# i

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

EPA Registration Division contact: Venus Eagle, 703

- 308

- 8045

[ Dow AgroSciences LLC ]

[ PP 4F8237 ]

EPA has received a pesticide petition ( [ PP 478237 ] ) from Dow AgroSciences LLC
, c/o Dow AgroSciences, 9330 Zionsville Road, Indianapolis, IN 46268 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.
1. by establishing a tolerance for residues of Sulfoxaflor (common name sulfoxaflor: ( N

- [methyloxido[1

- [6

- (trifluoromethyl)

- 3

- pyridinyl]ethyl]

- γ 4

- sulfanylidene]cyanamide) in or on the raw agricultural commodity corn, field, grain at 0.015 parts per million; corn, field, forage at 0.5 ppm; corn, field, stover at 0.8 ppm; corn, sweet, at 0.01 ppm; corn, sweet, forage at 0.6 ppm; corn, sweet, stover at 0.7 ppm; corn, pop at 0.015 ppm; corn, pop, stover at 0.8 ppm; teosinte, grain at 0.015 ppm; sor ghum, grain at 0.3 ppm;, sorghum, forage at 0.4 ppm; sorghum, stover at 0.9 ppm; millet, grain at 0.3 ppm; millet, forage at 0.4 ppm; cacao bean, dried bean at 0.15 ppm; pineapple at 0.09 ppm; alfalfa, seed at 30 ppm;, alfalfa, forage at 7 ppm; alfalfa, ha y at 20 ppm; alfalfa, silage at 9 ppm; clover forage at 15 ppm; clover hay at 20 ppm; clover silage at 8 ppm; animal feed, nongrass, group 18, forage at 15 ppm; animal feed, nongrass, group 18, hay at 20 ppm; animal feed, nongrass, group 18, silage at 9 pp m; buckwheat, grain at 0.08 ppm; buckwheat, forage at 1 ppm; buckwheat, hay at 1.5 ppm; buckwheat, straw at 2 ppm; triticale, grain at 0.08 ppm; triticale, forage at 1 ppm; triticale, hay at 1.5 ppm; triticale, straw at 2 ppm; rye, grain at 0.08 ppm; rye, forage at 1 ppm; rye, hay at 1.5 ppm; rye, straw at 2 ppm; teff, grain at 0.08 ppm; teff, forage at 1 ppm; teff, hay at 1.5 ppm; teff, straw at 2 ppm; oat, grain at 0.4 ppm; oat, hay at 1 ppm; oat, straw at 2 ppm. Revised tolerances of unchanged parent, sulfoxaflor are also proposed for milk at 1 ppm; fat of cattle, goat, horse and sheep at 0.6 ppm; meat of cattle, goat, horse and sheep at 1 ppm; meat byproducts of cattle, goat, horse and sheep at 2.5 ppm; hog, fat at 0.04 ppm; hog, meat at 0.07 ppm; hog, meat byproducts at 0.2 ppm; egg at 0.08 ppm; poultry, meat at 0.09 ppm; poultry, fat at 0.03 ppm; poultry, meat byproducts at 0.2 ppm

. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2 ) of F F DCA; however, EPA has not fully evaluated the sufficiency of the submitted d a ta 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 metab olism

. [ The nature of the residue in plants is adequately understood for the purpose of these tolerances. Based on the findings from these metabolism studies, the residue of concern in plants is Sulfoxaflor , expressed as the parent.]
2. Analytical method

. [ The residue profile of sulfoxaflor is adequately understood and an acceptable analytical method is available for enforcement purposes. Analytical method 091116, “Enforcement Method for the Determination of Sulfoxaflor (XDE

- 208) and its Main Metabolites in Agricultural Commodities using Offline Solid

- Phase Extraction and Liquid Chromatography with Tandem Mass Spectrometry Detection” was validated on a variety of plant matrices. The method was validated over the concentration range of2

0.010

- 5.0 mg/kg wit h a validated limit of detection (LOD) of 0.003 mg/kg and limit of quantitation (LOQ) of 0.010 mg/kg. ]
3. Magnitude of residues. [ The test material was GF

- 2032, a suspension concentrate (SC) containing 240 g ai/L. In several MOR studies ( field corn, sweet corn, sorghum, alfalfa, and clover ) the test material was GF

- 2732, a water dispersible granule (WG) which contains 50% active ingredient.
1. Field Corn: Residues of sulfoxaflor after two foliar broadcast applications of GF

- 2372 at a total rate of 0.089 lb a.i./A (100 g a.i./ha) in fifteen USA trials, ranged from 0.024 to 0.385 ppm in/on field corn forage harvested at 7

- day PHI, from ND (<0.003 ppm) to 0.011 ppm in/on field corn grain, and from 0.018 to 0.679 ppm in/on field corn stover harvested at 14

- day PHI.
2. Sweet Corn: Residues of sulfoxaflor after two foliar broadcast applications of GF

- 2372 at a total rate of 0.089 lb a.i./A (100 g a.i./ha) in nine USA trials, ranged from 0.0 51 to 0. 410 ppm in/on sweet co rn forage , ND (<0.003 ppm) in/on sweet corn k ernel plus cobs with husks removed, and from 0.088 to 0.506 ppm in/on sweet corn stover harvested at 7

- day PHI.
3. Sorghum: Residues of sulfoxaflor after two foliar broadcast applications of GF

- 2372 at a total rate of 0.089 lb a.i./A (100 g a.i./ha) in nin e USA trials, ranged from 0.017 to 0.202 ppm in/on sorghum forage harvested at 7

- day PHI, from 0.016 to 0.152 ppm in/on sorghum grain, and from 0.034 to 0.733 ppm in/on sorghum stover harvested at 14

- day PHI.
4

. Pineapple : Residues of sulfoxaflor after two foliar broadcast applications of GF

- 2 0 32 at a total rate of 0.1 7 8 lb a.i./A ( 2 00 g a.i./ha) in eight USA and Costa Rica trials, ranged from <LOQ (<0.01 ppm) to 0.059 ppm in/on pineapple fruit harvested at 7

- day PHI

. 5

. Cacao : Residues of sulfoxaflor after four foliar broadcast applications of GF

- 2032 at a total rate of 0.143 lb a.i./A ( 16 0 g a.i./ha) in eight Costa Rica trials, ranged from ND (<0.003 ppm) to 0.058 ppm in/on cacao dried beans harvested at 3

- day PHI

. 6

. Alfalfa/Clover : Residues of sulfoxaflo r after two foliar broadcast applications of GF

- 2372 at a total rate of 0.178 lb a.i./A ( 2 00 g a.i./ha) in eleven USA trials on alfalfa and in nine USA trials on clover, ranged from 0.562 to 4.18 ppm in/on alfalfa forage, from 1.45 to 12.5 ppm in/on alfalf a hay, from 1.56 to 4.37 ppm in/on alfalfa silage harvested at 7

- day PHI after third cutting, from 0.203 to 16.3 ppm in/on alfalfa seed, from 0.093 to 9.26 ppm in/on clover forage, from 0.294 to 12.7 ppm in/on clover hay, and from 0.087 to 3.80 ppm in/on c lover silage harvested at 7

- day PHI.]
B. Toxicological Profile

1. Acute toxicity. [ Sulfoxaflor has low acute toxicity with an oral LD50  750 mg/kg bw, no dermal toxicity at the limit dose of 5000 mg/kg bw and no inhalation toxicity at the highest achievable respirable concentration. Skin and eye irritation was minimal and there was no skin sensitization potential. ]

2. Genotoxic i ty. [ A c omplete battery of in vitro and in vivo genotoxicity studies were negative. ]

3. Reproductive and developmental toxicity. [ Standard regulatory studies comprised a two

- generation reproduction study in rats and a developmental study in rats and rabbits. Mod e of action studies investigated effects seen in rats. No effects were seen in rabbits. With the possible exception of a minimal delay in balano

- preputial separation in high dose level male rats, there were no reproduction or developmental effects of relev ance to humans. ]

4. Subchronic toxicity. [ In rat and mouse subchronic toxicity studies, the primary target organ was the liver. In the dog, the only effects were decreases in feed consumption and body weight gain. In a rat 28

- day dermal toxicity study t here were no effects at the limit dose of 1000 mg/kg/day. ]3

5. Chronic toxicity. [ Carcinogenicity was assessed in rats and mice. Treatment

related liver tumors occurred in high dose male rats and male and female mice. These effects have been shown not to be relevant to humans. ]

6. Animal metabolism. [ Sulfoxaflor has negligible metabolism in rats, mice, dogs and rabbits. ]

7. Metabolite toxicology

. [ The toxicological properties of the sulfoxaflor environmental metabolites have been characterized

. ]
8. E ndocrine disruption

. [ A minimal delay in balano

- preputial separation and effects on interstitial cells were seen in rats but not mice. ]

9. Neurotoxicity

. [ A part from transient cholinergic signs following a large bolus gavage dose of 750 mg/kg, sulfoxafl or demonstrated no neurotoxic potential. ]
10. Immunotoxicity

. [ There were no indications of immunotoxicity in rats (NOAEL ≥ 94.9 mg/kg/day)

. ]

C. Aggregate Exposure
1. Dietary exposure. [ Dietary exposures associated with the proposed uses of sulfoxaflor have been estimated using DEEM

- FCIDTM and conservative assumptions. The Tier 1 acute assessment assumes residues at maximum residue levels and 100% crop treated. The chronic assessment assumes residues at average values from field trials with processin g factors, average estimated residues in meat, milk, poultry and egg commodities, and 100% crop treated. Acute and chronic dietary (food + water) exposures are below the aPAD and cPAD, respectively, for all subpopulations. Exposures below the aPAD and cP AD indicate a reasonable certainty of no harm associated with the proposed uses of sulfoxaflor. Acute Dietary Expos u re

. For acute dietary sulfoxaflor exposures, the NOAEL is 25 mg/kg/d from the acute neurotoxicity study in rats. With the 100X uncertain ty factor, the acute population adjusted dose (aPAD) is 0.25 mg/kg/d. Acute dietary exposures associated with the proposed uses of sulfoxaflor were assessed using DEEM

- FCIDTM based on NHANES 2

- day food consumption for 2003

- 2008. For this conservative Tier 1 acute dietary exposure assessment, residues in commodities were assumed at the maximum r e sidue values from field trials for all commodities, and 100% crop treated was assumed for all commodities. Processing factors were used when necessary for processed commodities not otherwise covered by a specific tolerance. Drinking water was included directly in the acute dietary risk assessment for General Population at an adjusted parent

- equivalent residue of 0.0692 ppm for parent and 2 metabolites, , based on wa ter modeling . For acute dietary risk assessment of Females 13

- 49 years old, the Agency has determined that residues in groundwater are not appropriate for assessing the endpoint, and that surface water source residue of 0.0094 ppm is the appropriate sulf oxaflor water residue value

. Acute dietary exposures at the 95th percentile (the appropriate level for a Tier 1 assessment) range from 0.018151 mg/kg/d (7.3% aPAD) for adults 50+ years old to 0.109733mg/kg/d (43.9 % % aPAD) for children aged 1

- 2 years , th e most highly exposed subpopulation. The 95th percentile acute dietary exposure for the U.S. population is 0.035989 mg/kg/d (14.4 % aPAD) . Thus, acute dietary exposures correspond to 43.9 % of the acute population adjusted dose or less for all population subgroups. Chronic Dietary Expos u re

. For chronic dietary sulfoxaflor exposures, the NOAEL is 5.15 mg/kg/d from the chronic rat bioassay. With the 100X uncertainty factor, the chronic population adjusted dose (cPAD) is 0. 05 mg/kg/d. Chronic dietary exposur es associated with the proposed uses of sulfoxaflor were assessed using DEEM

- FCIDTM based on NHANES 2

- day food consumption data for 2008

- 2008 . For this refined chronic dietary exposure assessment, residues in commodities were assumed at the average residue s from field trials as calculated by DAS or at anticipated residues for meat, milk, poultry and eggs as calculated by DAS. Average residues from field trials are more reflective of potential exposures over time, so they result in a more representative yet conservative estimate of chronic dietary exposures4

than the use of MRLs. Also, 100% crop treated was assumed for all commodities. Processing factors were used to reflect the concentration or reduction of residues in processed commodities. Drinking wate r was included directly in the chronic dietary risk assessment representing the combined residues of 0.0183 ppm X11719474 and 0.083 ppm X11519540 metabolites at adjusted parent

- equivalent residue values. Chronic dietary exposures range from 0.004851 mg/kg /d (9.7% cPAD) for Adults 50+ years, to 0.028292 mg/kg/d (56.6% cPAD) for children aged 1

- 2 years , the most highly exposed subpopulation. The chronic dietary exposure for the U.S. population is 0.006738 mg/kg/d (13.5% cPAD) . Thus, chronic dietary exposu res correspond to 56.6 % of the chronic population adjusted dose or less for all population subgroups. ]
i. Food. [ NA

– remove]
ii. Drinking water

. [ B ased on the Pesticide Root Zone Model /Exposure Analysis Modeling System (PRZM/EXAMS) and Screening Conce ntration in Ground Water (SCI

GROW) models, the estimated drinking water concentrations (EDWCs) of sulfoxaflor for acute exposures are estimated to be 26.4 parts per billion (ppb) for surface water and 69.2 ppb for ground water. For acute dietary risk asse ssment of the general population , the groundwater EDWC is greater than the surface water EDWC and was used in the assessment. The residue profile in groundwater is 60.9 ppb X11719474 and 8.3 ppb X11519540 (totaling 69.2 ppb).

. For acute dietary risk ass essment of Females 13

- 49 years old , the Agency has determined that residues in groundwater are not appropriate for assessing the endpoint, and that surface water source residue of 0.0094 ppm is the appropriate sulfoxaflor water residue value Drinking water was included directly in the chronic dietary risk assessment. Chronic

- All Populations EDWC was determined to be 0.1013 ppm representing the combined residues of 0.0183 ppm X11719474 and 0.083 ppm X11519540

. ]
2. Non

- dietary exposure

. [ Sulfoxaflor is cur rently not registered for any residential

non - food site. Thus, the risk from non

- dietary exposure to sulfoxaflor residues is considered negligible

. ] D. Cumulative Effects [ At this time, EPA does not have available data to determine whether sulfoxaflor h as a common mechanism of toxicity with other substances. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, sulfoxaflor does not appear to produce a toxic metabolite generated by other

su bstances. For purposes of this assessment, therefore, it is assumed that sulfoxaflor does not have a mechanism of toxicity common with other substances and no cumulative risk assessment is required. ] E. Safety Determination
1. U.S. population. [ Using the above conservative exposure assumptions, and based on the completeness and reliability of the toxicity data, the aggregate exposure to sulfoxaflor from the proposed new tolerances in fruit and vegetable commodities will utilize 13.5 % or less of the chroni c population adjusted dose, cPAD, for the general U. S. population. The population subgroup with the highest exposure of 56.6 % of the cPAD is children (1

- 2 yrs old). Generally, EPA has no concern for exposures below 100% of the cPAD because the cPAD repre sents the l evel at or below which daily aggregate dietary (food+water) exposures over a lifetime will not pose appreciable risks to human health. Short

- term and intermediate

- term risks are considered to be negligible because of lack of significant toxic ological effects. Therefore, based on these risk assessments, Dow AgroSciences concludes that there is reasonable certainty that no harm will result to the U. S. population from aggregate exposure to sulfoxaflor residues from current and proposed new uses

. ]

2. Infants and children

. [ In assessing the potential for additional sensitivity of infants and children to residues of sulfoxaflor , data from developmental toxicity studies in rats5

and rabbits and a multi

- generation reproduction study in the rat are c onsidered. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism resulting from pesticide exposure during prenatal development. Reproduction studies provide information relating to effects from exposure of both parents to the pesticide on the reproductive capability and potential systemic toxicity of mating animals and on various parameters associated with the well

- being of offspring.

FFDCA section 408 provides that the U.S. EPA may apply an additional saf ety factor for infants and children in the case of threshold effects to account for pre

- and post

- natal toxicity and the completeness of the database. Based on the current toxicological data requirements, the database for sulfoxaflor relative to pre

- and post

- natal effects for children is complete. No effects were seen in rabbits at the highest dose level tested. E ffects in rats were shown to be due to sulfoxaflor agonism to the fetal rat muscle nicotinic acetylcholine receptor. S ulfoxaflor has also been shown not to have any agonism to the corresponding human receptors whereby it is possible to conclude that the effects in rats are not relevant to humans and therefore, do not trigger retention of the FQPA safety factor.

Using the conservative exposure assumptions, the percent RfD utilized by the potential exposure to residues of sulfoxaflor on a wide variety of fruit and vegetable crops and animal commodities is 56.6 % for children 1

- 2 years, the population subgroup predic ted to be potentially the most highly exposed. Risk for developmental toxicity from acute exposure to sulfoxaflor was evaluated for females (13

- 49 years old). The high

- end MOE value of 100 ( 29.9 % of aRfD) is acceptable. Therefore, based on the completen ess and reliability of the toxicity data and the conservative exposure assessment, Dow AgroSciences concludes with reasonable certainty that no harm will result to infants and children, females 13+ years old and the prenatal development of infants from the aggregate exposure to sulfoxaflor residues. ]

F. International Tolerances [ There are several countries around the globe that have established tolerances/MRLs for sulfoxaflor in meat, milk and eggs. By comparing them, it is concluded that the MRLs establ ished by different agencies on animal commodities are not harmonized. The disharmony may be attributed to the use on different feed commodities and composition of livestock diets which are used to calculate the MRL for these animal commodities. It is not reasonable to conclude that the US tolerance levels can be harmonized with MRLs on animal commodities from other countries, and therefore the condition of MRL incompatibility amongst different countries for sulfoxaflor will persist. ]