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                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460

                                                  OFFICE OF CHEMICAL SAFETY AND
                                                                                POLLUTION PREVENTION
MEMORANDUM

Date:	25-APR-2012

Subject:	Cyazofamid.   Petition for the Establishment of Permanent Tolerances and Registration for Use on Basil, Succulent Beans, the Fruiting Vegetable Group 8-10, the Leafy Greens Subgroup 4A, and the Tuberous and Corm Vegetable Subgroup 1C.  Summary of Analytical Chemistry and Residue Data.

PC Code: 085651
DP Barcode: D396051
MRID Nos.: See Below
Registration No.: 71512-3
Petition No.: 1E7929
Regulatory Action: Section 3 Registration
Assessment Type: Single Chemical/Aggregate
Case No.: NA
TXR No.: None
CAS No.: 120116-88-3
Decision No.: 456373
40 CFR 180.601

From:	Nancy Dodd, Chemist
	Risk Assessment Branch III (RAB3)
	Health Effects Division (HED) (7509P)

Through:	Leung Cheng, Senior Chemist
	RAB3/HED (7509P)

To: 	Barbara Madden/Laura Nollen, RM #5
	Risk Integration, Minor Use and Emergency Response Branch (RIMUERB)
	Registration Division (7505P)

MRID Summary Table
MRID No.
Study Type
Comments
48629401
860.1500
New DER; 48629401.der.doc
48629402
860.1500
New DER; 48629402.der.doc
48629403
860.1500
New DER; 48629403.der.doc
48629404
860.1500
New DER; 48629404.der.doc
48629405
860.1500
New DER; 48629401.der.doc
46537730
860.1520
No DER

                               Table of Contents

Background	3
Executive Summary	3
Pre-Registration Data Needs	5
Condition-of-Registration Data Needs	5
Tolerance Considerations	5
Analytical Method	5
Recommended Tolerances	5
International Harmonization	6
Revisions to Petitioned-For Tolerances	6
Residue Profile	7
Residue Chemistry Guidelines	9
Directions for Use (860.1200)	9
Nature of the Residue (860.1300/1850)	12
Residue Analytical Methods (860.1340)	14
Multiresidue Methods (860.1360)	15
Storage Stability (860.1380)	16
Water, Fish, and Irrigated Crops (860.1400)	17
Food Handling (860.1460)	17
Meat, Milk, Poultry, and Eggs (860.1480)	17
Crop Field Trials (860.1500)	19
Processed Food and Feed (860.1520)	28
Rotational Crops (Field; 860.1900)	29
Tolerance Derivation	29
Appendix A.  Field Trial Geographic Distribution	42
Appendix B: International Residue Limits	44
Appendix C: Chemical Names and Structures of Cyazofamid and Identified Metabolites	45

Background

The Interregional Research Project No. 4 (IR-4) has proposed establishment of permanent tolerances for residues of the fungicide cyazofamid [4-chloro-2-cyano-N, N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide] and its metabolite CCIM [4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile] on basil (fresh and dried), succulent beans, succulent shelled beans, the fruiting vegetable group 8-10, the leafy greens subgroup 4A, and the tuberous and corm vegetable subgroup 1C.  These proposed new uses are to be added to the Ranman 400SC label (EPA Reg. No. 71512-3).  Ranman 400SC is a soluble concentrate formulation which contains 3.33 lb active ingredient (ai) per gallon (400 grams ai/liter; 34.5% ai).

Cyazofamid is a fungicide which belongs to a novel chemical class based on the cyanoimidazole moiety.  Cyazofamid is a broad spectrum fungicide active against oomycete fungi (such as Phytophthora, Plasmopara, Pseudoperonospora, and Pythium) and Plasmodiophoromycetes (Plasmodiospora brassicae).  It specifically interferes with the cytochrome bc1 complex (ubiquinol cytochrome c oxidoreductase) in the mitochondrial respiratory chain of oomycetes fungi.

Permanent tolerances are established in 40 CFR §180.601 on various raw agricultural commodities (RACs) at levels ranging from 0.02 ppm on potato to 12.0 ppm on turnip greens and the Brassica leafy greens subgroup 5B.  A tolerance with regional registration is established on grape at 1.5 ppm.  Time-limited tolerances under a Section 18 have been established on dried basil at 144 ppm and fresh basil at 12 ppm; these tolerances will expire on 12/31/14.  No tolerances have been established on livestock commodities.

Ranman(R) 400SC can be applied using ground, aerial, or sprinkler irrigation equipment.  Multiple foliar applications can be made to all proposed crops.  Tomatoes grown for transplant and basil can be grown in the greenhouse.  A soil drench can be applied to fruiting vegetables at transplant or to tomatoes in the greenhouse.  A band or soil drench application can be made to the leafy greens subgroup 4A at transplant or seeding.   The tuberous and corm vegetable subgroup can be treated at-planting, in-furrow at planting, or lay-by/hilling. Maximum application rates per crop growing season are 0.43 lb ai/A for beans (succulent podded and succulent shelled), fruiting vegetables, and the leafy greens subgroup 4A; 0.7 lb ai/A for basil, and 0.71 lb ai/A for the tuberous and corm vegetable subgroup 4A.  The preharvest intervals are 0 days for basil, beans (succulent podded and succulent shelled), fruiting vegetables, and the leafy greens subgroup 4A, and 7 days for the tuberous and corm vegetable subgroup 1C.  The plantback interval is 0 days for crops on the label and 30 days for other crops.  The label indicates that Ranman 400SC should be tank mixed with an organosilicone surfactant, non-ionic surfactant, or a blend of an organosilicone and a non-ionic surfactant.

Executive Summary

The Interregional Research Project No. 4 (IR-4) has proposed establishment of permanent tolerances for residues of the fungicide cyazofamid and its metabolite CCIM on basil (fresh and dried), succulent beans, succulent shelled beans, the fruiting vegetable group 8-10, the leafy greens subgroup 4A, and the tuberous and corm vegetable subgroup 1C.

Ranman 400 SC is a suspension concentrate formulation.  Cyazofamid has limited systemic activity.  It can be applied using ground, aerial or sprinkler irrigation equipment.  It can be applied to the soil and as multiple foliar applications.  It can be applied to basil grown in the greenhouse and to tomato transplants in the greenhouse.  Maximum application rates per crop growing season are 0.43 lb ai/A for beans (succulent podded and succulent shelled), fruiting vegetables, and the leafy greens subgroup 4A; 0.7 lb ai/A for basil, and 0.71 lb ai/A for the tuberous and corm vegetable subgroup 4A.  The preharvest intervals are 0 days for basil, beans (succulent podded and succulent shelled), fruiting vegetables, and the leafy greens subgroup 4A, and 7 days for the tuberous and corm vegetable subgroup 1C.

The residues of concern for the tolerance expression and risk assessment are parent and the metabolite CCIM in treated plants and parent only in rotational crops.  No residues are expected to occur in livestock commodities.

Adequate enforcement methods are available, including a multiresidue method (Protocol D) and a high performance liquid chromatography/ultraviolet detection (HPLC/UV) method with a confirmatory method (liquid chromatography/tandem mass spectrometric detection; LC/MS/MS).  The methods determine cyazofamid and the metabolite CCIM.  The limit of quantitation (LOQ) of the HPLC/UV and LC/MS/MS methods is 0.01 ppm for each analyte.

Adequate storage stability data are available to support the storage intervals of the field trials and processing studies.

Provided the requested revisions are made to the Ranman 400 SC label, the field trials are adequate to establish tolerances on all the proposed commodities at levels recommended in Table 1 below.  Detectable residues may occur in food.  Field trial decline studies show that residues in agricultural commodities decline with increasing preharvest intervals.

Adequate processing studies are available.  The potato and tomato processing studies are adequate to indicate that combined residues of cyazofamid and CCIM are not likely to concentrate in processed commodities.

The proposed and registered uses fall under 40 CFR §180.6(a)(3) with respect to livestock commodities, i.e., there is no reasonable expectation that finite residues will occur in livestock commodities.

Based on a study on confined accumulation in rotational crops, cyazofamid (parent) is expected to be present at a level of less than 0.01 ppm at a plantback interval of 30 days.  The rotational crop plantback interval of 0 days for crops which are on the label and 30 days for other crops is appropriate.

Regulatory Recommendations

Provided the revisions to the Section B/label are made as requested below (in the Pre-Registration Data Needs section), the available residue chemistry data are adequate to support registration of the crop/crop group commodities requested by the petitioner at the tolerance levels recommended in Table 1 below (in the Recommended Tolerances section).

Pre-Registration Data Needs

Directions for Use (860.1200)

The Ranman 400 SC label should be amended to prohibit applications to cowpea grown for livestock feeds because no residue data are available for cowpea forage and hay.  The statement "Do not apply to cowpea used for livestock feed" should be added to the label.  Cowpea is a succulent shelled bean.

The label indicates that Ranman 400 SC should be tank mixed with an organosilicone surfactant, non-ionic surfactant, or a blend of an organosilicone and non-ionic surfactant.  The label should be revised to specify that an organosilicone surfactant can be used on basil, snap beans, lima beans, pepper, potato, spinach and tomato, and either a nonionic surfactant or an organosilicone surfactant can be used on head and leaf lettuce.

Meat, Milk, Poultry, and Eggs (860.1480)

Tolerances for residues of cyazofamid in poultry and swine commodities are not required provided that application to cowpea used for livestock feed is prohibited on the label.

Condition-of-Registration Data Needs

 None

Tolerance Considerations

Analytical Method

Adequate enforcement methods are available to determine residues of cyazofamid and its metabolite CCIM in lettuce, basil, snap bean, lima bean, pepper, potato, spinach, and tomato.  An enforcement method for non-fatty commodities is FDA's Multiresidue Protocol D (without cleanup), which completely recovers (>80% recovery) cyazofamid and metabolite CCIM.  In addition, the HPLC/UV method (MRID 45409020; revised in MRID 46550401) is acceptable for use as a single analyte enforcement method provided a confirmatory method such as the LC/MS/MS method is used.

Recommended Tolerances

Tolerances are established in 40 CFR §180.601 with the following tolerance expression, as per the Steve Knizner memo dated 5/27/09:

   Tolerances are established for residues of the fungicide cyazofamid, including its metabolites and degradates, in or on the commodities in the following table.  Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of 4-chloro-2-cyano-N, N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its metabolite, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the stoichiometric equivalent of cyazofamid, in or on the following commodities.

HED recommends for establishment of the tolerances on the commodities in Table 1 below using the same tolerance expression as above:

Table 1.     Tolerance Summary for Cyazofamid.
Commodity
                        Established/Proposed Tolerance
                                     (ppm)
                           Recommended Tolerance[1]
                                     (ppm)
Comments (correct commodity definition)
Bean, succulent
                                      0.4
                                      0.5

Bean, succulent, shelled
                                     0.07
                                     0.08

Leafy greens subgroup 4A
                                      9.0
                                      10

Basil, fresh leaves
                                      30
                                      30

Basil, dried leaves
                                      80
                                      90

Vegetable, tuberous and corm, subgroup 1C
                                     0.02
                                     0.02

Vegetable, fruiting, group 8-10
                                     0.40
                                      0.9

1 See "Revisions to Petitioned-For Tolerance" section.

When the above tolerances are established, the existing tolerances on spinach, potato, the fruiting vegetable group 8 and okra can be removed as requested by the petitioner.

International Harmonization

There are no Codex or Mexican maximum residue limits (MRLs) on the proposed crops.  Canada has a tolerance at 0.02 ppm on potatoes, which is the same level as the US tolerance on the crop group (vegetable, tuberous and corm, subgroup 1C).  Canada also has a tolerance of 0.2 ppm on tomatoes, which is less than the recommended US tolerance of 0.9 ppm on the crop group (vegetable, fruiting, group 8-10).

The tolerance definition for the US and Canada are the same.  Both the US and Canada include parent and the metabolite, 4- chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, in the tolerance expression.

Revisions to Petitioned-For Tolerances

Bean, succulent: HED recommends increasing the proposed tolerance from 0.4 ppm to 0.5 ppm for succulent bean.  The Organization for Economic Cooperation and Development (OECD) tolerance calculator gave a value of 0.5 for snap bean when average field trial values were entered (n = 8).

Bean, succulent, shelled: HED recommends increasing the proposed tolerance for succulent shelled bean from 0.07 ppm to 0.08 ppm since the OECD tolerance calculator gave a value of 0.08 ppm for lima bean when average field trial values were entered (n = 6).

Leafy greens subgroup 4A:  HED recommends increasing the proposed tolerance for the leafy greens subgroup 4A from 9 ppm to 10 ppm.  The established tolerance on spinach is 9.0 ppm.  The representative commodities for the leafy greens subgroup 4A are head lettuce, leaf lettuce, and spinach.  The OECD calculator gave values of 4 ppm for head lettuce, 8 ppm for leaf lettuce, and 10 ppm for spinach.  The highest value of the representative commodities is 10 ppm.

Basil, dried leaves:  HED recommends increasing the proposed tolerance for dried basil leaves from 80 ppm to 90 ppm.  The OECD calculator value for dried basil leaves is 90 ppm when average field trial values were entered (n = 4).

Vegetable, fruiting, group 8-10:  HED recommends increasing the proposed tolerance for the fruiting vegetable group 8-10 from 0.40 to 0.9 ppm.  A tolerance of 0.40 ppm is established for the fruiting vegetable group 8.  The representative commodities for Crop Group 8-10 are tomato, standard size, and one cultivar of small tomato; bell pepper and one cultivar of small nonbell pepper.  The residue data on the fruiting vegetable group 8 support the fruiting vegetable group 8-10.  The OECD calculator using average field trial values gives values of 0.2 ppm for tomato (n = 16), 0.4 ppm for bell pepper (n = 6) and 0.9 ppm for nonbell pepper (n = 3).  The highest value of the representative commodities is 0.9 ppm.

Residue Profile

Table 2.	Test Compound Nomenclature.
Compound
Chemical Structure

Common name
Cyazofamid
Company experimental name
N/A
IUPAC name
4-chloro-2-cyano-N, N-dimethyl-5-p-tolylimidazole-1-sulfonamide
CAS name
4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide
CAS registry number
120116-88-3
End-use product (EP)
Ranman(R) 400SC Agricultural Fungicide (EPA Reg. No. 71512-3)
Compound
Chemical Structure of metabolite

Common name
CCIM
IUPAC name
4-chloro-5-p-tolylimidazole-2-carbonitrile
CAS name
4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile

Table 3.	Physicochemical Properties of the Technical Grade Cyazofamid.
Parameter
                                     Value
                                   Reference
Melting point (°C)
                                     152.7
            PMRA Regulatory Note REG2006-05 on Cyazofamid, 12/6/06
pH
                                      4.9
                      e-Pesticide Manual, 13[th] Edition
Density at 20 °C (g/mL)
                                     1.446

Water solubility (at 20 °C)
                                      pH
                               Solubility (mg/L)
                                  REG2006-05

                                       5
                                       7
                                       9
                                     0.121
                                     0.107
                                     0.109

Solvent solubility (at 21.2°C)
                                    Solvent
                               Solubility (g/L)

                                    Acetone
                                 Ethyl acetate
                                   Methanol
                                Dichloromethane
                                    Toluene
                                    Hexane
                                   n-Octanol
                                 Acetonitrile
                                  2-Propanol
                                     43.1
                                     16.19
                                     1.74
                                     94.82
                                      6.0
                                     0.03
                                     0.04
                                    29.446
                                     0.43

Vapor pressure at 25°C
                             <1.33 x 10[-5] Pa

Dissociation constant (pKa)
         Does not dissociate in water. No pKa in the pH range of 2-12.

Octanol/water partition coefficient
                                 Log KOW = 3.2
                              KOW = 1.585 x 10[3]

UV/visible absorption spectrum
                                      pH
                                  Λmax (nm)

                                       2
                                       7
                                      10
                                      285
                                      279
                                      287

Cyazofamid technical is a solid at room temperature with low vapor pressure.  The formulation is a suspension concentrate.  Detectable residues may occur in food.  Field trial decline studies show that residues in agricultural commodities decline with increasing preharvest intervals.  According to EPA's Pesticide Fact Sheet (September 2004), cyazofamid has limited systemic activity so it is used as a protectant fungicide applied by ground or aerial spray.  Exposure to surface water is possible through water runoff, soil erosion, or spray drift.

Residue Chemistry Guidelines

Directions for Use (860.1200)

Table 4.     Summary of Proposed Directions for Use of Cyazofamid.
Applic. Timing, Type, and Equip.
                                  Formulation
                                [EPA Reg. No.]
                                 Applic. Rate
                                   (lb ai/A)
                          Max. No. Applic. per Season
                          Max. Seasonal Applic. Rate
                                   (lb ai/A)
                                      PHI
                                    (days)
                        Use Directions and Limitations*
                                     Basil
Post-emergence.
Foliar broadcast sprays using ground, aerial, or sprinkler irrigation equipment.  Can be grown in a greenhouse.
Ranman 400SC
[71512-3]
                                  0.072-0.078
                                       9
                                      0.7
                                       0
Normal water volume is 50-75 gals water per acre.

For downy mildew on basil, make applications on a 7 to 10 day schedule.

                 Beans, Succulent Podded and Succulent Shelled
Cicer arietinum (chickpea, garbanzo bean); Lupinus spp. (including sweet lupine, white sweet lupine, white lupine, and grain lupine).  Phaseolus spp. (including kidney bean, lima bean, mung bean, navy bean, pinto bean, snap bean, and waxbean); Vicia faba (broad bean, fava bean); Vigna spp. (including asparagus bean, blackeyed pea and cowpea)
Post-emergence.
Foliar broadcast sprays using ground, aerial, or sprinkler irrigation equipment.
                                 Ranman 400SC
                                   [71512-3]
                                     0.072
                                       6
                                     0.43
                                       0
Normal water volumes are 20-60 gals water per acre.

For downy mildew on lima beans: Make applications on a 7 to 10 day schedule.

For cottony leak control: Make the initial application at full bloom (1[st] pods) and repeat on a 7-14-day schedule.

For Phytophthora blight control: Make the 1[st] application at 100% bloom-pin pod development and a 2[nd] application at late pin-small pod development and repeat every seven days.
                     Fruiting Vegetables (Crop Group 8-10)
African eggplant; bush tomato; bell pepper; cocona; currant tomato; eggplant; garden huckleberry; goji berry; groundcherry; martynia; naranjilla; okra; pea eggplant; pepino; nonbell pepper; roselle; scarlet eggplant; sunberry; tomatillo; tomato; tree tomato; cultivars, varieties, and/or hybrids of these
Post-emergence. Broadcast foliar or soil drench to the base of the plants at transplanting or in transplant water. Ground, aerial, or sprinkler irrigation equipment.  Tomatoes for transplant can be grown in the greenhouse.  A soil drench can be applied to tomatoes in the greenhouse.
Ranman 400SC
[71512-3]
0.054-0.072

Soil drench: 0.078 lb ai/100 gals water
                                       6
                                     0.43
                                       0
Normal water volumes are 30-60 gals water per acre.

For late blight control, make applications on a 7 to 10 day schedule.

For Phytophthora blight control, apply to the base of the plants at the time of transplanting.  Alternatively, apply in transplant water at the time of transplanting.  Apply 0.072 lb ai/A in transplant water in a water volume of at least 50 gals/A for the initial application.  Apply on a 7 to 10 day schedule.

Tomato Greenhouse Transplant Production:  For control of Pythium spp., make a single fungicide application to the seeding tray at the time of planting or at any time thereafter up until 1 week before transplanting.  Apply the fungicide solution as a drench to thoroughly wet the growing medium (1 pt of solution per square foot if the growing medium is 4 inches deep).  Do not use a surfactant with this drench application.
                        Leafy Greens, Crop Subgroup 4A
Amaranth (leafy amaranth, Chinese spinach, tampala); arugula (Roquette); chervil; edible-leaved chrysanthemum; garland chrysanthemum; corn salad; garden cress; upland cress (yellow rocket, winter cress); dandelion; dock (sorrel); endive (escarole); lettuce (head and leaf); orach; parsley; garden purslane; winter purslane; radicchio (red chicory); spinach; New Zealand spinach; vine spinach (Malabar spinach, Indian spinach).
Post-transplant; Post-seeding; Post-emergence.
Foliar broadcast or soil drench band spray using ground, aerial, or sprinkler irrigation equipment.
                                 Ranman 400SC
                                   [71512-3]
                                    0.072**
                                       6
                                     0.43
                                       0
Downy mildew: Apply at 7-14-day intervals.

Pythium:  Make first application as a band to the soil as a directed, post- transplant or post-seeding application; alternatively, apply in transplant water at the time of transplant as a soil drench in at least 50 gals water per acre.    Apply at 7 to 10 day intervals.

Normal water volumes are 20-60 gals water per acre.
                Tuberous and Corm Vegetables, Crop Subgroup 1C
Arracacha; arrowroot; Chinese artichoke; Jerusalem artichoke; edible canna; bitter cassava; sweet cassava; chayote (root); chufa; dasheen (taro); ginger; leren; potato; sweet potato; tanier; turmeric; yam bean; true yam
Post-emergence foliar sprays using ground, aerial, or sprinkler irrigation equipment.

Can also be at-planting, in-furrow at planting, or lay-by/ hilling

                                 Ranman 400SC
                                   [71512-3]
                             Foliar: 0.036-0.072**

                 At planting: 0.42 fl oz per 1000 linear feet
                  (0.16 lb ai/A based on a 36" row spacing)

                            Lay-by/ Hilling: 0.072
                                      10
                                    0.72**
                                       7
Normal water volumes are 20-50 gals water per acre.

For foliar blight, make applications on a 7 to10 day schedule.

For tuber and corm rot control, make the last 2 to 3 applications prior to harvest at the rate of 0.072 lb ai/A applied weekly.

For pink rot, Phythium root and crown rot control at planting, apply 0.42 fl oz product per 1000 linear foot of row in-furrow at planting using a minimum of 5 gals water per acre.  Apply in a 6-8 inch band directly over the seed pieces prior to furrow closure.  Mefenoxam can be added as a tank mix.

For additional control of Pythium root and crown rot, in combination with an at-planting, in-furrow application, apply as a broadcast spray at 0.072 lb ai/A in a minimum of 20 gals of finished spray solution per acre at hilling.

* Use directions and limitations:
The plantback interval is 0 days for crops on the label and 30 days for other crops.

Spray volumes will usually range from 20-100 gals per acre for dilute sprays and 5-10 gals/A for concentrate sprays and aerial sprays.  Aerial sprays should be made in a minimum of 5 gals of water per acre.

Alternate sprays of Ranman 400SC with a fungicide with a different mode of action; do not make more than three consecutive applications of Ranman 400SC followed by at least three applications of fungicides having different modes of action before applying additional RANMAN 400SC.

Ranman 400SC should be tank mixed with an organosilicone surfactant, non-ionic surfactant, or a blend of an organosilicone and a non-ionic surfactant.

** 2.75 fl oz product /A = 0.0715 lb ai/A and 27.5 fl oz product /A= 0.715 lb ai/A.  HED rounds up to 0.072 and 0.72, respectively, as per EPA's Hot Sheet # 10.

Conclusions.

Provided the revisions given below are made, the Ranman 400SC label is adequate to allow evaluation of the residue data relative to the proposed use.

The Ranman 400 SC label should be amended to prohibit applications to legumes grown for livestock feeds because no residue data are available for cowpea forage and hay.  The statement "Do not apply to cowpea used for livestock feed" should be added to the label.  Cowpea is a succulent shelled bean.

An organosilicone surfactant (OSS) was used in all field trials on basil, snap beans, lima beans, pepper, potato, and spinach and on several field trials on tomato.  Either a nonionic surfactant (NIS) or OSS was used in all field trials on head lettuce and leaf lettuce.  The label indicates that Ranman 400 SC should be tank mixed with an organosilicone surfactant, non-ionic surfactant, or a blend of an organosilicone and non-ionic surfactant.  The label should be revised to specify that an organosilicone surfactant can be used on basil, snap beans, lima beans, pepper, potato, spinach and tomato, and either a nonionic surfactant or an organosilicone surfactant can be used on head and leaf lettuce.

Nature of the Residue (860.1300/1850)

Amelia Acierto, 2/18/04, DP# D298915, Cyazofamid  -  Meeting Report of the Metabolism Assessment Review Committee (MARC).

Amelia Acierto, 2/20/04, DP# D285680, PP#1F06305, Cyazofamid. Petition for the Establishment of Permanent Tolerances for Use on Cucurbits, Potatoes, Tomatoes, and Imported Wine Grapes.  Summary of Analytical Chemistry and Residue Data; Plants: 45409015.der, 45409016.der, 45409017.der; Goat: 45409018.der; Hen: 45409019.der; Rotational Crops: 45409036.der.

Breann Hanson, 8/3/10, DP# D376500, Cyazofamid.  Human Health Risk Assessment for Proposed Section 18 Use on Basil.

CHEMICAL: CYAZOFAMID
Date:  18-February-2004
Table 5.     Residues of Concern in Plants, Livestock, Rotational Crops, and Water
Matrix
For Risk Assessment
For Tolerance Expression
Plants
Parent and CCIM
Parent and CCIM
Livestock
No decision (For future cattle feeding studies, the MARC recommended that the petitioner analyze parent, CCIM, CCBA, and CCBA-cysteine conjugate.)
No decision
Rotational crops
Parent only
Parent only
Water
Parent, CCIM, CCIM-AM, and CTCA
N/A

Nature of the Residue - Plants

The nature of the residue in basil, lettuce, snap bean, lima bean, pepper, potato spinach, and tomato is adequately understood based on previously submitted metabolism studies conducted on grape, potato, and tomato.  The results of the metabolism studies in plants indicated that the parent and CCIM are the major residues (>10% TRR).  There are no specific toxicity concerns for all other minor metabolites.  For the risk assessment and tolerance expression, the parent cyazofamid and the metabolite CCIM are the residues of concern in primary (treated) plants.

Nature of the Residue  -  Livestock
Provided that application to cowpea used for livestock feed is prohibited on the label, the registered and proposed uses of cyazofamid fall under 40 CFR §180.6(a)(3) with respect to livestock commodities, i.e., there is no reasonable expectation that finite residues will occur in livestock commodities.

Goat and hen metabolism studies have been reviewed; however, residues of concern in livestock commodities have not been identified (A. Acierto, 2/18/04, DP# D298915).  Based on the available goat metabolism study, the MARC determined that the following metabolites should be analyzed for future cattle feeding studies: cyazofamid, CCIM, CCBA (4-(4-chloro-2-cyanoimidazol-5-yl)benzoic acid, and the CCBA-cysteine conjugate.  Provided that application to cowpea used for livestock feed is prohibited on the label, there are no poultry or swine feedstuffs associated with registered or proposed uses (Table 1 Feedstuffs, June 2008).

Confined Accumulation in Rotational Crops
A confined accumulation in rotational crop study was previously submitted in conjunction with an earlier petition (PP#1F06305; DP# D285680, A. Acierto, 2/20/04; 45409036.der).  The results of these data showed that cyazofamid and structurally related metabolites are each expected to be present at a level less than 0.01 ppm at a plantback interval of 30 days.  For the risk assessment and tolerance expression, parent is the only residue of concern in rotational crops.  Therefore, the rotational crop plantback interval (PBI) of 0 days for crops which are on the label and 30 days for other crops is appropriate.

Residue Analytical Methods (860.1340)

Amelia Acierto, 2/20/04, DP# D285680, PP#1F06305, Cyazofamid. Petition for the Establishment of Permanent Tolerances for Use on Cucurbits, Potatoes, Tomatoes, and Imported Wine Grapes.  Summary of Analytical Chemistry and Residue Data; Plants: 45409022.der, 45409020.der.

Breann Hanson, 8/3/10, DP# D376500, Cyazofamid.  Human Health Risk Assessment for Proposed Section 18 Use on Basil.

Elizabeth Kolbe, 10/22/03, DP# D286108, PP# 3F6595.  Cyazofamid on Potatoes, Tomatoes, Cucurbit and Grapes.  Tolerance Method Review and Multi-Residue Method Review.  PC Code 085651 (MRID#: 454090-33, 456385-08, 454090-34, 454090-32, 454090-20, 454090-22); ACB # B02-(58-61).

Elizabeth Kolbe, 2/27/06, DP# D326164, PP# 3F6595.  Review of Resubmitted Analytical Method for Cyazofamid and its Metabolite CCIM in Crops. PC Code 085651 (MRID#: 46550401); ACB Project # B06-13.

 Enforcement Methods   -   Plants

Adequate enforcement methodology is available to enforce the proposed tolerances.  Cyazofamid and metabolite CCIM are completely recovered (>80% recovery) in non-fatty commodities using FDA's Multiresidue Protocol D (without cleanup) (MRID 45409022).  Tomatoes were fortified with cyazofamid at 0.05 ppm and with CCIM at 0.1 ppm; recoveries were adequate.  The multiresidue method can be used as an enforcement method.

In addition, an HPLC/UV method (MRID 45409020; revised in MRID 46550401) is acceptable for use as a single analyte enforcement method provided a confirmatory method such as the LC/MS/MS method discussed below is used.  An independent laboratory validation of the HPLC/UV method (MRID 45409020) was conducted on tomatoes; adequate recoveries were obtained on tomatoes for cyazofamid and CCIM at an LOQ of 0.01 ppm for each analyte.  Successful radiovalidation of the HPLC/UV method was conducted on samples from the grape and potato metabolism studies (MRIDs 45409016 and 45409017).

Data Collection Method  -  Plants

48629401.der (includes MRID 48629405): Lettuce (head and leaf)
48629402.der: Basil
48629403.der: Snap bean (a succulent bean)
48629404.der : Lima bean (a succulent shelled bean)

Samples of lettuce, basil, snap bean and lima bean were analyzed for residues of cyazofamid and its metabolite CCIM using the LC/MS/MS method; the method is a modified version of the method in MRID 45409020.  The limits of quantitation (LOQs; determined as the lowest level of method validation, LLMV) were 0.01 ppm for each analyte in head lettuce, leaf lettuce, snap bean, lima bean, and fresh basil and 0.1 ppm for each analyte in dried basil.  The method was adequate for data collection based on acceptable method validation and concurrent recovery data.  The fortification levels used in concurrent method recovery and method validation were adequate to bracket expected residue levels.  Concurrent recoveries and residues in the treated samples were not corrected for residues in controls.  The analytical method does not specify conversion of metabolite residues to parent equivalents; therefore, quantifiable residues of CCIM were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.49 (MW of cyazofamid 324.79 / MW of CCIM 217.65).

Field trials on pepper, spinach, tomato and potato were previously reviewed.  The data collection method for pepper and spinach was the LC/MS/MS method.  The data collection method for tomato and potato was the HPLC/UV method.  All LOQs were 0.01 ppm for each analyte in each crop.

Conclusions.

The data collection and enforcement methods are adequate to determine residues of cyazofamid and its metabolite CCIM in lettuce, basil, snap bean, lima bean, pepper, potato, spinach, and tomato.  An enforcement method for non-fatty commodities is FDA's Multiresidue Protocol D (without cleanup), which completely recovers (>80% recovery) cyazofamid and metabolite CCIM.  In addition, an HPLC/UV method (MRID 45409020; revised in MRID 46550401) is acceptable for use as a single analyte enforcement method provided a confirmatory method such as the LC/MS/MS method is used.

The data collection method (LC/MS/MS), a modified version of the method in MRID 45409020, is adequate for determination of cyazofamid and CCIM in residue samples, based on adequate recoveries and limits of quantitation, which were 0.01 ppm for each analyte in head lettuce, leaf lettuce, snap bean, lima bean, fresh basil, pepper, and spinach and 0.1 ppm for each analyte in dried basil.  The HPLC/UV method is adequate for determination of residues of cyazofamid and CCIM in potato and tomato at the LOQ of 0.01 ppm for each analyte.

Multiresidue Methods (860.1360)

Amelia Acierto, 2/20/04, DP# D285680, PP#1F06305, Cyazofamid. Petition for the Establishment of Permanent Tolerances for Use on Cucurbits, Potatoes, Tomatoes, and Imported Wine Grapes.  Summary of Analytical Chemistry and Residue Data; 45409022.der

Elizabeth Kolbe, 10/22/03, DP# D286108, PP# 3F6595.  Cyazofamid on Potatoes, Tomatoes, Cucurbit and Grapes.  Tolerance Method Review and Multi-Residue Method Review.

Cyazofamid and its metabolite CCIM were analyzed according to the FDA Multiresidue Method (MRM) Test guidelines in PAM, Volume I, Appendix II (1/94).  Testing using Protocols A and B is not required because cyazofamid and CCIM do not have an N-methylcarbamate structure and are not acid or phenol compounds.  Using Protocol C, injections of cyazofamid and CCIM yielded adequate responses to several of the Section 302 GLC systems.  Cyazofamid and CCIM were completely recovered (>80% recovery) using Protocol D (without cleanup).  Cyazofamid was partially recovered (50-80% recovery) using Protocols E and F.  CCIM was not further tested with Protocols E and F because <30% of CCIM was recovered from the Florisil column cleanup tests.

Conclusions.

Adequate multiresidue methods data (MRID 45409022) have been submitted.  The FDA Multiresidue Method Protocol D (without cleanup) meets the requirement of OCSPP 860.1360 for non-fatty commodities.  Residues of cyazofamid and CCIM are completely recovered (>80% recovery) from non-fatty commodities through the FDA Multiresidue Method Protocol D (without cleanup).  In MRID 45409022, tomatoes were fortified with cyazofamid at 0.05 ppm and with CCIM at 0.1 ppm; recoveries using Protocol D were adequate.  The multiresidue method can be used as an enforcement method.  The multiresidue methods data have been forwarded by the Analytical Chemistry Branch of the Biological and Economic Analysis Branch (ACB/BEAD) to FDA (D286108, E. Kolbe, 10/22/03).

Storage Stability (860.1380)

48629401.der (includes MRID 48629405): Lettuce (head and leaf)
48629402.der: Basil
48629403.der: Snap bean
48629404.der: Lima bean

Storage stability data generated concurrently with the field trial studies are reported below.

Table 6.   Summary of Storage Conditions and Durations of Samples from Crop Field Trial Studies.
Matrix
                           Storage Temperature (°C)
                          Actual Storage Duration[1]

           Interval of Demonstrated Storage Stability (days)[2][,3]
Basil, fresh
                                      -20
                                  8-284 days
                               (0.3-9.3 months)
Residues of cyazofamid were stable in/on fresh basil stored frozen for up to 284 days (9.3 months).
 Residues of CCIM in/on fresh basil declined by 46% after 284 days (9.3 months) of freezer storage.
Basil, dried
                                      -20
                                 155-299 days
                               (5.1-9.8 months)
Residues of cyazofamid and CCIM were reasonably stable in/on dried basil stored frozen for up to 297 days (9.8 months).
Beans, lima
                                      -20
                                  63-147 days
                               (2.1-4.8 months)
Residues of cyazofamid and CCIM were stable in/on lima beans stored frozen for up to 140 days (4.6 months).
Beans, snap[3]
                                      -20
                                 861-946 days
                              (28.3-31.1 months)
Residues of cyazofamid and CCIM were stable in/on snap beans stored frozen for up to 887 days (29.2 months).
Lettuce, head
                                  -20 to -8.9
                                 208-634 days
                               (6.8-20.8 months)
Residues of cyazofamid and CCIM were stable in/on leaf lettuce stored frozen for up to 634 days (20.8 months).
Lettuce, leaf
                                  -20 to -8.9
                                 251-624 days
                               (8.3-20.5 months)

1  Storage duration is from collection to analysis.  Samples were analyzed within 0-1 day of extraction.
2  Storage stability data were generated concurrently with the field trial study.
3  No 0-day data were provided.
[4]  Pods with seeds

Conclusions.

The available storage stability data are adequate to support the storage durations and conditions of the field trial samples.  Except for residues of the metabolite CCIM in fresh basil, the data are adequate to conclude that residues of cyazofamid and CCIM in the field trial samples were stable during frozen storage.  Residues of CCIM in fresh basil declined by 46% after 284 days (9.3 months) of freezer storage; therefore, residues in fresh basil in the field trials were corrected for loss of CCIM in storage.

Water, Fish, and Irrigated Crops (860.1400)

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

Food Handling (860.1460)

DER Reference List

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

Meat, Milk, Poultry, and Eggs (860.1480)

Amelia Acierto, 2/20/04, DP# D285680, PP#1F06305, Cyazofamid. Petition for the Establishment of Permanent Tolerances for Use on Cucurbits, Potatoes, Tomatoes, and Imported Wine Grapes.  Summary of Analytical Chemistry and Residue Data; 45409018.der.

Livestock feed items are associated with the registered uses on carrots and potatoes and with the proposed uses on potato (as part of the tuberous and corm vegetable subgroup 1C) and cowpea.  Livestock feed items are carrot culls, potato culls, processed potato waste, and cowpea seed, forage, and hay.  There are no other proposed crops that are associated with significant livestock feed items (Table 1 Feedstuffs, June 2008).

The established tolerance on potato of 0.02 ppm is being converted into a tolerance on the tuberous and corm vegetable subgroup 1C at the same level.

There is an established tolerance on turnip greens.  Turnip greens are grown for human consumption and are not likely to be used as a livestock feed.

Since no residue data have been submitted for cowpea forage and hay, the Ranman 400SC label (EPA Reg. No. 71512-3) should be amended to prohibit application to cowpea grown for livestock feed.  The statement "Do not apply to cowpea used for livestock feed" should be added to the label.

With the restriction against use on cowpea used for livestock feed, there are no poultry or swine feed items associated with the registered or proposed uses.

Table 7.	Calculation of Dietary Burdens of Cyazofamid Residues to Livestock.
Feedstuff
                                    Type[1]
                                % Dry Matter[2]
                                   % Diet[2]
                                  Established
                          Tolerance or HAFT (ppm)[3]
                         Dietary Contribution (ppm)[4]
Beef Cattle
Untreated
                                       R
                                      --
                                      15
                                       0
                                       0
Potato, culls
                                      CC
                                      20
                                      30
                                     0.02
                                     0.03
Potato, processed waste
                                      CC
                                      15
                                      30
                                     0.02
                                     0.04
Untreated
                                      CC
                                      --
                                      20
                                       0
                                       0
Untreated
                                      PC
                                      --
                                       5
                                       0
                                       0
                                                                   TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                     0.07
Dairy Cattle
Untreated
                                       R
                                      --
                                      45
                                       0
                                       0
Carrots, culls[5]
                                      CC
                                      12
                                      10
                                     0.09
                                     0.075
Untreated
                                      CC
                                      --
                                      35
                                       0
                                       0
Untreated
                                      PC
                                      --
                                      10
                                       0
                                       0
                                                                   TOTAL BURDEN
                                      --
                                      --
                                      100
                                      --
                                     0.075
[1]  R:  Roughage; CC:  Carbohydrate concentrate; PC:  Protein concentrate.
[2]  Table 1 Feedstuffs (July 2008).
3  The established tolerance is used for the registered use (carrot); the highest average field trial (HAFT) value is used for the proposed use (potato).
[4]  Contribution for beef and dairy cattle = tolerance / % DM x % diet.
[5] Potato culls and potato processed waste can also be fed to dairy cattle; however, both carrot and potato feed items are not expected to be fed.

No ruminant feeding study has been submitted.  Based on the goat metabolism study (MRID 45409018; PP#1F06305), residues in milk and ruminant tissues reflecting a dosing level of 10 ppm are reported in Table 8 below.  In the metabolism study, two lactating goats per treatment group were orally dosed with the radiolabelled cyazofamid test substances for five consecutive days at a nominal rate of 10 ppm based on the food consumption during the acclimation period.  The dosing level of 10 ppm is equivalent to 143x and 133x the maximum dietary burden of cyazofamid in beef and dairy cattle, respectively

Table 8.  Total Radioactive Residues, Expressed as Cyazofamid Equivalents, in Goat Matrices from a Metabolism Study after Dosing with Radiolabelled Cyazofamid at 10 ppm.

Goat Matrix

                        [Benzene-[14]C]Cyazofamid (ppm)

                       [Imidazole-[14]C]Cyazofamid (ppm)

Milk

                                  0.004-0.006

                                  0.002-0.010

Liver

                                     0.126

                                     0.125

Kidney

                                     0.07

                                     0.106

Loin muscle

                                     0.004

                                     0.006

Rear leg muscle

                           nondetectable (<0.01)

                           nondetectable (<0.01)

Omental fat

                                     0.006

                                     0.01

Perirenal fat

                                     0.01

                                     0.01

Table 9.  Summary of Ruminant Metabolism Studies with Cyazofamid.
Commodity
                              Feeding Level (ppm)
                         Max. Residue in Tissue (ppm)
                             Tissue-to-Feed Ratio
                             Dietary Burden (ppm)
                            Expected Residue (ppm)
Milk
                                      10
                                     0.01
                                     0.001
                                     0.075
                                   0.000075
Muscle (cattle)

                                     0.01
                                     0.001
                                     0.07
                                    0.00007
Fat (cattle)

                                     0.01
                                     0.001
                                     0.07
                                    0.00007
Liver (cattle)

                                     0.126
                                    0.0126
                                     0.07
                                    0.00088
Kidney (cattle)

                                     0.106
                                    0.0106
                                     0.07
                                    0.00088

 Conclusions.

The results of the goat metabolism study indicate that tolerances for residues of cyazofamid in ruminant commodities are not required for the purpose of this petition since there is no reasonable expectation that finite residues will occur in ruminant commodities [40 CFR §180.6(a)(3)].

Tolerances for residues of cyazofamid in poultry and swine commodities are not required provided that application to cowpea used for livestock feed is prohibited on the label.  With that label prohibition, there are no poultry or swine feed items associated with the proposed or registered uses, and the proposed and registered uses fall under 40 CFR §180.6(a)(3) for poultry commodities.

Crop Field Trials (860.1500)

48629401.der (includes MRID 48629405) (Lettuce, Head and Leaf)
48629402.der (Basil)
48629403.der (Snap Bean)
48629404.der (Lima Bean)

Table 10.  Summary of Residues from Field Trials with Cyazofamid[1,2]
                                 Crop Matrix
                                    Analyte
                                 Applic. Rate
                                 (lb ai/acre)
                                  PHI (days)
                                       n
                                Residues (ppm)

                                     Min.
Max.
                                     LAFT
                                     HAFT
                                    Median
                                     Mean
                                      SD
     BASIL  Proposed Use = 0.7 lb ai/acre total application rate, 0-day PHI
Basil, fresh (leaves and stems)[3]
Cyazofamid  + CCIM
                                  0.693-0.721
                                       0
                                       6
                                      2.4
                                      15
                                      2.6
                                      14
                                      8.5
                                      8.4
                                      5.1
Basil, dried (leaves and stems)[3]
                              Cyazofamid  + CCIM
                                  0.693-0.721
                                       0
                                       4
                                      11
                                      46
                                      11
                                      43
                                      30
                                      28
                                      13
 BEAN, LIMA  Proposed Use = 0.43 lb ai/acre total application rate, 0-day PHI
Bean, lima (succulent seeds)
                              Cyazofamid  + CCIM
                                  0.427-0.523
                                      0-1
                                       6
                                   <0.02
<0.057
                                   <0.02
                                   <0.050
                                     0.020
                                     0.025
                                     0.012
 BEAN, SNAP  Proposed Use = 0.43 lb ai/acre total application rate, 0-day PHI
Bean, snap
(pods with seeds)
                              Cyazofamid  + CCIM
                                  0.426-0.507
                                       0
                                       8
                                   <0.022
                                   <0.23
                                   <0.029
                                   <0.21
                                     0.12
                                     0.12
                                     0.072
LETTUCE, HEAD  Proposed Use = 0.43 lb ai/acre total application rate, 0-day PHI
Lettuce, head (head with wrapper leaves)
                              Cyazofamid  + CCIM
                                  0.419-0.506
                                       0
                                      11
                                   <0.06
                                      2.0
                                   <0.080
                                      1.8
                                     0.65
                                     0.83
                                     0.61
LETTUCE, LEAF  Proposed Use = 0.43 lb ai/acre total application rate, 0-day PHI
Lettuce, leaf (leaves)
                              Cyazofamid  + CCIM
                                  0.427-0.587
                                       0
                                      11
                                   <0.49
                                      4.6
                                   <0.54
                                      4.5
                                      1.8
                                      2.1
                                      1.3
1 Except for sample min/max, values reflect per trial averages; n = no. of field trials.
2 LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial; SD = Standard Deviation.  For computation of the LAFT, HAFT, median, mean, and standard deviation, values < LOQ are assumed to be at the LOQ.
3 Data for fresh basil include field trials and greenhouse trials.  Data for dried basil reflect field trials.

The following data were previously reviewed and are included here for use in crop group establishment:

47528401.der (Pepper)
45409033.der (Potato)
47870704.der (Spinach)
45409031.de1 (includes MRIDs 45638507 and 45638508) (Tomato)

Table 11.  Summary of Residues from Field Trials on Pepper, Spinach, and Tomato with Cyazofamid) 1, 2
                                 Crop Matrix
                                    Analyte
                                 Applic. Rate
                                 (lb ai/acre)
                                  PHI (days)
                                       n
                                Residues (ppm)

                                     Min.
                                     Max.
                                     LAFT
                                     HAFT
                                    Median
                                     Mean
                                      SD
    PEPPER Proposed Use = 0.43 lb ai/acre total application rate, 0-day PHI
Pepper , Bell
Cyazofamid  + CCIM
                                  0.418-0.429
                                       0
                                       6
                                   <0.047
                                     0.297
                                   <0.048
                                   <0.236
                                     0.075
                                     0.101
                                     0.069
Pepper, Nonbell
Cyazofamid  + CCIM
                                  0.419-0.426
                                       0
                                       3
                                   <0.221
                                     0.331
                                   <0.258
                                     0.321
                                     0.259
                                     0.279
                                     0.036
     POTATO Proposed Use = 0.71 lb ai/A total application rate, 7-day PHI
Potato
Cyazofamid  + CCIM
                                  0.698-0.743
                                       7
                                      18
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
                                   <0.02
    SPINACH Proposed Use = 0.43 lb ai/acre total application rate, 0-day PHI
Spinach
Cyazofamid  + CCIM
                                  0.347-0.366
                                       0
                                      10
                                      1.5
                                      6.6
                                      1.6
                                      6.5
                                      3.1
                                      3.3
                                      1.5
     TOMATO Proposed Use = 0.43 lb ai/acre total application rate, 0-day PHI
Tomato
Cyazofamid  + CCIM
                                  0.413-0.434
                                       0
                                      16
                                   <0.02
                                   <0.17
                                   <0.02
                                   <0.16
                                     0.055
                                     0.063
                                     0.035
1  Except for sample min/max, values reflect per trial averages; n = no. of field trials.
2  LAFT = Lowest Average Field Trial; HAFT = Highest Average Field Trial; SD = Standard Deviation.  For computation of the LAFT, HAFT, median, mean, and standard deviation, values < LOQ are assumed to be at the LOQ of 0.01 ppm for each analyte.

Basil

The Interregional Research Project Number 4 (IR-4) has submitted field trial data for cyazofamid on basil.  Four field trials were conducted in the United States during the 2009-2010 growing seasons in the North American Free Trade Agreement (NAFTA) Growing Zones 2 (MD and NC; 2 trials) and 10 (CA and AZ; 2 trials).  In addition, two greenhouse trials were conducted in Zones 3 (FL) and 10 (CA).

Each trial consisted of one untreated plot and one treated plot.  At each trial location, the treated plot received nine foliar broadcast or directed applications of a 3.33 lb ai/gal suspension concentrate (SC) formulation of cyazofamid (Ranman(R) 400SC) at 0.074-0.083 lb ai/A/application, for a total seasonal rate of 0.693-0.721 lb ai/A.  Applications were made at 6- to 8-day retreatment intervals (RTIs) using ground equipment in spray volumes of 21.07-46.28 gal/A.  An organosilicone surfactant (OSS), Silwet L-77, was added to the spray mixture for each of the applications.  The use rates of adjuvant:formulated product were mostly 2:3 or 3:4, v/v.  Samples of fresh basil leaves and stems were harvested from all trials at a 0-day preharvest interval (PHI); additional samples were collected at PHIs of 4, 7, 10, and 14 days from one trial (MD04) to assess residue decline.  Additional leaves and stems were collected from four trials and dried for 1-3 days under ambient conditions or in an oven or forced air dryer to produce dried basil.

Samples were analyzed for residues of cyazofamid and its metabolite CCIM using an LC/MS/MS method adapted from a Pyxant Labs, Inc. analytical method.  The limits of quantitation (LOQs; determined as the lowest level of method validation, LLMV) in fresh and dried basil were 0.01 and 0.1 ppm, respectively, for each analyte.  The method was adequate for data collection based on acceptable method validation and concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries and residues in the treated samples were not corrected for residues in controls.  The analytical method does not specify conversion of metabolite residues to parent equivalents; therefore, quantifiable residues of CCIM were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.49 (MW of cyazofamid 324.79 / MW of CCIM 217.65).

Samples were stored frozen (-20 °C) from collection to analysis for 8-284 days (0.3-9.3 months) for fresh basil and 155-299 days (5.1-9.8 months) for dried basil.  Samples were analyzed within 0-1 days of extraction.  To support the sample storage intervals, a concurrent storage stability study was conducted with the field trial study.  The data demonstrate that residues of cyazofamid and CCIM were reasonably stable in/on dried basil stored frozen for up to 297 days and residues of cyazofamid were stable in/on fresh basil stored frozen for up to 284 days, but residues of CCIM in/on fresh basil declined by 46% after 284 days of freezer storage.  No 0-day data were provided.  Samples of fresh basil were stored up to 284 days prior to analysis; therefore, the CCIM residue values for fresh basil were adjusted for residue decline on storage.  No corrections for potential decline during storage are needed for residues of cyazofamid and CCIM in/on dried basil or for residues of cyazofamid in/on fresh basil from the submitted field trials; however, storage stability studies should always include a 0-day sampling interval to establish the residue levels present at the time samples are placed into storage [see OCSPP 860.1380(d)(6)(i)].

Following nine foliar broadcast or directed applications of the 3.33 lb ai/gal SC formulation of cyazofamid at 0.693-0.721 lb ai/A, residues (and per trial averages) of cyazofamid, CCIM, and combined residues, respectively, in/on fresh basil leaves and stems (from greenhouse and field trials) harvested at a 0-day PHI were 2.3-15 (2.5-14), 0.037-0.28 (0.040-0.28), and 2.4-15 (2.6-14) ppm; corresponding residues (and per trial averages) in/on dried basil leaves and stems (field trials only) were 9.3-43 (9.6-40), 1.5-16 (1.6-16), and 11-46 (11-43) ppm.

Residues were generally higher in samples from the greenhouse trials than in samples from the field trials.  In the field trials, residues (and per trial averages) of cyazofamid, CCIM, and combined residues, respectively, in/on fresh basil leaves and stems harvested at a 0-day PHI were 2.3-10 (2.5-9.4), 0.037-0.28 (0.040-0.28), and 2.4-10 (2.6-9.6) ppm; corresponding residues (and per trial averages) in/on fresh basil leaves and stems in the greenhouse trials were 12-15 (14-14), 0.092-0.15 (0.096-0.13), and 12-15 (14-14) ppm.  Dried basil leaves and stems were not collected in the greenhouse trials.

In the residue decline trial with fresh basil leaves and stems, average residues of cyazofamid and CCIM declined from 2.6 ppm at the 0-day PHI to <0.34 ppm at the 14-day PHI.

Bean, lima

IR-4 has submitted field trial data for cyazofamid on lima beans.  Eight field trials were conducted in the United States during the 2009 growing season in the NAFTA Growing Zones 2 (MD and NC; 4 trials), 5 (WI; 1 trial), 10 (CA; 2 trials), and 11 (ID; 1 trial).  Two trial pairs (MD15/MD24 and NC30/NC31) were each conducted at the same location.  Careful examination of the field trial records in accordance with ChemSAC guidance (Field Trial Differentiation, 2012 Protocol) indicates that the only differences between each pair of trials were: use of different varieties of lima beans (all trials), use of different tank mixes for all applications (all trials); and a 6-day off-set in application dates (NC30/NC31 trials only).  HED has concluded that the differences between the trials are insufficient to classify them as separate trials; therefore, each pair of trials constitutes a single trial with replicate samples for purposes of OCSPP 860.1500 data requirements.  The adjustment in trial numbers results in a total of six field trials, with two trials conducted in NAFTA Zone 2.

Each trial consisted of one untreated plot and one treated plot.  At each trial location, the treated plot received at least six foliar broadcast or directed applications of a 3.33 lb ai/gal SC formulation of cyazofamid (Ranman(R) 400SC) at 0.069-0.076 lb ai/A/application, for a total seasonal rate of 0.427-0.523 lb ai/A.  One additional application was required at three trial sites to allow the crop to mature (CA134) or due to unexpected rainfall occurring after the sixth application, thereby potentially impacting the residues if the samples were harvested following the rainfall (NC30 and NC31).  Applications were made at 6- to 8-day RTIs using ground equipment in spray volumes of 32.51-46.08 gal/A.  An OSS, Silwet L-77, was added to the spray mixture for each of the applications.  The use rate of adjuvant:formulated product was 3:4, v/v.  Samples of lima beans were harvested from all trials at a 0-day PHI, except for Trial NC31, where samples were harvested at a 1-day PHI to allow plants to dry following rainfall that occurred 3 hours after the last application.

Samples were analyzed for residues of cyazofamid and its metabolite CCIM using an LC/MS/MS method adapted from a Pyxant Labs, Inc. analytical method.  The LOQ, determined as the LLMV, was 0.01 ppm for each analyte.  The method was adequate for data collection based on acceptable method validation and concurrent recovery data.  The fortification levels used in method validation and concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries and residues in the treated samples were not corrected for residues in controls.  The analytical method does not specify conversion of metabolite residues to parent equivalents.  Residues of CCIM were not converted to parent equivalents in this study because residues of the metabolite were below the LOQ in/on all samples.

Samples were stored frozen (-20 °C) from collection to analysis for 63-147 days (2.1-4.8 months).  Samples were analyzed within 0-1 days of extraction.  Storage stability data generated concurrently with the field trial study demonstrate that residues of cyazofamid and CCIM were stable in/on samples of lima beans stored frozen for up to 140 days; no 0-day data were provided.  These data are acceptable to support the storage conditions and durations of samples from the submitted field trials; however, storage stability studies should always include a 0-day sampling interval to establish the residue levels present at the time samples are placed into storage [see OCSPP 860.1380(d)(6)(i)].

Following six to seven foliar broadcast or directed applications of the 3.33 lb ai/gal SC formulation of cyazofamid at 0.427-0.523 lb ai/A, residues (and per trial averages) of cyazofamid, CCIM, and combined residues, respectively, in/on lima bean succulent seeds harvested at a 0- to 1-day PHI were <0.01-0.047 (<0.01-0.040), <0.01 (<0.01), and <0.02-<0.057 (<0.02-<0.050) ppm.  Cyazofamid residues were only detected in the ID20 trial.  No residue decline data were submitted.

Bean, snap

IR-4 has submitted field trial data for cyazofamid on snap beans.  Eight field trials were conducted in the United States during the 2007 growing season in the NAFTA Growing Zones 2 (NJ, MD, and GA; 3 trials), 5 (MI and WI; 2 trials), 10 (CA; 2 trials), and 11 (WA; 1 trial).

Each trial consisted of one untreated plot and one treated plot.  At each trial location, the treated plot received at least six foliar broadcast or directed applications of a 3.33 lb ai/gal SC formulation of cyazofamid (Ranman(R) 400SC) at 0.069-0.079 lb ai/A/application, for a total seasonal rate of 0.426-0.507 lb ai/A.  One additional application was required at the CA10 trial to allow the crop to mature.  Applications were made at 6- to 9-day RTIs using ground equipment in spray volumes of 31.90-60.08 gal/A.  An OSS, Silwet L-77, was added to the spray mixture for each of the applications.  The use rate of adjuvant:formulated product was 3:4, v/v.  Samples of snap bean pods with seed and snap bean plants with pods were harvested from all trials at a 0-day PHI; additional samples of snap bean pods with seed were collected at PHIs of 2, 7, and 12 days from one trial (GA*11) to assess residue decline.

Samples were analyzed for residues of cyazofamid and its metabolite CCIM using an LC/MS/MS method adapted from a Pyxant Labs, Inc. analytical method.  The LOQ, determined as the LLMV, was 0.01 ppm for each analyte.  The method was adequate for data collection based on acceptable method validation and concurrent recovery data.  The fortification levels used in method validation and concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries and residues in the treated samples were not corrected for residues in controls.  The analytical method does not specify conversion of metabolite residues to parent equivalents; therefore, quantifiable residues of CCIM were converted to parent equivalents by the study reviewer using a molecular weight conversion factor of 1.49 (MW of cyazofamid 324.79 / MW of CCIM 217.65).

Samples were stored frozen (-20 °C) from collection to analysis for 861-946 days (28.3-31.1 months) for pods with seeds and 847-944 days (27.9-31.0 months) for plants with pods.  Samples were analyzed within 0-1 days of extraction.  Storage stability data generated concurrently with the field trial study demonstrate that residues of cyazofamid and CCIM were stable in/on samples of snap bean stored frozen for up to 887-889 days; no 0-day data were provided.  These data are acceptable to support the storage conditions and durations of samples from the submitted field trials; however, storage stability studies should always include a 0-day sampling interval to establish the residue levels present at the time samples are placed into storage [see OCSPP 860.1380(d)(6)(i)].

Following six to seven foliar broadcast or directed applications of the 3.33 lb ai/gal SC formulation of cyazofamid at 0.426-0.507 lb ai/A, residues (and per trial averages) of cyazofamid, CCIM, and combined residues, respectively, in/on snap bean pods with seeds harvested at a 0-day PHI were 0.012-0.22 (0.019-0.20), <0.01 (<0.01), and <0.022-<0.23 (<0.029-<0.21) ppm; corresponding residues (and per trial averages) in/on snap bean plants with pods were 1.0-3.6 (1.4-3.3), 0.017-0.099 (0.029-0.088), and 1.1-3.6 (1.4-3.3) ppm.

In the residue decline trial with snap bean pods with seeds, average residues of cyazofamid declined from 0.20 ppm at the 0-day PHI to 0.13 ppm at the 12-day PHI; residues of CCIM were <0.01 ppm in/on all samples.

Lettuce, head and leaf

IR-4 has submitted field trial data for cyazofamid on head and leaf lettuce.  Twenty-six field trials were conducted in the United States and Canada during the 2008-2009 growing seasons in the NAFTA Growing Zones.  Thirteen head lettuce trials were conducted in Zones 1 (NY; 1 trial), 3 (FL; 1 trial), 5 (ON; 2 trials), 5A (QC; 1 trial), 5B (QC; 1 trial), 10 (NM and CA; 6 trials), and 12 (BC; 1 trial), and thirteen leaf lettuce trials were conducted in Zones 2 (MD; 1 trial), 3 (FL; 1 trial), 5 (ON; 2 trials), 5A (QC; 1 trial), 5B (QC; 1 trial), 10 (NM and CA; 6 trials), and 12 (BC; 1 trial).

Four trial pairs [08-CA*04/08-CA*05 (Salinas, CA, head lettuce); 08-CA03/08-CA19 (Holtville, CA; head lettuce); 08-NM14/08-NM12 (Las Cruces, NM; leaf lettuce); and 08-CA*22/08-CA*21 (Salinas, CA; leaf lettuce)] were each conducted at the same location.  Careful examination of the field trial records in accordance with ChemSAC guidance (Field Trial Differentiation, 2012 Protocol) indicates that the only differences between each pair of trials were:  use of different varieties of lettuce (all trials), use of different tank mixes for all applications (all trials); an 8-day off-set in application dates (CA*22/CA*21 trials only); and a difference in soil type (loam vs. sandy loam; CA*22/CA*21 trials only).  HED has concluded that the differences between the trials are insufficient to classify them as separate trials; therefore, each pair of trials constitutes a single trial with replicate samples for purposes of OCSPP 860.1500 data requirements.  The adjustment in trial numbers results in a total of 22 field trials (11 head lettuce trials and 11 leaf lettuce trials), with four trials each for head lettuce and leaf lettuce conducted in NAFTA Zone 10.

Each trial consisted of one untreated plot and one treated plot.  At each trial location, the treated plot received at least six applications of a 3.33 lb ai/gal SC formulation of cyazofamid (Ranman(R) 400SC) at 0.065-0.079 lb ai/A/application (0.073-0.088 kg ai/ha/application), for a total seasonal rate of 0.419-0.587 lb ai/A (0.471-0.658 kg ai/ha).  The first application was made to soil as a post-plant application after seeding or a post-transplant application.  These applications were made on the day of or 1 day following planting or transplanting.  Subsequent applications were made as foliar broadcast or directed applications with RTIs of 6-78 days between applications 1 and 2 and 5-15 days (mostly 6-8 days) between applications 2 through 8; applications were timed so that mature lettuce could be collected immediately following the final application (after the test substance had dried).  One to two additional applications were required in five trials (CA*05, CA*04, NM11, NM14, and ON Trial 690) to allow the crop to mature.  All applications were made using ground equipment in spray volumes of 30-49 gal/A (283-460 L/ha).  A non-ionic surfactant (NIS; Sylgard 309) or OSS (Silwet L-77) was added to the spray mixture for each of the applications except for the first post-plant applications (all trials) and some post-transplant applications.  The use rate of adjuvant:formulated product was 3:4, v/v.  Samples of head lettuce with wrapper leaves and leaf lettuce were harvested from all trials at a 0-day PHI; additional samples were collected at PHIs of 4, 7, 15, and 21 days from one leaf lettuce trial (CA*22) to assess residue decline.  In addition, samples of head lettuce without wrapper leaves were also collected at the three 2009 Canadian head lettuce trials.

Samples were analyzed for residues of cyazofamid and metabolite CCIM using an LC/MS/MS method adapted from a Pyxant Labs, Inc. analytical method.  The LOQ, determined as the LLMV, was 0.01 ppm for each analyte.  The method was adequate for data collection based on acceptable method validation and concurrent recovery data.  The fortification levels used in concurrent method recovery were adequate to bracket expected residue levels.  Concurrent recoveries and residues in the treated samples were not corrected for residues in controls.  Since the analytical method does not specify conversion of metabolite residues to parent equivalents, quantifiable residues of CCIM were converted to parent equivalents by the study reviewer using a molecular weight (MW) conversion factor of 1.49 (MW of cyazofamid of 324.79 / MW of CCIM of 217.65).

Samples were stored frozen (-20 to -8.9 °C) from collection to analysis for 208-634 days (6.8-20.8 months) for head lettuce and 251-624 days (8.3-20.5 months) for leaf lettuce.  Samples were analyzed within 0-1 days of extraction.  Storage stability data generated concurrently with the field trial study demonstrate that residues of cyazofamid and CCIM were stable in/on samples of leaf lettuce stored frozen for up to 634 days; no 0-day data were provided.  These data are acceptable to support the storage conditions and durations of samples from the submitted field trials.  Any storage stability studies which may be submitted in the future should always include a 0-day sampling interval to establish the residue levels present at the time samples are placed into storage [see OCSPP 860.1380(d)(6)(i)].

Following one soil banded application made post-planting or post-transplant and five to seven foliar broadcast or directed applications (six to eight total applications) of the 3.33 lb ai/gal SC formulation of cyazofamid at 0.419-0.587 lb ai/A (0.471-0.658 kg ai/ha), residues (and per trial averages) of cyazofamid, CCIM, and combined residues, respectively, in/on head lettuce with wrapper leaves harvested at a 0-day PHI were 0.05-2.0 (0.070-1.8), <0.01-0.044 (<0.01-0.038), and <0.06-2.0 (<0.080-1.8) ppm; corresponding residues (and per trial averages) in/on head lettuce without wrapper leaves were <0.01-0.57 (<0.01-0.55), <0.01-0.019 (<0.01-0.018), and <0.02-0.59 (<0.02-0.58) ppm.  Residues (and per trial averages) of cyazofamid, CCIM, and combined residues, respectively, in/on leaf lettuce harvested at a 0-day PHI were 0.48-4.5 (0.53-4.5), <0.01-0.074 (<0.013-0.064), and <0.49-4.6 (<0.54-4.5) ppm.

In the residue decline trial with leaf lettuce, average combined residues of cyazofamid and CCIM declined from 2.8 ppm at the 0-day PHI to <0.12 ppm at the 21-day PHI.

Crop Groups

Fruiting Vegetable Group 8-10

A tolerance of 0.40 ppm is established for the fruiting vegetable group 8.  The representative commodities for Crop Group 8-10 are tomato, standard size, and one cultivar of small tomato; bell pepper and one cultivar of small nonbell pepper.

Tomato

Residue data have previously been reviewed for tomatoes (DP# D285680, A. Acierto, 2/20/04 and 10/1/04; 45409031.der).   The residue data included data on the standard size tomato and on Roma tomato, which is a small tomato.  Sixteen field trials were conducted on tomato with a PHI of 0 days.  Six broadcast foliar applications were made at the rate of approximately 0.071 lb ai/A/application for a total of 0.413-0.434 lb ai/A/season with retreatment intervals of mostly 6-8 days and a 0-day PHI.  An OSS was used in several field trials on tomato.  The use rate of adjuvant:formulated product was 3:4, v/v.

Pepper

Residue data have previously been reviewed for bell and nonbell pepper (DP# D357042, A. Acierto, 3/18/09; 47528401.der).  Six field trials were conducted on bell pepper and three field trials were conducted on nonbell pepper.  Six broadcast foliar applications were made at the rate of 0.067-0.075 lb ai/A/application for a total of 0.418-0.429 lb ai/A/season with retreatment intervals of 6-8 days and a 0-day PHI.  An OSS was used in all field trials on pepper. The use rate of adjuvant:formulated product was 3:4, v/v.

Conclusion re. fruiting vegetable group 8-10.

The currently registered label for fruiting vegetables (letter dated 8/13/10) and the proposed label for the fruiting vegetable group 8-10 are the same regarding the methods of application, number of applications, application rates, interval between foliar applications, and PHI.

The residue data supporting the established fruiting vegetable group 8 tolerance support the fruiting vegetable group 8-10 tolerance; however, the OECD calculator using average field trial residues gives tolerance levels of 0.2 ppm for tomato, 0.4 ppm for bell pepper, and 0.9 ppm for nonbell pepper; therefore, the tolerance for the fruiting vegetable crop group should be 0.9 ppm instead of the proposed 0.40 ppm.

Leafy greens subgroup 4A

The representative commodities for the leafy greens subgroup 4A are head lettuce, leaf lettuce, and spinach.  The head and leaf lettuce field trials adequately reflect the proposed use.  The spinach trials reflect five applications instead of the proposed six.

Head Lettuce: Six to seven applications were made to head lettuce, at 0.07-0.08 lb ai/A/application.  The first application was a post-plant or post-transplant directed band applied 0-1 day after seeding or transplanting.  Five or six foliar applications were made, mostly six to eight days apart.  The PHI was 0 days.  The total applied was 0.419-0.506 lb ai/A/crop.  An NIS or OSS surfactant was used with all foliar applications.

Leaf Lettuce: Six to eight applications were made to head lettuce, at 0.07 -0.08 lb ai/A/application.  The first application was a post-plant or post-transplant directed band applied 0-1 day after seeding or transplanting.  Five to seven foliar applications were made, six to eight days apart.  The PHI was 0 days.  The total applied was 0.427-0.587 lb ai/A/crop.  An NIS or OSS was used with all foliar applications.

Spinach: Field trials on spinach were previously reviewed (MRID 47870704; D371162, A. Acierto, 2/24/10).  At each test location, five foliar applications of Ranman 400SC were made at the target rate of 0.072 lb ai/A/application for a total of 0.347-0.366 lb ai/A/season, with 7 (+- 1) day intervals and a 0-day PHI.  An OSS, Silwet L-77, was used in all field trials.  Foliar broadcast applications were made at all field sites except TX*12, where foliar directed applications were made.

Five applications totaling 0.347-0.366 lb ai/A were made in the field trials, whereas the proposed use would allow six applications totaling 0.43 lb ai/A.  The current Ranman 400SC label (letter dated 8/13/10) restricts the number of applications on spinach to five.  The OECD calculator using average field trial residues gives a value of 10 ppm for spinach.

Conclusion re. leafy greens subgroup 4A.

The highest residue value for spinach was 6.6 ppm, reflecting five foliar applications.  A 10 ppm tolerance can be reasonably expected to be adequate to cover an additional sixth application.

Vegetable, tuberous and corm, subgroup 1C

A tolerance is established on potato at 0.02 ppm.  The only representative commodity for the tuberous and corm vegetable subgroup 1C is potato.

Field trial data on potato were previously reviewed (D285680, A. Acierto, 2/20/04; 45409033.der).  Residue data reflected seven to ten broadcast foliar applications for total application rates of 0.698-0.743 lb ai/A with retreatment intervals of 5-8 days and a 7-day PHI.   An OSS, Silwet L-77, was used in all field trials.  The LOQ of the HPLC/UV method (MRID 45409020) was 0.01 ppm for each analyte.  Combined residues of cyazofamid and CCIM were all <0.02 ppm.  The residue data on potato can be used to support a subgroup 1C tolerance.

The current Ranman 400SC label (letter dated 8/13/10) for potato is consistent with the proposed use directions for potato with respect to methods of application, number of applications, application rates, interval between foliar applications, and PHI.

Conclusion re. tuberous and corm vegetable subgroup 1C.  The previously submitted residue data on potato supports the proposed use and the proposed 0.02 ppm tolerance on the tuberous and corm vegetable subgroup 1C.

Processed Food and Feed (860.1520)

Amelia Acierto, 2/20/04, DP# D285680, PP#1F06305, Cyazofamid. Petition for the Establishment of Permanent Tolerances for Use on Cucurbits, Potatoes, Tomatoes, and Imported Wine Grapes.  Summary of Analytical Chemistry and Residue Data; 45409033.de2 (potato) and 45409031.de2 (tomato)

Amelia Acierto, 3/18/09, DP# D357042, Cyazofamid.  Amend Section 3 to Add Uses on Fruiting Vegetables, Okra, Grape (East of the Rocky Mountains), and Greenhouse Vegetable Transplants.  Summary of Analytical Chemistry and Residue Data.

No additional processing studies have been submitted.  Processing studies have previously been reviewed on potato and tomato.  The analytical method used in the potato and tomato processing studies was the HPLC/UV enforcement method (MRID 45409020).

Potato: No detectable residues of cyazofamid or CCIM were found in the potato tubers used for processing or the processed commodities (chips, flakes, and wet peel).  The reviewer requested that a study be conducted at 5x because the RAC samples that were used for processing bore nondetectable (<0.01 ppm) residues after treatments at an exaggerated rate of ~1.9x, which is less than the maximum theoretical concentration factor of 5.0x for potatoes.  The petitioner submitted the following response in MRID 46537730:

      "The maximum label application for cyazofamid to potatoes is 0.071 lb ai/A applied 10 times at 7-day intervals.  For the processing study, applications 1 through 6 were made at 0.070-0.073 lb ai/A and at 7-day intervals.  Applications 7 through 10 were made at 5- day intervals.  The final application was at a l0x rate (0.713 lb ai/A).  Cyazofamid has been shown to have a half-life of about 1 day on crops such as cucumber, cantaloupe, summer squash and tomato.  With this short half-life there is essentially no carryover from one application to the next even with the shorter 5-day interval.  Consequently the final application is the only application that will potentially result in residues on the RAC and it was applied at 10 X the label rate.  In addition, the label PHI is 7 days but in the potatoes grown for processing the samples were collected at a PHI of 3 days. The potatoes were delivered to the processor within a couple of hours of sampling since the processor was only 20 miles from the field site. The samples were stored for 19 days at 7 °C +- 3 °C prior to processing.

      The use of exaggerated rates of application is to assure that residues are present to determine the concentration or lack thereof after processing. Two representative samples were taken for analysis in the field. One sample had 0.02 ppm cyazofamid and 0.01 ppm CCIM.  The other sample had <0.01 ppm for both compounds.  Therefore, the desired residues were present in the field.  Samples taken 19 days later at the time of processing had residues <0.01 ppm for both compounds.  Storage for periods longer than 19 days is typical for potatoes being processed into chips or granules.  The processing loss is clearly in the storage phase of the processing, not in the production of the potatoes.  Considering
      that the last application rate used was 10X the proposed rate and the PHI was decreased to 3 days, it is unlikely that repeating the study with multiple applications at 5X at 7-day intervals would achieve residues any higher than those found in this study.  Consequently, it is ISK Biosciences Corporation's opinion that this study is scientifically valid and that a replacement is not needed."

The potato processing study is adequate to conclude that the combined residues in the processed commodities are not likely to exceed the 0.02 ppm tolerance level on the potato tuber.

Tomato:  The tomato processing data indicated that residues of cyazofamid do not concentrate in tomato paste and puree (processing factors of <0.3x) and residues of CCIM do not concentrate significantly in puree but concentrated by a factor of 4x in tomato paste.  Although concentration of CCIM in tomato paste was observed, combined residues of cyazofamid and CCIM are not likely to concentrate in tomato processed commodities to exceed the tolerance on the RAC.

Conclusions.   No additional processing studies have been submitted and none are required.  The previously submitted tomato and potato processing studies are adequate to show that residues in tomato and potato processed commodities will not concentrate above the tolerance levels for the raw agricultural commodities; therefore, separate tolerances on the processed commodities of tomato and potato are not required.

Rotational Crops (Field; 860.1900)

Breann Hanson, 8/3/10, DP# D376500, Cyazofamid.  Human Health Risk Assessment for Proposed Section 18 Use on Basil.

Since the results of the confined rotational crop study showed that cyazofamid and structurally related metabolites are each expected to be present at a level less than 0.01 ppm at a plantback interval of 30 days, no field rotational crop studies are required.

Tolerance Derivation

The Organization for Economic Cooperation and Development (OECD) tolerance calculation procedures were used to determine tolerance estimates for the raw agricultural commodities.  Average values of replicate samples for each field trial constituted the database.

For consideration of crop group or subgroup tolerances, the representative commodities were evaluated individually to determine a tolerance estimate for each representative crop; the highest tolerance estimate was used for the crop group or subgroup tolerance.

All trials were conducted within +-25% of the good agricultural practices (GAP) application rate and PHI.  Therefore, proportionality was not considered for any of the trials.

An organosilicone surfactant (OSS) was used in all field trials on basil, snap beans, lima beans, pepper, potato, and spinach and on several field trials on tomato.  A nonionic surfactant (NIS) or OSS was used in all field trials on head lettuce and leaf lettuce.  The adjuvant: Ranman 400SC use rate was 3:4 (v/v) for all crops except basil; for basil, the adjuvant use rate was mostly 2:3 or 3:4 (v/v).

The data collection methods were an HPLC/UV method or an LC/MS/MS method which is a modified version of the HPLC/UV method.  Both methods determine parent and CCIM with an LOQ of 0.01 for each analyte in basil, snap bean, lima bean, lettuce, pepper, potato, spinach, and tomato RACs, and an LOQ of 0.1 ppm for each analyte in dried basil.

An OECD tolerance calculation was not conducted for potato since all residues in the potato field trial were less than the LOQ.

Some censored data (combined residues <0.02 ppm) were included in the data set for lima bean.  The tomato data set contained one censored residue level.

The residue values used as inputs and the recommended tolerances are summarized below.

Basil, fresh (MRID 48629402)

A tolerance of 30 ppm is appropriate for fresh basil based on six trials (four field trials and two greenhouse trials) at a total seasonal application rate of 0.693-0.721 lb ai/A with a 0-day PHI.

0.693-0.721 lb ai/A; 0-day PHI
                               Residues (mg/kg)
                                       n
                                      2.6
                                       1
                                      2.9
                                       1
                                      7.4
                                       1
                                      9.6
                                       1
                                      14
                                       2

                                  Cyazofamid
                                 Basil -fresh
                                      USA
                        0.693-0.721 lb ai/A; 0-day PHI

Total number of data (n)
                                       6
Percentage of censored data
                                      0%
Number of non-censored data
                                       6
Lowest residue
                                     2.600
Highest residue
                                    14.000
Median residue
                                     8.500
Mean
                                     8.417
Standard deviation (SD)
                                     5.080
Correction factor for censoring (CF)
                                     1.000

Proposed MRL estimate

- Highest residue
                                    14.000
- Mean + 4 SD
                                    28.738
- CF x 3 Mean
                                    25.250
Unrounded MRL
                                    28.738

Rounded MRL
                                      30

 High uncertainty of MRL estimate.
[Small dataset]

Basil, dried (MRID 48629402)

A tolerance of 90 ppm is appropriate for dried basil.

0.693-0.721 lb ai/A; 0-day PHI
                               Residues (mg/kg)
                                       n
                                      11
                                       1
                                      29
                                       1
                                      30
                                       1
                                      43
                                       1

                                  Cyazofamid
                                  Basil-dried
                                      USA
                        0.693-0.721 lb ai/A; 0-day PHI

Total number of data (n)
                                       4
Percentage of censored data
                                      0%
Number of non-censored data
                                       4
Lowest residue
                                    11.000
Highest residue
                                    43.000
Median residue
                                    29.500
Mean
                                    28.250
Standard deviation (SD)
                                    13.150
Correction factor for censoring (CF)
                                     1.000

Proposed MRL estimate

- Highest residue
                                    43.000
- Mean + 4 SD
                                    80.849
- CF x 3 Mean
                                    84.750
Unrounded MRL
                                    84.750

Rounded MRL
                                      90

 High uncertainty of MRL estimate.
[Small dataset]

Bean, lima (MRID 48629404)

A tolerance of 0.08 ppm is appropriate for bean, succulent, shelled based on the residue data for lima bean.

0.427-0.523 lb ai/A; 0-1 day PHI
                               Residues (mg/kg)
                                       n
                                   < 0.02
                                       5
                                     0.05
                                       1

                                  Cyazofamid
                                     Crop
                                   Lima Bean
                        0.427-0.523 lb ai/A; 0-day PHI

Total number of data (n)
                                       6
Percentage of censored data
                                      83%
Number of non-censored data
                                       1
Lowest residue
                                     0.020
Highest residue
                                     0.050
Median residue
                                     0.020
Mean
                                     0.025
Standard deviation (SD)
                                     0.012
Correction factor for censoring (CF)
                                     0.444

Proposed MRL estimate

- Highest residue
                                     0.050
- Mean + 4 SD
                                     0.074
- CF x 3 Mean
                                     0.033
Unrounded MRL
                                     0.074

Rounded MRL
                                     0.08

 High uncertainty of MRL estimate.
[Small dataset and high level of censoring]

Bean, snap (MRID 48629403)

A tolerance of 0.5 ppm is appropriate for bean, succulent based on the residue data for snap bean.

0.426-0.507 lb ai/A; 0-day PHI
                               Residues (mg/kg)
                                       n
                                     0.029
                                       1
                                     0.056
                                       1
                                     0.068
                                       1
                                     0.11
                                       1
                                     0.12
                                       1
                                      0.2
                                       2
                                     0.21
                                       1

                                  Cyazofamid
                                   Snap bean
                                      USA
                        0.426-0.507 lb ai/A; 0-day PHI

Total number of data (n)
                                       8
Percentage of censored data
                                      0%
Number of non-censored data
                                       8
Lowest residue
                                     0.029
Highest residue
                                     0.210
Median residue
                                     0.115
Mean
                                     0.124
Standard deviation (SD)
                                     0.072
Correction factor for censoring (CF)
                                     1.000

Proposed MRL estimate

- Highest residue
                                     0.210
- Mean + 4 SD
                                     0.411
- CF x 3 Mean
                                     0.372
Unrounded MRL
                                     0.411

Rounded MRL
                                      0.5

Lettuce, head (MRIDs 48629401 and 48629405)

The appropriate tolerance for the leafy greens subgroup 4A is 10 ppm, which is the highest level for the representative crops of the subgroup: head lettuce (4 ppm), leaf lettuce (8 ppm), and spinach (10 ppm).

0.419-0.506 lb ai/A; 0-day PHI
                               Residues (mg/kg)
                                       n
                                     0.08
                                       1
                                      0.2
                                       1
                                     0.27
                                       1
                                     0.47
                                       1
                                     0.51
                                       1
                                     0.65
                                       1
                                     0.74
                                       1
                                      1.3
                                       1
                                      1.5
                                       1
                                      1.6
                                       1
                                      1.8
                                       1

                                  Cyazofamid

                                 Head lettuce

                                USA and Canada

                        0.419-0.506 lb ai/A; 0-day PHI

Total number of data (n)
                                      11

Percentage of censored data
                                      0%

Number of non-censored data
                                      11

Lowest residue
                                     0.080

Highest residue
                                     1.800

Median residue
                                     0.650

Mean
                                     0.829

Standard deviation (SD)
                                     0.612

Correction factor for censoring (CF)
                                     1.000

Proposed MRL estimate

- Highest residue
                                     1.800

- Mean + 4 SD
                                     3.278

- CF x 3 Mean
                                     2.487

Unrounded MRL
                                     3.278

Rounded MRL
                                       4

Lettuce, leaf (MRIDs 48629401 and 48629405)

The appropriate tolerance for the leafy greens subgroup 4A is 10 ppm, which is the highest level for the representative crops of the subgroup: head lettuce (4 ppm), leaf lettuce (8 ppm), and spinach (10 ppm).

0.427-0.587 lb ai/A; 0-day PHI
                               Residues (mg/kg)
                                       n
                                     0.54
                                       1
                                      0.8
                                       1
                                     0.91
                                       1
                                     0.93
                                       1
                                      1.4
                                       1
                                      1.8
                                       1
                                      2.8
                                       2
                                      2.9
                                       1
                                      3.6
                                       1
                                      4.5
                                       1

                                  cyazofamid
                                 Leaf lettuce
                                USA and Canada
                        0.427-0.587 lb ai/A; 0-day PHI

Total number of data (n)
                                      11
Percentage of censored data
                                      0%
Number of non-censored data
                                      11
Lowest residue
                                     0.540
Highest residue
                                     4.500
Median residue
                                     1.800
Mean
                                     2.089
Standard deviation (SD)
                                     1.308
Correction factor for censoring (CF)
                                     1.000

Proposed MRL estimate

- Highest residue
                                     4.500
- Mean + 4 SD
                                     7.322
- CF x 3 Mean
                                     6.267
Unrounded MRL
                                     7.322

Rounded MRL
                                       8

Pepper, bell (MRID 47528401)

The appropriate tolerance for the fruiting vegetable group 8-10 is 0.9 ppm, which is the highest level for the representative crops of the subgroup: bell pepper (0.4 ppm), nonbell pepper (0.9 ppm), and tomato (0.2 ppm).

0.418-0.429 lb ai/A; 0-day PHI
                               Residues (mg/kg)
                                       n
                                     0.048
                                       1
                                     0.065
                                       1
                                     0.068
                                       1
                                     0.082
                                       1
                                     0.108
                                       1
                                     0.236
                                       1

                                  Cyazofamid
                                  Bell Pepper
                                      USA
                        0.418-0.429 lb ai/A; 0-day PHI

Total number of data (n)
                                       6
Percentage of censored data
                                      0%
Number of non-censored data
                                       6
Lowest residue
                                     0.048
Highest residue
                                     0.236
Median residue
                                     0.075
Mean
                                     0.101
Standard deviation (SD)
                                     0.069
Correction factor for censoring (CF)
                                     1.000

Proposed MRL estimate

- Highest residue
                                     0.236
- Mean + 4 SD
                                     0.377
- CF x 3 Mean
                                     0.304
Unrounded MRL
                                     0.377

Rounded MRL
                                      0.4

 High uncertainty of MRL estimate.
[Small dataset]

Pepper, nonbell (MRID 47528401)

The appropriate tolerance for the fruiting vegetable group 8-10 is 0.9 ppm, which is the highest level for the representative crops of the subgroup: bell pepper (0.4 ppm), nonbell pepper (0.9 ppm), and tomato (0.2 ppm).

  0.419-0.426 lb ai/A; 0-day PHI
                               Residues (mg/kg)
                                       n
                                     0.258
                                       1
                                     0.259
                                       1
                                     0.321
                                       1

                                  Cyazofamid
                                Nonbell Pepper
                                      USA
                          0.419-0.426 lb ai/A; 0-day

Total number of data (n)
                                       3
Percentage of censored data
                                      0%
Number of non-censored data
                                       3
Lowest residue
                                     0.258
Highest residue
                                     0.321
Median residue
                                     0.259
Mean
                                     0.279
Standard deviation (SD)
                                     0.036
Correction factor for censoring (CF)
                                     1.000

Proposed MRL estimate

- Highest residue
                                     0.321
- Mean + 4 SD
                                     0.424
- CF x 3 Mean
                                     0.838
Unrounded MRL
                                     0.838

Rounded MRL
                                      0.9

 High uncertainty of MRL estimate.
[Small dataset]

Spinach (MRID 47870704)

The appropriate tolerance for the leafy greens subgroup 4A is 10 ppm, which is the highest level for the representative crops of the subgroup: head lettuce (4 ppm), leaf lettuce (8 ppm), and spinach (10 ppm).

0.347-0.366 lb ai/A; 0-day PHI
                               Residues (mg/kg)
                                       n
                                     1.61
                                       1
                                     2.03
                                       1
                                      2.1
                                       1
                                     2.18
                                       1
                                     2.94
                                       1
                                     3.34
                                       1
                                     3.49
                                       1
                                     3.64
                                       1
                                     4.74
                                       1
                                     6.52
                                       1

                                  Cyazofamid
                                    Spinach
                                      USA
                        0.347-0.366 lb ai/A; 0-Day PHI

Total number of data (n)
                                      10
Percentage of censored data
                                      0%
Number of non-censored data
                                      10
Lowest residue
                                     1.610
Highest residue
                                     6.520
Median residue
                                     3.140
Mean
                                     3.259
Standard deviation (SD)
                                     1.486
Correction factor for censoring (CF)
                                     1.000

Proposed MRL estimate

- Highest residue
                                     6.520
- Mean + 4 SD
                                     9.203
- CF x 3 Mean
                                     9.777
Unrounded MRL
                                     9.777

Rounded MRL
                                      10

Tomato (MRID #s 45409031, 45638507, 45638508)

The appropriate tolerance for the fruiting vegetable group 8-10 is 0.9 ppm, which is the highest level for the representative crops of the subgroup: bell pepper (0.4 ppm), nonbell pepper (0.9 ppm), and tomato (0.2 ppm).

0.413-0.434 lb ai/A; 0-day PHI
                               Residues (mg/kg)
                                       n
                                   < 0.02
                                       1
                                     0.035
                                       1
                                     0.04
                                       2
                                     0.045
                                       2
                                     0.05
                                       2
                                     0.06
                                       3
                                     0.065
                                       1
                                     0.075
                                       1
                                     0.085
                                       1
                                     0.12
                                       1
                                     0.16
                                       1

                                  Cyazofamid
                                    Tomato
                                      USA
                        0.413-0.434 lb ai/A; 0-day PHI

Total number of data (n)
                                      16
Percentage of censored data
                                      6%
Number of non-censored data
                                      15
Lowest residue
                                     0.020
Highest residue
                                     0.160
Median residue
                                     0.055
Mean
                                     0.063
Standard deviation (SD)
                                     0.035
Correction factor for censoring (CF)
                                     0.958

Proposed MRL estimate

- Highest residue
                                     0.160
- Mean + 4 SD
                                     0.202
- CF x 3 Mean
                                     0.181
Unrounded MRL
                                     0.202

Rounded MRL
                                      0.2

 References

Acierto, A., 2/18/04, DP# D298915, Cyazofamid  -  Meeting Report of the Metabolism Assessment Review

Acierto, A., 2/20/04, DP# D285680, PP#1F06305, Cyazofamid. Petition for the Establishment of Permanent Tolerances for Use on Cucurbits, Potatoes, Tomatoes, and Imported Wine Grapes.  Summary of Analytical Chemistry and Residue Data.

Acierto, A., 3/18/09, DP# D357042, Cyazofamid.  Amend Section 3 to Add Uses on Fruiting Vegetables, Okra, Grape (East of the Rocky Mountains), and Greenhouse Vegetable Transplants.  Summary of Analytical Chemistry and Residue Data.

Acierto, A., 2/24/10, DP# D371162, Cyazofamid.  Tolerance Petition for Uses on Brassica (Cole) Leafy Vegetables Crop Group 5, Turnip Greens, Spinach, and Hops.  Summary of Analytical Chemistry and Residue Data.

Hanson, B., 8/3/10, DP# D376500, Cyazofamid.  Human Health Risk Assessment for Proposed Section 18 Use on Basil.

Kolbe, E., 10/22/03, DP# D286108, PP# 3F6595.  Cyazofamid on Potatoes, Tomatoes, Cucurbit and Grapes.  Tolerance Method Review and Multi-Residue Method Review.  PC Code 085651 (MRID#: 454090-33, 456385-08, 454090-34, 454090-32, 454090-20, 454090-22); ACB # B02-(58-61).

Kolbe, E., 2/27/06, DP# D326164, PP# 3F6595.  Review of Resubmitted Analytical Method for Cyzofamid and its Metabolite CCIM in Crops. PC Code 085651 (MRID#: 46550401); ACB Project # B06-13.

OPPTS/US EPA, September 2004, Pesticide Fact Sheet: Cyazofamid

Appendix A.  Field Trial Geographic Distribution.

TABLE A.1.	Trial Numbers and Geographical Locations.

NAFTA Growing Zones
                                 Head Lettuce
                                 Leaf Lettuce

                                   Submitted
                                 Requested[1]
                                   Submitted
                                 Requested[1]

                                    Canada
                                      US

                                    Canada
                                      US
1
                                       1
                                      --
                                   1[2]/1[2]
                                      --
                                      --
                                   1[2]/1[2]
1A
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
2
                                      --
                                      --
                                   1[2]/1[2]
                                       1
                                      --
                                   1[2]/1[2]
3
                                       1
                                      --
                                      1/1
                                       1
                                      --
                                      1/1
4
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
5
                                       2
                                       1
                                      --
                                       2
                                       1
                                      --
5A
                                       1
                                      --
                                      --
                                       1
                                      --
                                      --
5B
                                       1
                                       3
                                      --
                                       1
                                       3
                                      --
6
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
7
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
7A
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
8
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
9
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
10
                                     4[3]
                                      --
                                      6/4
                                     4[3]
                                      --
                                      6/4
11
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
12
                                       1
                                       1
                                      --
                                       1
                                       1
                                      --
Total
                                     11[3]
                                       5
                                      8/6
                                     11[3]
                                       5
                                      8/6
[1] For the US, as per OCSPP 860.1500, Table 5 for head and leaf lettuce.   The second number reflects a 25% reduction in the number of trials allowed for the crop as a representative commodity in support of a crop group/subgroup tolerance or when application results in no quantifiable residues.  For Canada, as per Regulatory Directive - Dir98-02, Section 9 - Crop Field Trials. Appendix III, Table 2 for lettuce.
[2] Trial can be conducted in either Zone 1 or Zone 2.
[3] HED has concluded that trial pairs 08-CA*04/08-CA*05 and 08-CA03/08-CA19 for head lettuce, and trial pairs 08-NM14/08-NM12, and 08-CA*22/08-CA*21 for leaf lettuce each constitute a single trial with replicate samples for purposes of OCSPP 860.1500 data requirements.

TABLE A.2.	Trial Numbers and Geographical Locations.
NAFTA Growing Regions
                                     Basil

                                   Submitted
                                 Requested[1]

                                    Canada
                                     U.S.
1
                                      --
                                      --
                                      --
1A
                                      --
                                      --
                                      --
2
                               2 (field trials)
                                      --
                                      --
3
                             1 (greenhouse trial)
                                      --
                                      --
4
                                      --
                                      --
                                      --
5
                                      --
                                      --
                                      --
5A
                                      --
                                      --
                                      --
5B
                                      --
                                      --
                                      --
6
                                      --
                                      --
                                      --
7
                                      --
                                      --
                                      --
7A
                                      --
                                      --
                                      --
8
                                      --
                                      --
                                      --
9
                                      --
                                      --
                                      --
10
                               2 (field trials)
                             1 (greenhouse trial)
                                      --
                                      --
11
                                      --
                                      --
                                      --
12
                                      --
                                      --
                                      --
Total
                               4 (field trials)
                             2 (greenhouse trials)
                                      --
                                       3
[1] As per OCSPP 860.1500, Tables 2 and 3 for basil as a representative commodity of the herb crop group/subgroup; Tables 1 and 5 do not include basil.  Three field trials are required in major basil producing regions.

TABLE A.3.	Trial Numbers and Geographical Locations.

NAFTA Growing Zones
                                   Snap Bean
                                   Lima Bean

                                   Submitted
                                 Requested[1]
                                   Submitted
                                 Requested[1]

                                    Canada
                                      US

                                    Canada
                                      US
1
                                      --
                                      --
                                      1/1
                                      --
                                      --
                                      --
1A
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
2
                                       3
                                      --
                                      1/1
                                     2[2]
                                      --
                                      4/3
3
                                      --
                                      --
                                      1/1
                                      --
                                      --
                                      --
4
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
5
                                       2
                                      --
                                      3/2
                                       1
                                      --
                                      1/1
5A
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
5B
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
6
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
7
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
7A
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
8
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
9
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
10
                                       2
                                      --
                                      1/0
                                       2
                                      --
                                      2/1
11
                                       1
                                      --
                                      1/1
                                       1
                                      --
                                      1/1
12
                                      --
                                      --
                                      --
                                      --
                                      --
                                      --
Total
                                       8

                                      8/6
                                     6[2]

                                      8/6

[1] As per OCSPP 860.1500, Table 5 for snap bean or lima bean.   The second number reflects a 25% reduction in the number of trials allowed for the crop as a representative commodity in support of a crop group/subgroup tolerance or when application results in no quantifiable residues.

[2]  HED has concluded that lima bean trial pairs MD15/MD24 and NC30/NC31 each constitute a single trial with replicate samples for purposes of OCSPP 860.1500 data requirements.

Appendix B: International Residue Limits

                        Cyazofamid (085651; 02/01/2012)
Table B.  Summary of US and International Tolerances and Maximum Residue Limits
Residue Definition:
US
Canada
Mexico[2]
Codex[3]
40 CFR 180.601: