EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS 

EPA Registration Division contact: Sidney Jackson (703) 305-7610

Interregional Research Project Number 4 (IR-4) 

Pesticide Petition Number: 1E7881

EPA has received a pesticide petition (PP # 1E7881) from Interregional 

Research Project Number 4 (IR-4), 500 College Road East, Suite 201 W, 

Princeton, NJ 08540 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 combined residues of the insecticide fenpyroximate (E)-1,1-

dimethylethyl 4-[[[[(1,3-dimethyl- 5-phenoxy-1H-pyrazol-4-yl) methylene] 

amino]oxy]methyl] benzoate and its Z-isomer, (Z)-1,1-dimethylethyl 4-[[[[(1,3-

dimethyl-5- phenoxy-1H- pyrazol-4-yl)methylene] amino]oxy] methyl]benzoate in 

or on the raw agricultural commodities: Avocado at 0.20 parts per million (ppm), 

Sapote, black at 0.20 ppm, Canistel at 0.20 ppm, Sapote, mamey at 0.20 ppm,

Mango at 0.20 ppm, Papaya at 0.20 ppm, Sapodilla at 0.20 ppm, Star apple at 0.20 

ppm, Bean, snap, succulent, at 0.40 ppm, and Tea, plucked leaves at 15 ppm. 

Revisions to the existing tolerances are the following: Cucumber at 0.25 ppm, Fruit, 

citrus, citrus, group 10-10 tolerance at 0.60 ppm, Vegetable, fruiting, group 8-10 

tolerance at 0.20 ppm, and Fruit, pome, group 11-10 tolerance at 0.40 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 support 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. 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 acetone, 

filtration, partitioning and cleanup, and analysis by gas chromatography using a 

nitrogen/phosphorous detector. The method has undergone independent laboratory 

validation as required by PR Notice 88-5 and 96-1. 
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3. Magnitude of residues. Magnitude of residues in cropsField residue trials meeting EPA study requirements have been conducted at the 

maximum label rate for avocado, cucumbers, tea, and snap beans2. Results from 

these trials demonstrate that the highest fenpyroximate and z-isomer residues found 

will not exceed the proposed tolerances when the product is applied following the 

proposed use directions. 

B. Toxicological Profile

1.

1. An extensive battery of toxicology studies has been conducted with

fenpyroximate. EPA has evaluated the available toxicity data and considered their

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).

2. 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,

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. 

3. 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: 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. 
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i. Food. The acute dietary exposure was based on the following assumptions: 

residues at tolerance levels, 100% crop treated, and LifeLineTM version 5.0, default 

processing factors for all registered/proposed commodities/processed fractions

except for the following noted fractions (Tier 1). A processing factor of 0.11 was 

used apple, grape, pear, and tomato for juice based on processing study data and 

0.06 x for orange juice. No processing factors were used for oils since they were 

adequately represented by tolerance levels. 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 USDA 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 

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 the EWDCs of fenpyroximate 

for acute exposures are estimated to be 8.74 parts per billion (ppb) for surface water
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and 0.001 ppb for ground water. For chronic exposures for non-cancer assessments 

are estimated to be 0.51 ppb for surface water and 0.001 ppb for ground water. 

Modeled estimates of drinking water concentrations were directly entered into the 

dietary exposure model. For acute dietary risk assessment, the water concentration 

value of 8.74 ppb was used while for chronic dietary risk assessment, the water 

concentration of 0.51 ppb was used to assess the contribution to drinking water. 

The actual drinking water values 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

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 occupy at most 12. 1 % of the 

acute reference dose of females (13-49). 

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 to be 24.5 % of the estimated chronic population adjusted dose (cPAD).

2. Infants and children. Chronic exposure to food and water to children from 1-2 

years old, the highest exposed population subgroup, was 75.2 % 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 
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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 crops. Therefore, harmonization is not an issue.