Subject:	Minutes of May 7, 2008 ChemSAC meeting

To:		HED’s Chemistry Interest Group

From:		HED’s Chemistry Science Advisory Council

Attendance:	Tom Bloem, Lee Cheng, Bill Cutchin, Nancy Dodd, William
Donovan (Chair), Christine Olinger (minutes), and Debra Rate.

3.  Mefenoxam vs Metalaxyl common moiety analysis for caneberry and snap
bean  (M. Doherty for Dave Thompson, IR-4)

IR-4 is currently preparing a petition for use of mefenoxam (Ridomil
Gold Copper) on caneberry, snap beans and spinach.  The caneberry and
snap beans analysis was initially done using an enantiomeric specific
method that only analyzes for mefenoxam.  However, the tolerance is
currently expressed as the 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-hydroxy methyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl
ester.  The enforcement method is a common moiety method that converts
everything into 2,4-DCBA(Can anyone tell me what DCBA stands for? –
the IR-4 submission doesn’t – I think it should be DMA).  IR-4
re-analyzed a sub-set of the samples from the field trials, and then
used a ratio of mefenoxam to common moiety value to then estimate other
values, and requested ChemSAC comment on their approach.

Tom Bloem noted that the most recent risk assessment recommended a
change in the residues to be regulated (M. Ottley, 5/31/07, D325137). 
The tolerance expression will be modified to include residues of
mefenoxam per se and the residues of concern for dietary risk
assessments will be mefenoxam per se, its metabolites containing the
2,6-dimethylaniline (2,6-DMA) moiety, its metabolites containing the
2-hydroxymethyl-6-methylaniline (HMMA) moiety, its metabolites
containing the ring hydroxylated dimethylaniline (Ring-OH) moiety, and
its metabolites containing the benzoic acid moiety.

The ChemSAC agreed that IR-4’s proposal is acceptable for this
petition only.  Future studies should ensure that all residues of
concern are monitored since multiple analytical methods are available.

Subject:	Minutes of the 2/25/2009 ChemSAC Meeting 

To:		HED’s Chemistry Interest Group

From:		HED’s Chemistry Science Advisory Council (ChemSAC)

Attendees:	Don Wilbur, Will Donovan (Chair), Leung Cheng, Nancy Dodd,
Steve Funk, Julie Langsdale, Meheret Negussie, Debra Rate (Minutes),
Bill Cutchin, Mike Doherty, George Kramer, Rick Loranger

Minutes of the 2/18/09 ChemSAC meeting:  Approved with no edits or
corrections.

2.  IR-4:  Mefenoxam proposal to use sum of parent and metabolites to
parent ratios to determine residue levels in snap bean and caneberry
(Nancy Dodd).

Briefly, IR-4 determined residues for mefenoxam in/on snap bean and
caneberry using an enantiomeric specific method (chiral Method #456-98).
 However, Syngenta indicated that parent and metabolites should have
been determined.  In the absence of a complete set of metabolite data,
IR-4 reanalyzed a subset of the samples using Method AG-395, which
determines the combined residues of parent and metabolites as
2,6-dimethylaniline (2,6-DMA).  When compared to the parent only residue
data, IR-4 found that the ratio of  parent+ metabolites to parent was
1.8x for snap beans and 1.3x for caneberry.  In lieu of collecting a
full data set on the parent and metabolites, IR-4 would like the Agency
to accept the use of parent + metabolites to parent ratio when setting
residue values for the risk assessment.

Background: 

Previously, the HED Metabolism Assessment Review Committee (HED MARC
Decision Memo, 10/27/00) 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 one metabolite
containing the HMMA moiety,
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 one metabolite
containing the HMMA moiety,
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, except that
2-[(methoxyacetyl)(2-methoxy-1-methyl-2-oxoethyl)amino]-3-methylbenzoic
acid (CGA-108905, which contains the HMMA moiety) 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, which contains the Ring-OH moiety) would be included in the
risk assessment for leafy vegetables (Brassica and non-Brassica). 

The HED MARC further concluded that in order to determine whether the
metabolites CGA-108905 and CGA-100255 need to be included in the
tolerance expression for rotational crops, the petitioner was required
to conduct limited field rotational trials in which residues of
CGA-108905 and CGA-100255 are determined.

Later-

HED (DP#333767, Bonnie Cropp-Kolligian, 3/7/07; RARC, 2/14/07)
determined that the tolerance expression should contain only parent to
be consistent with Codex , and the risk assessment should include
metabolites.  The CFR has not been revised.

Current and Proposed Labeled use rates:

Snap bean: 

	Multiple applications not to exceed 0.7 lb ai/A/season

0- and 3-day PHIs

Caneberry: 

	Multiple applications not to exceed 3.6 lb ai/A/crop season

0- and 45- day PHIs

Submitted Re-analyzed Data:

Snap bean: 

	Data reviewed at 0- (ratio = 1), 6- (ratio = 1.8) and 14- (ratio = 3)
day PHIs.

	Data reviewed on use rate of 0.7 lb ai/A/crop season

Caneberry:

	Data reviewed is on 0-day PHI

	Data reviewed on use rate of 2 lb ai/A/crop season

	1.3x ratio was obtained

Question for ChemSAC:

Shall we use the 1.8x and 1.3x factors to calculate residues of parent
and metabolites from data on parent only?

Based on the presented data, ChemSAC agreed that the approach to use
parent + metabolites to parent ratios for snap beans (1.8x) and
caneberry (1.3x) in order to estimate residue levels for risk
assessments will be acceptable.  ChemSAC concluded that for caneberry
the 0-day PHI will likely be the worst-case scenario, so to base the
ratio on the 0-day PHI should be acceptable.  The ChemSAC confirmed that
the residue of concern for the tolerance expression is parent.  The
ChemSAC also concluded that for future risk assessments, if refinements
are necessary, a PDP data approach that incorporates these ratios will
not necessarily be correct/adequate for these commodities unless more
complete residue data are available.  This cautionary statement was
deemed appropriate in light of the dependence of the ratios on the PHI. 

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