UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 14 October 2014 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Sulfoxaflor - Addendum to the Human Health Risk Assessment of the FIFRA 

Section 18 Emergency Exemption Use on Sorghum. 

PC Code: 0052 10 

Decision No.: 487020 

Petition No.: 14TX02 

Risk Assessment Type: Single Chemical, 

Aggregate 

TXR No.: None 

MRID No.: None 

FROM: Michael A. Doherty, Ph.D., Senior Chemist 

Risk Assessment Branch II 

Health Effects Division (7509P) 

DP Barcode: 0423348 

Registration No.: 62719-625 

Regulatory Action: Section 18 

Registration Case No.: None 

CAS No.: 946578-00-3 

40 CFR 180.668 

THROUGH: Christina Swartz, Branch Chief ~ A ~ Risk Assessment Branch II U ~ Health Effects Division (7509P) 

TO: Keri Grinstead/Tawanda Maignan (Team 09) 

Risk Integration, Minor Use & Emergency Response Branch 

Registration Division (7505P) 

Jennifer Urbanski/Venus Eagle (Team 01) 

Insecticide-Rodenticide Branch 

Registration Division (7505P) 

This addendum to the subject risk assessment is being issued to correct the dietary exposure/risk 

summary presented on Page 6 of the original assessment (D417536, 5 March 2014). Aside from 

that paragraph, there are no other changes to the original memo. The entire assessment is 

presented below for completeness. 

Page 1 of 18 
CONCLUSIONS 

HED has evaluated the human health risks associated with the requested emergency exemption 

use of the insecticide sulfoxaflor on sorghum. There are no proposed or existing residential uses 

for sulfoxaflor; therefore, this risk assessment addresses the potential dietary (food+ drinking 

water) and occupational exposures associated with the proposed use. HED concludes that there 

is a reasonable certainty that no harm will result from aggregate exposure to sulfoxaflor 

associated with the requested Section 18 use; further, there are no concerns for occupational 

exposure and risk estimates associated with the proposed use pattern. The supported tolerances 

and the tolerance definition are summarized below. 

INTRODUCTION 

The state ofTexas1 is requesting an emergency exemption under FIFRA Section 18 for the use of 

sulfoxaflor on sorghum to control sugarcane aphid (Melanaphis sacchari). This is the first 

Section 18 request for this use. The Agency has been petitioned by Dow AgroSciences (the 

registrant for sulfoxaflor) to register additional uses of sulfoxaflor and establish tolerances for 

residues of sulfoxaflor in multiple crops, including sorghum (PP#4F8237). 

In 2012, HED completed a human health risk assessment for sulfoxaflor, addressing uses on 

numerous commodities (M. Doherty eta!., 0382604, 26 Sept 2012; subsequent citations ofthis 

assessment are listed as "0382604.''). 

ASSESSMENT SUMMARY 

Sulfoxaflor { N-[ methyloxido[ 1-[ 6-(trifluoromethyl)-3-pyridinyl]ethyl]-A. 4-sulfanylidene] 

cyanamide} is the first member of a new class of insecticides, the sulfoximines. The 

sulfoximines act through a unique interaction with the nicotinic acetylcholine receptor in insects. 

Sulfoxaflor is a highly efficacious agonist of the nicotinic receptor. The structural novelty of 

sulfoxaflor makes it stable in the presence of monooxygenase enzymes that degrade 

neonicotinoids and cause virtually all known cases of resistance in the field of this class of 

insecticides. 

The Section 18 request is for application ofTransformTM WG, a wettable granule containing 50% 

(w/w) sulfoxaflor. Under this exemption, sulfoxaflor may be applied to approximately 3 million 

acres of sorghum in Texas (however, see Footnote 1). Applications would be made from spring 

through late summer of the 2014 growing season using either ground-based, aerial, or 

chemigation equipment. The proposed use directions are summarized in Table 1. 

1 The exemption request notes that Lousianna, Oklahoma, and Mississippi have indicated that they will pursue a 

specific exemption for use of sulfoxaftor on sorghum. This risk assessment assumes that the entire U.S. sorghum 

crop is treated with sulfoxaflor. Provided the use rates and timing are the same as those described for the use in 

Texas, this risk assessment implicitly includes other states seeking this emergency exemption. 

Page 2 of 18 
Page 3 of 18

Table 1. Summary of Proposed Use Directions a Specific Exemption Use of Sulfoxaflor on Sorghum.

Use Timing; 

Type; and 

Equipment

Product

[File 

Symbol]

Single Use 

Rate

Maximu

m Uses 

per 

Season

Maximum 

Seasonal 

Use Rate

PHI

(Days)

Use Directions and 

Limitations

Foliar use. 

Application by 

ground, aerial, 

or chemigation 

equipment.

TransformTM

WG 

[62719-625]

0.023–0.047 

lb a.i./acre

2 0.09 lb 

a.i./acre/yr

7 

(grain)

14

(forage, 

stover)

Do not make applications less 

than 14 days apart. 

Do not make more than two 

applications per year. 

Do not apply more than 0.09 

lb a.i./acre per year.

The nomenclature of sulfoxaflor is summarized in Table 2, below. The physical/chemical 

properties of sulfoxaflor (Appendix B) indicate that the compound is not particularly volatile 

(vapor pressure ≤ 1.4 x 10-6 Pa) and based on the KOW (~6.35) it is not expected to partition into 

fatty tissue or bioaccumulate.

Table 2. Test Compound Nomenclature.

Compound

N

S

N O

N

F3C

Common name Sulfoxaflor

Company experimental name XDE-208

IUPAC name [methyl(oxo){1-[6-(trifluoromethyl)-3-pyridyl]ethyl}-λ

6

-

sulfanylidene]cyanamide

CAS name [N-methyloxido[1-[6-(trifluoromethyl)-3-pyridinyl]ethyl] λ4-

sulfanylidene] cyanamide

CAS # 946578-00-3

Toxicology

The toxicology database for sulfoxaflor is adequate for FQPA consideration, including the 

assessment of potential increased susceptibility of infants and children. The database includes a 

developmental toxicity study in rats and rabbits, a 2-generation reproduction study in rats, and 

acute, subchronic, and developmental neurotoxicity studies in rats. The Agency has not received 

a 28-day inhalation study in the rat; however, that study has been waived for sulfoxaflor (TXR# 

0056310). EPA waived the requirement for a subchronic inhalation data based on, among other 

things, its conclusion that even if an additional 10X safety factor were applied, inhalation 

exposure would not raise a risk of concern. The lack of a subchronic inhalation study is not 

considered a data gap and a database uncertainty factor is not required. Toxicity and mechanistic 

studies in rats, rabbits, dogs and mice indicate that the liver and the nervous systems are target 

organ systems. Liver effects in subchronic and chronic studies include organ weight and enzyme 

changes, hypertrophy, proliferation, and tumors; long-term studies resulted in hepatic effects at 

doses lower than in short-term studies. Based on the weight of evidence, the Cancer Assessment 

Review Committee (CARC) determined that there is a “Suggestive Evidence of Carcinogenic 

Potential” for sulfoxaflor and that quantification of risk using a non-linear approach [i.e., oral 
Page 4 of 18

reference dose (RfD)] will adequately account for all chronic toxicity, including carcinogenicity, 

that could result from exposure to sulfoxaflor (TXR# 0056301, 26 April 2012).

Sulfoxaflor also affects the neurological system by interacting with the fetal isoform of the 

intermuscular nicotinic acetylcholine receptor (nAChR). This interaction results in the 

contraction of skeletal muscles causing limb flexure and bent clavicle in fetuses and decreased 

neonatal survival due to the constriction of the diaphragm muscles. HED determined this mode 

of action (MOA) was plausible and supported by the available mechanistic data (D382604).

HED has recommended that the required 10X FQPA Safety Factor be reduced to 1X based on 

the following considerations: 1) the toxicology database for sulfoxaflor is complete with regard 

to FQPA consideration, including the required developmental and reproductive toxicity studies; 

2) the required neurotoxicity studies, including the developmental neurotoxicity study (DNT) 

have been submitted, are considered adequate; 3) although there is evidence of quantitative 

susceptibility in the DNT study, based on decreased survival of offspring up to postnatal day 4, 

the endpoints and doses selected for risk assessment are protective for these effects; further, 

HED’s degree of concern for human susceptibility is reduced based on the special studies 

submitted in support of the mode of action; and 4) although some refinements are used in the 

exposure assessment, the dietary and drinking water assessments still result in upper-bound 

estimates of exposure.

In addition, HED has reduced the 10X interspecies factor (UFA) to 3X for assessments based on 

nicotinic receptor-mediated effects (i.e., acute dietary risk assessment for women of reproductive 

age and for dermal and inhalation risk assessments). There is extensive mechanistic data 

indicating that rats may be uniquely sensitive to the developmental effects of sulfoxaflor: 1) there 

were no developmental effects observed in the rabbit and 2) when the different adult rat, adult 

human, or fetal human nAChR isoforms are expressed in Xenopus oocytes, there was no 

indication of activation in the receptors in the presence of sulfoxaflor. Therefore, only the rat 

fetal isoform of the nAChR appears to be responsive to perturbation by sulfoxaflor. 

Quantitatively, the human fetal nAChR is at least 500-fold less sensitive than the rat fetal nAChR 

based on the highest concentration tested in the human receptor studies compared to the effective 

dose in the rat fetal receptor study. The absence of nAChR activation in the human receptors 

precludes the manifestation of skeletal abnormalities and neonatal deaths. The Agency is 

reducing the UFA to 3X based on the evidence that the human nAChR is not more sensitive than 

the rat. For a full discussion of the receptor data, see D382604. Summaries of the sulfoxaflor 

endpoints used for risk assessment are shown in the tables below. 

Table 3a. Sulfoxaflor Toxicological Doses and Endpoints for Use in Dietary Human Health Risk Assessments.

Exposure/ Scenario Point of 

Departure

Uncertainty/ 

FQPA Safety 

Factors

RfD/PAD Study and Toxicological Effects

Acute Dietary (General 

Population, including 

Infants and Children)

NOAEL= 

25 mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Acute RfD = 

0.25 mg/kg/day

aPAD =

0.25 mg/kg/day

Acute Neurotoxicity Study

LOAEL = 75 mg/kg/day based on 

decreased motor activity.
Page 5 of 18

Table 3a. Sulfoxaflor Toxicological Doses and Endpoints for Use in Dietary Human Health Risk Assessments.

Exposure/ Scenario Point of 

Departure

Uncertainty/ 

FQPA Safety 

Factors

RfD/PAD Study and Toxicological Effects

Acute Dietary

(Females 13-49 years of 

age)

NOAEL = 

1.8 mg/kg/day

UFA= 3x

UFH=10x

FQPA SF= 1x

Acute RfD = 

0.06 mg/kg/day

aPAD =

0.06 mg/kg/day

Developmental Neurotoxicity

Study

LOAEL = 7.1 mg/kg/day based on 

nicotinic-receptor-mediated 

decreased neonatal survival on 

postnatal day (PND) 0 through 4

Chronic Dietary (All 

Populations)

NOAEL= 

5.13 mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Chronic RfD = 

0.05 mg/kg/day

cPAD = 

0.05 mg/kg/day

Chronic/Carcinogenicity Study in 

the Rat

LOAEL = 21.3 mg/kg/day based 

on liver effects including increased 

blood cholesterol, liver weight, 

hypertrophy, fatty change, single 

cell necrosis and macrophages 

observed in the males and females.

Cancer (oral, dermal, 

inhalation)

Sulfoxaflor is classified as “Suggestive Evidence of Carcinogenic Potential.” 

Quantification of risk using a non-linear approach (i.e., RfD) will adequately account for 

all chronic toxicity, including carcinogenicity.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose. 

Table 3b. Sulfoxaflor Toxicological Doses and Endpoints for Use in Occupational Human Health Risk 

Assessments.

Exposure/ 

Scenario

Point of Departure Uncertainty 

Factors

Level of Concern 

for Risk Assessment

Study and Toxicological Effects

Dermal 

Short-and 

Intermediate 

Term

NOAEL= 1.8 mg/kg/day

DAF = 2.4%

UFA=3x

UFH=10x

Occupational LOC 

for MOE = 30

Developmental Neurotoxicity Study

LOAEL = 7.1 mg/kg/day based on 

nicotinic-receptor-mediated 

decreased neonatal survival on 

postnatal day (PND) 0 through 4

Inhalation 

Short-and 

Intermediate 

Term 

NOAEL= 1.8 mg/kg/day

Inhalation and oral 

absorption are assumed 

to be equivalent

UFA=3x

UFH=10x

Occupational LOC 

for MOE = 30

Developmental Neurotoxicity Study

LOAEL = 7.1 mg/kg/day based on 

nicotinic-receptor-mediated 

decreased neonatal survival

(PND 0-4)

Cancer (oral, 

dermal, 

inhalation)

Sulfoxaflor is classified as “Suggestive Evidence of Carcinogenic Potential.” Quantification of risk 

using a non-linear approach (i.e., RfD) will adequately account for all chronic toxicity, including 

carcinogenicity.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of 

concern.
Page 6 of 18

Residue Profile and Dietary Risk

Residue data for sulfoxaflor in/on sorghum commodities were not provided with the Section 18 

submission; however, the Agency has recently received a tolerance petition for sulfoxaflor that 

includes a registration request and residue data for sorghum. Those residue data were used to 

derive the recommended tolerance levels. Sorghum commodities are significant livestock 

feedstuffs; therefore, HED has examined the impact of this specific exemption on livestock 

dietary burdens. The maximum reasonable dietary burden estimates increased relative to the 

previous assessment for all four livestock categories; however, the degree of the increase was 

small enough that revisions to tolerances for livestock commodities are not necessary.

The requested use may result in human exposure to sulfoxaflor and/or its metabolites in food and 

drinking water. Toxicology, residue chemistry, and environmental fate data submitted to the 

Agency show that there are a unique set of exposure profiles that need to be considered when 

assessing this insecticide. In short, given the toxicological endpoints being used for risk 

assessment, information on which chemical species can result in those effects, and differences in 

the residue profiles for foods, surface water, and groundwater, this assessment focuses on the 

following three combinations for evaluating dietary exposure:

 Acute dietary exposure, general population: sulfoxaflor in food and the metabolites 

designated X11719474 and X11519540 in groundwater;

 Acute dietary exposure, women of child-bearing age: sulfoxaflor in food and surface 

water;

 Chronic dietary exposure, all populations: sulfoxaflor in food and the metabolites 

designated X11719474 and X11519540 in groundwater, factoring in information on the 

relative potency of the metabolites to elicit the liver effects being used as the endpoint in 

the assessment. Relative to sulfoxaflor, these factors are 0.3X for X11719474 and 10X 

for X11519540.

Further information regarding these assessments, the rationale for selecting the exposure profiles, 

and the derivation of the toxicity factors is available in the Section 3 Human Health Risk 

Assessment (D382604). 

In evaluating dietary exposure, HED has noted that estimated drinking water concentrations 

(EDWCs) provided by the Environmental Fate and Effects Division (EFED; D418282, M. 

Ruhman, 28 February 2014) based on the sulfoxaflor use on sorghum resulted in lower estimates 

than those used in the previous risk assessment. Furthermore, the food consumption database 

used to support HED’s dietary exposure assessments (NHANES/WWEIA) does not report any 

consumption of sorghum, either as grain or as syrup. Therefore, new dietary exposure and risk 

estimates were not developed for this Section 18 assessment. Previous dietary risk estimates are 

below HED’s level of concern (typically 100% of the population-adjusted dose) for both acute 

and chronic dietary exposure and for all population subgroups. For acute exposures, the highest 

risk estimate is 16% aPAD for the “children 1-2 years old” and “females 13-49 years old”

population subgroups. For chronic exposures, the highest risk estimate is 18% cPAD for the all 

infants population subgroup.
Page 7 of 18

Occupational Exposure and Risk

The submitted Section 18 label lists 2 applications per season with a minimum 14-day 

retreatment interval; therefore, short- (1 to 30 days) and intermediate-term (1 to 6 months) 

exposures are expected for handlers. In the previous risk assessment (D382604), occupational 

margins of exposure (MOEs) were estimated for the “high-acreage field crops” scenario, which 

would include sorghum. Occupational activities addressed in the previous risk assessment 

include application-related tasks (mixing, loading, applying, etc.) as well as post-application 

tasks (scouting, weeding, irrigating, etc.). The application rates used in the previous assessment 

were greater than the rates currently proposed for the Section 18 use on sorghum; therefore, the 

occupational exposure and risk estimates for the proposed use are expected to be less than those 

assessed in the previous sulfoxaflor assessment (D382604). The current level of concern (LOC) 

for assessing short- and intermediate-term occupational exposure to sulfoxaflor is a margin of 

exposure (MOE) that is less than 30. At a baseline level of personal protective equipment (PPE), 

the previously estimated occupational MOEs range from 80 to 7,000,000, and the vast majority 

of the estimates are greater than 300. All estimated occupational MOEs indicate that risks are 

below HED’s level of concern, including those associated with the proposed use of sulfoxaflor 

on sorghum. 

Sulfoxaflor does not appear to have a mode of action in common with other pesticide active 

ingredients or their metabolites, nor does sulfoxaflor have metabolites common to other active 

ingredients. Therefore, HED has not conducted a cumulative risk assessment involving 

sulfoxaflor and other active ingredients. 

HED concludes that there is a reasonable certainty of no harm from aggregate exposure to 

sulfoxaflor associated with the requested Section 18 use. In addition, there are no identified risks 

of concern for occupational exposures associated with the use on sorghum and the most recent 

risk assessment is protective of the proposed use.

HED is recommending the establishment of time-limited tolerances for residues of the 

insecticide sulfoxaflor, including its metabolites and degradates, in or on the commodities in the 

table below. Compliance with the tolerance levels specified below is to be determined by 

measuring only sulfoxaflor in or on the commodity. An acceptable analytical method is 

available for enforcing these tolerances.

Table 4. Time-Limited Tolerances to Support the Emergency Exemption Use of Sulfoxaflor on Sorghum.

Commodity Recommended Tolerance, ppm

Sorghum, forage 0.40

Sorghum, grain 0.30

Sorghum, stover 0.90

The recommended tolerances were derived using the OECD tolerance/MRL calculation 

procedures. HED notes that there is already a permanent tolerance for sulfoxaflor residues in/on 

aspirated grain fractions at 20 ppm. That tolerance is sufficient to address residues in/on 

aspirated grain fractions that may come from sorghum.
Page 8 of 18

Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler 

Exposure Task Force (AHETF) database; and the Agricultural Re-entry Task Force (ARTF) 

database; are subject to ethics review pursuant to 40 CFR 26, have received that review, and are 

compliant with applicable ethics requirements. For certain studies that review may have 

included review by the Human Studies Review Board. Descriptions of data sources as well as 

guidance on their use can be found at: http://www.epa.gov/pesticides/science/handler-exposuredata.html and http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

DETAILED TOXICOLOGICAL CONSIDERATIONS

Based on the use pattern and the toxicological profile of sulfoxaflor, HED selected endpoints and 

doses for acute and chronic dietary risk assessment and for evaluating short- and intermediateterm exposure via dermal and inhalation pathways. As there are no residential uses at this time, 

endpoints for assessing incidental oral exposure were not selected, and exposure via the dermal 

and inhalation pathways is relevant for assessing occupational exposure only. 

In support of the Section 3 registration request, Dow AgroSciences has submitted a large number 

of mechanistic studies designed to elucidate the mode of action of sulfoxaflor for the 

developmental effects observed in rats and its relevance for human health effects. These data 

indicate that rats may be uniquely sensitive to the developmental effects resulting from agonism 

of the nicotinic receptor by sulfoxaflor. In fact, humans may not be susceptible to these effects 

based on the lack of responsiveness of the human nicotinic receptor to sulfoxaflor in the agonism 

study. Furthermore, the observation that no neonatal deaths or neuromuscular/skeletal effects 

were noted in the rabbit developmental toxicity study supports the conclusion that rats are 

uniquely sensitive to developmental toxicity due to sulfoxaflor exposure. In addition, there is 

support for the pharmacodynamic differences in how sulfoxaflor interacts with rat fetal receptors 

versus adult rat, fetal human, and adult human receptors. These differences suggest that to the 

extent that neonatal death in rats occurs as a result of sulfoxaflor binding to the fetal receptor, 

these effects would not be observed in humans. Overall, these data suggest as a conservative 

assumption that rats and humans are at most pharmacodynamically comparable. Consequently, 

HED has reduced the interspecies UF to 3x.

A comprehensive analysis of the mode-of-action studies was completed in conjunction with the 

Section 3 evaluation and is not presented herein; rather, this assessment focuses on the doseresponse portion of the toxicological database. However, since the developmental and 

reproductive MOA described in the Assessment Summary is critical to endpoint selection, a brief 

review is given here. The developmental and reproductive MOA for sulfoxaflor describes the 

ability of sulfoxaflor to act as an agonist rat fetal intermuscular nicotinic acetylcholine receptor 

(nAChR). That is, sulfoxaflor interacts with the nAChR, causing an increase in skeletal muscle 

contraction. This leads to skeletal abnormalities (i.e., forelimb flexure and bent clavicles) and 

increased neonatal deaths from constriction of the diaphragm muscles. These receptors, although 
Page 9 of 18

present, are slightly different in fetal and adult lifestages. The differences are such that 

sulfoxaflor only interacts with the fetal form. Therefore the developmental endpoints are only 

applicable to life stages with the fetal receptor isoform and, therefore, only appropriate for 

assessing risks to women of reproductive age.

HED has recommended that the required 10X FQPA Safety Factor be reduced to 1X based on 

the following considerations, which are further discussed below: 1) the toxicology database for 

sulfoxaflor is complete with regard to FQPA consideration, including the required developmental 

and reproductive toxicity studies; 2) the required neurotoxicity studies, including the 

developmental neurotoxicity study (DNT) have been submitted, are considered adequate; 3) 

although there is evidence of quantitative susceptibility in the DNT study, based on decreased 

survival of offspring up to postnatal day 4, the endpoints and doses selected for risk assessment 

are protective for these effects; further, HED’s degree of concern for human susceptibility is 

reduced based on the special studies submitted in support of the mode of action; and 4) although 

some refinements are used in the exposure assessment, the dietary and drinking water 

assessments still result in upper-bound estimates of exposure. 

Completeness of the Toxicology Database: The toxicology database for sulfoxaflor is adequate 

for FQPA consideration including a developmental toxicity study in rats and rabbits, a 2-

generation reproduction study in rats, and acute, subchronic, and developmental neurotoxicity 

studies in rats.

An acceptable guideline inhalation study is required for all food-use registrations; however in the 

case of sulfoxaflor, the use of an oral study is considered protective for inhalation exposure for 

the following reasons: 

1) The acute inhalation toxicity (Category IV) is lower than the acute oral LD50

(Category III); 

2) The vapor pressure is low (≤1.4×10-6 Pa = 1.05×10-8 mm Hg at 20°C); 

3) There is adequate characterization of toxicity; 

4) Oral absorption is >90% – substantially higher absorption via the inhalation route is 

not expected; 

5) Oral absorption is rapid; 

6) Sulfoxaflor is not subject to enterohepatic circulation, making the absorbed oral dose 

available systemically; and 

7) Sulfoxaflor is not subject to in vivo metabolism and therefore potential first-pass 

effects are not relevant. 

Therefore, the subchronic inhalation study is waived for sulfoxaflor. The lack of a subchronic 

inhalation study is not considered a data gap and a database uncertainty factor is not required 

(TXR# 0056310). 

Evidence of Neurotoxicity: The level of concern for neurotoxicity is low because the effects are 

well characterized, the dose-response curve for these effects is well characterized, and clear 

NOAELs have been identified. 

Evidence of Sensitivity/Susceptibility in the Developing or Young Animal: Although there was 

quantitative susceptibility observed in the DNT, there is no residual uncertainty because the 
Page 10 of 18

effects are well characterized, a clear NOAEL was identified, and the endpoints chosen for risk 

assessment are protective of potential in utero and developmental effects. Quantitative 

susceptibility in the DNT was based on an increased rate of neonatal deaths at a dose where no 

maternal toxicity was observed. However, the apparent enhanced sensitivity may be due to the 

limited number of evaluations conducted in dams in the study rather than a true sensitivity of the 

young. Qualitative susceptibility was observed in the 2-generation reproduction study since 

neonatal deaths were observed at the same dose that resulted in hepatotoxicity in parental 

animals. However, these effects occurred at a higher dose compared to the offspring effects 

observed in the DNT. Finally, there was no evidence of quantitative or qualitative susceptibility 

in the developmental studies in the rat or rabbit.

Residual Uncertainty in the Exposure Database: There are no residual uncertainties with regard 

to dietary and occupational exposure. The dietary exposure assessments are based on high-end 

health protective residue levels (that account for parent and metabolites of concern), processing 

factors, and percent crop treated assumptions (100%). Actual exposure to sulfoxaflor will likely 

be lower than the estimated exposure. Furthermore, conservative, upper-bound assumptions 

were used to determine exposure through drinking water sources, such that these exposures have 

not been underestimated.

Acute Dietary Endpoint for the General Population: The endpoint used for establishing the 

aPAD for the general population was selected from the acute neurotoxicity study in rats. An 

aPAD of 0.25 mg/kg/day was derived from a NOAEL of 25 mg/kg/day and a 100-fold 

uncertainty factor that included 10x for inter-species extrapolations, 10x for intra-species 

variations, and a 1x FQPA safety factor. The LOAEL of 75 mg/kg is based on decreased motor 

activity on Day 1 of dosing. More severe effects were observed at the high dose (750 mg/kg) 

including increased muscle tremors and twitches, convulsions, hindlimb splaying, increased 

lacrimation and salivation, decreased pupil size and response to touch, gait abnormalities and 

decreased rectal temperature. None of these effects were observed either 8 or 15 days after 

dosing. This endpoint is appropriate for the acute dietary exposure assessment because it is the 

result of a single dose, is an appropriate route of exposure (oral) and is protective of the general 

population.

Acute Dietary Endpoint for Females 13-49 years of age: The endpoint used for establishing the 

aPAD for females 13-49 years of age was selected from the DNT study in rats. An aPAD of 

0.06 mg/kg/day was derived from a developmental NOAEL of 1.8 mg/kg/day and a 30-fold 

uncertainty factor that included 3x for inter-species extrapolation, 10x for intra-species variation, 

and 1x FQPA safety factor. The endpoint of concern is decreased neonatal survival in postnatal 

day (PND) 0-4 offspring at the LOAEL of 7.1 mg/kg/day. This endpoint is appropriate because 

it is a single dose effect, is of a relevant route of exposure (oral), and is protective for fetuses in 

utero.

Non-guideline critical window studies support the use of this endpoint for an acute exposure 

assessment. A series of non-guideline studies were conducted to accurately define the critical 

window of exposure for developmental effects. These studies indicate that a maternal oral dose 

of sulfoxaflor between Gestation Day 20 and parturition will result in decreased neonatal 
Page 11 of 18

survival in rats. Due to the brevity of this critical window, it’s assumed that a single dose within 

this period can result in decreased offspring survival and skeletal abnormalities.

Chronic Dietary Endpoint for the General Population: The endpoint used for establishing the 

cPAD was selected from the chronic/carcinogenicity combined study in the rat. The cPAD of 

0.05 mg/kg/day was derived from a NOAEL of 5.13 mg/kg/day and a 100-fold uncertainty factor 

that included 10x for inter-species extrapolation, 10x for intra-species variability, and a 1x FQPA 

SF. The LOAEL of 21.3 mg/kg/day is based on liver effects including increased blood 

cholesterol, liver weight, hypertrophy, fatty change, single cell necrosis and macrophages in 

males and females. The selected study is appropriate for selecting the dose and endpoint based 

on duration and route of exposure.

Dermal Absorption Factor: HED has compared data depicting in vivo and in vitro dermal 

absorption of sulfoxaflor in rats with in vitro dermal absorption in human skin to derive a 

human-equivalent in vivo dermal absorption factor of 2.5%.

Dermal and Inhalation (short- and intermediate-term): The endpoint used for short- and 

intermediate-term dermal exposure was selected from the DNT study in rats. The endpoint of 

concern is decreased neonatal survival in PND 0-4 offspring with a NOAEL of 1.8 mg/kg/day 

and a LOAEL of 7.1 mg/kg/day. The level of concern (LOC) for these assessments is 30, which 

is derived from a 3X factor for inter-species extrapolation and a 10x factor for intra-species 

variability. Although a route-specific dermal study is available, the selected endpoint was 

chosen from the DNT because it is protective of developmental parameters not measured in the 

dermal study. As previously noted, the endpoint is appropriate for assessing risk to women of 

child-bearing age; nevertheless, this endpoint is protective of other effects and will be used to 

assess risk from dermal and/or inhalation exposure for other population groups as well.

The use of an oral study is considered protective for inhalation exposure for the following 

reasons: 1) The acute inhalation toxicity (Category IV) is lower than the acute oral LD50

(Category III); 2) the vapor pressure is low [≤1.4×10-6 Pa (1.05×10-8 mm Hg) at 20°C]; 3) there 

is adequate characterization of toxicity; 4) oral absorption is >90% – substantially higher 

absorption via the inhalation route is not expected; 5) oral absorption is rapid; 6) sulfoxaflor is 

not subject to enterohepatic circulation, making the absorbed oral dose available systemically; 

and 7) sulfoxaflor is not subject to in vivo metabolism and therefore potential first-pass effects 

are not relevant. EPA waived the requirement for a subchronic inhalation study (TXR# 

0056310) based on, among other things, its conclusion that even if an additional 10X safety 

factor were applied, inhalation exposure would not raise a risk of concern. The lack of a 

subchronic inhalation study is not considered a data gap and a database uncertainty factor is not 

required. 

Cancer Classification: 

The CARC, in accordance with the EPA's Final Guidelines for Carcinogen Risk Assessment 

(March, 2005), determined that there is a “Suggestive Evidence of Carcinogenic Potential” for 

sulfoxaflor based on the preputial gland tumor response in seen in rats. When there is suggestive 

evidence, the Agency does not attempt a dose-response assessment as the nature of the data 
Page 12 of 18

generally would not support one. Rather, the Agency has determined that quantification of risk 

using a non-linear approach [i.e., reference dose (RfD)] will adequately account for all chronic 

toxicity, including carcinogenicity, that could result from exposure to sulfoxaflor. The CARC 

considered the following factors in their weight-of-evidence deliberation on assessing the 

carcinogenic potential of sulfoxaflor.

i. The liver tumors observed in male rats and male and female mice were considered to be 

treatment-related; 

ii. The hypothesized mode of action (CAR mediated, mitogenic) for liver tumors was 

adequately supported by studies that clearly identified the sequence of key events, doseresponse concordance and temporal relationship to the tumor type. There is convincing 

evidence that the hepatocarcinogenic effects are not likely to occur below a defined dose 

range. The mode of action data met the criteria established by the Agency; 

iii. The Leydig cell tumors were not considered to be treatment-related in male rats because 

there is a high background rate for this tumor type in the particular strain of rats (F344) 

tested;

iv. There was evidence of a response for carcinomas of the preputial glands in male rats. 

Preputial gland tumors are not commonly diagnosed in bioassay studies. The available 

data were inadequate to draw confident conclusions regarding this response due to the 

small sample size and lack of histopathology data on all animals. Thus, it was not 

possible to determine whether the preputial gland tumors are due to treatment. If the 

response is positive, this would be an unusual finding. Because the tumors could not be 

discounted, they were used in the suggestive classification; and

v. There is no mutagenicity concern from the in vivo or in vitro genetic toxicity assays.

DETAILED RESIDUE CHEMISTRY CONSIDERATIONS

Pesticide Metabolism and Environmental Degradation

HED has reviewed extensive metabolism data submitted by the registrant to support the Section 

3 registrations and has concluded that the nature of the residue is adequately understood in 

plants, livestock and rotational crops. HED has determined that for plants and livestock the 

residue of concern for tolerance setting and risk assessment is the parent, sulfoxaflor. In 

drinking water, residues of concern for risk assessment are sulfoxaflor and its two metabolites 

designated X11719474 and X11519540 (E. Holman, D398294, 6 April 2012).

Table 5. Summary of Sulfoxaflor Metabolites and Degradates to be included in the Risk Assessment and 

Tolerance Expression.

Matrix Risk Assessment Tolerance Expression 

Plants Primary Crops Sulfoxaflor Sulfoxaflor 

Rotational Crop Sulfoxaflor 1 Sulfoxaflor

Livestock Ruminant Sulfoxaflor Sulfoxaflor

Poultry Sulfoxaflor Sulfoxaflor

Drinking Water Sulfoxaflor + X11719474 + X11519540 NA

1 Based on the proposed later season foliar application use pattern; decision may need to be revisited for future early season soil 

application uses. 
Page 13 of 18

Analytical Methods

HED has concluded that adequate analytical methods have been submitted for both data 

collection and for enforcement purposes. In the submitted field trials, residues of sulfoxaflor and 

its metabolites in crops were determined using the Dow analytical method designated as 091031. 

The proposed method for tolerance enforcement in plant commodities is 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. Method 091116 extracts residues with 

acetonitrile/water and includes use of a deuterated internal standard, hydrolysis with NaOH to 

release base-labile conjugates, and clean up via solid-phase extraction. This method is 

applicable for the quantitative determination of residues of sulfoxaflor, [1-(6-

trifluoromethylpyridin-3-yl)ethyl](methyl)-oxido-λ

6

-sulfanylidenecyanamide and its metabolites, 

X11719474, N-((methyl)oxido){1-[6-(trifluoromethyl)pyridine-3-yl]ethyl}-λ

6

-sulfanylidene)urea 

and X11721061, 1-[6-(trifluoromethyl)pyridin-3-yl]ethanol, in agricultural commodities and 

processed products. The method was adequately validated, with a limit of quantitation (LOQ) of 

0.010 mg/kg for all matrices, including sorghum.

The FDA MRM was reported by the registrant to be not suitable for analysis of sulfoxaflor 

and/or its metabolites; the German multiresidue method S-19 may be suitable.

Drinking Water Residue Profile

References: D418282. Ruhman, M. 28 February 2014. “Estimated Drinking Water Concentrations of the Proposed 

section 18 Use of Sulfoxaflor on Sorghum.”

D382617. Ruhman, M. 1 August 2012. “Estimated Drinking Water Concentrations of the New 

Chemical Sulfoxaflor from Proposed use on Beans, Berries, Canola, Citrus, Fruits (Pome & Stone), 

Ornamentals, Soybeans, Tree nuts, Turf grass, Vegetables (Brassica, Bulb, Cucurbits, Fruiting, Okra, 

Leafy, Root and Tuber) and Watercress for the Use in Human Health Risk Assessment.”

Monitoring data depicting residues of sulfoxaflor in drinking water are not available. In support 

of the 2012 Section 3 risk assessment for sulfoxaflor uses on multiple crops, the EFED used 

modeling to estimate upper-bound concentrations of sulfoxaflor in surface and ground water. 

The use on citrus resulted in the highest estimated drinking water concentrations (EDWCs) for 

sulfoxaflor (Table 6). The summed numbers in Table 6 reflect the combinations of residues and 

their toxicity profiles. A complete discussion of the rationale for the combinations is provided in 

the 2012 risk assessment (D382604).

Table 6. Estimated Drinking Water Concentrations (EDWCs) for Total Toxic Residues of Sulfoxaflor in Surface 

and Ground Waters from Use on Citrus.

Water Source*

Total Concentration, ppb

[Sulfoxaflor + X11719474 + X11519540]

Acute Peak 1 Non-cancer/Chronic 2 Cancer 3

Surface (PRZM/EXAMS)

26.4

[9.4 + 15.0 + 2.0]

13.5

[1.9 + 10.2 + 1.4]

9.3

[1.5 + 6.9 + 0.9]

Ground (SCI-GROW)

69.2

[0.0 + 60.9 + 8.3]

* Surface water EDWCs include sulfoxaflor + X11719474 + X11519540. Due to rapid degradation of sulfoxaflor 

in aerobic soil systems (half-life = 0.4 days), the EDWC for groundwater includes X11719474 + X11519540.
Page 14 of 18

1 Peak value, from Florida citrus; 2 1-in-10-year annual mean values, California citrus; 3 1-in-10-year overall annual 

mean values, California citrus.

For this Section 18, EFED has modeled the use of sulfoxaflor on sorghum (D418282) and 

determined that the EDWCs are expected to be less than those used in the 2012 assessment.

Food Residue Profile

No residue data were submitted with this Section 18 request for the use of sulfoxaflor on 

sorghum. However, HED is currently evaluating a Section 3 request for the use of sulfoxaflor on 

sorghum and other crops. In support of that request, Dow AgroSciences, LLC submitted field 

trial data for sulfoxaflor in/on soghum commodities (forage, grain, and stover) from 9 field trials 

conducted during 2012 in major sorghum-growing regions of the Unites States.

Each trial included three plots: an untreated control plot and two treated plots. Treated plots 

received two foliar applications of GF-2372, each at a target formulated product rate of 0.09 

lb/A, equivalent to 0.045 lb a.i./A based on the certified test substance concentration of 49.1%. 

Test substance was applied to one treated plot at approximately 21 and 7 days before typical 

commercial timing for forage collection, and to another treated plot at approximately 28 and 14 

days before typical commercial harvest. A locally available adjuvant that might typically be 

used with an insecticide on sorghum was included within the tank mixture at each application. 

Application spray volumes ranged from 19.9 to 30.0 gal/A. Applications were performed with 

pressurized ground spray equipment, using a tractor mounted boom or a backpack sprayer with a 

hand-held boom. All of the field trials are supported by adequate analytical methods and storage 

stability data. The results of the field trials are summarized in Table 7.

Table 7. Summary of residue data from sorghum field trials with Sulfoxaflor.a

Commodity EPb Total appl. rate

lb a.i./A

PHI 

(day) n

Sulfoxaflor Residue (ppm)

Min Max HAFTc Median

(STMdR)

Mean

(STMR)

Std. 

Dev.

Sorghum Forage WDG 0.0878-0.0907 7 9 0.017 0.202 0.198 0.082 0.094 0.059

Sorghum Grain WDG 0.0878-0.0907 14 9 0.016 0.152 0.150 0.039 0.063 0.049

Sorghum Stover WDG 0.0878-0.0907 14 9 0.034 0.733 0.601 0.199 0.221 0.172

a

 The LOQ (0.010 ppm) was used for all residue values reported as <LOQ in all calculations (mean, median, etc.). 

Minima and maxima are on a per-sample basis; all other summary values reflect per-trial averages.

b

 EP = End-use Product; Test item was GF-3272, a 49.1% a.i. water-dispersible granule formulation.

c HAFT = Highest Average Field Trial.

Sorghum grain is a commodity that may form aspirated grain fractions (AGF). Studies showing 

the degree to which sulfoxaflor concentrates in/on sorghum AGF were not provided. Previously 

submitted studies resulted in concentration factors of 21X and 95X for wheat and soybean AGF, 

respectively, and the establishment of a tolerance for residues of sulfoxaflor in/on AGF at 20 

ppm. For purposes of this Section 18 assessment, HED is using the soybean factor (95X) to 

estimate residues of sulfoxaflor in/on sorghum AGF. Multiplying the median grain residue 

(0.039 ppm) by 95 results in an anticipated residue of 3.7 ppm, which is well below the 

established tolerance.
Page 15 of 18

In addition to aspirated grain fractions, sorghum grain, fodder, and stover may be used as 

livestock feedstuffs; therefore, HED has estimated reasonably balanced livestock dietary burdens 

for cattle, poultry and swine (Table 8). The resulting dietary burdens are greater than those 

estimated previously; however, they do not result in a need for revised tolerances for residues of 

sulfoxaflor in livestock commodities (Table 9).

Table 8. Estimated Reasonably Balanced Livestock Dietary Burdens.*

Crop Commodity Classification

Highest Residue 

or Median Residue

%

DM

% of 

Diet

Contribution, 

ppm

Beef Cattle

Grain Aspirated fractions Carbohydrate Median 4.56 85 5 0.268

Beet, sugar Molasses Carbohydrate Median 0.23 75 10 0.031

Sorghum, grain Grain Carbohydrate Median 0.049 86 40 0.023

Barley Grain Carbohydrate Median 0.048 88 25 0.014

Soybean Meal Protein Median 0.135 92 5 0.007

Barley Straw Roughage Highest Residue 2.2 89 10 0.247

Wheat Straw Roughage Highest Residue 1.641 88 5 0.093

Total 100 0.683

Dairy Cattle

Beet, sugar Molasses Carbohydrate Median 0.23 75 10 0.031

Sorghum, grain Grain Carbohydrate Median 0.049 86 35 0.020

Soybean Meal Protein Median 0.135 92 10 0.015

Wheat Forage Roughage Highest Residue 1.4 25 20 1.120

Rape Forage Roughage Highest Residue 1.5 30 10 0.500

Triticale Forage Roughage Highest Residue 1.4 30 15 0.700

Total 100 2.386

Poultry

Sorghum, grain Grain Carbohydrate Median 0.049 75 0.037

Soybean Meal Protein Median 0.135 25 0.034

Total 100 0.071

Swine

Sorghum, grain Grain Carbohydrate Median 0.049 80 0.039

Barley Grain Carbohydrate Median 0.048 5 0.002

Soybean Meal Protein Median 0.135 15 0.020

Total 100 0.061

* For cattle, contribution = residue ÷ (% Dry Matter/100) × % of Diet/100. For poultry and swine, contribution = 

residue × % of Diet/100.

Table 9. Summary of Anticipated Sulfoxaflor Residues in Livestock Commodities.

Livestock 

Commodity

Matrix-to-Feed 

Ratio* Anticipated Residue, ppm Current Tolerance, ppm

Cattle (Dietary Burden = 2.27 ppm)

Milk 0.0476 0.1081 0.15

Muscle 0.0481 0.1092 0.15

Fat 0.0258 0.0586 0.10

Liver 0.1146 0.2601 0.40 (meat byproducts) Kidney 0.0700 0.1589

Poultry (Dietary Burden = 0.054 ppm)

Egg 0.0553 0.0030 0.01

Muscle 0.0612 0.0033 0.01

Fat 0.1119 0.0060 0.01

Liver 0.0174 0.0009 0.01

Swine (Dietary Burden = 0.03 ppm)
Page 16 of 18

Table 9. Summary of Anticipated Sulfoxaflor Residues in Livestock Commodities.

Livestock 

Commodity

Matrix-to-Feed 

Ratio* Anticipated Residue, ppm Current Tolerance, ppm

Muscle 0.0481 0.0014 0.01

Fat 0.0258 0.0008 0.01

Liver 0.1146 0.0034 0.01 (meat byproducts) Kidney 0.0700 0.0021

* From livestock feeding studies. See D398756 (D. McNeilly, 21 November 2012)

DETAILED EXPOSURE AND RISK ANALYSES

Dietary Exposure and Risk

HED has not generated new dietary exposure and risk estimates for this Section 18 risk 

assessment. HED currently uses the Dietary Exposure Evaluation Model DEEM-FCID, Version 

3.16. This model uses 2003-2008 food consumption data from the U.S. Department of 

Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA). The two sorghum entries in the food forms database are sorghum grain 

and sorghum syrup, both of which are reported as having no consumption. As previously noted, 

the sulfoxaflor residues in drinking water from the use on sorghum are expected to be lower than 

those previously assessed. Therefore, the dietary exposure estimates from the 2012 assessment 

(Table 10) are not changed by the proposed Section 18 use. Dietary risk estimates from 

exposure to sulfoxaflor through food and water are below HED’s level of concern.

Table 10. Summary of Acute and Chronic Dietary Exposure and Risk Estimates for Sulfoxaflor.

Population Subgroup

Acute (95th Percentile) Chronic Cancer

Estimated 

Exposure 

(mg/kg/day)

Estimated 

Risk, % 

aPAD

Estimated 

Exposure 

(mg/kg/day)

Estimated 

Risk, % 

cPAD

Exposure 

(mg/kg/day)

Estimated 

Risk

U.S. Population 0.015832 6 0.003343 7

See Chronic

All infants 0.031158 12 0.009110 18

Children 1-2 yrs 0.044887 16 0.007867 16

Children 3-5 yrs 0.032523 13 0.006210 12

Children 6-12 yrs 0.018338 7 0.003892 8

Youth 13-19 yrs 0.010829 4 0.002456 5

Adults 20-49 yrs 0.011137 4 0.002812 6

Adults 50+ yrs 0.011446 5 0.002992 6

Females 13-49 yrs 0.009495 16 0.002809 6

Entries with the highest acute and chronic risk estimates are bolded.

Residential Exposure and Risk

At this time, there are no uses of sulfoxaflor that will result in residential exposures. 

Spray drift is always a potential source of exposure to residents nearby spraying operations. This 

is particularly the case with aerial application, but, to a lesser extent could also be a potential 

source of exposure from ground applications of sulfoxaflor. The Agency has been working with 

the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide 

regulation and other parties to develop the best spray drift management practices. On a 

chemical-by-chemical basis, the Agency is now requiring interim mitigation measures for aerial 
Page 17 of 18

applications that must be placed on product labels/labeling. The Agency has completed its 

evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. 

pesticide registrants, and is developing a policy on how to appropriately apply the data and the 

AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast 

and ground hydraulic methods. After the policy is in place, the Agency may impose further 

refinements in spray drift management practices to reduce off-target drift with specific products 

with significant risks associated with drift.

Aggregate Exposure and Risk

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

In the case of sulfoxaflor, there are no residential uses at this time. Consequently, aggregate 

exposure and risk estimates are equivalent to the dietary (food + drinking water) exposure and 

risk estimates discussed above and summarized in Table 10. There are no aggregate risk issues 

that would preclude granting the Section 18 registration for use on sorghum or establishing timelimited tolerances for residues of sulfoxaflor in/on sorghum commodities.

Cumulative Exposure and Risk

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to sulfoxaflor and any other substances and sulfoxaflor does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that sulfoxaflor has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at: http://www.epa.gov/pesticides/cumulative/.

DETAILED OCCUPATIONAL EXPOSURE CONSIDERATIONS

The proposed use is on sorghum; therefore, there is the potential for occupational handler and 

post-application exposure. As noted previously, HED completed occupational handler and postapplication risk assessments in 2012 and the scenarios and application rates considered in that 

assessment are sufficient to cover occupational exposures/risks associated with the Section 18 

use on sorghum. Margins of exposure (MOEs) for combined (dermal + inhalation) exposures for

handler scenarios in the 2012 assessment range from 80 to 25,000. For post-application 

exposures, the MOEs range from 950 to 7,000,000. The occupational level of concern for 

sulfoxaflor is 30; therefore, these MOEs indicate that occupational risks are not of concern.
Page 18 of 18

Restricted Entry Interval (REI)

The REI on the TransformTM WG label is 24 hours. HED recommends that RD ensure that the 

proper REI is listed on both labels according to the acute toxicity profile and the formulation for 

each product.

REFERENCES FOR AGENCY MEMORANDA

D382604. 26 September 2012. M. Doherty, D. McNeilly, E. Scollon, Z. Figueroa. Sulfoxaflor –

New Active Ingredient Human Health Risk Assessment of Uses on Numerous Crops. 

D382617. 1 August 2012. Ruhman, M. Estimated Drinking Water Concentrations of the New 

Chemical Sulfoxaflor from Proposed use on Beans, Berries, Canola, Citrus, Fruits (Pome & 

Stone), Ornamentals, Soybeans, Tree nuts, Turf grass, Vegetables (Brassica, Bulb, Cucurbits, 

Fruiting, Okra, Leafy, Root and Tuber) and Watercress for the Use in Human Health Risk 

Assessment.

D398756. 12 September 2012. D. McNeilly. Sulfoxaflor. Petition for the Section 3 

Registration and Establishment of Tolerances for the New Insecticide Sulfoxaflor on: 

Barley, Brassica Leafy Vegetables, Bulb Vegetables, Canola (Rapeseed), Citrus, Cotton, 

Cucurbit Vegetables, Fruiting Vegetables, Leafy Vegetables (Except Brassica), Leaves of 

Root and Tuber Vegetables, Low Growing Berries, Okra, Ornamentals (Herbaceous and 

Woody), Pistachio, Pome Fruit, Root and Tuber Vegetables, Small Fruit Vine Climbing 

(Except Fuzzy Kiwifruit), Soybean, Stone Fruit, Beans (Succulent, Edible Podded, and Dry), 

Tree Nuts, Triticale, Turf Grass, Watercress, Wheat. Summary of Analytical Chemistry and 

Residue Chemistry Data.

D417536. 5 March 2014. Doherty, M. and Figueroa, Z. Sulfoxaflor – Human Health Risk 

Assessment of the FIFRA Section 18 Emergency Exemption Use on Sorghum.

D418282. 28 February 2014. Ruhman, M. Estimated Drinking Water Concentrations of the 

Proposed section 18 Use of Sulfoxaflor on Sorghum.