or T effect. 

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

first group of 67 chemicals, which contains 58 pesticide active ingredients and nine inert 

ingredients. This list of chemicals was selected based on the potential for human exposure 

through pathways such as food and water, residential activity, and certain post-application 

agricultural scenarios. This list should not be construed as a list of known or likely endocrine 

disruptors. 

P. fumosoroseus is not among the group of 58 pesticide active ingredients on the initial 

list to be screened under the EDSP. Under FFDCA section 408(p) the Agency must screen all 

pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP test 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/. 
P. fumosoroseus strain FE 9901 page 6 

Biopesticides Registration Action Document

B. Exposure 

 1. Occupational Exposure 

 NoFlyTM WP, which is limited to greenhouse use (indoor), can be applied using 

conventional spraying equipment, but use of manual sprayers is highly recommended. 

Occupational exposure via the inhalation and dermal is expected for persons who mix and/or 

applying this pesticide. Dermal exposure is expected for individuals who work in the 

greenhouse following application. 

2. Residential, School, and Day Care Exposure

 Individuals in residential, school, and day-care settings may be exposed to residues of 

P. fumosoroseus strain FE 9901 through the dermal route by touching treated ornamental 

plants, but EPA expects that exposure will be low due to the nature of this fungus. At warm 

temperatures, this MPCA does not grow well—at 80o F (26.7°C), growth is significantly reduced, 

and at 95o F (35°C), it does not grow at all. Sunlight further inhibits the growth of P. 

fumosoroseus (Fargues 1997; TSG 2008). Fargues et al. (1997) studied the effects of 

ultraviolet (UV) radiation on the germinability, survival, and infectivity of P. fumosoroseus. They 

found the UVB range of ultraviolet light (sunlight includes UVB light) to be the most important 

factor “for the detrimental effects of sunlight on the persistence of conidia of entomopathogenic 

fungi in insolated environments” (Fargues 1997). EPA expects that once the treated plants are 

out of the greenhouse, residues of P. fumosoroseus strain FE 9901 would rapidly decline due to 

temperature and sunlight. 

 C. Risk Characterization

 Occupational exposure may occur through the dermal and inhalation routes. P. fumosoroseus 

strain FE 9901 is not acutely toxic via these routes—the dermal LD50 is 5,050 mg/kg bw (limit dose) and 

inhalation LC50 is >2.18 mg/L (limit dose). There is concern, however, regarding sensitization. In a 

search of the open literature, EPA noted a number of hypersensitivity reports for the genus 

Paecilomyces. And, a skin sensitization assay using P. fumosoroseus strain FE 9901 as the test 

substance (MRID 477919-08) was positive—the test animals exhibited intense erythema and swelling 

in areas where the test material was applied. To mitigate potential sensitization, the label requires 

protective eyewear; chemical-resistant gloves; long-sleeved shirts and long pants; and, for 

mixer/loaders, a dust/mist-filtering respirator meeting NIOSH (National Institute for Occupational Safety 

and Health) standards of at least N-95, R-95, or P-95. 

 EPA concludes that there is a reasonable certainty that no harm will result from the intended 

use of P. fumosoroseus strain FE 9901 as a microbial pesticide. This is based on the available toxicity 

and exposure information—P. fumosoroseus strain FE 9901 does not demonstrate toxic, pathogenic, 

and/ or infective potential to mammals, and potential occupational and non-occupational exposure is 

expected to be very low. 

 
P. fumosoroseus strain FE 9901 page 7 

Biopesticides Registration Action Document

V. ENVIRONMENTAL ASSESSMENT 

A. Risk Characterization 

 EPA did not require any environmental effects data, including those for non-target organisms, 

because of the low toxicity of this MPCA and, low exposure from the intended use. P. fumosoroseus

strain FE 9901will only be used in greenhouses3

; therefore, the Agency does not expect that birds, 

honeybees, and other nontarget organisms such as insects and fish, will be exposed. In a letter to the 

applicant (EPA 2008), EPA pointed out that if “the intended use sites are restricted to indoors, then 

neither a honey bee study nor other nontarget assessments are likely to be needed.” For more details, 

including a complete list of the Nontarget Organisms and Environmental Fate Data requirements under 

40 CFR 158.2150, see Table A-3 of Appendix A. 

 B. Endangered Species Assessment

 EPA expects that nontarget organisms will not be exposed to P. fumosoroseus strain FE 9901. 

Thus, the Agency has determined that it will have “No Effect”4

 on any currently listed threatened or 

endangered species, or any designated critical habitat. 

VI. RISK MANAGEMENT 

 

 A. Decision 

 The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) section 3(c)(5) provides for the 

registration of new active ingredients if EPA determines that: 

 its composition is such as to warrant the proposed claims for it; 

 its labeling and other materials required to be submitted comply with the 

requirements of FIFRA; 

 it will perform its intended function without unreasonable adverse effects on 

the environment; and 

 when used in accordance with widespread and commonly recognized 

practice, it will not generally cause unreasonable adverse effects on the 

environment. 

 The four eligibility criteria for registration of new active ingredients are satisfied for NoFlyTM WP 

(73314-A) and NoFlyTM Technical (73314-T). These products are not expected to cause unreasonable 

adverse effects and are likely to provide protection as claimed when used according to label 

instructions. The new active ingredient P. fumosoroseus strain FE 9901 is eligible for registration for 

the labeled uses. Please note that certain terms of registration must be met. 

 

 

3

In a letter to the Agency (TSG 2008), Technology Sciences Group Inc. (the regulatory consultant) pointed out that 

“Natural Industries has decided not to make NoFlyTM for outdoor use because Paecilomyces fumosoroseus 

strain FE 9901is UV sensitive.” 

4

The U.S. Fish and Wildlife Service defines the term “No Effect” to mean that “its proposed action will not affect a listed 

species or designated critical habitat” (www.fws.gov/endangered/esa-library/pdf/CH1-3.PDF). 
P. fumosoroseus strain FE 9901 page 8 

Biopesticides Registration Action Document

 B. Terms of the Registration 

 As terms of registration, EPA requires that the following data requirements be completed within 

the next several months; specific time frames (from the date of registration) are noted below: 

40 CFR 158.2120 (Product Analysis)

Analysis and Certified Limits:

 Analysis of samples 

(OPPTS 885.1400) 

EP and MP 

A five-batch analysis of the EP and MP from the proposed 

manufacturing site must be submitted. 

DUE: 18 months 

Physical and Chemical Characteristics:

Stability to normal and 

elevated temperatures, 

metals and metal ions 

(OPPTS 830.6313) 

 EP 

This requirement has been satisfied for the MP (MRID 

480514-01); however, it must be completed for the EP. 

DUE: 12 months 

 

Storage stability 

(OPPTS 830.6317) 

EP and MP 

Regarding the MP, MRID 480514-01 reports that “a storage 

stability/corrosion study will be conducted as a condition of 

registration.” 

For the EP, a storage stability study (MRID 477919-02) was 

submitted; however, it is inadequate and will only support a 

three-month storage period. A storage stability study must be 

conducted using the proposed formulation of NoFlyTM WP, 

from the proposed manufacturing site. The study must 

support a storage period of at least six months. 

DUE: 18 months 

Corrosion 

characteristics 

(OPPTS 830.6320) 

EP and MP

MRID 480514-01 reports these will be completed as “a 

condition of registration.”

DUE: 18 months 

40 CFR 158.2140 (Toxicology data)

Acute injection toxicity/ 

pathogenicity: 

intraperitoneal 

(OPPTS 885.3200) 

 TGAI 

This study was submitted (MRID 477920-05); however, the 

registrant must submit additional data showing microbial 

clearance from matrices other than blood (e.g., organs, body 

fluids) (EPA 2010b). 

DUE: six months 

NOTE: EP=NoFlyTM WP and MP=NoFlyTM Technical. 

 
P. fumosoroseus strain FE 9901 page 9 

Biopesticides Registration Action Document

BIBLIOGRAPHY 

Studies, by MRID

477919-00. Natural Industries, Inc. 2009. Submission of Product Chemistry and Toxicity Data in Support of 

the Application for Registration of NoFlyTM WP and the Petition for Tolerance of Paecilomyces 

fumosoroseus strain FE 9901, blastospores. Transmittal of 8 Studies. May 7, 2009. 

477919-01. Curry, K.; Brookman, D. 2009. Product Chemistry of NoFLYTM WP. Project Number: 

NoFLYTM/PC/002. Unpublished study prepared by Technology Sciences Group, Inc. 64 p. April 

29, 2009. 

477919-02. Bell, A. 2006. Storage and Stability of NoFlyTM WP. Project Number: CEMS/2836. 

Unpublished study prepared by MGS Laboratories, Ltd., and CEM Analytical Services, Ltd. 14 p. 

August 22, 2006. 

477919-03. Kuhn, J. 2009. Futureco NoFlyTM: Acute Oral Toxicity Study (UDP) in Rats. Final Report. 

Project Number: 12412/08. Unpublished study prepared by Stillmeadow, Inc. 12 p. January 13, 

2009. 

477919-04. Kuhn, J. 2009. Futureco NoFlyTM: Acute Dermal Toxicity Study in Rats. Final Report. Project 

Number: 12413/08. Unpublished study prepared by Stillmeadow, Inc. 13 p. January 13, 2009. 

477919-05. Younger, C. 2009. Futureco NoFlyTM: Acute Inhalation Toxicity Study in Rats. Final Report. 

Project Number: 12414/08. Unpublished study prepared by Stillmeadow, Inc. 19 p. January 29, 

2009. 

477919-06. Stahl, J. 2004. NoFlyTM WP Acute Eye Irritation Study (in Rabbits). Project Number: 

04/831/005N. Unpublished study prepared by LAB International Research Centre Hungary, Ltd. 

22 p. September 2, 2004. 

477919-07. Stahl, J. 2004. NoFlyTM WP Primary Dermal Irritation Study (in Rabbits). Project Number: 

04/831/006N. Unpublished study prepared by LAB International Research Centre Hungary, Ltd. 

20 p. September 2, 2004. 

477919-08. Stahl, J. 2004. NoFlyTM WP Skin Sensitization Study (in Guinea Pig). Project Number: 

04/831/104T. Unpublished study prepared by LAB International Research Centre Hungary, Ltd. 

34 p. September 27, 2004. 

477920-00. Natural Industries, Inc. 2009. Submission of Product Chemistry and Toxicity Data in Support of 

the Application for Registration of NoFlyTM Technical and the Petition for Tolerance of 

Paecilomyces fumosoroseus Strain FE 9901, Blastospores. Transmittal of 7 Studies. May 7, 

2009. 

477920-01. Brookman, D.; Curry, K. 2009. Product Chemistry of NoFlyTM Technical. Project Number: 

NoFLYTM/PC/001. Unpublished study prepared by Technology Sciences Group, Inc. 247 p. May 

13, 2009. 

477920-02. Cerna, Z. 2004a. NoFlyTM Technical Acute Oral Toxicity (in Rats). Project Number: 006/04/C. 

Unpublished study prepared by BioTest, Ltd. 25 p. July 30, 2004. 

477920-03. Mier, T.; Olivares-Redonda, G.; Navarro-Barranco, H.; et al. 2005. Acute Oral Intragastric 

Pathogenicity and Toxicity in Mice of Paecilomyces fumosoroseus Isolated from Whiteflies. 

Antonie van Leeuwenhoek 88:103-111. February 9, 2005. 

477920-04. Marhan, J. 2004. NoFlyTM Technical Acute Pulmonary Toxicity/Pathogenicity (in Ferrets). 

Project Number: 004/04/C. Unpublished study prepared by BioTest, Ltd. 26 p. July 30, 2004. 

477920-05. Cerna, Z. 2004b. NoFlyTM Technical Acute Injection Toxicity/Pathogenicity (Intraperitoneal) (in 

Rats). Project Number: 005/04/C. Unpublished study prepared by BioTest, Ltd. 22 p. July 30, 

2004. 

477920-06. Even, M. 2009. Response to Tier 1 Microbial Pesticide Data Requirements for NoFlyTM 

Technical. Unpublished study prepared by Technology Sciences Group, Inc. 41 p. May 7, 2009. 

477920-07. Vertesr, A. 2004. NoFlyTM Technical Bacterial Reverse Mutation Assay. Project Number: 

04/831/007M. Unpublished study prepared by LAB International Research Centre Hungary, Ltd. 

41 p. September 2, 2004. 
P. fumosoroseus strain FE 9901 page 10 

Biopesticides Registration Action Document

479705-00. Natural Industries, Inc. 2010. Submission of Efficacy Data in Support of the Application for 

Registration of NoFlyTM WP. Transmittal of 1 Study. February 1, 2010. 

479705-01. Corts, V.; Aucejo, S. 2007. Laboratory Trials to Test the Side Effect of NoFlyTM WP and Adults 

of Apis Mellifera: One Acute Oral and One Contact Toxicity Trial. Unpublished study prepared 

by recerca agricola/SynTech Research Spain S.L. 49 p. July 12, 2007. 

480514-00. Natural Industries, Inc. 2010. Submission of Product Chemistry and Toxicity Data in Support of 

the Applications for Registration of NoFlyTM Technical and NoFlyTM WP. Transmittal of 3 Studies. 

April 2, 2010. 

480514-01. Bjornson, H.; Lara, J. 2010. NoFlyTM Technical and NoFlyTM WP Response to PMRA and EPA 

Clarifications. Unpublished study prepared by Technology Sciences Group, Inc. 18 p. April 2, 

2010. 

480514-02. Bjornson, H. 2010. NoFlyTM Technical and NoFlyTM WP Response to Hypersensitivity Data 

Requirement. Unpublished study prepared by Technology Sciences Group, Inc. 

 4 p. April 1, 2010. 

480514-03. Luangsa, J.; Hyel-Jones, N.; Manoch, L.; et al. 2005. On the Relationships of Paecilomyces 

sect. Isarioidea Species. Mycol. Res. 109(5):581-589. May 2005.

Reviews and other References

Altre, J.A. and Vandenberg, J. D. 2001. Penetration of cuticle and proliferation in hemolymph by Paecilomyces 

fumosoroseus isolates that differ in virulence against lepidopteran larvae. J. Invertebr. Pathol. 78:81-86. 

Bolckmans et aI. 1995. PreFeRal, (Paecilomyces fumosoroseus strain Apopka 97), a new microbial insecticide 

for the biological control of whiteflies in greenhouses. Med. Fac. Landbouww. Univ. Gent, 60/3a. 

Brown, A.H.S. and Smith, G. 1957. The genus Paecilomyces Bainier and its perfect stage Byssochlamys

Westling. Transactions of the British Mycological Society. 40(1); 17-89. 

Catalogue of Life. 2010. Bisby et al., editors. Catalogue of Life: 2010 Annual Checklist. Integrated Taxonomic 

Information System (ITIS) and Species 2000. Reading, United Kingdom. Information retrieved on August 24, 

2010. www.catalogueoflife.org/annual-checklist/2010. 

Fargues J. et.al. 1997. Inactivation of Conidia of Paecilomyces fumosoroseus by Near-Ultraviolet (UVB and 

UVA) and Visible Radiation. Journal of Invertebrate Pathology 69, 70-78 (1997). 

Lacey, L.A. et. al. 1999. Ovicidal and larvicidal activity of conidia and blastospores of Paecilomyces 

fumosoroseus (Deuteromycotina: Hyphomycetes) against Bemisia argentifolii (Homoptera: Aleyrodidae) with a 

description of a Bioassay System allowing prolonged survival of control insects. Biocontrol Science and 

Technology, 9:9-18. 

MycoBank. 2010. Species Paecilomyces fumosoroseus (Wize) A.H.S. Br. & G. Sm. 1957; MB302188. 

MycoBank Fungal Databases. Information Retrieved on August 25, 2010 (searching with the term "Paecilomyces 

fumosoroseus”). www.mycobank.org. 

Osborne, L.S. et. al. 1990. Prospects for biological control of Bemisia tabaci. International Organization for 

Biological Control/West Paleartic Regional Section (IOBC/WPRS). Bulletin 13:153-160. 

Osborne, L.S. and Landa, Z. 1992. Biological Control of whiteflies with entomopathogenic fungi. Florida Ent., 

75:457-471. 

Padilla, M., Hernández, E., Carnero, A., Amador, S. 2004. Evaluation of the side effects of the Microbial Pest 

Control Product FUTURECO NoFLYTM (BCA Paecilomyces fumosoroseus strain FE 9901) to whitefly natural 

enemies in the Canary Islands. Company Report No NF-04001. 

Riba, G. and Ravelojoana, M. 1984. The parasexual cycle in the entomopathogenic fungus Paecilomyces 

fumosoroseus (Wize) Brown and Smith. Can. J. Microbiol. 30:922-926. 

Smith, P. 1993. Control of Bemisia tabaci and the potential of Paecilomyces fumosoroseus as a Biopesticide. 

Biocontrol News and Information 14 (4):71N-78N. 

TSG. 2008. Letter from Heather Bjornson, Technology Sciences Group Inc. (TSG) on behalf of Natural 

Industries, Inc. to Jeannine Kaush, U.S. EPA. “NoFlyTM Pre-registration Meeting Minutes.” July 16, 2008. 
P. fumosoroseus strain FE 9901 page 11 

Biopesticides Registration Action Document

TSG. 2009a. Letter from Heather Bjornson, Technology Sciences Group Inc. (TSG) on behalf of Natural 

Industries, Inc. to Sheryl Reilly, U.S. EPA. "NoFlyTM Technical—Application for new product registration...." May 

7, 2009. 

TSG. 2009b. Letter from Heather Bjornson, Technology Sciences Group Inc. (TSG) on behalf of Natural 

Industries, Inc. to Sheryl Reilly, U.S. EPA. "NoFlyTM WP—Application for new product registration...." May 7, 

2009. 

TSG. 2009c. Letter from Heather Bjornson, Technology Sciences Group Inc. (TSG) on behalf of Natural 

Industries, Inc. to Sheryl Reilly, U.S. EPA. “Petition for an exemption from the requirement of a tolerance for 

residues of products containing the active ingredient “Paecilomyces fumosoroseus strain FE 9901” in or on all 

food commodities. May 7, 2009. 

TSG. 2010a. Letter from Heather R. Bjornson, Regulatory Consultant to Natural Industries to Sheryl Reilly and 

Kathleen Martin, U.S. EPA. “NoFlyTM Technical (EPA Reg. No. 73314-L). February 1, 2010. 

TSG. 2010b. Letter from Heather R. Bjornson, Regulatory Consultant to Natural Industries to Sheryl Reilly, U.S. 

EPA. Submission of Information to Support the Application to Register NoFlyTM Technical (EPA File 

Symbol:73314-L) and NoFlyTM WP (EPA File Symbol:73314-A). March 2, 2010. 

TSG. 2011. Letter from Heather R. Bjornson, Regulatory Consultant to Natural Industries to Sheryl Reilly, U.S. 

EPA. Withdrawal of the Petition for an exemption from the requirement of a tolerance for residues of products 

containing the active ingredient “Paecilomyces fumosoroseus strain FE 9901” in or on all food commodities. 

February 17, 2011. 

U.S. EPA. 2002. Product Properties Test Guidelines: OPPTS 830.6317—Storage Stability. U.S. EPA. EPA 

712-C-02-026. June 2002. 

U.S. EPA. 2008. Letter from Sheryl Reilly, U.S. EPA to Heather Bjornson, Technology Sciences Group Inc. 

(TSG). Biopesticides and Pollution Prevention Division (BPPD) response to summary of the January 22, 2008 

pre-registration meeting to discuss registration of a new microbial active ingredient, Paecilomyces fumosoroseus

strain FE 9901 blastospores. September 3, 2008. 

U.S. EPA. 2010a. Letter from Letter from Sheryl Reilly, U.S. EPA to Heather Bjornson, Technology Sciences 

Group Inc. Data Deficiencies for Paecilomyces fumosoroseus strain FE 9901. April 21, 2010. 

U.S. EPA. 2010b. Memorandum from Ibrahim Barsoum to Kathleen Martin. Joint Review of data for the 

registration of a new TGAI, NoFly Technical, and a new end use product formulation, NoFly Wettable Powder, 

containing the fungus Paecilomyces fumosoroseus strain FE 9001. September 15, 2010. 

U.S. EPA. 2011. Memorandum from Ibrahim Barsoum to Anna Gross. Review of the Registrant's response to 

the data deficiencies found by the Agency in its review of product chemistry, manufacturing process of two 

products: NoFly Technical and NoFly WP containing the new AI Paecilomyces fumosoroseus strain FE 9001. 

January 28, 2011. 
A‐1

APPENDIX A:  Data Requirements and How the Applicant Met Them

In reviewing its data, EPA’s Office of Pesticide Programs classifies each study as either ‘Acceptable,’

Supplemental,’ ‘Supplemental:  Upgradable,’ or ‘Unacceptable.’  An Acceptable study is one that the Agency

concludes is scientifically sound and is useful for risk assessment.  A Supplemental study is one that may provide

some information that can be useful in risk assessment; often a study is classified as Supplemental because it

was not required under 40 CFR 158.  A ‘Supplemental:  Upgradable’ study is one that has the potential to be

upgraded to Acceptable, provided certain addition information is submitted.  Finally, an Unacceptable study is

one that is not useful for risk assessment purposes.

Product Analysis.  Provided in Table A‐1 is a summary of the Product Analysis data requirements for

microbial pesticides (40 CFR 158.2120) with information regarding how the requirement was met.  Note that

four requirements—Analysis of samples; Stability to normal and elevated temperatures, metals and metal ions;

Storage stability; and Corrosion characteristics—need to be completed as terms of registration.    

Table A‐1.  Product Analysis Data Requirements for Paecilomyces fumosoroseus strain FE 9901 (EPA 2010b)

OPPTS

Guideline

Number

Data Requirement

HOW THE REQUIREMENT WAS MET3(Conclusion, Review, Notes, MRID)

End‐Use Product (73314‐A) Manufacturing‐Use Product (73314‐T)

Product Chemistry and Composition

885.1100 Product Identity Acceptable study (477919‐01) Acceptable study (477920‐01)

885.1200 Manufacturing Process Acceptable study (477919‐01) Acceptable study (477920‐01)

Deposition of a sample in a

nationally recognized culture

collection

A pure culture of P. fumosoroseus strain FE 9901 was deposited in the U.S. Department of

Agriculture’s Agricultural Research Service Collection of Entomopathogenic Fungal Cultures

(USDA ARS) under the accession number ARSEF 4490 (MRID 477920‐01).

885.1300 Discussion of formation of

unintentional ingredients

Acceptable study (477919‐01) Acceptable study (477920‐01)

Analysis and Certified Limits

885.1400 Analysis of samples Supplemental:  Upgradable1(477919‐01) Supplemental:  Upgradable1 (477920‐01)

885.1500 Certification of limits Acceptable study (477919‐01) Acceptable study (477920‐01)

Physical and Chemical Characteristics

830.6302 Color Acceptable study (477919‐01) Acceptable study (477920‐01)

830.6303 Physical state Acceptable study (477919‐01) Acceptable study (477920‐01)

830.6304 Odor Acceptable study (477919‐01) Acceptable study (477920‐01)

830.6313 Stability to normal and

elevated temperatures,

metals and metal ions

Term of registration Acceptable study (480514‐01)

830.6317 Storage stability Unacceptable study2 (477919‐02) Term of registration

830.6319 Miscibility   Only required for emulsifiable liquid forms of microbial pesticides.  Because this product is a

solid, this requirement does not apply.

830.6320 Corrosion characteristics Term of registration

830.7000 pH Acceptable study (477919‐01) Acceptable study (477920‐01)

830.7100 Viscosity Only required for liquid forms of microbial pesticides.  Because this product is a solid, this

requirement does not apply.

830.7300 Bulk density Acceptable study (477919‐01) Acceptable study (477920‐01) 1

A five‐batch analysis of EP and MP from the proposed manufacturing site must be submitted as a term of registration.   

2

As a term of registration, the applicant must conduct a storage stability study using the proposed formulation of NoFlyTM WP, from the

proposed manufacturing site.  The study must support a storage period of at least six months. 

 
A‐2  

Toxicology.  Provided in Table A‐2 is a summary of the Tier I Toxicology Data Requirements  

(40 CFR 158.2140) along with an explanation regarding how the requirement was met.  Toxicology testing was

limited to Tier I because the acute toxicity of P. fumosoroseus strain FE 9901 did not trigger the Tier II or III

studies.  

Table A‐2.  Tier I Toxicology Data Requirements for Paecilomyces fumosoroseus strain FE 9901 (EPA 2010b)

OPPTS  

Guideline  

Number

Data  

Requirement

HOW THE REQUIREMENT WAS MET3(Conclusion, Review, Notes, MRID)

End‐Use Product (73314‐A) Manufacturing‐Use Product (73314‐T)

870.1100 Acute oral toxicity Acceptable study (477919‐03) Acceptable study (477920‐02)  

870.1200 Acute dermal toxicity Acceptable study (477919‐04) Acceptable data waiver (477920‐06)

870.1300 Acute inhalation toxicity Acceptable study (477919‐05) Acceptable data waiver (477920‐06)

870.2400 Acute eye irritation Acceptable study (477919‐06) Acceptable data waiver (477920‐06)

870.2500   Primary dermal irritation Acceptable study ( 477919‐07) Acceptable data waiver (477920‐06)

885.3050 Acute oral toxicity/ pathogenicity TGAI:  Acceptable study (477920‐02; 477920‐03; 480514‐01)

885.3150 Acute pulmonary

toxicity/pathogenicity

TGAI:  Acceptable study (477920‐04; 477920‐06)

885.3200 Acute injection toxicity/pathogenicity TGAI:  Supplemental study; additional information is needed.1 (477920‐05)

885.3400 Hypersensitivity incidents Acceptable statement (480514‐02)

885.3500 Cell culture Data must be submitted only for products whose active ingredient is a virus;  

P. fumosoroseus is a fungus, therefore this requirement does not apply. 1

As a term of registration, EPA requires that the applicant submit data showing  microbial

clearance from matrices other than blood (e.g., organs, body fluids).   

3

See EPA 2010b for the data review.

Environmental Fate and Ecotoxicity.  Provided in Table A‐3 are explanations regarding why

environmental fate and ecotoxicity data were not required (40 CFR 158.2150).  

Table A‐3.  Tier I Nontarget Organisms and Environmental Fate Data Requirements  

for Paecilomyces fumosoroseus strain FE 9901  

OPPTS  

Guideline  

Number

Data Requirement How the Requirement Was Met (EPA 2010b)

885.4050 Avian oral toxicity Tests for pesticides intended solely for indoor application would be required on a

case‐by‐case basis...  In a letter to the applicant, EPA pointed out that if “the

intended use sites are restricted to indoors, then neither a honey bee study nor

other non‐target assessments are likely to be needed” (EPA 2008).

885.4100 Avian inhalation toxicity/pathogenicity

885.4150 Wild mammal toxicity/pathogenicity NR1 for greenhouse uses.

885.4200 Freshwater fish toxicity/ pathogenicity Tests for pesticides intended solely for indoor application would be required on a

case‐by‐case basis...  In a letter to the applicant, EPA pointed out that if “the

intended use sites are restricted to indoors, then neither a honey bee study nor

other non‐target assessments are likely to be needed” (EPA 2008).

885.4240 Freshwater invertebrate toxicity/

pathogenicity

885.4280 Estuarine/Marine fish testing; estuarine

and marine invertebrate testing

NR1 for greenhouse uses.

885.4300 Nontarget plant testing NR1 for greenhouse uses.

885.4340 Nontarget insect testing Tests for pesticides intended solely for indoor application would be required on a

case‐by‐case basis...  In a letter to the applicant, EPA pointed out that if “the

intended use sites are restricted to indoors, then neither a honey bee study nor

other non‐target assessments are likely to be needed” (EPA 2008).

885.4380 Honey bee testing

1

NR=not required under 40 CFR 158
B‐1

APPENDIX B:  Biology and Taxonomy of P. fumosoroseus and strain FE 9901

Provided below are additional biologic and taxonomic considerations.  Unless otherwise noted, the

source of the information is from the information submitted to support the registration of this new active

ingredient.  

Biology.  P. fumosoroseus is a naturally occurring fungus.  It is found in most countries of the world and

occurs in various soil types, at very low densities.  For example, it has frequently been isolated from

lepidopteran cadavers in Europe.  Isolates occur in the Netherlands, Ireland, and Spain.  And, it has been found

in various non‐European countries such as China, Japan, Ghana, Pakistan, India, and the United States.  In the

environment, P. fumosoroseus is dispersed as conidia, which are supported on conidiophores.  The

conidiophores are erect and can be about 100 μm in length and 1.5 to 2.0 μm in width (MycoBank 2010).  The

conidial structures consist of single phialides or in whorls occurring irregularly along aerial hyphae.   

Investigators have found that P. fumosoroseus strain FE 9901 grows best at 24.5oC (76.1oF).  When

grown on potato dextrose agar, P. fumosoroseus strain FE 9901 is floccose (i.e., it is covered with tufts of soft

hair) with a circular margin.  Colonies are white, often turning pale yellow from the margin out and changing to

brownish‐gray when forming conidia.  Colonies reach a diameter of 25 to 30 mm after seven days and 50 to 65

mm after 14 days.  (Brown and Smith 1957).  P. fumosoroseus has an asexual life cycle.  However, exposure to

ultraviolet light results in formation of auxotrophic mutants, suggesting that a parasexual life cycle also exists for

the organism (Riba and Ravelojoana 1984).   

Taxonomy.  The taxonomic classification P. fumosoroseus is provided below (Catalog of Life 2010).  For a

detailed explanation of the taxonomic designation, refer to the product characterization data review (EPA

2010b).  

Kingdom:    Fungi

Phylum:    Ascomycota

Class:    Eurotiomycetes

Order:    Eurotiales

Family:    Trichocomaceae

Genus: Paecilomyces  

Species: fumosoroseus

Strain: FE 9901

The strain FE 9901 is a wild type—it is neither a spontaneous nor an induced mutant and it has not been

genetically modified.  P. fumosoroseus strain FE 9901 was first isolated from an adult of Bemisia tabaci

(a species of whitefly) in Padappai, India in 1992.   

   Synonyms.  P. fumosoroseus, a mycoinsecticide, was first described by Wize in 1904 (Brown and

Smith 1957).  Synonyms (basionym, obligate, and taxonomic) for this fungus include (MycoBank 2010,

EPA 2010b).   

Isaria fumosorosea (basionym; first described by Wize in 1904),  

Spicaria fumosorosea (obligate synonym; Wize),  

Spicaria aphodii (Vuillemin in 1910),  

Penicillium aphodii (Vuillemin),  

Monilia aquatilis (Malguth, in 1928),  

Paecilomyces hibernicus (Kennelly & Grimes, in 1930), and  

Paecilomyces isarioides (Inagaki, in 1962).   
C‐1  

APPENDIX C:  Summary of Submitted Toxicity Studies  

Oral (OPPTS 870.1100; MRID 477919‐03).  Following the Up‐and‐Down Method (OECD Guideline 425),

three female Sprague‐Dawley rats were gavaged with P. fumosoroseus strain FE 9901(containing 2×109 colony

forming units per gram, or CFU/g) at a dose of 5,000 mg/kg bw.  Investigators terminated the study following

the stopping rules for this procedure.  Each animal was then observed for a period of up to 14 days.  None of the

animals died or showed any symptoms of intoxication following treatment.  The test material had no negative

effect upon the body weight, and no gross pathological changes were noted.  Based on the results of this study,

the oral LD50 is >5,000 mg/kg bw (which is the limit dose).  According to the regulations at 40 CFR 156.62, the

Acute Toxicity Category is IV.   

Dermal (OPPTS 870.1200; MRID 477919‐04).  A group of seven‐week‐old Sprague‐Dawley rats (five/sex)

was exposed dermally to P. fumosoroseus strain FE 9901(containing 2×109 CFU/g) at a limit dose of 5,050 mg/kg

bw for 24 hours to an area of not less than 10% of the total body surface.  Following exposure, the animals were

observed for a period of 14 days.  No mortalities were observed, and all the test animals appeared normal for

the duration of the study.  Very slight erythema and discoloration was observed in one female.  At necropsy, two

male rats had pale lungs at study termination.  Based on these results, the dermal LD50 is 5,050 mg/kg bw; the

Acute Toxicity  

Category is III.   

Inhalation (OPPTS 870.1300; MRID 477919‐05).  A group of 10‐week‐old Sprague‐Dawley rats (five/sex)

was exposed via the inhalation route to P. fumosoroseus strain FE 9901 (containing 2×109 CFU/g) for four hours

to nose only at a concentration of 2.18 mg/L (the limit dose is 2 mg/L).  Animals then were observed for 14 days.  

No mortalities were observed; clinical observations included piloerection and decreases in activity which both

resolved by Day 3.  All test animals gained body weight throughout the study period, and no observable

abnormalities were observed at gross necropsy.  Based on the findings of this study, the LC50 is >2.18 mg/L; the

Acute Toxicity Category is III.   

Eye Irritation (OPPTS 870.2400; MRID 477919‐06).  In a primary eye irritation study, 0.1g of NoFlyTM WP

(containing 88% P. fumosoroseus strain FE 9901) was instilled into the conjunctival sac of the left eye of three

adult male New Zealand White rabbits.  The treated eyes were not washed following application.  The untreated

right eye of each test animal served as a negative control.  Test animals then were observed for 72 hours.  

Irritation was scored by the Draize Method.  After one hour, some redness was observed in one rabbit, and

slight to moderate increases in excretion discharge were noted in three rabbits.  All test animals were free of

irritation at the 24‐, 48‐ and 72‐hour observation timepoints.  Based on the results of this study, NoFlyTM WP is

slightly irritating to the eyes of New Zealand White rabbits.  EPA determined that the Acute Toxicity Category is

IV.   

Primary Dermal Irritation (OPPTS 870.2500; MRID 477919‐07).  In a primary dermal irritation study,

three adult male New Zealand White rabbits were dermally exposed to 0.5g NoFlyTM WP (containing 88% P.

fumosoroseus strain FE 9901) in water for four hours to an area of skin of approximately six cm2

.  Animals then

were observed for 72 hours.  Irritation was scored by the method of Draize.  Very slight erythema was noted in

two test animals one hour after patch removal.  All test animals were free of irritation at the 24‐, 48‐ and 72‐

hour observation timepoints.  Based on the results of this study, NoFlyTM WP is slightly irritating to the skin of

male New Zealand White rabbits.  EPA determined that the Acute Toxicity Category is IV.   

   
C‐2  

Oral toxicity/pathogenicity (OPPTS 885.3050; MRID 47720‐02).  In an acute oral toxicity/pathogenicity

study, groups of fasted, young Wistar rats (15/sex) were given NoFlyTM Technical (1.0×109 CFU/g) in a single dose

of 100 mg of test material per animal, each dose contained 108 CFU.  The animals were then observed for a

period of up to 21 days with scheduled sacrifices 24 hours after application and on Days 3, 7, 14 and 21.  None of

the animals died, and no clinical observations were noted during the study period.  No gross pathological

changes were noted in sacrificed test animals.  Based on the findings of this study, P. fumosoroseus strain FE

9901 is not considered infective or pathogenic in the rat.  In terms of an LD50, the animals showed no signs of

toxicity at a dose of 600 mg/kg bw.5

  

Pulmonary toxicity/pathogenicity (OPPTS 885.3150; MRID 47720‐04).  In an acute pulmonary infectivity

and toxicity study, groups of young adult ferrets (14/sex) were exposed by the intranasal route to NoFlyTM

Technical at a nominal dose of 1×108 CFU (in 0.5 mL) per animal.  Animals were then observed for up to 21 days.  

None of the animals died or showed any symptoms of intoxication following treatment.  No gross pathological

changes were noted.  Microbiological examination of lungs, other prescribed organs, and body fluids proved

minimal persistence and no infectivity of the test material.  Based on the results of this study, P. fumosoroseus

strain FE 9901 is not considered infective or pathogenic in the ferret.  Please note that the rat is the preferred

species for acute pulmonary toxicity.pathogenicity testing.  For this MPCA, the applicant provided acceptable

justification for using ferrets instead of rats.   

Acute injection toxicity/pathogenicity—intraperitoneal (OPPTS 885.3200; MIRD 47720‐05).  In an acute

intraperitoneal infectivity study, a group of young adult Wistar rats (three/sex) were injected with NoFlyTM

Technical (1.0×109 CFU/g) in a single dose of 107 CFU per animal.  Animals were then observed for up to 21 days.  

None of the animals died or showed any symptoms of intoxication after treatment.  The test item had no

negative effect upon the body weight, and no gross pathological changes were noted.  Blood samples were

collected during necropsy to evaluate clearance.  Based on the available results from the study, P. fumosoroseus

strain FE 9901 is not considered infective or pathogenic in the rat via the intraperitoneal route of exposure.  As a

term of registration, EPA is requiring that the applicant submit data showing microbial clearance from matrices

other than blood (e.g., organs, body fluids).   

Hypersensitivity incidents (OPPTS 885.3400; MRID 480514‐02).  The applicant stated reported that no

hypersensitivity incidents have been reported through the research, development, and testing of NoFlyTM

Technical or WP.  However, the EP has been found to be a dermal sensitizer (EPA 2010b).  In addition, a

literature search of the PubMed database www.ncbi.nlm.nih.gov/pubmed) using the keywords “paecilomyces”

and “allergy” revealed 21 reports of hypersensitivity.  Based on the assumption that most microorganisms

contain substances that would elicit allergic reactions,  

P. fumosoroseus strain FE 9901 is considered a potential sensitizing agent.  

Supplemental Toxicity Test

Skin Sensitization.  In a skin sensitization test (477919‐08) using the Magnusson and Kligman Method,

female guinea pigs were exposed to NoFlyTM WP that was administered as a 1% intradermal injection and a 25%

topical application.  Later, a challenge dose was applied (25% topical application).  Study investigators observed

a localized area of intense erythema and swelling in treated animals.  EPA concluded that NoFlyTM WP is a skin

sensitizer.   

 

5 600mgNoFlyTMTechnical

0.163 kg bw

100mg NoFlyTMTechnical 