Proposed Regulatory Decision for the First Food Use of 

Is aria f umosorosea strain FE 9901 

(formerly Paecilomycesfumosoroseus strain FE 9901) 

Approved by: 

Date: 
Page 2 of 8

1. Summary

This document announces that the U.S. Environmental Protection Agency (EPA) has completed 

its initial evaluation of the proposed first food use of the currently registered active ingredient 

Isaria fumosorosea strain FE 9901, a microbial insecticide, and has concluded that this new use1

meets the regulatory and safety standards under the Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA). Therefore, EPA is proposing, under FIFRA section 3(c)(5), to amend 

the registrations of pesticide products containing Isaria fumosorosea strain FE 9901 to include 

food uses. EPA is seeking public comment on its proposed regulatory decision.

2. Background

On May 12, 2011, EPA issued registrations to Natural Industries, Incorporated (Natural 

Industries) for a manufacturing-use pesticide product (NoFly Technical, EPA Reg. No. 73314-7)

and an end-use pesticide product (NoFly WP, EPA Reg. No. 73314-6). Both products contained 

the new active ingredient Paecilomyces fumosoroseus strain FE 9901 (now known as Isaria 

fumosorosea strain FE 9901), an entomopathogenic fungus (i.e., a type of fungus that can act as a 

parasite of insects and kills or seriously disables them) that was isolated from an adult of Bemisia 

tabaci (a species of whitefly) in Padappai, India in 1992. NoFly WP could be used only on 

nonfood greenhouse and nursery crops to control certain insects such as aphids, weevils, and 

whiteflies. Natural Industries subsequently became Novozymes BioAg, Incorporated 

(Novozymes).

In 2012, EPA opened a registration review case for Paecilomyces, and this case included Isaria 

fumosorosea strain FE 9901.2 In a Final Work Plan dated March 27, 2013, EPA identified the 

following as data gaps for Isaria fumosorosea strain FE 9901:

(1) Stability to Normal and Elevated Temperatures, Metals, and Metal Ions (Guideline 830.6313)

(2) Storage Stability (Guideline 830.6317)

(3) Corrosion Characteristics (Guideline 830.6320)

Novozymes addressed these registration review data gaps with two letters (dated July 22, 2013) 

and with data submitted to support the new use applications described in the paragraph that 

follows.

On July 26, 2013, EPA received applications from Novozymes to amend the NoFly Technical 

and NoFly WP registrations to add food (e.g., fruiting and leafy vegetables) and outdoor uses. 

Along with these applications, Novozymes submitted a petition to establish a tolerance 

exemption for Isaria fumosorosea strain FE 9901 for all food commodities. In December 2015, 

Novozymes amended its applications to remove the request to add outdoor uses to the NoFly 

Technical and NoFly WP registrations. The NoFly Technical and NoFly WP registrations and 

supporting data were transferred to FuturEco Bioscience, S.A. (FuturEco) on March 7, 2016. As 

a result of the transfer, the NoFly Technical and NoFly WP registrations are now recognized by 

EPA Registration Numbers 88664-2 and 88664-1, respectively.

 1 In accordance with the definition in 40 CFR § 152.3, this action is considered a “new use” under the Federal 

Insecticide, Fungicide, and Rodenticide Act because it involves a “proposed use pattern [that requires] . . . the 

exemption from the requirement of a tolerance . . . under section 408 of the Federal Food, Drug and Cosmetic Act.”

2 Please see the registration review docket for Paecilomyces (EPA-HQ-OPP-2012-0403) at www.regulations.gov.
Page 3 of 8

3. Evaluation

In evaluating a pesticide application, EPA assesses a wide variety of studies to determine the 

likelihood of adverse effects (i.e., risk) from exposures associated with the proposed use of the 

product. Risk assessments are developed to evaluate how the compound might affect a wide 

range of nontarget organisms, including humans and terrestrial and aquatic wildlife (plants and 

animals). Based on these assessments, EPA evaluates and approves language for each pesticide 

label to ensure the directions for use and safety measures are appropriate to mitigate any 

potential risk. In this way, the pesticide’s label helps to communicate essential limitations and 

mitigations that are necessary for public and environmental safety. In fact, the pesticide law has a 

provision that indicates it is a violation to use a pesticide in a way that conflicts with the label.

3.1 Assessment of Risk to Human Health

To assess risks to human health from use of microbial pesticides, EPA typically requires a wide 

range of studies, including Tier I acute toxicity/pathogenicity data (oral, pulmonary, and 

injection), cell culture data, reports of hypersensitivity incidents, acute toxicity data (oral, 

dermal, and inhalation), and irritation data (dermal and eye). Tier II and III testing (e.g., 

subchronic toxicity/pathogenicity) is triggered only when there is indication, usually through 

lower tier testing, that a microbial pesticide has unusual toxicological characteristics such as 

infectivity or being suspected or known to be a carcinogen. For Isaria fumosorosea strain FE 

9901, the database of studies required to support the assessment of risk to human health is 

complete.

A. Toxicology Data/Information

FuturEco cited to previously submitted studies and scientific rationale and provided new data to 

address the microbial pesticide toxicology data requirements (40 CFR § 158.2140). 

Toxicity, Irritation, and Toxicity/Pathogenicity Testing – A toxicity test (acute oral toxicity) that 

addresses a potential route of exposure to Isaria fumosorosea strain FE 9901 is classified in 

Toxicity Category III3 and reveals no toxicity attributed to this microbial active ingredient. EPA 

waived acute dermal toxicity, acute inhalation toxicity, acute eye irritation, and primary dermal 

irritation testing for Isaria fumosorosea strain FE 9901, upon consideration of scientific 

rationale. Isaria fumosorosea strain FE 9901 does not grow at or above 35°C (normal human 

body temperature is 37°C), and there have been no reports of Isaria fumosorosea strain FE 9901 

infecting any organisms other than arthropods. Further, testing done with NoFly WP (active and 

inert ingredients) did not cause any dermal or inhalation toxicity and was only slightly irritating 

to the skin and eyes of the test animals. EPA believes this information, considered collectively,

indicates that this fungus would not be toxic through the dermal or inhalation routes of exposure 

or irritating to the skin or eyes and that further testing is not necessary. Lastly, during typical 

toxicity/pathogenicity testing done with microbial pesticides, Isaria fumosorosea strain FE 9901 

showed no toxicity, no pathogenicity, and no infectivity via the oral, pulmonary, and injection 

routes of exposure.

Hypersensitivity Incidents – Although no hypersensitivity incidents were reported to have 

occurred during research, development, and testing of Isaria fumosorosea strain FE 9901, EPA 

found 21 reports of hypersensitivity attributed to microorganisms of the genus Paecilomyces

 3 See Section II(B), Chapter 7 of the Label Review Manual for an explanation of the Toxicity Categories.
Page 4 of 8

(species not specified) in the literature, and testing with NoFly WP indicated this product is a 

sensitizer. Given the potential for Isaria fumosorosea strain FE 9901 to be a sensitizing agent, 

applicators and other handlers are directed to wear personal protective equipment that covers the 

skin (e.g., gloves) and advised of sensitizing potential with the following precautionary 

statement: “Prolonged or frequently repeated skin contact may cause allergic reactions in some 

individuals.”

Other Data – Isaria fumosorosea strain FE 9901 is capable of producing toxic metabolites during 

the manufacturing process. The suite of mammalian studies conducted with Isaria fumosorosea

strain FE 9901 (described above and in more detail in the supporting documents) showed no 

toxicity, confirming that metabolites that may be formed are not of toxicological concern.

B. Exposure

No adverse effects of concern were observed in toxicological testing done with Isaria 

fumosorosea strain FE 9901; therefore, EPA did not conduct a quantitative exposure assessment.

Food Exposure – EPA believes exposure to residues of Isaria fumosorosea strain FE 9901 in 

consumed food is possible. For suppression of several insect pests, Isaria fumosorosea strain FE 

9901 can be applied to numerous food crops (e.g., fruiting and leafy vegetables) by both foliar 

and soil applications up to and including the day of harvest. Once treated food commodities are 

removed from indoor facilities (e.g., after harvest) where the conditions may be more stable and 

conducive to fungal growth, fluctuating environmental factors, such as sunlight and temperature, 

would likely reduce residues of Isaria fumosorosea strain FE 9901 on food commodities. For 

instance, a study in the public literature evaluated effects of solar radiation on Paecilomyces 

fumosoroseus (= Isaria fumosorosea) and found that both ultraviolet-B (280–320 and 295–320 

nanometers) and ultraviolet-A (320–400 nanometers) were most detrimental to the germinability, 

survival, and infectivity of this fungus’ conidia. In addition to exposure to unfavorable 

conditions, processing procedures (e.g., peeling and washing) may also reduce Isaria 

fumosorosea strain FE 9901 residues on food commodities. Should Isaria fumosorosea strain FE 

9901 be present in or on food, supporting toxicological information indicates that human 

exposure to this fungus would not result in adverse effects.

Drinking Water Exposure – EPA does not expect residues of Isaria fumosorosea strain FE 9901 

in drinking water. This fungus will be applied indoors and not in places where it could readily 

contaminate open bodies of water through runoff or spray drift. Isaria fumosorosea strain FE 

9901 could inadvertently enter wastewater from indoor facilities through handling or application 

of the pesticide. In the event that such wastewater flows into surface waters, Isaria fumosorosea

strain FE 9901 is not expected to persist as this fungus does not thrive in the presence of 

sunlight. If Isaria fumosorosea strain FE 9901 were to somehow persist and be transferred to 

ground waters, it likely would not survive the conditions water is subjected to in wastewater 

treatment systems and drinking facilities (e.g., pH adjustments and chlorination). Should Isaria 

fumosorosea strain FE 9901 be present in drinking water, supporting toxicological information 

indicates that human exposure to this fungus would not result in adverse effects.

Non-occupational Exposure (Besides Dietary) – NoFly WP is labeled for applications within 

commercial greenhouses and indoor commercial nursery areas. EPA does not expect that the 

general population will be exposed to Isaria fumosorosea strain FE 9901. 
Page 5 of 8

Occupational Exposure – EPA expects occupational exposure to Isaria fumosorosea strain FE 

9901 to be low, as applicators and handlers must follow precautions and wear personal protective 

equipment (PPE) described on the NoFly WP label. Based on toxicological data/information, 

applicators and other handlers will be required to wear a long-sleeved shirt, long pants, shoes, 

socks, gloves, protective eyewear, and a National Institute for Occupational Safety and Health 

(NIOSH)-approved particulate or air purifying respirator with the appropriate filter. The PPE 

covering the skin (e.g., gloves and long-sleeved shirt) and covering the nose and mouth (e.g., 

respirator) will ensure that applicators and handlers, who may work with NoFly WP for 

prolonged periods of time and/or on several different occasions, are protected from possible 

sensitization.

C. Conclusions

EPA does not expect dietary (food and drinking water), other non-occupational, or occupational 

risks from the addition of food uses to the Isaria fumosorosea strain FE 9901 pesticide product 

registrations.

For more information on the human health risk assessment of Isaria fumosorosea strain FE 9901, 

please see the supporting documents contained in the associated regulatory dockets (search for 

“EPA-HQ-OPP-2014-0330” and/or “EPA-HQ-OPP-2010-0093” at www.regulations.gov).

3.2 Assessment of Ecological Risk 

To assess risks to the environment from use of microbial pesticides, In order to assess a 

microbial pesticide’s risk to the environment, EPA typically requires a wide range of studies, 

including Tier I testing done on the following nontarget organisms: birds (oral and inhalation), 

mammals, freshwater fish and invertebrates, estuarine/marine fish and invertebrates, plants, 

insects, and honeybees. Higher tier testing (II, III, and IV) generally encompasses definitive 

hazard determinations and longer term greenhouse or field testing and is implemented only when 

unacceptable effects are seen at the Tier I screening level.

The nontarget organism and environmental fate data requirements table for microbial pesticides 

(40 CFR § 158.2150) explains that EPA does not require certain data (e.g., wild mammal 

toxicity/pathogenicity testing) for indoor or greenhouse4 uses and may require certain data (e.g., 

freshwater aquatic invertebrate toxicity/pathogenicity testing) for these same uses on a case-bycase basis. For the registration of the Isaria fumosorosea strain FE 9901 pesticide products in 

2011, EPA did not require nontarget organism data to be submitted because exposure to 

nontarget organisms was expected to be limited given the uses (i.e., applications to nonfood 

greenhouse and nursery crops). EPA alluded to this approach in a September 3, 2008, letter to 

the applicant at the time (Natural Industries) by stating the following: “If the intended use sites 

are restricted to indoors, then neither a honey bee study [nor] other nontarget assessments are 

likely to be needed.”

With the current action, FuturEco is proposing that NoFly WP be labeled solely for use on 

greenhouse plants, on nursery crops grown indoors, or on food crops grown indoors. The only 

changes to the original registration is the addition of indoor food uses and clarification that the 

 4 Greenhouses are not defined in 40 CFR Part 158 (“Data Requirements for Pesticides”). But, the current Worker 

Protection Standard definition for greenhouses in 40 CFR § 170.3 is instructive with regard to the type of use site 

EPA considers a greenhouse to be: “Any operation engaged in the production of agricultural plants inside any 

structure or space that is enclosed with nonporous covering and that is of sufficient size to permit worker entry.”
Page 6 of 8

applications to nursery crops are to be done indoors. Because exposure of nontarget organisms to 

Isaria fumosorosea strain FE 9901 is still expected to be limited like the original registration and 

may actually be further reduced with the clarification that nursery crop applications are permitted 

indoors only, EPA maintains that submission of nontarget organism data are not required at this 

time. If FuturEco proposes to expand the uses of Isaria fumosorosea strain FE 9901 to include 

outdoor applications in the future, it would need to submit appropriate nontarget organism 

data/information in response to the data requirements in 40 CFR § 158.2150 and to support this

request.

Since EPA has determined that nontarget organisms are expected to have limited exposure to 

applications of Isaria fumosorosea strain FE 9901 because of the specifically prescribed indoor 

or greenhouse applications, it also makes a “no effect” determination for direct and indirect 

effects to endangered and threatened species and their habitats from the uses of Isaria 

fumosorosea strain FE 9901, as labeled.

For more information on the environmental risk assessment of Isaria fumosorosea strain FE 

9901, please see the supporting documents contained in the associated regulatory docket (search 

for “EPA-HQ-OPP-2010-0093” at www.regulations.gov).

4. Alternatives

This microbial insecticide, with the addition of indoor food uses, would augment the current 

technologies used to mitigate insect pests such as whiteflies, aphids, psyllids, thrips, fungus 

gnats, and other target insects and provide a useful tool that contributes to integrated pest 

management (IPM) programs and combats insect resistance. The alternate conventional products 

used against the same target pests and use sites as FuturEco’s NoFly WP end-use pesticide 

product that may be replaced or use of which may decrease include, but are not limited to, the 

following:

• Merit 2 Greenhouse and Nursery Insecticide (EPA Reg. No. 432-1369), containing the active 

ingredient imidacloprid (neonicotinoid);

• Merit 1 G Greenhouse and Nursery Insecticide (EPA Reg. No. 432-1329), containing the 

active ingredient imidacloprid (neonicotinoid);

• Marathon 1% Granular Greenhouse and Nursery Insecticide (EPA Reg. No. 59807-15), 

containing the active ingredient imidacloprid (neonicotinoid);

• IMI 2 LB Greenhouse & Nursery Insecticide (EPA Reg. No. 53883-232), containing the 

active ingredient imidacloprid (neonicotinoid);

• LADA 2F Insecticide (EPA Reg. No. 83100-6), containing the active ingredient imidacloprid 

(neonicotinoid);

• IMIGOLD 70 DF Turf, Ornamental, and Greenhouse Insecticide (EPA Reg. No. 70506-157), 

containing the active ingredient imidacloprid (neonicotinoid); and

• LYNX EC 1.4 (EPA Reg. No. 82074-6), containing the active ingredient pyrethrins.

Furthermore, Isaria fumosorosea strain FE 9901 will have an established exemption from the 

requirement of a tolerance (no limitations) for all food commodities; NoFly WP has a 12-hour 

restricted-entry interval; and NoFly WP is not classified as a restricted-use pesticide because of 
Page 7 of 8

human toxicity or environmental concerns; these characteristics, among others, may be appealing 

to some growers.

5. Benefits and Public Comments

Biopesticides are pesticides derived from such natural materials as animals, plants, bacteria, and 

certain minerals. Microbial pesticides, a class of biopesticides, consist of a microorganism (e.g., 

bacterium, fungus, virus, or protozoan) as the active ingredient and may have the following 

benefits:

• Usually are inherently less harmful than conventional pesticides.

• Generally affect only the target pest and closely related organisms, in contrast to broadspectrum conventional pesticides that may affect many different organisms (e.g., birds, 

insects, and mammals).

• Often effective in very small quantities and often decompose quickly, thereby resulting in 

lower exposures and largely avoiding the pollution problems caused by conventional 

pesticides.

• Can greatly decrease the use of conventional pesticides while crop yields remain high, when 

used as a component of integrated pest management programs.

• Can offer another tool for pest management in areas where pesticide resistance, niche 

markets, environmental concerns, and organic preference limit the use of conventional 

pesticides.

Like other microbial pesticides, Isaria fumosorosea strain FE 9901 aligns with a few of the 

potential benefits above as it exhibits no toxicity, is not pathogenic or infective, is not expected 

to be an eye or dermal irritant, and could fill particular needs in unique markets (e.g., organic 

production).

Overall, EPA has provided/will be providing the public three opportunities to comment on the 

Isaria fumosorosea strain FE 9901 amended registration and tolerance exemption actions.

In the Federal Register of July 21, 2014 (79 FR 42318), EPA announced receipt of applications 

to register new uses for the NoFly pesticide products that contain the active ingredient Isaria 

fumosorosea strain FE 9901 and opened a 30-day public comment period. EPA received no 

comments on this publication.

In the Federal Register of August 1, 2014 (79 FR 44729), EPA announced receipt of a petition 

that proposed to establish an exemption from the requirement of a tolerance for residues of Isaria 

fumosorosea strain FE 9901 in or on all food commodities and opened a 30-day comment period. 

EPA received no comments on this publication.

Because FuturEco’s applications involve the first food use of the active ingredient Isaria 

fumosorosea strain FE 9901, EPA is opening a 15-day public comment period in accordance 

with a policy, first implemented in October 2009, designed to provide a more meaningful 

opportunity for the public to participate in major registration actions.

6. Regulatory Decision

EPA received and reviewed a compilation of studies and information that fulfill the data 

requirements for and support the proposed new food uses of Isaria fumosorosea strain FE 9901.
Page 8 of 8

In considering the assessed risk to human health and the environment, EPA concludes that Isaria 

fumosorosea strain FE 9901 meets the regulatory and safety standards under FIFRA. Therefore, 

EPA is proposing to amend the registrations of the Isaria fumosorosea strain FE 9901 pesticide 

products under FIFRA section 3(c)(5).

Two pesticide products are proposed for amendment: NoFly Technical and NoFly WP. NoFly 

Technical is a manufacturing-use pesticide product, while NoFly WP is an end-use pesticide 

product; Isaria fumosorosea strain FE 9901 is the sole active ingredient in both pesticide 

products. In order to manage particular insect pests of greenhouse plants, nursery crops grown 

indoors, or food crops grown indoors, NoFly WP is proposed for application to plant foliar 

surfaces or soil through conventional spraying equipment or irrigation systems. For plants grown 

without soil, NoFly WP is proposed for application through hydroponics systems. The 

application rates vary depending upon how the pesticide is used and can be found on the 

proposed NoFly WP label in the docket (EPA-HQ-OPP-2014-0330).

The risk assessments and other documents supporting this proposed decision can be found in the

associated regulatory dockets (search for “EPA-HQ-OPP-2014-0330” and/or “EPA-HQ-OPP2010-0093” at www.regulations.gov).