UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

	OFFICE OF PREVENTION, PESTICIDE

	AND TOXIC SUBSTANCES

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:  June 17, 2009

SUBJECT:	Acetochlor.  Petition Request for New Uses on Cotton
(PP#8F7443) and Soybean (PP#8F7448).  Summary of Analytical Chemistry
and Residue Data.

PC Code:  121601	DP Barcodes:  D359990, D359992, D359994,		D359996, and
D363293

Decision Nos.:  400596, 400597, 400792, 		and 404070	Registration No.: 
524-LOR, 524-483

Petition Nos.:  8F7443 and 8F7448	Regulatory Action:  Section 3
Registration

Risk Assessment Type:  NA	Case No.:  NA

TXR No.:  NA	CAS No.:  34256-82-1

MRID No.:  See MRID Summary Table	40 CFR:  180.470

	Ver.Apr.08

FROM:	Susan V. Hummel, Chemist & Senior Scientist

		Risk Assessment Branch 4

		Health Effects Division (7509P)  SEQ CHAPTER \h \r 1 

		

THROUGH:	Thurston Morton, Chemist

		Risk Assessment Branch 4

		Health Effects Division (7509P)  SEQ CHAPTER \h \r 1 

TO:		Becky Daiss, Risk Assessor

		Risk Assessment Branch 4,	Health Effects Division (7509P)  SEQ CHAPTER
\h \r 1   SEQ CHAPTER \h \r 1 

		And

		Vickie Walters, PM25

		Herbicide Fungicide Branch, Registration Division (7505P)

		

MRID Summary Table

MRID No.	Study Type	Comments

47695701	860.1300 Cotton	New DER;  47695701.der.doc

47552201	860.1500 Cotton	New DER; 47552201.de1.doc

	860.1520 Cotton	New DER; 47552201.de2.doc

47555601	860.1500 Soybean	New DER; 47555601.de1.doc

	860.1520 Soybean	New DER; 47555601.de2.doc



  SEQ CHAPTER \h \r 1 This document was originally prepared under
contract by Dynamac Corporation (1901 Research Boulevard, Suite 220;
Rockville, MD 20850).  

Dynamac Program Manager:		Date:  5/15/09

	Danilo Martinez

	

The document has been reviewed by the Health Effects Division (HED) and
revised to reflect current Office of Pesticide Programs (OPP) policies.

Executive Summary

Acetochlor
[2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)acetamide], is a
chloroacetanilide herbicide (Group 15) registered for the control of
weeds in corn and sorghum.  

Under PP#8F7443 and PP#8F7448, Monsanto Company is proposing the
establishment of tolerances for residues of acetochlor,
2-chloro-2’-methyl-6-ethyl-N-ethoxymethylacetanilide, and its
metabolites containing the ethyl methyl aniline (EMA) moiety and the
hydroxyethyl methyl aniline (HEMA) moiety, to be analyzed as acetochlor
and expressed as acetochlor equivalents, in or on the following raw
agricultural commodities:

Cotton, undelinted seed	0.6 ppm

Cotton, gin byproducts	4.0 ppm

Soybean, seed	1.0 ppm

With the establishment of these tolerances, the petitioner requests that
the established indirect tolerance for soybean seed be removed.

Although the chemical name for acetochlor that Monsanto used in their
proposed tolerance expression is consistent with the chemical name that
appears in 40 CFR §180.470, this name does not appear to match either
the IUPAC or the CAS name for acetochlor.

In conjunction with the subject petitions, Monsanto is requesting
Section 3 registration for a 3 lb/gal microencapsulated (Mcap)
formulation of acetochlor (MON 63410 Herbicide; EPA File Symbol No.
324-LOR), on cotton (PP#8F7443) and soybean (PP#8F7448).  Preemergence
and/or postemergence applications to cotton and soybean are proposed,
each at up to 1.5 lb ai/A/application, for a maximum seasonal rate of 3
lb ai/A, using ground equipment.  Postemergence application may be made
no later than 15 days after first white flower for cotton or the R1-R2
growth stages of soybean; preharvest intervals (PHIs) are not specified.
 A restriction against the grazing/feeding of treated forage is
specified.

Monsanto is also requesting an amendment to their Section 3 registration
for MON 8435 (Tophand Grass Herbicide) (EPA Reg. No 524-438), an 81.15%
(7.5 lb/gal) emulsifiable concentrate (EC) formulation, proposing to add
the same uses described above on cotton and soybeans.

Tolerances for acetochlor are currently established under 40 CFR
§180.470(a) and (d) and are expressed in terms of acetochlor and its
metabolites containing the EMA moiety and the HEMA moiety, to be
analyzed as acetochlor and expressed as acetochlor equivalents. 
Tolerances for field corn, pop corn, sweet corn, and sorghum commodities
are established under 180.470(a) and range from 0.05 ppm for field and
pop corn grain, sweet corn kernels plus cob with husk removed, and
sorghum grain, to 3.0 ppm for field corn forage.  Tolerances for
rotational crops are established under 180.470(d) and include tolerances
for nongrass animal feeds, sugar beet root and tops, cereal grain
commodities, peas and beans, potato, soybean commodities, sunflower
seed, and wheat commodities; the soybean indirect tolerances are 0.1 ppm
for seed, 0.7 ppm for forage, and 1.0 ppm for hay.  No tolerances have
been established for livestock commodities.

  SEQ CHAPTER \h \r 1 The qualitative nature of acetochlor residues in
corn and sorghum is understood based on adequate corn metabolism
studies.  HED previously concluded that the regulated residues of
concern in corn for both risk assessment and tolerance enforcement
include parent and any metabolites containing the EMA or the HEMA
moiety, expressed in acetochlor equivalents.  The cotton metabolism
study submitted under the current action is acceptable and demonstrates
that metabolism of acetochlor in cotton is similar to that in corn.  The
available cotton and corn metabolism data are adequate to support the
proposed uses on cotton and soybean.  HED has determined that, for
purposes of the subject petitions, the residues of concern for risk
assessment and tolerance enforcement in cotton and soybean are the
parent and any metabolites containing the EMA or the HEMA moiety,
expressed in acetochlor equivalents.  

HED previously concluded that the qualitative nature of acetochlor
residues in animals was adequately understood based on adequate studies
examining the metabolism of various plant metabolites (acetochlor EMA,
HEMA, and Metabolite 57) in both ruminants and poultry.  The residues of
concern in ruminants and poultry include acetochlor, its EMA- and
HEMA-type metabolites, and Metabolite 57.  HED further concluded that
tolerances were not required for livestock commodities to support uses
on corn and sorghum based on the low levels of residues expected in
livestock commodities.  In determining the residues of concern in
livestock, the Agency noted the absence of fully acceptable metabolism
studies in ruminants or poultry in which acetochlor per se was dosed,
and concluded that additional metabolism data would be required for any
new use in which detectable residues in animal commodities were likely.

The proposed uses on cotton and soybean are not expected to increase the
dietary burdens of acetochlor for cattle; however, with the
establishment of a tolerance at 1.20 ppm for soybean meal, the dietary
burdens to poultry and swine will increase ~7x and ~4x over the
previously calculated values.  On re-examination of the available
feeding study data for livestock and the maximum reasonable dietary
burdens (MRDBs) for ruminants and swine, it appears that there is
potential for accumulation of residues of acetochlor in the tissues
(liver and kidney) of ruminant and swine.  Although a ruminant
metabolism study reflecting dosing with acetochlor per se is not fully
adequate, HED is not requiring that another ruminant metabolism study be
submitted for acetochlor at the present time.  No additional metabolism
data are required for poultry at this time.

An adequate high performance liquid chromatography (HPLC) method with
oxidative coulometric electrochemical detection (OCED) is available for
tolerance enforcement for plant commodities.  For this method, extracted
residues are base hydrolyzed to yield EMA and HEMA, HEMA is methylated,
and residues of EMA and methylated HEMA are separated and determined
using HPLC/OCED.  Residues of EMA and HEMA are expressed in acetochlor
equivalents, and the validated method limit of quantitation (LOQ) is
0.02 ppm for each analyte.  Samples from the submitted cotton and
soybean crop field trial and processing studies were analyzed using an
acceptable high performance liquid chromatography method with tandem
mass spectrometry detection (LC/MS/MS) that is similar to the
enforcement method.

The submitted crop field trial and processing studies are supported by
adequate storage stability data.  No storage stability issues or
corrections need be applied to the residue studies.

Acceptable cotton crop field trial studies have been submitted to
support the proposed use on cotton.  The data will support the proposed
tolerances of 0.6 ppm for cotton, undelinted seed and 4.0 ppm for
cotton, gin byproducts.

Acceptable soybean crop field trial studies have been submitted to
support the proposed use on soybean.  The data will support the proposed
tolerance of 1.0 ppm for soybean seed.  No data or tolerances are
required for soybean aspirated grain fractions based on the proposed
early season use pattern (postemergence application prior to pod
formation).  Provided the petitioner revises the proposed label to
prohibit the grazing or feeding of treated soybean forage and hay,
tolerances for soybean forage and hay are not needed in association with
direct application of acetochlor to soybean. 

The submitted cotton and soybean processing studies reflecting
application at ~3x the maximum proposed application rate are adequate. 
Residues do not appear to concentrate in the processed commodities of
cotton and soybean with the exception of soybean meal (1.2x processing
factor).  No tolerances are required for cotton hulls, meal, and refined
oil, or for soybean hulls and refined oil; however, a tolerance for
soybean meal must be proposed at 1.2 ppm.

The nature of the residue in rotational crops is adequately understood
based on the results of confined rotational crop studies in lettuce,
radishes, and wheat.  HED concluded that rotational tolerances should be
expressed as acetochlor and its EMA- and HEMA-producing metabolites, and
residues of hydroxymethyl ethyl aniline (HMEA) type metabolites would
not be included in the tolerance expression, but should be included in
the risk assessment.

Adequate field rotational crop data reflecting a maximum seasonal
application rate of 3.0 lb ai/A are available to support the established
tolerances for rotated crops and the label restrictions specified on the
proposed label.  Because the proposed uses on cotton and soybean will
not affect the maximum seasonal rate for acetochlor, the available data
will support the proposed plantback intervals (PBIs) and established
rotational crop tolerances.  

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

HED has examined the residue chemistry database for acetochlor.  Pending
submission of a revised Section B (see requirements under Directions for
Use) and a revised Section F (see requirements under Proposed
Tolerances), there are no residue chemistry issues that would preclude
granting conditional registration for the requested uses of acetochlor
or establishment of the following tolerances for residues of acetochlor:

Cotton, undelinted seed	0.6 ppm

Cotton, gin byproducts	4.0 ppm

Soybean, seed	1.0 ppm

Soybean, meal	1.2 ppm

Note to PM:  Concurrent with the establishment of the proposed tolerance
for soybean seed under 180.470(a), the tolerance for soybean seed listed
under 180.470(d) should be removed.

A human health risk assessment is forthcoming.

860.1200  Directions for Use

The proposed label must be revised to specify a minimum spray volume of
10 gal/A for applications made using ground equipment.

The grazing/feeding restriction that appears on the proposed label for
the 3 lb/gal Mcap formulation must be revised to state:  “Do not graze
or feed soybean forage or hay.”

860.1550 Proposed Tolerances

A tolerance must be proposed for soybean meal at 1.2 ppm. 

Concurrent with the establishment of the tolerance for soybean seed
under 180.470(a), the established tolerance for indirect or inadvertent
residues in soybean seed under 180.470(d) should be removed.

Background

The chemical structure and nomenclature of acetochlor, the EMA and HEMA
moieties, and Metabolite 57 are presented in Table 1.  The
physiochemical properties of the technical grade of acetochlor are
presented in Table 2.

Table 1.	Acetochlor Nomenclature.

Chemical structure	

Common name	Acetochlor

Company experimental name	None

IUPAC name	2-chloro-N-ethoxymethyl-6'-ethylacet-o-toluidide

CAS name	2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)acetamide

CAS registry number	34256-82-1

End-use product (EP)	3 lb/gal Mcap formulation (MON 63410 Herbicide, EPA
File Symbol No. 524-LOR)

Chemical structure of EMA moiety	

CAS Name:  2-ethyl-6-methylaniline

Acetochlor EMA-type metabolites 1	

Chemical structure of HEMA moiety	

CAS Name:  2-(1-hydroxyethyl)-6-methylaniline

Acetochlor HEMA-type metabolites 1	

Acetochlor Metabolite 57	

N-(6-ethyl-3-hydroxy-2-methylphenyl) oxamic acid

1 For the acetochlor EMA- and HEMA-type metabolites, the R1 functional
group can consist of –H or –CH2OCH2CH3 and the R2 functional group
may consist of many different moieties.  The R3 functional group for
acetochlor HEMA-type metabolites can consist of –H or a variety of
components such as sugars.

Table 2.	Physicochemical Properties of Acetochlor.

Parameter	Value	Reference

Melting point/range	163 ºC at 10 mm Hg; decomposition occurs before the
boiling point at atmospheric pressure (calculated by extrapolation of
vapor pressure at lower temperature)	Residue Chemistry Chapter of the
Acetochlor TRED (DP# 297062, 5/31/05, S. Ary)

pH	4.41, 1% solution in acetone:water (1:1, v:v)

	Density	1.123 g/mL at 20 ºC

	Water solubility	223 mg/L at 25 ºC

	Solvent solubility	Infinitely soluble in acetone, benzene, carbon
tetrachloride, ethanol, chloroform, and toluene at 25 ºC

	Vapor pressure	0.045 µm Hg (4.5 x 10-5 mm Hg) at 25 ºC

	Dissociation constant, pKa	Not applicable because acetochlor is neither
an acid nor a base. 

	Octanol/water partition coefficient, Log(KOW)	970 (Dow study) or 1082
(Monsanto study); differences are likely due to experimental error

	UV/visible absorption spectrum	Not available

	

860.1200 Directions for Use

Under PP#8F7443 and PP#8F7448, Monsanto Company has submitted a draft
label (undated) for the 3 lb/gal Mcap formulation of acetochlor (MON
63410 Herbicide; EPA File Symbol No. 524-LOR).  Monsanto is also
requesting an amendment to their Section 3 registration for MON 8435
(Tophand Grass Herbicide) (EPA Reg. No 524-438), an 81.15% (7.5 lb/gal)
emulsifiable concentrate (EC) formulation, proposing to add the same
uses described above on cotton and soybeans.  The proposed uses for weed
control in cotton and soybean are summarized in Table 3.



Table 3.	Summary of Directions for Use of Acetochlor.

Applic. Timing; Type; and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate, 

lb ai/A

[soil type]1	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations

Cotton

Preplant incorporated, 

Preemergence surface, and

Postemergence surface;

Broadcast boom or banded;

Ground	3 lb/gal Mcap

[524-LOR]	<1.5% OM	≥1.5% OM	1 

or

2 (split)	3.0	NS	Preplant and preemer-gence applications must be made
≥30 days prior to planting; no more than 1.5 lb ai/A may be applied as
a preplant or preemergence treatment.  Postemergence applications may be
made until 15 days after First White Flower stage; no more than 1.5 lb
ai/A may be applied as a postemer-gence application 



0.98-1.2

[coarse]

0.98-1.3

[medium]

0.98-1.4

[fine]	0.98-1.3

[coarse]

0.98-1.4

[medium]

0.98-1.5

[fine]





Preplant incorporated, 

Preemergence surface, and

Postemergence surface;

Broadcast boom or banded;

Ground	7.5 lb/ gal EC

≥1.5% OM	1 

or

2 (split)	3.0	NS	Preplant and preemer-gence applications must be made
≥30 days prior to planting; no more than 1.5 lb ai/A may be applied as
a preplant or preemergence treatment.  Postemergence applications may be
made until 15 days after First White Flower stage; no more than 1.5 lb
ai/A may be applied as a postemer-gence application 



1.0-1.2

[coarse]

1.0-1.3

[medium]

1.0-1.4

[fine]	1.0-1.3

[coarse]

1.0-1.4

[medium]

1.0-1.5

[fine]





Soybeans

0.98-1.2

[coarse]

0.98-1.3

[medium]

0.98-1.4

[fine]	0.98-1.3

[coarse]

0.98-1.4

[medium]

0.98-1.5

[fine]





Soybean	3 lb/gal Mcap

≥1.5% OM	1 

or

2 (split)	3.0	NS	Preplant and preemer-gence applications must be made
≥45 days prior to planting; no more than 1.5 lb ai/A may be applied as
a preplant or preemergence treatment.  Postemergence applications may be
made until plants reach R1-R2 growth stages; no more than 1.5 lb ai/A
may be applied as a postemer-gence application.



0.98-1.2

[coarse]

0.98-1.3

[medium]

0.98-1.4

[fine]	0.98-1.3

[coarse]

0.98-1.4

[medium]

0.98-1.5

[fine]





Soybean	7.5 lb/gal EC

[524-483]	<1.5% OM	≥1.5% OM	1 

or

2 (split)	3.0	NS	Preplant and preemer-gence applications must be made
≥45 days prior to planting; no more than 1.5 lb ai/A may be applied as
a preplant or preemergence treatment.  Postemergence applications may be
made until plants reach R1-R2 growth stages; no more than 1.5 lb ai/A
may be applied as a postemer-gence application.



1.0-1.2

[coarse]

1.0-1.3

[medium]

1.0-1.4

[fine]	1.0-1.3

[coarse]

1.0-1.4

[medium]

1.0-1.5

[fine]





1  OM = organic matter.  Coarse soils include sand, loamy sand, and
sandy loam; medium soils include loam, silt loam, silt, and sandy clay
loam; and fine soils include silty clay loam, clay loam, sandy clay,
silty clay, and clay.  

Application via aerial equipment or through any type of irrigation
system is prohibited; a minimum spray volume for application via ground
equipment is not specified.

A feeding/grazing restriction is proposed for both acetochlor products
as follows:  “Do not graze treated area or feed treated forage to
livestock following application.”  

The following rotational crop restrictions are specified on the MON
63410 Herbicide; EPA File Symbol No. 524-LOR) label:  (1)  field corn,
seed corn, silage corn, popcorn, or sweet corn may be replanted
immediately; do not exceed 3 lb ai/A if additional product is applied;
(2)  nongrass animal feeds such as alfalfa, clover, kudzu, lespedeza,
lupin, sanfoin, trefoil, velvet beans, and Vetch spp. may be planted 9
months after application; wheat may be planted 4 months after
application; and (3)  the following crops may be rotated the next
season:  cotton, soybeans, corn (all types), milo (sorghum), tobacco,
sugar beets, sunflowers, potatoes, barley, buckwheat, kudzu, millet
(pearl and proso), oats, rye, teonsinte, triticale, wild rice, dried
shelled bean group, Lupinus spp. (including grain lupin, sweet lupin and
white lupin); Phaseolus spp. (including field bean, kidney bean, lima
bean (dry), navy bean, pinto bean, and tepary bean); bean Vigna spp.
(including adzuki bean, blackeyed pea, catjang, cowpea, Crowder pea,
moth bean, mung bean, rice bean, southern pea, and urd bean), broad bean
(dry), chickpea, guar, lablab bean, lentil, pea (Pisum spp., including
field pea), and pigeon pea. 

The following rotational crop restrictions are specified on the MON 8435
(EPA Reg. No. 524-483) label:  “Do not rotate to crops other than 
soybeans, corn, milo (sorghum), wheat, or tobacco.”

Conclusions.  The proposed label is adequate to allow evaluation of the
residue data relative to the proposed use on cotton and soybean.  The
submitted data are representative of the proposed uses and application
timings.  PHIs are not needed because postemergence applications are
restricted to the flowering stage in both cotton and soybean, prior to
boll or pod formation.  

The use directions must be revised to specify a minimum spray volume for
applications made using ground equipment.  The submitted data will
support a minimum spray volume of 10 gal/A.

The proposed label contains the following statement:  “Do not graze
treated area or feed treated forage to livestock following application. 
Based on the proposed tolerance for soybean seed only, it appears that
the grazing/feeding restriction is intended to cover both soybean forage
and hay.  The label restriction must be revised to state:  “Do not
graze or feed soybean forage or hay.”

It should be noted that the field trials were conducted with Degree®
Herbicide, an Mcap formulation which contains a safener.  The petitioner
stated that the safener is not effective in cotton/soybean, and noted in
the field trial submissions that the new microencapsulated formulations
of acetochlor being developed for commercial use (and proposed for
registration in this petition) will not contain the safener.  HED does
not believe the presence of this safener in the formulation used in the
field trials would have an effect on the residues of acetochlor
determined in the field trial samples. 

860.1300 Nature of the Residue - Plants

DER Reference:  47695701.der.doc (Cotton)

Residue Chemistry Chapter of the TRED, DP# 297062, 5/31/05, S. Ary

Residue Chemistry Memo, No DP#, 9/15/93, M. Flood

  SEQ CHAPTER \h \r 1 The qualitative nature of acetochlor residues in
corn and sorghum is understood based on adequate corn metabolism
studies.  HED previously concluded that the regulated residues of
concern in corn for both risk assessment and tolerance enforcement
include parent and any metabolites containing the EMA or the HEMA
moiety, expressed in acetochlor equivalents.

In support of the proposed uses on cotton and soybean, Monsanto has
submitted a metabolism study on cotton.  The results of the corn
metabolism studies are summarized below for comparison purposes. 
Structures of acetochlor and its metabolite types are presented in Table
I.

Corn

In the first corn metabolism study submitted in 1984, [14C]acetochlor
was applied preemergence to greenhouse-grown corn at 1.5 lb ai/A; mature
crops were harvested 3.5 months later.  TRR were 0.2 ppm in grain and
26.7 ppm in foliage.  Parent was not detected in corn grain or foliage. 
Approximately 65 metabolites were observed in corn grain and foliage,
with individual metabolites accounting for <10% TRR.  Upon strong acid
hydrolysis, the majority of 14C-residues were converted to either EMA or
HEMA.

≤5.8% TRR) were identified, along with isomers of two
ring-hydroxylated metabolites, Metabolite 55 (3.2% TRR) and Metabolite
57 (12.7% TRR); results for forage were similar.  In corn grain, up to
four EMA-type metabolites were identified (each ≤3.6% TRR) along with
Metabolites 55 (3.0% TRR) and Metabolite 57 (8.8% TRR).  As in the
earlier study, no HEMA-type metabolites were directly identified, but
HEMA metabolites were released by strong base hydrolysis.

We note that based on an examination of metabolite structures, neither
Metabolite 55 nor Metabolite 57 was identified in the cotton metabolism
study in which a different numbering system was used for metabolites.  

Cotton

In support of the proposed use on cotton and soybean, Monsanto has
submitted a study investigating the metabolism of
[phenyl-U-14C]acetochlor (specific activity 8.78-9.36 mCi/mmol) in
cotton.  The radiolabeled test substance was prepared in acetone/water
for preplant or postemergence application to cotton grown outdoors.  A
preplant application was made to the soil at 3.24 lb ai/A 30 days prior
to planting.  At a separate plot, a postemergence foliar application was
made at 3.21 lb ai/A 15 days after the majority of the plants had
reached the first white flower stage.  A third plot of cotton was left
untreated for controls.  The application rates used in the study
correspond to ~1x the maximum proposed seasonal rate for cotton and
soybean.

Samples of mature leaves/stems and seed were harvested 205 days after
treatment (DAT) from the preplant treated plot and 91 DAT from the
postemergence treated plot.  Cotton was processed in a miniature gin at
the field site; leaves and stems were used as a surrogate for gin
byproducts to increase the amount of plant material for analysis.  The
in-life phase of the study was conducted by Excel Research Services
(Fresno, CA), and the analytical phase of the study was conducted at
PTRL West, Inc. (Hercules, CA).

  

TRR in cotton leaves/stems were determined by combustion/LSC; TRR in
cotton seed was calculated by summing extractable and nonextractable
radioactivity.  Following preplant application of
[phenyl-U-14C]acetochlor at an application rate of 3.24 lb ai/A, TRR
were 5.748 ppm in leaves/stems and 0.103 ppm in seed.  Following
postemergence foliar application at 3.21 lb ai/A, TRR were 63.899 ppm in
leaves/stems and 0.133 ppm in seed.  TRR were similar in seed whether
treated preplant or postemergence, but were much higher in leaves/stems
treated postemergence (~10x the preplant TRR), likely due to the direct
exposure with the foliar application.  The petitioner noted that the TRR
in leaves/stems would be expected to be much higher than in gin
byproducts because the leaves, which received direct application of the
test solution, would not be present in gin byproducts from commercial
production.

Cotton seed was initially extracted with hexane to remove oils; hexane
released 12% and 6% TRR from preplant and postemergence seed,
respectively.  Solvent extraction with acetonitrile (ACN)/water released
the majority of the radioactivity from cotton leaves/stems (~86-89%
TRR), and a significant amount of radioactivity from preplant seed (29%
TRR) and postemergence seed (44% TRR).  Further acid and base hydrolysis
released an additional 9-10% TRR from seed and 4% TRR from leaves/stems.
 Seed samples were further extracted with methanol, dimethylsulfoxide
(DMSO), tetrahydrofuran (THF), acid at reflux, 24% KOH, and sulfuric
acid releasing 34-42% TRR; KOH released the largest amount of
radioactivity (22-30% TRR) from both preplant and postemergence seeds. 
Nonextractable residues were 26.7-28.8% TRR (0.030-0.036 ppm) in seed,
and 3.3-7.7% TRR (0.444-2.111 ppm) in leaves/stems.  HED concludes that
the extraction/hydrolysis procedures were adequate in extracting the
majority of residues from cotton seed and leaves/stems. 
Accountabilities were 119-121% for seed and 96-102% for leaves/stems.   

Residues were quantitated and isolated by HPLC, and metabolites were
tentatively identified using LC/MS or LC/MS/MS.  The chemical names and
structures of acetochlor and its transformation products in cotton are
presented in Appendix I.  Because initial profiling was completed within
6 months of sample collection for both treatment studies, no supporting
storage stability data are required.

re not further identified.  Lipid residues from the hexane extract were
characterized as non-saponifiable lipids (≤1.9% TRR), fatty acids
(~4-7% TRR), and glycerol and polar compounds (~1-2% TRR).  Additional
residues were characterized, based on extraction/hydrolysis behavior, as
being associated with lignin (DMSO; ≤1% TRR), hemicellulose (KOH;
~22-25% TRR), and cellulose/polysaccharide (sulfuric acid; ~7% TRR). 
The petitioner concluded that the results suggest that the radioactivity
in cotton seed was either bound to or re-incorporated into natural
products.

e other metabolites were identified (2 EMA-type and 1 HEMA-type) at
≤6.1% TRR each.  Additional components were characterized by their
elution pattern (retention time; RT).  Major components, including RT
5.75, RT 8.25 and 9.25, and RT 10.75 and 11.75, were further
characterized by hydrolysis procedures.  Acid hydrolysis of RT 5.75
(4.3% TRR) and RT 10.75/11.75 (7.7% TRR) indicated that the regions were
multi-component, and suggested the likely hydrolysis of conjugates, such
as glucose conjugates.  Strong acid hydrolysis and reflux with dilute
acid of RT 8.25/9.25 (16.8% TRR) produced similar results, with a
possible EMA product; acid pressure hydrolysis of the RT 8.25/9.25
fraction produced o-toluidine and 2-ethylaniline products, demonstrating
that HEMA- and HMEA-type metabolites were present.  Following these
procedures, minor components, each ≤4.2% TRR, accounted for 57.1% TRR
(3.285 ppm).  Aqueous-soluble and acid/base-hydrolyzable residues each
accounted for ≤2.8% TRR.

Metabolites isolated from postemergence-treated leaves/stems were used
for the majority of identifications because residues were much higher. 
In postemergence-treated leaves/stems, metabolites accounting for ~78%
TRR were tentatively identified, of which 53.6% TRR (34.092 ppm) were
EMA-type metabolites and 24.0% TRR (15.451 ppm) were HEMA-type
metabolites.  Metabolite #14 (acetochlor sec-sulfinyllactic acid) was
the major EMA-type metabolite, accounting for 19.6% TRR; Metabolite #15
(acetochlor 5-hydroxy sec-sulfinyllactic acid) was present at 8.3% TRR,
and the remaining 10 EMA-type metabolites were each present at ≤4.8%
TRR.  Only one HEMA-type was present at ≥10% TRR, Metabolite #11
(acetochlor 1-hydroxyethyl sec-thiolactic acid; 10.9% TRR); the
remaining four HEMA-type metabolites were present at ≤5.6% TRR. 
Additional peaks characterized by elution patterns accounted for <9%
TRR, and aqueous-soluble and acid/base-hydrolyzable residues each
accounted for ≤3.4% TRR.

Based on the results of the cotton metabolism study, the petitioner
proposes that metabolism results from the initial conjugation of
acetochlor with glutathione, followed by the subsequent loss of
glutamate, then glycine.  The resulting cysteinyl product then undergoes
oxidation, deamination, dealkylation and further conjugation with
malonate or glucose to yield numerous metabolites.  The metabolism of
acetochlor following preplant or postemergence application, via the
glutathione pathway with subsequent oxidation and conjugation, is
consistent with known pathways of degradation of acetanilide herbicides
in soil, plants, and animals.

Conclusions:  The submitted cotton metabolism study is acceptable and
demonstrates that metabolism of acetochlor in cotton is similar to that
in corn.  The available cotton and corn metabolism data are adequate to
support the proposed uses on cotton and soybean.  HED has determined
that, for purposes of the subject petitions, the residues of concern for
risk assessment and tolerance enforcement in cotton and soybean are the
parent and any metabolites containing the EMA or the HEMA moiety,
expressed in acetochlor equivalents.  The need for additional plant
metabolism studies to support future uses will be decided on a
case-by-case basis.

860.1300 Nature of the Residue - Livestock

Residue Chemistry Memo  3G2797 and 2G2726, 6/6/83,  S. Malak, 

Residue Chemistry Memo DP# 349273, 5/13/08, D. Davis (PP#7F7306)

Residue Chemistry Chapter of the TRED, DP# 297062, 5/31/05, S. Ary

Residue Chemistry Memo, No DP#, 9/15/93, M. Flood

HED previously concluded that the qualitative nature of acetochlor
residues in animals is adequately understood based on adequate studies
examining the metabolism of various plant metabolites (acetochlor EMA
type metabolites, HEMA type metabolites, and Metabolite 57) in both
ruminants and poultry.  The residues of concern in ruminants and poultry
include acetochlor, its EMA- and HEMA-type metabolites, and Metabolite
57 (a ring hydroxylated metabolite)).  HED further concluded that
tolerances were not required for livestock commodities to support use on
corn and sorghum based on the low levels of residues expected in
livestock commodities.

Two additional studies examining the direct metabolism of radiolabeled
acetochlor in goats were found to be inadequate due to insufficient
characterization of 14C-residues in liver and kidney.  In determining
the residues of concern in livestock, the Agency noted the absence of
fully acceptable metabolism studies in ruminants or poultry in which
acetochlor per se was dosed, and concluded that additional metabolism
data would be required for any new use in which detectable residues in
animal commodities were likely.  However, the dietary burden for
ruminants has not increased significantly.

Conclusions.  The proposed uses on cotton and soybean are not expected
to increase the dietary burdens of acetochlor for cattle (see OPPTS
860.1480); however, with the establishment of a tolerance at 1.20 ppm
for soybean meal, the dietary burdens to poultry and swine will increase
~7x and ~4x over the previously calculated values.  On re-examination of
the available feeding study data for livestock and the maximum
reasonable dietary burdens (MRDBs) for ruminants and swine, it appears
that there is potential for accumulation of residues of acetochlor in
the tissues of ruminant and swine.  

Although a feeding study for acetochlor, per se, in ruminants was not
fully adequate, a new ruminant feeding study will not be required at
this time.  Acceptable ruminant metabolism data are available reflecting
the metabolism of the acetochlor EMA and HEMA metabolites and Metabolite
57.  No additional poultry metabolism data are needed at this time.

860.1340 Residue Analytical Methods

Residue Chemistry Chapter of the TRED, DP# 297062, 5/31/05, S. Ary

Crop Commodities

Enforcement method:  A tolerance enforcement method is available for
determining residues of acetochlor and its EMA- and HEMA-producing
metabolites in plant commodities.  The method is an HPLC/OCED method and
is listed as Method I in PAM Vol. II (section 180.470).

For this method, residues are extracted into aqueous ACN, concentrated,
and base hydrolyzed to yield EMA and HEMA.  The resulting residues are
steam-distilled into dilute acid, adjusted to a basic pH, and
partitioned into methylene chloride.  HEMA is methylated using acidic
methanol, and residues of EMA and methylated HEMA are separated and
determined using HPLC/OCED.  Residues of EMA and HEMA are expressed in
acetochlor equivalents, and the method LOQ is 0.02 ppm for each analyte.

Data collection method:  Samples from the submitted cotton and soybean
crop field trial and processing studies were analyzed for residues of
acetochlor, determined as the sum of EMA- and HEMA-producing
metabolites, and expressed as acetochlor equivalents using an LC/MS/MS
Method (Monsanto method ES-ME-1215-01).  The method is similar to the
tolerance enforcement method for plants, except that it uses online SPE
cleanup rather than partitioning and conventional SPE, and residues are
determined by LC/MS/MS rather than by HPLC/OCED; in addition,
methylation of HEMA is not required.

Briefly, samples were extracted with water:ACN (20:80; v:v).  Dry matrix
extracts were filtered and concentrated via rotary evaporation.  Oil
extracts were centrifuged, and the oil phase was removed for additional
extraction with water/ACN; the water/ACN phases were combined for
concentration via rotary evaporation.  Concentrated extracts were then
hydrolyzed with 50% sodium hydroxide to yield EMA and HEMA.  The
hydrolysate was steam distilled into dilute sulfuric acid.  The solution
was neutralized with NaOH and NaHCO3, and cleaned up by SPE for LC/MS/MS
analysis.  Residues of EMA and HEMA were expressed in acetochlor
equivalents; to facilitate calculations as acetochlor equivalents, the
standard levels were converted using the ratio of the molecular weight
of EMA to acetochlor (1.9952) or HEMA to acetochlor (1.7841).

For the field trials, the LOQs for acetochlor EMA and HEMA metabolites,
in acetochlor equivalents, were <0.005 each for cotton undelinted seed;
respective LOQs for each analyte in remaining commodities were 0.0596
and 0.0139 ppm, in acetochlor equivalents, for cotton gin byproducts,
0.0840 and 0.0295 ppm, in acetochlor equivalents, for soybean forage,
0.2142 and 0.0948 ppm, in acetochlor equivalents, for soybean hay, and
0.0059 and 0.0061 ppm, in acetochlor equivalents, for soybean seed,
respectively.  Based on these values, combined LOQs for total acetochlor
were <0.010 ppm for cotton undelinted seed, 0.0735 ppm for gin
byproducts, 0.114 ppm for soybean forage, 0.309 ppm for soybean hay, and
<0.012 ppm for soybean seed.  

For the processing studies, the LOQs for the raw agricultural
commodities of cotton and soybean seed were used by the petitioner for
the processed matrices.  The lowest levels of method validation (LLMVs)
in concurrent method validation for processed commodities were 0.005 ppm
for each analyte, in acetochlor equivalents, for cotton hulls, meal, and
oil, and 0.050 ppm, 0.010 ppm, and 0.005 ppm for each analyte, in
acetochlor equivalents, for soybean hulls, meal, and refined oil,
respectively.  

The LC/MS/MS method was adequate for data collection based on acceptable
concurrent method recoveries in the cotton and soybean field trial and
processing studies.  The fortification levels used in concurrent method
validation were adequate to bracket (within an order of magnitude)
expected residue levels for both analytes in all cotton and soybean
commodities except soybean hulls, for which residues of EMA metabolites
of acetochlor in meal slightly exceeded these criteria.

Conclusions.  The residue analytical methods data are adequate to
satisfy data requirements for the subject action.  An acceptable
enforcement method is available for the determination of residues of
acetochlor and its EMA- and HEMA-producing metabolites in plant
commodities, and residues of acetochlor EMA and HEMA metabolites in/on
cotton and soybean commodities from the crop field trial and processing
studies were determined using an acceptable data collection method.  

Livestock Commodities

An enforcement analytical method is available for determining residues
of acetochlor and its EMA- and HEMA-producing metabolites in milk and
cattle commodities.  This HPLC/OCED method is listed as Method A in PAM
Vol. II (180.470) and is similar to the enforcement method for crop
commodities.  No enforcement analytical method is available for
Metabolite 57.

There are currently no tolerances for residues of acetochlor on
livestock commodities; however, on re-examination of the available
feeding study data for livestock and the MRDBs for ruminants and swine,
it appears that there is potential for accumulation of residues of
acetochlor in the tissues of ruminant and swine.  

Conclusions.  Although the ruminant metabolism study reflecting dosing
with acetochlor per se was not fully adequate, no new ruminant
metabolism study is being required at the present time in support of
registered and proposed uses of acetochlor.  

860.1360 Multiresidue Methods

Residue Chemistry Chapter of the TRED, DP# 297062, 5/31/05, S. Ary

The FDA PESTDATA database dated 06/05 (PAM Volume I, Appendix I)
indicates that acetochlor per se is completely recovered using
Multiresidue Methods Section 302 (Luke Method; Protocol D) and 303
(Mills Method; Protocol E), but is only partially recovered by Method
304 (Protocol F).  Data have also been submitted reflecting testing of
six acetochlor metabolites (three acetochlor EMA metabolites, two
acetochlor HEMA metabolites, and an acetochlor ethyl hydroxymethyl
aniline (EHMA) metabolite) under the Multiresidue Method Testing
protocols.  None of these metabolites was recovered under the FDA
multiresidue protocols.  

860.1380 Storage Stability

Residue Chemistry Chapter of the TRED, DP# 297062, 5/31/05, S. Ary

Adequate storage stability data have been submitted which demonstrate
that residues of acetochlor per se are stable in frozen corn, soybean,
and peanut forage for up to 36 months, and residues of representative
acetochlor EMA and HEMA metabolites are stable in frozen corn grain,
forage, and fodder for up to 49 months.

Storage stability analyses were also conducted in conjunction with the
extensive field rotational crop studies that were previously submitted,
which indicated that residues of representative acetochlor EMA-, HEMA-,
and HMEA-type metabolites were stable at -18 °C for up to 13 months in
soybean seed, forage, and hay, and for up to 25 months in wheat forage,
grain, and straw, and sorghum grain and silage. 

Samples from the subject field trial and processing studies were stored
frozen (temperature unspecified) from harvest/processing to analysis. 
The storage durations and conditions of samples from the crop field
trial and processing studies submitted to support this petition are
presented in Table 4.  

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

Matrix 	Storage Temperature	Actual Storage

 Duration	Interval of Demonstrated Storage Stability

Cotton, undelinted seed	Frozen

(temperature

unspecified)	115-211 days (3.8-6.9 months)	Residues of acetochlor EMA
and HEMA metabolites are stable in/on soybean seed stored frozen for 13
months.

Cotton, seed 

(for processing)

161 days (5.3 months)

	Cotton, gin byproducts

176-261 days (5.8-8.6 months)	Residues of acetochlor EMA and HEMA
metabolites are stable in/on sorghum silage, and corn, soybean and wheat
forage, fodder, and/or straw stored frozen for 13-49 months.

Cotton, hulls

23 days	Stored <30 days from processing to analysis, therefore, none
required.

Cotton, meal

10 days

	Cotton, refined oil

6 days

	Soybean, seed	Frozen

 (temperature

unspecified)	125-186 days (4.1-6.1 months)	Residues of acetochlor EMA
and HEMA metabolites are stable in/on soybean seed, forage and hay
stored frozen for 13 months.

Soybean seed

(for processing)

131 days (4.3 months)

	Soybean, forage

261-330 days (8.6-10.9 months)

	Soybean, hay

270-325 days (8.9-10.7 months)

	Soybean, hulls

25 days	Stored <30 days from processing to analysis, therefore, none
required.

Soybean, refined oil

11 days

	Soybean, meal

acetochlor EMA metabolites:  63 days

(8 days sample; 55 days extract)

acetochlor HEMA metabolites:  12 days	No data are required for
acetochlor HEMA metabolites, since samples were stored <30 days from
processing to analysis, and the petitioner has adequately addressed the
storage stability of acetochlor EMA metabolites in extracts1; no
additional data are required.

1  Refer to 47555601.de2.doc

Conclusions.  The available storage stability data are adequate to
support the storage conditions and durations of samples from the cotton
and soybean field trial and processing studies.

860.1400 Water, Fish, and Irrigated Crops

There are no proposed uses that are relevant to this guideline topic.

860.1460 Food Handling

There are no proposed uses that are relevant to this guideline topic.

860.1480 Meat, Milk, Poultry, and Eggs

Residue Memo DP# 349273, 5/13/08, D. Davis (PP#7F7306)

Residue Chemistry Chapter of the TRED, DP# 297062, 5/31/05, S. Ary

Residue Chemistry Memo, No DP#, 9/15/93, M. Flood

Residue Chemistry Memo, DP# 156746, 4/29/91, N. Dodd

Residue Chemistry Meme, No DP#, 6/6/83, S. Malak

Acceptable feeding studies were previously submitted for cattle
reflecting feeding of acetochlor EMA- and HEMA-producing metabolites and
Metabolite 57, and for poultry and swine, reflecting feeding of
acetochlor EMA-producing metabolites only.  HED previously concluded
that tolerances were not required for livestock commodities to support
use on corn and sorghum based on the low levels of residues expected in
livestock commodities.

The livestock feedstuffs associated with the proposed uses on cotton and
soybean are cotton undelinted seed, gin byproducts, meal, and hulls, and
soybean seed, meal, and hulls.  The proposed label prohibits the
grazing/feeding of treated forage; based on the proposed tolerances, it
appears that the petitioner intends to prohibit the grazing/feeding of
soybean forage/silage and hay.  No data are required for soybean
aspirated grain fractions based on the proposed early season use
pattern.

The dietary burdens of acetochlor were recently calculated (DP# 349273,
5/13/08, D. Davis) based on reasonably balanced diets (Table 1
Feedstuffs, October 2006 version) and reflecting registered and amended
use on corn and sorghum as well as established tolerances for indirect
residues of acetochlor in rotated crops.  The calculated dietary burdens
were 4.54 and 5.66 ppm for beef and dairy cattle, respectively, and 0.06
ppm for poultry and swine.

In June 2008, HED issued new guidance concerning the construction of
maximum reasonably balanced diets for livestock.  Because the dietary
burden of acetochlor drives the need for livestock tolerances, the
dietary burdens for acetochlor have been recalculated herein, reflecting
the recent guidance and the proposed uses on cotton and soybean.  The
results are presented in Table 5.

Based on the new guidance, and the proposed and established tolerances
for acetochlor, the MRDBs are estimated to be 1.319 ppm for beef cattle,
3.821 ppm for dairy cattle, 0.415 ppm for poultry, and 0.223 ppm for
swine. 

Table 5.	Calculation of Dietary Burdens of Acetochlor Residues to
Livestock.

Feedstuff	Type1	% Dry Matter2	% Diet2	Recommended Tolerance (ppm)
Dietary Contribution (ppm)3

Beef Cattle

Corn, field, forage/silage	R	40	15	3.0	1.125

Corn, field, grain	CC	88	50	0.05	0.028

Potato, culls/processed waste	CC	15	30	0.05	0.100

Soybean, meal	PC	92	5	1.20	0.065

TOTAL BURDEN	--	--	100	--	1.319

Dairy Cattle

Corn, field, forage/silage	R	40	45	3.0	3.375

Corn, field, grain	CC	88	35	0.05	0.020

Potato, culls/processed waste	CC	15	30	0.05	0.033

Alfalfa, meal	PC	89	10	3.50	0.393

TOTAL BURDEN	--	--	100	--	3.821

Poultry

Sorghum, grain	CC	86	75	0.05	0.038

Alfalfa, meal	PC	89	5	3.5	0.175

Soybean, meal	PC	92	20	1.20	0.240

TOTAL BURDEN	--	--	100	--	0.415

Swine

Corn, field, grain	CC	88	85	0.05	0.043

Soybean, meal	PC	92	15	1.20	0.180

TOTAL BURDEN	--	--	100	--	0.223

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

2  OPPTS 860.1000 Table 1 Feedstuffs (June 2008).  

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

In evaluating prior petitions for use of acetochlor on corn and sorghum,
the Agency previously determined that there is no reasonable expectation
of finite residues occurring in animal commodities [40 CFR
§180.6(a)(3)] based on acceptable studies in which livestock were fed
four acetochlor EMA-producing metabolites, one acetochlor HEMA-producing
metabolite, and acetochlor Metabolite 57.  The results of these studies
are summarized in Table 5.

Table 5.	Summary of Available Livestock Feeding Study Data.

Matrix	Feeding Level, ppm (expressed as dosed metabolite)

	Acetochlor EMA-Producing Metabolites (ppm)1	Acetochlor
[14C]HEMA-Producing Metabolite (ppm)1	Acetochlor Metabolite 57 (ppm)1

	5	15	50	0.5	1.5	5	25

Cattle

Milk	<0.02	<0.02	<0.02	NA	NA	<0.01	NA

Fat	<0.02	<0.02	<0.02	NA	NA	<0.01	NA

Muscle	<0.02	<0.02	<0.02	NA	NA	<0.01	NA

Liver	<0.02	<0.02	0.02	NA	NA	<0.01	NA

Kidney	<0.02	0.04	0.09	NA	NA	<0.01	0.0062

Swine

Fat	<0.02	<0.02	<0.02





Muscle	<0.02	<0.02	<0.02





Liver	<0.02	<0.02	0.05





Kidney	<0.02	0.03 	0.27





Poultry

Eggs and Tissue	<0.02	<0.02	<0.02





1  Expressed as ppm metabolite.  NA = Not analyzed.  

2  Metabolism study result.  Calculated based on results reported in
memo dated 9/15/93:  TRR = 0.015 ppm in kidney; Metabolite 57 identified
at 43% of TRR.  

The dietary burden of acetochlor to beef and dairy cattle is not
expected to increase as a result of the inclusion of cotton and soybean
commodities in livestock diets; however, the calculated MRDB for dairy
cattle and the available feeding study data suggest the potential for
detectable residues of the acetochlor EMA metabolites in ruminant liver
and kidney at a 10x feeding level.  The feeding levels for the
acetochlor EMA-producing metabolites of 5, 15, and 50 ppm correspond to
1.3x, 3.9x, and 13x the MRDB for dairy cattle.  If the detectable
residues in liver and kidney are adjusted to a 10x feeding level,
expected residues would be 0.002 ppm in liver, and 0.007-0.010 ppm in
kidney.  

With the establishment of a tolerance at 1.20 ppm for soybean meal, the
dietary burdens to poultry and swine will increase ~7x and ~4x over the
previously calculated values.  In the previously submitted poultry and
swine feeding studies, acetochlor EMA-producing metabolites were fed to
poultry and swine at 5, 15, and 50 ppm in the diet; these feeding levels
correspond to 12x, 36x, 120x the MRDB for poultry, and 22x, 67x, and
224x the MRDB for swine.  Residues of the acetochlor EMA-producing
metabolites were nonquantifiable in poultry eggs and tissue and in hog
fat and muscle at all feeding levels.  Detectable residues of the
acetochlor EMA-producing metabolites were observed in hog liver at 0.05
ppm at the 50-ppm feeding level, and in hog kidney at 0.03 and 0.27 ppm
at the 15- and 50-ppm feeding levels.  If the detectable residues are
adjusted to a 10x feeding level, expected residues would be 0.002 ppm in
hog liver and 0.004-0.012 ppm in hog kidney.

Conclusions.  Based on re-examination of the available feeding study
data for livestock and the MRDBs for ruminants and swine, it appears
that there is potential for accumulation of residues of acetochlor in
the tissues of ruminants and swine.  The Agency previously (memo of
9/15/93, M. Flood) noted the absence of fully acceptable metabolism
studies in ruminants or poultry in which acetochlor, per se, was dosed,
and concluded that additional metabolism data would be required for any
new use in which detectable residues in animal commodities were likely.

Although an earlier ruminant metabolism study reflecting dosing of
acetochlor, per se, was not fully adequate, a ruminant metabolism study
reflecting dosing with acetochlor per se will not required in support of
registered and proposed uses of acetochlor at this time.  

HED further concludes that there remains no reasonable expectation of
finite residues occurring in poultry commodities [40 CFR §180.6(a)(3)]
as a result of feeding acetochlor-treated feedstuffs.  No additional
data are needed for poultry at this time.

860.1500 Crop Field Trials

DER References:  47552201.de1.doc (Cotton)

		 47555601.de1.doc (Soybean)

Monsanto has submitted field trial data in support of proposed uses on
cotton and soybean.

Cotton

Monsanto has submitted field trial data for acetochlor on conventional
and glyphosate-tolerant cotton.  Thirteen trials were conducted in the
United States in Zones 2 (GA; 1 trial), 4 (AR, LA; 3 trials), 6 (TX, 2
trials), 8 (TX, OK; 4 trials), and 10 (AZ, CA; 3 trials) during the 2007
growing season.  Glyphosate-tolerant cotton varieties were used in four
of the field trials.

At each test location, an untreated plot and multiple treated plots were
established.  At two treatment plots, a single postemergence broadcast
foliar application of a 3.8 lb ai/gal Mcap formulation was made at a
target rate of 3.0 lb ai/A to cotton plants 15 days after the first open
flower (Treatment plot #2) or at the 8-leaf growth stage (Treatment plot
#4).  At a third plot (Treatment plot #6), split applications of the 3.8
lb/gal Mcap formulation were made reflecting a preplant application to
the soil made ~30 days prior to planting and a single postemergence
broadcast foliar application made to cotton plants at the 8-leaf growth
stage; applications were made at target rates of 1.5 lb ai/A/application
for a total application rate of 3.0 lb ai/A.  RTIs were 64-91 days. 
Applications were made using ground equipment in 10-20 gal/A spray
volumes; an adjuvant was not used.  Additional plots at each site were
treated with the 3.8 lb/gal Mcap formulation and/or a 7 lb/gal
emulsifiable concentrate (EC) formulation of acetochlor at different
timings, but samples from these plots were not analyzed and therefore
are not further discussed herein.  

The application rates used in the cotton field trials correspond to 1x
the maximum proposed seasonal application rate for cotton, but none of
the treatment plots closely reflect the proposed use pattern. 

The 3.8 lb/gal Mcap formulation used in the field trials contains a
safener.  The petitioner noted that the safener included in the product
is not effective in cotton, and stated that the new Mcap formulations of
acetochlor being developed for commercial use will not contain a
safener.

Samples of mature cotton undelinted seed were harvested using
commercial-type equipment [picker (7 trials) or stripper (4 trials)] or
handheld clippers (2 trials) 64-154 days after the last treatment. 
Cotton gin byproducts were collected from ginning of undelinted seed in
seven of the trials.  Additional seed and gin byproduct samples were
collected from 1 trial (stripper cotton) 6 days prior to normal
maturity, and 7 and 15 days after normal maturity to investigate 
residue decline.

Samples of cotton undelinted seed and gin byproducts were analyzed for
residues of acetochlor and its EMA- and HEMA-producing metabolites,
determined as the EMA and HEMA moieties, using an adequate LC/MS/MS
Method, method ES-ME-1215-01.  Combined LOQs for total acetochlor were
<0.010 ppm for undelinted seed and 0.0735 ppm for gin byproducts. 
Sample storage intervals and conditions are presented in Table 4. 
Adequate storage stability data are available to support the study.

The results of the cotton field trials are presented in Table 6. 
Following postemergence application of the Mcap formulation to cotton
7-15 days after the first white flower at 2.95-3.07 lb ai/A (Treatment
plot #2), maximum total residues of acetochlor (determined as the sum of
EMA- and HEMA-producing metabolites, expressed in acetochlor
equivalents) were 0.408 ppm in/on undelinted seed and 2.501 ppm in/on
gin byproducts harvested 64-133 DAT.  

Following postemergence application of the Mcap formulation to cotton at
the 7- to 8-leaf growth stage at 2.96-3.12 lb ai/A (Treatment plot #4),
maximum total residues of acetochlor were 0.106 ppm in/on undelinted
seed and 0.392 ppm in/on gin byproducts harvested 100-154 DAT.  

Following split applications of the Mcap formulation (preplant
application made 26-32 days prior to planting and a subsequent
postemergence application to cotton at the 7- to 8-leaf growth stage)
for a total rate of 2.97-3.04 lb ai/A (Treatment plot #6), maximum total
residues of acetochlor were 0.070 ppm in/on undelinted seed and 0.290
ppm in/on gin byproducts harvested 100-154 days after the last
application.

As might be expected, the highest residues were observed in samples from
plants treated at a later growth stage with a single postemergence
application made ~15 days after the first white flower at 3.0 lb ai/A.

The results of the decline trial (Treatment plot #2) indicate that total
acetochlor residues generally declined from the early sampling interval
to target harvest; at subsequent sampling intervals, residues in/on seed
did not increase, but residues in gin byproducts increased slightly.  

Table 6.	Summary of Residue Data from Crop Field Trials with Acetochlor.

Crop Matrix	Total Applic. Rate

 (lb ai/A)	PHI

(days)	Total Acetochlor Residue Levels 

(Acetochlor EMA+HEMA Producing Metabolites, ppm) 1



	n	Min.	Max.	HAFT 2	Median

(STMdR)	Mean

(STMR)	Std.

 Dev.

COTTON (proposed use = 3.0 lb ai/A total application rate; 30-day
preplant and/or postemergence application made up to 15 days after first
white flower, each at 1.5 lb ai/A; no PHI specified)

Treatment Plot #2:  Postemergence 7-15 days after First White Flower

Cotton, undelinted seed	2.95-3.07	64-133	26	0.012	0.408	0.366	0.144
0.171	0.121

Cotton, gin byproducts	2.95-3.04	64-86	14	0.272	2.501	2.481	1.822	1.636
0.718

Treatment Plot #4:  Postemergence at the 7- to 8-leaf growth stage

Cotton, undelinted seed	2.96-3.12	100-154	26	<0.010	0.106	0.086	0.016
0.024	0.022

Cotton, gin byproducts	2.98-3.12	100-122	14	<0.074	0.392	0.391	0.130
0.182	0.119

Treatment Plot #6:  26-32 Days Preplant + Postemergence at the 7- to
8-leaf growth stage

Cotton, undelinted seed	2.97-3.04	100-154	26	<0.010	0.070	0.063	0.010
0.016	0.014

Cotton, gin byproducts	2.97-3.04	100-122	14	<0.074	0.290	0.285	0.082
0.138	0.084

1  The data reflect LOQs of 0.010 ppm for undelinted seed and 0.074 ppm
for gin byproducts.

2  HAFT = Highest Average Field Trial.

Conclusions.  The submitted cotton field trial data are adequate to
fulfill data requirements in support of the proposed use on cotton.  The
number and locations of the trials are in accordance with OPPTS
Guideline 860.1500 for cotton, and ample data were submitted for cotton
gin byproducts reflecting harvest by stripper equipment.  Samples were
analyzed for residues of acetochlor and its EMA- and HEMA-type
metabolites using an acceptable method, and the study is supported by
adequate storage stability data.  

≤1.5 lb ai/A/application).  Treatment plot #6 reflects split
applications at 1.5 lb ai/A/application, but postemergence application
was made at an earlier growth stage.  Treatment plot #2 reflects
postemergence application at the appropriate growth stage, but the
single application was made at 2x the maximum proposed postemergence
application rate.  

HED prefers that field trial use patterns more closely reflect the
proposed use pattern; however,  for purposes of the subject petition HED
concludes that the use pattern employed in Treatment plot #2 may be
considered to represent a worst-case scenario for cotton and thus
adequately supports the proposed use pattern for cotton.  

The available field trial data for Treatment plot #2 will support the
proposed tolerances of 0.6 ppm for cotton undelinted seed and 4.0 ppm
for cotton gin byproducts; refer to Appendix I for the tolerance
calculation.

Soybean

Monsanto has submitted field trial data for acetochlor on soybean. 
Twenty-one trials were conducted in the United States in Zones 2 (NC,
SC; 2 trials), 4 (AR, LA; 3 trials), and 5 (IA, IL, IN, MN, MO, NE, OH;
16 trials) during the 2007 growing season.  The soybeans used in the
trials were commercially available glyphosate-tolerant varieties.  

At each test location, an untreated plot and multiple treated plots were
established.  At one treatment plot (Treatment plot #2) a single
postemergence broadcast foliar application of a 3.8 lb/gal Mcap
formulation was made at a target rate of 3.0 lb ai/A to soybeans at the
R1-R2 growth stage (beginning flower to full flower).  At a second plot
(Treatment plot #5), split applications of the 3.8 lb/gal Mcap
formulation were made reflecting a preplant application to the soil made
43-46 days prior to planting and two postemergence broadcast foliar
applications to soybeans at the V3 (trifoliate leaves at three nodes)
and R1-R2 growth stages; applications were made at target rates of 1.0
lb ai/A/application for a total application rate of 3.0 lb ai/A.  RTIs
were 65-88 days between preplant and first postemergence applications,
and 12-40 days between the two postemergence applications.  Applications
were made using ground equipment in 12-20 gal/A spray volumes; an
adjuvant was not used.  Additional plots at each site were treated with
the 3.8 lb/gal Mcap formulation and/or a 7 lb/gal EC formulation of
acetochlor at different application rates and timings, but samples from
these plots were not analyzed and therefore are not further discussed
herein.  

The application rates used in the soybean field trials correspond to 1x
the maximum proposed seasonal application rate for soybean, but none of
the treatment plots closely reflect the proposed use pattern. 

The 3.8 lb/gal Mcap formulation used in the field trials contains a
safener.  The petitioner noted that the safener included in the product
is not effective in soybeans, and stated that the new Mcap formulations
of acetochlor being developed for commercial use will not contain a
safener.

	

Samples of soybean forage were harvested 6-8 days after the last
application (DALA), hay was harvested when the pods were ~50% developed,
12-40 DALA, and mature soybean seed was harvested 73-103 DALA; hay
samples were dried in the field for 1-7 days after harvest.  Additional
samples of forage, hay, and seed were collected from two trials ~7 days
prior to normal harvest, and ~7 and ~14 days after normal harvest to
investigate residue decline.

Samples of soybean forage, hay, and seed were analyzed for residues of
acetochlor and its EMA- and HEMA-producing metabolites, determined as
the EMA and HEMA moieties, using an adequate LC/MS/MS Method, method
ES-ME-1215-01.  Residues are expressed in acetochlor equivalents. 
Combined LOQs for total acetochlor were 0.114 ppm for forage, 0.309 ppm
for hay, and 0.012 ppm for seed.  Sample storage intervals and
conditions are presented in Table 4.  Adequate storage stability data
are available to support the study. 

The results of the soybean field trials are presented in Table 7. 
Following a single postemergence application of the 3.8 lb/gal Mcap
formulation to soybean plants at the R1-R2 growth stage at 2.97-3.12 lb
ai/A (Treatment plot #2), maximum residues of acetochlor (determined as
the sum of EMA- and HEMA-producing metabolites, expressed in acetochlor
equivalents) were 96.59 ppm in/on forage, 130.9 ppm in/on hay, and 1.058
ppm in/on seed.  

Following split applications of the 3.8 lb/gal Mcap formulation
(preplant application made 43-46 days prior to planting and two
subsequent postemergence applications to soybeans at the V3 and the
R1-R2 growth stages) for a total rate of 2.94-3.08 lb ai/A (Treatment
plot #5), maximum residues of acetochlor were 36.26 ppm in/on forage,
42.33 ppm in/on hay, and 0.465 ppm in/on seed.

As might be expected, the highest residues were observed in samples from
plants treated with a single postemergence application at the R1-R2
stage.  

The results of the two decline trials (Treatment plot #2) indicate that
total acetochlor residues generally declined in forage and hay at later
sampling intervals; residues in/on seed remained the same or declined
slightly over the sampling period.

Table 7.	Summary of Residue Data from Crop Field Trials with Acetochlor.

Crop Matrix	Total Applic. Rate

 (lb ai/A)	PHI

(days)	Total Acetochlor Residue Levels 

(Acetochlor EMA+HEMA Producing Metabolites, ppm) 1



	n	Min.	Max.	HAFT 2	Median

(STMdR)	Mean

(STMR)	Std.

 Dev.

SOYBEAN (proposed use = 3.0 lb ai/A total application rate; 45-day
preplant and/or postemergence application made up to R1-R2 stage, each
at 1.5 lb ai/A; no PHI specified)

Treatment Plot #2:  Postemergence at the R1-R2 growth stages

Soybean forage	2.97-3.12	6-8	42	<0.560	96.59	94.45	57.11	56.62	23.97

Soybean hay

12-40	42	<0.783	130.9	129.3	42.10	53.13	35.01

Soybean seed

73-103	42	<0.012	1.058	0.999	0.196	0.265	0.228

Treatment Plot #5:  43-46 Days Preplant + Postemergence at the V3 growth
stage + Postemergence at the R1-R2 growth stages

Soybean forage	2.94-3.08	6-8	42	<0.254	36.26	35.98	16.48	17.63	8.14

Soybean hay

12-40	42	<0.309	42.33	42.08	15.64	18.41	11.18

Soybean seed

73-103	42	<0.012	0.465	0.451	0.102	0.118	0.099

1  The data reflect combined LOQs of 0.012 ppm for seed, 0.114 ppm for
forage, and 0.309 ppm for hay.

2  HAFT = Highest Average Field Trial.

Conclusions.  The submitted soybean field trial data are adequate to
fulfill data requirements in support of the proposed use on soybean. 
The number and locations of the trials are in accordance with OPPTS
Guideline 860.1500 for soybean.  Samples were analyzed for residues of
acetochlor and its EMA- and HEMA-type metabolites using an acceptable
method, and the study is supported by adequate storage stability data.  

No residue data were submitted for soybean aspirated grain fractions;
however, no data are required because postemergence application may only
be made up to the R1-R2 growth stages, prior to pod formation.

on made up to the R1-R2 growth stages, each at ≤1.5 lb
ai/A/application).  Treatment plot #5 reflects split applications with a
postemergence application at the proper growth stage; however, two
postemergence applications were used, and all applications were made at
0.7x the maximum proposed application rate for pre- and postemergence
applications.  Treatment plot #2 reflects postemergence application at
the appropriate growth stage, but the single application was made at 2x
the maximum proposed postemergence application rate.

HED prefers that field trial use patterns more closely reflect the
proposed use pattern; however,  for purposes of the subject petition HED
concludes that the use pattern employed in Treatment plot #2 may be
considered to represent a worst-case scenario for soybean and thus
adequately supports the proposed use pattern for soybean.  

The available field trial data for Treatment plot #2 will support the
proposed tolerance of 1.0 ppm for soybean seed; refer to Appendix II for
the tolerance calculation.  

The proposed label prohibits the grazing/feeding of treated forage. 
Provided the petitioner revises the proposed label to prohibit the
grazing or feeding of treated soybean forage and hay, tolerances for
soybean forage and hay are not needed in association with direct
application of acetochlor to soybean.

860.1520 Processed Food and Feed

DER References:  47552201.de2.doc (Cotton)

		 47555601.de2.doc (Soybean)

Cotton

Monsanto has submitted a processing study for acetochlor on cotton seed.
 In a single trial conducted in TX, split applications were made
reflecting a preplant application of a 7.0 lb/gal EC formulation to the
soil 29 days prior to planting at 1.48 lb ai/A, and a postemergence
application of a 3.8 lb ai/gal Mcap formulation to cotton plants 15 days
after the first white flower at 7.93 lb ai/A for a total application
rate of 9.41 lb ai/A (~3x the maximum proposed seasonal application rate
for cotton).  The RTI was 122 days.  Applications were made using ground
equipment in 15-17 gal/A spray volumes; an adjuvant was not used.  Bulk
samples of cotton undelinted seed were harvested using picker equipment
84 days after the last treatment.  Cotton seed was processed into hulls,
meal, and refined oil using simulated industrial practices.

Samples of cotton undelinted seed and its processed commodities were
analyzed for residues of acetochlor and its EMA- and HEMA-producing
metabolites, determined as the EMA and HEMA moieties, using an adequate
LC/MS/MS Method, method ES-ME-1215-01.  Residues are expressed in
acetochlor equivalents.  The combined LOQ for total acetochlor in cotton
seed was <0.010 ppm; the LOQ for seed was used by the petitioner for the
processed commodities.  Sample storage intervals and conditions are
presented in Table 4.  Adequate storage stability data are available to
support the study.

The processing factors for cotton are presented in Table 8.  Following a
preplant application of the 7 lb/gal EC formulation and a subsequent
postemergence application of the 3.8 lb/gal Mcap formulation for a total
rate of 9.41 lb ai/A, average total acetochlor residues (determined as
the sum of EMA- and HEMA-producing metabolites, expressed in acetochlor
equivalents) were 0.0476 ppm in/on cotton undelinted seed (RAC). 
Following processing, total acetochlor residues were 0.0137 ppm in
hulls, 0.0213 ppm in meal, and 0.0035 ppm in refined oil.  Based on the
results of the processing study, residues of acetochlor do not appear to
concentrate in hulls (0.3x processing factor), meal (0.4x), and refined
oil (0.1x).

The observed processing factors are lower than the theoretical
concentration factors for cotton (860.1520, Table 3; based on separation
of components) of 3.8x for hulls, 2.2x for meal, and 6.3x for oil. 

Soybean

Monsanto has submitted a processing study for acetochlor on soybean
seed.  In a single trial conducted in IL, a postemergence foliar
broadcast application of a 3.8 lb ai/gal Mcap formulation of acetochlor
was made to soybean plants at the R1-R2 growth stage (beginning flower
to full flower) at 8.0 lb ai/A (2.7x the maximum proposed seasonal
application rate for soybean).  Application was made using ground
equipment in a 14 gal/A spray volume; an adjuvant was not used.  The
soybean plants used in the trial were a commercially available
glyphosate-tolerant variety.  Bulk samples of soybean seed were
harvested 91 days after application.  Soybean seed was processed into
hulls, meal, and refined oil using simulated commercial practices.

Samples of soybean seed and its processed commodities were analyzed for
residues of acetochlor and its EMA- and HEMA-producing metabolites,
determined as the EMA and HEMA moieties, using an adequate LC/MS/MS
Method, method ES-ME-1215-01.  Residues are expressed in acetochlor
equivalents.  The combined LOQ for total acetochlor in soybean seed was
0.012 ppm; the LOQ for seed was used by the petitioner for the processed
matrices.   Sample storage intervals and conditions are presented in
Table 4.  Adequate storage stability data are available to support the
study. 

The processing factors for soybean are presented in Table 8.  Following
a postemergence foliar application of a 3.8 lb ai/gal Mcap formulation
of acetochlor made to soybeans at the R1-R2 growth stage at 7.99 lb
ai/A, average total acetochlor residues (determined as the sum of EMA-
and HEMA-producing metabolites, expressed in acetochlor equivalents)
were 1.178 ppm in/on soybean seed (RAC).  Following processing, total
acetochlor residues were 0.850 ppm in hulls, 1.428 ppm in meal, and
0.128 ppm in refined oil.  Based on the results of the processing study,
residues of acetochlor do not appear to concentrate in hulls (0.7x
processing factor) and refined oil (0.1x), but may concentrate slightly
in meal (1.2x).

The observed processing factors are lower than the theoretical
concentration factors for soybean (860.1520, Table 3; based on
separation of components) of 11.3x for hulls, 2.2x for meal, and 12.0x
for oil. 

  SEQ CHAPTER \h \r 1 Table 8.	Summary of Processing Factors for
Acetochlor.

RAC	Processed Commodity	Processing Factor

Cotton seed	Hulls	0.3x

	Meal	0.4x

	Refined oil	0.1x

Soybean seed	Hulls	0.7x

	Meal	1.2x

	Refined oil	0.1x



Conclusions.  The processing studies for cotton and soybean are
adequate.  Samples were analyzed for residues of acetochlor and its EMA-
and HEMA-type metabolites using an acceptable method, and the studies
are supported by adequate storage stability data.

The data indicate that residues of acetochlor and its EMA- and HEMA-type
metabolites are unlikely to concentrate in cotton hulls, meal, and
refined oil, or in soybean hulls and refined oil.  Residues may
concentrate slightly in soybean meal (1.2x).  

No tolerances are required for cotton hulls, meal, and refined oil, or
for soybean hulls and refined oil.  Based on the HAFT for soybean seed
(0.999 ppm) and a 1.2x concentration factor, expected residues in
soybean meal would be 1.20 ppm, which exceeds the recommended tolerance
for soybean seed.  Therefore, a tolerance for soybean meal should be
proposed at 1.2 ppm.

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

Analytical standards for acetochlor and its EMA and HEMA metabolites are
currently available in the EPA National Pesticide Standards Repository
(personal communication with Dallas Wright, ACB, 4/22/09), with
expiration dates of 5/31/2009, 5/31/2010, and 7/31/2010, respectively. 
Since the standard for acetochlor will expire 5/31/2009, the registrant
must either recertify the lot in the repository and send in an updated
certificate of analysis (COA), or submit new standards (different lot #)
if the previous lots will not be recertified.  

If new COAs are being submitted, they should be faxed to the repository
at 410-305-2999.  If new standards are being submitted, they should be
sent to the Analytical Chemistry Lab, which is located at Fort Meade, to
the attention of either Theresa Cole or Thuy Ngygen 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 Chapter of the TRED, DP# 297062, 5/31/05, S. Ary

The requirement for confined accumulation in rotational crops is
satisfied.  Following an application of 14C-acetochlor to a sandy loam
soil at 3.0 lb ai/A (1x the maximum proposed seasonal application rate
for cotton and soybean), TRR were >0.01 ppm in all commodities of
lettuce, radish, and wheat that were planted 30, 120, and 365 DAT, with
14C-residues generally being the highest at the 120-day plant back
interval (PBI).  Acetochlor was detected only in radish foliage from one
interval (120-DAT) accounting for 4% of the TRR (0.03 ppm).  A total of
17 metabolites were identified in rotational crops, including 12
EMA-producing metabolites, 3 HEMA-producing metabolites, and 2
HMEA-producing metabolites.  In each commodity, the acetochlor EMA
producing metabolites were present at the highest concentrations,
followed by the acetochlor HEMA- and acetochlor HMEA-type metabolites,
respectively.  Metabolism in the rotational crops was similar to corn
except that acetochlor HMEA-type metabolites were not observed in corn,
and acetochlor Metabolite 57 was not observed in rotational crops.

Based on the above results and the data from extensive rotational crop
field trials HED has concluded that tolerances for rotational crops
should be expressed as acetochlor and its EMA- and HEMA-producing
metabolites.  Residues of acetochlor HMEA-containing metabolites,
expressed in acetochlor equivalents, should not be included in the
tolerance expression, but will be used for purposes of risk assessment.

860.1900 Field Accumulation in Rotational Crops

DP# 275019, 6/20/06, D. Davis (PP#s 6F4791 & 1F6263)

Residue Chemistry Chapter of the TRED, DP# 297062, 5/31/05, S. Ary

The requirements for field accumulation in rotational crops are
satisfied.  The available extensive rotational crop field trials
conducted at 3.0 lb ai/A (1x the maximum proposed seasonal application
rate for cotton and soybean) are adequate and support the PBIs specified
on the product labels and the tolerances for indirect or inadvertent
residues of acetochlor in/on the commodities of nongrass animal feeds;
sugar beets; cereal grains except corn, sorghum, rice, and wheat; dried
shelled peas and beans; potatoes; soybeans; sunflower seed; and wheat.  

The plantback restrictions on the proposed MON 63410 Herbicide label
(Mcap formulation) are the same as those established in association with
corn and sorghum uses, which were based on the available extensive
rotational crop field trial data.

The plantback restrictions on the proposed MON 8435 Herbicide label (EC
formulation) are more restrictive than those on the MON 63410 Herbicide
label.

Conclusions.  Because the proposed uses on cotton and soybean do not
exceed the maximum registered seasonal rate for acetochlor, the proposed
PBIs and established rotational crop tolerances remain appropriate.  

860.1550 Proposed Tolerances

The Agency previously determined that the residues of concern for
tolerance enforcement in primary and rotational crops include parent and
any metabolites containing the EMA or HEMA moiety, expressed in
acetochlor equivalents.  The tolerance expressions under 40 CFR
§180.470(a) and (d) are expressed in terms of acetochlor and its
metabolites containing the EMA moiety and the HEMA moiety, to be
analyzed as acetochlor and expressed as acetochlor equivalents.

There are currently no Codex or Canadian MRLs; a Mexican MRL is
established for residues of acetochlor per se, as “acetoclor” in/on
corn (maize) at 0.04 ppm.

Adequate field trial data sufficiently representative of the proposed
use patterns were submitted for cotton and soybean.  The Agency’s
Guidance for Setting Tolerances Based on Field Trial Data, along with
the tolerance spreadsheet, were used to establish the tolerances on
cotton seed and gin byproducts, and soybean seed, and are presented in
Appendix II.  The available data will support the proposed tolerances of
0.6 ppm for cotton undelinted seed, 4.0 ppm for cotton gin byproducts,
and 1.0 ppm for soybean seed.

Pending amendment of the proposed label to restrict feeding of forage
and hay, no tolerances will be required for soybean forage and hay in
association with direct application of acetochlor to soybean.  No data
or tolerances are required for soybean aspirated grain fractions because
postemergence application may only be made up to the R1-R2 growth
stages, prior to pod formation.

The cotton and soybean processing studies are adequate and indicate that
no tolerances are required for cotton hulls, meal, and refined oil, or
for soybean hulls and refined oil; however, a tolerance for soybean meal
must be proposed at 1.2 ppm.

Based on re-examination of the available feeding study data for
livestock and the MRDBs for ruminants and swine, it appears that there
is potential for accumulation of residues of acetochlor in the tissues
of ruminant and swine.  There remains no reasonable expectation of
finite residues occurring in poultry commodities [40 CFR §180.6(a)(3)]
as a result of feeding acetochlor-treated cotton and soybean feedstuffs.
 

Because the proposed uses on cotton and soybean will not affect the
maximum seasonal rate for acetochlor, the established rotational crop
tolerances remain appropriate with the proposed PBIs.  Concurrent with
the establishment of the tolerance for soybean seed under 180.470(a),
the established tolerance for indirect or inadvertent residues in
soybean seed under 180.470(d) should be removed.

The proposed tolerances should be revised to reflect the recommended
tolerance levels as specified in Table 9.  

Table 9. 	Tolerance Summary for Acetochlor.

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

180.470(a)

Cotton, undelinted seed	0.6	0.6

	Cotton, gin byproducts	4.0	4.0

	Soybean, seed	1.0	1.0

	Soybean, meal	--	1.2

	180.470(d)

Soybean, seed	0.1	Remove	Indirect residues will be covered under the
soybean seed tolerance from direct application to the crop.



References

DP#:	None

Subject:	PP #3G2797 and PP #2G2726.  Acetochlor in milk, eggs, and
tissues of livestock.  Evaluation of analytical method and residue data
including amendment of December 2, 1982 submitted in connection with PP
#2G2726.

From:	S. Malak

To:	R. Taylor and Toxicology Branch

Dated:	6/6/83

MRIDs:	Not listed

DP#:	156740

Subject:	PP#3F2966/1G2454 (CBTS #’s 7118, 7119, 7120, and 7121). 
Acetochlor on Corn, Corn Products, Meat, Milk, Poultry, and Eggs. 
Amendment dated 9/20/90.

From:	N. Dodd

To:	R. Taylor and Toxicology Branch

Dated:	4/29/91

MRIDs:	41633601, 41633500, and 41633501

DP#:	None

Subject:	Acetochlor.  Metabolism in Corn, Rotated Crops, Animals. 
Issues to be Presented to the HED Metabolism Committee on 9/15/93.

From:	M. Flood

To:	Metabolism Committee, HED

Dated:	9/15/93

MRID:		None

DP#:	297062

Subject:	Acetochlor.  Summary of Analytical Chemistry and Residue Data
for the Tolerance Reassessment Eligibility Decision (TRED) Document.

From:	S. Ary

To:	A. Protzel and R. Louie

Dated:	5/31/05

MRID:		None

DP#:	275019

Subject:	Acetochlor.  Petitions for Tolerances on Sweet Corn and
Rotational Crops of Nongrass Animal Feeds (Group 18), Sugar Beets, Dried
Shelled Beans and Peas (Subgroup 6C), Sunflowers, Potatoes, Cereal
Grains (Group 15), and Forage, Fodder, and Straw of Cereal Grains (Group
16).  Summary of Analytical Chemistry and Residue Data.  Petition
Numbers:  6F4791 and 1F6263.

From:	D. Davis

To:	V. Walters/J. Tompkins

Dated:	6/20/06

MRID:		44107101-07, 45322102-12, 45483301

DP#:	349273

Subject:	Acetochlor.  Petition for Increased Tolerances for Field Corn
Forage and Stover to Support Amended Use on Field Corn.  Summary of
Analytical Chemistry and Residue Data.  PP#7F7306.

From:	D. Davis

To:	V. Walters/J. Tompkins

Dated:	5/13/08

MRID:		47310901

  SEQ CHAPTER \h \r 1 Attachments:  

International Residue Limit Status sheet

Appendix I - Chemical Name and Structure Table

Appendix II - Tolerance Assessment Calculations

Template Version September 2005



INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 2-chloro N-(ethoxymethyl)-N-(2
ethyl-6-methylphenyl)-acetamide	Common Name:  Acetochlor

	( Proposed tolerance

( Reevaluated tolerance

( Other	Date:  6/22/2009

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:  8F7443, 8E7448

DP#:  359990, 359992, 359994,  359996, and 363293 	

Other Identifier:  

Residue definition (step 8/CXL): N/A	Reviewer/Branch:   S. Hummel, RAB4

	Residue definition:  Acetochlor and its metabolites containing the
ethyl methyl aniline (EMA) moiety and the hydroxyethyl methyl aniline
(HEMA) moiety, to be analyzed as acetochlor and expressed as acetochlor
equivalents

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



Cotton seed



	Soybeans

















Limits for Canada	Limits for Mexico

X No Limits

( No Limits for the crops requested	(  No Limits

X No Limits for the crops requested

Residue definition:  N/A

	Residue definition: acetoclor

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



Corn (maize)	0.04





















Notes/Special Instructions:

S. Funk, 06/16/2009





APPENDIX I.	Chemical Names and Structures of Acetochlor and
Metabolites.1

Company Code	Chemical name	Chemical structure1

#3	Acetochlor glucosylsulfate conjugate of hydroxy sec-methylsulfone
metabolite	

#4	Acetochlor-tert-malonylcysteine metabolite	

#5	Acetochlor-tert-malonylcysteine sulfoxide metabolite	

#6	Acetochlor tert-sulfinylacetic acid metabolite	

#7	Acetochlor sec-malonylcysteine conjugate 	

#8	Acetochlor sec-cysteine conjugate 	

#9	Acetochlor sec-thiolactic acid metabolite	

#10	Acetochlor malonyl conjugate of sec-thiolactic acid 	

#11	Acetochlor 1-hydroxyethyl sec-thiolactic 	acid metabolite	

#12	Acetochlor  glucose conjugate of sec-thiolactic acid 	

#13	Acetochlor sec-malonylcysteine sulfoxide metabolite	

#14	Acetochlor sec-sulfinyllactic acid metabolite	

#15	Acetochlor  5-hydroxy sec-sulfinyllactic acid  metabolite	

#16	Acetochlor sec-sulfinyllactic acid glucose conjugate 	

#17	Acetochlor 1-hydroxyethyl sec-sulfinyllactic acid metabolite	

#18	Acetochlor sec-sulfinylacetic acid metabolite	

#19	Acetochlor sec-sulfonic acid metabolite	

#20		Acetochlor sec-hydroxy glycosylsulfate conjugate 	

#21	Acetochlor glucose conjugate of hydroxyl sec-methylsulfone 	

#22	Acetochlor  glucosylsulfate conjugate of hydroxy tert-sulfinyllactic
acid 	

#23	Acetochlor  glucosylsulfate conjugate of hydroxy tert-thiolactic
acid 	

#24	Acetochlor  glucosylsulfate conjugate of 1-hydroxyethyl
sec-thiolactic acid 	

1  Structures were copied without alteration from MRID 47695701.

Appendix II.  Tolerance Assessment Calculations.

For each of the crops listed below, the Guidance for Setting Pesticide
Tolerances Based on Field Trial Data (SOP), along with the tolerance
spreadsheet (January 2008 version), was used for calculating recommended
tolerances.  As specified in the SOP, the minimum of the 95% upper
confidence limit (UCL) on the 95th percentile and the point estimate of
the 99th percentile was selected as the tolerance value in cases when
the dataset was large (greater than 15 samples) and reasonably
lognormal.  For datasets that were small (≤15 samples) and reasonably
lognormal, the upper bound estimate of the 95th percentile based on the
median residue value was compared to the minimum of the 95% UCL on the
95th percentile and the point estimate of the 99th percentile, and the
minimum value was selected as the tolerance value.  For datasets that
were not lognormal, the upper bound on the 89th percentile was selected
as the tolerance value (distribution-free method).  The rounding
procedures specified in the SOP were also used.

Cotton

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@er stage) with a 64- to 133-day PHI for seed and 64- to 86-day PHI for
gin byproducts.  The field trial application rates (and timing) are
within 25% of the maximum label application rate; no PHI is proposed. 
The residue values that were entered into the tolerance spreadsheet are
provided in Table II-1.

All field trial sample results for acetochlor and its EMA- and HEMA-type
metabolites in/on cotton seed and gin byproducts were above the combined
LOQs for acetochlor of 0.010 ppm for seed and 0.074 ppm for gin
byproducts.  The gin byproduct dataset was small (14 samples), while the
seed dataset was large (26 samples).  Visual inspection of the lognormal
probability plots (Figures II-1 and II-3) and the results from the
approximate Shapiro-Francia test statistic (Figures II-2 and II-4)
indicated that the assumption of lognormality should be rejected for
both cotton seed and gin byproducts.  

Using the tolerance spreadsheet, the recommended tolerances are 0.6 ppm
for cotton, undelinted seed and 4.0 ppm for cotton, gin byproducts.

Table II-1.	Residue data used to calculate tolerance for combined
residues of acetochlor and its EMA- and HEMA-type metabolites on cotton.

Regulator:	EPA

Chemical:	Acetochlor

Crop:	Cotton, undelinted seed	Cotton, gin byproducts

PHI:	64-133 days	64-85 days

App. Rate:	2.95-3.07 lb ai/A	2.95-3.04 lb ai/A

Submitter:	Monsanto Company	Monsanto Company

MRID Citation:	MRID 47552201	MRID 47552201

	Combined residues of Acetochlor, EMA metabolites, and HEMA metabolites,
as acetochlor equivalents (ppm)

	0.020	1.616

	0.022	1.946

	0.120	1.415

	0.219	1.926

	0.210	0.272

	0.375	0.370

	0.040	1.018

	0.050	1.181

	0.012	2.069

	0.015	2.473

	0.091	2.461

	0.106	2.501

	0.133	1.717

	0.172	1.937

	0.100



0.102



0.129



0.154



0.235



0.279



0.207



0.305



0.227



0.398



0.323



0.408

	

Figure II-1.  Lognormal probability plot of acetochlor field trial data
for cotton undelinted seed.

Figure II-2.  Tolerance spreadsheet summary of acetochlor field trial
data for cotton undelinted seed.

Figure II-3.  Lognormal probability plot of acetochlor field trial data
for cotton gin byproducts.

Figure II-4.  Tolerance spreadsheet summary of acetochlor field trial
data for cotton gin byproducts.

Soybean

The dataset used to establish a tolerance for acetochlor on soybean seed
consisted of field trial data representing application rates of
2.97-3.12 lb ai/A (one postemergence application at the R1-R2 growth
stage) with a 73- to 103-day PHI.  The field trial application rates
(and timing) are within 25% of the maximum label application rate; no
PHI is proposed.  The residue values that were entered into the
tolerance spreadsheet are provided in Table II-2.

All field trial sample results for acetochlor and EMA- and HEMA-type
metabolites in/on soybean seed were above the combined LOQ for
acetochlor of 0.012 ppm for all but 2 of the 42 samples.  The dataset
was large (42 samples).  Visual inspection of the lognormal probability
plot (Figure II-5) and the results from the approximate Shapiro-Francia
test statistic (Figure II-6) indicated that the assumption of
lognormality should be rejected for soybean seed.  

Using the tolerance spreadsheet, the recommended tolerance is 1.0 ppm
for soybean seed.

Table II-2.	Residue data used to calculate tolerance for combined
residues of acetochlor and its EMA- and HEMA-type metabolites on
soybean.

Regulator:	EPA

Chemical:	Acetochlor

Crop:	Soybean seed

PHI:	73-103 days

App. Rate:	2.97-3.12 lb ai/A

Submitter:	Monsanto Company

MRID Citation:	MRID 47555601

	Combined residues of Acetochlor, its EMA metabolites, and HEMA
metabolites, as acetochlor equivalents (ppm)1

	0.136

	0.138

	0.656

	0.694

	0.245

	0.249

	0.481

	0.599

	0.381

	0.386

	0.940

	1.058

	0.215

	0.240

	0.268

	0.275

	0.295

	0.331

	0.169

	0.176

	0.123

	0.123

	0.079

	0.083

	0.050

	0.051

	0.098

	0.137

	0.284

	0.309

	0.224

	0.239

	0.012

	0.012

	0.133

	0.163

	0.163

	0.241

	0.176

	0.177

	0.155

	0.155

1Italicized values are <LOQ.

Figure II-5.  Lognormal probability plot of acetochlor field trial data
for soybean seed.

Figure II-6.  Tolerance spreadsheet summary of acetochlor field trial
data for soybean seed.

Page   PAGE  1  of   NUMPAGES  44 

Acetochlor                          Summary of Analytical Chemistry and
Residue Data	DP#s:  359990, 359992, 359994, 

359996, and 363293 

