Document ID: EPA-HQ-OPP-2007-0114-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-12-28T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

	Date:	October 3, 2007

	Subject:	Fluroxypyr.  PP#6E7168.  Section 3 Registration Request for
Uses on Pome Fruit and Millet.  Summary of Analytical Chemistry and
Residue Data.  

		

DP Barcode:	336178	Decision Number:	373266

PC Codes:	128959 & 128968	MRID No.:	47017101, 47017102

40 CFR 180.	535

Chemical Class:	Pyridinoxy acid

	From:	Donna S. Davis, Chemist

		Reregistration Branch 1

		Health Effects Division (7509P)

	Through:	Toiya Goodlow, Chemist

		Michael S. Metzger, Chief

		Reregistration Branch 1

		Health Effects Division (7509P)

To:		Shaja Brothers, Risk Assessor

		Barbara Madden, Minor Use Team Leader

		Daniel Rosenblatt, Chief

		Risk Integration, Minor Use, and Emergency Response Branch

		Registration Division (7505P)

This document was originally prepared under contract by Dynamac
Corporation (2275 Research Blvd, Suite 300; Rockville, MD 20850;
submitted 06/13/2007).  The document has been reviewed by the Health
Effects Division (HED) and revised to reflect current Office of
Pesticide Programs (OPP) policies.

Executive Summary

Fluroxypyr [((4-amino-3, 5-dichloro-6-fluoro-2-pyridinyl) oxy) acetic
acid] is a selective herbicide intended for postemergence control of
annual and perennial broadleaf weeds.

The end-use product (EP) for this action is StaraneTM Herbicide (EPA
Reg. No. 62719-286), an emulsifiable concentrate formulation of 26.2%
fluroxypyr 1-methylheptyl ester (fluroxypyr 1-MHE), which is 1.5 lb acid
equivalent (ae)/gal (18.2% ae).  StaraneTM Herbicide is presently
registered for uses on cereal grains [barley, corn (field and sweet),
oats, sorghum, and wheat], grasses (pasture and rangeland), and onions
(dry bulb).

The Interregional Research Project No. 4 (IR-4), on behalf of the
Agricultural Experiment Stations of GA, NC, SC, ND, SD, TN and/or WA, is
proposing to establish tolerances for residues of fluroxypyr to support
new uses on pome fruit and millet.  The proposed pome fruit use would be
as a single broadcast spray application directed to the soil at a
maximum rate of 0.5 lb ae/A per year with a 14-day preharvest interval
(PHI).  For millet grown for grain, forage, or hay, the proposed use is
for up to two broadcast postemergence applications at a total rate of
0.25 lb ae/A with a 7-day PHI for hay or silage.  IR-4 has submitted a
petition, PP#6E7168, for the establishment of permanent tolerances for
the combined residues of fluroxypyr 1-MHE and its metabolite fluroxypyr
in/on the following raw agricultural commodities:

Pome, fruit, group 11	0.02 ppm

Millet, grain	0.5 ppm

Millet, forage	12.0 ppm

Millet, hay	20.0 ppm

Millet, proso, grain	0.5 ppm

Millet, proso, straw	12.0 ppm

Millet, proso, forage	12.0 ppm

Millet, proso, hay	20.0 ppm

Millet, pearl, grain	0.5 ppm

Millet, pearl, forage	12.0 ppm

Millet, pearl, hay	20.0 ppm

Tolerances have been established for the combined residues of fluroxypyr
1-methylheptyl ester [1-methylheptyl
((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetate] and its
metabolite fluroxypyr
[((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic acid] under 40
CFR 180.535. The established tolerances for plant commodities range from
0.02 ppm (field corn grain, sweet corn K+CWHR, and sorghum grain) to 160
ppm (grass hay) [40 CFR 180.535(a)].  The established tolerances for
livestock commodities range from 0.1 ppm (fat, meat, and meat
byproducts) to 1.5 ppm (kidney).  

A pome fruit metabolism study is not available to support the proposed
use on pome fruit.  Wheat and onion metabolism studies for fluroxypyr
are available.  HED would typically required the conduct of metabolism
studies on three diverse crops to define the nature of the residue in
all plant commodities, or would require the conduct of a pome fruit
metabolism study to support the requested new use on pome fruit. 
However, because the requested use of fluroxypyr in/on pome fruit
involves application to the orchard floor and available confined
rotational crops studies demonstrate low residue uptake, HED concludes
that significant fruit residues are not likely.  A pome fruit metabolism
study reflecting application to the orchard floor is not likely to
provide additional information, and is not required at this time.  

Acceptable wheat and onion metabolism studies are available, and the
results can be translated to support the proposed use on millet.  The
wheat study has shown that the metabolism of fluroxypyr 1-MHE proceeds
through ester hydrolysis to form fluroxypyr, followed by conjugation
into various fluroxypyr-based moieties.  The residues of concern in
wheat are fluroxypyr 1-methylheptyl ester and its metabolite fluroxypyr,
free and conjugated, all expressed as fluroxypy.  Similar results and
metabolic profiles were obtained in the recently submitted onion
metabolism study.

The nature of the residue in livestock has been adequately defined based
on acceptable hen and goat metabolism studies.  The Agency has
determined that the residues of concern in livestock for tolerance
enforcement are fluroxypyr 1-MHE and its metabolite fluroxypyr, free and
conjugated, all expressed as fluroxypyr.

There are adequate residue analytical methods for tolerance enforcement
and data collection.  The gas chromatography/mass selective detector
(GC/MSD) Methods GRM 96.02 and 96.03 are the current enforcement methods
for residues of fluroxypyr in/on cereal grain and ruminant commodities,
respectively.  The methods convert the methylheptyl ester form of
fluroxypyr to the acid, and results are reported as the acid equivalent.
 Method GRM 96.02, with minor modifications, was used for the analysis
of samples from the submitted field trial and processing study
associated with this Summary Document.  The concurrent method recoveries
demonstrated that the method is adequate for data-collection.  The
lowest level of method validation (LLMV) for fluroxypyr and fluroxypyr
1-MHE was 0.010 ppm in pear and apple fruit, apple wet pomace and apple
juice.  Fluroxypyr has been tested through FDA multiresidue methods,
Protocols C through E.  

There are adequate storage stability data to support the durations and
conditions of storage for the samples collected from the pome fruit
field trials and apple processing study.  Residues of fluroxypyr and
fluroxypyr 1-MHE were found to be stable in/on fortified apple fruit,
wet pomace and juice stored frozen for up to ~5 months, and in/on
fortified pear samples stored frozen for up to ~11 months.

  

The submitted residue data for apples and pears, the representative
commodities of the pome fruit crop group (crop group 11), are adequate
to fulfill data requirements.  The number and locations of crop field
trials are in accordance with OPPTS Guideline 860.1500.  The trials
reflect the proposed use pattern.

The available data for barley, oat, and wheat may be translated to
support the proposed use of fluroxypyr on millet provided the label
specifies a PHI of 14-days for hay and a PHI of 40-days for millet grain
and straw.

The submitted apple processing study is considered adequate to support
the proposed use.  While whole fruit samples treated at 1X the proposed
use pattern did not contain residues above the method LLMV, given that
this is a use to the orchard floor and confined rotational crop studies
do not show significant uptake of residues, it is unlikely that residues
will be detectable in whole fruit even from an exaggerated rate study. 
The submitted study is adequate to demonstrate that residues in wet
apple pomace and apple juice are not likely to exceed the established
tolerance for the apple RAC.  

The proposed new uses on pome fruit and millet are not expected to
significantly increase livestock dietary burdens given the currently
established uses and tolerances.  The existing livestock tolerances are
adequate to support the proposed new uses.  

Adequate rotation crop data are available to support the proposed new
uses on pome fruit and millet.  

Reference standards are available for fluroxypyr at the EPA National
Pesticide Standards Repository.  HED notes that this standard has an
expiration date of 7/2007.  HED recommends that the registrant for this
chemical provide a new standard or should recertify the lot in the
repository and send in an updated certificate of analysis (COA).

There are no Codex, Canadian or Mexican MRLs for fluroxypyr for pome
fruit or millet; therefore, there are no issues of international
harmonization raised by this action.

  SEQ CHAPTER \h \r 1 Regulatory Recommendations and Residue Chemistry
Deficiencies

Provided the deficiencies cited below are resolved, and further,
provided the forthcoming human health risk assessment does not identify
any risks of concern, there are no residue chemistry issues that would
preclude the establishment of the requested tolerances for the uses of
fluroxypyr on pome fruit and millet. 

The submitted and/or translated data support the following tolerances
for the combined residues of fluroxypyr 1-methylheptyl ester
[1-methylheptyl ((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetate]
and its metabolite fluroxypyr
[((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic acid] of
fluroxypyr in/on the following raw agricultural commodities:  

Fruit, pome, group 11	0.02 ppm

Millet, grain	0.5 ppm

Millet, forage	12.0 ppm

Millet, hay	20.0 ppm

Millet, proso, straw	12.0 ppm

Deficiencies

The use instructions for millet should be revised to reflect a PHI of
14-days for millet hay and a PHI of 40-days for grain and straw of
millet.

The petitioner should submit a revised Section F to reflect the revised
commodity definition presented in Table 9 on page 17 of this review.

Background

The chemical structure and nomenclature of fluroxypyr 1-MHE and
fluroxypyr (free acid) are presented in Table 1.  The physicochemical
properties of the technical grade of fluroxypyr 1-MHE are presented in
Table 2.

TABLE 1.	Fluroxypyr 1-MHE Nomenclature.

Compound	

Common name	Fluroxypyr 1-methylheptyl ester

Company experimental name	XRM-5316

IUPAC name
1-methylheptyl-4-amino-3,5-dichloro-6-fluoro-2-pyridyloxyacetate

CAS name	[(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy]acetic acid,
1-methylheptyl ester

CAS #	81406-37-3

End-use product/EP	1.5 lb ae/gal EC formulation (StaraneTM Herbicide;
EPA Reg. No. 62719-286) 

Fluroxypyr, free acid	

Common Name	Fluroxypyr

CAS name	[(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy]acetic acid

CAS #	69377-81-7

TABLE 2.	Physicochemical Properties of the Fluroxypyr 1-MHE.

Parameter	Value	Reference

Melting point/range	57.5°C 	44080303

pH	6.81 in solution containing 90.1 µg/L	44080303

Density	1.30 g/mL at 21°C	44080303

Water solubility ( 20 °C)	90.1 µg/L in purified water

294 µg/L in pH 5 buffer

136 µg/L in pH 7 buffer

57.2 g/L in pH 9 buffer	44080303

Solvent solubility (20 °C)	6.23 g/100 mL in n-heptane

>200 g/100 mL in xylene

377 g/100 mL in methanol

22.0 g/100 mL in n-octanol

>300 g/100 mL in acetone	44080303

Vapour pressure	2.0 x 10-5 kPa at 25 °C

1.0 x  10-5 kPa at 20 °C	44080303

Dissociation constant	Not applicable

	Octanol/water partition coefficient Log(KOW)	4.57 at pH 5

5.04 at pH 7

5.31 at pH 9	44080303

UV/visible absorption spectrum	Not available

	

860.1200  Directions for Use

The end-use product for this action is StaraneTM Herbicide (EPA Reg. No.
62719-286), an emulsifiable concentrate formulation of 26.2% fluroxypyr
1-methylheptyl ester (fluroxypyr 1-MHE), which is 1.5 lb acid equivalent
(ae)/gal (18.2% ae).  The proposed uses on pome fruit and millet are
detailed in Table 3.  

Table 3.  Summary of Directions for Use of Fluroxypyr 1-MHE.

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

(lb ae/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ae/A)	PHI

(days)	Use Directions and Limitations

Millet Grown for Grain, Forage or Hay

Postemergence, Broadcast,

Ground and aerial	1.5 lb ae/gal EC 

[62719-286]	0.125	2	0.25	7 (grass for hay or silage)	Apply to millet in
the spring; new plantings of millet may be treated from the 2 true leaf
stage prior to the early boot stage.  A second application may be made
with a minimum 14-day RTI.  Do not apply during boot, flowering, or seed
development if grass crop is to be harvested for seed.  No grazing
restrictions are imposed for lactating or non-lactating dairy animals,
but meat animals must be withdrawn from treated forage at least 2 days
before slaughter.

Pome Fruit 

Postemergence,

Broadcast,

Ground	1.5 lb ae/gal EC 

[62719-286]	0.5	1	0.5	14	Apply uniformly with ground equipment in 10
GPA, avoiding contact with foliage.  Do not apply to trees <4 years old
or during bloom.

ximum seasonal rate of 1⅓ pints product/A (equivalent to 0.25 lb
ae/A); and that if replanting is required, only crops listed on the
label (or approved supplemental labels) may be planted within 120 days
following application.  StaraneTM may be applied in tank mix combination
with other products provided (i) the tank mix product is labeled for the
timing and method of application for the use site to be treated; and
(ii) tank mixing is not prohibited by the label of the tank mix product.
 Use of an adjuvant labeled for the growing crops is recommended for
improved weed control.

Conclusions:  The supplemental label for StaraneTM Herbicide (EPA Reg.
No. 62719-286) is adequate to allow evaluation of the residue data
relative to the proposed use.  The available data for barley, oat, and
wheat were translated to support the proposed use of fluroxypyr on
millet provided the final label is revised to specify a PHI of 14-days
for hay and a PHI of 40-days for grain and straw of millet.

860.1300 Nature of the Residue - Plants

Waiver Request for the Conduct of Additional Metabolism Studies

Dow AgroSciences has a submitted an overview of fluroxypyr plant
metabolism data (MRID 47017103) to support a waiver request for the
conduct of additional metabolism studies.  The waiver request document
summarized the available data including two existing nature of the
residue studies (wheat and onion), two confined rotational crop studies,
and two independent university metabolism studies that were conducted on
broadleaf weed species.  The petitioner states that the available data
are sufficient to predict the residue profile in pome fruit and
demonstrate that there would be no significant uptake of any soil
metabolites which may add to that profile.

Based on the aggregate of data, the petitioner contends that the
metabolism of fluroxypyr 1-MHE in plants is similar in wheat, onions,
and broad-leaved weeds.  Metabolism involves cleavage of the ester to
the acid, followed by conjugation of the acid.  Cleavage of the ether
linkage to yield the pyridinol metabolite was insignificant. 
Furthermore, the primary route of uptake is through the plant cuticle,
and other forms of uptake (i.e., via the roots) are less significant. 
The petitioner presented the following metabolic pathway for fluroxypyr
MHE shown below and taken directly without alteration from MRID
47017103.

In addition to weed metabolites, pome fruit roots may also be exposed to
soil degradates of fluroxypyr.  An aerobic soil metabolism study
demonstrated that fluroxypyr MHE is rapidly hydrolyzed to the acid,
though not completely as some of the ester remained more than 5 months
after application.  Mineralization to CO2 was a significant route of
degradation in the soil.  Two soil metabolites were formed:  pyridinol
and methoxypyridine.  The confined rotational crop studies (30-day PBI
(plant back interval) with wheat, lettuce and turnips) demonstrated that
the two soil metabolites were present at ≤0.01 ppm fluroxypyr acid
equivalents in lettuce and turnip tops, and not present in wheat grain. 
Free or conjugated fluroxypyr acid was the most commonly observed
residue and fluroxypyr MHE was not detected at levels >0.01 ppm
fluroxypyr acid equivalents.

The proposed use of fluroxypyr in pome fruit orchards consists of
application to the weeds growing around the tree, not the tree foliage. 
Therefore the fruit are only exposed via the root system, which may be
exposed to fluroxypyr MHE, fluroxypyr acid, and low levels of the
pyridinol and methoxypyridine soil metabolites.  The confined rotational
crop study results (as discussed above) demonstrated that uptake of
fluroxypyr metabolites would be minimal and residue levels would be low
consisting mostly of fluroxypyr acid (free and conjugated).  The pome
fruit (apple and pear) field trial data indicate that little or no
(≤0.016 ppm) fluroxypyr is present in the fruit following treatment
with the fluroxypyr MHE formulation to the orchard floor at the proposed
application rate.

The petitioner cites that the European Union (EU) has decided to allow
use of fluroxypyr MHE on apples based on data that indicated that
residues are not significantly translocated within the plant and are
generally low in grain, with the bulk of the residue being either
fluroxypyr acid or its conjugate readily extractable with an alkali
methanol procedure.  The EU furthermore added that following hydrolysis
of the ester no other degradative step occurs, and that conjugation is
the route of detoxification in plants.

Conclusions:  The HED ChemSAC (see Minutes of the 1/17/2007 ChemSAC
Meeting) has determined that while OPP usually requires three metabolism
studies in diverse crops, a nature of the residue study on leafy crops
would not yet be needed in this case because fluroxypyr is applied to
the orchard floor and, therefore, significant residues are not expected,
as the confined rotational crop studies demonstrate.  ChemSAC concurred
that the available studies show a consistent metabolic profile, and that
an additional nature of the residue study would not provide significant
new information.  A nature of the residue study waiver was determined
appropriate for pome fruit only with the caveat that the application
rates for pome fruit are comparable to those used for the rotational
crop study.  The confined rotational crop study was conducted at 8.8 oz
ae/A (0.55 lb ae/A) which is consistent with the proposed seasonal rate
on pome fruit (0.5 lb ae/A).

860.1300 Nature of the Residue - Livestock

Residue Chemistry Memo DP# 285871, 8/20/03, M. Xue (PP#9F6050)

  SEQ CHAPTER \h \r 1 The nature of the residue in ruminants and poultry
has been adequately defined.  The residue of concern is fluroxypyr
1-methylheptyl ester and its metabolite fluroxypyr, free and conjugated,
all expressed as fluroxypyr (HED MARC, 4/21/98).

860.1340 Residue Analytical Methods

Enforcement methods:  The GC/MSD Methods GRM 96.02 and 96.03 are the
current enforcement methods for residues of fluroxypyr in/on cereal
grain and ruminant commodities, respectively.  In this method, residues
of fluroxypyr 1-MHE and fluroxypyr are extracted using acidic acetone,
and the extract is made basic with sodium hydroxide to hydrolyze any
fluroxypyr-MHE to the acid.  The extract is acid hydrolyzed at 90 ºC
for 2 hours and subjected to C18 solid phase extraction.  Fluroxypyr
residues are then derivatized with acidified 1-propanol, and the
1-propyl ester derivative is partitioned into isooctane containing
fluroxypyr 1-butyl ester (the internal standard) for GC/MSD analysis. 
Residues are reported as fluroxypyr acid equivalents.  The limits of
quantitation range from 0.01 to 0.08 ppm in plant commodities, and 0.01
ppm in animal commodities.

Data collection methods:  The GC/MSD enforcement method (GRM 96.02) for
cereal grains, with modifications, was used for the analysis of samples
from the submitted field trial and processing study associated with this
Summary Document.  Modifications made to the method were minor
(increased amounts of the extraction solvent and reactants).  The
concurrent method recoveries demonstrated that the method was adequate
for data-collection.  The lowest level of method validation (LLMV) for
fluroxypyr and fluroxypyr 1-MHE was 0.010 ppm in pear and apple fruit,
apple wet pomace and apple juice.  The limit of quantitation (LOQ) and
limit of detection (LOD) were also calculated/estimated for each matrix
based on recoveries of samples fortified separately at the LLMV.

Conclusions:  The GC/MSD method used for analysis of samples from the
apple and pear field trials and apple processing study is adequate for
data-collection based on acceptable concurrent method validation
recoveries.  The GC/MSD method is a modification of the established
enforcement method (GRM 96.02) for cereal grain commodities, and is
applicable as an enforcement method for the new uses proposed on pome
fruit and millet.

860.1360 Multiresidue Methods

HED Letter to L. Sawyer of FDA, 9/25/92, G.J. Herndon

Residue Chemistry Memo DP# 285871, 8/20/03, M. Xue (PP#9F6050)

Fluroxypyr was previously tested through FDA’s Multiresidue
Methodology, Protocols C, D, and E.  The results have been published in
the FDA Pesticide Analytical Manual, Volume I.

860.1380 Storage Stability

DER Reference:  47017101.de1.doc, D. Davis, 10/3/07

		47017101.de2.doc, D. Davis, 10/3/07

Residue Chemistry Memo DP# 285871, 8/20/03, M. Xue (PP#9F6050)

There are adequate storage stability data to support the storage
conditions and durations of samples collected from the pome fruit field
trials and apple processing study.  Concurrent storage stability studies
were conducted with each matrix over the study duration.  The results
indicate that residues of fluroxypyr and fluroxypyr 1-MHE are reasonably
stable in/on fortified apple fruit, wet pomace and juice stored frozen
for up to ~5 months, and in/on fortified pear samples stored frozen for
up to ~11 months.  

The storage durations and conditions of samples from the crop field
trials and processing study are presented in Table 4.

Table 4.		Summary of Storage Conditions and Durations of Samples from
Crop Field Trial and Processing Studies.

Matrix 	Storage

Temperature

(°C)	Maximum Storage Duration	Interval of Demonstrated Storage
Stability

Apples	-27 to -8	140 days (4.6 months)	4.7 months for fluroxypyr and
fluroxypyr 1-MHE in apples.

Apple, wet pomace	-27 to -8	104 days (3.4 months)	4.6 months for
fluroxypyr and fluroxypyr 1-MHE in apple wet pomace.

Apple, juice	-27 to -8	99 days (3.3 months)	4.9 months for fluroxypyr
and fluroxypyr 1-MHE in apple juice.

Pears	-21 ± 7	305 days (10.0 months)	10.7 months for fluroxypyr and
11.1 months for fluroxypyr 1-MHE in pears.

Conclusions:  There are adequate storage stability data to support the
sample storage conditions and durations of the apple and pear field
trials and apple processing study.

860.1480 Meat, Milk, Poultry, and Eggs

Residue Chemistry Memo DP# 285871, 8/20/03, M. Xue (PP#9F6050)

Livestock dietary burdens

The potential for secondary transfer of fluroxypyr residues of concern
in meat, milk, poultry, and eggs exists because there are livestock
feedstuffs associated with the proposed uses in the current petition. 
The livestock dietary burdens of fluroxypyr are presented in Table 5,
and reflect the most recent guidance from HED concerning revisions of
feedstuff percentages in OPPTS 860.1000 Table 1 and constructing
reasonably balanced livestock diets (RBDs).  The calculated dietary
burdens of fluroxypyr residues of concern are 3.8 ppm for beef cattle,
7.6 ppm for dairy cattle, 0.26 ppm for poultry, and 0.016 ppm for swine.



Table 5.    Calculation of Dietary Burdens of Fluroxypyr Residues of
Concern to Livestock.

Feedstuff	Type	% Dry Matter2	% Diet	Recommended Tolerance (ppm)	Dietary
Contribution (ppm)2

Beef Cattle    R: 15%; CC: 75-80 %;  PC: 5-10 %1

barley/millet/oat/wheat hay	R	85	15	20.0	3.53

corn, field, grain/ sorghum, grain, grain	CC	88	45	0.02	0.01

barley grain; wheat grain/milled bypdts	CC	188	30	0.5	0.17

grain, aspirated fractions	CC	85	5	0.6	0.04

untreated	PC	NA	5	NA	--

TOTAL BURDEN	--	--	100	NA	3.8

Dairy Cattle   R: 45%; CC: 45 %;  PC: 10%

barley/millet/oat/wheat hay	R	85	30	20.0	7.05

corn, field, forage	R	40	15	1.0	0.38

barley grain; wheat grain/milled bypdts	CC	88	30	0.5	0.17

corn, field, grain/ sorghum, grain, grain	CC	88	15	0.02	0.003

untreated	PC	NA	10	NA	--

TOTAL BURDEN	--	--	100	--	7.6

Poultry   CC: 75-80 %;  PC: 20-25%  (normally  no R, some exceptions)

corn, field, grain/milled bypdts; sorghum, grain, grain	CC	88	30	0.02
0.006

barley grain; wheat grain/milled bypdts	CC	88	50	0.5	0.25

Untreated	PC 	NA	20	NA	--

TOTAL BURDEN	--	--	100	--	0.26

Swine     CC: 80-85 %;  PC: 15-20%

corn, field, grain/milled bypdts; sorghum, grain, grain	CC	88	55	0.02
0.01

barley grain; wheat grain/milled bypdts	CC	85	30	0.5	0.15

Untreated	PC	NA	15	NA	--

TOTAL BURDEN	--	--	100	--	0.16

	1  R:  Roughage; CC:  Carbohydrate concentrate; PC:  Protein
concentrate.

	2  Contribution = ([tolerance /% DM] X % diet) for beef and dairy
cattle; contribution = ([tolerance] X % 	diet) for poultry and swine.

  SEQ CHAPTER \h \r 1 A cattle feeding study was submitted in
conjunction with PP#7G3541 (memo of 12/31/87, R. Loranger).  Cattle were
fed 20, 200, and 1000 ppm fluroxypyr in the daily diet for 28
consecutive days.  The results are shown below.

Table 6.  Maximum Fluroxypyr Residue Levels Found in Animal Commodities
At Different Feed Dose Levels.

Dose (ppm)	Muscle (ppm)	Fat (ppm)	Kidney (ppm)	Liver (ppm)	Milk (ppm)

0	<0.05	<0.05	<0.05	<0.05	<0.05

20	<0.05	<0.05	0.08	<0.05	<0.05

200	<0.05	0.07	0.63	0.08	0.15

1000	<0.05	0.14	2.12	0.10	0.49

  SEQ CHAPTER \h \r 1 Based on reasonably balanced dietary burdens
calculated above for cattle, residues of fluroxypyr would not be
expected to exceed the current tolerances of:  (i) 0.1 ppm in meat, fat,
and meat byproducts (except kidney); (ii) 0.3 ppm in milk, and (iii) 1.5
ppm in kidney.

A metabolism study on poultry at 10 ppm (>300x the RBDB of 0.026 ppm)
indicates that residues are not expected in poultry and eggs from the
proposed use on millet.  Therefore, no tolerances are needed for poultry
and eggs.

Conclusions:  The proposed use on millet and pome fruit are not expected
to significantly increase the dietary burdens.  There is an adequate
cattle feeding study to support the established fluroxypyr tolerances in
milk, meat, meat byproducts, fat, and kidney.  No tolerances are needed
for poultry and eggs.

860.1500 Crop Field Trials

Pome Fruit (Group 11)

DER Reference:  47017101.de1.doc, D. Davis, 10/3/07

IR-4 has submitted field trial data for fluroxypyr on apples and pears,
the representative commodities of the pome fruit crop group (Group 11). 
Twenty pome fruit field trials were conducted in the United States
during the 2001 growing season.  Thirteen apple trials were conducted in
Zones 1 (ME and NY; 2 trials), 2 (NJ and NC; 2 trials), 5 (MI; 3
trials), 9 (CO, 1 trial), 10 (CA; 1 trial) and 11 (ID and WA; 4 trials),
and seven pear trials were conducted in Zones 2 (NJ; 1 trial), 10 (CA; 3
trials) and 11 (ID and WA, 3 trials).

The test formulation used was StaraneTM Herbicide (EPA Reg. No.
62719-286), a 1.5 lb ae/gal emulsifiable concentrate formulation of
fluroxypyr 1-methylheptyl ester.  At each test location, a single
broadcast application of StaraneTM Herbicide was made to the orchard
floor at a nominal rate of 0.50 lb ae/A (1x the maximum proposed
seasonal rate).  Application was made during the tree’s fruiting stage
using ground equipment, without an adjuvant.  Mature apples or pears
were harvested 13-15 days after application.

The collected pome fruit samples were analyzed for fluroxypyr using
GC/MSD method GRM 96.02.  The method converts the methylheptyl ester
form of fluroxypyr to the acid, and the results are reported as the acid
equivalent.  The lowest level of method validation for fluroxypyr and
fluroxypyr 1-MHE was 0.01 ppm in apples and pears.  The adequacy of the
method for data collection was verified by fortifying untreated samples
of apples and pears with fluroxypyr and fluroxypyr-MHE at 0.01, 0.02,
and 0.1 ppm.  Method recoveries were well within the acceptable range of
70-120% from all fortified samples.  It is noted that Method GRM 96.02
is the current enforcement method for fluroxypyr residues in plants.

The maximum storage durations of crop samples, from harvest to analysis,
were 140 days (4.6 months) for apples and 305 days (10.0 months) for
pears.  Sample storage conditions and durations are supported by an
adequate concurrent storage stability study on apples and pears.

A summary of residue data from the pome fruit field trials is presented
in Table 7.  Residues of fluroxypyr were below the LLMV (<0.01 ppm)
in/on all apple and pear samples, except for one pear sample which bore
quantifiable residues at 0.016 ppm, harvested 13-15 days following
treatment to the orchard floor at 0.478-0.525 lb ae/A.

Table 7.    Summary of Residue Data from Pome Fruit Field Trials with
Fluroxypyr.

Commodity	Total Applic. Rate

 (lb ae/A)	PHI (days)	Residue Levels  (ppm)

	No. of samples	Min.	Max.	HAFT1	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Proposed Use Pattern:   Maximum Seasonal Rate of 0.5 lb ae/A with a
14-day PHI.

Apple, fruit	0.478-0.525	13-15	26	<0.01	<0.01	<0.01	NA 2	NA	NA

Pear, fruit	0.483-0.505	13-14	14	<0.01	0.016	<0.013	0.01	0.01	0.002

1  HAFT = Highest Average Field Trial.

2  NA = not applicable.

Conclusions:  The submitted residue data for apples and pears, the
representative commodities of Pome Fruit (Crop Group 11), are adequate
to fulfill data requirements.  The number and locations of crop field
trials are in accordance with OPPTS Guideline 860.1500.  The trials
reflect the proposed use pattern.  The available field trial data will
support the proposed tolerance for the residues of fluroxypyr in/on pome
fruit at 0.02 ppm.

Millet

Residue Chemistry Memo DP#s 174075 & 174388, 9/29/92, G.J. Herndon
(PP#2G4066)

No residue data were submitted to support the proposed RAC tolerances
for millet.  IR-4 has requested that the available residue data for
barley, oats, and wheat be translated to millet.  Fluroxypyr tolerances
are currently established for the grain (0.5 ppm), forage (12.0 ppm),
and hay (20.0 ppm) of barley, oat, and wheat.  Residue data used for
tolerance establishment were reviewed in PP#2G4066 (DP#s 174075 &
174388, 9/29/92, G.J. Herndon).

The Agency typically allows translation of residue data among members of
the same crop group with identical use pattern.  The proposed use
pattern on millet (see Table 3) specifies a maximum seasonal rate of
0.25 lb ae/A with a PHI of 7 days for hay or silage.  The registered
uses of barley, oats, and wheat specify a maximum seasonal rate of 0.25
lb ae/A with PHIs of 14 days for hay and 40 days for grain and straw.

Conclusions:  The available data for barley, oat, and wheat may be
translated to support the proposed use of fluroxypyr on millet pending
label revision to specify PHIs of 14 days for hay and 40 days for grain
and straw.

860.1520 Processed Food and Feed

Apple

DER Reference:  47017101.de2.doc

IR-4   SEQ CHAPTER \h \r 1 has submitted a processing study for
fluroxypyr on apples.  Samples used for processing were generated from a
trial conducted in WA during the 2001 growing season.  Apples were
harvested 14 days following a single broadcast spray application of
StaraneTM Herbicide (EPA Reg. No. 62719-286), a 1.5 lb ae/gal
emulsifiable concentrate formulation of fluroxypyr 1-methylheptyl ester
at 0.512 lb ae/A (~1x the nominal field trial rate).  The collected
apple samples were processed into wet pomace and juice using simulated
commercial practices.

Samples of apples and its processed commodities were analyzed for
fluroxypyr using GC/MSD method GRM 96.02.  The LLMV for fluroxypyr and
fluroxypyr 1-MHE was 0.01 ppm in apple matrices.

The maximum storage durations of crop samples, from harvest/processing
to analysis, were 108 days (3.6 months) for apples (RAC) and 99-104 days
(~3 months) for processed apple wet pomace and juice.  Storage
conditions and durations are supported by an adequate concurrent storage
stability study on apples, wet pomace and, juice.

Residues of fluroxypyr were below the LLMV (<0.01 ppm) in both the
treated RAC and the processed fractions (wet pomace and juice);
therefore, processing factors for fluroxypyr in apples could not be
calculated.  The maximum theoretical concentration factor for apple is
>14x (OPPTS 860.1520, Table 1, experimental factor).

Conclusions:  The submitted apple processing study is considered
adequate to support the proposed use.  While whole fruit samples treated
at 1X the proposed use pattern did not contain residues above the method
LLMV, given that this is a use to the orchard floor and confined
rotational crop studies do not show significant uptake of residues, it
is unlikely that residues will be detectable in whole fruit even from an
exaggerated rate study.  The submitted study is adequate to demonstrate
that residues in wet apple pomace and apple juice are not likely to
exceed the established tolerance for the apple RAC.  

  SEQ CHAPTER \h \r 1 860.1650 Submittal of Analytical Reference
Standards

Analytical standards for fluroxypyr 1-MHE and its metabolite fluroxypyr
are currently available in the EPA National Pesticide Standards
Repository (personal communication with Diane Raines, ACB, 5/25/07). 
However, the standard for fluroxypyr expired 7/2007.  In addition,
standards for fluroxypyr 1-propyl ester and 1-butyl ester are not
available at the repository; these standards, used for quantiation as
the derivative and internal standard, were requested by the Analytical
Chemistry Branch in conjunction with the method PMV results (DP# 253504,
2/25/99, W. Donovan).

The registrant must either recertify the lot in the repository for the
fluroxypyr standard and send in an updated certificate of analysis
(COA), or submit a new standard (different lot #) if the previous lot
will not be recertified.  If a new COA is being submitted, it should be
faxed to the repository at 410-305-2999.

Analytical reference standards of fluroxypyr 1-propyl ester and 1-butyl
ester must be supplied and supplies replenished as requested by the
Repository.  The reference standards should be sent to the Analytical
Chemistry Lab, which is located at Fort Meade, to the attention of
either Theresa Cole or Frederic Siegelman at the following address:

	USEPA

	National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

	701 Mapes Road

	Fort George G. Meade, MD  20755-5350

(Note that the mail will be returned if the extended zip code is not
used.)

860.1850 Confined Accumulation in Rotational Crops

Residue Chemistry Memo DP# 245073, 4/9/98, W. Donovan

Residue Chemistry Memo DP# 285871, 8/20/03, M. Xue (PP#9F6050)

A previously submitted confined rotational crop study (MRID 44080350)
was considered in conjunction with the field corn, sweet corn, sorghum
and grasses petition (PP#9F6050).  The study was conducted at 8.8 oz
ae/A (0.55 lb ae/A; 2.2x the maximum seasonal rate for crops which may
be rotated), and rotational crops wheat, lettuce, and turnips were
planted in the treated soil 30, 120 and 365 days after treatment; corn
was also planted at the 365-day plantback interval.  Fluroxypyr was the
free residue most frequently observed in the 30-day samples.  No free
metabolites were detected above 0.01 ppm in the rotated crop matrices by
the 120-day PBI.  Other metabolites detected were the methoxypyridine
and pyridinol at <0.01 ppm fluroxypyr acid equivalents and two unknowns
present as major residues in 30-day samples were determined conjugates
of fluroxypyr.  The HED MARC has determined that the residue of concern
in rotated crops is fluroxypyr 1-MHE and its metabolite fluroxypyr, free
and conjugated, all expressed as fluroxypyr (DP# 277058, 5/19/98, W.
Donovan).

860.1900 Field Accumulation in Rotational Crops

Field accumulation data for rotational crops are not required based on
the results of confined rotational crop studies.  The new uses proposed
for millet (a rotatable crop) are at the same maximum seasonal rate as
uses established for barley, oats and wheat; therefore there is no
change in the previous decision not to require limited field data for
rotational crops.

The most recently approved master label for StaraneTM Herbicide (EPA
Reg. No. 62719-286; dated 5/28/03) specifies that only crops listed on
the label (or approved supplemental labels) may be planted within 120
days following application.

860.1550 Proposed Tolerances

In PP#6E7168, the proposed tolerance expression is in terms of the
combined residues of the herbicide fluroxypyr 1-methylheptyl ester
[1-methylheptyl ((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetate]
and its metabolite fluroxypyr
[((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic acid].  The
proposed tolerance expression is consistent with the fluroxypyr
tolerances established in 40 CFR §180.535.

The tolerance spreadsheet in the Agency’s Guidance for Setting
Pesticide Tolerances Based on Field Trial Data was not utilized for
determining an appropriate tolerance level for the RACs of pome fruit
because a large number (>25%) of treated samples bore residues below the
LOQ.

Adequate field trial data are available for pome fruit.  The apple and
pear data support the proposed tolerance for pome fruit.

No field trial data were submitted for millet.  The available data for
barley, oat, and wheat may be translated to support the proposed use of
fluroxypyr on millet pending label revision to specify PHIs of 14 days
for hay and 40 days for grain and straw.

Pending submission of a revised Section B, the available barley, oat and
wheat data may be translated to millet and will support the proposed
tolerances for millet, proso millet, and pearl millet.

A summary of the recommended tolerances for the crop commodities
discussed in this Summary Document is presented in Table 9.  The
petitioner should submit a revised Section F reflecting the recommended
tolerances and commodity definitions presented in Table 9, below.



Table 9. 	Tolerance Summary for Fluroxypyr.

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Comments;
Correct Commodity Definition1

Pome, fruit, group 11	0.02	0.02	Fruit, pome, group 11

Millet, grain	0.5	0.5

	Millet, forage	12.0	12.0

	Millet, hay	20.0	20.0

	Millet, proso, grain	0.5

This use is covered by the millet grain tolerance.  A separate tolerance
for proso millet grain is not required

Millet, proso, straw	12.0	12.0

	Millet, proso, forage	12.0

This use is covered by the millet forage tolerance.  A separate
tolerance for proso millet forage is not required.

Millet, proso, hay	20.0

This use is covered by the millet hay tolerance.  A separate tolerance
for proso millet hay is not required.

Millet, pearl, grain	0.5

This use is covered by the millet grain tolerance.  A separate tolerance
for pearl millet grain is not required.

Millet, pearl, forage	12.0

This use is covered by the millet forage tolerance.  A separate
tolerance for pearl millet forage is not required.

Millet, pearl, hay	20.0

This use is covered by the millet hay tolerance.  A separate tolerance
for pearl millet hay is not required.

1Recommendations on tolerance definitions/need for tolerances from email
communication from Bernard Schneider on 6/25/07.

References

DP#:		174075 and 174388

Subject:	PP#2G4066.  Temporary Tolerance Petition and Experimental Use
Permit for Use of Fluroxypyr (Methylhepty Ester) on Barley, Oats, and
Wheat; 062719-EUP-RI.  Evaluation of Analytical Method and Residue Data.
CBTS#:  9300, 9620

From:		G.J. Herndon

To:		J. Miller/D. Kenny and A. Kocialski

Dated:		09/29/92

MRIDs:	42164503-06 and 42137344-55

DP#:		191904

Subject:	PP#2G4066.  Temporary Tolerance Petition and Experimental Use
Permit for Use of Fluroxypyr (Methylhepty Ester) on Barley, Oats, and
Wheat; 062719-EUP-RI.  Amendment of 4/19/93 Addressing Deficiencies in
the Goat Metabolism Study.  CBTS# 11961

From:		G.J. Herndon

To:		J. Miller/D. Kenny and A. Kocialski

Dated:		10/06/93

MRIDs:	42739301

DP#:		245073

Subject:	Fluroxypyr 1-methylhepty ester.  Issues to be Presented to the
HED Metabolism Assessment Review Committee.  Chemicals 128968 and
128959.  

From:		W. Donovan

To:		HED Metabolism Assessment Review Committee Members

Dated:		04/09/98

MRIDs:	None

DP#:		277058

Subject:	Fluroxypyr 1-methylhepty ester.  Chemicals 128968 and 128959. 
Results of the Metabolism Assessment Review Committee Meeting Held
21-APR-1998.

From:		W. Donovan

To:		G. Kramer and Metabolism Assessment Review Committee

Dated:		05/19/98

MRIDs:	None

DP#:		331225

Subject:	Fluroxypyr.  Petition for Tolerance to Support Use on Dry Bulb
Onions, Including Garlic and Shallots.  Summary of Analytical Chemistry
and Residue Data.  Petition Number:  3E6775.

From:		D. Davis

To:		M. Clock-Rust/B. Madden

Dated:		08/02/06

MRIDs:	46109601

  SEQ CHAPTER \h \r 1 Attachment:  

International Residue Limit Status sheet



INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 

((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy) acetic acid	Common
Name:

Fluroxypyr

	X Proposed tolerance

( Reevaluated tolerance

( Other	Date:  5/23/07

Codex Status (Maximum Residue Limits)	U. S. Tolerances

X No Codex proposal step 6 or above

( No Codex proposal step 6 or above for the crops requested	Petition
Number:  PP#6E7168

DP#:  336178

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 Decision #373266 

Residue definition (step 8/CXL): N/A	Reviewer/Branch:  P. Deschamp/RAB3

	Residue definition:  Residues of fluroxypyr 1-methylheptyl ester
[1-methylheptyl ((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetate]
and its metabolite fluroxypyr
[((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic acid], free and
conjugated, all expressed as fluroxypyr

Crop (s)	MRL (mg/kg)	Crop(s) 	Tolerance (ppm)

Pome, fruit, group 11	0.02

Millet, grain	0.5

Millet, forage	12.0

Millet, hay	20.0

Millet, proso, grain	0.5

Millet, proso, straw	12.0

Millet, proso, forage	12.0

Millet, proso, hay	20.0

Millet, pearl, grain	0.5

Millet, pearl, forage	12.0

Millet, pearl, hay	20.0

Limits for Canada	Limits for Mexico

X No Limits

⁯No Limits for the crops requested	X No Limits

⁯No Limits for the crops requested

Residue definition:  N/A

 h$ 

.2

	Notes/Special Instructions:  S.Funk, 05/24/2007

Page   PAGE  1  of   NUMPAGES  19 

Fluroxypyr                                 Summary of Analytical
Chemistry and Residue Data	DP# 336178