Document ID: EPA-HQ-OPP-2009-0713-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-01-26T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

	OFFICE OF CHEMICAL SAFETY 

	AND POLLUTION PREVENTION

	

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:  6/30/10

SUBJECT:	Mefenoxam.  Petition for Tolerances in Support of New Uses on
Snap Beans and the Caneberry Subgroup, Expanded Uses on the Bulb and
Green Onion Subgroups and the Bushberry Subgroup, and Amended Use on
Spinach.  Summary of Analytical Chemistry and Residue Data.

PC Code:  113502	DP Barcode:  D371307

Decision No.: 416985	Registration Nos.:  100-801, 100-804, 100-1202 

Petition No.:  9E7591	Regulatory Actions:  Section 3 Registration/
Amended Section 3 Registration

Risk Assessment Type:  NA	Case No.:  NA

TXR No.:  NA	CAS No.:  70630-17-0

MRID No.: See MRID Summary Table	40 CFR:  	180.546 (Mefenoxam)

	

		              									

FROM:	Nancy Dodd, Chemist

		Risk Assessment Branch III

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

		

THROUGH:	Leung Cheng, Senior Chemist

		Risk Assessment Branch III

		Health Effects Division (7509P)

		

TO:		Barbara Madden, RM#5

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

		

MRID Summary Table

MRID No.	Study Type	Comments

47803101	860.1500 Snap Bean	New DER; 47803101.der.doc 

47803102

47803103	860.1500 Caneberry	New DER; 47803103.der.doc

47803104

47803105	860.1500 Spinach	New DER; 47803105.der.doc

  SEQ CHAPTER \h \r 1 This document was originally prepared under
contract by Dynamac Corporation (1901 Research Boulevard, Suite 220;
Rockville, MD 20850).  The document has been reviewed by the Health
Effects Division (HED) and revised to reflect current Office of
Pesticide Programs (OPP) policies.

Executive Summary

  SEQ CHAPTER \h \r 1 Mefenoxam [methyl
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-D-alaninate] belongs to the
phenylamine class of systemic fungicides (Group 4).  Phenylamides are
effective against soil-borne diseases caused by Pythium and Phytophthora
and foliar diseases caused by Phycomycetes (downy mildews) on a wide
variety of crops.  

Mefenoxam is the enriched R-enantiomer of the fungicide metalaxyl, which
is a racemic mixture of R- and S-enantiomers (also referred to as the D-
and L-enantiomers, respectively).  Metalaxyl is a List A chemical; the
Residue Chemistry Chapter for the Metalaxyl Reregistration Eligibility
Decision (RED) Document was issued on 6/16/94.  Mefenoxam has replaced
metalaxyl in Syngenta Crop Protection, Inc. products.  Because it is the
most fungicidally active component of the mixture, it may be used at
half the application rates of metalaxyl.  HED has concluded (DP# 223261,
4/24/96, L. Kutney) that the established tolerances for metalaxyl will
be adequate to support the use of mefenoxam on the same crops provided
that (1) the use rates for mefenoxam are one-half the rate of metalaxyl;
(2) mefenoxam applications are made in the same way as for metalaxyl;
and (3) the labels restrict the use of both pesticides concurrently on
the same crop.  

The   SEQ CHAPTER \h \r 1 Interregional Research Project No. 4 (IR-4)
has submitted a request for amended registration for three Syngenta
products:  a 4 lb ai/gal emulsifiable concentrate (EC) formulation,
Ridomil Gold® EC (EPA Reg. No. 100-801); a 4 lb ai/gal liquid soluble
concentrate (SL) formulation, Ridomil Gold® SL (EPA Reg. No. 100-1202);
and a 5% wettable powder (WP) formulation, Ridomil Gold®/Copper (EPA
Reg. No. 100-804).  The 5% WP formulation is a multiple active
ingredient (MAI) product containing 5% mefenoxam and 60% copper
hydroxide.  For the 4 lb ai/gal EC and SL formulations, the petitioner
is proposing to:  (1) expand the registered use on onions to include
additional crops that are now included in the bulb vegetable crop group
3-07; (2) reduce the preharvest interval (PHI) for spinach from 21 to 3
days; (3) expand the registered foliar use of the 4 lb ai/gal EC and SL
formulations on head and leaf lettuce to cover all members of the leafy
vegetables group; (4) add new uses on the caneberry subgroup 13-07A; and
(5) expand the registered use on blueberries to cover the bushberry
subgroup 13-07B.  HED notes that mefenoxam is currently registered for
use on legume vegetables and raspberries; however, the proposed uses
reflect less restrictive use patterns than those currently registered. 
For the 5% WP formulation, the petitioner is proposing to:  (1) expand
the registered use on onions to include additional crops that are now
included in the bulb vegetable crop group 3-07 and snap beans; (2)
reduce the PHI for spinach from 21 to 3 days; (3) add new uses on snap
beans; and (4) add new uses on the caneberry subgroup.  

The use patterns addressed herein reflect a combination of proposed and
registered use directions for all crops except snap beans and
caneberries.  The 4 lb ai/gal EC and SL formulations are
proposed/registered for preplant incorporated and/or at-planting soil
applications to onions, leafy vegetables, caneberries, and bushberries
at 0.25-1.8 lb ai/A/application, for postemergence and/or post-planting
soil applications to caneberries and bushberries at 1.8 lb
ai/A/application, and for postemergence foliar application to leafy
vegetables/spinach at 0.125 lb ai/A/application.  The 5% WP formulation
is proposed/registered for one to four postemergence foliar applications
to onions, spinach, snap beans, and caneberries at 0.1-0.125 lb
ai/A/application, with applications generally to be made following soil
application of the EC or SL formulation.  The proposed/registered
maximum seasonal rates for combined soil and foliar applications are 1.3
lb ai/A for green bulb vegetables, 1.4 lb ai/A for spinach and snap
beans, 1.5 lb ai/A for onions, , and 3.6 lb ai/A for caneberries and
bushberries; and the proposed/registered PHIs are 10 and 7 days for dry
bulb and green onions, respectively, 7 days for leafy vegetables (except
spinach), 3 days for spinach, 6 days for snap beans, 45 days (soil
application) and 0 days (foliar application) for caneberries, and 0 days
for blueberries.  

In support of the proposed/registered uses, IR-4 is proposing under
PP#9E7591 the establishment of permanent tolerances for residues of the
fungicide mefenoxam, (R) and
(S)-2-[2,6-dimethyl(phenyl)-methoxyacetylamine]-propionic acid methyl
ester, and its metabolites containing the 2,6-dimethylaniline moiety,
and N-(2-hydroxy methyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl
ester  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 ,
in/on the following raw agricultural commodities:  

Bean, snap, succulent	0.35 ppm

Caneberry, subgroup 13-07A	0.80 ppm

Bushberry subgroup 13-07B	2.0 ppm

Onion, bulb, subgroup 3-07A	3.0 ppm

Onion, green, subgroup 3-07B	10.0 ppm

Spinach	8.0 ppm

IR-4 has also proposed that the established tolerance for lingonberry be
removed when the tolerance for the bushberry subgroup is established.  

Tolerances for mefenoxam are established under 40 CFR §180.546 and are
expressed in terms of combined residues of (R)- and
(S)-2-[2,6-dimethyl(phenyl)-methoxyacetylamine]-propionic acid methyl
ester and its metabolites containing the 2,6-dimethylaniline moiety, and
N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl
ester, each expressed as mefenoxam equivalents.  Tolerances are
established on globe artichoke, fresh and dried herbs, and a variety of
tropical fruits, and range 0.05-55 ppm.

Tolerances for metalaxyl are established under 40 CFR §180.408 and are
expressed in terms of the combined residues of the fungicide metalaxyl
[N-(2,6-dimethylphenyl)-N-(methoxyacetyl) alanine methyl ester], and its
metabolites containing the 2,6-dimethylaniline moiety, and
N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl
ester, each expressed as metalaxyl equivalents.  The established
tolerances for crop commodities ranged from 0.1-25 ppm, and established
tolerances for livestock commodities range from 0.02 ppm for milk to 0.4
ppm for fat, kidney, and liver of cattle, goat, hog, horse, poultry, and
sheep.  In addition, a tolerance with regional registration has been
established under 180.408(c) for papaya at 0.1 ppm, and tolerances for
indirect or inadvertent residues of metalaxyl are established under
180.408(d) for barley, cereal grain, oat, and wheat commodities ranging
from 0.2 ppm (grain) to 2.0 ppm (forage and straw).

The registered uses for mefenoxam that are relevant to the subject
petition are supported by the following metalaxyl tolerances:  blueberry
at 2.0 ppm, onion, bulb at 3.0 ppm; onion, green at 10.0 ppm; and
spinach at 10.0 ppm.  In addition, a tolerance on vegetable, legume,
group 6 is established at 0.2 ppm, and a tolerance on raspberry is
established at 0.5 ppm.

The nature of the residue in plants and livestock is adequately
understood for mefenoxam, based on metalaxyl metabolism studies on
potato, grape, lettuce, goat, and hen.  Metabolites can be separated
into four classes:  (1) those containing a 2,6-dimethylaniline (2,6-DMA)
moiety; (2) those containing a 2-hydroxymethyl-6-methylaniline (HMMA)
moiety; (3) those containing a ring hydroxylated dimethylaniline
(Ring-OH) moiety; and (4) those containing a benzoic acid moiety.  The
nature of the residue in rotational crops is adequately understood for
mefenoxam based on confined rotational crop studies conducted with
metalaxyl on lettuce, sugar beet, and wheat.  Metabolism in rotated
crops generally proceeds by the same pathways seen in primary crops,
resulting in the same four classes of metabolites.

HED originally concluded that the mefenoxam residues to be regulated for
the tolerance expression and for dietary assessments would be as
follows:

In plants:  (R)- and
(S)-2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid methyl
ester, its metabolites containing the 2,6-DMA moiety, and
N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)alanine methyl ester
(CGA-94689)  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1   SEQ CHAPTER \h
\r 1 , each expressed as mefenoxam equivalents.

In livestock:  (R)- and
(S)-2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid methyl
ester, its metabolites containing the 2,6-DMA moiety, and its
metabolites containing the HMMA moiety  SEQ CHAPTER \h \r 1   SEQ
CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 , each expressed as mefenoxam
equivalents.

In rotational crops:  (R)- and
(S)-2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid methyl
ester, its metabolites containing the 2,6-DMA moiety, and CGA-94689  SEQ
CHAPTER \h \r 1   SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 , each
expressed as mefenoxam equivalents, except that
2-[(methoxyacetyl)(2-methoxy-1-methyl-2-oxoethyl)amino]-3-methylbenzoic
acid (CGA-108905) would also be included in the risk assessment for
cereal grain rotational crops and
N-(3-hydroxy-2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methyl ester
(CGA-100255) would be included in the risk assessment for leafy
vegetable (Brassica and non-Brassica) rotational crops.

The HED Risk Assessment Review Committee (RARC) subsequently determined
(report dated 2/14/07) that: (1) the residue to be regulated (in the
tolerance expression) in plant and livestock commodities is (R)- and
(S)-2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid methyl
ester; (2) the current/reassessed tolerance levels should be retained;
(3) for risk assessment, the residues of concern in plant and livestock
commodities are metalaxyl/mefenoxam, its metabolites containing the
2,6-DMA moiety, its metabolites containing the HMMA moiety, its
metabolites containing the Ring-OH moiety, and its metabolites
containing the benzoic acid moiety; and (4) the available residue
chemistry data can be used and factors may be employed to estimate the
total residues of concern in dietary risk assessments.  

There are no livestock feedstuffs associated with the
proposed/registered uses on onions, leafy vegetables/spinach, snap
beans, caneberries, and bushberries.  Therefore, no livestock metabolism
data, enforcement methods, storage stability data, or feeding studies
are required to support this petition.

The residue analytical methods available for tolerance enforcement in
plant commodities are common moiety methods which determine residues of
metalaxyl/mefenoxam that are convertible to 2,6-DMA.  These methods
include: (1) Method I in the Pesticide Analytical Manual (PAM), Vol. II
(Method AG-348) which determines residues in plant commodities using
gas-liquid chromatography with alkali flame-ionization detection
(GLC/AFID); and (2) Method AG-395 (sent to FDA for inclusion in PAM,
Vol. II as Method III), an improved version of Method AG-348, which
determines residues in plant commodities using GLC with
nitrogen-phosphorus detection (NPD).  Neither Method AG-348 nor Method
AG-395 distinguish between the R- and S-enantiomers of
metalaxyl/mefenoxam; however, a confirmatory high performance liquid
chromatography method with mass spectrometric detection that utilizes a
chiral column (chiral LC/MS), Method 456-98, is available for the
enantioselective determination of the D- and L- enantiomers of metalaxyl
in crops.  This method has been adequately validated by ACB/BEAD, and a
revised version of the method has been submitted for inclusion in PAM,
Vol. II.   

HED has determined that the 2,6-DMA common moiety residue analytical
methods available for tolerance enforcement and used for data collection
will not adequately recover all of the metalaxyl/mefenoxam residues of
concern in the current tolerance expressions.  While these methods are
adequate to recover residues of metalaxyl/mefenoxam per se, they will
not adequately recover metabolites containing the HMMA moiety and may
not adequately recover all metabolites containing the 2,6-DMA moiety
with the certainty needed to set legal limits, nor are they likely to
recover metabolites containing the Ring-OH moiety or the benzoic acid
moiety.  As a result, in addition to the changes to the tolerance
expression and the residues of concern for risk assessment addressed
above, the HED RARC determined that: (1) the multiresidue method PAM,
Vol. I Section 302 (Protocol D), which completely recovers
metalaxyl/mefenoxam per se, is an adequate enforcement method for the
determination of metalaxyl/mefenoxam per se in plant and livestock
commodities; and (2) all future metalaxyl/mefenoxam magnitude of the
residue data should include (a) analysis for residues of parent only
using the multiresidue method PAM, Vol. I Section 302 in order to
establish more appropriate tolerance levels, and (b) analysis using a
2,6-DMA common moiety method, including recovery data for parent,
CGA-62826, and CGA-94689, in order to refine dietary risk assessments. 
SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 

Samples from the submitted snap bean and caneberry trials were initially
analyzed for residues of mefenoxam per se using a chiral LC/MS method,
Method 456-98.  Samples of spinach from the submitted field trials and
selected samples of snap bean and caneberries were analyzed for combined
residues of mefenoxam/metalaxyl, and metabolites convertible to 2,6-DMA
using a gas chromatography (GC)/MS method, defined by working method
numbers YARL-0601A (caneberry), -0601C (snap bean), and -0601D (spinach)
which was derived, with minor modifications, from Method AG-395.  The
data collection methods were adequate for data collection based on
acceptable method validation and concurrent recovery data for mefenoxam.
 The lowest level of method validation (LLMV) was 0.05 ppm for snap bean
and caneberries using Method 456-98, and the LLMVs were 0.1 ppm for
spinach and 0.05 ppm for snap bean and caneberries using Methods
YARL-0601A, -0601C, and -0601D. 

The study results for snap bean and caneberry, reflecting the original
analysis for mefenoxam only and re-analysis of the selected field trial
samples for parent + metabolites, were presented to HED’s Chemistry
Science Advisory Council (ChemSAC) with a request to use conversion
factors (calculated by dividing the residues obtained on re-analysis of
certain field trial samples by the original values) to calculate
residues in the remaining field trial samples for setting residue values
for the risk assessment.  The calculated conversion factors are:  for
snap beans, 1x for 0-day preharvest interval (PHI), 1.8x for the 6- to
7-day PHI, and 3x for the 13- to 14-day PHI; and 1.3x for caneberries. 
The ChemSAC agreed (see minutes of 2/25/09 meeting) that parent +
metabolites to parent ratios could be used to estimate residue levels
for risk assessments in snap beans and caneberries, with the provision
that these ratios would not necessarily be correct/adequate for these
commodities for future risk assessments if refinements were necessary.  

The submitted crop field trial studies are supported by adequate storage
stability data.  

Pending amendment of the proposed labels, adequate field trial data have
been submitted for snap beans, and adequate data have been submitted for
spinach treated with a soil application of the EC or SL formulation
followed by foliar application of the WP formulation.  For caneberries,
an additional field trial conducted in Zone 5 or 6 and including residue
decline data is required as a condition of registration; the proposed
use must also be amended.  The submitted data used to determine
tolerances for snap bean and caneberries reflected analysis of samples
for mefenoxam per se; the data for spinach reflected analysis for
combined residues of mefenoxam/metalaxyl and metabolites convertible to
2,6-DMA.  The crop field trial data for spinach will support a reduction
in PHI from 21 days to 3 days, pending label amendments.  Data are not
available to support expanded foliar use of the 4 lb ai/gal EC and SL
formulations on spinach or other members of the leafy vegetables group. 
The submitted crop field trial data for spinach will support a tolerance
of 8.0 ppm for spinach; however, because the submitted data are not
representative of all registered uses of mefenoxam on spinach, HED
recommends against establishing a reduced tolerance for mefenoxam on
spinach.  The existing tolerance of 10 ppm for spinach, established
under 40 CFR §180.408, is appropriate.  The proposed tolerances for
snap bean and the caneberry subgroup are too high; tolerances should be
established at 0.20 ppm for snap bean and 0.70 ppm for caneberry
subgroup 13-07A.

  

Adequate crop field trial data for metalaxyl are available to support
expanded use of mefenoxam on members of the bulb and green onion
subgroups and bushberry subgroup.  The available data will support
establishment of the proposed tolerances for residues of mefenoxam in/on
onion, bulb, subgroup 3-07A at 10 ppm; onion, green, subgroup 3-07B at
3.0 ppm; and bushberry subgroup 13-07B at 2.0 ppm.  In conjunction with
establishment of the proposed tolerance for the bushberry subgroup, the
mefenoxam tolerance for lingonberry can be removed.

Adequate field rotational crop data are available to support the
established plantback intervals for mefenoxam. 

Codex MRLs, expressed in terms of metalaxyl per se for plant
commodities, are established for spinach at 0.1 and onion at 0.03 ppm. 
Canadian (Pest Management Regulatory Agency; PMRA) MRLs for mefenoxam
(metalaxyl-M) are covered by MRLs established for metalaxyl, the
unresolved isomeric mixture, which are expressed in terms of
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alanine methyl ester,
including metabolites that can be converted to the 2,6-dimethylaniline
moiety, calculated as metalaxyl equivalents.  Canadian MRLs are
established for spinach at 10 ppm, bulb onion at 3.0 ppm, green onion at
10 ppm, bean at 0.2 ppm, raspberry at 0.2 ppm, and blueberry at 2.0 ppm.
 No Mexican MRLs are established for mefenoxam or metalaxyl.  With the
adoption of the tolerance expression recommended by the RARC, the U.S.
tolerance expression will be in harmonization with Codex MRLs but not
with PMRA MRLs. 

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

HED has examined the residue chemistry database for mefenoxam and
metalaxyl.  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 full registration for the requested uses of
mefenoxam on members of the bulb and green onion subgroups, spinach,
snap beans, and bushberry subgroup, or conditional registration for the
requested use on the caneberry subgroup.  Tolerances for residues of
mefenoxam per se are recommended as follow:  

Bean, snap, succulent	0.20 ppm

Caneberry subgroup 13-07A	0.70 ppm

Bushberry subgroup 13-07B	2.0 ppm

Onion, bulb, subgroup 3-07A	3.0 ppm

Onion, green, subgroup 3-07B	10 ppm

Spinach	10 ppm

 

As a condition of registration, additional crop field trial data are
required for caneberries (see requirements under Crop Field Trials).

In the absence of supporting crop field trial data, HED recommends
against expanding the registered foliar uses of the 4 lb ai/gal EC and
SL formulations on head and leaf lettuce to include spinach or any other
members of the leafy vegetables except Brassica crop group.

A human health risk assessment is forthcoming.

Note to PM:  Based on the tolerance expressions recommended by HED’s
Risk Assessment Review Committee (2/14/07, W. Britton) and by HED in the
metalaxyl/mefenoxam registration review (DP#368461, N. Dodd, 4/13/10),
and to be consistent with Codex, the tolerance expression for mefenoxam
should be revised according to HED’s Interim Guidance on Tolerance
Expressions (5/27/09, S. Knizner) to state:

“Tolerances are established for residues of mefenoxam, including its
metabolites and degradates, in or on the commodities in the table below.
 Compliance with the tolerance levels specified below is to be
determined by measuring only metalaxyl  (methyl
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate).”

Note to PM:  When the recommended tolerance on Bushberry subgroup 13-07B
is established, the tolerance for lingonberry should be removed.

860.1200 Directions for Use

A revised Section B must be submitted reflecting the following changes
to the proposed use directions.

For onions:

Since the WP label for bulb onions indicates a maximum of 0.4 lb
ai/A/season of foliar-applied mefenoxam, the proposed use directions for
the 4 lb ai/gal EC and SL formulations should be revised to reflect the
following maximum seasonal rate for bulb onion:  “Do not exceed the
equivalent of 1.0 lb ai/A per crop of soil-applied and 0.4 lb ai/A per
crop of foliar-applied mefenoxam-containing products.”

The proposed use directions for the 5% WP formulation should be revised
to reflect the following maximum seasonal rates:  (1) for bulb onion,
“Do not exceed the equivalent of 1.0 lb ai/A per crop of soil-applied
and 0.4 lb ai/A per crop of foliar-applied mefenoxam-containing
products”; and (2) for green onion, “Do not exceed the equivalent of
1.0 lb ai/A per crop of soil-applied and 0.3 lb ai/A per crop of
foliar-applied mefenoxam-containing products.”

For leafy vegetables/spinach:

The proposed labels for Leafy Vegetables and Spinach Only must be
revised.  The 3-day PHI for spinach can be applied only to application
types and rates supported  by the 3-day PHI data (i.e., soil application
at 1.0 lb ai/A/season and foliar application at 0.25 lb ai/A/season).  
Soil application of the EC formulation can be translated to the SL
formulation.  Based on the available data for spinach at the proposed
3-day PHI, the proposed use directions for Spinach Only should be
revised to specify soil surface application of the EC or SL formulations
and foliar directed or broadcast spray applications of the WP
formulation, and to specify the following maximum seasonal rates:  “Do
not exceed the equivalent of 1.0 lb ai/A per crop of soil-applied
mefenoxam containing products at planting and 0.25 lb ai/A of
foliar-applied mefenoxam containing products.”  The proposed changes
to the existing Leafy Vegetables section of the existing labels to
establish a 3-day PHI for spinach should be removed.

For the 4 lb ai/gal EC and SL formulations, spinach and all other
members of the leafy vegetables except Brassica crop group, except head
and leaf lettuce, must be removed from the use directions for Part 2 of
the proposed label; the reference to Part 2 of the label that appears in
Part 1 should be revised accordingly. 

On the 5% WP formulation label, the statement referring to a 21-day PHI
for spinach should be removed.

The proposed use directions for all three products must be amended to
specify that no adjuvants may be added to spray mixtures for foliar use
on spinach.

When HED approved the registered use of the 4 lb ai/gal EC formulation
on head and leaf lettuce (DP# 324493, 3/17/06, L. Cheng), certain label
revisions were required which have not been made.  These revisions also
apply to the label for the 4 lb ai/gal SL formulation.   As previously
required under DP# 324493, Part 1 of the labels for the 4 lb ai/gal EC
and SL formulations should be revised to specify that no more than one
soil-directed application may be made, and Part 2 should be revised to
specify a maximum of 4 foliar-directed applications.

Snap Beans:  

The proposed use directions for the 5% WP formulation must be revised to
specify a maximum of two applications per season at 0.1 lb
ai/A/application and to reflect the following maximum seasonal rate for
snap bean:  “Do not exceed the equivalent of 0.5 lb ai/A per crop of
soil-applied mefenoxam containing products at planting and 0.2 lb ai/A
per crop of foliar-applied mefenoxam-containing products.”

The proposed use directions for the 5% WP formulation must be revised to
propose a 7-day preharvest interval (PHI).  Four of eight field trials
have a 7-day PHI and four have a 6-day PHI.

The proposed use directions must be amended to specify that no adjuvants
may be added to spray mixtures for foliar use on snap beans.

Caneberries:

The proposed use directions for the 4 lb ai/gal EC and SL formulations
for the caneberry subgroup must be revised to specify a maximum of one
soil application per season at 1.8 lb ai/A and to reflect the following
maximum seasonal rate:  “Do not exceed the equivalent of 1.8 lb ai/A
per crop of soil-applied and 0.2 lb ai/A per crop of foliar-applied
mefenoxam-containing products for a maximum seasonal application rate of
2.0 lb ai/A.”

To clarify the use pattern for established plantings specified in Part 2
of the labels for the 4 lb ai/gal EC and SL formulations, the use
directions should be revised to indicate that applications are to be
directed toward the base of the plants.

The proposed use directions for the 5% WP formulation must be revised to
specify a maximum of two foliar applications per season at 0.1 lb
ai/A/application and to reflect the following maximum seasonal rate: 
“Do not exceed the equivalent of 1.8 lb ai/A per crop of soil-applied
and 0.2 lb ai/A per crop of foliar-applied mefenoxam-containing products
for a maximum seasonal application rate of 2.0 lb ai/A.”

For all three products, bromberre must be corrected to brombeere and
nectaberry must be corrected to nectarberry.

The proposed use directions for all three products must be amended to
specify that no adjuvants may be added to spray mixtures for foliar use
on caneberries.

Bushberries: 

The following berries are not members of bushberry subgroup 13-07B and
must be removed from the crops listed under the bushberry subgroup on
the labels for the 4 lb ai/gal EC and SL formulations:  bilberry,
bearberry, cloudberry, muntries, and partridgeberry.

To clarify the use pattern for established plantings specified in Part 2
of the labels for the 4 lb ai/gal EC and SL formulations, the use
directions should be revised to indicate that applications are to be
directed toward the base of the plants.

For both products, hostaberry must be corrected to jostaberry.

When the proposed use on bushberries is registered for the 4 lb ai/gal
EC and SL formulations, the separate use directions for lingonberries
may be removed from the labels. 

860.1550 Proposed Tolerances

Based on the tolerance expressions recommended by the RARC and by HED in
the metalaxyl/mefenoxam registration review, and to be consistent with
Codex, the tolerance expression proposed by IR-4 under PP#9E7591 must be
revised.  The tolerance expression should be stated as follows:

Tolerances are established for residues of mefenoxam, including its
metabolites and degradates, in or on the commodities in the table below.
 Compliance with the tolerance levels specified below is to be
determined by measuring only metalaxyl [methyl
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate].

The proposed tolerances for snap bean and the caneberry subgroup are too
high; tolerances should be established at 0.20 ppm for snap bean and
0.70 ppm for caneberry subgroup 13-07A.

The proposed tolerance for spinach is too low; a tolerance should be
established at 10 ppm.

In conjunction with establishment of the proposed tolerance for the
bushberry subgroup, the mefenoxam tolerance for lingonberry can be
removed.

The proposed tolerance for the caneberry subgroup must be revised to
reflect the correct commodity definition:  “Caneberry subgroup
13-07A.”

HED recommends that conversion of conditional registration to
unconditional registration for the requested uses on the caneberry
subgroup may be considered upon submission of the following crop field
trial data.

860.1500 Crop Field Trials

To fulfill geographic distribution requirements, an additional field
trial must be conducted in Zone 5 (raspberry) or 6 (blackberry).  The
required trial should include additional sampling intervals to assess
residue decline. 

Background

The chemical structure and nomenclature of mefenoxam and its regulated
metabolites/metabolite moieties are presented in Table 1.  The
physicochemical properties of the technical grade of mefenoxam are
presented in Table 2.  In addition, the chemical names and structures of
metabolites referenced herein are presented in Appendix I.  

Table 1.		Test Compound Nomenclature.

Compound	

Common name	mefenoxam; metalaxyl-M

Company experimental name	CGA-329351

IUPAC name	methyl N-(methoxyacetyl)-N-(2,6-xylyl)-D-alaninate

CAS name	methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-D-alaninate

CAS registry number	70630-17-0

End-use product (EP)	Ridomil Gold® EC (4 lb ai/gal EC; EPA Reg. No.
100-801)

Ridomil Gold® Copper (5% WP; EPA Reg. No. 100-804)

Ridomil® Gold SL (4 lb ai/gal EC; EPA Reg. No. 100-1202)

Regulated metabolite in plant and rotational crop commodities	

N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)alanine methyl
ester; CGA-94689

Regulated metabolite moiety in plant, livestock, and rotational crop
commodities	

2,6-dimethylaniline moiety (2,6-DMA when R1=R2=H)

Regulated metabolite moiety in livestock commodities	

2-hydroxymethyl-6-methylalanine (HMMA when R1=R2=H)

Table 2.		Physicochemical Properties of Mefenoxam. 

Parameter	Value1	Reference

Boiling point/range	>270 ºC (PAI)	MRID 43800301; DP# 223261, 4/24/96,
L. Kutney

pH	5-6 at 25 °C (1% aqueous dispersion; TGAI)

	Density	1.125 g/cm3 (20 °C; TGAI)

	Water solubility	26 g/L (25 °C; PAI)

	Solvent solubility	Completely miscible in acetone, dichloromethane,
ethyl acetate, methanol, n-octanol, and toluene; 59 g/L in n-hexane at
25 °C (TGAI).

	Vapor pressure	3.3 x 10-3 (25 °C; PAI)

	Dissociation constant, pKa	None in 1-10 pH range (PAI)

	Octanol/water partition coefficient, Log(KOW)	1.71 at 25 °C (TGAI)

	UV/visible absorption spectrum	Not available

	1  TGAI = Technical grade of the active ingredient; PAI = Purified
active ingredient.

860.1200 Directions for Use

IR-4 has submitted proposed amended use directions for three products
registered to Syngenta:  a 4 lb ai/gal EC formulation, Ridomil Gold® EC
(EPA Reg. No. 100-801; label dated 7/7/09); a 4 lb ai/gal SL
formulation, Ridomil Gold® SL (EPA Reg. No. 100-1202; label dated
7/30/09); and a 5% WP formulation, Ridomil Gold®/Copper (EPA Reg. No.
100-804; label dated 7/30/09).  The 5% WP formulation is an MAI product
containing 5% mefenoxam and 60% copper hydroxide.  

For the 4 lb ai/gal EC and SL formulations, the petitioner is proposing
to:  (1) expand the registered use on onions to include additional crops
that are now included in the bulb vegetable crop group 3-07; (2) reduce
the preharvest interval (PHI) for spinach from 21 to 3 days; (3) expand
the registered foliar use of the 4 lb ai/gal EC and SL formulations on
head and leaf lettuce to cover all members of the leafy vegetables
group; and (4) add new uses on the caneberry subgroup; and (5) expand
the registered use on blueberries to cover the bushberry subgroup.  For
the 5% WP formulation, the petitioner is proposing to:  (1) expand the
registered use on onions to include additional crops that are now
included in the bulb vegetable crop group 3-07; (2) reduce the PHI for
spinach from 21 to 3 days; (3) add new uses on snap beans; and (4) add
new uses on the caneberry subgroup.  

The proposed use directions for the EC and SL formulations are divided
into two parts on the labels:  “Part 1:  Soil-Injected or
Soil-Incorporated Applications” and “Part 2:  Soil Directed and
Other Foliar Applications.”  

The proposed changes to the crops or use patterns from those which
appear on the accepted labels are highlighted in Table 3.

Table 3.  Summary of Directions for Use of Mefenoxam.

Applic. Timing, Type, and Equipment1	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 Limitations2

Onions3:  Dry Bulb including Garlic, Onions (dry bulb), Shallots (dry
bulb); and Green including Green eschalots, Green onions, Green
shallots, Japanese bunching onions, Leeks, Spring onions, Scallions. 
Including hybrids, cultivars, and varieties of these.  Other Dry Bulb
Crops:  Great-headed Garlic, Serpent Garlic, Lily Bulb, Chinese Onion
Bulb, Pearl Onion, Potato Onion Bulb.  Other Green Bulb Crops:  Chive
(fresh leaves), Chinese Chive (fresh leaves), Hosta Elegans, Fritillaria
(leaves), Kurrat, Lady’s Leek, Beltsville Bunching Onion, Onion
(fresh), Macrostem Onion, Tree Tops Onion, Welsh Onion (tops), Shallot
(fresh leaves)

Preplant incorporated (broadcast or band)

At planting

Soil spray (broadcast or band)	4 lb/gal EC

[100-801]

4 lb/gal SL

[100-1202]	0.25-0.50	Not specified	1.0 soil + 0.5 foliar applied (dry
bulb)

1.0 soil + 0.3 foliar applied  (green)	Not specified	Part 1:  Apply in
water or liquid fertilizer.  For preplant incorporated application,
mechanically incorporate in the top 2 inches of soil.   For banded
applications, use a 7-inch band.

Postemergence

Foliar	5% WP

[100-804]	0.1	4

(dry bulb and seed)

3

(green)	0.4	10

(dry bulb)

7

(green)	Begin applications when conditions are favorable for disease,
but before infection; continue at a 14-day RTI.  Use of a suitable
spreader-sticker is recommended.

Leafy Vegetables (Except Brassica):  Celery, Endive (Escarole), Lettuce
(Head and Leaf), Parsley, Rhubarb, Spinach, Swiss chard.  Additional
Leafy Vegetable Crops:  Amaranth, Arugula, Cardoon, Celtuce, Chervil,
Chinese Celery, Chrysanthemum (edible-leaved), Chrysanthemum (garland),
Corn salad, Cress (garden), Cress (Upland), Dandelion, Dock (Sorrel),
Florence Fennel (finochio), Orach, Purslane (garden), Purslane (winter),
Radicchio (red chicory), Spinach (New Zealand), and Spinach (vine)

Preplant incorporated (broadcast or band)

At planting

Soil spray (broadcast or band) 	4 lb/gal EC

[100-801]

4 lb/gal SL

[100-1202]	0.50-1.0	Not specified	1.0 soil + 0.4 foliar applied (all
except spinach)

1.0 soil + 0.25 shank to soil or 0.4 foliar applied  (spinach)	7

(all except spinach)

3

(spinach)	Part 1:  Apply in water or liquid fertilizer.  For preplant
incorporated application, mechanically incorporate in the top 2 inches
of soil.   For banded applications, use a 7-inch band.  

Postemergence

Foliar	4 lb/gal EC

[100-801]

4 lb/gal SL

 [100-1202]	0.063-0.125	Not specified	1.0 soil + 0.4 foliar applied 	74

(all except spinach)

3

(spinach)	Part 2:  Apply only in a tank mix with other fungicides, when
conditions are favorable for disease; continue at a 14-day RTI.  

Spinach only

Shank injections

Soil	4 lb/gal EC

[100-801]

4 lb/gal SL

 [100-1202]	0.125	2	1.0 soil + 0.25 shank to soil or 0.4 foliar applied
3	Part 1:  Apply in addition to preplant incorporated or at-planting
soil spray applications5, 21 days after planting or first cutting; a
second application may be made after the next cutting at a 21-day
retreatment interval.  

Postemergence

Foliar	5% WP

[100-804]	0.125	2	Not specified	3	Apply 21 days after preplant or
at-planting application of the 4 lb/gal EC formulation at 0.5-1 lb ai/A
or immediately after each repeated cutting.  Make 1-2 applications at a
14-day RTI; avoid late season applications.

Snap Beans

Postemergence

Foliar	5% WP

[100-804]	0.1	4	0.4	6	Begin applications at onset of disease; continue
at a 7-day RTI.

Caneberry (Blackberry and Raspberry) Subgroup:  Blackberry, Raspberry
(Red and Black), Wild Raspberry Cultivars, Including hybrids, cultivars,
and varieties of these.

Subgroup includes Andean Blackberry, Arctic Blackberry, Bingleberry,
Black Satin Berry, Boysenberry, Bromberre, California Blackberry,
Cherokee Blackberry, Chesterberry, Cheyenne Blackberry, Common
Blackberry, Coryberry, Darrowberry, Dewberry, Dirksen Thornless Berry,
Evergreen Blackberry, Himalayaberry, Hullberry, Lavacaberry, Loganberry,
Lowberry, Lucretiaberry, Mammoth Blackberry, Marionberry, Mora, Mures
Deronce, Nectaberry, Northern Dewberry, Olallieberry, Oregon Evergreen
Berry, Phenomenalberry, Rangeberry, Ravenberry, Rossberry, Shawnee
Blackberry, Southern Dewberry, Tayberry, Youngberry, Zarzamora

At planting

Soil spray (broadcast or band)	4 lb/gal EC

[100-801]

4 lb/gal SL

[100-1202]	1.8	1

(implied)	3.6

soil applied	45	Part 1:  New plantings:  For banded applications, use an
18-inch band

Postemergence

Soil spray (band)

1.8	Not specified

	Part 2:  Established plantings:  Apply in a 3-ft band over the row
before plants start to grow in the spring.

Postemergence

Foliar	5% WP

[100-804]	0.1	4	3.6 soil + foliar applied	0	Begin applications when
conditions are favorable for disease, but before infection; continue at
a 7-day RTI.

Bushberry Subgroup:  Blueberries (High and Low Bush), Currants,
Elderberry, Gooseberry, Highbush Cranberry, Including hybrids,
cultivars, and varieties of these.

 Other Bushberries in Subgroup:  Aronia Berry, Highbush Blueberry,
Lowbush Blueberry, Bearberry, Bilberry, Buffalo Currant, Chilean Guava,
Cloudberry, Black Currant, Red Currant, Elderberry, European Barberry,
Gooseberry, Highbush Cranberry, Edible Honeysuckle, Huckleberry,
Hostaberry, Juneberry, Lingonberry, Muntries, Native Currant,
Partridgeberry, Salal, Sea Buckthorn.

At planting

Soil spray (broadcast or band)	4 lb/gal EC

[100-801]

4 lb/gal SL

[100-1202]	1.8	1

(implied)	3.6

soil applied	0	Part 1:  Application is to be made to new plantings.  For
banded applications, use an 18-inch band.

Post-planting

Soil spray (band)

1.8	1

	Part 2:  New plantings:  After initial at-planting application, reapply
once during a period favorable for root rot.

Postemergence

on the accepted labels; use of ground, aerial, and irrigation equipment
is approved for all products.  Ground applications are to be made in
≥20 gal/A of water, and aerial applications are to be made in ≥3
gal/A of water.

2  For the proposed and registered labels for the 4 lb/gal EC and SL
formulations, Part 1 = Soil-Injected or Soil-Incorporated Applications
and Part 2 = Soil Directed and Other Foliar Applications.  RTI =
Retreatment interval.

3  The proposed and accepted labels for the 5% WP formulation also list
onions grown for seed. 

4  For the 4 lb/gal SL formulation, Section B reflects foliar use on all
leafy vegetables listed; on the Data Package Label, the proposed use is
listed for head and leaf lettuce and spinach.  The registered labels for
both products reflect foliar use on head and leaf lettuce only.

5  This statement appears on the 4 lb/gal EC label only; use directions
for the 4 lb/gal SL state:  Shank in 21 days after planting or after the
first cutting.

The accepted labels include the following rotational crop restrictions: 
(1) 0 days for crops for which use of mefenoxam/metalaxyl is registered;
(2) 40 days (5% WP formulation) and 14 days (4 lb ai/gal EC and SL
formulations) for cereal grains other than corn; (3) 9 months for corn;
and (4) 12 months for any crop for which use of mefenoxam/metalaxyl is
not registered.  The directions on the 5% WP label further state that
deciduous fruit and nut crops and other perennial crops may be planted
immediately following last application of mefenoxam provided they will
not bear harvestable fruit within 12 months.

HED notes that the cover letters accompanying the accepted labels for
the 4 lb ai/gal EC and SL formulations and the 5% WP formulation require
that the following statement be added:  “Maximum usage when applying
both metalaxyl and mefenoxam containing products to the same crop within
the same season:  Do not apply more than the maximum seasonal total for
the active ingredient as stated on the label of the product containing
the lowest seasonal total on that crop.”

Conclusions.  The submitted use directions are sufficient to allow
evaluation of the submitted and available residue data relative to the
proposed use patterns and crops.  The submitted and available data for
mefenoxam and metalaxyl will support the requested uses of mefenoxam on
onions (and other green and dry bulb crops), snap beans, spinach, and
the caneberry and bushberry subgroups, pending revision of the proposed
labels as indicated below.

HED notes that as stated in OPPTS 860.1500, data may be translated among
the SL and EC formulation classes and other formulation types which are
diluted in water prior to application for applications directed to the
soil (as opposed to foliar treatments).

Onions:  Previously reviewed crop field trial data for metalaxyl on bulb
onions and green onions will support the proposed expanded use on the
onions listed in Table 3, provided the following changes to the use
directions are made:

The proposed use directions for the 4 lb ai/gal EC and SL formulations
should be revised to reflect the following maximum seasonal rate for
bulb onion:  “Do not exceed the equivalent of 1.0 lb ai/A per crop of
soil-applied and 0.4 lb ai/A per crop of foliar-applied
mefenoxam-containing products.”

The proposed use directions for the 5% WP formulation should be revised
to reflect the following maximum seasonal rates:  (1) for bulb onion,
“Do not exceed the equivalent of 1.0 lb ai/A per crop of soil-applied
and 0.4 lb ai/A per crop of foliar-applied mefenoxam-containing
products”; and (2) for green onion, “Do not exceed the equivalent of
1.0 lb ai/A per crop of soil-applied and 0.3 lb ai/A per crop of
foliar-applied mefenoxam-containing products.”

HED notes that the expanded list of onions that appears on each label
could additionally include the bulb onions daylily bulb and fritillaria
bulb, and the green onion wild leek. 

Leafy vegetables/spinach:  Revisions are needed to the proposed labels
as follow.

The proposed labels for Leafy Vegetables and Spinach Only must be
revised.  The 3-day PHI for spinach can be applied only to application
types and rates supported  by the 3-day PHI data.  The submitted spinach
crop field trial data reflect a single at-planting application of the 4
lb ai/gal EC formulation at 1.0 lb ai/A followed by two foliar
applications of the 5% WP formulation at 0.125 lb ai/A/application for a
total seasonal application rate of 1.25 lb ai/A.  Soil application of
the EC formulation can be translated to the SL formulation.  Based on
the available data for spinach at the proposed 3-day PHI, the proposed
use directions for Spinach Only should be revised to specify soil
surface application of the EC or SL formulations and foliar directed or
broadcast spray applications of the WP formulation, and to specify the
following maximum seasonal rates:  “Do not exceed the equivalent of
1.0 lb ai/A per crop of soil-applied mefenoxam containing products at
planting and 0.25 lb ai/A of foliar-applied mefenoxam containing
products.”  The proposed changes to the existing Leafy Vegetables
section of the existing labels to establish a 3-day PHI for spinach
should be removed.

The available and submitted crop field trial data for leafy vegetables
do not support expanding the registered foliar uses of the 4 lb ai/gal
EC and SL formulations on head and leaf lettuce to include spinach or
any other members of the leafy vegetables except Brassica crop group. 
For the 4 lb ai/gal EC and SL formulations, spinach and all other
members of the leafy vegetables except Brassica crop group, except head
and leaf lettuce, must be removed from the use directions for Part 2 of
the proposed label; the reference to Part 2 of the label that appears in
Part 1 should be revised accordingly. 

On the 5% WP formulation label, the statement referring to a 21-day PHI
for spinach should be removed.

No spray adjuvants were used in the submitted crop field trials on
spinach.  HED has concluded that spray adjuvant use must be prohibited
on product labels when the field trials did not include adjuvants (see
minutes of 4/16/08 ChemSAC meeting).  Therefore, the product label for
foliar applications must be amended to specify that no adjuvants may be
added to spray mixtures for foliar use on spinach.

When HED approved the registered use of the 4 lb ai/gal EC formulation
on head and leaf lettuce (DP# 324493, 3/17/06, L. Cheng), certain label
revisions were required which have not been made.  These revisions also
apply to the label for the 4 lb ai/gal SL formulation.   As previously
required under DP# 324493, Part 1 of the labels for the 4 lb ai/gal EC
and SL formulations should be revised to specify that no more than one
soil-directed application may be made, and Part 2 should be revised to
specify a maximum of 4 foliar-directed applications.

Snap Beans:  The submitted crop field trial data for snap bean do not
reflect the maximum proposed seasonal rate for snap bean.  The submitted
snap bean crop field trial data reflect a single at-planting application
of the 4 lb ai/gal EC formulation at 0.5 lb ai/A followed by two foliar
applications of the 5% WP formulation at 0.1 lb ai/A/application for a
total seasonal application rate of 0.70 lb ai/A.  The data may be used
to support foliar use of the 5% WP on snap bean provided the proposed
use directions are amended as specified below.

The proposed use directions for the 5% WP formulation must be revised to
specify a maximum of two applications per season at 0.1 lb
ai/A/application and to reflect the following maximum seasonal rate for
snap bean:  “Do not exceed the equivalent of 0.5 lb ai/A per crop of
soil-applied mefenoxam containing products at planting and 0.2 lb ai/A
per crop of foliar-applied mefenoxam-containing products.”

The proposed use directions for the 5% WP formulation must be revised to
propose a 7-day preharvest interval (PHI).  Four of eight field trials
have a 7-day PHI and four have a 6-day PHI.

No spray adjuvants were used in the submitted crop field trials on snap
bean.  Therefore, the product label for foliar applications must be
amended to specify that no adjuvants may be added to spray mixtures for
foliar use on snap bean.

If the petitioner wishes to support the proposed use pattern of a
maximum of four foliar applications to snap beans at 0.1 lb
ai/A/application following soil application at 0.5 lb ai/A, crop field
trial data reflecting that use pattern must be submitted.

Caneberries:  The submitted crop field trial data for blackberries and
raspberries do not reflect the maximum proposed seasonal rate for
caneberries.  The submitted caneberry field trial data reflect two
foliar applications of the 5% WP formulation at 0.1 lb ai/A/ application
following a single at-planting application of the 4 lb ai/gal EC
formulation at 1.8 lb ai/A for a total seasonal application rate of 2.0
lb ai/A.  The data may be used to support foliar use of the 5% WP on
caneberries provided the proposed use directions are amended as
specified below.

  

The proposed use directions for the 4 lb ai/gal EC and SL formulations
for the caneberry subgroup must be revised to specify a maximum of one
soil application per season at 1.8 lb ai/A and to reflect the following
maximum seasonal rate:  “Do not exceed the equivalent of 1.8 lb ai/A
per crop of soil-applied and 0.2 lb ai/A per crop of foliar-applied
mefenoxam-containing products for a maximum seasonal application rate of
2.0 lb ai/A.”

To clarify the use pattern for established plantings specified in Part 2
of the labels for the 4 lb ai/gal EC and SL formulations, the use
directions should be revised to indicate that applications are to be
directed toward the base of the plants.

The proposed use directions for the 5% WP formulation must be revised to
specify a maximum of two foliar applications per season at 0.1 lb
ai/A/application and to reflect the following maximum seasonal rate: 
“Do not exceed the equivalent of 1.8 lb ai/A per crop of soil-applied
and 0.2 lb ai/A per crop of foliar-applied mefenoxam-containing products
for a maximum seasonal application rate of 2.0 lb ai/A.”

For all three products, bromberre must be corrected to brombeere and
nectaberry must be corrected to nectarberry. 

No spray adjuvants were used in the submitted crop field trials on
caneberries.  Therefore, the product label for foliar applications for
all three products must be amended to specify that no adjuvants may be
added to spray mixtures for foliar use on caneberries.

If the petitioner wishes to support the proposed maximum seasonal rate
of 3.6 lb ai/A for soil and foliar applications to caneberries, crop
field trial data reflecting that use pattern must be submitted.

HED notes that the accepted labels for the 4 lb ai/gal EC and SL
formulations include use directions for raspberries reflecting
postemergence use at 0.125 lb ai/A/application in the spring and in the
fall after harvest with a 45-day PHI.  This use is supported by the
established tolerance for metalaxyl residues in/on raspberries at 0.5
ppm.

Bushberries:  Previously reviewed crop field trial data for metalaxyl on
blueberry will support the proposed expanded use of the 4 lb ai/gal EC
and SL formulations on the bushberries listed in Table 3, except as
noted below.  The accepted labels for the 4 lb ai/gal EC and SL
formulations include separate use directions for lingonberries that are
similar to the registered use on blueberries.  The following changes to
the use directions are recommended.

The following berries are not members of the bushberry subgroup 13-07B
and must be removed from the crops listed under the bushberry subgroup: 
bilberry, bearberry, cloudberry, muntries, and partridgeberry.

To clarify the use pattern for established plantings specified in Part 2
of the labels for the 4 lb ai/gal EC and SL formulations, the use
directions should be revised to indicate that applications are to be
directed toward the base of the plants.

For both products, hostaberry must be corrected to jostaberry.

When the proposed use on bushberries is registered for the 4 lb ai/gal
EC and SL formulations, the separate use directions for lingonberries
may be removed from the labels. 

Bilberry, bearberry, cloudberry, muntries, and partridgeberry are
members of crop subgroup 13-07G (lowgrowing berry) or 13-07H (lowgrowing
berry subgroup, except strawberry).  To support the proposed use
patterns for the 4 lb ai/gal EC and SL on these berries, additional crop
field trial data would be required reflecting application to the
representative commodities of strawberry (for subgroup 13-07G) or
cranberry (for subgroup 13-07H).  Although the accepted labels for the 4
lb ai/gal EC and SL formulations include use directions for cranberry
and strawberry, the use directions are more restrictive than the
proposed use pattern for bushberries:  maximum seasonal rate of 2.65 lb
ai/A and 45-day PHI for cranberry, and maximum seasonal rate of 1.5 lb
ai/A for strawberry.

860.1300 Nature of the Residue - Plants

Residue Chemistry Memo No DP#, 2/14/07, W. Britton (RARC Report)

Residue Chemistry Memo DP# 269910, 10/27/00, N. Dodd, A. Lowit, and M.
Bonner (MARC Decision)

Residue Chemistry Memo DP# 268454, 10/17/00, N. Dodd, A. Lowit, and M.
Bonner  (Issues to be presented to MARC)

The nature of the residue in plants is adequately understood for
mefenoxam, based on metalaxyl metabolism studies on potato, grape, and
lettuce.  The data indicate that metalaxyl is taken up, translocated,
and extensively metabolized by plants.  Metabolism involves oxidation of
a ring-methyl group to the alcohol and then the carboxylic acid,
hydroxylation of the phenyl group, hydrolysis of the methyl ester and
methyl ether bonds, and N-dealkylation.  

Metabolites can be separated into four classes:  (1) those containing a
2,6-DMA moiety; (2) those containing an HMMA moiety; (3) those
containing a Ring-OH moiety; and (4) those containing a benzoic acid
moiety.

HED originally concluded that the mefenoxam residues to be regulated for
the tolerance expression and for dietary assessments would be (R)- and
(S)-2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid methyl
ester, its metabolites containing the 2,6-DMA moiety, and CGA-94689  SEQ
CHAPTER \h \r 1   SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 , each
expressed as mefenoxam equivalents.

The HED Risk Assessment Review Committee (RARC) subsequently determined
(report dated 2/14/07) that: (1) the residue to be regulated (in the
tolerance expression) in plant and livestock commodities is (R)- and
(S)-2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid methyl
ester; (2) the current/reassessed tolerance levels should be retained;
(3) for risk assessment, the residues of concern in plant and livestock
commodities are metalaxyl/mefenoxam, its metabolites containing the
2,6-DMA moiety, its metabolites containing the HMMA moiety, its
metabolites containing the Ring-OH moiety, and its metabolites
containing the benzoic acid moiety; and (4) the available residue
chemistry data can be used and factors may be employed to estimate the
total residues of concern in dietary risk assessments.

In connection with registration review of mefenoxam (DP#368461, N. Dodd,
4/13/10), HED recommended for modification of the tolerance expression
for mefenoxam (40 CFR §180.546) according to the new
compliance/measurement policy (Interim Guidance on Tolerance
Expressions, Steve Knizner, May 27, 2009) as follows:			

Tolerances are established for residues of mefenoxam, including its
metabolites and degradates, in or on the commodities in the table below.
 Compliance with the tolerance levels specified below is to be
determined by measuring only metalaxyl [methyl
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate].

860.1300 Nature of the Residue - Livestock

There are no livestock feedstuffs associated with the proposed uses on
bulb vegetables, spinach, snap beans/edible-podded beans, caneberries,
and bushberries.  Therefore, data requirements for livestock metabolism
are not relevant to this tolerance petition.

860.1340 Residue Analytical Methods

Residue Chemistry Memo DP# 333767, 3/7/07, B. Cropp-Kohlligian

Residue Chemistry Memo No DP#, 2/14/07, W. Britton (RARC Report)

Residue Chemistry Memo DP# 274194, 4/20/01, N. Dodd

Residue Chemistry Memo DP# 269910, 10/27/00, N. Dodd, A. Lowit, and M.
Bonner (MARC Decision)

Residue Chemistry Memo DP# 268454, 10/17/00, N. Dodd, A. Lowit, and M.
Bonner  (Issues to be presented to MARC)

The residue analytical methods available for enforcement of tolerances
in crop commodities are common moiety methods which determine residues
of metalaxyl/mefenoxam and metabolites that are convertible to 2,6-DMA. 
These methods include:  (1) Method I in PAM, Vol. II (Method AG-348)
which determines residues in plant commodities using GLC/AFID; and (2)
Method AG-395 (sent to FDA for inclusion in PAM, Vol. II as Method III),
an improved version of Method AG-348, which determines residues in plant
commodities using GLC/NPD.  

Neither Method AG-348 nor Method AG-395 distinguish between the R- and
S-enantiomers of metalaxyl/mefenoxam; however, a chiral LC/MS method,
Method 456-98, for the enantioselective determination of the D- and
L-enantiomers of metalaxyl in crops has been adequately validated by
ACB/BEAD, and a revised version of the method has been submitted for
inclusion in PAM, Vol. II.  

HED has determined that the 2,6-DMA common moiety residue analytical
methods available for tolerance enforcement and used for data collection
will not adequately recover all of the metalaxyl/mefenoxam residues of
concern in the current tolerance expressions.  While these methods are
adequate to recover residues of metalaxyl/mefenoxam per se, they will
not adequately recover metabolites containing the HMMA moiety and may
not adequately recover all metabolites containing the 2,6-DMA moiety
with the certainty needed to set legal limits, nor are they likely to
recover metabolites containing the Ring-OH moiety or the benzoic acid
moiety.  As a result, in addition to the changes to the tolerance
expression and the residues of concern for risk assessment addressed
above, the HED RARC determined that:  1) the multiresidue method PAM,
Vol. I Section 302 (Protocol D), which completely recovers
metalaxyl/mefenoxam per se (>80% according to FDA PESTDATA) is an
adequate enforcement method for the determination of metalaxyl/mefenoxam
per se in plant and livestock commodities; and (2) all future
metalaxyl/mefenoxam magnitude of the residue data should include (a)
analysis for residues of parent only using the multiresidue method PAM,
Vol. I Section 302 (Protocol D) in order to establish more appropriate
tolerance levels; and (b) analysis with a 2,6-DMA common moiety method
and recovery data for parent, CGA-62826, and CGA-94689 in order to
refine dietary risk assessments.  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h
\r 1   SEQ CHAPTER \h \r 1 

Data collection methods:  Samples of snap bean and caneberries from the
crop field trial studies included in this petition were analyzed for
residues of mefenoxam per se using Method 456-98 with minor
modifications.  Samples of spinach, and selected samples of snap bean
and caneberries were analyzed for combined residues of mefenoxam,
metalaxyl, and metabolites convertible to 2,6-DMA using a GC/MS method,
defined by working method numbers YARL-0601A (caneberry), -0601C (snap
bean), and -0601D (spinach) which was derived, with minor modifications,
from Method AG-395.  The modifications included minor changes in
equipment and glassware, modification of the solid-phase extraction
(SPE) clean-up procedure to remove the use of trifluoroacetic acid for
derivatization, and MS instead of NPD.  

For Method 456-98, samples were extracted with methanol:water (80:20,
v:v) at reflux, then filtered and applied to a C18 SPE cartridge to
remove co-extractives.  The purified extract was reduced to aqueous,
acidified with 0.10 N HCl, diluted with water, and partitioned with
dichloromethane (DCM).  The DCM phase was cleaned up on a silica SPE
cartridge, using ethyl acetate in hexane (40% v:v) to elute residues. 
The extract was evaporated to dryness, reconstituted in mobile phase,
and filtered for analysis by chiral reverse-phase LC/MS.  The LLMV was
0.05 ppm for snap bean and caneberries. 

For Method YARL-0601A, C, and D, samples were extracted with
methanol:water (80:20, v:v) at reflux, then filtered.  An aliquot was
reduced to dryness, redissolved in water, and combined with
methanesulfonic acid, then refluxed to produce 2,6-DMA.  Water, hexane,
and 25% NaOH were added, and the mixture was subjected to reflux/steam
distillation.  The resulting hexane phase was collected and applied to a
silica SPE cartridge, using DCM to elute residues.  The DCM phase was
reduced to near dryness and reconstituted in DCM for analysis by GC/MS. 
Residues were converted to mefenoxam equivalents using a molecular
weight conversion factor of 2.305.  The LLMVs were 0.1 ppm for spinach
and 0.05 ppm for snap bean and caneberries.

The data collection methods were adequate for data collection based on
acceptable method validation and concurrent recovery data. 
Fortification levels were adequate to bracket residues found in treated
samples.  

Conclusions.    SEQ CHAPTER \h \r 1  The available and submitted residue
analytical methods data are adequate to satisfy data requirements for
this petition.  Adequate methodology is available for tolerance
enforcement purposes for the residue of concern in crop commodities,
mefenoxam per se, as determined by the RARC.  These methods include
Method 456-98 and PAM multiresidue method Protocol D.  Samples of crop
commodities from the submitted crop field trials were analyzed for
residues of mefenoxam per se and for combined residues of mefenoxam,
metalaxyl, and metabolites convertible to 2,6-DMA using adequate data
collection methods.  

HED notes that although samples from the submitted crop field trials
were analyzed using a 2,6-DMA common moiety method, recovery data were
provided for parent only; no recovery data were provided for metabolites
CGA-62826, and CGA-94689 as required in the RARC decision to refine
dietary risk assessments.

HED notes that the method used for determination of residues of
mefenoxam per se in snap beans and caneberries did not include
determination of the L-enantiomer, which is included in the tolerance
expression.  However, the ratio of D-enantiomer to L-enantiomer in
mefenoxam products is >90% (DP# 223261, 4/24/94, L. Kutney).  Therefore,
the lack of analysis for the L-enantiomer would not significantly affect
the residue results for snap bean and caneberry.    SEQ CHAPTER \h \r 1 
 SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1 The petitioner should note
for future submissions that the tolerance expression for mefenoxam
includes the L-enantiomer, and therefore, as stated above, analytical
methods should include determination of both the D- and L-enantiomers.  

860.1360 Multiresidue Methods

Residue Chemistry Memo No DP#, 2/14/07, W. Britton (RARC Report)

Residue Chemistry Memo DP# 268454, 10/17/00, N. Dodd, A. Lowit, and M.
Bonner  (Issues to be presented to MARC)

The FDA PESTDATA database (dated 06/05) indicates that metalaxyl is
completely recovered (>80%) using the multiresidue method in PAM, Vol.
I, Section 302 (Protocol D), but is not recovered using Sections 303 and
304 (Protocols E and F).  In addition, metabolite CGA-100255 was found
to have small, variable recovery (37-146%) using Section 302. 
Metabolite CGA-37734 was completely recovered using Section 302 but was
not recovered using Sections 303 and 304.  Metabolites CGA-94689A and
94689B had small, variable recovery (39-108%) using Section 302 but were
not recovered using Sections 303 and 304.  Metabolite CGA-62826 was not
recovered through any of the protocols.  

The HED RARC previously determined that the multiresidue method PAM,
Vol. I Section 302 (Protocol D), which completely recovers
metalaxyl/mefenoxam per se (>80% according to FDA PESTDATA) is an
adequate enforcement method for the determination of metalaxyl/mefenoxam
per se in plant and livestock commodities.

860.1380 Storage Stability

Residue Chemistry Memo DP#223261, 4/23/96, L. Kutney

Storage stability data are available for metalaxyl indicating that
weathered residues of metalaxyl and metabolites are stable in spinach
stored frozen (-20 ºC) for up to 39 months (MRID 43446901, DP# 223261,
L. Kutney, 4/23/96).

Concurrent storage stability studies were conducted to support the
storage intervals and conditions of samples from the submitted snap bean
and caneberry field trials; samples were fortified with mefenoxam per
se.  The data demonstrate that for samples analyzed for residues of
mefenoxam per se, residues were stable during frozen storage for up to
609 days (20.0 months) for snap bean and 296 days (9.7 months) for
caneberry, and that for samples analyzed for combined residues of
mefenoxam/metalaxyl and metabolites convertible to 2,6-DMA, residues
were stable for up to 1716 days (56.4 months) for snap bean and 1360
days (44.7 months) for caneberry.  No 0-day data were provided in the
concurrent storage stability studies; storage stability studies should
always include a 0-day sampling interval to establish the residue levels
present at the time samples are placed into storage [see OPPTS
860.1380(d)(6)(i)].

The storage intervals and conditions of samples from the field trials
submitted in association with the subject petition are presented in
Table 4.   

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

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

Storage Stability (months)

Spinach	≤-12	909-1168 days 

(29.9-38.4 months)	Adequate storage stability data are available
demonstrating that combined residues of metalaxyl and metabolites are
stable for up to 39 months in/on spinach.

Snap Bean

(Original analysis:

Method 456-98)	≤-12	479-655 days 

(15.8-21.5 months)	Concurrent storage stability data indicate that
residues of mefenoxam per se are stable for up to 609 days (20 months). 

Snap Bean

(Reanalysis:

Method YARL-0601C)	≤-12	1573-1595 days 

(51.7-52.5 months)	Concurrent storage stability data indicate that
residues of mefenoxam per se, determined as combined residues of
metalaxyl, mefenoxam, and metabolites convertible to 2,6-DMA, are stable
for up to 1716 (56 months).

Caneberries

(Original analysis:

≤-12	133-182 days 

(4.4-6.0 months)	Concurrent storage stability data indicate that
residues of mefenoxam per se are stable for up to 296 days (9.7 months).

Caneberries

(Reanalysis:

Method YARL-0601A)	≤-12 	1387-1402 days 

(45.6-46.1 months)	Concurrent storage stability data indicate that
residues of mefenoxam per se, determined as combined residues of
metalaxyl, mefenoxam, and metabolites convertible to 2,6-DMA, are stable
for up to 1360 days (44.7 months). 

Conclusions.  The available storage stability data for spinach and the
submitted concurrent storage stability data for snap beans and
caneberries are adequate to support the submitted crop field trials. 
The data indicate that there are no storage stability issues, and no
corrections for decline on storage are needed.  

860.1400 Water, Fish, and Irrigated Crops

This guideline topic is not relevant to the proposed uses.

860.1460 Food Handling

This guideline topic is not relevant to the proposed uses.

860.1480 Meat, Milk, Poultry, and Eggs

There are no livestock feedstuffs associated with the proposed uses on
bulb vegetables, spinach, snap beans/edible-podded beans, caneberries,
and bushberries.  Therefore, data requirements pertaining to meat, milk,
poultry, and eggs are not relevant to this tolerance petition.

860.1500 Crop Field Trials

DER References:	47803101.der.doc (Snap bean; includes review of MRID
47803102)

	47803103.der.doc (Caneberries; includes review of MRID 47803104)

	47803105.der.doc (Spinach)

Residue Chemistry Memo DP# 223261, 4/24/96, L. Kutney

Residue Chemistry RED Chapter, DP# 197037, 6/16/94, S. Hummel

HED has concluded (DP# 223261) that the established tolerances for
metalaxyl will be adequate to support the use of mefenoxam on the same
crops provided that (1) the use rates for mefenoxam are one-half the
rate of metalaxyl; (2) mefenoxam applications are made in the same way
as for metalaxyl; and (3) the labels restrict the use of both pesticides
concurrently on the same crop.  

Onion, bulb, subgroup 3-07A and onion, green, subgroup 3-07B

IR-4 is proposing to expand the registered use of mefenoxam on bulb and
green onions to support the new bulb onion subgroup 3-07A and the green
onion subgroup 3-07B.  Bulb onion is the representative commodity of the
bulb onion subgroup, and green onion is the representative commodity of
the green onion subgroup.

No residue data were provided in support of the proposed expanded use.  
The registered use of mefenoxam on bulb and green onions is supported by
crop field trial data for metalaxyl on these crops, reflecting a variety
of use patterns, which were summarized in the Metalaxyl Registration
Standard dated 6/22/87.  For bulb onion, the use patterns tested
included preemergence soil application of an EC formulation at 2 lb ai/A
followed by five foliar applications of a WP formulation at 0.2 lb
ai/A/application for a maximum seasonal rate of 3.0 lb ai/A; PHIs ranged
7-34 days.  For green onion, the use patterns tested included
preemergence soil application of an EC formulation at 2 lb ai/A followed
by three or four foliar applications of a WP formulation at 0.2 lb
ai/A/application for maximum seasonal rates of 2.6 or 2.8 lb ai/A; PHIs
ranged 7-14 days.  The available data were re-assessed for the Residue
Chemistry Chapter of the Metalaxyl RED where it was concluded that no
additional data were needed for dry bulb or green onion.  Tolerances of
3.0 and 10.0 ppm are established for metalaxyl on bulb and green onion,
respectively.  As specified in DP# 223261, the use rates for mefenoxam
are one-half the rate of metalaxyl, and mefenoxam applications are made
in the same way as for metalaxyl; therefore, the data for metalaxyl are
adequate to support the proposed use of mefenoxam.

Conclusions.  The proposed/registered use of mefenoxam on bulb and green
onion is supported by adequate crop field trial data for metalaxyl.  
Minor revisions to the EC, SL, and WP labels must be made as requested
under Section 860.1200.  Because bulb onion is the representative
commodity of the bulb onion subgroup, and green onion is the
representative commodity of the green onion subgroup, HED has no
objections to expanding the registered use to cover the members of the
crop subgroups.

The available data for bulb and green onion will support tolerances of
3.0 ppm for onion, bulb subgroup 3-07A, and 10 ppm for the onion, green,
subgroup 3-07B, respectively.

Spinach

Under PP#9E7591, IR-4 is proposing to reduce the established PHI for use
of mefenoxam on spinach from 21 days to 3 days.  In conjunction with
this request, IR-4 has submitted revised use directions for the 4 lb
ai/gal EC and the SL formulations indicating that they wish to expand
the registered foliar uses on head and leaf lettuce for one or both
products to include all members of the leafy vegetables crop group.  

In support of the reduced PHI for spinach, IR-4 submitted field trial
data for mefenoxam on spinach.  Nine spinach field trials were conducted
in Zones 1 (NY; 1 trial), 2 (MD and NJ; 3 trials), 6 (TX; 2 trials), 8
(CO; 1 trial), and 10 (CA; 2 trials) during 2004.    

At each test site, one untreated and one treated plot were established. 
Each treated plot received an initial soil surface spray application of
a 4 lb ai/gal EC formulation made at planting at ~1.0 lb ai/A.  Seed was
planted immediately before or following application on the same day,
except at the two CA sites and the CO and NJ sites, where seed was
planted the day before application.  The at-planting application was
followed by two foliar directed or broadcast spray applications of a 5%
WP formulation made at ~0.125 lb ai/A/application, for a total seasonal
rate of ~1.25 lb ai/A (1x the maximum proposed seasonal application rate
for this formulation on spinach).  The first foliar application was made
25-60 days after the soil application, and the second foliar application
was made 12-15 days after the first foliar application.  All
applications were made using ground equipment in spray volumes of 29-64
gal/A; no adjuvants were used.  Samples of mature spinach leaves were
collected 2-4 days following the final application.  

Samples were analyzed using an adequate GC/MS method that determines
combined residues of mefenoxam, metalaxyl, and metabolites convertible
to the 2,6-DMA moiety as 2,6-DMA.  The LLMV was 0.10 ppm.  Sample
storage intervals and conditions are reported in Table 4.  Adequate
storage stability data are available to support the crop field trials.

The results of the spinach field trials are presented in Table 5. 
Following one at-planting soil application of the 4 lb ai/gal EC
formulation at 0.97-1.0 lb ai/A and two broadcast foliar applications of
the 5% WP at 0.122-0.127 lb ai/A/application for total application rates
of 1.21-1.25 lb ai/A, combined residues of mefenoxam/metalaxyl and
metabolites determined as 2,6-DMA were 1.47-6.19 ppm in/on spinach
leaves harvested 2-4 days after application.

A residue decline trial was not included in the study.

Table 5.	Summary of Residue Data from Field Trials with Mefenoxam.

Crop matrix	Total Applic. Rate  (lb ai/A)	PHI (days)	Residue Levels
(ppm)1

	n	Min.	Max.	HAFT 2	Median	Mean	Std. Dev.

SPINACH (proposed use for 5% WP = 1.0 lb ai/A soil + 0.25 lb ai/A foliar
for 1.25 lb ai/A total application rate; 3-day PHI; proposed use for 4
lb ai/gal EC and SL = 1.0 lb ai/A soil + 0.4 lb ai/A foliar for 1.4 lb
ai/A total application rate; 3-day PHI)

Spinach leaves 	1.21-1.25	2-4	18	1.47	6.19	5.85	3.07	3.26	1.34

1  Combined residues of mefenoxam, metalaxyl, and metabolites
convertible to 2,6-DMA.

2  HAFT = Highest Average Field Trial.

The representative crops for the leafy vegetables (except Brassica
vegetables) crop group are celery, head lettuce, leaf lettuce, and
spinach.  

Conclusions.  The submitted field trial residue data for spinach are
adequate to support a reduction in PHI to 3 days for spinach treated
with a soil application of the EC or SL formulation followed by foliar
application of the WP formulation.  The submitted crop field trial data
will support a reduction in PHI for spinach treated with this
combination of products only.  Additional field trial data reflecting
foliar application of EC and SL formulations to spinach with a 3-day PHI
would be required to support a reduction in PHI for the proposed foliar
uses of the 4 lb ai/gal EC and SL formulations on spinach.  Based on
current Agency policy, data for the WP formulation cannot support EC or
SL foliar applications with short PHIs, and EC data cannot be translated
to SL for foliar applications with short PHIs.  The reviewer could not
find any data for metalaxyl/mefenoxam supporting foliar application of
an SL formulation on leafy vegetables.

In the absence of supporting crop field trial data, HED recommends
against expanding the registered foliar uses of the 4 lb ai/gal EC and
SL formulations on head and leaf lettuce to include spinach or any other
members of the leafy vegetables (except Brassica vegetables) crop group.
 To expand the registered foliar uses of the 4 lb ai/gal EC and SL
formulations on head and leaf lettuce to include all members of the
leafy vegetables (except Brassica vegetables) crop group, data
reflecting foliar uses of the EC and SL formulations on spinach and
celery reflecting the proposed use rate and PHI must be submitted or
referenced.  If spinach is to have a 3-day PHI while the others in the
crop group have a 7-day PHI, spinach would have to be excluded from the
crop group tolerance and have its own tolerance.

The number and location of field trials are in accordance with OPPTS
Guideline 860.1500 for spinach.  HED notes that one trial was conducted
in Zone 8 instead of Zone 9, but the trial was located near the border
between the two zones.  Samples were analyzed for combined residues of
mefenoxam and metabolites convertible to 2,6-DMA using an acceptable
method, and adequate storage stability data are available to support the
study.

Although no residue decline data were included in the submission,
adequate residue decline data are available for mefenoxam and metalaxyl
to support the submitted study.  Previously reviewed data indicate that
residues of mefenoxam/metalaxyl declined or did not increase with
increasing sampling interval in:  (1) basil harvested at 7, 14, and 21
days (DP#s 257785 and 266898, 4/20/01, N. Dodd); (2) broccoli,
cauliflower, and cabbage harvested at 7 and 14 days (PP# 2F04072,
1/15/93, M. Peters); and (3) lettuce harvested at 4-5, 7, and 14 days
(DP# 156811, 6/21/91, S. Bacchus). 

The submitted field trial data, reflecting combined residues of
mefenoxam/metalaxyl and metabolites convertible to 2,6-DMA, would
support a tolerance of 8.0 ppm and a reduced PHI of 3 days for spinach
treated with a soil application of the EC or SL formulation followed by
foliar application of the WP formulation.  (Refer to Appendix II for the
tolerance calculation.)  However, because the submitted data are not
representative of all registered uses of mefenoxam on spinach (see, for
example, the 2.5% granular formulation; EPA Reg. No. 100-798), HED
recommends against establishing a reduced tolerance for mefenoxam on
spinach.  The existing tolerance of 10 ppm for spinach, established
under 40 CFR §180.408, is appropriate.  

Snap bean

IR-4 submitted field trial data for mefenoxam on snap beans.  Eight
field trials were conducted in Zones 1 (NY; 1 trial), 2 (MD; 1 trial), 3
(FL; 1 trial), 5 (WI; 3 trials), 10 (CA; 1 trial), and 11 (WA; 1 trial)
during 2002.

At each test site, one untreated and one treated plot were established. 
Each treated plot received an initial soil surface spray application of
a 4 lb ai/gal EC formulation made at planting at ~0.50 lb ai/A; seed was
planted immediately following application on the same day.  The
at-planting application was followed by two foliar directed or broadcast
spray applications of a 5% WP formulation made at ~0.10 lb
ai/A/application, for a total seasonal rate of ~0.70 lb ai/A (~0.8x the
maximum seasonal application rate of 0.90 lb ai/A for snap bean based on
registered soil and proposed foliar application).  The first foliar
application was made  45-79 days after the soil application, and the
second foliar application was made 7-8 days after the first foliar
application.  All applications were made using ground equipment in spray
volumes of 30-57 gal/A; no adjuvants were used.  Samples of snap beans
were collected from each test site at commercial maturity, 6-7 days
after the final application.  At two sites, additional samples were
collected 0 and 13-14 days after final application to assess residue
decline.  

Samples from the snap bean field trials were initially analyzed for
residues of mefenoxam per se using an adequate chiral LC/MS method. 
Samples from the CA trial, including decline samples, were subsequently
reanalyzed using an adequate GC/MS method that determined combined
residues of mefenoxam, metalaxyl, and metabolites convertible to the
2,6-DMA moiety as 2,6-DMA.  The LLMV was 0.05 ppm for both methods. 
Sample storage intervals and conditions are reported in Table 4. 
Adequate concurrent storage stability data were submitted to support the
crop field trials. 

The study results, reflecting the original analysis for mefenoxam only
and re-analysis of the CA field trial samples for parent + metabolites,
were presented to ChemSAC with a request to use conversion factors
calculated by dividing the residues obtained on re-analysis of the CA
field trial samples by the original values to calculate residues in the
remaining field trial samples for setting residue values for the risk
assessment.  The calculated conversion factors are:  1x for 0-day PHI,
1.8x for the 6- to 7-day PHI, and 3x for the 13- to 14-day PHI.  ChemSAC
agreed (see minutes of 2/25/09 meeting) that parent + metabolites to
parent ratios could be used to estimate residue levels for risk
assessments in snap beans, with the provision that these ratios would
not necessarily be correct/adequate for these commodities for future
risk assessments if refinements were necessary.

The results of the snap bean field trials are presented in Table 6. 
Following one at-planting soil application of the 4 lb ai/gal EC
formulation at 0.48-0.51 lb ai/A and two broadcast foliar applications
of the 5% WP at 0.10 lb ai/A/application for total application rates of
0.68-0.71 lb ai/A, residues of mefenoxam per se were <0.05-0.168 ppm
in/on snap beans harvested at a 13- to 14-day PHI.  Following
re-analysis of samples from the CA trial, and recalculation of residues
in samples from the remaining field trials based on the results of the
CA trials, combined residues of mefenoxam/metalaxyl and metabolites
determined as 2,6-DMA were estimated to be <0.05-0.282 ppm.  

The residue decline data from the CA trial indicate that residues of
mefenoxam generally declined with increasing PHI.  Because residues were
<LLMV in/on all samples from the WI decline trial, residue decline could
not be assessed. 

Table 6.	Summary of Residue Data from Field Trials with Mefenoxam.

Crop matrix1	Total Applic. Rate  (lb ai/A)	PHI (days)	Residue Levels
(ppm)

	n	Min.	Max.	HAFT2	Median	Mean	Std. Dev.

SNAP BEAN (proposed use = 0.4 lb ai/A total application rate foliar
only; 6-day PHI)

(proposed + registered use = 0.5 lb ai/A soil + 0.4 lb ai/A foliar for
0.9 lb ai/A total application rate)

Mefenoxam per se

Snap Bean

(Original analysis)	0.68-0.71	6-7	16	<0.05	0.168	0.137	0.05	0.061	0.032

Combined residues of mefenoxam/metalaxyl and metabolites convertible to
2,6-DMA

Snap Bean

(Reanalysis/

calculation)	0.68-0.71	6-7	16	<0.05	0.282	0.246	0.05	0.075	0.068

1  Original analysis:  samples were originally analyzed for residues of
mefenoxam per se.  Reanalysis/calculation:  samples from the CA site
were re-analyzed for combined residues of mefenoxam/metalaxyl and
metabolites convertible to 2,6-DMA; for all other trials, the original
residue results were corrected using a conversion factor of 1.8x.

2  HAFT = Highest Average Field Trial.

Conclusions.  The submitted field trial residue data for snap bean are
adequate.  Provided the label is amended as indicated in OPPTS 860.1200
to specify a maximum of two foliar applications, a maximum seasonal
application rate of 0.50 lb ai/A for soil applications + 0.2 lb ai/A for
foliar applications, and a 7-day PHI, the study adequately reflects the
proposed use pattern for snap bean, and the number and location of field
trials are in accordance with OPPTS Guideline 860.1500.  Samples were
initially analyzed for residues of mefenoxam per se using an acceptable
method, and selected samples were re-analyzed for combined residues of
mefenoxam/metalaxyl and metabolites convertible to 2,6-DMA using an
acceptable method.  Calculation of combined residues in remaining crop
samples using a 1.8x conversion factor was approved by ChemSAC. 
Adequate concurrent storage stability data were submitted to support the
study.

The submitted field trial data, reflecting residues of mefenoxam per se,
will support the proposed tolerance of 0.20 ppm for snap bean.

  

Caneberry subgroup 13-07A

IR-4 submitted field trial data for mefenoxam on blackberries and
raspberries, the representative commodities of caneberry subgroup
13-07A.  Six caneberry field trials were conducted in the U.S. in Zones
2 (NC and NJ; 2 trials), 10 (CA; 2 trials), 11 (WA; 1 trial), and 12
(WA; 1 trial) during 2002.  Two trials were conducted using blackberry
varieties (blackberry and boysenberry), and four trials were conducted
using raspberry varieties (red and black).

At each test site, one untreated and one treated plot were established. 
Each treated plot received an initial soil surface spray application,
directed toward the base of the plants, of a 4 lb ai/gal EC formulation
made at flowering to early fruiting at ~1.8 lb ai/A.  The soil
application was followed by two foliar directed spray applications of a
5% WP formulation made at ~0.10 lb ai/A/application to plants bearing
fruit, for a total seasonal rate of ~2.0 lb ai/A (0.6x the maximum
proposed seasonal application rate for caneberries).  The first foliar
application was made 35-45 days after the soil application, and the
second foliar application was made 6-7 days after the first foliar
application.  All applications were made using ground equipment in spray
volumes of 30-101 gal/A; no adjuvants were used.  Berry samples were
collected from each test site at commercial maturity, on the day of the
final application (0-day PHI).  

Samples from the caneberry field trials were initially analyzed for
residues of mefenoxam per se using an adequate chiral LC/MS method. 
Samples from the NC and NJ trials and one CA trial (02-CA27) were
subsequently reanalyzed using an adequate GC/MS method that determines
combined residues of mefenoxam, metalaxyl, and metabolites convertible
to the 2,6-DMA moiety as 2,6-DMA.  The LLMV was 0.05 ppm for both
methods.  Sample storage intervals and conditions are reported in Table
4.  Adequate concurrent storage stability data were submitted to support
the crop field trials. 

The study results, reflecting the original analysis for mefenoxam only
and re-analysis of the NC, NJ, and CA field trial samples for parent +
metabolites, were presented to ChemSAC with a request to use a 1.3x
conversion factor, calculated by dividing the average residues obtained
on re-analysis for each of the three trials by the average residues
obtained on original analysis, to calculate residues in the remaining
field trial samples for setting residue values for the risk assessment. 
ChemSAC agreed (see minutes of 2/25/09 meeting) that parent +
metabolites to parent ratios could be used to estimate residue levels
for risk assessments in caneberry, with the provision that these ratios
would not necessarily be correct/adequate for these commodities for
future risk assessments if refinements were necessary.

The results of the caneberry field trials are presented in Table 7. 
Following one soil surface spray application of the 4 lb ai/gal EC
formulation at 1.75-1.98 lb ai/A and two broadcast foliar applications
of the 5% WP at 0.10 lb ai/A/application for total application rates of
1.95-2.18 lb ai/A, residues of mefenoxam per se were 0.213-0.554 ppm
in/on caneberries harvested at a 0-day PHI.  Following re-analysis of
samples from the NC, NJ, and one CA trials, and recalculation of
residues in samples from the remaining field trials based on the
reanalysis results, combined residues of mefenoxam/metalaxyl and
metabolites determined as 2,6-DMA were estimated to be 0.277-0.691 ppm. 

A residue decline trial was not included in the study.

Table 7.	Summary of Residue Data from Field Trials with Mefenoxam.

Crop matrix1	Total Applic. Rate  (lb ai/A)	PHI (days)	Residue Levels
(ppm)

	n	Min.	Max.	HAFT2	Median	Mean	Std. Dev.

CANEBERRY (proposed use = 3.6 lb ai/A total application rate, soil +
foliar applied; 0-day PHI for foliar application)

Mefenoxam per se

Caneberries

(Original analysis)	1.95-2.18	0	12	0.213	0.554	0.527	0.296	0.329	0.106

Combined residues of mefenoxam/metalaxyl and metabolites convertible to
2,6-DMA

Caneberries

(Reanalysis/

calculation)	1.95-2.18	0	12	0.277	0.691	0.686	0.370	0.412	0.135

1  Original analysis:  samples were originally analyzed for residues of
mefenoxam per se.  Reanalysis/calculation:  samples from the NC, NJ, and
one CA (02-CA27) trials were re-analyzed for combined residues of
mefenoxam/metalaxyl and metabolites convertible to 2,6-DMA; for all
other trials, the original residue results were corrected using a
conversion factor of 1.3x.

 2  HAFT = Highest Average Field Trial.

Conclusions.  The submitted field trial residue data for caneberries are
not adequate for a permanent registration but will support a conditional
registration.  The field trial locations are not in accordance with
860.1500, and no residue decline data were submitted.  To fulfill
geographic distribution requirements, one additional field trial must be
conducted in Zone 5 (raspberry) or 6 (blackberry).  The required field
trial should include additional sampling intervals to assess residue
decline.  (Note:  Three studies were conducted in Zones 10, 11, and 12
instead of three studies in Zone 12 as suggested in OPPTS 860.1500;
however, Bernard Schneider, contacted by Dynamac, indicated that the
three trials conducted in Zones 10, 11, and 12 would be sufficient in
lieu of three studies in Zone 12 as suggested in OPPTS 860.1500.)

The proposed use directions for caneberries on the EC, SL, and WP labels
must be amended as indicated in OPPTS 860.1200.  

Samples were initially analyzed for residues of mefenoxam per se using
an acceptable method, and selected samples were re-analyzed for combined
residues of mefenoxam and metabolites convertible to 2,6-DMA using an
acceptable method.  Calculation of combined residues in remaining crop
samples using a 1.3x conversion factor was approved by ChemSAC. 
Adequate concurrent storage stability data were submitted to support the
study.

The submitted field trial data, reflecting residues of mefenoxam per se,
will support a tolerance of 0.70 ppm for caneberry subgroup 13-07A. 
Refer to Appendix II for the tolerance calculation.

Pending submission of the additional required field trial data, the
tolerance will be recalculated and a revised tolerance proposal may be
needed.

Bushberry subgroup 13-07B

IR-4 is proposing to expand the registered use of mefenoxam on blueberry
to support the bushberry subgroup 13-07B.  Blueberry is the
representative commodity of the bushberry subgroup.

No residue data were provided in support of the proposed expanded use.  
The registered use of mefenoxam on blueberry is supported by crop field
trial data for metalaxyl on blueberry that were reviewed under
PP#7F3470/FAP#7H5520 (3/6/87, M. Nelson), reflecting two soil
applications at 3.6 lb ai/A/application for a maximum seasonal rate of
7.2 lb ai/A, with a 0-day PHI.  The available data were re-assessed for
the Residue Chemistry Chapter of the Metalaxyl RED which concluded that
no additional data were needed for blueberry.  A tolerance of 2.0 ppm is
established for metalaxyl on blueberry.  As specified in DP# 223261, the
use rates for mefenoxam are one-half the rate of metalaxyl, and
mefenoxam applications are made in the same way as for metalaxyl;
therefore, the data for metalaxyl are adequate to support the proposed
use of mefenoxam.

Conclusions.  The registered use of mefenoxam on blueberry is supported
by adequate crop field trial data for metalaxyl, and the proposed use
pattern for mefenoxam on bushberry subgroup 13-07B is identical to the
registered use on blueberry.  Because blueberry is the representative
commodity of the bushberry subgroup, HED has no objections to expanding
the registered use to cover the crop subgroup provided the revisions
requested under Section 860.1200 to the EC and SL labels for bushberries
are made.  The available data for blueberry will support a tolerance of
2.0 ppm for the bushberry subgroup 13-07B

860.1520 Processed Food and Feed

HED does not require residue data for any processed commodities
associated with onion, legume vegetables/spinach, snap beans,
caneberries, or bushberries.  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 mefenoxam (expiration date of 2/28/2014) is
currently available in the National Pesticide Standards Repository
(personal communication with Dallas Wright, ACB, 12/9/09).  

860.1850 Confined Accumulation in Rotational Crops

Residue Chemistry Memo No DP#, 2/14/07, W. Britton (RARC Report)

Residue Chemistry Memo DP# 269910, 10/27/00, N. Dodd, A. Lowit, and M.
Bonner (MARC Decision)

Residue Chemistry Memo DP# 268454, 10/17/00, N. Dodd, A. Lowit, and M.
Bonner  (Issues to be presented to MARC)

The nature of the residue in rotated crops is adequately understood for
mefenoxam, based on confined rotational crop studies conducted with
metalaxyl on lettuce, sugar beet, and wheat.  Metabolism of metalaxyl in
rotated crops generally proceeds by the same pathways as seen in primary
crops with the formation of four classes of metabolites:  (1) those
containing the 2,6-DMA moiety; (2) those containing the HMMA moiety; (3)
those containing a Ring-OH moiety; and (4) those containing a benzoic
acid moiety.  The following differences were noted.  Two
ring-hydroxylated metabolites were detected in rotated lettuce: 
Metabolite CGA-100255 accounted for 11% of the TRR in immature lettuce;
and a second compound, which would represent an N-dealkylation product
of CGA-100255, designated N1b aglycone, was detected in hydrolysates of
aqueous and insoluble fractions, at 16% of the immature lettuce TRR. 
These compounds were also found in mature lettuce with 8% of the TRR as
CGA-100255 and 11% as N1b aglycone; both were released from glucose
conjugates.  In rotated wheat grain, the majority of the identified
residues (35.2% out of 43.0% identified) were metabolites oxidized to
benzoic acid metabolites, including CGA-108905, which was found at 33.7%
TRR.  

HED previously concluded that the mefenoxam residues in rotational crops
to be regulated for the tolerance expression and for dietary assessments
are (R)- and (S)-2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic
acid methyl ester, its metabolites containing the 2,6-DMA moiety, and
CGA-94689  SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r 1   SEQ CHAPTER \h \r
1 , each expressed as mefenoxam equivalents, except that
2-[(methoxyacetyl)(2-methoxy-1-methyl-2-oxoethyl)amino]-3-methylbenzoic
acid (CGA-108905) would also be included in the risk assessment for
cereal grain rotational crops and
N-(3-hydroxy-2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methyl ester
(CGA-100255) would be included in the risk assessment for leafy
vegetable (Brassica and non-Brassica) rotational crops.

The HED RARC subsequently determined  that the residue to be regulated
(in the tolerance expression) in crop commodities is (R)- and
(S)-2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid methyl
ester and that for risk assessment, the residues of concern in crop
commodities are metalaxyl/mefenoxam, its metabolites containing the
2,6-DMA moiety, its metabolites containing the HMMA moiety, its
metabolites containing the Ring-OH moiety, and its metabolites
containing the benzoic acid moiety.  The RARC further noted that
CGA-100255 and CGA-108905 need not be included in future dietary risk
assessments since there is little likelihood that these metabolites
could be recovered by any of the 2,6-DMA common moiety methods. 

860.1900 Field Accumulation in Rotational Crops

Residue Chemistry Memo DP# 333767, 3/7/07, B. Cropp-Kohlligian.

Residue Chemistry Memo No DP#, 2/14/07, W. Britton (RARC Report)

Residue Chemistry Memo DP# 276001, 9/13/01, N. Dodd

Residue Chemistry Memo DP# 269910, 10/27/00, N. Dodd, A. Lowit, and M.
Bonner (MARC Decision)

Residue Chemistry Memo DP# 268454, 10/17/00, N. Dodd, A. Lowit, and M.
Bonner  (Issues to be presented to MARC)

Residue Chemistry Memo DP#s 203675 and 206108, 10/17/94, S. Hummel

Field rotational crop data for metalaxyl were previously reviewed. 
Residues were determined in the commodities of rotational broccoli,
cabbage, corn, lettuce, red beets, rye, soybeans, sugar beets, sweet
potatoes, and wheat planted following metalaxyl-treated potatoes,
tobacco, and wheat (soybean was planted after the wheat primary crop). 
Application rates were 3-6 lb ai/A for potatoes and tobacco and 1-2 lb
ai/A for wheat.  Plantback intervals ranged from 6-12 months, with the
exception of winter wheat and rye, which were planted 1-6 weeks after
treatment of potatoes and 3-19 months after treatment of tobacco. 
Combined residues of metalaxyl and metabolites convertible to 2,6-DMA
were determined; recovery data were only provided for metalaxyl per se. 

Under the metalaxyl reregistration process, HED concluded (DP#s 203675
and 206108) that the available field rotational crop studies were
inadequate but could be upgraded by providing additional recovery data
demonstrating that the enforcement method and the analytical methods
used for the field rotational crop studies would detect representative
metalaxyl metabolites containing the 2,6-DMA and HMMA moieties. 
Additional supporting recovery data for metabolites were submitted and
reviewed under DP# 276001 and DP# 333767, which indicated that the
established enforcement method, AG-395 was not adequate for the
determination of residues of metalaxyl/mefenoxam metabolites CGA-94689,
CGA-62826, and P1/P2 in crop commodities.  Method modifications to
improve recoveries for metabolites CGA-94689 and CGA-62826 were
required. 

In consideration of the RARC recommendations for mefenoxam, no
additional data are required to support the metalaxyl field rotational
crop studies.  The established plantback intervals for mefenoxam on
rotated crops are supported by adequate data.

HED notes that tolerances for indirect or inadvertent residues of
metalaxyl were previously established for a number of cereal grain
commodities primarily in support of rotation to cereal grains following
potato.  

860.1550 Proposed Tolerances

Residue Chemistry Memo No DP#, 2/14/07, W. Britton (RARC Report)

Residue Chemistry Memo 223261, 4/24/96, L. Kutney

IR-4, on behalf of the Agricultural Experiment Stations of CA, FL, OR,
and GA, is proposing the establishment of tolerances for residues of the
fungicide mefenoxam, (R)- and
(S)-[2,6-dimethyl(phenyl)-methoxyacetylamine]-propionic acid methyl
ester, and its metabolites containing the 2,6-dimethylaniline moiety,
and N-(2-hydroxy methyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl
ester.

The HED Risk Assessment Review Committee (RARC) has determined that the
residue to be regulated (in the tolerance expression) in plant and
livestock commodities is (R)- and
(S)-2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid methyl
ester, and that the current/reassessed tolerance levels should be
retained.  

In connection with registration review of metalaxyl/mefenoxam
(DP#368461, N. Dodd, 4/13/10), HED recommended for modification of the
tolerance expressions for metalaxyl (40 CFR §180.408) and mefenoxam (40
CFR §180.546) according to the new compliance/measurement policy
(Interim Guidance on Tolerance Expressions, Steve Knizner, May 27, 2009)
as follows:		

Tolerances are established for residues of metalaxyl, including its
metabolites and degradates, in or on the commodities in the table below.
 Compliance with the tolerance levels specified below is to be
determined by measuring only metalaxyl [methyl
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate].

Tolerances are established for residues of mefenoxam, including its
metabolites and degradates, in or on the commodities in the table below.
 Compliance with the tolerance levels specified below is to be
determined by measuring only metalaxyl [methyl
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate].

Tolerances for mefenoxam are currently established under 40 CFR
§180.546 and are expressed in terms of (R)- and
(S)-2-[(2,6-dimethyl(phenyl)-methoxyacetylamine]-propionic acid methyl
ester, its metabolites containing the 2,6-dimethylaniline moiety, and
N-(2-hydroxy methyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl
ester, each expressed as mefenoxam equivalents.

Tolerances for metalaxyl are currently established under 40 CFR
§180.408 and are expressed in terms of the combined residues of the
fungicide metalaxyl [N-(2,6-dimethylphenyl)-N-(methoxyacetyl) alanine
methylester], and its metabolites containing the 2,6-dimethylaniline
moiety, and N-(2-hydroxy
methyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl ester, each
expressed as metalaxyl equivalents.  

HED previously concluded (DP# 223261) that the established tolerances
for metalaxyl will be adequate to support the use of mefenoxam on the
same crops provided that (1) the use rates for mefenoxam are one-half
the rate of metalaxyl; (2) mefenoxam applications are made in the same
way as for metalaxyl; and (3) the labels restrict the use of both
pesticides concurrently on the same crop.  

The registered uses for mefenoxam that are relevant to the subject
petition are supported by the following metalaxyl tolerances:  blueberry
at 2.0 ppm, onion, bulb at 3.0 ppm; onion, green at 10.0 ppm; and
spinach at 10.0 ppm.  In addition, a tolerance on vegetable, legume,
group 6 is established at 0.2 ppm, and a tolerance on raspberry is
established at 0.5 ppm.

Based on the tolerance expressions recommended by the RARC and by HED in
the metalaxyl/mefenoxam registration review, and to be consistent with
Codex, the tolerance expression proposed by IR-4 under PP#9E7591 must be
revised.  The tolerance expression for mefenoxam should be stated as
follows:

Tolerances are established for residues of mefenoxam, including its
metabolites and degradates, in or on the commodities in the table below.
 Compliance with the tolerance levels specified below is to be
determined by measuring only metalaxyl [methyl
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate].

HED notes that measuring mefenoxam as metalaxyl would be consistent with
Codex.

The proposed and recommended tolerances for the petition are listed in
Table 8.  

Pending label amendments, adequate crop field trial data reflecting the
proposed use patterns were submitted for purposes of establishing
tolerances on spinach and snap bean.  For caneberries, an additional
field trial conducted in Zone 5 or 6 is required as a condition of
registration; label amendments are also needed.  The tolerance
spreadsheet in the Agency’s Guidance for Setting Pesticide Tolerances
Based on Field Trial Data was utilized in determining appropriate
tolerance levels for spinach and caneberries.  The tolerance spreadsheet
could not be used to calculate the tolerance for snap bean because ~88%
of residues were <LLMV; the recommended tolerance for snap bean was
based on the maximum observed residues.  The submitted data used to
determine tolerances for snap bean and caneberries reflected analysis of
samples for mefenoxam per se; the data for spinach reflected analysis
for combined residues of mefenoxam/metalaxyl and metabolites convertible
to 2,6-DMA.  The proposed tolerances for snap bean and the caneberry
subgroup are too high; tolerances should be established at 0.20 ppm for
snap bean and 0.70 ppm for caneberry subgroup 13-07A.

  

The submitted crop field trial data for spinach will support a tolerance
of 8.0 ppm for spinach; however, because the submitted data are not
representative of all registered uses of mefenoxam on spinach (see, for
example, the 2.5% granular formulation; EPA Reg. No. 100-798), HED
recommends against establishing a reduced tolerance for mefenoxam on
spinach.  The existing tolerance of 10 ppm for spinach, established
under 40 CFR §180.408, is appropriate.  

A tolerance for metalaxyl residues in/on legume vegetables exists under
40 CFR §180.408 at 0.2 ppm for combined residues of parent and
metabolites convertible to 2,6-DMA.  In IR-4’s submission, the data
for these combined residues showed values exceeding 0.2 ppm (maximum
value was 0.282 ppm, and this value was an actual residue value, as
opposed to a calculated value).  However, the HED Risk Assessment Review
Committee (RARC) determined (report dated 2/14/07) that the residue to
be regulated (in the tolerance expression) in plant commodities is (R)-
and (S)-2-[(2,6-dimethylphenyl)-methoxyacetylamino]-propionic acid
methyl ester.  Therefore, a tolerance under 40 CFR §180.546 for
residues of mefenoxam in/on snap beans at 0.20 ppm is appropriate.  

A tolerance exists under 40 CFR §180.408 for metalaxyl residues in/on
raspberry at 0.5 ppm whereas HED is now recommending a tolerance under
40 CFR §180.546 of 0.70 ppm on the caneberry subgroup.  The metalaxyl
tolerance will remain in 40 CFR §180.408 to support any uses of
metalaxyl on raspberry.  

Adequate crop field trial data for metalaxyl reflecting application
according to the proposed use patterns, but at rates corresponding to
twice the maximum proposed single application and seasonal rates for
mefenoxam, are available for purposes of establishing tolerances on
onions and bushberries.  The available data will support establishment
of the proposed tolerances for residues of mefenoxam in/on onion, bulb,
subgroup 3-07A at 3.0 ppm; onion, green, subgroup 3-07B at 10 ppm; and
bushberry subgroup 13-07B at 2.0 ppm.  

IR-4 noted that in conjunction with establishment of the proposed
tolerance for the bushberry subgroup, the mefenoxam tolerance for
lingonberry can be removed.

Codex MRLs, expressed in terms of metalaxyl per se for plant
commodities, are established for spinach at 0.1 and onion at 0.03 ppm. 
Canadian MRLs for mefenoxam (metalaxyl-M) are covered by MRLs
established for metalaxyl, the unresolved isomeric mixture, which are
expressed in terms of
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alanine methyl ester,
including metabolites that can be converted to the 2,6-dimethylaniline
moiety, calculated as metalaxyl equivalents.  Canadian MRLs are
established for spinach at 10 ppm, bulb onion at 3.0 ppm, green onion at
10 ppm, bean at 0.2 ppm, raspberry at 0.2 ppm, and blueberry at 2.0 ppm.
No Mexican MRLs are established for mefenoxam or metalaxyl.  With the
adoption of the tolerance expression recommended by the RARC, the U.S.
tolerance expression will be in harmonization with Codex MRLs but not
with PMRA MRLs.

Table 8. 	Tolerance Summary for Mefenoxam.

Commodity	Tolerance (ppm)	Comments; Correct Commodity Definition

	Established	Proposed 	Recommended 

	Bean, snap, succulent	--	0.35	0.20 

	Caneberry, subgroup 13-07A	--	0.80	0.70	Caneberry subgroup 13-07A

Bushberry subgroup 13-07B	--	2.0	2.0

	Onion, bulb, subgroup 3-07A	--	3.0	3.0

	Onion, green, subgroup 3-07B	--	10.0	10

	Spinach	--	8.0	 10	The existing tolerance for spinach, listed under 40
CFR §180.408, is 10.

Lingonberry	2.0	--	Remove	Residues on lingonberry will be covered by the
tolerance on bushberry subgroup 13-07B

References

DP#:	N/A

Subject:	PP# 7F3470/FAP# 7H5520/EPA Reg. No. 100-607.  Metalaxyl in or
on Blueberries, Walnuts, Almonds, Almond Hulls, Stone Fruits, Dried
Apricots, and Prunes.  Evaluation of Analytical Method and Residue Data.
 [Accession Nos. 265762, 265763, 265764, 265765.]  [CB Nos.:  1676,
1677, 1678.]

From: 	M. Nelson

To:	L. Rossi and Toxicology Branch

Date:	3/6/87

MRIDs:	00164649

DP#:	156811

Subject:	PP#0F3893 (EPA Reg. Nos. 100-607, 100-608):  Metalaxyl
Technical:  (Ridomil® 2E).  Tolerance In/On Leafy Vegetables (Excluding
Brassica Vegetables, Excluding Spinach).  Analysis of Residue Data and
Analytical Method.  CBTS #7171.

From: 	S. Bacchus

To:	R. Chambliss/S. Lewis

Date:	6/21/91

MRIDs:	41587800, 41587801

DP#:	N/A

Subject:	PP# 2F04072:  1.  Metalaxyl (Ridomil® 2E Fungicide, EPA Reg.
No. 100-607) in or on members of the Brassica (cole) leafy vegetables
crop grouping; evaluation of request for amended registration,
analytical method and residue data of mustard greens.

From: 	M. Peters

To:	B. Chambliss/S. Lewis

Date:	1/15/93

MRID:	42159801

DP#:	197037

Subject:	Metalaxyl (113501) - Case No. 0081.  Product and Residue
Chemistry Chapters for the Reregistration Eligibility Document (RED). 
CB No. 12906.

From: 	S. Hummel

To:	D. Edwards

Date:	6/14/94

MRIDs:	None

DP#s:	203675 and 206108

Subject:	Metalaxyl (113501) - Reregistration Case No. 0081.  Addendum to
RED Residue Chemistry Chapter, Rotational Crop Studies (GLN 165-1 and
165-2), Supporting Storage Stability Data.  CB Nos. 13740, 14131

From:	S. Hummel

To:	J. Loranger

Date:	10/17/94

MRIDs:	42195401, 42196502, 42196503, 41870308, 43317302

DP#:	223261

Subject:	Mefenoxam:  Replacement of Metalaxyl Technical with Mefenoxam
Technical; Review of Bridging Data,  CBTS No. 16909.  PRIORITY 6.  TOX
375AA, ID #:000100-TOR    PRAT CASE #: 039771

From:	L. Kutney

To:	D. Stubbs and D. McCall

Date:	4/24/96

MRIDs:	43800300, 43800301, 43800322, 43800323, 43889801-43889803,
43889821, 43896901-43896905

DP#:	268454

Subject:	Mefenoxam.  Issues to be Presented to the HED Metabolism
Assessment Review Committee.  PC Code 113502; Case No. 290692;
Submission No. S553336.

From: 	N. Dodd, A. Lowit, and M. Bonner

To:	G. Kramer

Date:	10/17/00

MRIDs:	None

DP#:	269910

Subject:	Mefenoxam.  Metabolism Assessment Review Committee (MARC)
Decision Document for Meeting Held on 10/24/00.  Chemical #113502. Case
#290692. Submission #S553336.

From: 	N. Dodd, A. Lowit, and M. Bonner

To:	G. Kramer

Date:	10/27/00

MRIDs:	None

DP#s:	257785 and 266898

Subject:	PP#9E06005.  Mefenoxam (Helix™) on Herb Subgroup (Crop
Subgroup 19-A) and Mint.  Section 3 Registration and Permanent Tolerance
Request.  Residue Chemistry Review:  Evaluation of Analytical Methods
and Residue Data.

From:	N. Dodd

To:	R. Forrest/S. Brothers

Date:	4/20/01

MRIDs:	44847601, 44847602

DP#:	274194

Subject:	PP#9F05044, 9E06005, and 9E06057.  Mefenoxam on Canola, Herb
Subgroup (Crop Subgroup 19-A), Fresh Mint, and Various Minor or Tropical
Fruits. Evaluation of Method Validation Report dated 2/22/01.

From:	N. Dodd

To:	S. Brothers/R. Forrest and T. Ellwanger/M. Waller

Date:	4/20/01

MRIDs:	None

DP#:	276001

Subject:	Metalaxyl/Mefenoxam Analytical Method Recovery Data in Plants.

From:	N. Dodd

To:	M. Waller/T. Ellwanger

Date:	9/13/01

MRID:	44208107

DP#:	324493

Subject:	Mefenoxam.  Ridomil Gold™ EC (EPA Reg. No. 100-801).  Label
Amendment for Cole Crops, Cucurbits, Lettuce and Grapes.

From:	L. Cheng

To:	R. Westin/M. Waller

Date:	3/17/06

MRIDs:	None

DP#:	None

Subject:	Metalaxyl/Mefenoxam.  Report of the Risk Assessment Review
Committee (RARC1).

From:	W. Britton

To:	B. Cropp-Kohlligian 

Date:	2/14/07

MRIDs:	None

DP#:	333767

Subject:	Mefenoxam.  Summary of Analytical Chemistry and Residue Data. 
PP#s 5F7018 and 9E6057.

From:	B. Cropp-Kohlligian

To:	M. Ottley

Date:	3/7/07

MRIDs:	46714701-46714707

DP#:	366407

Subject:	Mefenoxam.  Amendments for Grapes, Leafy Vegetables except
Brassica, and Potatoes.

From:	N. Dodd

To:	M. Waller/T. Gibson

Date:	11/12/09

MRIDs:	None

  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 April 2008



INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: methyl
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-D-alaninate	Common Name:

mefenoxam

(metalaxyl-M)	( Proposed tolerance

( Reevaluated tolerance

X Other - Recommended	Date:  03/03/10

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:  PP#9E7591 

DP Barcode:  D371307

Other Identifier:  

Residue definition (step 8/CXL): metalaxyl (plant); sum of metalaxyl and
metabolites containing the 2,6-dimethylaniline moiety, expressed as
metalaxyl (livestock).

Metalaxyl-M MRLs are at Step 6, pending resolution of the status of
metalaxyl CXLs. 	Reviewer/Branch:  RAB3 – Nancy Dodd

	Residue definition:  methyl
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate

Crop (s)	MRL (mg/kg) (Step 6)	Crop(s) 	Tolerance (ppm)

Caneberry subgroup 13-07A	0.70

Bean, snap, succulent	0.20

Spinach	0.1 (existing CXL 2 for metalaxyl)	Spinach	Remains at 10

Bushberry subgroup 13-07B	2.0

Lingonberry	Remove

Onion, bulb	0.03 (existing CXL 2 for metalaxyl)	Onion, bulb, subgroup
3-07A	3.0

Onion, green, subgroup 3-07B	10

Limits for Canada	Limits for Mexico1

X No Limits (metalaxyl MRLs apply)

( No Limits for the crops requested	X No Limits

(No Limits for the crops requested

Residue definition:  Residues of the resolved isomer metalaxyl-M are
covered by MRLs established for metalaxyl, the unresolved isomeric
mixture.

N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alanine methyl ester,
including metabolites that can be converted to the 2,6-dimethylaniline
moiety, each expressed as metalaxyl equivalents

The following are metalaxyl MRLs:	Residue definition: N/A

A 2004 listing gives numerous crops for both metalaxyl and metalaxyl-M,
but without tolerance values.

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

Raspberry	0.2

Bean	0.2

Spinach	10

Blueberry	2

Onion, bulb	3.0

Onion, green	10

Notes/Special Instructions:  S. Funk, 03/01/2010.  1 Mexico adopts Codex
MRLs or US tolerances for its export purposes.



APPENDIX I.	Chemical Names and Structures of Mefenoxam/Metalaxyl and
Metabolites.  

Common name;

Company code	Chemical name	Chemical structure

Mefenoxam;

CGA-329351	methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-D-alaninate	

Metalaxyl;

CGA-48988	methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate	

CGA-62826	N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine 

	

CGA-94689	N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)alanine
methyl ester	

CGA-108905
2-[(methoxyacetyl)(2-methoxy-1-methyl-2-oxoethyl)amino]-3-methylbenzoic
acid	

CGA-100255	N-(3-hydroxy-2,6-dimethylphenyl)-N-(methoxyacetyl)alanine
methyl ester	

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 (August 2009 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.  The rounding
procedures specified in the SOP were also used.

Caneberry (crop subgroup 13-07A)

The dataset used to establish a tolerance for mefenoxam on caneberries
consisted of field trial data for blackberries and raspberries (the
representative crops of subgroup 13-07A) representing application rates
of ~2.0 lb ai/A (one soil surface application at ~1.8 lb ai/A and two
foliar directed spray applications at ~0.10 lb ai/A/application) with a
0-day PHI.  Pending requested label revisions, the field trial
application rates and PHIs are within 25% of the maximum label
application rate and minimum label PHI, respectively.  The field trial
PHIs are within 25% of the minimum label PHI, the field trial
application rates are lower than the maximum label rate of 3.6 lb ai/A. 
Because no field trial data were submitted reflecting the maximum label
rate, we have assumed the petitioner intends to support the maximum
label rate used in the field trials, 2.0 lb ai/A.  The residue values
that were entered into the tolerance spreadsheet are provided in Table
II-1.

All field trial sample results for mefenoxam per se in/on caneberries
were above the LLMV (LLMV = 0.05 ppm).  The caneberry dataset contained
12 samples.  Visual inspection of the lognormal probability plot (Figure
II-1) and the results from the approximate Shapiro-Francia test
statistic (Figure II-2) indicated that the dataset was reasonably
lognormal.    

Using the tolerance spreadsheet, the recommended tolerance is 0.70 ppm
for caneberries.

Table II-1.	Residue data used to calculate tolerance for mefenoxam on
crop subgroup 13-07A.

Regulator:	EPA

Chemical:	Mefenoxam

Crop:	Caneberry

PHI:	0 days 

App. Rate:	1.95-2.18 lb ai/A

Submitter:	IR-4

MRID Citation:	MRID 47803103

	Residues of mefenoxam per se

	0.325

	0.359

	0.279

	0.382

	0.242

	0.213

	0.267

	0.233

	0.277

	0.313

	0.499

	0.554

Figure II-1.	Lognormal probability plot of mefenoxam field trial data
for caneberry.

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spreadsheet summary of mefenoxam field trial data for caneberry.

Spinach

The dataset used to establish a tolerance for mefenoxam on spinach
consisted of field trial data representing application rates of ~1.25 lb
ai/A (one soil surface application at ~1.0 lb ai/A/application and two
foliar directed spray applications at ~0.125 lb ai/A/application) with a
2- to 4-day PHI.  The field trial application rates and PHIs are within
25% of the maximum label application rate and minimum label PHI,
respectively.  The residue values that were entered into the tolerance
spreadsheet are provided in Table II-2.

All field trial sample results for combined residues of mefenoxam and
metabolites convertible to 2,6-DMA in/on spinach were above the LLMV
(LLMV = 0.10 ppm).  The spinach dataset contained 18 samples.  Visual
inspection of the lognormal probability plot (Figure II-3) and the
results from the approximate Shapiro-Francia test statistic (Figure
II-4) indicated that the spinach dataset was reasonably lognormal.

Using the tolerance spreadsheet, the recommended tolerance is 8.0 ppm
for spinach.

Table II-2.	Residue data used to calculate tolerance for mefenoxam on
spinach.

Regulator:	EPA

Chemical:	Mefenoxam

Crop:	Spinach

PHI:	2-4 days 

App. Rate:	1.211-1.253 lb ai/A

Submitter:	IR-4

MRID Citation:	MRID 47803105

	Combined residues of mefenoxam/metalaxyl + metabolites convertible to
2,6-DMA

	1.47

	1.72

	1.95

	1.98

	2.22

	2.39

	2.64

	3.02

	3.02

	3.11

	3.13

	3.16

	3.43

	4.01

	4.64

	5.02

	5.50

	6.19

Figure II-3.	Lognormal probability plot of mefenoxam field trial data
for spinach.

Figure II-4.	Tolerance spreadsheet summary of mefenoxam field trial data
for spinach.

Page   PAGE  1  of   NUMPAGES  49 

Mefenoxam	Summary of Analytical Chemistry and Residue Data	DP#: 371307