Document ID: EPA-HQ-OPP-2018-0088-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2018-07-24T04:00Z

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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 
PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER   
 
Syngenta Crop Protection, LLC 
 
PP #7F8640

 	EPA has received a pesticide petition PP #7F8640 from Syngenta Crop Protection. LLC, P.O. Box 18300, Greensboro, NC 27419 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 
 
emamectin benzoate, 4'-epi-methylamino- 4'-deoxyavermectin B1 benzoate (a mixture 
of a minimum of 90% 4'-epi-methylamino-4'- deoxyavermectin B1a and a maximum of 10% 4'-epi-methlyamino-4'deoxyavermectin B1b benzoate), and its metabolites 8,9 isomer of the B1a and B1b component of the parent insecticide in or on the processed agricultural commodity vegetable, cucurbit, group 9 at 0.03 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. 
 
 Residue Chemistry   
    
 Plant metabolism. The metabolism of emamectin benzoate in plants has been studied and the nature of the residue has been determined in lettuce, cabbage, and sweet corn. The major portion of the residue is parent compound and its delta 8,9- photoisomer.  The metabolism of emamectin has also been investigated in goats and poultry to characterize the fate of residues that may be present in animal feed items 
 
 Analytical method. Adequate analytical methods (HPLC-fluorescence methods) are available for enforcement purposes. 
 
Magnitude of residues.  In the appropriate growing areas of the US, IR-4 conducted magnitude of residue studies in cucumber (pickling and slicing varieties), cantaloupe, and squash, the representative commodities for crops in the crop group, vegetable, cucurbit, group 9. A total of approximately 0.090 lb ai/A was applied in six foliar applications of Proclaim 5SG at a rate of approximately 0.015 lbs ai/A. Raw agricultural commodities (RAC) samples were harvested 6-8 days after the last treatment. In addition, IR-4 also conducted residue decline trials in 4 locations (3 cucumber and 1 squash). In these decline trials, crop samples were collected at 0, 3, 10, 13, and/or 14 days PHI.

There were no detectable residues of any of the six emamectin benzoate analytes in the cucumber and squash RAC samples harvested at 6-8 days PHI. For thecantaloupe RAC samples harvested at 6-8 days PHI, one of the six analytes, NOA-426007 (emamectin B1a), was present in amounts above the lowest limit of method validation (LLMV). All other analytes were below the LLMV. In the decline trials, squash taken at 0 days PHI showed combined emamectin B1a + 8,9Z residues above the LLMV (all other analytes were below the LLMV) and declined to below the LLMV for all analytes at the subsequent sampling events.

Toxicological Profile  A full description of the studies regarding the toxicity, animal metabolism, and metabolite toxicology, of emamectin benzoate can be found in appendix 1 of EPA's memorandum, "Abamectin.  Human Health Risk Assessment for Uses on Caneberry Subgroup 13-07A; Soybean; Sweet Corn; Ear Tags for Lactating Dairy Cattle; Golf Course Turf; Bean; Onion, Green, Subgroup 3-07B; Fruit, Pome, Group 11-10; Fruit, Small Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13-07F; Berry, Low Growing, Subgroup 13-07G; Vegetable, Fruiting, Group 8-10; Greenhouse Tomato; Fruit, Citrus, Group 10-10; Fruit, Stone, Group 12-12; and Nut, Tree, Group 14-12; and Various Tropical Fruits.," PC Code:  122804, Decision No.:  480177, 495169, 495170, 478520, 476238, DP Barcode:  D426599, dated April 18, 2016.  
 
C. Aggregate Exposure 
 
1. Dietary exposure. Tier III acute and chronic aggregate exposure evaluations were made for emamectin benzoate using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM-FCIDTM , version 4.02), which incorporates food consumption data from the National Health and Nutrition Examination Survey/"What We Eat in America" (NHANES/WWEIA) dietary survey conducted in 2005-2010. These assessments included all current as well as a number of proposed new uses on cherries, chive, basil, and globe artichokes. Residue data were obtained from field trial residue studies in which emamectin benzoate was applied at the maximum intended use rate and samples were harvested at the minimum pre-harvest interval (PHI) to obtain maximum residue values. Drinking water estimates were incorporated directly into the dietary exposure assessment using the higher of the estimated drinking water concentrations (EDWCs) for surface and ground water. Empirically derived processing factors for apple juice (0.05X), apple pomace (4.3X), dried basil (15.2X), dried chive (1.3X), imported wine (0.29X), and cottonseed oil (0.39X) were used in these assessments. Percent crop treated (%CT) values were estimated based upon economic, pest, and competitive pressures. Residue values for meat, milk, and eggs of livestock were calculated using the "maximum reasonably balanced diet" (MRBD) dietary burden approach in conjunction with transfer factors obtained from livestock feeding and/or metabolism studies. For poultry, the EPA has determined that secondary residues are not anticipated. For swine, MRBDs constructed in the usual manner were used in conjunction with transfer factors from a dairy feeding study to predict residues in hog meat.
       
 Food.  
 
      Acute Exposure.  The emamectin benzoate acute dietary (food only) risk assessment was performed for all population subgroups with an acute reference dose of 0.0025 mg/kg-bw/day based on sub-chronic and chronic oral toxicity studies in dogs with a No Observed Adverse Effect Level (NOAEL) of 0.25 mg/kg-bw/day and an uncertainty factor of 100X. The 100-fold safety factor includes intra- and interspecies variations; no additional FQPA safety factors were included in these assessments. For the purpose of the aggregate risk assessment, exposure values were expressed in terms of margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure for each population subgroup. In addition, exposure was also expressed as a percentage of the acute reference dose (%aRfD). Acute (food only) exposure to the U.S. population resulted in a MOE of 1,558 (6.4% of the acute RfD of 0.0025 mg/kg-bw/day). The most sensitive sub-population was children (3-5 years old) with a MOE of 876 (11.4% of the aRfD). Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures above the benchmark or below 100% of the reference dose, Syngenta believes that there is a reasonable certainty that no harm will result from acute food exposure to residues arising from all current and proposed uses for emamectin benzoate.  
       
      Chronic Exposure.  The emamectin benzoate chronic dietary (food only) risk assessment was performed for all population subgroups with a chronic reference dose of 0.0025 mg/kg-bw/day based on sub-chronic and chronic oral toxicity studies in dogs with a No Observed Adverse Effect Level (NOAEL) of 0.25 mg/kg-bw/day and an uncertainty factor of 100X. The 100-fold safety factor includes intra- and interspecies variations; no additional FQPA safety factors were included in these assessments. For the purpose of the aggregate risk assessment, exposure values were expressed in terms of margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure for each population subgroup. In addition, exposure was also expressed as a percent of the chronic reference dose (%cRfD). Chronic (food only) exposure to the U.S. population resulted in a MOE of 42,127 (0.2% of the chronic RfD of 0.0025 mg/kg-bw/day). The most sensitive sub-population was children (1-2 years old) with a MOE of 15,238 (0.7% of the chronic RfD). Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures above the benchmark or below 100% of the reference dose, Syngenta believes that there is a reasonable certainty that no harm will result from chronic food exposure to residues arising from all current and proposed uses for emamectin benzoate.
 
      Cancer Risk.  Emamectin benzoate is considered "not likely to be a human carcinogen". Therefore, no cancer risk assessment was performed for emamectin benzoate.
 
 Drinking water. The estimated drinking water concentrations (EDWCs) of emamectin benzoate (expressed as total toxic residues of parent plus 8,9- Z isomer, AB, MFB, and FAB) were derived from the Pesticide Water Calculator (PWC, v1.52) graphical user interface which incorporates the Pesticide Root Zone Model/Variable Volume Water Model (PRZM/VVWM) Tier II surface water and Tier I PRZM ground water modelling platforms. Simulations were conducted to determine the highest EDWCs resulting from current labelled uses and proposed uses on cherries, artichoke, chives and basil. PWC ground water modelling showed incomplete breakthrough following a 100-year simulation. Tier II PWC surface water modelling of proposed applications to cucurbit vegetables provided the highest acute and chronic EDWCs of 0.980 ppb and 0.292 ppb, respectively. Surface water EDWCs were not adjusted for Percent Cropped Area (PCA) factor. Since surface water EDWCs exceed the ground water EDWC, surface water concentrations were used for risk assessment purposes and will be considered protective for any ground water exposure concerns.     
 
      Acute Exposure from Drinking Water:  The acute surface water EDWC of 0.980 ppb was input directly into the DEEM-FCID(TM) software as "water, direct and indirect, all sources" to model the acute drinking water exposures. Drinking water exposures at the 99.9th percentile were determined by taking the difference between the aggregate exposures (food + drinking water) and food exposures (food only) for each population subgroup. Acute drinking water exposure to the U.S. population resulted in a MOE of 3,521 (2.8% of the aRfD of 0.0025 mg/kg-bw/day). The most sensitive sub-population was all infants <1 year old, with a MOE of 2,137 (4.7% of the aRfD of 0.0025 mg/kg-bw/day). Since the benchmark MOE for this assessment is 100 and since EPA generally has no concern for exposures above the benchmark or below 100% of the aRfD, Syngenta believes that there is a reasonable certainty that no harm will result from acute drinking water exposures to residues arising from all current and proposed uses for emamectin benzoate.
 
Chronic Exposure from Drinking Water:  The chronic surface water EDWC of 0.292 ppb was input directly into the DEEM-FCID(TM) software as "water, direct and indirect, all sources" to model the chronic drinking water exposures. Chronic drinking water  exposure to the U.S. population resulted in a MOE of 42,375 (0.2% of the cRfD of 0.0025 mg/kg-bw/day). Chronic drinking water exposure to the most exposed sub-population (infants, <1 year old) resulted in a MOE of 11,344 (0.9% of the cRfD of 0.0025 mg/kg-bw/day). Since the Benchmark MOE for this assessment was 100 and since EPA generally has no concern for exposures above the benchmark or below 100% of the cRfD, Syngenta believes that there is a reasonable certainty that no harm will result from chronic drinking water exposure to residues arising from all current and proposed uses for emamectin benzoate.
       
D. Cumulative Effects 
 
Section 408(b)(2)(D)(v) of the Federal Food, Drug, and Cosmetic Act (FFDCA) requires EPA to consider available evidence concerning the cumulative effects of pesticide residues and other substances that have a common mechanism of toxicity (i.e., a common toxic effect to human health by the same, or essentially the same, sequence of major biochemical events). The agency determined in its April 18, 2016 human health risk assessments (D426599) that abamectin and emamectin benzoate form a candidate common mechanism group (CMG) for the avermectin macrocyclic lactones. Syngenta conducted screening-level acute, short-term, and chronic cumulative exposure analyses for the avermectin macrocyclic lactones abamectin and emamectin benzoate using the screening framework outlined in the Pesticide Cumulative Risk Assessment: Framework for Screening Analysis Purpose (USEPA, 2016). These screening-level assessments evaluate combined exposures of abamectin and emamectin, and are therefore an overestimate of exposure and risk since they assume a complete co-occurrence of residues of abamectin and emamectin from food, drinking water, and residential sources. 
The cumulative abamectin and emamectin cumulative assessments were performed for all population subgroups with acute and chronic reference doses of 0.0025 mg/kg-bw/day, based on oral toxicity studies in dogs with a NOAEL of 0.25 mg/kg-bw/day and an uncertainty factor of 100X. The 100-fold safety factor includes intra- and interspecies variations. The short-term cumulative assessments utilized the same NOAEL of 0.25 mg/kg-bw/day and an uncertainty factor of 100X (LOC = 100). 
In the acute cumulative assessments, exposures for the U.S. population resulted in a cumulative acute MOE of 273 (36.7% of the aRfD of 0.0025 mg/kg-bw/day). The most sensitive sub-population was children (1-2 years old) with a cumulative acute MOE of 138 (72.2% of the aRfD). In the short-term cumulative assessments, exposures for the U.S. population resulted in a cumulative short-term MOE of 3,095 (Level of Concern = 100). The most sensitive sub-population was children 1-2 years old with a cumulative short-term MOE of 1,559 (Level of Concern = 100). In the chronic cumulative assessments, exposures for the U.S. population resulted in a cumulative chronic MOE of 4,717 (2.1% of the cRfD of 0.0025 mg/kg-bw/day). The most sensitive sub-population was children 1-2 years old with a cumulative chronic MOE of 1,563 (6.4% of the cRfD). These screening-level cumulative aggregate acute, short-term, and chronic assessment indicate that cumulative exposures for abamectin and emamectin benzoate are below the Agency's level of concern.  
 
E. Safety Determination 
 
 U.S. population. The acute dietary exposure analysis (food plus drinking water) showed that exposure from all current and proposed emamectin benzoate crop uses result in a MOE of 1,082 (9.2% of the aRfD, Benchmark MOE = 100) for the general U.S. population. No short-term exposure risk assessment was performed, as there are no registered uses of emamectin benzoate that would result in residential handler exposure. The chronic dietary exposure analysis (food plus drinking water) showed that exposure from all current and proposed emamectin benzoate crop uses result in a MOE of 21,125 (0.4% of the cRfD, Benchmark MOE = 100) for the general U.S. population. Based on the completeness and reliability of the toxicity data supporting these uses, Syngenta believes that there is a reasonable certainty that no harm will result to the general U.S. population from aggregate exposure to residues arising from all current proposed emamectin benzoate uses, including anticipated dietary exposure from food and water.
       
 Infants and children. The acute dietary exposure analysis (food plus drinking water) showed that exposure from all current and proposed emamectin benzoate uses results in a MOE of 678 (14.8% of the aRfD) for infants less than 1 year old (the most sensitive population subgroup). The chronic dietary exposure analysis (food plus drinking water) showed that exposure from all current and proposed emamectin benzoate uses result in a MOE of 7,327 (1.4% of the cRfD) for infants less than 1 year old (the most sensitive population subgroup). Based on the completeness and reliability of the toxicity data supporting these uses, Syngenta believes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to residues arising from all current and proposed emamectin benzoate uses, including anticipated dietary exposure from food and water.   
       
F. International Tolerances 
 
Codex has established Maximum Residue Levels (MRLs) for emamectin benzoate on commodities including almond hulls, brassica vegetables, cotton seed, cucurbit vegetables, fruiting vegetables, leafy vegetables, pome fruits, tomato, tree nuts, turnips, and wine.