### Page 1 of 11 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### MEMORANDUM

Date: July 7, 2011

Subject: Fenamidone : Residue Chemistry Summary Document to Support Label Amendment to Permit Rotation to All Cereal Grains, Except Rice and Establishment of
Revised Tolerances for In advertent Residues.

PC Code: 046679 DP Barcode: D391039
MRID No.: N/A Registration No.: 264-693 and 264-695
Petition No.: 0F7764 Regulatory Action: Section 3 Registration Assessment Type: N/A Reregistration Case No.: N/A
T XR 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, RM22 Registration Division (7505P)

### Fenamidone Residue Chemistry Chapter D391039

Page 2 of 11 Bayer Crop Science is proposing to revise the fenamidone label for the formulated product, Reason® 500 SC to allow rotation to all crops, except rice, in the cereal crop group (CG 15, except rice and CG 16, except ri ce) with a 30-day plant back interval (PBI) after a maximum seasonal application of 0.8 lb ai/A to a primary crop. There are
no direct uses of fenamidone on these cr ops. There are currently tolerances for inadvertent residues on wheat, sweet corn and field corn to support allowing rotation to these commodities with a 30-day PBI. The re gistrant proposes to use data submitted to support wheat and corn rotational crop toleran ces to establish rotational crop tolerances for the remaining commodities except rice in the cereal grains crop group (CG 15, except rice) and the forage, fodder and straw of the cereal grains crop group (CG 16, except rice). HED concludes that th ere is sufficient data to suppor t the requested label revision
and revised tolerances. The submitted rotati onal crop data support a PBI of 30-days as specified on the proposed label and establishm ent of revised tolerances as specified
below.

The registrant has also requested that the existing soybean rotational crop data be translated to establish rotational crop tolera nces for dried shelled pea and bean (crop group 6C) and foliage of legume vegetables (crop group 7) at a 30 day PBI to fields
treated with fenamidone. At this time , HED cannot recommend for these requested rotational crop tolerances.

Additionally, the registrant woul d like to establish rotational crop tolerances in alfalfa. The registrant has proposed to reduce the numbe r of alfalfa rotational trials from 12 to 10, based on an overlap analysis between growi ng regions of primary and rotational crops. HED has no objection to a reduction in the numbe r of alfalfa trials based on the analysis provided by the registrant.

Regulatory Recommendations and Residue Chemistry Deficiencies

There are no residue chemistry deficiencies that would preclude the establishment of
tolerances for inadvertent residues of fena midone in/on the cereal crop group (CG 15 and 16, except rice). Provided the registrant submits a revised Section F reflecting the revised commodity definitions shown below and furt her provided the forthcoming human health risk assessment does not identify any issues of concern, the ava ilable data support the following tolerances under 40 CFR 180.579(d) fo r indirect or inadvertent residues of fenamidone (4-H-imidazol-4-one, 3,5-di hydro-5-methyl-2-(methylthio)-5-phenyl-3- (phenylamino, (S)-) and its metabolite RPA 717879 (2,4-imidazolidinedione, 5-methyl-5- phenyl) in or on the followi ng rotational crop commodities:

Grain, cereal, group 15, except rice.........................................................0.1 ppm Grain, cereal, forage, fodder a nd straw, group 16, forage...............................0.3 ppm Grain, cereal, forage, fodder and straw, group 16, hay..................................0.5 ppm Grain, cereal, forage, fodder a nd straw, group 16, stover ...............................0.5 ppm Grain, cereal, forage, fodder a nd straw, group 16, straw ...............................0.5 ppm

### Fenamidone Residue Chemistry Chapter D391039

Page 3 of 11 NOTE TO RD: The previously established rotationa l crop tolerances for the individual crops in the crop groups (sweet corn, field corn, and wheat) should be removed from the tolerance summary for fenamidone and replaced with the crop group tolerances above.

Background

Fenamidone is a broad-spectrum foliar fungicide currently registered for application to a variety of field crops includi ng bulb vegetables, tuberous a nd corm vegetables, fruiting vegetables and leafy vegetables. Fenamidone is a chiral compound with the technical product consisting of 98.5% S-fenamidone. Tole rances 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-(methylth io)-5-phenyl-3-(phenylamino)-4H-imidazol-4-one

CAS # 161326-34-7 End-use product/EP Reason® 500 SC



### Table 2. Physicochemical Propertie s of the Technical Grade Fenamidone

. Parameter Valu e 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 (pK
a ) No measurable dissociation constants in the pH range of 1 to 13 MRID 45385714

Octanol/water partition coefficient Log(K OW ) 631 (2.8) MRID 45385713 UV/visible absorption spectrum (nm) Primary: 203 Secondary: 230 MRID 45385709 N

N CH 3

O S CH 3

N H

### Fenamidone Residue Chemistry Chapter D391039

Page 4 of 11 Registrant Request for Cere al Grains (CG 15 and 16): The registrant, Bayer CropScience has petitioned the Agency to use data previously submitted to support wheat and corn rotational crop tolerances to es tablish rotational crop tolerances for the remaining commodities, except rice, in the cer eal grains crop group (CG 15, except rice) and the forage, fodder and straw of the cereal grains crop group (CG 16, except rice) at a 30 day plant back interval (PBI).

Bayer CropScience proposed the following tolera nces for indirect or inadvertent residues of fenamidone (4-H-imidazol-4-one, 3,5-di hydro-5-methyl-2-(methylthio)-5-phenyl-3- (phenylamino, (S)-) and its metabolite RPA 717879 (2,4-imidazolidinedione, 5-methyl-5- phenyl) in or on the followi ng rotational crop commodities:

Grain, cereal, group 15 (except rice) ...............................................0.1 ppm Grain, forage, group 16 ..............................................................0.3 ppm Grain, hay, stover or straw, group 16 ..............................................0.5 ppm

HED Comments: The rotational crop field trial data for wh eat and corn support the establishment of
tolerances for residues of fenamidone and its regulated metabolites in the cereal crop group (CG 15 and 16, excluding rice) commodities with a 30-day PBI at the levels shown below. The Chemistry Science Advisory C ouncil (ChemSAC) discussed this issue (see Minutes of the 04/28/2010 ChemSAC meeting). The wheat, sweet corn and field corn
residue results from the rotati onal crop trials were similar; there were no detectable residues in grain of field cor n, sweet corn and wheat; and th ere were low residues in the forage commodities (see Tables 3 - 5 below) . The representative commodities for CG 15 are sweet corn, field corn, rice, sorghum a nd wheat. Since a tole rance on rice is not requested, HED concurs that the rotational crop data for wheat and corn can be translated to all small grains in the cereal crop gr oup (CG 15 and 16, except rice) and support the proposed tolerance levels (s ee D357372, 2/24/09, A. LaMay for corn data; see D297216, 5/25/04, T. Bloem and D315563, 5/24/05, T. Bloem for wheat data).

Table 3. 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.

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 *Table taken directly from D357372, 2/24/09, A. LaMay

Table 4. Summary of Limited Field Rotational Crop Study.

### Fenamidone Residue Chemistry Chapter D391039

Page 5 of 11 Commodity Total Applic. Rate (lb ai/acre) PBI (days) Analyte Residue Levels 1 (ppm)

201/234 RPA 717879 <0.020

Wheat, forage 1.072-1.085 28/31 RPA 717879 <0.020-0.028

201/234 RPA 717879 <0.020-0.093

Wheat, hay 1.072-1.085 28/31 RPA 717879 <0.020-0.054

201/234 RPA 717879 <0.020-0.446

Wheat, straw 1.072-1.085 28/31 RPA 717879 <0.020-0.100

201/234 RPA 717879 <0.020-0.273

Wheat, grain 1.072-1.085 28/31 RPA 717879 <0.020-0.061

201/234 RPA 717879 <0.020

1 residues of fenamidone, RPA 408056, an d RPA 405862 were <LOQ in/on all samples * Table taken directly from D297216, 5/25/04, T. Bloem

Table 5. Summary of Extended Field Rotational Crop Study.

Commodity Total Applic. Rate (lb ai/acre) PBI (days) Analyte Residue Levels 1 (ppm)

wheat forage 1.05-1.10 28-30 RPA 717879 <0.020-0.045

RPA 408056 <0.020-0.071

87-223 RPA 717879 <0.020-0.071

RPA 408056 <0.020

wheat hay 1.05-1.10 28-30 RPA 717879 <0.020-0.321

RPA 408056 <0.020-0.020

87-223 RPA 717879 <0.020-0.161

RPA 408056 <0.020

wheat straw 1.05-1.10 28-30 RPA 717879 <0.020-0.200

RPA 408056 <0.020

87-223 RPA 717879 <0.020-0.033

RPA 408056 <0.020

wheat grain 1.05-1.10 28-30 RPA 717879 <0.020

RPA 408056 <0.020

87-223 RPA 717879 <0.020

RPA 408056 <0.020

1 residues of fenamidone and RPA 405862 were <LOQ in/on all samples * Table taken directly from D297216, 5/25/04, T. Bloem



### The only new processed commodities associated w ith this petition are th ose associated with barley grain, oats, and rye grai n processing. Given that (1) this request is for a rotational crop use and there were no detectable residues in gr ain of field corn, sweet corn, and wheat; (2) no
detectable residues were seen in field corn grain from a 30-day PBI with a 5X soil application rate; and (3) no detectable residues were seen in wheat processed commodities from a 30-day PBI with a 5X soil application rate, except for wheat germ wh ich had no detectable residues
of fenamidone but had residues near the LOQ for metabolite RPA 717879, however total residues were below the tolerance for the RAC; HED concludes that no additional processing data are required. Detectable residues of fenamidone are not expected in these processed

### Fenamidone Residue Chemistry Chapter D391039

Page 6 of 11 commodities and tolerances for processed commodities of crop group 15 and 16 are not required.

Approval of this action would permit rotation to the following feed items: barley grain, hay, and straw; popcorn grain and stover; mille t grain, forage, hay and straw; oat grain, forage, hay and straw; rye gr ain, forage, and straw, sorghum grain, forage, and stover. There are currently tolerances for inadvert ent residues on wheat, sweet corn and field corn. HED has previously calculated a di etary burden for lives tock which includes residues of fenamidone and its regulated metabol ites 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 likel y to result in residues in feed items which are higher than residues in feed items curren tly used to calculated dietary burden. The new feed items are not likely to be additional items to the burden, but would replace items already considered and since the residues would not be higher, the dietary burden is not increased by the addition of these rotati onal crops. Therefore, no new or revised animal commodity tolerances are required to support the requested label amendment to allow rotation to all cereal grains except rice with a 30-day PBI.

Registrant Request for Crop Group 6C and 7: The registrant has also requested that the exis ting soybean rotational crops data be used to establish rotational crop tolera nces for dried shelled pea and bean (crop group 6C) and foliage of legume vegetables (crop group 7) at a 30 day PBI after a maximum seasonal application of 0.8 lb ai /A to a primary crop.

HED comments: The HED ChemSAC reviewed the registrant’s proposal. The soybean rotational crop study included data from regions 2, 4 and 5. ChemSAC noted concern about the lack of rotational crop data from regions 7, 8, 9, 10 and 11 for the dried beans. There is a potential for rotating in region 10, but there is no data available for this region from the existing soybean rotational crop data. Furt hermore, soybeans are not included as a representative commodity for crop subgroup 6C ; therefore soybean data alone are not adequate as a representative crop for this s ubgroup. HED would likel y require dried bean and/or dried pea rotational crop data to s upport tolerance for this crop group. ChemSAC considered the impact of adding CG 7 foliage commodities, since they are livestock feed
items. It was concluded that the livestoc k dietary burden would not be substantially affected by the addition of the CG 7 commodities, as the livestock diet will most likely be comprised of the wheat and corn livestock commodities which have existing tolerances. ChemSAC recommended that the registrant conduct dried bean (s uch a cowpea) field rotational crop trials including forage and hay data in regions 7, 8, 9, 10 and 11. One trial each should be conducted for all regions, ex cept region 10, which should have 2 trials, resulting in a total of 6 tr ials (Minutes of the 04/28/2010 ChemSAC meeting). At this time, HED cannot recommend for rotational crop tolerances on CG 6C or CG 7
commodities.

Registrant Request for Alfalfa:

### Fenamidone Residue Chemistry Chapter D391039

Page 7 of 11 Additionally, the registrant woul d like to establish rotational crop tolerances in alfalfa. The registrant has proposed to reduce the numbe r of alfalfa rotational trials from 12 to 10 (reducing the number of required tr ials in Region 5 from 6 rotational trials to 4 rotational trials) based on an overlap analysis between growing regions of primary and rotational crops. The newly proposed trials would i nvolve a 30-day PBI and a maximum seasonal application rate of 0.8 lb a i/A with a minimum of three cuttings of forage and hay.

HED comments: ChemSAC discussed the registrant’s proposal and concurred that this proposal is reasonable (Minutes of the 04/28/2010 ChemSA C meeting). HED will allow this number
of alfalfa rotational trials.

The registrant’s proposal is to reduce the number of require d rotational crop trials based on the production of target cr ops for Region 5 rather than production of rotational crops for that region. In Region 5, the maximum number of target crop trials needed is 4 (for root vegetables), thus the re gistrant’s proposal is that no more than 4 rotational trials should be required in that region even though alfalfa production would call for 6 rotational trials in Region 5. ChemSAC has determined that this proposal is acceptable
because it has a minimal effect on the overall number of trials and does not affect the geographical distribution; ther e will still be rotational crop trials from all required regions.

Conclusion

Below is a summary of the proposed and HED-recommended tolerances and commodity
definitions for residues of fenamidone for ro tational crops of cereal crops (CG 15 and 16, except rice). The existing wh eat and corn rotational crop da ta were used to support the establishment of tolerances in/on barley, buckwheat, millet, oats, popcorn, rye, sorghum, teosinte, and triticale based on simila r residue levels and use patterns.

There are no Codex, Canadian or Mexican MR Ls (maximum residue levels) for residues of fenamidone in cereal crops (CG 15 and 16, except rice) (see Attachment 1). There are no issues with respect to international harmoni zation as a result of the proposed new uses that are the subject of this pe tition. The registrant must revi se the requested tolerances to reflect the revised commodity definitions shown below.

Table 6. Tolerance Summary for Fenamidone Commodity Established/Proposed Tolerance (ppm) Recommended Tolerance (ppm) Comments (correct commodity definition) Grain, cereal, group 15 (except rice) 0.1 0.1 Grain, cereal, group 15, except rice

Grain, forage, group 16 0.3 0.3 Grain, cereal, forage, fodder and straw, group 16, forage

Grain, hay, group 16 0.5 0.5 Grain, cereal, forage, fodder and straw, group 16, hay

Grain, stover, group 16 0.5 0.5 Grain, cereal, forage, fodder and straw, group 16, stover Grain, straw, group 16 0.5 0.5 Grain, cereal, forage, fodder and

### Fenamidone Residue Chemistry Chapter D391039

Page 8 of 11 straw, group 16, straw *The current rotational crop tolerances for the individual crops in the crop groups (sweet corn, field corn, and wheat) should be removed from the tolerance summary for fenamidone and replaced with the crop group tolerances above in Table 6.

### Fenamidone Residue Chemistry Chapter D391039

Page 9 of 11 Attachment 1: International Residue Limits



## Fenamidone (PC Code 046679; 05/03/2011)
Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 Codex 3

40 CFR 180.579: Plants: fenamidone (4H-Imidazol-4-one, 3,5- dihydro-5-methyl-2-(methylthio)-5-phenyl-3 (phenylamino)-, (S)-)

Livestock: fenamidone (4H-imidazol-4-one, 3,5-dihydro-5-methyl-2-(methylthio)-5- phenyl-3-(phenylamino), (S)-) and its metabolite RPA 717879 (2,4- imidazolidinedione, 5-methyl-5-phenyl), expressed as parent compound

Indirect or inadvertent residues:. fenamidone (4-H-imidazol-4-one, 3,5-dihydro-5-methyl-2- (methylthio)-5-phenyl-3-(phenylamino, (S)-) and its metabolite RPA 717879 (2,4- imidazolidinedione, 5-methyl-5-phenyl) Plants/Livestock (5 S )-3,5-dihydro-5-methyl-2- (methylthio)-5-phenyl-3- (phenylamino)-4 H -imidazol-4-

one None



### Commodity 1 

### Tolerance (ppm) /Maximum Residue Limit (mg/kg)
US Canada Mexico 2 

### Codex 3
Grain, cereal, group 15, except rice 0.1 Grain, cereal, forage, fodder and straw, group 16, forage 0.3

Grain, cereal, forage, fodder and straw, group 16, hay 0.5

Grain, cereal, forage, fodder and straw, group 16, stover 0.5

Grain, cereal, forage, fodder and straw, group 16, straw 0.5

Completed: M. Negussie; 05/03/2011

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

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

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

### Fenamidone Residue Chemistry Chapter D391039

Page 10 of 11 Attachment 2: Chemical Structures

Name Structure

Fenamidone ; RPA 407213

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

CH 3 N

N O S CH 3

N H

*

14 C-N-phenyl-fenamidone CH 3 N

N O S CH 3

N H *

14 C-C-phenyl-fenamidone

DA-Fen; RPA 408056 (racemic mixture)

5-methyl-2-methylthio-5-phenyl-3,5-dihydroimidazol-4-

one

RPA 405862 (racemic mixture) RPA 410193 (S enantiomer)

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

DADK-Fen; RPA 717879 (racemic mixture)

5-methyl-5-phenylimidazolidine-2,4-dione

RPA 413255

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

RPA 410914 (racemic mixture) N

N CH 3

O S CH 3

N H

N

N CH 3

O S CH 3

H

N H

N CH 3

O O

N H

N H

N CH 3

O O

H

### Fenamidone Residue Chemistry Chapter D391039

Page 11 of 11 Name Structure

RPA 411639

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

RPA 406012 (racemic mixture)

RPA 410995

(5 S )-5-methyl-3-[(2-nitrophenyl)amino]-5- phenylimidazolidine-2,4-dione

RPA 409446

(5 S )-5-methyl-3-[(4-nitrophenyl)amino]-5- phenylimidazolidine-2,4-dione

RPA 407213-dimer

(5 S ,5' S )-3,3'-(1,2-diphenylhydrazine-1,2-diyl)bis[5- methyl-2-(methylthio)-5-phenyl-3,5-dihydro-4 H

imidazol-4-one]

aniline