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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

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-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; sorghum, 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, hay 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 ppm; 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 FFDCA; 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 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 of 
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0.010-5.0 mg/kg with 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 0.051 to 0.410

ppm in/on sweet corn forage, ND (<0.003 ppm) in/on sweet corn kernel 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 nine 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-2032 at 

a total rate of 0.178 lb a.i./A (200 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 (160 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 sulfoxaflor after two foliar broadcast applications of GF-2372 

at a total rate of 0.178 lb a.i./A (200 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 alfalfa 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 clover 

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. Genotoxicity. [A complete 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. 

Mode 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 relevance 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 there were no 

effects at the limit dose of 1000 mg/kg/day.]
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5. Chronic toxicity. [Carcinogenicity was assessed in rats and mice. Treatmentrelated 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. Endocrine disruption. [A minimal delay in balano-preputial separation and effects 

on interstitial cells were seen in rats but not mice.]

9. Neurotoxicity. [Apart from transient cholinergic signs following a large bolus 

gavage dose of 750 mg/kg, sulfoxaflor 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 processing 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 cPAD indicate a reasonable certainty of no harm 

associated with the proposed uses of sulfoxaflor.

Acute Dietary Exposure. For acute dietary sulfoxaflor exposures, the NOAEL is 25 

mg/kg/d from the acute neurotoxicity study in rats. With the 100X uncertainty 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 residue 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 water 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 sulfoxaflor 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, the 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 Exposure. 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 exposures 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 residues 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 exposures 
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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 water 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 exposures correspond to 56.6% of the chronic 

population adjusted dose or less for all population subgroups.]

i. Food. [NA – remove]

ii. Drinking water. [Based on the Pesticide Root Zone Model /Exposure Analysis 

Modeling System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCIGROW) 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 assessment 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 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 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 currently 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 

has 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 

substances. 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 chronic 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 represents the level 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 toxicological 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 rats 
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and rabbits and a multi-generation reproduction study in the rat are considered. 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 safety 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. 

Effects in rats were shown to be due to sulfoxaflor agonism to the fetal rat muscle 

nicotinic acetylcholine receptor. Sulfoxaflor 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 predicted 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 completeness 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 established 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.]