EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OFCHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: 1/9/13 

SUBJECT: Emamectin Benzoate. Revised Human Health Risk Assessment for Proposed 

Uses on Cucurbits and Outdoor-Grown Plants in Commercial Nursery Production. 

PC Code: 122806 

Decision No.: 452138 

Petition No.: NA 

DP Barcode: 0393837 

Registration Nos.: 100-904, 100-RURR 

Regulatory Action: Section 3 Registration 

Risk Assessment Type: Single ChemicaVAggregate Case No.: NA 

TXRNo.: NA CAS No.: 155569-91-8 

MRID No.: NA 40 CFR: 180.505 

FROM: Nancy Dodd, Chemist and ~~..A~'li;...: rJ::--;rA-·e-tG/ 

Nancy Tsaur, Chemist i. NU ~ / 

Whang Phang, Toxicologist ../ .... ~~ 

Risk Assessment Branch III (RAB3) 0 

Health Effects Division (HED; 7509P) 

THROUGH: Jeff Dawson, Acting Branch Chief 

RAB3/HED (7509P) 

TO: Barbara Madden/Andrew Ertman, RM#S 

Risk Integration, Minor Use, and Emergency Response Branch 

Registration Division (RD; 7505P) 

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

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

ofOPP 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 emamectin benzoate (a benzoate salt 

mixture of a minimum of90% 4'-epi-methylamino-4'-deoxyavermectin B1a and a maximum of 

10% 4'-epi-methylamino-4'-deoxyavermectin B1b) and its isomers/metabolites/degradates. The 

Interregional Research Project No.4 (IR-4) has proposed to register the use and establish a 

tolerance on cucurbit vegetables (Crop Group 9). Syngenta has also proposed to register use on 

outdoor-grown ornamental plants in commercial nursery production, including field- and 

container-grown ornamentals. This revised memo incorporates results using the Dietary 

Exposure Evaluation Model software with the Food Commodity Intake Database (DEEMPage 1 of62 
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837 

FCID), Version 3.16. 

A summary of the findings and an assessment of human risk resulting from the registered and 

proposed uses for emamectin benzoate are provided in this document. The residue chemistry 

review, dietary assessment, and overall risk assessment were performed by Nancy Dodd. The 

occupational/residential assessment was performed by Nancy Tsaur. The toxicology assessment 

was performed by Whang Phang. The drinking water exposure assessment was performed by 

Tiffany Dowen of the Environmental Fate & Effects Division (EFED). 

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EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

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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.......................................................................................... 10

2.2.1 Enforcement Analytical Method............................................................................... 10

2.2.2 International Harmonization .................................................................................... 10

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

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

2.3 Label Recommendations............................................................................................ 11

2.3.1 Recommendations from Residue Reviews ............................................................... 11

2.3.2 Recommendations from Occupational Assessment ................................................ 11

2.3.3 Recommendations from Residential Assessment .................................................... 13

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

3.1 Chemical Identity ....................................................................................................... 13

3.2 Physical/Chemical Characteristics ........................................................................... 14

3.3 Pesticide Use Patterns................................................................................................ 15

3.4 Anticipated Exposure Pathways............................................................................... 17

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

4.0 Hazard Characterization and Dose-Response Assessment........................................... 18

4.1 Summary of Toxicological Effects............................................................................ 18

4.2 Safety factor for Infants and Children (FQPA Safety Factor) .............................. 21

4.2.1 Completeness of the Toxicology Database ............................................................... 21

4.2.2 Evidence of Neurotoxicity.......................................................................................... 22

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ......... 22

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

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

5.0 Dietary Exposure and Risk Assessment.......................................................................... 25

5.1 Residues of Concern Summary and Rationale ........................................................ 25

5.2 Food Residue Profile .................................................................................................. 27

5.3 Water Residue Profile................................................................................................ 28

5.4 Dietary Risk Assessment............................................................................................ 29

5.4.1 Description of Residue Data Used in Dietary Assessment...................................... 29

5.4.2 Percent Crop Treated Used in Dietary Assessment................................................ 30

5.4.3 Acute Dietary Risk Assessment................................................................................. 30

5.4.4 Chronic Dietary Risk Assessment............................................................................. 31

5.4.5 Cancer Dietary Risk Assessment .............................................................................. 31

5.4.6 Summary Tables......................................................................................................... 31

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .............................. 33

6.1 Residential Handler Exposure .................................................................................. 33

6.2 Post-Application Exposure ........................................................................................ 33

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

6.4 Spray Drift.................................................................................................................. 34
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7.0 Aggregate Exposure/Risk Characterization................................................................... 34

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

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

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

7.4 Cancer Aggregate Risk .............................................................................................. 35

8.0 Cumulative Exposure/Risk Characterization ................................................................ 35

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

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

9.2 Short-/Intermediate-Term Post-Application Risk .................................................. 39

9.2.1 Dermal Post-Application Risk................................................................................... 39

9.2.2 Occupational Post-Application Inhalation Exposure ............................................. 39

10.0 References.......................................................................................................................... 40

Appendix A. Toxicology Profile and Executive Summaries .................................................. 42

A.1 Toxicology Data Requirements................................................................................. 42

A.2 Toxicity Profiles.......................................................................................................... 43

Appendix B. Physical/Chemical Properties............................................................................. 51

Appendix C. Review of Human Research................................................................................ 52

Appendix D. Occupational Exposure/Risk Summary Tables................................................ 53

Appendix E. International Tolerances..................................................................................... 60

Appendix F. Toxicology Literature References ...................................................................... 61
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

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1.0 Executive Summary

Use Profile: Emamectin benzoate will be applied as a 5% soluble granule (SG) formulation 

(Proclaim® Insecticide; EPA Reg. No. 100-904) to cucurbits for control of armyworms, cabbage 

looper, corn earworm, melon worm, rindworms, tobacco budworm, pickleworm, and Lirioyza

leaf miners. Proclaim® Insecticide may be applied as a foliar spray via aircraft (except in New 

York State) or groundboom. Chemigation is prohibited. For high pest infestations, the 

maximum single application rate is 4.8 oz/A (0.015 lb ai/A). Applications may be repeated at a 

7-day interval to maintain control, up to a maximum seasonal application rate of 28.8 oz/A 

(0.090 lb ai/A/season). The preharvest interval (PHI) is 6 days. The proposed restricted entry 

interval (REI) is 12 hours. 

Emamectin benzoate is also proposed for use on outdoor-grown plants in commercial nursery 

production to control lepidopterous larvae (worms/caterpillars) and to suppress leaf miners and 

spider mites. EnfoldTM Insecticide (EPA Reg. No. 100-RURR), a 5% SG formulation, may be 

applied as a foliar spray via groundboom, airblast, or aircraft (except in New York State). 

Chemigation is prohibited. For high pest infestations, the maximum single application rate is 4.8 

oz/A (0.015 lb ai/A). Applications may be repeated at a 7- to 14- day interval to maintain 

control, up to a maximum seasonal application rate of 28.8 oz/A (0.090 lb ai/A/season). The 

proposed REI is 12 hours. 

Human Health Risk Assessment:

Toxicity/Hazard: Emamectin has moderate acute toxicity by the oral route and low acute 

toxicity by the dermal route. It is not irritating to the skin, nor is it a dermal sensitizer, but it is a 

severe eye irritant. The main target tissue is the nervous system, with neuropathology detected 

in many studies and several species. The dose-response curve was very steep in several studies 

(most notably with CF-1 mice and dogs), with severe effects (morbid sacrifice and 

neuropathology) sometimes seen at the lowest observable adverse effect levels (LOAELs). 

Although no increased sensitivity was seen in developmental toxicity studies in rats and rabbits, 

increased qualitative and/or quantitative sensitivity of rat pups was seen in the reproductive 

toxicity study and in the developmental neurotoxicity study. Review of acceptable oncogenicity 

and mutagenicity studies provide no indication that emamectin is carcinogenic or mutagenic. 

Emamectin is classified as “not likely to be carcinogenic to humans.”

Dietary Exposure (food/drinking water): Acute and chronic dietary (food and drinking water) 

exposure and risk assessments were conducted using the Dietary Exposure Evaluation Model 

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

dietary exposure assessment was a probabilistic assessment for food and drinking water using 

anticipated residues based on field trial data. The chronic dietary exposure assessment was a 

somewhat refined assessment for food and drinking water using single point estimates (averages)

of anticipated residues based on field trials. Refinements for both the acute and chronic 

assessments included using percent crop treated for some new and registered crops, DEEM 
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

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default processing factors where appropriate, chemical-specific processing factors where 

available, and anticipated residues based on field trial data for most crops. For the acute 

assessment, Pesticide Monitoring Program (PDP) monitoring data were used for apples since 

apple juice contributed significantly to the exposure. The 10X FQPA safety factor was retained 

for chronic assessments and reduced to 3X for acute assessments.

The estimated drinking water concentrations (EDWCs) of emamectin benzoate were provided by

EFED. A drinking water residue distribution based on the Pesticide Root Zone Model/Exposure 

Analysis Modeling System (PRZM/EXAMS) modeling of the use on ornamentals was used in 

the acute assessment. An EDWC based on the PRZM/EXAMS modeling of the use on 

ornamentals was used for the chronic assessment. 

The acute dietary exposure estimates for food and drinking water using the ornamentals scenario 

for drinking water are below HED’s level of concern at the 99.9th percentile of exposure for all 

population subgroups (36% of the acute population adjusted dose [aPAD] for the general U.S. 

population and 60% of the aPAD for children 1-2 years old, the population with the highest 

exposure).

The chronic dietary exposure estimates for food and drinking water using the ornamentals 

scenario for drinking water are below HED’s level of concern for all population subgroups (7.5% 

of the chronic population adjusted dose [cPAD] for the general U.S. population and 16% of the 

cPAD for all infants less than 1 year old, the population with the highest exposure).

Residential Exposure: There are no existing or proposed residential use sites; therefore, 

residential handler exposure and residential post-application exposure are not expected. 

Emamectin benzoate is registered for agricultural uses, as a tree injection use, and as a cockroach 

bait. Except for OptigardTM Cockroach Bait (EPA Reg. No. 100-1290), all registered emamectin 

benzoate end-use products are restricted use products (RUPs; restricted to use by professional 

certified operators [PCOs] only). OptigardTM Cockroach Bait is not a restricted use product but 

EPA has indicated that it is to be used only in commercial and industrial areas. Proclaim® 

Insecticide is an RUP which is proposed for use on cucurbits. EnfoldTM Insecticide is an RUP 

which is proposed for use on outdoor-grown plants in commercial nursery production. 

Residential exposures from commercial nursery production are expected to be negligible because 

the emamectin is expected to dissipate by the time the plant moves from a nursery, through a 

retail store, to the consumer.

 

Aggregate Risk: The acute aggregate risk assessment takes into account exposure estimates 

from dietary (food and drinking water) consumption of emamectin as discussed above. 

Short- and intermediate-term aggregate risk assessments were not conducted because residential 

exposure is not expected from existing or proposed uses.

The long-term aggregate risk assessment takes into account average exposure estimates from 
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dietary consumption of emamectin benzoate (food and drinking water) and residential uses. 

However, residential exposures are not expected; therefore, the chronic aggregate risk 

assessment will consider only exposure from food and drinking water, which is discussed above.

Occupational Exposure/Risk: 

Occupational Handlers

There is potential for short- and intermediate-term occupational exposure to emamectin benzoate 

during handling activities (e.g. mixing, loading, application) for the proposed uses (cucurbit 

vegetables and outdoor-grown ornamentals). However, intermediate-term exposure is less likely 

due to resistance management, and short-term scenarios are more realistic. Emamectin is a 

Group 6 insecticide that has inherent risks of resistance development. It is strongly advised to be 

used in a sound resistance management program. Due to changes in unit exposure values and 

body weight assumptions, all of the occupational handler exposure and risk estimate tables have 

been updated in this document since the two occupational and residential exposure (ORE) risk 

assessments previously conducted by Nancy Tsaur (DP390778, 12/07/2011; and DP393839, 

03/01/2012).

Based on the personal protective equipment (PPE) required on the labels, there are some risks of 

concern. Table 9.1 shows the PPE proposed on both labels (EPA Reg. No. 100-904 and EPA 

Reg. No. 100-RURR) along with mitigation recommendations based on short- and intermediateterm risk estimates. In order to achieve risk estimates that do not exceed HED’s level of concern 

(LOC; Aggregate Risk Indexes [ARIs] > 1.0), the recommendations based on intermediate-term 

exposure are more stringent. However, when considering resistance management, the short-term 

risk estimates are more representative of realistic exposure potential.

Occupational Post-Application

There is a potential for short- and intermediate-term occupational exposure during postapplication activities. However, intermediate-term exposure is less likely due to resistance 

management, and short-term scenarios are more realistic. HED recommends utilizing the results 

from the short-term quantitative risk assessment because the intermediate-term results are highly 

conservative and unlikely. For short-term exposure duration, all scenarios resulted in margins of 

exposure (MOEs) greater than the short-term LOC of 300 (ranging from 520 to 11,000) on day 0 

(12 hours after application) and, therefore, are not of concern to HED.

Restricted Entry Interval

Typically, under the Worker Protection Standard (WPS) for Agricultural Pesticides, active 

ingredients classified as acute Toxicity Category III or IV for acute dermal, eye irritation, and 

primary skin irritation are assigned a 12-hour REI. 

Environmental Justice Considerations:

Environmental justice concerns were considered in this assessment. Refer to Section 3.5.
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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 studies (listed in Appendix C) have 

been determined to require a review of their ethical conduct, and have received that review.

Additional Data Needs:

Provided a revised Section F and some analytical reference standards are submitted before 

registration, the dietary-exposure database will be adequate to support the proposed registration 

on cucurbits. There is sufficient information available to assess occupational handler exposure to 

emamectin benzoate. The toxicology database for emamectin benzoate is largely complete. 

However, an immunotoxicity study (OPPTS Guideline Number 870.7800) is now required for 

conventional pesticide registration (40 CFR Part 158). Additionally, a subchronic (28-day) 

inhalation toxicity study (OPPTS GLN 870.3465) is needed for a more accurate assessment of 

toxicity via the inhalation route, and for inhalation risk assessments for exposures associated 

with the existing and proposed use patterns. 

2.0 HED Recommendations

Provided a revised Section F and analytical reference standards are submitted, HED can 

recommend for a registration and tolerance for the use of emamectin benzoate on cucurbit 

vegetables and for registration of the use on outdoor-grown ornamental plants in commercial 

nursery production. Additional data are needed as outlined in Section 2.1 below. The specific 

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

Section 2.3.

2.1 Data Deficiencies

Data that needs to submitted prior to establishing a tolerance or allowing a registration:

Residue Chemistry

OPPTS 860.1550 Proposed Tolerance

A revised Section F must be submitted proposing a tolerance for Vegetable, cucurbit, 

group 9 at 0.02 ppm.
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OPPTS 860.1650 Submittal of Analytical Reference Standards

The standard for the 8,9-Z isomer of B1a (NOA 438376) expired on 3/31/2012. An 

updated certificate of analysis or a new analytical reference standard must be provided to 

the EPA National Pesticide Standards Repository.

Analytical reference standards for MFB1a (NOA415692) and 8,9-Z B1b are currently 

unavailable at the Repository. Analytical reference standards must be provided.

Toxicology

870.3465 Subchronic Inhalation

A subchronic inhalation study is needed. HED determined there was a data gap for a

28-day inhalation study. This study should be performed using the CF-1 mouse.

870.7800 Immunotoxicity

An immunotoxicity study is needed.

Occupational Exposure

Dislodgeable Foliar Residue (DFR): In accordance with the updated Part 158 data requirements 

(2007), one or more DFR studies are required when a pesticide has residential or occupational 

uses that could result in post-application dermal exposure. As part of the recent revision to the 

Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide 

Exposure Assessment, HED analyzed a number of DFR studies and selected a new default value 

for the fraction of the application rate available to be dislodged after a foliar application (FAR). 

This default value is 25% and is based on an analysis of 19 DFR studies where the FAR value 

ranged from 2% to 89%. This value is recommended for use in both residential and occupational 

postapplication assessments. Of the analyzed DFR studies, the maximum FAR value seen was 

89% or 3.6 times higher than the default residue transfer value. Therefore, the HED has decided 

that a calculated MOE of approximately 4 times higher than the level of concern (e.g., an MOE > 

400 if the LOC = 100) using the default dislodged residue values would provide an adequate 

margin of safety for any potentially higher residues seen in a chemical-specific DFR study 

(Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar 

Residue (DFR) Studies. 6/7/2012, Exposure Science Advisory Council). A DFR study is 

required for emamectin benzoate at this time since the dermal MOE is less than 4 times the LOC 

based on default values for the fraction of application rate available for transfer after a foliar

application.
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2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate methods (Method 244-92-3 and Method 244-92-3, Revision 1) are available for the 

enforcement of tolerances on plants. The methods determine residues of emamectin (the free 

base) and its regulated isomers and degradates/metabolites using high performance liquid 

chromatography with fluorescence detection (HPLC/FLD). The methods determine residues of 

emamectin in the following analyte combinations: MAB1a + 8,9-ZB1a, MAB1b + 8,9-ZB1b, AB1a, 

and MFB1a + FAB1a, with a limit of quantitation (LOQ) of 0.005 ppm for each analyte or analyte

combination, for a combined LOQ of 0.02 ppm. 

2.2.2 International Harmonization

Codex (Report of the Codex Alimentarius Commission, Rome, 2012) has a proposed tolerance 

on cucurbits at 0.007 ppm for residues of emamectin B1a benzoate, expressed as emamectin 

(free base). EPA is recommending a tolerance of 0.02 ppm for the use of emamectin benzoate 

on cucurbits; the tolerance is to be expressed as the combined residues of emamectin (free base)

as described in section 2.2.3 below. There are no established or proposed Canadian or Mexican 

MRLs for residues of emamectin benzoate on cucurbits (Appendix E).

2.2.3 Recommended Tolerances

The proposed and recommended tolerances for cucurbit vegetables are presented in Table 2.2.3. 

The tolerance expression proposed by the petitioner is appropriate, but should be revised by RD 

according to HED’s Interim Guidance on Tolerance Expressions (5/27/09, S. Knizner) as 

follows:

 Under 40 CFR §180.505(a)(1) for plant commodities: “Tolerances are established for 

emamectin, including its metabolites and degradates, in or on the commodities in the 

table below. Compliance with the tolerance levels specified below is to be determined by 

measuring only the sum of emamectin (a mixture of a minimum of 90% 4'-epimethylamino-4'-deoxyavermectin B1a and maximum of 10% 4'-epi-methylamino-4'-

deoxyavermectin B1b) and its metabolites 8,9-isomer of the B1a and B1b component of the 

parent (8,9-ZMA), or 4'-deoxy-4'-epi-amino-avermectin B1a and 4'-deoxy-4'-epi-aminoavermectin B1b; 4'-deoxy-4'-epi-amino avermectin B1a (AB1a); 4'-deoxy-4'-epi-(N-formylN-methyl)amino-avermectin (MFB1a); and 4'-deoxy-4'-epi-(N-formyl)amino-avermectin 

B1a (FAB1a), calculated as the stoichiometric equivalent of emamectin.”

Under 40 CFR §180.505(a)(2) for livestock commodities: “Tolerances are established 

for emamectin, including its metabolites and degradates, in or on the commodities in the 

table below. Compliance with the tolerance levels specified below is to be determined by 
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measuring only the sum of emamectin (MAB1a + MAB1b isomers) and the associated 8,9-

Z isomers (8,9-ZB1a and 8,9-ZB1b).”

Table 2.2.3. Tolerance Summary for Emamectin 

Commodity Proposed Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments

Correct Commodity Definition

Vegetable, cucurbit, 

group 9 0.03 0.02

2.2.4 Revisions to Petitioned-For Tolerances

HED attributes the difference between the recommended tolerance and the proposed tolerance 

(as shown in Table 2.2.3) to the difference in the way the petitioner reported combined residues 

in the cucumber submissions. The petitioner reported the combined LOQ in the cucumber study 

as 0.025 ppm, reflecting the sum of MAB1a/8,9-ZB1a + MAB1b/8,9-ZB1b + AB1a + MFB1a + 

FAB1a; however, the analytical method determines residues of MFB1a and FAB1a as a single 

component; therefore, the combined LOQ should have been 0.02 ppm.

2.3 Label Recommendations

2.3.1 Recommendations from Residue Reviews

None.

2.3.2 Recommendations from Occupational Assessment

Dislodgeable Foliar Residue (DFR): In accordance with the updated Part 158 data requirements 

(2007), one or more DFR studies are required when a pesticide has residential or occupational 

uses that could result in post-application dermal exposure. As part of the recent revision to the 

Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide 

Exposure Assessment, HED analyzed a number of DFR studies and selected a new default value 

for the fraction of the application rate available to be dislodged after a foliar application (FAR). 

This default value is 25% and is based on an analysis of 19 DFR studies where the FAR value 

ranged from 2% to 89%. This value is recommended for use in both residential and occupational 

postapplication assessments. Of the analyzed DFR studies, the maximum FAR value seen was 

89% or 3.6 times higher than the default residue transfer value. Therefore, the HED has decided 

that a calculated MOE of approximately 4 times higher than the level of concern (e.g., an MOE > 

400 if the LOC = 100) using the default dislodged residue values would provide an adequate 

margin of safety for any potentially higher residues seen in a chemical-specific DFR study 

(Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar 

Residue (DFR) Studies. 6/7/2012, Exposure Science Advisory Council). A DFR study is 

required for emamectin benzoate at this time since the dermal MOE is less than 4 times the LOC 

based on default values for the fraction of application rate available for transfer after a foliar

application.
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Occupational Handlers – Cucurbits (Proclaim® Insecticide)

There is potential for short- and intermediate-term occupational exposure to emamectin benzoate 

during handling activities (e.g. mixing, loading, application).

All the values in the tables have been updated since the ORE review (N. Tsaur, DP Number 

D393839, 03/01/2012) to reflect policy changes (i.e., inhalation toxicity uncertainty factors).

Based on the PPE required on the label (see Table 9.1), there are risks of concern. To achieve 

MOEs that do not exceed HED’s LOC (ARIs > 1.0), the following mitigation should be required

in addition to the current label requirements for the following scenarios:

For short-term exposure, mixing/loading dry flowables for groundboom application 

requires double layer clothing + gloves and PF10 respirators. Mixing/loading dry 

flowables for aerial application requires engineering controls of water soluble packaging.

For intermediate-term exposure, mixing/loading dry flowables for groundboom 

application and flagging for aerial application require double layer clothing + gloves and 

PF10 respirators. Mixing/loading dry flowables for aerial application requires 

engineering controls of water soluble packaging.

Occupational Handlers – Ornamentals (EnfoldTM Insecticide)

There is potential for short- and intermediate-term occupational exposure to emamectin benzoate 

during handling activities (e.g. mixing, loading, application).

All the values in the tables have been updated since the ORE review (N. Tsaur, DP Number 

D390788, 12/07/2011) to reflect policy changes (i.e., body weight assumptions and inhalation 

toxicity uncertainty factors).

Based on the PPE required on the label (see Table 9.1), there are risks of concern. To achieve 

MOEs that do not exceed HED’s LOC (ARIs > 1.0), the following mitigation should be required:

For short-term exposure, mixing/loading dry flowables for groundboom and airblast 

application require double layer clothing + gloves and PF10 respirators. Mixing/loading 

dry flowables for aerial application requires engineering controls of water soluble 

packaging. Open cab airblast is acceptable with PF10 respirators. Handheld equipment 

is acceptable if gloves are required.

For intermediate-term exposure, mixing/loading dry flowables for groundboom and 

airblast application require double layer clothing + gloves and PF10 respirators. 

Mixing/loading dry flowables for aerial application requires engineering controls of water 
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soluble packaging. The high exposures expected from open cab airblast applications are 

best mitigated by requiring an enclosed cab system. Handheld equipment is not of 

concern if PF5 respirators are required.

Label Recommendation (EnfoldTM Insecticide)

The label must indicate the required PPE for handheld applications as listed in Table 9.1 (i.e.,

applications via backpack sprayers or manually pressurized handwands).

2.3.3 Recommendations from Residential Assessment

Residential exposure is not expected from the registered/proposed products since they are 

agricultural uses rather than residential uses, restricted use products (restricted to use by certified 

applicators only), or limited to non-residential areas (commercial and industrial areas). There are 

no proposed/registered products that would lead to residential handler or post-application 

exposure. Residential exposures from commercial nursery production are expected to be 

negligible because the emamectin is expected to dissipate by the time the plant moves from a 

nursery, through a retail store, to the consumer.

3.0 Introduction

3.1 Chemical Identity

Emamectin benzoate is a semi-synthetic avermectin, consisting of two active homologous 

compounds (a benzoate salt mixture of a minimum of 90% 4'-epi-methylamino-4'-

deoxyavermectin B1a and a maximum of 10% 4'-epi-methylamino-4'-deoxyavermectin B1b). 
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Table 3.1 Test Compound Nomenclature

Chemical Structure

Empirical Formula

emamectin benzoate B1a: C49H75NO13 •C7H6O2

emamectin benzoate B1b: C48H73NO13 •C7H6O2

Common Name emamectin benzoate

Company experimental name MK244

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-3-O-methyl-4-O-(2,4,6-trideoxy-3-Omethyl-4-methylamino-α-L-lyxo-hexapyranosyl)-α-L-arabino-hexapyranoside 

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

dihydroxy-6'-isopropyl-5',11,13,22-tetramethyl-2-oxo-(3,7,19-

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

dihydro-2'H-pyran)-12-yl 2,6-dideoxy-3-O-methyl-4-O-(2,4,6-trideoxy-3-Omethyl-4-methylamino-α-L-lyxo-hexapyranosyl)-α-L-arabino-hexapyranoside 

benzoate

CAS Name (4''R)-4''-deoxy-4''-(methylamino)avermectin B1 benzoate (salt)

CAS Registry Number 155569-91-8 (formerly 137512-74-4)

End-use product/EP Proclaim® Insecticide; EPA Reg. No. 100-904; 5% SG formulation

EnfoldTM Insecticide; EPA Reg. No. 100-RURR; 5% WG formulation

Chemical Class Avermectin insecticide

Known Impurities of Concern None

3.2 Physical/Chemical Characteristics

Emamectin benzoate is a solid at room temperature with a low vapor pressure (3.0 x 10-8 mm Hg

at 21°C); thus, any losses due to volatilization/sublimation are expected to be minimal. 

COO

-

OCH3

O O

O

O

CH3

OH

H3C

O

CH3

CH3

R1

O

O

H3CO

O

H C O 3 CH3

OH

CH3

H3CH2N

+

B1a Component: R1 = CH2CH3

B1b Component: R1 = CH3
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Emamectin benzoate, the 8,9-Z isomer, AB, MFB, and FAB are expected to be persistent and 

relatively immobile in the environment due to a high degree of sorption to soil particles (KOC

from 25,363 to 730,000). Based upon fate data, significant concentrations of parent or formed 

degradates of toxicological concern are not expected to leach into groundwater.

Refer to a Table of Physicochemical Properties in Appendix B.

3.3 Pesticide Use Patterns

Cucurbits

IR-4 is proposing use of Proclaim® Insecticide (EPA Reg. No. 100-904), a 5% water-soluble 

granule (SG) formulation of emamectin benzoate, on the cucurbit vegetable group for the control 

of armyworms, cabbage looper, corn earworm, melon worm, rindworms, tobacco budworm, 

pickleworm, and Lirioyza leaf miners. 

Proclaim® Insecticide may be applied as a foliar spray via aircraft (except in New York State) or 

groundboom. Chemigation is prohibited. For high pest infestations, the maximum single 

application rate is 4.8 oz/A (0.015 lb ai/A). Applications may be repeated at a 7-day interval to 

maintain control, up to a maximum seasonal application rate of 28.8 oz/A (0.090 lb ai/A/season).

The preharvest interval (PHI) is 6 days. The REI on the proposed label is 12 hours.
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Table 3.3.1. Summary of Directions for Use of Emamectin Benzoate on Cucurbits.

Applic. Timing, 

Type, and Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate

(lb 

ai/A)

Max. No. 

Applic. 

per 

Season

Max. 

Seasonal 

Applic. Rate

(lb ai/A)

PHI1

(days)

Use Directions and Limitations

Vegetable, Cucurbit, Group 9: Chayote (fruit); Chinese waxgourd (Chinese preserving melon); citron melon; 

cucumber; gherkin; gourd, edible (includes hyotan, cucuzza); hechima; Chinese okra; Momordica spp. (includes 

balsam apple, balsam pear, bitter melon, Chinese cucumber); muskmelon (hybrids and/or cultivars of Cucumis 

melo - includes true cantaloupe, cantaloupe, casaba, Crenshaw melon, golden pershaw melon, honeydew melon, 

honey balls, mango melon, Persian melon, pineapple melon, Santa Claus melon, and snake melon); pumpkin; 

squash, summer (includes crookneck squash, scallop squash, straightneck squash, vegetable marrow, zucchini); 

squash, winter (includes butternut squash, calabaza, hubbard squash, acorn squash, spaghetti squash); watermelon 

(includes hybrids and/or varieties of Citrullus lanatus).

Postemergence, 

Broadcast,

Foliar, 

Ground or aerial 

equipment

Proclaim® 

Insecticide

5% SG

[100-904]

0.0094-

0.015

NS20.090 6 Begin applications when larvae 

are first observed; repeat 

applications at a minimum RTI3

of 7 days.

Apply in a minimum of 10 

gallons of water/A when using 

either ground or aerial 

equipment.

Use of a penetrating type of 

spray adjuvant is recommended; 

use of a sticker/binder type 

adjuvant is prohibited.

1

PHI = preharvest interval.

2 NS = not stated.

3 RTI = retreatment interval.

The following restrictions appear on the accepted Proclaim® Insecticide label (dated 1/26/10): 

(1) application through any type of irrigation system is prohibited; (2) for applications to 

vegetables, make no more than two sequential applications, then rotate to another insecticide 

with a different mode of action; (3) for applications to vegetables, do not use Proclaim in 

greenhouses, nurseries, in plant propagation houses, or on any plants grown for use as 

transplants; (4) do not apply with aircraft in NY state; and (5) there are no rotational crop plantback restrictions for emamectin benzoate.

Outdoor-Grown Ornamental Plants in Commercial Nursery Production

Syngenta is proposing use of EndfoldTM Insecticide (EPA Reg. No. 100-RURR), a 5% waterdispersible granule formulation of emamectin benzoate, on outdoor-grown ornamental plants in 

commercial nursery production for the control of the larval stages (worms/caterpillars) of several 

lepidopteran species and suppression of Liriomuza leafminer, Tetranychid mites, and pear psylla. 

It is a selective insecticide for use on herbaceous and woody ornamental plants grown outdoors 

(in containers or in the ground) in commercial nursery production. Woody ornamentals include 
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(but are not limited to) shrubs, non-bearing fruit and nut trees, Christmas trees, forest seedlings,

and shade trees. 

EnfoldTM Insecticide may be applied as a foliar spray via groundboom, airblast, or aircraft 

(except in New York State). Chemigation is prohibited. For high pest infestations, the 

maximum single application rate is 4.8 oz/A (0.015 lb ai/A). Applications may be repeated at a 

7- to 14- day interval to maintain control, up to a maximum seasonal application rate of 28.8 

oz/A (0.090 lb ai/A/season). The REI on the proposed label is 12 hours. 

Table 3.3.2. Use Profile for Proposed Emamectin Benzoate Use on Outdoor-Grown Ornamentals.

EnfoldTM Insecticide

EPA Reg. No. 100-RURR

water dispersible granule (WG),5.0% ai by weight

Use Site Application Equipment

Single Maximum

Application Rate

oz/A lb ai/A

Outdoor Ornamentals

(Ground or Container) Groundboom, Airblast, Aerial 2.4-4.8 0.00075-0.015

3.4 Anticipated Exposure Pathways

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

proposed new uses of emamectin benzoate on cucurbit vegetables and on outdoor-grown 

ornamental plants in commercial nursery production. Humans may be exposed to emamectin 

benzoate in food and drinking water, since emamectin benzoate may be applied directly to 

growing crops and application may result in emamectin benzoate reaching surface and ground

water sources of drinking water. There are no residential uses of emamectin benzoate as 

explained in Section 6.0, so there is not likely to be exposure in residential or non-occupational 

settings. In an occupational setting, applicators may be exposed while handling the pesticide 

prior to application, as well as during application. There is a potential for post-application 

exposure for workers re-entering treated fields. 

This risk assessment considers all of the aforementioned exposure pathways based on the 

proposed new uses of emamectin benzoate, but also considers the existing uses as well, 

particularly for the dietary exposure assessment.

 

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). 
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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 US Department of Agriculture (USDA) under the National Health and Nutrition 

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

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

categorized by subgroups based on age, season of the year, ethnic group, and region of the 

country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups 

and exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-application are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Reference: EMAMECTIN - 3

rd Report of the Hazard Identification Assessment Review Committee - (Memo, 

HED TXR. No. 0051605, 03/5/2003).

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

assessment includes summaries of prior assessments.

Details of the toxicology of emamectin, including executive summaries of the toxicity studies, 

are available in the HED memo, EPA ID#: 000618-RNI: Application for Establishment of 

Permanent Tolerance for the Use of Emamectin on Cole Crops and Leafy Vegetables, G. Reddy, 

06/30/98. A summary of the toxicology profile for emamectin is presented in Appendix A.

4.1 Summary of Toxicological Effects

Emamectin is a member of the naturally derived complex of 16-membered macrocyclic lactones, 

which include abamectin, avermectin, and ivermectin. On the cellular level, a member of this 

group of compounds has been shown to act by binding to gamma-aminobutyric acid (GABA) 

gated chloride channels at two different sites, a high affinity binding site that activates the 

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

1997; and Dawson et al., 2000). GABA plays a critical role in nervous system development 

through both non-synaptic (Represa and Ben-Ari, 2005) and synaptic (Nguyen et al., 2001) 

mechanisms. Consequently, emamectin may have the potential to influence GABA-mediated 

events important to brain development. Within the mammalian brain, a member of this class of 
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compound (abamectin) has been shown to have widespread binding but particularly abundant in 

the cerebellum (Wang and Pong, 1982). Through action on the enteric nervous system and 

induction of longitudinal rhythmic contractions in the isolated ileum, emamectin, like abamectin,

may therefore influence GABA-mediated regulation of metabolism, food intake and body weight 

at multiple sites (Kerr and Ong, 1986, 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.

Integral to its mechanism of action in mammals, this class of compounds is also a substrate for Pglycoprotein (P-gp). P-glycoprotein is a member of the ATP binding cassette transporter 

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

moving xenobiotics from the 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 or 

emamectin-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 (ABC) transporter proteins due to polymorphism in the gene encoding ABC transporter 

proteins (Dubin-Johnson Syndrome) (S. Habashi, 2006, A.T. Niles, 2007). In addition, collie 

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

Consistent with the mode of action, the main target organ for emamectin is the nervous system; 

clinical signs (tremors, ptosis, ataxia, and hunched posture) and neuropathology (neuronal

degeneration in the brain and in peripheral nerves, muscle fiber degeneration) were found in 

most of the emamectin studies in rats, dogs and mice. The dose-response curve was very steep 

in several studies (most notably with CF-1 mice and dogs), with severe effects (morbid sacrifice 

and neuropathology) sometimes seen at the LOAELs (0.1 mg/kg/day with a no observable 

adverse effect level (NOAEL) of 0.075 mg/kg/day). Although no increased sensitivity was seen 

in developmental toxicity studies in rats and rabbits, increased qualitative and/or quantitative 

sensitivity of rat pups was seen in the reproductive toxicity and in the developmental 

neurotoxicity studies. In the reproduction study, whole body tremors, hind limb extension, and 

hind limb splay were seen in the F1 and F2 pups while these clinical signs were not seen in F0 

parental animals at similar dose levels. In addition, a greater incidence of decreased fertility was 

seen in the F1 parental females than in the F0 females. In the developmental neurotoxicity study, 

no maternal effect was seen at the highest dose tested whereas dose-related decrease in openfield motor activity was seen in the mid-dose on PND 17. Body tremors, hind-limb extension, 
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and auditory startle were also found in the high dose pups. 

A degree-of-concern analysis was conducted to determine whether or not an additional safety 

factor is needed to account for the increased susceptibility in pups; it was concluded that the 

degree-of-concern was low for both 2-generation reproduction and developmental neurotoxicity 

studies. The reasons are as follows: 

∙ For the 2-generation reproduction study, (1) there was a clear NOAEL for the offspring 

toxicity, (2) effects unique to offspring (decreased fertility in F1 adults, and clinical signs 

[tremors and hind limb extensions during and following lactation]) were seen at the same 

dose that caused parental systemic toxicity (decreased body weight gain and 

histopathological lesions in the brain and spinal cord), and (3) the decreased fertility seen in 

F1 adults might have been due to histopathological lesions in the brain and central nervous 

system (seen in both F0 and F1 generations), rather than due to a direct effect on the 

reproductive system. 

∙ For the developmental neurotoxicity study, (1) although multiple offspring effects (including 

decreased pup body weight, head and body tremors, hindlimb extension and splay, changes 

in motor activity and auditory startle) were seen at the highest dose (3.6 mg/kg/day), and no 

maternal effects were seen at any dose, there was a clear NOAEL for offspring toxicity at the 

low dose, and (2) the offspring LOAEL (at the mid dose) is based on a single effect seen on 

only one day (decreased motor activity on PND 17) and no other offspring toxicity was seen 

at the LOAEL.

The carcinogenicity and mutagenicity studies provide no indication that emamectin is 

carcinogenic or mutagenic. Emamectin is classified as “not likely to be carcinogenic to 

humans.” A toxicity profile for emamectin is presented in Appendix A.

The acute toxicity studies indicate that emamectin has low to moderate acute toxicity by the oral, 

dermal and inhalation routes. It is not irritating to the skin, nor is it a dermal sensitizer. 

However, depending on the technical test substance, abamectin has been shown to be a severe 

eye irritant. A recent (as of 2008) submission of acute toxicity six-pack tests performed on a 

new technical product (Emamectin Benzoate Technical II, EPA Reg. No. 100-1270) resulted in 

new toxicity category assignments. Specifically, the toxicity category for inhalation changed 

from Category IV to Category II. Relevant to the REI, the eye irritation study changed from 

Category I to Category III. HED had concern for the possibility that a change in manufacturers 

and technical registrations could result in a different acute toxicity outcome, while the technical 

compound itself had not changed. Detailed information has been submitted which confirms the 

appropriateness of the REI reduction.

The most recent toxicity endpoints and points of departure for risk assessment were determined 

by HED in 2003. The available emamectin data show that there is a difference in species 

sensitivity, and the data suggest the following order: rat NOAELs/LOAELs > dog 
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NOAELs/LOAELs > mouse NOAELs/LOAELs. The toxicity endpoints and points of departure 

for risk were selected from the results of the 15-day CF-1 mouse oral toxicity study. No new 

toxicity studies have been submitted since 2003, and these selections are still valid.

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

Based on currently available data, HED recommends that the 10X FQPA safety factor be 

retained for chronic assessments and that a 3X FQPA safety factor is adequate for acute

assessments. For inhalation exposure assessment, additional uncertainty factors of 10X for lack 

of an inhalation toxicity study and of 3X for the steepness of the dose-response curve are to be 

applied; these are combined with the normal 100X safety factor resulting in the application of a 

maximal uncertainty factor of 3000X.

The 10X FQPA safety factor has been retained for chronic/long-term and intermediate-term 

assessments for oral and dermal exposure due to the steepness of the dose-response curve, 

severity of effects at the LOAEL (death and neuropathology), and the use of a short-term study 

for long-term risk assessment. (HED did not use a chronic study for the point of departure 

because the chronic studies were conducted in rats, dogs, and CD-1 mice. The 15-day study 

employed the CF-1 mice, which do not have the glycoprotein. As a result, the point of departure 

is protective of all population subgroups.) The steepness of the dose-response curve and the 

severity of the effects at the LOAEL also are the basis for HED retaining a 3X FQPA safety 

factor for acute assessments. A 3X FQPA safety factor was judged to be adequate (as opposed to 

a 10X) for the following reasons: (1) A NOAEL was established in the 15-day neurotoxicity CF1 mouse study used to determine the acute toxicity endpoint for risk assessment; (2) Although 

the effects of concern are seen after repeated dosing, the NOAEL here is used for a single 

exposure risk assessment; and (3) The most sensitive endpoint in the most sensitive species is 

selected.

4.2.1 Completeness of the Toxicology Database

The toxicology database used to assess pre- and post-natal exposure to emamectin is considered 

adequate. However, under the current data requirement guidelines, an immunotoxicity study and 

an inhalation toxicity study are required.

Immunotoxicity study

The risk assessment team evaluated subchronic, chronic, carcinogenicity, developmental and 

reproduction studies as well as acute and subchronic neurotoxicity studies for any effects which 

might indicate that emamectin induced changes in the organs generally associated with 

immunological toxicity. In the studies evaluated, only the 14-week oral toxicity study in dogs 

showed an increase in the incidence of thymus atrophy at 1 mg/kg/day. In the 1-year feeding 

study in the dog, thymus atrophy was not reported at similar dose levels tested. Currently, the 

point of departure for risk assessment is 0.075 mg/kg/day, which is more than 10x less than the 
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dose where thymus atrophy had been reported. At this time, the acute and chronic reference 

doses (RfD's) are 0.00025 mg/kg/day and 0.000075 mg/kg/day, respectively; therefore, database 

uncertainty factor is not necessary to account for the lack of an immunotoxicity study at this 

time. 

Inhalation toxicity study

Since no inhalation studies are available, the Agency selected an oral NOAEL of 0.075 

mg/kg/day established in the 15-day neurotoxicity study in mice for inhalation risk assessments. 

Therefore, a 28-day subchronic inhalation study is required for the reasons that the inhalation 

study (1) may provide route specific effects (route of entry effects) and (2) may result in changes 

to the endpoints and how the risks are quantified. In addition, the acute inhalation toxicity 

category for emamectin is II, and in a 5-day preliminary inhalation study, histopathological 

changes were found in the respiratory tract at all dose levels (1 μg/L to 125 μg/L). The study 

should be performed using the CF-1 mouse. In 2006, the registrant and the Agency held several 

meetings to discuss the conduct of the 28-day inhalation toxicity study (specifically the strain of 

test animal to be used). At this time, the Agency still maintains that this study should be 

conducted in the most sensitive strain of mice (CF-1 mice). A 10x uncertainty factor is 

recommended for lack of an inhalation toxicity study.

4.2.2 Evidence of Neurotoxicity

Following emamectin exposure, neurotoxicity has been seen in multiple studies with several 

species of test animals.

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

Although no increased sensitivity was seen in developmental toxicity studies in rats and rabbits, 

increased qualitative and/or quantitative sensitivity of rat pups was seen in the reproductive 

toxicity study and in the developmental neurotoxicity study (see details in Section 4.1: Summary 

of Toxicological Effects). 

4.2.4 Residual Uncertainty in the Exposure Database

The assessment for food incorporates somewhat refined anticipated residue estimates for most 

commodities that were derived from field trial data and percent crop treated (% CT) data. 

Monitoring data were used for apples in the acute assessment. The availability and use of more 

monitoring data and of food preparation-reduction factors for washing, cooking, etc. may have 

resulted in a more refined estimate of dietary exposure. Therefore, exposures to residues in food 

are not expected to be underestimated.

The dietary drinking water assessment utilizes water concentration values generated by model 

and associated modeling parameters which are designed to provide conservative, health 

protective, high-end estimates of water concentrations which will not likely be underestimated.
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Residential exposure is not expected from the established and proposed uses. Residential 

exposures from commercial nursery production are expected to be negligible because the 

emamectin is expected to dissipate by the time the plant moves from a nursery, through a retail 

store, to the consumer.

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.

The points of departure, uncertainty factors, and toxicity endpoints are presented in Tables 4.3.1 

and 4.3.2.

Table 4.3.1 Summary of Toxicological Doses and Endpoints for Emamectin Benzoate for Use in Dietary and 

Non-Occupational Human Health Risk Assessments1,2

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(All 

Populations)

NOAEL = 

0.075 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 3x

Acute RfD = 

0.00025 

mg/kg/day

aPAD 

=0.00025 

mg/kg/day

15-day mouse

LOAEL = 0.1 mg/kg/day based on 

tremors on day 3 of dosing. At the next 

higher dose (0.3 mg/kg/day), tremors 

were seen at day 2 of treatment.

Chronic 

Dietary (All 

Populations)

NOAEL = 

0.075 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 10x

Chronic RfD 

= 0.000075

mg/kg/day

cPAD = 

0.000075 

mg/kg/day

15-day mouse

LOAEL = 0.1 mg/kg/day based on 

moribund sacrifices, clinical signs of 

neurotoxicity, decreases in body weight 

and food consumption and 

histopathological lesions in the sciatic 

nerve.

Cancer (oral, 

dermal, 

inhalation)

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

tumor increases in two adequate rodent carcinogenicity studies.

1

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. (The 10X 

FQPA safety factor for chronic/long-term and intermediate-term assessments is to account for the steepness of the 

dose-response curve, severity of effects at the LOAEL (death and neuropathology), and the use of a short-term study 

for intermediate-term risk assessment. The 3X FQPA safety factor for acute assessments is to account for steepness 

of the dose-response curve and the severity of the effects at the LOAEL.) PAD = population adjusted dose (a = 

acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 

2 Dermal absorption of 1.8% is assumed.
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Table 4.3.2 Summary of Toxicological Doses and Endpoints for Emamectin Benzoate for Use in Occupational 

Human Health Risk Assessments1,2

Exposure/ 

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal ShortTerm (1-30 

days)

NOAEL = 

0.075 

mg/kg/day

(dermal 

absorption 

rate =1.8%)

UFA = 10x

UFH = 10x

FQPA = 3x

Occupational LOC 

for MOE = 300

15-day mouse

LOAEL = 0.1 mg/kg/day based on 

moribund sacrifices, clinical signs of 

neurotoxicity, decreases in body weight 

and food consumption and 

histopathological lesions in the sciatic 

nerve.

Dermal 

IntermediateTerm (1-6 

months)

NOAEL =

0.075 

mg/kg/day

(dermal 

absorption 

rate = 1.8%)

UFA = 10x

UFH = 10x

FQPA = 10x

Occupational LOC 

for MOE = 1000

15-day mouse

LOAEL = 0.1 mg/kg/day based on 

moribund sacrifices, clinical signs of 

neurotoxicity, decreases in body weight 

and food consumption and 

histopathological lesions in the sciatic 

nerve.

Inhalation 

Short-Term (1-

30 days)

NOAEL =

0.075 

mg/kg/day 

(assumed 

equivalent 

to oral 

absorption)

UFA = 10x

UFH = 10x

UFm = 30x

Occupational LOC 

for MOE = 3000

15-day mouse

LOAEL = 0.1 mg/kg/day based on 

moribund sacrifices, clinical signs of 

neurotoxicity, decreases in body weight 

and food consumption and 

histopathological lesions in the sciatic 

nerve.

Inhalation 

IntermediateTerm (1-6 

months)

NOAEL =

0.075 

mg/kg/day 

(assumed 

equivalent 

to oral 

absorption)

UFA = 10x

UFH = 10x

UFm = 30x

Occupational LOC 

for MOE = 3000

15-day mouse

LOAEL = 0.1 mg/kg/day based on 

moribund sacrifices, clinical signs of 

neurotoxicity, decreases in body weight 

and food consumption and 

histopathological lesions in the sciatic 

nerve.

Cancer (oral, 

dermal, 

inhalation)

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

tumor increases in two adequate rodent carcinogenicity studies.

1

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). UFm = modifying factor: the 30X consisted of 

3X to account for the steepness of the dose-response curve, severity of effects at the LOAEL (death and 

neuropathology) and 10 x for lack of an inhalation toxicity study. MOE = margin of exposure. LOC = level of 

concern. 

2 Dermal absorption of 1.8% is assumed.
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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), emamectin benzoate is 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

benzoate is not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Accordingly, as part of registration review, EPA will issue future 

EDSP orders/data call-ins, requiring the submission of EDSP screening assays for emamectin 

benzoate. 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

Plants: The major metabolite identified in lettuce, cabbage, and sweet corn treated with 

[

14C]emamectin B1a (MAB1a) was the parent MAB1a. The isomer 8,9-ZB1a and the 
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metabolites/degradates AB1a, MFB1a, and FAB1a were identified at <5% of the TRR. MAB1a

initially degrades rapidly to a large number of residues of MAB1a-like structures, nearly all 

contributing only a small amount to the total residue; these initial degradates undergo further 

degradation to yield a very complex residue. These degradations are probably a result of 

photolysis, and after this photolytic process, these degradates can be fragmented and 

incorporated into natural plant constituents. 

Ruminants: The parent compounds, emamectin (MAB1a + MAB1b), are the only major residue 

found in goat milk, fat, meat and meat byproducts. However, the analytical method for the 

determination of residues of emamectin and its metabolites in livestock commodities cannot 

distinguish between the parent compounds and its metabolites, 8,9-ZMA (8,9-ZB1a + 8,9-ZB1b). 

In the absence of toxicity data, the metabolites 8,9-ZMA (8,9-ZB1a + 8,9-ZB1b) are assumed to 

be of comparable toxicity to the parent.

Drinking water: Parent and degradates (refer to Table 5.1) were included in the drinking water 

assessment for emamectin benzoate. The degradates are assumed to be of equal or lesser toxicity 

to that of the parent compound.

The residues of concern for the dietary risk assessment and the tolerance expression are 

summarized in Table 5.1. 

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

Plants1Primary Crops emamectin (MAB1a + 

MAB1b), the associated 8,9-Z 

isomers (8,9-ZB1a + 8,9-

ZB1b), and 

metabolites/degradates AB1a, 

MFB1a and FAB1a

emamectin (MAB1a + 

MAB1b), the associated 8,9-Z 

isomers (8,9-ZB1a + 8,9-

ZB1b), and 

metabolites/degradates AB1a, 

MFB1a and FAB1a

Rotational Crops Same as for primary crops Same as for primary crops

Livestock1 Ruminant emamectin (MAB1a + MAB1b) 

and its 8,9-Z isomers (8,9-

ZB1a and 8,9-ZB1b)

emamectin (MAB1a + MAB1b) 

and its 8,9-Z isomers (8,9-

ZB1a and 8,9-ZB1b)

Poultry Not applicable Not applicable

Drinking Water2emamectin (MAB1a + 

MAB1b), the associated 8,9-Z 

isomers (8,9-ZB1a + 8,9-

ZB1b), and 

metabolites/degradates 

Not Applicable

1 TXR#0050315, Manying Xue, 1/28/02
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2 TXR#0050315 (Manying Xue, 1/28/02) indicated that drinking water residues should be emamectin (MAB1a + 

MAB1b), the associated 8,9-Z isomers (8,9-ZB1a + 8,9-ZB1b), and the metabolites/degradates AB1a, MF B1a, and 

FAB1a. DP#402307 (T. Dowen, 5/30/12) indicated that the drinking water analytes included emamectin and the 

following four degradates: (8,9-Z)-4"-epimethylamino-4"-deoxy avermectin B1 (8,9 ZMA isomer); 4"-epiamino-4"-

deoxyavermectin B1 (AB); avermectin B1 monosaccharide; and 4"-epi-(N-formyl)-4"-deoxyavermectin B1 (FAB).

5.2 Food Residue Profile

Crop Field Trials: IR-4 submitted crop field trial data on cucumber, squash, and cantaloupe in 

support of the proposed use of the 5% SG formulation of emamectin benzoate on cucurbit 

vegetables. The residue data are summarized in Table 5.2 below. All residues are <0.02 ppm.

Table 5.2. Summary of Residue Data from Crop Field Trials with Emamectin Benzoate (SG Formulation).

Commodity Total App. 

Rate

(lb ai/A)

PHI 

(days)

Combined Residues (ppm)1

n Sample

Min.

Sample

Max.

LAFT2 HAFT2 Median Mean Std. 

Dev.

Vegetable, Cucurbit, Group 9 (proposed use = 0.09 lb ai/A total application rate, 7-day PHI)

Cucumber 0.077-0.092 6-8 8 <0.02 <0.02 0.02 0.02 0.02 0.02 NA

Summer 

Squash

0.090-0.093 6-8 8 <0.02 <0.02 0.02 0.02 0.02 0.02 NA

Cantaloupe 0.089-0.092 6-8 10 <0.006 <0.0081 0.006 0.008 0.006 0.006 0.001

1 Combined residues include total emamectin (MAB1a and MAB1b), its 8,9-Z isomers (8,9-ZB1a and 8,9-ZB1b), and 

metabolites/degradates AB1a, MFB1a, and FAB1a. 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 (0.02 ppm for cucumber and 

squash and 0.006 ppm for cantaloupe) was used for any results reported as <LOQ. NA = Not applicable.

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

The submitted cucumber, summer squash, and cantaloupe crop field trial data are adequate and 

fulfill the field trial requirements for the cucurbit vegetable group 9. The studies reflect the 

maximum proposed use pattern for cucurbit vegetables, and the number and locations of the field 

trials are in accordance with OCSPP 860.1500 for each crop. An acceptable method was used 

for residue quantitation, and the data are supported by adequate storage stability data.

The available residue data are sufficient for establishing a tolerance of 0.02 ppm for vegetable, 

cucurbit, group 9 in association with the requested registration of the 5% SG formulation on 

cucurbit vegetables. 

Processing Studies: There are no regulated processed commodities associated with cucurbit 

vegetables.

Storage Stability: Adequate storage stability data are available to support the cucurbit vegetable 

field trial studies. No corrections for residue decline during storage are needed.
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Meat, Milk, Poultry, and Eggs: There are no livestock feedstuffs associated with use on cucurbit 

vegetables.

Rotational Crops: Total radioactive residues in a confined rotational crop study after application 

of [14C]MAB1a were <0.01 ppm in/on immature and mature head lettuce, carrots, and barley from 

all plantback intervals (30, 120/141, and 365 days); only barley straw had residues at >0.01 ppm 

(0.016 and 0.030 ppm) at the 30- and 141-day plantback intervals. Emamectin and its 

metabolites were not identified in 30- and 141-DAT (days after treatment) barley straw. There is 

no indication that emamectin residues of concern would be present in rotational crops at levels 

≥0.01 ppm, and no plantback restrictions are needed on the labels. 

5.3 Water Residue Profile

The drinking water residues used in the dietary risk assessment were provided by EFED in the 

following memorandum: “Amended Drinking Water Assessment for the Proposed Use of 

Emamectin Benzoate on Outdoor Ornamentals and Group 9 Cucurbit Vegetables” (Tiffany 

Dowen, 5/30/12, DP#402307) and incorporated directly into this dietary assessment. Water 

residues were incorporated in the DEEM-FCID into the food categories “water, direct, all 

sources” and “water, indirect, all sources.” 

EFED provided EDWCs for the proposed/registered uses of emamectin benzoate including the 

proposed uses on outdoor ornamentals (EPA Reg. No. 100-RURR) and cucurbit vegetables (EPA 

Reg. No. 100-904). EDWCs from use on outdoor-grown ornamentals are the highest. 

Emamectin benzoate residues (parent + degradation products), based on applications made to 

ornamentals and group 9 cucurbits, are not expected to exceed 0.465 μg/L for the 1 in 10 year 

daily peak, 0.150 μg/L for the 1 in 10 year annual average, and 0.112 μg/L for the 30 year annual 

average (Table 5.3). 

The Agency identified four degradates of concern based on structural similarity to emamectin 

benzoate that are formed via photolysis (MARC memo references: D238206, Sept 2, 1997; 

D255357, Aug 20, 2001; D277085, Aug 20, 2001): 

(8,9-Z)-4"-epimethylamino-4"-deoxy avermectin B1 (8,9 ZMA isomer); 

4"-epiamino-4"-deoxyavermectin B1 (AB);

avermectin B1 monosaccharide (MAB); and 

4"-epi-(N-formyl)-4"-deoxyavermectin B1 (FAB). 

These degradates were included in the drinking water assessment for emamectin benzoate and 

are assumed to be of equal or lesser toxicity to that of the parent compound. The total toxic 

residues approach is used for determining the environmental fate data parameters for modeling 

using the Guidance for Selecting Input Parameters in Modeling the Environmental Fate and 

Transport of Pesticides, Version 2.1, October 22, 2009, and the draft Guidance for Modeling 
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Pesticides Total Toxic Residues (TTR), dated May 20, 2009.

Table 5.3 Summary of Estimated Surface Water and Groundwater Concentrations for Emamectin 

Benzoate.a

Scenario Surface Water Conc., ppb b Groundwater Conc., ppb c

Acute 0.465 0.54 x 10-3

Chronic (non-cancer) 0.150 0.54 x 10-3

Chronic (cancer) 0.112 0.54 x 10-3

a Degradates of concern included in the calculation of EDWCs: (8,9-Z)-4"-epimethylamino-4"-deoxy avermectin 

B1, 4"-epiamino-4"-deoxyavermectin B1, avermectin B1 monosaccharide, and 4"-epi-(N-formyl)-4"-

deoxyavermectin B1 (the 8,9 ZMA isomer, AB, MAB, and FAB, respectively). 

b

From the Tier II PRZM-EXAMS - Index Reservoir model. Input parameters are based on the use on 

ornamentals. Typically, the values generated by the models for drinking water are multiplied by a percent crop 

area factor (PCA). The PCA accounts for the fact that is it unlikely for any basin to be completely planted to 

agricultural crops. The PCA adjustment factor is assumed to be 0.87 for the group 9 cucurbit vegetables and 1.0 

for the outdoor ornamentals crops as per the PCA guidance. 

c From the SCI-GROW model. Input parameters are based on the use on ornamentals/group 9 cucurbit vegetables.

d “Amended Drinking Water Assessment for the Proposed Use of Emamectin Benzoate on Outdoor Ornamentals 

and Group 9 Cucurbit Vegetables” (Tiffany Dowen, 5/30/12, DP#402307)

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Acute assessment: A probabilistic acute dietary exposure assessment was conducted. The 

anticipated residue estimates, used for most crops, were based on field trial data. Tolerance-level 

residues were used for tree nuts (including pistachios) and cottonseed oil. Pesticide Data 

Program (PDP) monitoring data for years 2009 and 2010 were used for apples since apple juice 

had a significant impact on exposure. DEEM default processing factors were used except for 

commodities with chemical-specific processing studies. Percent crop treated (% CT) data and 

percent crop treated data for new crops (PCTn) provided by the Biological and Economic 

Analysis Division (BEAD) in 2012 were used. The EDWCs of emamectin benzoate were 

provided by EFED. A drinking water residue distribution based on the Pesticide Root Zone 

Model/Exposure Analysis Modeling System (PRZM/EXAMS) modeling of the use on 

ornamentals was used in the acute assessment.

Chronic assessment: A somewhat refined chronic dietary exposure assessment was conducted. 

The anticipated residue estimates, used for most crops, were single point estimates (averages) 

based on field trial data. Tolerance-level residues were used for tree nuts (including pistachios) 

and cottonseed oil. DEEM default processing factors were used except for commodities with 

chemical-specific processing studies. Percent crop treated data and PCTn data provided by 

BEAD in 2012 were used. The EDWC of 0.150 μg/L (ppb) for the chronic exposure was based 

on PRZM/EXAMS modeling of the use on ornamentals, which resulted in the highest chronic 

EDWC considering all proposed/registered uses.
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5.4.2 Percent Crop Treated Used in Dietary Assessment

The following maximum percent crop treated estimates [D401786, Jihad Alsadek, 5/29/12; 

Screening Level Usage Analysis (SLUA) dated 5/29/12] were used in the acute dietary risk 

assessment for the following crops that are currently registered for emamectin benzoate: 

almonds, 2.5%; apples, 20%; broccoli, 20%; cabbage, 25%; cauliflower, 20%; celery, 40%; 

cotton, 2.5%; lettuce, 20%; pears, 20%; peppers, 15%; spinach, 10%; and tomatoes, 20%.

The following maximum percent crop treated estimates from the SLUA dated 5/29/12 were used 

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

emamectin benzoate: almonds, 1%; apples, 10%; broccoli, 5%; cabbage, 10%; cauliflower, 10%; 

celery, 25%; cotton, 1%; lettuce, 10%; pears, 5%; peppers, 5%; spinach, 5%; and tomatoes, 10%.

The following percent crop treated estimates for new crops (PCTn) (D403689, Jihad Alsadek, 

8/21/12) were used in the acute dietary risk assessment: cantaloupe, 51%; cucumber, 26%; 

squash, 46%; and watermelon, 21%.

The following PCTn estimates (D403689, Jihad Alsadek, 8/21/12) were used in the chronic 

dietary risk assessment: cantaloupe, 40%; cucumber, 14%; squash, 29%; and watermelon, 19%.

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+ years old.

As shown in Table 5.4.6.1, the most highly exposed subgroup was children 1-2 years old, with 

exposure of 60% of the aPAD. The risk estimates for all populations assessed were below the 

level of concern.

The acute assessment is a probabilistic assessment which incorporates anticipated residue 

estimates for most commodities that were derived from field trial data. Percent crop treated data 

were used for some new and registered crops. Monitoring data were used for apples in the acute 

assessment since apple juice had a significant impact on exposure. The use of more monitoring 

data and of food preparation-reduction factors for washing, cooking, etc. may have resulted in

more refined estimates of dietary exposure. More highly refined analyses are not needed at this 

time since the risk estimates are below HED’s level of concern.
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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+ years old.

As shown in Table 5.4.6.2, the most highly exposed subgroup was all infants less than one year 

old, with exposure of 16% of the cPAD. The risk estimates for all populations assessed were 

below HED’s level of concern.

The chronic assessment for food is a somewhat refined assessment which incorporates 

anticipated residue estimates for most commodities that were derived from field trial data. 

Percent crop treated data were used for some new and registered crops. The use of more 

monitoring data and of food preparation-reduction factors for washing, cooking, etc. may have 

resulted in more refined estimates of dietary exposure. More highly refined analyses are not 

needed at this time since the risk estimates are below HED’s level of concern.

5.4.5 Cancer Dietary Risk Assessment

Emamectin benzoate is classified as “not likely to be carcinogenic to humans” based on the 

absence of significant tumor increases in two adequate rodent carcinogenicity studies.

5.4.6 Summary Tables

The results of the acute dietary (food + drinking water) exposure analysis at the 95th, 99th, and 

99.9th percentiles of exposure are reported in Table 5.4.6.1 below. The acute dietary exposure 

estimates for food and drinking water using the ornamentals scenario for drinking water are 

below HED’s level of concern at the 99.9th percentile of exposure for the general U.S. population 

and all population subgroups (36% of the aPAD for the general U.S. population and 60% of the 

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

Table 5.4.6.1 Results of Acute Dietary (Food and Drinking Water) Exposure Analysis Using DEEM FCID 

Population Subgroup aPAD 

(mg/kg/day)

95th Percentile 99th Percentile 99.9th Percentile

Exposure 

(mg/kg/day)

% 

aPAD

Exposure 

(mg/kg/day)

% 

aPAD

Exposure 

(mg/kg/day)

% 

aPAD

General U.S. Population 0.00025 0.000019 7.4 0.000038 15 0.000091 36

All Infants (< 1 year old) 0.000037 15 0.000070 28 0.000138 55

Children 1-2 years old 0.000038 15 0.000074 29 0.000151 60

Children 3-5 years old 0.000028 11 0.000059 23 0.000135 54
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Table 5.4.6.1 Results of Acute Dietary (Food and Drinking Water) Exposure Analysis Using DEEM FCID 

Population Subgroup aPAD 

(mg/kg/day)

95th Percentile 99th Percentile 99.9th Percentile

Exposure 

(mg/kg/day)

% 

aPAD

Exposure 

(mg/kg/day)

% 

aPAD

Exposure 

(mg/kg/day)

% 

aPAD

Children 6-12 years old 0.000018 7.3 0.000042 17 0.000082 33

Youth 13-19 years old 0.000012 4.8 0.000025 10 0.000084 33

Adults 20-49 years old 0.000016 6.5 0.000032 13 0.000077 31

Adults 50+ years old 0.000018 7.3 0.000035 14 0.000093 37

Females 13-49 years old 0.000016 6.5 0.000033 13 0.000076 30

The results of the chronic dietary (food and drinking water) exposure analysis are reported in 

Table 5.4.6.2 below. The emamectin benzoate chronic dietary risk estimates for food and 

drinking water using the ornamental scenario for drinking water are below HED’s level of 

concern for the general U.S. population and all population subgroups, at 7.5% of the cPAD for 

the general U.S. population and 16% of the cPAD for all infants (<1 year old), the most highly 

exposed population subgroup.

Table 5.4.6.2. Summary of Dietary (Food and Drinking Water) Exposure and Risk for 

Emamectin Benzoate

Population Subgroup

Acute Dietary

(99.9 Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD*

Dietary 

Exposure

(mg/kg/day)

% cPAD*

General U.S. Population 0.000091 36 0.000006 7.5

All Infants (<1 year old)* 0.000138 55 0.000012 16

Children 1-2 years old* 0.000151 60 0.000011 15

Children 3-5 years old 0.000135 54 0.000009 12

Children 6-12 years old 0.000082 33 0.000006 7.4

Youth 13-19 years old 0.000084 33 0.000004 5.2

Adults 20-49 years old 0.000077 31 0.000005 6.9

Adults 50-99 years old 0.000093 37 0.000006 7.7

Females 13-49 years old 0.000076 30 0.000005 6.8

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

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

and residential post-application exposure are not expected. Emamectin benzoate is registered for 

agricultural uses, as a tree injection use, and as a cockroach bait. Except for OptigardTM 

Cockroach Bait (EPA Reg. No. 100-1290), all registered emamectin benzoate end-use products 

are restricted use products (RUPs; restricted to use by professional certified operators [PCOs] 

only). OptigardTM Cockroach Bait is not a restricted use product but EPA has indicated that it is 

to be used only in commercial and industrial areas. Proclaim® Insecticide is an RUP which is 

proposed for use on cucurbits. EnfoldTM Insecticide is an RUP which is proposed for use on 

outdoor-grown plants in commercial nursery production. 

6.1 Residential Handler Exposure

Residential exposure is not expected from the registered/proposed products since they are 

agricultural uses rather than residential uses, restricted use products (restricted to use by certified 

applicators only), or limited to non-residential areas (commercial and industrial areas). Neither 

the proposed uses nor currently registered products would lead to residential handler exposure. 

6.2 Post-Application Exposure

For reasons stated in Section 6.1 above, neither the proposed uses nor currently registered

products would lead to residential post-application exposure. Residential exposures from 

commercial nursery production are expected to be negligible because the emamectin is expected 

to dissipate by the time the plant moves from a nursery, through a retail store, to the consumer.

6.3 Residential Bystander Post-application Inhalation Exposure

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

assessment was not performed for emamectin benzoate at this time because the chemical has low 

vapor pressure (3.0 × 10-8 mm Hg at 21 oC) and is applied at a low rate (0.015 lb ai/A). 

However, volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/sap/meetings/2009/120109meeting.html). The 

Agency 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 postapplication 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 emamectin benzoate.
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6.4 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 emamectin 

benzoate. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices 

and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices (see the Agency’s Spray Drift website for more information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT computer model to 

its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. 

After the policy is in place, the Agency may impose further refinements in spray drift 

management practices to reduce off-target drift with specific products with significant risks 

associated with drift.

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

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation 

exposure assessment was performed for occupational 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.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

7.1 Acute Aggregate Risk

Only food and drinking water are included in the acute aggregate assessment, as the Agency does

not routinely assess any one-day residential exposures. Refer to section 5.4.3 for a detailed 

discussion of the acute dietary assessment. 

7.2 Short-/Intermediate-Term Aggregate Risk

Short- and intermediate-term aggregate risk assessments were not conducted because existing 

and proposed uses are not expected to result in residential exposure.
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7.3 Chronic Aggregate Risk

Chronic or long-term aggregate assessments include exposures that will exceed six months. 

Only food and drinking water are included in the chronic aggregate assessment, as the Agency 

does not routinely assess any long-term residential exposures. Refer to section 5.4.4 for a 

detailed discussion of the chronic dietary assessment.

7.4 Cancer Aggregate Risk

Emamectin benzoate is classified as “not likely to be carcinogenic to humans.”

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 emamectin benzoate and any other substances and emamectin benzoate 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 emamectin benzoate 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 

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, 
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

Page 36 of 62

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 application rate and label information, exposure from uses on cucurbits and 

ornamentals is expected to occur for short-and intermediate-term durations. However, 

intermediate-term exposure is less likely due to resistance management, and short-term scenarios 

are more realistic. Chronic exposure is not expected for the proposed use patterns.

9.1 Short-/Intermediate-Term Handler Risk

Occupational handler exposure to emamectin benzoate is expected for individuals involved in 

foliar applications to cucurbit vegetables (mixing, loading, flagging, and applying) and outdoor 

ornamentals (mixing, loading, and applying). 
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

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The toxicological effects for the dermal and inhalation routes were the same; however, since the 

levels of concern are not identical, the 1/ARI (aggregate risk index) approach was used. The risk 

estimates were calculated using the following formulas:

MOE = NOAEL/ Dose

ARI = MOE/ LOC

Combined ARI = 1 ÷ ((1/Dermal ARI) + (1/Inhalation ARI)).

All of the occupational handler exposure and risk estimate tables have been updated in this 

document since the two occupational and residential exposure (ORE) risk assessments 

previously conducted by Nancy Tsaur (DP390778, 12/07/2011; and DP393839, 03/01/2012). 

Summaries of the short- and intermediate-term risk estimates for occupational handlers from the 

uses on cucurbits and ornamentals are included in Appendix D, Tables D.1 through D.6. The 

maximum application rate for each exposure scenario is presented as the worst case scenario. 

The values in Tables D.1 through D.6 reflect current policies (i.e. changes to unit exposures, 

inhalation toxicity uncertainty factors, and body weights).

Based on the PPE required on the label, there are some risks of concern. Table 9.1 shows the 

PPE proposed on both labels (EPA Reg. No. 100-904 and EPA Reg. No. 100-RURR) along with 

mitigation recommendations based on short- and intermediate-term risk estimates. In order to 

achieve risk estimates that do not exceed HED’s LOC (ARIs > 1.0), the recommendations based 

on intermediate-term exposure are more stringent. However, when considering resistance 

management, the short-term risk estimates are more representative of realistic exposure potential.

Table 9.1. Occupational Exposure Mitigation Recommendations.

Proposed PPE on the Registered and Proposed Labels (EPA Reg. 

No. 100-904 and 100-RURR)

Recommended Mitigation 

Based on Short-Term Risk 

Estimates

Recommended Mitigation 

Based on Intermediate-Term 

Risk Estimates

Ground Application (except airblast sprayers)

Mixers, 

Loaders, 

Other 

Handlers

Long-sleeved shirt and long pants.

Chemical-resistant gloves made of any waterproof 

material such as polyvinyl chloride, nitrile rubber 

or butyl rubber.

Shoes plus socks.

Option 1: Add a PF5 respirator 

for ornamentals. Add a PF10 

respirator for cucurbit 

vegetables.

Option 2: Require engineering 

control of closed packaging.

Option 1: Add a PF5 respirator 

for ornamentals. Add a PF10 

respirator for cucurbit 

vegetables.

Option 2: Require engineering 

control of closed packaging.

Applicators

Long-sleeved shirt and long pants.

Chemical-resistant gloves made of any waterproof 

material such as polyvinyl chloride, nitrile rubber 

or butyl rubber.

Shoes plus socks.

Adequate. Adequate.

Handheld Application

Applicators, 

Mixers, 

Loaders, 

Other 

Handlers

Not explicitly listed. May be assumed to be 

equivalent to “Ground Application.”

Adequate if assumed to be 

equivalent to “Ground 

Application.”

Add a PF5 respirator specifically 

for backpack sprayer application 

to ornamentals.

Airblast Application
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

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Table 9.1. Occupational Exposure Mitigation Recommendations.

Mixers, 

Loaders, 

Other 

Handlers

Long-sleeved shirt and long pants.

Chemical-resistant gloves made of any waterproof 

material such as polyvinyl chloride, nitrile rubber 

or butyl rubber.

Shoes plus socks.

Option 1: Add a PF5 respirator 

for ornamentals.

Option 2: Require engineering 

control of closed packaging.

Option 1: Add a PF5 respirator 

for ornamentals.

Option 2: Require engineering 

control of closed packaging.

Applicators 

Using OPEN 

CAB

Coveralls over long-sleeved shirt and long pants.

Chemical-resistant gloves made of any waterproof 

material such as polyvinyl chloride, nitrile rubber 

or butyl rubber.

Shoes plus socks.

Option 1: Add a PF5 respirator.

Option 2: Prohibit OPEN CAB 

equipment.

Prohibit OPEN CAB equipment.

Applicators 

Using 

ENCLOSED 

CAB

While inside the 

cockpit must wear:

Long-sleeved shirt 

and long pants.

Shoes plus socks.

When entering or leaving 

the cockpit must also 

wear:

Chemical-resistant 

gloves made of any 

waterproof material such 

as polyvinyl chloride, 

nitrile rubber or butyl 

rubber.

Adequate. Adequate.

Aerial Application

Mixers, 

Loaders, 

Other 

Handlers

Coveralls over long-sleeved shirt and long pants.

Shoes plus socks.

Chemical-resistant gloves made of any waterproof 

material such as polyvinyl chloride, nitrile rubber 

or butyl rubber.

Dust/Mist-filtering respirator or a NIOSHapproved respirator with any N, R, P, or HE filter.

Adequate for ornamentals.

Require engineering control of 

closed packaging for cucurbit 

vegetables.

Adequate for ornamentals.

Require engineering control of 

closed packaging for cucurbit 

vegetables.

Applicators 

(ENCLOSED 

Cockpit)

NOTE: Once 

inside the 

cockpit, 

applicator 

must remove 

gloves and 

store them in a 

chemicalresistant 

container such 

as a plastic 

bag.

While inside the 

cockpit must wear:

Long-sleeved shirt 

and long pants.

Shoes plus socks.

When entering or leaving 

the cockpit must also 

wear:

Chemical-resistant 

gloves made of any 

waterproof material such 

as polyvinyl chloride, 

nitrile rubber or butyl 

rubber.

Adequate. Adequate.

Flaggers

Long-sleeved shirt and long pants.

Shoes plus socks.

Chemical-resistant gloves made of any waterproof 

material such as polyvinyl chloride, nitrile rubber 

or butyl rubber.

Adequate.

Adequate for ornamentals.

Add a PF5 respirator for 

cucurbit vegetables.
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9.2 Short-/Intermediate-Term Post-Application Risk

Agricultural workers performing typical post-application activities with cucurbits and 

ornamentals such as scouting, irrigation, and harvesting are likely to receive exposure to 

emamectin benzoate residues based on the repeated use pattern to maintain control of pests.

9.2.1 Dermal Post-Application Risk

There is a potential for short- and intermediate-term occupational exposure during postapplication activities. However, intermediate-term exposure is less likely due to resistance 

management, and short-term scenarios are more realistic. HED recommends utilizing the results 

from the short-term quantitative risk assessment because the intermediate-term results are highly 

conservative and unlikely due to the following reasons:

1. Due to resistance management of a Group 6 insecticide that has inherent risks of 

resistance development, the frequency of chemical application is expected to be limited 

to short-term use.

2. The intermediate-term day 0 assumptions are overly conservative and should be 

amortized if further refined (i.e., the likelihood of assuming day 0 residues every day for 

90 days is not realistic).

The dermal post-application exposures associated with ornamentals and cucurbits are

summarized in Appendix D, Table D.7. For short-term exposure, all scenarios resulted in MOEs 

greater than the short-term LOC of 300 (ranging from 520 to 11,000) on day 0 (12 hours after 

application) and, therefore, are not of concern to HED. For intermediate-term exposure, risk 

estimate MOEs are less than the intermediate-term LOC of 1000 and are of concern on day 0 (12 

hours after application).

Restricted Entry Interval

Typically, under WPS for Agricultural Pesticides, active ingredients classified as acute Toxicity 

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

hour REI.

 

9.2.2 Occupational Post-Application Inhalation Exposure

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

exposure assessment was not performed for emamectin benzoate at this time because the 

chemical has low vapor pressure (3.0 × 10-8 mm Hg at 21 oC) and is applied at a low rate (0.015 

lb ai/A). However, there are multiple potential sources of post-application inhalation exposure to 

individuals performing post-application activities in previously treated fields. These potential 

sources include volatilization of pesticides and resuspension of dusts and/or particulates that 

contain pesticides. The Agency sought expert advice and input on issues related to volatilization 

of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory 

Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

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(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

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

data generated by the Agricultural Reentry Task Force. The Agency may, as appropriate, 

develop policies and procedures to identify the need for and, subsequently, the way to 

incorporate occupational post-application inhalation exposure into the Agency's risk 

assessments. If new policies or procedures are put into place, the Agency may revisit the need 

for a quantitative occupational post-application inhalation exposure assessment for emamectin 

benzoate.

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

Dodd, N., O’Rourke, K., and Phang, W., 7/31/08, DP Number D345943, Emamectin 

Benzoate. Human Health Risk Assessment for Proposed Uses on Tree Nuts and 

Pistachios, and as an Injection Treatment for Ornamental/Nonbearing Trees.

Dodd, N., Phang, W., and Tsaur, N., 6/16/11, DP Number D385990, Emamectin 

Benzoate. Human Health Assessment Scoping Document in Support of Registration 

Review.

Dodd, N., 8/6/12, DP Number D392510, Emamectin Benzoate. Petition for the 

Establishment of a Permanent Tolerance on Vegetable, Cucurbit, Group 9. Summary of 

Analytical Chemistry and Residue Data.

Dodd, N., 12/19/12, DP Number 393838, Emamectin Benzoate: Revised Acute and 

Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments 

for the Section 3 Registration Action on Cucurbits and Outdoor-Grown Plants in 

Commercial Nursery Production.

Tsaur, N., 12/7/11, DP Number D390788, Emamectin Benzoate. Occupational Exposure 

Assessment for a Proposed Use on Outdoor-Grown Plants in Commercial Nursery 

Production.

Tsaur, N., 3/1/12, DP Number D393839, Emamectin Benzoate. Occupational Exposure 

Assessment for a Proposed Use on Cucurbit Vegetables (Crop Group 9).

Dowen, T., 5/30/12, DP Number 402307, Amended Drinking Water Assessment for the 

Proposed Use of Emamectin Benzoate on Outdoor Ornamentals and Group 9 Cucurbit 

Vegetables.

Alsadek, J., Ph.D., 8/21/12, DP Number 403689, Percent Crop Treated for Emamectin 

Benzoate on Proposed New Uses for Cantaloupe, Cucumber, Squash, and Watermelons.

Alsadek, J., Ph.D., 5/29/12, DP Number 401786, Emamectin Benzoate (122806) 

Screening Level Usage Analysis (SLUA).
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

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Xue, M., 1/28/02, TXR#050315, Emamectin. Conclusions of the 12/4/2001 Meeting of 

the HED Metabolism Assessment Review Committee (MARC) Meeting on Livestock 

Metabolism Studies.
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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food use for emamectin benzoate 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

-

yes

yes

yes

yes

-

no

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

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

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

yes

yes

yes

yes

yes

yes

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

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

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test ..

870.5385 Mutagenicity—Structural Chromosomal Aberrations...

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

yes

yes

yes

yes

yes

yes

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

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

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

yes

yes

CR

yes

yes

-

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

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

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

yes

yes

yes

yes

yes

no
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

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A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Profile – Emamectin Benzoate Technical (EPA Reg. No. 

100-902)

Guideline No. Study Type MRID Results Toxicity Category

870.1100 Acute oral - Rats 42851519 LD50 for L-656,748-

038 = 53 mg/kg

II

870.1200 Acute dermal - Rabbits (EC) 43850111 LD50 > 2.0 g/kg III

870.1300 Acute inhalation - Rats 43868101 0.44 mg/L <LC50<2.12 

mg/L

III

870.2400 Acute eye irritation - Rabbits 42743615 Severe irritation I

870.2500 Acute dermal irritation - Rabbits 42743616 No dermal irritation IV

870.2600 Skin sensitization - Guinea pigs 42743617 Not a dermal sensitizer -

Table A.2.2. Acute Toxicity Profile – Emamectin Benzoate Technical II (EPA Reg. No. 

100-1270)

Guideline No. Study Type MRID Results Toxicity Category

870.1100 Acute oral - Rats 47002104 LD50 for L-656,748-

038 = 53 mg/kg

II

870.1200 Acute dermal - Rabbits (EC) 47002106 LD50 > 2.0 g/kg III

870.1300 Acute inhalation - Rats 47002107 LC50 0.10 mg/L II

870.2400 Acute eye irritation - Rabbits 47002108 Severe irritation III

870.2500 Acute dermal irritation - Rabbits 47002109 No dermal irritation IV

870.2600 Skin sensitization - Guinea pigs 47002110 Not a dermal sensitizer Negative
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Table A. 2. 3. Repeated Dosing and Other Studies on Emamectin

Guideline 

No

Study Type MRID No. (Year)/ 

Classification/Doses

Results

Acute dermal toxicity study (Not a LD50 study)

Acute dermal tox.-

rabbits 

MK-0243 0.16 EC 

formulation

42743611 (1991)

Acceptable 

0, 0.5, 1.0, & 2.0 mg/kg

(2 groups: 4 hr exposure 

& 24 hr exposure) with 

collar on the test 

animals.

4 hr. exposure

NOAEL= 2.0 mg/kg/day (HDT)

24 hr. exposure

NOAEL = 0.5 mg/kg/day

LOAEL = 1.0 mg/kg/day one rabbit had neuron 

lesion occurred in cerebellar peduncle. 

Acute dermal tox. –

rabbits (24 hrs 

exposure with collar 

on all test animals) 

43850111 (1995)

Acceptable 

0, 10.4, 21.0, or 42.1 

mg/kg MK-0244 0.16 

EC

NOAEL = 42.1 mg/kg. No treatment-related 

systemic toxicity was seen in any dosed animals. 

The acute dermal LD50 > 2000 mg/kg for MK0244

Subchronic toxicity studies

870.3100 13-Wk oral-CD rats 42794201 (1992)

Acceptable

0, 0.5, 2.5, and 12.5 

mg/kg/day. 12.5 

mg/kg/day was reduced 

to 8 mg/kg/day at wk 3 

then to 5.0 mg/kg/day at 

wk 9.

Systemic Toxicity NOAEL=2.5 mg/kg/day; 

Systemic Toxicity LOAEL=5 mg/kg/day based

on moribundity, tremors, hindlimb splaying, 

urogenital staining, histological changes in brain 

and spinal cord, sciatic and optic nerves and 

skeletal muscles in males, emaciation, reduced 

body weight and reduced food consumption in 

both sexes.

13-Wk oral-CD-1 

mice

42743621 (1992)

Acceptable

0, 0.5, 4.5, & 15.0 

mg/kg/day. An 

additional group 

received a time weighted 

dose 5.4 mg/kg/day

NOAEL = 5.4 mg/kg/day

LOAEL = 15.0 mg/kg/day based on mean body 

weight decrease and decreased in cumulative 

body weight gain.

870.3150 90-Day oral – dogs 

(gavage)

42743623 (1992)

Acceptable

0, 1.0, or 1.5 mg/kg/day 

for the first 2 wks then 

reduced to 0.25, 0.5, or 

1.0 for the rest of the 

study.

NOAEL = 0.25 mg/kg/day

LOAEL = 0.50 mg/kg/day based skeletal 

muscle atrophy and white matter multifocal 

degeneration in the brains of both sexes and

white matter multifocal degeneration in the 

spinal cords of males.

14-Wk oral-dogs 

(gavage)

43868103 (1994)

Acceptable

0.5, 1.0, or 1.5 

mg/kg/day for 2 wks for 

mid and high dose 

groups and for 3 wks 

NOAEL = 0.29 mg/kg/day

LOAEL = 0.58 mg/kg/day based on microscopic 

lesions in the brain (multifocal white matter 

degeneration), atrophy of skeletal muscle, and 

spinal cord lesions. 
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Table A. 2. 3. Repeated Dosing and Other Studies on Emamectin

Guideline 

No

Study Type MRID No. (Year)/ 

Classification/Doses

Results

for low dose, then they 

were reduced to 0.25, 

0.5, or 2.0 mg/kg/day. 

The time weighted doses 

were 0.29. 0.58, or 

0.1.08 mg/kg/day.

870.3200 21-Day dermal toxrabbits 

MK-0244 0.16 EC 

formulation 

42743625 (1992

Acceptable 

0, 50, 100, or 250 

mg/kg/day (6 hrs/day)

Systemic tox. NOAEL = 100 mg/kg/day

LOAEL = 250 mg/kg/day based on axonal 

degeneration of the sciatic nerve. 

Application site irritation was seen in all treated 

rabbits.

22-Day dermal tox. 

– rabbits 

MK-0244 0.16 EC 

formulation 

44007902 (1996)

Acceptable

0, 250, 500, or 1000 

mg/kg/day (6 hrs/day)

NOAEL = 1000 mg/kg/day (highest dose tested 

[HDT]). No systemic toxicity was seen in any 

dose groups. 

Note: The test animals were collared to prevent 

oral ingestion of the test material. 

Chronic toxicity studies

870.4100 1-Year oral tox. –

dogs (gavage) 

42763624 (1992)

Acceptable

0, 0.25, 0.5, 0.75, or 1.0 

mg/kg/day (4 

dogs/sex/dose)

NOAEL= 0.25 mg/kg/day

LOAEL=0.5 mg/kg/day based on axonal 

degeneration in the pons, medulla, and 

peripheral nerves (sciatic, sural, and tibial); 

whole body tremors; stiffness of the hind legs, 

spinal cord axonal degeneration, and muscle 

fiber degeneration.

Chronic oral tox. –

rats (dietary)

(1 year)

42868902 (1992)

Acceptable

0, 0.1, 1.0, 2.5 mg/kg 

(initially females 

received 5.0 mg/kg then 

reduced to 2.5 mg/kg at 

wk 18 due to excessive 

toxicity )

NOAEL=1.0 mg/kg/day

LOAEL=2.5 mg/kg/day, based on increased 

incidence of neuronal degeneration in the brain 

and spinal cord, decreased rearing, and an 

increased incidence of animals with low arousal.

870.4200 Carcinogenicity 

study-mice (CD-1)

(dietary)

4386805 (1994)

Acceptable

0, 0.5, 2.5, or 12.5 

mg/kg/day (The highest 

dose was reduced to 7.5 

and 5.0 mg/kg/day for 

males at wk 9 and 

females at wk 3, 

respectively)

NOAEL=2.5 mg/kg/day.

LOAEL=5.0 mg/kg/day for males and 7.5 

mg/kg/day for females based on increased 

mortality, decreased weight gain, tremors, 

sciatic nerve degeneration , and increased 

incidence of severity of infections. 

No treatment-related increase in tumor incidence 

was seen.
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Table A. 2. 3. Repeated Dosing and Other Studies on Emamectin

Guideline 

No

Study Type MRID No. (Year)/ 

Classification/Doses

Results

Combined Chronic/

Carcinogenicity-Rat

43868104 (1994)

Acceptable

0, 0.25, 1.0, 2.5/5.0 

mg/kg (Initially, high 

dose level was 5.0 

mg/kg; it was reduced to 

2.5 mg/kg on wk 6 for 

males and wk 10 for 

females due to tremors 

seen in another study at 

5 mg/kg). 

NOAEL=1.0 mg/kg/day

LOAEL=2.5/5.0 mg/kg/day1based on marked 

neural degeneration in the brain and spinal cord 

of both sexes, brain white matter degeneration in 

males, and on decreased body weight, body 

weight gain, and food efficiency in males. 

No treatment-related increase in tumor incidence 

was seen.

Developmental and Reproduction Studies

870.3700 Developmental tox. 

–rat

42743632 (1992)

Acceptable

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

42743631 (range finding 

study)

Maternal Toxicity NOAEL=2 mg/kg/day, 

Maternal Toxicity LOAEL=4 mg/kg/day

based on a significant trend towards decreased 

body weight gain during the dosing period.

Developmental Toxicity NOAEL=4 

mg/kg/day, Developmental Toxicity 

LOAEL=8 mg/kg/day based on altered growth 

and an increased incidence of supernumerary 

rib.

Developmental tox.-

rabbits

42743636 (1992)

Acceptable 

0, 1.5, 3, or 6 mg/kg/day

42743635 (Range 

finding study)

Maternal Tox. NOAEL= 3 mg/kg/day, 

Maternal Tox. LOAEL= 6 mg/kg/day based 

on a significant trend towards decreased body 

weight gain during dosing period and increased 

clinical signs (mydriasis and decreased pupillary 

reaction).

Developmental Tox. NOAEL=6 mg/kg/day 

(HDT)

870.3800 2-Gen. reproduction 

study - rats

42851511 (1993)

Acceptable 

0, 0.1, 0.6, or 3.8/1.8 

mg/kg/day (F0 & F1a

females initially 

received 3.8 mg/kg, but 

it was reduced to 1.8 

mg/kg/day on GD 0 

following the second 

cohabitation of F0

females).

Parental NOAEL = 0.6 mg/kg/day.

Parental LOAEL = 1.8 mg/kg/day based on

decreased body weight gain and neuronal 

degeneration in the brain and spinal cord in both 

sexes and generations.

Reproductive NOAEL=0.6 mg/kg/day 

Reproductive LOAEL=1.8 mg/kg/day based on 

decreased fecundity and fertility indices.

Offspring NOAEL = 0.6 mg/kg/day

Offspring LOAEL = 1.8 mg/kg/day based on

tremors and hind limb extension in the offspring 
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

Page 47 of 62

Table A. 2. 3. Repeated Dosing and Other Studies on Emamectin

Guideline 

No

Study Type MRID No. (Year)/ 

Classification/Doses

Results

of both generations, neuronal degeneration in 

the brain and spinal cord.

Mutagenicity Studies

870.5100 870.5100

Gene Mutation -

Salmonella

MK-0243 and L660,599; L-657,831; 

L-695,638; L930,905 

(photometabolites of 

MK-0244)

42743637

42851514

42851515

42851516

42851517

Negative for the induction of reverse gene 

mutation.

870.5300 Gene Mutation in 

Cultured V-79 

Chinese Hamster 

Lung Cells

MK-0243

42743638 Negative for the induction of forward gene 

mutations in Chinese hamster lung fibroblast 

cells up to a severely cytotoxic nonactivated 

dose of 0.01 mM or a severely cytotoxic S9-

activated dose of 0.04 mM.

870.5385 Structural 

Chromosome 

Aberration-in vivo

mouse bone marrow

MK-0244

42851513 Negative for the induction of chromosome 

aberrations in the bone marrow cells of male 

CD-1 mice.

Neurotoxicity Studies

870.6200 Acute neurotox. 

study-rats (gavage)

42743618 (1992)

Acceptable

0, 27.4, 54.8 or 82.2 

mg/kg (range finding 

study)

NOAEL was not established. LOAEL= 27.4 

mg/kg/day (LDT); clinical signs (tremors, 

ataxia, loss of righting reflex, and reduced 

activities) and as histological lesions in the 

brain, spinal cord and sciatic nerve occurred at 

all doses tested.

Acute neurotox. 

study- rats 

(gavage)

42743619 (1992)

Supplementary

0, 0.5, 2.5, 5.0, 10.0, or 

25.0 mg/kg/day

NOAEL = 5.0

LOAEL = 10 mg/kg/day based on tremors 

irritability. At 25 mg/kg, all rats had tremor and 

neuronal lesions (white matter degeneration of 

the brain, degeneration of the spinal cord and 

sciatic nerve.

Subchronic 

neurotox. –SD rats

(dietary) (14 day)

42743628 (1992)

Acceptable 

0, 0.25, 1.0, or 5.0 

mg/kg/day 

NOAEL=1.0 mg/kg/day

LOAEL=5.0 mg/kg/day based on tremors, 

posture, rearing, excessive salivation, fur 

appearance, gait, strength, mobility and righting 
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

Page 48 of 62

Table A. 2. 3. Repeated Dosing and Other Studies on Emamectin

Guideline 

No

Study Type MRID No. (Year)/ 

Classification/Doses

Results

reflex. Neuronal vacuolation in brain and spinal 

cord; degeneration of nerve fiber in spinal cord 

and sciatic nerves. Skeletal muscle atrophy. 

Male rats appeared to be more affected than 

females.

Comparative 

neurotox. – dogs

(gavage) (14 days)

42743626 (1992)

Acceptable

2 dogs/sex/compound 

were given 1.5 

mg/kg/day of testing 

compound.

The following effects were seen with different 

compounds:

 Tremors 

Mydriasis 

MK-0243a 2/4 0/4 

L-682,901 0/4 0/4

L-653,648 0/4 4/4

L-653,649 2/4 3/4

L-655. 372 3/4 0/4 

Histopathology findings were not seen in L-682, 

901 and L-653,648 treated dogs. Neuronal 

degeneration of the brain, spinal cord, and 

sciatic nerves were seen in dogs treated with 

MK-0234, L-653, 649, and L-655,372.

15-Day neurotox. –

CD-1 mice

(dietary)

42743629 (1992)

Acceptable

0, 0.6, 1.2, & 2.0 

mg/kg/day

NOAEL=2.0 mg/kg/day (HDT). No 

characteristic neuronal lesions in the brain, 

spinal cord or sciatic nerve in mice of high dose 

group.

15-Day neurotox.-

CF-1 mice (dietary)

(L-660,599: 4”-epi-

(N-formyl-Nmethyl)- amino4”-

deoxy-avermectin 

B1

42851503 (1993)

Acceptable

0, 0.05, 0.075, 0.10, or 

0.30 mg/kg/day 

NOAEL=0.075 mg/kg/day

LOAEL=0.10 mg/kg/day based on tremors 

observed beginning on day 3, ptosis, hunched 

posture, decreases in body weight and food 

consumption as well as degeneration of the 

sciatic nerve. At 0.3 mg/kg, tremors were seen 

on day 2 and followed by hunched posture and 

ptosis, ataxia, and labored breathing.

15-Day neurotox. –

CF-1 mice (dietary)

(L695-638: 4”-

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

photoproduct of 

MK-0244b

42851504 (1993)

Acceptable 

0, 0.05, 0.075, 0.10, & 

0.30 mg/kg/day

NOAEL = 0.30 mg/kg/day (HDT) 

No treatment-related effects were seen in any 

dose groups.

15-Day neurotox. – 42851505(1993) NOAEL = 0.243 (HDT). The targeted dose was 
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

Page 49 of 62

Table A. 2. 3. Repeated Dosing and Other Studies on Emamectin

Guideline 

No

Study Type MRID No. (Year)/ 

Classification/Doses

Results

CF-1 mice (dietary)

(L695-638: 4”-

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

photoproduct of 

MK-0244

Acceptable

0, 0.05, 0.075, 0.10, & 

0.30 mg/kg/day

0.30 mg/kg/day. No treatment-related effects 

were seen in any dose groups.

Female mice only to repeat the exposure dose 

levels of MRID 42851504 because female mice 

received 15% less than the targeted dose in that 

study.

15-Day neurotox.-

CF-1 mice (dietary) 

(L-660,599; formyl 

methylamino plant 

metabolite of MK0244 )

42851506 (1993)

Acceptable 

0, 0.10, 0.30, 0.90 

mg/kg/day

LOAEL <0.1 mg/kg/day LDT) based on 

tremors, hunched posture and piloerection. 

However no treatment-related findings in 

histopathology were present.

15-Day neurotox.-

CF-1 mice (gavage) 

L-930,905; a complex mixture of 

polar MK-244 

photodegradates)

 

42851507 (1993)

Acceptable 

0, 3, 6, 12, or 18 

mg/kg/day

NOAEL = 18 mg/kg/day (HDT)

No treatment-related effects were found.

16-Day neurotox.-

CF-1 mice (dietary)

MK-0243

42743630 (1992)

Acceptable

0, 0.05, 0.10, 0.30, or 

0.90 mg/kg/day

NOAEL = 0.1 mg/kg/day

LOAEL = 0.30 mg/kg/day based on tremors, 

decreased activity, and moribund sacrifice 

starting on day 2. However, no histopathology 

findings were present. 

15-Day neurotox.-

CF-1 mice (dietary)

Formyl amino 

derivative of MK0244

42868901 (1991)

Acceptable 

0, 0.050, 0.075, 0.100, 

& 0.300 mg/kg/day

NOAEL = 0.07 mg/kg/day

LOAEL = 0.23 mg/kg/day based on decreased 

body weight gain.

870.6300 Develop. Neurotox.-

rats (SD) (gavage 

for maternal 

animals; no direct 

dosing for neonates)

MK-0244

42851508 (1993)

Acceptable

0, 0.1, 0.6, 3.6/2.5 

mg/kg/day (3.6 mg/kg 

was reduced to 2.5 

mg/kg between GD 17 

and 20)

Maternal NOAEL=3.6/2.5 mg/kg/day (highest 

dose tested)

Develo. Neurotox. NOAEL=0.10 mg/kg/day 

Develo. Neurotox. LOAEL = 0.60 mg/kg/day 

based on the dose-related decrease in open field 

motor activity in females at postnatal day 17. 

870.7485 Metabolism –rats

[

14C] 4”-deoxy-4’-

epi-methylamino 

avermectin B1a 

benzoate, (MAB1a)

42851523 & 42852524

(1993)

Acceptable 

Radiolabeled MAB1a benzoate is rapidly 

absorbed, distributed and excreted following 

oral and i.v. administration. The feces was the 

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

while <1% of the administered dose was 

recovered in the urine 7 days post dosing. 
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

Page 50 of 62

Table A. 2. 3. Repeated Dosing and Other Studies on Emamectin

Guideline 

No

Study Type MRID No. (Year)/ 

Classification/Doses

Results

Tissue distribution and bioaccumulation 

appeared minimal. The metabolism of MAB1 a 

benzoate appears to involve primarily Ndemethylation to AB1a. AB1a was the only 

metabolite detected in the feces while 

unmetabolized parent compound represented a 

large amount of the radioactivity.

Bioequivalence -

Dog

MK-0243 

solvate vs. monohydrate

42743641(1992)

Supplemental

The study demonstrated that MK-0243 benzoate 

MTBE solvate and MK-0243 benzoate 

monohydrate were bioequivalent in male dogs 

following oral administration as indicated by 

similar plasma levels for the two compounds.

Bioequivalence-Dog

MK-0243 benzoate

vs. HCL salts

42743640 (1992)

Supplemental

The study demonstrated that benzoate and HCl 

salts are bioequivalent after oral administration 

in male beagle dogs.

870.7600 Dermal AbsorptionRhesus Monkey43850113 (1994) Dermal Absorption was approximated at 1.79% 

of the administered dose.

870.7800 Immunotoxicity 

study

Not available
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

Page 51 of 62

Appendix B. Physical/Chemical Properties

Table B. Physicochemical Properties of Emamectin Benzoate Technical II.

Parameter Value Reference

Molecular Weight emamectin benzoate B1a: 1008.26

emamectin benzoate B1b: 994.23

DP#335159, Indira 

Gairola, 8/7/07 

Melting point/range 141-146°C MRID #47002103

pH (at 25°C) 6-7

Density 1.20 g/cm3

Water solubility (21°C)

(average of emamectin B1a + emamectin B1b )

105 mg/L at pure water

101 mg/L at pH 5.0

93 mg/L at pH 7.0

No peaks were observed at pH 9.0.

Solvent solubility (25°C) Toluene 20.8 mg/mL

Cyclohexane 0.23 mg/mL

NMP 576 mg/mL

Acetone 140 g/L

Dichloromethane >500 g/L

Ethyl acetate 81 g/L

Hexane 77 g/L

Methanol 270 g/L

Octanol 48 g/L

Toluene 26 g/L

Vapor pressure (21°C) 3.0 x 10-8

torr or 3.0 x 10-8 mmHg

Dissociation constant, pKa 4.2 (benzoic acid)

7.6 (methyl-amino)

Octanol/water partition coefficient Shake Flask Method

Log Pow = 5.7 (emamectin B1a)

Log Pow = 5.2 (emamectin B1b)

UV/visible absorption (molar absorption 

coefficients at the absorbance maxima)

Neutral: 37,367 l/mol•cm at 245 nm

22,584 l/mol•cm at 245 nm

Acidic: 36,841 l/mol•cm at 245 nm

22,131 l/mol•cm at 245 nm

Basic: 28,952 l/mol•cm at 245 nm

No further absorption maximum 

between 280 and 750 nm was observed.

Aerobic soil metabolism half-life 90th Percentile on the mean: 107.5 days;

Mean of all of the values (used in SCIGROW): 79 days.
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

Page 52 of 62

Appendix C. 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 studies, which comprise the 

Pesticide Handlers Exposure Database (PHED) and the Agricultural Handler Exposure Task 

Force (AHETF), have been determined to require a review of their ethical conduct, have received 

that review, and have been determined to be ethical.

Studies reviewed for ethical conduct:

No MRID - PHED Surrogate Exposure Guide, Agricultural Handler Exposure Task Force

Studies reviewed by the Human Studies Review Board:

None
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

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Appendix D. Occupational Exposure/Risk Summary Tables

Table D.1. Short-Term Occupational Handler Non-Cancer Exposure and Risk Estimates for Emamectin Benzoate at Baseline PPE (single layer, no gloves, no respirator).

Exposure Scenario Crop or Target

Dermal 

Unit 

Exposurea

Inhalation 

Unit 

Exposurea

Maximum

Application 

Rateb

Area Treated 

or Amount 

Handled 

Dailyc

ST Dermal ST Inhalation

Combined

ST ARIh Dosed MOEe Dosef MOEg

μg/lb ai lb ai/A acres mg/kg/day LOC = 300 mg/kg/day LOC = 3000 LOC = 1

Mixer/Loader at Baseline PPE (single layer, no gloves, no respirator)

Mixing/Loading Dry Flowables for 

Groundboom Application

Cucurbit Vegetables

227 8.96 0.015

80 0.0000612 1,200 0.000135 560 0.18

Ornamentals (Nursery) 60 0.0000459 1,600 0.000101 740 0.24

Ornamentals (Field-Grown) 40 0.0000306 2,500 0.0000673 1,100 0.35

Mixing/Loading Dry Flowables for 

Aerial Application

Cucurbit Vegetables 350 0.000268 280 0.000588 130 0.041

Ornamentals (Nursery) 60 0.0000459 1,600 0.000101 740 0.24

Mixing/Loading Dry Flowables for 

Airblast Application Ornamentals (Nursery) 20 0.0000153 4,900 0.0000336 2,200 0.70

Applicator at Baseline PPE* (single layer, no gloves, no respirator)

Applying Sprays via 

Groundboom Equipment

Cucurbit Vegetables

78.6 0.34

0.015

80 0.0000212 3,500 0.00000510 15,000 3.5

Ornamentals (Nursery) 60 0.0000159 4,700 0.00000383 20,000 4.7

Ornamentals (Field-Grown) 40 0.0000106 7,100 0.00000255 29,000 6.9

Applying Sprays via 

Aerial Equipment*

Cucurbit Vegetables 5 0.068 350 0.00000592 13,000 0.00000446 17,000 5.0

Ornamentals (Nursery) 5 0.068 60 0.00000101 74,000 0.000000765 98,000 29

Applying Sprays via 

Airblast Equipment Ornamentals (Nursery) 1770 4.71 20 0.000119 630 0.0000176 4,300 0.85

Flagger at Baseline PPE (single layer, no gloves, no respirator)

Flagging for 

Aerial Application

Cucurbit Vegetables 11 0.35 0.015 350 0.000013 5,800 0.0000230 3,300 1.0

Ornamentals (Nursery) 60 0.00000223 34,000 0.0000000394 19,000 6.0

Mixer/Loader/Applicator at Baseline PPE (single layer, no gloves, no respirator)

M/L/A for 

Backpack Sprayer Ornamentals (Nursery) 13200 140

0.00030

lb ai/gal

40

gallons

0.0000356 2,100 0.0000210 3,600 1.0

8260 2.58 0.0000223 3,400 0.000000388 190,000 9.6

M/ L/A for 

Manually-Pressurized Handwand Ornamentals (Nursery) 100000 30 0.00027 280 0.00000450 17,000 0.8

M/L/A for

Mechanically-Pressurized Handgun Ornamentals (Nursery) 1300 3.9 1000gallons 0.0000878 850 0.0000146 5,100 1.1

a Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012). 

*Baseline aircraft = engineering controls.

b Based on registered and proposed label (Reg. No. 100-904 EnfoldTM Insecticide for cucurbit vegetables and 100-RURR Proclaim® Insecticide for ornamentals).

c Based on Exposure Science Advisory Council Policy No. 9.1.

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

Absorption Factor (%) ÷ Body Weight (80 kg). Dermal absorption factor = 1.8%.

e Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). ST Dermal NOAEL = 0.075 mg/kg/day. Dermal level of concern = 300.

f Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 

kg). No inhalation absorption factor (inhalation is equivalent to oral).

g Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST Inhalation NOAEL = 0.075 mg/kg/day. Inhalation level of concern = 3000.

h ST ARI = MOE / LOC. Combined ST ARI = 1 ÷ ((1/Dermal ARI) + (1/Inhalation ARI)). ARI level of concern = 1.
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

Page 54 of 62

Table D.2. Short-Term Occupational Handler Non-Cancer Exposure and Risk Estimates for Emamectin Benzoate with PPE Required on Labels.

a

Exposure Scenario Crop or Target

Dermal 

Unit 

Exposureb

Inhalation

Unit 

Exposureb

Maximum

Application 

Ratec

Area Treated 

or Amount 

Handled 

Dailyd

ST Dermal ST Inhalation

Combined

ST ARIi Dosee MOEf Doseg MOEh

μg/lb ai lb ai/A acres mg/kg/day LOC = 300 mg/kg/day LOC = 3000 LOC = 1

Ground Equipment Mixer/Loader with Label-Required PPE (single layer, gloves, no respirator)

Mixing/Loading Dry Flowables for 

Groundboom Application

Cucurbit Vegetables

51.6 8.96 0.015

80 0.0000139 5,400 0.0000135 560 0.18

Ornamentals (Nursery) 60 0.0000104 7,200 0.000101 740 0.24

Ornamentals (Field-Grown) 40 0.00000698 11,000 0.0000673 1,100 0.36

Mixing/Loading Dry Flowables for 

Airblast Application Ornamentals (Nursery) 20 0.00000349 21,000 0.0000336 2,200 0.73

Aerial Equipment Mixer/Loader with Label-Required PPE (double layer, gloves, PF5)

Mixing/Loading Dry Flowables for 

Aerial Application

Cucurbit Vegetables 41.2 1.792 0.015 350 0.0000486 1,500 0.000118 640 0.20

Ornamentals (Nursery) 60 0.00000835 9,000 0.0000201 3,700 1.2

Applicator with Label-Required PPE (single layer, gloves, no respirator)

Applying Sprays via 

Groundboom Equipment

Cucurbit Vegetables

16.1 0.34

0.015

80 0.00000434 17,000 0.00000510 15,000 4.6

Ornamentals (Nursery) 60 0.00000326 23,000 0.00000383 20,000 6.1

Ornamentals (Field-Grown) 40 0.00000217 35,000 0.00000255 29,000 8.9

Applying Sprays via 

Aerial Equipment*

Cucurbit Vegetables 5 0.068 350 0.00000592 74,000 0.00000446 17,000 5.0

Ornamentals (Nursery) 60 0.00000101 13,000 0.000000765 98,000 29

Applicator with Label-Required PPE (double layer, gloves, no respirator)

Applying Sprays via 

Open Cab Airblast Equipment Ornamentals (Nursery) 1480 4.71 0.015 20 0.0000999 750 0.0000176 4,300 0.91

Flagger at Baseline PPE (single layer, gloves, no respirator)

Flagging for 

Aerial Application

Cucurbit Vegetables 12 0.35 0.015 350 0.0000142 5,300 0.0000230 3,300 1.0

Ornamentals (Nursery) 60 0.00000243 31,000 0.00000394 19,000 6.0

Handheld Equipment with Label-Required PPE (single layer, gloves, no respirator)

M/L/A for 

Backpack Sprayer Ornamentals (Nursery) 13200 140

0.00030

lb ai/gal

40

gallons

0.0000302 2,500 0.0000210 3,600 1.0

8260 2.58 0.0000223 3,400 0.000000388 190,000 9.6

M/ L/A for 

Manually-Pressurized Handwand Ornamentals (Nursery) 430 30 0.00000116 65,000 0.00000450 17,000 5.5

M/L/A for

Mechanically-Pressurized Handgun Ornamentals (Nursery) 390 3.9 1000gallons 0.0000263 2,900 0.0000146 5,100 1.4

a PPE = Personal Protective Equipment. PPE based on registered and proposed labels. See Table D.7.

b Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012). 

*Baseline aircraft = engineering controls.

c Based on registered and proposed labels (Reg. No. 100-904 EnfoldTM Insecticide for cucurbit vegetables and 100-RURR Proclaim® Insecticide for ornamentals).

d Based on Exposure Science Advisory Council Policy No. 9.1.

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

Absorption Factor (%) ÷ Body Weight (80 kg). Dermal absorption factor = 1.8%.

f Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). ST Dermal NOAEL = 0.075 mg/kg/day. Dermal level of concern = 300.

g Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 

kg). No inhalation absorption factor (inhalation is equivalent to oral).

h Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST Inhalation NOAEL = 0.075 mg/kg/day. Inhalation level of concern = 3000.

i ST ARI = MOE / LOC. Combined ST ARI = 1 ÷ ((1/Dermal ARI) + (1/Inhalation ARI)). ARI level of concern = 1.
EMAMECTIN BENZOATE Human Health Risk Assessment DP No. D393837

Page 55 of 62

Table D.3. Short-Term Occupational Handler Non-Cancer Exposure and Risk Estimates for Emamectin Benzoate with PPE Required on Labels and Additional Mitigation.

a

Exposure Scenario Crop or Target

Dermal 

Unit 

Exposureb

Inhalation

Unit 

Exposureb

Maximum

Application 

Ratec

Area Treated 

or Amount 

Handled 

Dailyd

ST Dermal ST Inhalation

Combined

ST ARIi Dosee MOEf Doseg MOEh

μg/lb ai lb ai/A acres mg/kg/day LOC = 300 mg/kg/day LOC = 3000 LOC = 1

GROUND EQUIPMENT M/L OPTION 1: Mixer/Loader with Label-Required PPE + PF5 Respirator (single layer, gloves, PF5 respirator)

Mixing/Loading Dry Flowables for 

Groundboom Application

Ornamentals (Nursery)

51.6 1.792 0.015

60 0.0000104 7,200 0.0000201 3,700 1.2

Ornamentals (Field-Grown) 40 0.00000698 11,000 0.0000135 5,600 1.8

Mixing/Loading Dry Flowables for 

Airblast Application Ornamentals (Nursery) 20 0.00000349 21,000 0.00000673 11,000 3.5

GROUND EQUIPMENT M/L OPTION 1: Mixer/Loader with Label-Required PPE + PF10 Respirator (single layer, gloves, PF10 respirator)

Mixing/Loading Dry Flowables for 

Groundboom Application Cucurbit Vegetables 51.6 0.896 0.015 80 0.0000139 5,400 0.0000135 5,600 1.7

GROUND EQUIPMENT M/L OPTION 2: Mixer/Loader with EC (engineering control of closed packaging)

Mixing/Loading Dry Flowables for 

Groundboom Application

Cucurbit Vegetables

9.8 0.24 0.015

80 0.00000266 28,000 0.00000360 21,000 6.5

Ornamentals (Nursery) 60 0.00000198 38,000 0.00000270 28,000 8.7

Ornamentals (Field-Grown) 40 0.00000132 57,000 0.00000180 42,000 13

Mixing/Loading Dry Flowables for 

Airblast Application Ornamentals (Nursery) 20 0.000000662 110,000 0.000000900 83,000 26

AERIAL EQUIPMENT M/L ONLY OPTION: Mixer/Loader with EC (engineering control of closed packaging)

Mixing/Loading Dry Flowables for 

Aerial Application Cucurbit Vegetables 9.8 0.24 0.015 350 0.0000116 6,500 0.0000158 4,700 1.5

AIRBLAST APP OPTION 1: Applicator with Label-Required PPE + PF5 Respirator (double layer, gloves, PF5 respirator)

Applying Sprays via 

Open Cab Airblast Equipment Ornamentals (Nursery) 1480 0.942 0.015 20 0.0000999 750 0.00000354 21,000 1.8

AIRBLAST APP OPTION 2: Applicator with EC (engineering control of closed cab equipment)

Applying Sprays via 

Closed Cab Airblast Equipment Ornamentals (Nursery) 14.6 0.068 0.015 20 0.000000986 76,000 0.000000255 290,000 70

a PPE = Personal Protective Equipment. PPE based on registered and proposed labels. See Table d.7.

b Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012).

c Based on registered and proposed labels (Reg. No. 100-904 EnfoldTM Insecticide for cucurbit vegetables and 100-RURR Proclaim® Insecticide for ornamentals).

d Based on Exposure Science Advisory Council Policy No. 9.1.

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

Absorption Factor (%) ÷ Body Weight (80 kg). Dermal absorption factor = 1.8%.

f Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). ST Dermal NOAEL = 0.075 mg/kg/day. Dermal level of concern = 300.

g Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 

kg). No inhalation absorption factor (inhalation is equivalent to oral).

h Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST Inhalation NOAEL = 0.075 mg/kg/day. Inhalation level of concern = 3000.

i ST ARI = MOE / LOC. Combined ST ARI = 1 ÷ ((1/Dermal ARI) + (1/Inhalation ARI)). ARI level of concern = 1.
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Table D.4. Intermediate-Term Occupational Handler Non-Cancer Exposure and Risk Estimates for Emamectin Benzoate at Baseline PPE (single layer, no gloves, no respirator).

Exposure Scenario Crop or Target

Dermal 

Unit 

Exposurea

Inhalation 

Unit 

Exposurea

Maximum

Application 

Rateb

Area Treated 

or Amount 

Handled 

Dailyc

IT Dermal IT Inhalation

Combined

IT ARIh Dosed MOEe Dosef MOEg

μg/lb ai lb ai/A acres mg/kg/day LOC = 1000 mg/kg/day LOC = 3000 LOC = 1

Mixer/Loader at Baseline PPE (single layer, no gloves, no respirator)

Mixing/Loading Dry Flowables for 

Groundboom Application

Cucurbit Vegetables

227 8.96 0.015

80 0.0000612 1,200 0.000135 560 0.16

Ornamentals (Nursery) 60 0.0000459 1,600 0.000101 740 0.21

Ornamentals (Field-Grown) 40 0.0000306 2,500 0.0000673 1,100 0.32

Mixing/Loading Dry Flowables for 

Aerial Application

Cucurbit Vegetables 350 0.000268 280 0.000588 130 0.038

Ornamentals (Nursery) 60 0.0000459 1,600 0.000101 740 0.21

Mixing/Loading Dry Flowables for 

Airblast Application Ornamentals (Nursery) 20 0.0000153 4,900 0.0000336 2,200 0.64

Applicator at Baseline PPE* (single layer, no gloves, no respirator)

Applying Sprays via 

Groundboom Equipment

Cucurbit Vegetables

78.6 0.34

0.015

80 0.0000212 3,500 0.00000510 15,000 2.1

Ornamentals (Nursery) 60 0.0000159 4,700 0.00000383 20,000 2.8

Ornamentals (Field-Grown) 40 0.0000106 7,100 0.00000255 29,000 4.1

Applying Sprays via 

Aerial Equipment*

Cucurbit Vegetables 5 0.068 350 0.00000592 74,000 0.00000446 17,000 3.9

Ornamentals (Nursery) 5 0.068 60 0.00000101 13,000 0.000000765 98,000 23

Applying Sprays via 

Airblast Equipment Ornamentals (Nursery) 1770 4.71 20 0.000119 630 0.0000176 4,300 0.44

Flagger at Baseline PPE (single layer, no gloves, no respirator)

Flagging for 

Aerial Application

Cucurbit Vegetables 11 0.35 0.015 350 0.000013 5,800 0.0000230 3,300 0.92

Ornamentals (Nursery) 60 0.00000223 34,000 0.0000000394 19,000 5.3

Mixer/Loader/Applicator at Baseline PPE (single layer, no gloves, no respirator)

M/L/A for 

Backpack Sprayer Ornamentals (Nursery) 13200 140

0.00030

lb ai/gal

40

gallons

0.0000356 2,100 0.0000210 3,600 0.76

8260 2.58 0.0000223 3,400 0.000000388 190,000 3.2

M/ L/A for 

Manually-Pressurized Handwand Ornamentals (Nursery) 100000 30 0.00027 280 0.00000450 17,000 0.27

M/L/A for

Mechanically-Pressurized Handgun Ornamentals (Nursery) 1300 3.9 1000gallons 0.0000878 850 0.0000146 5,100 0.57

a Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012). 

*Baseline aircraft = engineering controls.

b Based on registered and proposed label (Reg. No. 100-904 EnfoldTM Insecticide for cucurbit vegetables and 100-RURR Proclaim® Insecticide for ornamentals).

c Based on Exposure Science Advisory Council Policy No. 9.1.

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

Absorption Factor (%) ÷ Body Weight (80 kg). Dermal absorption factor = 1.8%.

e Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). IT Dermal NOAEL = 0.075 mg/kg/day. Dermal level of concern = 1000.

f Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 

kg). No inhalation absorption factor (inhalation is equivalent to oral).

g Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). IT Inhalation NOAEL = 0.075 mg/kg/day. Inhalation level of concern = 3000.

h IT ARI = MOE / LOC. Combined ARI = 1 ÷ ((1/Dermal ARI) + (1/Inhalation ARI)). ARI level of concern = 1.
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Table D.5. Intermediate-Term Occupational Handler Non-Cancer Exposure and Risk Estimates for Emamectin Benzoate with PPE Required on Labels.

a

Exposure Scenario Crop or Target

Dermal 

Unit 

Exposureb

Inhalation

Unit 

Exposureb

Maximum

Application 

Ratec

Area Treated 

or Amount 

Handled 

Dailyd

IT Dermal IT Inhalation

Combined

IT ARIi Dosee MOEf Doseg MOEh

μg/lb ai lb ai/A acres mg/kg/day LOC = 1000 mg/kg/day LOC = 3000 LOC = 1

Ground Equipment Mixer/Loader with Label-Required PPE (single layer, gloves, no respirator)

Mixing/Loading Dry Flowables for 

Groundboom Application

Cucurbit Vegetables

51.6 8.96 0.015

80 0.0000139 5,400 0.000135 560 0.18

Ornamentals (Nursery) 60 0.0000104 7,200 0.000101 740 0.24

Ornamentals (Field-Grown) 40 0.00000698 11,000 0.0000673 1,100 0.35

Mixing/Loading Dry Flowables for 

Airblast Application Ornamentals (Nursery) 20 0.00000349 21,000 0.0000336 2,200 0.71

Aerial Equipment Mixer/Loader with Label-Required PPE (double layer, gloves, PF5)

Mixing/Loading Dry Flowables for 

Aerial Application

Cucurbit Vegetables 41.2 1.792 0.015 350 0.0000486 1,500 0.000118 640 0.19

Ornamentals (Nursery) 60 0.00000835 9,000 0.0000201 3,700 1.1

Applicator with Label-Required PPE (single layer, gloves, no respirator)

Applying Sprays via 

Groundboom Equipment

Cucurbit Vegetables

16.1 0.34

0.015

80 0.00000434 17,000 0.00000510 15,000 3.9

Ornamentals (Nursery) 60 0.00000326 23,000 0.00000383 20,000 5.2

Ornamentals (Field-Grown) 40 0.00000217 35,000 0.00000255 29,000 7.6

Applying Sprays via 

Aerial Equipment*

Cucurbit Vegetables 5 0.068 350 0.00000592 13,000 0.00000446 17,000 3.9

Ornamentals (Nursery) 60 0.00000101 74,000 0.000000765 98,000 23

Applicator with Label-Required PPE (double layer, gloves, no respirator)

Applying Sprays via 

Open Cab Airblast Equipment Ornamentals (Nursery) 1480 4.71 0.015 20 0.0000999 750 0.0000176 4,300 0.49

Flagger at Label-Required PPE (single layer, gloves, no respirator)

Flagging for 

Aerial Application

Cucurbit Vegetables 12 0.35 0.015 350 0.0000142 5,300 0.0000230 3,300 0.91

Ornamentals (Nursery) 60 0.00000243 31,000 0.00000394 19,000 5.3

Handheld Equipment with Label-Required PPE (single layer, gloves, no respirator)

M/L/A for 

Backpack Sprayer Ornamentals (Nursery) 11200 140

0.00030

lb ai/gal

40

gallons

0.0000302 2,500 0.0000210 3,600 0.81

8260 2.58 0.0000223 3,400 0.000000388 190,000 3.2

M/ L/A for 

Manually-Pressurized Handwand Ornamentals (Nursery) 430 30 0.00000116 65,000 0.00000450 17,000 5.2

M/L/A for

Mechanically-Pressurized Handgun Ornamentals (Nursery) 390 3.9 1000gallons 0.0000263 2,900 0.0000146 5,100 1.1

a PPE = Personal Protective Equipment. PPE based on registered and proposed labels. See Table D.7.

b Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012). 

*Baseline aircraft = engineering controls.

c Based on registered and proposed labels (Reg. No. 100-904 EnfoldTM Insecticide for cucurbit vegetables and 100-RURR Proclaim® Insecticide for ornamentals).

d Based on Exposure Science Advisory Council Policy No. 9.1.

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

Absorption Factor (%) ÷ Body Weight (80 kg). Dermal absorption factor = 1.8%.

f Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). ST Dermal NOAEL = 0.075 mg/kg/day. Dermal level of concern = 300.

g Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 

kg). No inhalation absorption factor (inhalation is equivalent to oral).

h Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST Inhalation NOAEL = 0.075 mg/kg/day. Inhalation level of concern = 3000.

i IT ARI = MOE / LOC. Combined ST ARI = 1 ÷ ((1/Dermal ARI) + (1/Inhalation ARI)). ARI level of concern = 1.
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Table D.6. Intermediate-Term Occupational Handler Non-Cancer Exposure and Risk Estimates for Emamectin Benzoate with PPE Required on Labels and Recommended Mitigation.

a

Exposure Scenario Crop or Target

Dermal 

Unit 

Exposureb

Inhalation

Unit 

Exposureb

Maximum

Application 

Ratec

Area Treated 

or Amount 

Handled 

Dailyd

IT Dermal IT Inhalation

Combined

IT ARIi Dosee MOEf Doseg MOEh

μg/lb ai lb ai/A acres mg/kg/day LOC = 1000 mg/kg/day LOC = 3000 LOC = 1

GROUND EQUIPMENT M/L OPTION 1: Mixer/Loader with Label-Required PPE + PF5 Respirator (single layer, gloves, PF5 respirator)

Mixing/Loading Dry Flowables for 

Groundboom Application

Ornamentals (Nursery)

51.6 1.792 0.015

60 0.0000104 7,200 0.0000201 3,700 1.1

Ornamentals (Field-Grown) 40 0.00000698 11,000 0.0000135 5,600 1.6

Mixing/Loading Dry Flowables for 

Airblast Application Ornamentals (Nursery) 20 0.00000349 21,000 0.00000673 11,000 3.1

GROUND EQUIPMENT M/L OPTION 1: Mixer/Loader with Label-Required PPE + PF10 Respirator (single layer, gloves, PF10 respirator)

Mixing/Loading Dry Flowables for 

Groundboom Application Cucurbit Vegetables 51.6 0.896 0.015 80 0.0000139 5,400 0.0000135 5,600 1.4

GROUND EQUIPMENT M/L OPTION 2: Mixer/Loader with EC (engineering control of closed packaging)

Mixing/Loading Dry Flowables for 

Groundboom Application

Cucurbit Vegetables

9.8 0.24 0.015

80 0.00000266 28,000 0.00000360 21,000 5.6

Ornamentals (Nursery) 60 0.00000198 38,000 0.00000270 28,000 7.5

Ornamentals (Field-Grown) 40 0.00000132 57,000 0.00000180 42,000 11

Mixing/Loading Dry Flowables for 

Airblast Application Ornamentals (Nursery) 20 0.000000662 110,000 0.000000900 83,000 22

AERIAL EQUIPMENT M/L ONLY OPTION: Mixer/Loader with EC (engineering control of closed packaging)

Mixing/Loading Dry Flowables for 

Aerial Application Cucurbit Vegetables 9.8 0.24 0.015 350 0.0000116 6,500 0.0000158 4,700 1.3

AIRBLAST APP ONLY OPTION: Applicator with EC (engineering control of closed cab equipment)

Applying Sprays via 

Closed Cab Airblast Equipment Ornamentals (Nursery) 14.6 0.068 0.015 20 0.000000986 76,000 0.000000255 290,000 43

FLAGGER at Label-Required PPE + PF5 Respirator (single layer, gloves, PF5 respirator)

Flagging for 

Aerial Application Cucurbit Vegetables 12 0.07 0.015 350 0.0000142 5,300 0.00000460 16,000 2.7

HANDHELD EQUIPMENT with Label-Required PPE + PF5 Respirator (single layer, gloves, PF5 respirator)

M/L/A for 

Backpack Sprayer Ornamentals (Nursery) 11200 28 0.00030lb ai/gal

40

gallons 0.0000302 2,500 0.00000420 18,000 1.8

a PPE = Personal Protective Equipment. PPE based on registered and proposed labels. See Table.

b Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012).

c Based on registered and proposed labels (Reg. No. 100-904 EnfoldTM Insecticide for cucurbit vegetables and 100-RURR Proclaim® Insecticide for ornamentals).

d Based on Exposure Science Advisory Council Policy No. 9.1.

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

Absorption Factor (%) ÷ Body Weight (80 kg). Dermal absorption factor = 1.8%.

f Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). ST Dermal NOAEL = 0.075 mg/kg/day. Dermal level of concern = 300.

g Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 

kg). No inhalation absorption factor (inhalation is equivalent to oral).

h Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). ST Inhalation NOAEL = 0.075 mg/kg/day. Inhalation level of concern = 3000.

i IT ARI = MOE / LOC. Combined ST ARI = 1 ÷ ((1/Dermal ARI) + (1/Inhalation ARI)). ARI level of concern = 1.
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Table D.7. Short- and Intermediate-Term Post-Application Exposures and Risk Estimates for Emamectin

Benzoate for Commercially Grown Outdoor Ornamentals (Field- and Container-Grown)aand 

Cucurbit Vegetables (Crop Group 9).

Activity Transfer

Coefficient

Days After 

Treatment

DFR b Daily Dermal 

Dose c

Dermal

MOE d

μg/cm2 mg/kg/day ST LOC = 300

IT LOC = 1000

irrigation (hand set)

[ornamentals and CG9] 1,900

0

(12 hours) 0.0421 0.000144 520

1 0.0378 0.000129 580

2 0.0341 0.000116 640

3 0.0307 0.000105 720

4 0.0276 0.000094 790

5 0.0248 0.000085 880

6 0.0223 0.000076 980

7 0.0201 0.000069 1,100

harvesting

[ornamentals] 1,400

0

(12 hours) 0.0421 0.000106 710

1 0.0378 0.000095 790

2 0.0341 0.000086 870

3 0.0307 0.000077 970

4 0.0276 0.000070 1,100

scouting, shaping

[ornamentals] 580 0(12 hours) 0.0421 0.000044 1,700

hand harvesting, turning, training, 

mechanical harvesting

[CG9]

550 0

(12 hours) 0.0421 0.000042 1,800

hand harvesting, hand pruning, scouting, 

container moving, hand weeding, 

transplanting, grafting, propagating, 

pinching, tying/training

[ornamentals]

230 0

(12 hours) 0.0421 0.000017 4,300

transplanting

[CG9] 230 0(12 hours) 0.0421 0.000017 4,300

hand weeding, grading/tagging

[ornamentals] 100 0(12 hours) 0.0421 0.0000076 9,900

scouting, hand weeding, hand pruning, 

thinning fruit

[CG9]

90 0

(12 hours) 0.0421 0.0000068 11,000

a These values in this table have been updated since the ORE (N. Tsaur, DP390788, 12/07/2011) to reflect policy changes in 

body weight and day 0 residue assumptions.

b DFR (μg/cm2) = application rate (0.015 lb ai/acre) x fraction of application rate dislodgeable on day 0 (25%) x (1 - fraction of 

residue that dissipates daily 10%)tx 4.54E8 μg/lb x 2.47E-8 acre/cm2.

c Short-/Intermediate-Term Daily Dermal Dose = [DFR (μg/cm2) x Transfer Coefficient x 0.001 mg/μg x 8 hrs/day x dermal 

absorption 1.8%] body weight (80 kg adult).

d Short-/Intermediate-Term MOE = NOAEL (mg/kg/day)/Daily Dermal Dose (mg/kg/day). ST/IT NOAEL = 0.075 mg/kg/day. 

Short-term level of concern = 300. Intermediate-term level of concern = 1000.
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Appendix E. International Tolerances

Emamectin Benzoate (122806; 08/06/2012)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.505:

Plant: Combined residues of emamectin (a 

mixture of a minimum of 90% 4'-epimethylamino-4'-deoxyavermectin B1aand 

maximum of 10% 4'-epi-methylamino-4'-

deoxyavermectin B1b) and its metabolites 8,9-

isomer of the B1aand B1bcomponent of the parent 

(8,9-ZMA), or 4'-deoxy-4'-epi-amino-avermectin 

B1aand 4'-deoxy-4'-epi-amino-avermectin B1b; 4'-

deoxy-4'-epi-amino avermectin B1a(AB1a); 4'-

deoxy-4'-epi-(N-formyl-N-methyl)aminoavermectin (MFB1a); and 4'-deoxy-4'-epi-(Nformyl)amino-avermectin B1a(FAB1a).

Livestock: Combined residues of emamectin 

(MAB1a+ MAB1bisomers) and the associated 8,9-

Z isomers (8,9-ZB1a+ 8,9-ZB1b).

None Plants: emamectin 

B1a benzoate, 

expressed as

emamectin (free 

base).

animal commodities: 

emamectin B1a 

benzoate, expressed

as emamectin (free 

base).

The residue is not fatsoluble.

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

US Canada Mexico2 Codex3

Vegetable, cucurbit, group 9 0.02

0.007 fruiting 

vegetables, cucurbits

(proposed)

Completed: M. Negussie; 08/20/2012

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.
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Appendix F. Toxicology Literature References 

Dawson GR, Wafford KA, Smith A, Marshall GR, Bayley PJ, Schaeffer JM, Meinke PT, 

McKernan RM. (2000) Anticonvulsant and adverse effects of avermectin analogs in mice 

are mediated through the gama-aminobutyric acid (A) receptor. J. Pharmacol. Exp. Ther.

295: 1051-1060.

Huang J, Casida JE. (1997) Avermectin B1a binds to high- and low-affinity sites with dual 

effects on the gama-aminobutyric acid-gated chloride channel of cultured cerebellar 

granule neurons. J. Pharmacol. Exp. Ther. 281: 261-266.

Kerb R (2006) Implication of genetic polymorphism in drug transporters for pharmacotherapy.

Cancer Lett. 234: 4-33.

Kerr DI and Ong J. (1986) Gama-aminobutyric acid-dependent motility induced by avermectin 

B1a in the isolated intestine of the guinea pigs. Neurosci. Lett. 65: 7-10.

Lankas GR, Cartwright ME, and Umbenhauer D (1997) P-Glycoprotein deficiency in a 

subpopulation of CF-1 mice enhances avermectin-induced neurotoxicity. Toxicol. and 

Appl. Pharmacol. 143: 357-365.

Marzolini C, Paus E, Buclin T, and Kim RB (2004) Polymorphism I human MDR1 (Pglycoprotein): Recent advances and clinical relevance. Clin. Pharmacol. and Ther. 

75: 13-33.

Meister B. (2007) Neurotransmitters in key neurons of the hypothalamus that regulate feeding 

behavior and body weight. Physiol. Behav. 92: 263-271.

Nguyen L, Rigo JM, Rocher V, Belachew S, Malgrange B, Rogister B, Leprince P, Moonen G.

(2001) Neurotransmitters as early signals for central nervous system development. Cell 

Tissue Res. 305: 187-202.

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

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

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
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Wang CC, Pong SS. (1982) Actions of avermectin B1a on GABA nerves. Prog. Clin. Biol. Res. 

97: 373-395.