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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Maggie Rudick 703-347-0257; 

rudick.maggie@epa.gov

TEMPLATE:

Dow AgroSciences LLC

9330 Zionsville Road

Indianapolis, IN 46268-1054

2F8086

EPA has received a pesticide petition 2F8086 from Dow AgroSciences LLC, 

9330 Zionsville Road, Indianapolis, IN 46268 requesting, pursuant to section 408(d) of 

the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 

CFR part 180

1. by establishing a tolerance for residues of

the herbicide Halauxifen-methyl, including its metabolites and degradates, in or 

on the commodities listed below. Compliance with the tolerance levels specified is to be 

determined by measuring the combined residues of halauxifen-methyl (Methyl 4-amino3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylate) and halauxifen

(4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylic acid) 

expressed as halauxifen-methyl (parent) equivalents in or on the raw agricultural 

commodity barley, grain at 0.01 parts per million (ppm); barley, hay at 0.01 ppm; barley, 

straw at 0.01 ppm; cattle, fat at 0.01 ppm; cattle, meat at 0.01 ppm; cattle, meat 

byproducts at 0.01 ppm; goat, fat at 0.01 ppm; goat, meat at 0.01 ppm; goat, meat 

byproducts at 0.01 ppm; horse, fat at 0.01 ppm; horse, meat at 0.01 ppm; horse, meat 

byproducts at 0.01 ppm; milk at 0.01 ppm; sheep, fat at 0.01 ppm; sheep, meat at 0.01

ppm; sheep, meat byproducts at 0.01 ppm; wheat, forage at 0.5 ppm; wheat, grain at 0.01

ppm; wheat, hay at 0.04 ppm; wheat, straw at 0.015 ppm. EPA has determined that the 

petition contains data or information regarding the elements set forth in section 408 (d)(2) 

of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data 

at this time or whether the data supports granting of the petition. Additional data may be 

needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The nature of the residue in plants is adequately understood 
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for the purpose of establishing the proposed tolerances. Based on the findings from 

metabolism studies in wheat and turnips, the residue of concern in plants is the combined 

residue of halauxifen-methyl and halauxifen, expressed as halauxifen-methyl.

2. Analytical method. The residue profile of halauxifen-methyl and halauxifen is 

adequately understood and an acceptable analytical method is available for enforcement 

purposes. The DAS analytical method study number 110004 outlining the Method 

Validation for the Determination of Residues of Halauxifen-methyl Ester and Halauxifen

in Agricultural Commodities and Wheat Processed Products using Offline Solid-Phase 

Extraction and Liquid Chromatography with Mass Spectrometry Detection was validated 

on a variety of plant matrices. The method was validated over the concentration range of 

0.01-1.00 mg/kg with a limit of quantitation of 0.01 mg/kg.

3. Magnitude of residues. Good Agricultural Practices (GAP) for each crop have 

been harmonized as much as possible across countries. A significant number of 

supervised residue trials have been carried out at the critical GAP on wheat and barley in 

Australia, New Zealand, United States, and Canada to provide harmonized data for MRL 

setting. Data on oats was also generated in Australia, where it is a required representative 

crop. There were thirty-nine trials conducted on wheat, twenty-two trials conducted on 

barley, and four trials conducted on oats. Residues in food and feed commodities were 

rather homogeneous within each crop, and did not show significant statistical differences 

across geographies, varieties, or cultural practices. Therefore, it is adequate to propose 

and support harmonized MRLs.

Trials from NAFTA regions during the 2010 and 2011 growing seasons are summarized 

for the purpose of the US petition. For both barley and wheat, applications were made at 

the BBCH 39 growth stage at a target rate of 0.0089 lb a.e./A of applied halauxifenmethyl plus 0.0089 lb ai/A of the safener cloquintocet. The Limit of Detection (LOD) 

and Limit of Quantification (LOQ) values were validated for the analytical method as 

0.001 ppm and 0.003 ppm, respectively for each analyte in grain, straw, forage and hay. 

Observed residues support a suite of proposed US tolerances at the limit of quantitation 

(LOQ) for most commodities.

For barley, residues of halauxifen-methyl and halauxifen were determined following 1 

foliar application for 18 field locations. Grain and straw samples were collected at 

harvest, 43 to 83 days after treatment (DAT); hay was harvested 19 to 33 DAT and dried 

before collection. Residues of both halauxifen-methyl and halauxifen ranged from non 

detectable (< LOD) to <LOQ, in/on barley grain, barley straw harvested at normal 

commercial harvest (NCH) and barley hay harvested at 17-33 DAA.

For wheat, residues of halauxifen-methyl and halauxifen were determined following one 

foliar application for 27 field locations. Grain and straw samples were collected at 

harvest, 42 to 73 days after treatment (DAT); forage was collected 1 DAT and hay was 

harvested 17 to 31 DAT and dried before collection. For wheat grain, all residues were 

below the LOD. For wheat straw, all residues were below the LOQ. Residues of 

halauxifen-methyl and halauxifen ranged from 0.036 to 0.389 ppm and from below the 

LOD to <LOQ in wheat forage. For wheat hay, residues of halauxifen-methyl and 
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halauxifen ranged from below the LOD to 0.026 ppm and from below the LOD to <LOQ, 

respectively. Processed wheat commodities were also generated; results indicate that 

residues are not expected to concentrate above detectable levels in processed fractions 

derived from the processing of wheat grain. 

Because the proposed tolerances cover crops commonly used as feed for livestock, a 

proposal for animal commodity milk and meat tolerances at the LOQ of 0.01 ppm is 

included. The estimated animal burden was calculated based on NAFTA feeding diets in 

order to determine if these uses would result in detectable residues in meat and meat 

product commodities. The maximum dietary burden in ruminants estimated from 

proposed uses on potential feed crops was compared with the doses tested in the cattle 

feeding study conducted by Dow AgroSciences. All calculated residue levels in meat, 

meat products and milk were below the level of quantitation (LOQ). However, taking a 

conservative precautionary approach, Dow AgroSciences is proposing cow, sheep, goat 

and horse meat, meat products and milk tolerances at the LOQ (0.01 mg/kg).

B. Toxicological Profile A complete set of core toxicology studies were conducted on 

halauxifen and a bridging package of toxicology studies was conducted on halauxifenmethyl to demonstrate toxicological equivalence. This set of bridging toxicology studies 

conducted on halauxifen-methyl demonstrated that although having different NOAELs 

and target organs with high dose repeat exposure, halauxifen-methyl and halauxifen are 

toxicologically equivalent up to 10 mg/kg bw/day (mkd).

1. Acute toxicity. Halauxifen and halauxifen-methyl exhibited low acute oral and 

dermal toxicity with an LD50 >5000 mg/kg bw for all studies. An adequate test 

atmosphere was not able to be generated for halauxifen and halauxifen-methyl in the 

acute inhalation test; therefore, they were not conducted. Skin and eye irritation studies 

with halauxifen and halauxifen-methyl showed minimal irritation that cleared in 72 hours 

or less. Halauxifen and halauxifen-methyl were negative for sensitization potential.

2. Genotoxicty. Halauxifen and halauxifen-methyl were negative in a series of in 

vitro genotoxicity studies; halauxifen was also negative in an in vivo mouse micronucleus 

assay.

3. Reproductive and developmental toxicity. Halauxifen was assessed in a twogeneration reproduction study in rats and developmental studies in both rats and rabbits. 

There were no adverse, treatment-related effects on reproduction or development.

Halauxifen-methyl was assessed in developmental studies with both rats and rabbits. No 

treatment-related developmental toxicity was observed in rats. In the rabbit 

developmental study, there were no treatment-related fetal malformations in any group. 

The developmental NOAEL was based on a treatment-related decrease in fetal body 

weights and associated secondary effects at the high dose.

4. Subchronic toxicity. Sub-chronic dietary toxicity studies were conducted with 

halauxifen in rats, mice, and dogs. The primary target organs of halauxifen are the kidney
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in rats and dogs, and the urinary bladder in mice. No toxicity was observed at the limit 

dose with dermal administration in rats (NOEL > 1000 mkd) after 28 days.

Sub-chronic dietary toxicity studies were conducted with halauxifen-methyl in 

rats, with the primary target organ identified as the liver, with secondary effects observed 

in the thyroid and the thymus. The NOAEL in rats was 10 mkd (males) and 52 mkd 

(females) after 28 days and 10 mkd (males and females) after 90 days.]

5. Chronic toxicity. The NOAELs for the rat 2-year study and the mouse 18-

month study with halauxifen were based on kidney and urinary bladder effects. No 

tumors were observed in mouse and rat. Halauxifen-methyl is proposed as not likely to be 

carcinogenic to humans, based on the lack of evidence of carcinogenicity in rat and 

mouse studies with halauxifen, and the absence of a mutagenicity concern.

6. Animal metabolism. Halauxifen and halauxifen-methyl were rapidly and highly 

absorbed after oral administration in the rat and mouse. Halauxifen is poorly metabolized 

and readily eliminated in urine and feces. Data suggest rapid hydrolysis of halauxifenmethyl in vivo, and the systemic exposure is predominantly to the halauxifen. Minor 

metabolites of both test materials consisted of the acyl-glucuronide conjugate of 

halauxifen, demethylated halauxifen-methyl and halauxifen and their corresponding 

sulfate and glucuronide conjugates. Halauxifen and halauxifen-methyl do not accumulate 

in tissues.

7. Metabolite toxicology. The primary mammalian metabolite and main form of 

systemic exposure following dietary administration of halauxifen-methyl is halauxifen

and there is a complete set of toxicology studies demonstrating limited toxicity. Other 

mammalian metabolites observed include demethylated halauxifen-methyl and 

demethylated halauxifen and their sulfate and glucuronide conjugates following dietary

administration of halauxifen-methyl. The demethylated metabolites have been coinvestigated in the mammalian toxicology studies and both metabolites are considered to 

be of no toxicological significance. 

8. Endocrine disruption. A complete set of toxicology studies were conducted 

with halauxifen, and there was no evidence of any endocrine-related effects. Bridging 

toxicology studies with halauxifen-methyl demonstrated systemic exposure was to 

halauxifen and metabolites with negligible or no halauxifen-methyl found in blood, urine 

and fetuses. For this reason, the weight of evidence suggests halauxifen and halauxifenmethyl are not endocrine modulators.

C. Aggregate Exposure

1. Dietary exposure. A Dietary Assessment was conducted using the Dietary

Exposure Evaluation ModelTM (DEEM-FCID, ver. 3.14) software which contains food 

consumption data based on NHANES 2-day food Consumption data for 2003 to 2008 and 

food translation to RACs, as indicated by EPA/USDA FCID recipe set as of February

2012. This assessment evaluates potential risks due to chronic dietary exposures of the 
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U.S. population subgroups to residues of halauxifen-methyl. These analyses cover all 

proposed tolerances, including meat and milk.

i. Food. a). Acute exposure. No appropriate toxicological endpoint attributable to 

a single exposure was identified in the available toxicology studies on halauxifen-methyl 

and halauxifen. Since no acute toxicological endpoints are proposed, no acute assessment 

was performed.

b). The current chronic dietary assessment is an unrefined Tier I assessment using 

tolerance values and 100% crop-treated assumption to estimate dietary exposure. These 

results are conservative (health protective) risk estimates. Chronic assessments were 

conducted to evaluate potential risks due to chronic dietary exposure of the U.S 

population and sensitive subpopulations to residues of halauxifen-methyl against the 

proposed chronic reference dose (cRfD) of 0.1 mg/kg/day based on a NOAEL of 10 

mg/kg/day from the halauxifen-methyl 90-day rat toxicity study and an uncertainty factor 

of 100 (10X for intra-species variation and 10X for inter-species variation). The 

proposed FQPA Safety Factor (SF) = 1X; therefore, the proposed chronic population 

adjusted dose (cPAD) = cRfD.

ii. Drinking water. Because halauxifen-methyl is a new active ingredient there are 

no water-related data from monitoring to complete a quantitative drinking water exposure 

analysis and risk assessment. Screening level exposure levels to water were estimated 

from the Agency’s water models. The Index Drinking Water Reservoir (FIRST) was used 

to calculate estimated concentrations in surface waters. The screening concentration in 

ground water was estimated using the Screening Concentrations In Ground Water model 

(SCI-GROW). These models take into account the use patterns and the environmental 

profile of the pesticide, but do not include consideration of the impact that processing raw 

water for distribution as drinking water would likely have on the removal f pesticides 

from the source water. The primary use of these models is to provide a coarse screen for 

assessing whether a pesticide is likely to be present in drinking water at concentrations 

which would exceed human health levels of concern.

a). Acute exposure and risk. No acute dietary endpoint is proposed by Dow 

AgroSciences. Therefore, no acute assessment was conducted and it is proposed that 

there is a reasonable certainty of no harm from acute exposure from drinking water.

b). Chronic exposure and risk. Tier I screening level exposure assessments were 

conducted using SCI-GROW and FIRST. The models were run with input data for both 

halauxifen-methyl and halauxifen, as both theoretically could be found in the 

environment. The highest calculated water concentration was for halauxifen in surface 

water at 0.029 ppb. As a conservative approach, this water concentration was used in the 

DEEM-FCIDTM dietary risk assessment for all direct and indirect water sources. 

The Tier-I DEEM exposure for food and water with proposed tolerances resulted in an 

estimated exposure of 0.0001 mg/kg bw/day for the US general population which is 0.1% 

of the chronic RfD. For the most highly exposed population subgroup, children 1 to 2 
6

years old, the estimated exposure is 0. 0.0005 mg/kg/day at 0.5% of cPAD. These results 

are conservative (health protective) risk estimates. Refinements such as use of percent 

crop-treated information and/or anticipated residue values would yield lower estimates of 

chronic dietary exposure.

2. Non-dietary exposure. Halauxifen-methyl does not have any proposed 

residential non-food uses. Therefore, there is no non-dietary acute, chronic, short or 

intermediate-term exposure and the dietary assessment alone serves to cover the 

aggregate assessment. Dow AgroSciences concludes that residues of halauxifen-methyl 

and halauxifen in food and drinking water will not contribute significantly to human 

exposure and that the chronic aggregate exposure from halauxifen-methyl residues in 

food and drinking water will not exceed the proposed level of concern (100% of the 

chronic PAD) for any population subgroup. The Agency generally has no concern for 

exposures below 100% of the cPAD because the cPAD represents the level at or below 

which daily aggregate dietary exposure over a lifetime will not pose appreciable risks to 

human health.

D. Cumulative Effects

Section 408(b)(2)(D)(v) requires that, when considering whether to establish, 

modify, or revoke a tolerance, the Agency consider “available information” concerning 

the cumulative effects of a particular pesticide’s residues and “other substances that have 

a common mechanism of toxicity.” EPA does not have, at this time, available data to 

determine whether halauxifen-methyl has a common mechanism of toxicity with other 

substances or how to include this pesticide in a cumulative risk assessment. Unlike other 

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

mechanism of toxicity, halauxifen-methyl does not appear to produce a toxic metabolite 

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

assumed that halauxifen-methyl does not have a common mechanism of toxicity with 

other substances.

E. Safety Determination

1. U.S. population. The unrefined chronic dietary exposure for food and water 

(which covers the aggregate exposure) occupies up to 0.1% of the cRfD for the U.S. 

general population. EPA generally has no concern for exposures below 100% of the 

chronic cRfD, because the cRfD represents the level at or below which daily dietary

exposure over a lifetime will not pose appreciable risks to human health. Dow 

AgroSciences concludes that there is a reasonable certainty that no harm will result to the 

U.S. general population or any subpopulation from aggregate exposure to halauxifenmethyl residues.

2. Infants and children. The toxicology data available includes acceptable 

developmental studies in both rats and rabbits conducted using halauxifen-methyl and 

acceptable developmental studies (on rats and rabbits) and a two generation reproduction 

study using halauxifen. A complete toxicity database is available for to jointly support 
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halauxifen-methyl and halauxifen. Exposure estimates are highly conservative and 

protective and complete. Based on the completeness of the database and the lack of 

prenatal and postnatal toxicity, Dow AgroSciences proposes that an additional safety 

factor is not needed for the protection of infants and children (FQPA SF = 1X).

Since no acute toxicological endpoints are proposed by Dow AgroSciences, the acute 

aggregate risk is considered to be negligible. Using the exposure assumptions described 

above, Dow AgroSciences has concluded that chronic dietary exposure (food and water) 

to halauxifen-methyl from the proposed new tolerances will utilize 0.5% of the cPAD for 

infants and children. The Agency generally has no concern for exposures below 100% of 

the cPAD because the cPAD represents the level at or below which daily aggregate 

dietary exposure over a lifetime will not pose appreciable risks to human health. 

Based on these risk assessments, Dow AgroSciences concludes that there is a reasonable 

certainty that no harm will result to infants and children from aggregate exposure to 

halauxifen-methyl residues. The risk assessment is conservative in nature and results in a 

risk profile of halauxifen-methyl that is very protective of human health.

F. International Tolerances

There are no existing international MRLs in other countries at this time. The 

same tolerances values proposed in the USA have also been proposed as harmonized 

MRLs the countries that have generated data for the global residue package (Canada, 

Australia). In addition for Australia, MRLs are proposed for the small grain subgroup 

(grain at 0.01 ppm, straw at 0.015 ppm, forage, at 0.8 ppm and hay at 0.04 ppm). 

Specifically, the animal meat and milk tolerances are helpful for global harmonization 

with Australia’s MRL requirements for trade export.