Document ID: EPA-HQ-OPP-2008-0458-0007
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, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

	Date:	2/24/09

	Subject:	Fenamidone:  Residue Chemistry Summary Document to Support 			
New Rotational Crop Uses and Tolerances on Field Corn, Sweet 				Corn
and Soybean.

PC Code:  046679	DP Barcode:  D357372

MRID No.:  47514101, 47514102, 47514103, 47514104, 47514105	Registration
No.:  264-695

Petition No.:  8F7410 	Regulatory Action:   Section 3 Registration

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

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

		

	From:		Alexandra LaMay, Biologist

			Risk Assessment Branch VII

			Health Effects Division (7509P)

	Through:	Donna S. Davis, Senior Chemist

			Michael Metzger, Chief

			Risk Assessment Branch VII

			Health Effects Division (7509P)

	To:		Rosemary Kearns

			Tony Kish

			Registration Division (7505P)

Executive Summary 

 

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. 

The registrant, Bayer CropScience has petitioned the Agency to establish
rotational crop tolerances to support the planting of field corn, sweet
corn and soybeans at a 30 day plant back interval (PBI) to fields that
have been previously treated with fenamidone.

	

Adequate use directions have been provided to the Agency for all
commodities.  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.  An adequate number of field trials with appropriate
geographic representation have been provided to allow HED to establish
rotational crop tolerances on field corn, sweet corn and soybean
commodities.  Sufficient storage stability data are available to support
the field trials and the data were generated using an appropriate data
collection method.  

Crop field trial samples were analyzed for residues of fenamidone and
the combined residue of its metabolites RPA 717879 (DADK-Fen) and free
RPA 408056 (DA-Fen).  The method limit of quantitation (LOQ) for
fenamidone is 0.02 ppm and for the combined metabolites RPA 717879 and
RAP 408056 free, converted to 717879 is 0.02 ppm.  Combined residues of
fenamidone and its metabolites were <0.04 ppm in field corn grain, sweet
corn kernel plus cob with husk removed (K + CWHR), and soybean seed. 
Combined residues of parent and metabolites ranged from <0.04 ppm –
0.028 ppm in field corn forage and from <0.04 ppm – 0.17 ppm in field
corn stover.  Combined residues of fenamidone and its metabolites ranged
from <0.04 ppm – 0.12 ppm in sweet corn forage and from <0.04 ppm -
0.35 ppm in sweet corn stover.  Residues of parent and metabolites
ranged from <0.04 ppm – 0.10 ppm in soybean forage and from <0.04 ppm
– 0.17 ppm in soybean hay.

The rotational crop field trials support the establishment of tolerances
for residues of fenamidone and its regulated metabolites in field corn,
sweet corn and soybean commodities with a 30-day PBI at the levels shown
below.  Tolerance level recommendations for field corn grain, sweet corn
(K + CWHR) and soybean seed are based on the combined LOQs for the
parent compound and residues converted to RPA 717879.  Tolerance level
recommendations for the remaining commodities were derived using the MRL
calculator.  There are no Canadian, Mexican or CODEX MRLs currently
established for residues of fenamidone in/on field corn, sweet corn or
soybean commodities; therefore, there are no issues of international
harmonization associated with this petition.  

Regulatory Recommendations and Residue Chemistry Deficiencies

There are no residue chemistry deficiencies that would preclude the
establishment of rotational crop tolerances for residues of fenamidone
in/on the field corn, sweet corn, or soybeans.  Provided the registrant
submits a revised Section F reflecting the commodity definitions and
levels shown below and further provided the forthcoming human health
risk assessment does not identify any issues of concern, the available
data support the following tolerances under 40 CFR 180.579(d).

Corn, field,
grain…………………………………………………………
…..0.04 ppm

Corn, sweet, kernel plus cob with husks
removed.…………………….……..0.04 ppm

Corn, sweet,
forage…………………………………………………………
...0.20 ppm

Corn, field,
forage…………………………………………………………
…0.30 ppm

Corn, sweet,
stover…………………………………………………………
…0.45 ppm

Corn, field,
stover…………………………………………………………
….0.30 ppm

Soybean,
seed…………………………………………………………
……...0.04 ppm

Soybean,
forage…………………………………………………………
…....0.15 ppm

Soybean,
hay……………………………………………………………
……0.25 ppm

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.  Fenamidone  Nomenclature.

Compound	Chemical Structure

Common name	Fenamidone

Company experimental name	AE C649693, 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 #	161326-34-7

End-use product/EP	Reason® 500 SC

Table 2.  Physicochemical Properties of the Technical Grade Fenamidone. 

Parameter	Value	Reference

Melting point/range	Pure: 137

Technical: 135.5	MRID 45385708

pH	5.7	MRID 45385714

Density	Pure: 1.288	MRID 45385708

Water solubility ( 20°C)	0.0078 g/L	MRID 45385712

Solvent solubility (mg/L at RT)	330,000 methylene chloride;

250,000 acetone

106,000 ethyl acetate

86,000 acetonitrile

43,000 methanol

40,000 toluene

300 heptane	MRID 45385712

Vapour pressure at 20°C	2.60X10-9	MRID 45385711

Dissociation constant (pKa)	No measurable dissociation constants in the
pH range of 1 to 13	MRID 45385714

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

UV/visible absorption spectrum (nm)	Primary: 203

Secondary: 230	MRID 45385709

Directions for Use

The petitioner is proposing to expand the label for the formulated
product, Reason® 500 SC to allow rotation to field corn, soybean and
sweet corn with a 30-day plant back interval (PBI).  There are no direct
uses on these crops.  

HED concludes that there is sufficient data to evaluate the request for
rotational crop uses and tolerances for sweet corn, field corn and
soybean.  The submitted rotational crop data support a PBI of 30-days as
specified on the proposed label

860.1300 Nature of the Residue – Plants/ Livestock	

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

No new metabolism studies were submitted for this petition.  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 request
for rotational crop use on corn and soybeans.  The HED Metabolism
Assessment Review Committee (MARC) has reviewed metabolism studies,
rotational crop studies and environmental fate data (MARC memos- T.
Bloem et al., 11-July-2002; T. Bloem et al., 25-May-2004). 

   

The residues of concern for tolerance setting and risk assessment
purposes are summarized in the table below.



Table 3.  Residues of Concern in Primary Crops, Livestock, Rotational
Crops, and Water

Matrix	Tolerance Expression	Residues for Risk Assessment

Registered/proposed primary crops excluding root vegetables	fenamidone
fenamidone, RPA 717879 (DADK-Fen), RPA 408056 (DA-Fen), RPA 405862

Root vegetables	fenamidone	fenamidone, RPA 413255

Animal commodities 	fenamidone, RPA 717879 (DADK-Fen)	fenamidone, RPA
717879 (DADK-Fen), RPA 408056 (DA-Fen)

Rotational Crops	fenamidone, RPA 717879 (DADK-Fen)	fenamidone, RPA
717879 (DADK-Fen), and RPA 408056 (DA-Fen) (free and conjugated)

860.1340 Residue Analytical Methods

47514101.de2.doc (soybeans, sweet corn, field corn), 2/24/09, A. LaMay

Field trial data were generated using Bayer CropScience analytical
method RP0002P0801.  The method has been adequately validated and is
acceptable for determining residues of fenamidone, RPA 717879 and RPA
408056 (free) in field corn grain, field corn forage, field corn stover,
sweet corn kernel plus cob with husk removed (K + CWHR), sweet corn
forage sweet corn stover, soybean seed, soybean forage and soybean hay. 
 

The method involves extracting residues of fenamidone, RPA 717879, and
RPA 408056 from field corn, sweet corn and soybean samples with aqueous
acetone.  Extracts were filtered and acidified and residues were
quantified using HPLC/MS/MS (high performance liquid chromatography with
electrospray ionization/tandem mass spectrometry detection).  Residues
are reported as parent compound and the combined residues of RPA 717879
and RPA 408056.  HED notes that the residue of concern for risk
assessment purposes is RPA 408056 (free and conjugated).  The registrant
has not provided sufficient evidence to demonstrate that residues of RPA
408056 conjugated are converted to RPA 717879 during the hydrolysis step
of this analytical method.  Therefore, for the purpose of this review,
HED considers that the method has been validated for only free residues
of RPA 408056. 

The lower limit of method validation (LLMV) is 0.020 ppm for each
analyte in all matrices.  The limits of detection (LODs) for fenamidone
in field corn forage, grain and stover are 0.0048 ppm, 0.0049 ppm, and
0.0024 ppm, respectively.  The LODs for RPA 717879 in field corn forage,
grain, and stover are 0.0063 ppm, 0.0046 ppm, and 0.0063 ppm,
respectively. The LODs for fenamidone in sweet corn forage, K+CWHR, and
stover are 0.0014 ppm, 0.0028 ppm, and 0.0021 ppm, respectively.  The
LODs for RPA 717879 in sweet corn forage, K+CWHR, and stover are 0.0040
ppm, 0.0046 ppm, and 0.0058 ppm, respectively. The LODs for fenamidone
in soybean forage, hay and seed are 0.0064 ppm, 0.0026 ppm, and 0.0047
ppm, respectively.  The LODs for RPA 717879 in soybean forage, hay and
seed are 0.0047 ppm, 0.0052 ppm, and 0.0050 ppm, respectively.  All LODs
are those reported by the registrant.  The results of the method
validation are shown below in Tables 4-6.  

TABLE 4.	Recovery Results from Method Validation in Field Corn using
Method RP0002P0801. 

Matrix	Spiking Level

(ppm)	Recoveries Obtained

SD (CV)

(%)

Field Corn Forage

Fenamidone	0.02	79, 81, 83, 90, 79, 99, 93, 81, 72	84 ± 8

	0.20	129, 125, 106	120 ± 12

DADK-Fen (RPA 717879)	0.02	95, 71, 105, 86, 95, 105, 77, 95, 71	89 ± 13

	0.20	71, 78, 77	75 ± 4

	0.40	104, 100, 93	99 ± 5

DA-Fen (RPA 408056)	0.02	72, 90, 72, 71, 89, 84, 85, 71, 81	79 ± 8

	0.20	82, 79, 78	80 ± 2.1

Field Corn Grain

Fenamidone	0.02	91, 79, 79, 71, 86, 67, 84, 92	81 ± 9

	0.20	68, 74, 79	74 ± 5

DADK-Fen (RPA 717879)	0.02	70, 82, 74, 103, 86, 97, 75, 81, 78	83 ± 11

	0.20	73, 78, 77	76 ± 3

DA-Fen (RPA 408056)	0.02	70, 95, 79, 85, 84, 86, 74, 83, 86	82 ± 7

	0.20	79, 78, 72	76 ± 4

Field Corn Stover

Fenamidone	0.02	107, 93, 100, 96, 93, 97, 98, 98, 79	96  ± 8

	0.20	97, 106, 99	101 ± 5

DADK-Fen (RPA 717879)	0.02	102, 84, 95, 100, 86, 100, 89, 87, 100	94 ±
7

	0.20	79, 88, 83	83 ± 5

DA-Fen (RPA 408056)	0.02	79, 76, 74, 104, 80, 99, 108, 70, 70	84 ± 15

	0.20	81, 89, 84	85 ± 4

TABLE 5.	Recovery Results from Method Validation in Sweet Corn using
Method RP0002P0801. 

Matrix	Spiking Level

(ppm)	Recoveries Obtained

(%)	Mean Recovery ± SD (CV)

(%)

Sweet Corn Forage

Fenamidone 	0.02	97, 100, 101, 103, 102, 102, 102, 82, 95	98 ± 7

	0.20	73, 87, 90	83 ± 10

DADK-Fen (RPA 717879)	0.02	106, 98, 111, 108, 104, 90, 103, 117, 86	103
± 10

	0.20	77, 77, 74	76 ± 2

DA-Fen (RPA 408056)	0.02	109, 99, 92, 106, 94, 101, 95, 113, 107	102 ±
7

	0.20	81, 79, 79	80 ± 1

Sweet Corn K+CWHR

Fenamidone	0.02	90, 91, 98, 85, 98, 94, 92, 75, 87	90 ± 7

	0.20	94, 99, 104	99 ± 5

DADK-Fen (RPA 717879)	0.02	81, 83, 80, 78, 91, 92, 82, 78, 76	82 ± 6

	0.20	87, 87, 76	83 ± 6

DA-Fen (RPA 408056)	0.02	77, 79, 90, 87, 76, 88, 81, 86, 74	82 ± 6

	0.20	82, 84, 90	85 ± 4

Sweet Corn Stover

Fenamidone	0.02	85, 82, 82, 85, 84, 92, 87, 88, 87	86 ± 3

	0.20	81, 97, 77	85 ± 10

DADK-Fen (RPA 717879)	0.02	116, 107, 76, 88, 95, 106, 90, 101, 76	95 ±
14

	0.40	103, 92, 94	96 ± 6

DA-Fen (RPA 408056)	0.02	91, 102, 92, 90, 99, 105, 103, 103, 82	96 ± 8

	0.40	98, 95, 109	101 ± 7



TABLE 6.	Recovery Results from Method Validation in Soybeans using
Method RP0002P0801. 

Matrix	Spiking Level

(ppm)	Recoveries Obtained

(%)	Mean Recovery ± SD (CV)

(%)

Soybean Forage

Fenamidone	0.02	85, 94, 80, 88, 82, 80, 81, 92, 92, 102, 96, 87, 95, 94,
92, 89	89 ± 6

	0.20	85, 89, 91, 99, 99, 97	93 ± 6

DADK-Fen (RPA 717879)	0.02	77, 86, 98, 89, 100, 99, 98, 102, 115	96 ±
11

	0.20	107, 110, 90	102 ± 11

DA-Fen (RPA 408056)	0.02	72, 120, 104, 91, 91, 99, 86, 90, 104	95 ± 14

	0.20	88, 89, 103	93 ± 8

Soybean Hay

Fenamidone	0.02	88, 92, 94, 89, 92, 88, 90, 103, 87	92 ± 5

	0.20	87, 90, 95	91 ± 4

DADK-Fen (RPA 717879)	0.02	84, 79, 80, 68, 72, 87, 86, 100, 74	81 ± 10

	0.20	72, 72, 75	73 ± 2

DA-Fen (RPA 408056)	0.02	97, 89, 71, 96, 100, 82, 83, 87, 80	87 ± 9

	0.20	72, 74, 70	72 ± 2

Soybean Seed

Fenamidone	0.02	104, 111, 103, 118, 106, 106, 91, 95	104 ± 8

	0.20	100, 100, 104	102 ± 2

DADK-Fen (RPA 717879)	0.02	108, 111, 107, 96, 90, 90, 98, 95, 85	98 ± 9

	0.20	93, 90, 84	86 ± 4

DA-Fen (RPA 408056)	0.02	94, 80, 91, 97, 100, 89, 101, 84, 77	90 ± 9

	0.20	86, 87, 82, 83, 90, 84	85 ± 3

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, this protocol
can also serve as an enforcement methodology.

860.1360 Multiresidue 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 during
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

45385914.der.doc, Bloem, 7/18/2002

No new storage stability study was submitted for this tolerance
petition.  In previously submitted and reviewed data (MRID 45385914),
residues of fenamidone and metabolites have been shown to be stable in
various matrices.  The submitted storage stability data have been
validated and indicate that residues of fenamidone, RPA 717879, RPA
408056, and RPA 405862 are each relatively stable under frozen storage
conditions for  ~7 months in/on cottonseed and cotton gin byproducts, ~6
months in cottonseed hulls and meal, ~1 month in cottonseed oil, ~14
months in/on cucumber, ~13 months in/on leaf lettuce, ~12 months in/on
bulb onions, ~13 months in/on potato tubers and in potato chips, ~12
months in potato flakes and potato wet peel, ~12 months in/on tomatoes,
~13 months in tomato paste and tomato puree, and ~13 months in/on wheat
forage, grain, hay, and straw (45385914.der.doc).  These data support
the storage intervals for the specific rotational crops that are subject
of this petition.

If future uses for direct application to field corn, sweet corn or
soybean are requested, HED may require additional storage stability data
specific to these crops.

860.1480 Meat/Milk/Poultry/Eggs

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

Corn and soybeans can be used as feed items.  Beef cattle feed items
include soybean seed, field corn forage, and field corn stover; dairy
cattle feed items include soybean seed, forage and hay; sweet corn
forage and stover; and field corn grain, forage, and stover; poultry and
swine feed items include soybean seed and field corn grain.  As
previously noted, the residues of concern in livestock for purpose of
tolerance enforcement are fenamidone and RPA 717879 (RPA 717879) and RPA
408056 (free and conjugate).  

HED has previously calculated a dietary burden for livestock which
includes residues of fenamidone and its regulated metabolites in wheat,
sunflower, and cottonseed animal feed items.  (D314318, T.Bloem, 2007).

HED has determined that the animal feed items associated with this
action are not likely to result in residues in feed items which are
higher than residues in feed items currently used to calculated dietary
burden.  Therefore, these new rotational crop uses are not likely to
increase the dietary burden for ruminants, poultry or swine.  No new
animal commodity tolerances are required in conjunction with these new
rotational crop uses.

860.1500 Crop Field Trials

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

Since this petition does not involve the direct application to any raw
agricultural commodities, no field trial data were submitted and none
are required for this action.

860.1520 Processed Food and Feed

Field corn and soybean processing data were not submitted with this
petition.  Instead, the registrant submitted a data waiver request based
on a rotational crop study where either soybeans or field corn were
planted at a 30-day PBI following application to the soil at a 5X rate. 
  Given that this request is for a rotational crop use, that residues in
field corn grain and soybean seed were <LLMV (<0.04 ppm) in all the
rotational crops trials with a 30-PBI following treatment to the soil at
a 1X application rate, and that no detectable residues were seen in
field corn grain and soybean seed from a 30-day PBI with a 5X soil
application rate, HED concurs that no additional processing data are
required.  

For the purpose of this request for use on rotational field corn and
soybean, detectable residues are not expected in processed commodities
and tolerances for processed field corn and soybean seed commodities are
not required.    

860.1650 Submittal of Analytical Reference Standards

The analytical reference standards for fenamidone and RPA 717879 have
been submitted to the Agency’s Pesticide Repository (Email
correspondence with Theresa M. Cole,

US EPA National Pesticide Standard Repository, 2/17/2009). 

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

47514101.de1.doc (soybeans), 47514102.der.doc (sweet corn),
47514103.der.doc (field corn), 2/24/09, A. LaMay

Rotational crop data have been submitted for field corn, sweet corn and
soybeans.  Corn and soybean (rotational crops only) samples were
analyzed for residues of fenamidone and combined residues of RPA 717879
and RPA 408056 using the LC/MS/MS (high performance liquid
chromatography/triple stage quadrupole tandum mass spectrometry) Bayer
CropScience Method RP002P0801.  The lower limit of method validation
(LLMV) for both fenamidone and RPA 717879 was 0.02 ppm in all matrices. 
HED notes that residues of RPA 408056 (free) are converted to RPA 717879
by the hydrolysis step, so the method detects the combined residues of
both RPA 717879 and RPA 408056 expressed as RPA 717879. 

Nine field corn rotational crop trials were conducted in the states of
NY, GA, OH, IA, ON, MO, MN, NE and TX.  Combined residues of fenamidone
and its metabolites, RPA 717879 and RPA 408056 (free) ranged from <0.04
– 0.28 ppm in field corn forage and from <0.04 ppm – 0.17 ppm in
stover.  Combined residues in field corn grain were <0.04 ppm, the
combined LLMVs for the parent and RPA 717879 (which includes free RPA
408056 which has been converted by hydrolysis to RPA 717879) for all
samples.

12 sweet corn rotational crop trials were conducted in the states of PA,
NY, GA, FL, OH (2), IA, KS, MN, CA, ID and OR.  Combined residues of
fenamidone and its metabolites, RPA 717879 and RPA 408056 ranged from
<0.04 – 0.12 ppm in sweet corn forage and from <0.04 ppm – 0.35 ppm
in stover.  Combined residues in sweet corn K+CWHR were <0.04 ppm, the
combined LLMVs for the parent and RPA 717879 (which includes RPA 408056
which has been converted by hydrolysis to RPA 717879) for all samples.  

11 soybean rotational crop trials were conducted in the states of GA,
VA, AR (2), LA, IL, OH, IA, NE, IN, and ON.  Combined residues of
fenamidone and its metabolites, RPA 717879 and RPA 408056 ranged from
<0.04 – 0.1 ppm in soybean forage and from <0.04 ppm – 0.17 ppm in
hay.  Combined residues in soybean seed were <0.04 ppm, the combined
LLMVs for the parent and RPA 717879 (which includes RPA 408056 which has
been converted by hydrolysis to RPA 717879) for all samples.

Table 7 below summarizes the residues from the rotational crop trials of
fenamidone and its metabolites from analytical method RP002P0801.

Table 7.  Summary of Residues from the Rotational Crop Trials with
Fenamidone and Metabolites.       

Crop Matrix	Applic. Rate

(lb ai/A)	PBI (days)	Combined Residues (ppm)    

 	 	 	Mean	Std. Dev.	HAFT 	Min.	Max.

Soybean (proposed use = 0.27 lb ai/A total application rate, 30-day PBI)
      

Forage	0.796 – 0.813	 30	0.054	0.020	0.10 	<0.04 	0.10

Hay	0.796 – 0.813	 30	 0.072	 0.037	0.17 	 <0.04	 0.17

Seed	0.796 – 0.813	 30	 <0.04	 0.001	<0.04 	 <0.04	 <0.04

Field Corn (proposed use = 0.27 lb ai/A total application rate, 30-day
PBI)       

Forage	0.798 - 0.820 	 30	 0.066	0.055 	0.28 	<0.04 	0.28 

Grain	 0.798 – 0.820	 30	 <0.04	 0.001	<0.04	 <0.04	 <0.04

Stover	 0.798 – 0.820	30	0.062	0.038	0.17	<0.04	0.17

Sweet Corn (proposed use = 0.27 lb ai/A total application rate, 30-day
PBI)       

Forage 	0.797 – 0.826 	 30	 0.055	0.025 	0.12 	<0.04 	0.12 

K+CWHR	 0.797 – 0.826	 30	 <0.04	 0.001	<0.04	 <0.04	 <0.04

Stover	0.797 – 0.826	30	0.092	0.077	0.35	<0.04	0.35

An adequate number of rotational crop field trials for field corn, sweet
corn and soybean have been submitted.  The rotational crop trials have
adequate geological representation and support the requested PBI of 30
days.

Residues of conjugated RPA 405862 were not reported for field corn,
sweet corn, or soybean rotation crops, but are a residue of concern in
rotational crops for risk assessment purposes.  In the absence of data
on conjugated RPA 405862, HED will translate information on the relative
ratios of residues of conjugated RPA 405862 to RPA 717879 from related
crops to derive a conservative risk assessment.  

Residues of RPA 405862 were 8.5x residues of RPA 717879 from a
previously submitted wheat confined rotational crop study.  This ratio
of residues will be applied to field and sweet corn commodities to
estimate a total residue of concern for risk assessment purposes.  The
ration of 8.5x to yield an estimate of conjugated RPA 405862 residue is
multiplied by the combined residues of RPA 717879 and RPA 405862 (free).
 To determine the total fenamidone residue of concern for risk
assessment, that value is then added the residues of fenamidone and the
combined residues of RPA 717879 and RPA 405862 (free) determined in the
rotational crop field trials.  

Since there was not a single surrogate commodity for which to determine
residues of conjugated RPA 405862 in soybean commodities, HED selected
the confined rotational crop study that yielded the highest conversion
factor.  The conversion factor of 9.6x from the turn confined rotational
crop study will be used to estimate residues of conjugated RPA 405862
for risk assessment purposes.  The 9.6x ratio to yield conjugated RPA
405862 is multiplied by the combined residues of RPA 717879 and RPA
405862 (free) and then added the residues of fenamidone and the combined
residues of RPA 717879 and RPA 405862 (free) from the soybean rotational
crop data.

Residues to be used in dietary risk assessment are shown in Table 8,
below.  

Table 8.  Summary of Residue Values for Dietary Risk Assessment

Crop/Commodity	Residue Value (ppm)	Comment

Field Corn and processed commodities	0.218	Maximum rotational crop field
corn residue data reported <0.02 ppm for fenamidone and <0.02 ppm for
combined residues of RPA 717879 and RPA 405862 (free).  Residues of
conjugated RPA 405862 were not reported, but are a residue of concern in
rotational crops.  Residues of RPA 405862 were 8.5x residues of RPA
717879 from the wheat confined rotational crop study.  Total residue of
concern for field corn and processed commodities is calculated as 0.02
ppm (fenamidone) + 0.02 ppm (RPA 717879 and free RPA 405862) + 0.02 x
8.9 (ratio to yield conjugated RPA 405862) = 0.218 

Sweet Corn (K + CWHR)	0.218	Maximum rotational crop sweet corn (K+CWHR)
residue data reported <0.02 ppm for fenamidone and <0.02 ppm for
combined residues of RPA 717879 and RPA 405862 (free).  Residues of
conjugated RPA 405862 were not reported, but are a residue of concern in
rotational crops.  Residues of RPA 405862 were 8.5x residues of RPA
717879 from the wheat confined rotational crop study .  Total residue of
concern for sweet corn (K+CWHR) is calculated as 0.02 ppm (fenamidone) +
0.02 ppm (RPA 717879 and free RPA 405862) + 0.02 x 8.9 (ratio to yield
conjugated RPA 405862) = 0.218 

Soybean seed and processed commodities	0.232	Maximum rotational crop
soybean seed residue data reported <0.02 ppm for fenamidone and <0.02
ppm for combined residues of RPA 717879 and RPA 405862 (free).  Residues
of conjugated RPA 405862 were not reported, but are a residue of concern
in rotational crops.  Residues of RPA 405862 were 9.6x residues of RPA
717879 from the highest confined rotational crop study (turnips).  Total
residue of concern for soybean seed and processed commodities  is
calculated as 0.02 ppm (fenamidone) + 0.02 ppm (RPA 717879 and free RPA
405862) + 0.02 x 9.6 (ratio to yield conjugated RPA 405862) = 0.232 

860.1550 Proposed Tolerances

Table 7 below is a summary of the proposed and HED-recommended
tolerances and commodity definitions for residues of fenamidone for
rotational crops of corn and soybean only.  Tolerance level
recommendations for field corn grain, sweet corn (K + CWHR) and soybean
seed are based on the combined LOQs for the parent compound and residues
converted to RPA 717879.  Tolerance recommendations for the remaining
tolerances were derived using the MRL calculator [insert reference here]
with combined fenamidone and RPA 717879 residues.  For data points which
were reported as >LOQ (>0.04 ppm), the MLE calculator was used to obtain
a distribution of values to be used for those samples.  

There are no Codex, Canadian or Mexican MRLs (maximum residue levels)
for residues of fenamidone in field corn, sweet corn or soybeans.  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 9.  Tolerance Summary for Fenamidone   

Commodity	Established/Proposed Tolerance (ppm)	Recommended Tolerance
(ppm)	Comments (correct commodity definition)

Corn, field, grain*	0.02	0.04	 

Corn, sweet, kernel plus cob with husks removed*	0.02	0.04	 

Corn, sweet, forage	0.15	0.20

	Corn, field, forage	0.50	0.30

	Corn stover	0.35	0.30	Corn, field, stover

0.45	Corn, sweet, stover

Soybean, seed*	0.02	0.04

	Soybean, forage	0.20	0.15

	Soybean, hay	0.20	0.25

	*The residues for field corn grain, sweet corn grain, and soybean seed
were all <LOQ of 0.02 ppm for both the parent and combined metabolites
of the method.  Therefore, the tolerance was set adding LOQ for each
RAC, totaling 0.04 ppm.

Attachment 1: Chemical Structures

Name	Structure

Fenamidone; RPA 407213

 

 

14C-C-phenyl-fenamidone

DA-Fen; RPA 408056 (racemic mixture)

RPA 405862 (racemic mixture)

RPA 410193 (S enantiomer)

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

DADK-Fen; 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

RPA 411639

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

RPA 410995

RPA 409446

 

RPA 407213-dimer

Attachment 2:  Tolerance Spreadsheet Calculator Results

 

 

 

 

 

 

 

Fenamidone Residue Chemistry Chapter 		D357372

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