1

Proposed Registration of Enlist DuoTM Herbicide

Regulatory Rationale

The Agency is proposing to grant a registration for Enlist DuoTM, a herbicide containing the 

active ingredients 2,4-dichlorophenoxyacetic acid (2,4-D) choline salt and glyphosate 

dimethylammonium salt (glyphosate). Dow AgroSciences (DAS) submitted an application for 

registration to the Environmental Protection Agency (EPA or the Agency) for this registration, 

which proposes use on corn and soybean crops that are genetically engineered to be tolerant to 

2,4-D and glyphosate (GE crops). DAS has requested that its EnlistTM GE herbicide tolerant 

crops be deregulated under the Plant Protection Act. The United States Department of 

Agriculture (USDA) is currently reviewing this request. EPA intends to wait until USDA’s 

review is complete before making a final decision on the Enlist DuoTM application for 

registration.

2,4-D is a longstanding active ingredient that is used through a variety of salt and ester 

formulations and registered for a variety of food and feed uses, including corn and soybeans. 

The proposed use would expand the current timing of applications of 2,4-D on corn and 

soybeans, thereby enhancing the flexibility in weed control. 2,4-D is currently registered for 

over-the-top applications to corn up to 8 inches tall and only pre-plant applications to soybeans. 

The pending application would allow over-the-top applications of 2,4-D choline slat formulation 

to GE corn up to 48 inches tall and over-the-top applications to GE soybeans.

Although the use on GE crops is a new use pattern for the 2,4 D component of this product, it is 

not a new use for glyphosate containing products. All uses for this proposed product are already 

registered on other glyphosate products and are currently in use on GE corn and soybeans for the 

same use pattern. Since no new use pattern and no new exposures for glyphosate are being 

considered with this registration action, no new assessment is needed for glyphosate. However, 

as described above, the expanded timing of applications does change the current use pattern for 

the choline salt of 2,4-D. Therefore, this document is intended to discuss the results of the 

Agency’s findings specifically to the assessment of the choline salt of 2,4-D on GE corn and 

soybeans.

I. Chemical Information

Chemical Name: Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, 2-(2,4-dichlorophenoxy)acetic 

acid hydroxide (1:1:1)

EPA PC Code: 051505

Chemical Abstracts Service (CAS) Number: 1048373-72-3

Mode of Action: 2,4-D is an herbicide in the phenoxyacetic acid family that is used 

postemergence for selective control of broadleaf weeds. 2,4-D, a synthetic auxin herbicide, 

causes disruption of plant hormone responses.
2

Registrant: Dow AgroSciences LLC

Proposed Product: GF-2726 (Enlist DuoTM) – EPA File Symbol 62719-AUO, an end-use 

product containing 24.4% 2,4-D choline salt and 22.1% Glyphosate, to be used on EnlistTM

AAD-1 Corn (Trait Code: DAS-40278-9) and EnlistTM AAD-12 Soybean (Trait Code: DAS68416-4).

II. Human Health Risk

A summary of the human health effects and risk of 2,4-D choline salt as assessed in the EPA

document entitled, 2,4-D. Human Health Risk Assessment for a Proposed Use of 2,4-D Choline 

on Herbicide-Tolerant Corn and Soybean, is provided below.

A. Summary of Toxicological Effects

The toxicology database on 2,4-D is complete and sufficient for assessing the toxicity and 

characterizing the hazard of all formulations of 2,4-D, including the choline salt. Data on other 

forms of 2,4-D were also used to assess the choline formulation.

2,4-D has been classified as having low acute toxicity via the oral, dermal, and inhalation routes 

of exposure (Toxicity Category III). It is not a dermal irritant (Toxicity Category IV) or dermal 

sensitizer but it is a severe eye irritant (Toxicity Category I).

The toxicity profile of the active ingredient 2,4-D shows that the principal toxic effects are 

changes in the kidney, thyroid, liver, adrenal, eye, and ovaries/testes in the rat following 

exposure to 2,4-D via the oral route at dose levels above the threshold of saturation of renal 

clearance. No systemic toxicity was observed in rabbits following repeated exposure via the 

dermal route at dose levels up to the limit dose. Neurotoxicity was observed in the acute 

neurotoxicity study in rats at the high dose. In an extended one-generation reproductive toxicity 

study in rats, reproductive toxicity, developmental neurotoxicity, and immunotoxicity were not 

observed. The thyroid effects observed at dose levels up to/approaching renal saturation were 

considered treatment-related, although not adverse. Maternal and developmental toxicity were 

observed at high dose levels exceeding the threshold of saturation of renal clearance. There are 

no residual uncertainties for pre- and/or postnatal toxicity. 

2,4-D is classified as “not classifiable as to human carcinogenicity,” based upon bioassays in rats 

and mice that showed no statistically significant tumor response in either species. The Agency 

determined, based on several reviews of epidemiological studies, in addition to the animal 

studies, that the existing data did not support a conclusion that links human cancer to 2,4-D 

exposure.

B. Toxicological End Points and Doses Used in the Human Health Risk Assessment

Once a pesticide’s toxicological profile is determined, EPA identifies toxicological Points of 

Departure (POD) and Levels of Concern (LOC) to use in evaluating the risk posed by human 

exposure to the pesticide. For hazards that have a threshold below which there is no appreciable 
3

risk, the toxicological POD is used as the basis for derivation of reference values for risk 

assessment. PODs are developed based on a careful analysis of the doses in each toxicological 

study to determine the dose at which no adverse effects are observed (the NOAEL; No Observed 

Adverse Effect Level) and the lowest dose at which adverse effects of concern are identified (the 

LOAEL; Lowest Observed Adverse Effect Level). Uncertainty/safety factors are used in 

conjunction with the POD to calculate a safe exposure level - generally referred to as a 

Population-adjusted Dose (PAD) or a Reference Dose (RfD) - and a safe Margin of Exposure 

(MOE). For non-threshold risks, EPA assumes that any amount of exposure will lead to some 

degree of risk. Thus, EPA estimates risk in terms of the probability of an occurrence of the 

adverse effect expected in a lifetime. For more information on the general principles EPA uses in 

risk characterization and a complete description of the risk assessment process, see

http://www.epa.gov/pesticides/factsheets/riskassess.htm.

1. Acute Dietary

a. General Population (Including Infants and Children)

An acute dietary endpoint for the general population, including infants and children, was 

selected from the acute neurotoxicity study in rats with a NOAEL of 67 mg/kg. At the study 

LOAEL of 225 mg/kg, an increased incidence of incoordination and slight gait abnormalities 

(forepaw flexing or knuckling) and decreased motor activity were observed. A 100X 

uncertainty factor was applied to account for inter- and intra-species variability. As discussed 

in section C below, the Food Quality and Protection Act (FQPA) safety factor was reduced to 

1X resulting in an acute Population Adjusted Dose (aPAD) of 0.67 mg/kg/day.

b. Females of Child-Bearing Age (13-49 years old)

An acute dietary endpoint for females 13+ was selected from the developmental toxicity study 

in rats with a NOAEL of 25 mg/kg/day. At the study LOAEL of 75 mg/kg/day, fetal skeletal 

malformations (14th rudimentary ribs) were observed. A 100X uncertainty factor was applied 

to account for inter- and intra-species variability and the FQPA safety factor was reduced to 

1X resulting in an acute Population Adjusted Dose aPAD of 0.25 mg/kg/day.

2. Chronic Dietary

The chronic dietary endpoint was selected from the extended one-generation reproduction 

toxicity study in rats with a NOAEL of 21 mg/kg/day. At the study LOAEL of 55.6 mg/kg/day 

for males and 46.7 mg/kg/day for females, kidney toxicity, manifested as increased kidney 

weights and increased incidence of degeneration of the proximal convoluted tubules, was 

observed and decreased body weight in pups was observed throughout lactation. A 100X 

uncertainty factor was applied to account for inter- and intra-species variability and the FQPA 

safety factor was reduced to 1X resulting in a chronic Population Adjusted Dose (cPAD) of 

0.21 mg/kg/day.
4

3. Incidental Oral, Short and Intermediate Term

Short-term and intermediate-term incidental oral endpoints for risk assessment were selected 

from the extended one-generation reproduction toxicity study in rats with a NOAEL of 21 

mg/kg/day. At the study LOAEL of 55.6 mg/kg/day for males and 46.7 mg/kg/day for females, 

kidney toxicity, manifested as increased kidney weights and increased incidence of 

degeneration of the proximal convoluted tubules, was observed and decreased body weight in 

pups was observed throughout lactation. A 100X uncertainty factor was applied to account for 

inter- and intra-species variability and the FQPA safety factor was reduced to 1X resulting in a 

target MOE of 100 for non-dietary risk assessment.

4. Inhalation, Short and Intermediate Term

Short-term and intermediate-term inhalation endpoints for risk assessment were selected from 

the route-specific 28-day inhalation toxicity study in rats with a LOAEL of 0.05 mg/L/day. A 

NOAEL for portal-of-entry effects was not determined. At the study LOAEL of 0.05 mg/L/day, 

squamous metaplasia and epithelial hyperplasia with increased mixed inflammatory cells 

within the larynx, which was not totally resolved following a 4-week recovery period, were 

observed. Human Equivalent Concentrations (HEC)/Human Equivalent Doses (HED) for 

residential and occupational scenarios were calculated. A 3X uncertainty factor was applied to 

account for inter-species variability (to account for the pharmacodynamic differences), a 10X 

uncertainty factor was applied to account for intra-species variability, and a 10X uncertainty 

factor was applied to account for the lack of a NOAEL. Although there was no assessment of 

the thyroid in the inhalation study, the rat extended one-generation reproduction toxicity (oral) 

study performed an assessment of the thyroid for several age groups at dose levels up 

to/approaching renal saturation. The changes in thyroid hormones observed, along with thyroid 

histopathological findings, were considered treatment related, although not adverse. The lack of 

an assessment of the thyroid in the inhalation study is considered inconsequential because the 

portal of entry endpoint is protective of potential thyroid effects expected to occur at higher 

concentrations; i.e., at doses that exceed the level of renal clearance. Portal-of-entry effects 

were observed at all dose levels, and an additional 10X uncertainty factor is applied to the 

LOAEL to obtain an extrapolated NOAEL used for the inhalation risk assessments. The use 

pattern indicates that dose levels required to exceed the renal clearance mechanism would not 

be attained following human inhalation exposure.

5. Dermal (All Durations)

No quantification of dermal risk is required. Although the dermal toxicity study did not 

evaluate developmental endpoints, the following were noted:

a. There was no dermal or systemic toxicity observed following repeated dermal applications 

to rabbits at the Limit Dose (1000 mg/kg/day).

b. There was no quantitative susceptibility observed in the developmental or reproductive 

toxicity studies.
5

c. The use of a 10% human dermal absorption factor (DAF) with the oral developmental 

LOAEL of 90 mg/kg/day established in the rabbit developmental toxicity study yields a 

dermal equivalent dose (DED) of 900 mg/kg/day, which is numerically similar to the 

high-end dermal NOAEL (1000 mg/kg/day) in the dermal rabbit study.

d. The use of the 10% human DAF with the oral developmental LOAEL of 75 mg/kg/day 

established in the rat developmental study yields a DED of 750 mg/kg/day.

e. The developmental findings in the rat and rabbit occurred at oral dose levels exceeding 

renal clearance, and clear NOAELs were obtained (dermal equivalent doses of 250 and 

300 mg/kg/day).

f. Although there was no assessment of the thyroid in the dermal study, the rat extended 

one-generation reproduction toxicity (oral) study performed an assessment of the thyroid 

for several age groups at dose levels up to/approaching renal saturation. The changes in 

thyroid hormones (↓ T3 and T4 with ↑TSH levels) observed, along with thyroid 

histopathological findings, were considered treatment-related, and not adverse (NOAEL 

for thyroid effects is ≈40 mg/kg/day; DED of 400 mg/kg/day).

g. The use pattern indicates that dose levels required to exceed the renal clearance 

mechanism would not be attained following human dermal exposure.

6. Cancer

The Cancer Peer Review Committee (CPRC; TXR No. 0050017, dated January 29, 1997)

classified 2,4-D as “not classifiable as to human carcinogenicity,” based upon bioassays in rats 

and mice that showed no statistically significant tumor response in either species. EPA

determined, based on several reviews of epidemiological studies, in addition to the animal 

studies, that the existing data did not support a conclusion that links human cancer to 2,4-D 

exposure.

C. FQPA Safety Factor

EPA determined that the 10X FQPA Safety Factor (for the protection of infants and children

mentioned above) could be reduced to 1X for the following reasons:

The toxicity database is complete and adequate to assess safety for infants and children. There is 

evidence of increased susceptibility in the rat developmental toxicity study and in the rat twogeneration reproduction study; however, these studies have clearly defined NOAELs/LOAELs, 

and the points of departure used in the risk assessment are below where these findings occur and 

are protective. There are acute and subchronic neurotoxicity studies, a developmental 

neurotoxicity study, a detailed evaluation of thyroid function across life stages, and a 

developmental immunotoxicity study on 2,4-D. Therefore, the Agency has a complete database 

addressing potential hazard to infants and children. The exposure assessment will not 

underestimate children’s exposure to 2,4-D. Further details may be found in the following 

sections:
6

1. Completeness of the Toxicology Database

The toxicology database for 2,4-D is complete. Acceptable rat and rabbit developmental 

toxicity studies, a rat two-generation reproduction study, an extended one-generation rat 

reproduction toxicity study (F1 offspring evaluated for potential effects on the nervous system, 

immune system, reproductive and endocrine systems, thyroid function, and other systemic 

toxicity parameters), and acute, subchronic, and developmental neurotoxicity studies in rats are 

available.

2. Evidence of Neurotoxicity

Evidence of neurotoxicity was observed in the acute neurotoxicity study in rats, as evidenced 

by an increase in the incidence of incoordination and slight gait abnormalities (forepaw flexing 

or knuckling) during the Functional Observation Battery (FOB) assessment at the high dose in 

both sexes. In the subchronic neurotoxicity study, relative forelimb grip strength was 

significantly increased in rats of both sexes at the high-dose level, although there was no 

treatment-related change in absolute grip strength. Clinical signs of neurotoxicity (decreased 

motor activity, ataxia, loss of righting reflex, extremities cold to the touch) were observed in 

maternal rabbits in the developmental toxicity study. Developmental neurotoxicity was not 

observed in the developmental neurotoxicity study in rats. Neuropathological effects were not 

observed in any study.

3. Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There is evidence of increased susceptibility following in utero exposure to 2,4-D in the rat

developmental toxicity study and following in utero and/or pre-/post-natal exposure in the rat 

two-generation reproduction study. There is no evidence of increased susceptibility following 

in utero exposure to 2,4-D in the rabbit developmental toxicity study or following in utero 

and/or pre-/post-natal exposure in the rat extended one-generation reproduction toxicity study.

2,4-D has been evaluated for potential developmental effects in the rat and rabbit. Maternal

toxicity included decreased body weight gains in the rat study at the same dose level where

developmental effects (occurrence of skeletal malformations) were observed. Maternal toxicity

in the rabbit included decreased body weight gain, clinical signs of toxicity (decreased motor

activity, ataxia, loss of righting reflex, extremities cold to the touch), and abortions, the latter

being indicative of potential developmental toxicity. Decreased maternal body weight gains 

were observed in the rat two-generation reproduction study at a dose that exceeded renal 

saturation and resulted in reduced viability of the F1 pups. There are clearly established 

NOAELs and LOAELs for the population of concern, there are no data gaps in the toxicology 

database, and the PODs are protective of susceptibility.

4. Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. The dietary exposure estimates are 

unrefined and reflect primarily tolerance-level residue in food, 100% crop treated, and upperbound drinking water estimates based on modeling. Additionally, non-occupational exposure 
7

estimates were determined using the Residential Standard Operating Procedures which utilize a 

combination of central tendency and high end inputs designed to result in protective exposure 

estimates which will not underestimate residential exposures.

D. Cumulative Effects

2,4-D is an herbicide in the phenoxyacetic acid family of pesticides. This class also includes

MCPA, 2,4-DB, and 2,4-DP. A cumulative risk assessment has not been performed as part of

this human health risk assessment because EPA has not made a determination as to which of 

these compounds, if any, to which humans may be exposed, have a common mechanism of 

toxicity. 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 2,4-D and any other substances. For the purposes of this action, therefore, EPA has 

not assumed that 2,4-D 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/.

E. Dietary (Food + Drinking Water) Risk

2,4-D is a phenoxyacetic acid herbicide used to control a variety of broadleaf weeds. It is a 

longstanding active ingredient (ai) registered for a variety of food/feed uses. Permanent 

tolerances for 2,4-D are established under 40 CFR 180.142 for a wide variety of crops and 

livestock commodities.

Acute and chronic aggregate (food + dietary drinking water) exposure and risk assessments were 

conducted using the Dietary Exposure Evaluation Model software with the Food Commodity 

Intake Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 food consumption 

data from the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition 

Examination Survey, What We Eat in America, (NHANES/WWEIA).

1. Acute Dietary Risk

For acute exposure assessments, individual one-day food consumption data are used on an

individual-by-individual basis. The reported consumption amounts of each food item can be

multiplied by a residue point estimate and summed to obtain a total daily pesticide exposure for 

a deterministic exposure assessment, or “matched” in multiple random pairings with residue 

values and then summed in a probabilistic assessment. The resulting distribution of exposures 

is expressed as a percentage of the aPAD on both a user (i.e., only those who reported eating 

relevant commodities/food forms) and a per-capita (i.e., those who reported eating the relevant 

commodities as well as those who did not) basis. In accordance with EPA policy, per capita 

exposure and risk are reported for analyses. 
8

The resulting acute food plus drinking water risk estimates are not of concern to EPA (≤100%

aPAD) at the 95th percentile of the exposure distribution for the general population and all

population subgroups. The resulting acute risk estimate for children 1 to 2 years old, the 

subgroup with the greatest exposure, was 14% of the aPAD at the 95th percentile of the 

exposure. The acute dietary assessment is unrefined; to further refine the 2,4-D dietary

exposure and risk estimates, percent crop treated (%CT), anticipated residues, or monitoring 

data, if available, could be used.

2. Chronic Dietary Risk

For chronic dietary exposure assessment, an estimate of the residue level in each food or foodform (e.g., orange or orange juice) on the food commodity residue list is multiplied by the 

average daily consumption estimate for that food/food form to produce a residue intake 

estimate. The resulting residue intake estimate for each food/food form is summed with the 

residue intake estimates for all other food/food forms on the commodity residue list to arrive at 

the total average estimated exposure. Exposure is expressed in mg/kg body weight/day and as a 

percent of the cPAD. This procedure is performed for each population subgroup.

The resulting chronic food plus drinking water risk estimates are not of concern to EPA for the 

general population and all population subgroups. The most highly exposed population was 

children 1 to 2 years old utilizing 15% of the cPAD. The chronic dietary assessment is 

unrefined; to further refine the 2,4-D dietary exposure and risk estimates, percent crop treated, 

anticipated residues, or available monitoring data could be used.

F. Residential (Non-Occupational) Exposure/Risk Characterization

There are registered uses of 2,4-D on turf including golf courses and parks as well as aquatic 

uses; therefore, residential handler exposure and post-application exposure to treated turf and 

aquatic sites is possible. There is no hazard via the dermal route for 2,4-D, therefore the handler 

assessment included quantification of risks for only the inhalation route of exposure and the postapplication assessment included only the inhalation and incidental oral route of exposure. The 

residential handler and post-application risk estimates are not of concern for 2,4-D for all 

scenarios and all routes of exposure.

For non-dietary exposures, EPA uses the term Margin of Exposure (MOE) to refer to the risk 

associated with the exposure estimate. The MOE is defined as the ratio of the selected 

toxicological POD, usually the NOAEL, to the estimated human exposure. A target MOE of 300

means that the estimated level of human exposure is 300 times lower than the highest dose that 

produced no adverse effects in the relevant toxicology study. Risk estimates that are not of 

concern are indicated by an actual MOE of 300 or greater for residential handler exposure and 

100 or greater for post-application exposure.

1. Residential Handler Exposure

Residential handlers may receive short-term dermal and inhalation exposure to 2,4-D when 

mixing, loading, and applying the pesticide to ornamental turf as well as aquatic uses. Only 
9

inhalation risk estimates were quantitatively assessed because there is no hazard via the dermal 

route for 2,4-D. The handler inhalation exposure scenarios considered were mixing, loading 

and applying:

 Liquid/Wettable Powder (WP)/Dry Flowable (DF) to Lawns/Turf with Hose-End Sprayer

 Liquid/WP in Water Soluble Packets (WSP) to Lawns/Turf/Aquatic Sites with manuallypressurized handwand

 Ready-to-Use/WP in WSP to Lawns/Turf with Hose-End Sprayer

 Liquid to Lawns/Turf/Aquatic Sites with Backpack

 Liquid/WP/DF to Lawns/Turf with Manually-pressurized handwand or backpack

 Granule to Lawns/Turf with Push-type spreader, Belly Grinder, Spoon, Shaker Can, Cup or 

Hand dispersal

The MOEs for the six exposure scenarios range from 460 to 3,400,000. Since there is potential 

risk concern only when MOEs are less than 300, residential handler exposures are not a 

concern.

2. Post-Application Exposure

There is the potential for post-application exposure for individuals exposed as a result of being 

in an environment that has been previously treated with 2,4-D. The quantitative exposure/risk 

assessment for residential post-application exposures is based on the following scenarios:

 Incidental ingestion (i.e., hand-to-mouth, object-to-mouth, soil ingestion exposure) from

contact with treated turf (children 1 to < 2 years old only)

 Episodic granular ingestion on treated turf (children 1 to < 2 years old only)

 Incidental ingestion of water during recreational swimming (both adults and children 3 to <

6 years old).

Assessment of post-application exposure to turf treated with liquid formulations is protective of 

exposure to solid formulations. The lifestages selected for assessment are health protective for 

the exposures and risk estimates for any other potentially exposed lifestages.

a. Residential Post-application Exposure for Turf Use

Incidental oral risk estimates were quantitatively assessed for residential post-application 

exposure for turf use. The incidental oral scenarios (i.e., hand-to-mouth and object-to-mouth) 

have been considered inter-related as it is likely that they occur interspersed amongst each 

other over time. Episodic granular ingestion on treated turf was not combined as this 

exposure would not occur as a result of routine behavior and is considered an episodic event

related to poisoning. 

The residential post-application risk estimates for turf use have MOEs that range from 490 to 

430,000 for all incidental oral scenarios so are not of concern for 2,4-D.
10

b. Residential Post-application Exposure for Aquatic Use

2,4-D is used for aquatic weed control of surface and submerged weeds. Many treatments are 

applied to aquatic areas where recreational swimming is not likely to occur but some 

subsurface treatments are made at recreational lakes. Since this can result in individuals being 

exposed to 2,4-D residues in water by entering these areas if they have been previously 

treated, there is a 24-hour swimming restriction. The extent of exposure during recreational 

swimming is assumed to be short-term in duration. Risk estimates were calculated for postapplication incidental oral ingestion while swimming in treated lakes or ponds. Inhalation 

exposure is expected to be negligible for swimmers; therefore, a post-application inhalation 

assessment was not conducted. Furthermore, the inhalation assessment for residential handlers 

is expected to be protective of potential post-application exposure and risk.

The residential post-application risk estimates for aquatic use have MOEs that range from 690 

to 5,300 for incidental oral ingestion so are not of concern for 2,4-D.

3. Residential Bystander Post-application Inhalation Exposure (Volatilization)

The potential exposure to bystanders from vapor phase 2,4-D residues emitted from treated 

fields has been evaluated for the proposed use of 2,4-D choline salt on genetically engineered 

corn and soybean. The two main factors that bystander exposure depends on are the rate at 

which these chemicals come off of a treated field which is described as the off-gassing, 

emission or flux, and how those vapors are dispersed in the air over and around the treated 

field. Volatilization can occur during the application process or thereafter. It can result from 

aerosols evaporating during application, while deposited sprays are still drying or after as dried 

deposited residues volatilize. The volatilization assessment used an analysis after sprays dried.

Flux data was submitted measuring flux rates of 2,4-D ethylhexyl ester (EHE), 2,4-D 

dimethylamine salt (DMA salt) and 2,4-D choline salt. 2,4-D choline salt was found to have a 

reduced potential for volatility. For this assessment, the data from the 2,4-D choline salt

applications only were used as this action specifically seeks registration for 2,4-D choline salt

product use in conjunction with GE soybean and corn with resistance traits.

Volatilization modeling for a single day was completed using Probabilistic Exposure and Risk

model for fumigants (PERFUM). There are a variety of factors that potentially affect the

emission rates of 2,4-D choline salt and subsequent offsite transport and to the extent possible, 

these factors were considered. They include field condition (e.g., bare soil, growing, or mature 

crop canopy), field parameters (e.g., soil type, moisture, etc.), formulation type, meteorological 

conditions, and application scenario (e.g., rate, method). Flux estimates from all monitored 

trials, a number of field sizes, and various meteorological data were used with PERFUM to 

estimate risk based on the 2,4-D choline salt field volatility study data.

The field volatility study suggests that volatilization of 2,4-D choline salt from treated crops 

does occur and could result in bystander exposure to vapor phase 2,4-D choline salt. However, 

results of PERFUM modeling indicate that airborne concentrations, even at the edge of the 

treated fields, are not above our levels of concern. 
11

4. Spray Drift

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

Off-target movement of pesticides can occur via many types of pathways and it is governed by 

a variety of factors. Sprays that are released and do not deposit in the application area end up 

off-target and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g., children 

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling coupled with methods 

employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is 

based on a premise of compliant applications which, by definition, should not result in direct 

exposures to individuals because of existing label language and other regulatory requirements 

intended to prevent them. Direct exposures would include inhalation of the spray plume or 

being sprayed directly. Rather, the exposures addressed here are thought to occur indirectly 

through contact with impacted areas, such as residential lawns, when compliant applications are 

conducted. Given this premise, exposures for children (1 to 2 years old) and adults who have 

contact with turf where residues are assumed to have deposited via spray drift thus resulting in 

an indirect exposure are the focus of this analysis analogous to how exposures to turf products 

are considered in risk assessment.

Several 2,4-D products have existing labels for use on turf, thus it was considered whether the 

risk assessment for that use may be considered protective of any type of exposure that would be 

associated with spray drift. If the maximum application rate on crops adjusted by the amount of 

drift expected is less than or equal to existing turf application rates, the existing turf assessment 

is considered protective of spray drift exposure. The proposed maximum single application rate 

of 2,4-D choline salt on GE corn and soybean is 1 lb ae/acre. This is less than the registered 

application rate on turf of 1.5 lb ae/acre, which has been previously assessed and which was 

updated based on the revised Standard Operating Procedures (SOPs) for Residential Exposure 

Assessment. Thus, even if 100% of the application rate of the choline salt formulation on GE

corn and soybean is deposited on an adjacent lawn, calculated risk estimates from drift would 

not be of concern. This again is because all existing registered uses on lawns have been 

previously assessed and no risks of concern were identified.

5. Aggregate Risk Assessment

In accordance with the FQPA, EPA must aggregate 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, EPA considers both the route and duration of 

exposure.
12

a. Acute Aggregate Risk

The acute aggregate risk assessment includes only food and water exposure. The acute food 

plus drinking water risk estimates are not of concern to EPA (≤100% aPAD) at the 95th 

percentile of the exposure distribution for the general population and all population 

subgroups.

b. Short-Term Aggregate Risk

The short-term aggregate risk assessment includes food, water, and residential exposure. The 

resulting short-term aggregate risks are not of concern to EPA (MOEs > LOC of 100) for 

adults and children.

c. Intermediate-Term Aggregate Risk

Intermediate-term residential exposures are not likely because of the intermittent application 

of 2,4-D by homeowners; therefore, the intermediate-term aggregate risk assessment includes 

only food and drinking water exposure, and are less than or equivalent to the chronic food 

plus drinking water exposure. The chronic food plus drinking water risk estimates are not of 

concern to EPA for the general population and all population subgroups.

d. Long-Term Aggregate Risk

The chronic (long-term) aggregate risk assessment includes only food and water exposure. 

The chronic food plus drinking water risk estimates are not of concern to EPA for the general 

population and all population subgroups.

6. Occupational Risk Assessment

a. Short- and Intermediate-Term Handler Risk

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used (mixing/loading liquid groundboom application, applying spray 

by groundboom equipment), occupational handler exposure is expected from the new uses. 

Occupational handler risk estimates are not of concern (i.e., MOEs > LOC of 300) for all

scenarios for use of 2,4-D choline salt on GE corn and soybean. At baseline personal 

protective equipment (PPE) (i.e., no respirator), the occupational handler inhalation MOE is 

4,900 for mixer/loaders and 3,200 for applicators using groundboom equipment.

b. Short- and Intermediate-Term Post-Application Risk

EPA uses the term post-application to describe exposures that occur when individuals are

present in an environment that has been previously treated with a pesticide (also referred to as 

reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for 
13

pests or harvesting. Post-application exposure levels vary over time and depend on such 

things as the type of activity, the nature of the crop or target that was treated, the type of 

pesticide application, and the chemical’s degradation properties. In addition, the timing of 

pesticide applications, relative to harvest activities, can greatly reduce the potential for postapplication exposure.

i. Dermal Post-application Risk

There is no potential hazard via the dermal route for 2,4-D choline salt; therefore, a 

quantitative occupational post-application dermal risk assessment was not completed.

ii. Inhalation Post-application Risk

Based on the EPA’s current practices, a quantitative occupational post-application inhalation 

exposure assessment was not performed for 2,4-D choline salt at this time primarily because 

of the low acute inhalation toxicity (Toxicity Category III) and vapor pressure (1.4 x 10-7 

mm Hg at 25°C for 2,4-D acid).

Although a quantitative occupational post-application inhalation exposure assessment was 

not performed, an inhalation exposure assessment was performed for 

occupational/commercial handlers and showed no risks of concern. Handler exposure 

resulting from application of pesticides outdoors is anticipated to result in higher exposure 

than post-application exposure. Therefore, it is expected that these handler inhalation 

exposure estimates would be protective of most occupational post-application inhalation 

exposure scenarios. Furthermore, a quantitative volatilization inhalation exposure 

assessment was assessed for bystanders and indicates no risk of concern for bystanders.

III. Environmental Risk

A summary of the environmental fate and ecological effects and risks of 2,4-D choline salt as 

assessed in the Agency document titled, Ecological Risk Assessment for the Section 3 New Use 

Registration of 2,4-D Choline Salt on Soybean with DAS 68416-4 (2,4-D Tolerant) and 2,4-D + 

Glyphosate Tolerant Corn and Field Corn, is provided below.

A. Environmental Fate

1. Degradation

The degradation of 2,4-D occurs via oxidative microbially-mediated mineralization in 

terrestrial environments, and photodegradation in water. Degradation under aerobic soil 

conditions is rapid to moderately rapid with half-lives ranging from 1.4 to 12.4 days. In 

terrestrial field dissipation studies, 2,4-D acid half-lives range from 1.1 days to 42.5 days. 

There are three major degradates (2,4-DCP, 1,2,4-bezenetriol, and chlorohydroquinone 

(CHQ)) and three minor degradates (include 4-chlorophenol, 4-CPA and 2,4-DCA) of 2,4-D. 

Formation of these degradates varies by environmental component (e.g., soil vs. water), and 

availability of oxygen. Under natural conditions certain degradates may be less likely to occur.
14

2. Mobility

Under most environmental conditions 2,4-D is an anionic acid, hence it is expected to be 

mobile to moderately mobile. Risk of bioaccumulation is low for 2,4-D given the low value of 

the log octanol/water partition coefficient (log Kow = 0.18 at neutral pH). The vapor pressure 

(1.4 × 10-7 mm Hg) and Henry's Law Constant (8.56 x 10-6 atm-m3/mol) indicate that 2,4-D 

acid has a low volatility. Preliminary results from a field volatility study performed with 2,4-D 

choline salt, 2,4-D ethylhexyl ester (EHE), and 2,4-D dimethylamine salt (DMA salt) indicate

that the estimated volatility flux rate of 2,4-D choline salt is lower than the EHE and DMA salt 

formulations. 

B. Ecological Risk

Ecological risk characterization integrates the results of the exposure and ecotoxicity data to 

evaluate the likelihood of adverse ecological effects. The means of integrating the results of 

exposure and ecotoxicity data is called the quotient method. For this method, risk quotients 

(RQs) are calculated by dividing exposure estimates by ecotoxicity values, both acute and 

chronic (RQ = Exposure / Toxicity). RQs are then compared to EPA’s levels of concern (LOCs). 

The LOCs are criteria used by the agency to indicate potential risk to non-target organisms. The 

criteria indicate whether a pesticide, when used as directed, has the potential to cause adverse 

effects to non-target organisms. 

The risk quotient method was used to determine if 2,4-D choline salt has the potential to cause 

adverse effects to non-target organisms based on the proposed new use patterns for 2,4-D choline 

salt. Birds are considered a surrogate for terrestrial-phase amphibians and reptiles, in the 

absence of taxa-specific data. Submitted ecotoxicity data for 2,4-D choline salt (algae, 

freshwater fish, and honeybee) support bridging 2,4-D choline salt to 2,4-D acid ecotoxicity data. 

Only the most sensitive 2,4-D toxicity value from the broader 2,4-D dataset were used in risk 

quotient calculations, as needed. The major degradates of 2,4-D were considered, and all except 

2,4-DCP were eliminated as likely degradates of concern. 2,4-DCP is a major degradate in 

certain aquatic environments; therefore, 2,4-D and 2,4-DCP were considered stressors of concern 

in aquatic environments, and 2,4-D alone was considered in terrestrial environments. 

The results of this screening-level risk assessment indicate that risks did not result in RQ’s that 

exceeded the Agency’s LOC for freshwater fish, estuarine/marine fish, freshwater invertebrates, 

estuarine/marine invertebrates, terrestrial insects, or aquatic plants for either acute or chronic 

exposures. Risks for chronic exposures to birds, reptiles, and land-phase amphibians do not 

result in RQ’s that exceed the Agency’s LOC for chronic exposures only.

The screening-level analysis indicates that risks for acute exposures to birds, reptiles, and landphase amphibians do result in RQ’s that exceed the Agency’s LOC for acute exposures. 

Additionally, risks for mammals resulted in RQ’s that exceed the Agency’s LOC for both acute 

and chronic exposures. Risks for plants resulted in RQ’s that exceed the Agency’s LOC for both 

terrestrial monocots and terrestrial dicots. The following sections discuss the results of the risk 

quotient analyses for these taxonomic groups with potential risk above the Agency’s LOC, 
15

characterization of those risks, and describe mitigation measures to reduce these potential risks 

of exposure to 2,4-D choline salt. 

1. Risk to Birds:

The risk quotient analysis indicates that potential risks from the proposed 2,4-D choline salt 

uses result in RQ’s that exceed the Agency’s LOC for birds only on an acute basis. 

Acute Risk: The acute oral toxicity study was conducted with the northern bobwhite quail and 

resulted in a classification of “moderately toxic” to birds on an acute oral basis. Toxic 

symptoms prior to death were lethargy, reduced reaction to external stimuli, depression, lower 

limb weakness, wing droop, prostrate posture, loss of righting reflex, and a ruffled appearance. 

Sub-lethal effects included a drop in body weight at two of the treatment levels (218.7 and 135 

mg ae/kg-bw). There was also a decrease in food consumption at the 218.7 mg ae/kg-bw 

treatment level during the first 3 days after dosing, but this was compensated for by a 2-3 times 

higher food consumption rate from days 4 through 14.

Two acute dietary studies were available, classifying 2,4-D choline salt as “practically nontoxic” on an acute dietary basis to birds. No mortalities occurred in either study. The northern 

bobwhite quail study exhibited a slight decrease in body weight gain at the 3035 and 1706 mg 

ae/kg-diet treatment levels. The mallard duck study exhibited a decrease in body weight gain 

and feed consumption, but only at the highest treatment level (3035 mg ae/kg-diet).

In order to make the most conservative risk estimation, acute toxicity risk quotients were based 

on the oral toxicity study for the northern bobwhite quail. Risk quotients ranged from 0.01 to 

4.18. 

Risk quotients for birds span a range of 0.01 to 4.18 which are then compared to the Agency’s 

screening level of concern for non-listed species (RQ>0.5). The Agency risk screening 

assessment employed residue estimates based on reasonable upper bound assumptions and the 

maximum labeled rate of the pesticide to determine the RQ values. At this high end exposure, 

residues for a variety of food items combined with a variety of body sizes triggered the 

screening concern threshold when compared to the most sensitive oral dose toxicity 

estimate. While concern levels are triggered, further consideration of all lines of evidence does 

suggest that risks under more usually encountered circumstances may be lower. For example, 

high end residues compared to toxicity study endpoints using chemical actually incorporated in 

the animal’s diet do not trigger non-endangered species concerns, suggesting that 2,4-D choline 

consumed in the diet may possibly be less available than assumed using dose-based 

exposures. Further, more frequently expected residues levels, such as mean or median 

estimates of exposure would be lower by a factor of two or more, suggesting that residues are 

often not likely to trigger concerns for many food items. In addition, screening estimates of 

exposure and risk are maximal at the actual point of application, right on the field. Available 

information in the Agency risk assessment indicates that the transport of pesticide off field by 

spray drift decreases with distance, suggesting that exposures to 2,4-D choline salt and 

attendant risks can be substantially lower for organisms with territories established at distance 

from the field. With this last line of evidence in mind, a mitigation step has been incorporated 
16

into the pesticide label to require a 30 foot spray setback from areas likely to be habitat for 

birds in order to further reduce off-site exposure for birds.

2. Risk to Mammals:

The risk quotient analysis indicates that potential risks from the proposed 2,4-D choline salt 

uses result in RQ’s that exceed the Agency’s LOC for mammals in both acute and chronic 

scenarios.

Risk quotients for mammals exceeded the Agency’s LOCs for mammals for acute dose-based 

exposure and chronic dose-based and dietary-based exposure. The chronic dose-based LOC 

(1.0) was exceeded for all size classes of mammals consuming all food items except for seeds. 

The chronic dietary-based LOC (1.0) was exceeded for diets of short grass, tall grass, broadleaf 

plants, and arthropods for mammals. 

Acute Risk: The acute toxicity of 2,4-D choline salt to mammals was assessed using the oral 

gavage study conducted on laboratory rat. Based on the LD50, 2,4-D choline salt is moderately 

toxic to mammals on an acute basis. The dose-based acute mammalian risk quotients ranged 

from <0.01 to 0.57.

The acute LOC (0.5) was exceeded only for small mammals consuming short grass. All other 

scenarios resulted in RQ’s that did not exceed the Agency’s LOC. Because this assessment is 

conducted under screening level assumptions designed to be conservative (i.e., in the treated 

field, maximum use rates, eating only the single food source that is expected to result in the 

greatest exposure, high-end environmental exposures), EPA expects that actual risks to these 

mammals is lower. Any deviation from this worst case scenario would result in lower risk 

estimates and would be expected to result in RQ’s lower than the Agency’s LOC.

Chronic Risk: The two-generation chronic study with the laboratory rat indicated endpoints in 

parents and offspring growth to be the most sensitive. Some reproductive effects were also 

identified. Chronic dose based risk quotients ranged from 0.32 to 50.2. The chronic LOC of 

1.0 was exceeded for all size classes of mammals consuming all food items except for seeds. 

Chronic dietary based risk quotients ranged from 0.36 to 5.78.

As in the case for birds, risk quotients for mammals span an appreciable range of 

outcomes. The principal focus is on the concern levels for reproduction effects, where RQ 

values range from <1 to 50, and span the Agency’s screening level of concern for non-listed 

species (RQ>1). 

Again, the Agency risk screening assessment employed residue estimates based on reasonable 

upper bound assumptions and the maximum labeled rate of the pesticide to determine the RQ 

values. Consideration of more usual residue estimates and other lines of evidence such as food 

preferences and foraging ranges relative to distance from the site of application can lead to 

markedly reduced concerns for adverse effects in larger mammals with more varied diets, with 

larger home ranges with increased potential to be feeding well away from treatment areas. 
17

Consideration of these lines of evidence also produces reduced risk estimates for small 

herbivorous mammals but do not reduce risk estimates for these organisms to the point that 

concern levels are not exceeded. As in the case for birds, the provision of a 30-foot buffer from 

areas potentially comprising habitat for such mammals is intended to reduce the areas where 

such risks may occur.

3. Risk to Plants:

For this risk assessment, data from other forms of 2,4-D were used as surrogates for the 2,4-D 

choline salt and 2,4-D choline salt/glyphosate products. For seedling emergence, onion was the 

most sensitive monocot and lettuce was the most sensitive dicot. Shoot length was the most 

sensitive parameter for both species, as well as for four of the other species that were tested 

(tomato, cucumber, soybean, turnip). Seedling emergence was the most sensitive parameter for 

one species (cabbage) and other toxicological observations included chlorosis and leaf curl. 

Onion and lettuce were also the most sensitive species for the vegetative vigor test. The most 

sensitive parameter for onion was fresh weight. Leaf distortion and necrosis were also 

observed. The most sensitive parameter for lettuce was dry weight. Chlorosis, necrosis, leaf 

curl, stem curl, wilt, and adventitious growth were also reported as effects. Overall, the 

vegetative vigor and seedling emergence studies indicate that 2,4-D choline salt is slightly more 

toxic to dicots than monocots.

As is expected with herbicides, terrestrial plants are sensitive to 2,4-D residues. All terrestrial 

plant risk quotients exceeded the LOC (1.0). Risk quotients ranged from 1 to 90.62 for 

monocots and 12.35 to 1085.11 for dicots. Risk was attributed to both spray drift and runoff 

from treated fields. Thus, the risk quotient analysis indicates that effects are predicted from the 

proposed new uses of 2,4-D choline salt to terrestrial plants.

Although the risk quotient analysis indicates there may be risks to terrestrial plants from runoff 

and spray drift, data conducted on the 2,4-D choline salt formulation proposed for registration 

demonstrates that the formulation maintains some properties that may reduce spray drift to nontarget areas. The registrant submitted additional studies for spray drift analysis, using the 

AIXR 11004 nozzle and the specific 2,4-D choline salt formulation proposed for registration in 

this action. The analysis indicates that this 2,4-D choline salt formulation applied through the 

AIXR 11004 nozzle is protective of non-listed dicots from exposures of 2,4-D choline when an 

adequate buffer is incorporated between the application equipment and the downwind edge of 

the treated field. Therefore, to mitigate against potential risks to plants, the product labeling 

will require the use of a 30 foot buffer zone and specific nozzle specifications, thus reducing 

the potential exposure of non-target plants to 2,4-D choline salt residues.

4. Endangered Species for 2,4-D Choline Salt

A summary of the endangered species assessment for 2,4-D choline salt as assessed in the EPA 

document titled, Addendum to 2,4-D Choline Salt Section 3 Risk Assessment: Refined 

Endangered Species Assessment for Proposed New Uses on Herbicide-Tolerant Corn and 

Soybean, is provided below.
18

In the environmental risk assessment performed for new uses of 2,4-D choline salt on GE corn 

and soybean, EPA determined that direct concerns were unlikely for aquatic plants (vascular 

and non-vascular), freshwater fish (acute and chronic), estuarine/marine fish (acute and 

chronic), freshwater invertebrates (acute and chronic), estuarine/marine invertebrates (acute and 

chronic), and terrestrial insects. While direct concerns were found to be unlikely for birds, 

reptiles and terrestrial phase amphibians for chronic risk, they could not be excluded for acute 

risk. In addition, potential direct risk concerns could not be excluded for mammals (acute and 

chronic) and terrestrial plants. Indirect effect risk concerns are possible for any species that has 

dependencies on species that are directly affected.

Registration of Enlist DuoTM is currently being considered for use in the states of Illinois, 

Indiana, Iowa, Ohio, South Dakota, and Wisconsin. Based on EPAs LOCATES database and 

data submitted by DAS, 53 listed species were identified as inside the “action area” (area of 

concern where use of pesticide may result in exposure to endangered species) associated with 

the new GE corn and soybean uses within these six states. Additional states may be added to 

the labeling once an assessment is completed and demonstrates that a no effects determination 

is appropriate for any such state. 

The following criteria are used to make an effects determination:

 For listed individuals inside the action area but not part of an affected taxa nor relying on 

the affected taxa for services involving food, shelter, biological mediated resources 

necessary for survival and reproduction, use of a pesticide would be determined to have “no 

effect.”

 For listed individuals outside the action area, use of a pesticide would be determined to 

have “no effect.”

 Listed individuals inside the action area may either fall into the “no effect” or “may effect” 

categories depending upon their specific biological needs and circumstances of exposure. 

 Those that fall under the “may effect” category are found to be either “likely” or “not likely 

to adversely affect” the listed species. 

 A “likely” or “not likely to adversely affect” determination is made using criteria that 

categorizes the effect as insignificant, highly uncertain, or wholly beneficial. 

Spray drift mitigation language on the label is intended to limit off site transport of 2,4-D 

choline salt in spray drift. Therefore, EPA expects that spray drift will remain confined to the 

2,4-D choline treated field and that the action area is limited to this field. Consequently, 49 of 

the 53 species originally identified as potentially at-risk can be given a “no effect” 

determination based on the premise that they are not expected to occur on corn and soybean 

fields. 

The 4 remaining listed species that were not ruled out because their range contains areas that 

include treated fields were considered in more depth to refine the assessment. Species specific 

biological information and 2,4-D choline salt use patterns were considered. After utilizing 

processes such as refined modeling incorporating species specific information and migration 

habits, EPA made a determination of “no effect” for these species.
19

For more details on these findings, refer to the EPA document titled, Addendum to 2,4-D 

Choline Salt Section 3 Risk Assessment: Refined Endangered Species Assessment for Proposed 

New Uses on Herbicide-Tolerant Corn and Soybean.

As noted earlier in this decision, glyphosate is already registered for these uses and did not 

undergo review as part of the assessment for this pesticide product. However, glyphosate 

currently is in the registration review process and an ESA analysis will be part of that process.

IV. Resistance Management

The emergence of herbicide resistant weeds is an increasing problem that has become a 

significant economic issue to growers. This has led to a concern that the use of 2,4-D on GE 

crops may result in more resistant weeds. In an effort to address this issue going forward, EPA 

is requiring that DAS develop a stewardship program that will aggressively promote resistance 

management efforts. 

The overall goal of the stewardship plan is to assist and support responsible use of the product. 

With regard to weed resistance management, the plan mandates that DAS must immediately 

investigate any claims of non-performance. The initial mechanism users can use for 

communicating directly with DAS is a toll-free number to get advice on how to resolve any 

uncontrolled weeds.

Academia, growers, USDA, and other leaders involved with pest management acknowledge the 

importance of field scouting. For this reason, the Enlist DuoTM label includes a requirement to 

scout treated fields. Field scouting before application will be essential to determining the weed 

species present as well as their stage of growth. Scouting 7-21 days after herbicide application 

will be used to assess the performance of weed control. In the event that a user encounters a 

non-performance issue, the toll-free number could be used to initiate an intervention against that 

weed population.

The DAS response to reports of non-performance must be immediate and must ensure that 

possible incidents of resistance are promptly investigated and resolved. EPA proposes that when 

a non-performance issue is identified , DAS or its representative will conduct a site visit and 

evaluate the issue using decision criteria identified by leading weed science experts (Norsworthy, 

et al.), in order to determine if “likely herbicide resistance” is present. This is distinct from, and 

more broad than, the term “likely herbicide resistance,” as explained below. For purposes of this 

decision, a report of non-performance to DAS will be the trigger for a site visit. 

Non-performance refers to any cause that results in inadequate weed control after an herbicide 

application. “Lack of herbicide efficacy” refers to inadequate weed control with various possible 

causes, including but not limited to: application rate, stage of growth, environmental conditions,

herbicide resistance, plugged nozzle, boom shut off, tank dilution, post-application weed flush, 

unexpected rainfall event, weed misidentification, etc. EPA recognizes that it can be challenging 

to determine emerging weed resistance at an early stage. Therefore, EPA is selecting criteria that 

it feels will be helpful to DAS and to users in identifying when instances of “lack of herbicide 
20

efficacy” in fact constitute “likely herbicide resistance.” These “likely herbicide resistance” 

criteria are: (1) failure to control a weed species normally controlled by the herbicide at the dose 

applied, especially if control is achieved on adjacent weeds; (2) a spreading patch of 

uncontrolled plants of a particular weed species; and (3) surviving plants mixed with controlled 

individuals of the same species (Norsworthy, et al., 2012).

When DAS or its representative applies the Norsworthy, et al., criteria cited above and likely 

herbicide resistance is identified, then DAS must take immediate action to eradicate likely 

resistant weeds in the infested area. This may be accomplished by re-treating with an herbicide 

or using mechanical control methods. If herbicide re-treatment is used to eliminate the likely 

resistant weed(s), follow-up scouting will be required to confirm that the lack of herbicide 

efficacy has been resolved. DAS must also notify EPA that likely herbicide resistance has been 

identified and report this on a monthly basis. In addition, samples of the likely herbicide 

resistant weeds and/or seeds must be taken, and prior to the next growing season laboratory or 

greenhouse testing must be initiated in order to determine whether resistance is the reason for the 

lack of herbicide efficacy. DAS must also work to develop a laboratory diagnostic test to 

quickly identify herbicide resistance, and report to EPA its progress toward developing such a 

diagnostic test.

In addition to reporting incidents of likely resistance, on or before October 15 of each year, DAS 

will submit annual summary reports to EPA. These reports must include a summary of the 

number of instances of likely and confirmed resistance to Enlist DuoTM by weed species, crop, 

county and state. They will also summarize the status of laboratory or greenhouse testing for 

resistance, as well as the status of the development of a laboratory test. The annual reports will 

also address the disposition of incidents of likely or confirmed resistance reported in previous 

years.

Users and other stakeholders must be informed of reports of likely and confirmed herbicide 

resistance to Enlist DuoTM, if any. The information will include details of weed species and 

crop. To accomplish this, EPA expects that DAS will establish a website to facilitate delivery of 

resistance information.

Several management practices that are designed to help users avoid initial occurrences of weed 

resistance will appear on the product labeling under the Resistance Management heading of the 

label. These practices are discussed in Section VII.B.3 of this document.

Refer to Section VII.C below for EPA’s delineation of necessary terms of registration to address 

the issue of weed resistance.

V. Response to Comments

The Agency received more than 100,000 comments in response to the Notices of Receipt 

(Docket Numbers: EPA-HQ-OPP-2011-0835 and EPA-HQ-OPP-2012-0306) for the applications 

to register the use of 2,4-D choline salt on GE 2,4-D and glyphosate tolerant corn and soybeans. 

Some of the comments were in favor of a decision to register Enlist DuoTM, which is expected to 

provide growers with additional tools to control a broad spectrum of weeds. However, the large 
21

majority of comments expressed concern and requested that the Agency deny the proposed 

registrations. The EPA welcomes input from the public during the decision process when 

registering pesticides, and is committed to thoroughly evaluating and mitigating any potential 

risks from registered pesticides, consistent with applicable statutory standards. Also, EPA 

strives to document and explain the bases of its regulatory decisions through these and other 

public documents.

A. Human health

A common concern expressed in the submitted comments was regarding the human health 

effects of the potential increased use, and therefore exposure of, 2,4-D. 

1. Agent Orange/Dioxins

Comments were received that expressed concern regarding the dangers of dioxins, and their 

association with 2,4-D. The herbicide Agent Orange, which was used by the military during 

the 1960s, was a mixture of the herbicides 2,4,5-T and 2,4-D. Agent Orange was contaminated 

with dioxin, or 2,3,7,8-TCDD, a by-product of the manufacturing process at that time. In 1970, 

the United States Department of Agriculture (USDA) stopped the use of 2,4,5-T on all food 

crops except rice, and in 1985 EPA terminated all remaining uses in the U.S. The herbicide 2,4-

D has been reviewed extensively in past years. Since the 1980s, the manufacturers of 2,4-D 

have taken steps to decrease the chances that dioxin contaminants will be formed during the 

production process. In periodically reviewing 2,4-D, EPA has required the manufacturers to 

provide data on dioxin levels in 2,4-D products to confirm that the products can be used safely. 

Potential dioxin contamination is no longer a factor in the modern manufacturing processes for 

2, 4-D.

2. Toxicological Effects

Several comments were received expressing concern with a variety of potential adverse effects 

on humans. The comments included concerns with Non-Hodgkin’s Lymphoma, carcinogens, 

Parkinson’s disease, epidemiology, and other effects attributed to increased use of 2,4-D. 

These concerns are discussed below.

a. Non-Hodgkin’s Lymphoma 

Regarding the alleged association of exposure to 2, 4-D and non-Hodgkin’s lymphoma

(NHL), the Agency on numerous occasions has concluded that the data are inadequate to 

support a link between 2,4-D exposure and cancer of any type (most recent assessment can be 

found in the Agency’s response to NRDC petition, 2012). The Agency will further evaluate 

research related to 2,4-D under registration review, including any new epidemiology data.
22

b. Carcinogens

The Agency has evaluated on several occasions the issue of human carcinogenicity, based on 

epidemiological links of 2, 4-D to NHL, as well as mutagenicity potential. EPA has 

consistently found that these data do not support classification of 2,4-D as a carcinogen.

c. Parkinson’s Disease

Epidemiological studies in the open literature linking Parkinson’s disease with 2,4-D 

exposure will be addressed during the Registration Review of all 2,4-D formulations, taking 

into account the fact that 2,4-D use patterns have changed in agriculture since the timeframes 

where the cited data were generated and possible confounding aspects, such as potential 

dioxin contamination, which are no longer a factor in the modern manufacturing processes for 

2,4-D.

d. Epidemiology

The Agency has on several occasions reviewed epidemiology studies asserting a link between 

cancer and 2,4-D exposure. EPA concluded that the existing data did not support the link. 

During Registration Review, all new epidemiology information will be considered. During 

the registration review process, the Agency is also involved in many efforts to refine its risk 

assessment policies including establishing better methods for considering epidemiological 

research in the regulatory process; and more active participation with several epidemiological 

cohorts focused on agriculture and the use of pesticides. The Agency will further evaluate 

research related to 2,4-D under registration review. 

e. Other 

Commenters expressed concern about a range of other health effects. Prior to approval or 

registration by EPA, pesticides undergo a battery of scientific studies on a wide range of 

health effects, including cancer, reproductive effects, neurological effects, and acute and 

chronic toxic effects, and must demonstrate that the product meets the statutory standard and 

can be used without unreasonable risks. The Agency also periodically reviews all registered 

pesticides to make sure that they continue to meet current scientific and regulatory standards. 

If, at any time, EPA determines that there are urgent risks from exposure to a pesticide that 

require prompt attention, the Agency can initiate appropriate regulatory action.

EPA has a full and scientifically robust data set on 2,4-D, and has a conservative and protective 

risk assessment based on NOAEL considerations and protective safety factors. More detail on 

EPA’s assessment of human health risk is in Section II of this document. 

B. Environment

Another area of concern for many commenters was the risk of adverse environmental impacts 

from the increased application of 2,4-D.
23

1. Endangered Species

Comments were received concerning possible effects with respect to endangered species. The 

Agency has conducted a thorough evaluation of the 2,4-D choline salt component to determine 

the potential impacts from the proposed action to endangered species and has concluded that no 

impact to endangered species is expected. A discussion of the Agency’s endangered species 

assessment is included in this document and can be found in Section III of this document.

2. Spray Drift/Volatilization

A portion of commenters expressed concerns of spray drift and volatilization of 2,4-D affecting 

non-target plants. The Agency understands and has evaluated the risks regarding the potential 

drift of pesticides to sensitive crops adjacent to treatment areas, and other non-target plants. 

EPA has examined data confirming that the choline salt of 2,4-D will reduce spray drift and 

volatility compared to other forms of 2,4-D currently registered. As a result, the use of the 

choline salt of 2,4-D would result in reduced off-site movement of the herbicide. To ensure 

there is reduced off-target movement, the proposed regulatory decision pertains only to the use 

of the same formulation (the choline salt) and specific spray nozzle employed in the registrant’s 

submitted drift studies. In addition, the proposed registration decision requires a 30-foot onfield buffer zone to help minimize spray drift from the intended use area. The proposed label 

also specifies that Enlist DuoTM cannot be applied when the wind speed is over 15 mph, and no 

aerial application is permitted. With employment of these label restrictions, drift from the 

treated field in not expected, protecting non-target plant species. 

More details on the EPA and DAS’ efforts to minimize effects to non-target plant species can 

be found in Section IV of this document.

3. Weed Resistance

Commenters also expressed concerns that weeds resistant to 2,4-D and glyphosate will be more 

prevalent as a result of this proposed use. Weed resistance is an increasing problem that has 

become a significant economic issue to growers. In an effort to prevent new weed resistance 

from happening, while giving growers another essential tool in their integrated pest 

management programs, DAS will put into place a stewardship program to promote responsible 

use of the proposed product in order to minimize the potential for increased levels of weed 

resistance. This plan is discussed in detail in Section IV of this document. 

4. Risk to Bees

The concern of risk to bees was conveyed in the comments. Conservative, screening level risk 

assessments have determined 2,4-D choline salt to be practically non-toxic to bees. Therefore, 

the Agency expects that there will be no adverse impacts to bees or other pollinators as a result 

of the proposed action. Regardless, the Agency is working aggressively to protect bees and 

other pollinators from the potential effects of pesticides and is engaged in national and 

international efforts to address those concerns. The Agency works with beekeepers, growers, 

pesticide manufacturers, the U.S. Department of Agriculture (USDA) and States to apply 
24

technologies to reduce pesticide exposure to bees, advance best management practices, enhance 

enforcement guidance, and to ensure that real-world pollinator risks are accounted for in our 

pesticide regulatory decisions. 

5. Sensitive Non-target Plants

A portion of commenters expressed concerns of spray drift and volatilization of 2,4-D affecting 

non-target plants, particularly to growers of sensitive crops, such as vegetables. EPA has 

examined data confirming that the choline salt of 2,4-D will reduce spray drift and volatility 

compared to other forms of 2,4-D currently registered. As a result, the use of the choline salt of 

2,4-D would result in reduced off-site movement of the herbicide. 

Spray drift from the 2,4-D choline salt formulation is also reduced through the use of specific 

nozzles that produce a course droplet size. EPA has re-evaluated the spray drift buffers that 

would be required to protect the most sensitive taxonomic group, listed dicots. The spray drift 

buffer distances were calculated using the droplet spectrum for a specific nozzle/formulation 

combination (AIXR 11004 nozzle and Enlist DuoTM product formulation). The spray drift 

buffer analysis found drift from the treated field is not expected beyond a 30-foot buffer 

distance. 

To mitigate the risk of off-target movement, the proposed regulatory decision pertains only to

the use of the same formulation and specific spray nozzle employed in the registrant’s 

submitted drift studies. In addition, the proposed registration decision requires a 30-foot onfield buffer zone to help minimize spray drift from the intended use area. The proposed label 

also specifies that Enlist DuoTM cannot be applied when the wind speed is over 15 mph, and no 

aerial application is permitted.

C. Other Concerns

1. Competitive Advantage

Concerns that the Agency will be competitively favoring DAS by granting the proposed new 

uses were also communicated. Under the FIFRA pesticide registration process, the Agency 

reviews only those pesticides and only those uses requested by the requestor / pesticide 

registrant.

2. Glyphosate

Some comments were received regarding the active ingredient glyphosate. It is acknowledged 

that the proposed product contains glyphosate as well as 2,4-D choline salt as an active 

ingredient. However, although the use on GE crops is a new use pattern for the 2,4-D 

component of this product, it is not a new use for glyphosate. Glyphosate products are 

currently registered and used for corn and soybeans in the identical manner as specified in this 

proposed product. EPA affirms that the existing risk assessment for glyphosate fully considers 

its potential uses and exposures from use on corn and soybean and concludes that its use is 

protective of the public and meets the standards of FIFRA and FQPA. Because a new 
25

assessment for the application of glyphosate to EnlistTM crops does not require a new human 

health or environmental risk assessment, comments concerning glyphosate are not being 

requested in this public comment period. However, glyphosate is currently under registration 

review, and EPA will invite public comments throughout that process. The most recent 

information on risks for glyphosate can be found in the Registration Review Docket EPA-HQOPP-2009-0361. 

VI. Benefits

The need for additional tools to manage resistant weeds has become important as resistance to 

glyphosate and other herbicides has become a significant economic and pest management issue 

to growers. The new uses of 2,4-D choline salt could expand options for weed control in corn 

and soybean and enable control of some resistant biotypes. Current registered uses of noncholine 2,4-D in corn allow for over-the-top broadcast applications only up to 8 inches tall which 

would be increased to up to 48 inches tall with GE 2,4-D resistant corn. Similarly, the currently

registered use of non-choline 2,4-D in soybeans allows pre-plant applications only, however new 

uses of 2,4-D choline salt would expand uses to include over-the-top broadcast applications to 

GE soybeans. If registered, the addition of this new tool to the production of soybeans is 

expected to have a significant impact to broadleaf weed control.

The introduction of a premix formulation combining 2,4-D choline salt and glyphosate to be 

used on EnlistTM corn and soybeans can provide additional benefits. The use of a premix of 2,4-

D choline salt and glyphosate utilizes multiple mechanisms of action and it, if utilized as part of 

a weed resistance management plan, could delay the development of herbicide resistant weeds. 

The pairing of two herbicides into a systems approach with a GE crop will allow growers and 

applicators the opportunity to control many weeds in a way which fulfills the important principle 

of using multiple mechanisms of action, which the weed science community has been touting for 

many years. 

The use of 2,4-D choline salt and glyphosate on the EnlistTM corn and soybean seed technology 

would provide efficacious control of broadleaf weeds later in the growing season, resulting in 

reduced spread and persistence of many broadleaf weeds. When the two herbicides are 

controlling weeds that are not resistant to either herbicide, this weed control system could 

prolong the use of glyphosate technology. In addition, this system could maintain the positive 

effect of reducing the need for tillage, thus preventing unnecessary erosion, in areas where 2,4-D

choline salt will control glyphosate resistant broadleaf weeds.

The use of the 2,4-D choline salt offers environmental benefits over the use of traditional forms 

of 2,4-D as well. Specifically, EPA has determined that the choline salt is less volatile than other 

forms of 2,4-D. Data also indicates that 2,4-D choline salt has less potential for off-site 

movement through spray drift than other forms of this herbicide. This would reduce the potential 

for damage to non-target plants, including vulnerable crops, where 2,4-D choline salt is to be 

used.
26

VII. Proposed Registration Decision

Based on these considerations, consistent with the requirements of FIFRA Sec. 3(c)(5), EPA 

concludes that (i) the Agency has satisfactory data pertaining to the proposed uses of Enlist

DuoTM on corn and soybeans; and (ii) approving this application as set forth below will not cause 

any unreasonable adverse effect on the environment. Accordingly, the Agency proposes to grant 

this registration with certain terms necessary to ensure that if weed resistance is likely, EPA can 

act quickly to address the problem.

A. Data Requirements

There are no outstanding data requirements required to support the proposed registration of this 

action. Although there are data that may be required in connection with registration review 

activities for 2,4-D, those requirements would be generic to 2,4-D uses and products in general 

and would be handled in accordance with the registration review process.

B. Labeling Requirements

In order to mitigate risks to non-target plants and animals, label language will be required that is 

intended to keep the pesticide on the treatment area, thereby reducing the potential for exposure 

of non-target plants and animals. For example, spray drift management language will be 

required on the occupational/commercial labeling that advises users of applicator responsibilities 

and requires specific techniques to reduce the possibility of spray drift. In addition, surface and 

ground water advisories will be required on all labeling, which may further reduce residues in 

drinking water and exposure of non-target organisms.

1. Environmental Hazards

Do not apply directly to water, to areas where surface water is present, or to intertidal areas 

below the mean high water mark. Do not contaminate water when disposing of equipment 

washwaters or rinsate.

2. Worker Protection

Do not apply this product in a way that will contact workers or other persons, either directly or 

through drift. Only protected handlers may be in the area during application. For any 

requirements specific to your state or tribe, consult the agency responsible for pesticide 

regulation.

Do not enter or allow worker entry into treated areas during the restricted entry interval (REI) 

of 48 hours. PPE required for early entry to treated areas that is permitted under the Worker 

Protection Standard and that involves contact with anything that has been treated, such as 

plants, soil, or water, is:

 Coveralls

 Chemical resistant gloves made of any waterproof material
27

3. Resistance Management

a. Herbicide Selection:

 Apply full rates of GF-2726 for the most difficult to control weed in the field at the 

specified time (correct weed size) to minimize weed escapes.

 Rotate the use of this product with non-Group 4 and non-Group 9 herbicides.

 Utilize sequential applications of herbicides with alternative modes of action.

 Avoid using more than two applications of GF-2726 and any other Group 4 or Group 9 

herbicide within a single growing season unless mixed with another mode of action 

herbicide with overlapping weed spectrum.

 Use a broad spectrum soil applied herbicide with other modes of action as a foundation in 

a weed control program.

b. Crop Selection and Cultural Practices:

 Incorporate additional weed control practices whenever possible, such as mechanical 

cultivation, crop rotation, and weed-free crop seeds, as part of an integrated weed control 

program.

 Do not allow weed escapes to produce seeds, roots or tubers.

 Thoroughly clean plant residues from equipment before leaving fields suspected to 

contain resistant weeds.

 Scout fields before application to ensure herbicides and rates will be appropriate for the 

weed species and weed sizes present.

 Scout fields between 7 and 21 days after application to detect weed escapes or shifts in 

weed species.

 If resistance is suspected, treat weed escapes with an alternate mode of action or use nonchemical methods to remove escapes.

 User report any incidence of non-performance of this product against a particular weed 

species to the DAS representative.

4. Spray Drift Management

a. Droplet Size:

Use AIXR 110-04 spray nozzles with proper tank mix and pressure not to exceed 40 psi to 

reduce Enlist DuoTM Herbicide driftable fines.

b. Groundboom Application:

Use the minimum boom height based upon the nozzle manufacturer’s directions. Spray drift 

potential increases as boom height increases. Spray drift can be minimized if nozzle height is 

not greater than the maximum height specified by the nozzle manufacturer for the nozzle 

selected.
28

c. Wind Speed:

Do not apply at wind speeds greater than 15 mph.

d. Temperature and Humidity:

When making applications in low relative humidity, set up equipment to produce larger 

droplets to compensate for evaporation. Droplet evaporation is most severe when conditions 

are both hot and dry.

e. Temperature Inversions:

If applying at wind speeds less than 3 mph, the applicator must determine if: a) conditions of 

temperature inversion exists, or b) stable atmospheric conditions exist at or below nozzle 

height. Do not make applications into areas of temperature inversions or stable atmospheric 

conditions.

f. Application Restrictions

Do not aerially apply this product.

5. Protection of Sensitive Areas:

To ensure the protection of threatened or endangered species, residues of this product from 

spray drift must be below levels of concern for threatened and endangered species for any area 

adjacent to the application site that is not excluded as possible habitat for these organisms.

a. Buffer

You must maintain a 30-foot downwind buffer from any area that is not:

 Roads, paved or gravel surfaces.

 Planted agricultural fields.

 Agricultural fields that that have been prepared for planting.

 Areas covered by the footprint of a building, shade house, green house, silo, feed crib, or 

other man made structure with walls and or roof.

b. Wind Direction

To maintain the required downwind buffer zone:

 Measure wind direction prior to the start of any swath that is within 30 feet of a sensitive 

area.

 No application swath can be initiated in, or into an area that is within 30 feet of a sensitive 

area if the wind direction is towards the sensitive area.
29

6. Susceptible Plants:

Do not apply under circumstances where spray drift may occur to food, forage, or other 

plantings that might be damaged or crops thereof rendered unfit for sale, use or consumption. 

Avoid contact of herbicide with foliage, green stems, exposed non-woody roots of crops, 

desirable plants; including cotton and trees, because severe injury or destruction may result. 

Small amounts of spray drift that may not be visible may injure susceptible broadleaf plants. 

Before making an application, please refer to your state’s sensitive crop registry (if available) 

to identify any commercial specialty or certified organic crops that may be located nearby. 

Commercially grown tomatoes and other fruiting vegetables (EPA crop group 8), cucurbits 

(EPA crop group 9), and grapes are particularly sensitive to drift from this product. Do not 

apply when wind direction favors off-target movement onto these crops.

C. Registration Terms

EPA has determined that certain registration terms are needed to ensure that likely weed 

resistance as discussed in section IV can be adequately addressed. EPA believes that it is 

important to address likely weed resistance and not wait until confirmation of resistance has been 

found. EPA is basing the registration terms on a list of criteria, presented in the peer-reviewed 

publication, Norsworthy, et al., “Reducing the Risks of Herbicide Resistance: Best Management 

Practices and Recommendations,” Weed Science 2012 Special Issue: 31–62 (Norsworthy 

criteria).

1. Stewardship Program 

EPA has determined that the registration must contain a term that requires DAS to have a 

stewardship program for Enlist DuoTM. DAS has begun developing its program which it states 

is focused on educating and training retailers, farmers and applicators on the appropriate use of 

the EnlistTM technology. EPA has determined that the stewardship program must include the 

following measures (also to be included as terms on the registration) that would minimize the 

potential for off-target movement and avoid the development of weed resistance. 

a. Investigation

EPA has determined that the registration must contain a term that requires DAS or its 

representative to investigate reports of non-performance as reported by users following 

required “scouting” (in accordance with labeling requirements). When investigating these

reports, DAS or its representative would be required to conduct site visits. 

b. Reporting of the Incidence of Likely Herbicide Resistance

EPA has determined that the registration must contain a term that requires DAS to use the 

Norsworthy criteria for determining likely herbicide resistance and inform EPA if likely 

resistance has been identified. This information must be submitted to the Agency on a 

monthly basis.
30

c. Remediation

EPA has determined that the registration must contain a term that requires DAS to take 

immediate action to eradicate likely resistant weeds in the infested area as well as requiring 

DAS to collect material for further testing.

d. Annual Reporting of Herbicide Resistance to EPA

EPA has determined that the registration must contain a term that requires DAS to submit 

annual summary reports to EPA that include a summary of the number of instances of likely 

and confirmed weed resistance by weed species, crop, county and state. The annual reports 

must include summaries of the status of laboratory or greenhouse testing for resistance. The 

annual reports would also address the disposition of incidents of likely or confirmed 

resistance reported in previous years. These reports would not replace or supplement adverse 

effects reporting required under FIFRA 6(a)(2). 

e. Reporting of Likely Resistance to other Interested Parties

EPA has determined that the registration must contain a term that requires DAS to inform 

growers and other stakeholders of likely and confirmed resistance to Enlist DuoTM. The 

information will include details of weed species and crop. EPA understands that DAS already 

plans to provide this information though a devoted website. 

f. Reporting on the development of diagnostic tests

EPA has determined that the registration must contain a term that requires that DAS would 

inform EPA of DAS’s progress toward diagnostic testing for evaluating resistant weed 

species. 

g. Monitoring the use of Enlist DuoTM on EnlistTM Seed

EPA believes it is important to require DAS to monitor whether Enlist DuoTM is being used 

on the EnlistTM seed purchased from DAS. EPA has determined that the registration must 

contain a term that requires DAS to provide EPA with a protocol to survey whether Enlist 

DuoTM is being used on EnlistTM seed purchased from DAS and not the non-choline 2,4-D 

products that are not registered for these application windows. EPA expects that a protocol 

would be agreed upon quickly so that monitoring the use of Enlist DuoTM can begin shortly 

thereafter.

h. Training and Education

EPA has determined that the registration must contain a term that requires DAS to provide 

training on the use of Enlist DuoTM when it provides training on the EnlistTM Seed technology. 

The training would focus on proper use of the technology to avoid off-target movement as 

well as avoid weed resistance. 
31

2. EPA’s Continued Control over the Registration 

Because the issue of weed resistance is an extremely important issue to keep under control and 

can be very fast moving, EPA has determined that the registration must contain terms that

ensure that EPA retains control to easily and quickly modify or cancel the registration if 

necessary.

3. Geographic Limitation on Use of Enlist DuoTM

EPA has determined that Enlist DuoTM would be allowed to be sold and used only for those 

states for which an endangered species assessment has been completed and resulted in a “no 

effect” determination. Currently, the states of Illinois, Indiana, Iowa, Ohio, South Dakota, and 

Wisconsin have been found to comply with these criteria. Additional states may be added to 

the labeling if assessments for those states are completed and demonstrate that a “no effects” 

determination is appropriate.