Page 1 of 16 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND
POLLUTION PREVENTION MEMORANDUM

Date: March 17, 2016

Subject: PP 3F8200. Abamectin

. Review of a Section 3 Registration Request for Ear Tag Use on Lactating Dairy Cattle. Summary of Analytical Chemistry and Residue Data.

PC Code: 122804 DP Barcode: D41 0993
Decision No.: 47 6238 Registration No. : 39039

- 17
Petition No.: PP 3F8200 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: Christine Olinger, Chief
RAB3 / HED ( 7509P )

To: Mark Suarez , Jessica Rogala, RM #7 Registration Division (7505P)

Summary of Submitted Residue Chemistry Studies

O C S PP 860 Series
Guideline MRID
Number Title

860.1500 49078101 Smith, V. (2012) A GLP Milk Residue Study Using the Agressor Cattle Ear Tag (YT

- 2508) in Dairy Cattle in a Tropical Climate : Final Report. Project Number:
YTEX/GLP/11/01

- 1A . Unpublished study prepared by Agrisearch Services Pty, Ltd. 190 p.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 2 of 16 Table of Contents

1.0 Executive Summary

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

2.0 Regulatory Recommendations

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

2.1 Data Deficiencies/Data Needs

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

2.2 Tolerance Considerations

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

2. 2.1 Enforcement Analytical Method

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

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

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

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)

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

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

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

5.0 Residue Profile

................................ ................................ ................................ ................... 11

5.1 Residue Analytical Methods (860.1340)

................................ ................................ ........ 11

5.1.1 Data Collection Methods

................................ ................................ ........................ 11

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)

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

5.2 Storage Stability (860.1380)

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

5.3 Residue Data

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

5.3.1 Crop Field Trials (860.1500)

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

5.3.2 Field Rotational Crops (860.1900)

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

5.3.3 Processed Food and Feed (860.1520)

................................ ................................ ..... 13Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 3 of 16 5.3.4 Meat, Milk, Poultry and Eggs (860.1480)

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

5.3.5. Food Handling (860.1460)

................................ ................................ ...................... 14

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

................................ .......................... 14

5.4. Food Residue Profile

................................ ................................ ................................ ...... 14

6.0 Tolerance Derivatization

................................ ................................ ................................ .... 15
Appendix A. International Residue Limits Table

................................ ................................ ........ 16Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 4 of 16 1.0 Executive Summary

Y

- TEX Corporation has requested registration of an ear tag containing abamectin and piperonyl butoxide for use on lactating dairy cattle. An ear tag use has be en registered on beef cattle and

non

- lactating dairy cattle. Tolerances for abamectin on fat, meat, and meat byproducts of cattle
were increased to reflect that use. This review concerns residues in milk. No tolerance on milk has been proposed. T his re view concerns only abamectin; piperonyl butoxide is under separate
concurrent review.

Tolerances are established under 40 CFR §180.449 for residues of abamectin (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.

T he residue chemistry database is adequate for tolerance assessment and for registr ation of the ear tag on lactating dairy cattle. Residues of concern in livestock commodities are parent (avermectin B 1a and avermectin B 1b ) and the 8,9

- Z isomers. The trials reflect the proposed use
pattern. An adequate method was used for data collecti on. Adequate concurrent storage stability data are available to support the cattle ear tag study. The dairy cattle ear tag study indicates that use of the ear tags would add maximum residues of 0.0046 ppm to milk

.

2.0 R egulatory R ecommendations

Provided that a tolerance of 0.01 5 ppm is proposed for abamectin in milk t here are no residue chemistry considerations that would preclude granting the requested registration for use of the ear tag on lactating dairy cattle. The specific tolerance recomme ndations are discussed in
Section 2.2 . There are no recommended label modifications.

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 teAbamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 5 of 16 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 other 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) Y

- TEX Proposed
Tolerance

(ppm) HED

Recommended
Tolerance

(ppm) Comments ( correct commodity definition )

Milk 0.005 0.01 0.01 5

2.2.3 Revisions to Petitioned

- For Tolerances

The existing tolerance of 0.005 ppm for milk must be raised because residues were found in milk in the dairy cattle ear tag study. The r ecommended tolerance of 0.015 ppm for milk includes residues from pending/registered crops and dairy cattle ear tags (D414022, N. Dodd, 3/17/16)

.

2.2.4 International Harmonization

The livestock residue definitions are essentially the same for the US and Canada; the Codex residue definition includes only avermectin B 1a and its 8,9

- Z isomer, whereas the US and Canada
include both avermectin B 1a and avermec tin B 1b and their 8,9

- Z isomers. There are no Canadian
tolerances set on livestock commodities. There are some Codex maximum residue limits (MRLs) on livestock commodities, but fewer than US tolerances. None of the Codex MRLs are
set at the same level a s the US recommended tolerance levels. An International Residue Limits Status sheet is attached (Appendix A.)

2.3 Label Recommendations

None.

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) avermecti n A 1 )] and its delta

- 8,9

- isomer. 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.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 6 of 16 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

- 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

- dide oxy

- 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 )

- 21,22

- 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 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/EP Y

- TEX ® XP 820TM Insecticide Cattle Ear Tags

, EPA Reg. No. 39039

- 17, with an average weight of 9 grams per tag

, contain abamectin (80 g/kg ; 8% ) and piperonyl butoxide (200 g/kg ; 20% )

.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 7 of 16 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)

Y

- TEX Corporation has submi tted a request to register use of a cattle ear tag on beef and dairy (including lactating) cattle to control horn flies, gulf coast ticks, spinose ear ticks, and to aid in control of American dog ticks, cattle fever ticks ( Boophi lus species), Lone Star ticks, and to
reduce face flies. The ear tags with an average weight of 9 grams per tag contain a formulation
of 8% abamectin, 20% piperonyl butoxide, and 72% inerts. The tags can be r eappl ied as necessary with up to two treatmen ts per year. Remove tags before slaughter.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 8 of 16 Table 3.3. Summary of Proposed Directions for Use of Abamectin in Cattle Ear Tags

. Applic. Timing, Type, and Equip. Formulation 1 [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

Cattle Ear Tags

1 or 2 ear tags per animal for
2

- 5 months
per treatment depending on the target pest Y

- TEX® XP
820TM
Insecticide
Cattle Ear Tags [39039

- 17] NA NA NA Not
stated Use on beef and dairy (including lactating)
cattle. Reapply as necessary with up to two
treatments per year. Remove tags before slaughter.

1 Y

- TEX AGRESSOR Cattle Ear Tags (Code Number YT

- 2508) were used in MRID 49078101. The ear tags contain two active ingredients in the following nominal concentrations: abamectin (80 g/kg ; 8% ) and piperonyl butoxide (200 g/kg ; 20% ) . The name previously used in D357192 (T. Morton, 1/27/09) was BovamecTM (YT

- 2508) Cattle Ear Tags (EPA Reg. No. 39039

- RT).

Conclusions

. T he label is a dequate 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)

T he residue chemistry data requirements for the nature of the residue in plants are not pertinent
to this review.

4.1.2 Summary of Livestock Metabolism (860.1300)

DP Barcode D 380523 , N. Dodd, 7/18/11 DP Barcode D357192, T. Morton, 1/27/09

No new livestock metabolism data were submitted with this registration request.

The nature of the residue i n ruminants from dietary exposure as a result of application to crops is adequately understood based on a goat metabolism study using oral dosing of radiolabeled
abamectin (PP#7G3468, L. Cheng, 2/11/87; P P#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 1 a ) 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 may need to be included in theAbamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 9 of 16 tolerance expression and appropriate enforcement methods developed.

The nature of the residue in livestock reflecting dermal metabolism is adequately understood for the cattle ear tag use only. A dermal metabolism study was not required for the registered ear tag
use on beef and non

- lactating dairy cattle (D357192, T. Morton, 1/27/09). It was determined that
sufficient non

- guideline data have been submitted to support the waiving of the requirement of the dermal metabolism study for the ear tag use. Any additional dermal uses will require a dermal metabolism study. The resid ues of concern in cattle from the ear tag use for the tolerance expression and risk assessment are the parent compounds (avermectin B 1a and B 1b ) and their 8,9

- Z isomers.

4.1.3 Summary of Confined Rotational Crops (860.l850)

The residue chemistry dat a requirements for the nature of the residue in confined rotational crops are not pertinent to this review.

4.1.4. Summary of Metabolites and Degradates

4. 2 Comparison of Metabolic Pathways

DP Barcode D 380523 , N. Dodd, 7/18/11 DP Barcode D357192, T. Morton, 1/27/09

The residues of concern from oral dosing and dermal application for the tolerance expression and risk assessment are the parent compounds (avermectin B 1a and B 1b ) and their delta

- 8,9

- isomers.

4.3 Residues of Concern Summary and Rationale

DP Barcode D 380523 , 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, 12/15/8 9). 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 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 preharvest int erval ( 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). A s 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 toleranc e expression and risk assessment, the residues of concern in these crops are the parent compoundsAbamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 10 of 16 (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 qualitative 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 p olar degradates 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 a s 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 par ent 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 may 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 dat a. The residues of concern are the parent compounds (avermectin B 1a and B 1b ) and their delta

- 8,9

- isomers

.

Metabolism in Poultry : No poultry metabolism study has been submitted. Since no significant poultry feed items are associated with the proposed us es, as indicated 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 expression are summarized in Table
4.3 below.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 11 of 16 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 Express ion

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 submitted (D380524, G. Orrick, 1/31/11).

5.0 Residue Profile

5.1 Residue Analytical Methods (860.1340)

5.1 .1 Data Collection Methods

49078101.der

Samples were analyzed for residues of abamectin ( total avermectin B 1a and avermectin B 1b ) using a high performance liquid chromatography method with fluorescence detection (HPLC/FD), Agrisearch Analytical Pty Ltd method AATM

- R

- 53

. The limit of quantitation ( LOQ ; determined as the lowest level of method validation, LLMV) was 0.002 ppm

. The
method was adequate for data collection based on acceptable concurrent recovery data. The fortification levels used in concurrent method recovery were adequate to bracket expected
residue levels. C oncurrent recoveries were corrected for apparent residues in control s; r esidues in the treated samples were not corrected for residues in controls.

Conclusions. The HPLC/FD data collection method, Method AATM

- R

- 53, was adequate for
determination of total residues of avermectin B 1a /8,9

- Z isomer and avermectin B 1b / 8,9

- Z isomer based on acceptable concurrent recovery data. The LOQ of the method was 0.002 ppm for each analyte.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 12 of 16 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 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).

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

Econo mic Analysis Division (ACB/BEAD)].

5.2 Storage Stability (860.1380)

S amples were stored frozen (~

- 20 °C) from sampling to analysis for 9

- 68 days (0.3

- 2.2 months)

. The interval between extraction and analysis was not reported

. Storage stability data generated concurrently with the ear tag study demonstrate that residues of abamectin were stable in/on samples of milk stored frozen for up to 55 days; no 0

- day data were provided. These data are acceptable to support the storage conditions and durat ions of samples from the submitted study ; however, storage stability studies should always include a 0

- day sampling interval to establish the residue levels present at the time samples are placed into storage [see O CSPP 860.1380(d)(6)(i)].Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 13 of 16 TABLE 5.2

. Summary of Storage Conditions.

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

Milk

- 20 9

- 68 days (0.3

- 2.2 months) Residues of avermectin B 1a , avermectin B 1b and 8,9

- Z
avermectin B 1a were stable when stored frozen for 55 days
in milk

. 1 The interv al between extraction and analys is was not reported.

Conclusions

. T he storage stability data are adequate to support the storage intervals and
conditions for the residue samples of milk

.

5.3 Residue Data

5.3.1 Crop Field Trials (860.1500)

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

5.3.2 Field Rotational Crops (860.1900 )

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

5.3.3 Processed Food and Feed (860.1520)

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

5.3.4 Meat, Milk, Poultry and Eggs (860.1480)

An ear tag containing abamectin and piperonyl butoxide is registered for use on beef cattle and

non

- lactating dairy cattle. Tolerances for abamectin on fat, meat, and meat byproducts of cattle
were increased to reflect that use (D357192, T. Morton, 1/27/09)

. Y

- TEX Corporation has now
submitted a study to determine residues of abamectin in milk from use of the ear tag on lactating dairy cattle.

Twenty

- five lactating cattle were divided into one treatment group and one control group. The control group consisted of 3 cows and the treated group consisted of 22 cows, with two cows serving as spares. The test su bstance, Y

- TEX AGRESSOR CATTLE EAR TAGS, a 9

- gram ear tag containing 80 g/kg abamectin and 200 g/kg piperonyl butoxide, was applied at a rate of 2 tags per animal (one per ear). The treatment group was exposed to the ear tags for 28 days. The study was c onducted at Faraway Farm (Topaz, Queensland, Australia). The study report included residue data for abamectin and piperonyl butoxide. Only analytical results for abamectin are included in this DER; analytical results for piperonyl butoxide are included i n a separate DER for piperonyl butoxide.

Cows were milked twice daily , in the morning and in the afternoon. Individual morning and
afternoon milk s amples from Study Days

- 1, 0 (immediately after treatment), 1

- 19, 21, and 28 were analyzed ; no samples were combined for analysis.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 14 of 16 Samples were analyzed for residues of abamectin ( total avermectin B 1a and avermectin B 1b ) using a high performance liquid chromatography method with fluorescence detection (HPLC/FD), Agrisearch Analytical Pty Ltd method AATM

- R

- 53

. The limit of quantitation ( LOQ ; determined as the lowest level of method validation, LLMV) was 0.002 ppm

. The method was adequate for data collection based on acceptable concurrent recovery data. The
fortification levels used in concurrent method reco very were adequate to bracket expected
residue levels. C oncurrent recoveries were corrected for apparent residues in controls; r esidues in the treated samples were not corrected for residues in controls.

S amples were stored frozen (~

- 20 °C) from sampling to analysis for 9

- 68 days (0.3

- 2.2 months)

. The interval between extraction and analysis was not reported

. Storage stability data generated concurrently with the ear tag study demonstrate that residues of abamectin were stable in/on samples of milk stored frozen for up to 55 days; no 0

- day data were provided. These data are acceptable to support the storage conditions and durations of samples from the submitted study ; however, storage stability studies should always include a 0

- day sampling interval to establish the residue levels present at the time samples are placed into storage [see O CSPP 860.1380(d)(6)(i)].

Residues of abamectin in milk appeared to reach a plateau by Day 5. Residues of abamectin

were < 0.002

- 0.0046 ppm in milk samples following 0

- 28 days of exposure

. Average residues were generally constant throughout the exposure period.

Conclusion. The submitted dairy cattle ear tag study is adequate to quantify the magnitude of residues of abamectin in milk of dairy cows following treatment with two 9

- gram ear tags, each containing 8 g/kg abamectin and 200 g/kg piperonyl butoxide. Treatment lasted for 28 days of

exposure.

Residues of abamectin in milk appeared to reach a plateau by Day 5. Residues of abamectin

were < 0.002

- 0.0046 ppm in milk samples following 0

- 28 days of exposure

. Average residues were generally constant throughout the exposure period.

An acceptable method was used for residue quantitation, and a dequate data were submitted to support sample storag e intervals and conditions.

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 submitted dairy cattle ear tag study is adequate to quantify the magnitude of residues ofAbamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 15 of 16 abamectin in milk of dairy cows following treatment with two 9

- gram ear tags, each containing 8 g/kg abamectin and 200 g/kg piperonyl b utoxide. The maximum residues in milk from use of the ear tag was 0.0046 ppm

. The storage stability data are adequate to support the storage intervals and conditions for the residue samples of milk.

6.0 Tolerance Derivatization

The established tol erance for abamectin in milk is 0.01 ppm (40 CFR §180.449).

The dairy cattle ear tag study indicates that use of the ear tags would add maximum residues of 0.0046 ppm to milk

.

In a concurrent petition on crops with livestock feed items (D414022, N. Dodd 3 /1 7 /1 6 ) , HED
has reassessed the established livestock commodities. T he calculated residues in livestock commodities include residues from uses on proposed/registered crops and from beef and dairy cattle ear tags. It was determined tha t higher tolerances are needed for some livestock
commodities ; the recommended tolerances are shown in Appendix A

. T he recommended tolerance for milk is 0.015 ppm.Abamectin Summary of Analytical Chemistry and Residue Data Barcode D 410993

Page 16 of 16 Appendix A . 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 3

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

- isomer 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) A nimal
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 3

Cattle, fat 0.05 0.1 4
Cattle, meat 0.02 0.01 (*)

Cattle, meat byproducts 0.09 0.05 4 cattle kidney
0.1 4 cattle liver Goat, fat 0.03 Goat, meat 0.02 0.01 (*)

Goat, meat byproducts 0.04 0.1 goat edible
offal Hog, fat 0.01 Hog, meat 0.02 Hog, meat byproducts 0.02 Horse, fat 0.03 Horse, meat 0.02 Horse, meat byproducts 0.04

Milk 0.01 5 0.005 cattle milk 0.005 goat milk Poultry, meat 0.02 Poultry, meat byproducts 0.02 Sheep, fat 0.03 Sheep, meat 0.02 Sheep, meat byproducts 0.04 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.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MRLs indicated as proposed ha ve not been finalized by the CCPR and the CAC.

4 The MRL accom m odates external animal treatment.