EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER (1XX/2008)

EPA Registration Division contact: Mark Suarez (703) 305

- 0120

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In cases where the outline element does not apply, please insert “NA

- Remove” and maintain the outline. Please do not change the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green a nd brackets, i.e., “ [ insert company name ] ,” with the information specific to your action.

[ Nichino America, Inc. ]

[Pesticide Petition #xxxxxx ]

EPA has received a pesticide petition [ PP # xxxxxxx ] from Nichino America, Inc. 4550 New Linden Hi ll Road Suite 501 Wilmington,

DE 19808

, 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 .566 by establishing a tolerance for residues of fenpyroximate and

its z

- isomer in or on the raw agricultural commodit ies: corn, field, grain at 0. 02 parts per million (ppm)

, corn field forage/silage

at 2.0 parts per million (ppm), corn field stover at 7.0 parts per million (ppm), corn , field aspirated fractions at 2.0 parts per milli on (ppm)
, corn, pop, grain, at 0.02 parts per million (ppm), corn pop forage/silage at 2.0 parts per million (ppm), corn pop stover at 7.0 parts per million (ppm), corn, pop aspirated fractions at 2.0 parts per million (ppm)

. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the

submitted d a ta at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism of fenpyroximate and z

- isomer has been studied in cotton, apples, grapes, and citrus and is well understood. The major residue in plants is fenpyroximate and z

- isomer, with very low levels of several degradates. Metabolism in plants involves hydrolysis of the ester and methyleneamino ether links, N

- demethylation, oxidation, and conjugation of the polar metabolites.2

2. Analytical method

. B ased upon the metabolism of fenpyroximate in plants and the toxicology of the parent and metabolites, quantification of the parent, fenpyroximate and the z

- isomer, combined as fenpyroximate is sufficient to determine toxic residues in plants. As a result a n enforcement method has been developed which involves extraction of fenpyroximate from crops with ethyl acetate in the presence of anhydrous sodium sulfate, dilution with methanol, and then analysis by high performance liquid chromatography using tandem m ass spectrometric detection (LC/MS/MS)

. The method has undergone independent laboratory validation as required by PR Notice 88

- 5 and 96

- 1. This is a new enforcement method.

3. Magnitude of residues. Magnitude of residues in crops

Field residue trial s meeting EPA study requirements for a regional tolerance have
been conducted at the maximum label rate for corn . Results from these trials demonstrate that the highest fenpyroximate and z

- isomer residues found will no t exceed the proposed tolerances on c orn see d or fodder, forage when the product is applied following the proposed use directions.

4. Magnitude of the residue in animals “NA

- Remove”

B. Toxicological Profile

1. Acute toxicity. “NA

- Remove”

2. Genotoxic i ty. “NA

- Remove”

3

. Reproductive and developmental toxicity. “NA

- Remove”

4. Subchronic toxicity. “NA

- Remove”

5. Chronic toxicity. “NA

- Remove”

1. An extensive battery of toxicology studies has been conducted with fenpyroximate . EPA has evaluated the available tox icity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk The nature of the toxic effects caused by fenpyroximate is

discussed in Unit III.A. of the Final Rule on Fenpyrox imate Pesticide Tolerance published in the Federal Register on April 10 , 2001 (66 FR 18561) (FRL

- 6773

- 2 ). An assessment of toxic effects caused by fenpyroximate including the toxicological endpoints of concern is also discussed in Unit III.A. and Unit II I B. of the Federal Register dated June 10, 2004 (FRL

- 7362

- 9) (89 FR 32457 ).

6. Animal metabolism

. The qualitative nature of the residues of fenpyroximate and its z
- isomer, in animals is adequately understood. Fenpyroximate

was not metabolized to volat iles to any significant degree. The majority of either benzyl or pyrazole labels (approximately 70 % to 92 %) is excreted in the feces. Urinary excretion accounts for less (approximately 9 % to 18 %) of the label. Thus,3

feces and urine are the major rout es of excretion for fenpyroximate. Tissue did not accumulate fenpyroximate or its metabolites to any great extent. The greatest levels of label were in liver, kidneys, adrenals, and fat (to a lesser degree). In blood, nearly all of the label is in the p lasma.

7. Metabolite toxicology

. No toxicologically significant metabolites were detected in plant or animal metabolism studies for cotton, apples, or or grapes.

8. Endocrine disruption

. Chronic, lifespan, and multigenerational bioassays in

mammals and acute and subchronic studies on aquatic organisms and wildlife did not reveal any endocrine effects for fenpyroximate. Any endocrine related effects would have been detected in this comprehensive series of required tests. The probability of any such effect due to agricultural uses of fenpyroximate is negligible.

C. Aggregate Exposure

1. Dietary exposure. Acute and chronic dietary risk analyses were conducted to estimate to potential fenpyroximate residues in/on the following crops: corn,

avoca do, black sapote, canistel, mamey sapote, mango, papaya, sapodilla, bell and

non
- bell peppers, cantaloupe and other melons, cotton, cranberries, eggplant, grape, grape raisin s , okra, snap beans, cucumbers, strawberries, tomatoes , citrus fruits, hops, mint, pome fruits, tree nuts, tea, and meat, milk, and honey using LifeLineTM version 4.3. Residue estimates for water consumption were ba sed on
PRZM3/EXAMs and SCIGROW models and exposure assessments using

LifeLine TM version 5.0

. i. Food. The acute dietary exposure was based on the following assumptions: residues at tolerance levels, 100% crop treated, and DEEMTM (ver. 7.76) default processing factors for all registered/proposed commodities (Tier 1). A processing factor of 0.11 was used for juice based on pr ocessing study data. The acute dietary aPAD (acute population adjusted dose) was set at 0.05 mg/kg/day for females aged

13

- 50 years old based on a developmental toxicity study in rats that had an oral NOEL of 5 mg/kg/day. The chronic dietary exposure was based on the following assumptions: Residues at tolerance levels, 100% crop treated, and using UDDA survey data where available. A processing factor of 0.11 was used for juice based on processing study data. The chronic dietary cPAD (chronic Population Adjusted Dose) was determined to be 0.01 mg/kg/day for the general population, based on an oral NOAEL of 0.97 mg/kg/day in the two

- year rat chronic/oncogenicity study. The resultant safety factor used to establish the cPAD was 100. There was not likely a ny evidence of carcinogenicity.

ii. Drinking water

. The residue of concern in drinking water was determined to

be fenpyroximate and its z

- isomer . There are no established maximum contaminant levels or health advisory levels for residues of fenpyroximat e in drinking water. In the absence of comprehensive water monitoring data, the Agency uses the FQPA Index Reservoir Screening Tool or the Pesticide Root ZoneModel/Exposure Analysis Modeling System (PRZM/EXAMS) to produce estimates of pesticide concentrat ions

in an index resevoir. The SCI

- GROW model is used to predict pesticide concentrations in shallow ground water. For a screening

- level assessment for4

surface water EPA will use FIRST (a tier 1 model) before using PRZM/EXAMS (a tier 2 model). The FIRST model is a subset of the PRZM/EXAMS model that uses a specific high

- end runoff scenario for pesticides. Both FIRST and PRZM/EXAMS incorporate an index reservoir environment, and both models include a percent crop area factor as an adjustment to account for the maximum percent crop coverage within a watershed or drainage basin.

None of these models include consideration of the impact processing (mixing, dilution, or treatment) of raw water for distribution as drinking water would likely

have on the removal o f pesticides from the source water. The primary use of these models by the Agency at this stage is to provide a screen for sorting out pesticides for which it is unlikely that drinking water concentrations would exceed human

health levels of concern.

The e stimated drinking water concentrations (EDWCs) in surface water were determined using the Tier II PRZM (Pesticide Root Zone Model) and EXAM S (Exposure Analysis Modeling S ystem (PE4

- PL, version 01). PRZM is used to simulate pesticide transport as a result of runoff and erosion and spray drift from an agricultural field and EXAMS estimates environmental fate and transport of pesticides in surface water. The EPA estimated that based on the maximum use pattern of two applications at 0.2 lb ai/A per season for the acute and the chronic and long

- term esti mates. EDWCs of 0.00874 ppm and 0.00051 ppm were used in the acute and chronic analysis respectively. Levels in surface w ater for acute analysis are 8.74 ppb, and for chronic 0.51 ppb. In ground water, using Tier I SCI

GROW, the acute level and chronic level is 0.001 ppb. Concentrations in actual drinking water would be much lower than the levels predicted in the hypothetical, small, stagnant farm pond model since drinking water derived from surface water

wou ld normally be treated before consumption. Based on these analyses, the contribution of water to the dietary risk estimate is negligible. Therefore, based on the dietary and drinking water assessments, aggregate exposure to residues of fenpyroximate and it s z
- isomer in food and water can be considered to be negligible.

2. Non

- dietary exposure

. The term residential exposure is used in this

document to refer to non

- occupational, non

- dietary exposure (e.g. for lawn and garden pest control, indoor pest co ntrol, termiticides, and flea and tick control on pets). Fenpyroximate is not registered for use on any sites that would result in residential exposure

.

D. Cumulative Effects Fenpyroximate is a mitochondrial electron transport inhibitor acting at Site I, which is similar to pyridaben, but quite different than other established acaricides. All relevant toxicological data has been provided to the EPA. A determination has not been made that fenpyroximate has a common mechanism of toxicity with other

sub stances. Fenpyroximate does not appear to produce a common toxic metabolite with other substances. Therefore, for the purposes of this notice of filing, there should be no consideration of cumulative risk that would require assessment.

E. Safety Dete rmination5

1. U.S. population.

i. Acute risk. Using the conservative assumptions discussed above, based on the completeness and reliability of the toxicity data, it is concluded that aggregate exposure to the proposed uses of fenp yroximate will utiliz e 12 .2 % of the acute reference dose of females (13

- 49). This estimate is likely to be much less, as more realistic data and models are developed . Drinking water and other water

cons umption scenarios were included in the dietary risk assessment modeling.

ii. Chronic Risk. Based on the toxicology data base and available information on anticipated residues, the chronic dietary exposure to the U.S. Population (total) was

estimated as less than 25 % of the estimated chronic population adjusted dose (cPAD ). Drinking water and other potential water consumption scenarios were included in the dietary risk assessment modeling. Based on these assessments , it can be concluded that there is reasonable certainty of no harm to the U.S. Population or any population subgroup from exposure to fenpyroximate

.

2. Infants and children

. Chronic exposure to food and water to children from

1

- 2 years old , the highest exposed population subgroup, was approximately 76.1 %
of the cPAD . EPA has determined that reliable data s u pport the uncertainty factor (1 00 for intraspecies variability ) for fenpyroximate . EPA deemed an additional FQPA safety factor is not necessary to be protective of infants and children. EPA generally has no concern for exposures below 100% of the cPAD. T he Agency has considered the potential aggregate exposure from food, water and non
- occupation al exposure routes and has concluded aggregate exposure is not expected to exceed 100% of the chronic reference dose, and consequently, has determined there is a reasonable certainty that no harm will occur to infants and children from aggregate exposure t o residues of fenpyroximate

.

F. International Tolerances

Canada, Codex, and Mexico do not have maximum residue limits for residues of fenpyroximate in/on the proposed crop . Therefore, harmonization is not an issue.