EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION 

COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN 

THE FEDERAL REGISTER 

EPA Biopesticides and Pollution Prevention Division contact: Jeannine Kausch, 

703-347-8920

Novozymes BioAg, Inc.

3F8193

The EPA has received a pesticide petition (3F8193) from Novozymes BioAg, Inc., 13100 

West Lisbon Road, Suite 600, Brookfield, Wisconsin 53005 requesting, pursuant to 

section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 

346a(d), to amend 40 CFR part 180 to establish an exemption from the requirement of a 

tolerance for the microbial pesticide Isaria fumosoroseus strain FE 9901 in or on all food 

commodities.

Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, Novozymes BioAg, Inc., has 

submitted the following summary of information, data, and arguments in support of their 

pesticide petition. This summary was prepared by Novozymes BioAg, Inc., and the EPA 

has not fully evaluated the merits of the pesticide petition. The summary may have been 

edited by the EPA if the terminology used was unclear, the summary contained 

extraneous material, or the summary unintentionally made the reader conclude that the 

findings reflected the EPA’s position and not the position of the petitioner.

I. Novozymes BioAg, Inc., Petition Summary

3F8193

A. Product Name and Proposed Use Practices

The intended use of Isaria fumosoroseus strain FE 9901 in the end-use product

NOFLYTM WP (EPA Reg. No. 73314-6) is as an insecticide for use on greenhouse and 

outdoor ornamentals, trees and shrubs; nursery crops; turf; production agriculture crops; 

commercial landscapes; and residential/home and garden ornamentals, plants, and lawns 

by foliar spray or soil drench application, by chemigation, and/or by seed treatment. 

Target pests include whiteflies, aphids, thrips, Psyllids, Mealybugs, and fungus gnats. 

NOFLYTM WP can be applied at 5 – 15 day intervals at rates of 1⁄2 – 2 pounds per acre or 

2 – 8 ounces per 10,000 square feet of ornamentals, trees and shrubs, nonfood crops, and 

food crops (corn, potatoes, cucurbit vegetables, fruiting vegetables, grains, cereals, 

soybeans, cotton, oil crops, herbs and spices, leafy and cole vegetables, legume 

vegetables, root and tuber/bulb vegetables, berry crops, citrus, grape, pome fruit, stone 

fruit, nuts, tropical fruit, asparagus, banana, plantain, watercress, mushroom, olive, and 

hops) up to and including the day of harvest. 
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NOFLYTM WP can be applied to golf course tees, greens, fairways, and roughs, 

commercial and residential lawns, athletic fields, parks, cemeteries, sod farms, turf 

landscapes, herbaceous and woody ornamentals, trees and plants against whiteflies, 

aphids, thrips, Psyllids, Mealybugs, and fungus gnats at rates of 1⁄2 – 2 pounds per acre or 

2 – 8 ounces per 10,000 square feet at the same application interval (5 – 15 days) as crop 

use.

For residential/home and garden use, NOFLYTM WP can be applied as a foliar spray or 

soil drench to control whiteflies, aphids, thrips, Psyllids, Mealybugs, and fungus gnats on 

fruit and vegetable plants, annual and perennial bedding plants and flowers, roses, potted 

flowers, foliage plants, trees, shrubs, and lawns every 5 – 15 days at rates ranging from 2 

– 8 tablespoons per gallon of water to 1⁄2 – 2 1⁄2 cups per 5 gallons of water.

B. Product Identity/Chemistry

1. Identity of the pesticide and corresponding residues. Isaria fumosoroseus strain 

FE 9901 is a naturally occurring fungus found in most countries around the world and 

occurs in various soil types at very low densities. The fungus has frequently been isolated 

from Lepidoptera cadavers in Europe. Isolates occur in the Netherlands, Ireland, and 

Spain. The fungus has also been found in various non-European countries, including 

China, Japan, Ghana, Pakistan, India, and the United States. It is expected that, when 

used as directed, Isaria fumosoroseus strain FE 9901 will not result in residues that are of 

toxicological concern.

2. Magnitude of residues at the time of harvest and method used to determine the 

residue. It is expected that, when used as directed, Isaria fumosoroseus strain FE 9901

will not result in residues that are of toxicological concern.

3. A statement of why an analytical method of detecting and measuring the levels 

of the pesticide residue are not needed. An analytical method for residues is not 

applicable. It is expected that, when used as directed, Isaria fumosoroseus strain FE 9901

will not result in residues that are of toxicological concern.

C. Mammalian Toxicological Profile

Studies to evaluate the safety to mammals were conducted on the technical grade active 

ingredient Isaria fumosoroseus strain FE 9901 and are summarized herein (see Table 1). 

The studies performed include toxicity/pathogenicity studies via the oral, pulmonary, and 

intraperitoneal injection pathways, as well as the conventional acute toxicity (“6-pack”) 

studies to assess acute oral, dermal, and inhalation toxicity, eye and skin irritation, and 

dermal sensitization. The oral, dermal, and inhalation routes of exposure are the routes 

relevant for human health risk assessment. The results of these studies consistently 

demonstrated that Isaria fumosoroseus strain FE 9901 was non-toxic by all routes of 

exposure and only minimally irritating. Additionally, there was no evidence of 

pathogenically observed; the product was not infective or pathogenic to test animals 

when administered via the oral, pulmonary, or intraperitoneal routes. Even though 

positive for skin sensitization, no reports of hypersensitivity have been recorded from 
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personnel working with this organism. 

Table 1. Summary of I. fumosoroseus strain FE 9901 Mammalian Toxicity Data

Test Species Dose Tested Results

Acute oral toxicity

MRID No. 47791903

Rat Gavage dose of 

5,000 mg/kg

2.0x109 CFU/g

LD50 > 5,000 mg/kg 

Category IV

Acute dermal toxicity

MRID No. 47791904

Rat Undiluted dose of 

5,050 mg/kg

2.0x109 CFU/g

LD50 > 5,050 mg/kg 

Category III

Acute inhalation 

toxicity

MRID No. 47791905

Rat 2.18 mg/L for 4 

hours

2.0x109 CFU/g

LC50 > 2.18 mg/L

Category III

Primary eye irritation

MRID No. 47791906

Rabbit 0.1 gram undiluted 

product for 24 

hours

Slightly irritating

Category IV

Dermal irritation

MRID No. 47791907

Rabbit 0.5 gram undiluted 

product for 4 hours

Slightly irritating

Category IV

Dermal Sensitization

MRID No. 47791908

Guinea Pig 1% intradermal 

injection + 25% 

topical application

Localized area of 

erythema and swelling

Positive for skin 

sensitization

Acute oral 

toxicity/pathogenicity

MRID Nos. 47792002, 

47792003, and 

48291200

Rat 100 mg of 108

CFU/rat

Non-toxic, non-infective, 

non-pathogenic

Acute pulmonary 

toxicity/pathogenicity

MRID Nos. 47792004, 

47792006, 49044301, 

and 48291200

Ferret 1.0x108(in 0.5 mL) 

CFU/ferret

Non-toxic, non-infective, 

non-pathogenic 

Acute intraperitoneal

Toxicity/pathogenicity

MRID Nos. 47792005,

49044301, and 

48291200

Rat 107 CFU/rat Non-toxic, non-infective, 

non-pathogenic

The results of toxicity testing on the organism show there is no risk to human health from 

the active ingredient. Isaria fumosoroseus strain FE 9901 is not toxic, not pathogenic, not 

infective, and only minimally irritating to mammals. Further, it is important to note that 

Isaria fumosoroseus strain FE 9901 does not grow or develop at temperatures in excess 

of 35°C (95°F) and therefore is essentially inactivated in mammalian systems.
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Literature searches have been conducted against the EPA’s list of open literature database 

searches (July 26, 2010 edition). Those searches have demonstrated that there are no 

reports of ecological or human health hazards caused by Isaria fumosoroseus strain FE 

9901. It does not produce recognized toxins, enzymes, or virulence factors normally 

associated with mammalian invasiveness or toxicity.

A special analysis was conducted across five production batches of NOFLYTM Technical 

to determine the prevalence of beauverolide metabolites, beauvericin, and 2,6-

pyridinedicarboxylic acid (PDCA) following the fermentation process. The results of this 

analysis (MRID No. 49118301) concluded that there was no quantitation of beauvericin,

and 2,6-PDCA was only quantified at levels of 1 – 10μg/g. Across the fifteen 

beauverolide peptide species analyzed, Beauverolide I was determined to be the most 

prevalent (18% of the overall peptides combined), and 100% of the peptides combined 

were well below 0.1% of NOFLYTM Technical; therefore, no metabolite formation rises 

to a level of toxicological concern. This is further confirmed due to the low toxicity 

evidenced across the suite of mammalian studies on Isaria fumosoroseus strain FE 9901. 

As has been demonstrated, dietary exposure to Isaria fumosoroseus strain FE 9901 meets 

the Food Quality Protection Act (FQPA) 1996 safety standard. Studies submitted with 

this petition showed no evidence of toxicity, pathogenicity, or infectivity when this strain 

was tested in laboratory animals.

D. Aggregate Exposure

1. Dietary exposure.

i. Food. Dietary exposure from use of Isaria fumosoroseus strain FE 9901, as 

proposed, is minimal. The intended use of Isaria fumosoroseus strain FE 9901 is to 

agricultural crops, greenhouse and outdoor food and nonfood crops, nursery crops, trees 

and shrubs, commercial turf and landscapes, and residential lawns and gardens for the 

purposes of insect control. Isaria fumosoroseus strain FE 9901 does not grow or develop 

at temperatures in excess of 35°C (95°F), and residues are not expected due to its 

degradation in sunlight and in high temperatures (MRID No. 47792001). Any remaining 

residues would be removed during common postharvest treatments, including washing, 

packing, peeling, etc.

The results of toxicity testing indicate there is no risk to human health from Isaria 

fumosoroseus strain FE 9901. There are no reports of human health hazards caused by the 

microorganism Isaria fumosoroseus. It does not produce recognized toxins, enzymes, or 

virulence factors normally associated with mammalian invasiveness or toxicity. The 

absence of acute toxicity or pathogenicity in laboratory animals demonstrates the benign 

nature of this strain. Dietary exposures would not be expected to pose any quantifiable 

risk, due to a lack of residues of toxicological concern.

ii. Drinking water. Similarly, exposure to humans from residues of Isaria 

fumosoroseus strain FE 9901 in consumed drinking water would be unlikely. Potential 

exposure to surface water would be negligible and exposure to drinking water (well or 
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ground water) would be impossible to measure. The intended use of Isaria fumosoroseus

strain FE 9901 is to agricultural crops, greenhouse and outdoor food and nonfood crops, 

nursery crops, trees and shrubs, commercial turf and landscapes, and residential lawns 

and gardens for the purposes of insect control. The risk of the microorganism passing 

through the soil to ground water is minimal to unlikely. Additionally, the fungi would not 

tolerate the conditions water is subjected to in a drinking-water treatment facility 

(including chlorination, pH adjustments, high temperatures, and/or anaerobic conditions)

(MRID No. 47792001).

The results of toxicity testing indicate there is no risk to human health from Isaria 

fumosoroseus strain FE 9901. There are no reports of human health hazards caused by the 

microorganism Isaria fumosoroseus. It does not produce recognized toxins, enzymes, or 

virulence factors normally associated with mammalian invasiveness or toxicity. The 

absence of acute toxicity or pathogenicity in laboratory animals demonstrates the benign 

nature of this strain. Drinking water exposures would not be expected to pose any 

quantifiable risk, due to a lack of residues of toxicological concern.

2. Non-dietary exposure. The potential for non-dietary exposure to the general 

population, including infants and children, is unlikely. The intended use of Isaria 

fumosoroseus strain FE 9901 is to agricultural crops, greenhouse and outdoor food and 

nonfood crops, nursery crops, trees and shrubs, commercial turf and landscapes, and 

residential lawns and gardens for the purposes of insect control. The non-toxic and nonpathogenic nature of this product demonstrates that other incidental non-dietary 

exposures are not of concern.

The results of toxicity testing indicate there is no risk to human health from Isaria 

fumosoroseus strain FE 9901. There are no reports of human health hazards caused by the 

microorganism Isaria fumosoroseus. It does not produce recognized toxins, enzymes, or 

virulence factors normally associated with mammalian invasiveness or toxicity. The 

absence of acute toxicity or pathogenicity in laboratory animals demonstrates the benign 

nature of this strain. Non-dietary exposures would not be expected to pose any 

quantifiable risk due to a lack of residues of toxicological concern.

E. Cumulative Effects

It is not expected that, when used as proposed, Isaria fumosoroseus strain FE 9901 would 

result in residues that are of toxicological concern. The intended use of Isaria 

fumosoroseus strain FE 9901 is to agricultural crops, greenhouse and outdoor food and 

nonfood crops, nursery crops, trees and shrubs, commercial turf and landscapes, and 

residential lawns and gardens for the purposes of insect control. The results of toxicity 

testing indicate there is no risk to human health from Isaria fumosoroseus strain FE 9901. 

There are no reports of human health hazards caused by Isaria fumosoroseus strain FE 

9901. It does not produce recognized toxins, enzymes, or virulence factors normally 

associated with mammalian invasiveness or toxicity. The potential for toxic metabolite 

formation is diminutive in nature as demonstrated in the de minimus findings of 

beauverolide formation. The absence of acute toxicity or pathogenicity in laboratory 
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animals demonstrates the benign nature of this strain. Any exposures would not be 

expected to pose any quantifiable risk due to a lack of residues of toxicological concern.

F. Safety Determination

1. U.S. population. Acute toxicity studies have demonstrated that Isaria 

fumosoroseus strain FE 9901 is not toxic, pathogenic, or infective to mammals. The 

intended use of Isaria fumosoroseus strain FE 9901 is to agricultural crops, greenhouse 

and outdoor food and nonfood crops, nursery crops, trees and shrubs, commercial turf 

and landscapes, and residential lawns and gardens for the purposes of insect control. The 

results of toxicity testing indicate there is no risk to human health from Isaria 

fumosoroseus strain FE 9901, and there is a lack of residues on treated commodities. 

There are no reports of human hazards caused by the microorganism Isaria 

fumosoroseus. It does not produce recognized toxins, enzymes, or virulence factors 

normally associated with mammalian invasiveness or toxicity. The absence of acute 

toxicity or pathogenicity in laboratory animals demonstrates the benign nature of this 

strain. There is a reasonable certainty of no harm to the general US population from 

exposure to this active ingredient.

2. Infants and children. As mentioned above, it is not expected that, when used as 

proposed, Isaria fumosoroseus strain FE 9901 would result in residues that are of 

toxicological concern. There is a reasonable certainty of no harm for infants and children 

from exposure to Isaria fumosoroseus strain FE 9901 from the proposed uses.

G. Effects on the Immune and Endocrine Systems

To date there is no evidence to suggest that Isaria fumosoroseus strain FE 9901 functions 

in a manner similar to any known hormone, or that it acts as an endocrine disrupter.

H. Existing Tolerances

While there is not a specific tolerance for Isaria fumosoroseus strain FE 9901, there is an 

established and existing tolerance exemption for a similar fungal strain (Isaria 

fumosorosea Apopka strain 97), codified under 40 CFR § 180.1306, which states the 

following:

“An exemption from the requirement of a tolerance is established for residues of Isaria 

fumosorosea Apopka strain 97 in or on all food commodities when applied as an 

insecticide or miticide and used in accordance with good agricultural practices.”

I. International Tolerances

A Codex Alimentarius Commission Maximum Residue Level (MRL) is neither 

established nor required for Isaria fumosoroseus strain FE 9901.