Page 1 of 19 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND
POLLUTION PREVENTION MEMORANDUM

Date: March 17, 2016

Subject: Abamectin

. Petition for the Establishment of a Permanent Tolerance and Registra t ion for Use on the Caneberry Subgroup 13

- 07A. Summary of Analytical Chemistry and Residue Data.

PC Code: 122804 DP Barcode: D412860
Decision No.: 478520 Registration No s

. : 100

- 898 , 100

- 1 154
Petition No.: 3E8175 Regulatory Action: Section 3 Registration
Risk Assessment Type: NA Case No.: NA

T XR No.: N A CAS No.: 71751

- 41

- 2

MRID No.: See Below 40 CFR : 180. 449

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

Through: C hris tine Olinger, Chie f
RAB3 / HED ( 7509P )

To: Barbara Madden/Sidney Jackson, RM# 5 Registration Division (7505P)

Summary of Submitted Residue Chemistry Studies

O C S PP 860 Series
Guideline MRID
Number Title

860.1500 49080101 Dorschner, K. (2012) Abamectin: Magnitude of the Residue on Caneberry (Raspberry or Blackberry). Project Number: 06475 /OCR, 06475/00/BER01

. Unpublished study prepared by Interregional Research Project No. 4, Washington State University and North Carolina State University. 230 p.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 2 of 19 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 4

2.0 Regulatory Recommendations

................................ ................................ ............................. 4

2.1 Data Deficiencies/Data Needs

................................ ................................ .......................... 5

2.2 Tolerance Considerations

................................ ................................ ................................ . 5

2.2.1 Enforcement Analytical Method

................................ ................................ ............... 5

2.2.2 Recommended Tolerances

................................ ................................ ........................ 5

2.2.3 Revisions to Petitioned

- For Tolerances

................................ ................................ .... 5

2.2.4 International Harmonization

................................ ................................ ..................... 5

2.3 Label Recommendations

................................ ................................ ................................ .. 5

3.0 Introduction

................................ ................................ ................................ .......................... 6

3.1 Chemical Identity

................................ ................................ ................................ ............. 6

3.2 Physical/Chemical Characteristics

................................ ................................ ................... 7

3.3 Pesticide Use Pattern/Directions for Use (860.1200)

................................ ....................... 7

4.0 Metabolite/Degradate Residue Profile

................................ ................................ ................. 8

4.1 Nature of the Residue

................................ ................................ ................................ ....... 8

4.1.1 Summary of Plant Metabolism (860.1300)

................................ ............................... 8

4.1.2 Summary of Livestock Metabolism (860.1300)

................................ ....................... 9

4.1.3 Summary of Confined Rotational Crops (860.l850)

................................ ................. 9

4.1.4. Summary of Metabolites and Degradates

................................ ................................ . 9

4.2 Comparison of Metabolic Pathways

................................ ................................ ................ 9

4.3 Residues of Concern Summary and Rationale

................................ ............................... 10

5.0 Residue Profile

................................ ................................ ................................ ................... 12

5.1 Residue Analytical Methods (860.1340)

................................ ................................ ........ 12

5.1.1 Data Collection Methods

................................ ................................ ........................ 12

5.1.2 Multi

- Residue Methods (860.1360)

................................ ................................ ........ 12

5.1.3 Tolerance Enforcement Methods

................................ ................................ ............ 12

5.1.4 Submittal of Analytical Reference Standards (860.1650)

................................ ...... 13

5.2 Storage Stability (860.1380)

................................ ................................ .......................... 13

5.3 Residue Data

................................ ................................ ................................ .................. 13

5.3.1 Crop Field Trials (860.1500)

................................ ................................ .................. 13

5.3.2 Field Rotational Crops (860.1900)

................................ ................................ ......... 15

5.3.3 Processed Food and Feed (860.1520)

................................ ................................ ..... 15Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 3 of 19 5.3.4 Meat, Milk, Poultry and Eggs (860.1480)

................................ .............................. 15

5.3.5. Food Handling (860.1460)

................................ ................................ ...................... 15

5.3.6. Water, Fish, and Irrigated Crops (860.1400)

................................ .......................... 15

5.4. Food Residue Profile

................................ ................................ ................................ ...... 15

6. 0 Tolerance Derivation

................................ ................................ ................................ ......... 15

Appendix A. Field Trial Geographic Distribution

................................ ................................ ....... 17

Appendix B. International Residue Limits Table

................................ ................................ ........ 18

Appendix C. OECD MRL Calculation Procedure Inputs/Outputs

................................ .............. 19Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 4 of 19 1.0 Executive Summary

The Interregional Research Project No. 4 (IR

- 4) , on behalf of the Agricultural Experiment Stations of CA, SC, AR, NC, WA, and DE, has submitted a petition to propose use of abamectin
to control mites on caneberries and to establish a tolerance for the caneberry subgroup 13

- 07A. The petitioner proposes addition of the use on caneberries to the Agri

- Mek ® 0.15 EC and Epi

Mek ® 0.15 EC labels.

The petitioner has proposed a tolerance for residues of abamectin (avermectin), i ncluding its metabolites and degradates, in/ on the caneberry subgroup 13

- 07A at 0.20 ppm. Compliance with
the tolerance levels specified is to be determined by measuring only avermectin B 1 [a mixture of avermectins containing greater than or equal to 80% avermectin B 1a (5

- O

- demethyl avermectin

A 1 ) and less than or equal to 20% avermectin B 1b (5

- O

- demethyl

- 25

- de(1

- methylpropyl)

- 25

- (1

- methylethyl) avermectin A 1 )] and its delta

- 8,9

- isomer.

Tolerances are established under 40 CFR §180.449 for residues of abam ectin (avermectin), including its metabolites and degradates, in or on various crop and livestock commodities at levels ranging from 0.005 ppm to 1.0 ppm. Compliance with the tolerance levels is to be determined by measuring only avermectin B 1 [a mixture of avermectins containing greater than or equal to 80% avermectin B 1a (5

- O

- demethyl avermectin A 1 ) and less than or equal to 20%
avermectin B 1b (5

- O

- demethyl

- 25

- de(1

- methylpropyl)

- 25

- (1

- methylethyl) avermectin A 1 )] and
its delta

- 8,9

- isomer.

A gri

- Mek ® 0.15 EC (EPA Reg. No. 100

- 898 ) and Epi

- Mek ® 0.15 EC (EPA Reg. No. 100

- 1154 ) are to be applied to caneberries as broadcast foliar sprays usi ng ground or aerial equipment. M ultiple applications can be made with a retreatment interval of 7 days. Th e maximum application rates are 0.019 lb ai/A/application and 0.056 lb ai/ A/season

. The preharvest interval is 7 days.

T he residue chemistry database is adequate for tolerance assessment and for registration of the

two EC formulation s of abamectin on th e caneberry subgroup 13

- 07A. Residues of concern in plants are parent (avermectin B 1a and B 1b ) and the 8,9

- Z isomers. The field trials reflect the proposed use pattern. The number of field trials and the geographic representation are adequate. An adequate method was used for data collection. Field trial residues in caneberries (raspberries and blackberries) were low but quantifiable as combined residues . Residues in blac k be rr ies decline with increasing preharvest interval s (PHI s ). Adequate st orage stability data are available to support the field trials. No processed commodities or livestock feed items are associated with
caneberries. Caneberries are not considered to be rotated.

2.0 R egulatory R ecommendations

T here are no residue chemistry considerations that would preclude granting the requested registrations and establishing the recommended tolerance for abamectin on the caneberry subgroup 13

- 07A. The specific tolerance recommendations are discussed in Section 2.2 . There

are no recommen ded label m odifications

.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 5 of 19 2.1 Data Deficiencies/Data Needs

There are no data deficiencies.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate enforcement methods for abamectin in plant and livestock commodities are available
in the Pesticide Analytical Manual, Volume II ( 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 in plant and livestock commodities 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 de tection (LOD) of the methods for plant and livestock commodities is 0.001 ppm for each analyte, equivalent to 0.002 ppm for two analy te peaks (i.e., avermectin B 1a and its delta

- 8,9

- isomer in one peak and avermectin B 1b and its delta

8,9

- isomer in the othe r peak).

2.2.2 Recommended Tolerances

The current tolerance expression in 40 CFR §180.449 is consistent with the S. Knizner memo dated 5/27/09.

Table 2.2.2 . Tolerance Summary for Abamectin

. Commodity Established

Tolerance

(ppm) IR

- 4

- Proposed
Tolerance

(ppm) HED

Recommended
Tolerance

(ppm) Comments ( correct commodity definition )

Caneberry

, subgroup 13

- 07A none 0.20 0. 20 Caneberry subgroup 13

- 07A

2.2.3 Revisions to Petitioned

- For Tolerances

None.

2.2.4 International Harmonization

The tolerance definitions for plants are essentially the same for the US, Codex, and Canada. There are no Codex maximum residue limits (MRLs) for abamectin on caneberries. Canada and the US are concurrently establishing the new tolerance o n the caneberry subgroup 13

- 07A at 0.20 ppm

. Therefore, there are no harmonization issues at this time.

2.3 Label Recommendations

None.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 6 of 19 3.0 Introduction

Abamectin is an insecticide/miticide used to control mites, leaf miners, and other insects in commercially important crops. Avermectins are macrocyclic lactones produced as natural fermentation products of the soil bacterium Streptomyces avermitilis. Aba mectin is a mixture of
avermectin B 1 [a mixture of avermectins containing greater than or equal to 80% avermectin B 1a (5

- O

- demethyl avermectin A 1 ) and less than or equal to 20% avermectin B 1b (5

- O

- demethyl

- 25

- de(1

- methylpropyl)

- 25

- (1

- methylethyl) avermectin A 1 )] and its delta

- 8,9

- isomer. Abamectin has limited plant systemic activity, but does exhibit some translaminar movement. Abamectin acts as an insecticide by interfering with the nervous system of the insect, causing the insect to become para lyzed. Available mechanistic data indicate a neurotoxic mechanism of action,
related to interference with GABA

- mediated neurotransmission.

3.1 Chemical Identity

Table 3.1. Abamectin Nomenclature Compound

Abamectin Chemical Structure

Common Names abamectin, avermectin B 1 Company experimental name MK

- 0936

IUPAC name mixture of (10 E ,14 E ,16 E )

- (1 R ,4 S ,5 ' S ,6 S ,6 ' R ,8 R ,12 S ,13 S ,20 R ,21 R ,24 S )

- 6 '

- [( S )

-

sec

- butyl]

- 21,24

- dihydroxy

- 5 ',11,13,22

- tetramethyl

- 2

- oxo

- (3,7,19

-Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 7 of 19 Table 3.1. Abamectin Nomenclature 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 (10 E ,14 E ,16 E )

- (1 R ,4 S ,5 ' S ,6 S ,6 ' R ,8 R ,12 S ,13 S ,20 R ,21 R ,24 S )

- 21,2 2

- 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

- methy l

- α

- L

- arabino

- hexopyranoside

CAS n ame Avermectin B 1

CAS # Avermectin B 1 - 71751

- 41

- 2; Avermectin B 1a - 65195

- 55

- 3; Avermectin B 1b - 65195

- 56

- 4

End

- use product s /EP s Agri

- Mek® 0.15 EC Miticide/Insecticide , EPA Reg. No. 100

- 898 (contains 0.15 lb ai per gallon); Ep i

- Mek ® 0 .15 EC Miticide/Insecticide , EPA Reg. No. 100

- 1154 ( contains 0.15 lb ai per gallon).

3.2 Physical/Chemical Characteristics

Avermectin is a crystalline powder with very low vapor pressure. It has very low water solubility but is soluble in organic solvents. Residues do not readily leach to groundwater due to their affinity for soil particles. Abamectin is stable to abiotic hydrolysis. Refer to Table 3.2 for the table of physical/chemical properties.

TABLE 3.2. Physicochemical Properties of the Technical Grade of Abamectin

Parameter Value Reference

Molecular weight 873.1 MRID 48758002

Melting point/range 161.8

- 169.4°C (with thermal decomposition)

pH 8

- 9 at 25°C

Density 1.18 x 10 3 kg/m 3 at 22°C

Water solubility at 25oC 1.21 μg/mL at pH 7.57

Solubility in organic solvents Acetone 72 g/L
Dichloromethane 470 g/L Ethyl acetate 160 g/L

Hexane 0.110 g/L
Methanol 13 g/L
Octanol 83 g/L
Toluene 23 g/L

Vapor pressure at 25oC <3.7 x 10

- 6 Pa

Dissociation constant (pK a ) no dissociation constant in aqueous solution

Octanol/water partition coefficient, Log P ow 4.4 at pH 7.2

UV/visible absorption spectrum Absorbance maxima
Neutral: 32,549 l/mol•cm at 245 nm 18,983 l/mol•cm at 255 nm
Acidic: 34,515 l/mol•cm at 245 nm 20,977 l/mol•cm at 255 nm
Basic: 29,551 l/mol•cm at 245 nm

3.3 Pesticide Use Pattern/ Directions for Use (860.1200)Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 8 of 19 IR

- 4 has submi tted a petition to add use on the caneberry subgroup13

- 07A to the Agri

- Mek ®
0.15 EC ( EPA Reg. No. 100

- 898 ) and Epi

- Mek ® 0.15 EC ( EPA Reg. No. 100

- 1154 ) labels.
Both labels are emulsifiable concentrate (EC) formulations containing 0.15 lb ai/gal.

Table 3.3. Summary of Proposed Directions for Use of Abamectin on Caneberry.

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

Caneberry (Crop Subgroup 13

- 07A) (blackberry, loganberry, raspberry ( black and red), wild raspberry and cultivars/varieties, and/or hybrids of these) Postemergence;
Broadcast foliar spray; Ground
or aerial equipment Agri

- Mek ®
0.15 EC [100

- 898]

Epi

- Mek ®
0.15 EC [100

- 1154] 0.0094

- 0.019 not stated* 0.056 7 Restricted Use Pesticide Apply when spider mites
are first observed and repeat as needed. Do not apply with
aircraft in NY state. Apply in a minimum of 10 gals

. water by ground or 5 gal water by air.
The retreatment interval is 7 days.
Do not make more than 2 sequential applications
of an abamectin

containing product.
A nonionic activator type wetting, spreading, and/or penetrating adjuvant can be used.
Do not use binder sticker type adjuvants.

* The maximum number of applications at the maximum rate is 3.

Caneberry samples were analyzed for residues of avermectin B 1a , 8,9

- Z avermectin B 1a , and
avermectin B 1b using a high performance liquid chromatography ( HPLC ) method with fluorescence detection based on analytical method M

- 073.

Conclusions

. T he Agr i

- Mek ® 0.15 EC Miticide/ Ins ecticide label (EPA Reg. No. 100

- 898 ) and
the Epi

- Mek ® 0.15 EC Miticide / Insecticide label (EPA Reg. No. 100

- 1 154 ) are adequate to allow evaluation of the residue data relative to the proposed use.

4.0 Metabolite/Degradate Residue Profile

4.1 Nature of the Residue

4.1.1 Summary of Plant Metabolism (860.1300)

DP Barcode D 380523 , N. Dodd, 7/18/11Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 9 of 19 No new plant metabolism data were submitted with this registration request. The qualitative

natu re of the abamectin residues in the caneberry subgroup13

- 07A is adequately understood based on metabolism studies on cotton, citrus, and celery (PP#'s 5G3500, 5G3287, and 8F3649, respectively), as well as a report titled "Comparative Degradation of Avermectin B 1 a in Cotton Leaf, Citrus Fruit, Celery, and In Vitro " (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 c ompound, 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 vit ro (30 hour sample) have been tested for toxicity (in the developmental toxicity study in CF

- 1 mice) 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; D203 373, G. J. Herndon, 3/29/95).
As stated in The Pesticide Manual , Eleventh Edition, British Crop Protection Council (1997), abamectin has limited plant systemic activity, but does exhibit some translaminar movement. For the tolerance expression and risk assessment, the residues of concern in these crops are the parent compounds (avermectin B 1a and B 1b ) and their delta

- 8,9

- isomers (also known as 8,9

- Z
avermectin B 1a and 8,9

- Z avermectin B 1b ).

4.1.2 Summary of Livestock Metabolism (860.1300)

No livestock feed items are associated with use on caneberries ( Table 1 Feedstuffs , June 2008).

4.1.3 Summary of Confined Rotational Crops (860.l850)

Caneberries are not considered to be rotated (OCSPP 860.1850).

4.1.4. Summary of Metabolites and Degradates

4. 2 Co mparison of Metabolic Pathways

DP Barcode D 380523 , N. Dodd, 7/18/11

Metabolism studies on cottonseed , citrus, and celery 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 t he 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 t he pulp. For the tolerance assessment and risk assessment, the residues of concern in these crops are the parent compounds (avermectin B 1a and B 1b ) and their delta

- 8,9

- isomers (also known as 8,9

- Z isomers).Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 10 of 19 4.3 Residues of Concern Summary and Rationale

DP Barcode D380523, N. Dodd, 7/18/11 DP Barcode D357192, T. Morton, 1/27/09 DP Barcode D402677, N. Dodd, 12/20/12

Metabolism in Primary Crops : The qualitative nature of abamectin residues in cotton and strawberry is adequately understood based on metabolism studies on cotton, citrus, and celery (PP#'s 5G3500, 5G3287, and 8F3649, respectively), as well as a report titled "Comparative Degradation of Avermectin B 1 a in Cotton Leaf, Citrus Fruit, Celery, and In Vitro " (PP#9F3703, S. Willett, 12/15/89). The available studies on cotton, citrus, and celery indicate that the metabolism of abamectin in plants results in a complex mixture of residues, with the majority of the terminal residue composed of several unidentified polar degradates. The parent comp ound,
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 preharvest interva l (PHI)] and in vitro (30 hour sample) have been tested for toxicity (in the developmental toxicity study in CF

- 1 mice) 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). As stated in
The Pesticide Manual , Eleventh Edition, British Crop Protection Council (1997), abamectin has limited plant systemic activity, but does exhibit some translaminar movement. For the tolerance

ex pression and risk assessment, the residues of concern in these crops are the parent compounds (avermectin B 1a and B 1b ) and their delta

- 8,9

- isomers (also known as 8,9

- Z avermectin B 1a and 8,9

- Z avermectin B 1b ).

Metabolism in Rotational Crops : The qualitat ive nature of the residue in rotational crops is adequately defined. 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 degrada tes that were of little toxicological concern as compared to the parent compound avermectin B 1 and/ or the delta

- 8,9

- isomer (Memo, P. Mastradone, 4/24/88).

Metabolism in Ruminants : The qualitative nature of abamectin residues in ruminants as a result
of application to crops is adequately understood based on a goat metabolism study (PP#7G3468, L. Cheng, 2/11/87; PP#9F3703, S. Willett, 12/15/89). The residues of concern in ruminants for the tolerance expression and risk assessment are the parent compounds (avermectin B 1a and B 1b )
and their delta

- 8,9

- isomers. An additional metabolite (24

- hydroxymethyl avermectin B 1a ) was identified and is potentially of toxicological significance, but was not included in the tolerance expression because of its presence at low levels (PP#8F3592, F. Boyd, 6/21/89; DP#203373, G. J. Herndon, 3/29/95). 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 m ay need to be included in the tolerance expression and appropriate enforcement methods developed.

The qualitative nature of the residue in ruminants from use of the cattle ear tag is adequately
understood based on sufficient non

- guideline data. The resid ues of concern are the parent compounds (avermectin B 1a and B 1b ) and their delta

- 8,9

- isomers.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 11 of 19 Metabolism in Poultry : No poultry metabolism study has been submitted. Since no significant poultry feed items are associated with the proposed uses, as indica ted in Table 1 Feedstuffs (June 2008) , no poultry metabolism study is required. (Note: The tolerances for meat and meat byproducts of poultry and swine of 0.02 ppm were established for residues in food handling establishments.)

Metabolism in Rats: Avermectin B 1a does not bioaccumulate in rat tissues. Avermectin B 1a in
rats is metabolized to 24

- hydroxy

- methyl B 1a (i.e., 24

- OH

- Me

- B 1a ), which accounts for most of
the radiolabeled residues.

Residues of concern for the risk assessment and tolerance e xpression are summarized in Table
4.3 below.

Table 4.3. Summary of Metabolites and Degradates to be included in the Risk Assessment

and Tolerance Expression

Matrix Residues included in Risk

Assessment Residues included in Tolerance Expression

Plants Primary Crop Parent (avermectin B 1a and

B 1b ) and the delta

- 8,9

- isomers (also known as 8,9

- Z isomers) Parent (avermectin B 1a and

B 1b ) and the delta

- 8,9

- isomers (also known as 8,9

- Z isomers)

Rotational Crop Parent (avermectin B 1a and

B 1b ) and the delta

- 8,9

- isomers (also known as 8,9

- Z isomers) Parent (avermectin B 1a and

B 1b ) and the delta

- 8,9

- isomers (also known as 8,9

- Z isomers)**

Livestock Ruminant* Parent (avermectin B 1a and

B 1b ) and the delta

- 8,9

- isomers (also known as 8,9

- Z isomers) Parent (avermectin B 1a and

B 1b ) and the delta

- 8,9

- isomers (also known as 8,9

- Z isomers)

Poultry Not applicable Not applicable

Drinking Water Parent (avermectin B 1a and

B 1b ) *** Not applicable

* Residues of concern in ruminants include both use on crops and use in cattle ear tags.

** No rotational crop tolerances have been established.

*** T he delta

- 8,9

- isomers (also known as 8,9

- Z isomers) are not included in the drinking water assessment because they were not identified in the fate studies . The major soil degradate included in the previous assessment ( a mixture
of an 8

- alpha

- hydroxy and a ring opened aldehyde derivative ) was not included in the current assessment based on an assumption of stability of parent until acceptable environmental fate data are subm itted (D380524, G. Orrick, 1/31/11).Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 12 of 19 5.0 Residue Profile

5.1 Residue Analytical Methods (860.1340)

5.1 .1 Data Collection Methods

49080101.der caneberry

Caneberry

Caneberry samples were analyzed for residues of avermectin B 1a , 8,9

- Z avermectin B 1a , and
avermectin B 1b using an HPLC method with fluorescence detection based on analytical method

M

- 073. The limit quantitation (LOQ) for each analyte is 0.002 ppm, the lowest level of method validation (LLMV). The method was validated prior to sampl e analysis by spiking control blackberry samples with 0.002

- 0.1 ppm avermectin B 1a , 0.002

- 0.008 ppm avermectin B 1b , and
0.002

- 0.1 ppm 8,9

- Z avermectin B 1a

. All method validation recoveries were within the acceptable 70

- 120% range. Adequacy of the method was also confirmed during sample analysis by spiking control blackberry and raspberry samples with 0.002

- 0.12 ppm avermectin B 1a , 0.002

- 0.01 ppm avermectin B 1b , and 0.002

- 0.12 ppm 8,9

- Z avermectin B 1a

. F our low concurrent
recoveries were attributed to spiking errors. T he remaining recoveries , w ith the exception of one concurrent recovery of 68%, were all within the acceptable range of 70

- 120%. Given that the majority of recoveries were within the acceptable range, the working method bas ed on Method

M

- 073 is adequate for the determination of residues in blackberries and raspberries.

Conclusions. Caneberry samples were analyzed for residues of avermectin B 1a , 8,9

- Z avermectin

B 1a , and avermectin B 1b using a n HPLC method with fluorescenc e detection based on analytical
method M

- 073. The method ha s been adequately validated as data collection methods based on acceptable concurrent recovery data

. Method M

- 073 quantitates the sum of avermectin B 1a and 8,9

- Z avermectin B 1a as a single value , with residues of avermectin B 1b determined as a separate peak. T he LOQ

, determined as LLMV

, was 0.002 ppm for each analyte in each matrix.

5.1.2 Multi

- Residue Methods (860.1360)

DP Barcode D 380523 , N. Dodd, 7/18/11

The 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 diet ary exposure assessment and can not be used as the p rimary
enforcement method.

5.1 .3 Tolerance Enforcement Methods

DP Barcode D 380523 , N. Dodd, 7/18/11
DP Barcode D230333, G. Jeffrey Herndon, 1/10/97
DP Barcode D198491, Jerry Stokes, 2/2/94

Adequate enforcement methods for abamectin in plant and livestock commodities are available
in the Pesticide Analytical Manual, Volume II ( PAM II) . The methods have been validated forAbamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 13 of 19 citrus and processed fractions (Method I), ginned cottonseed (Method IA ), and bovine tissues and milk (Method II ). These methods determine residues in plant and livestock commodities 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 de tection (LOD) of the methods for plant and livestock commodities is 0.001 ppm for each analyte, equivalent to 0.002 ppm for two analy te peaks (i.e., avermectin B 1a and its delta

- 8,9

- isomer in one peak and avermectin B 1b and its delta

8,9

- isomer in the othe r peak).

5.1.4 Submittal of Analytical Reference Standards (860.1650)

Analytical reference standards are available at the EPA National Pesticide Standards Repository [Source: e

- mail from Gregory Verdin of the Analytical Chemistry Branch/Biological and

Ec ono mic Analysis Division (ACB/BEAD)].

5 .2 Storage Stability (860.1380)

49080101 .der

Caneberry s amples were stored frozen (≤

- 20 °C) from collection to analysis (3 3. 4 months). Adequate storage stability data are available demonstrating that residues of avermectin B 1a , avermectin B 1b , and 8,9

- Z avermectin B 1a are stable under frozen storage conditions for 33
months in blackbe rries.

TABLE 5.2

. Summary of Storage Conditions.

Matrix (RAC) Storage Temperature (°C) Actual Storage
Duration 1 Interval of Demonstrated Storage Stability (months)

Blackberry and raspberry ≤

- 20 1016 days ( 33.4 months) Residues of avermectin B 1a , avermectin B 1b and 8,9

- Z
avermectin B 1a were stable when stored frozen for 33
months in blackberries.

1 From harvest to extraction. Residues were determined within 5 days of extraction.

Conclusions

. The storage stability data are adequate to support the storage intervals and
conditions for the caneberry residue samples from the submitted field trials

.

5.3 Residue Data

5.3.1 Crop Field Trials (860.1500)

49080101 .der ( caneberries )

Caneberries :

The Interregional Research Project No. 4 (IR

- 4) ha s submitted field trial data for abamectin on blackberries and raspberries. Fo ur field trials were conducted on blackberries in Zones 1 (1 in NY), 2 (1 in NC; 1 in NJ), and 12 (1 in OR). Three field trials were conducted on raspberries in Zones 5A (1 in MI) and Zone 12 (1 trial in WA; 1 in OR). The geographic representation andAbamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 14 of 19 number of fi eld trials are adequate. Refer to Appendix A for the geographic distribution table.

At each trial site, abamectin, formulated as an emulsifiable concentrate (Agri

- Mek ® 0.15EC) was applied to caneberries in three foliar broadcast or directed application s at rates of 19.4

– 23.1 g ai/ha (0.017

- 0.021 lb ai/A), for total rates of 61.3

– 67.9 g ai/ha (0.055

- 0.061 lb ai/A) . A non

ionic surfactant was included in the spray mixture for all applications. The re

- treatment interval (RTI) was 6

– 8 days, and commer cially mature blackberries and raspberries were harvested at a PHI of 7 days at all trial sites. Additional samples were harvested at PHIs of 0, 3, and 9 days at one of the blackberry trial sites to determine residue decline behavior. There was one untreat ed control plot and one treated plot at each trial site.

As shown in Table 5.3.1 below, t otal combined residues of avermectin B 1a + 8,9

- Z avermectin

B 1a and avermectin B 1b + 8,9

- Z avermectin B 1b in blackberries and raspberries following a total application of 61.3

– 67.9 g ai/ha (0.055

- 0.061 lb ai/A) ranged from <0.0062

– 0.1215 ppm when samples were harvested at a PHI of 7 days. Total abamectin residues declined with increasing
PHI when blackberry samples were harvested at PHIs of 0, 3, 7, and 9 days.

A n acceptable method was used for residue quantitation, and adequate storage stability data are available to support sample storage intervals and conditions for all analytes.

TABLE 5.3.1

. Summary of Residue Data from Caneberr y F ield Trials with Abamectin Commodity Total Applic.

Rate

, g ai/ha (lb ai/A) PHI (days) Residue Levels 1 ,2 (ppm)

n Min. Max. LAFT 3 HAFT 3 Median (STMdR) Mean (STMR) Std. Dev.

C ANEBERRIES Proposed Use = 0.056 l b ai/acre/season total application rate, 7

- day PHI Blackberry 62.8

– 66.1 (0.056

- 0.059) 7 4 <0.0164 0.0632 <0.0171 0.0535 <0.0233 <0.029 0.01 7

Raspberry 61.3

– 67.9 (0.055

- 0.061) 7 3 <0.0062 0.1215 <0.0067 0.1184 0.0084 0.045 0.064

Blackberry
and Raspberry 61.3

- 67.9 (0.055

- 0.061) 7 7 <0.0062 0.1215 <0.0067 0.1184 <0.0204 <0.0358 0.040

1 Residues of avermectin B 1a , 8,9

- Z avermectin B 1a , and avermectin B 1b were reported.

2 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ (0.002 ppm for each analyte in each matrix) was used for any results reported as <LOQ.

3 LAFT = lowest average field trial; HAFT = highest average field trial.

Conclusions

. Adequate field trials were submitted for abamectin on caneberries. Seven field trials were conducted on blackberries and raspberries in Zones 1 (1 in NY), 2 (1 in NC; 1 in NJ), 5A (1 in MI), and 12 (2 in OR; 1 in WA). Abamectin, formulated as an emulsifiable concentrate, was applied to caneberries as three foliar broadcast or directed applications at total rates of 61.3

– 67.9 g ai/ha (0.055

- 0.061 lb ai/A) , and a non

- ionic surfactant was included in the spray mixture for all applications. Total combined residues of avermectin B 1a + 8,9

- Z avermectin B 1a and
avermectin B 1b in blackberries and raspberries ranged from < 0.0062

– 0.1215 ppm when samples were harvested at a PHI of 7 days. Total abamectin residues declined with increasing PHI when blackberry samples were harvested at PHIs of 0, 3, 7, and 9 days.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 15 of 19 The studies reflect the proposed use patterns. The number of trials and the geographic representation are adequate. The residue data are adequately supported by the storage stability studies. The analytical methods are adequate for the analysis of the residues of concern. The residue data adequately add ress the residues of concern.

5.3.2 Field Rotational Crops (860.1900 )

Caneberries are not considered to be rotated.

5.3.3 Processed Food and Feed (860.1520)

There are no processed commodities associated with caneberries.

5.3.4 Meat, Milk, Poultry and Eggs (860.1480)

There are no livestock feed items associated with caneberries.

5.3.5. Food Handling (860.1460)

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

5.3.6. Water, Fish, and Irrigated Crops (860.1400)

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

5.4. Food Residue Profile

The residue chemistry database is adequate for tolerance assessment and for registration of the
two EC f ormulations of abamectin on caneberries.

Crop field trials : The caneberry ( blackberry and raspberry ) field trials adequately reflect the proposed use pattern. The number of trials and the geographic representation are adequate.
Field trial residues were low but quantifiable in caneberries. Residues in blackberries d ecline with increasing PHI.

Processing Studies : There are no processed commodities associated with caneberries.

Storage Stability : Adequate storage stability data are available to support the field trials.

Meat, Milk, Poultry, and Eggs : There are no l ivestock feed items associated with caneberries.

Rotational Crops : Caneberries are not considered to be rotated

.

6.0 Tolerance Derivation

As shown in Appendix C, t he Organization for Economic Cooperation and Development ( OECD ) tolerance calculation proc edures were used for calculating the recommended toleranceAbamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 16 of 19 for caneberries. The statistical goal of the tolerance calculation procedures is to produce an MRL proposal in the region of the 95 th percentile of the underlying residues distribution.

Caneberry (MRID 49080101)

The dataset used to establish a tolerance for abamectin consisted of field trial data on blackberries and raspberries representing application rates of 0.0 56 lb ai/A abamectin with a 7

- day PHI. The combined dataset of blackberries and raspberries (seven field trials) was used since the representative crop for the caneberry subgroup 13

- 07A is either blackberry or raspberry. The field trial application rates and PHIs are within 25% of the maximum label application rate and minimum label PHI, respectively. The average residue values used to calculate the tolerance are provided below. Combined residues of avermectin B 1a , 8,9

- Z
avermectin B 1a , and avermectin B 1b were quantifiable in/on samples from all seven field trials. Using the OECD tolerance calculation procedures, the recommended tolerance is 0. 2 0 ppm for
combined residues of avermectin B 1a , 8,9

- Z avermectin B 1a , and avermectin B 1b in caneberries.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 17 of 19 Appendix A. Field Trial Geographic Distrib ution

TABLE A. Trial Numbers and Geographical Locations

.

NAFTA Growing

Zones Caneberry

Submitted Requested (DIR98

- 02)* Requested by US**

Blackberry Raspberry Raspberry

1 1

-- -- 1R

2 2

-- -- 1B

5

-- -- 1 1R

5A

-- 1

-- 5B

-- -- 1

6 1B

12 1 2 3 3B,3R

Total 4 3 5 5 *Since trials were conducted prior to January 2012, trials are required as indicated in DIR98

- 02. DIR98

- 02 does not specify trial requirements for blackberries. ** Table 4, OCSPP 860.1500 indicates that 5 trials (on any one blackberry (B) or any one raspberry (R)) should be conducted for the caneberry crop group. The five sites can be chosen from the requested locations for blackberry and raspberry (Table 5, OCSPP 860.1500).Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 18 of 19 Appendix B . International Residue Limits T able



### Abamectin ( 122804 ; 9/19/ 20 13 )
Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 2 Codex
40 CFR §180.449: avermectin B 1 [a mixture of avermectins containing greater than or equal to 80% avermectin

B 1a (5

- O

- demethyl avermectin A 1 ) and less than or equal to 20% avermectin B 1b (5

- O

- demethyl

- 25

- de(1

- methylpropyl)

- 25

- (1

- methylethyl) avermectin A 1 )] and
its delta

- 8,9

- isome r avermectin B 1 (a mixture of avermectins containing greater than or equal to 80%
avermectin B 1a (5

- O

demethyl avermectin A 1a ) and less than or equal to
20% avermectin B 1b (5

- O

demethyl

- 25

- de(1

- methylpropyl)

- 25

- ( 1

- methylethyl ) avermectin

A 1a ) 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 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 Codex Caneberry subgroup 13

- 07A 0.20 0.20 (pending)

Completed: M. Negussie; 9/19/2013

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

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 412860

Page 19 of 19 A ppendix C

. OECD MRL Calculation Procedure Inputs/Outputs

Blackberry and Raspberry ( MRID 49080101 )

0.056 lb ai/A; 7

- day PHI
**Residues (mg/kg) n** 

0.0067 1

0.0084 1

0.0171 1

0.0204 1

0.0262 1

0.0535 1

0.1184 1

**Abamectin**

**Black berry**  **/Raspberry**

**USA**

**0.056 lb ai/A ; 7** 

**- day**  **PHI**

**Total number of data (n)** 7
**Percentage of censored data** 0%

**Number of non**

**- censored data**  7

**Lowest residue** 0.007
**Highest residue** 0.118

**Median residue** 0.020

**Mean** 0.036

**Standard deviation (SD)** 0.040
**Correction factor for censoring (CF)** 1.000

**Proposed MRL estimate**

**- Highest residue**  0.118

**- Mean + 4 SD**  0.194

**- CF x 3 Mean**  0.107

**Unrounded MRL** 0.194

**Rounded MRL 0.2** 

High uncertainty of MRL estimate.

[Small dataset]