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

                                                 	OFFICE OF CHEMICAL SAFETY AND
	                                                                              POLLUTION PREVENTION
	


MEMORANDUM

Date:		5/18/11	

SUBJECT:			Abamectin.  Petition for Tolerances/Section 3 Registration on the Bulb Onion Subgroup 3-07A, Chives, and Dry Beans.  Summary of Analytical Chemistry and Residue Data.
		 
PC Code:  122804
DP Barcode:  380795   
Decision No.: 436528
Registration No.: 100-1351, 100-898, 100-1154 
Petition No.: 0E7738
Regulatory Action: Section 3 Registration
Risk Assessment Type: None
Case No.: None
TXR No.: None
CAS No.: 71751-41-2
MRID Nos.: 48135001, 48135002, 48135003 (see MRID Summary Table)
40 CFR: 180.449
	              																		   	
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, RM#5
		Registration Division (7505P)



MRID Summary Table 
Study Type
MRID
Comments
860.1500 - Crop Field Trial
48135001
New DER; 48135001.der; Bulb onion
860.1500 - Crop Field Trial
48135002
New DER; 48135002.der; Chives
860.1500 - Crop Field Trial
48135003
New DER; 48135003.der; Dry Beans

Note: This DER was originally prepared under contract by Versar, Inc. (6850 Versar Center, Springfield, VA 22151; submitted 12/21/10).  The DER has been reviewed by the Health Effects Division (HED) and revised to reflect current Office of Pesticide Programs (OPP) policies.
Executive Summary

Abamectin is a mixture of avermectin B1 [a mixture of avermectins containing greater than or equal to 80% avermectin B1a (5-O-demethyl avermectin A1) and less than or equal to 20% avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)] and its delta-8,9-isomer.  Abamectin is a natural fermentation product of the soil bacterium Streptomyces avermitilis.  Abamectin is an insecticide/miticide used to control mites, leafminers, and other insects in commercially important crops.  Abamectin acts as an insecticide by interfering with the nervous system of the insect, causing the insect to become paralyzed.  Available mechanistic data indicate a neurotoxic mechanism of action, related to interference with GABA-mediated neurotransmission.  

In this petition (PP#0E7738), the Interregional Research Project No. 4 (IR-4) has proposed label amendments for three products to include uses on the bulb onion subgroup 3-07A, chives, and dry beans.  The products include Agri-Mek(R) 0.15 EC Miticide/Insecticide (2% ai; EPA Reg No. 100-898), Agri-Mek(R) SC Miticide/Insecticide (8% ai; EPA Reg No. 100-1351), and Epi-Mek(R) 0.15 EC Miticide/Insecticide (2% ai; EPA Reg No. 100-1154).  The products are to be applied as foliar sprays using ground and aerial (except chive) methods.  The labels and Section B of the petition specify a maximum seasonal rate of 0.056 lb ai/A for bulb onion, chives, and dry beans.  The preharvest intervals (PHIs) specified are 30 days for bulb onion and 6 days for chives and dry beans.  The SC (suspension concentrate) label indicates that applications to all crops are required to be made with an adjuvant.  The emulsifiable concentrate (EC) labels indicate that an adjuvant is required for bulb onions, but is only suggested for use with chives and dry beans.  Section B of the petition only specifies the use of non-ionic adjuvant with bulb onions (SC and EC labels).

In conjunction with the proposed new uses, IR-4, on behalf of the Agricultural Experiment Stations of FL, CO, TX, HI, OR, NY, ID, WA, CA and TN, has proposed the establishment of permanent tolerances for the combined residues of abamectin [(10E,14E,16E)-(1R,4S,5′S,6S,6′R,8R,12S,13S,20R,21R,24S)-6′-[(S)-sec-butyl]-21,24-dihydroxy-5′,11,13,22-tetramethyl-2-oxo-(3,7,19 trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene)-6-spiro-2′-(5′,6′-dihydro-2′H-pyran)-12-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranosyl)-3-O-methyl-α-L-arabino-hexopyranoside] in/on the following raw agricultural and processed commodities:

            Onion, bulb, subgroup 3-07A	0.01 ppm
            Chive, fresh leaves	0.01 ppm
            Chive, dried leaves	0.07 ppm
            Bean, dry, seed	0.01 ppm

Tolerances have been established in 40 CFR §180.449(a) for the combined residues of the insecticide avermectin B1 [a mixture of avermectins containing greater than or equal to 80% avermectin B1a (5-O-demethyl avermectin A1) and less than or equal to 20% avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)] and its delta-8,9-isomer in/on various plant and livestock commodities at levels ranging from 0.005 to 0.20 ppm.  Time-limited tolerances are established in 40 CFR §180.449(b) for residues of avermectin B1 and its delta-8,9-isomer in/on onion, bulb at 0.005 ppm (to expire on 12/31/12) and in/on bean, lima, seed at 0.005 ppm (set to expire on 12/31/13).

The qualitative nature of the abamectin residues in plants is adequately understood based on metabolism studies on cottonseed, citrus, and celery.  The available studies indicate that the metabolism of abamectin in plants results in a complex mixture of residues.  The majority of the terminal residue is composed of several unidentified polar degradates.  The parent compound, its delta-8,9-isomer, and the alpha 8-OH degradate have been identified in plants, with only the parent and its delta-8,9-isomer each accounting for at least 10% of the total residue.  In citrus, the majority of the residue remained in the peel but a small amount translocated into the pulp.  For the tolerance expression and risk assessment, the residues of concern in these crops are the parent compounds (avermectin B1a and B1b) and their delta-8,9-isomers (also known as 8,9-Z isomers).

The qualitative nature of abamectin residues in ruminants is adequately understood based on a goat metabolism study.  The residues of concern in ruminants for the tolerance expression and risk assessment are the parent compounds (avermectin B1a and B1b) and their delta-8,9-isomers.  If the tolerances for residues in meat and milk need to be raised at some future time due to registration of abamectin on additional feed items, the 24-hydroxymethyl metabolite may need to be included in the tolerance expression and appropriate enforcement methods developed.
 
Since no significant poultry feed items (as indicated in Table 1 Feedstuffs, June 2008) are associated with the proposed uses, no poultry metabolism study is required.

The results of a confined rotational crop study indicated that avermectin residues accumulated in some rotational crops at levels up to 10-12 ppb; however, the radioactivity was due to polar degradates that were of little toxicological concern as compared to the parent compound avermectin B1 and/or the delta-8,9-isomer.  It is not likely that residues of concern will occur in rotational crops.

Analytical methods for enforcement of residues from the use of abamectin are available in PAM II for citrus and processed fractions (Method I), ginned cottonseed (Method IA), and bovine tissues and milk (Method II).  Method M-073 and M-936-95-2 have been validated by the Agency and submitted for inclusion in FDA's PAM II as enforcement methods (Memo, W. Wassell, PP#5E4556, 6/11/96).  These five methods are adequate for enforcement of the tolerances on plants and livestock.  The methods determine residues at limits of quantitation (LOQs) of 0.02 ppm for meat and meat byproducts and <=0.01 ppm for other plant/livestock commodities.

The 1990 Pestrak database indicates that abamectin and its metabolites are not recovered or not likely to be recovered by FDA multiresidue methods.  Therefore, the multiresidue methods cannot be used to determine residues for dietary exposure assessment and cannot be used as the primary enforcement method.

Storage stability studies submitted with the previous petitions were deemed adequate and can be translated to support the storage durations and conditions of dry bulb onions and chives (fresh and dried).  For dry beans, the petitioner needs to submit the storage temperature for the samples collected in the crop field trial study.

The submitted magnitude of the residue data for dry bulb onion, chives, and dry beans (except cowpea) are adequate pending label revisions.  The conducted trials reflect the proposed use patterns, except regarding the use of adjuvants for chives and dry beans.  Label revisions are required for the EC labels to remove the statement that adjuvants may be used for chives and dry beans since the residue data on chives and dry beans did not reflect use of adjuvants.  The ChemSAC determined on 5/18/11 that the available bridging studies for the SC formulation on leafy vegetables, fruiting vegetables, cucurbit vegetables, citrus fruits, and pome fruits (DP#364734, N. Dodd, 1/21/10) can be translated to support use of the SC formulation on the bulb onion subgroup 3-07A, chives, and dry beans provided the use directions for the SC formulation always require use of a non-ionic surfactant or a horticultural oil in the spray mix and the preharvest intervals are >= 7 days.  Residue data for cowpea forage and hay must be submitted before cowpea can be included in the "bean, dry, seed" tolerance.

An adequate processing study was conducted on chives.  Residues of abamectin concentrated in dried chives (processing factor of 2.9x).  Tolerance adjustment is required for dried chives in order to reflect the appropriate tolerance level.

Codex has recommended several MRLs for abamectin (Pesticide Residues in Food-1997, Part 1).  The Codex residue definition (step 8/CXL) is the "sum of avermectin B1a, avermectin B1b, 8,9-Z-avermectin B1a and 8,9-Z-avermectin B1b " for plants, and  the "sum of avermectin B1a and 8,9-Z-avermectin B1a" for livestock commodities.  The Codex limits of determination (equivalent to HED's limits of quantitation, LOQs) for plant and livestock commodities are <=0.01 ppm.  (For plants, the LOQ ranges from 0.002 to 0.005 ppm for each of two peaks, one peak representing avermectin B1a and its 8,9-Z-isomer and the other peak representing avermectin B1b and its 8,9-Z-isomer).  For cattle meat, the Codex LOQ is 0.01 ppm.  The tolerance expression in Canada for plants is "avermectin B1a, avermectin B1b, and the 8,9-Z-isomers."  The tolerance expression in Mexico for plants is avermectina.

Regulatory Recommendations and Residue Chemistry Deficiencies

HED has examined the residue chemistry database for abamectin.  Pending submission of revised Sections B (see 860.1200 Directions for Use) and F (see 860.1550 Proposed Tolerances),
there are no residue chemistry issues that would preclude granting conditional registrations of the emulsifiable concentrate (EC) and suspension concentrate (SC) formulations of abamectin and the following permanent tolerances for abamectin:

            Onion, bulb, subgroup 3-07A	0.01 ppm
            Chive, fresh leaves	0.01 ppm
            Chive, dried leaves	0.02 ppm
            Bean, dry, seed, except cowpea	0.01 ppm

Cowpea has been excluded from the tolerance for "bean, dry, seed" since residue data for cowpea forage and hay must be submitted to support use on cowpea.

As a condition of registration of the EC formulation, the petitioner needs to submit the storage temperature of the dry bean samples from the crop field trial.

A human health risk assessment is forthcoming.

Note to PM:  The tolerance expression for abamectin in 40 CFR §180.449 (a) and (b) should be revised according to HED's Interim Guidance on Tolerance Expressions (5/27/09, S. Knizner) to state:
  "Tolerances are established for residues of abamectin, including its metabolites and degradates, in or on the commodities in the table below.  Compliance with the tolerance levels specified below is to be determined by measuring only avermectin B1 [a mixture of avermectins containing greater than or equal to 80% avermectin B1a (5-O-demethyl avermectin A1) and less than or equal to 20% avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)] and its delta-8,9-isomer."

860.1200 Directions for Use

   * Label revisions are required for the EC labels to remove the statement that adjuvants may be used on chives and dry beans since the submitted crop field trials on chives and dry beans do not reflect the use of an adjuvant.   

   * The labels must be revised to specify a 7-day PHI for chives and dry beans since most of the chive and dry bean data reflect a 7-day PHI. 

   * The amount (v/v) of the non-ionic surfactant and/or horticultural oil is required to be specified in the Directions for Use for each crop on the SC label and is required to be within the range of the amount (v/v) used in the available SC field trials (D364734, N. Dodd, 1/21/10).

   * Cowpea must be removed from the label under dry bean since residue data for cowpea forage and hay must be submitted to support use on cowpea.

860.1500 Crop Field Trials

   * The petitioner needs to submit the storage temperature of the dry bean samples from the crop field trial.

   * Residue data for cowpea forage and hay must be submitted before cowpea can be included in the bean, dry, seed tolerance.

860.1550 Proposed Tolerances

   * The petitioner should submit a revised Section F reflecting the recommended tolerance levels and correct commodity definitions as presented in Table 6.  The proposed tolerance level for chives, dried leaves must be lowered from 0.07 ppm to 0.02 ppm.  Cowpea must be excluded from the dry bean seed tolerance since residue data for cowpea forage and hay must be submitted before cowpea can be included in the dry bean seed tolerance.

 
Background

Abamectin includes the combined residues of avermectin B1 [a mixture of avermectins containing >=80% avermectin B1a (5-O-demethyl avermectin A1) and <=20% avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)] and its delta-8,9-isomer.  Abamectin is a natural fermentation product of the soil bacterium Streptomyces avermitilis.  It is used as an insecticide/miticide on crops for the control of mites, leafminers, and other insects, as a seed protectant against nematodes, and in veterinary medicine for treatment of internal and external parasites and mites.

The nomenclature and physicochemical properties of abamectin are presented below in Tables 1 and 2.

Table 1.	Test Compound Nomenclature.
Compound

Common name
abamectin; avermectin B1
Company experimental name
MK-0936
IUPAC name
mixture of >= 80% (10E,14E,16E)-(1R,4S,5'S,6S,6'R,8R,12S,13S,20R,21R,24S)-6'-[(S)-sec-butyl]-21,24-dihydroxy-5',11,13,22-tetramethyl-2-oxo-(3,7,19-trioxatetracyclo[15.6.1.1[4,8].0[20,24]]pentacosa-10,14,16,22-tetraene)-6-spiro-2'-(5',6'-dihydro-2'H-pyran)-12-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranosyl)-3-O-methyl-α-L-arabino-hexopyranoside and <= 20% (10E,14E,16E)-(1R,4S,5'S,6S,6'R,8R,12S,13S,20R,21R,24S)-21,24-dihydroxy-6'-isopropyl-5',11,13,22-tetramethyl-2-oxo-(3,7,19-trioxatetracyclo[15.6.1.1[4,8].0[20,24]]pentacosa-10,14,16,22-tetraene)-6-spiro-2'-(5',6'-dihydro-2'H-pyran)-12-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranosyl)-3-O-methyl-α-L-arabino-hexopyranoside
CAS name
avermectin B1
CAS registry number
71751-41-2
End-use products (EPs)
0.15 lb ai/gal EC (Agri-Mek(R) 0.15 EC Miticide/Insecticide; EPA Reg. No. 100-898)
0.7 lb ai/gal SC (Agri-Mek(R) SC Miticide/Insecticide; EPA Reg. No. 100-1351)
0.15 lb ai/gal EC (Epi-Mek(R) EC Miticide/Insecticide; EPA Reg. No. 100-1154 



Table 2.  Physicochemical Properties of the Technical Grade Abamectin
Parameter
Value
Reference[1]
Melting point/range
155-157°C
Accession No. 260785
pH
not available

Density
1.16 g/cm[3] at 21°C
Accession No. 260785 
Water solubility (20°C)
< 0.01 mg/mL in distilled water
< 0.001 mg/mL in tap water 
< 0.001 mg/mL in buffer system pH 6, 7.4 & 9.0
< 0.001 mg/mL in 0.9% NaCl 
Accession No. 260785
Solvent solubility (mg/mL at 20°C)
> 3 mg/mL in ethanol; >2 mg/mL in isopropyl myristate, chloroform, dimethylacetamide, dimethylformamide, glycerol formal & polyethylene glycol 400.
Accession No. 260785
Vapor pressure at 25°C
1.5 x 10[-9] hPa  
Accession No. 260785
Dissociation constant (pKa)
Not available

Octanol/water partition coefficient Log(KOW)
9.9 x 10[-3]
Accession No. 260785
UV/visible absorption spectrum
not available

1  Product Chemistry data were reviewed by Leung Cheng (Accession No. 260785, RCB No. 388, 5/1/1986).

860.1200 Directions for Use

The petitioner has submitted draft labels for Agri-Mek(R) 0.15 EC Miticide/Insecticide (2% ai; EPA Reg No. 100-898), Agri-Mek(R) SC Miticide/Insecticide (8% ai; EPA Reg No. 100-1351), and Epi-Mek(R) 0.15 EC Miticide/Insecticide (2% ai; EPA Reg No. 100-1154).  The formulations are being proposed by IR-4 for use on the bulb onion subgroup 3-07A, chives, and dry beans.  All formulations are currently registered for use on a variety of crops.  A summary of the proposed use patterns is detailed in Table 3.


             Table 3.  Summary of Directions for Use of Abamectin.

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[1]
                                    (days)
                      Use Directions and Limitations[2]  
                       Onion, bulb (Crop Subgroup 3-07A)
(onion, bulb including daylily, bulb; fritillaria, bulb; garlic, bulb; garlic, great-headed, bulb; garlic, serpent, bulb; lily, bulb; onion, Chinese, bulb; onion, pearl; onion, potato, bulb; shallot, bulb; cultivars, varieties, and/or hybrids of these)
Foliar spray (ground or aerial)[4,5]
Agri-Mek(R) 0.15 EC Insecticide/Miticide [EPA  Reg. No. 100-898]

Agri-Mek(R) SC Insecticide/ Miticide [EPA  Reg. No. 100-1351]

Epi-Mek(R) 0.15 EC Insecticide/Miticide [EPA  Reg. No. 100-1154]
                                     0.019
Not stated
                                     0.056
                                      30
Do not apply in less than 20 gallons of water/A with ground application equipment.  Do not apply in less than 5 gallons of water/A with aircraft.

Include a non-ionic surfactant commercially used on dry bulb onions.

RTI[3] = 7 days.

Adjuvant Requirement
SC formulation:  To avoid illegal crop residues, the SC formulations must always be mixed with a non-ionic activator type wetting, spreading and/or penetrating adjuvant.  Do not use binder sticker type adjuvants.  (See Use Information and Use Restrictions.)

EC formulation: Add a non-ionic activator type wetting, spreading and/or penetrating adjuvant approved for use on bulb onion. Do not use binder sticker type adjuvants. 
                                    Chives
Foliar spray
(ground)[4]
Agri-Mek(R) 0.15 EC Insecticide/Miticide [EPA  Reg. No. 100-898]

Agri-Mek(R) SC Insecticide/ Miticide [EPA  Reg. No. 100-1351]

Epi-Mek(R) 0.15 EC Insecticide/Miticide [EPA  Reg. No. 100-1154]
                                     0.019
Not stated
                                     0.056
                                       6
Apply as a foliar spray in a minimum of 20 gallons of water per acre.

Adjuvant Requirement
SC formulation:  To avoid illegal crop residues, the SC formulations must always be mixed with a non-ionic activator type wetting, spreading and/or penetrating adjuvant.  Do not use binder sticker type adjuvants.  (See Use Information and Use Restrictions.)[6] 

RTI = 7 days.

EC formulation: When necessary to improve the wetting of foliage and to smooth out spray deposits, a nonionic surfactant is recommended.
                                  Beans, dry
[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 adzuki bean, asparagus bean, blackeyed pea, catjang, Chinese longbean, cowpea, crowder pea, moth bean, mung bean, rice bean, southern pea, urd bean, and yardlong bean)]
Foliar spray
(ground or 
aerial) [4,5]
Agri-Mek(R) 0.15 EC Insecticide/Miticide [EPA  Reg. No. 100-898]

Agri-Mek(R) SC Insecticide/ Miticide [EPA  Reg. No. 100-1351]

Epi-Mek(R) 0.15 EC Insecticide/Miticide [EPA  Reg. No. 100-1154]
                                     0.019
Not stated
                                     0.056
                                       6
Do not apply in less than 10 gallons of water/A with ground application equipment.  Do not apply in less than 5 gallons of water/A with aircraft.

Adjuvant Requirement
SC formulation: To avoid illegal crop residues, the SC formulations must always be mixed with a non-ionic activator type wetting, spreading and/or penetrating adjuvant. Do not use binder sticker type adjuvants.  (See Use Information and Use Restrictions.) [6]

RTI = 6 days.

EC formulation: A non-ionic activator type wetting, spreading and/or penetrating adjuvant approved for use on dry beans and peas can be used to help improve control. Do not use binder sticker type adjuvants. 
[1]PHI = preharvest interval.
[2]Onion, bulb - Make 2 consecutive applications then rotate to a chemistry (pesticide) with a different mode of action.  Make at least 2 applications of a chemistry (pesticide) with a different mode of action before making additional applications.  Do not make more than 2 sequential applications of any other foliarly applied abamectin containing product. 
Chives - Do not make more than 2 applications of any foliarly applied abamectin containing product per single cutting (harvest). 
Dry beans - Do not make more than 2 sequential applications of any foliarly applied abamectin containing product.
[3]RTI =retreatment interval.
[4]Do not apply through any type of irrigation system.
[5]Aerial applications are not allowed in NY.
[6] The use of an adjuvant is required on the Agri-Mek(R) SC Insecticide/Miticide label, but is not specified in the Section B use directions for chives and dry beans.

Conclusions:  The submitted labels for Agri-Mek(R) 0.15 EC Insecticide/Miticide (EPA  Registration No. 100-898), Agri-Mek(R) SC Insecticide/ Miticide (EPA  Registration No. 100-1351), and Epi-Mek(R) 0.15 EC Insecticide/Miticide (EPA  Registration No. 100-1154) are adequate to allow evaluation of the residue data relative to the proposed uses.  

Label revisions are required for the EC labels to remove the statement that adjuvants may be used on chives and dry beans since the submitted crop field trials on chives and dry beans do not reflect the use of an adjuvant.   

The ChemSAC determined on 5/18/11 that the available bridging studies for the SC formulation on leafy vegetables, fruiting vegetables, cucurbit vegetables, citrus fruits, and pome fruits (DP#364734, N. Dodd, 1/21/10) can be translated to support use of the SC formulation on the bulb onion subgroup 3-07A, chives, and dry beans provided the use directions for the SC formulation always require use of a non-ionic surfactant or a horticultural oil in the spray mix and the preharvest intervals are >= 7 days.   

The amount (v/v) of the non-ionic surfactant and/or horticultural oil is required to be specified in the Directions for Use for each crop on the SC label and is required to be within the range of the amount (v/v) used in the available SC field trials (D364734, N. Dodd, 1/21/10).

The labels must be revised to specify a 7-day PHI for chives and dry beans since most of the chive and dry bean data reflect a 7-day PHI.

Cowpea must be removed from the label under dry bean since residue data for cowpea forage and hay must be submitted to support use on cowpea.

860.1300 Nature of the Residue - Plants

Residue Chemistry Memo:
 			Dodd, N., 1/26/09, DP# D316756, PP#0F6146, Abamectin.  Petition for the Establishment of Permanent Tolerances for Section 3 Registration on Pasture and Rangeland Grass, Stone Fruit Crop Group 12, Tree Nut Crop Group 14, Pistachio, and the Tuberous and Corm Vegetables Subgroup 1C; and Request for Label Amendment to Add Aerial Application to Cucurbits, Fruiting Vegetables, and Leafy Vegetables on the Agri-Mek 0.15 EC Label.  Summary of Analytical Chemistry and Residue Data.

No new plant metabolism data were submitted with this tolerance petition.  Metabolism studies on cottonseed, citrus, and celery (PP#s 5G3500, 5G3287, and 8F3649, respectively) have previously been submitted.  In addition, a report titled "Comparative Degradation of Avermectin B1a in Cotton Leaf, Citrus Fruit, Celery, and In Vitro" was also submitted (PP#9F3703, S. Willett, 12/15/89).  The available studies indicate that the metabolism of abamectin in plants results in a complex mixture of residues.  The majority of the terminal residue is composed of several unidentified polar degradates.  The parent compound, its delta-8,9-isomer, and the alpha 8-OH degradate have been identified in plants, with only the parent and its delta-8,9-isomer each accounting for at least 10% of the total residue.  The polar degradates generated on citrus (7-day PHI) and in vitro (30 hour sample) have been tested for toxicity and were found to be of no toxicological significance at the levels tested (TOX memos 7080 and 7081, W. Dykstra, 3/15/89; PP#8F3592, F. Boyd, 6/21/89; D203373, G. J. Herndon, 3/29/95).  In citrus, the majority of the residue remained in the peel but a small amount translocated into the pulp (MRID 161182).

Conclusions:  The qualitative nature of the abamectin residues in dry bulb onion, chives and dry beans is adequately understood based on the metabolism studies on cottonseed, citrus, and celery.   For the tolerance assessment and risk assessment, the residues of concern in these crops are the parent compounds (avermectin B1a and B1b) and their delta-8,9-isomers (also known as 8,9-Z isomers).     
	
860.1300 Nature of the Residue - Livestock

Residue Chemistry Memo DP# D316756, 1/26/09, N. Dodd; PP#0F6146

No additional livestock metabolism data were submitted with this petition.  A goat metabolism study has previously been submitted (PP#7G3468, L. Cheng, 2/11/87; PP#9F3703, S Willett, 12/15/89).  No poultry metabolism study has been submitted.
 									
Conclusions:  The qualitative nature of abamectin residues in ruminants is adequately understood based on a goat metabolism study.   The residues of concern in ruminants for the tolerance expression and risk assessment are the parent compounds (avermectin B1a and B1b) and their delta-8,9-isomers.  If the tolerances for residues in meat and milk need to be raised at some future time due to registration of abamectin on additional feed items, the 24-hydroxymethyl metabolite may need to be included in the tolerance expression and appropriate enforcement methods developed (PP#8F3592, F. Boyd, 6/21/89; DP#203373, G. J. Herndon, 3/29/95).

 Since no significant poultry feed items are associated with the proposed uses (as indicated in Table 1 Feedstuffs, June 2008), no poultry metabolism study is required.      

860.1340 Residue Analytical Methods

Residue Chemistry Memo DP# D316756, 1/26/09, N. Dodd; PP#0F6146

Plant commodities

Enforcement methods for abamectin in plants are available in the Pesticide Analytical Manual, Volume II (PAM II), validated for citrus and processed fractions (Method I) and ginned cottonseed (Method IA). 

Method M-036.2 has been validated by the Agency and submitted for inclusion in FDA's PAM II as an enforcement method (Memo, W. Wassell, PP#5E4566, DP# D225120, 6/11/96).

EPA's Analytical Chemistry Laboratory evaluated Merck, Sharp, and Dohme Method 1009, Revision No. 2 ("HPLC-Fluorescence Determination for Avermectin B1 and its Delta-8,9-Isomer in Citrus Fruit) in whole oranges (PP#7G3468/FAP7H5518, Jay Wilner, 9/30/87). 
 
Data collection methods are described below. 

Onion, bulb - The modified high performance liquid chromatography (HPLC) method (Method M-073.1) was used for determining residues of avermectin B1a/8,9-Z avermectin B1a and avermectin B1b in onion.  Briefly, residues in dry bulb onion samples were extracted with acetonitrile/1% phosphoric acid and then partitioned into hexane.  The extract is purified and concentrated on an aminopropyl solid phase extraction column and the effluent is derivatized with trifluoroacetic anhydride.  Residues were analyzed by high performance liquid chromatography with fluorescence detection using the external standardization technique.  The lowest limit of method validation (LLMV) was 0.002 ppm for each analyte (avermectin B1a, avermectin B1b, and 8,9-Z avermectin B1a).  This method is adequate for data collection based on acceptable method validation and concurrent method recovery data.

Chive  -  Chive samples, fresh and dry, were extracted using method 936-95-2 and derivatized and analyzed for residues of avermectin B1a/8,9-Z avermectin B1a and avermectin B1b with method M-073.  The methods were adequately validated prior to and in conjunction with the analysis of field trial samples. Briefly, residues in fresh and dry chive samples were extracted with acetonitrile, diluted with deionized water, and purified using solid phase extraction.  The extract was then derivatized with 1-methylimidazole and trifluoroacetic anhydride.  Residues were analyzed by high performance liquid chromatography with fluorescence detection using the external standardization technique.  The lowest limit of method validation (LLMV) was 0.002 ppm for each analyte (avermectin B1a, avermectin B1b, and 8,9-Z avermectin B1a).  This method is adequate for data collection based on acceptable method validation and concurrent method recovery data.
       
Dry beans - Dry bean samples were analyzed for residues of avermectin B1a/8,9-Z avermectin B1a and avermectin B1b/8,9-Z avermectin B1b with the modified analytical Merck Method M-036.2.  Briefly, residues in dry bean samples were derivatized by mixing with 1-methylimidazole and sitting on ice.  Trifluoroacetic anhydride/acetonitrile (TFAA/ACN) was added to the samples, mixed, and brought to volume with ACN.  The samples were centrifuged and analyzed by high performance liquid chromatography with fluorescence detection using the external standardization technique.  The lowest limit of method validation (LLMV) was 0.002 ppm for each analyte (avermectin B1a, 8,9-Z avermectin B1a, and avermectin B1b).  This method is adequate for data collection based on acceptable method validation and concurrent method recovery data.

Livestock Commodities

An analytical enforcement method for abamectin in bovine tissues and milk is available in the Pesticide Analytical Manual (PAM II), designated as Method II. 

EPA's Analytical Chemistry Laboratory evaluated Merck, Sharp, and Dohme Method 32A ("HPLC-Fluorescence Assay for Avermectin B1a, B1b, and the Avermectin B1a Delta-8,9-Isomer in Bovine Tissues and Milk") in milk, beef liver, and beef muscle (PP#8F3592, DEB Nos. 3929 and 3920, V. Frank Boyd, Ph.D., 9/2/88). 

Conclusions:  Adequate enforcement methods for abamectin in plant and livestock commodities are available in PAM II.  The methods have been validated for citrus and processed fractions (Method I), ginned cottonseed (Method IA), and bovine tissues and milk (Method II).  These methods determine residues at limits of quantitation (LOQs) of 0.02 ppm for meat and meat byproducts and <=0.01 ppm for other plant/livestock commodities.  The limit of detection (LOD) of the methods for plant and livestock commodities is 0.001 ppm for each analyte, equivalent to 0.002 ppm for two analytes.
  
The plant methods described above are adequate for data collection.  

860.1360 Multiresidue Methods

Residue Chemistry Memo DP# D316756, 1/26/09, N. Dodd; PP#0F6146

The 1990 Pestrak database indicates that abamectin and its metabolites are not recovered or not likely to be recovered by FDA multiresidue methods.  Therefore, the multiresidue methods cannot be used to determine residues for dietary exposure assessment and cannot be used as the primary enforcement method.

860.1380 Storage Stability

Residue Chemistry Memo DP# D316756, 1/26/09, N. Dodd; PP#0F6146

Herndon, G.J., 3/29/95, DP# D203373, PP#4F04354. Abamectin (Avermectin B1) for Use in/on the Cucurbit Crop Group (Cucumbers, Melons, and Squash). Evaluation of Analytical Methodology and Residue Data.(MRIDs# 432038-01 (8 volumes), and 432286-01 (1 volume). CBTS#s 13706 and 13707.  
			
The maximum storage intervals of the residue samples were 208 days (6.8 months) for dry bulb onions, 992 days (32.6 months) for chives, and 422 days (13.9 months) for dry beans.  The dry bulb onion and chives were stored frozen at -20°C.  The storage temperature of the dry bean samples was not provided.

No storage stability studies have been submitted with this petition.  However, the available storage stability data (DP#203373, G. J. Herndon, 3/29/95) showed that avermectin B1a, avermectin B1b,, and 8,9-Z avermectin B1a are stable under frozen storage for 24 months in celery, strawberries, and tomatoes; 29 months in oranges, lemons, and grapefruit; and 35 months in pears.  The data (DP#203373) also show that B1a is stable in cottonseed for 14 months.  Storage stability data on Bahia grass also indicated that no significant degradation of avermectin B1a occurred in grass samples stored at -20°C for at least 5.6 months (MRID 161182; TRID 350120016).  The storage stability data can be translated to dry bulb onions, chives, and dry beans.  

 Conclusions:  The available storage stability data support the storage conditions and intervals of samples from all of the submitted field trials; however, the storage temperature of the dry bean samples must be submitted.

860.1400 Water, Fish, and Irrigated Crops

Residues in water, fish, and irrigated crops are not pertinent to the proposed uses of this petition.

860.1460 Food Handling

Residues in food handling establishments are not pertinent to the proposed uses of this petition.

860.1480 Meat, Milk, Poultry, and Eggs

Residue Chemistry Memo DP# D316756, 1/26/09, N. Dodd; PP#0F6146

Based on the Table 1 Feedstuffs (June 2008), no feed items are associated with the current petition; therefore, the established livestock tolerances need not be reassessed for the purpose of this petition.

860.1500 Crop Field Trials

DER References: 48135001.der (onion, bulb), 48135002.der (chives, fresh), 48135003.der (beans, dry)

IR-4 has submitted field trial data on dry bulb onion, chives (fresh and dried), and dry beans supporting the proposed uses of abamectin (EC and SC formulations).  The results from these field trials are discussed below and the residue data are summarized in Table 4.

Table 4.	Summary of Residue Data from Crop Field Trials with an Abamectin Formulation (EC).
Commodity
                              Total Applic. Rate
                                  (lb ai/A) 
                                  PHI (days)
                             Residue Levels  (ppm)

                                       
                                       
                                       n
                                     Min.
                                     Max.
                                     HAFT
                                    Median
                                     Mean
                                   Std. Dev.
                            Total Combined Residues
Dry bulb onion (proposed use = 0.056 lb ai/A total application rate, 30-day PHI)
                                Dry bulb onion
                                 0.0567-0.0767
                                     29-31
                                      16
                                   <0.004
                                    0.0046
                                    0.0043
                                     0.004
                                    0.0040
                                    0.0002
    Chive (proposed use = 0.056 lb ai/A total application rate, 6-day PHI)
                              Fresh chive leaves
                                  0.057-0.059
                                      5-7
                                       6
                                   <0.004
                                    0.0045
                                    0.0042
                                     0.004
                                    0.0041
                                      0.0
  Bean, dry (proposed use = 0.056 lb ai/A total application rate, 6-day PHI)
                                   Bean, dry
                                  0.054-0.061
                                      5-7
                                      24
                                   <0.004
                                     0.006
                                     0.005
                                     0.004
                                    0.0041
                                      0.0


Onion, bulb

IR-4 submitted field trial data for abamectin on onion (dry bulb).  Abamectin is a mixture of avermectins, including avermectin B1a (~80% ) and avermectin B1b (~20%).  Eight onion field trials were conducted in the United States during the 2000-2001 growing season in NAFTA Zones 1 (NY; 1 trial), 5 (OH; 1 trial), 6 (TX; 1 trial), 8 (CO; 1 trial), 10 (CA and NM; 2 trials), 11 (WA; 1 trial), and 12 (OR; 1 trial).  At each test location three to four applications of an EC formulation of abamectin (Agri-Mek 0.15 EC) were made to the treatment plots as a broadcast or directed foliar application at a target rate of 0.019 lb ai/A per application, for a total seasonal rate of 0.057 lb ai/A.  Actual total application rates ranged from 0.0567-0.0767 lb ai/A.  A fourth application was made to the CA trial site only as cooler than average weather conditions slowed bulb development and delayed the harvest.  The re-treatment interval (RTI) was 6 to 8 days, except for the fourth application at the CA site which had a RTI of 34 days.  A commonly used non-ionic surfactant was applied at the maximum label rate at each application at each trial site.  Duplicate control and treated samples of mature dry bulb onion were harvested from each plot 30+-2 days following the last application.

Onion samples were analyzed for residues of avermectin B1 and its isomer 8,9-Z avermectin B1 using Syngenta Crop Protection's method M-073.1, utilizing HPLC with fluorescence detection and the external standardization technique.  The method analyzes combined residues of avermectin B1a and 8,9-Z avermectin B1a.  The same is true for avermectin B1b; however, residues for 8,9-Z avermectin B1b are not reported as they were too small to be detected and not considered to be of consequence to the study.  The method was adequately validated prior to and in conjunction with the analysis of the field trial samples, using untreated samples fortified separately at 0.002 and 0.005 ppm or 0.002 and 0.004 ppm with avermectin B1a and avermectin B1b, respectively.  The LLMV was 0.002 ppm for each analyte (avermectin B1a/8,9-Z avermectin B1a and avermectin B1b).  The LOD and LOQ were calculated as 0.0003 ppm and 0.0009 ppm, respectively, for avermectin B1a and as 0.0004 ppm and 0.0011 ppm, respectively, for avermectin B1b.  The LOD and LOQ were not calculated for 8,9-Z avermectin B1a because the number of recoveries at the LLMV was not sufficient for the calculations.

The storage duration from harvest to extraction for analysis was 26-208 days (0.85-6.8 months) for dry bulb onion.  Samples were analyzed within 4 days of extraction.  Available data show that avermectin B1a, avermectin B1b,, and 8,9-Z avermectin B1a are stable under frozen storage for 24 months in celery, strawberries, and tomatoes; 29 months in oranges, lemons, and grapefruit;  and 35 months in pears.  The data also show that B1a is stable in cottonseed for 14 months (D203373, G. J. Herndon, 3/29/95).   These data can be translated to onions and are adequate to validate the storage interval and conditions for the samples analyzed as part of the current study. 

Following 3-4 foliar applications of abamectin at a total seasonal rate of 0.0567-0.0767 lb ai/A, avermectin B1a and 8,9-Z avermectin B1a residues in/on dry bulb onion at 29-31 days PHI were <0.002-0.0026 ppm.  Avermectin B1b residues in/on dry bulb onion at PHIs of 29-31 days were not detected above the LLMV.  Total combined residues in/on dry bulb onion at PHIs of 29-31 days were <0.004-0.0046 ppm.

Conclusions:  The number and locations of the dry bulb onion crop field trials are in accordance with OPPTS 860.1500.  The field trials reflect the proposed use pattern, including the use of an adjuvant in all trials.  The field trials were conducted with an EC formulation.   

The ChemSAC determined on 5/18/11 that the available bridging studies for the SC formulation on leafy vegetables, fruiting vegetables, cucurbit vegetables, citrus fruits, and pome fruits (DP#364734, N. Dodd, 1/21/10) can be translated to support use of the SC formulation on the bulb onion subgroup 3-07A provided the use directions for the SC formulation always require use of a non-ionic surfactant or a horticultural oil in the spray mix and the preharvest intervals are >= 7 days.   

The residue data for dry onion bulbs were not entered into the tolerance spreadsheet since >15% of treated samples bore residues below the LOQ.  For the purpose of setting tolerances, HED will rely on the maximum residues observed in/on the treated commodities which were 0.0046 ppm. Based on these data, HED recommends a tolerance of 0.01 ppm.

Chives (fresh and dried)

IR-4 submitted field trial data for abamectin on chives (fresh and dry leaves).  Three chive field trials were conducted between 1999 and 2001 in NAFTA Zones 2 (NJ and MD; 2 trials) and 11 (WA; 1 trial).  At each test location three applications of an EC formulation of abamectin (Agri-Mek 0.15 EC) were made to the treatment plots as a foliar broadcast application at a target rate of 0.019 lb ai/A per application, for a total seasonal rate of 0.057 lb ai/A.  The re-treatment interval was 5 to 7 days.  An adjuvant was not used for any of the applications.  Duplicate control and treated samples of mature fresh chive leaves were harvested from each plot at a PHI of 6 +- 1 days.  An additional fresh chive harvest was conducted 13 days after the final application at the WA trial site.  At this site, one control and one treated sample of fresh chives were also collected 7 days after the final application and dried in a drying cabinet for 2 days.  

Chive samples were analyzed for residues of avermectin B1 and its isomer 8,9-Z avermectin B1 using Syngenta Crop Protection's method M-073.  The method uses HPLC with fluorescence detection and the external standardization technique. The method analyzes combined residues of avermectin B1a and 8,9-Z avermectin B1a.  The same is true for avermectin B1b.  The method was adequately validated prior to and in conjunction with the analysis of the field trial samples.  The LLMV was 0.002 ppm for each analyte (avermectin B1a, avermectin B1b, and 8,9-Z avermectin B1a).  The LOD and LOQ were not calculated for avermectin B1a, avermectin B1b, and 8,9-Z avermectin B1a because the number of recoveries at the LLMV was not sufficient for the calculations.

The storage duration from harvest to extraction for analysis was 246-992 days (8.1-32.6 months) for fresh chive leaves and 644-671 days (21.2-22.1 months) for dry chive leaves.  Analysis took place within 1 day of extraction.  Available data show that avermectin B1a, avermectin B1b,, and 8,9-Z avermectin B1a are stable under frozen storage for 24 months in celery, strawberries, and tomatoes; 29 months in oranges, lemons, and grapefruit; and 35 months in pears.  The data also show that B1a is stable in cottonseed for 14 months (D203373, G. J. Herndon, 3/29/95).  These data can be translated to chives and are adequate to validate the storage interval and conditions for the samples analyzed as part of the current study. 

Following three foliar broadcast applications of abamectin at a total seasonal rate of 0.057-0.059 lb ai/A, avermectin B1a and 8,9-Z avermectin B1a residues in/on fresh chive leaves at PHIs of 5-7 days were <0.002-0.0025 ppm.  Avermectin B1b and 8,9-Z avermectin B1b residues were not detected above the LLMV; total combined residues were <0.004-0.0045 ppm.  At the WA site, avermectin B1a and 8,9-Z avermectin B1a residues declined from an average of 0.002 ppm at a 7-day PHI to <LLMV at the 13-day PHI.  Avermectin B1b and 8,9-Z avermectin B1b residues were not detected in the samples at the 7-day or 13-day PHI.  Avermectin B1a and 8,9-Z avermectin B1a residues in/on dried leaves prepared from fresh chives at a 7-day PHI were 0.010 ppm.  Avermectin B1b and 8,9-Z avermectin B1b residues were not detected above the LLMV.

Conclusions:  For fresh chives, the number and locations of the chive crop field trials are in accordance with OPPTS Guideline 860.1500.  The field trials, which were conducted with an EC formulation, reflect the proposed use pattern, including application rate and PHI.  An adjuvant was not used in the field trials.  Label revisions are required for the EC labels to remove the statement that adjuvants may be used on chives since the submitted chive field trials do not reflect the use of an adjuvant.  Also, the labels must be revised to specify a 7-day PHI for chives since most of the chive data reflect a 7-day PHI.  

 The ChemSAC determined on 5/18/11 that the available bridging studies for the SC formulation on leafy vegetables, fruiting vegetables, cucurbit vegetables, citrus fruits, and pome fruits (DP#364734, N. Dodd, 1/21/10) can be translated to support use of the SC formulation on chives provided the use directions for the SC formulation always require use of a non-ionic surfactant or a horticultural oil in the spray mix and the preharvest intervals are >= 7 days.   

The residue data for fresh chives were not entered into the tolerance spreadsheet since >15% of treated samples bore residues below the LOQ.  For the purpose of setting tolerances, HED will rely on the maximum residues observed in/on the fresh chives which were 0.0045 ppm.  Based on these data, HED recommends a tolerance of 0.01 ppm.

Beans, Dry

IR-4 submitted field trial data for abamectin on dry beans.  Twelve bean field trials were conducted during the 1999 growing season in NAFTA Zones 1 (OH; 2 trials), 2 (NJ; 1 trial), 5 (ND and WI; 5 trials), 10 (CA; 1 trial), and 11 (ID and WA; 3 trials).  At each test location, three applications of an EC formulation of abamectin (Agri-Mek 0.15 EC) were made to the treatment plots as a foliar (broadcast or directed) application at a target rate of 0.019 lb ai/A per application, for a total seasonal rate of 0.057 lb ai/A.  The re-treatment interval was 5 to 9 days.  An adjuvant was not used for any of the applications.  Duplicate control and treated samples of mature dry bean seeds were harvested from each plot at a 6+-1 day PHI. 

Bean samples were analyzed for residues of avermectin B1 and its isomer 8,9-Z avermectin B1 using Merck Method M-036.2, Revision 2.  The method uses HPLC with fluorescence detection and the external standardization technique.  The method analyzes combined residues of avermectin B1a and 8,9-Z avermectin B1a.  The same is true for avermectin B1b.  The method was adequately validated prior to and in conjunction with the analysis of the field trial samples.  The LLMV was 0.002 ppm for each analyte (avermectin B1a, avermectin B1b, and 8,9-Z avermectin B1a).  The LOD and LOQ were 0.0006 ppm and 0.0019 ppm, respectively, for avermectin B1a and 0.0007 ppm and 0.0022 ppm, respectively, for 8,9-Z avermectin B1a.  The LOD and LOQ were not calculated for avermectin B1b because the number of recoveries at the LLMV was not sufficient for the calculations.

The maximum storage duration from harvest to extraction for analysis was 422 days (13.9 months) for dry beans.  Analysis took place between 0 and 9 days after extraction.  Available data show that avermectin B1a, avermectin B1b,, and 8,9-Z avermectin B1a are stable under frozen storage for 24 months in celery, strawberries, and tomatoes; 29 months in oranges, lemons, and grapefruit;  and 35 months in pears.  The data also show that B1a is stable in cottonseed for 14 months (D203373, G. J. Herndon, 3/29/95).  These data can be translated to dry beans.  Pending submission of the storage temperature at the analytical laboratory, the data are adequate to validate the storage interval and conditions for the samples analyzed as part of the current study. 

Following three foliar applications of abamectin at a total seasonal rate of 0.054-0.061 lb ai/A, avermectin B1a and 8,9-Z avermectin B1a residues in/on dry beans at PHIs of 5-7 days were <0.002-0.004 ppm; only one replicate had residues detected above the LLMV.  Avermectin B1b and 8,9-Z avermectin B1b residues in/on dry beans at 5-7 days PHI were not detected above the LLMV.  Total combined residues in/on dry beans at PHIs of 5-7 days were <0.004-0.006 ppm.

Conclusions:  For dry beans, the number of the crop field trials are in accordance with OPPTS 860.1500.  The location of the crop field trials differed slightly from OPPTS 860.1500.  The petitioner is short two field trials in Zone 7 and one each in Zones 8 and 9 but submitted extra field trials in Zones 1, 2, and 11.  The location of the trials is adequate.  The field trials, which were conducted with an EC formulation, reflect the proposed use pattern, including application rate and PHI.  An adjuvant was not used in the field trials.  The EC label indicates than an adjuvant can be used with the applications, but is not required.  Label revisions are required for the EC labels to remove the statement that adjuvants may be used on dry beans since the submitted dry bean field trials do not reflect the use of an adjuvant.  The labels must be revised to specify a 7-day PHI for dry beans since most of the dry bean data reflect a 7-day PHI.  The petitioner should also submit the storage temperature of the dry bean samples. Residue data for cowpea forage and hay must be submitted before cowpea can be included in the bean, dry, seed tolerance.

The ChemSAC determined on 5/18/11 that the available bridging studies for the SC formulation on leafy vegetables, fruiting vegetables, cucurbit vegetables, citrus fruits, and pome fruits (DP#364734, N. Dodd, 1/21/10) can be translated to support use of the SC formulation on dry beans provided the use directions for the SC formulation always require use of a non-ionic surfactant or a horticultural oil in the spray mix and the preharvest intervals are >= 7 days.   

The residue data for dry beans were not entered into the tolerance spreadsheet since >15% of the treated samples bore residues below the LOQ.  For the purpose of setting tolerances, HED will rely on the maximum residues observed in/on the dry beans which were 0.006 ppm.  Based on these data, HED recommends a tolerance of 0.01 ppm.

860.1520 Processed Food and Feed

Chive

DER Reference: 48135002.der.doc

A processing study with abamectin on chives was submitted.  The sample used for processing was generated from a trial conducted in WA during the 2000 growing season.  Chives were harvested 7 days following the last of three foliar airblast applications of an EC formulation of abamectin (Agri-Mek 0.15 EC) for a total rate of 0.059 lb ai/A (~1x the maximum proposed seasonal rate).  The harvested chives were dried in a drying cabinet for 2 days.  

Chive samples were analyzed for residues of avermectin B1 and its isomer 8,9-Z avermectin B1 using Syngenta Crop Protection's method M-073.  The method uses HPLC with fluorescence detection and the external standardization technique.  The method analyzes combined residues of avermectin B1a and 8,9-Z avermectin B1a.  The same is true for avermectin B1b.  The method was adequately validated prior to and in conjunction with the analysis of the field trial samples.  The LLMV was 0.002 ppm for each analyte (avermectin B1a, avermectin B1b, and 8,9-Z avermectin B1a).  The LOD and LOQ were not calculated for avermectin B1a, avermectin B1b, and 8,9-Z avermectin B1a because the number of recoveries at the LLMV was not sufficient for the calculations.

The maximum storage duration from harvest to extraction for analysis was 636 days (20.9 months) for fresh chives and 671 days (22.1 months) for dried chives.  Analysis took place within 1 day of extraction.  Available data show that avermectin B1a, avermectin B1b, and 8,9-Z avermectin B1a are stable under frozen storage for 24 months in celery, strawberries, and tomatoes; 29 months in oranges, lemons, and grapefruit; and 35 months in pears.  The data also show that B1a is stable in cottonseed for 14 months (D203373, G. J. Herndon, 3/29/95).  These data can be translated to chives and are adequate to validate the storage interval and conditions for the samples analyzed as part of the current study. 

In/on fresh chives, avermectin B1a and 8,9-Z avermectin B1a residues were an average of 0.0021 ppm and avermectin B1b and 8,9-Z avermectin B1b residues were not detected above the LLMV.  Total combined residues were an average of 0.0041 ppm.  Residue in the dried chive sample was 0.010 ppm for avermectin B1a and 8,9-Z avermectin B1a, <0.002 ppm for avermectin B1b, and 0.012 ppm for total combined residues (resulting in a processing factor of 2.9x).  No theoretical concentration factors are available for dried herbs.



Table 5.  Residue Data from Chive Processing Study with Abamectin.
RAC
                              Processed Commodity
                                  Total Rate
                                 (lb a.i./A) 
                                     PHI 
                                    (days)
                                Residues (ppm)
                             Processing Factor[1]
                    Avermectin B1a and 8,9-Z Avermectin B1a
                                     Chive
                               Fresh chive (RAC)
                                     0.059
                                       7
                       0.00216, <0.002 (avg. 0.0021)
                                      --
                                       
                                  Dried chive
                                       
                                       
                                     0.010
                                      --
                                Avermectin B1b
                                     Chive
                               Fresh chive (RAC)
                                     0.059
                                       7
                             <0.002, <0.002
                               (avg. <0.002)
                                      --
                                       
                                  Dried chive
                                       
                                       
                                   <0.002
                                      --
                            Total Combined Residues
                                     Chive
                               Fresh chive (RAC)
                                     0.059
                                       7
                              0.00416, <0.004
                                (avg. 0.0041) 
                                      --
                                       
                                  Dried chive
                                       
                                       
                                     0.012
                                      2.9
[1] Processing factor = residue in processed sample/average residue in unprocessed RAC sample.  NC = not calculated.  

Conclusions:  The chive processing study is acceptable to satisfy data requirements.  Residues of abamectin concentrated in the dried chive sample (2.9x) following processing of the RAC (fresh chives).  Residues were only slightly above the LOQ in one RAC sample and below the LOQ in the second RAC sample.  These data suggest that a tolerance is needed for dried chives.  The maximum expected residue of abamectin in dried chives, resulting from the proposed use, is 0.012 ppm.  This value was calculated by multiplying the concentration factor of 2.9x by the HAFT residue of 0.0042 ppm (see Table 4).  The petitioner is required to submit a revised Section F to propose a tolerance of 0.02 ppm for residues of abamectin in/on "chive, dried leaves".  

860.1650 Submittal of Analytical Reference Standards
 
The analytical reference standards for abamectin (avermectin B1a and avermectin B1b) have been submitted to the USEPA National Pesticide Standards Repository.  Analytical standards have expired for 8,9-Z avermectin B1a  (NOA427011)  and 8a-hydroxy avermectin B1a (NOA 448112).  The petitioner should submit updated Certificates of Analysis or new material for these standards [Source: Personal Communication between T. Cole of the Analytical Chemistry Branch/Biological and Economic Analysis Division (ACB/BEAD) and Versar, 12/20/2010].  

860.1850 Confined Accumulation in Rotational Crops
and
860.1900 Field Accumulation in Rotational Crops

Residue Chemistry Memo DP# D316756, 1/26/09, N. Dodd; PP#0F6146
 
No rotational crop studies were submitted with this petition.  Review of the results of the confined rotational crop study indicated that avermectin residues accumulated in some rotational crops at levels up to 10-12 ppb.  However, the radioactivity was due to polar degradates that were of little toxicological concern as compared to the parent compound avermectin B1 and/or the delta-8,9-isomer (Memo, P. Mastradone, 4/24/88).  Therefore, field rotational crop studies are not required (PP#7F3500, PP#8F3592, and PP#5E4566, DP#s: D230333, D230352, and D230880, G. Herndon, 1/10/97).
						
860.1550 Proposed Tolerances

HED has determined that the nature of the residue in plants and livestock is adequately understood.  The residues of concern in plant and livestock commodities are the combined residues of avermectin B1 [ >=80% avermectin B1a (5-O-demethyl avermectin A1) and <=20% avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)] and its delta-8,9-isomer for tolerance and risk assessment. 

The petitioner has proposed the establishment of permanent tolerances for the combined residues of abamectin: (10E,14E,16E)-(1R,4S,5′S,6S,6′R,8R,12S,13S,20R,21R,24S)-6′-[(S)-sec-butyl]-21,24-dihydroxy-5′,11,13,22-tetramethyl-2-oxo-(3,7,19 trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene)-6-spiro-2′-(5′,6′-dihydro-2′H-pyran)-12-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranosyl)-3-O-methyl-α-L-arabino-hexopyranoside in/on the following raw agricultural and processed commodities:

            Onion, bulb, subgroup 3-07A	0.01 ppm
            Chive, fresh leaves	0.01 ppm
            Chive, dried leaves	0.07 ppm
            Bean, dry, seed	0.01 ppm

An adequate number of field trials at ~1x the proposed use rate are available for the RACs of the bulb onion subgroup 3-07A, chives, and dry beans.  The residue data were not entered into the tolerance spreadsheet because >15% of the treated samples bore residues below the LOQ.  For the purpose of setting tolerances, HED will rely on the maximum residues.

An adequate processing study was conducted on chives.  Residues of abamectin concentrated in the dried chive sample (2.9x) following processing of the RAC (fresh chives).  The processing study indicated that a tolerance of 0.02 ppm would be adequate for chives, dried leaves.

There are no Codex, Canadian, and Mexican maximum residue limits (MRLs)/tolerances on the bulb onion subgroup 3-07A, chive, or dry bean as indicated in Appendix 1.  

Codex has recommended several MRLs for plant and cattle commodities (Pesticide Residues in Food-1997, Part 1).  The Codex residue definition (step 8/CXL) is the "sum of avermectin B1a, avermectin B1b, 8,9-Z-avermectin B1a and 8,9-Z-avermectin B1b " for plants, and the "sum of avermectin B1a and 8,9-Z-avermectin B1a" for livestock commodities.  The tolerance expression in Canada for plants is "avermectin B1 (a mixture of avermectins containing greater than or equal to 80% avermectin B1a (5-O-demethyl avermectin A1a) and less than or equal to 20%
avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1a) and its delta-8,9-isomer)."
  
A tolerance summary for abamectin is presented in Table 6.   The petitioner should submit a revised section F reflecting the recommended tolerance levels as presented in Table 6.  The proposed tolerance level for chives, dried leaves must be lowered from 0.07 ppm to 0.02 ppm.  
Cowpea must be excluded from the dry bean seed tolerance since residue data for cowpea forage and hay must be submitted before cowpea can be included in the dry bean seed tolerance.


Table 6.  Tolerance Summary for Abamectin
                                   Commodity
                           Proposed Tolerance (ppm)
                          Recommended Tolerance (ppm)
Comments (correct commodity definition)
                          Onion, bulb, subgroup 3-07A
                                   0.01 ppm
                                       
(0.005 ppm established time limited tolerance on onion, bulb to expire on 12/31/12)
                                   0.01 ppm

Chive, fresh leaves
                                   0.01 ppm
                                   0.01 ppm

Chive, dried leaves
                                   0.07 ppm
                                   0.02 ppm

Bean, dry, seed
                                   0.01 ppm
                                   0.01 ppm
Bean, dry, seed, except cowpea


References

DP#:	379892
Subject:	Abamectin.  Amendment of Agri-Mek(R) SC Label to Add More Crops Currently on Agri-Mek 0.15 EC Label. 
From:	Nancy Dodd
To:	John Hebert/Thomas Harris
Date:	9/28/10
MRID:	None

DP#:	316756
Subject:	Abamectin.  Petition for the Establishment of Permanent Tolerances for Section 3 Registration on Pasture and Rangeland Grass, Stone Fruit Crop Group 12, Tree Nut Crop Group 14, Pistachio, and the Tuberous and Corm Vegetables Subgroup 1C; and Request for Label Amendment to Add Aerial Application to Cucurbits, Fruiting Vegetables, and Leafy Vegetables on the Agri-Mek 0.15 EC Label.  Summary of Analytical Chemistry and Residue Data.
From:	Nancy Dodd
To:	John Hebert
Date:	1/26/09
MRIDs:	45096702, 45096703, 45096704, 45096705, 45096707, 45096708, 45096709

DP#:	203373
Subject:	PP#4F04354. Abamectin (Avermectin B1) for Use in/on the Cucurbit Crop Group (Cucumbers, Melons, and Squash).  Evaluation of Analytical Methodology and Residue Data.  CBTS#s 13706 and 13707.  
From:	G. J. Herndon
To:	George LaRocca/Linda Arrington
Date:	3/29/95
MRIDs:	432038-01 (8 volumes) and 432286-01 (1 volume)


Attachments:  
Appendix I - 	International Residue Limit Status sheet

Template Version September 2005




                                                                               
Appendix I - International Residue Limits 

                    Abamectin (PC Code 122804; 03/31/2011)
Summary of US and International Tolerances and Maximum Residue Limits 
Residue Definition:
US
Canada
Mexico
Codex
40 CFR 180.449:
Plant/Livestock:  sum of avermectin B1 (a mixture of avermectins containing greater than or equal to 80% avermectin B1a (5-O-demethyl avermectin A1) and less than or equal to 20% avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)) and its delta-8,9-isomer 
avermectin B1 (a mixture of avermectins containing greater than or equal to 80% avermectin B1a (5-O-demethyl avermectin A1a) and less than or equal to 20%
avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1a) and its delta-8,9-isomer)

Plants: sum of avermectin B1a, avermectin B1b, 8,9-Z-avermectin B1a and 8,9-Z-avermectin B1b. Animal commodities: sum of avermectin
B1a and 8,9-Z-avermectin B1a.

Commodity
Tolerance (ppm) /Maximum Residue Limit (mg/kg)

                                      US
Canada
Mexico
Codex
Onion, bulb, subgroup 3-07A
                                     0.01


                                                                               
Chive, fresh leaves
                                     0.01


                                                                               
Chive, dried leaves
                                     0.02


                                                                               
Bean, dry, seed, except cowpea
                                     0.01


                                                                               

                                                                               


                                                                               

                                                                               


                                                                               

                                                                               


                                                                               

                                                                               


                                                                               

                                                                               


                                                                               

                                                                               
                                                                               

                                                                               

                                                                               
                                                                               

                                                                               

                                                                               
                                                                               

                                                                               

                                                                               
                                                                               

                                                                               

                                                                               
                                                                               

                                                                               

                                                                               
                                                                               

                                                                               

                                                                               
                                                                               

                                                                               

                                                                               
                                                                               

                                                                               

                                                                               
                                                                               

                                                                               

                                                                               
                                                                               

                                                                               

                                                                               
                                                                               

                                                                               
Completed:  M. Negussie; 03/31/2011
                                                                               

