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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: 12/20/12

SUBJECT: Abamectin. Human Health Risk Assessment for Uses of the SC Formulation 

on Cotton and Strawberry 

PC Code: 122804 DP Barcode: D402677, D405843

Decision No.: 463021, 463020 Registration Nos.: 100-1351, 100-1408

Petition No.: 2F8009 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical/Aggregate Case No.: NA

TXR No.: NA CAS No.: 71751-41-2

MRID No.: NA 40 CFR: 180.449

FROM: Nancy Dodd, Chemist/Risk Assessor

Whang Phang, Toxicologist

Nancy Tsaur, Chemist

Risk Assessment Branch III (RAB3)

Health Effects Division (HED) (7509P) 

THROUGH: Jeff Dawson, Acting Branch Chief

Risk Assessment Branch III (RAB3)

Health Effects Division (HED) (7509P) 

TO: John Hebert/Jessica Rogala, RM#7

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 uses of abamectin, also known as avermectin B1

[a mixture of avermectins containing ≥80% avermectin B1a (5-O-demethyl avermectin A1) and 

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

A1)], and its delta-8,9-isomer, as the suspension concentrate (SC) formulation on cotton and 

strawberry. Although tolerances are established for abamectin on cotton and strawberry based 

on use of the emulsifiable concentrate (EC) formulation, higher tolerances are needed to support 

use of the SC formulation since higher residues occurred on cotton and strawberry as a result of 

use of the SC formulation as compared to use of the registered EC formulation. Higher residues 

occurred in cotton and strawberry even though an adjuvant was used with the SC formulation; 
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the adjuvant was used with the SC formulation to increase photolytic degradation of abamectin 

and thereby reduce residues, as has been observed with the SC formulation of abamectin on other 

crops.

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

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

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

and to infants and children from aggregate exposure resulting from the proposed uses on cotton 

and strawberry.

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

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

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

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

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

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

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

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

2.3.1 Recommendations from Residue Reviews.............................................................. 10

2.3.2 Recommendations from Occupational Assessment............................................... 10

2.3.3 Recommendations from Residential Assessment................................................... 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.................................................................... 15

4.0 Hazard Characterization and Dose-Response Assessment.......................................... 16

4.1 Summary of Toxicological Effects.............................................................................. 16

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 17

4.2.1 Completeness of the Toxicology Database.............................................................. 17

4.2.2 Evidence of Neurotoxicity........................................................................................ 18

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 18

4.2.4 FQPA Safety Factor for Infants and Children ...................................................... 22

4.2.5 Residual Uncertainty in the Exposure Database ................................................... 23

4.3 Toxicity Endpoint and Point of Departure Selections.............................................. 24

4.4 Endocrine Disruption................................................................................................... 29

5.0 Dietary Exposure and Risk Assessment......................................................................... 30

5.1 Residues of Concern Summary and Rationale.......................................................... 30

5.2 Food Residue Profile .................................................................................................... 32

5.3 Water Residue Profile.................................................................................................. 35

5.4 Dietary Risk Assessment.............................................................................................. 36

5.4.1 Description of Residue Data Used in Dietary Assessment.................................... 36

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 36

5.4.3 Acute Dietary Risk Assessment............................................................................... 37

5.4.4 Chronic Dietary Risk Assessment........................................................................... 37

5.4.5 Cancer Dietary Risk Assessment............................................................................. 37

5.4.6 Summary Table......................................................................................................... 38

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 38

6.1 Residential Handler Exposure .................................................................................... 39

6.2 Residential Post-Application Exposure...................................................................... 41

6.3 Spray Drift.................................................................................................................... 41
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7.0 Aggregate Exposure/Risk Characterization.................................................................. 42

7.1 Acute Aggregate Risk................................................................................................... 42

7.2 Short- and Intermediate-Term Aggregate Risk ........................................................ 42

7.3 Chronic Aggregate Risk .............................................................................................. 43

7.4 Cancer Aggregate Risk ................................................................................................ 43

8.0 Cumulative Exposure/Risk Characterization ............................................................... 43

9.0 Occupational Exposure/Risk Characterization ............................................................ 44

9.1 Short-/Intermediate-Term Handler Risk................................................................... 45

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

10.0 References......................................................................................................................... 48

Appendix A. Toxicology Profile and Executive Summaries.................................................. 49

A.1 Toxicology Data Requirements................................................................................... 49

A.2 Toxicity Profiles............................................................................................................ 50

Appendix B. Toxicology Literature References...................................................................... 55

Appendix C. Physical/Chemical Properties............................................................................. 56

Appendix D. Review of Human Research ............................................................................... 57

Appendix E. International Residue Limits Table ................................................................... 58
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1.0 Executive Summary

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

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

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

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

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

leaf miners, and other insects in commercially important crops. Abamectin acts as an insecticide 

by interfering with the nervous system of the insect, causing the insect to become paralyzed.

 

Syngenta Crop Protection, LLC has submitted a petition to increase the established permanent 

tolerances on cotton and strawberry, and to add uses on cotton and strawberry to Agri-Mek® SC 

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

Reg. No. 100-1408) labels. Cotton and strawberry uses are currently registered on emulsifiable 

concentrate (EC) labels. The established tolerances are based on residue data using the EC 

formulation. Residues from crop field trials using the suspension concentrate (SC) formulation

of abamectin plus adjuvant are higher than the established tolerances on cotton and strawberry, 

which are based on the EC formulation; therefore, higher tolerances are needed for use of the SC 

formulation on cotton and strawberry.

The petitioner has proposed amendment of the established tolerances for 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 delta8,9-isomer to increase the tolerances on cotton, undelinted seed from 0.005 ppm to 0.015 ppm; 

on cotton, gin by-products from 0.15 ppm to 1.0 ppm; and on strawberry from 0.02 to 0.06 

ppm.

 

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 4.2.4.) 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 
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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 are not a single dose 

effect.

The immunotoxicity study (OCSPP 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 software with the Food Commodity Intake Database (DEEM-FCID), Version 3.16. 

Although tolerance-level residues and 100% crop treated were used for bulb onion, chives, dry

bean, 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% of the acute population adjusted dose (aPAD)] at the 99.9th percentile of 

exposure. Abamectin dietary exposure at the 99.9th percentile for food and drinking water is 

15% of the aPAD for the general U.S. population and 24% of the aPAD for children 1-2 years 

old, the most highly exposed population subgroup.

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

concern [<100% of the chronic population adjusted dose (cPAD)] for the general U.S. population 

and all population subgroups. Abamectin dietary exposure for food and drinking water is 17% of 

the cPAD for the general U.S. population and 53% of the cPAD for children 1-2 years old, the 

most highly exposed population subgroup.

Residential Exposure: There are no expected residential exposures from the proposed uses; 

however, there are existing residential uses. All existing residential exposures have been 

reassessed to reflect updates to HED’s 2012 Residential Standard Operating Procedures (SOPs)

along with policy changes for body weight assumptions. There are no registered products that 
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would lead to any residential handler or post-application risk estimates of concern. Short-term 

combined (dermal + inhalation) residential handler margins of exposure (MOEs) range from 

320,000 to 1,100,000,000. Residential post-application exposures are not expected. For outdoor 

treatments, adults and children are not expected to directly contact fire ant mounds. For indoor 

pest control, bait placements are intended to be placed in cracks and crevices where direct 

contact by adults and children is unlikely.

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 levels of concern (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). The results of the occupational handler exposure and risk assessment 

indicate that short- and intermediate-term dermal and inhalation risks do not exceed HED’s LOC 

(i.e., an MOE < 300) at some level of mitigation. The abamectin product labels direct mixers, 

loaders, applicators and other handlers to wear a long-sleeved shirt and long pants, chemicalresistant gloves, and shoes plus socks. For short- and intermediate-term exposure, the combined 

(dermal + inhalation) MOEs for mixer/loader scenarios range from 150 to 2,300 at baseline level 

of clothing (single layer long-sleeved shirt, long pants, and shoes plus socks). With single layer 

plus gloves as required by the label, the lowest MOE of 150 increases to 600. All uses have 

acceptable MOEs given the proposed label requirements. For flaggers, the MOE is 2,700 at 

baseline (no gloves, no respirator). Only engineering control (enclosed cockpit) data are 

available to assess risks to handlers operating aircrafts. For ground and aerial applicators, the 

MOEs range from 1,900 to 4,800 (no gloves, no respirator).

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 restricted entry interval (REI) on all the labels is acceptable. The postapplication MOEs do not exceed HED’s LOC of 300 (MOEs ranged from 1,800 to 28,000) on 

day 0 (12 hours after application).

Based on the Agency's current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment was not performed for abamectin at this time. If new policies or 

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

post-application inhalation exposure assessment for abamectin.
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Environmental Justice Considerations: Potential areas of environmental justice concerns, to 

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

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

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

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

and have received that review.

2.0 HED Recommendations

Provided revised Sections B (OCSPP 860.1200) and F (OCSPP 860.1550) and an analytical 

reference standard for 8,9-Z avermectin B1a (NOA427011) are submitted, HED can recommend 

for registration of abamectin for use of the SC formulation on cotton and strawberry and for 

permanent tolerances for the proposed uses on cotton and strawberry. Additional data are 

needed as outlined in Section 2.1 below. The specific tolerance recommendations are discussed 

in Section 2.2, and the label modifications are discussed in Section 2.3. 

2.1 Data Deficiencies

Data that needs to be submitted prior to a tolerance being established or registration 

allowed

Residue Chemistry

860.1200 Directions for Use

Refer to Section 2.3 for label recommendations.

860.1550 Proposed Tolerances

The petitioner should submit a revised Section F to propose tolerances of 0.02 ppm on cotton, 

undelinted seed and 0.05 ppm on strawberry.

860.1650 Submittal of Analytical Reference Standards

Because the supply has been depleted, the registrant must submit five grams of 8,9-Z avermectin 

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

Toxicology

870.7800 Immunotoxicity

Under the current data requirement guidelines (40 CFR §158.500), the immunotoxicity study is 

required. The risk assessment team was initially informed that the registrant was committed to 
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conduct this study, but currently the registrant is planning to submit a data waiver for the 

immunotoxicity study.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate enforcement methods for abamectin in plant and livestock commodities are available 

in the Pesticide Analytical Manual, Volume II (PAM II). The methods have been validated for 

citrus and processed fractions (Method I), ginned cottonseed (Method IA), and bovine tissues 

and milk (Method II). These methods determine residues in plant and livestock commodities at 

limits of quantitation (LOQs) of 0.02 ppm for meat and meat byproducts and ≤0.01 ppm for 

other plant/livestock commodities. The limit of detection (LOD) of the methods for plant and 

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

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

2.2.2 Recommended Tolerances

The current tolerance expression in 40 CFR §180.449 is consistent with the S. Knizner memo 

dated 5/27/09. Tolerances are established under 40 CFR §180.449 for residues of abamectin 

(avermectin), including its metabolites and degradates, in or on various crop and livestock 

commodities. Compliance with the tolerance levels is to be determined by measuring only

avermectin B1 [a mixture of avermectins containing greater than or equal to 80% avermectin B1a

(5- O -demethyl avermectin A1 ) and less than or equal to 20% avermectin B1b (5- O -demethyl25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1 )] and its delta-8,9-isomer.

Table 2.2.2. Tolerance Summary for Abamectin.

Commodity Established

Tolerance 

(ppm)

SyngentaProposed 

Tolerance 

(ppm)

HEDRecommended 

Tolerance 

(ppm)

Comments 

(correct commodity definition)

Cotton, undelinted seed 0.005 0.015 0.02

Cotton, gin by-products 0.15 1.0 1.0

Strawberry 0.02 0.06 0.05

2.2.3 Revisions to Petitioned-For Tolerances

As shown in Table 2.2.2 above, HED is recommending slightly different tolerance levels, as 

compared to Syngenta-proposed tolerance levels, for cotton, undelinted seed and strawberry. 

HED’s recommended tolerance levels are based on the Organization for Economic Co-operation 

and Development (OECD) tolerance calculation procedures.
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2.2.4 International Harmonization

The tolerance expressions for the US, Codex, and Canada include the same analytes for plants. 

There are currently maximum residue limits (MRLs) established by Codex on cotton seed at 0.01 

ppm and by Codex and Canada on strawberry at 0.02 ppm. The US is recommending higher 

tolerances for both undelinted cotton seed (0.02 ppm) and strawberry (0.05 ppm) based on 

residue data on the SC formulation. Codex MRLs are established for use of the EC formulation. 

Higher tolerances are found in cotton and strawberry from use of the SC formulation and, 

therefore, the US tolerance levels cannot be harmonized with Codex MRLs, which are based on 

the EC formulation. Higher residues occurred in cotton and strawberry even though an adjuvant 

was used with the SC formulation; the adjuvant was used to increase photolytic degradation of 

abamectin and thereby reduce residues. An International Residue Limit Status sheet is attached 

(Appendix E).

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

Both the Agri-Mek® SC Miticide/ Insecticide label [EPA Reg. No. 100-1351] and the Epi-MekTM

SC Miticide/ Insecticide label [EPA Reg. No. 100-1408] indicate under “Cotton” that 6.75 fl 

oz/A are 0.038 lb ai/A and under “Strawberries” that 14 fl oz/A are 0.075 lb ai/A. HED

calculated that 6.75 fl oz/A are 0.037 lb ai/A and 14 fl oz/A are 0.077 lb ai/A. These calculations 

should be corrected on both labels.

2.3.2 Recommendations from Occupational Assessment

Refer to Section 2.3.1.

2.3.3 Recommendations from Residential Assessment

Refer to Section 2.3.1.

3.0 Introduction

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

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

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

its delta-8,9-isomer. Avermectins are macrocyclic lactones produced as natural fermentation 

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

used to control mites, leaf miners, and other insects in commercially important crops. 

Abamectin acts as an insecticide by interfering with the nervous system of the insect, causing the 

insect to become paralyzed. Available mechanistic data indicate a neurotoxic mechanism of 

action, related to interference with GABA-mediated neurotransmission.
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Tolerances are established under 40 CFR §180.449 for residues of abamectin (avermectin), 

including its metabolites and degradates, in or on various crop and livestock commodities at 

levels ranging from 0.005 ppm to 0.20 ppm. Compliance with the tolerance levels is to be 

determined by measuring only avermectin B1 [a mixture of avermectins containing greater than 

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

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

its delta-8,9-isomer.

The 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). 

Agri-Mek® SC Miticide/Insecticide [100-1351] and Epi-MekTM SC Miticide/Insecticide [100-

1408] are to be applied to cotton as foliar applications using ground or aerial equipment. The 

maximum application rates are 0.019 lb ai/A/application and 0.038 lb ai/A/season. The 

retreatment interval is at least 21 days and the preharvest interval is 20 days.

Agri-Mek® SC Miticide/Insecticide [100-1351] and Epi-MekTM SC Miticide/Insecticide [100-

1408] are to be applied to strawberries as foliar applications using ground equipment only. A 

maximum of four applications can be made. The maximum application rates are 0.019 lb 

ai/A/application and 0.075 lb ai/A/season. The retreatment interval is at least 21 days and the 

preharvest interval is 3 days.
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3.1 Chemical Identity

Table 3.1. Abamectin Nomenclature

Chemical Structure

Empirical formula C48H72O14 (B1a); C47H70O14 (B1b)

Common Names abamectin, avermectin B1

Company experimental name MK-0936

IUPAC name

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

sec-butyl]-21,24-dihydroxy-5 ',11,13,22-tetramethyl-2-oxo-(3,7,19-

trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene)-6-spiro-2 '-(5 ',6 

'-dihydro-2 'H-pyran)-12-yl 2,6-dideoxy-4-O-(2,6-dideoxy-3-O-methyl-α-Larabino-hexopyranosyl)-3-O-methyl-α-L-arabino-hexopyranoside and 

(10E,14E,16E)-(1R,4S,5 'S,6S,6 'R,8R,12S,13S,20R,21R,24S)-21,22-dihydroxy-6 '-
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Table 3.1. Abamectin 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 Miticide/Insecticide, EPA Reg. No. 100-898 (contains 0.15 

lb ai per gallon);

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

lb ai per gallon);

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

per gallon);

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

per gallon)

Chemical class Macrocyclic lactone; 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. 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

Syngenta Crop Protection, LLC has submitted a petition to add cotton and strawberry uses to the 

Agri-Mek® SC and Epi-Mek® SC labels. Cotton and strawberry uses are currently registered on 

emulsifiable concentrate (EC) labels. Both Agri-Mek®SC and Epi-MekTM SC are suspension 

concentrate (SC) formulations which contain 0.7 lb abamectin per gallon. Both formulations 

contain 8.0% active ingredient and 92.0% inerts.
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Table 3.3. Summary of Directions for Proposed Amended Uses of Abamectin.

Application 

Timing, Type, 

and Equipment

Formulation

[EPA Reg. No.]

Application 

Rate

Max. No. 

Application 

per Season

Maximum 

Seasonal 

Application 

Rate

PHI 

(days)

Use Directions and Limitations1

Cotton

Foliar:

Ground or 

Air

Agri-Mek® 

SC Miticide/ 

Insecticide

[100-1351]

Epi-MekTM

SC Miticide/

Insecticide

[100-1408]

1.0-3.5 fl 

oz/A

(0.0055-

0.019 lb 

ai/A)

Not 

stated1

6.75 fl 

oz/A

(0.038 lb

ai/A)

20 Agri-Mek SC and EpiMek must always be 

mixed with an adjuvant.

Do not apply with 

aircraft in NY state.

Do not apply through 

any type of irrigation 

system.

Retreatment interval is 

at least 21 days.

Do not apply in fewer 

than 5 gals water per 

acre.

Strawberries

Foliar:

Ground Only

Agri-Mek®

SC Miticide/ 

Insecticide

[100-1351]

Epi-MekTM

SC Miticide/

Insecticide

[100-1408]

3.5 fl 

oz/A

(0.019 lb 

ai/A)

4 14 fl oz/A

(0.075 lb

ai/A)

3 Ground application 

only.

Do not apply with 

aircraft.

Apply with ground 

application equipment 

as a foliar spray and 

ensure thorough 

coverage on upper and 

lower leaf surfaces. 

Adjust spray volume 

and nozzle placement to 

ensure maximum 

coverage of tops and 

undersides of leaves. 

Retreatment interval is 

at least 21 days.

Do not apply in less 

than 50 gals water per 

acre with conventional 

ground application 

equipment, or in less 

than 10 gal of water per 

acre with electro-static 

sprayers.

1 Two applications per season could be made at the maximum application rate.
ABAMECTIN Human Health Risk Assessment DP No. D402677

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Conclusions. Refer to Section 2.3 for recommended modifications to the proposed labels. 

Provided the recommended label revisions are made, the labels are adequate to allow evaluation 

of the residue data relative to the proposed uses.

3.4 Anticipated Exposure Pathways

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

proposed new use of abamectin on cotton and strawberries. 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 cotton and strawberries do not include 

residential uses; however, there are registered residential uses of abamectin, so there is the 

possibility of exposure in 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. Risk assessments have been 

previously conducted for abamectin, but no new toxicity data have been received since the 

previous risk assessment. A detailed description of the toxicity data and metabolism information 

may be found in the risk assessment dated 7/18/11 (N. Dodd, D380523); an amendment is dated 

8/24/11 (N. Dodd, D393232).

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 postapplication 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.
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4.0 Hazard Characterization and Dose-Response Assessment

No new toxicity and/or metabolism data have been received since the last risk assessment.

4.1 Summary of Toxicological Effects

Mode of Action: In nematodes, abamectin blocks signal transmission from the central command 

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

toxicity studies submitted by the registrant, paralysis is also a common finding prior to moribund 

sacrifice. 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. 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). Although GABA 

receptor mediated neurotoxicity is a solid hypothesis, data in mammalian preparations linking 

alterations in GABA receptor function to disruptions in neuronal excitability in vitro and in vivo, 

and ultimately adverse outcome are currently lacking.

Metabolism in rats: The metabolism study was performed with avermectin B1a. With oral 

dosing, the test material in the gastrointestinal tract of the rat was almost completely absorbed 

and distributed throughout all major tissues and organs, with the highest residues found in fat. 

Maximum concentrations in blood were achieved within 4-8 h after administration. It was

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

body after repeated exposure. The major biotransformations of avermectin B1a in the rat were 

demethylation, hydroxylation, cleavage of the oleandrosyl ring and oxidation reactions. There 

were 11 isolated metabolites. In the rat, avermectin B1a was metabolized to 24-hydroxy-methyl 

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

[8, 9-Z]- isomer of avermectin B1a was not found in the rat metabolism studies. Avermectin B1a

did not bioaccumulate in rat tissues. 

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.2.1 of Appendix 

A.

In general, the results of available toxicity studies with single or repeated dosing 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. 
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Integral to its dose response in mammals, abamectin is also a substrate for P-glycoprotein (P-gp). 

P-glycoprotein is a member of the ATP binding cassette transporter proteins (ABC), 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 very small population of humans is also 

found to be deficient of ATP binding cassette transporter proteins due to polymorphism in the 

gene encoding ABC (Dubin-Johnson Syndrome) (S. Habashi, 2006; A.T. Niles, 2007). In 

addition, collie dogs have been shown to be deficient in P-gp (R. Kerb, 2005).

The dose/response curve is very steep in several studies, with 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. In CD-1 mice,

hind limb splay was seen at 3.0 mg/kg in dams; a similar effect, hind limb extension, was seen at 

0.75 mg/kg in the fetuses. In rabbits at 2.0 mg/kg, the maternal effects consisted of deceases in 

body weight and food consumption whereas in the fetuses cleft palate, clubbed foot, and death 

were found. In the rat reproduction study, at the highest dose tested (0.4 mg/kg/day) no effect 

was seen in parental animals whereas in the pups death and decreases in pub body weight were 

seen (please Section 4.2.3 for details). 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 Tables A.2.2 & A.2.3 of 

Appendix A.

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

4.2.1 Completeness of the Toxicology 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. 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. Data quality is acceptable and meets the criteria set in the OCSPP guidelines and 40 

CFR §158.500. 
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However, under the current data requirement guidelines (40 CFR §158.500), a subchronic 

dermal toxicity study and immunotoxicity study (OCSPP 870.7800) are missing. A subchronic 

dermal toxicity study is waived based on the results of a monkey dermal absorption study, which 

shows less than 1% of abamectin is absorbed (HASPOC, 11/19/12). In addition, a 22-day

dermal toxicity study in rabbits with a structurally related compound, emamectin, shows no 

adverse effect at 1000 mg/kg/day. However, the immunotoxicity study is required. The risk 

assessment team was initially informed that the registrant was committed to conduct this study, 

but currently the registrant is planning to submit a data waiver for the immunotoxicity study. An 

inhalation study in rats was available and showed no effect at the highest concentration tested 

(0.0025 mg/L) (≈0.68 mg/kg/day). The HASPOC considered all the available data and concluded 

that no additional inhalation study is needed at this time. 

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

factor, the RAB3 risk assessment and 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. 

4.2.2 Evidence of Neurotoxicity

The findings of neurotoxic signs are consistent with mode of actions for a chemical which acts 

on GABA receptors. 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 hindlimb grip strength, tip-toe gate, tremors, ataxia, or spastic movements of the limbs are reported in 

various studies with different durations of abamectin exposure. In dogs, mydriasis was the most 

common finding at doses as low as 0.5 mg/kg/day 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, the studies which reported the neurotoxicity findings are 

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

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

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 below. 

Quantitative increase in susceptibility was also shown in reproductive toxicity and 
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developmental neurotoxicity studies in rats where the LOAELs were substantially lower in the 

pups than those in the parental animals. 

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.2.2 and A.2.3 of 

Appendix A). 

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.

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.2.3, 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.2.3 of Appendix A). In CD1 mice and rabbits, cleft palate was found at slightly higher dose levels, 0.75 mg/kg/day and 2.0 

mg/kg/day, respectively.

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.

 
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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.2.2, 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 

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.
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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 pup body weight loss (detected at the low dose, 0.2 mg/kg/day ) leading to moribundity at the 

high dose (0.4 mg/kg/day), 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 (0.12/3) which is protective of the

slight body weight decrease seen in low-dose males (p<0.01 using Mixed Model Analysis).

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 (highest dose tested; 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 
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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 under the conditions of this study.

4.2.4 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. The approximately 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 /3 = 0.04 mg/kg/day). Additionally, this adjusted point of departure (0.04 

mg/kg/day) would also address the concerns for the increased susceptibility seen at higher doses 
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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 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 Pglycoprotein. The data on CF-1 mice show that most of the effects are seen at doses above 0.06 

mg/kg/day (Table A.2.3 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).

4.2.5 Residual Uncertainty in the Exposure Database

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

dietary food exposure assessment utilizes conservative assumptions including anticipated 

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

assessment utilized modeling results which included conservative assumptions for the parent and 

all degradates of concern. Conservative assumptions were used in the water models. Therefore, 

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
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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.

The exposure is not expected to be underestimated in this assessment. An 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. 

4.3 Toxicity Endpoint and Point of Departure Selections

There have been no changes to the prior dose-response assessment. There have been no changes 

to the prior recommendations for combining routes of exposure and/or cancer classification. 

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 Tables 4.3.2 and 4.3.3 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 Tables

4.3.2 and 4.3.3.

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

a 53-week study in dogs (HIARC report, Sept. 1998, TXR # 012854), 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 4.3.1. 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 
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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 dose-range-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 

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

Table 4.3.1. 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 On week On week 1, one On week 1, 
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Table 4.3.1. Mydriasis Seen in All the Available Toxicity Studies in Dogs

Study Dose Levels (mg/kg/day)

0.25 0.5 1 2 4 8

study feeding 

(1987)

(0.25, 0.5, & 1.0 

mg/kg/day) 

(6M/6F)

10, 1 dog 

was noted 

to have 

mydriasis, 

and none 

before that 

time.

dog was 

reported to 

have mydriasis. 

By week 6, 5 

dogs had 

mydriasis. 

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 the high-dose group (0.4 mg/kg/day), 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. 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). The results of the analysis was 

further evaluated with all the results of the pup body weight effects seen in three other 

reproduction studies in rats. The doses tested in these three reproduction studies ranged from 

0.05 to 1.5 mg/kg. The statistically and biologically significant reduction in body weight began 

at 0.4 mg/kg/day ranging from 7% to 33% (Table C.1 of Appendix C of D362615). No effect on 

pup body weight was seen at 0.12, 0.10, and 0.05 mg/kg/day levels. It was 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 
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departure for risk assessment. As discussed in the FQPA Safety Factor Section, the 10x 

intraspecies factor is 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 rodent (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: In 1998, the HIARC recommended the use of a dermal penetration factor 

of 1% for risk assessment purposes (HED document No. 012845; 9/15/1998) This value was 

based on the results from a dermal absorption study in monkeys which demonstrated that <1% of 

an applied dose was absorbed. The HASPOC at 11/19/12 meeting affirmed the use of 1% as

dermal absorption factor for abamectin.

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). 
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Table 4.3.2. 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.
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Table 4.3.3. 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).

4.4 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, 

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). 
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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 Residues of Concern Summary and Rationale

Metabolism in Primary Crops: The qualitative nature of abamectin residues in cotton and 

strawberry is adequately understood based on metabolism studies on cotton, citrus, and celery

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

Degradation of Avermectin B1a in Cotton Leaf, Citrus Fruit, Celery, and In Vitro" (PP#9F3703, 

S. Willett, 12/15/89). The available studies on cotton, citrus, and celery indicate that the 

metabolism of abamectin in plants results in a complex mixture of residues, with the majority of 

the terminal residue composed of several unidentified polar degradates. The parent compound, 

its delta-8,9-isomer, and the alpha 8-OH degradate have been identified in plants, with only the 

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

degradates generated on citrus [7-day preharvest interval (PHI)] and in vitro (30 hour sample) 

have been tested for toxicity (in the developmental toxicity study in CF-1 mice) and were found 

to be of no toxicological significance at the levels tested (TOX memos 7080 and 7081, W. 

Dykstra, 3/15/89; PP#8F3592, F. Boyd, 6/21/89; D203373, G. J. Herndon, 3/29/95). As stated in 

The Pesticide Manual, Eleventh Edition, British Crop Protection Council (1997), abamectin has 

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

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

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

8,9-Z avermectin B1b).
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Metabolism in Rotational Crops: The qualitative nature of the residue in rotational crops is 

adequately defined. The confined rotational crop study indicated that avermectin residues 

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

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

compound avermectin B1 and/or the delta-8,9-isomer (Memo, P. Mastradone, 4/24/88).

 

Metabolism in Ruminants: The qualitative nature of abamectin residues in ruminants as a result 

of application to crops is adequately understood based on a goat metabolism study (PP#7G3468, 

L. Cheng, 2/11/87; PP#9F3703, S. Willett, 12/15/89). The residues of concern in ruminants for 

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

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

identified and is potentially of toxicological significance, but was not included in the tolerance 

expression because of its presence at low levels (PP#8F3592, F. Boyd, 6/21/89; DP#203373, G. 

J. Herndon, 3/29/95). If the tolerances for residues in meat and milk need to be raised at some 

future time due to registration of abamectin on additional feed items, the 24-hydroxymethyl 

metabolite may need to be included in the tolerance expression and appropriate enforcement 

methods developed.

Metabolism in Poultry: No poultry metabolism study has been submitted. Since no significant 

poultry feed items are associated with the proposed uses, as indicated in Table 1 Feedstuffs (June 

2008), no poultry metabolism study is required. (Note: The tolerances for meat and meat 

byproducts of poultry and swine of 0.02 ppm were established for residues in food handling 

establishments.) 

Metabolism in Rats: Avermectin B1a does not bioaccumulate in rat tissues. Avermectin B1a in 

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

the radiolabeled residues. 

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

5.1 below.

Table 5.1 Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants Primary Crop Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Rotational Crop Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z isomers)

Parent (avermectin B1a and 

B1b) and the delta-8,9-isomers 

(also known as 8,9-Z

isomers)**
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Table 5.1 Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

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

Crop Field Trials

For both cotton and strawberry, the field trials reflect the proposed use pattern. The number of 

trials and the geographic representation are adequate. The residue data are adequately supported 

by the storage stability studies. The data collection methods [liquid chromatography/tandem 

mass spectrometry (LC/MS/MS) for cotton; LC/MS/MS or high performance liquid 

chromatography (HPLC) for strawberry] are adequate for the analysis of the residues of concern. 

The residue data adequately address the residues of concern. 

Residue decline in cottonseed and cotton gin byproducts was not determined because residues in 

the decline study were all <LOQ in cottonseed and were not determined in cotton gin 

byproducts. Residues declined in strawberries with increasing PHI. 

The field trials on cotton and strawberry are summarized in Table 5.2.1 below. Higher residues 

occurred on cotton and strawberry as a result of use of the SC formulation as compared to use of 

the registered EC formulation. Higher residues occurred in cotton and strawberry even though 

an adjuvant was used with the SC formulation; the adjuvant was used to increase photolytic 

degradation of abamectin and thereby reduce residues, as has been observed with the SC 

formulation of abamectin on other crops.
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TABLE 5.2. 1. Summary of Combined Residues of Avermectin B1a, 8,9-Z Avermectin B1a, and Avermectin B1b 

from Field Trials with Abamectin. 

Commodity Total Applic. 

Rate

(lb a.i./A)

PHI 

(days)

Residue Levels1

(ppm)

n Sample 

Min.

Sample 

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

COTTON Proposed Use = 0.038 lb ai/acre/season total application rate, 20-day PHI.

Cotton, 

undelinted seed

0.038-0.039 19-20 11 <0.006 <0.014 <0.006 <0.014 <0.006 <0.007 0.002

Cotton, gin 

byproducts

0.038-0.039 20 7 <0.009 0.688 <0.014 0.632 <0.018 <0.129 0.226

STRAWBERRY Proposed Use = 0.075 lb ai/acre/season total application rate, 3-day PHI.

Strawberry 0.075-0.078 3 6 <0.008 <0.028 <0.010 <0.025 <0.015 <0.017 0.006

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and 

standard deviation, the LOQ (0.002 ppm for each analyte in each matrix) was used for any results reported as <LOQ in Table 

C.3.

2

 LAFT = lowest average field trial; HAFT = highest average field trial.

Processing Studies

There are no processed commodities associated with strawberries. 

As shown in Table 5.2.2 below, residues are not expected to concentrate in the processed 

commodities of cotton (meal, hulls, or refined oil). The average processing factor is 0.6x for 

each matrix (meal, hulls, and refined oil). Separate tolerances are not needed for the processed 

commodities of cotton.

TABLE 5.2.2. Residue Data from Cotton Processing Study with Abamectin.

Location

(County, State; Year)

Trial ID

RAC Total Rate

(lb a.i./A) Commodity PHI(days)

Total Abamectin Residues (ppm)1

Processing 

Replicates Average Factor

Uvalde, TX; 2008 

(W07TX081024)

Cotton 0.190 Undelinted 

seed

20 <0.006, <0.013, <0.006 <0.009 N/A2

Hulls 20 <0.006, <0.006 <0.006 0.7x

Meal 20 <0.006, <0.006 <0.006 0.7x

Refined oil 20 <0.006, <0.006 <0.006 0.7x

Groom, TX; 2008 

(E13TX081026)

Cotton 0.191 Undelinted 

seed

20 <0.018, <0.014, <0.014 <0.016 N/A

Hulls 20 <0.006, <0.006 <0.006 0.4x

Meal 20 <0.006, <0.006 <0.006 0.4x

Refined oil 20 <0.006, <0.006 <0.006 0.4x

1

 Total residues of avermectin B1a, avermectin B1b and 8,9-Z avermectin B1a. The LOQ was 0.002 ppm for each analyte in each 

matrix, for a combined LOQ of 0.006 ppm. 

2

 N/A = Not applicable
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Storage Stability

The storage stability data are adequate to support the storage intervals and conditions for the 

field trials on strawberry and cotton (cottonseed and cotton gin byproducts). 

The available cottonseed storage stability data are adequate to support the storage intervals and 

conditions for undelinted seed, hulls, and oil samples from the cotton processing study.

Although storage stability data demonstrating the stability of abamectin in processed cotton meal 

frozen for up to 17.5 months are not available, the available storage stability data on cottonseed 

(14 months) and on other crops (fruits and vegetables) for longer intervals (24-35 months) allow 

HED to expect that residues in cotton meal will be stable for 17.5 months under frozen storage. 

Storage stability data are summarized in Table 5.2.3 below.

TABLE 5.2.3. Summary of Storage Conditions.

Matrix Storage Temperature 

(°C)

Actual Storage 

Duration1

Interval of Demonstrated Storage Stability

Strawberry 20  5 45-141 days1

(1.5-4.6 months)

Data are available demonstrating that residues of 

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

avermectin B1a are stable under frozen storage 

conditions for 24 months in strawberries (DP# 

191433, G. J. Herndon, 5/19/94). 

Cotton, undelinted seed 20  5 142-220 days2

(4.7-7.2 months)

Data are available demonstrating that residues of 

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

avermectin B1a are stable under frozen storage 

conditions in/on cottonseed (avermectin B1a only) 

for 14 months; in/on celery, tomato, and 

strawberries for 24 months; in/on oranges, lemons, 

and grapefruits for 29 months; and in/on pears for 

35 months (DP# 191433, G. J. Herndon, 5/19/94).

Cotton, gin byproducts 20  5 297-437 days2

(9.8-14.4 months)

Cotton, undelinted seed 

for processing

20  5 148-219 days3

(4.9-7.2 months)

Data are available demonstrating that residues of 

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

avermectin B1a are stable under frozen storage 

conditions in/on cottonseed (avermectin B1a only) 

for 14 months; in/on celery, tomato, and 

strawberries for 24 months; in/on oranges, lemons, 

and grapefruits for 29 months; and in/on pears for 

35 months (DP# 191433, G. J. Herndon, 5/19/94).

Cottonseed, hulls 59-152 days3

(1.9-5.0 months)

Cottonseed, meal 438-531 days3

(14.4-17.5 months)

Cottonseed, refined oil 313-406 days3

(10.3-13.3 months)

1

 Interval from harvest to extraction for analysis. Samples were analyzed within 0-5 days of extraction.

2

 Interval from sample collection to extraction for analysis. Extracts were analyzed within 0-7 days of extraction.

3

 Interval from sample collection (at harvest for RAC; after processing for processed commodities) to extraction for analysis. 

Extracts were analyzed within 0-16 days of extraction.

Meat, Milk, Poultry, and Eggs

An adequate ruminant feeding study was conducted. An adequate cattle ear tag study was 

conducted. No poultry feeding studies were submitted or required. 

The livestock dietary burdens were calculated based on the maximum reasonably balanced diets 

(Table 1 Feedstuffs, June 2008). The established tolerances on livestock commodities are 
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adequate to cover expected residues from livestock feed items and from the cattle ear tag use. 

The established tolerances for ruminants are 0.03 ppm for fat of cattle; 0.01 ppm for fat of goat, 

hog, horse, and sheep; 0.02 ppm for meat of cattle, goat, hog, horse, poultry, and sheep; 0.06 

ppm for meat byproducts of cattle; 0.02 ppm for meat byproducts of goat, hog, horse, poultry, 

and sheep; and 0.005 ppm for milk.

Rotational Crops

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).

5.3 Water Residue Profile

Estimated drinking water concentrations (EDWCs) were provided for 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. Abamectin is stable to 

abiotic hydrolysis; acceptable data are not available to estimate the formation and decline of 

residues of concern via other degradataion routes. 

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 groundwater. 

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 groundwater 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.
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Results from the SCI-GROW screening model predict that the maximum acute and chronic 

concentration of parent abamectin in shallow groundwater 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. 

Table 5.3. Summary of Estimated Surface Water and Groundwater Concentrations for Abamectinc,d

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 1.6 x 10-3

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.

d Bolded values are estimates used in the assessment.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Acute assessment: A refined acute dietary (food and drinking water) exposure assessment was 

conducted. Tolerance level residues were used for bulb onions, chives, dry beans, 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. 

EDWCs from 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 a percent cropped area (PCA) value 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 applications to dry

beans in Michigan. 

Chronic assessment: A refined chronic dietary (food and drinking water) exposure assessment 

was conducted. Tolerance level residues were used for bulb onions, chives, dry beans, 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-ten-year annual mean). The estimated 

surface water concentration of 1.3 ppb was based on the application to dry beans in Michigan.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The following maximum percent crop treated estimates (D382732, Arthur H. Grube, 10/21/10)

were used in the acute dietary risk assessment for the following crops that are currently 

registered for abamectin: almonds: 75%; apples: 10%; apricots: 5%; avocados: 60%; 
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cantaloupes: 30%; celery: 65%; cherries: 2.5%; cotton: 20%; cucumbers: 10%; grapefruit: 80%; 

grapes: 25%; honeydew: 35%; lemons: 55%; lettuce: 20%; oranges: 45%; peaches: 2.5%; pears:

80%; pecans: 2.5%; peppers: 25%; potatoes: 2.5%; prunes: 10%; pumpkins: 10%; spinach: 45%; 

squash: 10%; strawberries: 45%; tangerines: 65%; tomatoes: 20%; walnuts: 20%; and 

watermelons: 10%.

The following average percent crop treated estimates (D382732, Arthur H. Grube, 10/21/10)

were used in the chronic dietary risk assessment for the following crops that are currently

registered for abamectin: almonds: 50%; apples: 5%; apricots: 5%; avocados: 40%; cantaloupes:

15%; celery: 40%; cherries: 1%; cotton: 5%; cucumbers: 5%; grapefruit: 60%; grapes: 10%; 

honeydew: 20%; lemons: 35%; lettuce: 10 %; oranges: 25%; peaches: 1%; pears: 70%; pecans:

1%; peppers: 10%; potatoes: 1%; prunes: 2.5%; pumpkins: 2.5%; spinach: 20%; squash: 5%; 

strawberries: 30%; tangerines: 60%; tomatoes: 10%; walnuts: 10%; and watermelons: 5%.

Percent crop treated data are available for cotton and strawberry as registered crops since they

are registered for use of the EC formulation.

5.4.3 Acute Dietary Risk Assessment

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

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

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

As shown in Table 5.4.6, the most highly exposed subgroup was children 1-2 years old, with 

exposure of 24% of the acute population adjusted dose (aPAD). The risk estimates for all 

populations assessed were below the level of concern.

5.4.4 Chronic Dietary Risk Assessment

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

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

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

As shown in Table 5.4.6, the most highly exposed subgroup was children 1-2 years old, with 

exposure of 53% of the acute population adjusted dose (aPAD). The risk estimates for all 

populations assessed were below the level of concern.

5.4.5 Cancer Dietary Risk Assessment

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.
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5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Abamectin1

Population Subgroup

Acute Dietary

99.9th Percentile) Chronic Dietary

Dietary Exposure 

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

General U.S. Population 0.000726 15 0.000068 17

All Infants (< 1 year old) 0.001079 22 0.000127 32

Children 1-2 years old* 0.001215 24 0.000213 53

Children 3-5 years old 0.000882 18 0.000146 36

Children 6-12 years old 0.000544 11 0.000091 23

Youth 13-19 years old 0.000398 8.0 0.000055 14

Adults 20-49 years old 0.000409 8.2 0.000057 14

Adults 50-99 years old 0.000354 7.1 0.000054 13

Females 13-49 years old 0.000398 8.0 0.000055 14

*The subpopulation with the highest risk estimates is bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no proposed residential uses at this time; however, there are existing residential uses 

that have been reassessed in this document to reflect updates to HED’s 2012 Residential SOPs1

along with policy changes for body weight assumptions. The revision of residential exposure 

risk estimates will impact the human health aggregate risk assessment for abamectin.

The products registered for residential use sites include several formulations of homeowner bait 

and bait station products registered under multiple companies. These products include outdoor 

granular bait (GB) and indoor ready-to-use bait (RB) of both dust and gel formulations. For this 

assessment, the exposures and risk estimates for applying outdoor granular baits are assessed 

using the 2012 Residential SOPs2and exposure from indoor ready-to-use gel baits is considered 

negligible. In addition, exposure data for hand dispersal of granular bait is chosen as a surrogate 

to calculate risk estimates from indoor RBs.

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html

2 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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There are no registered products that would lead to any residential handler risk estimates of 

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

320,000 to 1,100,000,000. Residential post-application exposures are not expected.

6.1 Residential Handler Exposure

The quantitative exposure/risk assessment developed for residential handlers is based on the 

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

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

hand (as a surrogate for a ready-to-use dust bait).

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

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

320,000 to 1,100,000,000.
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Table 6.1. Residential Handler Non-Cancer Exposure and Risk Estimates for Abamectin.

Exposure

Scenario

Level of 

Concern

Dermal Unit 

Exposure

(mg/lb ai)

Inhalation 

Unit Exposure

(mg/lb ai)

Maximum 

Application 

Rate

(lb ai/A)a

Area Treated or 

Amount Handled 

Dailyb

Dermal Inhalation Total

Dose

(mg/kg/day)c MOEd Dose (mg/kg/day)e MOEf MOEg

Mixer/Loader/Applicator for Outdoor Bait Application

Push-Type

Spreaders

300

0.81 0.0026 0.5 0.5 0.000000014 8,800,000 0.0000000044 28,000,000 6,700,000

Belly Grinders 360 0.039 0.023 0.023 0.00000028 430,000 0.0000000030 40,000,000 430,000

Spoon 6.2 0.087

0.00023

0.0023 0.00000000048 250,000,000 0.00000000067 180,000,000 100,000,000

Cup 0.11 0.013 0.0023 0.0000000000085 14,000,000,000 0.00000000010 1,200,000,000 1,100,000,000

Hand Dispersal 160 0.38 0.0023 0.000000012 9,700,000 0.0000000029 41,000,000 7,900,000

Shaker Can 0.11 0.013 0.0023 0.0000000000085 14,000,000,000 0.00000000010 1,200,000,000 1,100,000,000

Mixer/Loader/Applicator for Indoor Bait Application

Bait (granular;

hand dispersal) 300 160 0.38 0.000013lb ai/package/day 0.00000031 390,000 0.000000073 1,600,000 320,000

a Based on registered labels:

EPA Reg. Nos. 100-893, 100-1029, 100-1452 (50 mg ai/lb product): Apply 7 tbsp/mound (1 tbsp ≈ 0.4 oz). Do not treat more than 12 ant mounds per acre 

(i.e. 12 mounds/A × 7 tbsp product/mound × 0.4 oz product/tbsp product × 0.0625 lb product/oz product × 50 mg ai/lb product × 2.20462×10-6lb ai/mg ai = 0.00023 lb ai/A)

EPA Reg. No. 499-383 (0.05% ai bait dust): Package contains 100 bait placements (12 grams of product). The label recommends up to 30 bait placements in an average sized 

kitchen (i.e. assuming one package can be used in one day, 12 g product/day × 0.05% ai/product × 0.00220462 lb ai/g ai = 0.000013 lb ai/day).

b Exposure Science Advisory Council Policy #9.1. Based on HED’s SOPs: Lawns/Turf (January 2012). 0.023 A = 1000 ft2. 0.0023 A = 100 ft2.

c Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gallons/day) × DAF (1%) ÷ BW (69 kg).

d Dermal MOE = Dermal NOAEL (mg/kg/day) / Dermal Dose (mg/kg/day). ST/IT Dermal NOAEL = 0.12 mg/kg/day. Level of concern = 300.

e Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gallons/day) ÷ BW (69 kg).

f Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST/IT Inhalation NOAEL = 0.12 mg/kg/day. Level of concern = 300.

g Total MOE = NOAEL (mg/kg/day) ÷ (Dermal Dose + Inhalation Dose). ST/IT Combined Dermal/Inhalation NOAEL = 0.12 mg/kg/day. Level of concern = 300.
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6.2 Residential Post-Application Exposure

Residential post-application exposure to adults and children is unlikely for all registered uses of 

abamectin. For outdoor treatments, adults and children are not expected to directly contact fire 

ant mounds. For indoor pest control, bait placements are intended to be placed in cracks and 

crevices where direct contact by adults and children is unlikely.

Residential Bystander Post-Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for abamectin at this time primarily because of the low proposed 

use rate and low vapor pressure. However, volatilization of pesticides may be a source of postapplication inhalation exposure to individuals nearby pesticide applications. The Agency sought 

expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, 

and received the SAP’s final report on March 2, 20103. The Agency is in the process of 

evaluating the SAP report and may, as appropriate, develop policies and procedures to identify

the need for and, subsequently, the way to incorporate post-application inhalation exposure into 

the Agency's risk assessments. If new policies or procedures are developed, the Agency may

revisit the need for a quantitative post-application inhalation exposure assessment for abamectin.

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)

4

. 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 risk estimates 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.

 

3 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

4 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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7.0 Aggregate Exposure/Risk Characterization

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.

7.1 Acute Aggregate Risk

The acute aggregate risk assessment considers exposure estimates from dietary consumption of 

abamectin (food and drinking water). The acute aggregate food and drinking water assessment 

results are presented in Section 5.4 above. The most highly exposed subgroup is children 1-2 

years old at 24% of the aPAD, which is below the level of concern.

7.2 Short- and Intermediate-Term Aggregate Risk

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

exposure to abamectin residues from food, drinking water, and residential pesticide uses. Highend estimates of residential exposure are used, while average values are used for food and 

drinking water exposure.

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 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

Population

Short- or Intermediate-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

U.S. Population 0.12 300 0.0004 0.000068 0.00000038 0.000068 1800

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 6.1 for 

residential exposure values used in the aggregate assessment. 

4Total Exposure = Avg Food & Water Exposure + Residential Exposure)

5 Aggregate MOE = [NOAEL  (Avg Food & Water Exposure + Residential Exposure)]
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7.3 Chronic Aggregate Risk

The chronic aggregate risk assessment considers average exposure estimates from dietary

consumption of abamectin (food and drinking water) and residential uses. However, due to the 

use patterns, no chronic residential exposures are expected. Therefore, the chronic aggregate risk 

assessment will consider exposure from food and drinking water only.

The chronic aggregate food and drinking water assessment results are presented in Section 5.4

above. The most highly exposed subgroup is children 1-2 years old at 53% of the cPAD, which 

is below the level of concern. 

7.4 Cancer Aggregate Risk

Abamectin is classified as “not likely to be carcinogenic to humans” based on the absence of a 

significant increase in tumor incidence in two adequate rodent carcinogenicity studies.

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity (CMT), 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.

OPP’s Guidance For Identifying Pesticide Chemicals and Other Substances that have a Common 

Mechanism of Toxicity (USEPA, 1999) describes the weight of the evidence approach for 

determining whether or not a group of pesticides share a common mechanism of toxicity. This 

guidance defines mechanism of toxicity as the major steps leading to a toxic effect following 

interaction of a pesticide with biological targets. All steps leading to an effect do not need to be 

specifically understood. Rather, it is the identification of the crucial events following chemical 

interaction that are required in order to describe a mechanism of toxicity. For example, a 

mechanism of toxicity may be described by knowing the following: a chemical binds to a given 

biological target in vitro, and causes the receptor-related molecular response; in vivo it also leads 

to the molecular response and causes a number of intervening biological and morphological steps 

that result in an adverse effect. In this context a common mechanism of toxicity pertains to two 

or more pesticide chemicals or other substances that cause a common toxic effect to human 

health by the same, or essentially the same, sequence of major biochemical events. Hence, the 

underlying basis of the toxicity is the same, or essentially the same, for each chemical. In the 

case of the macrocyclic lactone pesticides (e.g., abamectin, emamectin, and avermectin), there is 

a wealth of data on the insecticidal mechanism of action for avermectin: its insecticidal actions 

are mediated by interaction with the glutamate-gated chloride channels and GABAA gated 

chloride channels. This is presumed to be the insecticidal mechanism of action of emamectin and 

abamectin as well. Mammals lack glutamate-gated chloride channels; the toxic actions of 

avermectin appear to be mediated via interaction with GABAA and possibly glycine gated 
ABAMECTIN Human Health Risk Assessment DP No. D402677

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chloride channels (Kamijima M, Casida JE, 2000). There is evidence that avermectin B1a binds 

to GABAA receptors and activates Clflux into neurons (Abalis et al., 1986; Huang and Casida, 

1997). However, there is a paucity of data regarding the resultant alterations in cellular 

excitability of mammalian neurons and neural networks (i.e., changes in cellular excitability and 

altered network function as documented with pyrethroids), as well as in vivo measurements of 

altered excitability associated with adverse outcomes. Thus, while the downstream steps leading 

to toxicity via disruption of GABAA receptor function for avermectin can be postulated, 

experimental data supporting these actions are lacking. In addition, specific data demonstrating 

GABAA receptor interaction in mammalian preparations are lacking for abamectin and 

emamectin. Moreover, the specificity of such interaction on the adverse outcome would need to 

be shown experimentally. GABAA receptors have multiple binding sites which have been 

proposed to relate to adverse outcomes. For example, Dawson et al (2000) showed for a group 

of avermectin-like compounds that rank order for anticonvulsant activity did not parallel the rank 

order for affinity at the [3H]ivermectin site. The authors hypothesized that these findings may be 

related to differential affinity or efficacy at subtypes of the GABAA receptor. Other reports have 

indicated species differences in abamectin effects on GABAA receptor function in the mouse as 

compared to the rat (Soderlund et al., 1987).

In conclusion, although GABAA receptor mediated neurotoxicity is a strong hypothesis as a 

common mechanism endpoint for the macrocyclic lactone pesticides, data demonstrating the 

interactions of emamectin and abamectin with mammalian GABAA receptors are not available, 

and data in mammalian preparations linking alterations in GABAA receptor function to 

disruptions in neuronal excitability in vitro and in vivo, and ultimately adverse outcome, are also 

currently lacking for this class of compounds. In the absence of such data, the key biological 

steps leading to the adverse outcome (i.e, the mammalian mechanism of action) cannot be 

established and by extension a CMT cannot be established.

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 Characterization

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following scenarios: 

1. Mixing/loading liquids to support groundboom applications (cotton/strawberries), 

2. Mixing/loading liquids to support aerial applications (cotton only),

3. Flagging to support aerial application (cotton only),

4. Applying sprays with groundboom equipment (cotton/strawberries), and

5. Applying sprays with aerial equipment (cotton only).
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Agricultural workers performing typical post-application activities (e.g. scouting, irrigation, 

transplanting/harvesting, etc.) may receive short- and intermediate-term exposure to abamectin

residues.

9.1 Short-/Intermediate-Term Handler Risk

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

intermediate-term dermal and inhalation risks do not exceed HED’s LOC (i.e., an MOE < 300) at 

some level of mitigation. The abamectin product labels direct mixers, loaders, applicators and 

other handlers to wear a long-sleeved shirt and long pants, chemical-resistant gloves, and shoes 

plus socks. For short- and intermediate-term exposure, the combined (dermal + inhalation) 

MOEs for mixer/loader scenarios range from 150 to 2,300 at baseline level of clothing (single 

layer long-sleeved shirt, long pants, and shoes plus socks). With single layer plus gloves as 

required by the label, the lowest MOE of 150 increases to 600. All uses have acceptable MOEs 

given the proposed label requirements. For flaggers, the MOE is 2,700 at baseline (no gloves, no 

respirator). Only engineering control (enclosed cockpit) data are available to assess risks to 

handlers operating aircrafts. For ground and aerial applicators the MOEs range from 1,900 to 

4,800 (no gloves, no respirator).

The Agency has evaluated scenarios that may be limited in nature such as flagging during aerial 

applications because engineering controls (i.e., Global Positioning Satellite technology) are now 

predominantly used as indicated by the 1998 National Agricultural Aviation Association 

(NAAA) survey of their membership. It appears, however, flaggers are still used in 

approximately 10 to 15 percent of aerial application operations. In cases like these, the Agency

strongly encourages the use of the engineering control system but will continue to evaluate risks 

for flaggers and any other population where a clear exposure pathway exists until the potential 

for exposure is eliminated. The Agency is aware that NAAA is conducting another survey on 

exposure issues and will consider those results as are timely and appropriate.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for 

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); pilots are not required to wear protective gloves. With this level of protection, there 

are no risk estimates of concern for applicators.
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Table 9.1. Short- and Intermediate-Term Occupational Exposure and Risk Estimates for Abamectin Use on Cotton and Strawberries.a 

Crop Exposure Scenario

Dermal Unit 

Exposureb

Inhalation Unit 

Exposureb

Maximum 

Application 

Ratec

Area 

Treated 

Dailyd

Dermal Inhalation Total

Dosee

MOEf

Doseg

MOEh MOEi

ug/lb ai ug/lb ai lb ai/A A mg/kg/day mg/kg/day

Mixer/Loader at Baseline (No Gloves, No Respirator)

Strawberries Mixing/Loading Liquids for 

Groundboom Application 220 0.219 0.019 80 0.0000488 2,500 0.00000486 25,000 2,300

Cotton Mixing/Loading Liquids for 

Groundboom Application 220 0.219 0.019 200 0.000122 980 0.0000121 9,900 890

Cotton Mixing/Loading Liquids for 

Aerial Application 220 0.219 0.019 1200 0.000732 160 0.0000729 1,600 150

Mixer/Loader with PPE (Single Layer + Gloves, No Respirator)

Cotton Mixing/Loading Liquids for 

Aerial Application 37.6 0.219 0.019 1200 0.000125 960 0.0000729 1,600 600

Applicator at Baseline (No Gloves, No Respirator)

Strawberries Applying Sprays via 

Groundboom Equipment 78.6 0.34 0.019 80 0.0000174 6,900 0.00000755 16,000 4,800

Cotton Applying Sprays via 

Groundboom Equipment 78.6 0.34 0.019 200 0.0000436 2800 0.0000188 6,400 1,900

Cotton Applying Sprays via

Aerial Equipment* 5 0.068 0.019 1200 0.0000167 7200 0.0000226 5,300 3,100

Flagger at Baseline (No Gloves, No Respirator)

Cotton Flagging for

Aerial Application 11 0.35 0.019 350 0.0000107 11,000 0.0000339 3,500 2,700

a All estimates are at baseline mitigation except for aerial applicator which includes the engineering control of enclosed cockpits.

b Unit Exposures based on PHED Version 1.1. Baseline = no gloves, no respirator. 

*Baseline aircraft = engineering controls.

c Based on proposed label amendments (Reg. Nos. 100-1351 and 100-1408).

d Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1.

e Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated or Amount Handled (A) ×

DAF (%) ÷ BW (69 kg). Dermal absorption factor = 1%.

f Dermal MOE = Dermal NOAEL (mg/kg/day)/Dermal Dose (mg/kg/day). ST/IT Dermal NOAEL = 0.12 mg/kg/day. LOC = 300.

g Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) x Area Treated (A) ÷ BW (69 kg).

h Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST/IT Inhalation NOAEL = 0.12 mg/kg/day. LOC = 300.

i Total MOE = NOAEL (mg/kg/day) ÷ (Dermal Dose + Inhalation Dose). ST/IT NOAEL = 0.12 mg/kg/day. LOC = 300.
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9.2 Short-/Intermediate-Term Post-Application Exposures and Risks

The post-application MOEs do not exceed HED’s LOC of 300 (MOEs ranged from 1,800 to 

28,000) on day 0 (12 hours after application).

Table 9.2. Summary of Short- and Intermediate-Term Occupational/Commercial Post-Application Risk 

Estimates for Abamectin.

Crop Activities Transfer Coefficient 

(cm2/hr) DFR1 Dermal Dose (mg/kg/day)2 MOE3

Cotton/Strawberries Scouting 70

0.0533

0.00000433 28,000

Hand Weeding 210 0.0000130 9,200

Strawberries

Scouting, Canopy 

Management 70 0.00000433 28,000

Hand Weeding 210 0.0000130 9,200

Transplanting 230 0.0000142 8,500

Hand Harvesting 1,100 0.0000680 1,800

a DFR = Application Rate × F × (1-D)t× 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.25 and D = 0.10 per day.

b Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (1%)]  BW (69

kg).

c MOE = NOAEL (mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR/TTR (μg/cm2) × TC × 0.001 mg/μg × 8 

hrs/day × dermal absorption]  BW (69 kg). ST/IT Dermal NOAEL = 0.12 mg/kg/day. LOC = 300.

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of abamectin. Abamectin

is classified as Toxicity Category III via the dermal route and Toxicity Category III for skin 

irritation potential. It is not a skin sensitizer. Short- and intermediate-term post-application risk 

estimates were not a concern on day 0 (12 hours following application) for all post-application 

activities. Under 40 CFR 156.208 (c) (2) (iii), active ingredients classified as Acute Toxicity

Category III or IV for acute dermal, eye irritation and primary skin irrigation are assigned a 12-

hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim REI of 12 hours 

is adequate to protect agricultural workers from post-application exposures to abamectin.

Occupational Post-Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for abamectin at this time primarily because of the low proposed 

use rate (0.019 lb ai/A) and low vapor pressure (1.13 x 10-9 mmHg at 25oC). 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, 

and received the SAP’s final report on March 2, 20105. The Agency is in the process of 

evaluating the SAP report as well as available post-application inhalation exposure data 

generated by the the Agricultural Reentry Task Force (ARTF) and 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 

 

5 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
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policies or procedures are put into place, the Agency may revisit the need for a quantitative 

occupational post-application inhalation exposure assessment for abamectin.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

10.0 References

N. Dodd, 8/24/11, DP No. D393232, Abamectin. Amendment to the Human Health Risk 

Assessment for Proposed Uses on the Bulb Onion Subgroup 3-07A, Chives, and Dry Beans to 

include Cowpea in the Dry Bean Tolerance.

N. Dodd, 7/18/11, DP No. D380523, Abamectin. Human Health Risk Assessment for Proposed 

Uses on the Bulb Onion Subgroup 3-07A, Chives, and Dry Beans.

N. Dodd, 12/17/12, DP No. D401832, Abamectin. Petition to Increase the Established 

Permanent Tolerances on Strawberry and Cotton and to Add Uses on Strawberry and Cotton to 

Agri-Mek® SC and Epi-MekTM SC Labels. Summary of Analytical Chemistry and Residue Data.

N. Dodd, 12/19/12, DP No. D403715, Abamectin. Acute and Chronic Aggregate Dietary (Food 

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

Use of a Suspension Concentrate (SC) Formulation on Cotton and Strawberry.

N. Tsaur, 12/20/2012, DP No. D405841, Abamectin. Occupational Exposure Assessment for a 

Label Amendment for Use on Cotton and Strawberries with An Updated Residential Exposure 

Assessment of All Existing Residential Uses (Lawns/Turf and Indoor Environments).

G. Orrick, 1/31/11, DP No. D380524, Abamectin. Drinking Water Exposure Assessment for 

Proposed Section 3 New Uses on Chives, Dried Beans, and the Bulb Onion Subgroup 3-07A.
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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for [Type of Use (e.g., food vs. non food)] for abamectin are in Table 1. Use of 

the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Acute Eye Irritation .......................................................

870.2500 Acute Dermal Irritation .................................................

870.2600 Skin Sensitization ..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 90-Day Oral Toxicity in Rodents ..................................

870.3150 90-Day Oral Toxicity in Nonrodents.............................

870.3200 21/28-Day Dermal Toxicity...........................................

870.3250 90-Day Dermal Toxicity................................................

870.3465 90-Day Inhalation Toxicity ...........................................

yes

yes

yes

CR

CR

yes

yes

a

-

yes

870.3700a Prenatal Developmental Toxicity (rodent).....................

870.3700b Prenatal Developmental Toxicity (nonrodent)...............

870.3800 Reproduction and Fertility Effects.................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Carcinogenicity (rat)......................................................

870.4200b Carcinogenicity (mouse)................................................

870.4300 Combined Chronic Toxicity/Carcinogenicity................

yes

no

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Bacterial Reverse Mutation Test ..........

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test ..

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6200a Acute Neurotoxicity Screening Battery (rat) .................

870.6200b 90-Day Neurotoxicity Screening Battery (rat)...............

870.6300 Developmental Neurotoxicity........................................

yes

yes

yes

yes

yes

yes

870.7485 Metabolism and Pharmacokinetics................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

CR

Yes

yes

yes

no

a

: This study was waived.
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A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Profile of Abamectin Technical

Guideline No. Study Type MRID # Results Toxicity Category

870.1100 Acute Oral - rat 

(sesame oil vehicle)

006894 LD50 = 13.6 mg/kg I

870.1100 Acute Oral - rat

(methyl cellulose vehicle)

45607202 LD50=214-232 mg/kg II

870.1200 Acute Dermal - rabbit 00255978 LD50 = 2000 mg/kg III

870.1300 Acute Inhalation - rat 45623501 LC50 =<0.21 mg/L (nose only) I

870.2400 Primary Eye Irritation 45063501 not an irritant IV

870.2500 Primary Skin Irritation 41123904 slight irritation III

870.2600 Dermal Sensitization 00139564 negative in Buehler Negative

870.6200a Acute Neurotoxicity none none none

Table A.2.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3100

Subchronic feeding 

study-rats

00131081 (1982)

Acceptable/Non-guideline

0, 0.10, 0.20, 0.40 

mg/kg/day

NOAEL > 0.40 mg/kg/day

LOAEL = not established

870.3150

Subchronic toxicity

Dogs (18 week 

gavage study)

00131082 (1982)

Acceptable/Guideline

0, 0.25, 0.5, 2.0, 8.0 

mg/kg/day

NOAEL = 0.25 mg/kg/day

LOAEL = 0.50 mg/kg/day based on body tremors, one death, 

liver pathology, decreased body weight. Mydriasis was seen 

during week one in one dog.

870.3150

12-Week dose range 

finding study-dogs 

(feeding) 

00164152 (1982)

0.25, 0.50, 1.0, and 4.0/2.0 

mg/kg/day (during week 4, 

4.0 mg/kg/day was reduced 

to 2.0 mg/kg/day due to 

tremor, weakness, 

incoordination, and 

disorientation) 

The report stated that mydriasis was seen in 1.0 and 4.0 

mg/kg/day dogs during week 1.The effect was not seen at each 

examination day for any dog, but it was generally noted from 1 to 

5 times a week. However, mydriasis was never noted at 0.5 and 

0.25 mg/kg/day. 

870.3200

21/28-Day dermal 

toxicity

Study not available. Study requirement was waived due to very low dermal absorption 

(<1%).

870.3465

30-Day inhalation 

tox.-rats

46921502 (2006)

Acceptable/Guideline

NOAEL = >2.5 μg/L (0.0025 mg/L) (HDT) (≈0.68 mg/kg/day)
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Table A.2.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. (year)/ 

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.2.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

870.3800c

1-Generation 

Reproduction and 

fertility effects- rat

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.2.2. Toxicity Profile of Abamectin Technical for Repeated Dosing and Genotoxicity Studies

Guideline No./ 

Study Type

MRID No. (year)/ 

Classification /Doses

Results

Gene Mutation

870.5100

Ames/Salmonella

E.coli/mammalian 

gene mutation assay

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

The result showed the dermal absorption to be <1% of the 

applied dose. For risk assessment, a dermal penetration factor of 

1% was recommended.
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Table A.2.3. 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
ABAMECTIN Human Health Risk Assessment DP No. 402677

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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.

Niles, AT and Keppler, D (2007) The apical conjugate efflux pump ABCC2 (MRP2). Pfluger 

Arch-Eur J Physiol (2007) 453: 643-659.

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. Physicochemical Properties of the Technical Grade of Abamectin

Parameter Value Reference1

Molecular weight (g/mole) 873.11

Melting point/range (°C) 155-157°C Accession No. 260785

pH Not available

Density (g/cm3) 1.16 g/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

Aerobic soil metabolism half-life Not available DP No. D380524, G. 

Orrick, 1/31/11

1 Product Chemistry data were reviewed by Leung Cheng (Accession No. 260785, RCB No. 388, 5/1/1986).
ABAMECTIN Human Health Risk Assessment DP No. 402677

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Appendix D. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

PHED 1.1; the Agricultural Reentry Task Force (ARTF) database; and the Residential SOPs 

(Lawns/Turf and Indoor Environments) are (1) subject to ethics review pursuant to 40 CFR 26, 

(2) have received that review, and (3) are compliant with applicable ethics requirements. For 

certain studies, the ethics review may have included review by the Human Studies Review 

Board. Descriptions of data sources, as well as guidance on their use, can be found at the 

Agency website6.

 

6

http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
ABAMECTIN Human Health Risk Assessment DP No. 402677

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Appendix E. International Residue Limits Table

Abamectin (122804; 11/01/2012)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR §180.449: avermectin 

B1 [a mixture of avermectins 

containing greater than or equal 

to 80% avermectin B1a (5- O -

demethyl avermectin A1 ) and 

less than or equal to 20% 

avermectin B1b (5- O -

demethyl-25-de(1-

methylpropyl)-25-(1-

methylethyl) avermectin A1 )] 

and its delta-8,9-isomer

avermectin B1 (a mixture of 

avermectins containing 

greater than or equal to 

80% avermectin B1a (5-Odemethyl avermectin A1a) 

and less than or equal to 

20% avermectin B1b (5-Odemethyl-25-de(1-

methylpropyl)-25-(1-

methylethyl) avermectin 

A1a) and its delta-8,9-

isomer)

Plants: sum of 

avermectin B1a, 

avermectin B1b, 

8,9-Z-avermectin 

B1a and 8,9-Zavermectin B1b. 

Animal 

commodities: 

sum of 

avermectin

B1a and 8,9-Zavermectin B1a.

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

US Canada Mexico2 Codex3

Cotton, undelinted seed 0.02 0.01 (*)

Cotton, gin by-products 1.0

Strawberry 0.05 0.02 0.02

Completed: M. Negussie; 11/01/2012

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.