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 and 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 Hill 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 commodities: 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 million 

(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 data 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.
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2. Analytical method. Based 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 an 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 mass 

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 cropsField residue trials 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 not 

exceed the proposed tolerances on corn seed 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. Genotoxicity. “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 toxicity 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 Fenpyroximate 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 III 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 volatiles 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, 
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feces and urine are the major routes 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 plasma. 

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, 

avocado, black sapote, canistel, mamey sapote, mango, papaya, sapodilla, bell and 

non-bell peppers, cantaloupe and other melons, cotton, cranberries, eggplant, grape, 

grape raisins, 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 based on 

PRZM3/EXAMs and SCIGROW models and exposure assessments using 

LifeLineTM 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 processing 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 any 

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 fenpyroximate 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 concentrations 

in an index resevoir. The SCI-GROW model is used to predict pesticide 

concentrations in shallow ground water. For a screening-level assessment for 
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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 of 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 estimated drinking water concentrations (EDWCs) in surface water were 

determined using the Tier II PRZM (Pesticide Root Zone Model) and EXAMS 

(Exposure Analysis Modeling System (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 estimates. EDWCs of 0.00874 ppm and 0.00051 ppm were used in 

the acute and chronic analysis respectively. Levels in surface water for acute 

analysis are 8.74 ppb, and for chronic 0.51 ppb. In ground water, using Tier I SCIGROW, 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 

would 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 its 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 control, 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 

substances. 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 Determination
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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 fenpyroximate will utilize 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 

consumption 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 support the uncertainty factor 

(100 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. The Agency has 

considered the potential aggregate exposure from food, water and non-occupational 

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 to 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.