Document ID: EPA-HQ-OPP-2018-0143-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2018-07-24T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: Mr. Gene Benbow, 703-347-0235

Syngenta Crop Protection, LLC

Syngenta Crop Protection, LLC PP#

	EPA has received a pesticide petition PP # XX 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 
         
the insecticide avermectin B1(a mixture of avermectins containing greater than or equal to 80% avermectin B1a (5-O- demethyl avermectin A1) and less than or equal to 20% avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)) in or on the raw agricultural commodity 

      Edible-podded legume vegetables subgroup 6A at 0.03 parts per million
      Succulent shelled pea and bean subgroup 6B at 0.005 parts per million
      Dried shelled pea and bean (except soybean) subgroup 6C at 0.005 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.

A. Residue Chemistry

	1. Plant metabolism. The metabolism of abamectin in plants is adequately understood and the residues of concern include the parent insecticide abamectin (also referred to as avermectin B1 which is a mixture of a minimum of 80% avermectin B1a and a maximum of 20% avermectin B1b) and the delta 8,9-isomer of the B1a and of the B1b components of the parent insecticide.

 Analytical method. The analytical methods involve homogenization, filtration, partition, and cleanup with analysis by high performance liquid chromatography (HPLC)-fluorescence detection. The methods are sufficiently sensitive to detect residues at or above the tolerances proposed. All methods have undergone independent laboratory validation. 

 Magnitude of residues. Complete residue data to support the requested tolerances have been submitted.  The requested tolerances are adequately supported.  
	
B. Toxicological Profile A full description of the studies regarding the toxicity, animal metabolism, and metabolite toxicology, of emamectin benzoate can be found in 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 IV acute, short-term, and chronic aggregate exposure evaluations were made for abamectin 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 and revised crop groupings on legumes (Crop Group 6), blueberries (post-harvest, non-food), carrot (seed treatment), imported tea, and imported bananas.  Residue data were obtained from field trial residue studies in which abamectin 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.  Empirical processing factors were used for cottonseed oil (0.48x), grape juice (0.23x), grape raisins (0.75x), grapefruit juice (0.85x), orange juice (0.25x), orange peel (2.5x), dried prune (3.9x), tomato paste (0.84x), tomato puree (0.4x), field corn flour (1.96x), and papaya pulp (0.35x).  Percent crop treated values were taken from the EPAs April 14, 2016 acute and chronic dietary assessments (D424009, D421348).  Residue values for in the 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.  In addition to dietary sources of abamectin, beef and/or dairy cattle may be exposed to abamectin via impregnated ear tags.  In order to account for residues of abamectin in milk from either or both of these sources, an approach was developed to combine dietary abamectin residues with additional ear tag abamectin residues in a refined probabilistic dietary risk assessment.  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.  

	i. Food Acute Exposure.  The abamectin 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 395 (25.3% of the acute RfD of 0.0025 mg/kg-bw/day).  The most sensitive sub-population was children (1-2 years old) with a MOE of 178 (56.0% 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 abamectin.

Chronic Exposure.  The abamectin 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 (%RfD).  Chronic (food only) exposure to the U.S. population resulted in a MOE of 9,907 (1.0% 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 2,210 (4.5% 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 abamectin.

Cancer.  Abamectin is considered "not likely to be a human carcinogen".  Therefore, no cancer risk assessment was performed for abamectin.

	ii. Drinking water. The residues of concern in drinking water include abamectin (avermectin B1a and B1b), NOA448111 (8a-oxo-avermectin B1a), NOA448112 (8a-hydroxy-avermectin B1a), NOA426289 (4-oxo-avermectin B1a), NOA445495 (3-demethyl-avermectin B1a), NOA457464, and NOA457465. This mixture is referred to as abamectin TTR (total toxic residue).The estimated drinking water concentrations (EDWCs) of abamectin TTR 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 as well as proposed foliar uses on bulb and green onions, legume vegetables, and seed treatment for carrots.  PWC ground water modelling for golf course turf (tees, greens, and fairways) provided the highest acute EDWC of 0.105 ppb.  A chronic EDWC could not be determined because the model predicted incomplete breakthrough over the 100-yr. simulation.  Therefore, the chronic EDWC was derived from the SCI-GROW model (v 2.3) which predicted an EDWC of 0.00355 ppb. Tier II PWC surface water modelling of golf course turf (tees, greens, and fairways) provided the highest acute and chronic EDWCs of 1.85 ppb and 0.814 ppb, respectively.  Surface water EDWCs were not adjusted for Percent Cropped Area (PCA) factor.  Since surface water EDWCs exceed the ground water EDWCs, 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 1.85 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 99.9[th] 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 drinking water MOE of 4,630 (2.2% of the aRfD of 0.0025 mg/kg-bw/day).  The most sensitive sub-population was females 13-49 years old, with a drinking water MOE of 2,688 (3.7% 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 of abamectin.

Chronic Exposure from Drinking Water.  The chronic surface water EDWC of 0.814 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 drinking water MOE of 15,201 (0.7% of the cRfD of 0.0025 mg/kg-bw/day).  The most sensitive sub-population was infants <1 year old, with a drinking water MOE of 4,069 (2.5% 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 of abamectin.

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

	1. U.S. population. The acute dietary exposure analysis (food plus drinking water) showed that exposure from all current and proposed abamectin crop uses result in a MOE of 364 (27.5% of the aRfD, Benchmark MOE = 100) for the general U.S. population.  The short-term exposure analysis (food plus drinking water plus residential) showed that exposure from all current and proposed abamectin uses result in a MOE of 3,635 (Benchmark MOE = 100) for the general U.S. population.  The chronic dietary exposure analysis (food plus drinking water) showed that exposure from all current and proposed abamectin crop uses result in a MOE of 5,998 (1.7% 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 abamectin uses, including anticipated dietary exposure from food, water, and all other types of non-occupational residential exposures.

	2. Infants and children. The acute dietary exposure analysis (food plus drinking water) showed that exposure from all current and proposed abamectin uses results in a MOE of 169 (59.0% of the aRfD) for children 1-2 years old (the most sensitive population subgroup).  For the short-term aggregate assessments, children 1-2 years old had an aggregate MOE of 1,834 (Benchmark MOE = 100) for all current and proposed abamectin uses.  The chronic dietary exposure analysis (food plus drinking water) showed that exposure from all current and proposed abamectin uses result in a MOE of 1,842 (5.4% of the cRfD) for children 1-2 years 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 abamectin uses, including anticipated dietary exposure from food, water, and all other types of non-occupational residential exposures.

F. International Tolerances

Codex has established Maximum Residue Levels (MRLs) for abamectin on commodities including almond hulls, avocado, beans, blackberries, celery, cherries, citrus fruits, cotton seed, cucumber, dried grapes, eggplant, garlic, gherkin, grape juice, grapes, hops, leek, lettuce, mango, melons, onions, papaya, peaches, peanut, peppers, plums, pome fruits, potato, raspberries, rice, shallots, strawberries, sweet potato, tomato, tree nuts, and yams.