Document ID: EPA-HQ-OPP-2008-0458-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-07-15T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDE

	AND TOXIC SUBSTANCES

	

 

  SEQ CHAPTER \h \r 1 MEMORANDUM

Date:		12/18/08

SUBJECT:	Fenamidone:  Residue Chemistry Summary Document to Support New
Uses and 		Tolerances on the Root Vegetable Subgroup 1B (except radish),
Okra, Turnip 			Greens, Cilantro Leaves and Grapes Grown East of the
Rocky Mountains.  

 

PC Code:  046679	DP Barcode:  352806

MRID No.:  None	Registration No.:  264-695

Petition No.:  7E7350	Regulatory Action:   Section 3 Registration

Assessment Type:  N/A 	Reregistration Case No.: N/A

TXR No.:  N/A	CAS No.:  161326-34-7

	

          	

FROM:	Donna S. Davis, Chemist

		Reregistration Branch 1

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

		

THROUGH:	Toiya Goodlow, Chemist

		Michael S. Metzger, Chief

		Reregistration Branch 1

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

TO:		Susan Stanton

		Daniel Rosenblatt

		Registration Division (7505P)

Attached please find the Residue Chemistry Summary Document to support
requested new uses of fenamidone on the root vegetable subgroup 1B,
except radish, okra, turnip greens, cilantro leaves and grapes grown
east of the Rocky Mountains.  Executive Summary

IR-4 has submitted a petition to establish tolerances for residues of
the fungicide, fenamidone on the crop subgroup 1B (root vegetable,
except sugar beet), except radish.  This crop subgroup includes turnip
roots.  IR-4 has also petitioned for tolerances for the individual
commodities, okra, turnip greens, cilantro leaves and grapes grown east
of the Rocky Mountains.  

Adequate use directions have been provided to the Agency for all
commodities with the exception of turnips.  The use directions for
turnips should be modified to clearly specify use on cultivars grown for
root production only.  The nature of the residue in plants, animals and
rotational crops is considered adequately understood to support these
requested new uses.  An adequate analytical method exists to enforce the
proposed tolerances.  Additionally, fenamidone is recovered through FDA
multi-residue method protocol D, which could also serve as an
enforcement method.  The only animal commodity associated with this
petition is turnip greens.  HED has concluded that there is insufficient
information on the potential transfer of residues to milk and meat
resulting from feeding fenamidone treated turnip greens to ruminants;
therefore at this time, HED does not recommend in favor of establishing
a tolerance for residues of fenamidone on turnip greens.  No new field
trial data were submitted to support these new uses; all tolerances are
proposed to be established based on translation from previously
submitted data to the Agency.  HED concurs with the translations that
the petitioner has proposed for all the commodities which are the
subject of this petition and concludes that adequate information on the
magnitude of the residue in the commodities that are the subject of this
petition has been provided.   There are no issues of international
harmonization associated with these new uses.

Regulatory Recommendations

There are no residue chemistry deficiencies that would preclude the
establishment of tolerances for residues of fenamidone in/on the root
vegetable, except sugar beet subgroup 1B, except radish, and on the
individual commodities of okra, cilantro leaves and grapes grown east of
the Rocky Mountains.  Provided the forthcoming human health risk
assessment does not identify any issues of concern, the petitioner
submits a revised petition Section F amended to reflect the commodity
definitions below, and the label is amended to limit use on turnip
cultivars for root production only, the available data support the
following tolerances under 40 CFR §180. 579.

Vegetable, root, except sugar beet, subgroup 1B, except
radish…….…………….0.15 ppm

Okra…………………………………………………………
……………............…3.5 ppm

Cilantro,
leaves…………………………………………………………
…..……..…60 ppm

Grapes (East of the Rocky Mountains
Only)………………………………..………1.0 ppm

Note to RD:  The recommended tolerance of 0.15 ppm on crop subgroup 1B,
excluding radishes will cover residues of fenamidone in/on carrots. 
Since a separate carrot tolerance is no longer required, it can be
removed from the 40CFR §180. 579.  An import tolerance is currently
established for residues of fenamidone on grapes and is listed in the 40
CFR 180.579 as “grapes (imported)” at 1.0 ppm.  HED recommends that
the 40 CFR 180.579 be modified to delete “(imported)” and to add a
footnote to the grape stating that the grape tolerance is applicable
only to grapes grown east of the Rocky Mountains.

Background

Fenamidone is a broad-spectrum foliar fungicide currently registered for
application to a variety of field crops including, bulb vegetables,
tuberous and corm vegetables, fruiting vegetables and leafy vegetables. 
Fenamidone is a chiral compound with the technical product consisting of
98.5% S-fenamidone.  Tolerances are established for residues of
fenamidone in raw agricultural commodities, animal commodities and for
inadvertent residues under 40 CFR §180.579. 

Table 1, below is a summary of the test compound nomenclature and Table
2 is a summary of the physiochemical properties of fenamidone.

Table 1.  Test Compound Nomenclature.

Compound Chemical Structure	

Common name	fenamidone

Company experimental name	RPA 407213

IUPAC name	(S)-1-anilino-4-methyl-2-methylthio-4-phenylimidazolin-5-one

CAS name
(5S)-3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3-(phenylamino)-4H-imi
dazol-4-one

CAS registry number	161326-34-7

End-use product (EP)	Reason® 500 SC (44.4% S-fenamidone; 4.13 lb
ai/gal; EPA Reg. No. 264-695)

 

Table 2.  Physicochemical Properties of Technical Grade Fenamidone. 

Parameter	Value	Reference

Melting point/range	Pure:  137 °C, Technical:  135.5 °C	MRID 45385708

pH	5.7	MRID 45385714

Density	Pure:  1.290 g/mL	MRID 45385708

Water solubility 	0.0078 g/L at 20 °C	MRID 45385712

Solvent solubility (under ambient conditions)	330 g/L in methylene
chloride

250 g/L in acetone

106 g/L in ethyl acetate

86 g/L in acetonitrile

43 g/L in methanol

40 g/L in toluene

0.3 g/L in heptane	MRID 45385712

Vapor pressure	2.60 x 10-9 mm Hg at 20 °C	MRID 45385711

Dissociation constant, pKa	Does not dissociate in the pH range of 1-13
MRID 45385714

Octanol/water partition coefficient, Log(KOW)	631 (2.8)	MRID 45385713

UV/visible absorption spectrum	Primary absorbance:  203 nm

Secondary absorbance:  230 nm	MRID 45385709

Detailed Considerations

860.1200  Directions for Use

IR-4 is proposing to expand the label for the formulated product,
Reason® 500 SC (soluble concentrate) to include new uses on crop
subgroup 1B, excluding radishes, turnip greens, okra, cilantro and
grapes grown east of the Rocky Mountains.  The petitioner has provided
proposed label directions for the new uses.  A summary of the use
directions for these crops is shown in Table 3.  

Table 3.  Summary of Directions for Use of Fenamidone on New Crops.

App. Method	Formulation	App. Rate

(lb ai/acre)	Max. No. App. per Season	Max. Seasonal App. Rate (lb
ai/acre)	PHI (days)	Use Directions and Limitations

Crop Subgroup 1B (root vegetables except sugar beets), excluding
radishes which includes:

Beet, garden; burdock, edible; celeriac; chervil, turnip-rooted;
chicory; ginseng; horseradish; parsley, turnip-rooted; parsnip; radish,
oriental; rutabaga; salsify; salsify, black; salsify, Spanish; skirret;
turnip.

Foliar by ground, air or chemigation equipment	Reason® 500 SC

4.13 lb ai/gal	0.27	not specified	0.80	14	14-day RTI1

Okra

Foliar by ground, air or chemigation equipment.	Reason® 500 SC

4.13 lb ai/gal	0.18-0.27	not specified	0.80	14	14-day RT

Turnip Greens

Foliar by ground, air or chemigation equipment.	Reason® 500 SC

4.13 lb ai/gal	0.18-0.27	not specified	0.80	2	5- to 10-day RTI

Cilantro

Foliar by ground, air or chemigation equipment.	Reason® 500 SC

4.13 lb ai/gal	0.27	not specified	0.80	2	5- to 10-day RTI

Grapes – Grown East of the Rocky Mountains Only

Foliar by ground, air or chemigation equipment.	Reason® 500 SC

4.13 lb ai/gal	0.0892	not specified	0.27	30	10- to 14-day RTI

for use on grapes grown east of the Rocky Mountains only

1 RTI is retreatment interval

HED concludes that there is insufficient data on the likelihood of
transfer of residues of fenamidone to milk and meat as a result of
feeding treated turnip greens (see Section 860.1480
Meat/Milk/Poultry/Eggs, below).  At this time, HED is recommending
against the establishment of a tolerance for residues of fenamidone on
turnip greens; therefore, the label should be modified to specify use on
turnip cultivars grown for root production only.  The use directions for
the commodities in crop subgroup 1B, excluding radishes, and for the
individual commodities of okra, cilantro, and grapes grown east of the
Rockies are adequate to support those new uses.  

860.1300 Nature of the Residue - Plants/Livestock

D314318, 6/14/2007, T. Bloem, Residue Chemistry Summary Chapter

Based on data submitted on the metabolism of fenamidone on potatoes,
tomatoes, lettuce, grapes and carrots, HED concludes that the nature of
the residue in plants has been adequately delineated to support this
IR-4 request only. 

Carrot data can be translated to support the requested new use on crop
subgroup 1B (root vegetables except sugar beet), except radish.  For
tolerance setting purposes, the residue of concern in members of the
crop subgroup 1B, except radish is considered to be parent compound per
se.  The residue of concern for risk assessment purposes for this
subgroup is parent compound and metabolites, RPA 408056, RPA 717879 and
RPA 405862.  

HED has previously determined that the nature of the residue in leafy
vegetables, brassica (cole) leafy vegetables, fruiting vegetables
(excluding cucumber), cotton, sunflower and tobacco has been adequately
delineated.  This conclusion is translated to turnip greens, okra,
cilantro and grapes.  For tolerance setting purposes, the residue of
concern in these commodities is parent compound only.  The residue of
concern for risk assessment purposes for these commodities is parent and
metabolites, PRA408056, RPA 717879 and RPA 405862.  

The nature of the residue in livestock is adequately understood.  The
residue of concern in livestock for purpose of tolerance enforcement is
fenamidone and its metabolite, RPA 717879. The residue of concern for
purpose of risk assessment is fenamidone, RPA 717879, and RPA 408056.

Structures of regulated compounds are shown in Attachment 1 of this
memorandum.

860.1340 Residue Analytical Methods – Plants

D314318, 6/14/2007, T. Bloem, Residue Chemistry Summary Chapter

No new fenamidone residue data were provided to support this petition;
therefore, a discussion of residue analytical methods used for data
gathering purposes is not pertinent to this action.

The current tolerance enforcement method entitled RPA407213:  method of
Analysis for RPA 407213 and its Metabolites RPA 717879, RPA 408056 and
RPA 405862 (MRID No. 45385918), a liquid chromatographic method coupled
with tandem mass spectrum detection (LC/MS/MS) has been radiovalidated. 
Further the method has undergone successful ILV (independent laboratory
validation) as well as validation by the Agency on a number of
commodities including potato, cucumber, cantaloupe, lettuce, onion,
tomato (fruit, paste, and puree), spinach, and wheat (forage, hay,
straw, grain, bran, flour, shorts, germ, and middlings).  HED concludes
that this method is also suitable to enforce the new plant tolerances
proposed in this petition.  HED notes that since residues of fenamidone
are detected through FDA Multi-Residue Method Protocol D (see below),
this protocol can also serve as an enforcement methodology.

860.1340 Residue Analytical Methods - Livestock

The only animal feed item associated with this petition is turnip
greens.  HED has concluded that there is not sufficient data on the
likelihood of transfer of residues of fenamidone in meat and milk as a
result of feeding treated turnip tops; therefore, the use on turnips
will be limited to cultivars grown for root production only until such
time as additional livestock feeding study data are provided.  Since no
new animal tolerances will be established at this time, no further
discussion of residue analytical methods for livestock is required. 

860.1360 FDA Multi-Residue Methods

D314318, 6/14/2007, T. Bloem, Residue Chemistry Summary Chapter

Fenamidone, RPA 408056, RPA 717879, and RPA 405862 were tested through
FDA multi-residue methods.  Residues of fenamidone and all three
metabolites were completely recovered from fortified lettuce using
Protocol D.  Low recoveries of fenamidone were observed from Protocols E
(31%) and F (54%).  Metabolites RPA 408056, RPA 717879, and RPA 405862
were not recovered using Protocols E and F.  Protocol B was not tested
because fenamidone and its metabolites are not acids or phenols, and
Protocol A was not fully tested because the compounds were not found to
naturally fluoresce.  

860.1380 Storage Stability

No new stored residue data were submitted to support the proposed uses;
therefore, a discussion of storage stability is not pertinent to this
action.

860.1480 Meat/Milk/Poultry/Eggs

The only feed item associated with this petition is turnip greens. 
Turnip greens are fed exclusively to dairy cattle; therefore, for the
purpose of this action, only an update to the dairy cattle dietary
burden is required.  HED has calculated a maximum reasonably balanced
diet (MRBD) for dairy cattle based on the recent guidance on revised
Table 1 considerations (June 2008).  To maintain a reasonably balanced
diet, the constructed diet for dairy cattle included 45% roughage, 45%
carbohydrate, and 10% protein concentrate, consistent with the diet
described in the Table 1 (June 2008) guidance.  The revised diet for
dairy cattle includes need feed items, turnip roots at 5% and turnip
tops at the maximum allowable level of 30% of the diet.  To determine an
appropriate residue level for fenamidone for these feedstuffs, HED has
translated from the carrot field trial data (D314318, T. Bloem, 6/14/07,
46927101.der.doc) for turnip roots and from the mustard green field
trial data (D314318, T. Bloem, 6/14/07, 46518402.de1.doc) for turnip
greens.  Residues of fenamidone and its metabolites, RPA 717879, RPA
408056 and RPA 405862, which are the residues of concern for risk
assessment purposes are included for both feedstuffs.  The maximum field
trial residue value for the combined residues was used to calculate the
MRBD for dairy cattle.  



Table 4.  MRBD Calculations for Dairy Cattle

Crop1	Residue (ppm)2	%Dry Matter2	% Diet	Residue in Diet

	Dairy Cattle	Dairy Cattle

Wheat hay (R)	3.16	88	15	0.54

Turnip greens (R)	29.21	30	30	29.21

Wheat milled byproducts (CC)	0.62	88	30	0.21

Turnip root	0.17	15	5	0.06

Carrot (CC)	0.17	12	10	0.14

Cottonseed meal (PC)	0.08	89	10	0.01

Total	30.17

1  R= roughage; PC = protein concentrate; CC = carbohydrate concentrate.

2  For wheat, combined fenamidone, RPA 717879, and RPA 408056 (free and
conjugated); inadvertent residues in wheat as a result of crop rotation;
for calculation see D297216, T. Bloem, 25-May-2004); for the other
crops, combined fenamidone, RPA 717879, RPA 408056, and RPA 405862 –
highest field trial value used for combined residues.

A lactating dairy cattle feeding study was previously submitted and
reviewed by HED (45386004.der.wpd; D297216, T. Bloem, 25-May-2004).  The
cattle were dosed with fenamidone for 35 days at dietary feeding levels
of 0.8 ppm, 2.3 ppm, and 7.9 ppm.  Milk was collected throughout the
study and muscle, fat, liver, and kidney were collected at sacrifice. 
Because of low residue levels, only samples from the 7.9 ppm dosing
group were analyzed.  

Following dosing of cattle with fenamidone for 35 days at 7.9 ppm,
residues of fenamidone and its metabolites RPA 717879 and RPA 408056
were below the limit of detection (LOD = <0.0033 ppm each) in milk
samples collected over the course of the dosing period and were <LOD
(<0.017 ppm each) in samples of muscle, fat, liver, and kidney collected
at sacrifice.  Quantifiable residues of fenamidone were observed in one
sample of milk fat at 0.011 ppm; the other two samples bore detectable
residues of fenamidone at levels below the LOQ (<0.01 ppm).  Residues of
RPA 717879 and RPA 408056 were <LOD (<0.0033 ppm each) in the milk fat
samples.  

The current MRBD for dairy cattle including the newly proposed use on
turnip greens would results in a MRBD of 30 ppm which exceeds the
highest dose tested in the lactating dairy cattle study by more than
3-fold.   HED concludes that it is not possible to determine if revised
milk and meat tolerances might be required as a result of feeding dairy
cattle treated turnip greens; therefore, HED does not consider the
turnip green use adequately supported by residue data. 

A ruminant feeding study reflecting a concentration in the diet which
brackets the newly calculated MRBD would be required to support the
requested use on turnip greens. 

860.1500 Crop Field Trials

No new crop field trial data were provided to support this petition. 
IR-4 intends to extrapolate from data/tolerances on existing uses to
establish the requested new uses.  Rationales for translation are
summarized below followed by the Agency’s conclusion with respect to
each proposal.

Crop Subgroup 1B (Root Vegetables, Except Sugar Beet), Excluding Radish

IR-4 Proposal

IR-4 has requested a tolerance on crop subgroup 1B, excluding radish
based on translation of existing carrot data.   HED notes that this crop
subgroup includes turnip roots. 

Agency Response

Prior to formal submission, IR-4 consulted with the HED Chemistry
Science Advisory Council (ChemSAC).  At the April 2, 2008 committee
meeting, the ChemSAC discussed IR-4’s proposal and reached the
following conclusion (excerpted from the 4/2/08 meeting minutes).

Fenamidone: Translation of carrot data to crop subgroup 1B except radish
(W. Donovan for D. Thompson, IR-4):  IR-4 proposed to establish a
tolerance for a crop subgroup 1B (except radish) based on fenamidone
residue levels in carrot.  The SAC was in favor of this approach
provided the following information is included: Does the term
“radish” include Oriental radish.  For turnip, a crop included in
1B, since the tops of turnips may be consumed by humans or livestock,
the use would have to be restricted to cultivars for root production
only.

Post-Meeting Update:  B. Schneider provided the following information:
Radishes mature 3-6 weeks after seeding.  Oriental radish takes 8-12
weeks with at least some up to 24 weeks for maximum size.  Based on this
information, oriental radish may be included in crop subgroup 1B except
radish for this use.

For the purpose of this action, HED concludes that the translation from
carrot data to crop subgroup 1B, excluding radishes is appropriate.  HED
notes that this crop subgroup includes turnip roots.   HED has reviewed
the proposed use label for the crop subgroup 1B, excluding radishes and
concludes that the use pattern is identical to that proposed for carrots
and is adequately represented by the carrot field trial data.  HED
recommends that the tolerance for subgroup 1B, excluding radishes be set
at 0.15 ppm, the same level as the carrot tolerance.  Further, since the
residue of concern for risk assessment purposes includes additional
metabolites, HED will use the highest field trial values from the carrot
data to represent all the crops in subgroup 1B, excluding radishes for
the dietary risk assessment.

HED notes that the ChemSAC proposed restriction of the use of fenamidone
on turnips to turnip cultivars grown for root production only since a
tolerance had not been established for turnip leaves.  While the
registrant has proposed a reasonable basis on which to establish a
turnip green tolerance (see section directly below), HED does not have
adequate information to assess the potential for transfer of residues to
milk and meat resulting from feeding treated turnip greens to ruminants.
 At this time, HED cannot establish a tolerance on turnip greens and
continues to recommend that the turnip use be limited to cultivars grown
for root production only.  

Turnip Greens

IR-4 Proposal

IR-4 has cited an EPA document entitled Reviewer’s Guide and Summary
of HED ChemSAC Approvals for Amending Crop Group/Subgroups [40CFR180.41]
and Commodity Definitions [40 CFR 180.1(d)] (B. Schneider, 6/14/2006) to
support establishment of a tolerance on turnip leaves.  The petitioner
notes that turnip greens are slated to move from crop group 2 (Leaves of
root and tuber vegetables group) into crop group 5 (Brassica leafy
vegetables) and will become a member of crop subgroup 5B (Leafy brassica
greens).  A tolerance is already established for residues of fenamidone
on crop subgroup 5B at 55 pm; therefore, the petitioner proposes that a
tolerance be established for “turnip, leaves” at 55 ppm until the
crop grouping changes have been finalized.

Agency Response

HED notes that while the crop group adjustment for turnip tops contained
in the 2006 reviewers guide has not been made, it is still HED’s
position that this is an appropriate revision to the current crop group
structure and will be made when as part of a complete revisit of both
crop groups 2 and 5 (personal communication from B. Schneider to D.
Davis on 12/3/08).  As the petitioner notes, the reviewers guide states
that turnip greens will be moved to crop group 5 and will also be a
member of crop subgroup 5B and will be referred to as “turnip,
greens”.  Additionally the guide states that forage turnip varieties
grown only for livestock feed items will remain in crop group 2 and will
be referred to as “turnip, forage, tops”.  

HED has reviewed the submitted label and concludes that the proposed use
directions for turnips are identical to the use pattern for other
subgroup 5B commodities; therefore, HED concurs with the petitioner’s
recommendation that it would be appropriate to consider the turnip
greens with other members of the crop subgroup 5B.  However, at this
time, HED does not have adequate data to assess the potential transfer
of residues to meat and milk resulting from the feeding of fenamidone
treated turnip tops.  Until livestock feeding data are received which
include feeding levels which bracket the revised MRBD for dairy cattle
and allow HED to determine if revised meat and milk tolerances are
required, a turnip greens tolerance can not be established.

Okra

IR-4 Proposal

The petitioner is proposing to translate from fruiting vegetables to
okra, specifically from non-bell pepper data in order to establish a
tolerance for okra.

Agency Response

On Sept 10, 2008, HED’s ChemSAC considered and approved revisions to
crop group 8, fruiting vegetables, excluding cucurbits.  The
recommendations for revisions are codified in the B. Schneider memo
entitled Crop Grouping – Part VI:  Analysis of the USDA IR-4 Petition
to Amend the Crop Group Regulation 40 CFR §180.41 (c)(8) and Commodity
Definitions [40 CFR 180.1 (g)] Related to the Crop Group 8 Fruiting
Vegetable dated 10/20/08.  Okra will be formally included in crop group
8 and will further be part of the newly proposed crop subgroup 8B,
Peppers.  The representative commodities for subgroup 8B are bell and
one cultivar of a non-bell pepper. 

HED has reviewed the proposed use pattern for okra and finds it to be
identical to the use pattern for fruiting vegetables.  Since residues
and tolerances were found to be higher for non-bell peppers, HED concurs
that it is appropriate to translate fruiting vegetable data and to set
the tolerance and residues in the risk assessment based on the higher
residues found in the non-bell pepper field trials.  Since the 40 CFR
180.41 has not yet been revised to reflect the pending changes, a
tolerance for “okra” at 3.5 ppm will be required.  

Cilantro Leaves

IR-4 Proposal

IR-4 has cited an EPA document entitled Reviewer’s Guide and Summary
of HED ChemSAC Approvals for Amending Crop Group/Subgroups [40CFR180.41]
and Commodity Definitions [40 CFR 180.1(d)] (B. Schneider, 6/14/2006) to
support establishment of a tolerance on cilantro leaves.  The petitioner
indicates that the reviewers guide states that parsley and cilantro are
equivalent and that a tolerance for parsley has been established at 60
ppm as a member of crop group 4, leafy vegetables, except brassica, so
this tolerance can be extended to cilantro leaves.

Agency Response

HED concurs with the petitioner’s proposal.  The determination from
2006 that the term “parsley” includes both parsley and cilantro
still stands.  The proposed use pattern on cilantro is identical to the
use pattern for all other crop group 4 commodities; therefore it is
appropriate to translate data from the leafy vegetable, except brassica
crop group.  Until crop group 4 is revised to include cilantro leaves in
the definition of parsley, a separate tolerance for residues of
fenamidone on “cilantro, leaves” should be established at 60 ppm. 
For the dietary risk assessment, HED will use the highest field trial
values from the representative commodities from crop group 4 to
represent cilantro leaves in the dietary risk assessment.

Grapes East of the Rocky Mountains

IR-4 Proposal

The petitioner is proposing to use previously submitted European field
trial data to support a tolerance for grapes grown east of the Rocky
Mountains.  

Agency Response

IR-4 submitted this proposal directly to the HED ChemSAC, who met on
July 12, 2008 to discuss the proposal.  The ChemSAC noted that the
European grape fenamidone residue data were conducted on wine grapes in
Italy (n=10) and France (n=5), covered multiple years (n=3 1997 and n=12
1998), and were conducted at 1.7-3.9x the proposed seasonal rate. 
Further, the ChemSAC observed that based on the production figures in
guideline 860.1500 (from early 1990's), only about 5% of US grapes are
grown east of the Rockies (all in Region 1).  Finally, the ChemSAC also
stated that based on cultural practices, climatic conditions, and grape
varieties, residues in/on grapes grown in the eastern US are unlikely to
be higher than residues for grapes grown in Europe.  Therefore, the
ChemSAC concluded that translation of the European grape residue data
was acceptable provided the petition adequately addressed the following:
 (1) the maximum US application rate should be equal to or less than the
rate used in the European trials; (2) the US pre-harvest and
reapplication intervals should match the European trials; and (3) the
petition needs to address any differences in formulation and inert
ingredients between that used in the European trials and that proposed
in the US.  

The proposed use pattern submitted with this petition conforms to
conditions (1) and (2) required by the ChemSAC.  The petitioner has
stated that while the European field trials were conducted with a water
dispersion granule (WG) formulation and the U.S. use is for a SC
formulation, both formulations are water dispersible and are diluted
with water prior to application to grapes, so no difference in residues
should be noted.  The registrant also provided information on slight
differences in terms of the inert ingredients between the two
formulations which should have no appreciable impact on residue values. 
HED concurs with the petitioner’s conclusions with respect to the
differences in the formulations and concludes that it is appropriate to
translate European Field trial data to grapes grown east of the Rocky
Mountains for risk assessment and tolerance setting purposes.  

An import tolerance is currently established for residues of fenamidone
on grapes and is listed in the 40 CFR 180.579 as “grapes (imported)”
at 1.0 ppm.  HED recommends that the 40 CFR 180.579 be modified to
delete “(imported)” and to add a footnote to the grape tolerance at
the end of the table of tolerances stating that the grape tolerance is
applicable only to grapes grown east of the Rocky Mountains.  

860.1850 Confined Accumulation in Rotational Crops

D314318, 6/14/2007, T. Bloem, Residue Chemistry Summary Chapter

Confined rotational crop data on lettuce, turnip and barley were
previously submitted to the Agency.  The Agency has determined that the
residue of concern in rotational crops for purposes of tolerance setting
is fenamidone and its metabolite, RPA 717879.  The residue of concern in
rotational crops for purposes of risk assessment is fenamidone, and its
metabolites, RPA 717879, and RPA 408056 (free and conjugated).

 860.1900 Field Accumulation in Rotational Crops

 D314318, 6/14/2007, T. Bloem, Residue Chemistry Summary Chapter

The Reason® 500 SC label indicates that a treated field may be rotated
to a labeled crop immediately following the last application, to wheat
and strawberries 30 days after the last application, and all other crops
one year after the last application.  Based on the currently available
data HED concludes that these rotational crop restrictions are
appropriate.  

860.1550 Proposed/Recommended Tolerances

Table 5, below is a summary of the proposed and HED-recommended
tolerances and commodity definitions for residues of fenamidone per se. 
A revised Section F is requested to reflect the commodity definitions
and tolerance levels identified in Table 5, below.  There are no Codex,
Canadian or Mexican MRLs (maximum residue levels) for residues of
fenamidone in root vegetables, okra, or cilantro.  There is a Canadian
MRL for grapes.  The Canadian MRL is expressed as parent compound only
and is set at 1.0 ppm.  While slight nomenclature discrepancies exist,
both Canada and the US have included parent compound only in their
residue definition and tolerance levels for grapes are identical.  There
are no issues with respect to international harmonization as a result of
the proposed new uses that are the subject of this petition.  



Table 5. 	Tolerance Summary for Fenamidone.

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

40 CFR §180.579(a)

Vegetables, root, except sugar beet, subgroup 1B, except radish	0.2	0.15
Set at level of current carrot tolerance 0.15 ppm; Vegetable, root,
except sugar beet, subgroup 1B, except radish

Turnip, leaves	55	--	Cannot recommend for a tolerance at this time;
Turnip, greens

Okra	3.5	3.5

	Coriander, leaves	60	60	Cilantro, leaves

Grape	1.0	1.0	For use on grapes grown east of the Rocky Mountains only

Attachments

Attachment 1.  Chemical Structures

Attachment 2.  IRL Status Sheet

Attachment 1.  Chemical Structures

Name	Structure

fenamidone; RPA 407213

 

 

14C-C-phenyl-fenamidone

RPA 408056 (racemic mixture)

RPA 405862 (racemic mixture)

RPA 410193 (S enantiomer)

5-methyl-5-phenyl-3-phenylamino-imidazolidin-2,4-dione

RPA 717879 (racemic mixture)

RPA 413255

(5S)-5-methyl-2-(methylthio)-3-[(2-nitrophenyl)amino]-5-phenyl-3,5-dihyd
ro-4H-imidazol-4-one

Attachment 2.  International Residue Limit Status Sheet

  SEQ CHAPTER \h \r 1 INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name:

(4H-Imidazol-4-one, 3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3
(phenylamino)-, (S)-)	Common Name:

Fenamidone	v Proposed tolerance

( Reevaluated tolerance

( Other	Date:

12/10/2008

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: 7E7350

DP Barcode: 352806

Other Identifier:

Residue definition (step 8/CXL): N/A	Reviewer/Branch:  D. Davis & A.
LaMay/RRB1

	Residue definition: “Tolerances are established for residues of
fenamidone (4H-Imidazol-4-one,
3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3 (phenylamino)-, (S)-)
from the application of the fungicide fenamidone”

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

Crop Subgroup 1B (Root Vegetables, Except Sugar Beet), Excluding Radish
0.15 ppm

Turnip, forage, tops	55 ppm

Turnip, greens	55 ppm

Okra	3.5 ppm

Cilantro, leaves	60 ppm

Grapes (grown east of the Rockies only)	1.0 ppm

Field Corn grain (incl. processed commodities)	0.02 ppm

Sweet Corn Grain (K+CWHR)	0.02 ppm

Sweet Corn Forage	0.15 ppm

Field Corn Forage	0.50 ppm

Corn Stover	0.35 ppm

Soybean Seed	0.02 ppm

Soybean Forage	0.20 ppm

Soybean Hay	0.20 ppm

Limits for Canada	Limits for Mexico

( No Limits

√ No Limits

( No Limits for the crops requested

Residue definition:

(5S
)-3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3-(phenylamino)-4H-imidaz
ol-4-one

	Residue definition: N/A

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S.Funk, 12/12/2008.

Fenamidone Residue Chemistry Summary Document	D352806

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