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

**PETITION Docket ID Number: EPA**  **- HQ**  **- OPP**  **- 2012**  **- 0716**  **EPA Registration Division contact: Sidney Jackson (703) 305 -**  **7610 Interregional Research Project Number 4**  **Pesticide Petition Number: PP 2E8072**  EPA has received a pesticide petition **( PP 2E8072)**  from the Interregional Research Project No. 4 (IR

- 4), 500 college Road East, Suite 201 W, Princeton, NJ 08540 requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosme tic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of **fe npyroximate in**  **or on the raw agricultural commodities, Fruit, stone, group 12 -**  **12 at 2.0 parts per million (ppm); Vegetable, tuberous and corm, subgro**  **up 1C at 0.1 ppm; Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13**  **- 07F at 1.0 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 ful**  **ly 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 fenp yroximate and z

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

- isomer, with very low levels of several degradates. Metabolism in plants involves hydrol ys is of the ester and methyleneamino ether links, N
- demethylation, oxidation, and conjugation of the polar metabolites. **2. Analytical method.**  Based upon the metabolism of fenp yroximate in plants and the toxicology

of the parent and metabolites, quantification of the parent, fenpy roximate and the z

isomer, combined as fenpy roximate is sufficient to determine toxic residues in plants. As a result an enforcement method has been developed which involves extraction of fenpy roximate from crops with eth ylacetate in the presence of anh ydrous sodium sulfate, dilution with methanol, and then anal ys is by

high performance liquid chromatography using tandem mass spectrometric detection (LC/MS/MS). The method has undergone independent laboratory validation as required b y PR Notice 88

- 5 and 96

- 1. This is a new enforcement method. **3. Magnitude of residues.**  Field residue trials meeting EPA study requirements for a regional tolerance have been conducted at the maximum label rate for potatoes, cherries, plums, and peaches. Results from thes e trials demonstrate that the highest fenp yro ximate and z

- isomer residues found will not exceed the proposed tolerances on fruit, stone crop group 12

- 12, and vegetables, tuberous and corm subgroup 1C , when the product is applied following the proposed use directions.**B. Toxicological Profile**

An extensive battery

of toxicology

studies has been conducted with fenp yr oximate. EPA has evaluated the available toxicity data and considered their validity , completeness, and reliability as well as the relation ship of the results of the studies to human risk. The nature of the toxic effects caused b y fenpyroximate is discussed in Unit III.A. of the Final Rule on Fenp yroximate Pesticide Tolerance published in the Federal Register on April 10, 2001 (66 FR 18561) (FRL

- 6773
- 2). An assessment of toxic effects caused b y fenp yro ximate 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 m**  **etabolism.** The qualitative nature of the residues of fenp yroximate 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 (approxima tely 70 % to 92 %) is excreted in the feces. Urinary excretion accounts for less er amounts (approximately 9 % to 18 %) of the label. Thus, feces and urine are the major routes of excretion for fenpy roximate. Tissue did not accumulate fenpy

roximate or its metabolites to any great extent. The greatest levels of label were in liver, kidneys, adrenals, and fat (to a lesser degree). I n blood, nearly all the label amount is in the plasma. **7. Metabolite toxicology**  **.** No toxicologically significant metabolites were detected in plant or animal metabolism studies for cotton, apples, 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 an y endocrine effects for fenp yroximate. 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 fenp yr oximate is negligible. **C. Aggregate Expo sure**  **1. Dietary exposure.**  Tier 1 acute and chronic dietary risk anal ys es were conducted to estimate to potential fenpy roximate residues in/on crops with established tolerances as per 40 CFR §180.566 and the following proposed crops: fruit, stone, group 1 2
- 12; tuberous and corm vegetables, subgroup 1C; and fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13

- 07F using DEEMTM (version 2.16). Residue estimates for water consumption were based on PRZM3/EXAMs and SCIGROW models and exposure assessm ents using DEEMTM. **i. Food.**  The acute and chronic dietary exposure was based on the following assumptions: residues at tolerance levels, 100% crop treated, and DEEMTM(version 2.16) default processing factors for all registered/proposed commodities excludi ng apple, pear, and grape juice (0.11x); grape, raisin (2.7x); orange, grapefruit, tangerine, lemon and lime juice (0.06x); tomato paste (1.0x) and puree (1.0x); and peppermint and spearmint oil (0.08x). The acute dietary aPAD (acute population adjusted do se) 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 acute assessment concludes that the acute dietary

- exposure estimate is below HED’s level ofconcern (< 100% aPAD) for females 13

- 49 years old at 10.70 % aPAD. 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

- ye ar rat chronic/oncogen icity study . The resultant safety factor used to establish the cPAD was 100. There was not likel y an y evidence of carcinogenicity . The chronic assessment concludes that the chronic dietary

- exposure estimates are below HED’s level of concern (<100% cPAD) for the general U.S. population (18.8% cPAD) and all population subgroups. The most highly

- exposed population subgroup is children 1

- 2 years old at 60.7% cPAD. **ii. Drinking water.**  The residue of concern in drinking water was determined to be fenp yroximate and its z

- isomer. There are no established maximum contaminant levels or health advisory levels for residues of fenpy roximate in drinking water. In the absence of comprehensive water monitoring data, the Agency uses the FQPA Index Reservoir Screening Tool or the Pesticide Root Zone Model/Exposure Analy sis Modeling S ys tem (PRZM/EXAMS) to produce estimates of pesticide concentrations in an index reser voir. The SCI

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

- 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 likel y 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 sort ing out pesticides for which it is unlikely that drinking water concentrations would exceed human health levels of concern. Drinking water was incorporated directly into the dietary

assessments (“water, direct, all sources” and “water, indirect, all sources”) using the estimated drinking water concentrations (EDWCs) for surface water. E PA generated the surface water and water estimates using the Pesticide Root Zone Model/Exposure Analy sis Modeling S ys tem (Tier II) and groundwater estimates using the Scre ening Concentration in Ground Water) models. The acute and chronic non - cancer concentrations for Georgia pecan (highest exposure) are 0.0129 ppm and 0.0018 ppm for surface water. The SCI

- GROW model estimated a ground water concentration of 0.059 ppb but was not used in this dietary risk assessment (Fenpy

roximate: Pesticide Tolerance: FR 71, Vol 163, pp 49364

- 49368). 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 muc h lower than the levels predicted in the hy pothetical, small, stagnant farm pond model since drinking water derived from surface water would normall y be treated before consumption. Based on these anal ys es, the contribution of water to the dietary risk esti mate is negligible. Therefore, based on the dietary

and drinking water assessments, aggregate exposure to residues of fenpy roximate and its z

- isomer in food and water can be considered to be negligible. **2. Non**  **- dietary exposure**  **.** The term residential expos ure 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). Fenp yr oximate is not registered for useon any

sites that would r esult in residential exposure. **D. Cumulative Effects** Fenp yroximate is a mitochondrial electron transport inhibitor acting at Site I, which is similar to py

ridaben, but quite different than other established acaricides. All relevant toxicological data h ave been provided to the EPA. A determination has not been made that fenp yroximate has a common mechanism of toxicity with other substances. Fenp yroximate does not appear to produce a common toxic metabolite with other substances. Therefore, for the purpose s 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 fenp yroximate will utilize 10.7 % 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 was 18.8 % of the estimated chronic population adjusted dose (cPAD). Drinking water and other potential water consumption scenario s 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 fenpy roximate.
**2. Infants and child** 

**ren .**  Chronic exposure to food and water to children from 1

- 2 years old, the highest exposed population subgroup, was 60.7 % of the cPAD. EPA has determined that reliable data support the uncertainty factor (100 for intraspecies variability) for fenp yroxim ate. EPA deemed an additional FQPA safety factor is not necessary to be protective of infants and children. EPA generall y 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 aggre gate exposure to residues of fenp yroximate. **F. International Tolerances** Canada, Codex, and Mexico do not have maximum residue limits for residues of fenp yroximate in/on the proposed crops. Therefore, harmonization is not an issue.