ABAMECTIN Human Health Risk Assessment DP No. 426599 

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION

MEMORANDUM

 

Date: DRAFT June 30, 2015 

 

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

Subgroup 13-07A, Soybeans, Sweet Corn, Ear Tags for Lactating Dairy 

Cattle, and Golf Course Turf.

 

PC Code: 122804 

Decision No.: 480177

Petition Nos.: 3E8175, 3F8184 

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: Nancy Dodd, Chemist/Risk Assessor 

 Whang Phang, Senior Toxicologist 

 Nancy Keller, Chemist 

 Risk Assessment Branch III (RAB3) 

 Health Effects Division (HED) (7509P) 

 

THROUGH: Christine Olinger, Branch Chief 

 Risk Assessment Branch III (RAB3) 

 Health Effects Division (HED) (7509P) 

TO: Mark Suarez/Jessica Rogala, PM#7 

Invertebrate and Vertebrate Branch 3 

Registration Division (7505P) 

and 

Barbara Madden/Sidney Jackson, PM#5 

Minor Use and Emergency Response Branch 

 Registration Division (7505P) 

The Registration Division (RD) of the Office of Pesticide Programs (OPP) has requested the 

Health Effects Division (HED) to conduct dietary, occupational, residential, and aggregate 

exposure assessments, as needed, to estimate the risk to human health that will result from the 

proposed uses of abamectin, also known as avermectin B1 [a mixture of avermectins containing 

≥80% avermectin B1a (5-O-demethyl avermectin A1) and ≤20% avermectin B1b (5-O-demethyl25-de (1-methylpropyl)-25-(1-methylethyl) avermectin A1)], and its delta-8,9-isomer on the 
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caneberry subgroup 13-07A, soybeans, sweet corn, ear tags for lactating dairy cattle, and golf 

course turf. 

HED evaluated the abamectin petition and determined that potential exposure could occur via the 

dietary (food and drinking water), residential, and occupational exposure pathways. HED 

determined that there is reasonable certainty that no harm will result to the general population 

and to infants and children from aggregate exposure resulting from the proposed uses of 

abamectin on caneberries, soybeans, sweet corn, dairy cattle ear tags, and golf course turf. Also, 

HED has conducted a screening level cumulative assessment which indicates that there is 

reasonable certainty that no harm will result to the general population and to infants and children 

from aggregate exposure resulting from the combined proposed/registered uses of abamectin and 

the registered uses of emamectin. The Agency expects that the screening level cumulative 

residues overestimate actual cumulative residues. 

The HED team members contributing to this risk assessment include: Nancy Dodd (risk 

assessment/residue chemistry review/dietary exposure assessment), Nancy Keller 

(occupational/residential exposure assessment), and Whang Phang (toxicology assessment). 

Greg Orrick of the Environmental Fate & Effects Division (EFED) provided the drinking water 

exposure assessment. 
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TABLE OF CONTENTS 

1.0 Executive Summary ........................................................................................................... 5

2.0 HED Recommendations .................................................................................................... 8

2.1 Data Deficiencies ............................................................................................................ 8

2.2 Tolerance Considerations .............................................................................................. 8

2.2.1 Enforcement Analytical Method ............................................................................... 8

2.2.2 Recommended Tolerances ......................................................................................... 8

2.2.3 Revisions to Petitioned-For Tolerances .................................................................... 9

2.2.4 International Harmonization................................................................................... 10

3.0 Introduction ...................................................................................................................... 10

3.1 Chemical Identity ......................................................................................................... 11

3.2 Physical/Chemical Characteristics ............................................................................. 12

3.3 Pesticide Use Pattern .................................................................................................... 12

3.4 Anticipated Exposure Pathways ................................................................................. 16

3.5 Consideration of Environmental Justice .................................................................... 17

4.0 Hazard Characterization and Dose-Response Assessment .......................................... 17

4.1 Toxicological Studies Available for Analysis ............................................................. 19

4.2 Absorption, Distribution, Metabolism, and Excretion (ADME) ............................. 19

4.2.1 Dermal Absorption ................................................................................................... 20

4.3 Toxicological Effects .................................................................................................... 20

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 21

4.4.1 Completeness of the Toxicology Database .............................................................. 21

4.4.2 Evidence of Neurotoxicity ........................................................................................ 21

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ........ 21

4.4.4 Residual Uncertainty in the Exposure Database ................................................... 22

4.5 Toxicity Endpoint and Point of Departure Selections .............................................. 23

5.0 Dietary Exposure and Risk Assessment ......................................................................... 26

5.1 Residues of Concern Summary and Rationale .......................................................... 26

5.2 Food Residue Profile .................................................................................................... 26

5.3 Water Residue Profile .................................................................................................. 27

5.4.1 Description of Residue Data Used in Dietary Assessment .................................... 28

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 28

5.4.3 Acute Dietary Risk Assessment ............................................................................... 29

5.4.4 Background Dietary Exposure ................................................................................ 29

5.4.5 Cancer Dietary Risk Assessment............................................................................. 30

5.4.6 Summary Table......................................................................................................... 30

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 30

6.1 Residential Handler Exposure ........................................................................................ 31

6.2 Residential Post-Application Exposure and Risk Estimates .................................... 32

6.3 Residential Bystander Post-Application Inhalation Exposure ................................ 33

6.4 Spray Drift .................................................................................................................... 33

7.0 Aggregate Exposure/Risk Characterization .................................................................. 34

7.1 Acute Aggregate Risk ................................................................................................... 34

7.2 Short- and Intermediate-Term Aggregate Risk ........................................................ 34

7.3 Chronic Aggregate Risk ............................................................................................... 35

7.4 Cancer Aggregate Risk ................................................................................................ 35
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8.0 Cumulative Exposure/Risk Characterization ............................................................... 35

9.0 Occupational Exposure/Risk Characterization ............................................................ 36

9.1 Short-/Intermediate-Term Handler Risk ................................................................... 36

9.2 Short-/Intermediate-Term Post-Application Exposures and Risks ......................... 37

10.0 References ......................................................................................................................... 38

Appendix A. Abamectin Toxicology Profile and Executive Summaries ............................... 40

A.1 Toxicology Data Requirements ................................................................................... 40

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

Emamectin ............................................................................................................................... 41

Appendix B. Toxicology Literature References ...................................................................... 48

Appendix C. Abamectin Physical/Chemical Properties ......................................................... 50

Appendix D. Review of Human Research for Abamectin ...................................................... 51

Appendix E. International Residue Limits Table for Abamectin ......................................... 52

Appendix F. Abamectin Field Trial Tables ............................................................................. 54

Appendix G. Abamectin Occupational and Residential Exposure Tables ........................... 55

Appendix H. Abamectin and Emamectin Cumulative Screening Assessment ..................... 58

Appendix I. Emamectin Toxicity Profiles ................................................................................ 70

 
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1.0 Executive Summary 

Use Profile: Abamectin is a mixture of avermectin B1 [a mixture of avermectins containing 

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

equal to 20% avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) 

avermectin A1)] and its delta-8,9-isomer. Abamectin is a natural fermentation product of the soil 

bacterium Streptomyces avermitilis. Abamectin is an insecticide/miticide used to control mites, 

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 a petition to propose use of abamectin 

to control mites on caneberries and to establish a tolerance for the caneberry subgroup 13-07A. 

The petitioner proposed addition of the use on caneberries to the Agri-Mek 0.15 EC and EpiMek 0.15 EC labels. IR-4 proposed a tolerance for residues of abamectin in/on the caneberry 

subgroup 13-07A. 

Syngenta Crop Protection LLC (Syngenta) has submitted a petition to propose use of abamectin 

on soybeans and sweet corn. The petitioner proposes addition of the uses on soybeans and sweet 

corn to the labels for Agri-Flex® Miticide/Insecticide, Agri-Mek® SC Miticide/Insecticide, EpiMekTM SC Miticide/Insecticide, and Epi-MekTM SCL Miticide/Insecticide. Syngenta proposed 

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

and soybean commodities (forage, hay, and seed). 

Syngenta has also proposed use of two new end-use products (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). 

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

butoxide for use on lactating dairy cattle. An ear tag use has been registered on beef cattle and 

non-lactating dairy cattle. Tolerances for abamectin on fat, meat, and meat byproducts of cattle 

were previously increased to reflect that use. This review concerns residues in milk. No 

tolerance on milk was proposed. This review concerns only abamectin; piperonyl butoxide has 

been under separate review. 

Toxicity/Hazard: The most recent risk assessment for abamectin was conducted in 2012 (DP# 

D402677. Since then, the Agency has re-evaluated the entire abamectin and emamectin 

toxicological database along with additional studies published in the open literature. The points 

of departures (PODs), uncertainty factors (UFs) and safety factor (SFs) for abamectin and 

emamectin have been altered based on this re-evaluation. In addition, the toxicity of the two 

structurally related chemicals (abamectin and emamectin) have been compared for consistency, 

and all the toxicity data were considered together in a cumulative screen using similar endpoints. 
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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. The toxicity endpoints and PODs for all exposure scenarios were 

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

dogs. The PODs selected from the dog studies are based on clear NOAELs and protective of all 

the adverse effects seen in the studies conducted in rats, CD-1 mice, and rabbits. There are no 

residual uncertainties of pre and/or post-natal toxicity to infants and children. Therefore, the 

default 10X Food Quality Protection Act (FQPA) safety factor has been reduced to 1X. 

Dietary Exposure (Food/Water): 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 (%CT) 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 50% of the aPAD for the 

general U.S. population and 90% of the aPAD for children 1-2 years old, the most highly 

exposed population subgroup. 

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 3.3% of the 

cPAD for the general U.S. population and 16% of the cPAD for children 1-2 years old, the most 

highly exposed population subgroup. 

Residential Exposure: The level of concern (LOC) risk from residential exposure is a margin of 

exposure (MOE) of 100. Residential exposure estimates from the proposed golf course turf use 

are not of concern for adults and children 11-16 years old; the short-term 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 postapplication 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, and thus do not need to be updated. 

Aggregate Risk: For the proposed uses, human health aggregate risk assessments have been 

conducted for acute aggregate exposure (food + drinking water), short-/intermediate-term 

aggregate exposure (food + residential exposure + drinking water), and chronic aggregate 

exposure (food + drinking water) scenarios. For short-/intermediate-term aggregate exposure, 

the MOEs are greater than the LOC and thus there are no risks of concern. All potential 

exposure pathways were assessed in the aggregate risk assessment. None of the aggregate 
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exposure and risk estimates exceed HED's level of concern. An aggregate risk assessment for 

cancer is not required since abamectin is classified as “not likely to be carcinogenic to humans.” 

Occupational Exposure/Risk: The level of concern (LOC) risk from occupational exposure is 

a margin of exposure (MOE) of 100. Based on all of the proposed uses, occupational exposures 

to abamectin are expected for short- and intermediate-term durations when conducting handling 

and 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 

indicate that short- and intermediate-term combined (dermal + inhalation) risk estimates are not 

of concern at baseline mitigation without personal protective equipment (PPE). Short- and 

intermediate-term MOEs range from 360 to 25,000. Note that only engineering control 

(enclosed cockpit) data are available to assess risks to handlers operating aircraft. 

The results of the quantitative occupational post-application exposure and risk assessment 

indicate that short- and intermediate-term dermal risk estimates are not of concern at baseline 

mitigation without PPE. Short- and intermediate-term MOEs range from 3,700 to 5,400. 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. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for abamectin. 

Screening Cumulative Assessment of Abamectin and Emamectin: As discussed in Appendix 

H, HED has determined based on screening guidance (Pesticide Cumulative Risk Assessment: 

Framework for Screening Analysis, EPA draft memo dated 6/23/15) that abamectin and 

emamectin share a similar toxicological profile and a testable hypothesis can be identified. Thus, 

HED has developed a screening level cumulative analysis using highly conservative exposure 

assumptions. Specifically, dietary and residential exposures were assessed to determine whether 

there would be any potential cumulative concern. This screening assessment indicated that 

aggregate dietary and residential exposures for abamectin and emamectin are below the 

Agency’s levels of concern. 

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

the extent possible, were considered in this human health risk assessment. Dietary and nondietary exposures were considered. 

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 the requested analytical reference standard is provided and a revised Section F is 

submitted, there are no residue chemistry considerations that would preclude granting the 

requested registrations and establishing the recommended tolerance for abamectin on sweet corn, 

soybeans, and the caneberry subgroup 13-07A. 

Provided that a tolerance of 0.015 ppm is proposed for abamectin in milk and the requested 

analytical reference standard is submitted, there are no residue chemistry considerations that 

would preclude granting the requested registration for use of the ear tag on lactating dairy cattle. 

The specific tolerance recommendations are discussed in Section 2.2. There are no 

recommended label modifications. 

2.1 Data Deficiencies 

The registrants must submit five grams of the analytical reference standard for 8,9-Z avermectin 

B1a (NOA427011) to the EPA National Pesticide Standards Repository. 

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 

Syngenta must propose a tolerance of 0.40 ppm for grain, aspirated grain fractions and increase 

some of the established livestock tolerances, as indicated in Table 2.2.2 below. 

Table 2.2.2. Tolerance Summary for Abamectin. 

Commodity 

Established 

Tolerance 

(ppm) 

Proposed 

Tolerance 

(ppm) 

HEDRecommended 

Tolerance 

(ppm)* 

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 
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Table 2.2.2. Tolerance Summary for Abamectin. 

Commodity 

Established 

Tolerance 

(ppm) 

Proposed 

Tolerance 

(ppm) 

HEDRecommended 

Tolerance 

(ppm)* 

Comments 

(correct commodity definition) 

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 none 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 

* Changes from established/proposed tolerances are bolded. 

2.2.3 Revisions to Petitioned-For Tolerances 

As shown in Table 2.2.2 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. 

HED is 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. (There are no livestock feed items associated with the 

proposed use on the caneberry subgroup 13-07A.) 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; and milk from 0.005 to 0.015 

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 cattle. 
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2.2.4 International Harmonization 

The plant tolerance definitions are essentially the same for the US, 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) for abamectin on sweet corn or soybean 

commodities. There are no Codex MRLs for abamectin on caneberries. Canada and the US are 

concurrently establishing the new tolerance on the caneberry subgroup 13-07A at 0.20 ppm. 

Therefore, there are no harmonization issues at this time for plant commodities. 

The livestock residue definitions are essentially the same for the US and Canada; the Codex 

residue definition includes only avermectin B1a and its 8,9-Z isomer, whereas the US and Canada 

include both avermectin B1a and avermectin B1b and their 8,9-Z isomers. There are no Canadian 

tolerances set on livestock commodities. There are some Codex MRLs on livestock 

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

as the US recommended tolerance levels. 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 is attached (Appendix E). 

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. 

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

(SC), granular, bait, gel, and dust. The registered uses include food, food handling 

establishments, and residential uses. 

 
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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 

',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 
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Table 3.1. Abamectin Nomenclature 

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 0.150 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. It has very low water solubility 

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. 

Table 3.3. Summary of Proposed Directions for Use of Abamectin on Caneberry, Cattle Ear Tags, Sweet 

Corn, Soybeans, and Golf Course Turf 

Applic. Timing, 

Type, and 

Equip. 

Formulation1 

[EPA Reg. 

No.] 

Applic. 

Rate 

(lb 

ai/A) 

Max. 

No. 

Applic. 

per 

Season 

Max. 

Seasonal 

Applic. 

Rate 

(lb ai/A) 

PHI 

(days) 

Use Directions and 

Limitations2 

Caneberry (Crop Subgroup 13-07A) 

(Blackberry, loganberry, raspberry ( black and red), wild raspberry and cultivars/varieties, and/or hybrids of 

these)

Postemergence; 

Broadcast foliar 

spray; Ground or 

aerial equipment 

Agri-Mek® 

0.15 EC 

[100-898] 

0.0094-

0.019 

not 

stated 

0.056 7 Restricted Use Pesticide 

Apply when spider mites 

are first observed and 

repeat as needed. 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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Table 3.3. Summary of Proposed Directions for Use of Abamectin on Caneberry, Cattle Ear Tags, Sweet 

Corn, Soybeans, and Golf Course Turf 

Applic. Timing, 

Type, and 

Equip. 

Formulation1 

[EPA Reg. 

No.] 

Applic. 

Rate 

(lb 

ai/A) 

Max. 

No. 

Applic. 

per 

Season 

Max. 

Seasonal 

Applic. 

Rate 

(lb ai/A) 

PHI 

(days) 

Use Directions and 

Limitations2 

 Epi-Mek® 

0.15 EC 

[100-1154] 

Do not apply with aircraft 

in NY state. 

Apply in a minimum of 10 

gals. water by ground or 5 

gal water by air. 

The retreatment interval is 

7 days. The maximum 

number of applications at 

the maximum rate is 3. 

Do not make more than 2 

sequential applications of 

an abamectin- containing 

product. 

A nonionic activator type 

wetting, spreading, and/or 

penetrating adjuvant can be 

used. Do not use binder 

sticker type adjuvants. 

Cattle Ear Tags 

1 or 2 ear tags 

per animal for 2-

5 months per 

treatment 

depending on 

the target pest 

Y-TEX® XP 

820TM 

Insecticide 

Cattle Ear 

Tags 

[39039-17] 

NA NA NA Not 

stated 

Use on beef and dairy 

(including lactating) cattle. 

Reapply as necessary with 

up to two treatments per 

year. Remove tags before 

slaughter. 

Corn (Sweet) 

Postemergence; 

Broadcast foliar 

spray; 

Ground or aerial 

equipment 

Agri-Flex® 

Miticide/ 

Insecticide 

[100-1350]

0.012 –

0.018 

not 

stated 

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 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

Page 14 of 78 

Table 3.3. Summary of Proposed Directions for Use of Abamectin on Caneberry, Cattle Ear Tags, Sweet 

Corn, Soybeans, and Golf Course Turf 

Applic. Timing, 

Type, and 

Equip. 

Formulation1 

[EPA Reg. 

No.] 

Applic. 

Rate 

(lb 

ai/A) 

Max. 

No. 

Applic. 

per 

Season 

Max. 

Seasonal 

Applic. 

Rate 

(lb ai/A) 

PHI 

(days) 

Use Directions and 

Limitations2 

product or more than 0.172 

lb ai/A of any other foliar 

applied thiamethoxam 

containing product per 

season. 

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 

not 

stated 

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 AgriMek® 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 AgriMek® SC/ Epi-MekTM 

SC/Epi-MekTM SCL or any 

other foliarly applied 

abamectin-containing 

product in a growing 

season. 

Soybeans 

Postemergence; 

Broadcast foliar 

spray; 

Ground or aerial 

equipment 

Agri-Flex® 

Miticide/ 

Insecticide 

[100-1350]

0.011-

0.014 

not 

stated 

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. 

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 Human Health Risk Assessment DP No. 426599 

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Table 3.3. Summary of Proposed Directions for Use of Abamectin on Caneberry, Cattle Ear Tags, Sweet 

Corn, Soybeans, and Golf Course Turf 

Applic. Timing, 

Type, and 

Equip. 

Formulation1 

[EPA Reg. 

No.] 

Applic. 

Rate 

(lb 

ai/A) 

Max. 

No. 

Applic. 

per 

Season 

Max. 

Seasonal 

Applic. 

Rate 

(lb ai/A) 

PHI 

(days) 

Use Directions and 

Limitations2 

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; 

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 

not 

stated 

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. 

Do not apply more than 

0.019 lb ai/A of AgriMek® 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 AgriMek® SC/Epi-MekTM SC/ 

Epi-MekTM SCL or any 

other foliarly applied 

abamectin-containing 

product in a growing 

season. 

Turfgrass (including Golf Course Greens, Tees, and Fairways only) 

Broadcast 

(ground only) 

AgadorTM 

0.17 SC 

Nematicide 

[100-RLNO] 

0.069 

lb ai/A 

0.000803 

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 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

Page 16 of 78 

Table 3.3. Summary of Proposed Directions for Use of Abamectin on Caneberry, Cattle Ear Tags, Sweet 

Corn, Soybeans, and Golf Course Turf 

Applic. Timing, 

Type, and 

Equip. 

Formulation1 

[EPA Reg. 

No.] 

Applic. 

Rate 

(lb 

ai/A) 

Max. 

No. 

Applic. 

per 

Season 

Max. 

Seasonal 

Applic. 

Rate 

(lb ai/A) 

PHI 

(days) 

Use Directions and 

Limitations2 

DivanemTM 

0.15EC 

Nematicide 

[100-RLRN] 

0.067 

lb ai/A 

0.000803 

lb ai/gal 

0.267 NA 

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. 1 Formulation code: EC = emulsifiable concentrate, SC = suspension concentrate; SCL = suspension concentrate.

2

 Restrictions that apply to sweet corn and soybean labels: 

Restricted Use Pesticide 

To avoid illegal residues, Agri-Flex®/Agri-Mek® SC/ Epi-MekTM SC/Epi-MekTM SC must be mixed with a nonionic activator type wetting, spreading and/or penetrating spray adjuvant. Do not use binder or sticker type 

adjuvants. 

Do not apply with aircraft in NY state. 

Do not apply in less than 10 gal water /A by ground or 5 gal water/A by air. 

The retreatment interval is 7 days. 

For resistance management, do not make more than 2 sequential applications of Agri-Flex®/Agri-Mek® SC/ EpiMekTM 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 atplant 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. 3

 Application rate is based on use direction to “apply in 2 gallons of water per 1,000 square feet of turf.” 

3.4 Anticipated Exposure Pathways 

The Registration Division has requested an assessment of human health risk to support the 

proposed new uses of abamectin on the caneberry subgroup 13-07A, sweet corn, soybeans, 

beef/dairy cattle ear tags, and turf (golf course greens, tees, and fairways). 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 (11 to 16 years old) conducting recreational 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

Page 17 of 78 

golfing activities. There are proposed and registered residential uses of abamectin, so there is 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 

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

methylamine (circled groups in the following figures). 

Since the last risk assessment (D402677 & D405843, N. Dodd, 12/20/2012), the Agency has reevaluated the entire abamectin and emamectin toxicological database along with studies 

published in the open literature. Due to the similarity of the two chemicals the Agency has reevaluated 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 

macrocyclic lactone pesticides (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 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

Page 18 of 78 

Assessment: Framework for Screening Analysis, EPA draft memo dated 6/23/15) 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 

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 development 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 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

Page 19 of 78 

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 

The toxicology database is complete except for subchronic dermal toxicity and an 

immunotoxicity studies. HED’s HASPOC, however, based on a weight of evidence 

consideration has granted waivers to these studies (HASPOC Reports: TXR Numbers 0056687 

and 0056509). The toxicology database include the following studies: 

 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. 

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 abamectin was rapidly 

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

after repeated exposure. 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. 

 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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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 is 1% of the applied dose (HIARC report, 

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 that those for 

neurotoxicity. 

Integral to the dose response assessment in mammals for this class of compounds is Pglycoprotein (P-gp). 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). 

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, P-gp 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, at this time, does not 

believe that the early post-natal findings in the rat are relevant to human newborns or young 

children. 

The CF-1 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. 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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Many studies on human multidrug resistance (MDR-1) gene encoding P-gp and polymorphism of 

MDR-1 gene are available. The data are inconclusive with respect to the functional significance 

of the genetic variance in P-gp in human. At the present, 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 for risk assessment. Among the test animals 

with fully functional P-gp, the beagle dog is the most sensitive species (Appendix A). 

 

Abamectin is classified as a Group E chemical (Evidence of Non-carcinogenicity for Humans) 

based on the lack of evidence for carcinogenicity in mice or rats and no concern for mutagenicity 

(TXR No 0011983). 

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) 

The PODs and the toxicity endpoints of concern selected from the subchronic and chronic oral 

toxicity studies in the dogs are protective of all the adverse effects seen in the studies conducted 

with rats, CD-1 mice, and rabbits. There are no residual uncertainties for pre and/or post-natal 

toxicity to infants and children. Therefore, the 10X FQPA safety factor is reduced to 1x. The 

detailed rationale are presented in 4.4.1 to 4.4.4. 

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 (HASPOC Reports: TXR 0056687; 1/07/2013 and TXR 0056509; 1/30/2013). 

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 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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There was no evidence of increased susceptibity following in utero exposure to CD-1 mice or 

Sprague-Dawley rats for following pre/post-natal exposure to rats in a one-generation 

reproduction study 

In the developmental toxicity with rabbits, there was evidence for qualitative susceptibility 

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

mg/kg/day. In contrast, the fetal effects at this dose (2.0 mg/kg/day) were much more severe, 

consisting of cleft palate, clubbed foot, and death. The degree of concern is low for the observed 

susceptibility since the developmental effects were seen at a dose (2.0 mg/kg/day) that was 10-

fold higher than the POD (0.25 mg/kg/day) used for overall risk assessment. (i.e, the POD is 

protective of developmental effects seen in the rabbit fetuses). 

The rat reproduction toxicity and developmental neurotoxicity studies with abamectin 

demonstrated both qualitative and quantitative susceptibility in the pups to the effects of 

abamectin (observed as decreased 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 based on the following 

weight of evidence considerations: 1) there was no evidence of increased susceptibility following 

in utero exposure to mice and rats: 2) there was no evidence of increased susceptibity following 

pre and post-natal exposure in the one-generation study; 3) the findings in the DNT and the rat 

two-generation reproduction study are attributable to the rat pups being more susceptible since 

the P-gp is not fully developed and therefore are not relevant for human infants; 4) the 

developmental effects in the rabbit developmental study was seen a much higher dose than the 

POD used for overall risk assessment; and 5) there are no residual uncertainties for pre-and/or 

postnatal toxicity or in the exposure database. 

4.4.4 Residual Uncertainty in the Exposure Database

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

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 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 

assessments will not underestimate the risks to infants and children from the requested uses. 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

Page 23 of 78 

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 points of 

departure 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 were selected. The point of 

departure (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 three 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 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. 

Effects seen in the subchronic and chronic dog studies: The effects seen in the subchronic 

(gavage) and chronic dog studies were similar despite repeated dosing, suggesting the 

response could 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 point of departure. 

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 

point of departure (0.25 mg/kg/day) inhalation route is appropriate and protective for these 

exposure scenarios. 

For residential exposure risk assessments, the LOC is a MOE of 100 based on a total uncertainty 

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

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

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

Carcinogenicity: Abamectin is classified as a Group E Chemical; Evidence for Noncarcinogenicity in Humans based on lack of evidence for carcinogenicity in mice and rats and no 

concern for mutagenicity (TXR No. 0011983). 

Combined routes of exposure: Oral, dermal and inhalation routes of exposure could be 

combined since the toxicity endpoints were similar. 

Table 4.5.1 and 4.5.2 summarize the toxicity endpoints and points of departure 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 

Dermal mg/kg/day. 

(Short-Term 

and 

IntermediateTerm)

NOAEL = 

0.25 

mg/kg/day 

Dermal 

Absorption = 

1%

UFA = 10x 

UFH = 10x 

FQPA SF =1x 

LOC: MOE 

= 100
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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 

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 

Intermediate-Term) 

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 (Short-Term 

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 

Cancer (oral, dermal, 

inhalation) 

Classification: Group E Chemical based on the absence of evidence for carcinogenicity in 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 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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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. 

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 (N. Dodd, D402677, D405843, 12/20/2012). 

Residues of concern for the risk assessment and 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)** 

Livestock Ruminant* Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers) 

Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers) 

Poultry Not applicable Not applicable 

Drinking Water Parent (avermectin B1a and 

B1b), NOA 448111, NOA 

448112, NOA 426289, NOA 

445495, NOA 457464, and 

NOA 457465 

Not applicable 

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

** No rotational crop tolerances have been established. 

5.2 Food Residue Profile 

Plant Commodities 

Adequate field trials were submitted for abamectin on caneberries, sweet corn, and soybeans. 

The field trials for caneberries, sweet corn and soybeans 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. The field trials 

on caneberries, sweet corn, and soybeans are summarized below and tabulated in Table F.1 in 

Appendix F. A processing study on soybeans indicated that combined residues of avermectin 
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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). 

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 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 Agency has reevaluated the Maximum Reasonable Dietary Burden (MRDB) for livestock considering the 

proposed uses, and additional modifications to milk, meat by products, and fat tolerances are 

required. Note that the Agency generally set 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 may be found in the chemistry assessment of the 

proposed uses (D410993, N. Dodd, 5/14/14;D414022, N. Dodd, 5/15/14; D416280, N. Dodd, 

5/15/14). 

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

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

poultry commodities; therefore, no poultry feeding studies are required. 

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 
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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 background (chronic) dietary assessment, 

the annual mean concentration of 0.30 ppb in surface water was used. 

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 (% CT) 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. 

Background Dietary assessment: A refined background (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 % CT 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 

(D415573, Sepehr Haddad, 11/6/13 and D420218, Don Atwood, Ph.D., 7/23/14) were used in 

the acute dietary risk assessment for the following crops: almonds: 80%; apples: 20%; apricots: 

40%; avocados: 60%; blackberries: 55%; cantaloupes: 40%; celery: 70%; cherries: 15%; corn, 

sweet, kernel plus cob with husk removed: 44%; cotton: 25%; cucumbers: 10%; grapefruit: 85%; 

grapes: 25%; hazelnuts: 2.5%; honeydew: 35%; lemons: 55%; lettuce: 40%; nectarines: 20%; 

oranges: 60%; peaches: 20%; pears: 85%; pecans: 2.5%; peppers: 30%; pistachios: 2.5%; 

potatoes: 20%; prunes: 30%; pumpkins: 10%; raspberries: 55%; soybeans: 11%; spinach: 45%; 

squash: 15%; strawberries: 45%; tangerines: 55%; tomatoes: 25%; walnuts: 55%; and 

watermelons: 15%. For livestock commodities other than poultry and swine commodities, 85% 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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crop treated based on the feed item dried citrus pulp was used. For poultry and swine 

commodities, 25% crop treated based on cotton meal was used. 

The following average percent crop treated estimates for abamectin provided by BEAD 

(D415573, Sepehr Haddad, 11/6/13 and D420218, Don Atwood, Ph.D., 7/23/14) were used in 

the chronic dietary risk assessment for the following crops: almonds: 65%; apples: 10%; 

apricots: 15%; avocados: 35%; blackberries: 48%; cantaloupes: 20%; celery: 45%; cherries: 5%; 

corn, sweet, kernel plus cob with husk removed: 38%; cotton: 15%; cucumbers: 5%; grapefruit: 

70%; grapes: 15%; hazelnuts: 2.5%; honeydew: 20%; lemons: 40%; lettuce: 20 %; nectarines: 

20%; oranges: 40%; peaches: 5%; pears: 75%; pecans: 1%; peppers: 15%; pistachios:1%; 

potatoes: 5%; prunes: 5%; pumpkins: 5%; raspberries: 48%; soybeans: 8%; spinach: 30%; 

squash: 5%; strawberries: 35%; tangerines: 35%; tomatoes: 15%; walnuts: 25%; and 

watermelons: 10%. For livestock commodities other than poultry and swine commodities, 70% 

crop treated based on dried citrus pulp was used. For poultry and swine commodities, 15% crop 

treated based on cotton meal was used. 

All commodities included for food handling residues were assigned the value of 5% CT (DP# 

413125, J. Becker, 10/7/2014). 

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 50% of the aPAD for the general U.S. population and 

90% of the aPAD for children 1-2 years old, the most highly exposed population subgroup.

Although this assessment was refined to the extent possible with the data available, it could be 

further refined with monitoring data. Limited Pesticide Data Program (PDP) monitoring data are 

available for abamectin, but the data that are available indicate that generally actual residues are 

lower than those found in the crop field trials. Therefore, these risk estimates could be 

considerably lower if monitoring data were available to better assess actual exposure. A 

sensitivity analysis of the acute dietary risk assessment found that the commodity leading to the 

greatest contribution to abamectin risk estimates was milk. Since this assessment involves new 

uses monitoring data could not be used for milk, but many of the assumptions in this exposure 

estimates (deterministic value, high percent crop treated value), will overestimate exposure to 

abamectin in milk and therefore, represents a conservative representation of risk. 

5.4.4 Background Dietary Exposure

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

chronic dietary risk assessment was not conducted because the endpoints are acute in nature.
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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. 

Although this assessment was refined to the extent possible with the data available, it could be 

further refined with monitoring data. Limited Pesticide Data Program (PDP) monitoring data are 

available for abamectin, but the data that are available indicate that generally actual residues are 

lower than those found in the crop field trials. Therefore, these exposure estimates could be 

considerably lower if monitoring data were available to better assess actual exposure.

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) 

Background Dietary 

Exposure 

Dietary Exposure 

(mg/kg/day) % aPAD* (mg/kg/day) 

General U.S. Population 0.001249 50 0.000082 

All Infants (< 1 year old) 0.001683 67 0.000128 

Children 1-2 years old* 0.002243 90 0.000393 

Children 3-5 years old 0.001295 52 0.000239 

Children 6-12 years old 0.000824 33 0.000137 

Youth 13-19 years old 0.000549 22 0.000069 

Adults 20-49 years old 0.000448 18 0.000056 

Adults 50-99 years old 0.000357 14 0.000051 

Females 13-49 years old 0.000416 17 0.000054 

*

The subpopulation with the highest risk estimates is bolded. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

At this time, 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 

require a reassessment of all currently registered residential uses with all current policies. These 

revisions of residential exposures will impact the human health aggregate risk assessment.
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The proposed end-use products (for control of turf-parasitic nematodes on golf course greens, 

tees, and fairways) that may lead to these post-application exposures include the following: 

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

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

The products already registered for residential use sites 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) of both dust and gel formulations. For this assessment, the exposures 

and risk estimates for applying outdoor granular baits are 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/risk assessment developed for residential handlers is based on the 

following scenarios: loading/applying GB outdoor via (1) push-type spreaders, (2) belly grinders, 

(3) spoons, (4) hand, and (5) cup or shaker; and (6) applying granular bait indoor 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. 

 

Table 6.1. Residential Handler Non-Cancer Exposure and Risk Estimates for Abamectin.

Exposure 

Scenario 

Dermal 

Unit 

Exposure 

Inhalation 

Unit 

Exposure 

Maximum 

Application 

Rate 

Area Treated 

or Amount 

Handled 

Dailyb

Dermal Inhalation Total 

Dosec MOEd Dosee MOEf MOEg

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 0.000231 

lb ai/A 0.5 acres 1.20×10-8 21,000,000 3.8E-09 66,000,000 16,000,000 

Belly Grinders 360 0.039 

5.31×10-9 

lb ai/sq ft 

1200 sq ft 2.90×10-7 870,000 3.1E-09 80,000,000 860,000 

Spoon 6.2 0.087 

100 sq ft 

4.10×10-10 610,000,000 5.8E-10 430,000,000 250,000,000 

Cup 0.11 0.013 7.30×10-12 34,000,000,000 8.6E-11 2,900,000,000 2,700,000,000

Hand Dispersal 160 0.38 1.10×10-8 24,000,000 2.5E-09 99,000,000 19,000,000 

Shaker Can 0.11 0.013 7.30×10-12 34,000,000,000 8.6E-11 2,900,000,000 2,700,000,000

Mixer/Loader/Applicator for Indoor Bait Application 

Bait (granular; 160 0.38 0.0000132 2.60×10-7 940,000 6.30×10-8 4,000,000 760,000 

 

1

 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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Table 6.1. Residential Handler Non-Cancer Exposure and Risk Estimates for Abamectin.

Exposure 

Scenario 

Dermal 

Unit 

Exposure 

Inhalation 

Unit 

Exposure 

Maximum 

Application 

Rate 

Area Treated 

or Amount 

Handled 

Dailyb

Dermal Inhalation Total 

Dosec MOEd Dosee MOEf MOEg

mg/lb ai mg/kg/day LOC = 100 mg/kg/day LOC = 100

hand dispersal) lb ai/package/day 

a 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). 

b Exposure Science Advisory Council Policy #9.1. Based on HED’s SOPs: Lawns/Turf (January 2012). 

c 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). 

d 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. 

e 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). 

f 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. 

g 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) 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, bait 

placements are intended to be placed in cracks and crevices where direct contact by adults and 

children (1 to <2) is unlikely. 

However, residential post-application exposure for adults and children (6 to <11 and 11 to <16) 

is possible for the newly proposed use of abamectin on golf courses. Adults and children (6 to 

<11 and 11 to <16) 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 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 a

MOE b 

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 0.0000203 12,000 

Child 11 to < 16 years old Golfing 0.0000237 11,000 

Child 6 to < 11 years old Golfing 0.0000278 9,000 

a Dermal Dose = TTR/DFR (μg/cm2) × CF1 (0.001 mg/μg) × TC (cm2/hr) × Exposure Time (hrs) ÷ 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 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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old. Exposure time for golfing: 4 hrs. 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. 

b 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.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-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 Spray Drift 

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 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. 

 

2

 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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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 90% of the aPAD, which is below the level of concern. 

7.2 Short- and Intermediate-Term Aggregate Risk 

The short-/intermediate-term aggregate risk assessment estimates risks likely to result from 

exposure to abamectin residues from food, drinking water, and residential pesticide uses. Highend 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. 

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 Only Exposure 

(Liquid Application to Golf Course Turf) 0.0000203 12,000 

Children 11 to < 16 years old 

Post-Application: Dermal Only Exposure 

(Liquid Application to Golf Course Turf) 0.0000237 11,000 

Children 6 to < 11 years old 

Post-Application: Dermal Only Exposure 

(Liquid Application to Golf Course Turf) 0.0000278 9,000 

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. 
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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 0.000082 0.0000203 0.0001023 2400 

Children 11 to 

<16 years old 0.25 100 0.0025 0.000137 0.0000237 0.0001607 1600 

Children 6 to 

<11 years old 0.25 100 0.0025 0.000137 0.0000278 0.0001648 1500 

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. 

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. As noted in Section 4.5 the same 

point of departure can be used for all exposure durations, so the acute aggregate risk assessment 

will be protective of the chronic assessment as well. 

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

EPA’s Office of Pesticide Programs has developed a draft guidance document dated 2/23/15, 

entitled Pesticide Cumulative Risk Assessment: Framework for Screening Analysis. This draft 

document provides guidance on how to screen groups of pesticides for cumulative evaluation 

using a two-step approach beginning with the evaluation of available toxicological information 

and, if necessary, followed by a risk-based screening approach. This framework supplements the 

existing guidance documents for establishing common mechanism groups (CMGs) (Guidance 

for Identifying Pesticide Chemicals and Other Substances That Have a Common Mechanism of 

Toxicity, dated 1/29/99) and conducting cumulative risk assessments (CRAs) (Guidance on 

Cumulative Risk Assessment of Pesticide Chemicals That Have a Common Mechanism of 

Toxicity, dated 1/14/02). 

The Agency has utilized this screening framework for abamectin. and determined that abamectin 

along with emamectin form a candidate CMG. Although there is not adequate data at this time 

for establishing key events in a pathway as described in 1999 CMG guidance (e.g., lack of dose 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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or temporal concordance of proposed key events), there are sufficient toxicological data to 

suggest a common pathway; therefore, EPA has determined that these pesticides form a 

candidate CMG because they share characteristics to support a testable hypothesis for a common 

mechanism of action. Consistent with the guidance described in the cumulative screening 

framework, the Agency has conducted a screening-level cumulative exposure assessment. This 

screening assessment, included as Appendix H to this assessment, indicates that cumulative 

aggregate dietary and residential exposures for abamectin and emamectin are below the 

Agency’s levels of concern. 

9.0 Occupational Exposure/Risk Characterization

9.1 Short-/Intermediate-Term 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 exposure is expected from the proposed 

agricultural uses. The quantitative exposure/risk assessment developed for occupational handlers 

is based on several scenarios which include mixing/loading/applying the liquid formulations of 

abamectin. The use sites are summarized in Section 3.3. Methods of application include aerial, 

chemigation, groundboom, and handheld equipment. Flagging for aerial use is also a potential 

source of worker exposure. Refer to Table G.1 in Appendix G for a detailed list of each 

scenario. 

The results of the occupational handler exposure and risk assessment indicate that short- and 

intermediate-term inhalation risk estimates are not of concern (i.e. all MOEs ≥ 100) at baseline 

mitigation (no PPE). Since the short- and intermediate-term PODs are the same, the combined 

MOEs are also the same, ranging 360 to 25,000. Note that only engineering control (enclosed 

cockpit) data are available to assess risks to handlers operating aircrafts. 

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. 
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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 

Based on the proposed use patterns, post-application exposure to abamectin is possible. 

Agricultural workers and golf course maintenance workers performing typical post-application 

activities may receive dermal exposure to abamectin residues. 

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. 

The short- and intermediate-term post-application exposure scenarios associated with the newly 

proposed uses are summarized in Table G.2 in Appendix G. All risk estimates are not of concern 

(MOEs range from 530 to 67,000) on day 0 (12 hours after application). 

Guideline 875.2100 - Dislodgeable Foliar Residue (DFR):

Since the highest estimated occupational post-application exposure using default DFR values for 

abamectin is minimal in comparison to the LOC (i.e. the calculated MOE is greater than 2 times 

higher than the LOC, MOE = 530 compared to the LOC of 100; EPA is waiving the 40 CFR 

DFR data requirement. In this instance, it is unlikely that chemical-specific DFR data would be 

needed to further refine exposure assessments or would add appreciably to our overall 

understanding of the availability of dislodgeable foliar pesticide residues for abamectin. 

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. 

Occupational Post-Application Inhalation Exposure/Risk Estimates 

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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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. 

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. 

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. Thus, the 

12-hour REI on the proposed label is adequate to protect workers. 

10.0 References 

(Refer to Appendix B for toxicology literature references.)

D. Atwood, 7/23/14, 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, 5/15/14, 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. Becker, 10/7/14, D413125, Upper Bound Estimate of the Likelihood of Insecticide Residues 

on Food Resulting from Treatment in Food Handling Establishments. 
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N. Dodd, 4/15/15, DP No. 426800, Emamectin Benzoate: Acute and Chronic Aggregate 

Dietary (Food and Drinking Water) Exposure and Risk Assessments using Revised Toxicology 

Endpoints. 

N. Dodd, 5/15/14, 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, 5/15/14, 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, 5/15/14, 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, 10/28/14, DP No. D421348, Abamectin Acute and Chronic Aggregate Dietary (Food 

and Drinking Water) Exposure and Risk Assessments for the Section 3 Registration Actions for 

Uses on Caneberries, Sweet Corn, Soybeans, and Dairy Cattle Ear Tags. 

N. Dodd, 2/20/13, DP No. D402152, Emamectin Benzoate: Acute and Chronic Aggregate 

Dietary (Food and Drinking Water) Exposure and Risk Assessments for a Tolerance on Imported 

Wine. 

N. Dodd, 4/12/13, DP No. D402151, Emamectin Benzoate. Human Health Risk Assessment 

for a Proposed Tolerance on Imported Wine Grapes. 

N. Dodd, 12/20/12, DP No. D402677, Abamectin. Human Health Risk Assessment for Uses of 

the SC Formulation on Cotton and Strawberry. 

N. Keller, 12/18/14, DP No. D412860, 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). 

S. Haddad, 11/6/13, DP No. 415573, Usage Report Package in Support of Abamectin (PC Code 

122804). 

 
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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. 

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. 

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/Non-guideline 

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/carcinogenici

ty- rats 

 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/Carcinogenic

ity- mice 

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/Non-Guideline 

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 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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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/Non-guideline 

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/non-guideline 

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. 426599 

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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 S-9 

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/non-Guideline 

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. 

870.7800 

Immunotoxicity 

This study is waived (HASPOC Report: TXR 0056687, 01/07/2013) 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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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 

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 

Maternal LOAEL = = 0.075 

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 

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 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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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: 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

	 	
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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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 B1a binds 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 (P- 

 glycoprotein): 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. 426599 

Page 49 of 78 

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. 426599 

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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. 426599 

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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; and the Residential 

Standard Operating Procedures (SOPs: Lawns/Turf) 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 website3

. 

 

 

3 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. 426599 

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Appendix E. International Residue Limits Table for Abamectin 

Abamectin (122804; 11/01/12 and 9/19/13) 

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-Odemethyl avermectin A1a) 

and less than or equal to 

20% avermectin B1b (5-Odemethyl-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 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition: 

US Canada Mexico2 Codex3 

Soybean, forage 0.30 

Soybean, hay 1.0 

Soybean, seed 0.01 

Completed: M. Negussie; 11/01/12 and 9/19/13 

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.

 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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Appendix F. Abamectin Field Trial Tables 

Table F.1. Summary of Residue Data from Caneberry, Soybean, and Sweet Corn Field Trials with 

Abamectin 

Commodity Total 

Applic. 

Rate, 

 (lb ai/A) 

PHI 

(days) 

Residue Levels1,2

 (ppm) 

n 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. 

 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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Appendix G. Abamectin Occupational and Residential Exposure Tables 

Table G.1. Occupational Handler Exposure and Risk Estimates for Proposed Abamectin Uses

Exposure 

Scenario 

Crop or 

Targeta 

Unit Exposureb

Max 

App 

Ratec

Area 

Treated or 

Amount 

Handled 

Dailyd

Dosee MOEf 

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 

350 0.000183 0.0000183 1,400 14,000 1,300 Typical 

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 

Typical 350 0.00000416 0.00000565 60,000 44,000 25,000

Field Crops 

HighAcreage 

Field Crops 

1200 0.0000143 0.0000194 17,000 13,000 7,400 

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 

Orchard 11 0.35 0.019 350 0.00000915 0.0000291 27,000 8,600 6,500 
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Table G.1. Occupational Handler Exposure and Risk Estimates for Proposed Abamectin Uses

Exposure 

Scenario 

Crop or 

Targeta 

Unit Exposureb

Max 

App 

Ratec

Area 

Treated or 

Amount 

Handled 

Dailyd

Dosee MOEf 

Dermal Inhalation Dermal Inhalation Dermal Inhalation Total 

μg/lb ai lb ai/A Acres mg/kg/day ST/IT LOC = 100 

Flagging for 

Aerial 

Application 

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 

a “Orchard” includes caneberries (crop subgroup 13-07A). 

 “Typical Field Crops” include sweet corn. 

 “High-Acreage Field Crops” include corn and soybeans. 

b 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. 

c Based on the maximum application rates on the proposed labels (Reg. Nos. 100-898, -1154, -1350, -1351, -1408, -1439, RLNO, and -RLRN). 

d Exposure Science Advisory Council Policy #9.1. 

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. 

 Total MOE = NOAEL (mg/kg/day) ÷ (Dermal Dose + Inhalation Dose). ST/IT Combined Dermal/Inhalation NOAEL = 0.25 mg/kg/day.

 
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Table G.2. Short-Term Post-Application Exposures and Risk Estimates for Abamectin 

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. 

 
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Appendix H. Abamectin and Emamectin Cumulative Screening Assessment

H.1.0 Introduction 

EPA’s Office of Pesticide Programs has developed to a draft guidance document dated 6/23/15, 

entitled Pesticide Cumulative Risk Assessment: Framework for Screening Analysis. This 

document provides guidance on how to screen groups of pesticides for cumulative evaluation 

using a two-step approach beginning with the evaluation of available toxicological information 

and, if necessary, followed by a risk-based screening approach. This framework supplements the 

existing guidance documents for establishing common mechanism groups (CMGs)4 and 

conducting cumulative risk assessments (CRA)5. Abamectin and emamectin share a common 

toxicological profile and a testable hypothesis has been identified (Section H.2.0 below). 

Consistent with the framework, a screening-level cumulative assessment was conducted for the 

candidate CMG of avermectin macrocyclic lactones, which contains the insecticides abamectin 

and emamectin. This screen, which adds exposures of abamectin and emamectin, is expected 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 is registered for use on various food and feed crops, as well as some residential use 

sites including fire ant mounds and indoor sites. Additional food and residential uses are 

proposed. 

Emamectin is registered for use on various raw agricultural commodities, including cotton, 

turnip greens, pome fruit, tree nuts, Brassica and other leafy vegetables, cucurbits, fruiting 

vegetables, tobacco, and wine grapes. It is also registered as a cockroach bait and tree injection. 

Currently there are no proposed or registered residential uses of emamectin. 

Both insecticides are registered for use on the following crops: cotton, tree nuts, apples, pears, 

fruiting vegetables, cucurbits, and leafy vegetables, except Brassicas. Tolerances are also 

established for both chemicals for livestock commodities and grapes (the tolerance for 

emamectin applies to imported wine grapes only). Furthermore, since there is an “all foods” 

tolerance that applies to the use of abamectin in food handling establishments (FHE), there could 

be co-occurrence of residues in almost any food that bears residues of emamectin. The “all 

foods tolerance” is lower than tolerances based on agricultural uses, so the FHE uses are 

expected to be minor contributors to the exposure. 

Based on the use patterns for abamectin and emamectin, the potential routes and durations of 

exposure for cumulative consideration include acute exposure (dietary only) and short-term 

exposure (including dietary and residential, with residential exposure from abamectin only since 

there are no residential uses from emamectin).

 

4 Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common 

Mechanism of Toxicity (USEPA, 1999) 5 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common 

Mechanism of Toxicity (USEPA, 2002)
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H.2.0 Toxicological Considerations in Determining a Candidate CMG 

H. 2.1 Chemical Structural Similarity 

Emamectin is a derivative of abamectin, and they are structurally and toxicologically related. No 

other pesticides were identified with sufficient structural similarity for consideration in the 

candidate CMG. The only difference between abamectin and emamectin is that abamectin has a 

hydroxyl moiety at the 4” position of the tetrahydropyrane ring whereas, in emamectin, the 

hydroxyl group is replaced by a methylamine (circled groups in the following figures). 

Abamectin Emamectin 

H. 2.2 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 (Appendixes 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 occurred at the same LOAEL or above with a 

common NOAEL (0.25 mg/kg/day) for establishing the point of departure for risk 

assessment (POD). Although the dog studies on these two pesticides did not employ the 

same dose levels, the effects demonstrated a similar dose-response relationship for the 

two chemicals. 

 Both abamectin and emamectin have similarly low dermal absorption (i.e., 1% for 

abamectin and 1.8% for emamectin). 

 
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H. 2.3 Toxicological evaluation to determine a CMG 

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 a 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 (e.g., 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. there is not currently adequate data for establishing key 

events in a pathway as described in the mode of action/adverse outcome pathway (MOA/AOP) 
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framework6,7,8,9 (e.g., lack of dose or temporal concordance of proposed key events). In the 

absence of such data, the key biological steps leading to the adverse outcome (i.e., the 

mammalian mechanism of action) cannot be established and by extension a science policy 

document establishing a common mechanism group in accordance with EPA’s 1999 CMG 

guidance cannot be developed. 

Nevertheless, 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. 

H.3.0 Dose Response Assessment 

H.3.1 Selection of Points of Departure for Screening Cumulative Assessment 

As discussed in Section 4.0, the Agency has re-evaluated the entire toxicity databases for 

abamectin and emamectin and the available literature information on the polymorphism in the 

human gene encoding P-gp. The toxic effects observed in the CF-1 mouse and rat juvenile pup 

studies 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 Agency considered results from abamectin and emamectin toxicological studies conducted 

in the species which do not have diminished P-gp function for selecting PODs for risk 

assessment. 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 and emamectin. The 

cumulative screen relies on toxicity studies conducted in the dog, with neurotoxic effects for 

both abamectin and emamectin. The points of departure 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 point of departure used for both chemicals 

is the NOAEL of 0.25 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 points of departure 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. 

 

6

 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.

7 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. 8 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. 9 Sonich-Mullin, C. et al. (2001), IPCS Conceptual Framework for Evaluating a Mode of Action 

for Chemical Carcinogenesis, Regul Toxicol Pharmacol 34:146-152.
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Therefore, the extrapolation factor of 100x (10x for interspecies extrapolation and 10x for 

intraspecies difference) was applied for both chemicals. 

Finally, the toxicity endpoints and points of departure for the relevant exposure scenarios are the 

same for abamectin and emamectin; consequently, identification of an index chemical for 

developing screening level relative potency factor (RPF) is not needed for purposes of screening 

analysis. For dermal exposure assessment, 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 points of departure of the two chemicals are compared in Table H.3.1 

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.3.1. 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 

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. 

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 

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. 
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H.3.2 FQPA Safety Factor for Protection of Infants and Children 

For both abamectin and emamectin, the toxicity endpoint and point of departure for all exposure 

scenarios are selected from the subchronic and chronic oral toxicity studies in the dogs, whose 

sensitivity to the effects of the abamectin is next to CF-1 mice. 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 studies conducted in human relevant studies with rats, CD-1 mice, and rabbits. 

Therefore, the FQPA safety factor could be reduced to 1x. 

H.3.3 Incorporation of Uncertainty Factors/Extrapolation Factors and the Level of 

Concern MOE. 

The level of concern MOE is 100 for the cumulative screening analysis.

H.4.0 Dietary Cumulative Exposure and Risk Assessment/Characterization 

H.4.1 Food Exposure Pathway 

Abamectin is used on various raw agricultural commodities. Tolerance levels from 40 CFR 

§180.449 are shown in Table H.4.1 below. Abamectin is an 80/20 mixture of avermectin 

B1a/avermectin B1b. For crops and livestock commodities, compliance with the tolerance is 

determined by measuring avermectin B1a, avermectin B1b, and the 8,9-Z isomers. 

Emamectin is used on various raw agricultural commodities. Tolerance levels from 40 CFR 

§180.505 are shown in Table H.4.1 below. Emamectin is a 90/10 mixture of emamectin 

B1a/emamectin B1b. 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. 

Table H.4.1. Abamectin and Emamectin Established and Recommended Tolerances1

Crop Abamectin Tolerances (ppm) Emamectin Tolerances (ppm) 

Almond, hulls 0.10 0.20 

Apple 0.020 --- 

Apple, wet pomace 0.10 0.075 

Avocado 0.020 --- 

Bean, dry, seed 0.01 --- 

Caneberry subgroup 13-07A 0.20 --- 

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 --- 
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Table H.4.1. Abamectin and Emamectin Established and Recommended Tolerances1

Crop Abamectin Tolerances (ppm) Emamectin Tolerances (ppm) 

Citrus 0.02 --- 

Corn, sweet, forage 0.20 

Corn, sweet, kernel plus cob with 

husk removed 

0.01 --- 

Corn, sweet, stover 0.50 

Cotton, gin byproducts 1.0 0.050 

Cotton, undelinted seed 

(entered in DEEM as oil) 

0.02 0.025 

Food products in Food Handling 

Establishments 

0.01 --- 

Fruit, pome, group 11 --- 0.025 

Fruit, stone, group 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 0.02 --- 

Grape, wine1 --- 0.03 

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 

Milk 0.015 0.003 

Nut, tree, group 14 0.01 0.02 

Onion, bulb, subgroup 3-07A 0.01 --- 

Pear 0.02 --- 

Peppermint, tops 

(entered as peppermint and 

peppermint oil) 

0.010 --- 

Pistachio 0.01 0.02 

Plum, prune, dried 0.025 --- 

Poultry, meat 0.02 --- 

Poultry, meat byproducts 0.02 --- 

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 --- 
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Table H.4.1. Abamectin and Emamectin Established and Recommended Tolerances1

Crop Abamectin Tolerances (ppm) Emamectin Tolerances (ppm) 

Spearmint, tops 

(entered as spearmint and spearmint 

top) 

0.010 --- 

Strawberry 0.05 --- 

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 0.020 0.020 

Vegetable, leafy, except brassica, 

group 4 

0.10 0.100 

Vegetable, tuberous and corm, 

subgroup 01C 

0.01 --- 

1 Imported only; no US registrations. 

H.4.2 Drinking Water Pathway 

Residues of abamectin and emamectin were included in the dietary exposure assessments as 

residue distribution files rather than as point estimates. 

Abamectin: As discussed in Section 5.3, residues of abamectin 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.4.2.1. 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 were assessed in connection with an 

import tolerance on wine grapes (D402151, N. Dodd, 4/12/13; 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: 
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 (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.4.2.2. 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. 

H.4.3 Dietary (Food and Drinking Water) Assessment 

Acute: The screening-level cumulative acute dietary exposures from combined residues of 

abamectin and emamectin are calculated in Table H.4.3.1 below. The combined residues of 57% 

of the aPAD for the general U.S. population and 96% of the aPAD for children 1-2 years old, the 

most highly exposed subgroup, are below HED’s level of concern of 100%. 

Table H.4.3.1. Summary of Acute Dietary Exposure and Risk Assessment for Combined Abamectin and 

Emamectin

Abamectin 

Exposure 

Emamectin 

Exposure 

Combined 

Exposure aPAD 

Combined 

% aPAD 

Ratio 

Aba:EMA 

General U.S. Population 0.001249 0.000168 0.001417 0.0025 57 7.4 

All Infants (<1 year old) 0.001683 0.000138 0.001821 0.0025 73 12.2 

Children 1-2 years old* 0.002243 0.00015 0.002393 0.0025 96 15.0

Children 3-5 years old 0.001295 0.000136 0.001431 0.0025 57 9.5 

Children 6-12 years old 0.000824 0.000089 0.000913 0.0025 37 9.3 

Youth 13-19 years old 0.000549 0.000132 0.000681 0.0025 27 4.2 

Adults 20-49 years old 0.000448 0.000188 0.000636 0.0025 25 2.4 

Adults 50-99 years old 0.000357 0.000175 0.000532 0.0025 21 2.0 

Females 13-49 years old* 0.000416 0.000226 0.000642 0.0025 26 1.8 

 The subpopulation with the highest combined risk estimate is bolded. 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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Background Dietary Exposure: The screening-level cumulative background dietary exposures 

from combined residues of abamectin and emamectin are calculated in Table H.4.3.2 below. 

Table H.4.3.2. Aggregate Chronic Dietary Exposure and Risk Assessment for Combined Abamectin and 

Emamectin

Abamectin Exposure Emamectin Exposure Combined Exposure Ratio Aba:EMA 

General U.S. Population 0.000082 0.000008 0.000090 10.2 

All Infants (<1 year old) 0.000128 0.000012 0.000140 10.7 

Children 1-2 years old* 0.000393 0.000012 0.000405 32.8 

Children 3-5 years old 0.000239 0.000009 0.000248 26.6 

Children 6-12 years old 0.000137 0.000006 0.000143 22.8 

Youth 13-19 years old 0.000069 0.000004 0.000073 17.2 

Adults 20-49 years old 0.000056 0.000008 0.000064 7.0 

Adults 50-99 years old 0.000051 0.000009 0.000060 5.7 

Females 13-49 years old* 0.000054 0.000008 0.000062 6.8 

 The subpopulation with the highest combine risk estimate is bolded. 

H.5.0 Residential Pathway 

Abamectin: As discussed in detail in Section 6.0 above, there are proposed residential use sites 

that may lead to handler and post-application exposures. The proposed end-use products (for 

control of turf-parasitic nematodes on golf course greens, tees, and fairways) that may lead to 

these post-application exposures include the following: 

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

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

The products already registered for residential use sites 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) of both dust and gel formulations. For this assessment, the exposures 

and risk estimates for applying outdoor granular baits are assessed using the 2012 Residential 

SOPs10 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. 

Emamectin: There are no existing or proposed residential use sites; therefore, residential handler 

exposure and residential post-application exposure are not expected. 

 

 

10 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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H.6.0 Combined Screening Level Dietary + Residential Cumulative 

Short- and Intermediate-Term: The screening-level short-term aggregate risk is calculated in 

Table H.6.0 below. All short-term aggregate exposure estimates resulted in MOEs greater than 

100; therefore, they are not of concern. 

Table H.6.0. Short-Term Aggregate Risk Calculations for Combined Abamectin and Emamectin

Population 

Short-Term Scenario 

NOAEL 

mg/kg/day LOC1 

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day 

(abamectin + 

emamectin) 

Residential 

Exposure 

mg/kg/day3 

Total 

Exposure 

mg/kg/day4 

Aggregate 

MOE (food, 

water, and 

residential)5 

Adults 0.25 100 0.0025 

0.000082 + 

0.000008 = 

0.000090 

0.0000203 0.00011 2300 

Children 11 to 

<16 years old 0.25 100 0.0025 

0.000137 + 

0.000006 = 

0.000143 

0.0000237 0.00017 1500 

Children 6 to <11 

years old 0.25 100 0.0025 

0.000137 + 

0.000010 = 

0.000147 

0.0000278 0.00017 1500 

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)]. 

H.7.0 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 the candidate common 

mechanism group. This screening assessment uses conservative assumptions that are expected to 

overestimate exposures. It is unlikely that both chemicals would be used on the same crop at the 

maximum use rate; however, by adding exposures for food and water for both chemicals from 

field trial data this assessment implicitly assumes co-occurrence of residues at these levels 

reflecting the maximum use rate. For both chemicals, this assessment is based primarily on field 

trial data for food exposures (and monitoring data for emamectin in apples), percent crop treated 

data, and conservative water modeling for drinking water exposures based on maximum use 

rates. Although the acute dietary assessment is somewhat refined with the use of percent crop 

treated information and residue distribution files, the residue data used is based on crop field 

trials that reflect use patterns on product labels leading to the highest residues. The screening 

residential assessment is also conservative since high-end estimates of residential exposure are 

used, while average values are used for food and drinking water exposure. 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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The assessment could be more refined by using monitoring data that would reflect actual use 

patterns and weathering of residues during distribution and by modifying the screening level 

default assumption that crops (with registered uses of both chemicals) would be treated with 

abamectin and emamectin at the maximum use rate, resulting in co-occurrence of residues. 

HED believes that a more refined cumulative exposure assessment would continue to provide 

exposure estimates that are below HED’s level of concern since much of the high simulated 

exposures for abamectin are directly attributed to conservative inputs for milk. For the 

population with the highest exposure (children 1-2 years old), the main contributor to the dietary 

exposure is abamectin in milk. The relative inputs for this residue driver for abamectin is 0.011 

ppm with a percent crop treated of 85% based on dried citrus pulp, and the residue value for 

emamectin is 0.0003 ppm with a percent crop treated of 20% based on wet apple pomace. 

The residue distribution file for milk assumed that 85% of all milk contained a residue of 0.011 

ppm, based on the magnitude of residue data and assumptions; hence, the DEEM CEC report 

indicates that most of the outcomes at and above the per capita 99.9th percentile are attributed to 

a few children who drank considerable amounts of milk (e.g., 88% of the aPAD or 0.0022 mg 

ai/kg bw: 2L milk x 0.011 mg ai/L milk / 10 kg bw). If milk is removed from the acute dietary 

exposure assessment, then aggregate exposure at the per capita 99.9th percentile would fall from 

90% of the aPAD to about 35% of the aPAD for children 1-2 years old. 

H.8.0 Conclusion 

This conservative screening assessment indicates that combined aggregate dietary and residential 

risk estimates for abamectin and emamectin 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 and emamectin at this time. The Agency expects that the screening-level residues 

overestimate actual cumulative residues since co-occurrence is assumed in this assessment. Risk 

estimates in this screening assessment are below HED’s level of concern, so no additional data 

are required at this time. However, additional toxicological or exposure data may be required for 

any additional uses requested in the future that change the current conclusions. 

 
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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. 

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. 

 
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I.2 Toxicity Profiles

Table H.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 

 
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Table I.2.3. Repeated Dosing and Other Studies on Emamectin2, 3

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. 
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Table I.2.3. Repeated Dosing and Other Studies on Emamectin2, 3

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, 2.5 mg/kg 

(initially females 

received 5.0 mg/kg then 

reduced to 2.5 mg/kg at 

wk 18 due to excessive 

toxicity ) 

 

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. 

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 decreased body 

weight, body weight gain, and food efficiency 

in males. 

No treatment-related increase in tumor 

incidence was seen. 
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Table I.2.3. Repeated Dosing and Other Studies on Emamectin2, 3

Guideline No Study Type MRID No. (Year)/ 

Classification/Doses

Results

870.3700 Developmental tox. 

–rat 

42743632 (1992) 

Acceptable 

0, 2, 4, or 8 mg/kg/day 

42743631 (range finding 

study) 

Maternal Toxicity NOAEL=2 mg/kg/day, 

Maternal Toxicity LOAEL=4 mg/kg/day

based 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 

42851513 Negative for the induction of chromosome 

aberrations in the bone marrow cells of male 

CD-1 mice. 
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Table I.2.3. Repeated Dosing and Other Studies on Emamectin2, 3

Guideline No Study Type MRID No. (Year)/ 

Classification/Doses

Results

Aberration-in vivo

mouse bone marrow 

MK-0244 

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. 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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Table I.2.3. Repeated Dosing and Other Studies on Emamectin2, 3

Guideline No Study Type MRID No. (Year)/ 

Classification/Doses

Results

15-Day neurotox. –

CF-1 mice (dietary) 

(L695-638: 4”-

deoxy-4”-epimethylaminoavermectin B1adelta-8,9-isomer); 

photoproduct of 

MK-0244b

42851504 (1993) 

Acceptable 

0, 0.05, 0.075, 0.10, & 

0.30 mg/kg/day 

NOAEL = 0.30 mg/kg/day (HDT) 

No treatment-related effects were seen in any 

dose groups. 

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 

42851523 & 42852524 

(1993) 

Acceptable 

Radiolabeled MAB1a benzoate is rapidly 

absorbed, distributed and excreted following 

oral and i.v. administration. The feces was the 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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Table I.2.3. Repeated Dosing and Other Studies on Emamectin2, 3

Guideline No Study Type MRID No. (Year)/ 

Classification/Doses

Results

avermectin B1a 

benzoate, (MAB1a) 

major route of excretion in oral and i.v. groups, 

while <1% of the administered dose was 

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 Monkey 43850113 (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 and NonOccupational 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 

UFA= 10x 

UFH= 10x 

FQPA SF= 1x 

Residential LOC 

for MOE = 100 
ABAMECTIN Human Health Risk Assessment DP No. 426599 

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Table I.2.4. Summary of Toxicological Doses and Endpoints for Emamectin for Use in Dietary and NonOccupational Human Health Risk Assessments 

Exposure/ 

Scenario 

Point of Departure Uncertainty/ 

FQPA Safety 

Factors 

RfD, PAD, LOC 

for Risk 

Assessment 

Study and Toxicological Effects 

assumed to be 

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. .