Document ID: EPA-HQ-OPP-2012-0980-0007
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-12-20T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                             WASHINGTON, DC  20460
                                       
                         OFFICE OF CHEMICAL SAFETY AND
                             POLLUTION PREVENTION

MEMORANDUM

DATE:  	27 August 2013

SUBJECT:	Mandipropamid.  Petition to Establish Permanent Tolerances (and Section 3 Registration) for Residues Resulting from Use of the Fungicide on Basil, Succulent Beans, Cowpea Forage, Ginseng and Greenhouse Tomatoes; to Update Fruiting Vegetables Group 8 to Group 8-10; to Extend the Tolerance in Grapes to Subgroup 13-07F, the Tolerance in Dry Bulb Onions to Subgroup 3-07A, and the Tolerance in Green Onions to Subgroup 3-07B.  Summary of Analytical Chemistry and Residue Data.  

PC Code:  036602
DP Barcode:  D409363
Decision Number:  472747
Registration Number:  100-1254
Petition:  2E8126
Regulatory Action:  Section 3
Risk Assessment Type:  NA
Case Number:  7058
TXR Number:  NA
CAS Number:  374726-62-2
MRID Numbers:  48992001-04
40 CFR:  §180.637

FROM:  	 William T. Drew, Chemist
		 Risk Assessment Branch II (RAB2)
		 Health Effects Division (HED), 7509P

THRU:	Dennis McNeilly, Chemist
		Michael A. Doherty, PhD, Senior Chemist
		RAB2/HED, 7509P

TO:		Barbara Madden and Laura Nollen, RM Team 5
		Risk Integration, Minor Use, and Emergency Response Branch (RIMUERB)
		Registration Division (RD), 7505P

Table of Contents

1.0     Executive Summary	4
2.0     Regulatory Recommendations	7
2.1     Data Deficiencies/Data Needs	8
2.2     Tolerance Considerations	8
2.2.1      Enforcement Analytical Method/Multiresidue Methods	8
2.2.2      Recommended Tolerances	9
2.2.3      Revisions to Petitioned-For Tolerances	9
2.2.4      International Harmonization	9
2.3      Label Recommendations	10
2.4      Submittal of Analytical Reference Standards (860.1650)	10
3.0      Chemical Identity	11
3.1      Nomenclature	11
3.2      Physicochemical Characteristics	12
3.3      Pesticide Use Pattern/Directions for Use (860.1200)	12
4.0      Metabolite/Degradate Residue Profile	13
4.1      Nature of the Residue	13
4.1.1 	Summary of Plant and/or Livestock Metabolism (860.1300)	14
4.1.2	Summary of Confined Rotational Crops (860.l850)	14
4.1.3	Summary of Rat Metabolism	15
4.1.4	Summary of Environmental Degradation	15
5.0	Residue Profile	16
5.1       Residue Analytical Methods (860.1340)	16
5.1.1	Data Collection Methods	16
5.1.2	Multi-Residue Methods (860.1360)	21
5.1.3	Tolerance Enforcement Methods	21
5.2      Storage Stability (860.1380)	21
5.3      Residue Data	24
5.3.1	Crop Field Trials (860.1500)	24
5.3.2	Field Rotational Crops (860.1900)	27
5.3.3	Processed Food and Feed (860.1520)	27
5.3.4	Meat, Milk, Poultry and Eggs (860.1480)	28
5.3.5.	Food Handling (860.1460)	28
5.3.6	Water, Fish and Irrigated Crops (860.1400)	28
5.4      Food Residue Profile	28
6.0	Tolerance Derivation	29
References	30
Attachment 1:  International Residue Limit Status	32
Attachment 2:  OECD MRL (Tolerance) Assessment Calculations	33

1.0	Executive Summary

Mandipropamid (with CAS name 4-chloro-N-[2-[3-methoxy-4-(2-propynyloxy)phenyl]ethyl]-α-(2-propynyloxy)benzeneacetamide, and CAS number 374726-62-2) is a fungicide in the mandelamide class developed by Syngenta Crop Protection for the control of foliar oomycete pathogens in a range of crops including Plasmopara viticola in grapes, Phytophthora infestans in potatoes and tomatoes, and Pseudoperonospora cubensis in cucurbits.  The previous residue chemistry summary document for mandipropamid was completed in conjunction with its registration for use on hops and tobacco (D348229, D352322; D. Rate; 11 December 2008).  

Permanent tolerances are established for residues of mandipropamid in or on a variety of plant commodities, at levels ranging from 0.03 ppm in wet potato peels, to 50 ppm in dried hops cones (40CFR §180.637[a]).  Time-limited tolerances (associated with Section 18 emergency exemptions) are established for residues of mandipropamid in fresh and dried basil (40CFR §180. 637[b]); these tolerances expire on 31 December 2015.  

The Interregional Research Project Number 4 (IR-4) has submitted a petition requesting new uses on basil, ginseng, succulent beans, and greenhouse tomatoes.  In conjunction with the requested new uses, IR-4 has proposed the establishment of permanent tolerances for residues of mandipropamid in/on the following raw agricultural commodities (RACs) and dried basil, at the tolerance levels listed:  

Basil, fresh............................................................30 ppm
Basil, dried.........................................................200 ppm
Bean, succulent...................................................0.90 ppm
Ginseng.............................................................0.3 ppm
Cowpea, forage.....................................................15 ppm
Vegetable, fruiting, group 8-10...................................1.0 ppm
Fruit, small, vine climbing, subgroup 13-07F, 
except fuzzy kiwifruit..............................................2.0 ppm
Onion, bulb, subgroup 3-07A.....................................0.1 ppm
Onion, green, subgroup 3-07B....................................7.0 ppm

The proposed tolerances in fresh and dried basil, succulent beans, ginseng, and cowpea forage are based on crop field trial data entered into the Organization for Economic Development and Cooperation's (OECD's) tolerance calculation procedure.  Upon establishment of the permanent tolerances in fresh and dried basil (40CFR §180.637[a]), the time-limited tolerances in fresh and dried basil (40CFR §180.637[b]) would be removed.  

The proposed tolerance in fruiting vegetables (group 8-10) is based on updating the current tolerance in fruiting vegetables (group 8).  The tolerance of 1.0 ppm would match the existing Codex (bell and non-bell peppers) and Canadian (tomatoes, okra, eggplant and peppers) maximum residue limits (MRLs).  Upon establishment of the tolerance in group 8-10, the existing tolerances in group 8 and okra would be removed.  

The proposed tolerance in small vine climbing fruits except fuzzy kiwifruit (subgroup 13-07F) is based upon existing data for grapes (the representative commodity for the subgroup), and increasing the current tolerance (1.4 ppm) to harmonize with the existing Codex MRL in grapes.  Upon establishment of the tolerance in subgroup 13-07F, the existing tolerance in grapes would be removed.  

The proposed tolerance in bulb onions (subgroup 3-07A) is based upon existing data for dry bulb onions (the representative commodity for the subgroup), and increasing the current tolerance (0.05 ppm) to harmonize with the existing Codex MRL in bulb onions.  Upon establishment of the tolerance in subgroup 3-07A, the existing tolerance in dry bulb onions would be removed.  

The proposed tolerance in green onions (subgroup 3-07B) is based upon existing data for green onions (the representative commodity for the subgroup), and increasing the current tolerance (4 ppm) to harmonize with the existing Codex MRL in spring onions.  Upon establishment of the tolerance in subgroup 3-07B, the existing tolerance in green onions would be removed.  

This summary document addresses the data submitted in support of the proposed tolerances for residues of mandipropamid in the various commodities listed above.  

Crop Field Trials:  To support the requested uses, field trials were conducted on basil (along with 2 greenhouse trials), ginseng, and snap beans, and greenhouse trials were conducted on tomatoes.  

IR-4 has submitted basil field and greenhouse trial data with mandipropamid.  Four field trials were conducted in Canada and the US in North American Free Trade Agreement (NAFTA) Growing Zones 2 (1 trial in NC), 5A (1 trial in WI), 10 (1 trial in CA) and 11 (1 trial in BC) during the 2009 growing season, and two greenhouse trials were conducted in the US in Zones 2 (1 trial in MD) and 3 (1 trial in FL) during the 2009 and 2010 growing seasons.  Following 4 foliar directed applications of the Revus 2.08SC formulation, containing 2.08 pounds of active ingredient per gallon (lb ai/gal), at a total seasonal rate of 0.520-0.528 lb ai per acre (lb ai/A), to basil plants (stems and leaves) harvested at a pre-harvest interval (PHI) of 1 day, mandipropamid residues ranged from 3.5 ppm to 19 ppm in fresh basil, and 36 ppm to 91 ppm in dried basil grown in the field and greenhouse.  The adequate basil field trial data support a tolerance of 30 ppm in fresh basil, and a tolerance of 200 ppm in dried basil.  

Four ginseng field trials were conducted in Canada and the US in NAFTA Growing Zones 5A (3 trials in WI) and 11 (1 trial in BC) during the 2008 growing season.  Following 4 foliar broadcast applications of the Revus 2.08SC formulation, at a total seasonal rate of 0.521-0.547 lb ai/A, to ginseng plants harvested at a PHI of 2 days, mandipropamid residues ranged from 0.0222 ppm to 0.167 ppm in dried ginseng roots.  There were no quantifiable residues (<0.005 ppm) of metabolite SYN500003 in any of the dried root samples.  The adequate ginseng field trial data support a tolerance of 0.30 ppm in dried ginseng roots.  

Ten snap bean field trials were conducted in the US in NAFTA Growing Zones 1 (1 trial in NY), 2 (1 trial in MD and 1 trial in GA), 3 (1 trial in FL), 5 (1 trial in OH), 5A (1 trial in MI and 1 trial in WI), 10 (2 trials in CA) and 11 (1 trial in WA) during the 2010 growing season.  Following 4 foliar broadcast or directed applications of the Revus 2.08SC formulation, at a total seasonal rate of 0.490-0.540 lb ai/A, to snap bean plants harvested at a PHI of 1 day, mandipropamid residues ranged from 0.0858 ppm to 0.761 ppm in pods with seed, and 1.24 ppm to 9.84 ppm in plants with pods.  The adequate snap bean field trial data support a tolerance of 0.90 ppm in snap beans.  The submitted snap bean data do not support the proposed tolerances in all succulent beans or cowpea forage (see Section 2.1, below).  

Four tomato greenhouse trials were conducted in the US in NAFTA Growing Zones 2 (1 trial in MD), 4 (1 trial in AR), 5 (1 trial in WI) and 10 (1 trial in CA) during the 2010 growing season.  Following 4 (5 at trial site 10-AR05) foliar broadcast or directed applications of the Revus 2.08SC formulation, at a total seasonal rate of 0.480-0.651 lb ai/A, to tomato plants harvested at a PHI of 1 day, mandipropamid residues ranged from 0.045 ppm to 0.339 ppm in tomato fruit.  The adequate greenhouse trial data support the proposed use on greenhouse tomatoes, at a tolerance of 0.60 ppm (based on the OECD tolerance calculation procedure), which is covered by the proposed tolerance of 1.0 ppm in fruiting vegetables group 8-10.  

Processing Studies:  Because there are no processed commodities for ginseng or succulent beans, processing studies are not required for these RACs.  The processed commodity for basil is dried basil, samples of which were produced at the field trial sites, and subsequently analyzed along with the fresh basil samples.  A processing study is not needed for tomatoes, as this requirement was addressed in a previous summary document (D328534, D337543; D. McNeilly; 28 August 2007).  

Residue Analytical Methods:  There is an adequate enforcement method available for the quantitation of mandipropamid in plant commodities.  The Food and Drug Administration (FDA) multiresidue methods are not adequate for determining residues of mandipropamid.  

Storage Stability:  Adequate storage stability data are available to support the storage durations and conditions of samples from the submitted field trial studies.  

Meat, Milk, Poultry and Eggs:  Because the proposed tolerance in cowpea forage cannot be established at this time, the current action for the proposed new uses will not result in the need for tolerances in livestock commodities (see Section 2.1, below).  

MRL Harmonization:  Neither Codex nor Canada's Pest Management Regulatory Agency (PMRA) have established MRLs for mandipropamid in any of the commodities associated with the proposed new uses.  As such, there are no harmonization issues associated with Codex for the proposed new uses in the current action.  However, PMRA and EPA are jointly reviewing the basil, ginseng and snap bean data in the current action; EPA and PMRA are harmonized on the recommended tolerances/MRLs in fresh basil, dried basil, and ginseng.  PMRA is establishing an MRL in edible-podded beans at 0.9 ppm, while HED is recommending for a tolerance in snap beans at 0.90 ppm.  Although the tolerance/MRL level is harmonized, HED cannot harmonize with PMRA on the commodity definition, as the submitted snap bean data do not support use on all succulent beans, since no data were submitted for a succulent shelled bean, and do not meet the requirements of subgroup 6A, since no data were submitted for an edible-podded pea.  

Both the current tolerance in group 8 (1.0 ppm) and the proposed tolerance in group 8-10 (1.0 ppm) are harmonized with the Codex (bell and non-bell peppers) and PMRA (tomatoes, okra, eggplant and peppers) MRLs.  The proposed tolerance of 2.0 ppm in subgroup 13-07F, translated from grape data, would be harmonized with the Codex MRL in grapes, but would no longer be harmonized with PMRA's MRL of 1.4 mg/kg in grapes.  The proposed tolerance of 0.1 ppm in subgroup 3-07A, translated from dry bulb onion data, would be harmonized with the Codex MRL in bulb onions, but would no longer be harmonized with PMRA's MRL of 0.05 ppm in various bulb onions.  The proposed tolerance of 7.0 ppm in subgroup 3-07B, translated from green onion data, would be harmonized with the Codex MRL in spring onions, but would no longer be harmonized with PMRA's MRL of 4 ppm in various green onions.  

2.0	Regulatory Recommendations

HED has examined the residue chemistry database for mandipropamid.  Pending submission of a revised Section F (to propose tolerance levels in accordance with those recommended by HED, and to correct some of the commodity definitions), there are no residue chemistry issues that would preclude establishing tolerances in the requested basil and ginseng commodities, and in the updated/expanded crop groups and subgroups.  However, the submitted snap bean data do not support the proposed tolerances in succulent beans or cowpea forage (see Section 2.1, below).  The recommended tolerances are listed in Table 2.2.2, below.  

Note to RD:  Concurrent with the establishment of permanent tolerances in fresh and dried basil (40CFR §180.637[a]), the paragraph referring to, and the table containing, the time-limited tolerances in fresh and dried basil (40CFR §180.637[b]) should be removed, and replaced with "[Reserved]".  

Concurrent with the establishment of the tolerance in group 8-10, the existing tolerances in group 8 and okra should be removed (40CFR §180.637[a]).  

Concurrent with the establishment of the tolerance in subgroup 13-07F, the existing tolerance in grapes should be removed (40CFR §180.637[a]).  

Concurrent with the establishment of the tolerance in subgroup 3-07A, the existing tolerance in dry bulb onions should be removed (40CFR §180.637[a]).  

Concurrent with the establishment of the tolerance in subgroup 3-07B, the existing tolerance in green onions should be removed (40CFR §180.637[a]).  

Note to RD:  According to HED's Interim Guidance on Tolerance Expressions (S. Knizner; 27 May 2009), the tolerance expression for mandipropamid cited in 40CFR §180.637[a] should be revised to state:  

      Tolerances are established for residues of mandipropamid, including its metabolites and degradates, in or on the commodities listed in the table below.  Compliance with the tolerance levels specified below is to be determined by measuring only mandipropamid (4-chloro-N-[2-[3-methoxy-4-(2-propynyloxy)phenyl]ethyl]-α-(2-propynyloxy)benzeneacetamide) in or on the commodity.  

2.1	Data Deficiencies/Data Needs

HED's Chemistry Science Advisory Council (ChemSAC) has determined that the submitted snap bean data do not support the proposed tolerances in succulent beans and cowpea forage (ChemSAC meeting; 17 July 2013).  Additional field trial data on a succulent shelled bean cultivar (such as lima beans) would be necessary in order to establish a tolerance in all succulent beans.  Because of the possibility of detectable residues occurring in dairy cattle commodities (fat, milk and liver) arising from the feeding of treated cowpea forage, the concurrent establishment of mandipropamid tolerances at the limit of quantitation (LOQ) in those commodities would be necessary.  However, with no validated analytical method for enforcing tolerances in livestock commodities, it is not possible to establish tolerances in them.  Ergo, the proposed tolerance in cowpea forage cannot be established until a validated method for determining mandipropamid residues in livestock (cattle) commodities is available.  Also, if uses on additional significant livestock feed items are requested in any future petition, a livestock feeding study will be required.  

2.2	Tolerance Considerations

2.2.1	Enforcement Analytical Method/Multiresidue Methods

There is an adequate enforcement method available for the quantitation of mandipropamid in plant commodities.  Method RAM 415/01, using high performance liquid chromatography with tandem mass spectrometric detection (LC/MS/MS), has been adequately validated by an independent laboratory.  It has a validated LOQ of 0.01 ppm.  An acceptable confirmatory method is also available.  

The FDA Multiresidue methods are not adequate for determining residues of mandipropamid.  

2.2.2	Recommended Tolerances

TABLE 2.2.2	Tolerance Summary for Mandipropamid.  
                      Commodity as Proposed by Registrant
                           Proposed Tolerance (ppm)
                          Recommended Tolerance (ppm)
                    Comments; Correct Commodity Definition
Basil, fresh
                                      30
                                      30
Basil, fresh leaves
Basil, dried
                                      200
                                      200
Basil, dried leaves
Bean, succulent
                                     0.90
                                     None
Field trial data on a succulent shelled bean cultivar is needed.  
Bean, snap
                                     None
                                     0.90
The snap bean field trials support the establishment of this tolerance.  
Ginseng
                                      0.3
                                     0.30

Cowpea, forage
                                      15
                                     None
A validated method for residues in cattle commodities is needed.  
Vegetable, fruiting, group 8-10
                                      1.0
                                      1.0

Fruit, small, vine climbing, subgroup 13-07F, except fuzzy kiwifruit
                                      2.0
                                      2.0
Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F
Onion, bulb, subgroup 3-07A
                                      0.1
                                     0.10

Onion, green, subgroup 3-07B
                                      7.0
                                      7.0

2.2.3	Revisions to Petitioned-For Tolerances

Instead of the proposed tolerance in ginseng (0.3 ppm), HED recommends establishing the tolerance at 0.30 ppm, in order to avoid the situation where a field sample containing residues significantly above the tolerance (0.34 ppm, for example) would be considered non-violative.  For the same reason, HED recommends that the proposed tolerance of 0.1 ppm in bulb onions (subgroup 3-07A) be revised to 0.10 ppm.  

For the reasons discussed in Section 2.1 (above), the proposed tolerances in succulent beans and cowpea forage cannot be established.  However, the snap bean field trials support a tolerance of 0.90 ppm in snap beans.  

2.2.4	International Harmonization

Neither Codex nor PMRA have established MRLs for mandipropamid in any of the commodities associated with the proposed new uses.  As such, there are no harmonization issues associated with Codex for the proposed new uses in the current action.  However, PMRA and EPA are jointly reviewing the basil, ginseng and snap bean data in the current action; EPA and PMRA are harmonized on the recommended tolerances/MRLs in fresh basil, dried basil, and ginseng.  PMRA is establishing an MRL in edible-podded beans at 0.9 ppm, while HED is recommending for a tolerance in snap beans at 0.90 ppm.  Although the tolerance/MRL level is harmonized, HED cannot harmonize with PMRA on the commodity definition, as the submitted snap bean data do not support use on all succulent beans, since no data were submitted for a succulent shelled bean, and do not meet the requirements of subgroup 6A, since no data were submitted for an edible-podded pea.  

Both the current tolerance in group 8 (1.0 ppm) and the proposed tolerance in group 8-10 (1.0 ppm) are harmonized with the Codex (bell and non-bell peppers) and PMRA (tomatoes, okras and peppers) MRLs.  The proposed tolerance of 2.0 ppm in subgroup 13-07F, translated from grape data, would be harmonized with the Codex MRL in grapes, but would no longer be harmonized with PMRA's MRL of 1.4 mg/kg in grapes.  The proposed tolerance of 0.1 ppm in subgroup 3-07A, translated from dry bulb onion data, would be harmonized with the Codex MRL in bulb onions, but would no longer be harmonized with PMRA's MRL of 0.05 ppm in various bulb onions.  The proposed tolerance of 7.0 ppm in subgroup 3-07B, translated from green onion data, would be harmonized with the Codex MRL in spring onions, but would no longer be harmonized with PMRA's MRL of 4 ppm in various green onions.  

2.3	Label Recommendations

Because the submitted snap bean data do not support the proposed use on all succulent beans, the label section containing directions for the requested use on succulent beans ("Bean, succulent") should instead refer only to snap beans ("Bean, snap"), and the listing of all other succulent bean commodities should be deleted from the proposed label.  The requested use on greenhouse tomatoes listed in the proposed label is supported by the submitted greenhouse trial data.

2.4	Submittal of Analytical Reference Standards (860.1650)

	The analytical standard for mandipropamid, with an expiration date of 30 July 2016, is currently available in the EPA's National Pesticide Standards Repository (NPSR), per Email communication from Theresa Cole of the Biological and Economic Analysis Division's (BEAD's) Analytical Chemistry Branch (ACB) on 25 June 2013.  The registrant is required to maintain reasonable amounts of the analytical reference standard for mandipropamid.  The mandipropamid metabolite, SYN 500003, is not in stock.  However, as this metabolite is not included in the tolerance expression, it is not required to be stocked in the NPSR.  When necessary, a new reference standard, or updated certificate of analysis (COA), should be sent to the ACB, which is located at Fort Meade, MD.  It should be sent to the attention of either Theresa Cole or Thuy Nguyen at the address listed below, along with a letter of transmittal.  Please note that the full 9-digit ZIP Code is required, or the mail will be returned to the registrant.  

		USEPA
		National Pesticide Standards Repository
		Analytical Chemistry Branch/BEAD/OPP
		701 Mapes Road
		Fort George G. Meade, MD  20755-5350

The letter of transmittal should include the assay of the standard, name of the analytical method used, a statement of principal impurities, purification procedures employed, storage requirements, and special precautions for safe handling.  Replacement of standards may be required periodically if supplies are exhausted, if the standards expire, or if decomposition occurs during storage.  Material Safety Data Sheets (MSDSs) must accompany all analytical standards as specified by the Occupational Safety and Health Administration (OSHA) in 29CFR§1910.1200.  

3.0	Chemical Identity

Mandipropamid is a mandelamide and belongs to the chemical family of the carboxylic acid amides (CAA) or, more specifically, the mandelic acid amides.  It was developed by Syngenta for the control of foliar oomycete pathogens in a range of crops including Plasmopara viticola in grapes, Phytophthora infestans in potatoes and tomatoes, and Pseudoperonospora cubensis in cucurbits.  Mandipropamid is also used on leafy vegetables to control downy mildew (Bremia lactucae) and blue mold (Peronospora effuse).  The biochemical mode of action of mandipropamid is not fully known.  However, preliminary results indicate that it inhibits the biosynthesis of phospholipids (phosphatidyl choline, lecithin).  Based on a review of its chemistry, resistance profile, and toxicological attributes, mandipropamid is mechanistically unique, and its mode of action is different from other fungicides, including those within the CAA group.  The chemical structure and nomenclature of mandipropamid are listed in Table 3.1, and its physicochemical properties are presented in Table 3.2 (below).  

3.1	Nomenclature

TABLE 3.1	Mandipropamid Nomenclature.
Compound

Common name
Mandipropamid
Company experimental name
NOA 446510
Molecular formula
C23H22ClNO4
Molecular weight
411.88
IUPAC name
(RS)-2-(4-chloro-phenyl)-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-2-prop-2-ynyloxy-acetamide
CAS name
4-chloro-N-[2-[3-methoxy-4-(2-propynyloxy)phenyl]ethyl]-α-(2-propynyloxy)- benzeneacetamide
CAS registry number
374726-62-2
End-use product (EP)
Revus 2.08SC Fungicide (2.08 lb ai/gal; EPA Registration #100-1254)

3.2	Physicochemical Characteristics

TABLE 3.2	Physicochemical Properties of Mandipropamid.
                                   Parameter
                                     Value
                                   Reference
Melting point/range (ºC)
96.4-97.3
MRID #46800006 (100-REIR.doc; S. Mathur; 22 May 2007)
pH (at 25ºC in a 1% aqueous dispersion)
6-8

Density (g/cm[3] at 22ºC)
1.24

Water solubility (mg/L at 25ºC)
4.2

Solvent solubility (g/L at 25ºC)
n-hexane		0.042
n-octanol		4.8
toluene			29
methanol		66
ethyl acetate		120
acetone			300
dichloromethane		400

Vapor pressure (Pa [mm Hg] at 25ºC)
<9.4 x 10[-7] [<7.1 x 10[-9]]

Dissociation constant, pKa
No dissociation in the pH range of 1 to 12

Octanol/water partition coefficient (Log [KOW] at 25ºC)
3.3

UV/visible absorption spectrum
Molar absorption coefficients for the absorbance maximums were:  
Neutral solution
20,144 L/mol cm at 223 nm
2,724 L/mol cm at 276 nm
Acidic solution
20,313 L/mol cm at 223 nm
2,845 L/mol cm at 276 nm
Basic solution
19,414 L/mol cm at 223 nm
2,864 L/mol cm at 276 nm

Mandipropamid is a solid under ambient conditions, and has very low volatility.  The compound has a relatively low solubility in water, and moderate to high solubility in organic solvents.  Its octanol/water partition coefficient suggests that accumulation of mandipropamid in fatty tissues is possible.  

3.3      Pesticide Use Pattern/Directions for Use (860.1200)

IR-4 has requested that new Section 3 uses of the fungicide mandipropamid be added to the label for Revus 2.08SC (EPA Registration #100-1254).  The proposed new uses would be for the treatment of basil, ginseng, succulent beans, and greenhouse tomatoes.  Revus 2.08SC is a suspension concentrate (SC) formulation containing 23.3% ai by weight, which is equivalent to 2.08 lb ai/gal.  An example of the proposed label for Revus 2.08SC was provided, and the proposed use directions therein are summarized in Table 3.3, below.  

TABLE 3.3	Summary of Proposed Directions for Use of Mandipropamid.  
                        Application Type; Equipment[1]
                                   Use Rate
                                   (lb ai/A)
                             Max. Uses Per Season
                            Max. Seasonal Use Rate
                                   (lb ai/A)
                                 PHI[2] (Days)
            Use Directions, Application Timing, and Limitations[3]
                                     Basil
                    Foliar; any ground or aerial equipment.
                                  0.09 - 0.13
                                       4
                                     0.52
                                       1
RTI[4] of 7-10 days.  

                                    Ginseng
                    Foliar; any ground or aerial equipment.
                                  0.09 - 0.13
                                       4
                                     0.52
                                       2
RTI of 7-10 days.  

                                Succulent Beans
                    Foliar; any ground or aerial equipment.
                                  0.09 - 0.13
                                       4
                                     0.52
                                       1
RTI of 7-10 days.  

                              Greenhouse Tomatoes
                    Foliar; any ground or aerial equipment.
                                  0.09 - 0.13
                                       4
                                     0.52
                                       1
RTI of 7-10 days.  May be applied via chemigation.  
1. For ground application, apply in a minimum of 10 gallons of water per acre (GPA), unless specified otherwise on the label.  Do not apply through any ultra-low volume (ULV) spray system.  For aerial application, use only on crops where aerial applications are indicated.  Apply in a minimum of 5 GPA, unless specified otherwise on this label.  Do not apply through any ULV spray system.  For chemigation, use only on crops where chemigation is specified on the label.  Apply no more than 2 sequential applications unless otherwise stated in the crop-specific section. Do not use in transplant production.  
2. PHI = Pre-Harvest Interval.  
3. Begin applications prior to disease development.  Use the shorter interval and/or higher rates under high pressure, or when conditions are conducive to disease.  The addition of a spreading/penetrating type adjuvant such as a non-ionic based surfactant (NIS) or crop oil concentrate (COC) or blend is recommended.  
4. RTI = Re-Treatment Interval.  

Conclusions:  The proposed use directions for application to basil, ginseng, succulent beans, and greenhouse tomatoes are sufficient to allow for evaluation of the submitted residue data relative to the proposed use patterns.  However, as the submitted snap bean data do not support the proposed use on succulent beans, the label section containing directions for use on succulent beans ("Bean, succulent") should instead refer to snap beans ("Bean, snap"), and the listing of all other succulent bean commodities in that section should be deleted.  

4.0	Metabolite/Degradate Residue Profile

4.1	Nature of the Residue
	D328534, D337543; D. McNeilly; 28 August 2007

The nature of the residue in plants, rotational crops, and ruminants is adequately understood.  For the purposes of tolerance enforcement and risk assessment, the terminal residue of concern (ROC) in primary crops, rotational crops, and ruminants is the parent mandipropamid, with the exception of root and tuber vegetables, where the metabolite SYN 500003 is included for risk assessment.  

4.1.1	Summary of Plant and/or Livestock Metabolism (860.1300)

Data have been submitted and reviewed depicting the metabolism/degradation of mandipropamid in numerous crops and the environment.  HED has determined the plant and livestock ROCs for purposes of tolerance enforcement and risk assessment; see Table 4.1.1, below.  

Table 4.1.1	Summary of Mandipropamid Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expression.
                                    Matrix
                     Residues Included in Risk Assessment
                   Residues Included in Tolerance Expression
Plants
Primary crops (except root and tuber vegetables)
Mandipropamid
Mandipropamid

Root and tuber vegetables
Mandipropamid and SYN 500003
Mandipropamid

Rotational crops
Not applicable
Mandipropamid*
Livestock
Ruminants
Not applicable
Not applicable

Poultry
Not applicable
Not applicable
Drinking water
Mandipropamid, SYN 504851 and SYN 500003
Not applicable
*Although the parent compound is a ROC in rotational crops, tolerances are not needed for the present uses, based on the absence of residues in the field rotational crop study following the 30 day plant-back interval (PBI) stipulated on the label.  

Conclusions:  The nature of the residue in plants and animals has been adequately delineated.  

4.1.2	Summary of Confined Rotational Crops (860.l850)
	D328534, D337543; D. McNeilly; 28 August 2007

An acceptable confined rotational crop study was reviewed in Petitions #6F7057 and #7F7184.  In this study, the extent and nature of the residue uptake by crops planted 29, 58, 120, and/or 365 days post-application in soil treated with [chlorophenyl-[14]C]-mandipropamid or [methoxyphenyl-[14]C]-mandipropamid at 0.806-0.832 lb ai/A was determined.  Total radioactive residues accumulated at >=0.01 ppm in all rotated crop matrices except radish roots and tops planted at the 120-day PBI, and lettuce, wheat forage, and wheat grain (chlorophenyl label only) planted at the 365-day PBI.  The distribution and nature of the residue in the rotated crops was similar between the two radiolabels.  The parent mandipropamid was identified at low levels.  Unchanged parent was detected at a level greater than 0.01 ppm only in wheat straw (<=0.023 ppm), but was less than 0.01 ppm in lettuce, radish root, radish top, wheat forage, and wheat grain.  Two other residue components, CGA 380778 and NOA 458422, were also detected at low levels.  Metabolite CGA 380778 was identified at <=0.006 ppm in lettuce, radish roots and tops, wheat forage, and wheat straw.  Metabolite NOA 458422 was identified only in wheat straw at 0.008-0.016 ppm.  

The study results showed that mandipropamid is extensively metabolized in rotational crops via pathways similar to that in primary crops.  The principal metabolic routes include the removal of either or both of the propargyl side chains to generate the corresponding alcohol or phenol functionalities.  Extensive metabolism may occur, yielding small carbon units, followed by incorporation into natural plant constituents (such as cellulose, glucose, proteins, pectins and lignin) or, alternatively, some radioactive components may become covalently bound to macromolecules in the plant.  

4.1.3	Summary of Rat Metabolism
	Risk Assessment Document D365918; D. Rate; 8 June 2009 (PP#8F7342)

In rat metabolism studies, [[14]C]-mandipropamid, as single oral or repeated oral methoxy or methoxy/chloro radiolabels, was administered to Wistar-derived rats.  To examine biliary excretion, bile duct cannulation was performed.  After 48 hours, absorption was 67-74% at 3 mg/kg, and 30-45% at 300 mg/kg.  Blood Tmax at 3 mg/kg was 8.5 hours for males, and 4.5 hours for females; at 300 mg/kg it was 24 hours for males, and 10 hours for females.  The rate of resorption was greater in females; the extent and rate of absorption was greater in the low dose animals.  Recoveries at 168 hours were 88-99%, with most being eliminated by 48 hours.  Excluding the females dosed at 3 mg/kg, most of the radioactivity was excreted in the feces; in the 3-mg/kg females, feces and urine were similar.  Elimination after 48 hours in bile was high at 3 mg/kg (55-73%), but was 22-28% at 300 mg/kg.  Liver had the highest concentration at all measurements.  More radioactivity was found in plasma than in whole blood.  Identified compounds were 66-94% of the administered dose in each group (168 hours).  The parent and the following metabolites were >=5% at 3 and/or 300 mg/kg: NOA 458422, NOA 458422 glucuronide, SYN 534133 and CGA 380778.  Differences in metabolic profile were due to sex, dose and radiolabel position.  Each unknown compound was less than 5%.  Major metabolic transformations involved loss of one or both propargyl groups, followed by glucuronidation and O-demethylation.  

4.1.4	Summary of Environmental Degradation
	EFED Memo; D382369; C. Wendel; 26 July 2011

The major route of dissipation is degradation under aerobic aquatic conditions.  Mandipropamid appears to be stable to hydrolysis in the environmental pH range of 5-9, but is susceptible to photolysis in soil and water.  The environmental photolysis half-lives of mandipropamid at pH 7 in aqueous solutions were estimated at 0.63-1.1 days.  The soil photolysis half-life of mandipropamid was estimated at 16.4-23.9 days.  Based on its vapor pressure and Henry's Law constant, volatilization from water and soil are not expected to be important environmental fate processes.  

The linear biodegradation half-life of mandipropamid in six European soils, and one US soil, ranged from approximately 26 to 103 days under aerobic conditions.  Under anaerobic conditions, the rate of biodegradation appears to be much slower.  Mandipropamid degraded with a linear half-life of 151 days in a silt loam soil from Switzerland maintained under anaerobic conditions.  The aerobic aquatic degradation half-lives of mandipropamid were 17.8-18.5 days in two river water/silt loam sediment systems from England and Germany.  Acceptable anaerobic aquatic degradation data have not been submitted.  

Terrestrial field dissipation studies on mandipropamid were conducted in California (sandy loam soil), New York (loamy sandy soil), and Georgia (sandy loam soil).  The field dissipation half-lives of mandipropamid were 75.3 days (California site), l00.5 days (New York), and 81.5 days (Georgia).  These studies confirm the persistence of mandipropamid in the environment.  

Mandipropamid is moderately mobile, and some of its metabolites are mobile to highly mobile in soils, and therefore have the potential to leach into ground water.   Mandipropamid can reach surface waters via spray drift and rainfall events that cause runoff.  

5.0	Residue Profile

5.1	Residue Analytical Methods (860.1340)

5.1.1	Data Collection Methods
	MRIDs #48992001 to -04

Basil:  Residues of mandipropamid in treated and control samples of basil were determined using a working method derived from reference method RAM 415/01, titled NOA446510: Validation of Residue Analytical Method RAM 415/01 for the Determination of Residue in Crops.  Method RAM 415/01 was previously reviewed, and deemed acceptable for both data collection and tolerance enforcement.  The modifications included a change in the volume of the subsample from 10 mL to 5 mL, which was diluted to 10 mL with acetonitrile (ACN)/water (1:4, v/v).  Further dilutions were made with ACN/water (1:1, v/v), and the SPE cleanup step was replaced with an on-line cleanup step.  

Briefly, samples were extracted by homogenization with ACN/water.  Extracts were centrifuged, and aliquots were diluted with ACN/water.  Residues of mandipropamid were determined via LC/MS/MS coupled with on-line cleanup.  

The reported limit of detection (LOD) and limit of LOQ were 0.0013 ppm and 0.0038 ppm, respectively, for fresh basil, and 0.0028 ppm and 0.0085 ppm, respectively, for dried basil.  The lowest level of method validation (LLMV) was 0.01 ppm for fresh and dried basil.  Given that the LLMV was 0.01 ppm for mandipropamid, the LOQ of the method will be set at 0.01 ppm for mandipropamid in fresh and dried basil.  The analytical method was validated prior to sample analysis.  The method validation recoveries at spiking levels of 0.01 ppm (LOQ), 0.10 ppm (10X LOQ), 1.0 ppm (100X LOQ) and 20 ppm (2000X LOQ) mandipropamid ranged from 92-102%, 91-98%, 96-100% and 100-105%, respectively from fresh basil.  The method validation recoveries at spiking levels of 0.01 ppm (LOQ) and 0.10 ppm (10X LOQ), 1.0 ppm (100X LOQ) and 100 ppm (10000X LOQ) mandipropamid ranged from 83-104%, 93-106%, 95-100% and 98-100%, respectively from dried basil.  The method suitability was also verified concurrently with sample analysis.  Concurrent recoveries ranged from 93-103% and 95-116% from fresh basil spiked with 1.0 ppm (100X LOQ) and 10 ppm (1000X LOQ) mandipropamid, respectively, and ranged from 88-112% and 97-103% from dried basil spiked with 1.0 ppm (100X LOQ) and 10 ppm (1000X LOQ) mandipropamid, respectively.  All recoveries were within the generally recognized acceptable range of 70 to 120%.  Therefore, the working method is adequate for the determination of residues of mandipropamid in fresh and dried basil samples (see Tables 5.1.1.1 and 5.1.1.2).  

TABLE 5.1.1.1	Summary of Method Validation Recoveries of Mandipropamid from Basil
                                    Matrix
                               Spike Level (ppm)
                                Sample Size (n)
                                Recoveries (%)
                             Mean +- Std. Dev. (%)
                                  Fresh basil
                                     0.01
                                       6
                            94, 94, 95, 92, 92, 102
                                    95 +- 4
                                       
                                     0.10
                                       3
                                  91, 98, 96
                                    95 +- 4
                                       
                                      1.0
                                       3
                                  96, 96, 100
                                    97 +- 2
                                       
                                      20
                                       3
                                 105, 100, 100
                                   102 +- 3
                                  Dried basil
                                     0.01
                                       6
                            98, 104, 98, 83, 85, 88
                                    93 +- 8
                                       
                                     0.10
                                       3
                                 93, 106, 103
                                   101 +- 7
                                       
                                      1.0
                                       3
                                  97, 95, 100
                                    97 +- 3
                                       
                                      100
                                       3
                                 100, 100, 98
                                    99 +- 1

TABLE 5.1.1.2	Summary of Concurrent Recoveries of Mandipropamid from Basil
                                    Matrix
                               Spike Level (ppm)
                                Sample Size (n)
                                Recoveries (%)
                             Mean +- Std. Dev. (%)
                                  Fresh basil
                                      1.0
                                       4
                                103, 97, 94, 93
                                    97 +- 5
                                       
                                      10
                                       3
                                 116, 95, 108
                                   106 +- 11
                                  Dried basil
                                      1.0
                                       4
                               105, 112, 95, 88
                                   100 +- 11
                                       
                                      10
                                       2
                                    97, 103
                                      100

Ginseng:  Residues of mandipropamid and metabolite SYN500003 in treated and control samples of ginseng were determined using a working method derived from method RAM 415/01, titled NOA446510: Validation of Residue Analytical Method RAM 415/01 for the Determination of Residue in Crops, and GRM001.01A, titled Mandipropamid (NOA446510): Method for the Determination of Residues of SYN500003 in Potato Tubers and Process Potato Commodities. Final Determination by LC-MS/MS.  Method RAM 415/01 was previously reviewed, and deemed acceptable as a data gathering and enforcement method.  Method GRM001.01A was not previously reviewed, but is similar to method GRM001.01B, which was previously deemed adequate for data gathering purposes.  The modifications include a change in the volume of the subsample from 10 mL to 5 mL, which was diluted to 10 mL with ACN/water (1:4, v/v).  Further dilutions were made with ACN/water (1:1, v/v), and the SPE cleanup step was replaced with an on-line cleanup step for the analysis of parent only.  

Briefly, residues of mandipropamid and metabolite SYN500003 were extracted with ACN/water in a tissumizer.  Extracts were analyzed for mandipropamid residues by LC-MS/MS coupled with online cleanup.  For the analysis of residues of metabolite SYN500003, an aliquot was cleaned up by SPE prior to analysis by LC/MS/MS in combination with online cleanup.  

The reported LOD and LOQ were 0.0072 ppm and 0.022 ppm, respectively, for mandipropamid, and 0.0019 ppm and 0.0056 ppm, respectively, for metabolite SYN500003.  The LLMV was 0.01 ppm for mandipropamid, and 0.005 ppm for metabolite SYN500003.  Given that the LLMV was 0.01 ppm for mandipropamid, and 0.005 ppm for metabolite SYN500003, the LOQ of the method will be set at 0.01 ppm for mandipropamid, and 0.005 ppm for metabolite SYN500003.  The analytical method was validated prior to sample analysis.  The method validation recoveries at spiking levels of 0.01 ppm (LOQ), 0.10 ppm (10X LOQ) and 1.0 ppm (100X LOQ) mandipropamid ranged from 72-113%, 89-98% and 95-99%, respectively.  The method validation recoveries at spiking levels of 0.005 ppm (LOQ) and 0.10 ppm (20X LOQ) metabolite SYN500003 ranged from 84-116% and 85-97%, respectively.  The method suitability was also verified concurrently with sample analysis.  Concurrent recoveries ranged from 103-108% from ginseng roots spiked with 0.10 ppm mandipropamid, and ranged from 102-127% from ginseng roots spiked with 0.10 ppm of metabolite SYN500003.  All recoveries were within the generally recognized acceptable range of 70 to 120%, with the exception of two concurrent recoveries of 121% and 127% from ginseng roots spiked with 0.10 ppm of metabolite SYN500003.  Therefore, the working method is adequate for the determination of residues of mandipropamid and metabolite SYN500003 in ginseng roots (see Tables 5.1.1.3 and 5.1.1.4).  

TABLE 5.1.1.3	Summary of Method Validation Recoveries of Mandipropamid from Ginseng.
                                    Matrix
                               Spike Level (ppm)
                                Sample Size (n)
                                Recoveries (%)
                             Mean +- Std. Dev. (%)
                                 Mandipropamid
                                 Ginseng roots
                                     0.01
                                       6
                           73, 74, 72, 113, 112, 112
                                   93 +- 22
                                       
                                     0.10
                                       3
                                  98, 96, 89
                                    94 +- 5
                                       
                                      1.0
                                       3
                                  99, 97, 95
                                    97 +- 2
                             Metabolite SYN500003
                                 Ginseng roots
                                     0.005
                                       6
                           107, 116, 99, 108, 99, 84
                                   102 +- 11
                                       
                                     0.10
                                       3
                                  97, 85, 90
                                    91 +- 6

TABLE 5.1.1.4	Summary of Concurrent Recoveries of Mandipropamid from Ginseng.
                                    Matrix
                               Spike Level (ppm)
                                Sample Size (n)
                                Recoveries (%)
                             Mean +- Std. Dev. (%)
                                 Mandipropamid
                                 Ginseng roots
                                     0.10
                                       4
                              104, 103, 105, 108
                                   105 +- 2
                             Metabolite SYN500003
                                 Ginseng roots
                                     0.10
                                       4
                              116, 127, 102, 121
                                   117 +- 11

Snap beans:  Residues of mandipropamid in treated and control samples of snap beans were determined using a working method based on method RAM 415/01, titled NOA446510: Validation of Residue Analytical Method RAM 415/01 for the Determination of Residue in Crops.  The modifications included a change in the volume of the subsample from 10 mL to 5 mL, which was diluted to 10 mL with ACN/water (1:4, v/v).  Further dilutions were made with ACN/water (1:1, v/v), and the SPE cleanup step was replaced with an on-line cleanup step.  This method was previously reviewed, and deemed acceptable for data gathering and enforcement purposes.  

Briefly, samples are extracted by homogenization with ACN/water.  Extracts are centrifuged and aliquots are diluted with ACN/water.  Residues of mandipropamid are determined by high performance liquid chromatography with tandem quadrupole mass spectrometric detection (LC/MS/MS) coupled with on-line cleanup.

The reported LOD and LOQ were 0.00165 ppm and 0.00495 ppm, respectively, for pods with seeds, and 0.00122 ppm and 0.00365 ppm, respectively, for plants with pods.  The LLMV was 0.01 ppm for pods with seeds and plants with pods.  Given that the LLMV was 0.01 ppm for mandipropamid in pods with seeds and plants with pods, the LOQ of the method will be set at 0.01 ppm.  The analytical method was validated prior to sample analysis.  The method validation mean recoveries at spiking levels of 0.01 ppm (LOQ), 0.10 ppm (10X LOQ) and 1.0 ppm (100X LOQ) mandipropamid were 102 +- 5% (n = 6), 102 +- 4% (n = 3) and 101 +- 3% (n = 3), respectively, from pods with seeds.  The method validation mean recoveries at spiking levels of 0.01 ppm (LOQ), 0.10 ppm (10X LOQ), 1.0 ppm (100X LOQ) and 20 ppm (2000X LOQ) mandipropamid were 102 +- 4% (n = 4), 99 +- 3% (n = 3), 94 +- 1% (n = 3) and 101 +- 4% (n = 3), respectively, from plants with pods.  The method suitability was also verified concurrently with sample analysis.  Concurrent mean recoveries were 94 +- 9% (n = 10) from pods with seeds spiked at 0.10 ppm, and were 99% (n = 2) and 104 +- 12% (n = 8) from plants with pods spiked at 0.10 ppm and 1.0 ppm, respectively.  All method validation and concurrent recoveries were within the generally recognized acceptable range (70 to 120%) with the exception of one concurrent recovery of 124% from plants with pods at a spiking level of 1.0 ppm.  As such, method RAM 415/01 is adequate for the determination of residues of mandipropamid in snap beans (see Tables 5.1.1.5 and 5.1.1.6).  

TABLE 5.1.1.5	Summary of Method Validation Recoveries of Mandipropamid from Snap Beans.
                                    Matrix
                               Spike Level (ppm)
                                Sample Size (n)
                                Recoveries (%)
                             Mean +- Std. Dev. (%)
Pods with seed
                                     0.01
                                       6
                           99, 104, 110, 98, 98, 100
                                   102 +- 5

                                     0.10
                                       3
                                 106, 102, 99
                                   102 +- 4

                                      1.0
                                       3
                                 99, 105, 100
                                   101 +- 3
Plants with pods
                                     0.01
                                       6
                          103, 103, 107, 100, 99, 97
                                   102 +- 4
                                       
                                     0.10
                                       3
                                  97, 102, 99
                                    99 +- 3
                                       
                                      1.0
                                       3
                                  95, 95, 93
                                    94 +- 1
                                       
                                      20
                                       3
                                 105, 101, 98
                                   101 +- 4

TABLE 5.1.1.6	Summary of Concurrent Recoveries of Mandipropamid from Snap Beans.
                                    Matrix
                                  Spike Level
                                     (ppm)
                                Sample Size (n)
                                  Recoveries
                                      (%)
                               Mean +- Std. Dev.
                                      (%)
Pods with seed
                                     0.10
                                      10
                  102, 94, 79, 101, 84, 85, 100, 107, 93, 91
                                    94 +- 9
Plants with pods
                                     0.10
                                       2
                                    103, 95
                                      99

                                      1.0
                                       8
                     104, 124, 98, 101, 111, 102, 83, 107
                                   104 +- 12

Greenhouse tomatoes:  Residues of mandipropamid in treated and control samples of tomatoes were determined using a working method derived from reference method RAM 415/01, titled NOA446510: Validation of Residue Analytical Method RAM 415/01 for the Determination of Residue in Crops.  Method RAM 415/01 was previously reviewed, and deemed acceptable for both data collection and tolerance enforcement.  The modifications included a change in the volume of the subsample from 10 mL to 5 mL, which was diluted to 10 mL with acetonitrile (ACN)/water (1:4, v/v).  Further dilutions were made with ACN/water (1:1, v/v), and the SPE cleanup step was replaced with an on-line cleanup step.  

Briefly, samples were extracted by homogenization with ACN/water.  Extracts were centrifuged, and aliquots were diluted with ACN/water.  Residues of mandipropamid were determined via LC/MS/MS coupled with on-line cleanup.  

The reported LOD and limit of LOQ were 0.019 ppm and 0.056 ppm, respectively, for tomatoes.  The LLMV was 0.01 ppm for tomatoes.  Given that the LLMV was 0.01 ppm for mandipropamid, the LOQ of the method will be set at 0.01 ppm for mandipropamid in tomatoes.  The analytical method was validated prior to sample analysis.  The method validation recoveries at spiking levels of 0.01 ppm (LOQ), 0.10 ppm (10X LOQ) and 1.0 ppm (100X LOQ) mandipropamid ranged from 94-107%, 89-94%, and 86-91%, respectively, from tomatoes.  The method suitability was also verified concurrently with sample analysis.  Concurrent recoveries ranged from 87-101% from tomatoes spiked with 0.10 ppm (10X LOQ) mandipropamid.  All recoveries were within the generally recognized acceptable range of 70 to 120%.  Therefore, the working method is adequate for the determination of residues of mandipropamid in tomatoes (see Tables 5.1.1.7 and 5.1.1.8).  

TABLE 5.1.1.7	Summary of Method Validation Recoveries of Mandipropamid from Tomatoes.
                                    Matrix
                               Spike Level (ppm)
                                Sample Size (n)
                                Recoveries (%)
                             Mean +- Std. Dev. (%)
                                 Tomato fruit
                                     0.01
                                       6
                          102, 96, 94, 106, 104, 107
                                   101 +- 6
                                       
                                     0.10
                                       3
                                  89, 89, 94
                                    90 +- 3
                                       
                                      1.0
                                       3
                                  88, 91, 86
                                    88 +- 3

TABLE 5.1.1.8	Summary of Concurrent Recoveries of Mandipropamid from Tomatoes.
                                    Matrix
                               Spike Level (ppm)
                                Sample Size (n)
                                Recoveries (%)
                             Mean +- Std. Dev. (%)
                                 Tomato fruit
                                     0.10
                                       5
                                101, 87, 94, 87
                                    92 +- 7

Conclusions:  Adequate method validation data have been submitted on the LC/MS/MS method used for the determination of mandipropamid residues in the various commodities.  No additional data are required in support of this data collection method.  

5.1.2	Multi-Residue Methods (860.1360)
	D328534, D337543; D. McNeilly; 28 August 2007

Multiresidue method testing data for mandipropamid were submitted.  The study was performed according to the FDA Multi-Residue Method Test guidelines in PAM Vol. I.  Mandipropamid was tested only through Protocol C (Section 302).  It was not tested under Protocols A, B, D, E, F or G.  The petitioner simply stated these protocols were not applicable without further explanation.  

Mandipropamid was tested according to Protocol C using GLC systems DG5, DG13, DG17 and DG 18.  No significant responses were obtained with GLC systems DG5 and DG17, and low or multiple peak responses were achieved with GLC systems DG13 and DG18.  Further testing with mandipropamid was therefore terminated.  

Conclusions:  Mandipropamid was tested under Protocol C which appears to be the only appropriate protocol to evaluate given the results achieved using that protocol.  The FDA Multiresidue methods do not appear to be adequate for determining residues of mandipropamid.  These data were forwarded to the US FDA for further evaluation.  

5.1.3	Tolerance Enforcement Methods
	D328534, D337543; D. McNeilly; 28 August 2007
	D348229, D352322, D. Rate; 11 December 2008

There is an adequate enforcement method for determination of mandipropamid in plant commodities.  LC/MS/MS method RAM 415/01, which was previously submitted under Petitions #6F7057 and #7F7184, has a validated method LOQ of 0.01 ppm.  Method 415/01 has been adequately validated by an independent laboratory and was forwarded to ACB/BEAD for a petition method validation.  The ACB concluded (D336257; C. Stafford; 15 August 2007), without conducting a laboratory trial, that the method appears to meet OCSPP Residue Chemistry Test Guideline 860.1340 for an acceptable tolerance enforcement method, with the exception of the general requirement for a confirmatory method since only one MS/MS ion transition was documented.  The ACB recommended that the petitioner provide an alternate chromatographic column and/or mobile-phase combination to add an additional degree of specificity, and further reduce the possibility of false positive residues.  An acceptable confirmatory method is available.  

5.2	Storage Stability (860.1380)
	MRIDs #48992001 to -04

Basil:  Sample storage conditions and durations are reported in Table 5.2.1, below.  Treated fresh and dried basil samples were stored frozen (<-20ºC/<-4ºF) for up to 723 days and 671 days, respectively, from harvest to extraction.  All samples were analyzed within 9 days of extraction.  The freezer storage stability of residues of mandipropamid fresh and dried basil samples from this study was demonstrated concurrently with the sample analysis (see Table 5.2.2.).  Untreated fresh and dried basil were spiked with 1.0 ppm of mandipropamid.  The corrected mean recovery of mandipropamid from fresh and dried basil samples stored frozen for 700 days was 87 +- 8% and 115 +- 0%, respectively.  The concurrent recoveries of mandipropamid from freshly fortified samples of fresh and dried basil spiked at 1.0 ppm were 105% and 85%, respectively.  The demonstrated storage stability interval of mandipropamid in dried basil covers the actual storage duration, and is only slightly shorter than the actual storage duration for fresh basil.  As such, there are no concerns with the stability of mandipropamid residues in fresh and dried basil samples from this study.  

TABLE 5.2.1	Summary of Storage Conditions.  
                                    Matrix
                              Storage Temperature
                                   (°C/°F)
                        Actual Storage Duration (Days)*
               Interval of Demonstrated Storage Stability (Days)
Fresh basil
                                <-20/<-4
                                      723
                                      700
Dried basil
                                <-20/<-4
                                      671
                                      700
* Storage duration between harvest and extraction.  Samples were analyzed within 9 days of extraction.

TABLE 5.2.2	Stability of Residues of Mandipropamid Following Frozen Storage.
                                    Matrix
                              Storage Temperature
                                   (°C/°F)
                                 Spiking Level
                                     (ppm)
                               Storage Interval
                                    (Days)
                            Concurrent Recovery (%)
                                  Recoveries
                                      (%)
                        Mean Recovery +- Std. Dev. (%)
                   Corrected* Mean Recovery +- Std. Dev. (%)
Fresh basil
                                <-20/<-4
                                      1.0
                                      700
                                      105
                                  82, 95, 98
                                    92 +- 9
                                    87 +- 8
Dried basil
                                <-20/<-4
                                      1.0
                                      700
                                      85
                                  98, 98, 98
                                    98 +- 0
                                   115 +- 0
* Corrected for concurrent recovery.  Mean of recoveries from three stored samples, divided by the recovery from the freshly fortified sample, multiplied by 100%.  

Ginseng:  Treated ginseng root samples were stored frozen (<-20ºC/<-4ºF) for up to 939 days from harvest to extraction (see Table 5.2.3).  All samples were analyzed within 11 days of extraction.  The freezer storage stability of residues of mandipropamid and metabolite SYN500003 in ginseng root samples from this study was demonstrated concurrently with the sample analysis (see Table 5.2.4).  Untreated ginseng root samples were spiked with 0.10 ppm of mandipropamid and metabolite SYN500003.  The corrected mean recoveries of mandipropamid and metabolite SYN500003 from ginseng root samples stored frozen for 922 days were 107 +- 12% and 119 +- 10%, respectively.  The concurrent recoveries of mandipropamid and metabolite SYN500003 from a freshly fortified sample spiked at 0.10 ppm were 99% and 84%, respectively.  The demonstrated storage stability interval of mandipropamid in ginseng is similar to the actual storage duration.  Therefore, there are no concerns with the stability of mandipropamid residues in ginseng root samples from this study.  

TABLE 5.2.3	Summary of Storage Conditions.  
                                    Matrix
                              Storage Temperature
                                   (°C/°F)
                        Actual Storage Duration (Days)*
              Interval of Demonstrated Storage Stability  (Days)
                                 Ginseng roots
                                <-20/<-4
                                      939
                                      922
* Storage duration between harvest and extraction.  Samples were analyzed within 11 days of extraction.  

TABLE 5.2.4	Stability of Residues of Mandipropamid and Metabolite SYN500003 in Ginseng Roots 		Following Frozen Storage.  
                                    Matrix
                              Storage Temperature
                                   (°C/°F)
                                 Spiking Level
                                     (ppm)
                               Storage Interval
                                    (Days)
                            Concurrent Recovery (%)
                                  Recoveries
                                      (%)
                        Mean Recovery +- Std. Dev. (%)
                   Corrected* Mean Recovery +- Std. Dev. (%)
                                 Mandipropamid
                                 Ginseng roots
                                <-20/<-4
                                     0.10
                                      922
                                      99
                                 96, 102, 119
                                   106 +- 12
                                   107 +- 12
                             Metabolite SYN500003
                                 Ginseng roots
                                <-20/<-4
                                     0.10
                                      922
                                      84
                                 90, 105, 105
                                   100 +- 9
                                   119 +- 10
* Corrected for concurrent recovery.  Mean of recoveries from three stored samples, divided by the recovery from the freshly fortified sample, multiplied by 100%.  

Snap beans:  Treated snap bean samples were stored frozen (<-20ºC/<-4ºF) for up to 359 days from harvest to extraction (see Table 5.2.5).  All samples were analyzed within 21 days of extraction.  The freezer storage stability of residues in snap bean samples from this study was demonstrated concurrently with the sample analysis.  Untreated snap bean samples (pods with seed and plants with pods) were spiked with 0.10 ppm of mandipropamid (see Table 5.2.6).  The corrected mean recoveries from pods with seed and plants with pod samples stored frozen for 357 days were 86 +- 3% and 92 +- 2%, respectively.  The concurrent recoveries of mandipropamid from freshly fortified samples spiked at 0.10 ppm were 107% from pods with seed, and 103% from plants with pods.  The demonstrated storage stability interval of mandipropamid in snap beans is almost the same (2 days shorter) as the actual storage duration.  Therefore, there are no concerns with the stability of mandipropamid residues in snap bean samples from this study.  

TABLE 5.2.5	Summary of Storage Conditions.  
                                    Matrix
                              Storage Temperature
                                   (°C/°F)
                        Actual Storage Duration (Days)*
               Interval of Demonstrated Storage Stability (Days)
Pods with seed
                                <-20/<-4
                                      359
                                      357
Plants with pods
                                       
                                       
                                       
* Storage duration between harvest and extraction.  Samples were analyzed within 21 days of extraction.

TABLE 5.2.6	Stability of Mandipropamid Residues in Snap Beans Following Frozen Storage.
                                    Matrix
                              Storage Temperature
                                   (°C/°F)
                                 Spiking Level
                                     (ppm)
                               Storage Interval
                                    (Days)
                            Concurrent Recovery (%)
                                  Recoveries
                                      (%)
                        Mean Recovery +- Std. Dev. (%)
                   Corrected* Mean Recovery +- Std. Dev. (%)
Pods with seed
                                <-20/<-4
                                      0.1
                                      357
                                      107
                                  91, 90, 95
                                    92 +- 3
                                    86 +- 3
Plants with pods
                                       
                                       
                                       
                                      103
                                  94, 93, 97
                                    95 +- 2
                                    92 +- 2
* Corrected for concurrent recovery.  Mean of recoveries from three stored samples, divided by the recovery from the freshly fortified sample, multiplied by 100%.  

Greenhouse tomatoes:  Treated tomato fruit samples were stored frozen (<-20ºC/<-4ºF) for up to 352 days from harvest to extraction (see Table 5.2.7).  All samples were analyzed within 4 days of extraction.  The freezer storage stability of residues in tomato samples from this study was demonstrated concurrently with the sample analysis.  Untreated tomato samples were spiked with 0.103 ppm of mandipropamid (see Table 5.2.8).  The corrected mean recovery from tomato fruit stored frozen for 358 days was 91 +- 4%.  The concurrent recovery of mandipropamid from a freshly fortified tomato sample spiked at 0.10 ppm was 90%.  The demonstrated storage stability interval of mandipropamid in tomato fruit covers the actual storage duration.  Therefore, there are no concerns with the stability of mandipropamid residues in tomato fruit samples from this study.  

TABLE 5.2.3	Summary of Storage Conditions.  
                                    Matrix
                              Storage Temperature
                                   (°C/°F)
                        Actual Storage Duration (Days)*
              Interval of Demonstrated Storage Stability  (Days)
                                 Tomato fruit
                                <-20/<-4
                                      352
                                      358
* Storage duration between harvest and extraction.  Samples were analyzed within 4 days of extraction.  

TABLE 5.2.4	Stability of Residues of Mandipropamid in Tomato Fruit Following Frozen Storage.  
                                    Matrix
                              Storage Temperature
                                   (°C/°F)
                                 Spiking Level
                                     (ppm)
                               Storage Interval
                                    (Days)
                            Concurrent Recovery (%)
                                  Recoveries
                                      (%)
                        Mean Recovery +- Std. Dev. (%)
                   Corrected* Mean Recovery +- Std. Dev. (%)
                                 Tomato fruit
                                <-20/<-4
                                     0.103
                                      358
                                      90
                                  83, 85, 78
                                    82 +- 4
                                    91 +- 4
* Corrected for concurrent recovery.  Mean of recoveries from three stored samples, divided by the recovery from the freshly fortified sample, multiplied by 100%.  

Conclusions:  There are no storage stability issues associated with any of the field trial studies.  Therefore, no corrections for potential decline during storage are needed in reviewing the residue studies submitted for the various commodities.  

5.3	Residue Data

5.3.1	Crop Field Trials (860.1500)
	MRIDs #48992001 to -04

Basil:  IR-4 submitted field and greenhouse trial data for mandipropamid in basil (fresh and dried).  A total of 4 field trials were conducted in Canada and the US in Zones 2 (1 trial in NC), 5A (1 trial in WI), 10 (1 trial in CA) and 11 (1 trial in BC) during the 2009 growing season, and a total of 2 greenhouse trials were conducted in the US in Zones 2 (1 trial in MD) and 3 (1 trial in FL) during the 2009 and 2010 growing seasons.  Two trials (in 2 separate greenhouses) were required to support the proposed use expansion to greenhouse basil; the growing regions in which these were conducted were not specified by OCSPP Residue Chemistry Test Guideline 860.1500.  

At each trial site, mandipropamid formulated as Revus 2.08SC was applied as 4 foliar directed applications at a rate of 0.128-0.139 lb ai/A, with re-treatment intervals (RTIs) of 6 to 8 days, for a total seasonal rate of 0.520-0.528 lb ai/A.  All applications included a non-ionic surfactant (NIS) in the spray mixture.  Fresh basil (stems and leaves) was harvested at a PHI of 1 day.  At one trial site, fresh basil samples (stems and leaves) were harvested at PHIs of 3, 7 and 11 days to assess residue decline.  Samples of fresh basil (stems and leaves) used for drying were also collected at a PHI of 1 day, and dried for up to 3 days according to local commercial practices.  

The results from this study indicated that mandipropamid residues ranged from 3.5 ppm to 19 ppm in fresh basil, and ranged from 36 ppm to 91 ppm in dried basil, grown in the field and greenhouse (see Table 5.3.1.1, below).  The residue decline data indicated that residues of mandipropamid in fresh basil decreased with increasing PHIs.  

TABLE 5.3.1.1	Summary of Residue Data from Basil Field and Greenhouse Trials with Mandipropamid.  
                                Basil Commodity
                                Total Use Rate
                                   (lb ai/A)
                                  PHI (Days)
                             Residue Levels (ppm)
                                       
                                       
                                       
                                       n
                                     Min.
                                     Max.
                                     LAFT*
                                     HAFT*
                                    Median
                                     Mean
                                   Std. Dev.
                            Fresh stems and leaves
                                  0.520-0.528
                                       1
                                     12[1]
                                      3.5
                                      19
                                       -
                                       -
                                      9.0
                                      9.3
                                      4.8
                                       
                                       
                                       
                                     6[2]
                                       -
                                       -
                                      3.6
                                      19
                                      8.8
                                      9.4
                                      5.0
                            Dried stems and leaves
                                  0.520-0.528
                                       1
                                    6[1,2]
                                      36
                                      91
                                       -
                                       -
                                      63
                                      63
                                      20
* LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.  
1. n = total number of samples.  
2. n = total number of field trials.  

Ginseng:  IR-4 submitted field trial data for mandipropamid in ginseng.  A total of 4 trials were conducted in Canada and the US in Zones 5A (3 trials in WI) and 11 (1 trial in BC) during the 2008 growing season.  At each trial site, mandipropamid formulated as Revus 2.08SC was applied as 4 foliar broadcast applications at a rate of 0.129-0.141 lb ai/A, with RTIs of 6 to 9 days, for a total seasonal rate of 0.521-0.547 lb ai/A.  All applications included an NIS in the spray mixture.  Ginseng roots were harvested at a PHI of 2 days.  At one trial site, additional samples of ginseng roots were harvested at PHIs of 0, 7, 15 and 21 days to assess residue decline.  The roots were dried for up to 19 days in commercial facilities simulating commercial practices.  

The results from this study indicated that mandipropamid residues ranged from 0.0222 ppm to 0.167 ppm in dried ginseng root samples (see Table 5.3.1.2, below).  Results also showed that there were no quantifiable residues (<0.005 ppm) of metabolite SYN500003 in dried roots.   The residue decline data indicated that residues of mandipropamid in dried roots remained fairly stable between PHIs of 0 and 21 days.  

TABLE 5.3.1.2	Summary of Residue Data from Ginseng Field Trials with Mandipropamid.  
                                   Commodity
                                Total Use Rate
                                   (lb ai/A)
                                  PHI (Days)
                             Residue Levels (ppm)
                                       
                                       
                                       
                                       n
                                     Min.
                                     Max.
                                     LAFT*
                                     HAFT*
                                    Median
                                     Mean
                                   Std. Dev.
                                 Mandipropamid
                                 Ginseng roots
                                  0.521-0.547
                                       2
                                     8[1]
                                    0.0222
                                     0.167
                                       -
                                       -
                                    0.0586
                                    0.0717
                                    0.0551
                                       
                                       
                                       
                                     4[2]
                                       -
                                       -
                                    0.0271
                                     0.119
                                    0.0705
                                    0.0718
                                    0.0475
                             Metabolite SYN500003
                                 Ginseng roots
                                  0.521-0.547
                                       2
                                     8[1]
                                   <0.005
                                   <0.005
                                       -
                                       -
                                   <0.005
                                   <0.005
                                       -
                                       
                                       
                                       
                                     4[2]
                                       -
                                       -
                                   <0.005
                                   <0.005
                                   <0.005
                                   <0.005
                                       -
* LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.  
1. n = total number of samples.  
2. n = total number of field trials.  

Snap beans:  IR-4 submitted field trial data for mandipropamid in snap beans.  A total of 10 trials were conducted in the US in Zones 1 (1 trial in NY), 2 (1 trial in MD and 1 trial in GA), 3 (1 trial in FL), 5 (1 trial in OH), 5A (1 trial in MI and 1 trial in WI), 10 (2 trials in CA) and 11 (1 trial in WA) during the 2010 growing season.  At each trial site, mandipropamid formulated as Revus 2.08 SC was applied as 4 foliar (broadcast or directed) applications at a rate of 0.094-0.138 lb ai/A, with RTIs of 6 to 8 days, for a total seasonal rate of 0.490-0.540 lb ai/A.  All applications included an NIS or a crop oil concentrate (COC) in the spray mixture.  Snap beans (pods with seed and plants with pods) were harvested at a PHI of 1 day.  At one trial site, snap beans were harvested at PHIs of 3, 7 and 10 days to assess residue decline.  

The results from this study indicated that mandipropamid residues ranged from 0.0858 ppm to 0.761 ppm in pods with seed, and 1.24 ppm to 9.84 ppm in plants with pods (see Table 5.3.1.3, below).  Results from the residue decline study indicated that residues decreased over time.  

TABLE 5.3.1.3	Summary of Residue Data from Snap Bean Field Trials with Mandipropamid.  
                                   Commodity
                                Total Use Rate
                                   (lb ai/A)
                                  PHI (Days)
                             Residue Levels (ppm)
                                       
                                       
                                       
                                       n
                                     Min.
                                     Max.
                                    LAFT[*]
                                    HAFT[*]
                                    Median
                                     Mean
                                   Std. Dev.
                                Pods with seed
                                  0.490-0.540
                                       1
                                     20[1]
                                    0.0858
                                     0.761
                                       -
                                       -
                                     0.210
                                     0.256
                                     0.175
                                       
                                       
                                       
                                     10[2]
                                       -
                                       -
                                     0.10
                                     0.58
                                     0.220
                                     0.256
                                     0.164
                               Plants with pods
                                  0.490-0.540
                                       1
                                     20[1]
                                     1.24
                                     9.84
                                       -
                                       -
                                     4.15
                                     4.14
                                     2.34
                                       
                                       
                                       
                                     10[2]
                                       -
                                       -
                                     1.27
                                     9.27
                                     4.35
                                     4.14
                                     2.36
* LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.  
1. n = total number of samples.  
2. n = total number of field trials.  

Greenhouse tomatoes:  IR-4 submitted greenhouse trial data for mandipropamid in tomatoes grown in greenhouses.  A total of 4 greenhouse trials were conducted in the US in Zones 2 (1 trial in MD), 4 (1 trial in AR), 5 (1 trial in WI) and 10 (1 trial in CA), during the 2010 growing season. At each trial site, mandipropamid formulated as Revus 2.08 SC was applied as 4 foliar (broadcast or directed) applications (5 at trial site 10-AR05) at a rate of 0.120-0.136 lb ai/A, with RTIs of 6 to 8 days, for a total seasonal rate of 0.480-0.651 lb ai/A.  The fifth application was made at trial site 10-AR05 in order to obtain commercial-size tomatoes at the proposed 1-day PHI.  All applications included an NIS in the spray mixture.  The applications were made starting 22 days before harvest, except at trial site 10-AR05, where the first application was made 30 days prior to harvest.  Commercially mature tomatoes (large and small-sized varieties) were harvested at a PHI of 1 day.   

The results from this study indicated that mandipropamid residues ranged from 0.045 ppm to 0.339 ppm in tomato fruit (see Table 5.3.1.4, below).  

TABLE 5.3.1.4	Summary of Residue Data from Tomato Greenhouse Trials with Mandipropamid.  
                                   Commodity
                                Total Use Rate
                                   (lb ai/A)
                                  PHI (Days)
                             Residue Levels (ppm)
                                       
                                       
                                       
                                       n
                                     Min.
                                     Max.
                                    LAFT[*]
                                    HAFT[*]
                                    Median
                                     Mean
                                   Std. Dev.
                                 Tomato fruit
                                  0.480-0.651
                                       1
                                     8[1]
                                     0.045
                                     0.339
                                       -
                                       -
                                     0.147
                                     0.168
                                     0.101
                                       
                                       
                                       
                                     4[2]
                                       -
                                       -
                                     0.059
                                     0.289
                                     0.115
                                     0.168
                                     0.105
* LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial.  
1. n = total number of samples.  
2. n = total number of field trials.  

Conclusions:  The submitted crop field trial data are adequate, and support the establishment of permanent tolerances in basil (field and greenhouse), ginseng and snap beans, as listed in Table 6.0 (see Section 6.0, below).  The submitted greenhouse trial data are adequate to support the requested use on greenhouse tomatoes.  Additional field trial data on a succulent shelled bean cultivar (such as lima beans) would be necessary in order to establish the proposed tolerance in all succulent beans.  

5.3.2	Field Rotational Crops (860.1900)
	D328534, D337543; D. McNeilly; 28 August 2007

An adequate limited field rotational crop study was reviewed in Petitions #6F7057 and #7F7184.  Mandipropamid residues were below the LOQ (<0.01 ppm) in all samples of rotated radish roots, radish tops, spinach leaves, fall wheat forage, spring wheat forage, wheat hay, wheat grain, and wheat straw planted at the 28/31-day and 61-day PBIs.  HED has determined that the rotational crop restriction on the label which states "[d]o not plant any crop which is not registered for use with mandipropamid for a period of 30 days after the last application" is appropriate.  Given the label restriction, tolerances in rotational crops are not needed.  

5.3.3	Processed Food and Feed (860.1520)

Because there are no processed commodities for ginseng or succulent beans, processing studies are not required for these RACs.  The processed commodity for basil is dried basil, samples of which were produced at the field trial sites, and subsequently analyzed along with the fresh basil samples.  A processing study is not needed for tomatoes, as this requirement was addressed in a previous summary document (D328534, D337543; D. McNeilly; 28 August 2007).  

5.3.4	Meat, Milk, Poultry and Eggs (860.1480)
	D328534, D337543; D. McNeilly; 28 August 2007

The only significant livestock feed item associated with the proposed new uses is cowpea forage, which is not fed to beef cattle, swine nor poultry.  It is fed to dairy cattle at up to 20% of the diet in select locations, or as seasonally available.  At the proposed tolerance level of 15 ppm, the calculated dietary burden to dairy cattle is 10 ppm (the contribution to dietary burden from the only current feed items, potato culls and processed waste, is negligible at 0.025 ppm).  

No livestock feeding studies were submitted with this petition.  An acceptable ruminant metabolism study is available.  Goats were dosed with radiolabeled mandipropamid at 30-36 ppm (3-3.6X the dietary burden to dairy cattle) in the feed for 7 consecutive days.  The parent compound was identified only in fat (0.013-0.019 ppm), milk (0.013 ppm), and liver (0.004-0.007 ppm).  Based on the highest detected residue of 0.019 ppm in goat fat, anticipated residues from feeding cowpea forage containing mandipropamid at the recommended tolerance level of 15 ppm would be roughly 0.006 ppm.  HED's ChemSAC determined that it is not possible to establish a tolerance in cowpea forage, as the potential for finite residues in cattle commodities (fat, milk and liver) exists.  Establishing a tolerance in cowpea forage would necessitate the concurrent establishment of tolerances at the LOQ in cattle fat, milk and liver, which would require a suitable method for the enforcement of tolerances in these commodities.  However, with no validated method for enforcing tolerances in cattle commodities, it is not possible to establish tolerances in them (minutes from ChemSAC meeting of 17 July 2013).  

Conclusions:  The proposed tolerance in cowpea forage cannot be established until a validated method for determining mandipropamid residues in livestock (cattle) commodities is available.  Also, if uses on additional significant livestock feed items are requested in any future petition, a livestock feeding study will be required.  

5.3.5	Food Handling (860.1460)

There are no proposed uses that are relevant to this guideline topic.

5.3.6	Water, Fish and Irrigated Crops (860.1400)

There are no proposed uses that are relevant to this guideline topic

5.4	Food Residue Profile

Residues of mandipropamid are expected to occur at low (up to 0.10 ppm in bulb onions) to high levels (up to 200 ppm in dried basil) from the new uses proposed in the current action.  

6.0	  Tolerance Derivation

Instead of the proposed tolerance in ginseng (0.3 ppm), HED recommends establishing the tolerance at 0.30 ppm, in order to avoid the situation where a field sample containing residues significantly above the tolerance (0.34 ppm, for example) would be considered non-violative.  For the same reason, HED recommends that the proposed tolerance of 0.1 ppm in bulb onions (subgroup 3-07A) be revised to 0.10 ppm.  

The recommended tolerances in fresh and dried basil, snap beans, and ginseng are based on crop field trial data entered into OECD's tolerance calculation procedure.  Upon establishment of the permanent tolerances in fresh and dried basil (40CFR §180.637[a]), the time-limited tolerances in fresh and dried basil (40CFR §180.637[b]) should be removed.  

The recommended tolerance in fruiting vegetables (group 8-10) is based on updating the current tolerance in fruiting vegetables (group 8).  The tolerance of 1.0 ppm would match the existing Codex (bell and non-bell peppers) and PMRA (tomatoes, okras and peppers) MRLs.  Upon establishment of the tolerance in group 8-10, the tolerances in group 8 and okra should be removed.  

The recommended tolerance in small vine climbing fruits except fuzzy kiwifruit (subgroup 13-07F) is based upon expanding the current tolerance in grapes (1.4 ppm), and raising the US tolerance to harmonize with the existing Codex MRL in grapes.  Upon establishment of the tolerance in subgroup 13-07F, the tolerance in grapes should be removed.  

The recommended tolerance in bulb onions (subgroup 3-07A) is based upon expanding the current tolerance in dry bulb onions (0.05 ppm), and raising the US tolerance to harmonize with the existing Codex MRL in bulb onions.  Upon establishment of the tolerance in subgroup 3-07A, the tolerance in dry bulb onions should be removed.  

The recommended tolerance in green onions (subgroup 3-07B) is based upon expanding the current tolerance in green onions (4 ppm), and raising the US tolerance to harmonize with the existing Codex MRL in spring onions.  Upon establishment of the tolerance in subgroup 3-07B, the tolerance in green onions should be removed.  

The rationales for the establishment (or not) and concurrent removal of tolerances associated with the current action are listed in Table 6.0, below.  

An International Residue Limit Status sheet is appended as Attachment 1.  Data sets and results from the OECD tolerance calculation procedure for the various commodities are appended as Attachment 2.  

TABLE 6.0	Tolerance Recommendations for Mandipropamid.  
                                   Commodity
                           Existing Tolerance (ppm)
                          Recommended Tolerance (ppm)
                                   Rationale
                              40CFR §180.637[a]
Basil, fresh leaves
                                     None
                                      30
Based on submitted crop field trial data.  
Basil, dried leaves
                                     None
                                      200

Bean, succulent
                                     None
                                     None
Field trial data on a succulent shelled bean cultivar is needed.  
Bean, snap
                                     None
                                     0.90
Based on submitted crop field trial data.  
Ginseng
                                     None
                                     0.30

Cowpea, forage
                                     None
                                     None
A validated method for residues in cattle commodities is needed.  
Vegetable, fruiting, group 8-10
                                     None
                                      1.0
Updated from fruiting vegetables group 8.
Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F
                                     None
                                      2.0
Translated from grape data, and harmonized with Codex MRL in grapes.  
Onion, bulb, subgroup 3-07A
                                     None
                                     0.10
Translated from bulb onion data, and harmonized with Codex MRL in bulb onions.  
Onion, green, subgroup 3-07B
                                     None
                                      7.0
Translated from green onion data, and harmonized with Codex MRL in spring onions.  
Vegetable, fruiting, group 8
                                      1.0
                                     None
Remove; updated to group 8-10 tolerance.  
Okra
                                      1.0
                                     None
Remove; covered by group 8-10 tolerance.  
Grape
                                      1.4
                                     None
Remove; covered by subgroup 13-07F tolerance.  
Onion, dry bulb
                                     0.05
                                     None
Remove; updated to subgroup 3-07A tolerance.
Onion, green
                                       4
                                     None
Remove; updated to subgroup 3-07B tolerance.
                              40CFR §180.637[b]
Basil, dried
                                      240
                                     None
Remove time-limited tolerances, establish permanent tolerances under 180.637[a].  
Basil, fresh
                                      20
                                     None

References

Mandipropamid.  Section 3 Registration Request to Register New Uses on Hops and Tobacco and Confirmatory Residue Analytical Method for Determination of Residues in Crop Matrices.  Summary of Analytical Chemistry and Residue Data.; D348229, D352322, D. Rate; 11 December 2008.  

Mandipropamid.  Request to Register New Food/Feed Uses on Head and Stem Brassica, Leafy Brassica Greens, Cucurbit Vegetables, Fruiting Vegetables, Leafy Vegetables (except Brassica), Tuberous and Corm Vegetables, Grapes, and Onions (Dry Bulb and Green).  Summary of Analytical Chemistry and Residue Data.  Petition Numbers 6F7057 and 7F7184.; D328534, D337543; D. McNeilly; 28 August 2007.  

Ecological Risk Assessment for the Mandipropamid Section 3 New Use on Outdoor/Non-food Ornamentals and Listed Vegetables Grown for Transplant and Retail Sale to Consumers; D382369; C. Wendel; 26 July 2011.  

Minutes from ChemSAC meeting; 17 July 2013.  

Attachments

Attachment 1:  International Residue Limit Status sheet.  
Attachment 2:  OECD MRL (tolerance) assessment calculations.  

Attachment 1:  International Residue Limit Status.  

                        Mandipropamid (PC Code 036602)
      Summary of US Tolerances and International Maximum Residue Limits.
                              Residue Definitions
                             US (40CFR §180.637)
                                    Canada
                                     Codex
Plants:  Mandipropamid (4-chloro-N-[2-[3-methoxy-4-(2-propynyloxy)phenyl] ethyl]-α-(2-propynyloxy)- benzeneacetamide).  
Mandipropamid (4-chloro-N-[2-[3-methoxy-4-(2-propynyloxy) phenyl]ethyl]-α-(2-propynyloxy)- benzeneacetamide).  
Mandipropamid.  

                                 Commodity[2]
                              Tolerance (ppm)[3]
                                   Commodity
                                  MRL (mg/kg)
                                   Commodity
                                MRL[4] (mg/kg)
Basil, fresh leaves
                                      30

                                       

                                       
Basil, dried leaves
                                      200

                                       

                                       
Bean, succulent
                                     0.90

                                       

                                       
Ginseng
                                     0.30

                                       

                                       
Cowpea, forage
                                      15

                                       

                                       
Vegetable, fruiting, group 8-10
                                      1.0
Bell peppers, eggplants, ground-cherries, non-bell peppers, okras, pepinos, pepper hybrids, tomatillos, tomatoes
                                       1
Bell peppers, non-bell peppers
                                       1

                                       

                                       
Dried chili peppers
                                      10

                                       

                                       
Tomatoes
                                      0.3
Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13-07F
                                      2.0
Grapes
                                      1.4
                                       
Grapes
                                       2
Onion, bulb, subgroup 3-07A
                                     0.10
Chinese onions, daylilies, dry bulb onions, fritillaria, bulbs, garlic, great-headed garlic, lilies, pearl onions, potato onions, serpent garlic, shallot bulbs
                                     0.05
Bulb onions
                                      0.1
Onion, green, subgroup 3-07B
                                      7.0
Beltsville bunching onions, elegans hosta, fresh Chinese chive leaves, fresh chive leaves), fresh onions, fritillaria leaves, green onions, kurrats, lady's leek, leeks, macrostem onions, shallot leaves, tree onion tops, Welsh onion tops, wild leeks
                                       4
Spring onions
                                       7

                                       

                                       

                                       
Completed:  M. Negussie, 27 June 2013.  
1. Mexico adopts US tolerances, and/or Codex MRLs, for its export purposes.  
2. Includes only commodities of interest for this action.  
3. Tolerance values are those recommended by HED, not those proposed by the petitioner.  
4. * = absent at the LOQ.  Po = post-harvest treatment, such as treatment of stored grains.  PoP = processed post-harvest treated commodity, such as a processed commodity of post-harvest treated stored wheat.  (Fat) = to be measured in the fat portion of the sample.  MRLs indicated as "proposed" have not been finalized by the CCPR and the CAC.  

Attachment 2:  OECD MRL (Tolerance) Assessment Calculations.  

Basil, Dried

Residues (ppm)
                                    63.000
                                    36.000
                                    62.000
                                    91.000
                                    48.000
                                    78.000

                                       
                                 Mandipropamid
                                 Basil, dried
                                  Canada/USA
                                 0.52 lb ai/A
 
 
Total number of data (n)
                                       6
Percentage of censored data
                                      0%
Number of non-censored data
                                       6
Lowest residue
                                    36.000
Highest residue
                                    91.000
Median residue
                                    62.500
Mean
                                    63.000
Standard deviation (SD)
                                    19.819
Correction factor for censoring (CF)
                                     1.000
 
                                       
Proposed MRL estimate
 
 
                                       
- Highest residue
                                    91.000
- Mean + 4 SD
                                    142.277
- CF x 3 Mean
                                    189.000
Unrounded MRL
                                    189.000
 
                                       
Rounded MRL
                                      200
 
                                       

Basil, Fresh

Residues (ppm)
                                     6.500
                                    19.000
                                     8.500
                                     9.000
                                     3.600
                                     9.600

                                       
                                 Mandipropamid
                                 Basil, fresh
                                  Canada/USA
                                 0.52 lb ai/A
 
 
Total number of data (n)
                                       6
Percentage of censored data
                                      0%
Number of non-censored data
                                       6
Lowest residue
                                     3.600
Highest residue
                                    19.000
Median residue
                                     8.750
Mean
                                     9.367
Standard deviation (SD)
                                     5.200
Correction factor for censoring (CF)
                                     1.000
 
                                       
Proposed MRL estimate
 
 
                                       
- Highest residue
                                    19.000
- Mean + 4 SD
                                    30.168
- CF x 3 Mean
                                    28.100
Unrounded MRL
                                    30.168
 
                                       
Rounded MRL
                                      30
 
                                       

Ginseng

Residues (ppm)
                                     0.119
                                     0.106
                                     0.035
                                     0.027

                                       
                                 Mandipropamid
                                    Ginseng
                                  Canada/USA
                                 0.52 lb ai/A
 
 
Total number of data (n)
                                       4
Percentage of censored data
                                      0%
Number of non-censored data
                                       4
Lowest residue
                                     0.027
Highest residue
                                     0.119
Median residue
                                     0.070
Mean
                                     0.072
Standard deviation (SD)
                                     0.047
Correction factor for censoring (CF)
                                     1.000
 
                                       
Proposed MRL estimate
 
 
                                       
- Highest residue
                                     0.119
- Mean + 4 SD
                                     0.262
- CF x 3 Mean
                                     0.215
Unrounded MRL
                                     0.262
 
                                       
Rounded MRL
                                      0.3

                                       

Snap Bean, Pods with Seed (for Succulent Bean)

                                Residues (ppm)
                                     0.100
                                     0.191
                                     0.114
                                     0.248
                                     0.399
                                     0.130
                                     0.113
                                     0.580
                                     0.429
                                     0.254

 
 
 
 
 
                                 Mandipropamid
                                       
 
                          Snap beans (pods with seed)
                                       
 
                                      USA
                                       
 
                                 0.52 lb ai/A
                                       
 
 
 
 
 
Total number of data (n)
                                      10
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                      10
                                       
 
Lowest residue
                                     0.100
                                       
 
Highest residue
                                     0.580
                                       
 
Median residue
                                     0.220
                                       
 
Mean
                                     0.256
                                       
 
Standard deviation (SD)
                                     0.163
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     0.580
 
 
- Mean + 4 SD
                                     0.910
 
 
- CF x 3 Mean
                                     0.767
 
 
Unrounded MRL
                                     0.910
                                       
 
 
                                       
 
 
Rounded MRL
                                      0.9
                                       
 
 
                                       
                                       

Snap Bean, Plants with Pods (for Cowpea Forage)

Residues (ppm)
                                     1.360
                                     3.320
                                     4.200
                                     4.490
                                     9.270
                                     2.210
                                     1.270
                                     5.030
                                     5.740
                                     4.540

 
 
 
 
 
                                 Mandipropamid
                                       
 
                         Snap beans (plants with pods)
                                       
 
                                      USA
                                       
 
                                 0.52 lb ai/A
                                       
 
 
 
 
 
Total number of data (n)
                                      10
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                      10
                                       
 
Lowest residue
                                     1.270
                                       
 
Highest residue
                                     9.270
                                       
 
Median residue
                                     4.345
                                       
 
Mean
                                     4.143
                                       
 
Standard deviation (SD)
                                     2.364
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     9.270
 
 
- Mean + 4 SD
                                    13.601
 
 
- CF x 3 Mean
                                    12.429
 
 
Unrounded MRL
                                    13.601
                                       
 
 
                                       
 
 
Rounded MRL
                                      15
                                       
 
 
 
 

Greenhouse Tomato

Residues (ppm)
                                     0.059
                                     0.289
                                     0.219
                                     0.104

 
 
 
 
 
                                 Mandipropamid
                                       
 
                               Greenhouse Tomato
                                       
 
                                      USA
                                       
 
                                 0.52 lb ai/A
                                       
 
 
 
 
 
Total number of data (n)
                                       4
                                       
 
Percentage of censored data
                                      0%
                                       
 
Number of non-censored data
                                       4
                                       
 
Lowest residue
                                     0.059
                                       
 
Highest residue
                                     0.289
                                       
 
Median residue
                                     0.162
                                       
 
Mean
                                     0.168
                                       
 
Standard deviation (SD)
                                     0.105
                                       
 
Correction factor for censoring (CF)
                                     1.000
                                       
 
 
                                       
                                       
 
Proposed MRL estimate
 
 
 
 
                                       
 
 
- Highest residue
                                     0.289
 
 
- Mean + 4 SD
                                     0.589
 
 
- CF x 3 Mean
                                     0.503
 
 
Unrounded MRL
                                     0.589
                                       
 
 
                                       
 
 
Rounded MRL
                                      0.6