Document ID: EPA-HQ-OPP-2007-0301-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-03-11T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

Date:	  	01/06/2009

Subject:		Chlorimuron-Ethyl.  Petition for Tolerances on Cranberry,
Bearberry, Bilberry, Lowbush Blueberry, Cloudberry, Lingonberry,
Muntries and Partridgeberry (Lowgrowing Berry Subgroup 13-07H, Except
Strawberry).  Summary of Analytical Chemistry and Residue Data.  

PC Code:  128901	DP Barcodes:  D335807, 346842

Decision Nos.:  372736	Registration No.:  352-436

Petition Nos.:  6E7153	Regulatory Action:  Section 3

Risk Assessment Type:  NA	Case No.:  NA

TXR No.:  NA	CAS No.:  90982-32-4

MRID Nos.:  47004901, 43483707 	40 CFR:  180.429

FROM:	Anant Parmar, Biologist  	  SEQ CHAPTER \h \r 1 

		Registration Action Branch II

		Health Effects Division (7509P)

THROUGH:	Michael A. Doherty, Ph.D., Chemist

		Richard Loranger, Ph.D., Senior Scientist

	Registration Action Branch II

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

			

TO:		Daniel Rosenblatt/Sidney Jackson/Barbara Madden, RIMUERB

		Registration Division (7505P)

This document was originally prepared under contract by Dynamac
Corporation (1910 Sedwick Road, Building 100, Suite B, Durham, NC 27713;
submitted 1/07/2008).  The document has been reviewed by the Health
Effects Division (HED) and revised to reflect current Office of
Pesticide Programs (OPP) policies.

Executive Summary

Chlorimuron-ethyl [ethyl
2-(4-chloro-6-methoxypyrimidin-2-ylcarbamoylsulfamoyl)

benzoate] is a sulfonylurea herbicide registered for use on peanuts and
soybeans in the U.S. for  the postemergence control of broadleaf weeds
and yellow nutsedge.  Chlorimuron-ethyl is formulated as a
water-dispersible granular formulation (WDG) at concentrations ranging
from 8.3-31.8% a.i., with end-use products registered to FMC Corporation
(2 products), E.I. du Pont de Nemours and Co. (DuPont; 12 products), and
Valent U.S.A. Corporation (2 products).

In the current petition, Interregional Research Project No. 4 (IR-4) is
proposing use of a 25% WDG formulation of chlorimuron-ethyl (DuPont
Classic® Herbicide; EPA Reg. No. 352-436) on members of the low-growing
berry subgroup (13-07H) for postemergence control of various broadleaf
weeds and yellow nutsedge.  The proposed use is for a single broadcast
foliar application at up to 0.0156 lb ai/A during fruit development. 
Applications can be made using only ground equipment in a minimum of 15
gal/A, and the directions allow for the use of a non-ionic surfactant
(NIS) as a adjuvant at up to 0.25% of the spray volume.  The proposed
preharvest interval (PHI) is 60 days.  In conjunction with this use,
IR-4 is proposing permanent tolerances for chlorimuron-ethyl on the
following members of the low-growing berry subgroup, except strawberry
(subgroup 13-07H):

Bearberry	0.02 ppm

Bilberry	0.02 ppm

Blueberry, lowbush	0.02 ppm

Cloudberry	0.02 ppm

Cranberry	0.02 ppm

Lingonberry	0.02 ppm

Muntries	0.02 ppm

Partridgeberry	0.02 ppm 

Tolerances have been established for residues of chlorimuron-ethyl in/on
peanuts and soybeans at 0.02 ppm and 0.05 ppm, respectively [40 CFR
§180.429].  The nature of chlorimuron-ethyl residues in plants is
adequately understood for purposes of this petition.  Studies are
available on peanuts, soybeans, and corn.  For peanuts, the data
indicated a lack of significant translocation of the active ingredient
in nutmeats or hulls.  For soybeans, only parent chlorimuron-ethyl was
observed.  For corn, the data indicated a lack of significant
translocation of the active ingredient in grain.  Based on these
findings and the status of the requested commodities as minor crops, the
requirement for an additional metabolism study on a fruit crop is being
waived for purposes of this petition.  The residue of concern is
chlorimuron-ethyl per se.  

As the crop uses being proposed in this petition do not include any
regulated livestock feedstuffs, issues pertaining to livestock
metabolism, analytical methods and storage stability data for animal
commodities, and residues in livestock commodities are not relevant to
the current petition.

Adequate HPLC methods are available for enforcing the current tolerances
on soybeans and peanuts; however, these methods have not been validated
using crop matrices similar to berries.  Typically, an independent
laboratory validation (ILV) trial should be conducted to determine if
either of these methods is adequate for enforcing the proposed
tolerances.  In lieu of the cranberry ILV, IR-4 has now submitted
sufficient information for HED to conclude that the rice analytical
method is a viable surrogate for the cranberry ILV trial.  The HPLC
method used in the cranberry field trial is adequate for enforcing the
proposed tolerance on berries of the low-growing berries subgroup,
except strawberry (subgroup 13-07H).

An adequate HPLC/photoconductivity method was used for collecting data
on residues of chlorimuron-ethyl in/on cranberry samples.  For this
method, residues were extracted with 0.1 M aqueous phosphate buffer,
adjusted to pH 5, and cleaned up by elution through C18 extraction disc
and partitioning into dichloromethane.  Residues were then determined by
normal-phase HPLC using a silica column with an isocratic mobile phase
and a photoconductivity detector.  The statistically calculated limits
of quantitation and detection (LOQ and LOD) were 0.0084 and 0.0028 ppm,
respectively.  The lowest level of method validation (LLMV) was 0.020
ppm.

Frozen storage stability data for chlorimuron-ethyl in cranberries at
-20°C were submitted along with the cranberry field trial data.  These
data indicate that chlorimuron-ethyl declined by 34% in cranberries over
24.5 months of frozen storage (↓1.39% per month).  However, the
storage stability data are not fully acceptable as no 0-day analysis was
conducted on the fortified samples prior to storage.  For purposes of
this petition, HED will use the available data to correct the cranberry
residue data for potential declines of 1.39% per month during frozen
storage.

Adequate field trial data are available supporting the proposed use on
cranberry, which is the representative crop for the low-growing berry
subgroup, except strawberry.  Following a single broadcast foliar
application of chlorimuron-ethyl (WDG) at 1x the proposed rate,
uncorrected residues chlorimuron-ethyl were non-detectable (<0.0028 ppm)
in/on all samples of cranberries harvested at 57-63 days after treatment
(DAT).  Even if residue values are corrected to account for a potential
37% decline during frozen storage, the resulting residues (<0.0044 ppm)
are below the LOQ as well as the validated method LLMV (0.02 ppm), which
is also the proposed tolerance.

As there are no regulated processed commodities associated with this
crop subgroup, no processing data are required for this petition.  In
addition, no data pertaining to rotational crops are required for this
petition as members of this crop subgroup are not rotated.

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

Deficiencies were noted in the submitted data pertaining to plant
metabolism, enforcement analytical methods, and storage stability (see
below).  However, sufficient data are available to allow for the
establishment of permanent tolerances for chlorimuron-ethyl on
low-growing berries, except strawberry.

	•	Plant metabolism studies have only been conducted on soybeans,
peanuts, and corn which are not similar to the proposed use on
low-growing berries.  Typically, a new metabolism study would be
required; however, as the proposed uses are for minor crops and residues
are expected to be low (<LOQ), no additional plant metabolism data are
required for this petition.  The residue of concern is chlorimuron-ethyl
per se.

	•	Adequate HPLC methods are available for enforcing the current
tolerances on soybeans and peanuts; however, these methods have not been
validated using crop matrices similar to berries.  Typically, an
independent laboratory validation (ILV) trial should be conducted to
determine if either of these methods is adequate for enforcing the
proposed tolerances.  In lieu of the cranberry ILV, IR-4 has now
submitted sufficient information for HED to conclude that the rice
analytical method is a viable surrogate for the cranberry ILV trial. 
The HPLC method used in the cranberry field trials is adequate for
enforcing the proposed tolerance on berries of the low-growing berries
subgroup, except strawberry (subgroup 13-07H).

	•	The submitted storage stability data are not fully acceptable as no
0-day analysis was conducted on the fortified sample prior to frozen
storage.  However, for purposes of this petition, HED will use the
available data to correct the cranberry residue data for potential
declines of 1.39% per month during frozen storage.

	

	•	The petitioner should provide confirmatory data for the corn
metabolism study verifying that the majority of the immature samples
were initially analyzed within ~6 months of harvest.  This information
may be provided in a future tolerance petition.

HED recommends for establishing a permanent tolerance for residues of
chlorimuron-ethyl at 0.02 ppm in/on Berry, lowgrowing, subgroup 13-07H,
except strawberry.  A separate tolerance for each member of the subgroup
is not necessary as the proposed revisions to the berry crop group have
been finalized (72 FR 69150, 12/7/2007).  A human health risk assessment
for chlorimuron-ethyl is forthcoming.

Background

Chlorimuron-ethyl is a sulfonylurea herbicide registered for use on
peanuts and soybeans in the U.S. for the postemergence control of
broadleaf weeds and yellow nutsedge.  It is formulated as a WDG at
8.3-31.8% ai.  For peanuts, chlorimuron-ethyl may be applied as a
postemergence broadcast, banded or low volume application at up to
0.0117 lb ai/A/season.  For soybeans, chlorimuron-ethyl may be applied
early-preplant, preplant, postplant, preemergence, postemergence, or
postharvest as either a broadcast, banded or low volume application at
up to 0.01172-0.0803 lb ai/A/season.  The PHIs are 45 days for peanuts
and 60 days for soybean.

IR-4 has submitted a petition (PP#6E7153) supporting the use of
chlorimuron-ethyl on low-growing berries, except strawberry (subgroup
13-07H), for the postemergence control of various broadleaf weeds and
yellow nutsedge.  The nomenclature and physicochemical properties of
chlorimuron-ethyl are presented below in Tables 1 and 2.

Table 1.	Chlorimuron-Ethyl Nomenclature.

Compound	

Common name	Chlorimuron-ethyl

Company experimental name	DPX-F6025

IUPAC name	ethyl 2-(4-chloro-6-methoxypyrimidin-2- ylcarbamoylsulfamoyl)
benzoate

CAS name	ethyl
2-[[[[(4-chloro-6-methoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]
benzoate

CAS registry number	90982-32-4

End-use product (EP)	25% WDG; DuPont CLASSIC® Herbicide (EPA Reg. No.
352-436)

Table 2.	Physicochemical Properties of Chlorimuron-Ethyl.

Parameter	Value	Reference

Melting point/range	181°C	PP#3G2959; 1/10/84; S. Creeger

pH	4.4

	Density	1.51 g/ml

	Water solubility (mg/L)	pH 1.3 = 1.5

pH 1.9 = 1.5

pH 2.5 = 1.5

pH 4.2 = 4.1

pH 5.0 = 9.0

pH 5.8 = 99

pH 6.5 = 450

pH 7.0 = 1200

	Solvent solubility (mg/100 mL at 25°C)	Acetone = 7.05

Acetonitrile = 3.10

Benzene = 0.815

Ethyl Acetate = 2.36

Ethyl Alcohol = 0.392

n-Hexane = 0.006

Methyl Alcohol = 0.740

Methylene Chloride = 15.3

Xylene = 0.283

	Vapor pressure (25°C)	1.5 x 10-5 mm Hg 

	Dissociation constant, pKa (25°C)	4.2

	Octanol/water partition coefficient, Log(KOW)	1.3

	UV/visible absorption spectrum	Not available

	

860.1200  Directions for Use

There are currently 16 end-use products containing chlorimuron-ethyl
registered in the U.S.  These products are all WDG formulations
containing 8.3-31.8% of chlorimuron-ethyl.  Two products are registered
to FMC Corporation, 12 products are registered to DuPont, and 2 products
are registered to Valent U.S.A. Corporation.

IR-4 is proposing use of a 25% WDG formulation of chlorimuron-ethyl
(Classic® Herbicide; EPA Reg. No. 352-436) on members of the
low-growing berry subgroup (13-07H) for postemergence control of various
broadleaf weeds and yellow nutsedge.  This formulation is currently
registered to DuPont for use on soybeans, peanuts and noncrop areas.  An
example supplemental label for this formulation was provided, and the
proposed use directions are summarized below in Table 3.

Table 3.	Summary of Proposed Directions for Use of Chlorimuron-Ethyl.

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

Low-growing Berry Subgroup 13-07H, except Strawberry 

(including cranberry, bearberry, bilberry, lowbush blueberry,
cloudberry, ligonberry muntries and partridgeberry)

Broadcast foliar application during late spring after bloom; Ground
equipment only	25% WDG

[352-436]	0.0156	1	0.0156	60	Include a non-ionic surfactant at 0.25%.

Apply in a minimum of 15 gal/A

Conclusions.  The proposed use directions are adequate and are supported
by available field trial data.

860.1300 Nature of the Residue - Plants

DP# 301317, R. Griffin, 8/31/2004

DER Reference:	43483707.der.doc (Corn)

IR-4 submitted a corn metabolism study with the current petition.  The
most recent risk assessment summarized soybean and peanut metabolism
studies (D301317, R. Griffin, 8/31/2004).  Studies on soybean and peanut
were previously determined to be acceptable.  

In the corn metabolism study, corn (maize) was treated with
[14C-phenyl]chlorimuron-ethyl and [14C-pyrimidine]chlorimuron-ethyl at a
target rate of 0.315 lb ai/A (5 oz ai/A).  Two treatment regimes were
established, reflecting a single preemergence application (soil surface
spray after planting) or postemergence application (foliar broadcast
spray to plants at the 3-leaf growth stage) to greenhouse-grown corn.  

Corn plants were harvested 28, 44, 89, and 196 days after preemergence
treatment and 0, 10, 20, 41, and 164 days after postemergence treatment;
samples of mature plants (196-day and 164-day samples) were separated
into grain and mature forage (shoots, leaves, husks, and cob after
removal of grain).  

Total radioactive residues (TRR) were similar between the two labels for
each treatment type.  Overall, TRR were low in grain ((0.01 ppm) and
mature forage ((0.09 ppm), and higher in immature plants.  As expected,
higher TRR were observed in immature plants following postemergence
treatment ((61.1 ppm); whereas as the highest TRR observed in immature
plants following preemergence treatment was ((0.489 ppm).  Results of
the corn metabolism study are summarized in Tables 4, 5, 6, and 7.

TABLE 4.	Summary of Characterization and Identification of Radioactive
Residues in Corn Matrices Following Preemergence Application of
[14C-phenyl]Chlorimuron-ethyl at 0.315 lb ai/A.  

Metabolite Fraction	Immature Plant

(28 DAT)	Immature Plant

(44 DAT)	Immature Plant

(89 DAT)	Mature Forage

(196 DAT)

	TRR = 0.461 ppm	TRR = 0.219 ppm	TRR = 0.439 ppm	TRR = 0.090 ppm

	%TRR	ppm	%TRR	ppm	%TRR	ppm	%TRR	ppm

IN-B4450	33.3	0.153	25.5	0.056	6.9	0.03	1.4	0.001

Conjugated IN-B4450	--	--	--	--	45.4	0.198	--	--

IN-L9130	3.6	0.016	2.2	0.005	4.5	0.019	--	--

Unidentified metabolites	20.2	0.093	6.8	0.015	2.3	0.01	--	--

Polar metabolites	39.1	0.18	42.0	0.091	15.9	0.070	55.3	0.05

Acid hydrolysate; aqueous soluble	--	--	--	--	15.6	0.069	--	--

ACN/water extract	--	--	17	0.037	--	--	--	--

EDTA	--	--	--	--	--	--	7.2	0.006

Methanol reflux	--	--	--	--	--	--	8.9	0.008

0.1 M NaOH	--	--	--	--	--	--	8.2	0.007

0.1 M HCl	--	--	--	--	--	--	2.5	0.002

0.1 M HCl reflux	--	--	--	--	--	--	7.2	0.006

Total identified	36.9	0.169	27.7	0.061	56.8	0.247	1.4	0.001

Total characterized	59.3	0.273	65.8	0.143	33.8	0.149	89.3	0.079

Total extractable	98	0.451	96	0.209	93	0.406	91	0.081

Unextractable (PES)1	2	0.010	5	0.010	7	0.033	6.3	0.006

Accountability2	100	100	100	97

TABLE 5.	Summary of Characterization and Identification of Radioactive
Residues in Corn Matrices Following Preemergence Application of
[14C-pyrimidine]Chlorimuron-ethyl at 0.315 lb ai/A.  

Metabolite Fraction	Immature Plant

(28 DAT)	Immature Plant

(44 DAT)	Immature Plant

(89 DAT)	Mature Forage

(196 DAT)

	TRR = 0.489 ppm	TRR = 0.311 ppm	TRR = 0.400 ppm	TRR = 0.078 ppm

	%TRR	ppm	%TRR	ppm	%TRR	ppm	%TRR	ppm

IN-N6186	11.1	0.054	10.4	0.032	5.2	0.021	2.1	0.002

Conjugated IN-N6186	--	--	--	--	24.6	0.098	--	--

IN-L9130	5.5	0.027	0.9	0.003	3.7	0.015	--	--

Unidentified metabolites	23.1	0.113	2.6	0.008	8.3	0.033	--	--

Polar metabolites	54.6	0.266	51.9	0.162	14.4	0.058	46.4	0.036

Acid hydrolysate; aqueous soluble	--	--	--	--	28.6	0.114	--	--

ACN/water extract	--	--	18	0.055	--	--	--	--

EDTA	--	--	--	--	--	--	3.6	0.003

Methanol reflux	--	--	--	--	--	--	7.4	0.006

0.1 M NaOH	--	--	--	--	--	--	3.1	0.002

0.1 M HCl	--	--	--	--	--	--	1.6	0.001

0.1 M HCl reflux	--	--	--	--	--	--	9.2	0.007

Total identified	16.6	0.081	11.3	0.035	33.5	0.134	2.1	0.002

Total characterized	77.7	0.379	72.5	0.225	51.3	0.205	71.3	0.055

Total extractable	96	0.468	91	0.283	90	0.360	75.9	0.059

Unextractable (PES)1	4	0.021	9	0.028	10	0.040	14.4	0.011

Accountability2	100	100	100	90

TABLE 6.	Summary of Characterization and Identification of Radioactive
Residues in Corn Matrices Following Postemergence Application of
[14C-phenyl]Chlorimuron-ethyl at 0.311 lb ai/A.  

Metabolite Fraction	Immature Plant

(0 DAT)	Immature Plant

(10 DAT)	Immature Plant

(20 DAT)	Immature Plant

(41 DAT)

	TRR = 59.3 ppm	TRR = 50.8 ppm	TRR = 35.0 ppm	TRR = 36.0 ppm

	%TRR	ppm	%TRR	ppm	%TRR	ppm	%TRR	ppm

Chlorimuron-ethyl	88.2	52.29	91.4	46.73	90.4	31.58	77.8	28.09

IN-B4450	--	--	6.0	3.03	3.4	1.19	3.5	1.25

IN-L9130	--	--	--	--	--	--	1.8	0.64

Unidentified metabolites	9.3	5.5	--	--	5.2	1.82	6.3	2.27

Polar metabolites	--	--	0.6	0.37	--	--	8.5	3.07

Total identified	88.2	52.29	97.4	49.76	93.8	32.77	83.1	29.98

Total characterized	9.3	5.5	0.6	0.37	5.2	1.82	14.8	5.34

Total extractable	99.8	59.2	99.6	50.6	99	34.6	98	35.4

Unextractable (PES)1	0.2	0.12	0.4	0.18	1	0.47	2	0.64

Accountability2	100	100	100	100

TABLE 7.	Summary of Characterization and Identification of Radioactive
Residues in Corn Matrices Following Postemergence Application of
[14C-pyrimidine]Chlorimuron-ethyl at 0.315 lb ai/A.  

Metabolite Fraction	Immature Plant

(0 DAT)	Immature Plant

(10 DAT)	Immature Plant

(20 DAT)	Immature Plant

(41 DAT)

	TRR = 43.4 ppm	TRR = 61.1 ppm	TRR = 23.5 ppm	TRR = 19.4 ppm

	%TRR	ppm	%TRR	ppm	%TRR	ppm	%TRR	ppm

Chlorimuron-ethyl	88.0	38.21	89.4	54.35	66.6	15.62	75.3	14.58

IN-N6186	--	--	6.9	4.18	9.8	2.30	2.7	0.53

IN-L9130	--	--	1.0	1.6	--	--	--	--

Unidentified metabolites	10.3	4.48	0.2	0.12	7.0	1.63	6.2	1.2

Polar metabolites	--	--	0.9	0.53	7.6	1.79	9.9	1.93

Total identified	88.0	38.21	97.3	60.13	76.4	17.92	78.0	15.11

Total characterized	10.3	4.48	1.1	0.65	14.6	3.42	16.1	3.13

Total extractable	99.7	43.3	99.3	60.7	99	23.2	95	18.4

Unextractable (PES)1	0.3	0.12	0.7	0.42	1	0.31	5	0.97

Accountability2	100	100	100	100

0.007 ppm) from grain and in mature forage treated postemergence,
extraction with ACN/water released 56-92% TRR (~0.01 ppm);
nonextractable residues for these matrices were ≤0.008 ppm.  The
extraction and hydrolysis procedures adequately extracted the majority
of residues from corn matrices.  Because extraction results were
normalized for immature corn plants, accountabilities were 100%;
accountabilities for mature forage treated preemergence, reflecting
additional hydrolysis procedures, were ~90-97%.

Sample extraction and analysis dates were not provided; however, based
on the harvest and experimental end dates, immature plant samples may
have been stored frozen for up to 7.6 months, and mature grain and
forage samples may have been stored for up to 2.1 months prior to
completion of analysis.  The metabolite profile in immature plants was
similar by treatment for both labels across the various sampling
interval.  Provided the petitioner submits the dates of sample
extraction and analysis to confirm that the majority of the immature
samples were initially analyzed within ~6 months of harvest, no
supporting storage stability data are required for the study. 

Approximately 11-57% TRR was identified in immature plants treated
preemergence, and 76-97% TRR was identified in immature plants treated
postemergence.  In mature forage treated preemergence, 1-2% TRR was
identified.  The metabolite profiles were similar for the two labels by
treatment, except that a different cleavage product was observed for
each label:  IN-B4450 (sulfonamide) for the phenyl label and IN-N6186
(pyrimidine amide) for the pyrimidine label.  

Residues were quantified by HPLC and/or TLC; HPLC quantification data
were summarized by the petitioner.  The petitioner reported that
identification of metabolites was confirmed by HPLC and TLC
co-chromatography with reference standards; however, representative
chromatograms reflecting co-chromatography were not provided.

Chlorimuron-ethyl was not detected in immature plants or mature forage
treated preemergence, but was the major identified residue in immature
plants (both labels) treated postemergence, at 88% TRR in 0-DAT samples,
89-91% TRR in 10-DAT samples, 67-90% TRR in 20-DAT samples, and 75-78%
TRR in 41-DAT samples.  The metabolite 4-hydroxy-chlorimuron-ethyl
(IN-L9130) was identified as a minor residue in immature plants treated
preemergence (28, 44, and 89 DAT; <6% TRR) and postemergence (10 and 41
DAT, <2% TRR).  

The cleavage products IN-B4450 and IN-N6186 were both significant
metabolites.  Following application of phenyl-labeled chlorimuron-ethyl,
IN-B4450 was a major residue in preemergence 28- and 44-DAT immature
plants (33.3% and 25.5% TRR, respectively), and a minor residue in
preemergence 89-DAT immature plants (6.9% TRR) and mature forage (1.4%
TRR); in postemergence 10-, 20-, and 41-DAT immature plants, residues
were 3.4-6% TRR.  In addition, conjugated IN-B4450 (released with acid
hydrolysis) accounted for 45.4% TRR in preemergence 89-DAT immature
plants.  Following application of pyrimidine-labeled chlorimuron-ethyl,
IN-N6186 was a major residue in preemergence 28- and 44-DAT immature
plants (11.1% and 10.4% TRR, respectively), and a minor residue in
preemergence 89-DAT immature plants (5.2% TRR) and mature forage (2.1%
TRR); in postemergence 10-, 20-, and 41-DAT immature plants, residues
were 2.7-9.8% TRR.  Conjugated IN-N6186 (released with acid hydrolysis)
accounted for 24.6% TRR in preemergence 89-DAT immature plants.

Based on the corn metabolism study, the petitioner concluded that the
overall metabolic pathway involves cleavage of the sulfonylurea linkage
to yield the corresponding sulfonamide and pyrimidine amine, and
hydroxylation of the parent to yield 4-hydroxy-chlorimuron-ethyl.  The
fate of chlorimuron-ethyl was consistent in both pre- and postemergence
treatments.  The petitioner stated that the study results were similar
to those of the peanut and soybean metabolism studies which were
previously reviewed (PP#8F3694; DEB# 4691, 2/7/89, H. Fonouni; and
PP#5F3186; 12/16/85, C. Deyrup).

The proposed metabolic pathway for chlorimuron-ethyl in corn is
presented in Figure 1, which was copied without alteration from MRID
43483707.

FIGURE 1. 	Proposed Metabolic Profile of Chlorimuron-ethyl in Corn.

	

The most recent risk assessment summarized soybean and peanut metabolism
studies ((D301317, R. Griffin, 8/31/2004).  These studies included tests
in which [14C phenyl]chlorimuron-ethyl or
[14C-pyrimidine-2]chlorimuron-ethyl was applied to soybean and peanut. 
Studies on soybean and peanut were previously determined to be
acceptable.  

Soybean plants in the first to third trifoliate leaf stage were sprayed
with [14C-phenyl] or [14C-pyrimidine-2]chlorimuron-ethyl at a rate of
0.031 lbs ai/A (2x rate).  Plants were sampled on 0, 19, and 35 DAT and
mature beans were harvested at 103 DAT.  Only parent compound
chlorimuron-ethyl was observed in the plant wash (94-100%).  Growth
chamber studies were also submitted in which cut soybean plants were
immersed in solutions of [14C]chlorimuron-ethyl for several hours to 2
days.  These studies resulted in the identification of the following
metabolites: chlorimuron-ethyl homoglutathione conjugate,
chlorimuron-ethyl acid, pyrimidine amine, desmethyl pyrimidine amine,
and saccharin.  Considering the low level of residues in/on mature
soybeans expected from the use on soybeans (6-7 metabolites equivalent
to a total of <0.02 ppm chlorimuron-ethyl), HED did not require further
work to identify the metabolites comprising the terminal radioactive
residues.

In a greenhouse metabolism study, peanuts were treated with [14C-phenyl]
and [2-14C-pyrimidine]chlorimuron-ethyl at 0.031 lb ai/A (4x rate), 60
days prior to harvest.  The data indicated a lack of significant
translocation of the active ingredient.  Less than 1% of the total
radioactive residues (extractable and unextractable) were found in
either nutmeats or hulls, and over 99% of the radioactivity was present
in vines at harvest.  The total radioactive residues were found to be
about 0.02 and 0.05 ppm in nutmeat and hulls, respectively.  The
extractable residues in nut meats are between 51-63% whereas those in
the corresponding hulls are 54-75%.  The identified metabolites
constitute <15-28% and 29-33% of the total radioactive residues in
peanut nutmeats and hulls, respectively.  The residue of concern in both
soybeans and peanuts is chlorimuron-ethyl per se.

Conclusions.  As cranberries are a fresh acidic fruit and
chlorimuron-ethyl is applied to the crop when the berries are present,
HED would not typically consider the metabolism data on soybeans,
peanuts, and corn to be representative of berries.  However, because the
proposed uses are on minor crops (low-growing berries) and the harvest
interval (60 days) is similar to the minimum harvest intervals for
soybean and peanuts, HED will not require a new metabolism study for
this petition.  For purpose of this petition only, the residue of
concern in/on berries is chlorimuron-ethyl per se.

For the corn metabolism study the petitioner should provide the dates of
sample extraction and analysis to confirm that the majority of the
immature samples were initially analyzed within ~6 months of harvest. 
Confirmatory data should be submitted to validate that these samples
were analyzed within ~6 months of harvest.  This information may be
provided in a future tolerance petition.

860.1300 Nature of the Residue - Livestock

There are no livestock feedstuffs associated with the proposed use on
low-growing berries.  Therefore, data requirements for livestock
metabolism are not relevant to this tolerance petition. 

860.1340 Residue Analytical Methods

HED previously identified and addressed the following analytical method
deficiencies given below in the review of the current petition (DP#
346842, A. Parmar, 3/12/2007) and (E-Mail Communication, A. Parmar to B.
Madden 7/01/2008).

Proposed Enforcement Methods Deficiency 

DP# 346842, A. Parmar, 3/12/2007

Deficiency:  The petition states that there is an adequate enforcement
method.  However, though the current enforcement method is adequate for
soybeans and peanuts; there has been no testing to ensure the method is
adequate for chlorimuron-ethyl in cranberries.  Since the cranberry data
collection method is very different from the current enforcement method,
the EPA cannot conclude that the enforcement method would be likely to
be sufficient for cranberry (and other berries).  Since there's no
metabolism study with cranberry, radiovalidation data cannot be
generated.  Data where cranberry samples were analyzed using the
proposed (existing) enforcement method, to determine if it would be
adequate should be provided.

Petitioner’s Response:  The registrant has recently submitted
analytical method AMR 3210-94 Entitled: Analytical Method (Column
Switching/Heart Cut) For the Determination of Residues of
Chlorimuron-ethyl (DPX-F6025) and Metsulfuron Methyl (DPX-T6376) in Rice
Grain (MRID# 47263901).  This method includes the extraction procedure
used in study 03023 chlorimuron-ethyl: Magnitude of the Residue in
Cranberry and this method would now be considered the enforcement method
for cranberry (MRID# 47004901).  Since the concurrent recoveries were
satisfactory (average recovery was above 80%), the method was
demonstrated to be adequate for cranberry.

HED’s Conclusion:  Until the petitioner submits an independent lab
validation of the proposed plant enforcement method or can demonstrate
that the existing enforcement method provides satisfactory performance
on cranberries, HED cannot conclude this deficiency is resolved.

E-Mail Communication, A. Parmar to B. Madden, 7/01/2008

Petitioner’s Follow-up Response:  IR-4 provided a rationale supporting
a waiver of the ILV.  During IR-4 communications with the Analytical
Chemistry Branch (ACB) (C. Stafford) it was agreed that the rice
analytical method trial would be a viable surrogate for the cranberry
ILV.

HED’s Follow-up Conclusion:  IR-4 has now submitted sufficient
information for HED to conclude that the rice analytical method is a
viable surrogate for the cranberry ILV trial.  ACB agrees that in lieu
of a cranberry ILV, the review of the cranberry method and rice method
can together serve as the primary method plus ILV data (Personal
Communications C. Stafford to R. Loranger).  After further consideration
and extensive consultation with ACB, HED will accept the rice analytical
method as a surrogate for the cranberry analytical method ILV based on
the following:

ACB feels that given the aqueous solubilities of sulfonylureas, the
aqueous extraction is likely to be adequate.

The methods employ similar extraction procedures, solvents, and
equipment.

The methods were performed at separate labs belonging to DuPont & IR-4. 

Both methods resulted in adequate recoveries with similar recovery
efficiencies.  The cranberry method validation recovery was 82% with a
standard deviation of 3%.  The rice method validation recovery was 75%
with a standard deviation of 8% (Table 8).

TABLE 8.	Summary of Recoveries of Chlorimuron-Ethyl from Fortified
Cranberry and Rice Samples.

Matrix	Spike Level

(ppm)	Sample Size

(n)	Recoveries

(%)	Mean ± Std. Dev.

(%)

Method validation

Cranberries	0.02	3	81, 77, 87	82  ± 5

	0.2	3	82, 83, 81	82 ± 1

	Total	6	77-87	82 ± 3

Concurrent Recovery

Cranberries	0.02	8	84, 81, 82, 81, 77, 87, 80, 75	81 ± 4

Method validation

Rice	0.02	7	57, 82, 83, 85, 59*, 79, 65	73 ± 12

	0.04	7	78, 75, 76, 80, 75*, 82, 70 	77 ± 3.9

	0.10	7	74, 69, 85, 80, 81*, 80, 67	77 ± 6.7

	Total	21	57-85	75 ± 8.1

* net % recoveries are: (ppm found fortified sample - ppm found control
sample)

Current Enforcement Methods

Two HPLC methods are available for enforcing tolerances of
chlorimuron-ethyl in soybeans and peanuts. The original enforcement
method for soybeans (AMR-459-85) is found in Pesticide Analytical Manual
(PAM) Volume II.  For this method, residues are extracted with
dichloromethane, filtered, diluted with water, and concentrated to an
aqueous remainder.  The aqueous fraction is partitioned against hexane,
discarding the hexane phase, and residues are then partitioned into
dichloromethane and cleaned up using a silica gel cartridge.  Residues
are concentrated to dryness and redissolved in HPLC mobile phase
(hexane/isopropanol/methanol /glacial acetic acid/water;
750:125:125:2:1).  Residues are then determined by HPLC using a
photoconductivity detector.  The method LOQ is 0.01 ppm.

An HPLC/UV method is also available for peanuts (AMR-990-87).  This
method differs slightly from the above method primarily in the use of
different solvents for the sample preparation step.  The method LOQ is
0.02 ppm for peanut nutmeat and 0.05 ppm for peanut hulls.

Neither current enforcement method has been validated using a crop
matrix similar to berries.

Data Collection Method Deficiency

DP# 346842, A. Parmar, 3/12/2007

Deficiency:  The petition states that the data collection method is
adequate to conclude the submitted field trial data support the proposed
tolerances.  However, the aqueous extraction method used in the analysis
of the cranberry field trial samples is untested.

Further, there is no record of the EPA having received the extraction
method cited in the study report (DuPont method AMR 3210-94 for rice).

Petitioner’s Response:  With respect to responses given above for the
proposed enforcement method, we feel that the existing information
should address this concern.

HED’s Conclusion:  The registrant has submitted the DuPont method AMR
3210-94 containing the aqueous extraction method employed in the
cranberry field trial.  The aqueous extraction method has been tested in
rice, and demonstrated adequate recoveries.  HED considers this
deficiency resolved.

Data Collection Method Review

47004901.der (cranberry)

Samples from the cranberry field trials were analyzed for
chlorimuron-ethyl using an HPLC/photoconductivity method that was
derived from two other methods.  Samples were extracted and purified
using procedures from “Analytical Method (Column Switching/Heart Cut)
for the Determination of Residues of Chlorimuron-ethyl (DPX-F6025) and
Metasulfuron Methyl (DPX-T6376) in Rice Grain, DuPont Report No. AMD
3210-94”.  Residues were then quantified using procedures from
“Analysis of Chlorimuron-ethyl in Crops by High Performance Liquid
Chromatography”.

For this method, cranberry samples were extracted with 0.1 M phosphate
buffer, centrifuged, adjusted to pH 5, and filtered.  The filtrate was
then eluted through an EMPORE ™ C18 extraction disk, which retained
the chlorimuron-ethyl.  Residues were eluted from the C18 disk with
ethyl acetate, concentrated to dryness, and redissolved in 0.03 M
phosphate buffer (pH 5).  Residues were next partitioned into
dichloromethane, concentrated to dryness and then redissolved in the
HPLC mobile phase (hexane/isopropanol/methanol, 80:10:10 (v/v/v), with
0.2% glacial acetic acid and 0.1% water).  Residues of chlorimuron-ethyl
were determined by normal-phase HPLC using a silica column with an
isocratic mobile phase and a photoconductivity detector.  The
statistically calculated LOQ and LOD were 0.0084 and 0.0028 ppm,
respectively.  The lowest level of method validation was 0.020 ppm.

The method was adequately validated in conjunction with the analysis of
field trial samples using control samples of cranberry fortified with
chlorimuron-ethyl at 0.02 and 0.2 ppm. 

Conclusions.  An adequate HPLC photoconductivity method was used for
data collection.  The validated LOQ for chlorimuron-ethyl residues in
berries is 0.02 ppm.  

860.1360 Multiresidue Methods

Multiresidue method testing data are available for chlorimuron-ethyl
(Pesticide Analytical Manual, Vol. I, Appendix I).  Chlorimuron-ethyl is
poorly recovered (<50%) through Method 302 and not recovered through
Method 303.

860.1380 Storage Stability

The petitioner cited data from earlier petitions from DuPont on soybeans
and corn indicating that chlorimuron-ethyl is stable at -20°C for up to
24 months in homogenized samples of soybeans and field corn grain,
forage and fodder.  

% over 24.5 months of storage (↓1.39% per month).  

In comparing the stability data from soybean and corn with the above
cranberry study, the petitioner noted that the instability of
chlorimuron-ethyl in cranberries during frozen storage may be
attributable to the acidic nature of the fruit.

The storage durations and conditions of samples from the cranberry field
trials submitted to support this petition are presented in Table 9.  

Table 9.	Summary of Storage Conditions and Durations of Samples from
Cranberry Field Trial Studies.  

Matrix 	Storage Temperature   (°C)	Actual Storage Duration (days)
Interval of Demonstrated Storage Stability (days)

Cranberry	-20	807-817	747 1

1	Chlorimuron-ethyl residues declined by 34% after 24.5 months of
storage at -20°C.

Conclusions.  As no 0-day analysis was conducted on the fortified
samples of cranberry prior to storage, the cranberry storage stability
study is not fully acceptable.  However, for purposes of this petition,
HED will use the available data to correct the cranberry residue data
for potential declines of 1.39% per month during frozen storage.

 

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

There are no livestock feedstuffs associated with the proposed use on
low-growing berries.  Therefore, data requirements pertaining to meat,
milk, poultry and eggs are not relevant to this tolerance petition.  

860.1500 Crop Field Trials

47004901.der (Cranberry)

IR-4 submitted cranberry field trial data supporting the proposed uses
of chlorimuron-ethyl (WDG) on low-growing berries, except strawberry. 
Cranberry is the representative crop for subgroup 13-07H.  The results
from these studies are discussed below and the residue data are
summarized in Table 10.

TABLE 10.	Summary of Residue Data from Crop Field Trials with
Chlorimuron-Ethyl (WDG).

Commodity	Total Applic. Rate

(lb ai/A)	PHI (days)	Residue Levels (ppm) 1,3

	n	Min.	Max.	HAFT 2	Median

(STMdR)	Mean

(STMR)	Std. Dev.

Cranberry	0.015-0.017	57-63	10	<0.0044	<0.0044	<0.0044	--	<0.0044	0

1	The calculated LOQ and LOD were 0.0084 and 0.0028 ppm, respectively. 
The LLMV was 0.02 ppm.

2	HAFT = Highest Average Field Trial.

3	The value of <0.0044 ppm was derived by correcting non-detectable
residues (<0.0028 ppm) for a potential storage stability declines of
37%.  Corrected Residue Value: 0.0044 ppm = 0.0028 ppm (LOD) / 37%
(Potential Storage Decline)

In 5 field trials conducted during 2001 in EPA Growing Regions 1, 5 and
12, a 25% water-dispersible granular (WDG) formulation of
chlorimuron-ethyl was applied to cranberries as a single broadcast
foliar application during fruit development at 0.015-0.017 lb ai/A. 
Applications were made using ground equipment in volumes of 20-22 gal/A,
and included the use of either a crop oil concentrate (COC) at 1.0% (1
test) or non-ionic surfactant (NIS) at 0.25% (4 tests).  Single control
and duplicate treated samples of mature cranberries were harvested from
each test at 57-63 days after treatment (DAT).

Samples were stored frozen (-20°C) for up to ~27 months prior to
extraction for analysis.  The available storage stability data indicate
that chlorimuron-ethyl residues can decline by 34% over 25 months for
frozen storage.  Therefore, residues in cranberry samples have been
corrected based on a decline of 1.39% per month of storage.

Residues in/on cranberries were determined using an
HPLC/photoconductivity detector method that was adequately validated
prior to an in conjunction with the analysis of field trial samples. 
The statistically calculated LOQ and LOD were 0.0084 and 0.0028 ppm,
respectively, and the LLMV was 0.020 ppm.

Following a single broadcast foliar application of chlorimuron-ethyl
(WDG) at a 1x rate, uncorrected residues of chlorimuron-ethyl were
non-detectable (<0.0028 ppm) in/on all 10 samples of cranberries
harvested at 57-63 DAT.  If residue values are corrected to account for
a potential 37% decline during frozen storage, the resulting residues
(<0.0044 ppm) are still well below the method LOQ (0.0084 ppm) and the
LLMV (0.02 ppm).

Conclusions.  The cranberry field trial data are adequate and support
the proposed use pattern for low-growing berries, except strawberry.  An
adequate number of tests were conducted in the appropriate geographical
regions, and samples were analyzed for residues of concern using an
adequate data collection method.  Although the available storage
stability data indicate that residues in/on cranberries should be
corrected for a potential decline of 37% during frozen storage, the
corrected residue data still indicate that residues in/on cranberries
would be well below the proposed 0.02 ppm tolerance.

860.1520 Processed Food and Feed

HED does not require residue data for any processed commodities
associated with low-growing berries.  Therefore, data requirements for
processed food and feed are not relevant to this tolerance petition.

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

An analytical standard for chlorimuron-ethyl is currently available in
the National Pesticide Standards Repository (T. Cole, personal
communication, 9/27/07).

860.1850-1900 Confined and Field Accumulation in Rotational Crops

Because low-growing berries are not rotated crops, no data pertaining to
rotational crops are required to support the proposed use.  

860.1550 Proposed Tolerances

For the registered uses on soybeans and peanuts, HED has concluded that
the residues of concern for tolerance expression and risk assessment
should include only chlorimuron-ethyl.  Tolerances are presently
established for residues of chlorimuron-ethyl at 0.02 and 0.05 ppm in/on
peanut and soybean seed, respectively [40 CFR §180.429(a)].  For
purposes of this petition on low-growing berries, HED will also consider
the parent compound to be the only residue of concern.

Residues of chlorimuron-ethyl were ND (<0.0028 ppm) on all samples of
cranberries harvested ~60 days (proposed PHI) after an application at a
1x rate.  Even if residues are corrected for potential decline during
storage, the maximum residues in/on cranberries (<0.0044 ppm) would
still be well below the validated method LOQ of 0.02 ppm.  Therefore,
the proposed 0.02 ppm tolerance is adequate.  Due to all residues being
non-quantifiable, the NAFTA harmonization spreadsheet was not used to
derive the recommended tolerance level.

IR-4 has proposed establishing separate tolerances at 0.02 ppm on the
members of the low-growing berries subgroup (except strawberry; subgroup
13H).  However, as the proposed revisions to the berry crop group have
been finalized (72 FR 69150, 12/7/2007), a separate tolerance for each
member of the subgroup is not necessary.  Provided the registration is
granted, a single tolerance should be established for residues of
chlorimuron-ethyl at 0.02 ppm in/on the low-growing berry subgroup
13-07H, except strawberry. 

  SEQ CHAPTER \h \r 1 No international harmonization issues are
associated with this petition, as there are no established or proposed
Canadian, Mexican or Codex MRLs for residues of chlorimuron-ethyl on the
proposed crops (Appendix I).

Table 11. 	Tolerance Summary for Chlorimuron-Ethyl.

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

Bearberry	0.02	0.02	Adequate data are available on the representative
crop of cranberry.  

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References

DP Number:	None

Subject:	PP#3G2959 

From:	S. Creeger

To:	not available

Dated:	1/10/1984

MRID(s):	not available

DP Number:	301317

Subject:	Chlorimuron-Ethyl.  Human Health Risk Assessment

From:	R. Griffin

To:	S. Sherman

Dated:	8/31/2004

MRID(s):	none

  SEQ CHAPTER \h \r 1 Attachments:  

Appendix I - International Tolerances

Appendix I - International Tolerances

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: ethyl
2-[[[[(4-chloro-6-methoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]
benzoate	Common Name:  Chlorimuron-ethyl	(  Proposed tolerance

 Reevaluated tolerance

 Other	Date: 1/03/08

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

( No Codex proposal step 6 or above

 No Codex proposal step 6 or above for the crops requested	Petition
Number:  6E7153

DP Number:  335807

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 No Limits

( No Limits for the crops requested	( No Limits

 No Limits for the crops requested

Residue definition: N/A	Residue definition: N/A

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

	Notes/Special Instructions:

Page   PAGE  1  of   NUMPAGES  19 

Chlorimuron-Ethyl	Summary of Analytical Chemistry and Residue Data	DP#: 
335807