UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDE

	AND TOXIC SUBSTANCES

	

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:  23 May 2008

SUBJECT:	Sethoxydim:  Petition Proposing Tolerances for Sethoxydim Use
in the Rapeseed Crop Subgroup.  

 

PC Code:  121001	DP Barcode: D342808  

MRID No.:  None	Registration No.: None

Petition No.: 7E7232	Regulatory Action: None

Assessment Type: None	Reregistration Case No.: None

TXR No.: None	CAS No.: 74051-80-2



	          	

FROM:	David Soderberg, Chemist

		RRB3, Health Effects division (7509P)  SEQ CHAPTER \h \r 1 

THROUGH:	William Donovan, Senior Chemist

		RRB3, Health Effects Division (7509P)

		

TO:		Barbara Madden, Risk Manager Reviewer

		Registration Division (7505P)  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r
1 

		

USDA’s IR-4 has submitted a petition to translate the existing
tolerance for sethoxydim on rapeseed (Canola) to all members of the
proposed rapeseed oilseed crop subgroup (20a) except Borage and Flax.  
These additional crops are:  Gold of Pleasure, Crambe, Cuphea, Echium,
Hare’s ear mustard, Lesquerella, Lunaria, Meadowfoam, Milkweed,
Mustard, Oil Radish, Poppy, Sesame, and Sweet Rocket.  The two other
crops in this crop subgroup, Borage and Flax, already have tolerances. 
The submitted petition does not include any new data.  

This memorandum provides the HED response to this submitted petition. 
HED has already agreed in principle to formation of this crop subgroup
(ChemSAC 21 February 2007), but the crop subgroup has not been formally
enacted into law yet.  Therefore, HED agrees that the translation can be
allowed, but to have the force of law, the translation will require
individual tolerances for each of the individual members of this crop
subgroup.  A subgroup tolerance, per se, would not be legal at this
time.  Since individual tolerances apply to individual crops there is
also no difficulty with the proposed exceptions for borage and flax from
the crop-group tolerance at this time. Upon Official establishment of
the rapeseed crop subgroup, a formal crop group tolerance may become
appropriate, and at that time it may become necessary to address
inclusion of these two crops within the crop subgroup.

The qualitative nature of the sethoxydim residue in plants and animals
is adequately understood. The residues of concern for tolerances and
risk assessment in both plants and livestock are the combined residues
of sethoxydim and its metabolites containing the 2-cyclohexen-1-one
moiety (calculated as sethoxydim).  These residues are measured by GC/MS
following oxidation and methylation.  For risk assessment purposes the
residues in water are parent and its MSO (sulfoxide), MSO2 (sulfone),
M1S (loss of ethoxy group on the imino nitrogen) and M2S (formation of
oxazole ring) degradates (MARC meeting 5/14/98; MARC memo dated
5/27/98).  

Tolerances have been established under 40 CFR §180.412 for the combined
residues of sethoxydim
[2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen
-1-one] and its metabolites containing the 2-cyclohexen-1-one moiety
(calculated as sethoxydim) in or on numerous agricultural commodities. 
Similarly, permanent tolerances are established (40 CFR §180.412) for
residues of the herbicide sethoxydim and its metabolites containing the
2-cyclohexen-1-one moiety in tissues of various livestock, and poultry,
and in eggs and milk.  The tolerance expression for plant and livestock
commodities includes the combined residues of sethoxydim and its
metabolites containing the 2-cyclohexen-1-one moiety (calculated as the
parent herbicide) as specified in 40 CFR §180.412 and as measured
above.

Current tolerances and the proposed new tolerances are listed below. 
There are no Codex tolerances for sethoxydim, but Canada and Mexico do
have MRLs.  The Canadian MRLs take the same tolerance expression as the
U.S. tolerances.  The Mexican MRLs are all expressed as parent
sethoxydim only.  These values are presented in Table 5 Summary of
International Tolerances and Maximum Residue Limits for Sethoxydim.   

The current tolerance petition supports translating the current
tolerance on rapeseed to all members of the rapeseed crop subgroup
except borage and flax.  Borage and flax already have tolerances (borage
seed 6 ppm, borage meal 10 ppm; flax seed 5.0 ppm flax meal 7 ppm, flax
straw 2.0 ppm).  Because a tolerance for each member of this crop
subgroup will need to be separately translated from rapeseed for this
proposed action, borage and flax can be retained at their current
tolerances.  However, when this crop subgroup is finalized it may be
necessary to determine a single crop subgroup tolerance to cover all of
these oilseeds.  When that happens it may become necessary to change
flax and borage to the same tolerance as the other oilseeds of this crop
subgroup.  

		

BASF Wyandotte Corporation's (BWC's) Methods No. 30, 30G, 30H and A9003
have been determined to be adequate analytical methods for data
collection and/or enforcement of tolerances for residues of sethoxydim
and its metabolites in or on plant and livestock commodities.  Method
30, is a PAM II method and can be used as the enforcement method for
sethoxydim in the 20a crop subgroup.  In method 30 and its
modifications, residues are extracted with water/methanol in various
ratios, and the extract is crudely cleaned up with alkaline
precipitation and partitioning.  Then the residues are oxidized with
peroxide, further cleaned up, and then derivatized to two dimethyl
esters: 3-[2-(ethylsulfonyl) propyl]-pentanedioic acid dimethyl ester
(DME) and 3-[2-(ethylsulfonyl) propyl]-3-hydroxy-pentanedioic acid
dimethyl ester (DME-OH); and the esters are subsequently determined by
GC/FPD in the sulfur mode.   This procedure has been shown to detect the
analytes down to 0.05 ppm in all matrices tested.   

Sethoxydim is applied postemergence, by ground or aerial broadcast
spray, to rapeseed/Canola at a maximum of 0.5 lbs ai/A/treatment and a
maximum of 1.0 lbs ai/A/season, with a minimum 14 day retreatment
interval and a 60 day PHI.  Sethoxydim can also be applied in bands or
used as a spot treatment.  Usually one to three applications are used,
with retreatment intervals ranging from 14 days to 30 days, after
applications of 0.3 – 0.5 lbs ai/A/application, usually totaling to
the 1 lb ai/A maximum seasonal rate and retaining the 60 day PHI.  

Residue Chemistry Deficiencies

There are no outstanding residue chemistry deficiencies associated with
these proposed new uses.  

Background

  SEQ CHAPTER \h \r 1 Sethoxydim is a selective, systemic, postemergence
herbicide used for the control of annual and perennial grass weeds in
broadleaf crops.  Sethoxydim is a member of the cyclohexenone class
(cycloxydim, clethodim, and tralkoxydim) of pesticides.  Current
formulations of sethoxydim include a soluble concentrate (SC) and an
emulsifiable concentrate (EC).  The active ingredient (ai) sethoxydim in
these formulations ranges from 11.15% to 43%.  Sethoxydim is registered
for application to a large number of crops.  Application rates and
pre-harvest interval (PHI) requirements vary depending on the crop. 

Table 1 presents the chemical structure and nomenclature of sethoxydim
and its two most important oxidized metabolites, which are also used as
the fortification standards.  In addition, the structures of the
ultimate methylated analytes DME and DME-OH are shown.  

Table 1.	Sethoxydim Nomenclature.

Chemical structure	

Common name	Sethoxydim

Company experimental name	BAS 9052 H or BAS 562 05H

IUPAC name
(±)-(EZ)-2-(1-ethoxyiminobutyl)-5-[2-(ethylthio)propyl]-3-hydroxycycloh
ex-2-enone

CAS name
(±)-2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-3-hydroxy-2-cycloh
exen-1-one

CAS registry number	74051-80-2

End-use product (EP)	1.5 lb/gal EC formulation (Poast® Herbicide; EPA
Reg. No. 7969-58)

Chemical structure of 2-cyclohexen-1-one metabolites	

Derivatized residues determined by the analytical method		

Common and chemical names	DME; 3-[2-(ethylsulfonyl)propyl]-pentanedioic
acid dimethyl ester	DME-OH;
3-[2-ethylsulfonyl)propyl]-3-hydroxypentanedioic acid dimethyl ester

Metabolites used for sample fortification 1		

Common and chemical names	MSO;
2-[1-(ethoxyimino)butyl]-5-[2-(ethylsulfinyl)propyl]-3-hydroxy-2-cyclohe
xen-1-one	5-OH-MSO2;
2-[1-(ethoxyimino)butyl]-5-[2-(ethylsulfonyl)propyl]-3,5-dihydroxy-2-cyc
lohexen-1-one

1  Sethoxydim is readily oxidized to MSO and 5-OH-MSO2 in air;
therefore, these metabolites are used for sample fortification.

860.1200  Directions for Use

Table 2.  Summary of Directions for Use of Sethoxydim on Rapeseed/Canola
and Other members of the 20a.   Oilseed crop subgroup. 

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

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

(lb ai/A)	PHI

(days)	Use Directions and Limitations



Postemergence

Broadcast, band, or spot

Ground or aerial	POAST EC 1.5 lbs/gal

7969-58	0.5 lbs ai/A	2 (with a minimum 14 day retreatment interval)	1.0
lbs ai/A	60	See Footnote1

1.  The master label includes the following general use directions:  (1)
use with spray adjuvants, including crop oil concentrate or
modified/methylated seed oil is recommended; and (2) a 30-day plant back
interval is established for any crop for which there is no registered
use of sethoxydim.  

Conclusions.  The submitted labels are adequate to support translation
of rapeseed data to the other oilseed of crop subgroup 20a.  

860.1300 Nature of the Residue - Plants

The qualitative nature of the residue in plants is adequately understood
based on soybean, tomato, and sugar beet metabolism studies.  Sethoxydim
is rapidly metabolized in plants to a multitude of cyclohexenone
derivatives including the corresponding parent sulfoxide, parent
sulfone, their hydroxylated and desethoxylated analogs, and oxazole
compounds; very little (≤0.5%) sethoxydim is left un-metabolized.  The
tolerance expression and the residues of concern in plants are the
combined residues of sethoxydim and its metabolites containing the
2-cyclohexen-1-one moiety (calculated as sethoxydim).

860.1300 Nature of the Residue - Livestock

There are no new significant livestock feed items associated with the
proposed new uses, and the existing livestock tolerances have been used
for the dietary exposure assessment.  The tolerance expression and the
residues of concern in poultry and livestock are the combined residues
of sethoxydim and its metabolites containing the 2-cyclohexen-1-one
moiety (calculated as sethoxydim).

860.1340 Residue Analytical Methods

The methods used in the rape seed field trials were adapted by minor
modifications from “Determination of BAS 9052H and its Metabolite
Residues in Soybean Seed, Soybean Seed Process Fractions, Chicken
Tissues, Beef Tissues, Milk and Eggs Analytical Method 30 with
modifications 30B, 30G and 30H, BASF Wyandotte Corporation,
1982-1985.”  These methods are expected to work equally well for
determining residues of sethoxydim in the other members of crop subgroup
20a.  

Method 30

BWC's Method No. 30, "Determination of BAS 9052H and its Metabolites in
Soybean Seed, Soybean Seed Process Fractions, Chicken Tissues, Beef
Tissues, Milk and Eggs", is designed to determine residues of sethoxydim
and its metabolites, including the parent sulfoxide (MSO), the parent
sulfone (MSO2) and hydroxylated derivatives (e.g. 5-OH-MSO2).  Residues
are determined as 3-[2-(ethylsulfonyl)-propyl] pentanedioic acid
dimethyl ester (DME) and its 3-hydroxy derivative: 3-[2-(ethoxysulfonyl)
propyl]-3-hydroxypentanedioic acid dimethyl ester (DME-OH),
respectively. The limit of quantitation for each analyte is reported to
be 0.05 ppm sethoxydim equivalents.  Method 30 is included as Sethoxydim
Method I in PAM II, and is therefore approved as an enforcement method. 


In Method 30, samples are extracted with aqueous methanol, methanol, or
acetonitrile, depending on the sample matrix.  The sample extracts are
cleaned up by alkaline precipitation, filtration, then acidification and
partitioning into methylene chloride, evaporation to dryness, and
addition of 1% barium hydroxide and oxidation by reflux with hydrogen
peroxide X 25 minutes.  This converts Sethoxydim and its metabolites to
3-[2-(ethoxysulfonyl) propyl] pentanedioic acid and
3-[2-(ethoxysulfonyl) propyl]-3-hydroxypentanedioic acid. The resulting
solutions are purged of peroxide; derivatives are partitioned into
methylene chloride and cleaned up by silica gel column chromatography. 
Some samples require an additional HPLC cleanup on silica.  These
oxidized products are then derivatized to two dimethyl esters:
3-[2-(ethylsulfonyl) propyl]-pentanedioic acid dimethyl ester (DME) and
3-[2-(ethylsulfonyl) propyl]-3-hydroxy-pentanedioic acid dimethyl ester
(DME-OH); and these esters are subsequently determined by GC/FPD in the
sulfur mode at 394 nm.  

Sethoxydim can be unstable to oxidation.  Therefore, recovery samples
were fortified with two oxidation products of sethoxydim.  These
products are
2-[1-(ethoxyimino)butyl]-5-[2-ethylsulfinyl)propyl]-3-hydroxy-2-cyclohex
en-1-one (MSO) and
2-[1-(ethoxyimino)butyl]-5-[2-ethylsulfonyl)propyl]-3,
5-dihydroxy-2-cyclohexen-1-one (5-OH-MSO).  Successful EPA petition
method validation trials were conducted for Method 30 on soybeans, beef
liver, and milk.  In the soybean validation trial, recoveries were
73-85% for sethoxydim and the metabolites MSO2, M2SO2, and 5-OH-MSO2
from duplicate soybean samples fortified with each compound at 0.1 ppm.
The lower limit of method validation (LLMV) of Method 30 is 0.05 ppm
each for MSO and MSO2 for all commodities tested.  This LLMV is correct
for all commodities and all modifications of Method 30 in the current
submission.  Recoveries were generally acceptable.

Calibration curves for the various versions of Method 30 were non-linear
and were instead fitted with quadratic equations.  In some specific
cases some recoveries bordered on, or exceeded, acceptable limits, but
overall recoveries were deemed acceptable for data gathering purposes to
address the needs for each commodity. 

 

860.1360 Multi-residue Methods

Sethoxydim is not recovered through the PAM I multi-residue protocols.  

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

Analytical standards for sethoxydim and the sulfoxide (MSO), sulfone
(MSO2), and 5-hydroxysulfone (5-OH-MSO2) metabolites, as well as for the
derivatives DME and DME-OH determined by the analytical method, are
currently available in the National Pesticide Standards Repository.  

860.1380 Storage Stability

Since no new data were submitted, no storage stability data are required
to support this action.  

 860.1400 Water, Fish, and Irrigated Crops

Not Applicable

860.1460 Food Handling

Not applicable

860.1480 Meat, Milk, Poultry, and Eggs

No major new feedstuffs are associated with these proposed new uses for
sethoxydim, so data requirements related to meat, poultry milk or eggs
are not relevant to the current action

CONCLUSIONS

An extension of the tolerance for sethoxydim to all members of crop
subgroup 20a, except flax and borage is reasonable, provided that
individual tolerances are created for each member of this crop subgroup,
and provided that the currently labeled application directions apply to
all members of crop subgroup 20a as described in the submitted
supplemental label.  ChemSAC has agreed, in principle, to the creation
of crop subgroup 20a, however, this crop subgroup has not yet been
formally created yet.  So long as no crop subgroup tolerance is yet
invoked the crops borage and flax can also be excepted from the crop
subgroup.  No additional information or data are required to support
this proposed action.  

Table 4.  Recommended New Tolerances1

Commodity	Established Tolerance (ppm)	Recommended Tolerance (ppm)

Gold of Pleasure, seed	None	35.0

Gold of Pleasure, meal	None	40.0

Crambe, seed	None	35.0

Crambe, meal	None	40.0

Cuphea, seed	None	35.0

Echium, seed	None	35.0

Hare’s Ear Mustard, seed	None	35.0

Lesquerella, seed	None	35.0

Lunaria, seed	None	35.0

Meadowfoam, seed	None	35.0

Milkweed, seed	None	35.0

Mustard, seed	None	35.0

Oil Radish, seed	None	35.0

Poppy, seed	None	35.0

Sesame, seed	None	35.0

Sweet Rocket, seed	None	35.0

	1.  Tolerances are expressed for combined residues of the herbicide
2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-
1-one (CAS Reg. No. 74051–80–2) and its metabolites containing the
2-cyclohexen-1-one moiety (calculated as the herbicide)

Table 6.  Summary of US and International Tolerances and Maximum Residue
Limits for Sethoxydim

US	Canada	Mexico	Codex

Residue Definition:

40CFR180.412

(±)-2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio)
propyl]-3-hydroxy-2-cyclohexene—1-one and metabolites containing the
cyclohexene-2-one moiety expressed as sethoxydim
(±)-2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio)
propyl]-3-hydroxy-2-cyclohexene—1-one and metabolites containing the
cyclohexene-2-one moiety expressed as sethoxydim	Sethoxydim	None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

Commodity	US	Canada	Mexico	Codex

Alfalfa, forage	40.0

	None

Alfalfa, hay	40.0



	        Alfalfa

	40

	Almond, hulls	2.0



	Apple, dry pomace	0.8



	Apple, wet pomace	0.8



	Apricot	0.2



	Asparagus	4.0	0.5



Bean, dry, seed	20.0	10



       “Beans”

	20

	Bean, forage	15.0



	Bean, hay	50.0



	Bean, succulent	15.0	5



Beet, sugar, molasses	10.0



	Beet, sugar, tops	3.0



	Blueberry	4.0	4



Borage, meal	10



	Borage, seed	6.0



	Buckwheat, flour	25



	Buckwheat, grain	19



	Caneberry subgroup 13A	5.0	5



Canola/rapeseed	35.0



	Canola/rapeseed, meal	40.0



	Cattle, fat	0.2



	Cattle, meat	0.2



	Cattle, meat byproducts	1.0



	Cherry, sweet	0.2



	Cherry, tart	0.2



	Citrus, molasses	1.5



	Citrus, dried pulp	1.5



	Clover, forage	35.0



	Clover, hay	50.0



	Coriander	4.0



	Corn, field, grain	0.5	0.5



Corn fodder	2.5



	Corn forage	2.0



	Corn, sweet, forage	3.0



	Corn, sweet, kernel plus cob with husks removed	0.4



	Corn, sweet, stover	3.5



	Cotton, seed, soapstock	15



	Cotton, undelinted seed	5.0

5

	Cranberry	2.0	2



Dillweed, fresh leaves	10



	Egg	2.0	2



Flax, meal	7



	Flax, seed	5.0	0.2



Flax, straw	2.0



	Fruit, citrus	0.5



	       Lime

	0.5

	       Lemon

	0.5

	       Mandarin Orange

	0.5

	       Orange

	0.5

	       Grapefruit

	0.5

	Fruit, pome	0.2



	        Apple

	0.2

	Goat, fat	0.2



	Goat, meat	0.2



	Goat, meat byproducts	1.0



	Grape	1.0

0.2

	Grape, raisin	2.0



	Hog, fat	0.2



	Hog, meat	0.2



	Hog, meat byproducts	1.0



	Horse, fat	0.2



	Horse, meat	0.2



	Horse, meat byproducts	1.0



	Juneberry	5.0



	Lentil, seed	30.0	30	30

	Lingonberry	5.0



	Milk	0.5



	Nectarine	0.2



	Nut, tree, group 14	0.2



	Okra	2.5



	Peach	0.2



	Pea, dry, seed	40.0	10	10

	Pea, field, hay	40.0



	Pea, field, vines	20.0



	Peanut	25.0

25

	Peanut, soapstock	75.0



	Pea, succulent	10.0



	Peppermint, tops	30.0



	Pistachio	0.2



	Potato, flakes	8.0



	Potato, granules	8.0



	Potato, processed potato waste	8.0



	Poultry, fat	0.2



	Poultry, meat	0.2	0.2



Poultry, meat byproducts	2.0



	Poulytu, Liver

0.5



Radish, tops	4.5



	Salal	5.0



	Safflower	15.0



	Sheep, fat	0.2



	Sheep, meat	0.2



	Sheep, meat byproducts	1.0



	Soybean	16.0	5	10

	Soybean, hay	10.0



	Spearmint, tops	30.0



	Strawberry	10.0	10	10

	Sunflower, meal	20.0



	Sunflower, seed	7.0	7



Tomato, concentrated products	24



	Tomato Paste

15



Tomato, dry pomace	12.0



	Turnip, greens	5.0



	Vegetable, brassica, leafy, group 5	5.0



	       Broccoli

0.5	5

	       Cabbage

2	5

	       Brussels Sprouts

	5

	       Cauliflower

	5

	       Mustard Greens

2



Vegetable, bulb, group 3	1.0



	       Garlic

	1

	       Onion

0.2	1

	Vegetable, cucurbit, group 9	4.0



	       Pumpkin/squash

1	2

	       Melon

	2

	       Cantaloupe

2



       Watermelon

	2

	       Cucumber

1



Vegetable, fruiting, group 8	4.0



	       Eggplant

2	4

	       Chili Pepper

	4

	       Pepper

0.5	2

	       Tomato

4	4

	Vegetable, leafy, except brassica, group 4	4.0



	       Celery

1	1

	       Spinach

2	4

	       Lettuce

1	1

	Vegetable, root and tuber, group 1	4.0



	       Potato

4	4

	       Carrot

0.1



       Turnip

0.2



U.S. Section 18 Emergency Exemptions

Artichoke, globe	5.0	2



Rhubarb	0.3



	Proposed





Gold of Pleasure, seed	35.0



	Gold of Pleasure, meal	40.0



	Crambe, seed	35.0



	Crambe, meal	40.0



	Cuphea, seed	35.0



	Echium, seed	35.0



	Hare’s Ear Mustard, seed	35.0



	Lesquerella, seed	35.0



	Lunaria, seed	35.0



	Meadowfoam, seed	35.0



	Milkweed, seed	35.0



	Mustard, seed	35.0



	Oil Radish, seed	35.0



	Poppy, seed	35.0



	Sesame, seed	35.0



	Sweet Rocket, seed	35.0



	

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