**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR**

**PESTICIDE PETITIONS EPA Registration Division contact:**  **Sidney Jackson (703) 305**  **- 761**  **0 I**  **nterregional Research Project Number 4 (I R** **- 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** fenp yroximate **(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**  **- dim**  **ethylet hyl 4**  **- [[[[(1,3**  **- dimethyl** **- 5**  **- phenoxy** **- 1H**  **- pyrazol** **- 4**  **- yl)methylene]**  **am ino]oxy]**  **methyl]benzoate** in or on the raw agricultural commodities: **A vocado at 0.20 parts per million (ppm),**  **Sapote, b lack**  **at 0.20**  **ppm ,**  **C anistel**  **at 0.20 ppm,**  **Sapote, m amey**  **at 0.20**  **ppm ,**  **M a**  **ngo at**  **0.20 ppm**  **, P**  **apaya at**  **0.20 ppm,**  **S apodilla**  **at 0.20**  **ppm, S**  **tar apple at**  **0.20 ppm,**  **B ean**  **, snap, succulent,**  **at 0.40**  **ppm, and**  **Tea, plucked leaves at 15 ppm**  **. Revisions to the existing**  **tolerances are the following: C**  **ucumber at 0.25 ppm**  **, Fruit,**  **citrus, citrus , group 10**  **- 10 tolerance at 0.6**  **0 ppm, Vegetable, fruiting, group 8**  **- 10**  **tolerance at 0.2 0**  **ppm , and Fruit, pome, group 11**  **- 10 tolerance at 0.4**  **0 ppm**  **.** EPA has determined that the petition contains data or information regarding the elements set forth in section 40 8 (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. Metabolis**  **m 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 f**  **rom 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.**2

3. Magnitude of residues. **Magnitude of residues in crops**   ** Field 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 no**  **t 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**  **. EP A 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 I**  **II.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 d iscussed 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.**  **Fenpyro ximate**  **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 mul tigenerational bioassays in**  **ma mmals 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, mame y**  **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, tomatoe**  **s , 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 .** 3 i. Food. **The acute dietary exposure was based on the following assumptions: residues at tolerance levels, 100% crop treated, and**  **LifeLine TM 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, g**  **ra pe,**  **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 b**  **y 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 US DA 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 A djusted 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 an y**  **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 concentrati ons**  **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 m**  **odel 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 es**  **timated 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 o**  **f 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 b illion (ppb) for**  **surface water** 4

**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 c oncentrations**  **were direc tly 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 drinki ng 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**  **anal yses, 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 negligibl e.**  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).**  **Fenpy roximate**  **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 ot**  **her 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 to**  **xic 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 c**  **onservative 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**  **yr oximate**  **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. Pop**  **ulation (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 s**  **upport the uncertainty factor (1 00 for**  **intraspecies vari ability** **) for fenpyroximate**  **. EPA deemed an additional FQPA safety factor is not necessary to be protective of infants and children. EPA generally has** 5

**no concern for exposures below 100% of the cPAD. The Agency has considered the potential aggregate exposu**  **re 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.**