EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION

COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN

THE FEDERAL REGISTER

LAM International Corporation

5 F8411

EPA has received a pesticide petition 5 F8411 from LAM International Corporation

, 117 South Parkmont

, Butte, MT 59701 proposing, 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 f or the microbial pesticide Purpureocillium lilacinum strain PL11

.

Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, LAM International Corporation has submitted the following summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by Technology Sciences Group, Inc. and EPA has not fully evaluated the merits of the pesticide petition. The summary may have been edited by EPA if the terminology used was unclear, the summary contained extraneous material, or the summary unintentionally made the reader conclude that the findings reflected EPA’s position and not the position of the petitioner.

I. LAM International Corporation ’ s Petition Summary

5 F8411

A. Product Name and Proposed Use Practices

Purpureocillium lilacinum strain PL11 Technical is a 100% ai Technical Grade Active Ingredient (TGAI) of Purpureocillium lilacinum strain PL11 and is proposed for manufacturing use only, for further formulation into registered end

use products.

BIOSTAT® WP is a 2% ai formulated end

- use product that is intended for use as a soil incorporated treatment for application and incorporation into soil before planting or transplanting crops, or application by drip irrigation after pl anting or transplanting crops, to control plant parasitic nematodes.

B. Product Identity/Chemistry

1. Identity of the pesticide and corresponding residues

. Purpureocillium

lilacinum strain PL11 (CAS No. Not applicable)

2. Magnitude of residues at the time of harvest and method used to determine the2

residue

. An analytical method for residues is not applicable. It is expected that, when used as proposed, Purpureocillium lilacinum strain PL11 would 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. It is expected that, when used as proposed, Purpureocil lium lilacinum strain PL11 would not result in residues that are of toxicological concern.

C. Mammalian Toxicological Profile

Acute Oral Toxicity/Pathogenicity Study in Rats (OCSPP 885.3050): Purpureocillium lilacinum strain PL11 was not toxic or patho genic in an acute oral toxicity / pathogenicity study in rats (MRID No. 496395

- 03). In this study, groups of 3 males and 3 females received an oral dose of the test material by gavage and were sacrificed 1, 3, 7 or 14 da ys after exposure to evaluate clearance of the microbe. The dose given to all groups of both male and female rats in the toxicity / pathogenicity study was 0.5 mL of the undiluted test material. The resulting doses were 1,361 mg/kg in males and 2,421 mg/ kg in females. There were no clinical signs of toxicity reported for any of the rats that received test material in this study, no macroscopic effects reported in the necropsy, and no histopathologic findings. The results of this study are appropriate fo r evaluation of potential effects in wild mammals.

Acute Pulmonary Toxicity/Pathogenicity Study in Rats (OCSPP 885.3150): Purpureocillium lilacinum strain PL11 was not toxic or pathogenic in an acute pulmonary toxicity / pathogenicity study in rats (MRID No. 496395

- 04). Groups of 3 males and 3 females received a single intranasal dose of the test material and were sacrificed 1 hour or 3, 7, 14, or 21 days after exposure to evaluate clearance of the microbe, and potential adverse effects. The dose given to all test groups of both male and female rats in the pulmonary study was 0.05 mL (50 μl) of a 2% dilution of the

test material in Tween

- 80, a non

- ionic surfactant. This dose resulted in 1 X 10 8 CFU per rat. All dosed rats in all pulmonary exposure grou ps survived the exposure and gained weight at each interval measured after exposure. The groups most relevant to the acute inhalation toxicity data requirement are the groups that were followed for 14 or 21 days after exposure, which corresponds to the du ration of the acute inhalation toxicity study follow

- up or longer. No clinical signs of toxicity were observed in any group during the study. The No Observed Effect Levels for males and females were the high doses tested of 1 X 10 8 CFU per rat.

Acute In traperitoneal Toxicity/Pathogenicity Study in Rats (OCSPP 885.3200): Purpureocillium lilacinum strain PL11 was not toxic or pathogenic in an acute intraperitoneal toxicity / pathogenicity study in rats (MRID No. 496395

- 05). Five groups of 3 females and 3 males each received at least 1.0 x 10 9 units of test material by intraperitoneal route. No clinical signs of evident toxicity or agent pathogenesis were observed in tested groups. No macroscopic alterations were observed in control and treated groups. Re covery of the microbe reached > 1.5 x 10 3 on the 1 hour and 3 days groups, and until 1.2 x 10 2 on the group of 7 days. For the groups of3

14 and 21 days, recovery was below the limit of detection (< 1 x 10 1 ). Clearance was considered to be until 14 days. Un der the test conditions, test substance Purpureocillium lilacinum strain PL11 was classified as non

- pathogenic, non

- toxic

and non

- infective

.

Acute Dermal Toxicity (OCSPP 870.1200): An acute dermal toxicity study conducted on the proposed TGAI, Purpureocill ium lilacinum strain PL11 addressed the endpoints of concern for dermal irritation and so fulfills the data requirement for a Primary Dermal Irritation study (MRID No. 496395

- 06). In the acute dermal toxicity study, 5 male and 5 female Wistar rats receive d a 2,000 mg/kg body weight dose of test substance diluted in carboxymethyl cellulose applied over approximately 10% of the total body surface area. After a 24

- hour exposure the test material was removed using de

- mineralized water. The normal duration of exposure for dermal irritation studies is 4 hours, so any irritation following a 24 hour exposure is expected to be more severe than the effect after 4 hours of exposure.

Primary Eye Irritation (OCSPP 870.2400): Purpureocillium lilacinum strain PL11

wa s identified as a dermal irritant following a 24

- hour exposure to a dose of 2,000 mg/kg; consequently, the TGAI also is expected to be an eye irritant (MRID No.

496395

- 06). Quantitative structure activity (QSAR) models and supporting data

indicate that a common molecular mechanism of irritant action exists for eye and dermal irritation (MRID No. 496395

- 17). The common mechanism of action described involves 3 factors: 1) irritation increases as the concentration of the irritant in an aqueous medium availab le for membrane uptake increases, 2) the strength of irritant interaction with the cellular membrane is directly proportional to irritation potency, and 3) both skin and eye irritation are dependent upon the chemical reactivity of the irritant. It is expe cted that the TGAI Purpureocillium

lilacinum strain PL11, is an eye irritant based on the identification of the TGAI as a dermal irritant and the fact that data and models suggest that dermal and eye

irritation share common molecular modes of action.

The registrant has noted that no incidents of hypersensitivity or any other adverse effects have occurred through the research, development or testing of the active ingredient and its related end

- use product. Should any incidents occur, they will be reported per FIFRA Section 6(a)(2) (MRID No. 496395

- 17).

Data on metabolites (OCSPP 885.1300): A study was carried out to identify secondary metabolites in the fungus Purpureocillium lilacinum strain PL11 technical grade active ingredient in samples of eight batc hes of material as manufactured (MRID No. 496395

- 02).

The results of toxicity and metabolite testing show there is no risk to human health from the active ingredient. Purpureocillium lilacinum strain PL11 is not toxic, pathogenic, or infective to mamma ls and does not produce metabolites of toxicological concern.4

D

. Aggregate Exposure

1. Dietary exposure. Dietary exposure from use of Purpureocillium lilacinum strain PL11, as proposed, is minimal. The intended use of Purpureocillium lilacinum

strain PL 11 is as a soil incorporated treatment for application and incorporation into soil before planting or transplanting crops, or application by drip irrigation after planting or transplanting crops, to control plant parasitic nematodes. Purpureocillium lilac inum is ubiquitous in the environment as a naturally

- occurring filamentous fungus found in soils (MRID No. 496395

- 01).

i. Food. Dietary exposure from use of Purpureocillium lilacinum strain PL11, as proposed, is minimal. The intended use of Purpureocillium lilacinum strain PL11 is as a soil incorporated treatment for application and incorporation into soil before planting or transplanting crops, or application by drip irrigation after planting or transplanting crops, to control plant parasiti c nematodes. Purpureocillium

lilacinum is ubiquitous in the environment as a naturally

- occurring filamentous fungus found in soils (MRID No. 496395

- 01).

ii. Drinking water

. E xposure to humans from residues of Purpureocillium

lilacinum strain PL11 in con sumed drinking water would be unlikely. Potential exposure to surface water would be negligible and exposure to drinking water (well or ground water) would be impossible to measure. Purpureocillium lilacinum is ubiquitous in the environment as a naturally

- occurring filamentous fungus found in soils (MRID No. 496395

- 01).

2. Non

- dietary exposure

. The intended use of Purpureocillium lilacinum strain PL11 is as a soil incorporated treatment for application and incorporation into soil before planting or t ransplanting crops, or application by drip irrigation after planting or transplanting crops, to control plant parasitic nematodes. Personal Protective Equipment (PPE) mitigates the potential for exposure to applicators and handlers of the proposed products , when used in agricultural settings. Purpureocillium lilacinum is ubiquitous in the environment as a naturally

- occurring filamentous fungus found in soils (MRID No. 496395

- 01).

E . Cumulative Effects

It is not expected that, when used as proposed, Purp ureocillium lilacinum strain PL11 would result in residues that are of toxicological concern. The intended

use of Purpureocillium lilacinum strain PL11 is as a soil incorporated treatment for application and incorporation into soil before planting or trans planting crops, or application by drip irrigation after planting or transplanting crops, to control plant parasitic nematodes. The results of toxicity testing indicate there is no risk to human

health or the environment from Purpureocillium lilacinum s train PL11. There are no reports of ecological or human health hazards caused by this microorganism. It does not produce recognized toxins, enzymes, or virulence factors normally associated with mammalian invasiveness or toxicity. The absence of acute tox icity or pathogenicity in laboratory animals demonstrates the benign nature of this strain5

F

. Safety Determination

1. U.S. population. Acute toxicity studies have shown that Purpureocillium

lilacinum strain PL11 is not toxic, pathogenic, infective or ir ritating to mammals.

The intended use of Purpureocillium lilacinum strain PL11 is as a soil incorporated treatment for application and incorporation into soil before planting or transplanting crops, or application by drip irrigation after planting or tran splanting crops, to control plant parasitic nematodes. The results of toxicity testing indicate

there is no risk to human health or the environment from Purpureocillium lilacinum strain PL11. There are no reports of ecological or human health hazards c aused by this microorganism. 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

nat ure 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

. I t is not expected that, when used as proposed, Purpureocillium lilacinum strain PL11 would result in residues that are of toxicological concern. There is a reasonable certainty of no harm for infants and children from exposure to Purpureocillium lilacinum strain PL11 from the proposed

uses.

G. Effects on the Immune and Endo crine Systems

To date there is no evidence to suggest that Purpureocillium lilacinum strain PL11 functions in a manner similar to any known hormone, or that it acts as an endocrine disrupter.

H. Existing Tolerances

There is no US EPA tolerance or tole rance exemption for Purpureocillium

lilacinum strain PL11.

I

. International Tolerances

A Codex Alimentarium Commission Maximum Residue Level (MRL) is not

established for Purpureocillium lilacinum strain PL11.