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Summary

This document announces that the U.S. Environmental Protection Agency (EPA) is proposing to 

grant a conditional registration under section 3(c)(7)(c) of the Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) for the new active ingredient, halauxifen-methyl (methyl 4-amino-3-

chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylate).

Halauxifen-methyl, an herbicide, is formulated as one technical product and two end-use 

products (GF-2685 and GF2686, the latter also referred to as QuelexTM). The product QuelexTM 

contains 10.4% halauxifen-methyl and 10% florasulam. The product GF-2685 contains 10.4% 

halauxifen-methyl. The labels specify that halauxifen-methyl is to be applied as a post-emergent 

herbicide on actively growing wheat, barley and triticale. Single or split applications can be 

made per crop provided there is a 14-day interval between treatments. Halauxifen-methyl 

applications are limited to two times per crop per year. Halauxifen-methyl use is intended to 

control or suppress broadleaf weeds that have been shown to cause significant economic damage 

through yield losses, such as bedstraw, common chickweed, flixweed, henbit, volunteer flax, 

horseweed (marestail), lambs quarters and redroot pigweed, including biotypes having shown 

resistance to acetolactate synthase (ALS) enzyme and glyphosate herbicides.

Although halauxifen-methyl is a new active ingredient (a chemistry never before registered in 

the United States), florasulam, a co-formulated active ingredient in QuelexTM, is a currently 

registered active ingredient which includes uses on wheat, barley and triticale. Since no new 

exposures for florasulam are being considered with this registration action, no new assessments 

were performed for florasulam. Therefore, this document is intended to discuss the results of the 

Agency’s findings on the assessment of the proposed new active ingredient halauxifen-methyl 

and its use on wheat, barley, and triticale.

Background

On September 7, 2012, EPA received an application to register products containing the new 

active ingredient halauxifen-methyl (CAS Number 943831-98-9), an herbicide for use on wheat, 

barley, and triticale from Dow AgroSciences (DAS). The application also requested the 

establishment of permanent tolerances for residues resulting from these uses. DAS also 

submitted applications for simultaneous review to the Pest Management Regulatory Agency 

(PMRA) of Canada and the Australian Pesticides and Veterinary Medicines Authority 

(APVMA). The EPA, PMRA, and APVMA combined scientific and regulatory expertise to 

conduct a joint review. Each country's team of scientists peer-reviewed the primary reviews of 

their counterparts. While continuing to consult and coordinate, each country individually 

developed its own human health and ecological risk assessments in accordance with its Agency’s 

regulatory and scientific policies.

Halauxifen-methyl (also known as XDE-729 methyl) is a synthetic auxin (HRAC group O, 

WSSA Group 4) herbicide and the first member of the new arylpicolinate class of chemistry. 

Halauxifen-methyl readily undergoes rapid de-esterification to its corresponding free acid 

halauxifen-acid (also known as XDE-729 acid). Halauxifen-methyl, like other synthetic auxins, 

mimics the plant growth hormone auxin, resulting in the disruption of growth processes in 
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susceptible plants. The product GF 2686, QuelexTM, contains 10.4% halauxifen-methyl and 10% 

florasulam, giving the product two different modes of action (MOA). Florasulam is an ALS

inhibitor (HRAC group B, WSSA Group 2) of the triazolopyrimidine chemical class, which 

leads to the inhibition of DNA synthesis. The product GF-2685 will contain 10.4% halauxifenmethyl only. DAS submitted two additional end-use products which were later withdrawn, GF2687 and GF-2688. 

The proposed labels specify that halauxifen-methyl is to be applied as a post-emergent herbicide 

on actively growing wheat, barley and triticale at a maximum single application rate of 0.0091

pounds active ingredient per acre (lbs ai/acre). Single or split applications can be made provided 

there is a 14-day interval between treatments. Halauxifen-methyl applications may not exceed 

0.018 lbs ai/acre per year. The pre-harvest interval (PHI) is 60 days. The pre-grazing interval is 

7 days. Additionally, a 21-day interval must be observed prior to the cutting of hay. 

Evaluation of Risk to Human Health and the Environment

In evaluating a pesticide registration application, the EPA assesses a wide variety of exposure 

information (i.e., where and how the pesticide is used), environmental fate studies (i.e., how the 

chemical will move in the environment) and toxicity studies (i.e., effects on humans and other 

non-target organisms) to determine the likelihood of adverse effects (i.e., risk) from exposures 

associated with the proposed use of the product. Risk assessments are developed to evaluate the 

environmental fate of the compound as well as how it might affect a wide range of non-target 

organisms including humans, terrestrial and aquatic wildlife and plants. On the basis of these 

assessments, EPA evaluates and, as appropriate, approves language for each pesticide label to 

ensure the directions for use and safety measures are appropriate to mitigate any potential risk. 

The pesticide's label helps to communicate essential limitations and mitigations that are 

necessary for public safety. It is a violation of federal law to use a pesticide in a way that 

conflicts with the label.

Assessment of Risk to Human Health

EPA has evaluated the available toxicity data and considered its validity, completeness, and 

reliability as well as the relationship of the results of the studies to human risk. EPA has also 

considered available information concerning the variability of the sensitivities of major 

identifiable subgroups of consumers, including infants and children. The toxicology database for 

halauxifen-methyl is considered adequate and no additional data are required at this time. 

Toxicological Profile

Halauxifen-methyl rapidly metabolizes in the liver to XDE-729 acid. The parent targets the 

liver, while the acid metabolite causes kidney effects. Due to the distinct toxicities of the two 

compounds and the unique mode of action (MOA, activation of liver aryl hydrocarbon receptor, 

or AhR) for liver toxicity of halauxifen-methyl that was identified in mechanistic studies, risk 

from the two compounds was assessed separately using distinct endpoints. Based upon review 

of the database, there is no evidence of acute dietary toxicity, neurotoxicity, genotoxicity or 

immunotoxicity for either compound. Neither compound was acutely toxic (Category IV). Both 
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are mild eye irritants (Category III) but not dermal irritants or sensitizers. XDE-729 acid is 

classified as “not likely to be carcinogenic to humans.” Halauxifen-methyl is classified as “not 

likely to be carcinogenic to humans at doses that do not induce Cyp1a1 expression (a biomarker 

for AhR activation),” based on the premise that AhR activation and subsequent promotion of 

hepatocellular tumors, a well-known non-genotoxic mechanism of liver carcinogenesis, depend 

upon this molecular initiating event (MIE). Moreover, based on its rapid in vivo metabolism to 

XDE-729 acid, halauxifen-methyl is not expected to persist in the body; therefore, progression of 

liver toxicity (including carcinogenic potential) from sustained AhR activation is not expected. 

There is no evidence of increased prenatal susceptibility to either compound and no evidence of 

postnatal susceptibility to XDE-729 acid. Parental toxicity in the rat two-generation reproductive 

toxicity study was observed at the highest dose, but no offspring or reproductive toxicity was 

reported. Specific information on the studies received and the nature of the adverse effects 

caused by halauxifen-methyl and its metabolite, XDE-729 acid, as well as the no-observedadverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) from the 

toxicity studies, can be found at http://www.regulations.gov in document, “Halauxifen-methyl –

New Active Ingredient Human Health Risk Assessment for Proposed Uses on Cereal Grains 

(Barley, Wheat, and Triticale)” in docket ID number EPA-HQ-OPP-2012-0919.

Dietary Assessment

Dietary risk estimates for halauxifen-methyl and XDE-729 acid are well below EPA’s level of 

concern. Quantitative acute dietary exposure and risk assessments are performed for a food-use 

pesticide if a toxicological study has indicated the possibility of an effect of concern occurring as 

a result of a 1-day or single exposure. No such effects were identified in the toxicological studies 

for halauxifen-methyl or XDE-729 acid; therefore, quantitative acute dietary exposure 

assessments were unnecessary.

In conducting individual chronic dietary exposure assessments for these two compounds, EPA 

used the food consumption data collected between 2003 and 2008 for USDA’s National Health 

and Nutrition Survey/What We Eat in America. As to residue levels in food, EPA used tolerancelevel residues (the highest estimated residue level based on the proposed application rates) and 

conservative modeled drinking-water estimates, while also assuming that 100 percent of all 

wheat, barley and triticale acres are treated. No processing factors were used due to the lack of 

residue concentration in processed commodities. 

Even while using these highly conservative assumptions, EPA has concluded that chronic 

exposure to halauxifen-methyl from food and water will use < 1 % of the chronic population 

adjusted dose (cPAD) for all infants, the population group receiving the greatest exposure. In 

addition, EPA has concluded that chronic exposure to XDE-729 acid from drinking water will 

also use < 1 % of the cPAD for all infants. Therefore, the chronic dietary exposure and risk 

estimates do not exceed the Agency’s level of concern (> 100% of the cPAD). Additional details 

of this dietary assessment can be found at http://www.regulations.gov in document, “Halauxifenmethyl Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment 

for the Section 3 Registration Action on Barley, Wheat, and Triticale” in docket ID number 

EPA-HQ-OPP-2012-0919.
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Aggregate Risk Assessment

Assessment of aggregate risk takes into account the combined risk potential that results from 

dietary exposure through food and water, as well as any additive residential handler exposures. 

Since there are no residential uses for halauxifen-methyl being proposed at this time, the chronic 

aggregate risk reflects only exposure to potential residues in food and drinking water. Therefore, 

the aggregate chronic risk is equal to the chronic dietary risk, which is well below the EPA’s 

level of concern.

Handler and Post-application Exposure

Since no short- or intermediate-term dermal effects were identified, a quantitative dermal 

exposure assessment was not conducted. Occupational handler and post-application assessments 

for halauxifen-methyl are based on inhalation exposures only. Risk estimates based on shortand intermediate-term occupational (worker/applicator) inhalation exposure to halauxifen-methyl

for handlers (mixing, loading, and application) are not of concern with baseline attire and 

personal protective equipment (PPE) for ground applications and enclosed cockpits for aerial 

applications. Although a quantitative post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

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

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

scenarios. Based on the acute toxicity of halauxifen-methyl, the [156 subpart K] Worker 

Protection Statement interim restricted entry interval (REI) of 12 hours is adequate to protect 

agricultural workers from post-application exposures (i.e., entering areas that has been 

previously treated with halauxifen-methyl). Additional details of this occupational handler and 

post-application assessment can be found at http://www.regulations.gov in document, 

“Halauxifen-methyl. Occupational and Residential Exposure and Risk Assessment to Support 

the Registration of the New Active Ingredient on Wheat, Barley, and Triticale.” in docket ID 

number EPA-HQ-OPP-2012-0919.

Assessment of Ecological Risk 

Halauxifen-methyl, a methyl ester, undergoes rapid de-esterification to the corresponding free 

acid (halauxifen-acid; XDE-729 acid) and is considered moderately mobile. The primary 

mechanisms of transport of halauxifen-methyl away from the treated field will be spray drift, 

runoff, and leaching. The specific label language and requirements for the reduction of these 

transport pathways are further explained in the “Mitigation and Labeling Requirements” section 

of this document. Halauxifen-methyl and the XDE-729 acid are not considered volatile and, 

therefore, are not likely prone to vapor phase atmospheric transport. In the environment,

halauxifen-methyl is characterized as moderately persistent with adjusted half-lives ranging from 

9-42 days conservatively accounting for the discrepancy between laboratory and field-measured 

degradation and dissipation. 
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Based on the ecological toxicity data, halauxifen-methyl is not likely to result in direct risk to 

insects1, birds, reptiles, amphibians (terrestrial and aquatic phase), mammals, fish, aquatic 

invertebrates, or aquatic nonvascular plants as a result of the proposed use. However, risks to 

terrestrial, semi-aquatic and aquatic vascular plants were identified, as is expected with an 

herbicide that has been formulated to target vascular plants. For aerial and ground applications, 

the expected exposure results in risk quotients (RQ) that exceed the level of concern (LOC) for 

many non-target vascular plant species. Though the RQ values range widely based on the type of 

vascular plant being exposed, the Agency assumes the most conservative estimates when 

determining mitigation measures in order to protect the most sensitive species. Label 

requirements for keeping the applications on the target area will effectively reduce exposures to 

these non-target vascular plants. The specific label requirements are further explained in the 

“Mitigation and Labeling Requirements” section of this document. Information on the studies 

received and the nature of the adverse effects caused by halauxifen-methyl and its degradate, 

XDE-729 acid can be found at http://www.regulations.gov in document, “Ecological Risk 

Assessment for the New Herbicide Halauxifen-methyl” in docket ID number EPA-HQ-OPP2012-0919. 

Other chemicals belonging to the synthetic auxin class of chemistry are considered persistent and 

have been detected in compost as a result of the composting of agricultural material, including 

plant material and manure, which contain synthetic auxin residues. Several non-guideline 

studies were submitted by DAS to evaluate the risk of halauxifen-methyl in compost. These 

studies attempted to address the potential exposure of non-target plants to halauxifen-methyl in 

compost by evaluating the degradation kinetics of halauxifen-methyl in compost and conducting 

bioassay studies with compost 1) generated from halauxifen-methyl-treated plant material and 2) 

compost treated directly with halauxifen-methyl to represent no degradation. Upon review, these 

studies have been classified as “supplemental,” meaning that there is information that can be 

used to characterize the potential risk associated with compost; however, issues with the study 

methodology and conduct limited the Agency’s ability to rule out the potential of such risk. 

Though effects were observed in these studies, they could not be directly attributed to 

halauxifen-methyl. However, due to the current uncertainty regarding the potential presence of 

halauxifen-methyl in compost, label mitigation has been identified to effectively remove this 

exposure pathway by restricting the use of treated plant materials in compost. The specific label 

requirements are further explained in the “Mitigation and Labeling Requirements” section of this 

document. 

Benefits

Growers throughout the United States have experienced yield and economic losses due to weeds 

developing resistance to heavily used herbicides. The need for additional tools to manage these 

resistant weeds has become important as resistance to glyphosate, ALS inhibitors, and other 

herbicides has become a significant financial, production and pest management issue. Wheat 

 1 The full suite of pollinator studies was not submitted for this chemical in 2012. Current tier I toxicity data on adult 

bees is adequate for registration and shows no toxicological concern. Further, wheat, barley and triticale are windpollinated and not attractive to pollinators, therefore there is no expected added risk to pollinators. However, it is 

noted that EPA is moving towards the practice of requiring the full suite of pollinator data for all pesticide active 

ingredients in the future. Therefore EPA intends to require this data as a condition of registration.
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and barley are high-valued national agricultural commodities and are major U.S. exports. The 

2012 USDA Agriculture Census indicates approximately 85 million acres of wheat were 

harvested, valued at over 17 billion dollars. Weeds such as bedstraw, common chickweed, 

flixweed, henbit, volunteer flax, horseweed (marestail), lambs quarters and redroot pigweed can 

be difficult to control during the growing season, particularly those that have shown to develop 

resistance to ALS inhibitors. The availability of active ingredients of new chemistries 

(arylpicolinate group in this case) is generally considered beneficial because new chemistries 

broaden the spectrum of target pests that can be controlled. New chemicals can be helpful in 

pest-management and resistance-management programs as additional resources for weed control, 

especially where current treatments are less successful. The proposed registration for 

halauxifen-methyl includes herbicide resistance management labeling outlined in PRN 2001-5. 

For instance, the WSSA mode of action group is listed on the label as well as other statements 

which will help sustain the use of the herbicide. In addition, one of the formulations, Quelex, is 

itself a combination of pesticides that contains two different weed control chemicals. This is 

considered to be a component of a season-long control strategy by extension and crop advisors. 

The EPA expects halauxifen-methyl would provide an additional tool for growers to include in 

resistance-management programs, in order to control biotypes of weeds that have shown 

resistance to other common herbicides, such as glyphosate and ALS inhibitors. 

The toxicity profile for halauxifen-methyl identifies no risks of concern to human health from

occupational or dietary exposure, and may provide a better alternative to older chemistries that 

require higher levels of risk mitigation practices in order to reduce dietary and occupational 

exposures. For example, applicators and other pesticide handlers of halauxifen-methyl are safe 

with baseline PPE, compared to currently registered older chemistries whose labels may contain 

additional PPE. In addition, the time interval that must be observed before re-entering a treated 

field for various cultural activities, such as scouting for weeds, is much shorter than with some of 

the older chemistries being used today; the halauxifen-methyl labels require a 12-hour re-entry 

interval (REI). Additionally, growers will have more flexible crop rotation options with shorter 

plant-back restrictions compared to ALS inhibitors currently in the marketplace. For instance the 

plant-back interval for soybeans, corn and several other crops is 14 days. This provides growers 

with greater flexibility than many other alternative materials registered for wheat, such as the 

ALS class of chemicals which tend to have longer plant back terms. 

With respect to non-target risks, halauxifen-methyl has low toxicity for non-target wildlife, 

which may provide a better alternative to the comparable products being used on wheat, barley 

and triticale. Overall, EPA expects that there may be meaningful benefits for halauxifen-methyl 

for controlling difficult weeds in these crops and also in helping to reduce weed resistance.

Regulatory Rationale

The database submitted to support the assessments of human health risk and environmental fate 

and ecological risk is adequate to support the proposed uses and tolerances. There are no risk 

estimates of concern for human health. Halauxifen-methyl is not likely to result in direct risk to 

non-target terrestrial animals, including insects, birds, reptiles, terrestrial-phase amphibians, and 

mammals, nor to aquatic animals including amphibians, fish, invertebrates, and nonvascular 

plants. As expected of an herbicide, halauxifen-methyl may pose a risk to terrestrial and aquatic 
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vascular plants. Label language as outlined in the "Mitigation and Labeling Requirements" 

section below will reduce the risk to these organisms.

Mitigation and Labeling Requirements

Leaching/Run-off Potential 

Because of the potential for leaching of halauxifen-methyl and degradates, labels have language 

including surface and ground water advisories that stress the potential for runoff after treatment and 

descriptions of conditions that may promote leaching to groundwater.

“Groundwater Advisory: This chemical has properties and characteristics associated 

with chemicals detected in groundwater. The use of this chemical in areas where soils are 

permeable, particularly where the water table is shallow, may result in groundwater 

contamination.

Surface Water Advisory: This product has a potential for reaching surface water via 

runoff after application. A level, well-maintained vegetative buffer strip between areas to 

which this product is applied and surface water features such as ponds, streams, and 

springs, will reduce the potential loading of halauxifen-methyl from runoff water. Runoff 

of this product will be reduced by avoiding applications when rainfall or irrigation is 

expected to occur within 48 hours.”

Potential for Contamination of Compost

With the current uncertainty that exists regarding the potential for adverse effects to nontarget plants exposed to compost containing residues of halauxifen-methyl, the EPA

proposed the following label restriction until additional compost studies are provided that can 

allow the Agency to definitively rule out this uncertainty:

“Do not compost any plant material from the treated area.”

The inclusion of this language on the label is intended to prevent potential contamination of 

compost by restricting the use of plant material treated with halauxifen-methyl to be used as 

a compost input. 

Potential for Off-site Transport via Spray Drift

In order to minimize the risks of spray drift, language is included on the label that is intended 

to reduce off-site transport, thereby reducing the potential for exposure to non-target plants. 

This includes; minimum droplet size restrictions of coarse and above (VMD ≥ 340 microns 

according to ASABE S572.1), use of low-drift nozzles, application pressures less than 30 psi, 

maximum wind speed restriction of 15 mph during application, and extensive Spray Drift 

Management language. 
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Uncertainty in Potential Synergistic Effects related to Tank-mixes

A common agricultural practice involves tank mixing of pesticides, resulting in the cooccurrence of multiple chemical stressors to target pests. The practice of tank mixing can 

result in significant economic benefits to the grower by allowing control of a wider variety of 

pests in a single application without incurring the expense of sequential applications. 

Additionally, by reducing the number of visits to the agricultural field, the grower is also 

reducing fossil fuel use and emissions from large agricultural equipment, as well as the 

potential exposure to pesticides that can result from multiple visits to the same area being 

treated. It is also widely accepted that the practice of mixing products with different modes 

of action is essential to the management of weed resistance. Because weed resistance is 

known to have a very costly impact to overall crop yields, which in turn negatively impacts 

growers’ harvests and the price of commodities to the consumer, tools that aid in the 

prevention of resistance are considered to be a very important benefit to agriculture. 

Recently, in some cases, chemical companies have made claims that certain combined 

mixtures elicit enhanced activity or synergistic effects, meaning that when the chemicals 

interact, the overall effect is greater than the sum of the individual effects of each chemical. 

In EPA’s risk assessments for non-target plants, the Agency uses GLP guideline studies to 

determine potential toxicity to plants, involving endpoints such as biomass and reproductive 

health. EPA believes this approach is very reliable for these purposes. The proposed 

registration for halauxifen-methyl includes the EPA’s evaluation of vegetative vigor studies 

on the combination product, QuelexTM, containing both halauxifen-methyl and florasulam. 

These studies showed no synergistic toxicity to non-target plants, therefore EPA concluded 

that there is no synergy between halauxifen-methyl and florasulam. However, if there is 

evidence to suggest that there are potential synergistic effects with other combinations, EPA 

may require such data since the current database for the individual chemicals may not 

provide adequate information on the risk to non-target organisms from such combinations. 

At this time, the topic of synergy and multiple stressors is an uncertainty in assessing risk 

with tank-mix combinations. EPA must weigh this uncertainty against the benefits of 

applying tank mixes when considering a regulatory decision. Therefore, EPA is considering 

whether restrictions on tank-mixing are necessary to prevent unreasonable adverse effects, 

and is inviting comments on the issue of synergism and the potential for tank mix 

restrictions, which will be taken into further consideration for the final risk-benefit analysis 

of halauxifen-methyl.

International Harmonization

Maximum Residue Limits (MRLs) have not been established by Codex for halauxifen-methyl on 

the commodities affected by this action. 

Proposed Regulatory Decision

In cooperation with our regulatory partners in Australia and Canada, and considering the 

assessed risk to human health and the environment, the Agency concludes that halauxifen-methyl

meets the regulatory standard under FIFRA. The Agency is proposing that, in light of the 
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approaches described above, the risks, including to non-target plants, are not unreasonable when 

considered in conjunction with the benefits of no risks of concern to human health and the 

addition of a chemical class that can help to minimize herbicide resistance. New data 

requirements for pollinators are being required as a condition of registration for halauxifenmethyl. Therefore, the EPA is proposing to grant a conditional registration of halauxifen-methyl

under Section 3(c)(7)(c) of FIFRA. 

The Agency is proposing to register the following three products:

XDE-729 Methyl Technical

• 95.9% halauxifen-methyl

• Only for formulation into a herbicide for use on actively growing wheat, barley and 

triticale

GF-2685 

• 10.4% halauxifen-methyl

• Only for use on actively growing wheat, barley and triticale

GF-2686 (QuelexTM)

• 10.4% halauxifen-methyl

• 10.0% florasulam

• Only for use on actively growing wheat, barley and triticale