## 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 use 1 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
th e 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 produc ts 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 Industrie s 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
follo wing as data gaps for Isaria fumosorosea strain FE 9901:

(1) Stability to Normal and Elevated Temperatures, Metal s , 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 letter s ( 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 re ceived applications from Novozymes t o amend the NoFly Technical and NoFly WP registration s 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 990 1 for all food commodities. In December 2015, Novozymes amende d 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 transferre d to FuturEco Bioscience, S.A. (FuturEco) on March 7, 2016. As a result of the transfer, t he 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 invo lves 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 eval uating 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 a ssessments are develop ed to evaluate how the compound m ight affect a wide range of non target organisms

, including humans and terrestrial and aquatic wildlife (plants and animals)

. Based on these assessments, EPA evaluates and approves language for e ach pesticide label to ensure the directions for use and safety measures are appr opriate to mitigate any potential risk. In this way, the pesticide’s label helps to communicate essential limitations and mitigations that ar e 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

T o assess risks to human health from use of microbial pesticide s , EP A 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 t oxicity data (oral, dermal, and inhalation), and irritation data (dermal and eye)

. Tier II and III testing (e.g.,
subchronic toxi city/pathogenicity) is triggered only when there is indication, usually through lower tier testing, that a micr obial pesticide has unusua l toxicological characteristics such as infectivity or being suspected or known to be a carcin ogen. For Isaria fumosoro sea strain FE
9901

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

A. Toxicol ogy 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 Testin g

– A toxicity test (acu te oral toxicity) that addresses a potential route of exposure to Isaria fumosorosea strain FE 9901 is classified in Toxicity Category III 3 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 (nor mal 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 inhalatio n 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, d uring typical toxicity/pathogenicity testing done with microbial pesticides, Isaria fumosorosea strain FE 9901 showed no toxicity, no pathogenicity, and no infectivity via the oral, pulm onary, and injection routes of exposure.

Hypersensitivity Incidents

– A lthough 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 frequent ly repeated skin contact may cause allergic reactions in some
individuals.”

Other Data

– Isaria fumosorosea strain FE 9901 is capable of producing toxic metaboli tes during the manufacturing process

. T he suite of mammalian studies conducted with Isaria fumosorosea strain FE 9901 (described above and in more detail in the supporting documents ) showed no toxicity

, confirm ing 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 ar e 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
in stance, a study in the p ublic 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 99 01 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 no t 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 i nadvertently 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., p H 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 (Beside s 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,

a pp licators 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 a ppropriate 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 dieta ry (food and drinking water), other non

- occupational , or occupational
risks from the addition of food uses to the Isaria fumosorosea strain FE 9901 pestici de product registrations

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

, please see the supporting documents contained in t he associated regulatory docket s (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 require s a wide range of studies, including Tier I testing done on the following nontarget organisms: bi rds (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 an d is implemented only when unacceptable effects are seen at the Tier I screening level.

T he 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 greenhouse 4 uses and may require certain data (e.g., freshwater aq uatic invertebrate toxicity/pathogenicity testing) for these same uses on a case

- by

case 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 ex posure to nontarget organism s 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 t he following: “ I f 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
Protectio n Standard definition for greenhouses in 40 CFR § 170.3 is instructive with regard to the type of use site EPA considers a greenh ouse to be: “A ny operation engaged in the production of agricultural plants inside any structure or space that is enclosed with nonporous covering and that is of sufficie nt size to permit worker entry.”Page 6 of 8 applications to nursery crops are t o 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 per mitted 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 futu re, 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.

S ince EPA has det ermined that nontarget organisms are expected to have limited exposure to applications of Isaria fumosorosea strain FE 9901 because of the specifically pres cribed 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 insecti cide , 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

manageme nt (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 , b ut are not limited to, the following:

• Merit 2 Greenhouse and Nursery Insecticide (EPA Reg. No. 432

- 1369), containing the active ingredient imidacloprid (neonic otinoid);

• Merit 1 G Greenhouse and Nursery Insecticide (EPA Reg. No. 432

- 1329), containing the active ingredient imidacloprid (neonicotino id);

• Marathon 1% Granular Greenhouse and Nursery Insecticide (EPA Reg. No. 59807

- 15), containing the active ingredient imidacloprid (neonicotino id);

• IMI 2 LB Greenhouse & Nurs ery Insecticide (EPA Reg. No. 53 883

- 23 2), containing the active ingredient imidacloprid (neonicotino id);

• 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 i s not classified as a restricted

- use pesticide because ofPage 7 of 8 human toxicity or environmental concerns ; t hese 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 t he following
benefits :

• Usually are inherently less harmful than conventional pesticides

.

• Generally affect only the target pest and closely related organisms , in contrast to broad

spectrum 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 poll ution problems caused by conventional pesticides

.

• C an greatly decrease the use of convent ional 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 wh ere pesticide resistance, niche markets, environmental concerns, and organic preference limit the use of conventional pesticides.

Like other microbial pesticides, Isaria fumosorosea strain FE 9901 align s 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 announ ced 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 n o 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 requ irement of a toleran ce 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 activ e 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 s tudies 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 ris k to human health and the environment, EPA concludes that Isaria fumosorosea strain FE 9901 meets the regulatory and safety standard s under FIFRA . Therefor e, EPA is proposing to amend the registrations of the Isaria fumosorosea strain FE 9901 pesticide

pro ducts 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 thro ugh 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 N oFly WP label in the docket (EPA

- HQ

- OPP

- 2014

- 0330).

The risk assessment s 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

- OPP

2010

- 0093 ” at www.regulations.gov ).