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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

Date: 7/18/11

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

Onion Subgroup 3-07A, Chives, and Dry Beans

PC Code: 122804

Decision No.: 436528

Petition No.: 0E7738

Risk Assessment Type: Single 

Chemical/Aggregate

TXR No.: None

MRID No.: None

DP Barcode: 380523

Registration Nos.: 100-898, 100-1351, 100-1154

Regulatory Action: Section 3 Registration

Case No.: None

CAS No.: 71751-41-2

40 CFR: 180.449

FROM: Nancy Dodd, Chemist/Risk Assessor

Nancy Tsaur, Chemist

Whang Phang, Toxicologist

Risk Assessment Branch III (RAB3)

Health Effects Division (HED) (7509P)

THROUGH: Paula Deschamp, Branch Chief

RAB3/HED (7509P)

TO: Barbara Madden/Laura Nollen, RM#5

Registration Division (7505P)

The Health Effects Division (HED) of the Office of Pesticide Programs (OPP) is charged with 

estimating the risk to human health from exposure to pesticides. The Registration Division (RD) 

of OPP has requested that HED evaluate hazard and exposure data and conduct dietary, 

occupational, residential, and aggregate exposure assessments, as needed, to estimate the risk to 

human health that will result from the proposed use 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-demethyl-25-de (1-methylpropyl)-25-(1-methylethyl) avermectin 

A1)], and its delta-8,9-isomer on the bulb onion subgroup 3-07A, chives, and dry beans.

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

dietary (food and drinking water), residential, and occupational 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 uses on the bulb onion subgroup 3-07A, 

chives, and dry beans.
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A summary of the findings and an assessment of human health risk resulting from the registered 

and proposed uses for abamectin are provided in this document. The HED team members 

contributing to this risk assessment include: Nancy Dodd (risk assessment/residue chemistry

review/dietary exposure assessment), Nancy Tsaur (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....................................................................................... 7

2.1 Data Deficiencies/Conditions of Registration..................................................... 8

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

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

2.2.2 International Harmonization............................................................................... 9

2.2.3 Recommended Tolerances.................................................................................. 10

2.2.4 Revisions to Petitioned-For Tolerances ............................................................ 10

2.3 Label Recommendations.................................................................................... 10

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

3.1 Chemical Identity................................................................................................ 12

3.2 Physical/Chemical Characteristics.................................................................... 13

3.3 Pesticide Use Pattern .......................................................................................... 13

3.4 Anticipated Exposure Pathways........................................................................ 15

3.5 Consideration of Environmental Justice .......................................................... 16

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

4.1 Adequacy of the Toxicity Database ................................................................... 17

4.2 Mode of Action .................................................................................................... 17

4.3 Toxicological Effects........................................................................................... 18

4.4 FQPA Considerations......................................................................................... 18

4.4.1 Adequacy of the toxicity database for FQPA consideration........................... 18

4.4.2 Evidence of Neurotoxicity .................................................................................. 19

4.4.3 Developmental Toxicity...................................................................................... 19

4.4.4 Reproductive Toxicity ........................................................................................ 20

4.4.5 Additional Information from Literature Sources............................................ 22

4.4.6 Determination of Susceptibility ......................................................................... 22

4.5 FQPA Safety Factor for Infants and Children................................................. 23

4.6 Dose-Response Assessment ................................................................................ 25

4.7 Endocrine Disruption ......................................................................................... 30

5.0 Dietary Exposure and Risk Assessment............................................................ 31

5.1 Metabolite/Degradate Residue Profile .............................................................. 31

5.1.1 Summary of Plant and Animal Metabolism Studies ....................................... 31

5.1.2 Summary of Environmental Degradation ........................................................ 32

5.1.3 Comparison of Metabolic Pathways.................................................................. 33

5.1.4 Residues of Concern Summary and Rationale................................................. 33

5.2 Food Residue Profile........................................................................................... 34

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

5.4 Dietary Risk Assessment .................................................................................... 37

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

5.4.2 Percent Crop Treated Used in Dietary Assessment......................................... 38

5.4.3 Acute Dietary Risk Assessment ......................................................................... 39

5.4.4 Chronic Dietary Risk Assessment ..................................................................... 39

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

5.4.6 Summary Table................................................................................................... 40

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ................ 41
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6.1 Residential Handler Exposure........................................................................... 41

6.2 Residential Post-Application Exposure............................................................. 43

6.3 Spray Drift........................................................................................................... 45

7.0 Aggregate Risk Assessments and Risk Characterization................................ 45

7.1 Acute Aggregate Risk ......................................................................................... 45

7.2 Short- and Intermediate-Term Aggregate Risk............................................... 46

7.3 Long-Term (Chronic) Aggregate Risk.............................................................. 47

7.4 Cancer Risk ......................................................................................................... 47

8.0 Cumulative Risk Characterization/Assessment............................................... 47

9.0 Occupational Exposure/Risk Pathway.............................................................. 47

9.1 Short-/Intermediate-Term Handler Risk ......................................................... 48

9.2 Occupational Post-Application Exposures and Risks ..................................... 51

10.0 References............................................................................................................ 53

Appendix A: Toxicology Assessment ....................................................................................... 54

Appendix B: Toxicology Literature References ..................................................................... 59

Appendix C: Physical/Chemical Properties............................................................................ 60

Appendix D: Review of Human Research............................................................................... 61

Appendix E: International Residue Limits............................................................................. 62
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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, 

leafminers, 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.

 

IR-4 proposed registration of Agri-Mek® 0.15 EC Miticide/Insecticide (2% ai; EPA Reg. No. 

100-898), Agri-Mek® SC Miticide/Insecticide (8% ai; EPA Reg No. 100-1351), and Epi-Mek® 

0.15 EC Miticide/Insecticide (2% ai; EPA Reg. No. 100-1154) on the bulb onion subgroup 3-

07A, chives, and dry beans. All formulations are currently registered for use on a variety of 

crops.

 

Human Health Risk Assessment:

Toxicity/Hazard: 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. The 

main target organ is the nervous system, and the reduced body weight effect is one of the most 

frequent findings. Neurotoxicity and developmental effects were detected in multiple studies 

and species of test animals. The dose/response curve is very steep in several studies, with severe 

effects (including death and morbid sacrifice) seen at dose levels as low as 0.4 mg/kg/day and 

0.1 mg/kg/day in rats and mice, respectively, following repeated/chronic exposures. (For details, 

refer to Section 4.5.) Increased susceptibility (qualitative and/or quantitative) was seen in 

prenatal developmental toxicity studies in mice and rabbits, and an increase in quantitative and 

qualitative susceptibility was seen in the rat reproductive toxicity study. Review of acceptable 

oncogenicity and mutagenicity studies provides no indication that abamectin is carcinogenic or 

mutagenic. 

The RAB3 Risk Assessment Team has evaluated the entire toxicity database of abamectin and 

determined that an additional 3x FQPA safety factor is needed to address residual concerns as to 

all risk assessments other than acute dietary. For all risk assessments involving repeat exposures, 

the selected toxicity endpoint is based on the decrease in pup body weight seen in the 

developmental neurotoxicity study (2007) and three reproduction studies in the rat.

With respect to acute dietary exposure, the endpoint selected for risk assessment is based on 

mydriasis observed in dogs. The additional 3x factor applied to chronic and other exposure 

scenarios is not applicable to acute exposure because steepness of the dose/response curve and 

severity of effects were not seen in the studies where mydriasis occurred. In addition, the 

reduced body weights as toxicity endpoints for other exposure scenarios is not a single dose 

effect.
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The immunotoxicity study (870.7800) is required to fulfill current 40 CFR Part 158 data 

requirements. However, the RAB3 toxicity team examined the entire database of abamectin and 

determined that an additional uncertainty factor is not needed to account for potential 

immunotoxicity. 

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 DEEM-FCIDTM, Version 2.03. Although tolerance-level residues and 100% crop treated 

were used for the proposed crops and okra, the acute and chronic dietary exposure assessments 

were refined assessments using anticipated or average residues derived from field trial data for 

most crops. Default processing factors and percent crop treated (%CT) were used as available. 

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

and Effects Division (EFED). The maximum (acute) concentration of abamectin and its major 

soil degradate (a mixture of an 8-alpha-hydroxy and a ring opened aldehyde derivative) in 

surface water is not likely to exceed 2.3 ppb. The mean (chronic) estimated surface water 

concentration is 1.3 ppb.

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. Abamectin dietary exposure at the 

99.9th percentile for food and drinking water is 16% of the aPAD for the general U.S. population 

and 30% of the aPAD for all infants (<1 year old), the most highly exposed population subgroup.

The chronic dietary exposure estimates for food and drinking water are below HED’s level of 

concern (<100% cPAD) for the general U.S. population and all population subgroups. 

Abamectin dietary exposure for food and drinking water is 18% of the cPAD for the general U.S. 

population and 50% of the cPAD for children 1-2 years old, the most highly exposed population 

subgroup.

Residential Exposure: Abamectin is currently registered for a number of residential insecticidal 

uses. Because the FQPA requires consideration of aggregate exposure to all likely nonoccupational uses, this assessment includes contact with abamectin from residential crack and 

crevice and lawn treatments as the most common and worst-case contributors to such exposures. 

The Margins of Exposure (MOEs) for applicable residential scenarios were calculated using 

exposure monitoring data and the HED Standard Operating Procedures for Residential Exposure 

Assessments (Draft, December 18, 1997), along with interim changes presented in HED Science 

Advisory Council for Exposure SOP No.11 (February 22, 2001). In addition, for the indoor 

crack and crevice treatment, measured airborne and surface residue data were available to 

perform an assessment of post-application inhalation, dermal, and incidental oral risks. 

Combined residential exposures/risks were estimated for adults and for children. Children’s 

exposure from incidental ingestion of granules on treated lawns was compared to the acute 

dietary NOAEL of 0.5 mg/kg/day. The exposure/risk from this latter scenario was not combined 

with other scenarios, nor was it included in the aggregate assessment, because it is considered to 

be a one-time, episodic event, rather than occurring for several days (or several months). The

MOEs for all residential scenarios are greater than the levels of concern (LOCs) of 300, and 

therefore, are not of concern.
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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 residential LOCs are 300 and the MOEs are greater than 300, and thus are not of risk 

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

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

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

level of concern. 

Occupational Exposure/Risk: Based on the proposed uses, there is a potential for short- and 

intermediate-term occupational exposure to abamectin during handling activities (e.g. mixing, 

loading, application). No chemical-specific exposure data were submitted in support of this 

Section 3 registration. To assess handler exposures for regulatory actions when chemicalspecific monitoring data are not available, HED relies on the most scientifically-reliable 

surrogate data currently available from various sources. The abamectin labels contain specific 

requirements for personal protective equipment (PPE) for applicators and other handlers. All 

handler activities result in MOEs >300 with baseline clothing or baseline plus gloves, and, 

therefore, do not exceed HED’s level of concern since the occupational LOCs are 300. 

There is a potential for short- and intermediate-term occupational exposure during postapplication activities. Based on a post-application assessment of common agricultural practices, 

the proposed 12-hour re-entry interval (REI) on all the labels is acceptable. All MOEs are >300 

on the day of application, and therefore, are not of concern to HED since the LOC is 300. 

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: As discussed in Appendix D, this risk assessment relies on the 

most scientifically-reliable surrogate data currently available from various sources such as the 

Pesticide Handler Exposure Database (PHED), the Agricultural Handler Exposure Task Force 

(AHETF), and the Outdoor Residential Exposure Task Force (ORETF). Some of this data, such 

as the industry task force data, is compensatory, subject to the data protection provisions of 

FIFRA. HED policy on use of surrogate data is described in more detail on the Agency’s 

website (htpp://www.epa.gov/pesticides/science/handler-exposure-data.html). Scenario-specific 

surrogate exposure data, including their sources, are presented in the “Occupational Pesticide 

Handler Unit Exposure Surrogate Reference Table” 

(http://www.epa.gov/pesticides/science/handler-exposure-table.pdf).

2.0 HED Recommendations

Provided revised Sections B (OPPTS 860.1200) and F (OPPTS 860.1550) are submitted, HED 

can recommend for a conditional registration of abamectin for use on the bulb onion subgroup 3-

07A, chives, and dry beans except cowpea and for permanent tolerances for the proposed uses on 
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the bulb onion subgroup 3-07A, chive, and dry bean except cowpea. Additional data are needed 

as a condition of registration as outlined in Section 2.1 below. The specific tolerance 

recommendations are discussed in Section 2.2, and label modifications are discussed in Section 

2.3.

2.1 Data Deficiencies/Conditions of Registration

The following must be provided prior to a tolerance being established or registration 

allowed:

860.1200 Directions for Use

 Label revisions are required for the EC labels to remove the statement that adjuvants may

be used on chives and dry beans since the submitted crop field trials on chives and dry

beans do not reflect the use of an adjuvant. 

 The labels must be revised to specify a 7-day PHI for chives and dry beans since most of 

the chive and dry bean data reflect a 7-day PHI. 

 The amount (v/v) of the non-ionic surfactant and/or horticultural oil is required to be 

specified in the Directions for Use for each crop on the SC label and is required to be 

within the range of the amount (v/v) used in the available SC field trials (D364734, N. 

Dodd, 1/21/10).

 Cowpea must be removed from the label under dry bean since residue data for cowpea 

forage and hay must be submitted to support use on cowpea.

860.1550 Proposed Tolerances

 The petitioner should submit a revised Section F reflecting the recommended tolerance 

levels and correct commodity definitions as presented in Table 2.2.4. The proposed 

tolerance level for chives, dried leaves must be lowered from 0.07 ppm to 0.02 ppm. 

Cowpea must be excluded from the dry bean seed tolerance since residue data for cowpea 

forage and hay must be submitted before cowpea can be included in the dry bean seed 

tolerance.

The following data are required as conditions of registration:

TOXICOLOGY

870.7800 Immunotoxicity

 ● Under the current data requirement guidelines, the immunotoxicity study is required to 

fulfill current 40 CFR Part 158 data requirements. The registrant has committed to 

provide this data in 2012.
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RESIDUE CHEMISTRY

860.1500 Crop Field Trials

 The petitioner needs to submit the storage temperature of the dry bean samples from the 

crop field trial.

The following data must be submitted for future uses on cowpea:

RESIDUE CHEMISTRY

860.1500 Crop Field Trials

 Residue data for cowpea forage and hay must be submitted before cowpea can be 

included in the dry bean seed tolerance.

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).

 

The plant methods used for data collection, using high performance liquid chromatography 

(HPLC) with fluorescence detection, adequately measure the residues of concern. The methods 

have been validated at 0.002 for each analyte (avermectin B1a, avermectin B1b, and 8,9-Z

avermectin B1a).

The Pestrak database indicates that abamectin and its metabolites are not recovered or not likely

to be recovered by FDA multiresidue methods. Therefore, the multiresidue methods can not be 

used to determine residues for dietary exposure assessment and can not be used as the primary

enforcement method.

2.2.2 International Harmonization

There are currently no maximum residue limits (MRLs) established by Codex, Canada, or

Mexico for abamectin on the bulb onion subgroup 3-07A, chive, or dry beans. Therefore, there 

are no issues regarding international harmonization raised by this action. An International 

Residue Limit Status sheet is attached (Appendix E).
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2.2.3 Recommended Tolerances

HED recommends for the following tolerances and residue definition:

“Tolerances are established for residues of abamectin, including its metabolites and 

degradates, in or on the commodities in the table below. Compliance with the tolerance levels 

specified below is to be determined by measuring only avermectin B1 [a mixture of 

avermectins containing greater than or equal to 80% avermectin B1a (5-O-demethyl 

avermectin A1) and less than or equal to 20% avermectin B1b (5-O-demethyl-25-de(1-

methylpropyl)-25-(1-methylethyl) avermectin A1)] and its delta-8,9-isomer.”

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

Chive, fresh leaves...................................................0.01 ppm

Chive, dried leaves...................................................0.02 ppm

Bean, dry, seed, except cowpea ...............................0.01 ppm

2.2.4 Revisions to Petitioned-For Tolerances

Table 2.2.4 compares proposed and recommended tolerance levels and tolerance expressions. 

The recommended tolerance levels are based on the submitted magnitude of the residue data and 

the chive processing study. EPA is recommending that the proposed tolerance for chive, dried 

leaves be reduced from 0.07 ppm to 0.02 ppm based on the results of the chive processing study.

The Agency’s tolerance spreadsheet from the Guidance for Setting Pesticide Tolerances Based 

on Field Trial Data was not used because all of the treated samples from the field trials bore 

residues below the LOQ. The correct commodity definitions were obtained from the “Food and 

Feed Commodity Vocabulary”, which can be found at http://www.epa.gov/pesticides/foodfeed. 

Table 2.2.4. Tolerance Summary for Abamectin

Commodity Established/Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments

Correct Commodity Definition

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

Chive, fresh leaves 0.01 0.01

Chive, dried leaves 0.07 0.02

Bean, dry, seed 0.01 0.01 Bean, dry, seed, except cowpea

*An established time-limited tolerance of 0.05 ppm on onion, bulb will expire on 12/31/12.

2.3 Label Recommendations

Refer to Section 2.1 above for label recommendations from residue chemistry reviews.

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 
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products of the soil bacterium Streptomyces avermitilis. Abamectin is an insecticide/miticide 

used to control mites, leafminers, 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 have been established in 40 CFR §180.449(a) for the combined residues of the 

insecticide 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 

in/on various plant and livestock commodities at levels ranging from 0.005 to 0.20 ppm. Timelimited tolerances are established in 40 CFR §180.449(b) for residues of avermectin B1 and its 

delta-8,9-isomer in/on onion, bulb at 0.005 ppm (to expire on 12/31/12) and in/on bean, lima, 

seed at 0.005 ppm (set to expire on 12/31/13).

The registered formulation types include emulsifiable concentrate, granular, bait, gel, and dust. 

The registered uses include food, food handling establishments, and residential uses. Clinch® 

Ant Bait is registered for control of fire ants in citrus, almonds, walnuts, potatoes, around barns 

and equipment, and around chicken houses. There are registered granular products for the 

application of abamectin to lawns to control fire ants (e.g., Affirm Fire Ant Insecticide Bait/EPA 

Reg. No. 100-893 and PT 370 Ascend Fire Ant Stopper Bait/EPA Reg. No. 499-370). 

New uses involving three formulations have been proposed for registration: Agri-Mek® 0.15 

EC, Agri-Mek® SC, and Epi-Mek® 0.15 EC. Agri-Mek® 0.15 EC and and Epi-Mek® 0.15 EC 

are emulsifiable concentrate formulations containing 0.15 lb ai/gal. Agri-Mek® SC is a 

suspension concentrate containing 0.7 lb ai/gal. The products are to be applied as multiple foliar 

sprays using ground and aerial (except chive) methods. The maximum seasonal rate is 0.056 lb

ai/A for bulb onion, chives, and dry beans. The preharvest intervals (PHIs) are 30 days for bulb 

onion and 6 days for chives and dry beans. 
3.1 Chemical Identity

Table 3.1. Test Compound Nomenclature

Chemical Structure

Empirical Formula C48H

Common Names abamectin, avermectin B

Company experimental name MK-0936

IUPAC name

mixture of (10

sec-butyl]

trioxatetracyclo[15.6.1.1

'-dihydro

arabino

(10E,14

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Table 3.1. Test Compound Nomenclature

H72O14 (B1a); C47H70O14 (B1b)

abamectin, avermectin B1

0936

mixture of (10E,14E,16E)-(1R,4S,5 'S,6S,6 'R,8R,12S,13S,20R

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)

dihydro-2 'H-pyran)-12-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O

arabino-hexopyranosyl)-3-O-methyl-α-L-arabino-hexopyranoside and 

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

R,21R,24S)-6 '-[(S)-

(3,7,19-

tetraene)-6-spiro-2 '-(5 ',6 

O-methyl-α-Lhexopyranoside and 

21,22-dihydroxy-6 '-
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Table 3.1. Test Compound Nomenclature

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

End-use product/EP

Agri-Mek® 0.15 EC, EPA Reg. No. 100-898 (contains 0.15 lb ai per gallon);

Clinch® Ant Bait, EPA Reg. No. 100-894 (contains 0.011% ai);

Y-TEX BOVAMECTM Cattle Ear Tags, EPA Reg. No. 39039-RT (contains 8.0% 

abamectin and 20.0% piperonyl butoxide technical, w/w)

Chemical Class Insecticide/Miticide

Known Impurities of Concern None

3.2 Physical/Chemical Characteristics

Avermectin is a crystalline powder with very low vapor pressure. It has very low water 

solubility but is soluble in organic solvents. Residues do not readily leach to groundwater due to 

their affinity for soil particles. Abamectin is stable to abiotic hydrolysis. Acceptable data are not 

available to determine stability via other routes. Abamectin is stable to abiotic hydrolysis; 

determination of stability to photolysis and biodegradation is pending submission of acceptable 

data. Refer to Appendix C for the table of physical/chemical properties.

3.3 Pesticide Use Pattern

Table 3.3. Summary of Directions for Use of Abamectin.

Applic. 

Timing, 

Type, 

and 

Equip.

Formulation

[EPA Reg. No.]

Applic. 

Rate 

(lb 

ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

(lb ai/A)

PHI1

(days)

Use Directions and Limitations2 

Onion, bulb (Crop Subgroup 3-07A)

(onion, bulb including daylily, bulb; fritillaria, bulb; garlic, bulb; garlic, great-headed, bulb; garlic, serpent, bulb; lily, 

bulb; onion, Chinese, bulb; onion, pearl; onion, potato, bulb; shallot, bulb; cultivars, varieties, and/or hybrids of 

these)

Foliar 

spray

(ground 

or 

aerial)4,5

Agri-Mek® 0.15

EC

Insecticide/Miticide 

[EPA Reg. No. 

100-898]

Agri-Mek® SC 

Insecticide/ 

Miticide [EPA 

Reg. No. 100-1351]

Epi-Mek® 0.15 EC 

Insecticide/Miticide 

0.019 Not 

stated

0.056 30 Do not apply in less than 20 gallons of 

water/A with ground application equipment. 

Do not apply in less than 5 gallons of water/A 

with aircraft.

Include a non-ionic surfactant commercially 

used on dry bulb onions.

RTI3= 7 days.

Adjuvant Requirement

SC formulation: To avoid illegal crop 

residues, the SC formulations must always be 
Page 14 of 62

Table 3.3. Summary of Directions for Use of Abamectin.

Applic. 

Timing, 

Type, 

and 

Equip.

Formulation

[EPA Reg. No.]

Applic. 

Rate 

(lb 

ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

(lb ai/A)

PHI1

(days)

Use Directions and Limitations2 

[EPA Reg. No. 

100-1154]

mixed with a non-ionic activator type wetting, 

spreading and/or penetrating adjuvant. Do 

not use binder sticker type adjuvants. (See 

Use Information and Use Restrictions.)

EC formulation: Add a non-ionic activator 

type wetting, spreading and/or penetrating 

adjuvant approved for use on bulb onion. Do 

not use binder sticker type adjuvants.

Chives

Foliar 

spray

(ground)

4

Agri-Mek® 0.15

EC 

Insecticide/Miticide 

[EPA Reg. No. 

100-898]

Agri-Mek® SC 

Insecticide/ 

Miticide [EPA 

Reg. No. 100-1351]

Epi-Mek® 0.15 EC 

Insecticide/Miticide 

[EPA Reg. No. 

100-1154]

0.019 Not 

stated

0.056 6 Apply as a foliar spray in a minimum of 20 

gallons of water per acre.

Adjuvant Requirement

SC formulation: To avoid illegal crop 

residues, the SC formulations must always be 

mixed with a non-ionic activator type wetting, 

spreading and/or penetrating adjuvant. Do 

not use binder sticker type adjuvants. (See 

Use Information and Use Restrictions.)

6 

RTI = 7 days.

EC formulation: When necessary to improve 

the wetting of foliage and to smooth out spray 

deposits, a nonionic surfactant is 

recommended.

Beans, dry

[Cicer arietinum (chickpea, garbanzo bean); Lupinus spp. (including sweet lupine, white sweet lupine, white lupine, 

and grain lupine); Phaseolus spp. (including kidney bean, lima bean, mung bean, navy bean, pinto bean, snap bean 

and waxbean); Vicia faba (broad bean, fava bean); Vigna spp. (including adzuki bean, asparagus bean, blackeyed 

pea, catjang, Chinese longbean, cowpea, crowder pea, moth bean, mung bean, rice bean, southern pea, urd bean, and 

yardlong bean)]

Foliar 

spray

(ground 

or 

aerial)

4,5

Agri-Mek® 0.15

EC 

Insecticide/Miticide 

[EPA Reg. No. 

100-898]

Agri-Mek® SC 

Insecticide/ 

Miticide [EPA 

Reg. No. 100-1351]

Epi-Mek® 0.15 EC 

Insecticide/Miticide 

0.019 Not 

stated

0.056 6 Do not apply in less than 10 gallons of 

water/A with ground application equipment. 

Do not apply in less than 5 gallons of water/A 

with aircraft.

Adjuvant Requirement

SC formulation: To avoid illegal crop 

residues, the SC formulations must always be 

mixed with a non-ionic activator type wetting, 

spreading and/or penetrating adjuvant. Do not 

use binder sticker type adjuvants. (See Use 

Information and Use Restrictions.)

6
Page 15 of 62

Table 3.3. Summary of Directions for Use of Abamectin.

Applic. 

Timing, 

Type, 

and 

Equip.

Formulation

[EPA Reg. No.]

Applic. 

Rate 

(lb 

ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. 

Rate

(lb ai/A)

PHI1

(days)

Use Directions and Limitations2 

[EPA Reg. No. 

100-1154]

RTI = 6 days.

EC formulation: A non-ionic activator type 

wetting, spreading and/or penetrating 

adjuvant approved for use on dry beans and 

peas can be used to help improve control. Do 

not use binder sticker type adjuvants.

1

PHI = preharvest interval.

2 Onion, bulb - Make 2 consecutive applications then rotate to a chemistry (pesticide) with a different mode of 

action. Make at least 2 applications of a chemistry (pesticide) with a different mode of action before making 

additional applications. Do not make more than 2 sequential applications of any other foliarly applied abamectin 

containing product. 

Chives - Do not make more than 2 applications of any foliarly applied abamectin containing product per single 

cutting (harvest). 

Dry beans - Do not make more than 2 sequential applications of any foliarly applied abamectin containing product.

3 RTI =retreatment interval.

4 Do not apply through any type of irrigation system.

5 Aerial applications are not allowed in NY.

6 The use of an adjuvant is required on the Agri-Mek® SC Insecticide/Miticide label, but is not specified in the 

Section B use directions for chives and dry beans.

Conclusions: The submitted labels for Agri-Mek® 0.15 EC Insecticide/Miticide (EPA 

Registration No. 100-898), Agri-Mek® SC Insecticide/ Miticide (EPA Registration No. 100-

1351), and Epi-Mek® 0.15 EC Insecticide/Miticide (EPA Registration No. 100-1154) are 

adequate to allow evaluation of the residue data relative to the proposed uses.

The ChemSAC determined on 5/18/11 that the available bridging studies for the SC formulation 

on leafy vegetables, fruiting vegetables, cucurbit vegetables, citrus fruits, and pome fruits 

(DP#364734, N. Dodd, 1/21/10) can be translated to support use of the SC formulation on the 

bulb onion subgroup 3-07A, chives, and dry beans provided the use directions for the SC 

formulation always require use of a non-ionic surfactant or a horticultural oil in the spray mix 

and the preharvest intervals are ≥ 7 days. 

Refer to Section 2.3 for recommended modifications to the proposed label.

3.4 Anticipated Exposure Pathways

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 

groundwater 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. The proposed uses 

on the bulb onion subgroup 3-07A, chive, and dry bean do not include residential uses; however, 

there are registered residential uses of abamectin, so there is the possibility of exposure in 
Page 16 of 62

residential or non-occupational settings. In an occupational setting, applicators may be exposed 

while handling and applying abamectin. There is a potential for post-application exposure for 

workers re-entering treated fields. 

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 USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) 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, season of the year, ethnic group, and region of the country. 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.

Although not applicable to a specific environmental justice demographic, this risk assessment 

gives consideration to genetic polymorphism and the potential for susceptibilities in human 

populations. CF-1 mice were the most sensitive strain of test animals due to the lack of Pglycoprotein. In mammals, P-glycoprotein 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 the fetus. Because abamectin is a substrate 

for p-glycoprotein, this protective mechanism may be less effective, as demonstrated in test 

animals where genetic polymorphisms compromise P-glycoprotein expression. An example is 

the CF-1 mouse, some of which are deficient in P-glycoprotein and highly sensitive to the 

neurotoxicity of abamectin. A small population of humans is also found to be deficient in pglycoprotein due to polymorphism in the gene encoding P-glycoprotein. It was determined that 

the 10x factor for intraspecies variability adequately protects the most sensitive population.

An additional factor of 3x for the steepness of the dose-response curve and the severity of effects

is applied to all risk assessments other than acute dietary. 

 
Page 17 of 62

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Adequacy of the Toxicity Database

The toxicology database for abamectin is sufficient to characterize the hazard to humans, to 

conduct FQPA assessment, and to select toxicity endpoints for risk assessment. Data quality is 

acceptable and meets the criteria set in the OPPTS guidelines and 40 CFR §158.500. However, 

under the current data requirement guidelines, immunotoxicity data (OPPTS 870.7800) shall be 

required as a condition of registration. An immunotoxicity study is specifically designed to 

detect any deficit in the ability of the immune system to respond to a challenge (chemical). 

Refer to Appendix B for toxicology citations.

To address the issue of the immunotoxicity data gap and the associated database uncertainty 

factor, the RAB3 toxicity team examined the entire database of abamectin and determined that 

an additional uncertainty factor is not needed to account for potential immunotoxicity. For 

abamectin, a complete battery of subchronic, chronic, carcinogenicity, developmental and 

reproductive studies as well as acute and subchronic neurotoxicity screening studies are available 

for consideration. In addition, two developmental neurotoxicity studies have been conducted on 

abamectin. At the dose levels tested, abamectin did not induce effects which can be associated 

with immunotoxicity, and abamectin does not belong to a class of chemicals that would be 

expected to be immunotoxic. Therefore, based on the above considerations, HED does not 

believe that conducting a special series 870.7800 immunotoxicity study will result in a NOAEL 

that is less than any which is used for point of departure for this risk assessment. An additional 

uncertainty factor (UFDB) for database uncertainties does not need to be applied at this time. 

4.2 Mode of Action

In nematodes, abamectin blocks the 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. 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. 

Consequently, abamectin may have the potential to influence GABA-mediated events important 

to brain development. Within the mammalian brain, abamectin binding is widespread but 

particularly abundant in the cerebellum (Wang and Pong, 1982). Abamectin also acts 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). This is 

consistent with the results seen in some submitted studies because the body weight effect is a 

frequent finding and is generally seen at dose levels lower than those producing a neurological 

effect in the test animals.

Integral to its mechanism of action in mammals, abamectin is also a substrate for P-glycoprotein 
Page 18 of 62

(P-gp). P-glycoprotein is a member of the ATP binding cassette transporter proteins, which 

reside in the plasma membrane and function as a transmembrane efflux pump, moving 

xenobiotics from intracellular to the extracellular domain against a steep concentration gradient 

with ATP-hydrolysis providing the energy for active transport (Marzolini et al., 2004). 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 the fetus. Therefore, some test animals, in which genetic polymorphisms compromise P-gp 

expression, are particularly susceptible to abamectin-induced neurotoxicity (Lankas et al., 1997). 

An example is the CF-1 mouse. Some CF-1 mice are deficient in P-gp and are found to be 

highly sensitive to the neurotoxicity of abamectin. A small population of humans is also found 

to be deficient of p-glycoprotein due to polymorphism in the gene encoding P-gp (DubinJohnson Syndrome) (S. Habashi, 2006). In addition, collie dogs have been known to be deficient 

in P-gp (R. Kerb, 2005).

4.3 Toxicological Effects

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. The acute toxicity of 

abamectin technical is summarized in Table A.1 of Appendix A.

In general, the results of available toxicity studies with single or repeated dosing reflect the mode 

of action of abamectin discussed in Section 3.2, and they indicate that the main target organ is 

the nervous system, and that decreased body weight is also one of the most frequent findings. 

Neurotoxicity and developmental effects are detected in multiple studies and species of test 

animals. The dose/response curve is very steep in several studies, with severe effects (including 

death and morbid sacrifice) seen at dose levels as low as 0.4 mg/kg/day and 0.1 mg/kg/day in 

rats and mice, respectively, following repeated exposures. Increased susceptibility (qualitative 

and/or quantitative) was seen in prenatal developmental toxicity studies in mice and rabbits, and 

an increase in quantitative and qualitative susceptibility was also seen in the rat reproductive 

toxicity studies. Review of acceptable oncogenicity and mutagenicity studies provide no 

indication that abamectin is carcinogenic or mutagenic. The studies, which demonstrated 

neurotoxicity as well as other effects, are summarized in Section 3.4.2 and in Tables A.2 & A.3 

of the Appendix A. 

4.4 FQPA Considerations

4.4.1 Adequacy of the toxicity database for FQPA consideration
Page 19 of 62

As mentioned before, the toxicology database is sufficient to conduct an FQPA assessment. 

Some of the toxicity studies conducted in the 1980’s do not fully meet the current guideline 

requirements. However, when considered in conjunction with acceptable guideline studies, they

provide adequate information for determining the toxicity of abamectin in adult, fetal, and young 

animals. 

4.4.2 Evidence of Neurotoxicity

Signs of neurotoxicity ranging from decrease 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 duration of abamectin exposure. These neurotoxicity signs are seen singularly or in 

combination in rats, mice (CD-1 and CF-1 mice), or dogs. In dogs, mydriasis was the most 

common finding at doses as low as 0.5 mg/kg/day after one week of treatment. In CF-1 mice, 

tremor was seen prior to death at doses of 0.1 mg/kg/day and above following repeated exposure. 

In comparison to dogs and CF-1 mice, neurotoxic signs were seen at higher dose levels (1.0 

mg/kg/day or above) in rats. The studies which reported the neurotoxicity findings are 

summarized in Appendix B of D362615 (N. Dodd, 3/11/09).

4.4.3 Developmental Toxicity

There are several developmental toxicity studies available indicating that there is a qualitative 

and quantitative increase in sensitivity and susceptibility in the developing mouse and rabbit 

fetuses to the effects of abamectin (MRIDs 44179901 and 00130819) (Tables A.2 and A.3 of 

Appendix A). Three representative prenatal developmental toxicity studies are summarized 

below.

Prenatal developmental toxicity study in rats (MRID 00130819; 1982): Pregnant Crl:CD rats 

were dosed with avermectin B1 (95% pure, sesame oil as vehicle) at dose levels of 0.4, 0.8, and 

1.6 mg/kg/day on gestation day 6 through 19. No treatment related maternal or developmental 

toxicity was seen in the study. Both maternal and developmental toxicity NOAELs were 

considered to be at the highest-dose tested (1.6 mg/kg/day). A range finding study was 

performed; the results indicated that at 2.0 mg/kg/day, one dam had tremors and lost weight and 

was sacrificed after 12 doses. The results of the dose-range-finding study indicated that the 

highest dose employed in the final study was approaching the level which would lead to severe 

toxicity.

Prenatal developmental toxicity in rabbits (MRID 00130819; 1982): Pregnant New Zealand 

White rabbits were administered abamectin (94% pure) at dose levels of 0.5, 1.0, and 2.0 

mg/kg/day on gestation days 6 through 16. At 2.0 mg/kg/day, decreases in body weights and 

food/water consumptions were seen. Developmental toxicity was reported in fetuses of the 2 

mg/kg/day group; the findings were cleft palate, clubbed foot, increased pup deaths at birth, and 

delayed ossification of sternebrae, metacarpals, and phalanges. No effects were seen in dose 

levels of 1.0 and 0.5 mg/kg/day. The maternal LOAEL was 2.0 mg/kg/day; the maternal 

NOAEL was 1.0 mg/kg/day. The developmental toxicity LOAEL was 2.0 mg/kg/day and the 

NOAEL was 1.0 mg/kg/day.
Page 20 of 62

Prenatal developmental toxicity study in CD-1 mice (MRID 44179901; 1996): Pregnant CD-1 

mice were administered abamectin at doses of 0, 0.75, 1.5, and 3.0 mg/kg/day from gestation 

days 6 through 15. At 3.0 gm/kg/day, maternal toxicity was reported as limb splay. This dose 

was considered to be the maternal LOAEL, and the NOAEL was 1.5 mg/kg/day. Hindlimb 

extension was found in 2 fetuses from 2 litters each for 0.75, 1.5, & 3.0 mg/kg/day groups. 

Therefore, the developmental LOAEL was 0.75 mg/kg/day, and a NOAEL could not be 

established. 

In addition, the data indicate that the most sensitive effect of abamectin on the fetuses is the 

increase in the incidence of cleft palates in mice and rabbits in the presence of no or minimal 

maternal toxicity. This effect is particularly apparent in CF-1 mice (Table A.3, Appendix A). In 

CF-1 mice, cleft palate was seen at doses as low as 0.1 mg/kg/day in developmental toxicity

studies; but no effect was seen at 0.06 mg/kg/day or below (Table A.3 of Appendix A). In CD-1 

mice and rabbits, cleft palate was found at slightly higher dose levels, 0.75 mg/kg/day and 2.0 

mg/kg/day, respectively. In general, most of the maternal effects were found at 2 mg/kg/day or 

above in CD-1 mice or rabbits. 

It should be noted that the CF-1 mouse developmental toxicity studies were thoroughly reviewed 

by the Developmental and Reproductive Toxicity Peer Review group in 1993 (Memorandum: R. 

Gardner to G. LaRocca, July 8, 1993). Subsequently, additional data were submitted by the 

registrant demonstrating that the sensitivity of some CF-1 mice to abamectin was correlated with 

a deficiency in P-gp. In consideration of this information, a decision was made in 1998 by the 

Hazard Identification and Assessment Review Committee (HIARC) not to employ the results 

from the CF-1 mice studies for establishing toxicity endpoints (HIARC Report, Sept. 15, 1998). 

Currently, HED establishes a point of departure of 0.12 mg/kg/day for risk assessment of 

chronic, short, and intermediate terms of exposure based on the combined data from three 

reproduction studies and two developmental neurotoxicity studies. With the intraspecies safety 

factor of 10x, the effects seen in the most sensitive subpopulation (CF-1 mice) are protected. 

(Details are presented in Section 4.5). 

4.4.4 Reproductive Toxicity 

There are three available reproduction studies in rats: two one-generation reproduction studies 

and a two-generation reproduction study (MRIDs 00096450, 00096451, and 00164151) (Table 

A.2, Appendix A). The results of all three studies show the effects (decreased pup body weights 

and/or survival) in the pups at lower dose levels (0.4 mg/kg/day) than the LOAELs of the 

parental animals (>0.4 mg/kg/day or 1.5/2.0 mg/kg/day). A similar lower offspring LOAEL, 

based on decreased pup body weight, than that of the maternal animals was also found in the 

developmental neurotoxicity study (offspring LOAEL=0.2 mg/kg/day; maternal LOAEL >0.4 

mg/kg/day). 

Two-generation reproduction study in rats (MRID 00164151; 1984): Groups of 30 SD 

rats/sex/dose were administered abamectin by gavage at dose levels of 0, 0.05, 0.12, and 0.4 

mg/kg/day. F0 males were dosed for a total of 259 days while F0 females were treated for a 

minimum of 177 days. For F0 animals, mating and fertility indexes and body weights were 
Page 21 of 62

comparable among all dose groups. For the pups, F1a and F1b pups had decreases in viability

and lactation indexes and a decrease in body weights at 0.4 mg/kg/day. Similar decreases were 

also seen in F2a and F2b groups. In the F2b weanlings, there was a treatment-related increase in 

the incidence of retinal rosettes. The parental NOAEL was 0.4 mg/kg/day (highest dose tested). 

The reproductive NOAEL was also 0.4 mg/kg/day. The offspring NOAEL was 0.12 mg/kg/day, 

while the LOAEL was 0.4 mg/kg/day based on increased incidence of retinal rosettes in F2b 

pups, increased dead pups at birth (decreased viability index), decreased lactation index, and 

reduced pup body weights.

Developmental neurotoxicity study in rats (MRID 47116201; 2007): Abamectin (96.2% a.i. 

on dry basis; Batch No.: VS094KO) in sesame oil was administered via gavage (10 mL/kg) to 

pregnant Alpk:APfSD rats (30/dose) from gestation day (GD) 7 through lactation day (LD) 22 at 

doses of 0, 0.12, 0.20, or 0.40 mg/kg/day. The pups were not directly dosed. Maternal toxicity: 

There were no effects of treatment on mortality, clinical signs, functional observational battery

parameters, body weights, body weight gains, food consumption, reproductive performance, or

gestation length. The maternal LOAEL was not observed. The maternal NOAEL was 0.4 

mg/kg/day.

Offspring toxicity: At 0.40 mg/kg/day, pup death was seen. The pups were generally small and 

presented with dehydration and tremors. Additionally, at this dose, pup body weights were 

decreased (p≤0.05) by 10-35% compared to controls from post-natal day (PND) 8 to 36 for 

males and females. There were no surviving pups at this dose level after PND 38. Since these 

deaths left an insufficient number of pups to complete all of the study objectives, all dams and 

pups at this dose were removed from the study during PND 15-38.

At 0.12 and 0.20 mg/kg/day, no treatment-related effects were observed on litter parameters 

(number born live, number born dead, sex ratio (% male), mean litter size, live birth index, and 

viability index), clinical signs, FOB parameters, motor activity, auditory startle reflex, learning 

and memory, sexual maturation, brain weight, or gross or microscopic pathology.

Decreases (p≤0.05) in post-weaning body weight were observed in the 0.12 and 0.20 mg/kg/day

males throughout the post-weaning interval (PND 36-63). The individual pup body weight data 

were re-evaluated using Mixed Model Analysis of Body Weight Data from the Developmental 

Neurotoxicity Study. The results indicated that there was a statistically significant difference for 

mid- and low-dose males from the corresponding controls, and for females no statistically

significant difference existed at either the low- or mid-dose level. However, the body weight 

decrease in low-dose males was approximately 3% relative to the controls, and it was determined 

not to be toxicologically significant. The offspring LOAEL for this effect is established at 0.2 

mg/kg/day based on statistically and biologically significant body weight reductions (6%). The 

NOAEL for this effect is established at 0.12 mg/kg/day. Because the dose-response to abamectin 

is body weight loss (detected at the low dose) leading to moribundity at the high dose, an 

additional 3X uncertainty factor, for steepness of the dose-response curve, is included in the 

reference dose and Level of Concern calculations. This additional 3X safety factor yields a de 

facto NOAEL of 0.04 mg/kg/day which is protective of the slight body weight decrease seen in 

low-dose males (p<0.01 using Mixed Model Analysis).
Page 22 of 62

Developmental neurotoxicity study in rats (MRIDs 46727403, 46727402, and 46727401; all 

2005): Abamectin (96.2% a.i. on dry basis; Batch No.: VS094KO) in sesame oil was 

administered via gavage (10 mL/kg) to pregnant Alpk:APfSD rats (30/dose) from gestation day

(GD) 7 through lactation day (LD) 22 at doses of 0, 0.12, 0.20, or 0.40 mg/kg/day. The pups 

were not directly dosed. Dams were allowed to deliver naturally and were killed at weaning on 

LD 29. On post-natal day (PND) 5, litters were standardized to 8 pups/litter; the remaining 

offspring and dams were sacrificed and not examined further. Subsequently, 1 

pup/sex/litter/group (at least 10 pups/sex/dose when available) were allocated to the following 

subsets: Subset 1: functional observational battery (FOB) on PND 5, 12, 22, 36, 46, and 61; 

motor activity on PND 14, 18, 22, and 60; and brain weight and neuropathology on PND 63. 

Subset 2: FOB on PND 5, 12, 22, 36, 46, and 61; water maze on PND 24 and 27; and brain 

weight and neuropathology on PND 63. Subset 3: FOB on PND 5 and 12; auditory startle on 

PND 23 and 61 (for animals not sacrificed on PND 12); and brain weight and neuropathology on 

PND 12. Subset 4: FOB on PND 5, 12, 22, 36, 46, and 61; water maze on PND 59 and 62. 

Maternal toxicity: There were no effects of treatment on mortality, clinical signs, functional 

observational battery parameters, body weights, body weight gains, food consumption, 

reproductive performance, or gestation length. The maternal LOAEL was not observed. The 

maternal NOAEL is 0.4 mg/kg/day (HDT).

Offspring toxicity: No treatment-related effects were observed on litter parameters (number 

born live, number born dead, sex ratio (% male), mean litter size, live birth index, and viability

index), clinical signs, FOB parameters, motor activity, auditory startle reflex, learning and 

memory, sexual maturation, brain weight, or gross or microscopic pathology.

On the day of weaning (PND 29), minor decreases (p≤0.05) in pup body weights of 5-7% were 

observed at 0.40 mg/kg/day. Pup body weights continued to be decreased (p<=0.01) by 5-6% in 

the males and by 8-10% in the females throughout the post-weaning interval (PND 36-63). The 

offspring LOAEL is 0.4 mg/kg/day, due to decreased body weights in both sexes. The NOAEL 

is 0.2 mg/kg/day.

There was no evidence of neurotoxicity in the offspring.

4.4.5 Additional Information from Literature Sources

No additional information relevant to potential susceptibility in the developing young was found 

in open literature sources.

4.4.6 Determination of Susceptibility

Increased susceptibility was demonstrated in the fetuses of CD-1 and CF-1 mice and rabbits in 

the developmental toxicity studies both quantitatively and qualitatively as discussed in Section 

4.4.3. Quantitative increase in susceptibility was also shown in reproductive toxicity and 

developmental neurotoxicity studies in rats where the LOAELs were substantially lower in the 

pups than those in the parental animals. 
Page 23 of 62

4.5 FQPA Safety Factor for Infants and Children

In previous abamectin risk assessments, the 10X FQPA safety factor was retained as a database 

uncertainty factor for the lack of a developmental neurotoxicity study. Two developmental 

neurotoxicity studies have now been submitted and reviewed and the findings in these studies 

were considered in the identification of toxicological points of departure and uncertainty/safety 

factors.

With the addition of the developmental neurotoxicity (DNT) studies, the toxicity database for 

abamectin is complete, except for immunotoxicity studies. EPA began requiring functional 

immunotoxicity testing of all food and non-food use pesticides on December 26, 2007. To 

address the issue of an immunotoxicity data gap and the associated database uncertainty factor, 

RAB3 examined the entire database of abamectin and determined that an additional uncertainty

factor is not needed to account for potential immunotoxicity. Abamectin has not been found to 

induce effects associated with immunotoxicity and abamectin does not belong to a class of 

chemicals that would be expected to be immunotoxic. Therefore, based on the above 

considerations, HED does not believe that conducting a special series 870.7800 immunotoxicity

study will result in a NOAEL less than the NOAELs of 0.5 and 0.12 mg/kg/day already set for 

abamectin acute and repeated exposures, respectively. An additional uncertainty factor (UFDB)

for database uncertainties associated with immunotoxicity does not need to be applied at this 

time. 

The RAB3 Risk Assessment Team has evaluated the entire toxicity database of abamectin and 

determined that an additional 3x FQPA safety factor is needed to address residual concerns as to 

all risk assessments other than acute dietary. For all risk assessments involving repeat exposures,

the selected toxicity endpoint is based on the decrease in pup body weight seen in the 

developmental neurotoxicity study (2007) and three reproduction studies in the rat. Although the 

study identified a NOAEL for the effects observed in the pups, the data clearly indicate that the 

decrease in pup body weight seen at 0.2 mg/kg/day rapidly progresses to death at the next higher 

tested dose level (0.4 mg/kg/day) in both reproduction and developmental neurotoxicity studies. 

As shown in Figure 1, the combined data from several reproduction toxicity and developmental 

neurotoxicity studies have documented a very narrow dose range from NOAEL (0.12 

mg/kg/day) to adverse effect (0.2 mg/kg/day) to severe adverse effect (0.4 mg/kg/day). Dose 

spacing is commonly greater than the <2x between NOAEL and LOAEL here, and the 3x 

difference between the NOAEL and the dose that induced mortality in the pups in the 

developmental neurotoxicity study provides little margin of safety for such a severe effect. 

Retaining an additional 3x FQPA safety factor effectively provides a 10x margin between the 

dose which causes death (0.4 mg/kg/day) and the NOAEL adjusted by the additional safety 

factor (0.12 mg/kg/day /3x = 0.04 mg/kg/day). A dose spacing of 10x between a NOAEL and 

LOAEL is as broad, if not broader, than the dose spacing generally used in animal testing and 

thus removes the residual concern with the steepness of the dose response curve and the severe 

effects seen here. Additionally, this adjusted point of departure (0.04 mg/kg/day) would also 

address the concerns for the increased susceptibility seen at higher doses in the two-generation 

reproduction study in rats (LOAEL = 0.4 mg/kg/day), prenatal developmental study in CD-1 

mice (LOAEL = 0.75 mg/kg/day), the prenatal developmental toxicity study in rabbits (LOAEL 

= 2 mg/kg/day), and the one-generation reproduction study (LOAEL = 0.2 mg/kg/day). The 10x 
Page 24 of 62

intraspecies factor is protective of the effects seen in CF-1 mice which were found to be the most 

sensitive strain of test animals due to the lack of P-glycoprotein. The data on CF-1 mice show 

that most of the effects are seen at doses above 0.06 mg/kg/day (Table A.3 of Appendix A.) 

Therefore, the additional 3x factor for the steepness of the dose-response curve and severity of 

effects is adequate.

With respect to acute dietary exposure, the endpoint selected for risk assessment is based on 

mydriasis observed in dogs. The additional 3x factor applied to chronic and other exposure 

scenarios is not applicable to acute exposure because steepness of the dose and severity of effects 

were not seen in the studies where mydriasis occurred. In addition, the reduced body weights as 

toxicity endpoints for other exposure scenarios is not a single dose effect.

Figure 1. Dose response for pup body weight decrease and pup mortality seen in developmental 

neurotoxicity study in rats (MRID 47116201).

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 modeling results which included conservative assumptions for the parent and 

all degradates of concern. Conservative assumptions were used in the water models. 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 exposures that should not underestimate the risks to infants and children 

from these requested uses.

Abamectin Dose Response

0

5

10

15

20

25

30

35

0.12 0.2 0.4

Dose (mg/kg/day)

% Body Wt Decrease

0

20

40

60

80

100

120

Mortality

% Body Wt Decrease

Mortality
Page 25 of 62

4.6 Dose-Response Assessment 

On June 19, 2008, the ToxSAC evaluated the previous toxicity endpoints and points of 

departures based on the current toxicity database with newly added studies, such as a second 

developmental neurotoxicity study, and acute and subchronic neurotoxicity studies on abamectin. 

The Committee recommended new toxicity endpoints and points of departures for risk 

assessment. On September 25, 2008, the ToxSAC met a second time to discuss the decrease in 

pup body weight seen in the 2007 developmental neurotoxicity study. Subsequent to the 

ToxSAC consultation, the RAB3 Risk Assessment Team determined the toxicity endpoints 

presented in Table 4.6.2 to be most protective and appropriate for risk assessment. The rationale 

for the endpoint selection is summarized below, and the toxicity endpoints and the points of 

departure for risk assessment for various exposure scenarios are presented in Table 4.6.2.

Acute Dietary Endpoint: Previously, the acute toxicity endpoint was based on mydriasis seen in 

a 53-week study in dogs (HIARC report, Sept. 1998), and the selected point of departure for risk 

assessment was a NOAEL of 0.25 mg/kg/day based on mydriasis as a likely single-dose effect. 

As mentioned before, at that time, acute neurotoxicity and developmental neurotoxicity studies 

were not available. On June 19, 2008, the ToxSAC evaluated all the toxicity studies relevant to 

establishing an acute oral toxicity endpoint and focused on the mydriasis seen in the toxicity

studies in the dog and other effects demonstrated in the acute neurotoxicity study in the rat. The 

results of the mydriasis seen in the dog studies are compiled and presented in Table 4.6.1. The 

dog toxicity studies were conducted in the 1980’s, and significant mydriasis was reported. The 

data show that mydriasis was not reported in treated dogs at dose levels equal to or less than 0.5 

mg/kg/day with a single dose administration. However, at 0.25 mg/kg/day, mydriasis was noted 

only after at least 9 weeks of treatment, and at 0.5 mg/kg/day, mydriasis was seen at treatment 

day 7. As treatment time progressed, the incidence of this effect was increased as indicated by

the finding that at treatment week 6, 5/12 dogs showed signs of mydriasis. With increasing dose 

levels, the time for mydriasis to occur was shortened. At 8 mg/kg/day, mydriasis was seen 

within 24 hrs of treatment. In dogs treated with 1 mg/kg/day, mydriasis was noted from 1 to 5

times during the first week of treatment. It was entirely possible that after a single dose at 1 

mg/kg, mydriasis was present. Therefore, the LOAEL for mydriasis resulting from a single dose 

is 1 mg/kg and the NOAEL is 0.5 mg/kg. The point of departure for acute oral exposure 

assessment is 0.5 mg/kg/day, and the toxicity endpoint is mydriasis seen in the 12-week doserange-finding toxicity study. This point of departure for risk assessment is also supported by the 

results of the acute neurotoxicity study in rats (MRID 46959202). This study showed the 

reduced splay reflex in males and females at 1.5 mg/kg/day (LOAEL). At the next higher dose

level, decreased motor activity, reduced splay reflex, and tip toe gait were seen. All the data 

considered together, the 12-week range-finding study in dogs and the acute neurotoxicity study

in rats are considered as critical studies in establishing the acute dietary endpoint. 

For acute dietary exposure, the FQPA safety factor may be reduced to 1x, based on mydriasis in 

dogs. The additional 3x factor for chronic and other exposure scenarios is not applicable to acute 

exposure because steepness of the dose and severity of effects were not seen in the studies where 

mydriasis occurred. In addition, the reduced body weights as toxicity endpoints for other 

exposure scenarios is not a single dose effect. Based on the safety factor of 100x (10x for 
Page 26 of 62

interspecies difference and 10x for intraspecies variability), the acute RfD is 0.005 mg/kg/day. 

Table 4.6.1. Mydriasis seen in all the available toxicity studies in dogs

Study Dose Levels (mg/kg/day)

0.25 0.5 1 2 4 8

12-Week dose 

range finding 

study (feeding) 

(1984)

(0.25, 0.5, 1, 4/2 

mg/kg/day)

(2M/2F)

Mydriasis 

was never 

noted.

Mydriasis was 

never noted.

Mydriasis was 

noted from 1 

to 5 times/ 

week, 

beginning on 

week 1.

Mydriasis was 

noted. Food 

consumption 

was markedly 

reduced. 

4 mg/kg was 

reduced to 2 

mg/kg due 

to marked 

reduction in 

FC.

Mydriasis 

was noted. 

Tremor, 

rapid 

respiration, 

& weakness 

were seen.

18-Week toxicity 

study (gavage) 

(1982)

(0.5, 2, & 8 

mg/kg/day) 

(3M/3F)

On treatment 

day 7, 

mydriasis was 

seen in 1 dog. 

On week 2, 

mydriasis was 

seen in 4/6 

dogs. Whole

body tremor, 

ataxia, & 

ptyalism was 

seen in one dog 

at week 2 and 

persisted until 

the end of the 

study.

Mydriasis, 

ataxia, 

ptyalism, and 

anorexia were 

seen in all 

dogs by day 3 

of dosing. 

After the third 

day of dosing,

1 dog died 

with signs of 

convulsion 

prior to death.

Mydrasis was 

reported 24 hrs 

after dosing. 

4/6 dogs had 

tremor, ataxia, 

ptyalism 

within 3 to 6 

hours after 

dosing, & 2/6 

dogs died 

within 4 hrs.

53-Week toxicity 

study feeding 

(1987)

(0.25, 0.5, & 1.0 

mg/kg/day) 

(6M/6F)

On week 

10, 1 dog 

was noted 

to have 

mydriasis, 

and none 

before that 

time.

On week 1, one 

dog was 

reported to 

have mydriasis. 

By week 6, 5 

dogs had 

mydriasis. 

On week 1, 

one dog had 

mydriasis. By

week 3, 4 

dogs had 

mydriasis. By 

week 33, 3 

males died.

Chronic Dietary Endpoint: Considering all the available toxicity data, it was determined that 

the decrease in pup body weights in the three reproduction studies and the recent developmental 

neurotoxicity study (2007; MRID 47116201) was found to be the most sensitive effect and to 

occur in young animals which were exposed to abamectin pre- and post-natally. [The pup body 

weight data are summarized in Tables C.2 (2005 DNT study) and C.3 (2007 DNT study) of 

Appendix C of D362615 (N. Dodd, 3/11/09).] In the 2007 developmental neurotoxicity study, a 

decrease in pup body weight was demonstrated in the pups at 0.12 and 0.2 mg/kg/day starting on 

PND 36 to the end of the study (PND 63) (Table C.3 of Appendix C of D362615. In addition, in 
Page 27 of 62

the high-dose group, the pup body weight decrease was present starting on PND 8 and the 

percent decrease relative to the controls was progressive (from 11% on PND 8 and reaching 

greater than 30% on PND 36). By PND 38, there were no surviving pups at this dose level. The 

pup body weight data of this study were analyzed using a statistical Mixed Model Analysis of 

Body Weight Data. 

This model takes into account the correlations of animals in the same litter and of measures of 

the same animal, can select the best covariance, uses all information available from the data, and 

is more appropriate for DNT body weight data structure than the ANOVA or Repeated Measures 

ANOVA. The model provides a measurement of the rate of body weight changes with time 

among the test groups. The analysis showed that there was a statistically significant decrease in 

male pup body weights in 0.12 and 0.2 mg/kg dose groups relative to the controls (p<0.0001 for 

0.2 mg/kg males and p<0.002 for 0.12 mg/kg males) (Table C.4 of Appendix C of D362615). 

The decrease was 6% and 3.3 % in 0.2 and 0.12 mg/kg males, respectively. The decrease in 

mid- and low-dose females was not statistically significant (0.12 mg/kg: 3.2 % with p<0.141; 0.2 

mg/kg: 4.3% with p<0.053). To further evaluate the pup body weight reduction affected by

abamectin, RAB3 conducted a comparative evaluation of all the pup body weight changes from 

PND 7 to 21 in all the available reproduction studies with abamectin. The results are 

summarized in Table C.1 of Appendix C of D362615. The two one-generation studies appeared 

to be dose-range finding studies because one study (MRID 00096450, 1982) employed dose 

levels which were too high (0.5, 1.00 and 1.5 mg/kg/day). In this study, decreased body weight 

was seen at all dose levels and death occurred in the high dose group at PND 14. The other onegeneration study (MRID 00096451, 1982) employed dose levels of 0.10, 0.2, and 0.4 mg/kg/day, 

which were less than the lowest dose of the first study. The mean pup body weights were 

decreased from PND 7 to 21 by as much as 16% at the highest dose tested (0.4 mg/kg/day). No 

pup body weight decrease was seen in the 0.2 and 0.1 dose groups. The two-generation studies 

used dose levels of 0.05, 0.12 and 0.40 mg/kg/day. Decreased pup body weights were 

consistently seen in F1a, F1b, F2a, and F2b pups at 0.4 mg/kg/day.

The above data and discussion were presented to the ToxSAC on Sept. 25, 2008, to request the 

Committee’s opinion on determining the offspring LOAEL based on the pup body weight data 

for offspring toxicity. The ToxSAC recommended three scenarios for choosing the 

NOAEL/LOAEL for the DNT study which were then thoroughly considered by the RAB3 Risk 

Assessment Team. The RAB3 Risk Assessment Team concluded that the decrease in male pup 

body weight at the 0.2 mg/kg/day dose in the 2007 developmental neurotoxicity study was 

statistically and biologically significant, while decreased body weight at the 0.12 mg/kg/day dose 

was not biologically significant. The 0.2 mg/kg/day dose is considered to be statistically and 

biologically significant for the following reasons: 1) At 0.2 mg/kg/day, other effects such as 

spastic movement and delayed incisor eruption were also seen in the pups; and 2) The body 

weight decrease was 6%, whereas an approximately 5% decrease in body weight in pups is 

generally considered to be biologically significant. Therefore, the NOAEL was established at 

0.12 mg/kg/day and the LOAEL was established at 0.2 mg/kg/day based on decreased pup body

weight seen in the developmental neurotoxicity study. Therefore, the decrease in male pup body 

weight at the 0.2 mg/kg/day dose in the developmental neurotoxicity study is established as the 

toxicity endpoint, and the NOAEL of 0.12 mg/kg/day is the point of departure for risk 

assessment. As discussed in the FQPA Safety Factor Section, the 10x intraspecies factor is 
Page 28 of 62

protective of the most sensitive subpopulation as represented by CF-1 mice. An additional 3x 

factor for the steepness of the dose-response curve and the severity of effects is applied. With 

that 3x factor and the standard safety factor of 100x (10x for intraspecies and 10x for interspecies 

differences), the chronic RfD is 0.0004 mg/kg/day. 

Carcinogenicity: Abamectin is characterized as “not likely to be carcinogenic to humans” 

based on the absence of significant increase in tumor incidence in two adequate (rat and mouse) 

carcinogenicity studies.

Incidental Oral, Dermal, and Inhalation Endpoints (all durations): The endpoints for these 

routes of exposure were decreased pup body weight seen at the LOAEL of 0.2 mg/kg/day from 

combined results of three reproduction studies and two developmental neurotoxicity studies in 

the rat. The details for selecting this endpoint and safety factor are discussed in the Chronic 

Dietary Endpoint Section. This endpoint was selected because it best represented the exposure 

scenario time frames (appropriate duration), was relevant due to evidence of increased 

susceptibility to the offspring following pre- and postnatal exposure to abamectin, and 

adequately reflected all the populations at risk. Because an oral study was selected for all 

durations of dermal and inhalation exposure, a 1% dermal absorption factor and a 100% 

inhalation absorption factor will be used in the route-to-route extrapolation.

Dermal Absorption: According to the HIARC report dated September 15, 1998 (HED document 

No. 012845), a dermal penetration factor of 1% should be used for risk assessment purposes. 

This value was based on the results from a dermal absorption study in monkeys which 

demonstrated that <1% of an applied dose is absorbed. Because of the physical-chemical 

properties, and known pharmacokinetics and excretion pattern of avermectin B1a, the monkey is 

considered to be an appropriate model to use in determining dermal absorption for this chemical.

Level of Concern (LOC) for Residential Risk Assessment: For residential exposure risk 

assessments, the uncertainty factor is 300 (10x for interspecies extrapolation, 10x for intraspecies 

variations, and a 3x factor for the steepness of the dose/response curve in several studies and the 

severity of effects [death] seen at the slightly higher dose level).

Level of Concern (LOC) for Occupational Risk Assessment: For occupational exposure risk 

assessments, the uncertainty factor is 300 (10x for interspecies extrapolation, 10x for intraspecies 

variations, and an additional factor of 3x for the steepness of the dose-response curve and the 

severity of effects). 
Page 29 of 62

Table 4.6.2.1. Summary of Toxicological Doses and Endpoints for Abamectin for Use in Dietary and NonOccupational Human Health Risk Assessments

Exposure/ 

Scenarios

Point of 

Departure

Uncertainty/

FQPA Safety 

Factor

RFD, PAD, 

Level of 

Concern 

(LOC) 

Study and Toxicological Effects

Acute Dietary

(General 

population, 

including infants 

and children)

NOAEL = 

0.5 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF=1x

aRfD = 0.005 

mg/kg/day

12-Week dose-range finding study in dogs

LOAEL = 1.0 mg/kg/day based on mydriasis 

seen 1-5 times during the first week of 

treatment. 

Acute neurotoxicity study in rats

LOAEL= 1.5 mg/kg/day based on increased 

incidence of foot splay.

Chronic Dietary

(All populations)

NOAEL = 

0.12 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF=3x*

cPAD = 

0.0004 

mg/kg/day

Combined data from three reproduction 

studies and two developmental 

neurotoxicity studies (please see the 

discussion on Chronic Dietary Endpoint)

LOAEL = 0.2 mg/kg/day based on decreased 

pup body weight in pups at 0.2 mg/kg/day. 

Short-Term and 

Intermediate 

Term

Incidental Oral 

NOAEL = 

0.12 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF=3x*

Residential 

LOC for 

MOE = 300

Combined data from three reproduction 

studies and two developmental 

neurotoxicity studies (please see the 

discussion on Chronic Dietary Endpoint)

LOAEL = 0.2 mg/kg/day based on decreased 

pup body weight. 

Dermal (All 

Durations)

NOAEL = 

0.12 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF=3x*

Residential 

LOC for 

MOE = 300

Combined data from three reproduction 

studies and two developmental 

neurotoxicity studies (please see the 

discussion on Chronic Dietary Endpoint)

LOAEL = 0.2 mg/kg/day based on decreased 

pup body weight. 

Inhalation (All 

durations)

NOAEL = 

0.12 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF=3x*

Residential 

LOC for 

MOE = 300

Combined data from three reproduction 

studies and two developmental 

neurotoxicity studies (please see the 

discussion on Chronic Dietary Endpoint)

LOAEL = 0.2 mg/kg/day based on decreased 

pup body weight. 

Cancer (oral, 

dermal, 

inhalation)

Classification: Not likely to be carcinogenic to humans 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). 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.

* The additional FQPA safety factor of 3x is for the steepness of the dose-response curve and the severity of effects.
Page 30 of 62

Table 4.6.2.2. Summary of Toxicological Doses and Endpoints for Abamectin for Use in Occupational

Human Health Risk Assessments

Exposure/ Scenarios Point of 

Departure

Uncertainty/ 

Safety Factor

RFD, PAD, 

LOC* Study and Toxicological Effects

Dermal (Short-Term

and IntermediateTerm)

NOAEL = 0.12 

mg/kg/day

1% Dermal 

Absorption 

Factor

UFA = 10X

UFH = 10X

SF = 3X

LOC: MOE = 300

Combined data from three 

reproduction studies and two 

developmental neurotoxicity 

studies.

LOAEL = 0.2 mg/kg/day based 

on decreased pup body weight in 

pups. 

Inhalation (ShortTerm and 

Intermediate-Term)

NOAEL = 0.12 

mg/kg/day

UFA = 10X

UFH = 10X

SF = 3X

LOC: MOE = 300

Combined data from three 

reproduction studies and two 

developmental neurotoxicity 

studies.

LOAEL = 0.2 mg/kg/day based 

on decreased pup body weight in 

pups. 

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. N/A = 

not applicable. 

* Level of Concern (LOC): For occupational exposure risk assessments, the uncertainty factor is 300X (10X for 

interspecies extrapolation; 10X for intraspecies variations; and 3X for the steepness of the dose-response curve in 

several studies and the severity of effects [death] seen at the slightly higher dose level).

Recommendation for Aggregate Exposure Risk Assessments

As per FQPA, 1996, when there are potential residential exposures to the pesticide, aggregate 

risk assessment must consider exposures from three major sources: oral, dermal and inhalation 

exposures. The toxicity endpoints selected for these routes of exposure may be aggregated as 

follows: the oral, dermal, and inhalation routes of exposure can be combined to assess aggregate 

risks because of the selection of a common toxicity endpoint for all routes and durations of 

exposure.

4.7 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 
Page 31 of 62

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision, EPA reviewed these data and 

selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), abamectin is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Abamectin 

was included on that list and has been issued an order to conduct the Tier 1 testing. Once all 

required Tier 1 and Tier 2 data have been received and reviewed, the endpoints and safety factors 

used for risk assessment purposes will be examined and a new risk assessment performed if 

necessary. For further information on the status of the EDSP, the policies and procedures, the 

list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit 

our website: http://www.epa.gov/endo/. 

5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

Metabolism in Primary Crops: No new plant metabolism data were submitted with this 

registration request. The qualitative nature of the abamectin residues in the bulb onion subgroup 

3-07A, chives, and dry beans is adequately understood based on metabolism studies on cotton, 

citrus, and celery (PP#'s 5G3500, 5G3287, and 8F3649, respectively), as well as a report titled 

"Comparative Degradation of Avermectin B1a in Cotton Leaf, Citrus Fruit, Celery, and In Vitro" 

(PP#9F3703, S. Willett, 12/15/89). The available studies indicate that the metabolism of 

abamectin in plants results in a complex mixture of residues. The majority of the terminal residue 

is composed of several unidentified polar degradates. The parent compound, its delta-8,9-

isomer, and the alpha 8-OH degradate have been identified in plants, with only the parent and its 

delta-8,9-isomer each accounting for at least 10% of the total residue. The polar degradates 

generated on citrus (7-day PHI) and in vitro (30 hour sample) have been tested for toxicity
Page 32 of 62

(in the developmental toxicity study in CF-1 mice) and were found to be of no toxicological 

significance at the levels tested (TOX memos 7080 and 7081, W. Dykstra, 3/15/89; 

PP#8F3592, F. Boyd, 6/21/89; D203373, G. J. Herndon, 3/29/95). As stated in The Pesticide 

Manual, Eleventh Edition, British Crop Protection Council (1997), abamectin has limited plant 

systemic activity, but does exhibit some translaminar movement. For the tolerance expression 

and risk assessment, the residues of concern in these crops are the parent compounds (avermectin 

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

avermectin B1b).

Metabolism in Rotational Crops: No rotational crop studies were submitted with this registration 

request. Review of the results of the confined rotational crop study indicated that avermectin 

residues accumulated in some rotational crops at levels up to 10-12 ppb. However, the 

radioactivity was due to polar degradates that were of little toxicological concern as compared to 

the parent compound avermectin B1 and/or the delta-8,9-isomer (Memo, P. Mastradone, 

4/24/88). Therefore, field rotational crop studies are not required (PP#7F3500, PP#8F3592, and 

PP#5E4566, DP#s 230333, 230352, and 230880, G. Herndon, 1/10/97).

Metabolism in Livestock: No new livestock metabolism data were submitted with this 

registration request. The qualitative nature of abamectin residues in ruminants as a result of 

application to crops is adequately understood based on a goat metabolism study which was 

previously submitted (PP#7G3468, L. Cheng, 2/11/87; PP#9F3703, S. Willett, 12/15/89). The 

residues of concern in ruminants for the tolerance expression and risk assessment are the parent 

compounds (avermectin B1a and B1b) and their delta-8,9-isomers. An additional metabolite (24-

hydroxymethyl avermectin B1a) was identified and is potentially of toxicological significance, 

but was not included in the tolerance expression because of its presence at low levels 

(PP#8F3592, F. Boyd, 6/21/89; DP#203373, G. J. Herndon, 3/29/95). If the tolerances for 

residues in meat and milk need to be raised at some future time due to registration of abamectin 

on additional feed items, the 24-hydroxymethyl metabolite may need to be included in the 

tolerance expression and appropriate enforcement methods developed.

No poultry metabolism study has been submitted. Since no significant poultry feed items are 

associated with the proposed uses, as indicated in Table 1 Feedstuffs (June 2008), no poultry

metabolism study is required.

Metabolism in Rats:

Avermectin B1a does not bioaccumulate in rat tissues. Avermectin B1a in rats is metabolized to 

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

residues. 

5.1.2 Summary of Environmental Degradation

Abamectin is stable to abiotic hydrolysis; determination of stability to photolysis and 

biodegradation is pending submission of acceptable data. Abamectin has very low water 

solubility but is soluble in organic solvents. Abamectin is not expected to leach since it is not 

soluble in water and binds to soil. Abamectin is degraded by soil microorganisms. 
Page 33 of 62

The previous screening assessment of estimated drinking water concentrations (EDWCs) 

included abamectin and its major soil degradate (a mixture of an 8-α-hydroxy and a ring opened 

aldehyde derivative). The delta-8,9-isomers (also known as 8,9-Z isomers) were not included in 

the drinking water assessment because they were not identified in the fate studies.

This current drinking water exposure assessment conservatively models only parent abamectin 

based on an assumption of stability until acceptable environmental fate data are submitted 

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

5.1.3 Comparison of Metabolic Pathways

Avermectin B1a does not bioaccumulate in rat tissues. Avermectin B1a in rats is metabolized to 

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

residues. 

Metabolism of abamectin in ruminants (goats) appears to be similar to its metabolism in rats in 

that the 24-hydroxy-methyl metabolite is formed, although it is a minor metabolite in ruminants. 

Based on the goat metabolism study, the residues of concern in ruminants for the tolerance 

expression and risk assessment are the parent compounds (avermectin B1a and B1b) and their 

delta-8,9-isomers. 

A poultry metabolism study has not been conducted. Since no significant poultry feed items, as 

indicated in Table 1 Feedstuffs (June 2008), are associated with the proposed uses, no poultry

metabolism study is required.

Metabolism studies on cottonseed, citrus, and celery indicate that the metabolism of abamectin in 

plants results in a complex mixture of residues. The majority of the terminal residue is 

composed of several unidentified polar degradates. The parent compound, its delta-8,9-isomer, 

and the alpha 8-OH degradate have been identified in plants, with only the parent and its delta8,9-isomer each accounting for at least 10% of the total residue. In citrus, the majority of the 

residue remained in the peel but a small amount translocated into the pulp. For the tolerance 

assessment and risk assessment, the residues of concern in these crops are the parent compounds 

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

The results of a confined rotational crop study indicated that avermectin residues accumulated in 

some rotational crops at levels up to 10-12 ppb; however, the radioactivity was due to polar 

degradates that were of little toxicological concern as compared to the parent compound 

avermectin B1 and/or the delta-8,9-isomer. It is not likely that residues of concern will occur in 

rotational crops.

5.1.4 Residues of Concern Summary and Rationale

The metabolism studies on cotton, citrus, and celery indicate that the metabolism of abamectin in 

plants results in a complex mixture of residues, with the majority of the terminal residue 

composed of several unidentified polar degradates. The parent compound, its delta-8,9-isomer, 
Page 34 of 62

and the alpha 8-OH degradate have been identified in plants, with only the parent and its delta8,9-isomer each accounting for at least 10% of the total residue. The polar degradates 

generated on citrus (7-day PHI) and in vitro (30 hour sample) have been tested for toxicity

(in the developmental toxicity study in CF-1 mice) and were found to be of no toxicological 

significance at the levels tested (TOX memos 7080 and 7081, W. Dykstra, 3/15/89; 

PP#8F3592, F. Boyd, 6/21/89; D203373, G. J. Herndon, 3/29/95). 

Table 5.1.4 Summary of Metabolites and Degradates to be included in the Risk Assessment 

and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants Primary Crop Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Rotational Crop Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z

isomers)**

Livestock Ruminant* Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Poultry Not applicable Not applicable

Drinking Water Parent (avermectin B1a and 

B1b)***

Not applicable

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

** No rotational crop tolerances have been established.

*** The delta-8,9-isomers (also known as 8,9-Z isomers) are not included in the drinking water assessment because 

they were not identified in the fate studies. The major soil degradate included in the previous assessment (a mixture 

of an 8-alpha-hydroxy and a ring opened aldehyde derivative) was not included in the current assessment based on 

an assumption of stability of parent until acceptable environmental fate data are submitted (D380524, G. Orrick, 

1/31/11). 

5.2 Food Residue Profile

References: Abamectin. Petition for Tolerances/Section 3 Registration on the Bulb Onion Subgroup 3-07A, 

Chives, and Dry Beans. Summary of Analytical Chemistry and Residue Data, DP#380795, N. Dodd, 

5/18/11.

DER References: 48135001.der (onion, bulb), 48135002.der (chives, fresh), 48135003.der (beans, dry)

As stated in The Pesticide Manual, Eleventh Edition, British Crop Protection Council (1997), 

abamectin has limited plant systemic activity, but does exhibit some translaminar movement. In 

the citrus metabolism study, the majority of the residues remained in the peel but a small amount 

translocated into the pulp.

Residues from application to dry bulb onion, chive (fresh), and dry bean are reported in Table 

5.2 below. The number and geographic representation of the field trials are adequate. 
Page 35 of 62

The field trials were conducted using the emulsifiable concentrate (EC) formulation. The 

ChemSAC determined on 5/18/11 that the available bridging studies for the suspension

concentrate (SC) formulation on leafy vegetables, fruiting vegetables, cucurbit vegetables, citrus 

fruits, and pome fruits (DP#364734, N. Dodd, 1/21/10) can be translated to support use of the SC 

formulation on the bulb onion subgroup 3-07A, chive, and dry bean provided the use directions 

for the SC formulation always require use of a non-ionic surfactant or a horticultural oil in the 

spray mix and the preharvest intervals are ≥ 7 days. 

The dry bulb onion field trials reflect the proposed use pattern, including the use of an adjuvant 

in all trials.

The fresh chive field trials reflect the proposed use pattern, including application rate and PHI. 

An adjuvant was not used in the field trials. Label revisions are required for the EC labels to 

remove the statement that adjuvants may be used on chives since the submitted chive field trials 

do not reflect the use of an adjuvant. Also, the labels must be revised to specify a 7-day PHI for 

chives since most of the chive data reflect a 7-day PHI. 

The dry bean field trials reflect the proposed use pattern, including application rate and PHI. An 

adjuvant was not used in the field trials. The EC label indicates than an adjuvant can be used 

with the applications, but is not required. Label revisions are required for the EC labels to 

remove the statement that adjuvants may be used on dry beans since the submitted dry bean field 

trials do not reflect the use of an adjuvant. The labels must be revised to specify a 7-day PHI for 

dry beans since most of the dry bean data reflect a 7-day PHI. The petitioner should also submit 

the storage temperature of the dry bean samples. Residue data for cowpea forage and hay must 

be submitted before cowpea can be included in the dry bean seed tolerance.

The residue data for fresh chive, dry bulb onion, and dry bean were not entered into the tolerance 

spreadsheet since >15% of treated samples bore residues below the LOQ. For the purpose of 

setting tolerances, HED will rely on the maximum residues observed in the field trials (i.e.,

0.0046 ppm for dry bulb onion; 0.0045 ppm for fresh chives; and 0.006 ppm for dry bean). 

Based on these data, HED recommends tolerances of 0.01 ppm for dry bulb onion, chive, and dry

bean.

Table 5.2. Summary of Residue Data from Crop Field Trials with an Abamectin Formulation 

 (EC formulation).

Commodity Total 

Applic. 

Rate

(lb ai/A) 

PHI 

(days)

Residue Levels (ppm)

n Min. Max. HAFT Median Mean Std. Dev.

Total Combined Residues

Bean, dry (proposed use = 0.056 lb ai/A total application rate, 6-day PHI)

Bean, dry 0.054-

0.061 5-7 24 <0.004 0.006 0.005 0.004 0.0041 0.0

Chive (proposed use = 0.056 lb ai/A total application rate, 6-day PHI)

Chive, 

fresh 

leaves

0.057-0.059 5-7 6 <0.004 0.0045 0.0042 0.004 0.0041 0.0

Onion, dry bulb (proposed use = 0.056 lb ai/A total application rate, 30-day PHI)
Page 36 of 62

Table 5.2. Summary of Residue Data from Crop Field Trials with an Abamectin Formulation 

 (EC formulation).

Commodity Total 

Applic. 

Rate

(lb ai/A) 

PHI 

(days)

Residue Levels (ppm)

n Min. Max. HAFT Median Mean Std. Dev.

Onion, dry 

bulb

0.0567-

0.0767 29-31 16 <0.004 0.0046 0.0043 0.004 0.0040 0.0002

5.3 Water Residue Profile

Reference: Abamectin: Drinking Water Exposure Assessment for Proposed Section 3 New Uses on Chives, Dried 

Beans, and the Bulb Onion Subgroup 3-07A, DP#380524, G. Orrick, 1/31/11.

Estimated drinking water concentrations (EDWCs) were provided for parent abamectin. The 

aquatic photodegradation products, which are polar and of low molecular weight, appear to be 

sugars with low toxicity relative to the parent. The delta-8,9-isomers (also known as 8,9-Z

isomers) are not included in the drinking water assessment because they were not identified in 

the fate studies. The previously included major soil degradate (a mixture of an 8-α-hydroxy and 

a ring opened aldehyde derivative) was not included in the current assessment based on an 

assumption of stability of parent until acceptable environmental fate data are submitted. 

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 estimated residues in surface water 

were derived using the Tier II model PRZM/EXAMS (Pesticide Root Zone Model/Exposure 

Analysis Modeling System). The Tier I SCI-GROW (Screening Concentration in Ground 

Water) model was used to derive the estimated concentration in ground water. 

The modeled values used in this assessment for drinking water were based on residues in surface 

water from the use of abamectin on dry beans in Michigan. The surface water residue estimates 

were adjusted for the national default percent cropped area (PCA) adjustment factor of 87%. 

The estimated residues in ground water were lower than those in surface water.

 

Results from the PRZM/EXAMS screening model predict that the maximum acute (1-in-10 year 

peak) concentration of parent abamectin in surface water is not expected to exceed 2.3 ug/L

(ppb), based on the current maximum seasonal use rate of 0.056 lb ai/A/year on dry beans in MI. 

The maximum chronic (1-in-10 year annual mean) concentration of parent abamectin in surface 

water is not expected to exceed 1.3 ug/L (ppb), based on the one-in-10 year annual mean and the 

current maximum seasonal use rate in the MI dry bean scenario.

 

Results from the SCI-GROW screening model predict that the maximum acute and chronic 

concentration of parent abamectin in shallow ground water is not expected to exceed 1.6 x 10-3

ug/L (ppb) based on the current maximum seasonal use rate on tomatoes and cucurbits of 0.18 lb 

ai/A/year. 
Page 37 of 62

Table 5.3. Summary of Estimated Surface Water and Groundwater Concentrations for Abamectin 

and its Major Soil Degradates.c

Abamectin

Surface Water Conc., ppb a Groundwater Conc., ppb b

Acute 2.3 1.6 x 10-3

Chronic (non-cancer) 1.3 1.6 x 10-3

Chronic (cancer) 0.94 Not applicable

a

From the Tier II PRZM-EXAMS model. Input parameters for acute and chronic are based on the MI dry bean 

scenario of 0.056 lb ai/A/year with the percent cropped area adjustment factor of 87%.

b

From the SCI-GROW model based on the tomato and cucurbits scenario of 0.18 lb ai/A/year.

c Data source: D380524, G. Orrick, 1/31/11.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

References: Abamectin: Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk 

Assessments for the Section 3 on Bulb Onions, Chives, and Dry Beans, DP#380796, N. Dodd, 6/13/11.

Abamectin: Drinking Water Exposure Assessment for Proposed Section 3 New Uses on Chives, Dried Beans, and 

the Bulb Onion Subgroup 3-07A, DP#380524, G. Orrick, 1/31/11.

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model DEEM-FCIDTM, Version 2.03 

which uses food consumption data from the U.S. Department of Agriculture’s Continuing 

Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. These analyses were

performed to support Section 3 requests for use on the bulb onion subgroup 3-07A, chives, and 

dry bean. 

Tolerance-level residues and 100% crop treated were used for the proposed crops. No 

monitoring data were used. Anticipated residues based on field trial data were used. 

Empirical/default processing factors and percent crop treated (%CT) data were also used. Also, 

for the chronic dietary assessment, residues of abamectin in foods exposed in a food-handling 

establishment were assumed to be 1⁄2 LOD (0.0002 ppm) (DP#283668, J. Morales, 20-NOV2003). As shown in Section 5.3 above, drinking water values were 2.3 ppb for the acute 

assessment and 1.3 ppb for the chronic assessment.
Page 38 of 62

5.4.2 Percent Crop Treated Used in Dietary Assessment

Reference: Usage Report Package in Support of Registration for the Insecticide Abamectin (122804), 

DP#382732, Arthur H. Grube, 10/21/10.

A Screening Level Usage Analysis (SLUA) was provided by BEAD based on data years 2001-

2008; the SLUA as provided by BEAD is included in the dietary exposure assessment memo 

(DP#380796, N. Dodd, 6/13/11). The estimated maximum percent crop treated was used for the 

acute dietary risk assessment; the estimated weighted average percent crop treated was used for 

the chronic dietary risk assessment. The percent crop treated data, as used in the acute and 

chronic food residue input files in the DEEM, are summarized in Table 5.4.2 below. For other 

crops, 100% CT was assumed.

Table 5.4.2. Screening Level Estimates of Agricultural Uses of Abamectin dated October 6, 20101,2

Crop Percent Crop Treated

Average Maximum

Almonds 50 75

Apples 5 10

Apricots 5 5

Avocados 40 60

Cantaloupes 15 30

Celery 40 65

Cherries <1 <2.5

Cotton 5 20

Cucumbers 5 10

Grapefruit 60 80

Grapes 10 25

Honeydew 20 35

Lemons 35 55

Lettuce 10 20

Oranges 25 45

Peaches <1 <2.5

Pears 70 80

Pecans <1 <2.5

Peppers 10 25

Potatoes <1 <2.5

Prunes <2.5 10

Pumpkins <2.5 10

Spinach 20 45

Squash 5 10

Strawberries 30 45

Tangerines 60 65

Tomatoes 10 20

Walnuts 10 20

Watermelons 5 10

1

SLUA data sources include the USDA-NASS (United States Department of Agriculture’s National Agricultural 

Statistics Service); Private Pesticide Market Research; and California DPR (Department of Pesticide Regulation).

2

For chronic, the % CT was used in calculations; if the food handling establishment (FHE) value of 0.0002 ppm 

was greater than the product of residue level x processing factor x % crop treated, then the FHE value was used.
Page 39 of 62

5.4.3 Acute Dietary Risk Assessment

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

proposed and established food uses of abamectin. Tolerance level residues were used for the 

proposed crops and okra. Acute anticipated residues for the remaining commodities were 

derived from field trial data. Empirical and default processing factors and percent crop treated 

(%CT) were used as available. Estimated drinking water concentrations (EDWCs) from the 

Environmental Fate and Effects Division (EFED) were also included. Surface drinking water 

concentrations were estimated using the Tier II PRZM/EXAMS (Pesticide Root Zone 

Model/Exposure Analysis Modeling System) computer model and percent cropped area (PCA) 

of 87%. The model predicts that the maximum concentration of total residues of abamectin in 

surface water (the 1-in-10-year peak exposure) is not likely to exceed 2.3 ppb from the use of 

aerial/ground application to dry beans in Michigan. 

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 16% of the aPAD for the general U.S. population and 

30% of the aPAD for all infants (<1 year old), the most highly exposed population subgroup.

5.4.4 Chronic Dietary Risk Assessment

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

proposed and established food uses of abamectin. Tolerance level residues were used for the 

proposed crops and okra. Average residues from field trials were used for the remaining crops. 

Empirical and default processing factors and %CT were used as available. Drinking water was 

represented by a single point estimate of average abamectin residues (the 1-in-10-year annual 

mean). The estimated surface water concentration of 1.3 ppb was based on the application to dry

beans in Michigan.

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

below HED’s level of concern (<100% cPAD) for the general U.S. population and all population 

subgroups. Abamectin dietary exposure for food and drinking water is 18% of the cPAD for the 

general U.S. population and 50% of the cPAD for children 1-2 yrs old, the most highly exposed 

population subgroup.

5.4.5 Cancer Dietary Risk Assessment

The HED RfD/Peer Review Committee classified abamectin 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. 
Page 40 of 62

5.4.6 Summary Table

Table 5.4.6. Results of Acute and Chronic Dietary (Food and Drinking Water) Exposure 

and Risk Estimates for Abamectin.

Population Subgroup PAD, 

mg/kg/day

DEEM-FCID

Exposure, 

mg/kg/day % PAD

Acute Dietary Estimates (99.9th Percentile of Exposure)

U.S. Population 0.005 0.000777 16

All infants (< 1 yr) 0.005 0.001501 30

Children 1-2 yrs 0.005 0.001230 25

Children 3-5 yrs 0.005 0.000976 20

Children 6-12 yrs 0.005 0.000599 12

Youth 13-19 yrs 0.005 0.000554 11

Adults 20-49 yrs 0.005 0.000464 9

Adults 50+ yrs 0.005 0.000355 7

Females 13-49 yrs 0.005 0.000467 9

Chronic Dietary Estimates

U.S. Population 0.0004 0.000070 18

All infants (< 1 yr) 0.0004 0.000151 38

Children 1-2 yrs 0.0004 0.000199 50

Children 3-5 yrs 0.0004 0.000152 38

Children 6-12 yrs 0.0004 0.000098 24

Youth 13-19 yrs 0.0004 0.000059 15

Adults 20-49 yrs 0.0004 0.000056 14

Adults 50+ yrs 0.0004 0.000054 13

Females 13-49 yrs 0.0004 0.000054 13

Cancer Dietary Estimate

U.S. Population Classification: “Not likely to be carcinogenic to humans” based 

on the absence of a significant increase in tumor incidence in 

two adequate rodent carcinogenicity studies. 
Page 41 of 62

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

References: Abamectin. Occupational and Residential Exposure Assessment for Proposed IR-4 Foliar Uses 

on Bulb Onions (Subgroup 3-07A), Chives, and Dry Beans, N. Tsaur, DP#380797, 3/29/11.

Abamectin: Occupational and Residential Risk Assessment to Support Section 3 Request for Uses 

on Various Food Crops and Food-Handling Establishments, J. Arthur, DP#306906, 10/29/04

6.1 Residential Handler Exposure

While no residential uses are proposed in the current petition, there are residential uses currently

registered for abamectin. Short- to intermediate-term exposures may occur to adults from 

handling the pesticide. Residential handler exposures are assessed below for two uses which are 

considered to represent the reasonable high-end residential exposure potential: 1) granular baits 

used to treat lawns; and 2) indoor crack and crevice dust products. The critical exposure (worst 

case scenario) of all residential uses are accounted for in the aggregate.

Lawn Applications

Short-/Intermediate-term total MOEs (dermal + inhalation exposures) for residential handlers 

range from 110,000 to 17,000,000 which are greater than the LOC of 300, and are not of 

concern. Exposure and risk assessment inputs and results for residential lawn applicators are 

summarized in Table 6.1.1.

Crack and Crevice Applications

The short- and intermediate-term MOEs for dermal and inhalation exposure are each 5,000,000. 

The combined dermal and inhalation MOE is 2,500,000, which is greater than the LOC of 300 

and is not of concern. Exposure and risk inputs and estimates are summarized in Table 6.1.2.
Page 42 of 62

Table 6.1.1. Exposure and Risk Estimate for Residential Lawn Applicators

PHED Scenario

Exposure 

Scenario 

Personal 

Protective 

Equipment

Exposure 

Route

Application 

Rate

(lb ai/acre) 

Acres 

Treated

(acres/

day)

Unit 

Exposure

(mg/lb ai) 

Data

Confidence

Absorption 

Factor

Body

Weight 

(kg)

Daily Dose1

(mg/kg/day)

Short- and 

IntermediateTerm NOAEL

(mg/kg/day)

Short- and 

Intermediate 

Term

MOE2

Granular Bait 

Dispersed by 

Hand

short sleeves

short pants

no gloves

Dermal 1.1E-4 0.023 430 Medium 0.01 60 1.8.0E-7 0.12 6.7E+5

Inhalation 1.1E-4 0.023 0.47 Medium 1.0 60 2.0E-8 0.12 6.0E+6

Total 2.0E-7 0.12 6.0E+5

Belly Grinder 

Granular Open 

Pour (Mix, Load, 

and Apply)

short sleeves

short pants

no gloves

Dermal 1.1E-4 0.5 110 Medium 0.01 60 1.0E-6 0.12 1.2E+5

Inhalation 1.1E-4 0.5 0.062 High 1.0 60 5.7E-8 0.12 2.2E+6

Total 1.1E-6 0.12 1.1E+5

Push Type 

Granular (Mix, 

Load, and Apply)

short sleeves 

short pants

no gloves

Dermal 1.1E-4 0.5 0.68 Note 1. 0.01 60 6.0E-9 0.12 2.0E+7

Inhalation 1.1E-4 0.5 9.1E-4 Note 1. 1.0 60 1.0E-9 0.12 1.2E+8

Total 7.0E-9 0.12 1.7E+7

1 Daily Dose =[Application Rate (lb ai/A) x Acres Treated (A/day) x Unit Exposure (mg/lb ai handled) x Absorption Factor]/Body Weight 

2

Short- and Intermediate-Term MOE = Short- and Intermediate-Term NOAEL/Daily Dose

Note 1. Unit exposure values taken from ORETF study (OMA003) and are considered to be more reliable and applicable than PHED values for this scenario.

Table 6.1.2. Exposure and Risk Estimate for Residential Application of 0.05% Crack & Crevice Powder

PHED Scenario

Selected from Draft 

SOP for Residential 

Exposure Assessments 

Clothing Exposure 

Route

Application 

Rate1

(lb ai/day) 

PHED 

Unit 

Exposure

(mg/lb ai) 

PHED

Data

Confidence

Absorption 

Factor

Body

Weight 

(kg)

Daily Dose 2

(mg/kg/day)

Short- and 

IntermediateTerm NOAEL

(mg/kg/day)

Short- and 

IntermediateTerm

MOE3

Wettable powder, open 

mixing and loading

short sleeves

short pants

no gloves

Dermal 3.3 E-5 4.4 Low 0.01 60 2.4E-8 0.12 5.0E+6

Inhalation 3.3 E-5 0.043 Medium 1.0 60 2.4E-8 0.12 5.0E+6

Total: 4.8E-8 0.12 2.5E+6

1Application rate = 5.0E-4 (0.05% ai) x 30 g/day (weight of 1 package) x 2.2E-3 lb/g = 3.3E-5 lb ai/day

2 Daily Dose =[Application rate (lb ai handled/day) x PHED Unit Exposure (mg/lb ai handled) x Absorption Factor]/Body Weight (BW) 

3

Short- & Intermediate-Term Dermal or Inhalation MOE = Short- & Intermediate-Term Dermal or Inhalation NOAEL/Daily Dose
Page 43 of 62

6.2 Residential Post-Application Exposure

Since residential uses of abamectin are currently registered, short- to intermediate-term 

exposures may occur to both adults and children from contact with treated areas following 

application. Residential post-application exposures are assessed below for two uses which are 

considered to represent the reasonable high-end residential exposure potential: 1) granular baits 

used to treat lawns; and 2) indoor crack and crevice dust products. Recreational exposures to

turf are expected to be similar to, or less than, those evaluated in this section. 

Treated Lawns

The only post-application scenario applicable to the granular abamectin formulations used on 

lawns is ingestion of granules by toddlers. The maximum rate for all registered lawn uses and 

representative high end exposures were used to calculate the margin of exposure.

Children’s exposure and risk from incidental ingestion of granules from treated lawns is 

summarized in Table 6.2.1. The acute ingestion MOE for children is 68,000. Since this MOE 

is above 300, the risk presented by children’s incidental ingestion of granules is not of 

concern to HED.

Table 6.2.1. Incidental Ingestion of Granules Exposure and Risk for Children from Treated Lawns 

Fraction

Available

Ingestion Rate

(g/day)

Body Weight

(kg)

Daily Dose1

(mg/kg/day)

NOAEL 

(mg/kg/day)

MOE2

0.00011 0.001* 15 0.0000073 0.5 68,000

1 Daily Dose = [Fraction available x Ingestion rate (g/day) x 1000 mg/g] / [Body Weight (kg)]

2 MOE = Acute Dietary NOAEL/Daily Dose. 

* It should be noted that HED’s Draft Residential SOPs give a standard value of 0.3 g product/day for the ingestion 

rate (IgR). This value is based on the application of 300 lbs of product distributed evenly over an acre, which results 

in approximately 3 grams of product per ft2. An assumption that a child will ingest one-tenth of what is available in 

one ft2of lawn leads to the IgR value of 0.3 g product/day. Because the abamectin lawn product application rate is 

only 1 pound of product per acre, it is appropriate to scale down the standard IgR value, proportionately. Using the 

SOP methodology, one pound of product, spread evenly over an acre results in 0.01 g/ft2. One tenth of this gives an 

ingestion rate of 0.001 g/day. 

Crack and Crevice

Post-application exposure from the use of Avert Prescription Treatment 310 for crack and 

crevice applications was estimated for adults (dermal and inhalation routes) and children 

(dermal, inhalation, and incidental oral routes).

 

Children's combined post-application exposure (dermal, incidental oral, and inhalation) and risk, 

and adults combined post-application exposure (dermal and inhalation) and risk are summarized 

in Table 6.2.2. Since short-/intermediate-term MOEs from all exposure scenarios are above 300,

the risk from combined adult and combined children’s post-application exposure to crack and 

crevice products containing abamectin are not of concern. 
Page 44 of 62

Table 6.2.2. Combined Exposure and Risk from Crack & Crevice Treatment

Exposure Route Data Source 1 Daily Dose 

(mg/kg/day)

Short- and 

Intermediate-Term 

NOAEL (mg/kg/day)

Short- and 

IntermediateTerm MOE

Children's Combined Dermal, Oral and Inhalation Post-Application Exposure and Risk

Dermal 1990 Study 2.2E-7

0.12

5.5E+5

1995 Study 4.4E-8 2.5E+6

Oral Hand-to-Mouth 1990 Study 7.5E-7

0.12

1.6E+5

1995 Study 1.6E-7 7.5E+5

Oral Object-to-Mouth 1990 Study 4.7E-8

0.12

2.6E+6

1995 Study 1.0E-8 1.2E+7

Inhalation 1990 Study 1.3E-4

0.12

920

1995 Study 4.7E-5 2,600

Total: 1990 Study 1.3E-4

0.12

920

1995 Study 4.7E-5 2,600

Adult Combined Handler and Post-Application Dermal and Inhalation Exposure and Risk

Handler Dermal PHED 2.4E-8 0.12 5.0E+6

Handler Inhalation PHED 2.4E-8 0.12 5.0E+6

Post-application Dermal 1990 Study 1.6E-7

0.12

7.5E+5

1995 Study 2.9E-8 4.1E+6

Post-application 

Inhalation

1990 Study 8.4E-5

0.12

1,400

1995 Study 3.0E-5 4,000

Total: PHED & 1990 Study 8.4E-5

0.12

1,400

PHED & 1995 Study 3.0E-5 4,000

1

 1990 Study: Evaluation of Avert Prescription Treatment 310 Residual Study in Air, Food and on Surfaces, November 8, 

1990 (MRID No. 44665901)

 1995 Study: Evaluation of Indoor Exposure to a Crack and Crevice Application of Whitmire Avert Crack and Crevice 

Prescription Treatment 310 and Prescription TC 93A Bait, October 27, 1995 (MRID No. 44147801) 
Page 45 of 62

6.3 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for abamectin. The 

Agency has been working with the Spray Drift Task Force, 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 at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT computer model to 

its risk assessments for pesticides applied by air, orchard airblast, and ground hydraulic methods. 

After the policy is in place, the Agency may impose further refinements in spray drift 

management practices to reduce off-target drift with specific products with significant risks 

associated with drift.

Although a quantitative residential post-application inhalation exposure assessment was not 

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation 

exposure assessment was performed for flaggers. This exposure scenario is representative of a 

worse case inhalation (drift) exposure and may be considered protective of most outdoor 

agricultural and commercial post-application inhalation exposure scenarios. 

Sometimes the risk presented from direct application of lawn treatment products can supersede 

potential risk concerns from agricultural spray drift. However, in the case of abamectin, 

agricultural use rates are higher than those for residential lawn treatment, and the assessment of 

post-application risks for abamectin lawn products did not include a dermal exposure 

component.

7.0 Aggregate Risk Assessments and Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

7.1 Acute Aggregate Risk

The acute aggregate risk assessment takes into account exposure estimates from dietary

consumption of abamectin (food and drinking water). The acute aggregate food and drinking 

water assessment results are presented in Section 5.2 above. The most highly exposed subgroup 

is all infants (<1 year old) at 30% of the aPAD, which is below the level of concern.
Page 46 of 62

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.

A short-/intermediate-term risk assessment is required for adults because there are potential 

residential handler and post-application exposures from the crack and crevice use. In addition, a 

short-/intermediate-term risk assessment is required for infants and children because there is a 

residential post-application exposure scenario for crack and crevice treatment. The ingestion of 

granules (from the lawn treatment for fire ants) is not included in the aggregate assessment 

because it is considered to be a one-time, episodic event, rather than occurring for several days 

(or several months).

The results of the short-/intermediate-term aggregate assessments are presented in Table 7.2. 

HED is generally not concerned if the MOEs remain above the LOC, which for this assessment 

is 300. The MOEs for all scenarios are greater than 300, and therefore, are not of concern.

Table 7.2. Short-Term and/or Intermediate-Term Aggregate Risk Calculations

 (Inhalation/Oral/Dermal Endpoints and NOAELs are the Same.)

Population

Short- or Intermediate-Term Scenario

NOAEL

mg/kg/day LOC1

Max 

Allowable

Exposure2

mg/kg/day

Average

Food & 

Water

Exposure

mg/kg/day

Residential 

Exposure3

mg/kg/day

Aggregate MOE

(food and

residential)4

U.S. 

Population

0.12 300 0.0004 0.000070 0.000030 1200

Children (1-2 

years old)

0.12 300 0.0004 0.000200 0.000047 500

1

The LOC includes the standard inter- and intra- species uncertainty factors (UFA and UFH, respectively) totaling 

100, and an additional factor of 3x for the steepness of the dose-response curve and the severity of effects.

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Residential Exposure = [Oral exposure + Dermal exposure + Inhalation exposure]. Refer to Table 6.2.2 for

residential exposure values used in the aggregate assessment. 

4 Aggregate MOE = [NOAEL  (Avg Food & Water Exposure + Residential Exposure)]
Page 47 of 62

7.3 Long-Term (Chronic) Aggregate Risk

The chronic aggregate risk assessment takes into account average exposure estimates from 

dietary consumption of abamectin (food and drinking water) and residential uses. However, due 

to the use patterns, no chronic residential exposures are expected. Therefore, the chronic 

aggregate risk assessment will consider exposure from food and drinking water only.

The chronic aggregate food and drinking water assessment results are presented in Section 5.2 

above. The most highly exposed subgroup is children 1-2 years old at 50% of the cPAD, which 

is below the level of concern. 

7.4 Cancer 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 Risk Characterization/Assessment

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to abamectin and any other substances and abamectin does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that abamectin has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Pathway

Reference: Abamectin. Occupational and Residential Exposure Assessment for Proposed IR-4 Foliar Uses 

on Bulb Onions (Subgroup 3-07A), Chives, and Dry Beans, D380797, N. Tsaur, 3/29/11.

Occupational handler exposure to abamectin is expected for individuals involved in foliar 

applications to bulb onions (subgroup 3-07A), chives, and dry beans (mixing, loading, and 

applying). Handler exposure is expected to be short- or intermediate-term based on information 

provided on the proposed label. 

Agricultural workers performing typical post-application activities (e.g. scouting, irrigation, 

transplanting/harvesting, etc.) may receive short- and intermediate-term exposure to abamectin

residues.
Page 48 of 62

9.1 Short-/Intermediate-Term Handler Risk

Handler’s exposure and risk were estimated for the following scenarios: mixer/loaders (mixing/ 

loading liquid to support groundboom or aerial applications); flaggers (flagging to support aerial 

application); applicators (applying sprays with groundboom or aerial equipment with enclosed 

cockpit).

The minimum level of PPE for handlers is based on acute toxicity for the end-use product. All 

three labels state that all handlers must wear the proper PPE: coveralls worn over a short-sleeved 

shirt with short pants, chemical resistant gloves, chemical-resistant footwear with socks, 

protective eyewear, chemical-resistant headgear for overhead exposure, and a chemical resistant 

apron when cleaning equipment, mixing, or loading. The Registration Division (RD) is

responsible for ensuring that PPE listed on the label is in compliance with the Worker Protection 

Standard (WPS).

No chemical-specific handler exposure data were submitted in support of this Section 3 

registration. In accordance with HED’s Exposure Science Advisory Council (SAC) policy, 

exposure data from the Pesticide Handlers Exposure Database (PHED), Version 1.1, as 

presented in PHED Surrogate Exposure Guide (8/98), were used with other HED standard values 

for acres treated per day, body weight, and the level of personal protective equipment to assess 

handler exposures. 

Exposure/risk assessments were performed using applicable toxicity endpoints. Daily dermal 

and inhalation exposures were calculated separately, applying a dermal absorption factor of 1%, 

and an inhalation absorption factor of 100%. The dermal and inhalation exposures were added 

together and compared to the common NOAEL of 0.12 mg/kg/day (from combined data from 

three reproduction studies and two developmental neurotoxicity studies where the LOAEL = 0.2 

mg/kg/day based on decreased pup body weight) to determine the handler risk (from total dermal 

and inhalation exposure) for short- and intermediate-term exposures.

The total MOEs (when gloves are added to the mixing/loading scenarios) range from 750 (for 

open mixing/loading of liquid to support aerial application with PPE including gloves) to 9100 

(for applying sprays via aerial equipment (enclosed cockpit). These MOEs do not exceed HED’s 

level of concern of 300 (when gloves are added to the mixing/loading scenarios). 

Assumptions and estimates for occupational handler exposure are summarized in Tables 9.1.1 

and 9.1.2.

 
Page 49 of 62

Table 9.1.1. Abamectin Short- and Intermediate-Term Agricultural Occupational Exposures and Risks (Baseline: single layer, no gloves, no respirator).

Exposure Scenario

Application 

Rate a

Area 

Treated 

Daily b

Dermal

UE c

Inhalation 

UE c

Dermal 

Dose d

Dermal 

MOE e

Inhalation 

Dose f

Inhalation 

MOE g

Combined 

Dose h

ST/IT

Combined 

MOE i

lb ai/A acres mg/lb ai mg/lb ai mg/kg/day LOC = 300 mg/kg/day LOC = 300 mg/kg/day LOC = 300

Mixer/Loader

Mixing/Loading Liquid for

Groundboom Applications 0.0191 80 2.9 0.0012 0.00074 160 0.000031 3900 0.00077 160

Mixing/Loading Liquid for

Aerial Applications 0.0191 350 2.9 0.0012 0.0032 37 0.00013 900 0.0034 36

Flagger

Flagging for

Aerial Application 0.0191 350 0.011 0.00035 0.000012 9800 0.000039 3100 0.000051 2300

Applicator

Applying Sprays via

Groundboom Equipment 0.0191 80 0.014 0.00074 0.0000036 34,000 0.000019 6000 0.000022 5300

Applying Sprays via

Aerial Equipment j 0.0191 350 0.0050 0.00007 0.0000056 21,000 0.0000076 16,000 0.000013 9100

a Application Rates based on maximum proposed use rates for abamectin labels: EPA Reg. No. 100-898, EPA Reg. No. 100-1351, EPA Reg. No. 100-1154.

b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1.

c UE = Unit Exposures based on PHED Version 1.1 data. Baseline = single layer, no gloves, no respirator.

d Dermal Dose (mg/kg/day) = application rate (lb ai/acre) x amount handled /day (acres/day) x daily unit exposure (mg/lb ai) x absorption factor (1%) / body weight (60 kg).

e Dermal Margin of Exposure = NOAEL (mg/kg/day) / Dermal Dose (mg/kg/day). Level of concern = 300. Short- and Intermediate-Term NOAEL = 0.12 mg/kg/day.

f Inhalation Dose (mg/kg/day) = application rate (lb ai/acre) x amount handled /day (acres/day) x daily unit exposure (mg/lb ai) x absorption factor (100%) / body weight (60 kg).

g Inhalation Margin of Exposure = NOAEL (mg/kg/day) / Inhalation Dose (mg/kg/day). Level of concern = 300. Short- and Intermediate-Term NOAEL = 0.12 mg/kg/day.

h Combined Dose = Dermal Dose (mg/kg/day) + Inhalation Dose (mg/kg/day).

i Short- and Intermediate-Term Combined Margin of Exposure = NOAEL (mg/kg/day) / Combined Dose (mg/kg/day). Level of concern = 300. ST/IT NOAEL = 0.12 mg/kg/day.

j Only engineering control (enclosed cockpit) data are available to assess risks to handlers operating aircraft (enclosed cab, no gloves, no respirator).
Page 50 of 62

Table 9.1.2. Abamectin Short- and Intermediate-Term Agricultural Occupational Exposures and Risks (PPE: single layer, gloves, no respirator).

Exposure Scenario

Application 

Rate a

Area 

Treated 

Daily b

Dermal

UEs c

Inhalation 

UEs c

Dermal 

Dose d

Dermal 

MOE e

Inhalation 

Dose f

Inhalation 

MOE g

Combined 

Dose h

ST/IT 

Combined 

MOE i

lb ai/A acres mg/lb ai mg/lb ai mg/kg/day LOC = 300 mg/kg/day LOC = 300 mg/kg/day LOC = 300

Mixer/Loader

Mixing/Loading Liquid for

Groundboom Applications 0.0191 80 0.023 0.0012 0.0000059 20,000 0.000031 3900 0.000036 3300

Mixing/Loading Liquid for

Aerial Applications 0.0191 350 0.023 0.0012 0.000026 4700 0.00013 900 0.00016 750

a Application Rates based on maximum proposed use rates for abamectin labels: EPA Reg. No. 100-898, EPA Reg. No. 100-1351, EPA Reg. No. 100-1154.

b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1.

c UE = Unit Exposures based on PHED Version 1.1 data. PPE = single layer, gloves, no respirator.

d Dermal Dose (mg/kg/day) = application rate (lb ai/acre) x amount handled /day (acres/day) x daily unit exposure (mg/lb ai) x absorption factor (1%) / body weight (60 kg).

e Dermal Margin of Exposure = NOAEL (mg/kg/day) / Dermal Dose (mg/kg/day). Level of concern = 300. Short- and Intermediate-Term NOAEL = 0.12 mg/kg/day.

f Inhalation Dose (mg/kg/day) = application rate (lb ai/acre) x amount handled /day (acres/day) x daily unit exposure (mg/lb ai) x absorption factor (100%) / body weight (60 kg).

g Inhalation Margin of Exposure = NOAEL (mg/kg/day) / Inhalation Dose (mg/kg/day). Level of concern = 300. Short- and Intermediate-Term NOAEL = 0.12 mg/kg/day.

h Combined Dose = Dermal Dose (mg/kg/day) + Inhalation Dose (mg/kg/day).

i Short- and Intermediate-Term Combined Margin of Exposure = NOAEL (mg/kg/day) / Combined Dose (mg/kg/day). Level of concern = 300. ST/IT NOAEL = 0.12 mg/kg/day.
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9.2 Occupational Post-Application Exposures and Risks 

Short-/Intermediate-/Long-Term Post-Application Risk

There is a potential for post-application exposure to scouts, harvesters and other field workers 

following foliar application to agricultural crops. Chemical-specific post-application exposure 

data were not provided. The transfer coefficients used in this assessment are from the transfer 

coefficient standard operating procedure (SOP) developed by HED’s Science Advisory Council 

(SAC) for Exposure (Exposure SAC Policy No. 3.1, “Agricultural Transfer Coefficients,” 

August 2000) using proprietary data from the Agricultural Re-entry Task Force (ARTF)

database). Also, this assessment uses HED’s default assumption that 20% of the application rate 

is available for transfer on the day of treatment, and that the residue dissipates at a rate of 10% 

per day thereafter. 

The short- and intermediate-term MOEs for post-application exposure on day 0 (12 hours after 

application) range from 840 to 21,000. Since these calculated MOEs are greater than 300 on the 

day of application, they do not exceed HED’s level of concern. A summary of the postapplication exposure and risk assessment is presented in Table 9.2.

HED’s post-application exposure estimates are based on surrogate data. The transfer coefficients 

are considered to be central tendency. Maximum application rates were used in this assessment. 

Overall, the post-application risks are characterized as being central to high-end estimates.

The post-application exposure associated with agricultural crops is summarized in Table 9.2. All

scenarios resulted in MOEs greater than 300 (ranging from 840 to 21,000) on day 0 (12 hours 

after application) and, therefore, are not of concern to HED. 
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Table 9.2. Short- and Intermediate-Term Post-Application Exposures and Risk for Abamectin.

Crop 

Grouping/Crop Activity TransferCoefficient

Days After 

Treatment

DFR a Daily Dermal 

Dose b

Dermal

MOE c

μg/cm2 mg/kg/day LOC = 300

Bulb Onions

(Subgroup 3-07A)

irrigation, scouting,

thinning, hand weeding 300 0(12 hours) 0.0429 0.000017 7,000

Chives

hand harvesting, thinning 2500 0

(12 hours) 0.0429 0.000143 840

irrigation, scouting 1500 0

(12 hours) 0.0429 0.000086 1,400

hand weeding 500 0

(12 hours) 0.0429 0.000029 4,200

Dry Beans

hand harvesting 2500 0

(12 hours) 0.0429 0.000143 840

irrigation, scouting 1500 0

(12 hours) 0.0429 0.000086 1,400

hand weeding 100 0

(12 hours) 0.0429 0.0000057 21,000

a DFR (μg/cm2) = application rate (lb ai/acre) x fraction of application rate dislodgeable on day 0 (20%) x (1 - fraction of 

residue that dissipates daily 10%)tx 4.54E8 μg/lb x 2.47E-8 acre/cm2.

b Short-/Intermediate-Term Daily Dermal Dose = [DFR (μg/cm2) x Transfer Coefficient x 0.001 mg/μg x 8 hrs/day x dermal 

absorption 1%]  body weight (60 kg adult).

c Short-/Intermediate-Term MOE = NOAEL (mg/kg/day)/Daily Dermal Dose (mg/kg/day). ST/IT NOAEL = 0.12 mg/kg/day.

Restricted Entry Interval

Since both short- and intermediate-term post-application risks were not a concern on day 0 (12 

hours following application), the REI is based on the acute toxicity of abamectin technical 

material. Under WPS for Agricultural Pesticides, active ingredients classified as acute Toxicity

Category III or IV for Acute Dermal, Eye Irritation, and Primary Skin Irritation are assigned a 

12-hour REI. Thus, the 12-hour REI on the proposed labels are acceptable.

Occupational Post-Application Inhalation Exposure

Based on the Agency's current practices, a quantitative occupational post-application inhalation 

exposure assessment was not performed for abamectin at this time. However, there are multiple 

potential sources of post-application inhalation exposure to individuals performing postapplication activities in previously treated fields. These potential sources include volatilization 

of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. 

The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html) and is in the process of 

evaluating the SAP report as well as available post-application inhalation exposure data 

generated by the Agricultural Reentry Task Force. The Agency may, as appropriate, develop 

policies and procedures to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the Agency's risk assessments. 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.
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10.0 References

N. Dodd, 5/18/11, DP#380795, Abamectin. Petition for Tolerances/Section 3 Registration on 

the Bulb Onion Subgroup 3-07A, Chives, and Dry Beans. Summary of Analytical Chemistry and 

Residue Data.

N. Dodd, 6/13/11, DP#380796, Abamectin. Acute and Chronic Aggregate Dietary (Food and 

Drinking Water) Exposure and Risk Assessments for the Section 3 on Bulb Onions, Chives, and 

Dry Beans.

A. Grube, 10/21/10, DP#382732, Usage Report Package in Support of Registration for the 

Insecticide Abamectin (122804).

N. Tsaur, 3/29/11, DP#380797, Abamectin. Occupational and Residential Exposure Assessment 

for Proposed IR-4 Foliar Uses on Bulb Onions (Subgroup 3-07A), Chives, and Dry Beans.

J. Arthur, 10/29/04, DP#306906, Abamectin: Occupational and Residential Risk Assessment to 

Support Section 3 Request for Uses on Various Food Crops and Food-Handling Establishments.

G. Orrick, 1/31/11, DP#380524, Abamectin: Drinking Water Exposure Assessment for Proposed

Section 3 New Uses on Chives, Dried Beans, and the Bulb Onion Subgroup 3-07A.

N. Dodd et al., 3/11/09, DP#362615, Abamectin. Revised Human Health Risk Assessment for 

Proposed Uses on Pasture and Rangeland Grass, Stone Fruit Crop Group 12, Tree Nut Crop 

Group 14, Pistachio, Tuberous and Corm Vegetables Subgroup 1C and Request for Cattle Ear 

Tag Use.
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Appendix A: Toxicology Assessment

Table A.1. Acute Toxicity 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.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. / Classification 

/Doses

Results

870.3100

Subchronic feeding 

study-rats

00131081 (1982)

Unacceptable/Nonguideline

0, 0.10, 0.20, 0.40 

mg/kg/day

NOAEL > 0.40 mg/kg/day

LOAEL = not established

870.3150

Subchronic toxicity

Dogs (18 week 

gavage study)

00131082 (1982)

Acceptable/Guideline

0, 0.25, 0.5, 2.0, 8.0 

mg/kg/day

NOAEL = 0.25 mg/kg/day

LOAEL = 0.50 mg/kg/day based on body tremors, one death, 

liver pathology, decreased body weight. Mydriasis was seen 

during week one in one dog.

870.3150

12-Week dose range 

finding study-dogs 

(feeding) 

00164152 (1982)

0.25, 0.50, 1.0, and 4.0/2.0 

mg/kg/day (during week 4, 

4.0 mg/kg/day was reduced 

to 2.0 mg/kg/day due to 

tremor, weakness, 

incoordination, and 

disorientation) 

The report stated that mydriasis was seen in 1.0 and 4.0 

mg/kg/day dogs during week 1.The effect was not seen at each 

examination day for any dog, but it was generally noted from 1 to 

5 times a week. However, mydriasis was never noted at 0.5 and 

0.25 mg/kg/day. 

870.3200

21/28-Day dermal 

toxicity

Study not available. Study not available.
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Table A.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. / Classification 

/Doses

Results

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

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 < 0.75 mg/kg/day

Developmental LOAEL = 0.75 mg/kg/day based on hind limb 

extension

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

870.3800b

1-Generation 

Reproduction and 

fertility effects-rat 

00096450

Unacceptable/NonGuideline

0, 0.5, 1.0, 1.5/2.0 

mg/kg/day

Parental/Systemic NOAEL = 1.0 mg/kg/day. 

LOAEL=1.5/2.0 based on whole body tremors, ataxia, ptyalis, 

ocular/nasal discharges and mortality

Reproductive NOAEL = 3.0 mg/kg/day

Offspring NOAEL < 0.5 mg/kg/day

LOAEL = 0.5 mg/kg/day based on decreased pup survival and 

body weight between days 1-21 and delay in opening of eyes
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Table A.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. / Classification 

/Doses

Results

870.3800c

1-Generation 

Reproduction and 

fertility effects- rat

00096451

Unacceptable/Nonguideline

0, 0.1, 0.2, 0.4 mg/kg/day

Parental/Systemic NOAEL = 0.4 mg/kg/day

LOAEL = not established

Reproductive NOAEL = 0.4 mg/kg/day

Offspring NOAEL =0.1 mg/kg/day

LOAEL = 0.2 mg/kg/day based on spastic movements and, 

delayed incisor eruption

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

Offspring NOAEL =0.4 mg/kg/day

LOAEL = not established

Gene Mutation

870.5100

Ames/Salmonella

E.coli/mammalian 

gene mutation assay

Accession: 246894, 

265568, 265569 (1986)

Acceptable/Guideline

Three studies: (1) 0, 3, 10, 

30, 100, 1000 ug/plate, (2) 

0, 100, 300, 1000, 3000, 

10,000 ug/plate both with 

and without S-9, (3) doses 

not specified.

negative both with and without S-9

870-6100 

Acute neurotoxicity 

in rats (gavage)

46959202 (2006)

Acceptable/guideline

0.5, 1.5, and 6.0 mg/kg

NOAEL = 0.5 mg/kg/day

LOAEL = 1.5 mg/kg/day based on reduced splay reflex in males 

and females. At high dose, decreased motor activity, reduced 

splay reflex, & tip toe gait were seen. No death or 

histopathological changes in nervous system were found.

870-6200

Subchronic 

neurotoxicity in rats 

(gavage)

46959201 (2006)

Acceptable/guideline

0.4, 1.6, and 4.0 mg/kg/day

NOAEL = 1.6 mg/kg/day

LOAEL = 4.0 mg/kg/day based on upward curvature of the spine, 

tip-toe gate, decreased fore- and hind-limb grip strength. 

Decreased body was also seen. This dose group was terminated 

prematurely at week 7. 

870-630

Developmental 

neurotoxicity study in 

rats 

46727403, 46727402, 

46727401 (2005)

Acceptable/nonguideline

0.12, 0.20, and 0.40 

mg/kg/day. Pups were not 

directly dose.

Maternal NOAEL = 0.4 mg/kg/day (HDT)

Offspring NOAEL = 0.2 mg/kg/day.

Offspring LOAEL= 0.4 mg/kg/day based on decreased body 

weight in males and females.. 

870-6200

Developmental 

neurotoxicity study in 

rats 

47116201 (2007)

Acceptable/nonguideline

0.12, 0.20, and 0.40 

mg/kg/day. Pups were not 

directly dosed. 

Maternal NOAEL = 0.4 mg/kg/day (HDT)

Offspring NOAEL =0.12 mg/kg/day.

Offspring LOAEL = 0.2 mg/kg/day based on slight but 

statistically significant decrease in pup body weight. 
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Table A.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. / Classification 

/Doses

Results

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

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 Unavailable

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 Unavailable

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 Unavailable

(1983)

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 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 No MRID

(1985)

Nonguideline

Avermectin B1a did not bioaccumulate in rat tissues. Half-life 

slightly longer in females than in males for several tissues.

Metabolism No MRID

(1985)

Nonguideline

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/

Nonguideline in Monkeys

Dermal penetration is 1%. 
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Table A.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

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

870.3700a

Prenatal 

developmental in 

rodents-CF1 mouse

Accession: 265564 (1985)

Acceptable/Guideline

0, 0.01, 0.03, 0.06 mg/kg/day with 

delta-8,9 isomer

Maternal NOAEL > 0.06 mg/kg/day

Maternal LOAEL = not established

Developmental NOAEL > 0.06 mg/kg/day

LOAEL = not established

870.3700a

Prenatal 

developmental in 

rodents-CF1 mouse

Accession: 40713406 (1986)

Acceptable/Guideline

0, 0.25, 0.50, 1.0 mg/kg/day with 

polar degradates of abamectin

Maternal NOAEL > 1.0 mg/kg/day

Maternal LOAEL = not established

Developmental NOAEL > 1.0 mg/kg/day

LOAEL = not established
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Appendix B: Toxicology Literature References

Dawson GR, Wafford KA, Smith A, Marshall GR, Bayley PJ, Schaeffer JM, Meinke PT, 

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.

Kerb R (2006) Implication of genetic polymorphism in drug transporters for pharmacotherapy.

Cancer Lett. 234: 4-33.

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 I human MDR1 (Pglycoprotein): Recent advances and clinical relevance. Clin. Pharmacol. and Ther. 

75: 13-33.

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, Moonen G.

(2001) Neurotransmitters as early signals for central nervous system development. Cell 

Tissue Res. 305: 187-202.

Pong SS, DeHaven R, 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, Ben-Ari Y. (2005) Trophic actions of GABA on neuronal development. Trends 

Neurosci. 28: 278-283. 

Habashi, SL (2006) Dubin-Johnson Syndrome. http://www.emedicine.com/med/topic 588.htm

Wang CC, Pong SS. (1982) Actions of avermectin B1a on GABA nerves. Prog. Clin. Biol. Res. 

97: 373-395.
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Appendix C: Physical/Chemical Properties

Table C. Physiochemical Properties

Parameter Value Reference1

Molecular Weight 873.11

Melting point/range 155-157°C Accession No. 260785

pH Not available

Density 1.16 g/cm3at 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 10-9hPa Accession No. 260785

Dissociation constant, pKa Not available

Octanol/water partition coefficient, 

Log(KOW)

9.9 x 10-3 Accession No. 260785

UV/visible absorption spectrum Not available

1 Product Chemistry data were reviewed by Leung Cheng (Accession No. 260785, RCB No. 388, 5/1/1986).
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Appendix D: Review of Human Research

This risk assessment relies in part on data from Pesticide Handlers Exposure Database (PHED) 

and the Agricultural Reentry Task Force (ARTF) database in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These studies have been reviewed for 

ethical conduct and have been determined to be ethical.

The two studies used to estimate residential post-application exposure from abamectin crack and 

crevice products [ref: “Evaluation of Avert Prescription Treatment 310 Residual Study in Air, 

Food and on Surfaces,” dated November 8, 1990 (MRID No. 44665901), and “Evaluation of 

Indoor Exposure to a Crack and Crevice Application of Whitmire Avert Crack and Crevice 

Prescription Treatment 310 and Prescription TC 93A Bait,” dated October 27, 1995 (MRID No. 

44147801)] measured only ambient concentrations of abamectin in treated areas and did not 

involve collection of data for estimation of direct human exposure from the application activity. 

Therefore, the requirements for ethical review or for review by the Human Studies Review 

Board are not applicable to these studies.
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Appendix E: International Residue Limits

Abamectin (PC Code 122804; 03/31/2011)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico Codex

40 CFR 180.449:

Plant/Livestock: sum 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 

avermectin B1 (a mixture 

of avermectins containing 

greater than or equal to 

80% avermectin B1a (5-

O-demethyl avermectin 

A1a) and less than or 

equal to 20%

avermectin B1b (5-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.

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

US Canada Mexico Codex

Onion, bulb, subgroup 3-07A 0.01

Chive, fresh leaves 0.01

Chive, dried leaves 0.02

Bean, dry, seed, except cowpea 0.01

Completed: M. Negussie; 03/31/2011