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.

3F8 193

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

, 13100 West Lisbon Road, Suite 600, Brookfield, Wisconsin 53005 request ing, 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 Bi oAg, 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 sum mary 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 petition er.

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

outdoo r 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, n onfood 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.2

NOFLYTM WP can be applied to golf course tees, greens, fairways, and roughs,

commercial and resid ential 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 inte rval (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 wat er

.

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 e xpected 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 neede d. 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 intraperiton eal 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 rout es 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 patho genically 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 from3

person nel 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

2.0x10 9 CFU/g LD 50 > 5,000 mg/kg Category IV

Acute dermal toxicity

MRID No. 47791904 Rat Undiluted dose of 5,050 mg/kg

2.0x10 9 CFU/g LD 50 > 5,050 mg/kg Category III

Acute inhalation toxicity

MRID No. 47791905 Rat 2.18 mg/L for 4

hours

2.0x10 9 CFU/g LC 50 > 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 No s . 47792002

, 47792003, and

48291200 Rat 100 mg of 10 8

CFU/rat Non

- to xic, non

- infective,

non

- pathogenic

Acute pulmonary toxicity/pathogenicity

MRID Nos. 47792004

, 47792006, 49044301

, and 48291200 Ferret 1.0x10 8 (in 0.5 mL)

CFU/ferret Non

- toxic, non

- infective,

non

- pathogenic

Acute intraperitoneal Toxicity/pathogenicity

MR ID Nos. 47792005

, 49044301 , and

48291200 Rat 10 7 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 inactiva ted in mammalian systems.4

Literature searches have b een 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

t o 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 bee n demonstrated, dietary exposure to Isaria fumosoroseus strain FE 9901 meets
the F ood Quality Protection Act (F QPA ) 1996 safety standard. Studies submitted with this petition showed no evidence of toxicity, pathogenicity, or infectivity when this strain

wa s 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. Isari a 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 woul d be removed during c ommon post harvest 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 microorga nism 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 d rinking water would be unlikely. Potential exposure to surface water would be negligible and exposure to drinking water (well or5

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

- wate r treatment facility (including chlorination, pH adju stments, high temperatures, and/ or anaerobic conditions) (MRID No. 47792001).

The r esults 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

v irulence 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

qua ntifiable 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 9 901 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 non

pathogenic nature of t his product demonstrates that other incidental non

- dietary exposures are not of concern.

The results of toxicity testing indicate t here is no risk to human health from Isaria fumosoroseus strain FE 9901. There are no reports of human health hazards cause d 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 str ain 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 lan dscapes, and residential lawns and gardens for the purposes of insect control. The results of toxicity testing indicate there is no risk to human health f rom 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 mi nimus findings of beauverolide formation. The absence of acute toxicity or pathogenicity in laboratory6

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 tox icological 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 n o 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, o r 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 U S 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 re asonable 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 exe mption 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 i n 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 requir ed for Isaria fumosoroseus strain FE 9901

.