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: D410993

Decision No.: 476238 Registration No.: 39039-17

Petition No.: PP 3F8200 Regulatory Action: Section 3 Registration

Risk Assessment Type: NA Case No.: NA

TXR No.: NA 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

OCSPP 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 Unpublished study prepared by Agrisearch Services Pty, 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 D410993

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)..................................................................... 13
Abamectin Summary of Analytical Chemistry and Residue Data Barcode D410993

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 ........................................................................ 16
Abamectin Summary of Analytical Chemistry and Residue Data Barcode D410993

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 been 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. This review 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 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.

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

ear tag on lactating dairy cattle. Residues of concern in livestock commodities are parent 

(avermectin B1a and avermectin B1b) and the 8,9-Z isomers. The trials reflect the proposed use 

pattern. An adequate method was used for data collection. 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 Regulatory Recommendations

Provided that a tolerance of 0.015 ppm is proposed for abamectin in milk there 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 recommendations 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 detection (LOD) of the methods for plant and 

livestock commodities is 0.001 ppm for each analyte, equivalent to 0.002 ppm for two analyte 
Abamectin Summary of Analytical Chemistry and Residue Data Barcode D410993

Page 5 of 16

peaks (i.e., avermectin B1a and its delta-8,9-isomer in one peak and avermectin B1b and its delta8,9-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)

HEDRecommended 

Tolerance 

(ppm)

Comments 

(correct commodity definition)

Milk 0.005 0.01 0.015

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 recommended 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 B1a and its 8,9-Z isomer, whereas the US and Canada 

include both avermectin B1a and avermectin B1b 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 as 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. 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 

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 D410993

Page 6 of 16

3.1 Chemical Identity

Table 3.1. Abamectin Nomenclature

Compound

Abamectin

Chemical Structure

Common Names abamectin, avermectin B1

Company experimental name MK-0936

IUPAC name

mixture of (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-Larabino-hexopyranosyl)-3-O-methyl-α-L-arabino-hexopyranoside and 

(10E,14E,16E)-(1R,4S,5 'S,6S,6 'R,8R,12S,13S,20R,21R,24S)-21,22-dihydroxy-6 

'-isopropyl-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-Larabino-hexopyranosyl)-3-O-methyl-α-L-arabino-hexopyranoside

CAS name Avermectin B1

CAS # Avermectin B1 - 71751-41-2; Avermectin B1a - 65195-55-3; Avermectin B1b -

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 D410993

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 103 kg/m3 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 (pKa) no dissociation constant in aqueous solution

Octanol/water partition coefficient, 

Log Pow

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 submitted 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 (Boophilus 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 reapplied as 

necessary with up to two treatments per year. Remove tags before slaughter.
Abamectin Summary of Analytical Chemistry and Residue Data Barcode D410993

Page 8 of 16

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

Applic. 

Timing, Type, 

and Equip.

Formulation1

[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. The label is 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)

The 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 D380523, 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 in 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; 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 B1a and B1b) and their delta-8,9-isomers. An additional metabolite (24-

hydroxymethyl avermectin B1a) 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 
Abamectin Summary of Analytical Chemistry and Residue Data Barcode D410993

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 residues of concern in cattle from the ear tag use for the tolerance 

expression and risk assessment are the parent compounds (avermectin B1a and B1b) and their 8,9-

Z isomers. 

4.1.3 Summary of Confined Rotational Crops (860.l850)

The residue chemistry data 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 D380523, 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 B1a and B1b) and their delta-8,9-isomers. 

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 B1a 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 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 interval (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 

expression and risk assessment, the residues of concern in these crops are the parent compounds 
Abamectin Summary of Analytical Chemistry and Residue Data Barcode D410993

Page 10 of 16

(avermectin B1a and B1b) and their delta-8,9-isomers (also known as 8,9-Z avermectin B1a and 

8,9-Z avermectin B1b).

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 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).

 

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 B1a and B1b) 

and their delta-8,9-isomers. An additional metabolite (24-hydroxymethyl avermectin B1a) 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 data. The residues of concern are the parent 

compounds (avermectin B1a and B1b) 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 uses, 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 B1a does not bioaccumulate in rat tissues. Avermectin B1a in 

rats is metabolized to 24-hydroxy-methyl B1a (i.e., 24-OH-Me-B1a), 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 D410993

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 Expression

Plants Primary Crop Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Rotational Crop Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z

isomers)**

Livestock Ruminant* Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Poultry Not applicable Not applicable

Drinking Water Parent (avermectin B1a and 

B1b)***

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.

*** The 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 B1a and avermectin B1b) 

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. Concurrent recoveries were corrected for apparent residues in controls; residues 

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 B1a/8,9-Z isomer and avermectin B1b/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 D410993

Page 12 of 16

5.1.2 Multi-Residue Methods (860.1360)

DP Barcode D380523, 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 dietary exposure assessment and cannot be used as the primary 

enforcement method.

5.1.3 Tolerance Enforcement Methods

DP Barcode D380523, 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 detection (LOD) of the methods for plant and 

livestock commodities is 0.001 ppm for each analyte, equivalent to 0.002 ppm for two analyte 

peaks (i.e., avermectin B1a and its delta-8,9-isomer in one peak and avermectin B1b and its delta8,9-isomer in the other 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 

Economic Analysis Division (ACB/BEAD)].

5.2 Storage Stability (860.1380)

Samples 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 OCSPP

860.1380(d)(6)(i)].
Abamectin Summary of Analytical Chemistry and Residue Data Barcode D410993

Page 13 of 16

TABLE 5.2. Summary of Storage Conditions.

Matrix 

(RAC)

Storage 

Temperature

(°C)

Actual Storage 

Duration1

Interval of Demonstrated Storage Stability

(months)

Milk -20 9-68 days 

(0.3-2.2 months)

Residues of avermectin B1a, avermectin B1b and 8,9-Z 

avermectin B1a were stable when stored frozen for 55 days 

in milk. 1

The interval between extraction and analysis was not reported.

Conclusions. The 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 substance, 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 conducted 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 in a 

separate DER for piperonyl butoxide.

Cows were milked twice daily, in the morning and in the afternoon. Individual morning and 

afternoon milk samples 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 D410993

Page 14 of 16

Samples were analyzed for residues of abamectin (total avermectin B1a and avermectin B1b) 

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. Concurrent recoveries were corrected for apparent residues in controls; residues 

in the treated samples were not corrected for residues in controls.

Samples 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 OCSPP

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 adequate data were submitted to 

support sample storage 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 of 
Abamectin Summary of Analytical Chemistry and Residue Data Barcode D410993

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 butoxide. 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 tolerance 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 3/17/16), HED 

has reassessed the established livestock commodities. The calculated residues in livestock 

commodities include residues from uses on proposed/registered crops and from beef and dairy 

cattle ear tags. It was determined that higher tolerances are needed for some livestock 

commodities; the recommended tolerances are shown in Appendix A. The recommended 

tolerance for milk is 0.015 ppm.

 
Abamectin Summary of Analytical Chemistry and Residue Data Barcode D410993

Page 16 of 16

Appendix A. International Residue Limits Table

Abamectin (122804; 9/19/2013)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR §180.449: 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)

Animal 

commodities: sum 

of avermectin

B1a and 8,9-Zavermectin B1a.

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex3

Cattle, fat 0.05 0.14

Cattle, meat 0.02 0.01 (*)

Cattle, meat byproducts 0.09

0.054 cattle 

kidney

0.14 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 0.015 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 have not been finalized by the CCPR and the CAC.

4 The MRL accommodates external animal treatment.