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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 Inadvertent 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 

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, RM22 

 Registration Division (7505P) 
Fenamidone Residue Chemistry Chapter D391039 

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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 rice) 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 crops. 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 registrant proposes to use data submitted to 

support wheat and corn rotational crop tolerances 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 there is sufficient data to support the requested label revision 

and revised tolerances. The submitted rotational crop data support a PBI of 30-days as 

specified on the proposed label and establishment of revised tolerances as specified 

below. 

The registrant has also requested that the existing soybean rotational crop data be 

translated to establish rotational crop tolerances 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 would like to establish rotational crop tolerances in alfalfa. 

The registrant has proposed to reduce the number of alfalfa rotational trials from 12 to 10, 

based on an overlap analysis between growing regions of primary and rotational crops. 

HED has no objection to a reduction in the number 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 fenamidone 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 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) for indirect or inadvertent residues of 

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) in or on the following rotational crop commodities: 

Grain, cereal, group 15, except rice.........................................................0.1 ppm 

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

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

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

Grain, cereal, forage, fodder and straw, group 16, straw ...............................0.5 ppm 
Fenamidone Residue Chemistry Chapter D391039 

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NOTE TO RD: The previously established 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. 

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-imidazol-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 

N

N

CH3

O S CH3

N H
Fenamidone Residue Chemistry Chapter D391039 

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Registrant Request for Cereal 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 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) at a 30 day plant back interval (PBI). 

Bayer CropScience proposed the following tolerances for indirect or inadvertent residues 

of 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) in or on the following 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 wheat 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 Council (ChemSAC) discussed this issue (see 

Minutes of the 04/28/2010 ChemSAC meeting). The wheat, sweet corn and field corn 

residue results from the rotational crop trials were similar; there were no detectable 

residues in grain of field corn, sweet corn and wheat; and there 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 and wheat. Since a tolerance 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 group (CG 15 and 16, except rice) and support the 

proposed tolerance levels (see 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 

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Commodity Total Applic. Rate (lb ai/acre) PBI (days) Analyte Residue Levels1

 (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, and 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 Levels1 (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 with this petition are those associated with 

barley grain, oats, and rye grain processing. Given that (1) this request is for a rotational crop 

use and there were no detectable residues in grain 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 which 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 

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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; millet grain, forage, hay and straw; oat grain, 

forage, hay and straw; rye grain, forage, and straw, sorghum grain, forage, and stover. 

There are currently tolerances for inadvertent residues on wheat, sweet corn and field 

corn. 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. 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 rotational 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 existing soybean rotational crops data be used to 

establish rotational crop tolerances 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. Furthermore, 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 subgroup. HED would likely require dried bean 

and/or dried pea rotational crop data to support 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 livestock 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 (such 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, except region 10, which should have 2 trials, 

resulting in a total of 6 trials (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 

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Additionally, the registrant would like to establish rotational crop tolerances in alfalfa. 

The registrant has proposed to reduce the number of alfalfa rotational trials from 12 to 10 

(reducing the number of required trials 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 involve a 30-day PBI and a maximum seasonal 

application rate of 0.8 lb ai/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 ChemSAC meeting). HED will allow this number 

of alfalfa rotational trials. 

The registrant’s proposal is to reduce the number of required rotational crop trials based 

on the production of target crops 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 registrant’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; there 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 rotational crops of cereal crops (CG 15 and 16, 

except rice). The existing wheat and corn rotational crop data were used to support the 

establishment of tolerances in/on barley, buckwheat, millet, oats, popcorn, rye, sorghum, 

teosinte, and triticale based on similar residue levels and use patterns. 

There are no Codex, Canadian or Mexican MRLs (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 harmonization as a result of the proposed new uses 

that are the subject of this petition. The registrant must revise 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 

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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 

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 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 Mexico2 Codex3

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 

(5S)-3,5-dihydro-5-methyl-2-

(methylthio)-5-phenyl-3- 

(phenylamino)-4H-imidazol-4-

one 

 None 

Commodity1 

Tolerance (ppm) /Maximum Residue Limit 

(mg/kg) 

US Canada Mexico2 Codex3

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 commodity, such as processing of treated 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. 

 
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Attachment 2: Chemical Structures

Name Structure 

Fenamidone; RPA 407213 

(5S)-3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3-

(phenylamino)-4H-imidazol-4-one 

CH3

N

O N S

CH3

HN

*

14C-N-phenyl-fenamidone 

CH3

N

O N S

CH3

HN

*

14C-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 

(5S)-5-methyl-2-(methylthio)-3-[(2-nitrophenyl)amino]-5-

phenyl-3,5-dihydro-4H-imidazol-4-one 

RPA 410914 (racemic mixture) 

N

N

CH3

O S

CH3

N

H

N

N

CH3

O S

CH3

H

N

H

N

CH3

O O

N

H

N

H

N

CH3

O O

H
Fenamidone Residue Chemistry Chapter D391039 

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Name Structure 

RPA 411639 

(5S)-5-methyl-2-(methylthio)-3-[(4-nitrophenyl)amino]-5-

phenyl-3,5-dihydro-4H-imidazol-4-one 

RPA 406012 (racemic mixture) 

RPA 410995 

(5S)-5-methyl-3-[(2-nitrophenyl)amino]-5-

phenylimidazolidine-2,4-dione 

RPA 409446 

(5S)-5-methyl-3-[(4-nitrophenyl)amino]-5-

phenylimidazolidine-2,4-dione 

RPA 407213-dimer 

(5S,5'S)-3,3'-(1,2-diphenylhydrazine-1,2-diyl)bis[5-

methyl-2-(methylthio)-5-phenyl-3,5-dihydro-4Himidazol-4-one] 

aniline