ABAMECTIN Human Health Risk Assessment DP No. D426599 

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: April 18, 2016

SUBJECT: Abamectin. Human Health Risk Assessment for Uses on Caneberry Subgroup 

13-07A; Soybean; Sweet Corn; Ear Tags for Lactating Dairy Cattle; Golf Course 

Turf; Bean; Onion, Green, Subgroup 3-07B; Fruit, Pome, Group 11-10; Fruit, 

Small Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13-07F; Berry, Low 

Growing, Subgroup 13-07G; Vegetable, Fruiting, Group 8-10; Greenhouse 

Tomato; Fruit, Citrus, Group 10-10; Fruit, Stone, Group 12-12; and Nut, Tree, 

Group 14-12; and Various Tropical Fruits.

PC Code: 122804

Decision Nos.: 480177, 495169, 495170, 478520, 

476238

Petition Nos.: 3E8175, 3F8184, 4E8309

Risk Assessment Type: Single Chemical/Aggregate

TXR No.: NA

MRID No.: NA

DP Barcode: D426599

Registration Nos.: 100-898, 100-1154, 100-1350, 

100-1351, 100-1408, 100-1439, 100-RLNO, 100-

RLRN, 39039-17

Regulatory Action: Section 3 Registration

Case No.: NA

CAS No.: 71751-41-2

40 CFR: 180.449

FROM: Laura Nollen, Biologist, Risk Assessor

Kristin Rickard, Biologist

Whang Phang, Senior Toxicologist

Nancy Dodd, Chemist

Nancy Keller, Chemist

Risk Assessment Branch III (RAB3)

Health Effects Division (HED) (7509P) 

THROUGH: Christine Olinger, Branch Chief, RAB3

Health Effects Division (HED) (7509P) 

TO: Barbara Madden/Andrew Ertman, PM#5

Minor Use and Emergency Response Branch

Registration Division (7505P)

and

Mark Suarez/Jessica Rogala, PM#7

Invertebrate and Vertebrate Branch 3

Registration Division (7505P)
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The Registration Division (RD) requested that the Health Effects Division (HED) conduct a risk 

assessment for the active ingredient (ai) abamectin. A summary of the findings and an 

assessment of human health risks resulting from the proposed and registered uses of abamectin 

are provided in this document.

The HED team members contributing to this risk assessment are Laura Nollen 

(occupational/residential exposure assessment and risk assessment), Kristin Rickard (dietary 

exposure assessment), Whang Phang (toxicology assessment), Nancy Dodd (dietary exposure 

assessment, residue chemistry and risk assessment) and Nancy Keller (occupational/residential 

exposure assessment). Greg Orrick of the Environmental Fate & Effects Division (EFED) 

provided the drinking water exposure assessment.
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1.0 Executive Summary........................................................................................................... 5

2.0 HED Recommendations.................................................................................................... 9

2.1 Data Deficiencies ............................................................................................................ 9

2.2 Tolerance Considerations.............................................................................................. 9

2.2.1 Enforcement Analytical Method ............................................................................... 9

2.2.2 Recommended Tolerances......................................................................................... 9

2.2.3 Revisions to Petitioned-For Tolerances.................................................................. 11

2.2.4 International Harmonization................................................................................... 12

2.3 Label Recommendations.............................................................................................. 13

2.3.1 Label Recommendations from Residue Reviews................................................... 13

3.0 Introduction...................................................................................................................... 13

3.1 Chemical Identity ......................................................................................................... 14

3.2 Physical/Chemical Characteristics ............................................................................. 15

3.3 Pesticide Use Pattern.................................................................................................... 15

3.4 Anticipated Exposure Pathways................................................................................. 25

3.5 Consideration of Environmental Justice.................................................................... 25

4.0 Hazard Characterization and Dose-Response Assessment.......................................... 25

4.1 Toxicological Studies Available for Analysis............................................................. 27

4.2 Absorption, Distribution, Metabolism, and Excretion (ADME) ............................. 28

4.2.1 Dermal Absorption................................................................................................... 28

4.3 Toxicological Effects .................................................................................................... 28

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 29

4.4.1 Completeness of the Toxicology Database.............................................................. 30

4.4.2 Evidence of Neurotoxicity........................................................................................ 30

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 30

4.4.4 Residual Uncertainty in the Exposure Database ................................................... 30

4.5 Toxicity Endpoint and Point of Departure Selections.............................................. 31

4.5.1 Combined Routes of Exposure ................................................................................ 32

4.5.2 Carcinogenicity:........................................................................................................ 32

5.0 Dietary Exposure and Risk Assessment......................................................................... 34

5.1 Residues of Concern Summary and Rationale.......................................................... 34

5.2 Food Residue Profile .................................................................................................... 35

5.3 Water Residue Profile.................................................................................................. 36

5.4.1 Description of Residue Data Used in Dietary Assessment.................................... 37

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 37

5.4.3 Acute Dietary Risk Assessment............................................................................... 38

5.4.4 Chronic Dietary Exposure ....................................................................................... 38

5.4.5 Cancer Dietary Risk Assessment............................................................................. 39

5.4.6 Summary Table......................................................................................................... 39

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 40

6.1 Residential Handler Exposure........................................................................................ 40

6.2 Residential Post-Application Exposure and Risk Estimates........................................ 41

6.3 Residential Bystander Post-Application Inhalation Exposure ................................ 42

6.4 Non-Occupational Spray Drift Exposure and Risk Estimates................................. 42

7.0 Aggregate Exposure/Risk Characterization.................................................................. 43

7.1 Acute Aggregate Risk................................................................................................... 43
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7.2 Short-Term Aggregate Risk........................................................................................ 43

7.3 Chronic Aggregate Risk .............................................................................................. 44

7.4 Cancer Aggregate Risk ................................................................................................ 45

8.0 Cumulative Exposure/Risk Characterization ............................................................... 45

9.0 Occupational Exposure/Risk Characterization ............................................................ 46

9.1 Short-/Intermediate-Term Occupational Handler Risk........................................... 46

9.2 Short-/Intermediate-Term Post-Application Exposures and Risks ........................ 47

9.2.1 Short-/Intermediate-Term Post-Application Dermal Exposures and Risks....... 47

9.2.2 Short-/Intermediate-Term Post-Application Inhalation Exposures and Risks.. 48

10.0 References......................................................................................................................... 49

Appendix A. Abamectin Toxicology Profile and Executive Summaries............................... 52

A.1 Toxicology Data Requirements................................................................................... 52

A.2 Data Demonstrating the Sensitivity of Beagle Dogs to the Effects of Abamectin and 

Emamectin............................................................................................................................... 53

Appendix B. Toxicology Literature References...................................................................... 60

Appendix C. Abamectin Physical/Chemical Properties......................................................... 62

Appendix D. Review of Human Research for Abamectin...................................................... 63

Appendix E. International Residue Limits Table for Abamectin ......................................... 64

Appendix F. Abamectin Field Trial Tables............................................................................. 66

Appendix G. Abamectin Occupational Exposure Tables....................................................... 68

Appendix H. Avermectin Macrocyclic Lactones Cumulative Screening Assessment......... 75

H.1.0 Executive Summary.................................................................................................. 75

H.2.0 Introduction .............................................................................................................. 75

H.3.0 Toxicological Considerations in Determining a Candidate CMG ....................... 76

H.4.0 Dose Response Assessment ...................................................................................... 79

H.5.0 Dietary Cumulative Exposure and Risk Assessment/Characterization .............. 81

H.6.0 Residential Pathway ................................................................................................. 87

H.7.0 Combined Screening-Level Cumulative Assessment (Dietary + Residential) .... 88

H.8.0 Characterizing the Screening-Level Cumulative Estimates................................. 88

H.9.0 Conclusion................................................................................................................. 89

Appendix I. Emamectin Toxicity Profiles................................................................................ 90
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1.0 Executive Summary

The Health Effects Division (HED) has prepared a human health risk assessment in response to 

several requests for new uses of the insecticide abamectin. This document also includes a 

screening-level cumulative exposure and risk analysis for abamectin and a similar insecticide, 

emamectin benzoate.

Abamectin is a mixture of avermectin B1 [a mixture of avermectins containing greater than or 

equal to 80% avermectin B1a (5-O-demethyl avermectin A1) and less than or equal to 20% 

avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)] and 

its delta-8,9-isomer. Abamectin is a natural fermentation product of the soil bacterium 

Streptomyces avermitilis and is an insecticide/miticide used to control mites, leaf miners, and 

other insects in commercially important crops. Abamectin acts as an insecticide by interfering 

with the nervous system of the insect, causing the insect to become paralyzed. Abamectin is a 

member of a sub-class of macrocyclic lactone pesticides known as the avermectins. Currently,

only abamectin and emamectin are members of this group with active registrations of pesticides.

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 pesticide petition (PP#) 3E8175 to 

request the establishment of a permanent tolerance for residues of abamectin on Caneberry 

subgroup 13-07A. In conjunction with this petition, section 3 registration requests were 

submitted for the end-use products (EPs) Agri-Mek® 0.15 EC (EPA Reg. No. 100-898) and EpiMek® 0.15 EC Miticide/Insecticide (EPA Reg. No. 100-1154).

IR-4, on behalf of the Agricultural Experiment Stations of CA, HI, OR, SC, TN, FL, DE, and 

PR, additionally submitted PP# 4E8309 to request the establishment of permanent tolerances for 

residues of abamectin on bean; papaya; star apple; black sapote; sapodilla; canistel; mamey 

sapote; guava; feijoa; jaboticaba; wax jambu; starfruit; passionfruit; acerola; lychee; longan;

Spanish lime; rambutan; pulasan; pineapple; Onion, green, subgroup 3-07B; Fruit, pome, group 

11-10; Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F; Berry, low growing, 

subgroup 13-07G; Vegetable, fruiting, group 8-10; Fruit, citrus, group 10-10; Fruit, stone, group 

12-12; and Nut, tree, group 14-12. These uses are associated with one or more of four EPs: EpiMek® 0.15 EC Miticide/Insecticide (EPA Reg. No. 100-1154), Agri-Mek® SC 

Miticide/Insecticide (EPA Reg. No. 100-1351), Epi-Mek TM SC Miticide/Insecticide (EPA Reg. 

No. 100-1408), and Epi-MekTM SCL Miticide/Insecticide (EPA Reg. No. 100-1439).

Syngenta Crop Protection LLC (Syngenta) has submitted PP# 3F8184 to request the 

establishment of permanent tolerances for residues of abamectin on sweet corn commodities 

(forage, kernel plus cob with husk removed, and stover) and soybean commodities (forage, hay, 

and seed). The petitioner has proposed the addition of sweet corn and soybean to the following 

EPs: Agri-Flex® Miticide/Insecticide (EPA Reg. No. 100-1350), Agri-Mek® SC 

Miticide/Insecticide (EPA Reg. No. 100-1351), Epi-MekTM SC Miticide/Insecticide (EPA Reg. 

No. 100-1408), and Epi-MekTM SCL Miticide/Insecticide (EPA Reg. No. 100-1439). Syngenta 

proposed tolerances for sweet corn commodities (forage, kernel plus cob with husk removed, and 

stover) and soybean commodities (forage, hay, and seed).
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Syngenta has also proposed use of two new EPs on golf course greens, tees, and fairways. The 

new EPs are AgadorTM 0.17 SC Nematicide (EPA Reg. No. 100-RLNO), and DivanemTM 

0.15EC Nematicide (EPA Reg. No. 100-RLRN).

Finally, Y-TEX Corporation has requested registration of an ear tag containing abamectin and 

piperonyl butoxide for use on lactating dairy cattle to the EP, Y-TEX® XP 820TM Insecticide 

Cattle Ear Tags (EPA Reg. No. 39039-17). In association with this request, Y-TEX Corporation 

submitted PP# 3F8200 in order to request an amended tolerance in milk at 0.01 ppm. An ear tag 

use has previously been registered on beef cattle and non-lactating dairy cattle. Tolerances for 

abamectin on fat, meat, and meat byproducts of cattle were previously increased to reflect that 

use. This review concerns only abamectin; piperonyl butoxide has been considered under a 

separate review.

Toxicity/Hazard: Since the last risk assessment, the Agency has re-evaluated the entire 

abamectin and emamectin toxicological databases, along with additional literature information 

on the sensitivity of laboratory animals and the human population to the toxicity of abamectin 

and emamectin. The points of departure (PODs) and uncertainty factors (UFs) for abamectin and 

emamectin have been changed based on this re-evaluation. The updated hazard characterization 

represents a more refined analysis of the hazard for abamectin. In addition, the hazard 

characterizations of abamectin and emamectin have been evaluated and compared for 

consistency, and all the toxicity data were considered together in a cumulative screen using 

similar endpoints.

In general, available toxicity data showed that with a single dose or repeated dose administration, 

the primary target organ was the nervous system and that decreased body weight was also one of 

the most frequent findings. The toxicity endpoints and PODs for all exposure scenarios were 

recently reevaluated and selected from the subchronic and chronic oral toxicity studies in the 

dogs. The PODs selected from the dog studies are based on clear no observed adverse effect 

levels (NOAELs) that are protective of all the adverse effects seen in the studies conducted in 

rats, CD-1 mice, and rabbits. Therefore, the Food Quality Protection Act (FQPA) safety factor 

has been reduced to 1X, and the level of concern (LOC) is a margin of exposure (MOE) of 100

for all exposure scenarios.

Dietary Exposure (Food/Water) and Risk Estimates: The residue chemistry and 

environmental fate data are adequate to assess human exposure. Acute and chronic aggregate 

dietary (food and drinking water) exposure and risk assessments were conducted using the 

Dietary Exposure Evaluation Model software with the Food Commodity Intake Database 

(DEEM-FCID), Version 3.16. The acute and chronic dietary exposure assessments were refined 

assessments using anticipated or average residues derived from field trial data. Empirical and 

default processing factors and percent crop treated (PCT) estimates were used as available. 

Estimated drinking water concentrations (EDWCs) were provided by the Environmental Fate 

and Effects Division (EFED).

The acute dietary exposure estimates for food and drinking water are below HED’s LOC [<100% 

of the acute population adjusted dose (aPAD)] at the 99.9th percentile of exposure. Abamectin 

dietary exposure at the 99.9th percentile for food and drinking water is 45% of the aPAD for the 
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general U.S. population and 88% of the aPAD for children 1-2 years old, the most highly 

exposed population subgroup.

Although the acute and chronic dietary PODs are the same for both durations, a chronic dietary 

exposure assessment was conducted for abamectin for the purposes of aggregate risk assessment 

and to incorporate residues/exposures from the registered food handling establishment (FHE) 

uses as per HED policy. The chronic dietary exposure estimates for food and drinking water are 

below HED’s LOC [<100% of the chronic population adjusted dose (cPAD)] for the general U.S. 

population and all population subgroups. Abamectin dietary exposure for food and drinking 

water is 2.2% of the cPAD for the general U.S. population and 11% of the cPAD for children 1-2 

years old, the most highly exposed population subgroup.

Residential Exposure and Risk Estimates: For the proposed golf course turf use, residential 

handler exposure is not expected. Dermal post-application residential exposure estimates from 

the proposed turf use are not of concern for adults and children 6 to < 16 years old; the shortterm post-application MOEs range from 9,000 to 12,000. Furthermore, all existing residential 

exposures have been reassessed, and there are no registered products that would lead to 

residential handler or post-application risk estimates of concern. Short-term combined (dermal + 

inhalation) residential handler MOEs range from 860,000 to 2,700,000,000. Post-application 

exposures from existing uses are not expected.

Aggregate Exposure Risk Estimates: For the proposed uses, human health aggregate risk 

assessments have been conducted for acute aggregate exposure (food + drinking water), shortterm aggregate exposure (food + residential exposure + drinking water), and chronic aggregate 

exposure (food + drinking water) scenarios. For short-term aggregate exposure, the residential 

level of concern (LOCs) is 100 and the MOEs are greater than 100, and thus are not of risk 

concern. A cancer aggregate risk assessment was not performed because abamectin is classified 

as not likely to be carcinogenic to humans. All potential exposure pathways were assessed in the 

aggregate risk assessment. None of the aggregate exposure and risk estimates exceed HED's 

level of concern. 

Occupational Handler and Post-Application Exposures and Risk Estimates: Based on all 

proposed uses, occupational exposures to abamectin are expected for short- and intermediateterm durations when handling abamectin or from post-application activities. Potential routes of 

exposure include both dermal and inhalation for occupational workers.

The results of the occupational handler exposure and risk assessment associated with PP#s 

3E8175 and 3F8184 indicate that short-/intermediate-term combined (dermal + inhalation) risk 

estimates are not of concern at baseline mitigation without personal protective equipment (PPE); 

MOEs range from 360 to 25,000. The results of the occupational handler assessment associated 

with PP# 4E8309 indicate that short-/intermediate-term combined risk estimates are not of 

concern with a single layer of clothing, no respirator, and the PPE of gloves, which are required 

for all occupational handlers; MOEs ranged from 150 to 97,000. Note that only engineering 

controls (enclosed cockpit) data are available to assess risks to handlers operating aircraft.
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Quantitative occupational post-application exposure and risk assessments indicate that short- and 

intermediate-term dermal risk estimates are not of concern at baseline mitigation without PPE on 

Day 0 (12 hours following application) for all proposed uses (LOC = 100). MOEs ranged from 

3,700 to 5,400 for the uses associated with PP#s 3E8175 and 3F8184; MOEs ranged from 240 to 

67,000 for PP# 4E8309. Based on the Agency's current practices, a quantitative non-cancer 

occupational post-application inhalation exposure assessment was not performed for abamectin

at this time. 

Screening-Level Cumulative Assessment of the Avermectin Macrocyclic Lactones: HED has 

developed cumulative screening framework entitled Pesticide Cumulative Risk Assessment: 

Framework for Screening Analysis Purpose (USEPA, 2016). Utilizing this framework, HED has 

determined that abamectin and emamectin form a candidate common mechanism group (CMG). 

Therefore, HED has conducted a screening-level cumulative exposure analysis for the 

avermectin macrocyclic lactones, which contain the insecticides abamectin and emamectin. This

assessment indicated that aggregate dietary and residential exposures for abamectin and 

emamectin are below the Agency’s levels of concern. Additional information regarding this 

cumulative exposure and risk assessment may be found in Appendix H.

Environmental Justice Considerations: Potential areas of environmental justice concerns, to 

the extent possible, were considered in this human health risk assessment, in accordance with 

U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority 

Populations and Low-Income Populations," 

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf). 

Review of Human Research: This risk assessment relies in part on data from studies in which 

adult human subjects were intentionally exposed to a pesticide or other chemical. As indicated in 

Appendix D, these studies have been determined to require a review of their ethical conduct, and 

have received that review.
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2.0 HED Recommendations

Provided that revised Sections B and F are submitted, there are no residue chemistry 

considerations that would preclude granting the requested registrations and establishing the 

recommended tolerances for abamectin on sweet corn; soybeans; Caneberry subgroup 13-07A; 

bean, papaya, star apple, black sapote, sapodilla, canistel, mamey sapote, guava, feijoa, 

jaboticaba, wax jambu, starfruit, passionfruit, acerola, lychee, longan, Spanish lime, rambutan, 

pulasan, pineapple, Onion, green, subgroup 3-07B; Fruit, small vine climbing, except fuzzy 

kiwifruit, subgroup 13-07F; Berry, low growing, subgroup 13-07G; Fruit, pome, group 11-10; 

Vegetable, fruiting, group 8-10 (including greenhouse tomato); Fruit, citrus, group 10-10; Fruit, 

stone, group 12-12; Nut, tree, group 14-12; and milk (associated with the registration request for 

ear tags on lactating dairy cattle).

For all proposed uses, the specific tolerance recommendations are discussed in Section 2.2, and 

the recommended label modifications are discussed in Section 2.3.

2.1 Data Deficiencies

There are no data deficiencies at this time.

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 

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 currently established tolerance expression for abamectin is adequate, and includes coverage 

and compliance statements for enforcement purposes. HED recommends that 40 CFR §180.449 

be amended by establishing, revising or removing the tolerances as listed in Tables 2.2.2.1 and 

2.2.2.2, below.
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Table 2.2.2.1. Tolerance Summary for Abamectin.

Commodity

Established

Tolerance 

(ppm)

Proposed 

Tolerance

(ppm)

HEDRecommended 

Tolerance 

(ppm)1

Comments

(correct commodity definition)

Caneberry subgroup 13-07A none 0.20 0.20

Cattle, fat 0.03 none 0.05

Cattle, meat 0.02 none 0.02

Cattle, meat byproducts 0.06 none 0.09

Corn, sweet, forage none 0.2 0.20

Corn, sweet, kernel plus cob 

with husk removed

none 0.01 0.01

Corn, sweet, stover none 0.5 0.50

Goat, fat 0.01 none 0.03

Goat, meat 0.02 none 0.02

Goat, meat byproducts 0.02 none 0.04

Grain, aspirated grain 

fractions

none none 0.40

Hog, fat 0.01 none 0.01

Hog, meat 0.02 none 0.02

Hog, meat byproducts 0.02 none 0.02

Horse, fat 0.01 none 0.03

Horse, meat 0.02 none 0.02

Horse, meat byproducts 0.02 none 0.04

Milk 0.005 0.01 0.015

Poultry, meat 0.02 none 0.02

Poultry, meat byproducts 0.02 none 0.02

Sheep, fat 0.01 none 0.03

Sheep, meat 0.02 none 0.02

Sheep, meat byproducts 0.02 none 0.04

Soybean, forage none 0.3 0.30

Soybean, hay none 1 1.0

Soybean, seed none 0.01 0.01

Vegetable, fruiting, group 8-

10

0.07 0.07 Includes greenhouse-grown 

tomatoes.

Fruit, citrus, group 10-10

0.02 0.02 Retain established tolerances of

0.10 ppm on citrus, dried pulp 

and citrus, oil.

Fruit, small, vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

none 0.02 0.02 (Fruit, small vine climbing, 

except fuzzy kiwifruit, subgroup 

13-07F)

Berry, low growing, 

subgroup 13-07G

none 0.05 0.05

Fruit, stone, group 12-12 none 0.09 0.09

Fruit, pome, group 11-10 none 0.02 0.02

Nut, tree, group 14-12 none 0.01 0.01 Retain tolerance on almond,

hulls at 0.10 ppm.

Papaya none 0.40 0.40

Star apple none 0.40 0.40

Black sapote none 0.40 0.40

Sapodilla none 0.40 0.40

Canistel none 0.40 0.40
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Table 2.2.2.1. Tolerance Summary for Abamectin.

Commodity

Established

Tolerance 

(ppm)

Proposed 

Tolerance

(ppm)

HEDRecommended 

Tolerance 

(ppm)1

Comments

(correct commodity definition)

Mamey sapote none 0.40 0.40

Guava none 0.015 0.015

Feijoa none 0.015 0.015

Jaboticaba none 0.015 0.015

Wax jambu none 0.015 0.015

Starfruit none 0.015 0.015

Passionfruit none 0.015 0.015

Acerola none 0.015 0.015

Lychee none 0.01 0.01

Longan none 0.01 0.01

Spanish lime none 0.01 0.01

Rambutan none 0.01 0.01

Pulasan none 0.01 0.01

Pineapple none 0.015 0.015

Bean none 0.015 0.015

Onion, green, subgroup 3-

07B

none 0.08 0.08

1 Changes from established/proposed tolerances are bolded.

Table 2.2.2.2. Established Tolerances to be Removed upon Establishment of Tolerances in Table 2.2.2.1.

Commodity Established 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments

Bean, dry, seed 0.01 Revoke Covered by Bean tolerance 

Citrus 0.02 Revoke Covered by Fruit, citrus, group 10-10 

tolerance

Apple 0.02 Revoke Covered by Fruit, pome, group 11-10 

Pear 0.02 Revoke tolerance

Fruit, stone, group 

12

0.09 Revoke Covered by Fruit, stone, group 12-12 

tolerance

Nut, tree, group 14 0.01 Revoke Covered by Nut, tree, group 14-12 tolerance

Pistachio 0.01 Revoke

Grape 0.02 Revoke Covered by Fruit, small vine climbing, 

except fuzzy kiwifruit, subgroup 13-07F 

tolerance

Strawberry 0.05 Revoke Covered by Berry, low growing, subgroup 

13-07G tolerance

Vegetable, fruiting, 

group 8

0.020 Revoke Covered by Vegetable, fruiting, group 8-10 

tolerance

2.2.3 Revisions to Petitioned-For Tolerances

As shown in Table 2.2.2.1 above, HED is recommending a tolerance of 0.40 ppm for grain, 

aspirated grain fractions, since aspirated grain fractions are associated with soybeans (Table 1 

Feedstuffs, June 2008; in that document, refer to Part V, Table A under aspirated grain fractions

and to Attachment 1, Table 1 under grain). The recommended tolerance of 0.40 ppm for grain, 

aspirated grain fractions is based on residues of <0.006 ppm in soybean seed and a concentration 

factor of 59X in aspirated grain fractions.
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HED is also recommending that some of the established livestock tolerances be increased based 

on a new dietary burden calculation, which includes the proposed uses on soybeans, sweet corn, 

and ear tags for lactating dairy cattle. Because of these calculations, HED is recommending 

increasing the established tolerances on cattle fat from 0.03 to 0.05 ppm; cattle meat byproducts

from 0.06 to 0.09 ppm; fat of goat, horse and sheep from 0.01 to 0.03 ppm; meat byproducts of 

goat, horse, and sheep from 0.02 to 0.04 ppm. The higher tolerances on cattle fat and meat 

byproducts as compared to goat, horse and sheep fat and meat byproducts are due to the 

proposed use of ear tags on lactating dairy cattle. Additionally, the amended tolerance for milk, 

proposed at 0.01 ppm, is recommended to be established at 0.015 ppm. There are no livestock 

feed items associated with the proposed use on Caneberry subgroup 13-07A. Further, because of 

limited feed items associated with PP# 4E8309, the established livestock tolerances were not 

reassessed for those proposed uses.

Finally, the commodity definition should be revised to reflect the correct nomenclature for 

Subgroup 13-07F.

2.2.4 International Harmonization

The plant tolerance definitions are essentially the same for the U.S., Codex, and Canada, all 

including avermectin B1a, avermectin B1b, and the 8,9-Z isomers. There are no Codex or 

Canadian maximum residue limits (MRLs) established for abamectin for the following 

commodities: sweet corn, soybean, papaya, star apple, black sapote, sapodilla, canistel, mamey 

sapote, guava, feijoa, jaboticaba, wax jambu, starfruit, passionfruit, acerola, lychee, longan, 

Spanish lime, rambutan, pulasan, pineapple, bean or green onion commodities. Additionally, 

there are no Codex MRLs for abamectin on the commodities in Caneberry subgroup 13-07A; 

Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F; or Fruit, stone, group 12-12. 

The following recommended U.S. tolerances are harmonized with established, related Codex 

MRLs: Fruit, pome, group 11-10; and Nut, tree, group 14-12. The recommended U.S. tolerances 

for Caneberry subgroup 13-07A at 0.20 ppm; Fruit, citrus, group 10-10 at 0.02 ppm; Fruit, small 

vine climbing, except fuzzy kiwifruit, subgroup 13-07F; and Fruit, pome, group 11-10 are 

harmonized with the proposed or established related Canadian MRLs.

The Codex MRL on citrus is not harmonized with the U.S. tolerance on Fruit, citrus, group 10-

10. The established Canadian MRLs on tree nut commodities are not harmonized with the U.S. 

tolerance recommendation for Nut, tree, group 14-12. Finally, the established Codex and 

Canadian MRL on strawberry is not harmonized with the recommended U.S. tolerance on Berry, 

low-growing, subgroup 13-07G. Residue data underlying these recommended U.S. tolerances 

resulted in tolerance recommendations that are higher than the established Codex or Canadian 

MRLs on these related commodities.

Codex and Canadian MRLs for abamectin on fruiting vegetable commodities are not harmonized 

with the recommended U.S. tolerance on Vegetable, fruiting, group 8-10. The residue data 

underlying the recommended U.S. fruiting vegetable tolerance resulted in a tolerance 

recommendation that is higher than the established Codex MRL on sweet peppers and the 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Canadian MRLs on pepper and tomato. Codex has also established a separate tolerance on dried 

chili pepper that is higher than the recommended U.S. fruiting vegetable tolerance. 

The livestock residue definitions are essentially the same for the U.S. 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 MRLs on livestock 

commodities, but fewer than US tolerances. None of the Codex MRLs are set at the same level 

as the U.S. recommended tolerance levels. The US cannot harmonize with the Codex MRLs on 

livestock commodities since they reflect different uses (i.e., different dietary burdens) as 

compared to the US.

An International Residue Limit Status sheet may be found in Appendix E.

2.3 Label Recommendations

2.3.1 Label Recommendations from Residue Reviews

860.1200 Directions for Use

The petitioner needs to resolve the following inconsistencies: On the Epi-MekTM SCL label for 

greenhouse-grown tomatoes, the maximum rate is given as 3.5 fl oz/A. Because Epi-MekTM SCL 

contains only 0.35 lb ai/gal, 3.5 fl oz is 0.0096 lb ai/A, not 0.019 lb ai/A as stated under Use 

Restrictions on page 29. Other greenhouse-grown tomato labels have the maximum single 

application rate of 0.019 lb ai/A. Additionally, the use restrictions on pages 28-29 refer to EpiMekTM SC rather than Epi-MekTM SCL. 

3.0 Introduction

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. Avermectins are macrocyclic lactones produced as natural fermentation 

products of the soil bacterium Streptomyces avermitilis. Currently abamectin and emamectin are 

the only members of this group with active pesticide registrations. Abamectin is an 

insecticide/miticide used to control mites, leaf miners, and other insects in commercially 

important crops. Abamectin acts as an insecticide by interfering with the nervous system of the 

insect, causing the insect to become paralyzed. Available mechanistic data indicate a neurotoxic 

mechanism of action, related to interference with GABA-mediated neurotransmission.

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 0.002 ppm to 0.20 ppm. Compliance with the tolerance levels is to be 

determined by measuring only avermectin B1 and its delta-8,9-isomer.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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The registered formulation types include emulsifiable concentrate (EC), suspension concentrate 

(SC), granular, bait, gel, dust, and impregnated materials (e.g., ear tags). The registered uses 

include food, food handling establishments, and residential uses. 

3.1 Chemical Identity

Table 3.1. Abamectin Nomenclature

Chemical Structure

Empirical formula C48H72O14 (B1a); C47H70O14 (B1b)

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 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table 3.1. Abamectin Nomenclature

',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 Registry Number Avermectin B1 - 71751-41-2; Avermectin B1a - 65195-55-3; Avermectin B1b -

65195-56-4

End-use products/EPs1

AgadorTM 0.17 SC Nematicide, EPA Reg. No. 100-RLNO (contains 0.170 lb 

ai/gallon; 13.7% abamectin); 

Agri-Flex® Miticide/Insecticide, EPA Reg. No. 100-1350 (contains 0.277 lb 

abamectin and 1.27 lb thiamethoxam per gallon; 3.0% abamectin and 13.9% 

thiamethoxam);

Agri-Mek® 0.15 EC Miticide/Insecticide, EPA Reg. No. 100-898 (contains 0.15 

lb ai per gallon; 2.0% abamectin);

Agri-Mek® SC Miticide/Insecticide, EPA Reg. No. 100-1351 (contains 0.7 lb ai 

per gallon; 8.0% abamectin);

DivanemTM 0.15EC Nematicide, EPA Reg. No. 100-RLRN (contains 0.15 lb 

ai/gallon; 2.0% abamectin); 

Epi-MekTM 0.15 EC Miticide/Insecticide, EPA Reg. No. 100-1154 (contains 0.15 

lb ai per gallon; 2.0% abamectin);

Epi-MekTM SC Miticide/Insecticide, EPA Reg. No. 100-1408 (contains 0.7 lb ai 

per gallon; 8.0% abamectin);

Epi-MekTM SCL Miticide/Insecticide, EPA Reg. No. 100-1439 (contains 0.35 lb 

ai per gallon; 4.2% abamectin);

Y-TEX® XP 820TM Insecticide Cattle Ear Tags, EPA Reg. No. 39039-17 (have 

an average weight of 9 grams per tag and contain a formulation of 8% 

abamectin, 20% piperonyl butoxide, and 72% inerts).

Chemical class Macrocyclic lactone; Insecticide/Miticide

Known impurities of concern None

1

EC = emulsifiable concentrate; SC = suspension concentrate; SCL= suspension concentrate.

3.2 Physical/Chemical Characteristics

Abamectin is a crystalline powder with very low vapor pressure (1.5x10-9 hPa). It has very low 

water solubility (<0.001 to 0.01 mg/ml); but, is soluble in organic solvents. Abamectin is stable 

to hydrolysis. Abamectin has low dermal absorption (≤ 1% of the applied dose). Refer to 

Appendix C for the table of physical/chemical properties.

3.3 Pesticide Use Pattern

The labels are adequate to allow evaluation of the residue and exposure data relative to the 

proposed uses. A summary of the use profile is provided in Table 3.3 below.
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Table 3.3. Summary of Proposed Directions for Use of Abamectin 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

App. Rate 

(lb ai/A)

Max. No. 

App. per 

Season

Max.

Seasonal 

App. Rate

(lb ai/A)

PHI2

(days) Use Directions and Limitations3

Caneberry Subgroup 13-07A

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 NS4 0.056 7

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.

RTI is 7 days. The maximum number of applications at the 

maximum rate is 3.

Do not make more than 2 sequential applications of an 

abamectin.

Cattle Ear Tag

1 or 2 ear tags per 

animal for 2-5 

months per treatment 

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.

Corn, Sweet

Postemergence;

Broadcast foliar 

spray;

Ground or aerial 

equipment

Agri-Flex® Miticide/

Insecticide

[100-1350]

0.012 –

0.018 NS 0.037

7 (forage 

or ears)

14

(stover)

Apply to thoroughly cover the crop to control spider mites 

and insects.

Apply when spider mites first appear. Repeat as needed to 

maintain control.

Do not apply more than 0.018 lb ai/A of Agri-Flex® or 

more than 0.019 lb ai/A of any other foliar applied 

abamectin containing product or more than 0.086 lb ai/A of 

any other foliar applied thiamethoxam containing product 

per application.

Do not apply more than 0.037 lb ai/A of Agri-Flex® or 

more than 0.038 lb ai/A of any other foliar applied 

abamectin containing product or more than 0.172 lb ai/A of 

any other foliar applied thiamethoxam containing product 

per season.
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Table 3.3. Summary of Proposed Directions for Use of Abamectin 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

App. Rate 

(lb ai/A)

Max. No. 

App. per 

Season

Max.

Seasonal 

App. Rate

(lb ai/A)

PHI2

(days) Use Directions and Limitations3

Postemergence;

Broadcast foliar 

spray;

Ground or aerial 

equipment

Agri-Mek® SC 

Miticide/Insecticide

[100-1351]

Epi-MekTM SC 

Miticide/Insecticide

[100-1408]

Epi-MekTM SCL 

Miticide/Insecticide

[100-1439]

0.0096-

0.019 NS 0.038

7 

(forage, 

ears, or 

stover)

Apply to thoroughly cover the crop to control spider mites.

Apply when spider mites first appear. Repeat as needed to 

maintain control.

Do not apply more than 0.019 lb ai/A of Agri-Mek® 

SC/Epi-MekTM SC/Epi-MekTM SCL or any other foliarly 

applied abamectin per application.

Do not apply more than 0.038 lb ai/A of Agri-Mek® SC/ 

Epi-MekTM SC/Epi-MekTM SCL or any other foliarly 

applied abamectin-containing product in a growing season.

Soybean

Postemergence;

Broadcast foliar 

spray;

Ground or aerial 

equipment

Agri-Flex® Miticide/

Insecticide

[100-1350]

0.011-0.014 NS 0.028 28

Apply to thoroughly cover the crop to control spider mites 

and insects. Apply when spider mites first appear. Repeat 

as needed to maintain control. RTI = 7 days.

Do not apply more than 0.014 lb ai/A of Agri-Flex® or 

more than 0.019 lb ai/A of any other foliar applied 

abamectin containing product or more than 0.063 lb ai/A of 

any other foliar applied thiamethoxam containing product 

per application.

Do not apply more than 0.028 lb ai/A of Agri-Flex® or 

more than 0.038 lb ai/A of any other foliar applied 

abamectin containing product or more than 0.125 lb ai/A of 

any other foliar applied thiamethoxam containing product 

per season.

Do not allow livestock to graze in treated areas or harvest 

treated soybean forage, straw or hay as feed for meat or 

dairy animals.

Do not feed treated soybean fodder or silage to meat or 

dairy animals.

Postemergence;

Broadcast foliar 

spray;

Agri-Mek® SC 

Miticide/Insecticide

[100-1351]

0.0096-

0.019 NS 0.038 

7 (forage 

or hay)

28 (seed)

Apply to thoroughly cover the crop to control spider mites.

Apply when spider mites first appear. Repeat as needed to 

maintain control. RTI = 7 days.
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Table 3.3. Summary of Proposed Directions for Use of Abamectin 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

App. Rate 

(lb ai/A)

Max. No. 

App. per 

Season

Max.

Seasonal 

App. Rate

(lb ai/A)

PHI2

(days) Use Directions and Limitations3

Ground or aerial 

equipment

Epi-MekTM SC 

Miticide/Insecticide

[100-1408]

Epi-MekTM SCL 

Miticide/nsecticide

[100-1439]

Do not apply more than 0.019 lb ai/A of Agri-Mek® 

SC/Epi-MekTM SC/ Epi-MekTM SCL or any other foliarly 

applied abamectin- containing product per application.

Do not apply more than 0.038 lb ai/A of Agri-Mek® 

SC/Epi-MekTM SC/ Epi-MekTM SCL or any other foliarly 

applied abamectin-containing product in a growing season.

Turf (Golf Course Greens, Tees, and Fairways)

Broadcast

(ground only)

AgadorTM 0.17 SC 

Nematicide

[100-RLNO]

0.069

lb ai/A

0.000805

lb ai/gal 4

0.276 NA

Multiple applications may be required before improvements 

in turf quality are observed. For best results, irrigate before 

the spray droplets have dried on the turf. Do not apply to golf 

course roughs. Do not apply to residential turf, sports fields, 

or commercial turf. Do not use aerial application. Do not 

apply this product through any type of irrigation system or 

ultra-low volume spray. Apply in 2 gallons of water per 

1,000 square feet of turf.

DivanemTM 0.15EC 

Nematicide

[100-RLRN]

0.067

lb ai/A

0.000805

lb ai/gal

0.267 NA

Green Onion Subgroup 3-07B

Ground, Aerial

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

0.019 2 

sequential 0.056 7 Apply with a minimum of 20 gal/A for ground applications. 

RTI is 7 days.

Fruiting Vegetable Group 8-10

Ground, Aerial

8% SC Agri-Mek® SC 

Miticide/Insecticide

[100-1351] (0.7 lb ai/gal)

0.019 2 

sequential 0.056 7 Apply with a minimum of 20 gal/A for ground applications. 

RTI is 7 days.
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Table 3.3. Summary of Proposed Directions for Use of Abamectin 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

App. Rate 

(lb ai/A)

Max. No. 

App. per 

Season

Max.

Seasonal 

App. Rate

(lb ai/A)

PHI2

(days) Use Directions and Limitations3

8% SC Epi-Mek® SC 

Miticide/Insecticide [100-

1408]

(0.7 lb ai/gal)

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

4.2% SC Epi-MekTM SCL 

Miticide/Insecticide [100-

1439] (0.35 lb ai/gal)

Greenhouse Tomato

Ground

8% SC Agri-Mek® SC 

Miticide/Insecticide

[100-1351] (0.7 lb ai/gal)

0.019 lb ai/A 2 

sequential 0.056 1 Apply with a minimum of 20 gal/A. RTI is 7 days.

8% SC Epi-Mek® SC 

Miticide/Insecticide [100-

1408]

(0.7 lb ai/gal)

4.2% SC Epi-MekTM SCL 

Miticide/Insecticide [100-

1439] (0.35 lb ai/gal)

Citrus Fruit Group 10-10

Ground, Aerial

8% SC Agri-Mek® SC 

Miticide/Insecticide

[100-1351] (0.7 lb ai/gal)

0.023 lb ai/A 3 0.047 1 Apply with a minimum of 150 gal/A for ground applications. 

RTI is 30 days.
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Table 3.3. Summary of Proposed Directions for Use of Abamectin 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

App. Rate 

(lb ai/A)

Max. No. 

App. per 

Season

Max.

Seasonal 

App. Rate

(lb ai/A)

PHI2

(days) Use Directions and Limitations3

8% SC Epi-Mek® SC 

Miticide/Insecticide [100-

1408]

(0.7 lb ai/gal)

4.2% SC Epi-MekTM SCL 

Miticide/Insecticide [100-

1439] (0.35 lb ai/gal)

Pome Fruit Group 11-10

Ground

8% SC Agri-Mek® SC 

Miticide/Insecticide

[100-1351] (0.7 lb ai/gal)

0.023 2 0.047 28 Apply with a minimum of 40 gal/A for ground applications. 

RTI is 21 days.

8% SC Epi-Mek® SC 

Miticide/Insecticide [100-

1408]

(0.7 lb ai/gal)

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

4.2% SC Epi-MekTM SCL 

Miticide/Insecticide [100-

1439] (0.35 lb ai/gal)

Stone Fruit Group 12-12

Ground

8% SC Agri-Mek® SC 

Miticide/Insecticide

[100-1351] (0.7 lb ai/gal)

0.023 2 0.047 21 Apply with a minimum of 40 gal/A for ground applications. 

RTI is 21 days.
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Table 3.3. Summary of Proposed Directions for Use of Abamectin 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

App. Rate 

(lb ai/A)

Max. No. 

App. per 

Season

Max.

Seasonal 

App. Rate

(lb ai/A)

PHI2

(days) Use Directions and Limitations3

8% SC Epi-Mek® SC 

Miticide/Insecticide [100-

1408]

(0.7 lb ai/gal)

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

4.2% SC Epi-MekTM SCL 

Miticide/Insecticide [100-

1439] (0.35 lb ai/gal)

Small Fruit, Vine Climbing, Subgroup 13-07F

Ground

8% SC Agri-Mek® SC 

Miticide/Insecticide

[100-1351] (0.7 lb ai/gal)

0.019 2 0.038 28

Apply with a minimum of 50 gal/A for ground applications; 

as low 5 gal/A may be used for an electro-static sprayer. RTI 

is 21 days.

8% SC Epi-Mek® SC 

Miticide/Insecticide [100-

1408]

(0.7 lb ai/gal)

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

4.2% SC Epi-MekTM SCL 

Miticide/Insecticide [100-

1439] (0.35 lb ai/gal)

Low-growing Berry Subgroup 13-07G
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Table 3.3. Summary of Proposed Directions for Use of Abamectin 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

App. Rate 

(lb ai/A)

Max. No. 

App. per 

Season

Max.

Seasonal 

App. Rate

(lb ai/A)

PHI2

(days) Use Directions and Limitations3

Ground

8% SC Agri-Mek® SC 

Miticide/Insecticide

[100-1351] (0.7 lb ai/gal)

0.019 NS 0.075 3

Apply with a minimum of 50 gal/A for ground applications; 

as low 10 gal/A may be used for an electro-static sprayer. 

RTI is 7 days.

8% SC Epi-Mek® SC 

Miticide/Insecticide [100-

1408]

(0.7 lb ai/gal)

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

4.2% SC Epi-MekTM SCL 

Miticide/Insecticide [100-

1439] (0.35 lb ai/gal)

Tree Nut Group 14-12

Ground

8% SC Agri-Mek® SC 

Miticide/Insecticide

[100-1351] (0.7 lb ai/gal)

0.023 2 0.047 21 Apply with a minimum of 40 gal/A for ground applications. 

RTI is 21 days.

8% SC Epi-Mek® SC 

Miticide/Insecticide [100-

1408]

(0.7 lb ai/gal)

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)
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Table 3.3. Summary of Proposed Directions for Use of Abamectin 

Applic. Timing, 

Type, and Equip.

Formulation1

[EPA Reg. No.]

App. Rate 

(lb ai/A)

Max. No. 

App. per 

Season

Max.

Seasonal 

App. Rate

(lb ai/A)

PHI2

(days) Use Directions and Limitations3

4.2% SC Epi-MekTM SCL 

Miticide/Insecticide [100-

1439] (0.35 lb ai/gal)

Guava, Feijoa, Jaboticaba, Wax Jambu, Starfruit, Passionfruit, Acerola

Ground

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

0.023 0.07 3 7

Apply with a minimum of 50 gal/A for ground applications; 

as low 5 gal/A may be used for an electro-static sprayer. RTI 

is 14 days.

Lychee, Longan, Spanish Lime, Rambutan

Ground

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

0.023 0.045 2 14

Apply with a minimum of 50 gal/A for ground applications; 

as low 5 gal/A may be used for an electro-static sprayer. RTI 

is 30 days.

Papaya, Star Apple, Black Sapote, Sapodilla, Canistel, Mamey Sapote

Ground

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

0.023 3 0.07 3

Apply with a minimum of 50 gal/A for ground applications; 

as low 5 gal/A may be used for an electro-static sprayer. RTI 

is 3 days.

Bean

Ground, Aerial

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

0.019 2 0.056 7 Apply with a minimum of 10 gal/A for ground applications. 

RTI is 6 days.

Pineapple

Ground

2% EC

Epi-Mek® 0.15 EC 

Miticide/Insecticide

[100-1154] (0.15 lb ai/gal)

0.023 2 0.046 112

Apply with a minimum of 50 gal/A for ground applications; 

as low 5 gal/A may be used for an electro-static sprayer. RTI 

is 7 days.

1 Formulation code: EC = emulsifiable concentrate, SC = suspension concentrate; SCL = suspension concentrate.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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2 PHI = Pre-harvest interval 3 Restrictions that apply to proposed labels: All end-use products are classified as Restricted Use Pesticide. The following apply to EPs other than the Cattle Ear Tag: To avoid 

illegal residues, end-use products must be mixed with a non-ionic activator type wetting, spreading and/or penetrating spray adjuvant. Do not use binder or sticker type adjuvants.

Do not apply with aircraft in NY (for commodities that allow aerial applications). RTI = Re-treatment interval

For resistance management, do not make more than 2 sequential applications of Agri-Flex®/Agri-Mek® SC/ Epi-MekTM SC/ Epi-MekTM SCL or any other foliar applied 

abamectin containing product.

Unless specifically restricted in the individual Crop Use Directions on the Agri-Mek® SC, Agri-Flex®, 

Epi-MekTM SC, or Epi-MekTM SCL labels, those products may be used in the same year abamectin is used as an at-plant seed treatment. Abamectin is registered as a seed treatment 

on the Avicta® 500 FS label (EPA Reg. No. 100-1204) at rates of 0.20-0.25 mg ai/seed for corn and 0.10-0.15 mg ai/seed for soybean. 4 NS = Not specified 5 Turf application rate is based on use direction to “apply in 2 gallons of water per 1,000 square feet of turf.”
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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3.4 Anticipated Exposure Pathways

Abamectin has been proposed for use on multiple agricultural commodities, in cattle ear tags, 

and on golf course turf. Based on the proposed and registered uses of abamectin, humans may be 

exposed to abamectin in food and drinking water since abamectin may be applied directly to 

growing crops. Although significant residues are not expected to occur in ground water because 

of the low water solubility of residues and their affinity to soil particles, residues may occur in 

surface water due to runoff, erosion, and spray drift. 

Based on all of the proposed uses, occupational exposures to abamectin are expected for shortand intermediate-term durations when conducting handling and post-application activities.

Potential routes of exposure include both dermal and inhalation for occupational workers.

Furthermore, the proposed golf course use results in a potential for residential short-term dermal 

post-application exposures for adults and children (6 to 16 years old) resulting from recreational 

golfing activities. Finally, the registered residential uses of abamectin result in the possibility of 

exposure in residential or non-occupational settings.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from pesticide 

exposures that are based on patterns of that subgroup’s food and water consumption, and 

activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture (USDA) using 2003-2008 food consumption data from USDA’s National Health and 

Nutrition Examination Survey, What We Eat in America (NHANES/WWEIA) and are used in 

pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and 

categorized by subgroups based on age and ethnic group. Additionally, OPP is able to assess 

dietary exposure to smaller, specialized subgroups and exposure assessments are performed 

when conditions or circumstances warrant. Whenever appropriate, non-dietary exposures based 

on home use of pesticide products and associated risks for adult applicators and for toddlers, 

youths, and adults entering or playing on treated areas post-application are evaluated. Further 

considerations are currently in development as OPP has committed resources and expertise to the 

development of specialized software and models that consider exposure to bystanders and farm 

workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

As mentioned in Section 3.0, abamectin consists of two components, B1a and B1b, which have 

very similar biological and toxicological properties. Emamectin is a structurally and 
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toxicologically related chemical which is a derivative of abamectin. The only difference between 

abamectin and emamectin is that abamectin has a hydroxyl moiety at the 4” position of the 

tetrahydropyran ring whereas, in emamectin, the hydroxyl group is replaced by a methylamine 

(circled groups in the following figures).

Since the last risk assessment (D402677 and D405843, N. Dodd, 12/20/2012), the Agency has 

re-evaluated the abamectin and emamectin toxicological databases along with currently available 

literature information to ensure consistent hazard evaluation for these structurally related 

pesticides. This hazard characterization and dose-response assessment represents a more refined 

analysis than previous assessments, using the literature data to enhance the characterization of 

the studies submitted to the Agency. Due to the similarity of the two chemicals the Agency has 

re-evaluated the toxicity of both abamectin and emamectin to ensure consistency of approach. 

The evaluation of abamectin is presented in this section, since this risk assessment has been 

prepared to address new uses of abamectin. The revised toxicity profile tables for emamectin are

presented in Appendix I. While no common mechanism group has been established for the 

avermectin macrocyclic lactones, abamectin and emamectin (i.e., key events leading from the 

molecular initiating event to apical neurotoxicity cannot be causally determined), the Agency has 

presented a screening level cumulative evaluation (Appendix H) based on screening guidance 

(Pesticide Cumulative Risk Assessment: Framework for Screening Analysis Purpose, USEPA 

2016) to assess the potential for cumulative risk and the extent to which additional toxicity 

information is needed to determine the key events for a common mechanism grouping. 

 Abamectin

Emamectin
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Mode of Action: 

In nematodes, abamectin blocks signal transmission from the central command interneurons to 

the peripheral motoneurons, leading to paralysis and death. In the mammalian toxicity studies 

submitted by the registrant, paralysis is also a common finding prior to moribund sacrifice. The 

in vitro data derived from a primary culture of rat cerebellar granular neurons show that, on the 

cellular level, abamectin acts by binding to gamma-aminobutyric acid (GABA) gated chloride 

channels at two different sites, a high affinity binding site that activates the channel and a low 

affinity site that blocks the channel (Pong et. al., 1982; Huang and Casida, 1997; and Dawson et.

al., 2000). GABA plays a critical role in nervous system through both non-synaptic (Represa and 

Ben-Ari, 2005) and synaptic (Nguyen et. al., 2001) mechanisms. The literature data show that 

within the mammalian brain abamectin binding to GABA receptors is widespread but 

particularly abundant in the cerebellum (Wang and Pong, 1982). Abamectin also has been 

suggested to act on GABA receptors in the enteric nervous system and induces longitudinal 

rhythmic contractions in the isolated ileum (Kerr and Ong, 1986). Abamectin may therefore 

influence GABA-mediated regulation of metabolism, food intake and body weight at multiple 

sites (Meister, 2007). Although GABA receptor mediated neurotoxicity is a solid hypothesis, as 

described in detail in Appendix H, data in mammalian preparations linking alterations in GABA 

receptor function to disruptions in neuronal excitability in vitro and in vivo, and ultimately 

adverse outcomes, are currently lacking.

4.1 Toxicological Studies Available for Analysis

Most of the required toxicity studies on abamectin are available. The requirements for 

subchronic dermal toxicity and immunotoxicity studies have been waived (TXR 0056687, U. 

Habiba, 01/07/2013 and TXR 0056509, K. Rury, 01/30/2013). The studies currently available for

abamectin are: 

• subchronic oral toxicity studies in rats and dogs,

• combined chronic toxicity/carcinogenicity study in rats,

• chronic toxicity study in dogs,

• carcinogenicity study in mice,

• developmental toxicity studies in rats, rabbits, and CD-1 mice,

• reproduction study in rats,

• acute and subchronic neurotoxicity studies in rats,

• subchronic inhalation study in rats,

• developmental neurotoxicity (DNT) studies in rats,

• mutagenicity studies,

• metabolism study in rats, and

• dermal absorption study in monkeys. 

The toxicity profile table with a brief summary of all studies submitted may be found in 

Appendix A. Several literature studies were used for characterization and are cited throughout 

this document.
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4.2 Absorption, Distribution, Metabolism, and Excretion (ADME)

The metabolism study was performed with avermectin B1a. With oral dosing, the test material in 

the gastrointestinal tract of the rat was almost completely absorbed and distributed throughout all 

major tissues and organs, with the highest residues found in fat. Maximum concentrations in 

blood were achieved within 4-8 hours after administration. The absorbed avermectin was rapidly 

eliminated from the body, almost exclusively in the feces, and did not accumulate in the body 

after repeated exposure. The parent compound represented 46-56% of the total radioactivity 

found in the fecal samples of the low dose groups. The major biotransformation pathways of 

avermectin B1a in the rat were demethylation, hydroxylation, cleavage of the oleandrosyl ring, 

and oxidation reactions. There were 11 isolated metabolites. In the rat, avermectin B1a was 

metabolized to 24-hydroxy-methyl B1a (i.e., 24-OH-Me-B1a), which accounts for most of the 

radiolabeled residues. However, the [8, 9-Z]-isomer of avermectin B1a was not found in the rat 

metabolism studies. Avermectin B1a did not bioaccumulate in rat tissues. 

4.2.1 Dermal Absorption

A dermal absorption study was conducted with rhesus monkey using 3

H-avermectin B1a. The 

maximal dermal absorption of avermectin B1a was 1% of the applied dose (J. Rowland, TXR 

0012854, 9/15/1998).

4.3 Toxicological Effects

The toxicological effects observed in the test animals are consistent to the proposed MOA as 

described in the section 4.0, Mode of Action. In general, available toxicity data showed that, with 

single dose or repeated dose administration, the primary target organ was the nervous system, 

and that decreased body weight was also one of the most frequent findings. Neurotoxicity 

(including tremors, mydriasis, ataxia, and death) was seen in mice, dogs, and rats. 

Developmental effects such as cleft palate were reported in rabbits. GABA also plays a role in 

development; cleft palate findings may reflect the interaction of abamectin on the GABA 

receptor. Generally, the finding of cleft palate was seen at higher dose levels than those for 

neurotoxicity.

Integral to the dose response assessment in mammals for this class of compounds is the role of Pglycoprotein (P-gp) in target tissues. P-gp is a member of adenosine triphosphate (ATP) binding 

cassette transporter proteins, which reside in the plasma membrane and function as a 

transmembrane efflux pump, moving xenobiotics from the intracellular to the extracellular 

domain. P-gp is found in the canallicular surface of hepatocytes, the apical surface of proximal 

tubular cells in the kidneys, brush border surface of enterocytes, luminal surface of blood 

capillaries of the brain (blood brain barrier), placenta, ovaries, and the testes. As an efflux 

transporter, P-gp acts as a protective barrier to keep xenobiotics out of the body by excreting 

them into bile, urine, and intestinal lumen and prevents accumulation of these compounds in the 

brain and gonads, as well as in the fetus. Therefore, test animals with genetic polymorphisms that 

compromise P-gp expression are particularly susceptible to abamectin induced neurotoxicity 

(Lankas et al., 1997). 
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In this connection, the CF-1 strain of mouse is also uniquely sensitive to abamectin and 

emamectin. Some CF-1 mice have a polymorphism for the gene encoding P-gp and are either 

devoid (homozygous) or have diminished (heterozygous) levels of P-gp. These mice are found to 

be uniquely sensitive to the neurotoxic effects of abamectin and its derivative, emamectin. 

In addition, the neonatal rat is also particularly sensitive to abamectin and emamectin. P-gp is 

undetectable in the neonatal rat brain; the first detection of P-gp is on post-natal day (PND) 7 and 

does not reach adult levels until approximately PND 28 (Matsuoka, 1998). As shown in the 

reproductive and DNT studies, neonatal rats are sensitive to the effects of abamectin induced pup 

body weight reductions and death. In contrast, in the developing human fetus, the presence of Pgp was found as early as 22 weeks of gestation (Daood, 2008; van Kalken, et al., 1991). Based 

on the difference in the ontogeny of P-gp in neonatal rats and human newborns, the Agency does 

not believe that the early post-natal findings in the rat are relevant to human newborns or young 

children at this time.

The human multidrug resistance (MDR-1) gene encoding P-gp and polymorphism of MDR-1

gene are well studied. The literature data are inconclusive with respect to the functional 

significance of the genetic variance in P-gp in human. Currently, the reported cases of 

polymorphism of the MDR-1 gene in human populations have not been shown to result in a loss 

of P-gp function similar to that found in CF-1 mice (Macdonald & Gledhill, 2007). Given the 

ontogeny of P-gp and the lack of convincing evidence from the literature on human 

polymorphism of MDR-1 gene resulting in diminished P-gp function, the Agency considers the 

results of the studies with CF-1 mice not relevant for human health risk assessment. Therefore, 

the Agency is using results from toxicological studies conducted in the species that do not have 

diminished P-gp function for selecting toxicity endpoints and points of departure (PODs) for risk 

assessment. Among the test animals with fully functional P-gp, the beagle dog is the most 

sensitive species (Appendix A). 

Carcinogenicity studies in rats and mice (CD-1) and mutagenicity studies provide no indication 

that abamectin is carcinogenic or mutagenic.

Abamectin has high to moderate acute toxicity by the oral route (depending on the vehicle), high 

acute toxicity by the inhalation route, and low acute toxicity by the dermal route. It is slightly 

irritating to the skin, but is not an ocular irritant or a dermal sensitizer. 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

Currently, the toxicity endpoint and point of departure for all exposure scenarios were selected 

from the subchronic and chronic oral toxicity studies in dogs. The points of departure selected 

from the dog studies are based on clear NOAELs and are protective of all the adverse effects 

seen in the available human-relevant studies with rats, CD-1 mice, and rabbits. Therefore, the 

FQPA safety factor has been reduced to 1x. Detailed rationale is presented in 4.4.1 to 4.4.4.
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4.4.1 Completeness of the Toxicology Database

The toxicology database for abamectin is complete for human health risk assessment. As 

mentioned in Section 4.1, waivers have been granted for immunotoxicity and subchronic dermal 

toxicity studies (TXR 0056687, U. Habiba, 01/07/2013 and TXR 0056509; K. Rury, 

01/30/2013). No additional toxicology studies are required at this time.

4.4.2 Evidence of Neurotoxicity 

The proposed MOA is interaction with GABA receptors leading to neurotoxicity. The findings of 

neurotoxic signs observed in the abamectin database are consistent with the proposed MOA. 

Signs of neurotoxicity ranging from decreases in foot splay reflex, mydriasis (i.e., excessive 

dilation of the pupil), curvature of the spine, decreased fore- and hind-limb grip strength, tip-toe 

gate, tremors, ataxia, or spastic movements of the limbs are reported in various studies with 

different durations of abamectin exposure. In dogs, mydriasis was the most common finding at 

doses as low as 0.5 mg/kg/day at one week of treatment.

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

An increase in qualitative susceptibility was seen in the rabbit developmental toxicity study, 

where deceases in body weight and food consumption were seen in maternal animals at 2.0 

mg/kg/day. In contrast, the fetal effects were much more severe, consisting of cleft palate, 

clubbed foot, and death at 2.0 mg/kg/day. The POD (0.25 mg/kg/day) selected from the dog 

studies is 8x lower than the dose where rabbit fetal effects were seen. Therefore, it is protective 

of fetal effects seen in the rabbit developmental toxicity study.

The rat reproduction toxicity and developmental neurotoxicity studies demonstrated both 

qualitative and quantitative susceptibility in the pups to the effects of abamectin (decrease pup 

weights and increased postnatal pup mortality). This observation is consistent with the finding 

that P-gp is not fully developed in rat pups until postnatal day 28. Therefore, during the period 

from birth to postnatal day 28, the rat pups are substantially more susceptible to the effects of 

abamectin than adult rats. However, in humans, P-gp has been detected in the fetus at 22 weeks 

of pregnancy, and the human newborns have functioning P-gp. Therefore, human infants and 

children are not expected to have enhanced sensitivity as seen in rat pups. The 10x FQPA safety 

factor for infants and children is reduced to 1x.

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual concerns with respect to the exposure databases. The acute and chronic

dietary food exposure assessment utilizes conservative assumptions including anticipated 

residues, default processing factors, and percent crop treated. The dietary drinking water 

assessment utilized conservative modeling inputs which included conservative assumptions for 

the parent chemicals and all degradates of concern. Therefore, the water exposure assessment 

will not underestimate the potential risks for infants and children. Likewise, the use of maximum 

application rates and central-to-high end inputs results in calculated residential exposure
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assessments will not underestimate the risks to infants and children from the requested uses.

4.5 Toxicity Endpoint and Point of Departure Selections

The toxicity studies in rats, CD-1 mice and beagle dogs demonstrated that the beagle dog is the 

most appropriate species to assess the risk of abamectin. The toxicity endpoints and PODs for 

human health risk assessment are presented in Tables 4.5.1 and 4.5.2. 

Dietary Exposure and Incidental Oral Endpoint (all durations):

For all oral exposure scenarios, clinical signs (tremors and mydriasis) of neurotoxicity were 

observed in the subchronic (12- and 18-weeks) and chronic oral toxicity studies in dogs at the 

lowest observed adverse effect level (LOAEL) of 0.5 mg/kg. The POD (no observed adverse 

effect level; NOAEL) is 0.25 mg/kg (Tables 4.5.1 and 4.5.2). Tremors and mydriasis were 

observed as early as the first week of exposure. After extended exposure in the chronic toxicity 

study, adverse effects were observed at similar dose levels as the shorter-term studies. The 

Agency assumes that these clinical signs could result from a single dose.

There are 3 lines of evidence which support the use of the 0.25 mg/kg for all oral exposure 

scenarios and durations: (1) kinetic data supports rapid absorption/excretion, (2) acute 

neurotoxicity was observed in rats, and (3) the neurotoxic effects produced by abamectin in 

beagle dogs did not progress with time. 

Kinetic data: Given the rapid absorption and elimination of abamectin, the Agency has 

concluded that some of the neurotoxic effects seen in the subchronic and chronic toxicity 

studies in dogs could be elicited by a single dose. As described previously, the kinetic data of 

abamectin show a pattern of rapid absorption and elimination. With oral dosing in rats and 

mice, abamectin was absorbed rapidly, and maximum concentration in blood was achieved 

within 4-8 hours after administration. It was rapidly eliminated from the body, almost 

exclusively in the feces, and did not accumulate in the body after repeated exposure. 

Acute neurotoxicity study in rats: The use of the subchronic and chronic dog studies is

supported by the acute neurotoxicity (ACN) study in rat (range finding and main studies). 

The ACN shows that clinical signs of neurotoxicity, such as reduced foot splay reflex, ataxia, 

tremors and mydriasis (decreased pupillary light response), were observed from a single 

dose. Most of the effects observed in the rat ACN were consistent with those seen in the 

subchronic and chronic dog studies.

Subchronic and chronic dog studies: The effects seen in the subchronic (gavage) and chronic 

dog studies were similar despite repeated dosing, suggesting the response may be due to each 

individual exposure rather than to accumulation of abamectin in tissues. Clinical signs such 

as ataxia and or whole body tremors were reported within 3 hours of the first dose at higher 

dose levels.
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Dermal and Inhalation Exposure Endpoints (all durations):

For short-term dermal and inhalation exposures, oral subchronic and chronic toxicity studies in 

dog were chosen as co-critical studies to establish the toxicity endpoint and POD. The dermal 

absorption factor is 1%, which represents maximal dermal absorption seen in the dermal 

absorption study. The adverse effects for establishing the toxicity endpoints are tremors and 

mydriasis, and the POD is 0.25 mg/kg/day. There is no repeat dose dermal toxicity study 

available. For inhalation, a 30-day inhalation study in rats is available, but the results show no 

toxicity at the highest tested concentration (2.5 μg/L, approximately equivalent to 0.568 

mg/kg/day). The use of the results from the dog studies in establishing the toxicity endpoint and 

POD (0.25 mg/kg/day) for the inhalation route is appropriate and protective for these exposure 

scenarios. 

The LOC is 100 for residential exposure risk assessments, based on a total uncertainty factor of 

100x (10 for interspecies extrapolation, 10x for intraspecies variations). 

For occupational exposure risk assessments, the LOC is 100 based on a total uncertainty factor of 

100x (10x for interspecies extrapolation, 10x for intraspecies variations). 

4.5.1 Combined Routes of Exposure

Oral, dermal and inhalation routes of exposure could be combined since the toxicity endpoints 

were chosen from the same co-critical studies.

4.5.2 Carcinogenicity: 

Abamectin is characterized as not likely to be carcinogenic to humans based on the absence of 

significant increase in tumor incidence in two adequate rodent (rats and mice) carcinogenicity 

studies. Quantification of cancer risk assessment is not required.

Tables 4.5.1 and 4.5.2 summarize the toxicity endpoints and PODs for risk assessment for 

abamectin.

Table 4.5.1. Summary of Toxicological Doses and Endpoints for Abamectin for Use in Dietary and NonOccupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA SF

RfD, PAD, 

LOC for 

Risk 

Assessment

Study and Toxicological Effects

Dietary (all 

durations) 

(General 

Population, 

including 

Infants and 

Children) & 

Incidental 

Oral

NOAEL=0.25 

mg/kg/day

UFA= 10x

UFH= 10x

FQPA SF =1x

Acute RfD = 

aPAD = 

0.0025 

mg/kg/day

Subchronic & chronic oral toxicity studies in 

dogs 

Chronic LOAEL = 0.50 mg/kg/day based on 

body tremors, one death, liver pathology, 

decreased body weight. Mydriasis was seen 

during week one in one dog

Subchronic LOAEL=0.5 mg/kg/day based on 

mydriasis during week one, death at 1.0 

mg/kg/day.
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Table 4.5.1. Summary of Toxicological Doses and Endpoints for Abamectin for Use in Dietary and NonOccupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA SF

RfD, PAD, 

LOC for 

Risk 

Assessment

Study and Toxicological Effects

Dermal 

(Short-Term 

and 

IntermediateTerm)

NOAEL = 

0.25 

mg/kg/day

Dermal 

Absorption = 

1%

UFA = 10x

UFH = 10x 

FQPA SF =1x

LOC: MOE 

= 100

Inhalation 

(Short-Term 

and 

IntermediateTerm)

NOAEL = 

0.25 

mg/kg/day

Toxicity via 

the inhalation 

route 

assumed to be 

equivalent to 

oral route.

UFA = 10x

UFH =10x 

FQPA SF =1x

LOC: MOE 

= 100

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant 

tumor increases in two adequate rodent carcinogenicity studies.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level 

of concern. N/A = not applicable.

Table 4.5.2. Summary of Toxicological Doses and Endpoints for Abamectin for Use in Occupational 

Human Health Risk Assessments

Exposure/ Scenarios Point of 

Departure

Uncertainty/ 

Safety Factor LOC Study and Toxicological Effects

Dermal (Short-Term 

and IntermediateTerm)

NOAEL = 0.25 

mg/kg/day

Dermal 

Absorption = 

1%

UFA = 10x

UFH = 10x LOC: MOE = 100

Subchronic & Chronic oral 

Toxicity studies in Dogs

Chronic LOAEL = 0.50 

mg/kg/day based on body 

tremors, one death, liver 

pathology, decreased body 

weight. Mydriasis was seen 

during week one in one dog

Subchronic LOAEL=0.5 

mg/kg/day based on mydriasis 

during week one, death at 1.0 

mg/kg/day.

Inhalation (ShortTerm and 

Intermediate-Term)

NOAEL = 0.25 

mg/kg/day

Toxicity via the 

inhalation route 

assumed to be 

equivalent to 

oral route.

UFA = 10x

UFH =10x LOC: MOE = 100
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Table 4.5.2. Summary of Toxicological Doses and Endpoints for Abamectin for Use in Occupational 

Human Health Risk Assessments

Exposure/ Scenarios Point of 

Departure

Uncertainty/ 

Safety Factor LOC Study and Toxicological Effects

Cancer (oral, dermal,

inhalation)

Classification: Not likely to be carcinogenic to human based on the absence of significant 

increase in tumor incidence in two adequate rodent carcinogenicity studies.

Point of Departure (PoD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). . MOE = margin of exposure. LOC = level of 

concern.

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

A detailed discussion of the residues of concern for primary crops, rotational crops and livestock

is presented in the previous risk assessment (D402677 and D405843, N. Dodd, 12/20/2012). The 

residues of concern for the risk assessment and the tolerance expression are summarized in Table 

5.1 below.

Table 5.1 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)2

Livestock Ruminant1

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), NOA 448111, NOA 

448112, NOA 426289, NOA 

445495, NOA 457464, and 

NOA 457465

Not applicable

1 Residues of concern in ruminants include both use on crops used as animal feed and use in cattle ear tags.

2 No rotational crop tolerances have been established.
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5.2 Food Residue Profile

Plant Commodities:

Adequate field trials were submitted for abamectin on caneberries (blackberry and raspberry), 

sweet corn, soybeans, greenhouse-grown tomato, green onion, guava, lima bean, lychee, papaya, 

pineapple and snap bean that adequately reflect the proposed use pattern. The number of field 

trials and the geographic representation are adequate. Decline studies show decreasing residues 

with increasing PHI. Adequate storage stability data are available to support the field trials. 

Adequate data collection methods were used. These field trials are summarized in Tables F.1 and 

F.2 in Appendix F. 

There are no processed commodities for caneberries, sweet corn, green onion, guava, lima bean, 

lychee, papaya, or snap bean. The processed commodities for soybean are meal, hulls, refined 

oil, and aspirated grain fractions (AGF). A processing study on soybeans indicated that 

combined residues of avermectin B1a, avermectin B1b, and 8,9-Z avermectin B1a may concentrate 

significantly in/on aspirated grain fractions (average processing factor of 59x), and slightly in 

meal (1.1x), and hulls (1.2x). Additionally, a processing study on tomatoes was previously 

reviewed (N. Dodd, MRID 47702806; D364734, 1/21/10). Based on the results from the 5x rate 

field trials, the average processing factors for total abamectin residues were 0.52x in puree and 

0.94x in paste. These data indicate that abamectin residues do not concentrate in tomato 

processed fractions; therefore, separate tolerances are not required for tomato paste or puree. The 

processed commodities for pineapple are process residue (also known as wet bran) and juice. No 

processing studies have been submitted for pineapple, however, crop field trials were conducted 

at exaggerated application rates (in addition to the proposed label rate) and residues of abamectin 

were not detected. Therefore, a processing study for pineapple is not needed, and tolerances for 

pineapple processed commodities are not required.

Residues in rotational crops are not expected from the proposed uses.

Livestock Commodities:

Abamectin is currently registered for use in cattle ear tags applied to beef cattle and non-lactating 

dairy cattle. Y-TEX Corporation submitted a study to determine residues of abamectin in milk 

from use of the ear tag on lactating dairy cattle. Although some of the samples analyzed showed 

minimal transfer of residues to milk, there was one sample with residues close to the existing 

tolerance that is based on secondary residues from cattle consuming treated feed. Therefore, the 

tolerance for milk needs to be increased to accommodate this use. Syngenta has proposed use of 

abamectin on sweet corn and soybeans, which are both livestock feed items. The IR-4 has 

proposed a tolerance on pineapple, and pineapple process residue, a by-product of pineapple 

processing, is a cattle feed item. The Agency has re-evaluated the Maximum Reasonable Dietary 

Burden (MRDB) for livestock considering the proposed uses, and additional modifications to 

milk, meat byproducts, and fat tolerances are required. Note that the Agency generally 

establishes tolerances for the edible commodities of sheep, goats, and horses at the same level of 

cattle. However, since the ear tags containing abamectin are registered for use only on cattle, 

tolerances on cattle commodities are based on potential resides from ear tags and feed items, 

while the residues in the remaining types of livestock can only be as a result of secondary residue 

from consuming treated feed. Further details on the reassessment of the livestock dietary burden 
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may be found in the chemistry assessment of the proposed uses (D410993, N. Dodd, 03/17/2016;

D414022, N. Dodd, 03/17/2016; D416280, N. Dodd, 03/17/2016; D424008, N. Dodd, 

12/22/2015).

No poultry feeding studies have been submitted or are required. Based on dietary burden 

calculations using Table 1 Feedstuffs (June 2008), no secondary residues are expected to occur in 

poultry commodities.

5.3 Water Residue Profile

EDWCs were provided by EFED for abamectin. The abamectin residues of concern include the 

parent compound mixture and the structurally similar degradates: NOA 448111, NOA 448112, 

NOA 426289, NOA 445495, NOA 457464, and NOA 457465. In absence of toxicity data on 

these degradates, they are assumed to have toxicity profiles similar to that of abamectin on the 

basis of the structural similarities.

Groundwater and surface water monitoring data are not available for abamectin at this time. 

Therefore, screening models were used to determine estimated concentrations for abamectin in 

groundwater and surface water for the proposed uses.

The Tier I Pesticide Root Zone Model - Ground Water (PRZM-GW) and Tier I Screening 

Concentration in Ground Water (SCI-GROW) models were used to assess residues in ground 

water. Surface drinking water concentrations were estimated using the Tier II surface water 

concentration calculator (SWCC) computer model. The EDWCs used in the acute and chronic 

assessments are the residues in surface water since the residues in ground water are lower. 

Considering all registered/proposed uses, the proposed use on soybeans in MS at 0.037 lb 

ai/A/year results in the highest acute drinking water exposure and the registered use on beans in 

MI at 0.056 lb ai/A/year results in the highest chronic drinking water exposure. The acute 

EDWC is 0.76 ppb, the 1-in-10 year annual maximum concentration in surface water, as shown 

in Table 5.3 below; however, for the acute dietary assessment, a drinking water residue 

distribution file provided by EFED was used. For the chronic dietary assessment, the annual 

mean concentration of 0.30 ppb in surface water was used. 
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Table 5.3. Screening-Level EDWCs for Proposed Uses of Abamectin1

Source (Tier: Model) Use Site

(Max. Annual App. Rate)

Acute EDWC 

(μg/L)

Chronic 

EDWC (μg/L)

Surface water (Tier II: SWCC) Soybeans (0.037 lbs ai/A)/ Beans 

(0.056 lbs ai/A)

0.76 

(soybeans)

0.30

(beans)

Ground water (Tier I: PRZM-GW) Golf courses (0.27 lbs ai/A) 0.074 N/A

Ground water (Tier I: SCI-GROW) Golf courses (0.27 lbs ai/A) ≤0.0031 1 Maximum values in bold. Values include parent compound and several structurally similar degradates.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Acute assessment:

A refined acute dietary (food and drinking water) exposure assessment was conducted for all 

proposed and established food uses of abamectin. Acute anticipated residues derived from field 

trial data were used. Empirical and default processing factors and percent crop treated (PCT) 

estimates were used, as available. No monitoring data were used. Drinking water residues were 

represented by a residue distribution file based on the application to soybeans. 

Chronic assessment:

A refined chronic dietary (food and drinking water) exposure assessment was conducted for all 

proposed and established food uses of abamectin. Average residues from field trials were used. 

Residues from use in food handling establishments were included. Empirical and default 

processing factors and PCT estimates were used, as available. Drinking water was represented by 

a single point estimate of average abamectin residues (the 1-in-ten-year annual mean). The 

estimated surface water concentration of 0.30 ppb was based on the application to beans.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The following maximum percent crop treated estimates for abamectin provided by BEAD (J. 

Alsadek, No DP number, 07/01/2015 and D. Atwood, D428074, 08/27/2015) were used in the 

acute dietary risk assessment for the following crops: almond: 80%; apple: 30%; apricot: 30%; 

avocado: 60%; bean, dry: 2.5%; blackberry: 68%; boysenberry: 68%; cantaloupe: 45%; celery: 

70%; cherry: 20%; corn, sweet: 57%; cotton: 30%; cucumber: 10%; grape: 35%; grapefruit: 

90%; hazelnut: 2.5%; honeydew: 35%; lemon: 55%; lettuce: 45%; loganberry: 68%; nectarine: 

20%; onion, bulb: 10%; orange: 70%; peach: 25%; pear: 85%; pecan: 2.5%; pepper: 30%; 

pistachio: 2.5%; plum/prune: 35%; potato: 20%; pumpkin: 10%; raspberry: 68%; soybean: 11%; 

spinach: 45%; squash: 15%; strawberry: 45%; tangerine: 55%; tomato: 25%; walnut: 55%; and 

watermelon: 15%. 

The percent crop treated values that were used to refine the livestock commodities for the acute 

assessment were based on: sweet corn (44%) for beef, goat, horse, and sheep commodities; and 

the food handling establishment uses (5%) for hog and poultry meat and meat byproducts. 
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The following average percent crop treated estimates for abamectin provided by BEAD (J. 

Alsadek, No DP number, 07/01/2015 and D. Atwood, D428074, 08/27/2015) were used in the 

chronic dietary risk assessment for the following crops: almond: 70%; apple: 10%; apricot: 15%; 

avocado: 35%; bean, dry: 2.5%; blackberry: 56%; boysenberry: 56%; cantaloupe: 25%; celery: 

45%; cherry: 5%; corn, sweet: 45%; cotton: 20%; cucumber: 5%; grape: 15%; grapefruit: 70%; 

hazelnut: 2.5%; honeydew: 20%; lemon: 40%; lettuce: 20%; loganberry: 56%; nectarine: 20%; 

onion, bulb: 2.5%; orange: 40%; peach: 10%; pear: 70%; pecan: 1%; pepper: 15%; pistachio: 

2.5%; plum/prune: 10%; potato: 5%; pumpkin: 5%; raspberry: 56%; soybeans: 8%; spinach: 

25%; squash: 5%; strawberry: 30%; tangerine: 35%; tomato: 10%; walnuts: 25%; and 

watermelons: 5%.

The percent crop treated values that were used to refine the livestock commodities for the 

chronic assessment were based on: cotton (30%), soybean (8%), and sweet corn (38%). The PCT 

for poultry and hog commodities is based on the food handling establishment (FHE) PCT (%)

since the tolerances for FHE uses result in residues considerably higher than secondary residues 

from hogs and poultry consuming treated feed.

All commodities included for food handling residues were assigned the value of 5 PCT 

(D413125, J. Becker, 10/07/2014).

5.4.3 Acute Dietary Risk Assessment

The general U.S. population and the following population subgroups were assessed: all infants 

(<1 year old), children 1-2 years old, children 3-5 years old, children 6-12 years old, youth 13-19 

years old, adults 20-49 years old, females 13-49 years old, and adults 50-99 years old.

As shown in Table 5.4.6, the acute dietary exposure estimates for food and drinking water are 

below HED’s level of concern (<100% aPAD) at the 99.9th percentile of exposure for the general 

U.S. population and all population subgroups. Abamectin dietary exposure at the 99.9th

percentile for food and drinking water is 45% of the aPAD for the general U.S. population and 

88% of the aPAD for children 1-2 years old, the most highly exposed population subgroup.

Limited Pesticide Data Program (PDP) monitoring data are available and virtually all samples do 

not have detectable residues of abamectin. Incorporating PDP monitoring data would not lower 

the risk estimates for abamectin because the limit of detection for PDP monitoring (0.02 ppm) 

tends to be higher than those used in the abamectin crop field trials (0.002 ppm or 2.0 ppb). 

Additionally, there are numerous non-detects in the crop field trials with abamectin indicating 

low residues in growing crops.

5.4.4 Chronic Dietary Exposure

Table 5.4.6 shows the background dietary exposure estimates for food and drinking water. HED

notes that the PODs selected for assessing acute and chronic dietary exposure are the same; 

because of the conservative, nature of the inputs into an acute dietary exposure assessment, 

usually if the PODs are the same for both acute and chronic durations, only an acute dietary 

exposure assessment is conducted. However, a chronic dietary exposure assessment has been 
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conducted for abamectin for the purposes of generating a food exposure value for the aggregate 

assessment and to incorporate residues/exposure from the food handling establishment (FHE) 

uses. Residues in food resulting from food handling establishment uses are not included in acute 

dietary exposure assessments because of the conservative nature of the survey data used in the 

acute dietary exposure assessments, as per HED policy. Acute assessments rely on individual 

food consumption events over two days. If the food handling establishment uses were included 

in the acute assessment, it would assume that a person ate all meals in a restaurant/food handling 

establishment for two days and that all food was treated with abamectin at the established 

tolerance-level; which is considered extremely conservative.

The general U.S. population and the following population subgroups were assessed: all infants 

(<1 year old), children 1-2 years old, children 3-5 years old, children 6-12 years old, youth 13-19 

years old, adults 20-49 years old, females 13-49 years old, and adults 50-99 years old.

Incorporating PDP monitoring data would not lower the risk estimates for abamectin because the 

limit of detection for PDP monitoring (0.02 ppm) tends to be higher than those used in the 

abamectin crop field trials (0.002 ppm or 2.0 ppb). Additionally, there are numerous non-detects 

in the crop field trials with abamectin indicating low residues in growing crops. 

5.4.5 Cancer Dietary Risk Assessment

Since abamectin is classified as “not likely to be carcinogenic to humans,” a cancer dietary 

exposure assessment is not required.

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Abamectin

Population Subgroup

Acute Dietary

(99.9th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD* Dietary Exposure(mg/kg/day) % cPAD*

General U.S. Population 0.001135 45 0.000056 2.2

All Infants (< 1 year old) 0.001584 63 0.000096 3.9

Children 1-2 years old* 0.002192 88 0.000268 11

Children 3-5 years old 0.001553 62 0.000160 6.4

Children 6-12 years old 0.000729 29 0.000090 3.6

Youth 13-19 years old 0.000475 19 0.000045 1.8

Adults 20-49 years old 0.000446 18 0.000038 1.5

Adults 50-99 years old 0.000345 14 0.000037 1.5

Females 13-49 years old 0.000427 17 0.000038 1.5

*The subpopulation with the highest risk estimates is bolded.
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6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are proposed residential use sites that may lead to handler and post-application exposures. 

Furthermore, recent revisions to the toxicity endpoints and PODs for abamectin required a 

reassessment of all currently registered residential uses to be consistent with all current policies. 

These revisions of residential exposures will impact the human health aggregate risk assessment.

The proposed EPs (for control of turf-parasitic nematodes on golf course greens, tees, and 

fairways) that may lead to post-application exposures include:

1. AgadorTM 0.17 SC (EPA Reg. No. 100-RLNO), and

2. DivanemTM 0.15EC (EPA Reg. No. 100-RLRN).

Previously-registered end-use products that may result in residential handler or post-application 

exposures include several formulations of homeowner bait and bait station products registered 

under multiple companies. These products include an outdoor granular bait (GB) formulation for 

use on fire ant mounds, and several indoor ready-to-use baits (RBs). For this assessment, the 

exposures and risk estimates for applying outdoor granular baits were assessed using the 2012 

Residential SOPs1 and exposure from indoor ready-to-use gel baits is considered negligible. In 

addition, exposure data for hand dispersal of granular bait is chosen as a surrogate to calculate 

risk estimates from indoor RBs.

6.1 Residential Handler Exposure

HED uses the term “handlers” to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct tasks related to applications and that 

exposures can vary depending on the specifics of each task as was described above for 

occupational handlers. Residential handlers are addressed somewhat differently by HED, as 

homeowners are assumed to complete all elements of an application without use of any 

protective equipment.

The quantitative exposure and risk assessment developed for residential handlers is based on: (1) 

loading/applying GB outdoors via push-type spreaders, belly grinders, spoons, hand, and cup or 

shaker; and (2) applying granular bait indoors by hand (as a surrogate for a ready-to-use dust 

bait).

There are no registered products that would lead to any residential handler risk estimates of 

concern. Short-term combined (dermal + inhalation) residential handler MOEs range from 

860,000 to 2,700,000,000.

 1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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Table 6.1. Residential Handler Non-Cancer Exposure and Risk Estimates for Abamectin.

Exposure

Scenario1

Dermal Unit 

Exposure

Inhalation Unit 

Exposure Max

App.

Rate

Area Treated or 

Amount Handled 

Daily2

Dermal Inhalation Total

Dose3 MOE4 Dose5 MOE6 MOE7

mg/lb ai mg/kg/day LOC = 

100 mg/kg/day LOC = 100

Mixer/Loader/Applicator for Outdoor Bait Application

Push-Type

Spreaders 0.81 0.0026 2.3×10-4lb ai/A 0.5 acres 1.20×10-8 2.1×107 3.8×10-9 6.6×107 1.6×107

Belly 

Grinders 360 0.039

5.31×10-

9

lb ai/sq 

ft

1.2×103 sq ft 2.90×10-7 8.7×105 3.1×10-9 8.0×107 8.6×105

Spoon 6.2 0.087

100 sq ft

4.10×10-

10 6.1×108 5.8×10-10 4.3×108 2.5×108

Cup 0.11 0.013 7.30×10-

12 3.4×1011 8.6×10-11 2.9×109 2.7×109

Hand 

Dispersal 160 0.38 1.10×10-8 2.4×107 2.5×10-9 9.9×107 1.9×107

Shaker Can 0.11 0.013 7.30×10-

12 3.4×1010 8.6×10-11 2.9×109 2.7×109

Mixer/Loader/Applicator for Indoor Bait Application

Bait 

(granular;

dispersal)

160 0.38 1.3×10-5

lb ai/package/day 2.60×10-7 9.4×105 6.30×10-8 4.0×106 7.6×105

1 Based on registered labels:

EPA Reg. Nos. 100-893, 100-1029, 100-1452 (50 mg ai/lb product): Apply 7 tbsp/mound (1 tbsp ≈ 0.4 oz). Do not treat more 

than 12 ant mounds per acre (i.e. 12 mounds/A × 7 tbsp product/mound × 0.4 oz product/tbsp product × 0.0625 lb product/oz 

product × 50 mg ai/lb product × 2.20462×10-6 lb ai/mg ai = 0.00023 lb ai/A). 0.00023 lb ai/A × (1 A/43560 ft2) = 5.31×10-9 ft2.

EPA Reg. No. 499-383 (0.05% ai bait dust): Package contains 100 bait placements (12 grams of product). The label 

recommends up to 30 bait placements in an average sized kitchen (i.e. assuming one package can be used in one day, 12 g 

product/day × 0.05% ai/product × 0.00220462 lb ai/g ai = 0.000013 lb ai/day).

2 Exposure Science Advisory Council Policy #9.1. Based on HED’s SOPs: Lawns/Turf (January 2012).

3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A 

or gallons/day) × DAF (1%) ÷ BW (80 kg).

4 Dermal MOE = Dermal NOAEL (mg/kg/day) / Dermal Dose (mg/kg/day). ST/IT Dermal NOAEL = 0.25 mg/kg/day. Level of 

concern = 100.

5 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount 

Handled (A or gallons/day) ÷ BW (80 kg).

6 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST/IT Inhalation NOAEL = 0.25 

mg/kg/day. Level of concern = 100.

7 Total MOE = NOAEL (mg/kg/day) ÷ (Dermal Dose + Inhalation Dose). ST/IT Combined Dermal/Inhalation NOAEL = 0.25 

mg/kg/day. Level of concern = 100.

6.2 Residential Post-Application Exposure and Risk Estimates 

Post-application exposure for adults and children (1 to < 2 years old) is unlikely for the currently

registered uses of abamectin. For currently registered outdoor treatments, adults and children are 

not expected to directly contact fire ant mounds. For currently registered indoor pest control, 

baits are intended to be placed in cracks and crevices where direct contact by adults and children 

(1 to < 2 years old) is unlikely.

However, residential post-application exposure for adults and children (6 to < 11 and 11 to < 16

years old) is possible for the newly proposed use of abamectin on golf courses. Adults and 

children (6 to < 11 and 11 to < 16 years old) performing physical post-application activities on 

golf course turf may receive dermal exposure to abamectin residues. The scenarios, lifestages,

and routes of exposure include: golfing for adults (dermal), children 11 to < 16 years old 

(dermal), and children 6 to < 11 years old (dermal). Table 6.2 presents the post-application 
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dermal MOEs calculated after applications of abamectin to golf course turf (greens, tees, and 

fairways only). Post-application risk estimates for all scenarios are greater than the LOC of 100 

and therefore are not of concern (MOEs range from 9,000 to 12,000). 

Table 6.2. Short-Term Residential Post-Application Exposure and Risk Estimates for Abamectin on Turf

Lifestage Post-Application Exposure Activity 

Scenario

Dose 1

MOE 2

mg/kg/day

Liquid Formulation on Turf (Golf Course Greens, Tees, and Fairways)

max single application rate: 0.34 lb ai/A

Adult

Dermal Exposure

Golfing 0.000020 12,000

Child 6 to < 11 years old Golfing 0.000028 9,000

Child 11 to < 16 years old Golfing 0.000024 11,000

1 Dermal Dose = TTR/DFR (μg/cm2) × CF1 (0.001 mg/μg) × TC (cm2/hr) × Exposure Time (hr) ÷ body weight (kg). TCs for 

golfing: 300 cm2/hr for adults, 4,400 cm2/hr for children 11 to < 16 years old, and 2,900 cm2/hr for children 6 to < 11 years 

old. Exposure time for golfing: 4 hr. Body weight for adult: 80 kg. Body weight for children 11 to < 16 years old: 57 kg. Body 

weight for children 6 to < 11 years old: 32 kg.

2 MOE = NOAEL ÷ Daily Dose (mg/kg/day). Dermal NOAEL= 0.25 mg/kg/day. Level of concern = 100.

Guideline 875.2100 - Turf Transferable Residues (TTR):

Since the estimated residential turf post-application exposure for residential golf course using 

default TTR values for abamectin is minimal in comparison to the LOC (i.e. the calculated MOE 

is greater than 10 times higher than the LOC; MOE = 9,000 compared to the LOC of 100); EPA 

is waiving the 40 CFR TTR data requirement. In this instance, it is unlikely that chemicalspecific TTR data would be needed to further refine exposure assessments or would add 

appreciably to our general understanding of the availability of turf transferable pesticide 

residues.

6.3 Residential Bystander Post-Application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0687-

0037). The Agency has evaluated the SAP report and has developed a Volatilization Screening 

Tool and a subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the Agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for abamectin.

6.4 Non-Occupational Spray Drift Exposure and Risk Estimates

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for abamectin. The Agency has been working with the Spray Drift Task Force

(a task force composed of various registrants which was developed as a result of a Data Call-In 

issued by EPA), EPA Regional Offices, and State Lead Agencies for pesticide regulation and 
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other parties to develop the best spray drift management practices (see the Agency’s Spray Drift 

website for more information). 2 The Agency has also developed a policy on how to 

appropriately consider spray drift as a potential source of exposure in risk assessments for 

pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during 

the Registration Review process which ensures that all uses for that pesticide will be considered 

concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures For 

Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification 

of indirect non-occupational exposure to drift.

7.0 Aggregate Exposure/Risk Characterization

In accordance with FQPA, HED must consider and aggregate pesticide exposures and risks from 

three major sources: food, drinking water, and residential exposures when considering tolerance 

petitions. The aggregate risk assessment must consider exposures from oral, dermal and 

inhalation exposures. The toxicity endpoints selected for these routes of exposure may be 

aggregated together due to their common toxicity endpoint and effects for all routes and 

durations of exposure.

7.1 Acute Aggregate Risk

The acute aggregate risk assessment considers exposure estimates from dietary consumption of 

abamectin (food and drinking water). The acute aggregate food and drinking water assessment 

results are presented in Section 5.4 above. The most highly exposed subgroup is children 1-2 

years old at 88% of the aPAD, which is below the level of concern.

7.2 Short-Term Aggregate Risk

The short-term aggregate risk assessment estimates risks likely to result from exposure to 

abamectin residues from food, drinking water, and residential pesticide uses. High-end estimates 

of residential exposure are used, while average values are used for food and drinking water 

exposure.

For the purpose of this human health risk assessment, a summary of the worst-case residential 

exposure estimates are provided in Table 7.2.1. The recommended residential exposure for use in 

the adult and youth aggregate assessments reflect dermal exposure from golfing activities 

following applications to golf course turf. There is no recommended residential risk estimate for 

children under the age of six for use in the aggregate assessment, because residential risk 

estimates are expected to be negligible to infants and young children.

 2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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Table 7.2.1. Scenarios Recommended for Aggregate Risk Assessment of Abamectin (Short-Term Only)

Scenario Daily Dose1 MOE2

mg/kg/day LOC = 100

Adults

Post-Application: Dermal Exposure

(Liquid Application to Golf Course Turf) 0.000020 12,000

Children 6 to < 11 years old

Post-Application: Dermal Only Exposure

(Liquid Application to Golf Course Turf) 0.000028 9,000

Children 11 to < 16 years old

Post-Application: Dermal Exposure

(Liquid Application to Golf Course Turf) 0.000024 11,000

1 Daily Dose = See Table 5.2 for all adult and children golfing scenarios (dermal dose + inhalation dose).

2 MOE = NOAEL/Daily Dose (mg/kg/day). ST Dermal = NOAEL = 0.25 mg/kg/day. LOC = 100.

Short-term aggregate risk is calculated in Table 7.2.2, below. All short-term aggregate exposure 

estimates resulted in MOEs greater than 100, and were not of concern.

Table 7.2.2 Short-Term Aggregate Risk Calculations

Population

Short-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

Adults 

0.25 100 0.0025

0.000037 0.000020 0.000057 4,400

Children 6 to 

<11 years old 0.000090 0.000028 0.00012 2,100

Children 11 to 

<16 years old 0.000045 0.000024 0.000069 3,600

1 The LOC = 100 and includes the standard inter- and intra-species uncertainty factors (UFA and UFH, respectively) 2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC. 3 Residential Exposure = [Oral exposure + Dermal exposure + Inhalation Exposure] from Tables 6.2 and 7.2.1. 4 Total Exposure = Avg Food & Water Exposure + Residential Exposure). 5 Aggregate MOE = [NOAEL ÷ (Avg Food & Water Exposure + Residential Exposure)].

7.3 Chronic Aggregate Risk

The chronic aggregate risk assessment considers average exposure estimates from dietary 

consumption of abamectin (food and drinking water) and residential uses. However, due to the 

use patterns, no chronic residential exposures are expected. Therefore, the chronic aggregate risk 

assessment will consider exposure from food and drinking water only.

The chronic aggregate food and drinking water assessment results are presented in Section 5.4

above. The result of this assessment is 2.2% of the cPAD for the general U.S. population. The 

most highly exposed subgroup is children 1-2 years old at 11% of the cPAD, which is below the 

level of concern. 
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7.4 Cancer Aggregate Risk

Abamectin is classified as not likely to be carcinogenic to humans based on the absence of a 

significant increase in tumor incidence in two adequate rodent carcinogenicity studies.

8.0 Cumulative Exposure/Risk Characterization

Section 408(b)(2)(D)(v) of the Federal Food, Drug, and Cosmetic Act (FFDCA) requires EPA to 

consider available evidence concerning the cumulative effects of pesticide residues and other 

substances that have a common mechanism of toxicity (i.e., a common toxic effect to human 

health by the same, or essentially the same, sequence of major biochemical events). EPA’s 

Office of Pesticide Programs (OPP) has previously developed guidance documents for 

establishing common mechanism groups (CMGs) 3 and conducting cumulative risk assessments 

(CRAs) 4. OPP recently developed an additional guidance document, entitled Pesticide 

Cumulative Risk Assessment: Framework for Screening Analysis Purpose (USEPA, 2016). This 

document builds upon those previous guidance documents in order to provide a tiered approach 

to screening pesticides for potential common mechanism groupings and conducting screeninglevel CRAs. Using the framework, pesticides are screened for potential cumulative evaluation 

using a two-step approach: (1) evaluation and comparison of available toxicological information 

(e.g., chemical structures, hazard profiles); and, (2) depending upon the results of step 1, a riskbased screening approach. 

Using this weight of evidence approach, the Agency will conclude one of three options as the 

outcome of the CMG screening analysis: (1) no CMG and no further cumulative analysis; (2) 

candidate CMG can be formed and a screening-level exposure analysis is conducted; or (3) CMG 

can be established and a CRA is conducted. 

OPP has utilized this framework for abamectin and has determined that abamectin and 

emamectin form a candidate CMG of the avermectin macrocyclic lactones. A candidate CMG 

(option 2) shares characteristics to support a testable hypothesis for a common mechanism of 

action and there is sufficient toxicological data to suggest a common pathway. However, there 

are not adequate data to establish those key events in a pathway as described in the mode of 

action/adverse outcome pathway (MOA/AOP) framework (e.g., lack of dose or temporal 

concordance of proposed key events). Subsequently, the Agency has conducted a screening-level 

cumulative exposure analysis consistent with the guidance described in the cumulative screening 

framework. The screening-level cumulative assessment for the avermectin macrocyclic lactones,

abamectin and emamectin, indicates that cumulative aggregate dietary and residential exposures 

for abamectin and emamectin are below the Agency’s levels of concern.

 3 Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common 

Mechanism of Toxicity (USEPA, 1999)

4 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common 

Mechanism of Toxicity (USEPA, 2002)
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Additional information regarding cumulative exposure and risk characterization, in general, as 

well as the screening assessment for the avermectin macrocyclic lactones, in particular, may be 

found in Appendix H. 

9.0 Occupational Exposure/Risk Characterization

Occupational exposure and risk estimates have been quantified for all proposed uses in two 

separate assessments: The proposed uses associated with PP#s 3F8184 and 3E8175 (Caneberry 

subgroup 13-07A, corn, soybeans, and proposed golf course turf) were assessed in a memo 

completed on 12/18/2014 (D414874, N. Keller, 12/18/2014). The proposed uses associated with 

PP# 4E8309 (Green onion subgroup 3-07B; Stone fruit group 12-12; Small fruit, vine climbing, 

except fuzzy kiwifruit, subgroup 13-07f; Tree nut group 14-12; Fruiting vegetable group 8-10; 

Citrus fruit group 10-10; Low growing berry subgroup 13-07G; Pome fruit group 11-10; bean; 

and various tropical fruit commodities) were assessed in a memo completed on 2/25/2016 

(D424010, L. Nollen, 2/25/2016).

9.1 Short-/Intermediate-Term Occupational Handler Risk

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event.

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposures are expected from the proposed 

uses. The quantitative exposure/risk assessment developed for occupational handlers is based on 

several scenarios which include mixing/loading/applying liquid formulations of abamectin. The 

use sites are summarized in Section 3.3. Methods of application include aerial, chemigation, 

groundboom, and/or handheld equipment. Flagging for aerial use is also a potential source of 

worker exposure. For these uses, both short- and intermediate-term exposures are expected from 

occupational use. Since the PODs for short- and intermediate-term exposure are the same, the 

assumptions and risk calculations are protective of both durations. Refer to Tables G.1 and G.2

in Appendix G for a detailed list of each scenario.

The results of the occupational handler exposure and risk assessment associated with PP#s 

3E8175 and 3F8184 indicate that short-/intermediate-term combined (dermal + inhalation) risk 

estimates are not of concern at baseline mitigation without personal protective equipment (PPE). 

The combined MOEs ranged from 360 to 25,000. 

The results of the occupational handler assessment associated with PP# 4E8309 indicate that 

short-/intermediate-term combined risk estimates are not of concern with a single layer of 

clothing, no respirator, and the PPE of gloves, which are required for all occupational users. 

Short- /intermediate-term combined dermal and inhalation MOEs ranged from 150 to 97,000.
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The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for human 

flaggers where appropriate, agricultural aviation has changed dramatically over the past two 

decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily 

from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide 

applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent 

(2012) NAAA survey. The Agency will continue to monitor all available information sources to 

best assess and characterize the exposure potential for human flaggers in agricultural aerial 

applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for 

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 

pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are no risk estimates of concern for applicators.

9.2 Short-/Intermediate-Term Post-Application Exposures and Risks

9.2.1 Short-/Intermediate-Term Post-Application Dermal Exposures and Risks

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational post-application exposures are expected from the 

proposed uses. Agricultural workers and golf course maintenance workers performing typical 

post-application activities may have dermal exposure to abamectin residues.

Quantitative occupational post-application exposure and risk assessments indicate that short- and 

intermediate-term dermal risk estimates are not of concern at baseline mitigation without PPE on 

Day 0 (12 hours following application) for all proposed uses. Short-/intermediate-term postapplication dermal MOEs ranged from 3,700 to 5,400 for the uses associated with PP#s 3E8175 

and 3F8184; MOEs ranged from 240 to 67,000 for PP# 4E8309. Based on the Agency's current 

practices, a quantitative non-cancer occupational post-application inhalation exposure 

assessment was not performed for abamectin at this time. The short- and intermediate-term postapplication exposure scenarios associated with the newly proposed uses are summarized in 

Tables G.3 and G.4 in Appendix G.
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Guideline 875.2100 - Dislodgeable Foliar Residue (DFR):

In accordance with 40CFR158, DFR data are required for all occupational (e.g., crop, nursery, 

greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own 

farms, retail tree farms) uses that could result in post-application exposure to foliage. Chemicalspecific DFR studies are currently available for abamectin. Studies have been submitted for 

citrus, as well as greenhouse and field-grown ornamentals. These data are currently under review 

by the Agency; however, the initial review of these studies show that the default values described 

above are likely to be more conservative than the values obtained from the submitted studies. 

Once the Agency has completed the review of each of these DFR studies, results will be 

considered in future assessments of post-application exposure in order to estimate chemicalspecific post-application exposure to foliage treated with abamectin. Therefore, EPA used the 

default value of 25%. 

Guideline 875.2100 - Turf Transferable Residues (TTR):

Since the estimated occupational post-application exposure for golf courses using default TTR 

values for abamectin is minimal in comparison to the LOC (i.e. the calculated MOE is greater 

than 10 times higher than the LOC (MOE = 8,700 compared to the LOC of 100); EPA is waiving 

the 40 CFR TTR data requirement. In this instance, it is unlikely that chemical-specific TTR data 

would be needed to further refine exposure assessments or would add appreciably to our general 

understanding of the availability of turf transferable pesticide residues.

Restricted Entry Interval: 

Abamectin is classified as Toxicity Category III via the dermal route, IV for eye irritation, III for 

skin irritation, and it is not a sensitizer. Typically, the REI specified on the proposed label is 

based on the acute toxicity of the active ingredient. Under 40 CFR 156.208 (c) (2) (iii), active 

ingredients classified as Acute III or IV for acute dermal, eye irritation, and primary skin 

irritation are assigned a minimum of 12 hours for the REI. This is the REI listed on the proposed 

labels, with the exception of activities associated with grapes (grape girdling, cane turning and 

tying in grapes), which have a 4-day REI restriction. These REIs are considered protective of 

post-application exposure to abamectin. 

9.2.2 Short-/Intermediate-Term Post-Application Inhalation Exposures and Risks

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency has 

evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent 

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the Agency will utilize this analysis to determine 

if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is 

required for abamectin.
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In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the Agency's risk assessments.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

10.0 References

(Refer to Appendix B for toxicology literature references.)

D. Atwood, 07/23/2014, DP Nos. 420312 and 420218, Percent Crop Treated for Abamectin 

(122804) on IR4 Proposed New Use on Caneberries and New Foliar Use on Soybeans 

and Sweet Corn.

G. Orrick, 05/15/2014, DP No. D412861, Abamectin: Drinking Water Exposure Assessment for 

Proposed New Uses on Soybeans, Sweet Corn, Caneberries (Crop Group 13-07A), and 

Golf Course Tees, Greens, and Fairways.

J. Alsadek, 07/01/2015, No DP Number, Updated Screening Level Usage Analysis (SLUA) 

Report for Abamectin, PC Code (122804)

J. Becker, 10/7/2014, DP No. 413125, Upper Bound Estimate of the Likelihood of Insecticide 

Residues on Food Resulting from Treatment in Food Handling Establishments.

K. Rickard, 01/30/2013, TXR0056509, Abamectin: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting of November 8, 2012: Recommendations on the 

Requirement of a Subchronic Inhalation Study and Dermal Toxicity Study. 

K. Rickard, 04/14/2016, DP Nos. 424009 and D421348, Abamectin: PP# 4E8309, 3E8175, and 

3F8184 Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and 

Risk Assessments for Section 3 Registration Actions for Four Separate New Use Actions 

and Tolerance Petitions: (1) New Uses on Bean, Papaya, Star Apple, Black Sapote, 

Sapodilla, Canistel, Mamey Sapote, Guava, Feijoa, Jaboticaba, Wax Jambu, Starfruit, 

Passionfruit, Acerola, Lychee, Longan, Spanish Lime, Rambutan, Pulasan, Pineapple;

Onion, Green, Subgroup 3-07B; Fruit, Pome, Group 11-10; Fruit, Small Vine Climbing, 

except Fuzzy Kiwifruit, Subgroup 13-07F; Berry, Low Growing, Subgroup 13-07G; and 

Conversion of Existing Crop Groups to Vegetable, Fruiting, Group 8-10 (and Addition of 

Greenhouse-grown Tomato); Fruit, Citrus, Group 10-10; Fruit, Stone, Group 12-12; and 

Nut, Tree, Group 14-12. (2) New Uses on Caneberry Subgroup 13-07A. (3) Sweet Corn 

and Soybeans. And (4) Cattle Ear Tag on Lactating Cattle.
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L. Nollen, 02/25/2016, DP No. 424010, Abamectin. Occupational and Residential Exposure 

Assessment for a Proposed Use on Green Onion Subgroup 3-07B; Stone Fruit Group 12-

12; Small Fruit, Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13-07F; Tree Nut 

Group 14-12; Fruiting Vegetable Group 8-10; Citrus Fruit Group 10-10; Low Growing 

Berry Subgroup 13-07G; Pome Fruit Group 11-10; Bean; and Various Tropical Fruit 

Commodities.

N. Dodd, 12/20/2012, DP No. D402677 and D405843, Abamectin. Human Health Risk 

Assessment for Uses of the SC Formulation on Cotton and Strawberry.

N. Dodd, 04/12/2013, DP No. D402151, Emamectin Benzoate. Human Health Risk 

Assessment for a Proposed Tolerance on Imported Wine Grapes. 

N. Dodd, 12/23/2015, DP No. D430706, Emamectin Benzoate: Acute and Chronic Aggregate 

Dietary (Food and Drinking Water) Exposure and Risk Assessments using Updated 

Percent Crop Treated. 

N. Dodd, 03/17/2016, DP No. D410993, Abamectin. Review of a Section 3 Registration 

Request for Ear Tag Use on Lactating Dairy Cattle. Summary of Analytical Chemistry 

and Residue Data.

N. Dodd, 03/17/2016, DP No. D412860, Abamectin. Petition for the Establishment of a 

Permanent Tolerance and Registration for Use on the Caneberry Subgroup 13-07A. 

Summary of Analytical Chemistry and Residue Data.

N. Dodd, 03/17/2016, DP No. D414022, Abamectin. Petition for the Establishment of 

Permanent Tolerances and Registration for Use on Sweet Corn and Soybeans. Summary 

of Analytical Chemistry and Residue Data. 

N. Dodd, 03/17/2016, DP No. D24008, Abamectin. Petition for the Establishment of Permanent 

Tolerances and Registration for New Uses on Bean, Various Tropical Fruits, Onion, 

Green, Subgroup 3-07B; Fruit, Pome, Group 11-10; Fruit, Small Vine Climbing, except 

Fuzzy Kiwifruit, Subgroup 13-07F; Berry, Low Growing, Subgroup 13-07G; and 

Conversion of Existing Crop Groups to Vegetable, Fruiting, Group 8-10 (and Addition of 

Greenhouse-grown Tomato); Fruit, Citrus, Group 10-10; Fruit, Stone, Group 12-12; and 

Nut, Tree, Group 14-12. Summary of Analytical Chemistry and Residue Data.

N. Keller, 12/18/2014, DP No. 414874, Abamectin. Occupational Exposure and Risk 

Assessment for the Proposed Agricultural Uses on Caneberries (Crop Subgroup 13-07A), 

Corn, and Soybeans; and Turf Use on Golf Courses (Greens, Tees, and Fairways).

U. Habiba, 08/15/2014, TXR0056775, Abamectin: Immunotoxicity Study (870.7800) Waiver 

Decision.
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USEPA, 2016, Pesticide Cumulative Risk Assessment: Framework for Screening Analysis 

Purpose.
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Appendix A. Abamectin Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food use for abamectin are in Table 1. Use of the new guideline numbers 

does not imply that the new (1998) guideline protocols were used.

Table A.1. Toxicology Data Requirements for Abamectin

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Acute Eye Irritation.......................................................

870.2500 Acute Dermal Irritation .................................................

870.2600 Skin Sensitization..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 90-Day Oral Toxicity in Rodents..................................

870.3150 90-Day Oral Toxicity in Nonrodents.............................

870.3200 21/28-Day Dermal Toxicity ..........................................

870.3250 90-Day Dermal Toxicity ...............................................

870.3465 90-Day Inhalation Toxicity ...........................................

yes

yes

yes

CR

CR

yes

yes

waiveda

-

yes

870.3700a Prenatal Developmental Toxicity (rodent) ....................

870.3700b Prenatal Developmental Toxicity (nonrodent) ..............

870.3800 Reproduction and Fertility Effects ................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Carcinogenicity (rat)......................................................

870.4200b Carcinogenicity (mouse) ...............................................

870.4300 Combined Chronic Toxicity/Carcinogenicity ...............

yes

no

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Bacterial Reverse Mutation Test..........

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test..

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6200a Acute Neurotoxicity Screening Battery (rat).................

870.6200b 90-Day Neurotoxicity Screening Battery (rat) ..............

870.6300 Developmental Neurotoxicity .......................................

yes

yes

yes

yes

yes

yes

870.7485 Metabolism and Pharmacokinetics................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

CR

Yes

yes

yes

waivedb

 a HASPOC Report: TXR 0056509, 01/30/2013. b HASPOC Report: : TXR 0056687, 01/07/2013 
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A.2 Data Demonstrating the Sensitivity of Beagle Dogs to the Effects of Abamectin and 

Emamectin

To illustrate the order of sensitivity to the effects of abamectin and emamectin in test animals 

that have fully functioning P-gp, the results of the subchronic (90-day) oral toxicity studies on 

emamectin with rats, CD-1 mice, and dogs were used for comparison. The data indicate that the 

effects produced in the dogs are qualitatively more severe and have a substantially lower LOAEL 

relative to those produced in the rats and CD-1 mice, as shown in the table below. Similar data 

on abamectin also demonstrate this order of sensitivity.

Table A.2. Comparison of the results of subchronic (90-day) oral toxicity studies on emamectin 

Test 

species

NOAEL 

(mg/kg/day)

LOAEL Effects seen at LOAEL

Beagle 

dogs

0.25 0.50 Skeletal muscle atrophy and white matter multifocal degeneration in the 

brains of both sexes and white matter multifocal degeneration in the spinal 

cords of males.

Rats 2.5 5 Tremors, hindlimb splaying, urogenital staining, histological changes in 

brain and spinal cord, sciatic and optic nerves and skeletal muscles in 

males, emaciation, reduced body weight and reduced food consumption in 

both sexes, and moribundity.

CD-1 

mice

5.4 15.0 Mean body weight decrease 
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A.3 Toxicity Profiles

Table A.3.1. Acute Toxicity Profile of Abamectin Technical

Guideline No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral - rat 

(sesame oil vehicle)

006894 LD50 = 13.6 mg/kg I

870.1100 Acute Oral - rat

(methyl cellulose vehicle)

45607202 LD50=214-232 mg/kg II

870.1200 Acute Dermal - rabbit 00255978 LD50 = 2000 mg/kg III

870.1300 Acute Inhalation - rat 45623501 LC50 =<0.21 mg/L (nose only) I

870.2400 Primary Eye Irritation 45063501 not an irritant IV

870.2500 Primary Skin Irritation 41123904 slight irritation III

870.2600 Dermal Sensitization 00139564 negative in Buehler Negative

870.6200a Acute Neurotoxicity none none none

Table A.3.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.3100

Subchronic feeding 

study-rats

00131081 (1982)

Acceptable/Nonguideline

0, 0.10, 0.20, 0.40 

mg/kg/day

NOAEL > 0.40 mg/kg/day

LOAEL = not established

870.3150

Subchronic toxicity

Dogs (18 week gavage 

study)

00131082 (1982)

Acceptable/Guideline

0, 0.25, 0.5, 2.0, 8.0 

mg/kg/day

NOAEL = 0.25 mg/kg/day

LOAEL = 0.50 mg/kg/day based on body tremors, one death, 

liver pathology, decreased body weight. Mydriasis was seen 

during week one in one dog.

870.3150

12-Week dose range 

finding study-dogs 

(feeding) 

00164152 (1982)

0.25, 0.50, 1.0, and 

4.0/2.0 mg/kg/day 

(during week 4, 4.0 

mg/kg/day was reduced 

to 2.0 mg/kg/day due to 

tremor, weakness, 

incoordination, and 

disorientation) 

The report stated that mydriasis was seen in 1.0 and 4.0 

mg/kg/day dogs during week 1.The effect was not seen at 

each examination day for any dog, but it was generally noted 

from 1 to 5 times a week. However, mydriasis was never 

noted at 0.5 and 0.25 mg/kg/day. 

870-3465

30-Day inhalation 

toxicity rats 

46921502 (2006)

0, 0.0001, 0.0005, and 

0.0025 mg/L

46921501 (5 day 

preliminary study; 2006)

No effect was found at the highest concentration tested.

NOAEL ≥ 0.0025 mg/L 

(Equivalent to 0.568 mg/kg)
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Table A.3.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.3200

21/28-Day dermal 

toxicity

Study not available. Study requirement was waived due to very low dermal 

absorption (<1%) (HASPOC Report: TXR 0056509, 

01/30/2013).

870.3465

30-Day inhalation tox.-

rats

46921502 (2006)

Acceptable/Guideline

NOAEL = >2.5 μg/L (0.0025 mg/L) (HDT) (≈0.68 

mg/kg/day)

870.4300a

Combined Chronic 

toxicity/carcinogenicityrats

40069601, 40375511, 

40517801 (1985)

Acceptable/Guideline 

0, 0.75, 1.5, 2.0 

mg/kg/day

NOAEL = 1.5 mg/kg/day

LOAEL = 2.0 mg/kg/day based on tremors

No evidence of carcinogenicity

870.4100b

Chronic toxicity dogs 

(dietary)

40375510 (1987)

Acceptable/Guideline

0, 0.25, 0.5, 1.0 

mg/kg/day

NOAEL = 0.25 mg/kg/day

LOAEL = 0.5 mg/kg/day based on mydriasis during week 

one, death at 1.0 mg/kg/day

870.4300b

Combined Chronic 

toxicity/Carcinogenicitymice

40069602, 40375512, 

40517801 (1985)

Acceptable/Guideline

0, 2, 4, 8 mg/kg/day

NOAEL = 4.0 mg/kg/day

LOAEL = 8.0 mg/kg/day based on increased mortality in 

males, tremors, body weight decreases in females, dermatitis 

in males, extramedullary hematopoiesis in spleen of males

No evidence of carcinogenicity

870.3700a

Prenatal developmental

in rodents-rats

Accession: 00130819 

(1982)

Acceptable/guideline

0, 0.4, 0.8, 1.6 

mg/kg/day

Maternal NOAEL > 1.6 mg/kg/day

Maternal LOAEL = not established

Developmental NOAEL > 1.6 mg/kg/day

LOAEL = not established

870.3700a

Prenatal developmental 

in rodents-CD-1 mouse

44179901 (1999)

Acceptable/NonGuideline

0, 0.75, 1.5, 3.0 

mg/kg/day

Maternal NOAEL = 1.5 mg/kg/day

Maternal LOAEL = 3.0 mg/kg/day based on hind limb splay

Developmental NOAEL > 3.0 mg/kg/day. No adverse 

developmental effects were seen at the doses tested.

870.3700b

Prenatal developmental

in nonrodents-rabbits

Accession: 00130819 

(1982)

Acceptable./Guideline

0, 0.5, 1.0, 2.0 

mg/kg/day 

Maternal NOAEL = 1.0 mg/kg/day

Maternal LOAEL = 2.0 mg/kg/day based on decreased body 

weight, food consumption and water consumption 

Developmental NOAEL = 1.0 mg/kg/day

LOAEL = 2.0 mg/kg/day based on cleft palate, clubbed foot, 

delayed ossification of sternebrae, metacarpals, phalanges 

870.3800a

2-Generation 

Reproduction and 

fertility effects-rat

00164151 (1984)

Acceptable/Guideline

0, 0.05, 0.12, 0.40 

mg/kg/day

Parental/Systemic NOAEL = 0.40 mg/kg/day

LOAEL =not established

Reproductive NOAEL = 0.40 mg/kg/day

LOAEL = not established

Offspring NOAEL = 0.12 mg/kg/day

LOAEL = 0.40 mg/kg/day based on increased retinal folds, 

increased dead pups at birth, decreased viability and lactation 

indices, decreased pup body weight
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Table A.3.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.3800c

1-Generation 

Reproduction and 

fertility effects- rat

40713404 (1988)

Acceptable/Nonguideline

0, 0.1, 0.2, 0.4 

mg/kg/day

with delta-8,9 isomer

0, 0.06, 0.12, 0.40 

mg/kg/day

Parental/Systemic NOAEL = 0.4 mg/kg/day

LOAEL = not established

Reproductive NOAEL = 0.4 mg/kg/day

LOAEL = not established

Offspring NOAEL =0.4 mg/kg/day

LOAEL = not established

Gene Mutation

870.5100

Ames/Salmonella

E.coli/mammalian gene 

mutation assay

Accession: 246894, 

265568, 265569 (1986)

Acceptable/Guideline

Three studies: (1) 0, 3, 

10, 30, 100, 1000 

ug/plate, (2) 0, 100, 300, 

1000, 3000, 10,000 

ug/plate both with and 

without S-9, (3) doses 

not specified.

Negative both with and without S-9

870-6100 

Acute neurotoxicity in 

rats (gavage)

46959202 (2006)

Acceptable/guideline

0.5, 1.5, and 6.0 mg/kg

NOAEL = 0.5 mg/kg/day

LOAEL = 1.5 mg/kg/day based on reduced splay reflex in 

males and females. At high dose, decreased motor activity, 

reduced splay reflex, & tip toe gait were seen. No death or 

histopathological changes in nervous system were found.

870-6200

Subchronic 

neurotoxicity in rats 

(gavage)

46959201 (2006)

Acceptable/guideline

0.4, 1.6, and 4.0 

mg/kg/day

NOAEL = 1.6 mg/kg/day

LOAEL = 4.0 mg/kg/day based on upward curvature of the 

spine, tip-toe gate, decreased fore- and hind-limb grip 

strength. Decreased body was also seen. This dose group was 

terminated prematurely at week 7. 

870-630

Developmental 

neurotoxicity study in 

rats 

46727403, 46727402, 

46727401 (2005)

Acceptable/nonguideline

0.12, 0.20, and 0.40 

mg/kg/day. Pups were 

not directly dose.

Maternal NOAEL = 0.4 mg/kg/day (HDT)

Offspring NOAEL = 0.2 mg/kg/day.

Offspring LOAEL= 0.4 mg/kg/day based on decreased body 

weight in males and females.

870-6200

Developmental 

neurotoxicity study in 

rats 

47116201 (2007)

Acceptable/nonguideline

0.12, 0.20, and 0.40 

mg/kg/day. Pups were 

not directly dosed. 

Maternal NOAEL = 0.4 mg/kg/day (HDT)

Offspring NOAEL =0.12 mg/kg/day.

Offspring LOAEL = 0.2 mg/kg/day based on slight but 

statistically significant decrease in pup body weight. 

Gene Mutation

870.5100

Ames/Salmonella

E.coli/mammalian gene 

mutation assay

40713402 (1988)

Acceptable/Guideline

doses not specified up to 

3000 ug/plate both with 

and without S-9 using 

delta-8,9 isomer

negative both with and without S-9 up to 3000 ug/plate
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table A.3.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

Gene Mutation

870.5100

Ames/Salmonella

E.coli/mammalian gene 

mutation assay

40713405 (1988)

Acceptable/Guideline

doses up to 10,000 

ug/plate both with and 

without S-9 using polar 

degradates

negative both with and without S-9

Gene Mutation

870.5300

CHO/HGPRT

Forward Mutation Assay

265570 (1986)

Acceptable/Guideline

both with and without S9

Negative

Gene Mutation

870.5300

Mammalian cells in 

culture in V79 cells

MRID 00139572 (1983)

Acceptable/Guideline

Not mutagenic for V79 cells in absence of S-9, but in the 

presence of S-9 appeared to have a mutagenic potential, 

provided the test cells had an appropriate level of sensitivity

Cytogenetics 

870.5395

in vivo micronucleus 

assay -male mice

MRID 00139574 

(1983)

Acceptable/nonGuideline

0, 1.2, 12.0 mg/kg i.p.

No chromosomal aberrations in male mice, but females not 

tested

Other Effects 

870.5550 

MRID 00139573 

(1983)

Acceptable

0.3 and 0.6 mM

single strand DNA breaks at 0.3 and 0.6 mM in rat 

hepatocytes in vitro, but negative when hepatocytes from rat 

at LD50 dose level was used

Metabolism –CF 1 mice 

Wild type for P-gp (+/+) 

and mutant (-/-) 

49009003 (2008)

(

14C- abamectin) 0.1 & 

0.2 mg/kg in sesame oil 

Abamectin was rapidly absorbed; Tmax was approximately 4 

hours for blood and plasma. Within 48 hours after 

administration greater than 90% of the administered dose was 

eliminated via fecal route (primarily route). 

Metabolism Accession: 252114

Unacceptable/NonGuideline

69-82% of label is excreted in feces by day 7; T1⁄2=1.2 days. 

The reliability of these data is questionable.

Metabolism MRID 00145888

(1985)

Non-guideline

Avermectin B1a did not bioaccumulate in rat tissues. Half-life 

slightly longer in females than in males for several tissues.

Metabolism MRID 00145907

(1985)

Non-guideline

The metabolism of avermectin B1 in rats results in the 

formation of 24-OH-Me-B1a and accounts for most of the 

radiolabeled residues. Avermectin B1a does not 

bioaccumulate.

870.7600

Dermal penetration

Accession: 265590 

(1986)

Acceptable/

Non-guideline in 

Monkeys

The result showed the dermal absorption to be <1% of the 

applied dose. For risk assessment, a dermal penetration factor 

of 1% was recommended.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table A.3.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses

Results

870.7800

Immunotoxicity

This study is waived (HASPOC Report: TXR 0056687, 01/07/2013)

Table A.3.3 Toxicity Profile of Abamectin Technical - for CF1 Mice

Guideline No./ Study 

Type

MRID No. / Classification /Doses Results

870.3700a

Prenatal 

developmental in 

rodents- CF1 mouse

44160501 (1996)

Acceptable/Non-Guideline

0, 1.5 mg/kg/day on gestation days 

(GD) 6-15 to females which were 

heterozygous (+/-) and homozygous 

(-/-, +/+) for p-glycoprotein and then 

mated to heterozygous and 

homozygous males 

Maternal NOAEL = 1.5 mg/kg/day

Maternal LOAEL = not established

97% of (-,-) fetuses, 40% of (+,-) fetuses, and 0% of (+,+) 

fetuses had cleft palate. It was determined that the 

observed increase in cleft palate in CF-1 mice following 

treatment appears to be a consequence of fetal Pglycoprotein genotype.

870.3700a

Prenatal 

developmental

in rodents-CF1 mouse

00096446 (1985)

0, 0.025, 0.050, 0.075, 0.10 

mg/kg/day (GD 6-15)

Dose range finding study 

(Study #: TT 77-17-1)

Maternal NOAEL = 0.05 mg/kg/day

Maternal LOAEL = 0.075 mg/kg/day

Based on one mouse was sacrificed in comatose state 

after 4 dosing. After 3 dosing, one mouse was dead at 0.1 

mg/kg/day group. Before death or moribund sacrifice, 

tremors and coma were observed.

870.3700a

Prenatal 

developmental

in rodents-CF1 mouse

00164020 (1985) (Main study)

0, 0.025, 0.050, 0.075, 0.10 

mg/kg/day (GD 6-15)

( Study #: TT 84-721-0)

Maternal NOAEL = 0.05 mg/kg/day

Maternal LOAEL = 0.075 mg/kg/day

Based on 2 deaths (one occurred on day 11 and the other 

on day 12). Before death, tremors occurred.

Developmental NOAEL = 0.1 mg/kg/day (HDT)

870.3700a

Prenatal 

developmental

in rodents-CF1 mouse

Accession: 265564 (1986)

Acceptable/Guideline

0, 1.5, 3.0, 6.25, 12.5, 25, 50 

mg/kg/day with delta-8,9 isomer

Maternal NOAEL < 1.5 mg/kg/day

Maternal LOAEL = 1.5 mg/kg/day (mortality)

Developmental NOAEL < 1.5 mg/kg/day

LOAEL = 1.5 mg/kg/day based on increased cleft palate

870.3700a

Prenatal 

developmental in 

rodents-CF1 mouse

Accession: 265564 (1986)

Acceptable/Guideline

0, 0.03, 0.1, 0.5 mg/kg/day with 

delta-8,9 isomer

Maternal NOAEL = 0.1 mg/kg/day

Maternal LOAEL = 0.5 mg/kg/day (mortality)

Developmental NOAEL = 0.03 mg/kg/day

LOAEL = 0.1 mg/kg/day based on increased cleft palate

870.3700a

Prenatal 

developmental in 

rodents-CF1 mouse

Accession: 265564 (1985)

Acceptable/Guideline

0, 0.05, 0.1, 0.5, 1.0 mg/kg/day with 

deta-8,9 isomer

Maternal NOAEL = 0.1 mg/kg/day

Maternal LOAEL = 0.5 mg/kg/day (mortality)

Developmental NOAEL = 0.05 mg/kg/day

LOAEL = 0.1 mg/kg/day based on increased cleft palate

870.3700a

Prenatal 

developmental in 

rodents-CF1 mouse

Accession: 40912701 (1988)

Acceptable/Guideline

0, 0.25, 0.50, 1.0 mg/kg/day with 

citrus derived polar degradates

Maternal NOAEL > 1.0 mg/kg/day

Maternal LOAEL = not established

Developmental NOAEL > 1.0 mg/kg/day

LOAEL =not established
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Table A.3.3 Toxicity Profile of Abamectin Technical - for CF1 Mice

Guideline No./ Study 

Type

MRID No. / Classification /Doses Results

870.3700a

Prenatal 

developmental in 

rodents-CF1 mouse

Accession: 073759, 073761 (1984)

Acceptable/Non-Guideline

0, 0.1, 0.3, 0.6 mg/kg/day

Maternal NOAEL = 0.1 mg/kg/day

Maternal LOAEL = 0.3 mg/kg/day (mortality, tremors)

870.3700a

Prenatal 

developmental in 

rodents-CF1 mouse

00096446 (1986)

Acceptable/Guideline

0, 0.1, 0.2, 0.4, 0.8 mg/kg/day

Maternal NOAEL < 0.1 mg/kg/day

Maternal LOAEL = 0.1 mg/kg/day (mortality)

Developmental NOAEL = 0.2 mg/kg/day

LOAEL = 0.4 mg/kg/day based on increased cleft palate

870.3700a

Prenatal 

developmental in 

rodents-CF1 mouse

Accession: 265564 (1985)

Acceptable/Guideline

0, 0.01, 0.03, 0.06 mg/kg/day with 

delta-8,9 isomer

Maternal NOAEL > 0.06 mg/kg/day

Maternal LOAEL = not established

Developmental NOAEL > 0.06 mg/kg/day

LOAEL = not established

870.3700a

Prenatal 

developmental in 

rodents-CF1 mouse

Accession: 40713406 (1986)

Acceptable/Guideline

0, 0.25, 0.50, 1.0 mg/kg/day with 

polar degradates of abamectin

Maternal NOAEL > 1.0 mg/kg/day

Maternal LOAEL = not established

Developmental NOAEL > 1.0 mg/kg/day

LOAEL = not established
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Appendix B. Toxicology Literature References

Daood., MJ, Tsai, C., Ahdab-Barmada, M., and Watchko, JF (2008). ABC transporter 

(P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing Human 

CNS. Neuropediatrics. 2008 August ; 39(4) : 211.

Dawson, GR, Wafford, KA, Smith, A, Marshall, GR, Bayley, PJ, Schaeffer, JM, Meinke, PT, 

and McKernan, RM. (2000) Anticonvulsant and adverse effects of avermectin analogs in 

mice 

are mediated through the gama-aminobutyric acid (A) receptor. J. Pharmacol. Exp. Ther. 

295: 1051-1060.

Huang, J, Casida, JE. (1997) Avermectin B1abinds to high- and low-affinity sites with dual 

effects on the gama-aminobutyric acid-gated chloride channel of cultured cerebellar 

granule neurons. J. Pharmacol. Exp. Ther. 281: 261-266.

Kerr, DI and Ong, J. (1986) Gama-aminobutyric acid-dependent motility induced by avermectin 

B1a in the isolated intestine of the guinea pigs. Neurosci. Lett. 65: 7-10.

Lankas, GR, Cartwright, ME, and Umbenhauer, D. (1997) P-Glycoprotein deficiency in a 

subpopulation of CF-1 mice enhances avermectin-induced neurotoxicity. Toxicol. and 

Appl. Pharmacol. 143: 357-365.

Marzolini, C., Paus, E., Buclin, T., and Kim, RB (2004) Polymorphism In human MDR1 (Pglycoprotein): Recent advances and clinical relevance. Clin. Pharmacol. and Ther. 

75: 13-33.

Macdonald, N. and Gledhill, A. (2007). Potential impact of ABCB1 (p-glycoprotein) 

polymorphisms on avermectin toxicity in human. Arch Toxicol (2007) 81:553-563.

Matsukoa, Y., Okazaki, M., Kitamura, Y., and Taniguchi, T. (1999). Developmental expression 

of P-glycoprotein (multidrug resistance gene product) in the rat brain. Journal of 

Neurobiology, 39(3), 383-392.

Meister, B. (2007) Neurotransmitters in key neurons of the hypothalamus that regulate feeding 

behavior and body weight. Physiol. Behav. 92: 263-271.

Nguyen, L., Rigo, JM, Rocher, V., Belachew, S., Malgrange, B., Rogister, B., Leprince, P., and 

Moonen G. (2001) Neurotransmitters as early signals for central nervous system 

development. Cell Tissue Res. 305: 187-202.

Pong, SS, DeHaven, R., and Wang, CC. (1982) A comparative study of avermectin B1a and other 

modulators of the gama-aminobutyric receptor- chloride ion channel complex. J. 

Neurosci. 2: 966-971.

Represa, A. and Ben-Ari, Y. (2005) Trophic actions of GABA on neuronal development. Trends 

Neurosci. 28: 278-283. 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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van Kalken, CK, Giaccone, G., van der Valk, P., Kuiper, CM, Hadisaputro, MMN, Bosma, SAA,

Scheper, RJ, Meijer, CJLM, and Pinedo, HM (1992). Multidrug resistance gene (Pglycoprotein) expression in the human fetus. American Journal of Pathology, vol 141 

No.5, November 1992.

Wang, CC and Pong, SS. (1982) Actions of avermectin B1a on GABA nerves. Prog. Clin. Biol. 

Res. 97: 373-395.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Appendix C. Abamectin Physical/Chemical Properties

Table C. Physicochemical Properties of the Technical Grade of Abamectin

Parameter Value Reference1

Molecular weight (g/mole) 873.11

Melting point/range (°C) 155-157°C Accession No. 260785

pH Not available

Density (g/cm3) 1.16 g/cm3 at 21°C Accession No. 260785

Water solubility (20°C)

< 0.01 mg/mL in distilled water

< 0.001 mg/mL in tap water 

< 0.001 mg/mL in buffer system pH 6, 7.4 

& 9.0

< 0.001 mg/mL in 0.9% NaCl

Accession No. 260785

Solvent solubility (20°C to 25°C)

> 3 mg/mL in ethanol; >2 mg/mL in 

isopropyl myristate, chloroform, 

dimethylacetamide, dimethylformamide, 

glycerol formal & polyethylene glycol 400.

Accession No. 260785

Vapor pressure (25°C) 1.5 x 10-9 hPa Accession No. 260785

Dissociation constant, pKa Not available

Octanol/water partition coefficient, 

Log(KOW) 9.9 x 10-3 Accession No. 260785

Aerobic soil metabolism half-life Not available DP No. D380524, G. 

Orrick, 1/31/11 1 Product Chemistry data were reviewed by Leung Cheng (Accession No. 260785, RCB No. 388, 5/1/1986).
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Appendix D. Review of Human Research for Abamectin

This abamectin risk assessment relies in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide or other chemical. These data, which include studies 

from the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural 

Handler Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force 

(ORETF) database, the Agricultural Reentry Task Force (ARTF) database; the Residential 

Standard Operating Procedures (SOPs: Lawns/Turf); and Registrant-submitted data, MRID 

#44339801, are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that 

review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics 

review may have included review by the Human Studies Review Board. Descriptions of data 

sources, as well as guidance on their use, can be found at the Agency website5

.

 5 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Appendix E. International Residue Limits Table for Abamectin

Table E.1. 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)

Plants: sum of 

avermectin B1a, 

avermectin B1b, 

8,9-Z-avermectin 

B1a and 8,9-Zavermectin B1b. 

Animal 

commodities: sum 

of avermectin

B1a and 8,9-Zavermectin B1a..

Animals: sum of 

avermectin

B1a and 8,9-Zavermectin B1a..

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

US Canada Mexico2 Codex3

Caneberry subgroup 13-07A 0.20 0.20 (pending)

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

Corn, sweet, forage 0.20

Corn, sweet, kernel plus cob with 

husks removed 0.01

Corn, sweet, stover 0.50

Goat, meat 0.02 0.01 (*)

Goat, meat byproducts 0.04 0.1 goat edible 

offal

Grain, aspirated grain fractions 0.40

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

Soybean, forage 0.30

Soybean, hay 1.0

Soybean, seed 0.01

Vegetable, fruiting, group 8-10 0.07 0.01 peppers, 

tomatoes

0.2 peppers chili, 

dried
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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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.

0.02 Peppers, 

sweet (including 

pimento or 

pimiento), tomato

Fruit, citrus, group 10-10 0.02 0.02 0.01 (*)

Fruit, small, vine climbing, except

fuzzy kiwifruit, subgroup 13-07F

0.02 0.02 grapes

Berry, low growing, subgroup 13-

07G

0.05 0.02 strawberries 0.02 strawberry

Fruit, stone, group 12-12 0.09

Fruit, pome, group 11-10 0.02 0.02 apples, pears 0.02 apple, pear

Nut, tree, group 14-12 0.01 0.005 almond 

nuts, black 

walnuts, English 

walnuts

0.01 (*) almonds, 

walnuts

Papaya 0.40

Star apple 0.40

Black sapote 0.40

Sapodilla 0.40

Canistel 0.40

Mamey sapote 0.40

Guava 0.015

Feijoa 0.015

Jaboticaba 0.015

Wax jambu 0.015

Starfruit 0.015

Passionfruit 0.015

Acerola 0.015

Lychee 0.01

Longan 0.01

Spanish lime 0.01

Rambutan 0.01

Pulasan 0.01

Pineapple 0.015

Bean 0.015

Onion, green, subgroup 3-07B 0.08

Completed: M. Negussie; 11/01/12, 9/19/13, and 10/302015
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Appendix F. Abamectin Field Trial Tables

Table F.1. Summary of Residue Data from Soybean and Sweet Corn (PP# 3F8184) and Caneberry (PP# 

3E8175) Field Trials with Abamectin 

Commodity Total 

Applic. 

Rate,

(lb ai/A)

PHI 

(days)

Residue Levels1,2

(ppm)

n2 Sample 

Min.

Sample 

Max.

LAFT3 HAFT3 Median Mean Std. 

Dev.

CANEBERRY Proposed Use = 0.056 lb ai/acre/season, 7-day PHI

Blackberry 0.056-

0.059

7 4 <0.0164 0.0632 <0.0171 0.0535 <0.0233 <0.029 0.017

Raspberry 0.055-

0.061

7 3 <0.0062 0.1215 <0.0067 0.1184 0.0084 0.045 0.064

Blackberry 

and 

Raspberry

0.055-

0.061

7 7 <0.0062 0.1215 <0.0067 0.1184 <0.0204 <0.0358 0.040

SOYBEAN Proposed Use = 0.038 lb ai/acre/season; 7-day PHI for forage and hay; 28-day PHI for seed

Soybean, 

forage

0.0776-

0.127

6-8 20 <0.0120 0.165 <0.0138 <0.158 0.037 0.059 0.047

Soybean, hay 0.0776-

0.127

6-8 20 <0.0420 0.741 <0.0448 0.607 0.200 0.240 0.174

Soybean, 

seed

0.0770-

0.127

27-29 20 <0.006 <0.006 <0.006 <0.006 <0.006 <0.006 N/A

SWEET CORN Proposed Use = 0.038 lb ai/acre/season, 7-day PHI 

Sweet corn, 

forage

0.0504-

0.0795

6-7 12 <0.0129 <0.115 <0.0146 <0.102 0.063 0.056 0.029

Sweet corn, 

K+CWHR

0.0504-

0.0795

6-7 12 <0.006 <0.006 <0.006 <0.006 0.006 0.006 N/A

Sweet corn, 

stover

0.0504-

0.0795

6-7 12 <0.0158 0.363 <0.0221 0.329 0.065 0.101 0.094

1 Combined residues of avermectin B1a, 8,9-Z avermectin B1a, and avermectin B1b 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. N/A = Not

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

Table F.2. Summary of Residue Data from Greenhouse Tomato, Green Onion, Guava, Lima Bean, Lychee, 

Papaya, Pineapple, and Snap Bean (PP# 4E8309) Trials with Abamectin

Commodity 

Total Application

Rate 

(lbs ai/A) 

PHI 

(days) n1

Abamectin Residues2 (ppm)

Min.3 Max.3 LAFT4 HAFT4 Median4 Mean4 SD4

GREENHOUSE-GROWN TOMATO Proposed Use = 0.056 lb ai/acre total application rate, 1-day PHI

Agri-Mek SC

Tomato fruit 0.0597-0.0625 1 4 0.00663 0.02706 0.00684 0.02476 0.01540 0.01560 0.007

3 4 0.00562 0.01971 0.00621 0.01699 0.01306 0.01233 0.004

Agri-Mek 0.15EC

Tomato fruit 0.0593-0.0626 1 4 0.00519 0.04491 0.00587 0.04120 0.01285 0.01819 0.014

3 4 0.00566 0.03372 0.00573 0.03248 0.01088 0.01499 0.010

GREEN ONION Proposed Use = 0.076 lb ai/acre total application rate, 7-day PHI

Green onion 0.079 – 0.082 6-8 5 <0.004 <0.0048 <0.004 <0.0046 <0.004 <0.004 0.00025
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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GUAVA Proposed Use = 0.070 lb ai/acre total application rate, 7-day PHI

Guava 0.073-0.074 8 3 <0.004 <0.0059 <0.004 <0.0050 0.0040 0.0043 0.0005

LIMA BEAN Proposed Use = 0.056 lb ai/acre total application rate, 7-day PHI

Lima bean 0.0551-0.05666 6-8 7 <0.004 <0.004 <0.004 <0.004 0.004 0.004 N/A5

LYCHEE Proposed Use = 0.046 lb ai/acre total application rate, 14-day PHI

Lychee 0.048-0.050 8-13 3 <0.002 0.0034 <0.002 <0.0027 0.0024 0.0024 0.0004

PAPAYA Proposed Use = 0.070 lb ai/acre total application rate, 3-day PHI

Papaya 0.074-0.082 3-5 3 <0.0047 0.164 <0.005

1

0.131 0.123 0.0863 0.0705

PINEAPPLE Proposed Use = 0.047 lb ai/acre total application rate, 16-week PHI

Pineapple 0.0465-0.0475 78-112 8 <0.004 <0.004 <0.004 <0.004 0.004 0.004 N/A5

0.231-0.238 98-108 3 <0.004 <0.004 <0.004 <0.004 0.004 0.004 N/A5

SNAP BEAN Proposed Use = 0.056 lb ai/acre total application rate, 7-day PHI

Snap bean 0.0378-0.09447 5-7 7 <0.004 <0.004 <0.004 <0.004 0.004 0.004 N/A5

1 n = number of trials.

2 Combined residues of abamectin:

Greenhouse-grown tomato, green onion, guava, and pineapple: Combined residues of avermectin B1a/8,9-Z avermectin B1a and 

avermectin B1b 

Papaya, lima bean and snap bean: Combined residues of avermectin B1a/8,9-Z avermectin B1a, and avermectin B1b/8,9-Z 

avermectin B1b.

Lychee: Combined residues of avermectin B1a/8,9-Z avermectin B1a. The B1b residue component was not monitored in this study. 3 Values based on total number of samples.

4 Values based on per-trial averages. LAFT = lowest average field trial, HAFT = highest average field trial, SD = standard 

deviation. For computation of the LAFT, HAFT, median, mean, and standard deviation, values < LOQ are assumed to be at the 

LOQ (0.002 ppm for greenhouse-grown tomatoes and lychee; 0.004 ppm for green onion, guava, lima bean, papaya, pineapple, 

and snap bean).

5 N/A = not applicable.

6 The lima bean trials included one SC trial at 0.0751 lb ai/A.

7 The snap bean trials targeted three applications, but the data reflect two to five applications; the number of applications 

depended on the rate of crop maturation.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Appendix G. Abamectin Occupational Exposure Tables

Table G.1. Occupational Handler Exposure and Risk Estimates for Proposed Abamectin Uses Associated 

with PP#s 3E8175 and 3F8184

Exposure 

Scenario

Crop 

/Target1

Unit Exposure2

Max

App 

Rate3

Area 

Treated/

Amount

Handled 

Daily4

Dose5 MOE6

Dermal Inhalation Dermal Inhalation Dermal Inhalation Total

μg/lb ai lb ai/A Acres mg/kg/day ST/IT LOC = 100

Mixer/Loader

Mixing/Loading 

Liquids for 

Aerial 

Application

Orchard

220 0.219

0.019

Typical 350 0.000183 0.0000183 1,400 14,000 1,300

Field 

Crops

HighAcreage 

Field 

Crops

1200 0.000628 0.0000624 400 4,000 360

Mixing/Loading 

Liquids for 

Airblast 

Application

Orchard 40 0.0000209 0.00000208 12,000 120,000 11,000

Mixing/Loading 

Liquids for 

Chemigation 

Application

Orchard

350 0.000183 0.0000183 1,400 14,000 1,300

Typical 

Field 

Crops

HighAcreage 

Field 

Crops

Mixing/Loading 

Liquids for 

Groundboom 

Application

Golf 

Courses

(fairways, 

tees, and 

greens)

0.069 40 0.0000759 0.00000755 3,300 33,000 3,000

Typical 

Field 

Crops

0.019

80 0.0000418 0.00000416 6,000 60,000 5,500

HighAcreage 

Field 

Crops

200 0.000105 0.0000104 2,400 24,000 2,200

Applicator

Applying 

Sprays for 

Aerial 

Application

Orchard

5 0.068 0.019

350 0.00000416 0.00000565 60,000 44,000 25,000 Typical 

Field 

Crops

HighAcreage 

Field 

Crops

1200 0.0000143 0.0000194 17,000 13,000 7,400
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Table G.1. Occupational Handler Exposure and Risk Estimates for Proposed Abamectin Uses Associated 

with PP#s 3E8175 and 3F8184

Exposure 

Scenario

Crop 

/Target1

Unit Exposure2

Max

App 

Rate3

Area 

Treated/

Amount

Handled 

Daily4

Dose5 MOE6

Dermal Inhalation Dermal Inhalation Dermal Inhalation Total

μg/lb ai lb ai/A Acres mg/kg/day ST/IT LOC = 100

Applying 

Sprays for 

Airblast 

Application

Orchard 1770 4.71 40 0.00000139 0.000000646 180,000 5,600 1,200

Applying 

Sprays for 

Groundboom 

Application

Golf 

Courses

(fairways, 

tees, and 

greens)

78.6 0.34

0.069 40 0.0000271 0.0000117 21,000 9,200 6,400

Typical 

Field 

Crops

0.019

80 0.0000149 0.00000646 39,000 17,000 12,000

HighAcreage 

Field 

Crops

200 0.0000374 0.0000161 16,000 6,700 4,700

Flagger

Flagging for 

Aerial 

Application

Orchard

11 0.35 0.019 350 0.00000915 0.0000291 27,000 8,600 6,500

Typical 

Field 

Crops

HighAcreage 

Field 

Crops

Mixer/Loader/Applicator

M/L/A Liquids 

for 

MechanicallyPressurized 

Handgun 

Sprayers

Golf 

Courses

(fairways, 

tees, and 

greens)

1,140 1.9 0.069 5

acres

0.0000491 0.00000820 5,100 30,000 4,400

Orchard

1,300 3.9 0.0019 1000

gallons 0.000309 0.0000926 810 2,700 620 Typical 

Field 

Crops

1 “Orchard” includes caneberries (crop subgroup 13-07A).

“Typical Field Crops” include sweet corn.

“High-Acreage Field Crops” include corn and soybeans.

2 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012); Level of mitigation = Baseline 

except for aerial applicator which includes engineering controls.

3 Based on the maximum application rates on the proposed labels (Reg. Nos. 100-898, -1154, -1350, -1351, -1408, -1439, RLNO, and -RLRN).

4 Exposure Science Advisory Council Policy #9.1.

5 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or 

Amount Handled Daily (A or gal/day) × DAF (1%) ÷ BW (80 kg).

Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or 

Amount Handled Daily (A or gal/day) ÷ BW (80 kg).

6 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). ST/IT Dermal NOAEL = 0.25 mg/kg/day.

Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST/IT Inhalation NOAEL = 0.25 mg/kg/day.

Total MOE = NOAEL (mg/kg/day) ÷ (Dermal Dose + Inhalation Dose). ST/IT Combined Dermal/Inhalation NOAEL = 0.25 mg/kg/day.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table G.2. Occupational Handler Non-Cancer Exposure and Risk Estimates for Abamectin Associated with 

PP# 4E8309

Exposure 

Scenario

Crop or 

Target1 LOC

Unit Exposure2

Max

App. 

Rate3

Area 

Treated 

Amount

Handled 

Daily4

Dermal Inhalation

Total 

MOE6

Dermal Inhalation Dose

(mg/kg/ 

day)5

MOE6

Dose 

(mg/kg/

day)5

MOE6

(μg/lb ai)

Mixer/Loader

Mixing Loading 

Liquids for 

Aerial 

Application

Orchard/

Vineyard

100 37.6 0.219

0.023 350 0.000038 6600 0.000022 11,000 4100

Field 

crop, 

typical

0.023 350 0.000038 6600 0.000022 11,000 4100

Field 

crop, 

highacreage

0.019 1200 0.00011 2300 0.000062 4,000 1500

Mixing Loading 

Liquids for 

Airblast 

Application

Orchard/

Vineyard 0.023 40 0.0000043 58,000 0.0000025 100,000 37,000

Mixing Loading 

Liquids for 

Groundboom 

Application

Orchard/

Vineyard 0.023 40 0.0000043 58,000 0.0000025 100,000 37,000

Field 

crop, 

typical

0.023 80 0.0000087 29,000 0.0000050 50,000 18,000

Field 

crop,

highacreage

0.019 200 0.000018 14,000 0.000010 24,000 8800

Applicator

Applying 

Sprays for 

Aerial 

Application

Orchard/

Vineyard

100

2.08

0.0049

0.023 350 0.0000021 120,000 0.00000049 510,000 97,000 Field 

crop, 

typical

Field 

crop, 

highacreage

0.19 0.019 1200 0.0000059 42,000 0.0000014 180,000 34,000

Applying 

Sprays for 

Airblast 

Application

Orchard/

Vineyard 1590 4.71 0.023 40 0.00018 1400 0.000054 4,600 1100

Applying 

Sprays for 

Groundboom 

Orchard/

Vineyard 16.1 0.34

0.023 40 0.0000019 140,000 0.0000039 64,000 44,000

Field 0.023 80 0.0000037 68,000 0.0000078 32,000 22,000
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Table G.2. Occupational Handler Non-Cancer Exposure and Risk Estimates for Abamectin Associated with 

PP# 4E8309

Exposure 

Scenario

Crop or 

Target1 LOC

Unit Exposure2

Max

App. 

Rate3

Area 

Treated 

Amount

Handled 

Daily4

Dermal Inhalation

Total 

MOE6

Dermal Inhalation Dose

(mg/kg/ 

day)5

MOE6

Dose 

(mg/kg/

day)5

MOE6

(μg/lb ai)

Application crop, 

typical

Field 

crop, 

highacreage

0.019 200 0.0000077 33,000 0.000016 16,000 11,000

Flagger

Flagging for 

Aerial 

Application

Orchard/

Vineyard

100 11 0.35

0.023

350

0.000012 21,000 0.000035 7100 5300

Field 

crop, 

typical

0.023 0.000012 21,000 0.000035 7100 5300

Field 

crop, 

highacreage

0.019 0.000010 25,000 0.000029 8600 6400

Mixer/Loader/Applicator

M/L/A Liquids 

for 

MechanicallyPressurized 

Handgun 

Sprayers

Orchard/

Vineyard

100

2050 8.68 0.0046 1000 gal 0.0012 210 0.00050 500 150 Field 

crop, 

typical

M/L/A Liquids 

for Backpack 

Sprayers

Orchard/

Vineyard 8260 2.58 0.0046 40 gal 0.00019 1300 0.0000059 4200 2400

a Orchard/Vineyard = Citrus Group 10-10, Pome Fruit Group 11-10, Stone Fruit Group 12-12, Tree Nuts Group 14-12, Guava, 

Feijoa, Jaboticaba, Wax jambu, Starfruit, Passionfruit, Acerola, Lychee, Longan, Spanish lime, Rambutan, Pulasan, Papaya, 

Star apple, Black sapote, Sapodilla, Canistel, Mamey sapote (Small Fruit, Vine-Climbing Subgroup 13-07F maximum 

application rate is lower, at 0.019 lb ai/A);

Field crop, typical = Fruiting Vegetable Group 8-10, Greenhouse tomato, Low Growing Berry Subgroup 13-07G, Green 

Onion Subgroup 3-07B, Pineapple; 

Field crop, high-acreage = Beans

b Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 2015); Level of 

mitigation = Single layer of clothing + gloves and no respirator, except for aerial applicator, which includes engineering 

controls

c Based on the maximum application rates on the proposed labels (Reg. Nos. 100-1351, -1408, -1154, -1439).

d Exposure Science Advisory Council Policy #9.1. Units in acres, unless otherwise noted.

e Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × 

Area Treated or Amount Handled Daily (A or gal/day) × DAF (1%) ÷ BW (80 kg).

Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × 

Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 kg).

f Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). ST/IT Dermal NOAEL = 0.25 mg/kg/day.

Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST/IT Inhalation NOAEL = 0.25 

mg/kg/day.
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Total MOE = NOAEL (mg/kg/day) ÷ (Dermal Dose + Inhalation Dose). ST/IT Combined Dermal/Inhalation NOAEL = 0.25 

mg/kg/day.

Table G.3. Short-Term Post-Application Exposures and Risk Estimates for Abamectin Associated with 

PP#s 3E8175 and 3F8184

Activity Transfer

Coefficient

Days After 

Treatment

DFR a Daily Dermal Dose b Dermal MOE c

μg/cm2 mg/kg/day LOC = 100

Caneberries (Crop Subgroup 13-07A): Vine/Trellis

irrigation (hand set) 1,900

0

(12 hours) 0.053

0.000101 2,500

hand harvesting, 

tying/training 1,400 0.0000746 3,400

scouting, hand pruning, 

hand weeding, 

tying/training

640 0.0000341 7,300

transplanting 230 0.0000123 20,000

Corn: Field/Row Crop, Tall

hand detasseling, 

hand harvestingd 8,800

0

(12 hours) 0.053

0.000469 530

irrigation (hand set) 1,900 0.000101 2,500

scouting 1,100 0.0000586 4,300

scouting 210 0.0000112 22,000

hand weeding 70 0.00000373 67,000

Soybean: Field/Row Crop, Low/Medium

scouting 1,100 0

(12 hours) 0.053

0.0000586 4,300

hand weeding 70 0.00000373 67,000

Golf Course: Turf/Sod

maintenance 3,700 0

(12 hours) 0.0077

0.0000286 8,700

maintenance,

greens only 2,500 0.0000194 13,000

a DFR (μg/cm2) = application rate (0.019 or 0.069 lb ai/acre) × fraction of application rate dislodgeable on day 0 (25%) × (1 -

fraction of residue that dissipates daily 10%)t × 4.54×108 μg/lb × 2.47×-8 acre/cm2

.

b Short-Term Daily Dermal Dose = [DFR (μg/cm2

) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day ÷ body weight (80 kg).

c Short-Term MOE = NOAEL (mg/kg/day) ÷ Daily Dermal Dose (mg/kg/day). ST NOAEL = 0.25 mg/kg/day. LOC = 100.

Table G.4. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Abamectin, 

Associated with PP# 4E8309

Crop/Sitea

Policy Crop 

Group 

Category

Activities

Transfer 

Coefficient 

(cm2/hr)

DFR/

TTRb

Dermal Dose 

(mg/kg/day)c MOEd

Short-/Intermediate-terme

Almond, 

Hazelnut, Tree, “nut”

Mechanical harvesting (shaking) 190

0.06

0.000012 20,000

Scouting, Hand pruning 580 0.000037 6,700

Transplanting 230 0.000015 17,000
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Table G.4. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Abamectin, 

Associated with PP# 4E8309

Crop/Sitea

Policy Crop 

Group 

Category

Activities

Transfer 

Coefficient 

(cm2/hr)

DFR/

TTRb

Dermal Dose 

(mg/kg/day)c MOEd

Short-/Intermediate-terme

Macadamia 

nut,

Pecan,

Pistachio,

English Walnut 

Orchard maintenance, Poling, Hand 

weeding 100 0.0000065 39,000

Apple,

Pear

Tree, "fruit", 

deciduous

Hand harvesting 1,400

0.06

0.000090 2,800

Propping, Orchard maintenance, 

Hand weeding, Propping 100 0.0000065 39,000

Pruning, Hand; Training; Scouting; 

Hand pruning 580 0.000037 6,700

Thinning Fruit 3,600 0.00023 1,100

Transplanting 230 0.000015 17,000

Apricot

Cherry

Nectarine

Peach

Tree, "fruit", 

deciduous

Scouting 580

0.06

0.000037 6,700

Orchard maintenance, Propping, 

Bird control, Hand weeding 100 0.0000065 39,000

Thinning Fruit 3,600 0.00023 1,100

Hand harvesting 1,400 0.000090 2,800

Hand pruning, Training 580 0.000037 6,700

Transplanting 230 0.000015 17,000

Bean, dry; Pea, 

dry

Chickpea

Bean, snap

Field / row 

crop, low / 

medium

Irrigation (hand set) 1,900

0.05

0.00010 2,500

Hand weeding 70 0.0000037 67,000

Scouting 1,100 0.000059 4,300

Blueberry, 

lowbush

Berry, low

Hand harvesting; Scouting 1,100

0.05

0.000059 4,300

Hand weeding 70 0.0000037 67,000

Irrigation (hand set) 1,900 0.00010 2,500

Transplanting 230 0.000012 20,000

Pepper, bell

Pepper, chili

Eggplant, 

Tomato

Vegetable, 

fruiting

Hand harvesting, Tying/Training 1,100

0.05

0.000059 4,300

Hand pruning, Hand weeding; 

Thinning fruit 90 0.0000048 52,000

Irrigation (hand set) 1,900 0.00010 2,500

Scouting 210 0.000011 22,000

Transplanting 230 0.000012 20,000

Grape, table

Grape, wine

Grape juice

Vine / trellis

Girdling, Turning 19,300 0.05 0.0010 240

Scouting, Propagating, Hand 

pruning, Hand weeding, Bird 

control, Trellis repair

640

0.05

0.000034 7,300

Tying/Training, Hand harvesting, 

Leaf pulling, 10,100 0.00054 460
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Table G.4. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Abamectin, 

Associated with PP# 4E8309

Crop/Sitea

Policy Crop 

Group 

Category

Activities

Transfer 

Coefficient 

(cm2/hr)

DFR/

TTRb

Dermal Dose 

(mg/kg/day)c MOEd

Short-/Intermediate-terme

Transplanting 230 0.000012 20,000

Irrigation (hand set) 1,900 0.00010 2,500

Grapefruit

Lemon

Orange

Tree, "fruit", 

evergreen

Orchard maintenance, Hand 

weeding, Baiting/Trapping 100

0.06

0.0000065 39,000

Scouting, Hand pruning 580 0.000037 6,700

Transplanting 230 0.000015 17,000

Hand harvesting 1,400 0.000090 2,800

Greenhouse 

vegetable 

(tomato)

Unassigned

Hand harvesting, Pinching, 

Pollination, Hand pruning, Scouting, 

Turning, Tying/Training, Hand 

weeding, Propagating

1,200

0.03

0.000032 7,800

Transplanting, Irrigation (hand 

watering) 230 0.0000061 41,000

Onion, green Vegetable, 

"root"

Hand harvesting, Scouting 1,400

0.05

0.000075 3,400

Irrigation (hand set) 1,900 0.00010 2,500

Thinning plants 330 0.000018 14,000

Hand weeding 4,200 0.00022 1,100

Pineapple Vegetable, 

stem / stalk

Hand harvesting 1,100

0.06

0.000071 3,500

Scouting 210 0.000014 18,000

Hand weeding 70 0.0000045 55,000

Strawberry Berry, low

Harvesting, Hand 1,100

0.05

0.000059 4,300

Transplanting 230 0.000012 20,000

Scouting 210 0.000011 22,000

Hand weeding, Canopy management 70 0.0000037 67,000

a Crop/Site = Proposed crops or representative crops within proposed crop groups or subgroups. 

b DFR = Application Rate (varies)× F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.25 and D = 0.10 per day 

TTR = Application Rate × F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.1 and D = 0.10 per day. 

c Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (1%)] ÷ BW (80 

kg).

d MOE = POD (mg/kg/day) / Daily Dermal Dose. 

The MOEs presented for each exposure activity scenario for crop groups represent the lowest available calculated MOEs for 

any commodity within a crop group for any given scenario. 

e Short- and Intermediate-term Post-Application exposures are considered equivalent, because the PODs are equal. 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Appendix H. Avermectin Macrocyclic Lactones Cumulative Screening Assessment

H.1.0 Executive Summary

Using the cumulative screening framework outlined in the Pesticide Cumulative Risk 

Assessment: Framework for Screening Analysis Purpose (USEPA, 2016) for candidate common 

mechanism groups (CMGs), the Agency has conducted a screening-level cumulative exposure 

analysis for the avermectin macrocyclic lactones, which contain the insecticides abamectin and 

emamectin. This screening-level assessment adds exposures of abamectin and emamectin and is

designed to be an overestimate of exposure and risk (i.e., this screen assumes co-occurrence of 

residues in water and some crops from both abamectin and emamectin). 

Abamectin and emamectin are registered for use on a variety of food and feed crops and have 

tolerances established for use on: cotton, tree nuts, apples, pears, fruiting vegetables, cucurbits, 

and leafy vegetables, except Brassicas. Tolerances have been established for both chemicals in 

livestock commodities and grapes, although the tolerance for emamectin applies to imported 

wine grapes. Abamectin is also registered for use in food handling establishments (FHE); an allfoods tolerance has been established to support that use pattern. The all-foods FHE tolerance is 

lower than tolerances that have been established based on agricultural uses, so the FHE uses are 

expected to be minor contributors to the overall exposure to abamectin residues. Finally, 

abamectin is registered for use in or on fire ant mounds and other indoor sites that could result in 

residential handler exposure and is proposed for use on turf that could result in post-application 

residential exposure. There are currently no registered residential uses of emamectin. 

Based on the use patterns for abamectin and emamectin, the potential routes and durations of 

exposure for consideration in the screening-level cumulative analysis include acute dietary 

exposure as well as short-term dietary and residential exposure.

The screening-level cumulative assessment for the avermectin macrocyclic lactones, abamectin 

and emamectin, indicates that combined aggregate dietary and residential risk estimates are 

below the Agency’s levels of concern. Given the conservatisms underlying the cumulative 

assessment (i.e., point-estimate aggregate methodology combined with high-end dietary and 

residential exposures while assuming complete co-exposure for all available exposure scenarios 

without any related co-exposure refinements), EPA expects that the screening-level residues 

overestimate actual cumulative residues; therefore, no additional data are required at this time.

H.2.0 Introduction

Section 408(b)(2)(D)(v) of the Federal Food, Drug, and Cosmetic Act (FFDCA) requires EPA to 

consider available evidence concerning the cumulative effects of pesticide residues and other 

substances that have a common mechanism of toxicity. EPA has developed guidance that defines 

a common mechanism of toxicity as a common toxic effect to human health by the same, or 

essentially the same, sequence of major biochemical events. To facilitate compliance with this 

provision, EPA’s Office of Pesticide Programs (OPP) has previously developed guidance 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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documents in 1999 for establishing common mechanism groups (CMGs) 6 and in 2002 for 

conducting cumulative risk assessments (CRAs) 7. OPP recently developed an additional 

guidance document, entitled Pesticide Cumulative Risk Assessment: Framework for Screening 

Analysis Purpose (USEPA, 2016). This document builds upon those previous guidance 

documents by providing a framework for screening pesticides for potential common mechanism 

groupings, called candidate CMGs, and conducting screening-level CRAs. 

Using the framework, pesticides are screened for potential cumulative evaluation using a twostep approach. First, OPP evaluates and compares available toxicological information (e.g., 

chemical structures, hazard profiles) to determine if a candidate CMG can be formed. The 

Agency will use a weight of evidence approach to evaluate this information and reach one of 

three conclusions: 

(1) the data do not support establishing a CMG, and no further cumulative analysis is 

required; 

(2) the data support forming a candidate CMG, and the Agency will conduct a screeninglevel exposure analysis consistent with the Framework; or 

(3) the data support establishing a CMG consistent with the 1999 CMG guidance, and the 

Agency will conduct a CRA consistent with the 2002 CRA guidance. 

OPP has utilized this framework for abamectin and has determined that abamectin and 

emamectin form a candidate CMG (option 2). These pesticides form a candidate CMG because 

they shares characteristics to support a testable hypothesis for a common mechanism of action 

and there are sufficient toxicological data to suggest a common pathway. However, the Agency 

does not have adequate data to establish a CMG consistent with the 1999 CMG guidance 

document. Adequate data are lacking to determine those key events in a pathway as described in 

the mode of action/adverse outcome pathway (MOA/AOP) framework (e.g., lack of dose or 

temporal concordance of proposed key events). Further information regarding the common 

toxicological profile and testable hypothesis identified for abamectin and emamectin may be 

found in Section H.3.0.

H.3.0 Toxicological Considerations in Determining a Candidate CMG 

Consistent with the Agency’s mixture risk assessment guidance (USEPA 1986; USEPA, 2000), 

OPP assumes dose additivity in CRA unless data are available to support an alternative 

approach. Then, OPP will evaluate the toxicological database for dose response data to identify 

an index chemical and to develop screening-level relative potency factors (RPFs) and PODs for 

purposes of screening exposure analysis. The data and mathematical approach used in the 

derivation of the screening RPFs and PODs should be described, including characterization of 

their refinement (or lack thereof). Screening-level RPFs and PODs should, to the extent possible, 

be related to hypothesized MOA/AOP and the common toxic effect for the class. However, in 

 6 Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common 

Mechanism of Toxicity (USEPA, 1999) 7 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common 

Mechanism of Toxicity (USEPA, 2002)
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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some analyses, the same POD values may be used for each chemical in the CMG and no RPF 

would be developed.

H. 3.1 Chemical Structural Similarity

Similarities in chemical structure may translate to shared toxicophore (i.e., a feature or group 

within a chemical structure that is associated with toxic properties) and ultimately to a common 

mechanism of toxicity. When evaluated in combination with other toxicological considerations, a 

shared chemical structure may support the finding of a CMG or candidate CMG.

Emamectin is a derivative of abamectin, and the two compounds are structurally and 

toxicologically related. The only structural difference between abamectin and emamectin a 

hydroxyl moiety at the 4” position of the tetrahydropyran ring of abamectin; for emamectin, the 

hydroxyl group is replaced by a methylamine. These differences are shown within the circled 

groups in the following figures.

Abamectin Emamectin

H. 3.2 Hazard Profile Comparison for Candidate CMG

Abamectin and emamectin share a common toxicological profile as summarized below:

• Both abamectin and emamectin share a common toxicity profile consistent with GABA 

receptor interaction (Appendices A and I).

• Both pesticides elicit similar clinical signs of neurotoxicity such as tremors, mydriasis, 

and abnormal gaits in dogs, rats, and mice. 

• The dog is the most sensitive and human-relevant species for studying the effects of 

abamectin and emamectin. In dogs treated with these two pesticides, a set of common 

clinical signs indicative of neurotoxicity demonstrated a similar dose-response 

relationship for the two chemicals, occurred at similar LOAELs and yield a common 

NOAEL (0.25 mg/kg/day) for establishing the POD for risk assessment. .

• Both abamectin and emamectin have similarly low dermal absorption (i.e., 1% for 

abamectin and 1.8% for emamectin).
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H. 3.3 Toxicological Evaluation to determine a CMG for Abamectin and Emamectin

OPP’s Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common 

Mechanism of Toxicity (USEPA, 1999) describes the weight of the evidence approach for 

determining whether or not a group of pesticides share a common mechanism of toxicity. This 

guidance defines mechanism of toxicity as the major steps leading to a toxic effect following 

interaction of a pesticide with biological targets. All steps leading to an effect do not need to be 

specifically understood. Rather, it is the identification of the crucial events following chemical 

interaction that are required in order to describe a mechanism of toxicity. For example, a 

mechanism of toxicity may be described by knowing the following: a chemical binds to a given 

biological target in vitro, and causes the receptor-related molecular response; in vivo it also leads 

to the molecular response and causes a number of intervening biological and morphological steps 

that result in an adverse effect. In this context a common mechanism of toxicity pertains to two 

or more pesticide chemicals or other substances that cause a common toxic effect to human 

health by the same, or essentially the same, sequence of major biochemical events. Hence, the 

underlying basis of the toxicity is the same, or essentially the same, for each chemical.

In the case of the macrocyclic lactones of the avermectin class (i.e.., abamectin and emamectin), 

there is a wealth of data on the insecticidal mechanism of action for avermectin: its insecticidal 

actions are mediated by interaction with the glutamate-gated chloride channels and GABAA

gated chloride channels. This is presumed to be the insecticidal mechanism of action of 

emamectin and abamectin as well. There is evidence that avermectin B1a binds to GABAA

receptors and activates Cl- flux into neurons (Abalis et al., 1986; Huang and Casida, 1997). 

However, there is a paucity of data regarding the resultant alterations in cellular excitability of 

mammalian neurons and neural networks (i.e., changes in cellular excitability and altered 

network function as documented with pyrethroids), as well as in vivo measurements of altered 

excitability associated with adverse outcomes. Thus, while the downstream steps leading to 

toxicity via disruption of GABAA receptor function for avermectin can be postulated, 

experimental data supporting these actions are lacking. In addition, specific data demonstrating 

GABAA receptor interaction in mammalian preparations are lacking for abamectin and 

emamectin. Moreover, the specificity of such interaction on the adverse outcome would need to 

be shown experimentally. GABAA receptors have multiple binding sites which have been 

proposed to relate to adverse outcomes. For example, Dawson et al (2000) showed for a group of 

avermectin-like compounds that rank order for anticonvulsant activity did not parallel the rank 

order for affinity at the [3H]ivermectin site. The authors hypothesized that these findings may be 

related to differential affinity or efficacy at subtypes of the GABAA receptor. Other reports have 

indicated species differences in abamectin effects on GABAA receptor function in the mouse as 

compared to the rat (Soderlund et al., 1987).

Although GABAA receptor mediated neurotoxicity is a strong hypothesis as a common 

mechanism endpoint for the macrocyclic lactone pesticides, data demonstrating the interactions 

of emamectin and abamectin with mammalian GABAA receptors are not available, and data in 

mammalian preparations linking alterations in GABAA receptor function to disruptions in 

neuronal excitability in vitro and in vivo, and ultimately adverse outcome, are also currently 

lacking for this class of compounds. In the absence of such data, the key biological steps leading 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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to the adverse outcome (i.e., the mammalian mechanism of action) cannot be established and by 

extension a common mechanism group cannot be established.

The Agency has determined that abamectin and emamectin should be considered a candidate 

CMG due to their structural similarity, the fact that they share characteristics to support a testable 

hypothesis for a common mechanism of action, and that there is sufficient toxicological data to 

suggest a common pathway. However, there are not currently adequate data for establishing key 

events in a pathway as described in the MOA/AOP framework8,9,10,11.

H.4.0 Dose Response Assessment

An important component in cumulative hazard assessment is the derivation of a uniform measure 

of dose response that accurately represents all members of a CMG. For example, toxicity values 

may be derived from the PODs from single chemical risk assessments, from NOAELs or 

LOAELs from specific toxicology studies or possibly benchmark doses (BMDs). In some 

analyses, the same value may be used for each chemical in the candidate group.

H.4.1 Selection of Points of Departure for Screening Cumulative Assessment

The Agency has re-evaluated the toxicity databases for abamectin and emamectin, as well as the 

available literature information on a polymorphism in the human gene encoding the P 

glycoprotein (P-gp). Because of species and life stage differences in the expression of P-gp, toxic 

effects of macrocyclic lactones observed in the CF-1 mouse and the juvenile rat are not 

considered representative of abamectin and emamectin effects in humans and will not be 

considered for toxicity endpoints and points of departure selections. The CF-1 mouse and rats 

younger than 28 days have diminished P-gp function compared to other mammals (including 

humans). 

The Agency considered results from abamectin and emamectin toxicological studies conducted 

in the species that do not have diminished P-gp function (adult rats, CD-1 mice, rabbits and 

dogs) for selecting PODs for risk assessment. Based on that assessment, the dog was determined

to be the most appropriate species to assess the risk of abamectin and emamectin. The 

cumulative screen relies on toxicity studies conducted in the dog, with neurotoxic effects for 

both abamectin and emamectin. The PODs used in the screen are also those used for single 

chemical assessment of the individual chemicals and represent the most sensitive points of 

departure that are relevant to humans. The POD used for both chemicals is the NOAEL of 0.25 

 8 USEPA (2005), Guidelines for Carcinogen Risk Assessment, Risk Assessment Forum, 

Washington, DC; EPA/630/P-03/001F. Federal Register 70(66):17765-17817; 

http://www.epa.gov/raf. 9 Boobis, A.R. et al. (2008), IPCS Framework for Analyzing the Relevance of a Noncancer Mode 

of Action for Humans, Crit Rev Toxicol 38:87-96. 10 Seed, J. et al. (2005), Overview: Using Mode of Action and Life Stage Information to Evaluate 

the Human Relevance of Animal Toxicity Data, Crit Rev Toxicol 35(8-9): 664-672. 11 Sonich-Mullin, C. et al. (2001), IPCS Conceptual Framework for Evaluating a Mode of Action 

for Chemical Carcinogenesis, Regul Toxicol Pharmacol 34:146-152.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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mg/kg/day; the adverse effects noted at the LOAEL consist of mydriasis, tremors, and 

neuropathology. Mydriasis and tremors are produced by both chemicals at similar dose levels, 

while neuropathology is seen with emamectin. The POD selected from the dog studies are based 

on clear NOAELs and are protective of all the adverse effects seen in the studies conducted in 

human relevant studies with rats, CD-1 mice, and rabbits. Therefore, the uncertainty factor of 

100x (10x for interspecies extrapolation and 10x for intraspecies variation) was applied for both 

chemicals.

The framework describes the use of Relative Potency Factors (RPFs) for higher tier screening 

assessments. As noted above, the toxicity endpoints and PODs for the relevant exposure 

scenarios are the same, so RPFs are not needed for purposes of screening analysis. For dermal 

exposure assessments, the dermal absorption for both abamectin and emamectin is quite similar 

with rather low dermal absorption factors, 1% for abamectin and 1.8% for emamectin.

The toxicity endpoints and PODs of the two chemicals are compared in Table H.4.1 below. The 

Toxicology profile tables and summaries of toxicity endpoints and points of departure for human 

health risk assessment are presented in Appendix A (abamectin) and Appendix I (emamectin). 

Table H.4.1. Comparison of Toxicological Doses and Endpoints for Abamectin and Emamectin for Use in 

Dietary and Non-Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

LOC for Risk 

Assessment

Study and 

Toxicological Effects of 

Abamectin

Study and 

Toxicological Effects of 

Emamectin

Acute 

Dietary

(General 

Population, 

including 

Infants and 

Children) 

NOAEL= 

0.25 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

Acute RfD = 

aPAD = 

0.0025 

mg/kg/day

Subchronic & chronic 

oral toxicity studies in 

dogs 

Subchronic 

LOAEL=0.5 mg/kg/day 

based on mydriasis 

during week one, death 

at 1.0 mg/kg/day.

Chronic LOAEL = 0.50 

mg/kg/day based on 

body tremors, one 

death, liver pathology, 

decreased body weight. 

Mydriasis was seen 

during week one in one 

dog

Subchronic and chronic 

oral toxicity studies in

dogs

Subchronic LOAEL = 

0.5 mg/kg/day based 

skeletal muscle atrophy 

and white matter 

multifocal degeneration 

in the brains of both 

sexes and white matter 

multifocal degeneration 

in the spinal cords of 

males.

Chronic LOAEL=0.5 

mg/kg/day based on 

axonal degeneration in 

the pons, medulla, and 

peripheral nerves 

(sciatic, sural, and 

tibial) ; whole body 

tremors; stiffness of the 

hind legs, spinal cord 

axonal degeneration, 

and muscle fiber 

degeneration.

Incidental 

Oral

Short- and 

IntermediateTerm 

NOAEL= 

0.25 

mg/kg/day

UFA= 10x

UFH= 10x

Residential 

LOC for MOE 

= 100

Dermal

Short- and 

IntermediateTerm

NOAEL= 

0.25 

mg/kg/day

UFA= 10x

UFH= 10x

Residential 

LOC for MOE 

= 100

Inhalation

Short- and 

IntermediateTerm

NOAEL= 

0.25 

mg/kg/day

UFA= 10x

UFH= 10x

Residential 

LOC for MOE 

= 100
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Table H.4.1. Comparison of Toxicological Doses and Endpoints for Abamectin and Emamectin for Use in 

Dietary and Non-Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

LOC for Risk 

Assessment

Study and 

Toxicological Effects of 

Abamectin

Study and 

Toxicological Effects of 

Emamectin

Cancer (oral, 

dermal, 

inhalation)

Classification for abamectin and emamectin: “Not likely to be Carcinogenic to Humans” based on 

the absence of significant tumor increases in two adequate rodent carcinogenicity studies.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level 

of concern. N/A = not applicable.

H.4.2 FQPA Safety Factor for Protection of Infants and Children

For both abamectin and emamectin, the toxicity endpoint and POD for all exposure scenarios 

was selected from the subchronic and chronic oral toxicity studies in the dogs, whose sensitivity 

to the effects of the abamectin is second only to CF-1 mice. The Agency does not consider these 

more sensitive effects to be representative of abamectin and emamectin effects in humans 

because the diminished P-gp function seen in CF-1 mice is not seen in humans. The POD

selected from the dog studies is based on clear NOAELs, which are protective of all the adverse 

effects seen in the human relevant studies conducted with rats, DC-1 mice, and rabbits. 

Therefore, the FQPA safety factor has been reduced to 1x. The FQPA safety factors for the 

cumulative screening-level assessment are the same as the single chemical assessment; further 

details on all of these considerations may be found in the single chemical discussions.

H.4.3 Incorporation of Uncertainty Factors/Extrapolation Factors and the Level of 

Concern MOE.

The level of concern MOE is 100 for the screening-level cumulative analysis, as described in 

section H.4.1.

H.5.0 Dietary Cumulative Exposure and Risk Assessment/Characterization

The cumulative screening framework outlined in the Pesticide Cumulative Risk Assessment: 

Framework for Screening Analysis Purpose (USEPA, 2016) presents a tiered approach for the 

cumulative screening-level dietary exposure analysis. Four tiers, with increasing refinements at 

each tier, allow reviewers to systematically analyze dietary data for the candidate CMG 

beginning at the first tier (i.e., combined food + water exposures from each member in a 

candidate CMG are extracted and summed and then compared to the POD of the most potent 

member of the candidate CMG) and continue until reaching the tier of refinements where the 

dietary risk does not exceed the level of concern. 
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H.5.1 Food Exposure Pathway

EPA conducted a screening-level cumulative exposure analysis for the avermectin macrocyclic 

lactones, which contain the insecticides abamectin and emamectin. Humans may be exposed to 

abamectin and emamectin residues in food since these two chemicals may be applied directly to 

growing crops. 

Abamectin: Abamectin is an 80/20 mixture of avermectin B1a/avermectin B1b that may be 

applied on various raw agricultural commodities. For crops and livestock commodities, 

compliance with the tolerance is determined by measuring avermectin B1a, avermectin B1b, and 

the 8,9-Z isomers. Tolerances for abamectin have been established or are being recommended as 

a part of this action in 40 CFR §180.449, as presented in Table H.5.1, below.

Emamectin: Emamectin is a 90/10 mixture of emamectin B1a/emamectin B1b that may be applied 

on various raw agricultural commodities. For crops, compliance with the tolerance is determined 

by measuring emamectin B1a, emamectin B1b, the 8,9-Z isomers, and additional metabolites: 

AB1a, MFB1a, and FAB1a. For livestock commodities, compliance with the tolerance is 

determined by measuring emamectin B1a, emamectin B1b, and the 8,9-Z isomers.

Tolerances for emamectin have been established in 40 CFR §180.505, as presented in Table 

H.5.1, below. 

Table H.5.1. Abamectin and Emamectin Established and Recommended Tolerances

Crop Abamectin Tolerances (ppm) Emamectin Tolerances (ppm)

Acerola 0.015

Almond, hulls 0.10 0.20

Apple 0.0202 ---

Apple, wet pomace 0.10 0.075

Avocado 0.020 ---

Bean 0.015

Bean, dry, seed2 0.01 ---

Berry, low growing, subgroup 13-

07G

0.05

Black sapote 0.40

Caneberry subgroup 13-07A 0.20 ---

Canistel 0.40

Cattle, fat 0.05 0.010

Cattle, liver --- 0.050

Cattle, meat 0.02 0.003

Cattle, meat byproducts 0.09 ---

Cattle, meat byproducts, except liver --- 0.020

Celeriac, roots 0.05 ---

Celeriac, tops 0.05 ---

Chive, dried leaves 0.02 ---

Chive, fresh leaves 0.01 ---

Citrus, dried pulp 0.10 ---

Citrus, oil 0.10 ---

Citrus 0.022 ---

Corn, sweet, forage 0.20

Corn, sweet, kernel plus cob with 

husk removed 

0.01 ---
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Table H.5.1. Abamectin and Emamectin Established and Recommended Tolerances

Crop Abamectin Tolerances (ppm) Emamectin Tolerances (ppm)

Corn, sweet, stover 0.50

Cotton, gin byproducts 1.0 0.050

Cotton, undelinted seed3 0.02 0.025

Feijoa 0.015

Food products in Food Handling 

Establishments

0.01 ---

Fruit, citrus, group 10-10 0.02

Fruit, pome, group 11 --- 0.025

Fruit, pome, group 11-10 0.02

Fruit, small, vine climbing, except 

fuzzy kiwifruit, subgroup 13-07F

0.02

Fruit, stone, group 12 0.092

Fruit, stone, group 12-12 0.09 ---

Goat, fat 0.03 0.010

Goat, liver --- 0.050

Goat, meat 0.02 0.003

Goat, meat byproducts 0.04 ---

Goat, meat byproducts, except liver --- 0.020

Grain, aspirated grain fractions 0.40 ---

Grape 0.022 ---

Grape, wine1 --- 0.03

Guava 0.015

Herb subgroup 19A, except chive 0.030 ---

Hog, fat 0.01 0.003

Hog, liver --- 0.020

Hog, meat 0.02 0.002

Hog, meat byproducts 0.02 ---

Hog, meat byproducts, except liver --- 0.005

Hop, dried cones 0.20 ---

Horse, fat 0.03 0.010

Horse, liver --- 0.050

Horse, meat 0.02 0.003

Horse, meat byproducts 0.04 ---

Horse, meat byproducts, except liver --- 0.020

Jaboticaba 0.015

Lychee 0.01

Longan 0.01

Mamey sapote 0.40

Milk 0.015 0.003

Nut, tree, group 14 0.012 0.02

Nut, tree, group 14-12 0.01

Onion, bulb, subgroup 3-07A 0.01 ---

Onion, green, subgroup 3-07B 0.08

Papaya 0.40

Passionfruit 0.015

Pear 0.022 ---

Peppermint, tops

(entered as peppermint and 

peppermint oil)

0.010 ---

Pineapple 0.015

Pistachio 0.012 0.02

Plum, prune, dried 0.025 ---
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Table H.5.1. Abamectin and Emamectin Established and Recommended Tolerances

Crop Abamectin Tolerances (ppm) Emamectin Tolerances (ppm)

Poultry, meat 0.02 ---

Poultry, meat byproducts 0.02 ---

Pulasan 0.01

Rambutan 0.01

Sapodilla 0.40

Sheep, fat 0.03 0.010

Sheep, liver --- 0.050

Sheep, meat 0.02 0.003

Sheep, meat byproducts 0.04 ---

Sheep, meat byproducts, except liver --- 0.020

Soybean, forage 0.30 ---

Soybean, hay 1.0 ---

Soybean, seed 0.01 ---

Spanish lime 0.01

Spearmint, tops

(entered as spearmint and spearmint 

top)

0.010 ---

Star apple 0.40

Starfruit 0.015

Strawberry 0.052 ---

Tomato, paste --- 0.150

Turnip, greens --- 0.050

Vegetable, Brassica, leafy, group 5 --- 0.050

Vegetable, cucurbit, group 9 0.005 0.02

Vegetable, fruiting, group 8 0.0202 0.020

Vegetable, fruiting, group 8-10 0.07

Vegetable, leafy, except brassica, 

group 4

0.10 0.100

Vegetable, tuberous and corm, 

subgroup 01C

0.01 ---

Wax jambu 0.015 1 Imported only; no US registrations. 2 These tolerances are proposed for revocation as part of this action, as the tolerances will be superseded by tolerances established

by this action.

3 This commodity was entered in DEEM as oil

H.5.2 Drinking Water Pathway

EPA used the screening-level drinking water exposure assessments from the single chemical 

assessments for the screening-level cumulative assessment of the avermectin macrocyclic 

lactones, which contain the insecticides abamectin and emamectin. Residues of abamectin and 

emamectin resulting from exposure to drinking water were included in the dietary exposure 

assessments as residue distribution files rather than as point estimates in the acute assessment. 

Single point estimates were used in the short-term aggregate, based on the chronic exposure 

assessment. 
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Abamectin: Residues of abamectin in drinking water may occur in ground and surface water, 

with higher residues in surface water (0.76 μg/L or ppb for acute exposure; 0.30 ppb for chronic 

exposure). The abamectin residues of concern include avermectin B1a, avermectin B1b, and the 

structurally similar degradates: NOA 448111, NOA 448112, NOA 426289, NOA 445495, NOA 

457464, and NOA 457465. In absence of toxicity data on these degradates, they are assumed to 

have toxicity profiles similar to that of abamectin on the basis of the structural similarities.

Table H.5.2.1. Screening-Level EDWCs for Proposed Uses of Abamectin1

Source (Tier: Model)2 Use Site

(Max. Annual App. Rate)

Acute EDWC 

(μg/L)

Chronic 

EDWC (μg/L)

Surface water (Tier II: SWCC) Soybeans (0.037 lbs ai/A)/ Beans 

(0.056 lbs ai/A)

0.76 

(soybeans)

0.30

(beans)

Ground water (Tier I: PRZM-GW) Golf courses (0.27 lbs ai/A) 0.074 N/A

Ground water (Tier I: SCI-GROW) Golf courses (0.27 lbs ai/A) ≤0.0031 1 Maximum values are in bold. Values include parent compound and degradates. 2 SWCC = Surface Water Concentration Calculator; PRZM-GW = Pesticide Root Zone Model – Ground Water; SCI-GROW = 

Screening Concentration in Ground Water.

Emamectin: Residues of emamectin in drinking water may occur in ground and surface water. 

Estimated drinking water concentrations were previously assessed as part of an action requesting 

an import tolerance on wine grapes (D402152, N. Dodd, 2/20/13). Residues of emamectin may 

occur in ground and surface water, with higher residues in surface water (0.465 ppb for acute 

exposure; 0.150 ppb for chronic exposure). The emamectin residues of concern include 

emamectin B1a, emamectin B1b, and four metabolites, which are assumed to be of equal or lesser 

toxicity to that of the parent compound: (8,9-Z)-4"-epimethylamino-4"-deoxy avermectin B1 

(8,9 ZMA isomer); 4"-epiamino-4"-deoxyavermectin B1 (AB); avermectin B1 monosaccharide 

(MAB); and 4"-epi-(N-formyl)-4"-deoxyavermectin B1 (FAB). 

Table H.5.2.2. EDWCs for Emamectin Residues from Use on Outdoor Ornamentals and Group 9 

Cucurbit Vegetables1

Use Model2

1 in 10 year 30 year Annual 

Peak Annual Mean Average

μg/L

Surface Water

Ornamentals PRZM/EXAMS3 0.465 0.150 0.112

Ground Water

Ornamentals/Group 9 

Cucurbit Vegetables SCI-GROW 0.54 x 10-3 0.54 x 10-3 0.54 x 10-3

1 Maximum values are in bold. Values include parent and degradates. 2 PRZM-EXAMS = Pesticide Root Zone Model and Exposure Analysis Modeling System; SCI-GROW = Screening 

Concentration in Ground Water.

3 Typically, the values generated by the models for drinking water are multiplied by a percent crop area factor (PCA). The PCA 

accounts for the fact that is it unlikely for any basin to be completely planted to agricultural crops. The PCA adjustment factor is 

assumed to be 0.87 for the group 9 cucurbit vegetables and 1.0 for the outdoor ornamentals crops as per the PCA guidance. 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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H.5.3 Dietary (Food and Drinking Water) Assessment

The Agency has determined to use the Tier I approach for this cumulative screening-level dietary 

exposure assessment. In this, combined dietary (food + water) exposures from each of the most 

recent single pesticide chemical risk assessments for abamectin and emamectin have been

extracted and added together. Tier 1 assessments also call for the exposures of each chemical to 

be RPF-scaled. However, in the case of the avermectin macrocyclic lactones, the POD is the 

same for both abamectin and emamectin, so this was not necessary. This tier assumes complete 

co-occurrence of all food and drinking water residues for abamectin and emamectin. The 

assumptions for the most recent single pesticide chemical dietary assessments for abamectin and 

emamectin were refined with field trial residue data and percent crop treated (PCT) estimates. 

Further information regarding the dietary assumptions may be found in the single chemical 

dietary assessments for emamectin and abamectin (D430736, N. Dodd, 12/23/2015 and 

D424009, K. Rickard, 04/14/2016).

Acute: The screening-level cumulative acute dietary exposures from combined residues of 

abamectin and emamectin are calculated in Table H.5.3.1, below. The combined residues result 

in 52% of the aPAD for the general U.S. population and 95% of the aPAD for children 1-2 years 

old, the most highly exposed subgroup. These acute cumulative dietary exposures are below 

HED’s level of concern of 100%.

Table H.5.3.1. Summary of Acute Dietary Exposure and Risk Assessment for Combined Abamectin and 

Emamectin

Population 

subgroup

Abamectin 

Exposure

Emamectin 

Exposure

Combined 

Exposure aPAD Combined % aPAD

Ratio 

Aba:Ema

General U.S. Population 0.001135 0.000172 0.001307 0.0025 52 6.6

All Infants (<1 year old) 0.001584 0.000160 0.001744 0.0025 70 9.9

Children 1-2 years old* 0.002192 0.000187 0.002379 0.0025 95 12

Children 3-5 years old 0.001553 0.000205 0.001758 0.0025 70 7.6

Children 6-12 years old 0.000729 0.000101 0.00083 0.0025 33 7.2

Youth 13-19 years old 0.000475 0.000132 0.000607 0.0025 24 3.6

Adults 20-49 years old 0.000446 0.000186 0.000632 0.0025 25 2.4

Adults 50-99 years old 0.000345 0.000176 0.000521 0.0025 21 2.0

Females 13-49 years old 0.000427 0.000226 0.000653 0.0025 26 1.9

*The subpopulation with the highest combined risk estimate is bolded.

Chronic Dietary Exposure: The screening-level cumulative background dietary exposures 

from combined residues of abamectin and emamectin are calculated in Table H.5.3.2 below.

Table H.5.3.2. Summary of Chronic Dietary Exposure and Risk Assessment for Combined Abamectin and 

Emamectin

Population 

subgroup

Abamectin 

Exposure

Emamectin 

Exposure

Combined 

Exposure cPAD Combined % cPAD

General U.S. Population 0.000056 0.000008 0.000064 0.0025 2.6

All Infants (<1 year old) 0.000096 0.000014 0.000110 0.0025 4.4
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table H.5.3.2. Summary of Chronic Dietary Exposure and Risk Assessment for Combined Abamectin and 

Emamectin

Population 

subgroup

Abamectin 

Exposure

Emamectin 

Exposure

Combined 

Exposure cPAD Combined % cPAD

Children 1-2 years old* 0.000268 0.000014 0.000282 0.0025 11

Children 3-5 years old 0.000160 0.00001 0.000170 0.0025 6.8

Children 6-12 years old 0.000090 0.000007 0.000097 0.0025 3.9

Youth 13-19 years old 0.000045 0.000005 0.000050 0.0025 2.0

Adults 20-49 years old 0.000038 0.000008 0.000046 0.0025 1.8

Adults 50-99 years old 0.000037 0.000009 0.000046 0.0025 1.8

Females 13-49 years old* 0.000038 0.000008 0.000046 0.0025 1.8

* The subpopulation with the highest combined risk estimate is bolded.

H.6.0 Residential Pathway

The cumulative screening framework presents a tiered approach for the cumulative screeninglevel residential exposure analysis. Each tier provides increasing refinements, which allows

reviewers to systematically analyze CMG residential exposures and risk data until reaching the 

tier of refinements where residential risks do not exceed the level of concern. 

It should be noted that most residential exposure assessments conducted by OPP include highend, default assumptions with regard to surface residues (i.e., turf residues). Any refinements 

used in the cumulative screening-level residential exposure analysis would be in addition to 

those already in place in the single pesticide chemical assessments. 

The Agency has determined to use the Tier I, or unrefined, approach for this cumulative 

screening-level residential exposure assessment. In this approach, residential exposures from the 

most recent risk assessment(s) are extracted and added together.

Abamectin: As discussed in detail in Section 6.0, above, there are proposed and registered use 

sites that may lead to residential handler and post-application exposures to abamectin, including 

a proposed use for control of turf-parasitic nematodes on golf course greens, tees, and fairways. 

Adults and youth (6 to <16 years old) may receive dermal exposure from golfing activities 

following applications of abamectin to golf course turf. This use scenario was used in the shortterm aggregate risk calculations in the adult and youth aggregate assessment, and therefore the 

cumulative assessment. There is no recommended residential risk estimate for children under the 

age of six, because residential risk estimates are expected to be negligible to infants and young 

children

Emamectin: There are no existing or proposed residential use sites; therefore, there are no 

residential handler exposure or residential post-application exposures to be extracted for use in 

the cumulative assessment.

Because there are no registered uses of emamectin that are expected to result in residential 

handler or post-application exposures, residential exposures for use in the cumulative risk 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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assessment are from the proposed liquid formulation on turf (golf courses, greens, tees, and 

fairways).

H.7.0 Combined Screening-Level Cumulative Assessment (Dietary + Residential)

Short-Term: The screening-level short-term aggregate risk is calculated in Table H.7.0 below. 

All short-term aggregate exposure estimates resulted in MOEs greater than 100; therefore, they 

are not of concern. Intermediate-term residential exposures are not expected. 

Table H.7.0. Short-Term Aggregate Risk Calculations for Combined Abamectin and Emamectin

Population

Short-Term Scenario

NOAEL LOC1

Max 

Exposure2

Abamectin Emamectin Combined 

Residential 

Exposure3

Total 

Exposure4

Aggregate 

MOE (food, 

water + 

residential)5

Average Food and Water Exposure

mg/kg/day

Adults 

0.25 100 0.0025

0.0000376 0.00000906 0.000046 0.00002 0.000066 3,800

Children 6 

to <11 

years old

0.0000907 0.00000507 0.000095 0.000028 0.00012 2,000

Children 

11 to <16 

years old

0.0000458 0.00000708 0.000052 0.000024 0.000076 3,300

1 The LOC includes the standard inter- and intra-species uncertainty factors (UFA and UFH, respectively) totaling 100. 2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC.

3 Residential Exposure = [Oral exposure + Dermal exposure + Inhalation Exposure] from Tables 6.2 and 7.2.1. Residential 

exposure is from abamectin only; there is no residential exposure from emamectin. The abamectin residential exposure scenario 

is a liquid formulation on turf (golf courses, greens, tees, and fairways) at the maximum single application rate of 0.34 lb ai/A. 4 Total Exposure = Avg Food & Water Exposure + Residential Exposure).

5 Aggregate MOE = [NOAEL ÷ (Avg Food & Water Exposure + Residential Exposure)].

6 Adult population subgroup utilized dietary exposure estimates for Adults 50-99 years old. 7 Children 6 to <11 years old population subgroup utilized dietary exposure estimates for Children 6-12 years old 8 Children 11 to <16 years old population subgroup utilized dietary exposure estimates for Youth 13-19 years old.

H.8.0 Characterizing the Screening-Level Cumulative Estimates

HED screened combined aggregate abamectin and emamectin dietary and residential exposures 

to determine whether there would be any potential cumulative concern for this CMG, the 

avermectin macrocyclic lactones. This screening-level assessment used conservative 

assumptions that are expected to overestimate exposures, including Tier 1 dietary (food + water) 

and residential cumulative screening assessment assumptions. The screening-level dietary 

assessment included the conservatism of complete co-occurrence of both food and drinking 

water residues for abamectin and emamectin. 

HED believes that a more refined cumulative exposure assessment is not required at this time 

since the exposure estimates using a Tier 1 approach are below HED’s levels of concern.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

Page 89 of 98

H.9.0 Conclusion

The screening-level cumulative assessment for the candidate CMG of the avermectin 

macrocyclic lactones, abamectin and emamectin, utilized conservative dietary and residential 

exposure assumptions and indicates that combined aggregate dietary and residential risk 

estimates are below the Agency’s levels of concern. Therefore, the Agency has no concern for 

the cumulative exposure to the existing and proposed uses of abamectin or emamectin at this 

time. Given the conservatisms underlying the abamectin and emamectin cumulative assessment 

(i.e., point-estimate aggregate methodology combined with high-end dietary and residential 

exposures while assuming complete co-exposure for all available exposure scenarios without any 

related co-exposure refinements), EPA expects that the screening-level residues overestimate 

actual cumulative residues.

Although this assessment is an unrefined screening-level for the purposes of the cumulative 

screen, the assumptions underlying the single chemical dietary assessments for abamectin and 

emamectin have been refined. Further information regarding the dietary assumptions may be 

found in the single chemical dietary assessments for emamectin and abamectin (D430736, N. 

Dodd, 12/23/2015 and D424009, K. Rickard, 04/14/2016). 

Since risk estimates in this cumulative screening-level assessment are below HED’s levels of 

concern, no additional data are required at this time. Should future uses result in risk estimates 

above the LOCs, the Agency will review whether additional toxicological or exposure data may 

be required in order to reevaluate the assumptions and resulting conclusions of the avermectin 

macrocyclic lactones cumulative assessment.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

Page 90 of 98

Appendix I. Emamectin Toxicity Profiles

I.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food use for emamectin are in Table I.1. Use of the new guideline numbers 

does not imply that the new (1998) guideline protocols were used.

Table I.1. Toxicology Data Requirements for Emamectin

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Acute Eye Irritation.......................................................

870.2500 Acute Dermal Irritation .................................................

870.2600 Skin Sensitization..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 90-Day Oral Toxicity in Rodents..................................

870.3150 90-Day Oral Toxicity in Nonrodents.............................

870.3200 21/28-Day Dermal Toxicity ..........................................

870.3250 90-Day Dermal Toxicity ...............................................

870.3465 90-Day Inhalation Toxicity (5-Day study in rats) ...

yes

yes

yes

-

yes

yes

yes

yes

-

Waived a

870.3700a Prenatal Developmental Toxicity (rodent) ....................

870.3700b Prenatal Developmental Toxicity (nonrodent) ..............

870.3800 Reproduction and Fertility Effects ................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Carcinogenicity (rat)......................................................

870.4200b Carcinogenicity (mouse) ...............................................

870.4300 Combined Chronic Toxicity/Carcinogenicity ...............

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Bacterial Reverse Mutation Test..........

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test..

870.5385 Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

870.6200a Acute Neurotoxicity Screening Battery (rat).................

870.6200b 90-Day Neurotoxicity Screening Battery (rat) ..............

870.6300 Developmental Neurotoxicity .......................................

yes

yes

CR

yes

yes

-

870.7485 Metabolism and Pharmacokinetics................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

yes

yes

yes

yes

yes

 a HASPOC Report: TXR 0051377, 03/12/2015.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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I.2 Toxicity Profiles

Table I.2.1. Acute Toxicity Profile – Emamectin Benzoate Technical (EPA Reg. No. 100-902)

Guideline No. Study Type MRID Results Toxicity Category

870.1100 Acute oral - Rats 42851519 LD50 for L-656,748-

038 = 53 mg/kg

II

870.1200 Acute dermal - Rabbits (EC) 43850111 LD50 > 2.0 g/kg III

870.1300 Acute inhalation - Rats 43868101 0.44 mg/L <LC50<2.12 

mg/L

III

870.2400 Acute eye irritation - Rabbits 42743615 Severe irritation I

870.2500 Acute dermal irritation - Rabbits 42743616 No dermal irritation IV

870.2600 Skin sensitization - Guinea pigs 42743617 Not a dermal sensitizer -

Table I.2.2. Acute Toxicity Profile – Emamectin Benzoate Technical II (EPA Reg. No. 100-1270)

Guideline No. Study Type MRID Results Toxicity Category

870.1100 Acute oral - Rats 47002104 LD50 for L-656,748-

038 = 53 mg/kg

II

870.1200 Acute dermal - Rabbits (EC) 47002106 LD50 > 2.0 g/kg III

870.1300 Acute inhalation - Rats 47002107 LC50 0.10 mg/L II

870.2400 Acute eye irritation - Rabbits 47002108 Severe irritation III

870.2500 Acute dermal irritation - Rabbits 47002109 No dermal irritation IV

870.2600 Skin sensitization - Guinea pigs 47002110 Not a dermal sensitizer Negative
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table I.2.3. Repeated Dosing and Other Studies on Emamectin

Guideline No Study Type MRID No. (Year)/ 

Classification/Doses

Results

Acute dermal tox.-

rabbits 

MK-0243 0.16 EC 

formulation

42743611 (1991)

Acceptable 

0, 0.5, 1.0, & 2.0 mg/kg

(2 groups: 4 hr exposure 

& 24 hr exposure) with 

collar on the test animals.

4 hr. exposure

NOAEL= 2.0 mg/kg/day (HDT)

24 hr. exposure

NOAEL = 0.5 mg/kg/day

LOAEL = 1.0 mg/kg/day one rabbit had 

neuron lesion occurred in cerebellar peduncle. 

Acute dermal tox. –

rabbits (24 hrs 

exposure with collar 

on all test animals) 

43850111 (1995)

Acceptable 

0, 10.4, 21.0, or 42.1 

mg/kg MK-0244 0.16 

EC

NOAEL = 42.1 mg/kg. No treatment-related 

systemic toxicity was seen in any dosed 

animals. 

The acute dermal LD50 > 2000 mg/kg for MK0244

870.3100 13-Wk oral-CD rats 42794201 (1992)

Acceptable

0, 0.5, 2.5, and 12.5 

mg/kg/day. 12.5 

mg/kg/day was reduced

to 8 mg/kg/day at wk 3 

then to 5.0 mg/kg/day at 

wk 9.

Systemic Toxicity NOAEL=2.5 mg/kg/day; 

Systemic Toxicity LOAEL=5 mg/kg/day based 

on moribundity, tremors, hindlimb splaying, 

urogenital staining, histological changes in 

brain and spinal cord, sciatic and optic nerves 

and skeletal muscles in males, emaciation, 

reduced body weight and reduced food 

consumption in both sexes.

13-Wk oral-CD-1 

mice

42743621 (1992)

Acceptable

0, 0.5, 4.5, & 15.0 

mg/kg/day. An 

additional group received 

a time weighted dose 5.4 

mg/kg/day

NOAEL = 5.4 mg/kg/day

LOAEL = 15.0 mg/kg/day based on mean body 

weight decrease and decreased in cumulative 

body weight gain.

870.3150 90-Day oral – dogs 

(gavage)

42743623 (1992)

Acceptable

0, 1.0, or 1.5 mg/kg/day 

for the first 2 wks then 

reduced to 0.25, 0.5, or 

1.0 for the rest of the 

study.

NOAEL = 0.25 mg/kg/day

LOAEL = 0.50 mg/kg/day based skeletal 

muscle atrophy and white matter multifocal 

degeneration in the brains of both sexes and 

white matter multifocal degeneration in the 

spinal cords of males.

14-Wk oral-dogs 

(gavage)

43868103 (1994)

Acceptable

0.5, 1.0, or 1.5 

mg/kg/day for 2 wks for 

mid and high dose 

groups and for 3 wks for 

low dose, then they were 

reduced to 0.25, 0.5, or 

2.0 mg/kg/day. The time 

weighted doses were 

0.29. 0.58, or 0.1.08 

mg/kg/day.

NOAEL = 0.29 mg/kg/day

LOAEL = 0.58 mg/kg/day based on 

microscopic lesions in the brain (multifocal 

white matter degeneration), atrophy of skeletal 

muscle, and spinal cord lesions. 

870.3200 21-Day dermal toxrabbits 

MK-0244 0.16 EC 

formulation 

42743625 (1992

Acceptable 

0, 50, 100, or 250 

mg/kg/day (6 hrs/day)

Systemic tox. NOAEL = 100 mg/kg/day

LOAEL = 250 mg/kg/day based on axonal 

degeneration of the sciatic nerve. 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table I.2.3. Repeated Dosing and Other Studies on Emamectin

Guideline No Study Type MRID No. (Year)/ 

Classification/Doses

Results

Application site irritation was seen in all 

treated rabbits.

22-Day dermal tox. –

rabbits 

MK-0244 0.16 EC 

formulation 

44007902 (1996)

Acceptable

0, 250, 500, or 1000 

mg/kg/day (6 hrs/day)

NOAEL = 1000 mg/kg/day (highest dose 

tested [HDT]). No systemic toxicity was seen 

in any dose groups. 

Note: The test animals were collared to 

prevent oral ingestion of the test material. 

870.3465 Subchronic 

inhalation -5-day 

inhalation tox.-rats

(emamectin 

benzoate)

49395601 (2014)

Acceptable/nonguideline

0, 1, 3, 10, and 30 μg/L

0, 0.26, 0.74, 2.4, and 7.4 

mg/kg/day

Systemic tox: NOAEL = 0.74 mg/kg/day

LOAEL = 2.4 mg/kg/day based on tremors, 

abnormal gaits, and vocalization (at day 5 or 

day 6)

Portal of entry tox: NOAEL = 0.5 mg/kg/day

LOAEL = 0.74 mg/kg/day based on borderline 

effects of metaplasia along with inflammation 

in the larynx. 

870.4100 1-Year oral tox. –

dogs (gavage) 

42763624 (1992)

Acceptable

0, 0.25, 0.5, 0.75, or 1.0 

mg/kg/day (4 

dogs/sex/dose)

NOAEL= 0.25 mg/kg/day

LOAEL=0.5 mg/kg/day based on axonal 

degeneration in the pons, medulla, and 

peripheral nerves (sciatic, sural, and tibial); 

whole body tremors; stiffness of the hind legs, 

spinal cord axonal degeneration, and muscle 

fiber degeneration.

Chronic oral tox. –

rats (dietary)

(1 year)

42868902 (1992)

Acceptable

0, 0.1, 1.0, 5.0/2.5 

mg/kg/day

NOAEL=1.0 mg/kg/day

LOAEL=2.5 mg/kg/day, based on increased 

incidence of neuronal degeneration in the brain 

and spinal cord, decreased rearing, and an 

increased incidence of animals with low 

arousal.

Note: Females dose reduced on week 18 from 

5.0 to 2.5 mg/kg/day due to excessive toxicity

870.4200 Carcinogenicity 

study-mice (CD-1)

(dietary)

4386805 (1994)

Acceptable

0, 0.5, 2.5, or 12.5 

mg/kg/day (The highest 

dose was reduced to 7.5 

and 5.0 mg/kg/day for 

males at wk 9 and 

females at wk 3, 

respectively)

NOAEL=2.5 mg/kg/day.

LOAEL=5.0 mg/kg/day for males and 7.5 

mg/kg/day for females based on increased 

mortality, decreased weight gain, tremors, 

sciatic nerve degeneration , and increased 

incidence of severity of infections. 

No treatment-related increase in tumor 

incidence was seen.

Combined Chronic/

Carcinogenicity-Rat

43868104 (1994)

Acceptable

0, 0.25, 1.0, 2.5/5.0 

mg/kg (Initially, high 

dose level was 5.0 

mg/kg; it was reduced to 

2.5 mg/kg on wk 6 for 

males and wk 10 for 

females due to tremors 

seen in another study at 

5 mg/kg). 

NOAEL=1.0 mg/kg/day

LOAEL=2.5/5.0 mg/kg/day1 based on marked 

neural degeneration in the brain and spinal 

cord of both sexes, brain white matter 

degeneration in males, and on dec reased body 

weight, body weight gain, and food efficiency 

in males. 

No treatment-related increase in tumor 

incidence was seen.

870.3700 Developmental tox. 

–rat

42743632 (1992)

Acceptable

Maternal Toxicity NOAEL=2 mg/kg/day, 

Maternal Toxicity LOAEL=4 mg/kg/day based 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table I.2.3. Repeated Dosing and Other Studies on Emamectin

Guideline No Study Type MRID No. (Year)/ 

Classification/Doses

Results

0, 2, 4, or 8 mg/kg/day

42743631 (range finding 

study)

on a significant trend towards decreased body 

weight gain during the dosing period.

Developmental Toxicity NOAEL=4 

mg/kg/day, Developmental Toxicity 

LOAEL=8 mg/kg/day based on altered growth 

and an increased incidence of supernumerary 

rib.

Developmental tox.-

rabbits

42743636 (1992)

Acceptable 

0, 1.5, 3, or 6 mg/kg/day

42743635 (Range finding 

study)

Maternal Tox. NOAEL= 3 mg/kg/day, 

Maternal Tox. LOAEL= 6 mg/kg/day based on 

a significant trend towards decreased body 

weight gain during dosing period and increased 

clinical signs (mydriasis and decreased 

pupillary reaction).

Developmental Tox. NOAEL=6 mg/kg/day 

(HDT)

870.3800 2-Gen. reproduction 

study - rats

42851511 (1993)

Acceptable 

0, 0.1, 0.6, or 3.8/1.8 

mg/kg/day (F0 & F1a 

females initially received 

3.8 mg/kg, but it was 

reduced to 1.8 mg/kg/day 

on GD 0 following the 

second cohabitation of 

F0 females).

Parental NOAEL = 0.6 mg/kg/day.

Parental LOAEL = 1.8 mg/kg/day based on 

decreased body weight gain and neuronal 

degeneration in the brain and spinal cord in 

both sexes and generations.

Reproductive NOAEL=0.6 mg/kg/day 

Reproductive LOAEL=1.8 mg/kg/day based 

on decreased fecundity and fertility indices.

Offspring NOAEL = 0.6 mg/kg/day

Offspring LOAEL = 1.8 mg/kg/day based on 

tremors and hind limb extension in the 

offspring of both generations, neuronal 

degeneration in the brain and spinal cord.

870.5100 870.5100

Gene Mutation -

Salmonella

MK-0243 and L660,599; L-657,831; 

L-695,638; L930,905 

(photometabolites of 

MK-0244)

42743637

42851514

42851515

42851516

42851517

Negative for the induction of reverse gene 

mutation.

870.5300 Gene Mutation in 

Cultured V-79 

Chinese Hamster 

Lung Cells

MK-0243

42743638 Negative for the induction of forward gene 

mutations in Chinese hamster lung fibroblast 

cells up to a severely cytotoxic nonactivated 

dose of 0.01 mM or a severely cytotoxic S9-

activated dose of 0.04 mM.

870.5385 Structural 

Chromosome 

Aberration-in vivo

mouse bone marrow

MK-0244

42851513 Negative for the induction of chromosome 

aberrations in the bone marrow cells of male 

CD-1 mice.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table I.2.3. Repeated Dosing and Other Studies on Emamectin

Guideline No Study Type MRID No. (Year)/ 

Classification/Doses

Results

870.6200 Acute neurotox. 

study-rats (gavage)

42743618 (1992)

Acceptable

0, 27.4, 54.8 or 82.2 

mg/kg (range finding 

study)

NOAEL was not established. LOAEL= 27.4 

mg/kg/day (LDT); clinical signs (tremors, 

ataxia, loss of righting reflex, and reduced 

activities) and as histological lesions in the 

brain, spinal cord and sciatic nerve occurred at 

all doses tested.

Acute neurotox. 

study- rats 

(gavage)

42743619 (1992)

Supplementary

0, 0.5, 2.5, 5.0, 10.0, or 

25.0 mg/kg/day

NOAEL = 5.0

LOAEL = 10 mg/kg/day based on tremors 

irritability. At 25 mg/kg, all rats had tremor 

and neuronal lesions (white matter 

degeneration of the brain, degeneration of the 

spinal cord and sciatic nerve.

Subchronic 

neurotox. –SD rats

(dietary) (14 day)

42743628 (1992)

Acceptable 

0, 0.25, 1.0, or 5.0 

mg/kg/day 

NOAEL=1.0 mg/kg/day

LOAEL=5.0 mg/kg/day based on tremors, 

posture, rearing, excessive salivation, fur 

appearance, gait, strength, mobility and 

righting reflex. Neuronal vacuolation in brain 

and spinal cord; degeneration of nerve fiber in 

spinal cord and sciatic nerves. Skeletal muscle 

atrophy. Male rats appeared to be more 

affected than females.

Comparative 

neurotox. – dogs

(gavage) (14 days)

42743626 (1992)

Acceptable

2 dogs/sex/compound 

were given 1.5 

mg/kg/day of testing 

compound.

The following effects were seen with different 

compounds:

 Tremors 

Mydriasis 

MK-0243a

 2/4 0/4 

L-682,901 0/4 0/4

L-653,648 0/4 4/4

L-653,649 2/4 3/4

L-655. 372 3/4 0/4 

Histopathology findings were not seen in L682, 901 and L-653,648 treated dogs. 

Neuronal degeneration of the brain, spinal 

cord, and sciatic nerves were seen in dogs 

treated with MK-0234, L-653, 649, and L655,372.

15-Day neurotox. –

CD-1 mice

(dietary)

42743629 (1992)

Acceptable

0, 0.6, 1.2, & 2.0 

mg/kg/day

NOAEL=2.0 mg/kg/day (HDT). No 

characteristic neuronal lesions in the brain, 

spinal cord or sciatic nerve in mice of high 

dose group. 

15-Day neurotox.-

CF-1 mice (dietary)

(L-660,599: 4”-epi-

(N-formyl-Nmethyl)- amino4”-

deoxy-avermectin 

B1

42851503 (1993)

Acceptable

0, 0.05, 0.075, 0.10, or 

0.30 mg/kg/day 

NOAEL=0.075 mg/kg/day

LOAEL=0.10 mg/kg/day based on tremors 

observed beginning on day 3, ptosis, hunched 

posture, decreases in body weight and food 

consumption as well as degeneration of the 

sciatic nerve. At 0.3 mg/kg, tremors were seen 

on day 2 and followed by hunched posture and 

ptosis, ataxia, and labored breathing.

15-Day neurotox. –

CF-1 mice (dietary)

42851504 (1993)

Acceptable 

NOAEL = 0.30 mg/kg/day (HDT) 

No treatment-related effects were seen in any 

dose groups.
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table I.2.3. Repeated Dosing and Other Studies on Emamectin

Guideline No Study Type MRID No. (Year)/ 

Classification/Doses

Results

(L695-638: 4”-

deoxy-4”-epimethylaminoavermectin B1adelta-8,9-isomer); 

photoproduct of 

MK-0244b

0, 0.05, 0.075, 0.10, & 

0.30 mg/kg/day

15-Day neurotox. –

CF-1 mice (dietary)

(L695-638: 4”-

deoxy-4”-epimethylaminoavermectin B1adelta-8,9-isomer); 

photoproduct of 

MK-0244

42851505(1993)

Acceptable

0, 0.05, 0.075, 0.10, & 

0.30 mg/kg/day

NOAEL = 0.243 (HDT). The targeted dose 

was 0.30 mg/kg/day. No treatment-related 

effects were seen in any dose groups.

Female mice only to repeat the exposure dose 

levels of MRID 42851504 because female 

mice received 15% less than the targeted dose 

in that study.

15-Day neurotox.-

CF-1 mice (dietary) 

(L-660,599; formyl 

methylamino plant 

metabolite of MK0244 )

42851506 (1993)

Acceptable 

0, 0.10, 0.30, 0.90 

mg/kg/day

LOAEL <0.1 mg/kg/day LDT) based on 

tremors, hunched posture and piloerection. 

However no treatment-related findings in 

histopathology were present.

15-Day neurotox.-

CF-1 mice (gavage) 

L-930,905; a complex mixture of polar 

MK-244 

photodegradates) 

42851507 (1993)

Acceptable 

0, 3, 6, 12, or 18 

mg/kg/day

NOAEL = 18 mg/kg/day (HDT)

No treatment-related effects were found.

16-Day neurotox.-

CF-1 mice (dietary)

MK-0243

42743630 (1992)

Acceptable

0, 0.05, 0.10, 0.30, or 

0.90 mg/kg/day

NOAEL = 0.1 mg/kg/day

LOAEL = 0.30 mg/kg/day based on tremors, 

decreased activity, and moribund sacrifice 

starting on day 2. However, no histopathology 

findings were present. 

15-Day neurotox.-

CF-1 mice (dietary)

Formyl amino 

derivative of MK0244

42868901 (1991)

Acceptable 

0, 0.050, 0.075, 0.100, & 

0.300 mg/kg/day

NOAEL = 0.07 mg/kg/day

LOAEL = 0.23 mg/kg/day based on decreased 

body weight gain.

870.6300 Develop. Neurotox.-

rats (SD) (gavage 

for maternal 

animals; no direct 

dosing for neonates)

MK-0244

42851508 (1993)

Acceptable

0, 0.1, 0.6, 3.6/2.5 

mg/kg/day (3.6 mg/kg 

was reduced to 2.5 

mg/kg between GD 17 

and 20)

Maternal NOAEL=3.6/2.5 mg/kg/day (highest 

dose tested)

Develo. Neurotox. NOAEL=0.10 mg/kg/day 

Develo. Neurotox. LOAEL = 0.60 mg/kg/day 

based on the dose-related decrease in open 

field motor activity in females at postnatal day 

17. 

870.7485 Metabolism –rats

[ 14C] 4”-deoxy-4’-

epi-methylamino 

avermectin B1a 

benzoate, (MAB1a)

42851523 & 42852524

(1993)

Acceptable 

Radiolabeled MAB1a benzoate is rapidly 

absorbed, distributed and excreted following 

oral and i.v. administration. The feces was the 

major route of excretion in oral and i.v. groups, 

while <1% of the administered dose was 
ABAMECTIN Human Health Risk Assessment DP No. D426599 

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Table I.2.3. Repeated Dosing and Other Studies on Emamectin

Guideline No Study Type MRID No. (Year)/ 

Classification/Doses

Results

recovered in the urine 7 days post dosing. 

Tissue distribution and bioaccumulation 

appeared minimal. The metabolism of MAB1 

a benzoate appears to involve primarily Ndemethylation to AB1a. AB1a was the only 

metabolite detected in the feces while 

unmetabolized parent compound represented a 

large amount of the radioactivity.

Bioequivalence -Dog

MK-0243 

solvate vs. monohydrate

42743641(1992)

Supplemental

The study demonstrated that MK-0243 

benzoate MTBE solvate and MK-0243 

benzoate monohydrate were bioequivalent in 

male dogs following oral administration as 

indicated by similar plasma levels for the two 

compounds.

Bioequivalence-Dog

MK-0243 benzoate

vs. HCL salts

42743640 (1992)

Supplemental

The study demonstrated that benzoate and HCl 

salts are bioequivalent after oral administration 

in male beagle dogs.

870.7600 Dermal AbsorptionRhesus Monkey43850113 (1994) Dermal Absorption was approximated at 

1.79% of the administered dose.

870.7800 Immunotoxicity 

study (female CD-1 

mice)

48980301 (2012)

Acceptable/guideline

0, 10, 30, 60 ppm

1.7, 4.8, 10.6 mg/kg/day 

(free base)

1.9, 5.5, 12.1 mg/kg/day

(benzoate sat)

No systemic toxicity was seen.

No evidence of a serum T-cell dependent 

antibody (IgM) response to sRBC.

Table I.2.4. Summary of Toxicological Doses and Endpoints for Emamectin for Use in Dietary Human Health 

Risk Assessments

Exposure/

Scenario

Point of Departure Uncertainty/

FQPA Safety 

Factors

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

Dietary (all 

durations) 

(General 

Population, 

including 

Infants and 

Children) & 

Incidental Oral

NOAEL= 0.25 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

Acute RfD = 

0.0025 

mg/kg/day

aPAD = 0.0025 

mg/kg/day

Subchronic and chronic oral toxicity 

studies in dogs

Subchronic LOAEL = 0.5 

mg/kg/day based skeletal muscle 

atrophy and white matter multifocal 

degeneration in the brains of both 

sexes and white matter multifocal 

degeneration in the spinal cords of 

males.

Chronic LOAEL=0.5 mg/kg/day 

based on axonal degeneration in the 

pons, medulla, and peripheral nerves 

(sciatic, sural, and tibial); whole 

body tremors; stiffness of the hind 

legs, spinal cord axonal 

degeneration, and muscle fiber 

degeneration.

Dermal

Short- and 

Intermediate 

Term 

NOAEL= 0.25 

mg/kg/day

Dermal Absorption 

= 1.8 %

UFA= 10x

UFH= 10x

FQPA SF= 1x

Residential LOC 

for MOE = 100

Inhalation

Short- and 

IntermediateTerm 

NOAEL= 0.25 

mg/kg/day

Toxicity via the 

inhalation route 

assumed to be 

UFA= 10x

UFH= 10x

FQPA SF= 1x

Residential LOC 

for MOE = 100
ABAMECTIN Human Health Risk Assessment DP No. D426599 

Page 98 of 98

Table I.2.4. Summary of Toxicological Doses and Endpoints for Emamectin for Use in Dietary Human Health 

Risk Assessments

Exposure/

Scenario

Point of Departure Uncertainty/

FQPA Safety 

Factors

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

equivalent to the 

oral route 

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant 

tumor increases in two adequate rodent carcinogenicity studies.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level 

of concern. N/A = not applicable.

Table I.2.5. Summary of Toxicological Doses and Endpoints for Emamectin for Use in Occupational Human 

Health Risk Assessments

Exposure/ 

Scenarios

Point of 

Departure

Uncertainty/ 

Safety Factor RFD, PAD, LOC Study and Toxicological Effects

Dermal 

(Short-Term 

and 

IntermediateTerm)

NOAEL= 0.25 

mg/kg/day

Dermal 

Absorption = 

1.8 % 

UFA = 10x

UFH = 10x

LOC: MOE =100 Subchronic and chronic oral toxicity 

studies in dogs

Subchronic LOAEL = 0.5 mg/kg/day 

based skeletal muscle atrophy and white 

matter multifocal degeneration in the 

brains of both sexes and white matter 

multifocal degeneration in the spinal 

cords of males.

Chronic LOAEL=0.5 mg/kg/day based 

on axonal degeneration in the pons, 

medulla, and peripheral nerves (sciatic, 

sural, and tibial); whole body tremors;

stiffness of the hind legs, spinal cord 

axonal degeneration, and muscle fiber 

degeneration.

Inhalation 

(Short-Term 

and 

IntermediateTerm)

NOAEL= 0.25 

mg/kg/day

Toxicity via the 

inhalation route 

assumed to be 

equivalent to 

the oral route 

UFA = 10x

UFH = 10x

LOC: MOE = 100

Cancer (oral, 

dermal, 

inhalation)

Classification: Not likely to be carcinogenic to human based on the absence of significant increase in 

tumor incidence in two adequate rodent carcinogenicity studies.

Point of Departure (PoD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity 

among members of the human population (intraspecies). SF = Safety Factor. PAD = population adjusted dose (a = 

acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. .