Document ID: EPA-HQ-OPP-2012-0716-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-11-07T05:00Z

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 Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of fenpyroximate in or on the raw agricultural commodities, Fruit, stone, group 12-12 at 2.0 parts per million (ppm); Vegetable, tuberous and corm, subgroup 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 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 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. 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 these trials demonstrate that the highest fenpyroximate 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 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).

	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 lesser amounts (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 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 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. Tier 1 acute and chronic dietary risk analyses were conducted to estimate to potential fenpyroximate residues in/on crops with established tolerances as per 40 CFR §180.566 and the following proposed crops: fruit, stone, group 12-12; tuberous and corm vegetables, subgroup 1C; and fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F using DEEM(TM) (version 2.16).  Residue estimates for water consumption were based on PRZM3/EXAMs and SCIGROW models and exposure assessments using DEEM(TM).

	i. Food. The acute and chronic dietary exposure was based on the following assumptions: residues at tolerance levels, 100% crop treated, and DEEM(TM)(version  2.16) default processing factors for all registered/proposed commodities excluding 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 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 acute assessment concludes that the acute dietary-exposure estimate is below HED's level of concern (<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-year rat chronic/oncogenicity study.  The resultant safety factor used to establish the cPAD was 100.  There was not likely any 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 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 Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS) to produce estimates of pesticide concentrations in an index reservoir.  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.
	
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.  EPA generated the surface water and water estimates using the Pesticide Root Zone Model/Exposure Analysis Modeling System (Tier II) and groundwater estimates using the Screening 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 (Fenpyroximate: 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 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 have 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 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.  
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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 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 60.7 % 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 crops.  Therefore, harmonization is not an issue.