Document ID: EPA-HQ-OPP-2011-0657-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-08-15T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF	

CHEMICAL SAFETY AND

POLLUTION PREVENTION

Date: 	December 6, 2011

MEMORANDUM

SUBJECT:	S-Metolachlor.  Petition for the Use on Coriander (Cilantro)
and Garden Beet Leaves.  Summary of Analytical Chemistry and Residue
Data.

 

PC Code:  108800	DP Barcode:  D392447

Decision No.:  451816	Registration No.: 100-816

Petition No.: 1E7898	Regulatory Action: Section 3

Risk Assessment Type: Single Chemical	Case No.: 0001

TXR No.:  NA	CAS No.: 87392-12-9

MRID No.:   48536501	40 CFR:  180.368

FROM:	W. Cutchin, Chemist

Alternative Risk Integration Assessment Team (ARIA)

Inert Ingredients Assessment Branch (IIAB)

Registration Division (RD; 7505P)

THROUGH:	S. Hummel, Senior Scientist

		Registration Action Branch 4 (RAB4)

		Health Effects Division (HED; 7509P)

TO:	D. Rate, Ph.D., Team Co-Leader

Section 18 Team

	Minor Use and Emergency Response Branch

		RD (7505P)

Executive Summary

Under PP#1E7898, the petitioner, Interregional Research Project No.4
(IR-4), on behalf of the Agricultural Experiment Station of the IR-4
Project and the Agricultural Experiment Stations of New York, North
Carolina and South Carolina (coriander (cilantro)); and California,
Oklahoma, Texas and Tennessee (beet, garden, leaves), request the
establishment of tolerances for residues of S-metolachlor, including its
metabolites and degradates, in or on the commodities in the table below.
 

Commodity	Proposed Tolerance

ppm

Cilantro, leaves, fresh	8.0

Cilantro, leaves, dried	8.0

Coriander, seed	0.13

Beet, garden, leaves	1.8

S-Metolachlor (an isomer enriched form of metolachlor) is a selective,
chloroacetanilide herbicide that is applied to a variety of crops as a
preplant, preplant incorporated, preemergence, or postemergence
application, primarily for the control of grass weeds.  S-Metolachlor is
registered for use on a wide variety of crops including: corn, cotton,
grasses grown for seed, legume vegetables, peanuts, potatoes, safflower,
sorghum, sunflower, and tomatoes (40 CFR:  180.368).  Compliance with
the tolerance levels specified below is to be determined by measuring
only the sum of free and bound S-metolachlor,
S-2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetami
de, its R-enantiomer, and its metabolites, determined as the derivatives
2-(2-ethyl-6-methylphenyl)amino-1-propanol (SYN506357 (S-enantiomer of
CGA 37913)) and
4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-morpholinone (SYN 508500
(S-enantiomer of CGA-49751)), calculated as the stoichiometric
equivalent of S-metolachlor, in or on the commodities.

S-metolachlor is to be applied to coriander (cilantro) as a broadcast,
foliar application at 0.64-0.96 lbs ai/A 30 days before the leaf harvest
and 70 days before seed.  Use the lower end of S-metolachlor rate range
for soils that are relatively coarse textured and the higher rates on
fine textured soils.  S-metolachlor is to be applied to beets grown for
leaves as a broadcast, pre-emergence soil surface treatment at 0.63
-1.26 lbs ai/A after the crop has been planted but before the crop and
weeds emerge.  A second application of S-metolachlor may be made to
beets as one post emergence, broadcast treatment at 0.63 -1.26 lbs ai/A
when plants are at 1 to 2 true leaf stage.  Use the lower end of
S-metolachlor rate range for soils that are relatively coarse textured
and the higher rates on fine textured soils.

The qualitative nature of metolachlor residues in plants is adequately
understood based upon the adequate corn, potato, and soybean metabolism
studies.  The metabolism of metolachlor involves conjugation with
glutathione, breakage of this bond to form the mercaptan, conjugation of
the mercaptan with glucuronic acid, O-demethylation of the methyl ether,
and conjugation of the resultant alcohol with a neutral sugar.  Residues
of concern in plants include metolachlor and its metabolites, determined
as the derivatives CGA-37913 and CGA-49751.  The Agency previously
concluded that the residues of concern for S-metolachlor are the same as
for metolachlor.

Adequate studies are available depicting the metabolism of metolachlor
in ruminants and poultry.  As in plants, metolachlor residues of concern
in livestock commodities include metolachlor and its metabolites,
determined as the derivatives CGA-37913 and CGA-49751.  The residues of
concern for S-metolachlor in livestock are the same as those for
metolachlor.

Adequate methodology is available for enforcing the established and
recommended tolerances.  PAM Vol. II, lists a gas chromatography with
nitrogen phosphorous detector (GC/NPD) method (Method I) for determining
residues in/on crop commodities and a gas chromatography with mass
spectroscopy detector (GC/MSD) method (Method II) for determining
residues in livestock commodities.  These methods determine residues of
metolachlor and its metabolites as either CGA-37913 or CGA-49751
following acid hydrolysis.  IR-4 and Syngenta have proposed a high
pressure liquid chromatography with mass spectroscopy/mass spectroscopy
(HPLC/MS/MS) enantiomer-specific method for the enforcement of the
proposed tolerances, Method 1848-01.  The method uses a chiral HPLC
column to separate out the S-enantiomers (SYN506357 and SYN508500) of
the hydrolysis products CGA-37913 and CGA-49751.  This method has been
determined to be adequate for enforcement purposes.

Adequate data are available on the recovery of metolachlor through
Multiresidue Method Testing Protocols.  The FDA PESTDATA database
indicates that metolachlor is completely recovered through Method 302,
PAM Vol. I.

Coriander (cilantro) fresh, dried and seed samples were analyzed using
the “Working Method for PR 09595: Analysis of s-Metolachlor in
Cilantro as Metabolites s-CGA-37913 (SYN-506357) and s-CGA-49751
(SYN-508500), A. Le, Document I.D. Working Method for
09595.06-BER06.doc, Effective Date: 04-18-08,” a modification of
Syngenta Method No. 1848-01.  Samples of the raw agricultural
commodities, leaves and stems, and seed were refluxed in acid and
partitioned into dichloromethane (DCM).  An aliquot was purified with
column chromatography and concentrated into aqueous acetonitrile.  The
lower limit of method validation (LLMV) for residues of SYN 506357 and
SYN 508500 was 0.05 ppm in all matrices.  Based on the LLMV, the
calculated limits of detection (LOD) ranged from 0.0132-0.0175 ppm for
SYN 506357 and SYN 508500 in coriander (cilantro) fresh, dried and seed
samples.  The calculated limits of quantitation (LOQ) ranged from
0.0359-0.0526 ppm for SYN 506357 and SYN 508500 in coriander (cilantro)
fresh, dried and seed samples, respectively.  The method is adequate for
data collection.

Previously submitted storage stability data indicates that the residues
of metolachlor are stable on a variety of commodities for up to 2 yrs. 
Coriander (cilantro) fresh leaves and stems, dried leaves and stems and
seed samples were stored frozen for a maximum of 708 days, 702 days, and
416 days, respectively.  The results of the storage stability study with
coriander (cilantro) samples and previously submitted storage stability
data are adequate to show that residues of S-metolachlor were stable for
the duration of this study.

There are no proposed uses in water, fish, irrigated crops and food
handling establishments; therefore, discussions of S-metolachlor
residues on these topics are not are germane to this petition.

There are no coriander (cilantro) or garden beet leaf livestock feed
items of regulatory interest; therefore, a discussion of S-metolachlor
residues on livestock food items is not germane to this petition.

The submitted study is adequate in number and geographic location of
residue field trials.  Five field trials were conducted in EPA Regions 2
(2), 6, 9, and 10.  At all sites, two plots received a single broadcast
application of S-metolachlor at the approximate rate of 0.64 lb ai/A or
0.96 lb ai/A.  Coriander (cilantro) fresh leaf and stem samples were
harvested approximately 30 (27-34) days pre-harvest interval (PHI),
after the application and placed into frozen storage shortly after
harvest.  At one site, additional treated plots received a single
broadcast application of S-metolachlor at the approximate rate of 0.64
lb ai/A or 0.96 lb ai/A, where coriander (cilantro) seed were collected.
 At another site, additional treated plots received a single broadcast
application of S-metolachlor at the approximate rate of 0.64 lb ai/A or
0.96 lb ai/A, and coriander (cilantro) leaves and stems were collected
at 27 days and dried in an oven.  No spray adjuvant was used at the
trials.  No residue decline studies were submitted.

The analytical results show that after a single foliar broadcast
application of S-metolachlor at the approximate rate of 0.64 lb ai/A and
0.96 lb ai/A with a 27 to 34-days PHI, the maximum total S-metolachlor
residues as parent equivalents were approximately 3.7 ppm and 4.1 ppm in
coriander (cilantro) fresh leaves and stems, respectively.  The maximum
total S-metolachlor residues as parent equivalents were increased from
approximately <0.131 ppm (fresh samples) to 0.834 ppm (dried samples) in
the 0.64 lb ai/A treated plot.  The maximum total S-metolachlor residues
as parent equivalents were increased from approximately 0.170 ppm (fresh
samples) to 2.031 ppm (dried samples) in the 0.96 lb ai/A treated plot. 
The maximum total S-metolachlor residues as parent equivalents were
<0.131 ppm in coriander (cilantro) seed at both application rates. 
Based on the results of these trials, the appropriate tolerance for
residues of S-metolachlor in/on coriander (cilantro) leaves is 8.0 ppm. 
However, the Agency uses the preferred name coriander not cilantro for
this raw agricultural commodity and, in addition, does not differentiate
between dry and fresh leaves for coriander (cilantro).  Therefore, a
revised Section F should be submitted to indicate a request for
coriander, leaves at 8.0 ppm and the cilantro dried and fresh leaves
should be removed.  The study data indicates that the requested
tolerance on coriander, seed at 0.13 ppm is adequate.  

No new data have been submitted in support of the requested tolerance on
beet, garden, leaves.  The request is based on the currently established
tolerance for residues of S-metolachlor on Brassica leafy vegetables
(Sub-group 5B), of 1.8 ppm.  The Chemistry Science Advisory Council
(ChemSAC) has considered the issue and determined that since the use
pattern for beet greens is the same as that for leafy Brassica (sub
group 5B), and beet greens are similar to the commodities in the leafy
Brassica subgroup 5B, it is appropriate to translate this tolerance of
1.8 ppm to beet greens.  Based on the CHEMSAC determination and that the
proposed use pattern for beet, garden, leaves is the same as leafy
Brassica greens, subgroup 5B, IIAB recommends for the proposed tolerance
of 1.8 ppm on beet, garden, leaves.

There is no crop associated with this petition which requires residue
data for processed fractions.  

Analytical standards for the following compounds related to metolachlor
are currently available in the EPA National Pesticide Standards
Repository.

The rotational crop restrictions listed on the label are appropriate for
these proposed uses.

Regulatory Recommendations and Residue Chemistry Deficiencies

IIAB has examined the residue chemistry database for S-metolachlor. 
Pending receipt of an updated Section F for coriander, leaves at 8.0 ppm
with the cilantro, dried and fresh leaves removed, IIAB has no objection
to the establishment of the tolerances described in Table 9, below.

A human health risk assessment is forthcoming.

860.1500 Crop Field Trials

The Agency uses the preferred name coriander not cilantro for this raw
agricultural commodity and, in addition, does not differentiate between
dry and fresh leaves for coriander (cilantro).  Therefore, a revised
Section F should be submitted to indicate a request for coriander,
leaves at 8.0 ppm and the cilantro dried and fresh leaves should be
removed.

Background

The chemical structure and nomenclature of S-metolachlor and its
regulated hydrolytic derivatives are presented in Table 1, and the
physicochemical properties of S-metolachlor are presented in Table 2.  

Table 1.  Nomenclature of S-Metolachlor and its Regulated Derivatives

Compound	

 

 

Company experimental name	SYN 508500 (S-enantiomer of CGA-49751)

IUPAC name
(S)-4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-methylmorpholin-3-one

CAS name 	4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-morpholone

CAS #	61520-54-5

Table 2.  Physicochemical Properties of the Technical Grade
S-Metolachlor

Parameter	Value	References (MRID)

Melting point/range	Not applicable, liquid at room temperature	46829503

pH	7.8 at 25°C (1% aqueous dispersion)

	Density	1.117 g/cm3 at 20°C

	Water solubility (25°C)	0.48 g/L

	Solvent solubility mg/L at 25°C	Completely miscible with methanol,
acetone, toluene, n-octanol, n-hexane, ethyl acetate, dichloromethane

	Vapor pressure at 25°C	2.8 x 10-5 mm Hg

	Dissociation constant (pKa)	No dissociation constant in pH range 2-12

	Octanol/water partition coefficient Log (Kow)	3.05 at 25°C

	UV/visible absorption spectrum	Neutral: 534 l/mol.cm @ 266.4 nm

             443 l/mol.cm @ 274.4 nm

Acidic: 534 l/mol.cm @ 266.4 nm

             444 l/mol.cm @ 274.4 nm

Basic: 534 l/mol.cm @ 266.4 nm

             411 l/mol.cm @ 274.4 nm

	

860.1200 Directions for Use

The petitioner provided a text listing of proposed uses in Section B of
the petition.  Apply S-metolachlor to coriander (cilantro) formulated as
Dual MAGNUM (EPA Reg. No.: 100-816) as a broadcast, foliar application
(0.64-0.96 lbs ai/A) at 30 days before the leaf harvest and 70 days
before seed.  Use the lower end of S-metolachlor rate range for soils
that are relatively coarse textured and the higher rates on fine
textured soils.  Apply S-metolachlor to beets grown for leaves as a
broadcast, pre-emergence soil surface treatment at 0.63 -1.26 lbs ai/A
after the crop has been planted but before the crop and weeds emerge.  A
second application of S-metolachlor to beets may be made as one post
emergence, broadcast treatment at 0.63 -1.26 lbs ai/A when plants are at
1 to 2 true leaf stage.  Use the lower end of S-metolachlor rate range
for soils that are relatively coarse textured and the higher rates on
fine textured soils.

The proposed uses are presented below in Table 3.  

Table 3.	Summary of Proposed Directions for Use of S-Metolachlor.

Applic. Timing; Type; and Equip.

(minimum volume)	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

Coriander (cilantro)

Broadcast Foliar

(20 GPA)	7.62 lb/gal EC

[100-816]	0.64-0.96	1	0.96	30-leaves

70-seeds	REI: 24hrs

Beet, garden, leaves (for varieties grown for tops only)

Postemergence to Soil & Broadcast Foliar

 (10-40 GPA)	7.62 lb/gal

EC

[100-816]	0.63-1.26	2	2.52	30	First appl. broadcast, pre-emergence soil
surface treatment Second appl. when plants are at 1 to 2 true leaf
stage.

REI: 24hrs

Conclusions:  The proposed use directions are adequate.

860.1300 Nature of the Residue - Plants

The qualitative nature of metolachlor residues in plants is adequately
understood based upon the adequate corn, potato, and soybean metabolism
studies.  The metabolism of metolachlor involves conjugation with
glutathione, breakage of this bond to form the mercaptan, conjugation of
the mercaptan with glucuronic acid, O-demethylation of the methyl ether,
and conjugation of the resultant alcohol with a neutral sugar.  A minor
pathway may involve sugar conjugation of metolachlor directly to the
corresponding oxo-compounds.  Residues of concern in plants include
metolachlor and its metabolites, determined as the derivatives CGA-37913
and CGA-49751.  The Agency previously concluded that the residues of
concern for S-metolachlor are the same as for metolachlor (DP# 226780,
L. Kutney, 11/15/96).

The Agency has also reviewed plant metabolism data on S-metolachlor from
field tests on soybeans and corn, in vitro tests on corn seedlings, and
greenhouse tests on seedlings of corn, sorghum, soybeans and peanuts
(DP#s 278742 and 279110, S. Kinard, 8/15/03).  These data support
Syngenta’s assertion that the metabolism of S-metolachlor in plants is
similar to that for the racemic mixture.  The data did not address
whether there is any conversion of the S-isomers of metolachlor or its
metabolites to the R-isomer forms; however, HED previously concluded
that such conversion of isomers in plants is not likely to be
significant.

860.1300 Nature of the Residue - Livestock

Adequate studies are available depicting the metabolism of metolachlor
in ruminants and poultry.  Metolachlor is rapidly metabolized and almost
totally eliminated in the urine and feces of ruminants (goats),
non-ruminants (rats), and poultry.  Metolachlor per se was not detected
in any of the excreta or tissues.  As in plants, metolachlor residues of
concern in livestock commodities include metolachlor and its
metabolites, determined as the derivatives CGA-37913 and CGA-49751.  The
residues of concern for S-metolachlor in livestock are the same as those
for metolachlor.

The Agency has also reviewed livestock metabolism data on S-metolachlor
(DP#s 278742, S. Kinard, 8/15/03).  Data from a goat metabolism study
indicated that S-metolachlor was readily absorbed and extensively
metabolized by goats via glutathione conjugation and/or oxidation
reactions.  Oxidized metabolites were also conjugated with glucuronic
acid.  Data from a poultry metabolism study indicated that S-metolachlor
was also extensively metabolized via O demethylation and subsequent
glucuronic acid conjugation or oxidation to dihydroxy or carboxylic acid
metabolites that may also be conjugated with glucuronic acid.

860.1340 Residue Analytical Methods

Enforcement methods:  Adequate methodology is available for enforcing
the established and recommended tolerances.  PAM Vol. II, Pesticide
Regulation Section 180.368, lists a GC/NPD method (Method I) for
determining residues in/on crop commodities and a GC/MSD method (Method
II) for determining residues in livestock commodities.  These methods
determine residues of metolachlor and its metabolites as either
CGA-37913 or CGA-49751 following acid hydrolysis.  

IR-4 and Syngenta have proposed an HPLC/MS/MS enantiomer-specific method
for the enforcement of the proposed tolerances, Method 1848-01.  This
method has been previously reviewed by HED (DP# 296904, R. Loranger,
4/17/06).  The method uses a chiral HPLC column to separate out the
S-enantiomers (SYN506357 and SYN508500) of the hydrolysis products
CGA-37913 and CGA-49751.  

Data-gathering methods:  Coriander (cilantro) fresh, dried and seed
samples were analyzed for residues of S-metolachor using the “Working
Method for PR 09595: Analysis of s-Metolachlor in Cilantro as
Metabolites s-CGA-37913 (SYN-506357) and s-CGA-49751 (SYN-508500), A.
Le, Document I.D. Working Method for 09595.06-BER06.doc, Effective Date:
04-18-08,” a modification of Syngenta Method No. 1848-01, dated June
26, 2003 entitled “Analytical Method for the Enantioselective
Determination of Residues of s-Metolachlor as Metabolites SYN-506357 and
SYN-508500 in Agricultural Commodities by Chiral High Performance Liquid
Chromatograph with Mass Spectrometric Detection.”  

Samples of the raw agricultural commodities, leaves and stems, and seed
were refluxed in 6N HCL.  The cooled extract was filtered and residues
were partitioned from a pH adjusted aliquot into DCM and dried with
sodium sulfate.  An aliquot was purified with alumina column
chromatography and concentrated into 30% acetonitrile (aqueous).  The
residues were quantified by reversed phase HPLC with positive ion
atmosphere pressure chemical ionization tandem mass spectrometric
detection (MS/MS). 

The residue analytical method for S-metolachlor residues in/on coriander
(cilantro) samples was validated both prior to and concurrently with
field samples.  For method validation, control samples of coriander
(cilantro) fresh, dried and seed were fortified with SYN 506357 and SYN
508500 at 0.05, 0.5, 2, and 5.0 ppm.  Concurrent recoveries were
conducted at 0.05, 0.5, and 1 ppm.  The LLMV for residues of SYN 506357
and SYN 508500 was 0.05 ppm in all matrices.  

Several validation recoveries for SNY-508500 (s-CGA 49751) on seed were
lower than the acceptable range of 70-120%.  Method validation
recoveries on seed ranged from 59-72% (avg. 66 ± 5%) and concurrent
recoveries ranged from 50-84% (avg. 67 ± 14%).  

Table 4.  Summary of Recoveries of S-Metolachlor from Coriander
(cilantro) 

Matrix	Analyte	Spike level (mg/kg)	Sample size (n)	Recoveries (%)	Mean
± std dev

Method Validation

Fresh leaves and stems

Fruit	SYN-506357

(s-CGA 37913)

Clopyralid	0.05

0.5	6	94, 92, 78, 80, 81	83 ± 8	85.2 ± 7

0.5	6	92, 87, 86, 82, 81, 83	85 ± 4

	5.0	6	72, 93, 92, 92, 81, 93	87 ± 9

	Fresh leaves and stems

Fruit	SYN-508500

(s-CGA 49751)

Clopyralid	0.05	6	74, 76, 78, 76, 76, 74	76 ± 2	77.6 ± 3

0.5	6	79, 78, 79, 72, 81, 82	79 ± 4

	0.5	6	79, 78, 76, 79, 85, 74	78 ± 4

	Dried leaves and stems

	SYN-506357

(s-CGA 37913)

	0.05	3	89, 100, 96	95 ± 6	89.3 ± 16

0.5	3	77, 77, 74	76 ± 2

	2	6	71, 83, 85, 120, 81, 118	93 ± 21

	Dried leaves and stems

	SYN-508500

(s-CGA 49751)

	0.05	3	72, 84, 74	77 ± 6	83.0 ± 18

0.5	3	62, 62, 62	62 ± 0

	2	6	87, 105, 113, 110, 77, 88	97 ± 15

	Seed	SYN-506357

(s-CGA 37913)	0.05	3	78, 84, 85	82 ± 4	81 ± 3

0.5	3	82, 82, 76	80 ± 3

	Seed	SYN-508500

(s-CGA 49751)	0.05	5	66, 64, 64	65 ± 1	66 ± 5

0.5	3	72, 70, 59	67 ± 7

	Concurrent Validation

Fresh leaves and stems	SYN-506357

(s-CGA 37913)	0.05	7	96, 84, 108, 100, 92, 86	91 ± 12	86 ± 11

0.5	5	84, 90, 86, 74, 74	82 ± 7

	Fresh leaves and stems	SYN-508500

(s-CGA 49751)	0.05	7	70, 84, 72, 80, 92, 100, 98	83 ± 12	82 ± 11

0.5	4	80, 78, 76, 70	76 ± 4

	Dried leaves and stems	SYN-506357

(s-CGA 37913)	0.05	3	84, 108, 86	93 ± 13	82 ± 11

0.5	3	71, 79, 73	74 ± 4

	1.0	3	80, 82, 77	79 ± 2

	Dried leaves and stems	SYN-508500

(s-CGA 49751)	0.05	3	76, 85, 101	87 ± 12	88 ± 16

0.5	3	72, 72, 74	73 ± 1

	1.0	3	109, 108, 96	104 ± 7

	Seed	SYN-506357

(s-CGA 37913)	0.05	5	80, 76, 94, 106, 84	88 ± 4	81 ± 13

0.5	3	67, 71, 71	70 ± 2

	Seed	SYN-508500

(s-CGA 49751)	0.05	5	65, 76, 78, 78, 84	76 ± 7	67 ± 14

0.5	3	50, 50, 52	51 ± 1

	

Based on recoveries at the LLMV, the LOD (std. dev. x one-tailed
t-statistic) were calculated.  The LOQ (3 x LOD) were also calculated. 
The LLMV, LOD and LOQ for SYN-506357 and SYN-508500 in/on the three
matrices are listed below:

Table 5.  Summary of  S-Metolachlor Analytical Method Limits

Commodity	Analyte	Calculated LOD

(ppm)	Calculated LOQ

(ppm)	LLMV

(ppm)

Coriander (cilantro) Fresh Samples	SYN-506357

SYN-508500	0.0145

0.0132	0.0436

0.0396	0.05

0.05

Coriander (cilantro) Dried Samples	SYN-506357

SYN-508500	0.0160

0.0175	0.0480

0.0526	0.05

0.05

Coriander (cilantro) Seed Samples	SYN-506357

SYN-508500	0.0154

0.0120	0.0463

0.0359	0.05

0.05

Conclusions:  There are adequate enforcement methods available.  The
data collection method was adequate for the determination of
S-metolachlor residues in coriander (cilantro) commodities.

860.1360 Multiresidue Methods

Adequate data are available on the recovery of metolachlor through
Multiresidue Method Testing Protocols.  The FDA PESTDATA database
indicates that metolachlor is completely recovered through Method 302,
PAM Vol. I (3rd ed., revised 10/97).

CGA-37913 is stable at ≤-10°C for at least 2 years in corn (grain and
forage), peanut, potato (tubers, wet peel and flakes), soybean (hulls
and meal) and tomatoes, for at least 29 months in cottonseed oil, and
for at least 37 months in cottonseed and corn oil; and CGA-49751 is
stable at ≤-10°C for at least 2 years in corn (grain, forage, and
oil), peanuts, potatoes (tubers, wet peel and flakes), soybeans (hulls
and meal) and tomatoes, and for at least 37 months in cotton seed and
cottonseed oil.  In addition, storage stability studies conducted
concurrently with previously submitted asparagus, carrot, and green
onion field trials indicate that both analytes are stable at -20ºC for
at least 14.1 months in asparagus, 24.3 months in carrots, and 21.7
months in green onions. 

Coriander (cilantro) fresh leaves and stems, dried leaves and stems and
seed samples were stored frozen for a maximum of 708 days, 702 days, and
416 days, respectively.  Recoveries of SYN-506357 and SYN-508500 from
stored coriander (cilantro) samples were corrected for concurrent
recoveries.

The maximum frozen storage intervals for field treated coriander
(cilantro) fresh leaves and stems, dried leaves and stems, and seed
samples in this study were 708 days, 702 days, and 416 days
respectively.  The results of the storage stability study showed that
recoveries of S-metolachlor residues in/on coriander (cilantro) fresh
leaves and stems were 52% (corrected 70%) and 72% (corrected 87%) for
SYN-506357 and SYN-508500, respectively.  The recoveries of
S-metolachlor residues in/on coriander (cilantro) dried leaves were 84%
(corrected 88%) and 62% (corrected 82%) for SYN-506357 and SYN-508500,
respectively.  The recoveries of S-metolachlor residues in/on coriander
(cilantro) seed were 92% (corrected 110%) and 63% (corrected 80%) for
SYN-506357 and SYN-508500, respectively.    

Table 6.  Stability of S-Metolachlor in Coriander (cilantro) Samples
Following Storage at -20oC

Matrix 

(RAC or Extract)	Analyte	Stored Sample Recovery (%)	Concurrent Recovery
(%)	Stored Sample Average Corrected Recovery (%)1 	Actual Storage
Duration

(days)	Interval of Demonstrated Storage Stability (days)

Coriander (cilantro) fresh leaves and stems	SYN-506357	53, 52, 52	75	70
708	720

	SYN-508500	71, 70, 74	82	87

Coriander (cilantro) dried leaves and stems	SYN-506357	67/83

70/106

72/104	

81/111

	88	624 - 702	678 - 686

	SYN-508500	58/76

52/66

55/66	71/80	82

Coriander (cilantro)            seed	SYN-506357	72/112

99/70

83/114	85/81	110	366 - 416	399 - 413

	SYN-508500	50/79

73/54

50/69	80/77	80

1Average Corrected Recovery (%) = 100 x [Average Stored Sample Recovery
(%) ÷ Average Concurrent Recovery (%)] 

Conclusions:  The previously submitted storage stability data indicates
that the residues of metolachlor are stable on a variety of commodities
for up to 2 yrs.  The results of the storage stability study with
coriander (cilantro) samples and previously submitted data are adequate
to show that residues of S-metolachlor were stable for the duration of
this study. 

860.1400 Water, Fish, and Irrigated Crops

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

860.1460 Food Handling

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

860.1480 Meat, Milk, Poultry, and Eggs

There are no coriander (cilantro) or garden beet leaf feed items of
regulatory interest, therefore a discussion of S-metolachlor residues on
livestock food items is not germane to this guideline topic.

860.1500 Crop Field Trials

Coriander (cilantro)

DER References:	48536501.der.doc

The IR-4 has submitted field trial data for S-metolachlor on coriander
(cilantro).  Five field trials were conducted in the 2006-growing
season, one in South Carolina (EPA Region 2), one in Georgia (EPA Region
2), one in Texas (EPA Region 6), one in New Mexico (EPA Region 9), and
one in California (EPA Region 10).  

At each trial, there were at least two treated plots.  At all sites, two
of the plots received a single broadcast application of S-metolachlor at
the approximate rate of 0.64 lb ai/A or 0.96 lb ai/A.  Coriander
(cilantro) fresh leaf and stem samples were harvested approximately 30
(27-34) days after the application and placed into frozen storage
shortly after harvest.  At the New Mexico trial, additional treated
plots received a single broadcast application of S-metolachlor at the
approximate rate of 0.64 lb ai/A or 0.96 lb ai/A, where coriander
(cilantro) seed were collected.  At the California trial, additional
treated plots received a single broadcast application of S-metolachlor
at the approximate rate of 0.64 lb ai/A or 0.96 lb ai/A, timed to be
approximately 30 days before harvest, when coriander (cilantro) fresh
leaves and stems were dried.  All applications were made within 17-36
gallons per acre spray solution and no spray adjuvant was used at the
trials.  

Coriander (cilantro) fresh leaves and stems samples were collected
between 27-34 days after the final application at all sites.  Coriander
(cilantro) seed samples were collected at 70 days after the application.
 Coriander (cilantro) leaves and stems were collected at 27 days and
dried in an oven at 155° F before sampling.

The analytical results show that after a single foliar broadcast
application of S-metolachlor at the approximate rate of 0.64 lb ai/A and
0.96 lb ai/A with a 27 to 34-days pre-harvest interval (PHI), the
maximum total S-metolachlor residues as parent equivalents were
approximately 3.7 ppm and 4.1 ppm in coriander (cilantro) fresh leaves
and stems, respectively.  The maximum total S-metolachlor residues as
parent equivalents were increased from approximately <0.131 ppm (fresh
samples) to 0.834 ppm (dried samples) in the 0.64 lb ai/A treated plot. 
The maximum total S-metolachlor residues as parent equivalents were
increased from approximately 0.170 ppm (fresh samples) to 2.031 ppm
(dried samples) in the 0.96 lb ai/A treated plot.  The concentration
factor from fresh samples to dried samples was 6-12X.  The maximum total
S-metolachlor residues as parent equivalents were <0.131 ppm in
coriander (cilantro) seed at both application rates.  No residue decline
studies were submitted.

Table 7.  Residue Data from Coriander (cilantro) Crop Field Trials with
S-Metolachlor

Trial ID

(City,State/Year)	Region	Crop/    Variety	Commodity	Total Rate

(lbs ai/A)	PHI (days)	Residue SYN-506357

(ppm)	Residue SYN-508500

(ppm)	SYN-506357 as parent equivalents1 (ppm) 	SYN-508500 as parent
equivalents2 (ppm)	S-metolachlor total residues as parent equivalents
(ppm)

06-SC*09

(Charleston, SC, 2006)	2	Coriander (cilantro)/  Santo	Fresh leaves	0.63
34	0.090 0.096	0.103 0.092	0.132

 0.141	0.117

 0.105	0.249

0.246

0.88

0.124 0.118	0.153 0.122	0.182

 0.173	0.174

 0.139	0.356              0.312

06-GA*11

(Tifton, GA, 2006)	2	Coriander (cilantro)/  Santo Monogerm	Fresh leaves
0.64	27	1.682 2.008	0.821 0.924	2.473

 2.952	0.936

 1.053	3.409

4.005

0.97

1.992 1.873	1.163 1.112	2.928

 2.753	1.326 

1.268	4.254

4.021

06-TX*37

(Weslaco, TX, 2006)	6	Coriander (cilantro)/ leisure	Fresh leaves	0.64	32
<0.05 <0.05	<0.05 <0.05	<0.074 <0.074	<0.057 <0.057	<0.131

<0.131

0.96

0.068 0.056	0.059 0.055	0.100 

0.082	0.067

 0.063 	0.167

0.145

06-CA*109

(Salinas, CA, 2006)	10	Coriander (cilantro)/  Santo	Fresh leaves	0.65	27
<0.05 <0.05	<0.05 <0.05	<0.074 <0.074	<0.057 <0.057	<0.131

<0.131

0.97

<0.05 <0.05	0.079 0.089	<0.074 <0.074	0.090 

0.101	0.164

0.175

	Dried Leaves	0.66	28	0.174*	0.507*	0.256	0.578	0.834

0.98

0.594*	1.016*	0.873	1.158	2.031

06-NM14

(Las Cruces, NM, 2006)	9	Coriander (cilantro)/  Santo	Fresh leaves	0.64
28	<0.05 <0.05	<0.05 0.05	<0.074 <0.074	<0.057

 0.057	<0.131

<0.131

0.97

0.090 0.057	0.112 0.066	0.132

 0.084	0.128

 0.075	0.260

0.159

	Seed	0.64	70	<0.05 <0.05	<0.05* <0.05*	<0.074 <0.074	<0.057 <0.057
<0.131

<0.131

0.96

<0.05 <0.05	<0.05* <0.05*	<0.074 <0.074	<0.057 <0.057	<0.131

<0.131

*Result is the average of the duplicate analyses of a single sample.

1SYN-506357 values were multiplied by 1.47 to obtain parent equivalents.
 Values of 0.074 ppm represent the method’s LOQ as parent equivalents.

2SYN-508500 values were multiplied by 1.14 to obtain parent equivalents.
 Values of 0.057 ppm represent the method’s LOQ as parent equivalents.

Table 8.  Summary of Residue Data from Crop Field Trials with
S-Metolachlor

Commodity

	Total Applic. Rate

(lb ai/A)	PHI1

(days)	Analyte	Residue Levels (ppm)2

n	Min.	Max.	HAFT3	Median	Mean	Std. Dev.

Coriander (cilantro) fresh leaves/stems	0.63 – 0.65	27 – 34	Total
S-metolachlor as parent equivalents	10	<0.13	4.0	3.7	<0.13	0.87	1.53

Coriander (cilantro) fresh leaves/stems	0.88 – 0.97	27 – 34

10	0.14	4.2	4.1	0.22	1.0	1.6

Coriander (cilantro) dried leaves/stems	0.66	27

1	0.83	0.83	-	0.83	0.83	-

Coriander (cilantro) dried leaves/stems	0.98	27

1	1.6	1.6	-	1.6	1.6	-

Coriander (cilantro)               seed	0.64	70

2	<0.13	0.13	-	<0.13	<0.13	-

Coriander (cilantro)                seed	0.96	70

2	<0.13	<0.13	-	<0.13	<0.13	-

1PHI = Post harvest interval

2Sum of SYN-506357 and SYN-508500 residues as parent equivalents

3HAFT = Highest Average Field Trial

Conclusions:  The submitted study is adequate in number and geographic
location of residue field trials.  The study data indicates that the
highest residues for coriander (cilantro) were found in fresh leaves at
the higher application rate.  This data was entered into the OECD MRL
Calculator.  Based on the results of these trials, the Calculator
indicates that the appropriate tolerance for residues of S-metolachlor
in/on coriander (cilantro) leaves is 8.0 ppm.  However, the Agency uses
the preferred name coriander not cilantro for this raw agricultural
commodity and, in addition, does not differentiate between dry and fresh
leaves for coriander (cilantro).  Therefore, a revised Section F should
be submitted to indicate a request for coriander, leaves at 8.0 ppm and
the cilantro dried and fresh leaves should be removed.

The study data indicates that the requested tolerance on coriander, seed
at 0.13 ppm is adequate.  IIAB recommends for the requested tolerance.

Beet, Garden, Leaves

No new data have been submitted in support of the requested tolerance on
beet, garden, leaves.

The IR-4 Project Headquarters received a request from California, Texas,
Tennessee, and Oklahoma for the use of S-metolachlor as herbicide to
control weeds in beet, garden, leaves production.  The request is based
on the currently established tolerance for residues of S-metolachlor on
Brassica leafy vegetables (Sub-group 5B), of 1.8 ppm.  The ChemSAC
(4/6/2011) has considered the issue:

	“…Tolerances for S-metolachlor are published in 40 CFR § 180.368
(a) (2).  Both the 	Brassica leafy vegetables and the turnip greens
tolerances were established 17-Sep-2010, 	in connection with PP#9E7607,
based on data on the representative commodity mustard 	greens.  These
data were translated to turnip greens.

	Tolerances have already been established for residues of S-metolachlor
on vegetable, 	root, exc sugarbeet, subgroup 1B at 0.3 ppm (Established
17-Sep-2008, in connection 	with PP#3E6787), and beet, sugar, root at
0.5 ppm and beet, sugar, tops, at 15 ppm (also 	established 17-Sep-2008,
but in connection with PP#6E4638).  A tolerance for residues 	of
S-metolachlor on leaves of root and tuber vegetables (Crop Group 2)
would not be 	appropriate because there are not tolerances on the
corresponding roots (all of Crop 	Group 1).  A tolerance for residues of
S-metolachlor on Carrot of 0.20 ppm was proposed 	in connection with
PP#7E4916, and was increased to 0.40 ppm in connection with 	PP#9E7607.

	The maximum seasonal application rate on sugarbeets is 3.81 lb ai/A,
with no more than 	2.53 lb ai/A applied postemergence.  The single
application rate on sugarbeets is 2.53 lb 	ai/A.  On carrots, a maximum
of one application of 1.9 lb ai/A is allowed with a 64 day 	PHI.  On
leafy Brassica (sub-group 5B), a maximum of one application of 1.27 lb
ai/A is 	allowed with a 30 day PHI.

	The use pattern for sugar beets allows much more S-metolachlor to be
applied than to 	leafy Brassica (sub-group 5B); therefore, it would be
inappropriate to translate the 	sugarbeet data to beet greens.  However,
since the use pattern for beet greens is the same 	as that for leafy
Brassica (sub group 5B), and beet greens are similar to the commodities 
in the leafy Brassica subgroup 5B, it is appropriate to translate this
tolerance of 1.8 ppm 	to beet greens.”

Conclusions:  Based on the CHEMSAC determination and that the proposed
use pattern for beet, garden, leaves is the same as leafy Brassica
greens, subgroup 5B, IIAB recommends for the proposed tolerance of 1.8
ppm on beet, garden, leaves.

860.1520 Processed Food and Feed

There is no crop associated with this petition which requires residue
data for processed fractions.  

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

Analytical standards for the following compounds related to metolachlor
are currently available in the EPA National Pesticide Standards
Repository (DP#s 369005 & 375955, S. Hummel, 6/15/10; expiration data in
parentheses):  metolachlor (11/10/2010); S-metolachlor (8/1/2012);
metolachlor derivative CGA-37913 (4/30/2010); metolachlor derivative
CGA-49751 (4/30/2011); metolachlor, ethane sulfonic acid sodium salt
(CGA-354743, 4/1/2011); and metolachlor, oxanilic acid (CGA-51202,
4/1/2011).

860.1850/860.1900 Confined/Field Accumulation in Rotational Crops

D369005 and D375955, S. Hummel, 6/15/10

Confined and field rotational data requirements were recently examined
(DP# 369005 and 375955, S. Hummel, 6/15/10).  An adequate confined
rotational crop study is available, although additional information
pertaining to the study remains outstanding.  The residues of concern in
rotated crops are the same as in the primary crops, S-metolachlor, its
R-enantiomer, and its metabolites determined as CGA-37913 and CGA-49751.
 HED has determined that adequate field rotational crop data have been
submitted which support the existing rotational crop restrictions on the
label for EPA Reg. Nos. 100-816 pending additional label amendments
(i.e., Rotational crop directions for crops with a 60-day plantback
interval must be amended to prohibit a second application of
S-metolachlor to any of these crops replanted within 60 days of the
original application.). 

Conclusions:  Although additional data for the confined rotational crop
study remains outstanding, it is not a deficiency for this petition. 
Rotational crop directions for crops with a 60-day plantback interval
have been amended to prohibit a second application of S-metolachlor to
any of these crops replanted within 60 days of the original application.
 This is no longer a deficiency for S-metolachlor petitions.

860.1550 Proposed Tolerances

Tolerances are currently established under 40 CFR §180.368 for residues
of S-metolachlor, including its metabolites and degradates, in or on the
commodity(s), as defined. Compliance with the tolerance levels specified
in the following table below is to be determined by measuring only the
sum of free and bound S-metolachlor,
S-2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetami
de, its R-enantiomer, and its metabolites, determined as the
derivatives, 2-(2-ethyl-6-methylphenyl)amino-1-propanol and
4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-morpholinone, calculated
as the stoichiometric equivalent of S-metolachlor, in or on the
commodity.  

The submitted coriander (cilantro) study is adequate in number and
geographic location of residue field trials and supports the proposed
tolerance.  The Agency uses the preferred name coriander not cilantro
for this raw agricultural commodity and, in addition, does not
differentiate between dry and fresh leaves for coriander (cilantro). 
Therefore, a revised Section F should be submitted to indicate a request
for coriander, leaves at 8.0 ppm and the cilantro dried and fresh leaves
should be removed.  The study data indicates that the requested
tolerance on coriander, seed at 0.13 ppm is adequate.  

Based on the CHEMSAC determination and that the proposed use pattern for
beet, garden, leaves is the same as leafy Brassica greens, subgroup 5B,
IIAB recommends for the proposed tolerance of 1.8 ppm on beet, garden,
leaves.

No maximum residue limits (MRLs) for S-metolachlor on coriander have
been established or proposed by Codex, Canada, or Mexico.  No MRLs for
S-metolachlor on beet, garden, leaves have been established or proposed
by Codex or Mexico.  An MRL for S-metolachlor on beet, garden, leaves
has been established in Canada.  However, beet, garden, leaves are not a
significant import/export commodity and are not expected to be a trade
irritant with Canada.  

Table 9.  Tolerance Summary for S-metolachlor.

Commodity	Proposed Tolerance (ppm)	RD-Recommended Tolerance (ppm)
Correct Commodity Definition

Cilantro, leaves, fresh	8.0	NA

	Cilantro, leaves, dried	8.0	NA

	Coriander, seed	0.13	0.13

	Beet, garden, leaves	1.8	1.8

	Coriander, leaves	NA	8.0

	

References

DP Number:	D369005, D375955

Subject:	S-Metolachlor.  Petition for the Establishment of Permanent
Tolerances for New Uses on Bushberry Subgroup 13-07B; Caneberry Subgroup
13-07A; Carrot; Cucumber; Leafy Brassica Greens Subgroup 5B; Melon
Subgroup 9A; Okra; Bulb Onion Subgroup 3-07A; Green Onion Subgroup
3-07B; Sesame Seed; Sorghum; and Turnip Greens.  Summary of Analytical
Chemistry and Residue Data. 

From:		S. Hummel 

To:		B. Daiss

Dated:		6/15/10

MRIDs:	47829401-08, 48020601

DP#:	D226780

Subject:	Replacement of Metolachlor Technical (Racemic Metolachlor) with
Alpha-Metolachlor (formerly called Chiral Metolachlor) Technical; Review
of Bridging Data.

From:	L. Kutney

To:	R. Griffin

Dated:	11/15/96

MRIDs:	43928901-03, 43928939-42

DP Number:	D274328

Subject:	Metolachlor and S-Metolachlor Residue Chemistry Chapter for the
Tolerance 			Reassessment Eligibility Decision (TRED)

From:		S. Kinard

To:		C. Jarvis

Dated:		2/28/02

MRIDs:	NA

DP Number:	D278742, D279110

Subject:	S-Metolachlor.  Information Supporting the Assertion That the
Metabolism of S-			metolachlor Is Essentially the Same as for the
Racemic Mixture.

From:		S. Kinard

To:		S. Kinard

Dated:		8/15/03

MRIDs:	45499603, 45499604, 45499605, 45533103

DP#:	D296904

Subject:	PP# 3E6787.  S-Metolachlor.  Petition for Tolerances on Various
Crops, Crop Groups, and Livestock Commodities.  Summary of Analytical
Chemistry and Residue Data.

From:	R. Loranger

To:	B. Madden/S. Jackson

Dated:	4/17/06

MRIDs:	45499609, 45499610, 46046501-06

DP#:	D292881

Subject:	PP#s:  7F04897, 9E06055, 7E04916, 2E06374, 4E04420, 8E05029,
and 8E05030. Revised Metolachlor and S-metolachlor Residue Chemistry
Chapter for the Tolerance Reassessment Eligibility Decision (TRED) and
Registration for Use on Asparagus, Carrots, Cotton, Horseradish, Green
Onions, Peppers, Rhubarb, Sugar Beet, Sunflower, and Swiss Chard.

From:	S. Kinard

To:	H. Jamerson

Dated:	8/15/03

MRIDs:	44378401, 44908701, 45544701

DP#s:	D332846, D332847, D332848, D332849, D350604, D350942, D351174,
D351226

Subject:	S-Metolachlor.  Amended Use Directions for Sorghum and
Soybeans; Revisions to Rotational Crop Restrictions; Registrant’s
Responses to Deficiencies Noted in the Revised S-Metolachlor TRED. 
Summary of Analytical Chemistry and Residue Data.

From:	D. McNeilly

To:	E. Wilson/J. Miller and R. Louie/N. Anderson

Dated:	10/21/08

MRIDs:	46829501-04, 47121701-02, 47304701-02

Attachments:  

International Residue Limit Status Sheet

Tolerance/MRL Spreadsheet

ATTACHMENT I  

International Residue Limits 

S-metolachlor (108800; 11/28/2011)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US	Canada	Mexico2	Codex3

40 CFR: 180.368   sum of free and bound S-metolachlor,
S-2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetami
de, its R-enantiomer, and its metabolites, determined as the
derivatives, 2-(2-ethyl-6-methylphenyl)amino-1-propanol and
4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-morpholinone calculated
as the stoichiometric equivalent of S-metolachlor 
2-chloro-N-(2-ethyl-6-methylphenyl)-N-[(1S)-2-methoxy-1-methylethyl)acet
amide and 2-chloro-N-(2-ethyl-6-methylphenyl)-N-[(1R)-2-methoxy-1-

methylethyl)acetamide, including the metabolites
2-[(2-ethyl-6-methylphenyl)amino]-1-propanol and
4-(2-ethyl-6-methylphenyl)-2-hydroxy-5-methyl-3-morpholinone

None

Commodity1	Tolerance (ppm) /Maximum Residue Limit (mg/kg)

	US	Canada	Mexico2	Codex3

Coriander, seed	0.13

	Beet, garden, tops	1.8	0.8 garden beet tops

Coriander, leaves	8.0

	Completed:  M. Negussie; 11/29/2011

1 Includes only commodities of interest for this action.  Tolerance
values should be the HED recommendations and not those proposed by the
applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment,
such as treatment of stored grains.  PoP = processed postharvest treated
commodity, such as processing of treated stored wheat. (fat) = to be
measured on the fat portion of the sample. MRLs indicated as proposed
have not been finalized by the CCPR and the CAC.

ATTACHMENT II  

Tolerance-Assessment Calculations

The submitted U.S. residue data for coriander (cilantro), fresh leaves
(10 data points) were entered into the OECD MRL Calculator in order to
determine appropriate tolerance levels.

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Number of non-censored data	10	 	 

 	 	Lowest residue	0.145	 	 

 	 	Highest residue	4.254	 	 

 	 	Median residue	0.218	 	 

 	 	Mean	1.001	 	 

 	 	Standard deviation (SD)	1.655	 	 

 	 	Correction factor for censoring (CF)	1.000	 	 

 	 	 	 	 	 

 	 	Proposed MRL estimate	 	 	 

 	 	 	 	 	 

 	 	- Highest residue	4.254	 	 

 	 	- Mean + 4 SD	7.623	 	 

 	 	- CF x 3 Mean	3.004	 	 

 	 	Unrounded MRL	7.623	 	 

 	 	 	 	 	 

 	 	Rounded MRL	8	 	 

 	 	 	 	 	 

 	 	 	 	 

 	 	 	 	 

 	 	 	 	 	 

 	 	 	 	 	 

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