Acetamiprid DP No.: 369474

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Dec 1, 2009

MEMORANDUM

SUBJECT: Acetamiprid: Human Health Risk Assessment for Proposed Food Uses on Clover

Grown for Seed, Small Vine Climbing Fruits, except Kiwifruit, Subgroup 13-07F, 

Greenhouse Grown Tomatoes and Tea. 

PC Code: 099050 DP Barcode: D369474

Decision No.: 408298 Registration Nos.: 8033-23, 8033-36, 8033-94

Petition No.: 9E7544 Regulatory Action: Amended Section 3

Risk Assessment Type: Single Chemical 

Aggregate

Case No.: N/A

TXR No.: N/A CAS No.: 135410-20-7

MRID Nos.: N/A 40 CFR: §180.578

FROM: Dennis McNeilly, Chemist

Suku Oonnithan, Biologist

Edward J. Scollon, Ph.D., Toxicologist

Registration Action Branch 2

Health Effects Division (7509P)

THROUGH: Mike Doherty, Ph.D, Senior Chemist

Alan Levy, Ph.D., Senior Toxicologist

Shih-Chi Wang, Biologist

and

Christina Swartz, Branch Chief

Richard Loranger, Ph.D., Senior Scientist

Registration Action Branch 2

Health Effects Division (7509P)

TO: Laura Nollen, Risk Manager Reviewer

Barbara Madden, Team Leader (RM Team 5)

RIMUERB/Registration Division (RD) (7505P)
Acetamiprid DP No.: 369474

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Table of Contents

1.0 Executive Summary............................................................................................................... 4

1.1 Summary of Recommendations............................................................................................... 7

1.2 Summary of Proposed Uses..................................................................................................... 8

2.0 Ingredient Profile................................................................................................................. 11

3.0 Hazard Characterization/Assessment........................................................................... 12

3.1 Hazard and Dose-Response Characterization....................................................... 12

3.1.1 Database Summary ................................................................................... 12

3.1.1.1 Studies available and considered (animal, human, general 

literature)....................................................................................... 12

3.1.1.2 Mode of action .............................................................................. 12

3.1.1.3 Sufficiency of studies/data............................................................ 13

3.1.2 Toxicological Effects................................................................................ 13

3.1.3 Dose-response ........................................................................................... 15

3.1.4 FQPA 15

3.2 Absorption, Distribution, Metabolism, Excretion (ADME)................................. 16

3.3 FQPA Considerations ........................................................................................... 16

3.3.1 Adequacy of the Toxicity Database.......................................................... 16

3.3.2 Evidence of Neurotoxicity ........................................................................ 16

3.3.3 Developmental Toxicity Studies............................................................... 17

3.3.4 Reproductive Toxicity Study .................................................................... 17

3.3.5 Additional Information from Literature Sources...................................... 17

3.3.6 Pre-and/or Postnatal Toxicity ................................................................... 17

3.3.6.1 Determination of Susceptibility.................................................... 17

3.3.6.2 Degree of Concern Analysis and Residual Uncertainties for Preand/or Postnatal Susceptibility...................................................... 17

3.3.7 Recommendation for a Developmental Neurotoxicity Study................... 18

3.4 Safety Factor for Infants and Children.................................................................. 18

3.5 Hazard Identification and Toxicity Endpoint Selection........................................ 19

3.5.1 Acute Reference Dose (aRfD) - Females age 13-49................................. 19

3.5.2 Acute Reference Dose (aRfD) - General Population................................ 19

3.5.3 Chronic Reference Dose (cRfD)............................................................... 19

3.5.4 Incidental Oral Exposure (Short- and Intermediate-Term)....................... 20

3.5.5 Dermal Absorption.................................................................................... 20

3.5.6 Dermal Exposure (Short-, Intermediate- and Long-Term)....................... 21

3.5.7 Inhalation Exposure (Short-, Intermediate- and Long-Term)................... 22

3.5.8 Level of Concern for Margin of Exposure................................................ 23

3.5.9 Recommendation for Aggregate Exposure Risk Assessments................. 24

3.5.10 Classification of Carcinogenic Potential................................................... 24

3.5.11 Summary of Toxicological Doses and Endpoints for Use in Human Risk 

Assessments.............................................................................................. 25

3.6 Endocrine disruption............................................................................................. 27

4.0 Public Health and Pesticide Epidemiology Data.......................................................... 27

4.1 Other Pesticide Epidemiology Published Literature............................................. 27
Acetamiprid DP No.: 369474

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5.0 Dietary Exposure/Risk Characterization ..................................................................... 27

5.1 Pesticide Metabolism and Environmental Degradation........................................ 27

5.1.1 Metabolism in Primary Crops................................................................... 27

5.1.2 Metabolism in Rotational Crops............................................................... 27

5.1.3 Metabolism in Livestock........................................................................... 28

5.1.4 Analytical Methodology ........................................................................... 28

5.1.5 Environmental Degradation...................................................................... 29

5.1.6 Comparative Metabolic Profile................................................................. 29

5.1.7 Pesticide Metabolites and Degradates of Concern.................................... 30

5.1.8 Drinking Water Residue Profile................................................................ 30

5.1.9 Food Residue Profile................................................................................. 31

5.1.10 International Residue Limits..................................................................... 37

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

6.1 Residential Handler Exposure............................................................................... 41

6.2. Residential Postapplication Exposure................................................................... 41

6.3 Other (Spray Drift, etc.)........................................................................................ 43

7.0 Aggregate Risk Assessments and Risk Characterization............................................ 43

7.1 Acute Term Aggregate Risk ................................................................................. 43

7.2 Short- and Intermediate-Term Aggregate Risk..................................................... 43

7.3 Chronic-Term Aggregate Risk.............................................................................. 44

8.0 Cumulative Risk Characterization/Assessment........................................................... 45

9.0 Occupational Exposure/Risk Pathway.......................................................................... 46

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

9.2 Handler and Pesticide Control Operator Risk Characterization ........................... 46

9.3 Postapplication Exposure and Risk....................................................................... 46

10.0 Data Needs and Label Recommendations.................................................................... 47

References:................................................................................................................................... 48

Appendix A: Occupational Exposure and Risk Tables.............................................. 50

Appendix B: Toxicology Assessment ........................................................................... 57

Appendix C: Tolerance Summary................................................................................ 62

Appendix D: International Residue Limit Status....................................................... 63
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1.0 Executive Summary

Acetamiprid {N 1-[(6-chloro-3-pyridyl)methyl]-N

2

-cyano-N 1-methylacetamidine} is a 

chloronicotinyl insecticide registered to control sucking type insects (e.g., aphids, whitefly, etc.) 

on a wide variety of crops including cotton, leafy vegetables, fruiting vegetables, and citrus 

fruits. Tolerances are established for acetamiprid residues in assorted crops and livestock 

commodities under 40 CFR §180.578. The majority of the agricultural uses are for broadcast 

foliar spray (via ground or aerial equipment), but there are also registered seed treatment uses on 

mustard and canola. Ready-to-use, bait, and water soluble packet formulations are registered for 

residential uses. The Interregional Research Project Number 4 (IR-4) has submitted amended 

Section 3 registration requests for new uses of acetamiprid on clover grown for seed, small vine 

climbing fruits, except kiwifruit, subgroup 13-07F (amending the established grape use),

greenhouse-grown tomatoes, and tea. Tea was not included in the original petition, but was 

added in a June 10, 2009 letter from IR-4 stating that the tolerance was submitted to support both 

tea grown in South Carolina and tea imported into the U.S.

The acute toxicity data indicate that acetamiprid is moderately toxic via the oral route and is 

minimally toxic via the dermal and inhalation routes. Acetamiprid is not an eye or skin irritant, 

and it is not a dermal sensitizer. The toxicological database for acetamiprid is not complete. As 

part of the new 40 CFR Part 158 guidelines, an immunotoxicity study in rats and/or mice is 

required. However, a database uncertainty factor is not needed because acetamiprid does not 

show any evidence of treatment-related effects on the immune system. The overall weight of 

evidence suggests that this chemical does not directly target the immune system and the Agency

does not believe that conducting a functional immunotoxicity study will result in a lower point of 

departure (POD) than that currently used for overall risk assessment. Based on subchronic, 

chronic, developmental and reproductive studies in rats, rabbits, and dogs, acetamiprid does not 

appear to have specific target organ toxicity. An acceptable developmental neurotoxicity (DNT) 

study has been submitted and reviewed.

Developmental studies showed no evidence of either quantitative or qualitative susceptibility of 

the rat or rabbit fetuses from in utero exposure. However, both the DNT study and the multigeneration reproduction studies showed an increase in qualitative susceptibility of pups; effects 

in pups consisted of decreased pup viability, and maternal toxicity consisted of decreased body

weight and body weight gain. HED has reduced the FQPA Safety Factor to 1X, because: (i) the 

endpoints selected for risk assessment are based upon the effects of concern in offspring; (ii) 

there is a clear NOAEL for the offspring effects; and, (iii) HED has no residual uncertainties

with regards to pre- and postnatal toxicity. HED has determined that acetamiprid is not likely to 

be carcinogenic to humans.

With the exception of chronic dietary, HED has chosen the NOAEL (10 mg/kg/day) from the 

DNT study (LOAEL = 45 mg/kg/day) as the endpoint and dose for dietary, non-occupational and 

occupational risk assessments for all durations and all routes of exposure. For the chronic 

dietary assessment, HED has chosen the NOAEL (7.1 mg/kg/day) from the chronic toxicity/

carcinogenicity study (LOAEL = 17.5 mg/kg/day).
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HED has used the refined dermal penetration value of 10%. The default 100% absorption factor 

was used for all inhalation exposure scenarios.

The nature of the residue is adequately understood for both plants and animals, and an acceptable 

method validation has been submitted. Acceptable residue data have been submitted to support 

the proposed uses as well as the tolerances recommended in Appendix C. The submitted clover 

field trial data are not completely adequate to satisfy data requirements. The three clover field 

trials were all conducted in Zone 11 (OR) at the same location and within a very short time 

period of each other. As a condition of registration, HED recommends that two additional clover 

field trials be required, as confirmatory data. In addition, the submitted reside data included field 

trial data for only the 70WP formulation. However, additional residue chemistry field trial data 

are not required to support registration of the 30SG formulation. Since the residue chemistry

data submitted for clover hay reflect PHIs of between 56-63 days, the PHI for clover should be 

increased to 56 days for any crop which will be harvested for hay.

The submitted grape residue data included field trial data for only the 70WP formulation 

(original field trials also used only a 70WP formulation). Although HED’s residue chemistry

review (D364833, 10/14/09) recommended that as a condition of registration, three side-by-side 

field trials be conducted and submitted to determine if residues are comparable for the two 

different formulations, additional information provided by the registrant has convinced HED 

such data are not necessary. In addition, the submitted grape field trials were not conducted 

using an adjuvant. The label for Assail® 30SG (EPA Reg. No. 8033-36) should be revised to 

remove the use of a spreader, methylated seed oil or crop oil from the product label. 

Furthermore, in line with present OPP policy for a late season foliar use, a statement should be 

added to both the 30SG and 70WP labels prohibiting addition of adjuvants for application to 

grapes. If use of an adjuvant is desired then one should be used in side-by-side testing.

Although the greenhouse trials were conducted at a 2x rate and the number of trials is marginal, 

no additional residue data will be required to support the proposed greenhouse use pattern for 

tomatoes. The tomato greenhouse data indicate that acetamiprid residues resulting from 

applications of Assail 70WP formulation of acetamiprid according to the proposed use pattern 

would not exceed the established tolerance for residues of acetamiprid in fruiting vegetables, 

Crop Group 8 (0.20 ppm). Although no data were provided for the proposed use of Tristar® 

30SG on greenhouse tomatoes, HED now concludes the WP data support use of this additional 

formulation.

The submitted magnitude of the residue data for tea reflect application of a 20% SP formulation 

of acetamiprid to green tea grown in Japan at 0.13 lb ai/A (0.15 kg ai/ha) and 0.27 lb ai/A (0.30 

kg ai/ha) and to black tea grown in India at 0.022 lb ai/A (0.025 kg ai/ha) and 0.045 lb ai/A 

(0.050 kg ai/ha). Acceptable methods were used for determination residues of acetamiprid and 

metabolites determined as acetamiprid. No U.S. residue field trial data were submitted and 

proposed domestic use directions were not provided. At least one U.S. residue field trial study is 

required to establish a domestic registration for use of acetamiprid on tea.

The dietary assessment is partially refined, using field trial data, percent crop-treated values, and 

various empirical processing factors. Estimated drinking water concentrations (EDWCs), which 
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are based upon the highest application values of all registered and proposed uses, have been

incorporated directly into the dietary exposure model. Acute and chronic dietary risk estimates 

for all population subgroups do not indicate a risk of concern. Children 1-2 years old are the 

highest exposed population subgroup for both acute and chronic exposure scenarios. Acute 

exposure constitutes 41% of the acute population adjusted dose (aPAD), and the chronic

exposure constitutes 12% of the chronic population adjusted dose (cPAD).

Aggregate risk assessments for acute, short-term, and chronic durations were conducted.

Residential exposures incorporated into the aggregate assessments are based on currently 

registered residential uses (indoor crack and crevice, and outdoor perimeter treatment). All 

aggregate assessments indicate no risks of concern (aggregate MOEs ≥ 290).

Occupational handler (mixer/loaders, applicators, and flaggers) assessments were conducted for 

the proposed agricultural uses of acetamiprid. HED’s assessment indicates that exposures to 

occupational handlers are not a risk concern, provided they wear baseline personal protective 

equipment (PPE) consisting of long-sleeved shirt, long pants, and shoes with socks plus gloves

(MOEs > 280). HED identified no post-application risk concerns (MOEs > 330) for the 

proposed uses on the day of application, and set the restricted entry interval (REI) at 12 hours 

based upon the acute toxicity categories of acetamiprid.

Environmental Justice Considerations

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

human health risk assessment, in accordance with US Executive Order 12898, Federal Actions to 

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

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

As a part of every pesticide risk assessment, OPP considers a large variety of consumer 

subgroups according to well-established procedures. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup’s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

by USDA under the CSFII, and are used in pesticide risk assessments for all registered food uses 

of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the 

year, ethnic group, and region of the country. Whenever appropriate, non-dietary exposures 

based on home use of pesticide products, 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.

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), have been determined to require a review of 
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their ethical conduct, and have received that review. The studies in PHED were considered 

appropriate (or ethically conducted) for use in risk assessments.

1.1 Summary of Recommendations (see also Section 10.0)

Directions for Use:

No proposed use was submitted for the use on tea in South Carolina. HED cannot evaluate the 

domestic use without a proposed use, application methods, and a proposed formulation. Good 

Agricultural Practice (GAP) information was provided for Japan and India. The use directions 

are adequate to establish a tolerance without U.S. registrations (an “import” tolerance).

Because the grape field trial data submitted with this petition did not reflect the use of a 

surfactant in the application sprays, the label directions regarding use of a spreader, methylated 

seed oil or crop oil should be removed from the product label of Assail® 30SG (EPA Reg. No. 

8033-36). Furthermore, in line with present OPP policy for a late season foliar use, a statement 

should be added to both the 30SG and 70WP labels prohibiting addition of adjuvants for 

application to grapes. If use of an adjuvant is desired then one should be used in side-by-side 

testing.

The PHI for clover harvested for hay should be increased to 56 days on the 30SG and 70WP 

labels.

Tolerances:

a) HED recommends tolerances for acetamiprid be established as specified in Appendix C.

b) Additionally, the tolerance expression in section (a)(1) should be revised to read as follows:

Tolerances are established for residues of the insecticide acetamiprid [N 1-[(6-chloro-3-

pyridyl)methyl]-N

2

-cyano-N 1-methylacetamidine], including its metabolites and 

degradates, in or on the commodities in the table below as a result of the application of 

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

measuring only acetamiprid [N 1-[(6-chloro-3-pyridyl)methyl]-N

2

-cyano-N 1-

methylacetamidine] in or on the following commodities.

c) The tolerance expression in section (a)(2) should be revised to read as follows:

Tolerances are established for residues of the insecticide acetamiprid [N 1-[(6-chloro-3-

pyridyl)methyl]-N

2

-cyano-N 1-methylacetamidine], including its metabolites and 

degradates, in or on the commodities in the table below as a result of the application of 

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

measuring acetamiprid [N 1-[(6-chloro-3-pyridyl)methyl]-N

2

-cyano-N 1-

methylacetamidine] and N 1-[(6-chloro-3-pyridyl)methyl]-N

2

-cyano-acetamidine in or on 

the following commodities.
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d) The final tolerances for subgroup 13-07F should reflect the correct commodity definition as 

specified in Appendix C. A revised Section F is not needed for this minor change. The 

established individual tolerance for grape at 0.20 ppm should be concomitantly removed with 

establishment of the subgroup 13-07F tolerance.

Conditional Data:

 Two clover field trials reflecting the same use pattern utilized in the submitted studies.

Submittal of Analytical Reference Standards:

Analytical standards for the IM-2-1 and IM-2-1-amide metabolites are not available at the 

Repository and should be supplied. The reference standards should be sent to the Analytical 

Chemistry Lab, which is located at Fort Meade, to the attention of Theresa Cole at the following 

address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

(Note that the mail will be returned if the extended zip code is not used.)

1.2 Summary of Proposed Uses

A list of acetamiprid end-use products (EPs) relevant to this registration action is presented 

below in Table 1.2.1. All listed EPs are registered to Nippon Soda Co., Ltd. (c/o Nisso America, 

Inc.).

Table 1.2.1. List of Acetamiprid End-Use Products Associated with PP#9E7544.

Trade Name Reg. No. ai (% of formulation) Formulation Type Label Date

Assail® 30SG Insecticide 8033-36 30% by wt Soluble granule 3/4/2009 (draft)

Assail® 70WP Insecticide 8033-23 70% by wt Wettable powder 3/4/2009 (draft)

Tristar® 30SG Insecticide 8033-94 30% by wt Soluble granule 3/4/2009 (draft)

A summary of the proposed or amended use patterns is presented in Table 1.2.2. For clover, new 

use is proposed for Assail® 30SG and Assail® 70WP. For grapes, a change to the registered use 

pattern is proposed. The current labels permit up to two foliar applications on grapes at 0.05 lb 

ai/A/application for a maximum seasonal rate of 0.1 lb ai/A with a 7-day preharvest interval 

(PHI). The requested new use on grapes (and small vine climbing fruits, except kiwifruit, 

subgroup 13-07F) will permit up to two applications of Assail® 30SG or Assail® 70WP at 0.1 lb

ai/A/application for a seasonal rate of 0.2 lb ai/A with a 3-day PHI. For tomatoes, new use is 

proposed for greenhouse-grown tomatoes. The current Assail® 30SG and Assail® 70WP labels 

permit up to four foliar applications on field-grown tomatoes at 0.075 lb ai/A/application for a 

maximum seasonal rate of 0.3 lb ai/A with a 7-day PHI. The requested new use on tomatoes 
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adds a greenhouse use pattern using Tristar® 30SG, with a maximum of two applications 

(reduced from four for resistance management) at 0.075 lb ai/A/application (based on 10,000 

plants per acre) for a maximum seasonal rate of 0.15 lb ai/A, applied via chemigation with a 1-

day PHI. 

No use directions were proposed for the domestic use of acetamiprid on tea grown in South 

Carolina. The following GAP information was provided for the 20% SP formulation in Japan: 

one application at 0.10-0.40 kg ai/ha applied in 2000-4000 L/ha, with a 14-day PHI. GAP 

information was also provided for India: one application at 0.022 lb ai/A (0.025 kg ai/ha) or 

0.045 lb ai/A (0.050 kg ai/ha), shoots along with bud are typically harvested at a 7-day PHI.

There were no rotational crop restrictions listed on any of the acetamiprid draft labels.

Table 1.2.2. Summary of Directions for Use of Acetamiprid.

Applic. Timing, 

Type, and 

Equip.

Trade Name

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. per 

Season 1

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Clover 2

Post emergence

Broadcast foliar

 spray

Ground/aerial

Assail®

30SG;

[8033-36]

Assail® 

70WP

[8033-23]

0.047-

0.075 1 0.075 28

Proposed use is limited to 

clover grown in ID, OR, 

and WA only. Begin 

applications when 

treatment thresholds have 

been reached. Apply in 

minimum spray volumes 

of 5 GPA by air or 20 

GPA by ground.

Grapes and Other Climbing Vine Small Fruits (Except Fuzzy Kiwifruit) (Within Crop Subgroup 13-07F): Amur 

River Grape; Gooseberry; Hardy Kiwifruit; Maypop; Schisandra Berry; and Cultivars, Varieties, and/or Hybrids

Post emergence

Broadcast foliar

 spray

Ground/aerial

Assail®

30SG;

[8033-36]

Assail® 

70WP

[8033-23]

0.047-0.1 2 0.2 3

Begin applications when 

treatment thresholds have 

been reached. Do not 

apply more than once 

every 14 days. Apply in 

minimum spray volumes 

of 5 GPA by air or 20 

GPA by ground. Assail® 

30SG states that the 

addition of a spreader, 

methylated seed oil or 

crop oil will enhance 

pest control.3
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Table 1.2.2. Summary of Directions for Use of Acetamiprid.

Applic. Timing, 

Type, and 

Equip.

Trade Name

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. per 

Season 1

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Greenhouse-Grown Tomatoes

Post emergence

Drip or micro

 Irrigation

Tristar®

30SG

[8033-94]

0.075 lb 

ai/A of

crop 

(based on 

10,000

plants/A)

2 0.15 1

For use in greenhousegrown tomato production. 

May be applied by 

injection into drip 

irrigation or microirrigation (spaghetti tube 

or emitter) systems, soil 

drenching, or by handheld or motorized 

calibrated irrigation 

equipment directed to the 

plant roots. Application 

should be made only to 

mature tomato plants 

grown in non-soil media 

such as rock wool, 

vermiculite, perlite, or 

other soil-less media. 

Some cultivars may 

exhibit sensitivity and 

therefore treatment of a 

few plants is 

recommended prior to 

treating an entire 

greenhouse. Begin 

applications when 

treatment thresholds have 

been reached. 

1 The number of treatments allowed per season when the EP is applied at the maximum single application rate.

2 Section G of the petition specifies that the EP is proposed for use on red clover grown for seed. The draft label

 does not specify that use is for clover grown for seed.

3 HED recommends that this be removed from the label until side-by-side residue data are submitted. Furthermore,

 in line with present OPP policy for a late season foliar use, a statement should be added to both the 30SG and

 70WP labels prohibiting addition of adjuvants for application to grapes. If use of an adjuvant is desired then one

 should be used in side-by-side testing.

Conclusions. The submitted labels are adequate to allow evaluation of the residue data relative 

to the proposed use, except for the use on tea in South Carolina for which directions were not 

proposed. The available field trial data reflect the proposed use patterns for all of the submitted 

field trials except those submitted for grapes and clover hay. Because the grape field trial data 

submitted with this petition did not reflect the use of a surfactant in the application sprays, the 

label directions regarding use of a spreader, methylated seed oil or crop oil should be removed 

from the product label of Assail® 30SG (EPA Reg. No. 8033-36). Furthermore, in line with 

present OPP policy for a late season foliar use, a statement should be added to both the 30SG and 
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70WP labels prohibiting addition of adjuvants for application to grapes. If use of an adjuvant is 

desired then one should be used in side-by-side testing. The PHI for clover harvested for hay

should be increased to 56 days on the 30SG and 70 WP labels.

2.0 Ingredient Profile

Acetamiprid is an insecticide in the chloronicotinyl class of compounds. It has a molecular 

weight of 222.68 Daltons and is not volatile (vapor pressure = 7.510-9Torr at 25C; Henry’s 

Law Constant = 5.17 x10-11 atm M3/mole at 25C). Acetamiprid is quite soluble in water (4.25 

g/L) as well as organic solvents (>200 g/L in ethanol, acetone, and dichloromethane). The log 

KOW of acetamiprid is 0.8. Based on these data, acetamiprid vapors should not present a 

significant inhalation risk and this compound is not expected to concentrate in fatty tissues. 

Technical-grade acetamiprid does not contain impurities of known or potential toxicological 

concern. The nomenclature and physiochemical properties of acetamiprid are presented below in 

Tables 2.a and 2.b.

Table 2.a. Test Compound Nomenclature

Compound

Chemical Structure

Common Name Acetamiprid

Company Experimental Name EXP-61842A, AEF124370, NI-25

IUPAC Name (E)-N 1-[(6-chloro-3-pyridyl)methyl]-N

2

-cyano-N 1-methylacetamidine

CAS Name (1E)-N-[(6-chloro-3-pyridinyl)methyl]-N'-cyano-N-methylethanimidamide

CAS # 135410-20-7

End-Use Product Assail® 70WP, Assail® 30SG, F4688 50WSP

Chemical Name of Acetamiprid 

Metabolite IM-2-1

N 1-[(6-chloro-3-pyridyl)methyl]-N

2

-cyano-acetamidine

Chemical Name of Acetamiprid 

Metabolite IM-2-1-amide (also 

referred to as IM-2-2)

N

2

-aminocarbonyl-N 1-[(6-chloro-3-pyridyl)methyl]acetamidine
Page 12 of 63

Table 2.b. Physicochemical Properties of Acetamiprid

Parameter Value

Melting Point/Range (C) 98.9

pH (20C) 6.08 (Aqueous Solution)

Density (20C) 1.33 g/cm3

Water Solubility (25C) 4.25 g/L

Solvent Solubility (25C) in: 

Acetone

Ethanol

Dichloromethane

n-Hexane

>20 g/100 g

>20 g/100 g

>20 g/100 g

6.54 ppm

Vapor Pressure (mm Hg) 7.5 x 10-9

Dissociation Constant (pKa) 0.7

Octanol/Water Partition Coefficient, Log KOW (20C) 0.8

UV/Visible Absorption Spectrum Not Available.

3.0 Hazard Characterization/Assessment

3.1 Hazard and Dose-Response Characterization

3.1.1 Database Summary

3.1.1.1 Studies available and considered (animal, human, general literature)

The toxicity data base contains: 1) subchronic oral toxicity studies in rats, mice, and dogs; 2) a 

chronic oral toxicity study in dogs and carcinogenicity studies in rats and mice; 3) developmental 

and reproduction studies in rats and a developmental study in rabbits; 4) acute, subchronic, and 

developmental neurotoxicity studies in rats; and, 5) subchronic dermal toxicity and dermal 

penetration studies in rats. There is also a complete mutagenicity battery, as well as metabolism 

studies in the rat.

3.1.1.2 Mode of action

Acetamiprid is a chloronicotinyl insecticide registered to control sucking type insects (e.g., 

aphids, whitefly, etc.) on a wide variety of crops including cotton, leafy vegetables, fruiting 

vegetables, and citrus fruits. Acetamiprid acts as an agonist of the nicotinic acetylcholine 

receptor, affecting the synapses in the insect central nervous system. 
Page 13 of 63

3.1.1.3 Sufficiency of studies/data

The toxicological database for acetamiprid is not complete. As part of the new 40 CFR Part 158 

guidelines, an immunotoxicity study in rats and/or mice is required. However, acetamiprid does 

not show any evidence of treatment-related effects on the immune system. The overall weight of 

evidence suggests that this chemical does not directly target the immune system and the Agency

does not believe that conducting a functional immunotoxicity study will result in a lower point of 

departure (POD) than that currently used for overall risk assessment. Therefore, a database 

uncertainty factor (UFDB) is not needed to account for lack of this study. The scientific quality of 

the available studies is relatively high and the toxicity profile of acetamiprid can be characterized 

for most effects, including potential carcinogenicity, mutagenicity, developmental toxicity and 

neurotoxicity.

3.1.2 Toxicological Effects

The acute toxicity data indicate that acetamiprid is moderately toxic via the oral route of 

exposure (Toxicity Category II) and is minimally toxic via the dermal and inhalation routes of 

exposure (Toxicity Category III). Acetamiprid is not an eye or skin irritant, nor is it a dermal 

sensitizer.

Acetamiprid does not appear to have specific target organ toxicity. In all species tested, 

generalized nonspecific toxicity was observed as decreases in body weight, body weight gain, 

food consumption and food efficiency. Generalized effects were also observed in the liver in the 

form of hepatocellular hypertrophy in both mice and rats and hepatocellular vacuolation in the 

rat. Hepatocellular hypertrophy was observed in the rat subchronic feeding study at doses of 50 

mg/kg/day and above, and in the rat chronic feeding study at doses of 17.5 mg/kg/day and above 

at both the 12-month sacrifice and study termination. In mouse studies, hepatocellular 

hypertrophy was observed at 430 mg/kg/day at 90 days and at 186 mg/kg/day at 12 and 18 

months. These effects are considered to be adaptive. Hepatocellular vacuolation was observed 

at 17.5 mg/kg/day in the rat chronic study. In light of the lack of major liver effects in the rat 

studies, it is likely that the vacuolization is more related to liver activity in response to the 

presence of the chemical rather than frank toxicity. Other effects observed in the oral studies 

include amyloidosis of multiple organs in the mouse oncogenicity study, tremors in high dose 

females in the mouse subchronic study, and microconcretions in the kidney papilla and 

mammary hyperplasia in the rat chronic feeding/oncogenicity study.

No effects were observed in the 21-day dermal study in the rabbit and no inhalation studies were 

conducted.

A dermal absorption study with acetamiprid was conducted using male rats with exposure 

durations of 0.5, 1, 2, 4, 10 and 24 hours. Measured absorption was small and increased with 

duration of exposure. The quantity absorbed also generally increased with dose. In the previous 

acetamiprid risk assessment, the highest dermal absorption value (6.34% at 24 hours) was added 

to the residue remaining on the skin at 24 hours (25%) to estimate a 30% dermal absorption 

value. However, HED has refined the dermal absorption value (to 10%) based upon comparison 

to clothianidin, which is structurally related. HED believes that a refined dermal penetration 
Page 14 of 63

value for acetamiprid of 10% is reasonable and protective. See Section 3.5.3 for more details.

There is no quantitative or qualitative evidence of increased susceptibility of rat or rabbit fetuses 

to in utero exposure in the developmental studies. In the rat, an increase in the incidence of

shortening of the 13th rib was observed in fetuses at the same LOAEL as the dams. Maternal 

effects included reduced mean body weight, body weight gain and food consumption and 

increased liver weights. No developmental toxicity was observed in the rabbit fetuses at dose 

levels that induced maternal effects including body weight loss and decreased food consumption. 

In the 2-generation reproduction study, qualitative evidence of increased susceptibility of rat 

pups was observed. The parental and offspring systemic LOAELs were 51.0/60.1 (M/F) 

mg/kg/day based on a decrease in mean body weight, body weight gain, and food consumption 

in the parents and significant reductions in pup weights in both generations. Also observed were

reduction in litter size, and viability and weaning indices among F2 offspring as well as 

significant delays in the age to attain vaginal opening and preputial separation in the offspring. 

These offspring effects were considered to be more severe than the parental effects.

In the DNT study there was evidence of increased qualitative susceptibility. The purpose of the 

DNT study is to evaluate the potential functional and morphological effects to the nervous 

system which may arise in the offspring from exposure of the mother during pregnancy and 

lactation. It provides data on sensorimotor function and on habituation which is considered to be 

a simple form of learning. In the acetamiprid DNT, the offspring LOAEL was 45 mg/kg/day

based on decreased body weights and body weight gains in males and females, decreased preweaning survival (PND 0-1), and decreased maximum auditory startle response in males on PND 

20 and PND 60. This was observed in the presence of decreased maternal body weight and body

weight gains during gestation. Although there were reductions in the maximum auditory startle 

response in the 10 mg/kg/day in males on PND 20 and PND 60, the mean response was within 

the range of historical control means and standard deviations among other DNT studies 

conducted (by the same laboratory) within a 5-year span of the acetamiprid DNT study. HED 

noted that statistical significance could only be achieved by combining data for both sexes at 

both time points (PND 20, and PND 60). Agency scientists agreed that it was appropriate to 

combine the data for the sexes, but there was no definitive consensus regarding combining the 

data from the different time points. The discussion regarding the combining of data from the two 

time points centered around the equipment used to measure the auditory startle reflex, and how it 

is calibrated differently to account for increases in body weight as the animals grow. Based upon 

the analysis of the DNT, technical arguments submitted by the registrant, and consideration of all 

other data in the acetamiprid toxicity profile, HED believes that the decrease in maximum startle 

response in males is only treatment related at the high-dose level of 45 mg/kg/day. The 

decreased auditory startle response in males in conjunction with the decreases in pup body

weight and body weight gains and decreased pup viability lead the Agency to a weight-ofevidence LOAEL determination of 45 mg/kg/day. For a more detailed discussion of the DNT 

study refer to the DNT DER (MRID 46255619) and cover memo entitled Acetamiprid: Data 

Evaluation Record for Acetamiprid Developmental Neurotoxicity Study and EPA Response to 

Rebuttals Submitted by Nisso America, (TXR 0054508). 

In an acute rat neurotoxicity study, a decrease in locomotor activity was observed in both sexes 
Page 15 of 63

on the day of dosing. A slight decrease in the duration of movements persisted in some males on 

days 7 and 14. Functional observational battery evaluations revealed several treatment-related 

observations on the day of dosing. High-dose males exhibited tremors, difficulty in handling, 

walking on toes, dilated pupils and coldness to the touch. High-dose males also had decreased 

forelimb grip strength and hind limb foot splay. High-dose females displayed tremors, chewing, 

coldness to the touch, and dilated pupils. High-dose females had decreased hind limb foot splay

and were seen to have abnormal gaits and/or posture, including walking on toes and hunched 

posture. However, in a subchronic rat neurotoxicity study, the only effects observed were related 

to decreases in body weight/body weight gain, food consumption and food efficiency. No 

neuropathology was observed in any of the three neurotoxicity studies. Tremors in high dose 

female mice in the subchronic feeding study were the only other potentially neurotoxic effects 

observed in any other studies. 

Acetamiprid tested negative in a Salmonella typhimurium (Ames) assay, a forward mutation 

assay in Chinese hamster ovary cells, an in vivo chromosome aberration assay in SpragueDawley (CD) rats, a mouse micronucleus assay, and in repeat assays for unscheduled DNA 

synthesis (UDS) in rat liver primary cell cultures. Acetamiprid tested positive as a clastogen in 

an in vitro mammalian chromosome aberration assay in Chinese hamster ovary (CHO) cells. 

However, the in vivo chromosomal aberration study does not support the results of the in vitro 

study. All acetamiprid metabolites tested were negative for mutagenicity.

3.1.3 Dose-response

Since HED’s last hazard assessment of acetamiprid in 2007, endpoints have been selected to 

account for occupational long-term oral, dermal, and inhalation exposures. For acute dietary

exposure, the DNT and acute neurotoxicity studies were co-critical for determining the acute 

reference dose (aRfD) of 0.1 mg/kg/day for all populations. These studies share a NOAEL of 10 

mg/kg/day. In the DNT, the maternal LOAEL (45 mg/kg/day) is based on decreased body 

weight and body weight gain during gestation and the offspring LOAEL (45 mg/kg/day) is based 

on decreased body weights and body weight gains in males and females, decreased pre-weaning 

survival (PND 0-1), and decreased maximum auditory startle response in males on PND 20 and 

PND 60. The LOAEL in the acute neurotoxicity study, 30 mg/kg, is based on reduction in

locomotor activity in males. For the chronic dietary exposure, the chronic/oncogenicity study 

was used to calculate the chronic reference dose (cRfD) of 0.071 mg/kg/day for all populations. 

The NOAEL, 7.1 mg/kg/day, is based on reduced body weight and body weight gains for 

females and hepatocellular vacuolation for males. The LOAEL is 17.5 mg/kg/day. 

For the incidental-oral (short- and intermediate-term), as well as short- and intermediate-term 

dermal and inhalation exposures, the DNT was used. For long-term inhalation and dermal 

exposures, the chronic/carcinogenicity study in rats was used for endpoint selection.

3.1.4 FQPA

See Section 3.3.
Page 16 of 63

3.2 Absorption, Distribution, Metabolism, Excretion (ADME)

Several studies have examined the in vivo metabolism and distribution of acetamiprid in the rat 

including single dose, 15-day repeated dose, biliary excretion, and metabolite characterization 

studies. 

Acetamiprid is rapidly absorbed and eliminated. Metabolite studies indicate 96-99% absorption 

following an oral administration. Peak blood concentrations in the rat occur within 1-2 hours, 

with nearly complete clearance from the blood by 48 hours. Acetamiprid distributes widely in 

the body but tissue burdens rarely exceed 1% of the administered dose. Acetamiprid is 

extensively metabolized with metabolites accounting for 79-86%of the administered 

radioactivity. 6-Chloronicotinic acid is the most abundant metabolite, accounting for 24-28% of 

the dose in single-dose studies and 8-10% in repeated-dose studies. Urinary excretion was the 

major route of elimination, accounting for 79-97% of the administered dose within 24 hours in 

single oral dose groups. Fecal excretion accounted for 21-35% of the administered radioactivity, 

with males being slightly higher. Excretion rates for the IV and repeated dose studies were 

similar.

As a result of the rapid absorption, metabolism, and clearance of acetamiprid in the rat, the 

pharmacokinetic parameters derived from the 15-day repeated dose study were similar to the 

single dose study. Therefore, the potential for acetamiprid to bioaccumulate is minimal. 

A dermal absorption factor of 10% is proposed for risk assessment. The factor is based on an 

acetamiprid dermal absorption study in rats, a dermal absorption study in monkeys, and a 

comparison of structurally similar neonicotinoid pesticides. 

3.3 FQPA Considerations

3.3.1 Adequacy of the Toxicity Database

Acceptable guideline studies for developmental and reproductive toxicity are available for FQPA 

assessment, including an acceptable DNT study. However, an immunotoxicity study is required 

as a part of new data requirements in the 40 CFR Part 158 for conventional pesticide registration. 

Therefore, the lack of an immunotoxicity study is considered to be a data gap. (Note: An 

immunotoxicity study was previously requested in D352925, W. Drew, 11/25/2008.)

3.3.2 Evidence of Neurotoxicity

Acetamiprid produced signs of neurotoxicity in the high dose groups in the acute and 

developmental neurotoxicity studies in rats. In the acute neurotoxicity study, male and female 

rats displayed decreased motor activity, tremors, walking and posture abnormalities, dilated 

pupils, coldness to the touch, and decreased grip strength and foot splay. There was a decrease 

in the auditory startle response in male rats in the DNT. Tremors in the high dose female mice in 

the subchronic feeding study were the only other potentially neurotoxic effects observed in the 

other studies.
Page 17 of 63

3.3.3 Developmental Toxicity Studies

In the gavage developmental studies, fetal effects were observed at the doses associated with 

maternal effects. In the rat developmental study, fetal shortening of the 13th rib and reduced 

maternal body weight and body weight gain were observed at the same LOAEL. No 

developmental effects were observed in the rabbit at doses that reduced maternal body weight 

and food consumption. In the DNT, parental and offspring systemic LOAELs were the same, 

51.0/60.1 (M/F) mg/kg/day. Offspring and parental LOAELs were based on decreased auditory

startle response in male pups and decreased body weight and body weight gain during gestation, 

respectively.

3.3.4 Reproductive Toxicity Study

In the 2-generation reproduction study, the LOAEL for the parental and offspring systemic 

effects, 17.9/21.7 (M/F) mg/kg/day, were based on a decrease in mean body weight, body weight 

gain, and food consumption in the parents, and reductions in pup weights, litter size, viability, 

and weanling indices, as well as age to attain vaginal opening and preputial separation in the 

offspring.

3.3.5 Additional Information from Literature Sources

A literature search did not reveal information that would impact the risk assessment.

3.3.6 Pre-and/or Postnatal Toxicity

3.3.6.1 Determination of Susceptibility

HED determined that neither quantitative nor qualitative evidence of increased susceptibility of 

fetuses to in utero exposure to acetamiprid was observed in either the developmental toxicity

study in rat, or in rabbit. However, in the 2-generation reproduction study, qualitative evidence 

of increased susceptibility of rat pups was observed. While parental and offspring NOAELs and 

LOAELs are set at the same doses (17.9 and 51.0 mg/kg/day, respectively), the effects in the 

offspring are considered to be more severe than the parental effects. Likewise, in the DNT study

maternal and offspring effects were observed at the same dose (45 mg/kg/day). However, the 

offspring effects included decreased pup viability which is considered to be more severe than the 

maternal body weight effects. Therefore, HED concluded that there was evidence of increased 

qualitative susceptibility to fetuses exposed in utero and/or during lactation in the DNT study. 

Quantitative evidence of increased susceptibility was not observed in any study. 

3.3.6.2 Degree of Concern Analysis and Residual Uncertainties for Pre- and/or Postnatal 

Susceptibility

Since there is evidence of increased qualitative susceptibility of the young following in utero 

exposure to acetamiprid in the rat reproduction study, and increased qualitative susceptibility to 

pups in the DNT study, HED performed a degree of concern analysis to: 1) determine the level 
Page 18 of 63

of concern for the effects observed when considered in the context of all available toxicity data; 

and, 2) identify any residual uncertainties after establishing toxicity endpoints and traditional 

uncertainty factors to be used in the acetamiprid risk assessment. If residual uncertainties are 

identified, HED examines whether the residual uncertainties can be addressed by a FQPA safety 

factor, and if so, what factors should be retained.

Considering the overall toxicity profile and the endpoints and doses selected for the acetamiprid 

risk assessment, HED characterized the degree of concern for the effects observed in the 

acetamiprid DNT study as low, noting that there is a clear NOAEL for the offspring effects and 

regulatory doses were selected to be protective of these effects. No other residual uncertainties 

were identified. Based on the available data, HED determined that changes in motor activity, 

auditory startle reflex, learning and memory assessments, and even changes in the brain 

morphometrics can occur as the result of a single exposure at a critical junction during pregnancy

or from multiple exposures throughout pregnancy and lactation. Therefore, the NOAEL for 

offspring effects observed in the DNT was selected as the dose for acute dietary exposures (cocritical with the acute neurotoxicity study), as well as short-term and long-term non-dietary risk 

assessment. The chronic dietary study in rats yielded a lower long-term NOAEL (7.1 

mg/kg/day) and will be used for assessing chronic dietary risk. HED believes that the endpoints 

and doses selected for acetamiprid are protective of adverse effects in both offspring and adults.

3.3.7 Recommendation for a Developmental Neurotoxicity Study

A developmental neurotoxicity study has been requested, received, and reviewed by the Agency

(see Section 3.3.2).

3.4 FQPA Safety Factor for Infants and Children

HED recommends the FQPA SF be reduced to 1X for the following reasons: (1) HED is 

regulating based upon the effects of concern, i.e., developmental effects in pups following preand/or post-natal exposure; (2) the rat appears to be the most sensitive species tested, and the 

NOAEL and LOAEL selected from the DNT study in rats are protective of effects observed in 

other species throughout the toxicology database; and, (3) there are no residual uncertainties for 

pre- and/or post-natal toxicity. The recommended FQPA safety factor also reflects HED’s 

conclusion that the exposure databases (dietary food, drinking water, and residential) are 

complete and that the risk assessment for each potential exposure scenario includes all 

metabolites and/or degradates of concern and does not underestimate the potential risk to infants 

or children.

The lack of an immunotoxicity study is considered a data gap. However, because there was no 

indication in any of the submitted toxicity studies that there was an effect on the immune system, 

a 10x safety factor for a data gap is not required at this time. (Note: An immunotoxicity study

was requested in: D352925, W. Drew; Nov 25, 2008.)
Page 19 of 63

3.5 Hazard Identification and Toxicity Endpoint Selection

3.5.1 Acute Reference Dose (aRfD) - Females age 13-49

A separate aRFD is not being used for females age 13-49. Females in this age group will be 

assessed using the aRFD for the general population (see 3.5.2). 

3.5.2 Acute Reference Dose (aRfD) - General Population

Co-Critical Studies Selected: Developmental Neurotoxicity Study in Rats (MRID 46255619)

 Acute Neurotoxicity Study in Rats (MRID 44651842)

Dose and Endpoint for Risk Assessment: NOAEL = 10 mg/kg/day based on offspring decreased 

body weights and body weight gains, decreased pre-weaning survival (PND 0-1), and decreased 

maximum auditory startle response in males on PND 20 and PND 60 of the DNT study at 45 

mg/kg/day, as well as decreased locomotor activity in males in the ACN study at 30 mg/kg bw. 

The DNT and acute neurotoxicity studies are considered co-critical due to similar LOAELs and 

signs of toxicity.

Acute RfD   0.1 mg/kg

100 (UF)

10 mg/kg

Comments about Study/Endpoint/Uncertainty Factors: These endpoints and dose were selected 

because: 1) the oral route of exposure is relevant to dietary risk assessment, 2) the duration of 

exposure is relevant to acute dietary risk (both endpoints can be considered the result of a single 

dose), and 3) they are protective of potential offspring effects. Based on the available data, HED 

determined that changes in motor activity, auditory startle reflex, learning and memory

assessments, and changes in the brain morphometrics can occur as the result of a single exposure 

at a critical junction during pregnancy or from multiple exposures throughout pregnancy and 

lactation. The standard uncertainty factors (100x) were applied to all dietary exposure scenarios 

(10x for intraspecies variability and 10x for interspecies extrapolation).

3.5.3 Chronic Reference Dose (cRfD)

Studies Selected: Chronic/Carcinogenicity Study in the Rat

MRID Nos.: 44988429, 45245304

Dose and Endpoint for Risk Assessment: NOAEL = 7.1 mg/kg/day based on decreased body

weights and body weight gains in females and hepatocellular vacuolation in males observed at 

the LOAEL of 17.5 mg/kg/day. 

Chronic RfD   0.071 mg/kg/day

100 (UF)

7.1mg/kg/day
Page 20 of 63

Comments about Study/Endpoint/Uncertainty Factors: This endpoint and dose was selected 

because: 1) the oral route of exposure is relevant to dietary risk assessment, 2) the duration of 

exposure is relevant to chronic risk scenarios, and 3) it is the lowest endpoint in the toxicology

database and is therefore protective of both chronic effects and potential qualitative sensitivity of 

offspring. The standard uncertainty factors were applied to all dietary exposure scenarios (10x 

for intraspecies variability and 10x for interspecies extrapolation).

3.5.4 Incidental Oral Exposure (Short- and Intermediate-Term) 

Short- and Intermediate-Term Incidental Exposure (1-30 days and 1-6 months)

Study Selected: Developmental Neurotoxicity Study in Rats (MRID 46255619)

Dose and Endpoint for Risk Assessment: NOAEL = 10 mg/kg/day based on offspring decreased 

body weights and body weight gains, decreased pre-weaning survival (PND 0-1), and decreased 

maximum auditory startle response in males on PND 20 and PND 60 of the DNT study at 45 

mg/kg/day.

Comments about Study/Endpoint/Uncertainty Factors: The NOAEL and LOAEL from the DNT 

study were selected for the short- and intermediate-term dermal risk assessment because they are 

protective of developmental effects present in rat pups observed in the presence of less severe 

maternal effects at similar doses. The standard uncertainty factors (100x) were applied (10x for 

intraspecies variability and 10x for interspecies extrapolation).

3.5.5 Dermal Absorption

In the previous risk assessment (D303171; Tom Moriarty; 25 October 2007), HED used a 30% 

dermal penetration value derived from an acetamiprid dermal penetration study in rats (MRID 

44651858), in which multiple doses were tested for durations ranging from 0.5 to 24 hours. To 

arrive at the 30% value, HED added the highest dermal absorption value (6.34%) to the amount 

sequestered in the skin at 24 hours (approximately 25%). To validate this estimate and determine 

whether further refinement was needed, HED reexamined the dermal penetration study with 

acetamiprid, and reviewed the dermal penetration information of several other neonicotinoid 

insecticides.

To refine its assumption regarding treatment of sequestered acetamiprid on the skin, HED looked 

at the amount of radioactivity remaining at the application site. The amount of radiolabeled 

material remaining at the application site at various intervals varied between 0–5% percent 

between time points. If the radioactivity remaining at the application site is added to that which 

is absorbed, a maximum penetration value for acetamiprid would be 11%. However, since the 

duration of the acetamiprid study was only 24 hours, HED examined the thiamethoxam dermal 

penetration study, another neonicotinoid, which was terminated after 336 hours (14 days). 

Results from that study indicate little additional absorption (1 – 3%) occurred between 24 hours 

post dosing and 14 days post dosing. 
Page 21 of 63

HED also considered the Kow and octanol/water coefficient data of other neonicotinoid 

compounds, and found acetamiprid is most closely related to clothianidin with respect to its log 

Kow and octanol/water coefficient, and therefore would likely act most similarly to clothianidin 

when applied to the skin. The dermal penetration value for clothianidin (1%) is based upon 

dermal penetration study with monkeys (see Table 3.5.5. below).

Table 3.5.5. Absorption Parameters for Selected Neonicitinoids.

Compound Log Kow Octanol/Water Coefficient Dermal Penetration Value

Acetamiprid 0.8 6.3 30% 

(dermal penetration study with rat)

Clothianidin 0.9 81% 

(dermal penetration study in monkeys)

Adjustment of the monkey dermal penetration value for clothianidin to account for the 2-10 fold 

increased dermal sensitivity of rats compared to humans (dermal penetration of monkey is 

considered equivalent to human) would yield a comparative rat dermal penetration value for 

acetamiprid of 2 – 10%. Likewise, if the current dermal penetration value for acetamiprid is 

adjusted downward to account for the increased sensitivity of rats to humans, then a value of 10 -

15% results. Since the acetamiprid study shows 6% dermal penetration at 24 hours, a refined 

dermal penetration value reflecting a longer dermal exposure would likely be greater than 6%, 

and may lie between 10 - 15 %. 

Based upon its reconsideration of the acetamiprid dermal penetration study, and on comparison 

of acetamiprid to the structurally related clothianidin, HED determined that a refined dermal 

penetration value for acetamiprid of 10% is reasonable and protective. Based upon this, HED 

would not require any additional dermal penetration data for acetamiprid.

3.5.6 Dermal Exposure (Short-, Intermediate- and Long-Term)

Short- and Intermediate-Term Dermal Exposures (1-30 days and 1-6 months)

Study Selected: Developmental Neurotoxicity Study in Rats

MRID No.: 46255619

Dose and Endpoint for Risk Assessment: NOAEL = 10 mg/kg/day based on decreased body

weights and body weight gains in males and females, decreased pre-weaning survival (PND 0-1), 

and decreased maximum auditory startle response in males on PND 20 and PND 60 of the DNT 

study at 45 mg/kg/day, as well as decreased locomotor activity in males in the ACN study at 30 

mg/kg bw.

Comments about Study/Endpoint/Uncertainty Factors: The NOAEL and LOAEL from the DNT 

study were selected for the short- and intermediate-term dermal risk assessment because they are 

protective of developmental effects present in rat pups observed in the presence of less severe 

maternal effects at similar doses.

Although a dermal (route specific) toxicity study in rabbits was submitted, no effects were seen 
Page 22 of 63

at the highest dose tested of 1000 mg/kg/day. Use of the route-specific study for dermal risk 

assessment would not be protective of the offspring effects observed in both the DNT and the 2-

generation reproduction studies because the effects seen could occur as a result of a single 

exposure at a critical junction during pregnancy or from multiple exposures throughout 

pregnancy lactation. Therefore, the NOAEL for offspring effects observed in the DNT was 

selected as the dose for both short-term and intermediate-term dermal exposure scenarios. Since 

the dermal endpoint is based on an oral study, a 10% dermal absorption factor is used to 

determine dermal exposure and risk. The standard uncertainty factors were applied to all 

exposure scenarios (10x for intraspecies variability and 10x for interspecies extrapolation).

Long-Term Dermal Exposure (> 6 months)

Study Selected: Chronic/Carcinogenicity Study in Rats

MRID No.: 44988429, 45245304

Dose and Endpoint for Risk Assessment: NOAEL = 7.1 mg/kg/day based on decreases in mean 

body weight and body weight gain in females and hepatocellular vacuolation in males. 

Comments about Study/Endpoint/Uncertainty Factors: The NOAEL and LOAEL from the 

chronic/carcinogenicity study were selected for the long-term dermal risk assessment because 

they are protective of developmental effects seen in the 2-generation and DNT studies and the 

study is of an appropriate duration.

Although a dermal (route specific) toxicity study in rabbits was submitted, no effects were seen 

at the highest dose tested of 1000 mg/kg/day. Use of the route-specific study for dermal risk 

assessment would not be protective of the offspring effects observed in both the DNT and the 2-

generation reproduction studies because the effects seen could occur as a result of a single 

exposure at a critical junction during pregnancy or from multiple exposures throughout 

pregnancy lactation. Since the dermal endpoint is based on an oral study, a 10% dermal 

absorption factor (DAF) is used to determine dermal exposure and risk. The standard uncertainty 

factors were applied to all exposure scenarios (10x for intraspecies variability and 10x for 

interspecies extrapolation).

3.5.7 Inhalation Exposure (Short-, Intermediate- and Long-Term)

Short- and Intermediate-Term Inhalation Exposures (1-30 days and 1-6 months)

Study Selected: Developmental Neurotoxicity Study in Rats

MRID No.: 46255619

Dose and Endpoint for Risk Assessment: NOAEL = 10 mg/kg/day based on decreased body

weights and body weight gains in males and females, decreased pre-weaning survival (PND 0-1), 

and decreased maximum auditory startle response in males on PND 20 and PND 60 of the DNT 

study at 45 mg/kg/day.

Comments about Study/Endpoint/Uncertainty Factors: No route-specific information is 
Page 23 of 63

available for the inhalation toxicity of acetamiprid. In the absence of a route-specific study, the 

NOAEL and LOAEL from an oral study, along with an inhalation absorption factor (IAF, 

100%), are used to estimate inhalation exposure and the associated risk. In this case, the 

NOAEL and LOAEL from the DNT study were selected because the duration is appropriate for 

short- and intermediate-term exposures and it is protective of potential effects in offspring. 

Because effects seen in the DNT can occur as the result of a single exposure at a critical junction 

during pregnancy or from multiple exposures throughout pregnancy and lactation, the NOAEL 

for offspring effects observed in the DNT was selected as the dose for short- and intermediateterm inhalation exposure scenarios. The standard uncertainty factors were applied to all exposure 

scenarios (10x for intraspecies variability and 10x for interspecies extrapolation).

Long-Term Inhalation Exposures (> 6 months)

Study Selected: Chronic/Carcinogenicity Study in Rats

MRID No.: 44988429, 45245304

Dose and Endpoint for Risk Assessment: NOAEL = 7.1 mg/kg/day based on decreases in mean 

body weight and body weight gain in females and hepatocellular vacuolation in males. 

Comments about Study/Endpoint/Uncertainty Factors: No route-specific information is 

available for the inhalation toxicity of acetamiprid. In the absence of a route-specific study, the 

NOAEL and LOAEL from an oral study, along with an IAF (100%), are used to estimate 

inhalation exposure and the associated risk. In this case, the NOAEL and LOAEL from the 

chronic/carcinogenic study were selected because the duration is appropriate for long-term 

exposures and it is protective of potential effects in offspring observed in the DNT and 2-

generation study in rats. The standard uncertainty factors were applied to all exposure scenarios 

(10x for intraspecies variability and 10x for interspecies extrapolation).

3.5.8 Level of Concern for Margin of Exposure

Table 3.5.8. Summary of Levels of Concern for Risk Assessment.

Route

Short-Term

(1 - 30 Days)

Intermediate-Term

(1 - 6 Months)

Long-Term

(> 6 Months)

Occupational (Worker) Exposure

Dermal 100 100 100

Inhalation 100 100 100

Residential Exposure

Dermal 100 100 100

Inhalation 100 100 100

Incidental Oral 100 100 100
Page 24 of 63

3.5.9 Recommendation for Aggregate Exposure Risk Assessments

The FQPA requires that HED aggregate pesticide exposures from the three major exposure 

routes (oral, dermal, and inhalation) when there is potential residential exposure to a pesticide. 

HED has chosen a single endpoint and dose from the DNT study for short- and intermediateterm exposure scenarios. Therefore, the short- and intermediate dermal, oral, and inhalation 

exposure can be combined and aggregated with the dietary (food + water) exposures.

3.5.10 Classification of Carcinogenic Potential

HED has determined that acetamiprid is “not likely to be carcinogenic to humans.” The 

classification is based on the absence of a dose-response and the lack of a statistically significant 

increase in the mammary adenocarcinoma incidence by pair-wise comparison of the mid- and 

high- dose groups with the controls; although the incidence exceeded the historical control data 

from the same laboratory, it was within the range of values from the supplier.
Page 25 of 63

3.5.11 Summary of Toxicological Doses and Endpoints for Use in Human Risk Assessments

Table 3.5.11a. Summary of Toxicological Doses and Endpoints of Acetamiprid for Use in Dietary and Non-Occupational Human Health Risk 

Assessment

Exposure Scenario Dose Used in 

Risk Assessment

Uncertainty 

Factors/FQPA 

Safety Factors

RfD, PAD Level 

of Concern for 

Risk Assessment

Study and Toxicological Effect

Acute Dietary (All 

populations)

NOAEL = 10 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

aPAD = 0.10 

mg/kg/day

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and 

body weight gains in offspring, decreased early pup survival on 

PND 0-1, and decreased startle response on PND 20/60 in 

males.

Acute Neurotoxicity Study in rat

LOAEL = 30 mg/kg/day based on decreased locomotor activity

Chronic Dietary

all populations

NOAEL = 7.1 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

cPAD = 0.071 

mg/kg/day

Chronic Toxicity/Oncogenicity Study in rats

LOAEL = 17.5 mg/kg/day based on decreased body weight and 

body weight gains in females and hepatocellular vacuolation in 

males.

Short- and IntermediateTerm Incidental Oral 

(1-30 days and 1-6 mo.)

NOAEL = 10 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

LOCfor MOE = 

100

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and 

body weight gains in offspring, decreased early pup survival on 

PND 0-1, and decreased startle response on PND 20/60 in 

males.

Short- and Intermediateterm Dermal

(1-30 days, 1–6 mo.)

NOAEL = 10 

mg/kg/day

DAF = 10%

UFA = 10x

UFH = 10x

FQPA SF = 1x

LOC for MOE = 

100

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and 

body weight gains in offspring, decreased early pup survival on 

PND 0-1, and decreased startle response on PND 20/60 in 

males.

Short- and Intermediateterm Inhalation

(1-30 days, 1–6 mo.)

NOAEL = 10 

mg/kg/day

IAF = 100%

UFA = 10x

UFH = 10x

FQPA SF = 1x

LOC for MOE = 

100

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and 

body weight gains in offspring, decreased early pup survival on 

PND 0-1, and decreased startle response on PND 20/60 in 

males.

Cancer (oral, dermal, inhalation) - not likely to be carcinogenic to humans.

DAF = dermal absorption factor. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning of extrapolation to 

determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. 

UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.
Page 26 of 63

Table 3.5.11b. Summary of Toxicological Doses and Endpoints of Acetamiprid for Use in Occupational Human Health Risk Assessment

Exposure Scenario Dose Used in Risk 

Assessment

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effect

Short-, Intermediate-term

Dermal 

(1 - 30 days, 1 - 6 mo.)

oral study 

NOAEL= 

10 mg/kg/day

dermal absorption 

rate = 10%

UFA = 10x

UFH = 10x

LOCfor MOE = 

100

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and 

body weight gains in offspring, decreased early pup survival on 

PND 0-1, and decreased startle response on PND 20/60 in 

males.

Long-term Dermal

(> 6 mo.)

NOAEL = 7.1 

mg/kg/day

UFA = 10x

UFH = 10x

FQPA SF = 1x

dermal absorption 

rate = 10%

LOC for MOE = 

100

Chronic Toxicity/Oncogenicity Study in rats

LOAEL = 17.5 mg/kg/day based on decreased body weight and 

body weight gains in females and hepatocellular vacuolation in 

males.

Short- and Intermediateterm Inhalation 

(1 - 30 days, 1 - 6 mo.)

Oral study 

NOAEL=

10 mg/kg/day

inhalation 

absorption rate = 

100%

UFA = 10x

UFH = 10x

LOC for MOE = 

100 

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and 

body weight gains in offspring, decreased early pup survival on 

PND 0-1, and decreased startle response on PND 20/60 in 

males.

Long-term Inhalation

(1-30 days, 1 – 6 mo.)

NOAEL = 7.1 

mg/kg/day

inhalation 

absorption rate = 

100%

UFA = 10x

UFH = 10x

FQPA SF = 1x

LOC for MOE = 

100

Chronic Toxicity/Oncogenicity Study in rats

LOAEL = 17.5 mg/kg/day based on decreased body weight and 

body weight gains in females and hepatocellular vacuolation in 

males.

Cancer (oral, dermal, inhalation) - not likely to be carcinogenic to humans.

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). UFL = use of a 

LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key date (i.e., lack of a critical study). 

FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = 

not applicable.
Page 27 of 63

3.6 Endocrine disruption

EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to 

determine whether certain substances (including all pesticide active and other ingredients) “may 

have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, 

or other such endocrine effects as the Administrator may designate.” Following the 

recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee 

(EDSTAC), EPA determined that there were scientific bases for including, as part of the 

program, androgen and thyroid hormone systems, in addition to the estrogen hormone system. 

EPA also adopted EDSTAC’s recommendation that the Program include evaluations of potential 

effects in wildlife. When the appropriate screening and/or testing protocols being considered 

under the Agency’s Endocrine Disrupter Screening Program (EDSP) have been developed and 

vetted, acetamiprid may be subjected to additional screening and/or testing to better characterize 

effects related to endocrine disruption.

4.0 Public Health and Pesticide Epidemiology Data

No public health data were considered at this time.

4.1 Other Pesticide Epidemiology Published Literature

A literature search did not reveal information that would impact the risk assessment.

5.0 Dietary Exposure/Risk Characterization

5.1 Pesticide Metabolism and Environmental Degradation

5.1.1 Metabolism in Primary Crops

Residue Chemistry Memo D264154, 12/31/2001, M. Doherty (PP#0F6082)

MARC Decision Memo, D278652, 11/13/2001, M. Doherty

The nature of acetamiprid residue in plants has been adequately delineated and is based on 

radiolabeled studies with carrot, cabbage, cotton, apple, and eggplant. In plants, there appears to 

be little translocation of acetamiprid following foliar application. In cabbage, there was 

significant uptake and translocation of acetamiprid to the above-ground portions of the plant 

following a soil application. However, due to the rapid dissipation of acetamiprid in the field, 

root uptake is not a likely source of residues in plants.

5.1.2 Metabolism in Rotational Crops

Residue Chemistry Memo D328216, 10/23/2007, W. Drew (PP#6F7051 and PP#6E7163)

Residue Chemistry Memo D264154, 12/31/2001, M. Doherty (PP#0F6082)

No new confined rotational crop data were submitted with this petition; the nature of the residue 

in rotational crops is understood. A confined rotational crop study was reviewed in conjunction 
Page 28 of 63

with PP#0F6082. In the study, acetamiprid was not detected in any rotational crop matrix 

(mustard greens, radish, and grain crops) at any of the plantback intervals (PBIs), which were 30-

, 58-, 120- and 365 days after treatment (DAT) following application to bare soil at 0.66 lb ai/A. 

The major metabolite identified in rotational crops was IM-1-4, at 2.94-56.65% TRR (<0.001-

0.040 ppm). Two other metabolites were identified in most rotational crops: IM-0-Glc, at 1.11-

15.23% TRR (<0.001-0.010 ppm), and IC-0, at 2.75-24.19% TRR (<0.001-0.014 ppm). Storage 

stability data, required as a condition of registration in the original petition PP#0F6082, have 

been submitted and determined to rectify deficiencies under PP#6F7051.

HED has determined that the residue of concern in rotational crops for enforcement purposes is 

the parent only, and that tolerances would not be needed on rotational crops. The available 

rotational crop data are adequate to support the uses proposed in this petition.

5.1.3 Metabolism in Livestock

Residue Chemistry Memo D264154, 12/31/2001, M. Doherty (PP#0F6082)

MARC Decision Memo, D278652, 11/13/2001, M. Doherty

The qualitative nature of acetamiprid residue in livestock is also adequately understood based 

upon metabolism studies in ruminants (lactating goat) and laying hens. HED has determined that 

for risk assessment purposes, the residues of concern in livestock tissue (except ruminant 

muscle) are acetamiprid, plus its IM-2-1 metabolite. In ruminant muscle, the residues of concern 

for risk assessment are acetamiprid plus IM-2-1 plus IM-2-1-amide. Residues of IM-2-1-amide 

in ruminant muscle tissue can be estimated by applying a 10-fold factor to residues of IM-2-1 in 

muscle.

5.1.4 Analytical Methodology

Residue Chemistry Memo D342549, 11/05/2008, W. Drew

Residue Chemistry Memo D328216, 10/23/2007, W. Drew (PP#6F7051 and PP#6E7163)

Residue Chemistry Memo D303623, 11/05/2004, W. Drew (PP#4F6833)

Residue Chemistry Memo D264154, 12/31/2001, M. Doherty (PP#0F6082)

Adequate gas chromatography with electron capture detection (GC/ECD) and high performance 

liquid chromatography with ultraviolet detection (HPLC/UV) residue analytical methods are 

available for the enforcement of established tolerances on plant commodities. The method limits 

of quantitation (LOQ) are 0.01 ppm for vegetables and non-citrus fruits (GC/ECD), and 0.050 

ppm for citrus fruits (HPLC/UV). A secondary liquid chromatography with tandem mass 

spectrometric detection (LC/MS/MS) method, designated by the petitioner as an alternative to 

the established GC/ECD tolerance enforcement method, has been determined suitable for 

tolerance enforcement, and confirmatory analysis of vegetables and non-citrus fruits. The 

GC/ECD method or LC/MS/MS Method #KP-216R1 (or its modification) was used for the 

analysis of samples from the clover, grape, and tomato field trials. Acceptable recoveries were 

obtained in method validation efforts conducted prior to the analysis of field trial samples.

Samples of dried green tea leaves and brewed tea from the Japan study were analyzed for 

residues of acetamiprid and its metabolites convertible to 6-chloronicotinic acid (Metabolite IC-
Page 29 of 63

0) using a common moiety gas chromatography method with electron capture detection 

(GC/ECD). Using this method, acetamiprid and metabolites are converted to Metabolite IC-0 

and methylated prior to determination by GC/ECD; residues are expressed as acetamiprid. The 

reported method limit of detection (LOD) is 0.05 ppm as acetamiprid. Samples of green shoots, 

dried black tea leaves, brewed tea, and spent leaves from the India study were analyzed for 

residues of acetamiprid using a high performance liquid chromatography method with ultraviolet 

detection (HPLC/UV) similar to the HPLC/UV method discussed above.

Regarding the common moiety method used in the Japan study, it was noted that, although 

Metabolite IC-0 is not a residue of concern for tolerance enforcement or risk assessment, based 

on the available plant metabolism studies, it may constitute a significant portion of the total 

residues (e.g., up to 24% total radioactive residues (TRR) in cotton seed and 31% TRR in carrot 

flesh; refer to D278652, 11/13/01, H. Bietlot and M. Doherty). Therefore, the residues reported 

for the Japan study may reflect an overestimation of expected residues of acetamiprid per se in 

green tea.

Adequate multiresidue methods testing data have been submitted. These data indicate that the 

multiresidue methods are not appropriate for determining residues of acetamiprid.

5.1.5 Environmental Degradation

Acetamiprid is a mobile, rapidly biodegradable compound in most soils. The primary

degradation pathway is aerobic soil metabolism. Acetamiprid is stable to hydrolysis at 

environmental temperatures, and photo degrades relatively slowly in water. Acetamiprid is 

metabolized moderately rapidly in aerobic aquatic systems, but is only slowly metabolized in 

anaerobic aquatic systems. Acetamiprid is expected to be moderately to highly mobile in most 

soils and aquatic sediments; however, based on guideline study data, it is not expected to be 

persistent in the environment. In environmental fate studies, residues of acetamiprid, IB-1-1, ICO, IM-1-2, IM-1-3, IM-1-4, and IM-1-5 were identified.

5.1.6 Comparative Metabolic Profile

Radiolabeled metabolism studies are available for carrot, cabbage, cotton, apple, eggplant, 

lactating goat, laying hen, and rat. In plants, there appears to be little translocation of acetamiprid 

following foliar application. In cabbage, there was uptake and translocation of acetamiprid to the 

above-ground portions of the plant following a soil application. Due to the rapid dissipation of 

acetamiprid in the field, root uptake is not considered to be a likely source of residues in plants. 

Parent acetamiprid is the predominant residue (>90% TRR) in three of the five metabolism 

studies. Confined rotational crop studies showed no residues of acetamiprid at the 30-day plantback interval.

Acetamiprid and metabolite IM-2-1 are the major residues in all ruminant tissues except muscle, 

where IM-2-1-amide accounts for nearly 50% of the TRR. IM-2-1-amide was not found in any 

other ruminant tissue. Metabolite IM-2-1 is the major residue in poultry tissues and eggs (50-

80% TRR). IM-2-5 is also a major residue in eggs (~20% TRR). Parent acetamiprid was not
Page 30 of 63

detected in poultry tissues or eggs. The metabolism of acetamiprid in lactating goat was similar 

to the profile observed in laying hen and rat. The initial transformation appears to be 

demethylation of the parent compound. The most abundant metabolite identified (both sexes) 

resulted from the removal of the cyanoacetamide group from demethylated parent. This removal 

(and direct removal of the group from the parent) resulted in cyanoacetamide metabolites.

5.1.7 Pesticide Metabolites and Degradates of Concern

A comparison of the available acute toxicity data for the parent versus the metabolites indicates 

that the metabolites IC-0, IM-0, IM-2-1, IM-1-4, IM-1-2, are either similar, or less acutely toxic 

than the parent. In subchronic feeding and mutagenicity studies the tested metabolites were 

shown to be either equivalent to, or less toxic than the parent. The acute toxicity and 

mutagenicity data indicate that the metabolite of concern in livestock, IM-2-1, is less toxic than 

the parent and is of similar mutagenic potential to the parent. Subchronic studies were not 

submitted to address the long-term toxicity of the IM-2-1 metabolite. Table 5.1.2 summarizes

the residues of concern (parent and metabolites) that will be considered for regulation.

Table 5.1.7 Summary of Metabolites and Degradates to be included in the Risk

 Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants Primary Crop Acetamiprid Acetamiprid

Rotational Crop Not applicable None at this time

Livestock Ruminant Acetamiprid and IM-2-1 (and 

IM-2-1-amide in ruminant 

muscle only)

Acetamiprid and IM-2-1

Poultry Acetamiprid and IM-2-1 Acetamiprid and IM-2-1

Drinking Water Acetamiprid Not Applicable

5.1.8 Drinking Water Residue Profile

D364248, D. Lieu 6/10/09. Tier I Drinking Water Assessment for Acetamiprid Proposed Uses on Red Clover 

(Grown for Seed Only), Grape, and Tomato (Greenhouse).

In a memo dated 6/10/09 [D364248, D. Lieu], EFED notified RD that new drinking water 

estimates would not be provided for the proposed use on red clover (grown for seed only), grape, 

and tomato (greenhouse) because the drinking water estimates derived from the uses on citrus 

and tree nuts reflect the maximum use patterns for acetamiprid. (Note: No proposed use 

information has been submitted for U.S.-grown tea.)

In conjunction with the uses on citrus and tree nuts, the Environmental Fate and Effects Division 

(EFED) prepared an estimate of potential residues in drinking water [G. Orrick, Tier I Drinking 
Page 31 of 63

Water Exposure Assessment for Acetamiprid on Cucurbit, Stone Fruit and Tree Nut Crop 

Groups, 6/21/05, D303582]. Estimated drinking water concentrations for acetamiprid in surface 

water were generated using the FIRST (FQPA Index Reservoir Screening Tool, v. 1.0) model. 

The results of the model reflect potential residues in a small drinking water reservoir surrounded 

by a runoff-prone watershed, assuming maximum pesticide application rates and no buffer 

between the reservoir and treated fields. Acetamiprid residues in ground water sources of 

drinking water were estimated using the screening regression model SCI-GROW (Screening 

Concentration In Ground Water, v. 2.3). The SCI-GROW residue estimate is based on 

environmental fate properties of the pesticide, maximum application rates, and existing data from 

small-scale prospective ground-water monitoring studies in vulnerable sites.

For surface water, the maximum application rate for the existing use of acetamiprid on citrus was 

used to provide model estimates of drinking water concentrations; for ground water, the 

proposed use on tree nut crops was used. However, since modeled surface water residues were 

considerably higher than ground water residues (Table 5.1.8), only the surface water residues 

were used quantitatively in the dietary (food + water) assessment.

Table 5.1.8. Tier I Analysis

1-in-10-year EDWCs in surface water and ground water for acetamiprid.

Drinking Water 

Source

Maximum Use Pattern Exposure EDWC

Surface water Citrus fruit Peak 20.1 ppb

Annual average 4.9 ppb

Ground water Tree nut Peak & annual 

average

 0.0016 ppb

For the acute assessment, an estimated drinking water concentration of 20.1 ppb was entered into 

the DEEMTM-FCID model for “water, direct, all sources” and “water, indirect, all sources.” For 

the chronic assessment, the value of 4.9 ppb was used. The ground water estimate of 1.6 ppt was 

much lower than surface water residues; therefore, dietary exposure and risk calculated using 

surface water residues are considered protective of potential exposure through ground water.

5.1.9 Food Residue Profile

D364833, Acetamiprid. Request for Label Amendments for New Uses on Clover; Small Vine Climbing Fruits, 

except Kiwifruit, Subgroup 13-07F (amending grape use); Greenhouse-grown Tomatoes; and a Regional 

Registration for Tea. Summary of Analytical Chemistry and Residue Data. D. McNeilly, 10/14/2009.

IR-4 has submitted magnitude of the residue data for acetamiprid on red clover, grapes, and 

tomato to support the new uses on clover and greenhouse tomatoes, and amended use on grapes 

(also expanded to small vine climbing fruits, except fuzzy kiwifruit, subgroup 13-07F). A 

summary of the residue data is presented in Table 5.1.9a. Residue data for tea, dried leaves; 

black brewed tea, green brewed tea, and spent leaves (for mass balance purposes only) are 

summarized in Table 5.1.9b.
Page 32 of 63

Table 5.1.9a. Summary of Residue Data from Tea Crop Field Trials with Acetamiprid.

Crop Matrix

Total Applic. 

Rate

(lb ai/A)

PHI 

(days)

Residue Levels (ppm)

n Min. Max. HAFT1 Median Mean Std. 

Dev.

Clover (Proposed use = One broadcast foliar spray treatment at a maximum of 0.075 lb ai/A; 28-day PHI)

Clover forage 0.074-0.079 28-34 6 <0.01 0.05 0.05 0.05 0.04 0.02

Clover hay 56-63 6 <0.01 <0.01 <0.01 0.01 0.01 --

Grapes and Other Climbing Vine Small Fruits (Except Fuzzy Kiwifruit) (Within Crop Subgroup 13-07F)

(Current registered use on Grapes = 0.1 lb ai/A total application rate; 7-day PHI)

(Proposed amended use = 0.2 lb ai/A total application rate; 3-day PHI)

Grape 0.195-0.206 2-3 36 0.01 0.25 0.25 0.08 0.11 0.07

Tomatoes (Current registered field use = 0.3 lb ai/A total application rate; 7-day PHI)

 (Proposed greenhouse use = 0.15 lb ai/A total application rate; 1-day PHI)

Tomato 0.300-0.324 1 6 <0.01 0.052 0.050 0.027 0.029 0.018

1 HAFT = Highest average field trial result.

TABLE 5.1.9b. Summary of Residue Data from Crop Field Trials with Acetamiprid.

Commodity Total Applic. 

Rate, 

lb ai/A

[kg ai/ha]

PHI

(days)

Residue Levels (ppm)

n Min. Max. HAFT1 Median

(STMdR)

Mean

(STMR)

Std. Dev.

Japan Study - Combined residues of acetamiprid and residues convertible to Metabolite IC-0

Green tea - dried 

leaves

0.13-0.27

[0.15-0.30]

6-7 8 13.6 40.9 39.3 23.9 25.3 9.82

13-14 8 8.15 17.2 16.6 13.1 12.8 4.19

20-21 8 2.30 5.44 5.44 3.64 3.75 1.19

Green tea -

brewed tea*

0.13-0.27

[0.15-0.30

6-7 8 7.74 27.7 27.0 17.3 17.4 7.29

13-14 8 5.17 12.7 12.6 9.21 9.07 3.38

20-21 8 1.57 3.30 3.27 1.87 2.15 0.70

India Study (wet and dry season tea) - Residues of acetamiprid per se (only mean values reported)2

Black tea - green 

shoots

0.022-0.045

[0.025-0.050]

0 12 3.96 9.53 9.53 NC36.54 NC

7 12 0.20 0.51 0.51 NC 0.33 NC

15 12 0.03 0.11 0.11 NC 0.06 NC

21 12 <0.05 <0.05 <0.05 <0.05 <0.05 0

Black tea - dried 

leaves

0.022-0.045

[0.025-0.050]

0 12 11.2 26.4 26.4 NC 18.5 NC

7 12 0.54 1.47 1.47 NC 0.95 NC

15 12 <0.05 0.26 0.26 NC 0.11 NC

21 12 <0.05 <0.05 <0.05 <0.05 <0.05 0

Black tea -

brewed tea*

0.022-0.045

[0.025-0.050]

0 12 5.4 12.6 12.6 NC 8.92 NC

7 12 0.24 0.61 0.61 NC 0.41 NC

15 12 <0.05 0.13 0.13 NC 0.07 NC

21 12 <0.05 <0.05 <0.05 <0.05 <0.05 0

Black tea - spent 

leaves

0.022-0.045

[0.025-0.050]

0 12 4.6 10.2 10.2 NC 7.5 NC

7 12 0.20 0.51 0.51 NC 0.36 NC

15 12 <0.05 0.09 0.09 NC 0.06 NC

21 12 <0.05 <0.05 <0.05 <0.05 <0.05 0

HAFT = Highest Average Field Trial. 2 The reported LOD (0.05 ppm) was used for calculation of median, mean, and standard 

deviation where appropriate. Only the 0-day PHI and PHIs relevant for comparison to the Japan trials were included in the 

summary. 3 NC = Not calculated. Median and standard deviation could not be calculated because only mean values were 

reported for each sample set. * The relatively high residues in the brewed tea, which HED expected to be much lower than the 

residues in or on the dried tea leaves, may reflect a back calculation of what the residues would have been on the dried tea leaves. 

Otherwise, HED can not account for why the residues were not diluted by the water used for making the tea.
Page 33 of 63

Clover

Three red clover field trials were conducted in the U.S. in Zone 11 (OR) during the 2006 

growing season. Each trial site consisted of one untreated plot and one treated plot. Red clover 

was treated with a single broadcast foliar application of Assail® 30SG, a 30% SG formulation of 

acetamiprid, at a rate of 0.074-0.079 lb ai/A (ca. 1x the maximum proposed seasonal rate on 

clover). Application was made when the crop was in the vegetative stage to blooming stage 

using ground equipment in 23-25 GPA spray volumes, without an adjuvant. Samples of clover 

forage were harvested 28 to 34 days following application. Additionally, hay samples were cut 

at a normal harvest time (coinciding with preharvest intervals of 56-63 days) and allowed to dry 

in the field prior to collection.

Residues of acetamiprid were <0.01-0.05 ppm in/on red clover forage harvested 28-34 days 

following a single broadcast foliar application of the 30% SG at 0.074-0.079 lb ai/A. Residues 

were below the LLMV (<0.01 ppm) in/on clover hay harvested 56-63 days following treatment.

Conclusions: The use pattern of the clover field trials adequately reflects the proposed label use 

pattern with the exception of the PHI for hay. The available field trial data indicate a regional 

tolerances for residues of acetamiprid in clover forage at 0.10 ppm and clover hay at 0.01 ppm, 

are appropriate. However, the submitted clover field trial data are not completely adequate to 

satisfy data requirements. The three clover field trials were all conducted in Zone 11 (OR) 

during the 2006 growing season, at the same location and within a very short time period of each 

other. The number of trials are adequate to support restricted use on clover in ID, OR and WA 

(Zones 11 and 12) according to OPPTS Guideline 860.1500, Attachment 11; however the 

guidelines state that for crops requiring 8 or more trials nationally (12 are required for clover), 

the trials for regional registrations must be conducted in multiple years to account for variability

due to climate conditions. As a condition of registration, HED recommends that two additional 

clover field trials be required, as confirmatory data. In addition, the submitted reside data 

included field trial data for only the 30SG formulation. However, additional residue chemistry

field trial data are not required to support registration of the 70 WP formulation. Use on clover 

grown for seed is to be limited to clover grown in ID, OR, and WA. Since the residue chemistry

data submitted for clover hay reflect PHIs of between 56-63 days, the PHI for acetamiprid use on 

clover should be increased to 56 days for any clover crop which will be harvested for hay.

No residue decline data were included in the clover field trials. However, residue decline studies 

on cotton, head lettuce, oranges, pears, and peppers were submitted in conjunction with 

PP#0F6082 (D264154, 12/31/2001, M. Doherty). These data indicated that residues of 

acetamiprid did not increase in the subject crops with increasing harvest intervals. Given the 

long PHI (28-days) for clover and available residue decline data on other crops, residue decline 

data will not be required to support the clover field trials. The available field trial data will 

support tolerances with regional registration for residues of acetamiprid in clover forage at 0.10 

ppm (with a 28-day PHI) and clover hay at 0.01 ppm (with a 56-day PHI).
Page 34 of 63

Grape; Fruit, Small Vine Climbing, Subgroup 13-07F, Except Fuzzy Kiwifruit

Eighteen grape field trials were conducted in the U.S. and Canada in Zones 1 (NY; 1 trial), 2 

(NJ; 2 trials), 5 (ON; 4 trials), 5A (MI; 1 trial), 10 (CA; 8 trials), 11 (BC; 1 trial), and 11/12 

(WA; 1 trial) during the 2005 growing season. Mature grape vines in established orchards were 

treated with two directed foliar applications of Assail® 70WP, a 70% WP formulation of 

acetamiprid, at 0.096-0.103 lb ai/A/application, with a 13- to 14-day retreatment interval, for a 

total rate of 0.195-0.206 lb ai/A (ca. 1x the maximum proposed seasonal rate on grapes and other 

climbing vine small fruits.

Residues of acetamiprid were 0.01-0.25 ppm in/on grapes harvested 2-3 days following the last 

of two directed foliar applications of the 70% WP for a total rate of 0.195-0.206 lb ai/A. No 

residue decline data were included in the field study.

Conclusions: The submitted grape residue data included field trial data for only the 70WP 

formulation (the original field trials also used a 70WP formulation). Although HED’s residue 

chemistry review (D364833, 10/14/09) recommended that additional residue chemistry field trial 

data are needed to support registration of the 30SG formulation, additional information provided 

by the registrant has convinced HED that such data are not necessary. HED agrees that both 

products are likely to produce a solution of acetamiprid due to its high water solubility.

The submitted grape field trial data are adequate for the 70 WP formulation pending label 

revision. Because the grape field trial data did not reflect the use of a surfactant in the 

application sprays, the label directions regarding use of a spreader, methylated seed oil or crop 

oil should be removed from the product label of Assail® 30SG (EPA Reg. No. 8033-36). 

Furthermore, in line with present OPP policy for a late season foliar use, a statement should be 

added to both the 30SG and 70WP labels prohibiting addition of adjuvants for application to 

grapes. If use of an adjuvant is desired then one should be used in side-by-side testing. The 

number and locations of the field trials are in accordance with OPPTS Guideline 860.1500 for 

grapes, and the use pattern of the field trials reflects the use pattern proposed for grapes (and 

other climbing vine small fruits, except fuzzy kiwifruit, within subgroup 13-07F), except for the 

adjuvant use. 

No residue decline data were included in the grape field trials. The residue decline studies from 

PP#0F6082 (D264154, M. Doherty, 12/31/2001), which indicated that residues of acetamiprid 

did not increase in various crops with increasing harvest intervals, will be used to fulfill the 

requirements for residue decline data. The available field trial data from the current submission, 

which reflect a higher seasonal rate and a shortened PHI from that which is currently registered 

for grape, will support a tolerance for residues of acetamiprid at 0.35 ppm. 

Grape is the representative crop of the fruit, small vine climbing, subgroup 13-07F, except fuzzy

kiwifruit, and the available grape data will support a subgroup tolerance at 0.35 ppm. The 

established individual tolerance for grape at 0.20 ppm should be deleted when the subgroup 13-

07F tolerance is established.
Page 35 of 63

Tomatoes (Greenhouse Study)

Three trials were conducted on tomatoes in the U.S. and Canada in Zones 4 (TN), 5 (ON), and 6

(TX) during the 2002 and 2003 growing seasons. Each trial site included one untreated plot and 

one treated plot. Tomato plants grown in rock wool substrate under greenhouse conditions were 

treated at the fruiting stage with four simulated drip-irrigation (chemigation) treatments of 

Assail® 70WP, a 70% WP formulation of acetamiprid, at rates equivalent to 0.074-0.081 lb 

ai/A/application. Applications were made with 7-day retreatment intervals, for a total rate of 

0.300-0.324 lb ai/A (ca. 2x the maximum proposed seasonal rate for greenhouse-grown tomato); 

no adjuvant was used. Samples of mature tomato were harvested one day after the last 

application. At the TX trial, additional treated samples were harvested 3, 5, and 7 days after the 

last application to generate residue decline data.

Residues of acetamiprid ranged from below the LLMV (<0.01 ppm) to 0.052 ppm in/on 

greenhouse-grown tomatoes harvested one day following the last of four drip-irrigation 

(chemigation) treatments of the 70% WP for a total rate equivalent to 0.300-0.324 lb ai/A. The 

decline data show that residues accumulated slightly, from an average of 0.027 ppm at the 1-day

PHI to an average of 0.037 ppm at the 7-day PHI.

Conclusions: Although the greenhouse trials were conducted at a 2x rate and the number of 

trials is marginal, no additional residue data will be required to support the proposed greenhouse 

use pattern for tomatoes. The tomato greenhouse data indicate that acetamiprid residues 

resulting from applications of Assail 70WP formulation of acetamiprid according to the proposed 

use pattern would not exceed the established tolerance for residues of acetamiprid in fruiting 

vegetables, crop group 8 (0.20 ppm). Although no data were provided for the proposed use of 

Tristar® 30SG on greenhouse tomatoes, HED now concludes the WP data support use of this 

additional formulation based on the water solubility of the active ingredient and the application 

being made to the roots of the plants by soil drench or irrigation water.

Tea

The Interregional Research Project No. 4 (IR-4) has submitted a report summarizing the results 

of two studies on tea conducted in Japan (by Nippon Soda Co., Ltd.) and India (by the Institute 

of Himalayan Bioresource Technology; IHBT). No raw data were included in the submission, 

all data presented herein are as reported in the original studies.

Nippon Soda Co, Ltd. conducted two trials in the Mie Prefecture and the Fukuoka Prefecture of 

Japan investigating the magnitude of the residue in dried green tea leaves and brewed tea 

following a single foliar application of a 20% water-soluble powder (SP) formulation of 

acetamiprid made to green tea in separate plots at 0.13 lb ai/A (0.15 kg ai/ha) and 0.27 lb ai/A 

(0.30 kg ai/ha). Applications were made in spray volumes of 321 gal/A (3000 L/ha). The 

following Good Agricultural Practice (GAP) information was provided for the 20% SP 

formulation in Japan: one foliar application at 0.10-0.40 kg ai/ha applied in 2000-4000 L/ha, 

with a 14-day preharvest interval (PHI). In a separate study, the Institute of Himalayan 

Bioresource Technology (IHBT) conducted two sets of trials in Palampur (Himachal Pradesh, 
Page 36 of 63

India) investigating the magnitude of the residue in black tea for green shoots, dried tea leaves, 

brewed tea, and spent leaves after brewing. Acetamiprid was applied to black tea in separate 

plots as a single foliar application of a 20% SP formulation of acetamiprid at 0.022 lb ai/A 

(0.025 kg ai/ha) and 0.045 lb ai/A (0.050 kg ai/ha) in spray volumes of 43 gal/A (400 L/ha). The 

application rates were reported to be 1x and 2x the recommended application rate for acetamiprid 

on tea. Two sets of trials were conducted, one during the dry season (June) and the second 

during the wet season (August). The following GAP information was provided for India: shoots 

along with bud are typically harvested at a 7-day PHI.

Samples of dried green tea leaves and brewed tea from the Japan study were analyzed for 

residues of acetamiprid and its metabolites convertible to 6-chloronicotinic acid (Metabolite IC0) using a common moiety gas chromatography method with electron capture detection 

(GC/ECD). Using this method, acetamiprid and metabolites are converted to Metabolite IC-0 

and methylated prior to determination by GC/ECD; residues are expressed as acetamiprid. The 

reported method limit of detection (LOD) is 0.05 ppm as acetamiprid. Samples of green shoots, 

dried black tea leaves, brewed tea, and spent leaves from the India study were analyzed for 

residues of acetamiprid using a high performance liquid chromatography method with ultraviolet 

detection (HPLC/UV). The reported LOD was 0.05 ppm. Both methods are adequate for data 

collection based on the submitted concurrent recovery data.

Regarding the common moiety method used in the Japan study, we note that, although 

Metabolite IC-0 is not a residue of concern for tolerance enforcement or risk assessment, based 

on the available plant metabolism studies, it may constitute a significant portion of the total 

residues (e.g., up to 24% total radioactive residues (TRR) in cotton seed and 31% TRR in carrot 

flesh; refer to D278652, 11/13/01, H. Bietlot and M. Doherty). Therefore, the residues reported 

for the Japan study may reflect an overestimation of expected residues of acetamiprid per se in 

green tea.

Samples of dried green tea leaves and brewed tea from the Japan study were stored frozen from 

collection to analysis for up to 3.5 and 1.7 months, respectively. HED believes there are 

sufficient storage stability data available for acetamiprid, demonstrating that residues are stable 

in crop commodities stored frozen for up to 12 months and crop commodities stored at ambient 

temperatures for up to 7 days, to support both studies (refer to D264154, M. Doherty, 12/31/01).

The study report also contained a list of multiresidue method analysis results for residues of 

acetamiprid in tea received in commercial shipments from various countries. Although residues 

were nondetectable in the majority of green and black tea samples received from Argentina, 

Bangladesh, Burundi, China, Ecuador, Ethiopia, India, Indonesia, Iran, Kenya, Malawi, 

Mozambique, Rwanda, Sri Lanka, South Africa, Tanzania, Turkey, Uganda, Vietnam, 

Zimbabwe, detectable residues of acetamiprid were found in tea samples from China (0.03-0.04 

ppm; n=3), Indonesia (0.03 ppm; n=1), and Vietnam (0.03-0.12 ppm; n=7). The source of these 

data was not identified.

Conclusions: No use was proposed for domestically grown tea. The acetamiprid data for tea 

grown in Japan and India consisted of field trial data representing application rates of 0.022-0.27 
Page 37 of 63

lb ai/A (1 foliar application) with a 6- to 14-day PHI and were entered into the tolerance 

spreadsheet as it matched the global GAP of 7-14 day PHIs. All 38 field trial sample results 

were equal to or greater than the LOD (LOD = 0.05 ppm ). HED believes that the 50.0 ppm 

tolerance (without U.S. registrations, i.e., an import tolerance) is adequate to cover residues in or 

on tea and instant tea and hence is not recommending for a separate instant tea tolerance. HED 

notes that the 50.0 ppm tolerance harmonizes with Japan. The residue data from Japan included 

the IC-0 metabolite, which is not in the U.S. tolerance expression and is considered conservative.

A summary table of proposed and recommended tolerances for acetamiprid associated with all 

the proposed commodities and uses can be found in Appendix C.

5.1.10 International Residue Limits

There are no Codex maximum residue limits (MRLs) established for residues of acetamiprid on 

crop or animal commodities; no Mexican MRLs are established on crops associated with this 

petition. Canada has established an MRL for acetamiprid residues in grapes at 0.20 ppm. The 

recommended U.S. tolerance for Subgroup 13-07F tolerance at 0.35 ppm is not harmonized with 

the Canadian MRL, presumably because of differences in good agricultural practices. Japan has 

a 50 ppm MRL for tea and HED recommends setting the tolerance at the same level. An 

International Residue Limit Status (IRLS) sheet is appended to this document.

5.2 Dietary Exposure/Risk Pathway

Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For acute 

and chronic dietary risk assessments, the risk is expressed as a percentage of the population 

adjusted dose (PAD). The acute PAD (aPAD) is derived by dividing the selected acute dietary

dose (NOAEL) by the appropriate uncertainty and FQPA safety factors. The chronic PAD 

(cPAD) is derived by dividing the selected chronic dietary dose (NOAEL) by the appropriate 

uncertainty and FQPA safety factors. Typically, HED has dietary risk concerns when the 

estimated exposure exceeds 100% of the aPAD and/or cPAD. 

5.2.1 Dietary Exposure and Risk

Acute and chronic dietary risk assessments were conducted for acetamiprid using the Dietary

Exposure Evaluation Model (DEEM-FCID, Version 2.03) which uses food consumption data 

from the USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII, 1994-1996 and 

1998). The acute and chronic dietary analyses are considered partially refined by the inclusion 

of percent crop treated values and processing data. The full dietary analysis for the subject 

peitions can be found in the HED memorandum: Acetamiprid. Acute and Chronic Dietary 

Exposure Assessments to Support Section 3 Registration of Uses on Clover, Small Vine Climbing 

Fruits, except Kiwifruit, Subgroup 13-07F, Greenhouse Grown Tomatoes and Tea. D369019, 

12/01/09.

The current acute and chronic dietary exposure assessments include existing uses and the 

tolerances proposed by the Interregional Research Project Number 4 (IR-4) for new uses of 

acetamiprid on clover grown for seed, small vine climbing fruits, except kiwifruit, subgroup 13-
Page 38 of 63

07F (amending established grape uses), greenhouse-grown tomatoes, and tea.

For the acute dietary assessment, field trial residues were refined when possible. If field trial 

residues were reported below the limit of quantification (LOQ), HED assumed 1⁄2 LOQ (i.e., 

0.005 ppm). In certain cases where it was appropriate, HED translated field trial data from one 

commodity to another (e.g., peaches to nectarines, or plum to apricots). Percent crop treated 

estimates, which exist for only several of the subject crops (apples, broccoli, celery, lettuce, 

pears, grapefruit, grapes, oranges, peppers, spinach, and tomatoes), were incorporated into the

dietary assessments as a refinement. Average percent crop treated values for commodities were

applied to the chronic dietary assessment, and maximum percent crop treated values were

applied to the acute dietary assessment (see Table 5.2.1). Processing factors based on submitted

studies were incorporated into the acute dietary analyses for the following commodities: apple 

juice, orange juice, grape juice, raisins, dried prunes, tomato paste, and tomato puree. For all 

other commodities included in the acute assessment, the DEEMTM Version 7.87 default 

processing factors were used. Those default factors were used for all processed commodities in 

the chronic assessment except for dried prunes. Finally, tolerance level residues were also used 

for livestock commodities.

Usage Data

In order to refine the dietary exposure estimates for acetamiprid, HED requested a Screening 

Level Usage Analysis (SLUA), which was conducted by the Biological and Economic Analysis 

Division (BEAD), 6/11/09. The SLUA includes estimates of maximum %CT for the acute 

assessment and average %CT for determining chronic exposure (Table 5.2.1.). Commodities 

with the most significant acetamiprid usage in terms of maximum %CT include pears (60%), 

apples (30%), celery (45%), and lettuce (20%). Commodities with the most significant usage in 

terms of lbs ai applied include apples (10,000), cotton (20,000), and pears (5,000).

Table 5.2.1. Percent Crop Treated Data Used in DEEM

Commodity Avg Max

Apples 20 30

Broccoli 5 15

Cabbage 5 10

Cauliflower 10 15

Celery 25 45

Cotton 5 5

Grapefruit 2.5 2.5

Grapes 5 10

Lemons 5 5

Lettuce 10 20

Oranges 2.5 5
Page 39 of 63

Table 5.2.1. Percent Crop Treated Data Used in DEEM

Commodity Avg Max

Peaches 1 2.5

Pears 35 60

Peppers 2.5 5

Potatoes 2.5 2.5

Pumpkins 1 2.5

Spinach 5 15

Squash 2.5 2.5

Tomatoes 5 10

For the acute analysis, %CT was incorporated into RDFs. For the chronic analysis, average 

%CT was included for the commodities listed in the table above.

As mentioned above, under Section 5.1.8, HED incorporated EDWCs directly into the DEEMTM

FCID model for “water, direct, all sources” and “water, indirect, all sources.” For the acute 

assessment, an EDWC of 20.1 ppb was entered into the model, and for the chronic assessment, 

the value of 4.9 ppb was used.

5.2.2 Exposure and Risk Characterization

The dietary analyses reflect all currently registered and proposed acetamiprid uses and indicate 

that both the acute and chronic dietary exposure do not present a risk concern for HED for the 

general U.S. population or any of population subgroup (Table 5.2.2).

Acute Dietary (Food and Drinking Water) Exposure Results and Characterization

The probabilistic acute dietary exposure assessment included anticipated residues from field 

residue trials, processing factors, maximum %CT estimates (for existing uses only) generated by

the Biological and Economic Analysis Division (BEAD), and the modeled peak concentration of 

acetamiprid residues in surface water sources of drinking water. 100 %CT was assumed for 

crops where % crop treated information was not available. Although the acute assessment has

been refined, the resulting exposure estimates are still considered conservative since field trial 

data were the basis for the anticipated residues, and because a lower tier drinking water model 

(FIRST) was used to estimate residues in drinking water.

Acute dietary exposure estimates at the 99.9th percentile are below HED’s level of concern for 

the general US population and all other population subgroups. For the US population, the 

estimated exposure of 0.020 mg/kg/day corresponds to 20% aPAD; for children 1-2 years old, 

the estimated exposure of 0.041 mg/kg/day corresponds to an acute dietary risk of 41% aPAD.
Page 40 of 63

Chronic Dietary (Food and Drinking Water) Exposure Results and Characterization

For the chronic analysis, tolerance-level residues were assumed for all food commodities with 

existing and proposed acetamiprid tolerances. Percent crop treated was used for many 

commodities as detailed in Table 5.2.1. The chronic analysis also included the modeled surface 

water annual average residue in drinking water. Even though %CT information was used in the 

chronic analysis, the exposure and risk estimates are still conservative since tolerance level 

residues were used, because 100 %CT was assumed for crops where % crop treated information 

was not available, and because a lower tier drinking water model (FIRST) was used.

Chronic dietary exposure to acetamiprid, including existing and proposed uses, is below HED’s 

level of concern for the US population and all other population subgroups. For the general US 

population, an estimated exposure of 0.0024 mg/kg/day corresponds to 3% of the chronic 

population adjusted dose (cPAD); children 1-2 years old were the highest exposed population 

subgroup, with an estimate of 0.0087 mg/kg/day, or 12% cPAD. Risks for all population 

subgroups are less than 100% cPAD, and are not of concern.

Table 5.2.2. Summary of Dietary (Food + Water) Exposure and Risk for Acetamiprid

Population Subgroup

Acute Dietary

(99.9th Percentile) Chronic Dietary

Dietary Exposure 

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

General U.S. Population 0.020190 20 0.002375 3.3

All Infants (< 1 year old) 0.026336 26 0.004780 6.7

Children 1-2 years old 0.040892 41 0.008693 12

Children 3-5 years old 0.029647 30 0.006066 8.5

Children 6-12 years old 0.016429 16 0.003396 4.8

Youth 13-19 years old 0.013137 13 0.001739 2.5

Adults 20-49 years old 0.013988 14 0.001683 2.4

Adults 50+ years old 0.012372 12 0.001808 2.5

Females 13-49 years old 0.011917 12 0.001708 2.4

5.2.3 Cancer Dietary Risk

HED has classified acetamiprid as “not likely to be carcinogenic to humans.” Based upon this 

classification, HED has determined there is no cancer risk associated with the existing and 

proposed uses.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

The registrant has not proposed new or revised residential uses. Therefore, new residential 

handler and postapplication exposure assessments were not conducted. Acetamiprid is 
Page 41 of 63

registered for controlling a wide variety of indoor and outdoor insect pests in residential settings. 

The MOEs for residents applying bait and gel products were 1500-3500 (D303171, T. Moriarity, 

10/25/07). In a more recent assessment of exposures to residential handlers from products used 

on indoor and outdoor residential settings, the risks were found to be not of concern for all 

scenarios identified (D353040, Z. Figueroa, 12/1/08). An analysis of the postapplication risks to 

adults and children from contacting treated areas has also been performed recently (D353012, C. 

Swartz, 12/12/08). In the tables below, only the risk to children are shown since as noted in the 

12/12/08 memo they are the worse case versus those for adults.

Table 6a. Acetamiprid: Short- and Intermediate-Term Postapplication Exposures and Risks to Toddlers Following

 Turf Treatments in Residential Settings.1

Exposure Scenario

Application 

Rate

(lb AI/acre)

Exposure (mg/kg/day) MOE 2

Short-term Interm. term Short-term Interm. term

Residential turf (dermal) 

0.187

0.0072 0.0036 1,400 2,800

Hand to mouth (oral) 0.0028 0.0013 3,600 7,600

Object to mouth (oral) 0.00069 NA 14,500 NA

Incidental soil ingestion (oral) 0.0000093 NA 1,100,000 NA

Total exposure (dermal & oral) N/A 0.0107 0.0049 900 2,000

1. From C. Swartz, D353012, 12/12/08.

2. Short- & intermediate-term dermal or oral NOAEL (10 mg/kg/day)/exposure (mg/kg/day).

TABLE 6b: Acetamiprid: Short-term Postapplication Exposure and Risk to Toddlers Following Indoor Crack 

 and Crevice Treatments 1

Exposure Scenario Descriptor Exposure (mg/kg/day) MOE 2

Dermal exposure

Carpet and hard surfaces

0.0195 510

Incidental oral exposure 0.0065 1500

Total dermal & oral exposures 0.026 380

1. From C. Swartz, D353012, 12/12/08.

2. Short- & intermediate-term dermal or oral NOAEL (10 mg/kg/day)/exposure (mg/kg/day).

Aggregate exposures of acetamiprid include the short- and intermediate-term postapplication 

exposures following turf treatment and the short-term postapplication exposure following indoor 

crack and crevice treatment.

6.1 Residential Handler Exposure

The MOEs for residents applying bait and gel products were 1500-3500 (D303171, T. Moriarity, 

10/25/07). In a recent assessment of exposures to residential handlers from products used on 

indoor and outdoor residential settings, the risks are not of concern for all applicable scenarios 

identified (D353040, Z. Figueroa, 12/1/08).

6.2. Residential Postapplication Exposure

An evaluation of postapplication exposure resulting from the proposed use and label change was 
Page 42 of 63

completed (D353040, Z. Figueroa, 12/1/08 and D366701, S. Oonnithan, 10/9/09); risks were not 

of concern for any of the scenarios identified and assessed. Detailed discussions of the 

assumptions and methods used for assessing residential exposure from the proposed use are 

provided in the 12/1/08 memorandum.

The postapplication scenarios assessed for toddlers’ exposure following perimeter treatment 

include:

 Dermal exposure from treated lawns due to high contact lawn activities; 

 Hand-to-mouth transfer of pesticide residues on lawns; 

 Object-to-mouth transfer of pesticide residues on lawns; and 

 Incidental ingestion of soil from pesticide-treated residential areas.

Risks for these scenarios are provided in Table 6.2a.

Table 6.2a. Short- and Intermediate-Term Dermal & Indirect Ingestion - Toddler Residential Risk Estimates 

for Postapplication Exposure on Turf

Exposure Scenario Route of 

Exposure

Application 

Rate

(lb ai/acre)

Dermal Transfer 

Coefficient (μg/cm2)

Absorbed Dose 

(mg/kg/day) MOE

Residential Turf Dermal

0.187

5,200

(Short-term)

0.0072

(Short-term) 1,400

2,600

(Intermediate-term)

0.0036

(Intermediate-term) 2,800

Hand to Mouth Oral NA

0.0028

(Short-term) 3,600

0.0013

(Intermediate-term) 7,600

Object to Mouth Oral NA 0.00069 14,500

Incidental Soil 

Ingestion Oral NA 0.0000093 1,100,000

Combined Exposure1 N/A N/A N/A

0.01071

(Short-term) 9001

0.00491

(Intermediate-term) 2,000

1

1- Combined exposure is the sum of dermal and oral exposures.

Table 6.2b summarizes the postapplication exposure and risk for toddlers resulting from contact 

with carpet and hard surfaces following crack and crevice application of F4688 50 WP 

Insecticide/Termiticide on indoor surfaces. The bolded values represent the exposure to be 

aggregated with exposure from food and drinking water.

TABLE 6.2b: Postapplication Exposure and Risk Following Indoor Crack/Crevice 

Treatment.

Scenario Descriptor Daily Dose

(mg/kg/day) MOE

Dermal Exposure Carpet and

Hard Surfaces 0.0195 510
Page 43 of 63

Incidental Oral 

Exposure

Carpet and Hard 

Surfaces 0.0065 1500

Combined Dermal 

Incidental Oral 

Exposure

Carpet and Hard 

Surfaces 0.0260 380

6.3 Other (Spray Drift, etc.)

Spray drift is a potential source of exposure for residents living in close proximity to spraying 

operations. This situation is particularly the case with aerial application. However, to a lesser 

extent, spray drift resulting from the ground application of acetamiprid could also be a potential 

source of exposure. The Agency has been working with the Spray Drift Task Force (a 

membership of US pesticide registrants), EPA Regional Offices, State lead Agencies for 

pesticide regulation, and other parties to develop the best spray drift management practices. 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, 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

and risks associated with pesticide application.

7.0 Aggregate Risk Assessments and Risk Characterization

Consistent with FQPA, HED considers aggregate risk to a pesticide from the three major routes 

(dermal, oral, and inhalation) when potential residential exposures exist. In its acetamiprid

aggregate assessment, HED combined dietary (food + water) and non-dietary (residential) 

exposure sources to obtain an estimated aggregate exposure. When aggregating exposures and 

risks from various sources, HED considers both the route and duration of exposure. Based upon 

the residential use pattern of acetamiprid products, HED has determined that acute, short-term, 

intermediate-term and chronic aggregate risk assessments are appropriate. 

7.1 Acute Term Aggregate Risk

The acute aggregate risk is equal to the acute dietary exposure via food and drinking water, and 

therefore is identical to the exposure and risk characterization found in Section 5.2.2. The acute 

aggregate risks for acetamiprid are less than 100% of the aPAD for all population subgroups and,

therefore, do not pose a risk concern for HED.

7.2 Short- and Intermediate-Term Aggregate Risk

Short-term aggregate risk is based on the chronic (average) dietary exposure (food + water) 

combined with short-term residential exposure. Intermediate-term aggregate risk is based on the 

chronic (average) dietary exposure combined with intermediate-term residential exposure.
Page 44 of 63

Short- and intermediate-term aggregate risks for residential handlers were assessed previously by

T. Moriarity (see Table 15, D303171, 10/25/07). The aggregate MOEs for two adult populations 

(20-49 years; 50+ years) were 900 to 930. Since the dietary exposure estimates are now more 

refined due to the greater use of percent crop treated, these aggregate risks would be even lower 

and are not of concern. 

For short-term and intermediate-term aggregate risks, the combined chronic dietary (food + 

water) exposure is combined with short- and intermediate-term residential postapplication 

exposures for toddlers. The combined food, water and residential exposures are then compared 

to the dose for risk assessment to determine the resulting margin of exposure (MOE). HED has 

updated the dietary component (food and water) in this assessment. In the case of acetamiprid, 

all short- and intermediate-term risk assessments are based on the effects observed in the DNT 

study, and therefore exposures from dermal and oral routes have been combined. See Table 7.2 

for a summary of short- and intermediate-term aggregate risks for toddlers.

TABLE 7.2: Acetamiprid Short- and Intermediate-Term Aggregate Exposure

 and Risk for Toddlers.

Scenario

Combined 

Dermal/Oral 

Exposure

(mg/kg/day)1

Chronic Food Exposure 

Food

(mg/kg/day)2

Aggregate 

Exposure

(mg/kg/day)3

MOE4

Indoor Exposure 

Crack and Crevice 

Treatment

(short-term)

0.0260 0.008693 0.0347 290

Turf Exposure

(short-term) 0.0107 0.008693 0.0194 520

Turf Exposure 

(intermediate-term) 0.0049 0.008693 0.0136 740

1. Combined dermal and oral exposures were taken from D366701, S. Oonnithan, 10/9/09.

2. Chronic food exposure does not change with each scenario; see Table 5.2.2.

3. Aggregate exposure = Combined dermal/oral exposure + chronic food exposure.

4. MOE = NOAEL/Aggregate Exposure = 10 (mg/kg/day)/aggregate exposure (mg/kg/day).

Short- and intermediate-term aggregate risks (MOEs) are not of concern. HED notes that the 

lowest aggregate MOE of 290 is based on the indoor use. The MOEs calculated for exposure 

from turf are higher, but are considered to be more conservative, because the intended use 

pattern does not include broadcast treatment of lawns, but has been assessed as such in order to 

be protective. Adult aggregate risks due to postapplication exposure have not been assessed 

since the toddler risks are the worst case.

7.3 Chronic-Term Aggregate Risk

The dietary exposure pathway (food and drinking water) is the only source of chronic exposure 

to acetamiprid (i.e., 180 consecutive days or more). Therefore, the chronic aggregate exposure 
Page 45 of 63

and risk estimates are equivalent to the chronic dietary exposure and risk estimates discussed in 

Section 5.2.2 above. The chronic aggregate risks for acetamiprid are less than 100% of the 

cPAD for all population subgroups and, do not pose a risk concern for HED.

8.0 Cumulative Risk Characterization/Assessment

FQPA (1996) stipulates that when determining the safety of a pesticide chemical, EPA shall base 

its assessment of the risk posed by the chemical on, among other things, available information 

concerning the cumulative effects to human health that may result from dietary, residential, or 

other non-occupational exposure to other substances that have a common mechanism of toxicity. 

The reason for consideration of other substances is due to the possibility that low-level exposures 

to multiple chemical substances that cause a common toxic effect by a common mechanism 

could lead to the same adverse health effect as would a higher level of exposure to any of the 

other substances individually. A person exposed to a pesticide at a level that is considered safe 

may, in fact, experience harm if that person is also exposed to other substances that cause a 

common toxic effect by a mechanism common with that of the subject pesticide, even if the 

individual exposure levels to the other substances are also considered safe.

Acetamiprid is a member of the neonicotinoid class of pesticides which also includes 

thiamethoxam, clothianidin, imidacloprid and several other active ingredients. Structural 

similarities or common effects do not constitute a common mechanism of toxicity. Evidence is 

needed to establish that the chemicals operate by the same, or essentially the same sequence of 

major biochemical events (EPA, 2002). Although the neonicotinoids bind selectively to insect 

nicotinic acetylcholine receptors (nAChR), the specific binding site(s)/receptor(s) are unknown 

at this time. Additionally, the commonality of the binding activity itself is uncertain, as 

preliminary evidence suggests that clothianidin operates by direct competitive inhibition, while 

thiamethoxam is a non-competitive inhibitor. Furthermore, even if future research shows that 

neonicotinoids share a common binding activity to a specific site on insect nicotinic 

acetylcholine receptors, there is not necessarily a relationship between this pesticidal action and a 

mechanism of toxicity in mammals. Structural variations between the insect and mammalian 

nAChRs produce quantitative differences in the binding affinity of the neonicotinoids towards 

these receptors, which, in turn, confers the notably greater selective toxicity of this class towards 

insects, including aphids and leafhoppers, compared to mammals. Additionally, the most 

sensitive toxicological effect in mammals differs across the neonicotinoids (e.g., testicular 

tubular atrophy with thiamethoxam; mineralized particles in thyroid colloid with imidacloprid). 

Thus, there is currently no evidence to indicate that neonicotinoids share common mechanisms 

of toxicity, and EPA is not following a cumulative risk approach based on a common mechanism 

of toxicity for the neonicotinoids. In addition, acetamiprid does not appear to produce a toxic 

metabolite produced by other substances. Therefore, for the purposes of this tolerance action, 

EPA has not assumed that acetamiprid has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements concerning common mechanism determinations and procedures for cumulating 

effects from substances found to have a common mechanism released by EPA’s Office of 

Pesticide Programs on EPA’s website at http://www.epa.gov/pesticides/cumulative/.
Page 46 of 63

9.0 Occupational Exposure/Risk Pathway

9.1 Short-/Intermediate-/Long-Term Handler Risk

No chemical-specific data for assessing handler exposures were submitted to the Agency in 

support of the proposed uses associated with the three subject petitions. Therefore, when 

estimating occupational exposures, HED used: 1) surrogate data from the Pesticide Handlers 

Exposure Data Base (PHED v1.1; 2) Outdoor Residential Exposure Task Force (ORETF) data; 

3) standard assessment variables established by the Health Effects Division Science Advisory

Council for Exposure (e.g. maximum application rates, standard acres treated per day, 70 kg 

body weight for workers); and, 4) standard protection factors assumed with specified personal 

protective equipment). The estimated exposures are believed to be reasonable high-end 

estimates.

The proposed use patterns of acetamiprid indicate that the Assail® 70WP and Assail® 30SG are 

applied 1-2 times per season at 1-14 day intervals on clover and grapes resulting in short-term 

exposure to mixers, loaders, and applicators. Repeated use of these products by commercial 

handlers on several farms growing clover and/or grapes would also result in intermediate-term 

exposure to handlers as well. In the case of greenhouse grown tomatoes using TriStar® 30SG, 

the handlers are subjected to short-, intermediate, and long-term exposures due to the year-round 

growing operations.

9.2 Handler and Pesticide Control Operator (PCO) Risk Characterization

Since both dermal (short- and intermediate-term) and inhalation (short- and intermediate-term) 

endpoints for occupational exposures were the same, the route specific exposure values were 

combined to calculate a total exposure which was compared to the NOAEL (10 mg/kg/day from 

the DNT study) to determine the MOEs. Estimated exposures for all scenarios of the three 

product labels do not present a risk concern to HED when the PPE stated on the proposed label is 

assumed. Exposures to agricultural handlers associated with the proposed uses on Assail® 

70WP, and Assail® 30SG are not a risk concern to HED, provided handlers obey the personal 

protection directions specified on the proposed labels. In addition, exposures to PCO’s from the

proposed labeled uses are not a risk concern to HED provided PCO’s comply with the personal 

protection directions specified on the label. MOEs for handlers are attached in Appendix A.

9.3 Postapplication Exposure and Risk

The registrant has not submitted a chemical-specific postapplication exposure study to quantify 

postapplication exposure for proposed crops of clover, grape, and tomatoes. In the absence of 

chemical-specific data, dermal exposures were estimated using default dislodgeable foliar 

residue (DFR) and surrogate transfer coefficient (TC) values.

In Appendix A, Table A.5 is a summary of the short- and intermediate-term risk to workers who 

enter treated fields of clover, grape, and tomatoes on day "0". The estimated postapplication risk 

for all crop-related activities is MOE ≥ 330 (the LOC=100); therefore, not of concern. Long-
Page 47 of 63

term risk to workers performing scouting, irrigation, and harvesting of tomatoes grown in 

greenhouses also is not of concern. The use of acetamiprid in the greenhouse as a soil drench 

and micro-irrigation is also not of concern with regard to postapplication exposure to workers.

Restricted Entry Interval (REI)

All three labels, Assail®70WP, Assail®30SG, and TriStar®30SG have CAUTION as the 

SIGNAL WORD. An REI of 12 hours is set based on the acute toxicity of acetamiprid technical,

which is classified as Category III and IV for acute dermal toxicity, dermal irritation, and eye 

irritation. Acetamiprid is not a dermal sensitizer. Acute toxicity Category III and IV chemicals 

are assigned a 12-hour REI. The current assessment of postapplication exposures and risks for 

the proposed uses on clover, grapes, and greenhouse grown tomatoes indicates that the 12-hour 

REI set for acetamiprid is adequate to protect the workers who may enter treated fields to do any 

crop-related agricultural activities. 

10.0 Data Needs and Label Recommendations

Directions for Use:

No proposed use was submitted for the use on tea in South Carolina. HED cannot evaluate the 

domestic use without a proposed use, application methods, and a proposed formulation. GAP 

information was provided for Japan and India. The use directions are adequate to establish a 

tolerance without U.S. registrations (an “import” tolerance).

Because the grape field trial data submitted with this petition did not reflect the use of a 

surfactant in the application sprays, the label directions regarding use of a spreader, methylated 

seed oil or crop oil should be removed from the product label of Assail® 30SG (EPA Reg. No. 

8033-36). Furthermore, in line with present OPP policy for a late season foliar use, a statement 

should be added to both the 30SG and 70WP labels prohibiting addition of adjuvants for 

application to grapes. If use of an adjuvant is desired then one should be used in side-by-side 

testing.

The PHI for clover harvested for hay should be increased to 56 days on the 30SG and 70WP 

labels.

Tolerances:

HED recommends tolerances for acetamiprid be established as specified in Appendix C. The 

tolerance expression should be revised as stated in Section 1.1.

The final tolerances for subgroup 13-07F should reflect the correct commodity definition as 

specified in Appendix C. A revised Section F is not needed for this minor change. The 

established individual tolerance for grape at 0.20 ppm should be concomitantly removed with 

establishment of the subgroup 13-07F tolerance.
Page 48 of 63

Conditional Data:

 Two clover field trials reflecting the same use pattern utilized in the submitted studies.

Submittal of Analytical Reference Standards:

Analytical standards for the IM-2-1 and IM-2-1-amide metabolites are not available at the 

Repository and should be supplied. The reference standards should be sent to the Analytical 

Chemistry Lab, which is located at Fort Meade, to the attention of Theresa Cole at the following 

address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

(Note that the mail will be returned if the extended zip code is not used.)

References:

Acetamiprid. Request for Label Amendments for New Uses on Clover; Small Vine Climbing 

Fruits, except Kiwifruit, Subgroup 13-07F (amending grape use); Greenhouse-grown Tomatoes; 

and a Regional Registration for Tea. Summary of Analytical Chemistry and Residue Data. 

D364833, 10/14/09, D. McNeilly.

Acetamiprid. Acute and Chronic Dietary Exposure Assessments to Support Section 3 

Registration of Uses on Clover, Small Vine Climbing Fruits, except Kiwifruit, Subgroup 13-07F, 

Greenhouse Grown Tomatoes and Tea. D369019, D. McNeilly, Dec 1, 2009.

Acetamiprid: Occupational and Residential Exposure Assessment for the New Uses on Clover 

and Greenhouse Grown Tomatoes and for Increasing the Application Rate on Grapes. 

D366701, S. Oonnithan, 10/9/09.

Acetamiprid: Occupational/Residential Exposure and Risk Assessment for Proposed Use on 

Indoor/Outdoor Household Pest Control. 12/1/08, Z. Figueroa.

Tier I Drinking Water Assessment for Acetamiprid Proposed Uses on Red Clover (Grown for 

Seed Only), Grape and Tomato (Greenhouse). David Lieu, June 10, 2009.

Acetamiprid New Uses (Bulb Vegetables, Succulent Legumes, Strawberries, and Other Berries): 

Transmittal of Tier I Drinking Water Exposure Assessment. July 24, 2007; D331596, and 

D336256.

Acetamiprid. Human Health Risk Assessment for a Proposed Label Amendment Allowing 

Food/Feed Use on Vegetable Transplants. D352925, 11/25/08, W. Drew.
Page 49 of 63

Acetamiprid: Occupational and Residential Exposure Assessment for Proposed Section 3 

Registration for General Pest Control Uses. 02/17/05; D304214.

Acetamiprid: Aggregate Risk Assessment Associated with the Proposed Use on Indoor/Outdoor 

Household Pest Control. 12/12/08, Christina Swartz.

Acetamiprid: Human Health Risk Assessment for Proposed Food Uses on Stone Fruits, Cucurbit 

Vegetables, Tree Nuts, Berries, Strawberries, Bulb Vegetables, Legumes (Peas and Beans) and

for Residential/Commercial Insecticide/Termiticide Uses. 10/25/07, T. Moriarity.

Acetamiprid. Petitions Requesting the Establishment of Permanent Tolerances (Associated with 

Section 3 Registration) for New Food/Feed Uses of the Insecticide on Berries (Crop Group 13), 

Bulb Vegetables (Crop Group 3), Edible Podded Legume Vegetables (Crop Subgroup 6A), 

Succulent Shelled Pea and Bean (Crop Subgroup 6B), and Strawberry and Other Low-growing 

Berries. Summary of Analytical Chemistry and Residue Data. Petition Numbers 6F7051 

(Various Crops) and 6E7163 (Strawberry). 10/23/2007; W. Drew; D328216.
Page 50 of 63

Appendix A: Occupational Exposure and Risk Tables

Table A.1. Acetamiprid: Potential Short-term Exposure Scenarios Resulting from Its Use on Clover, 

Grape, and Greenhouse Grown Tomatoes.

Crop Formulation 1Scen. No. Appl. equipment Handler Comments 2

Clover

Assail® 70WP

and WP/WSB 

1 foliar/aerial, fixed wing M/L

2 " " applicator

3 " " flagger

4 foliar/ground boom M/L

5 " " applicator

Assail® 30SG

6 foliar/aerial, fixed wing M/L

7 " " applicator same as # 2

8 " " flagger same as # 3

9 foliar/ground boom M/L

10 " " applicator same as # 5

Grape

Assail® 70WP

and WP/WSB 

11 foliar/aerial, fixed wing M/L

12 " " applicator

13 " " flagger

14 foliar/air blast M/L

15 " " applicator

Assail®30SG

16 foliar/aerial, fixed wing M/L

17 " " applicator same as # 12

18 " " flagger same as # 13

19 foliar/air blast M/L

20 " " applicator same as # 15

Tomatoes 

grown in 

greenhouse

TriStar®30SG

21 drip/micro irrigation M/L/A no unit exposures

22 back-pack sprayer M/L/A root zone spray 

23 low-pr. Hand wand M/L/A root zone spray 

24 high pr. Hand wand M/L/A soil drench

1. Assail 70WP is sold as WP (powder) and as water soluble bags (WSB).

2. Duplicate scenarios (indicated) having identical inputs were not assessed. 
Page 51 of 63

Table A.2. Acetamiprid: Short- and Intermediate-term Occupational Risks to Handlers Resulting From the Use of Assail 70WP Assail 30SG 

Insecticides on Clover.

Crop 

Scen.

No.1

Formulation, 

Appl. method 

& Rate (AI/A)

Handler PPE & 

Mitigation 2

Acres 

treated/ 

day

Unit exposure (mg/lb AI handled) 

and Exposed dose mg/kg/day) 3

Total exp, 

(mg/kg/ day) 

4

Short/Interm. 

term MOE 5

Dermal Inhal.

Clover

1A Assail 70WP, 

Aerial, 0.075 M/L Baseline 350

3.7

1.62E-01

0.04342

1.90E-02

0.18087 55

1B " M/L Baseline + 

gloves

350

0.17

7.44E-03

0.04342

1.90E-02

0.02643 380

1C

Assail 70WP/WSB

Aerial, 0.075 M/L Baseline 350

0.021

9.19E-04

0.00024

1.05E-04

0.00102 9,800

2

Assail 70WP 

Aerial, 0.075 Applic. Baseline + 

cl. Cockpit

350

0.005

2.19E-04

0.00007

3.06E-05

0.00025 40,000

3

Assail 70WP, 

Aerial, 0.075 Flagger Baseline 350

0.011

4.81E-04

0.00035

1.53E-04

0.00063 16,000

4A

Assail 70WP 

Ground boom, 0.075 M/L Baseline 80

3.7

3.70E-02

0.04342

4.34E-03

0.04134 240

4B " M/L Baseline +

gloves

80

0.17

1.70E-03

0.04342

4.34E-03

0.00604 1,700

4C

Assail 70WP/WSB

Aerial, 0.075 M/L Baseline 80

0.021

2.10E-04

0.00024

2.40E-05

0.00023 43,000

5

Assail 70WP, 

Ground boom, 0.075 Applic. Baseline + 

open cab

80

0.014

1.40E-04

0.00074

7.40E-05

0.00021 47,000

6

Assail 30SG 

Aerial, 0.075 M/L Baseline 350

0.066

2.89E-03

0.00077

3.37E-04

0.00322 3,100
Page 52 of 63

Table A.2 contd ...

Clover

7

Assail 30SG 

Aerial, 0.075 

Applic. same as # 2 - - - - -

8

Assail 30SG 

Aerial, 0.075 

Flagger same as # 3 - - - - -

9

Assail 30SG 

Ground boom, 0.075 M/L Baseline 80

0.066

6.60E-04

0.00077

7.70E-05

0.00074 14,000

10 Assail 30SG 

Ground boom, 0.075 

Applic. same as # 5 - - - - -

1. The scenario numbers are from Table A.1. The Assail 70WP may be sold as free flowing powder and as water soluble bags (WSB); therefore, both products were 

included in the exposure evaluations. 

2. Baseline PPE includes long sleeved shirt, long pants and shoes with socks. Additional PPE such as gloves, respirators and engineering controls (open/closed 

cab/cockpit, etc.) are added if the exposure exceeds the Agency's LOC (MOE = ≤ 100). 

3. Dermal exposure/day = (appl. rate * area treated/day * dermal unit exp. * dermal absorption (10%) / body wt (60 kg). Inhalation exposure/day = (appl. rate * 

area treated/day * inhalation unit exp. * inhalation absorption rate (100%) / body wt (60 kg). 

4. Since the dermal and inhalation endpoints are the same; the dermal and inhalation exposures were combined. 

5. Short- and intermediate-term MOE = short- and intermediate-term POD (10 mg/kg/day) / combined exposure (mg/kg/day). Since the short- and intermediateterm dermal and inhalation PODs are the same the short- and intermediate-term dermal and inhalation MOEs also are the same. The bolded MOE is of concern and 

adding gloves to the baseline clothing reduces the exposure.
Page 53 of 63

Table A.3. Acetamiprid: Short- and Intermediate-term Occupational Risks to Handlers Resulting From the Use of Assail 70WP and Assail 30SG 

Insecticides on Grapes.1 

Crop Scen.N

os.1

Formulation, Appl. 

equipment & App. 

rate

Handler PPE & 

Mitigation 2

Acres 

Treated/day

Unit exposure (mg AI/lb handled)

and Exposed dose (mg/kg/day) 3

Total 

exposure. 

(mg/kg/day) 

4

Short/Interm. 

term MOE 5

Dermal Inhal.

Grape

11A

Assail 70WP 

Aerial, 0.1 lb AI/A M/L Baseline 350

3.7

2.16E-01

0.04342

2.53E-02

0.2416 41

11B

Assail 70WP 

Aerial, 0.1 lb AI/A M/L Baseline + 

gloves 350

0.17

9.92E-03

0.04342

2.53E-02

0.03505 280

11C

Assail 70WP/WSB 

Aerial, 0.1 lb AI/A M/L Baseline 350

0.021

1.23E-03

0.00024

1.40E-04

0.00137 7,300

12

Assail 70WP, 

Aerial (fixed wing), 

0.1 lb AI/A

Applic.

Baseline + 

closed 

cockpit

350

0.005

2.92E-04

0.00007

4.08E-05

0.00033 30,000

13

Assail 70WP 

Aerial, 0.1 lb AI/A Flagger Baseline 350

0.011

6.42E-04

0.00035

2.04E-04

0.00085 12,000

14A

Assail 70WP 

Air blast, 0.1 lb 

AI/A 

M/L Baseline 40

3.7

2.47E-02

0.04342

2.89E-03

0.02756 360

14B

Assail 70WP 

Air blast, 0.1 lb 

AI/A 

M/L Baseline + 

gloves 40

0.17

1.13E-03

0.04342

2.89E-03

0.00403 2,500

14C

Assail 70WP/WSB 

Air blast, 0.1 lb 

AI/A 

M/L Baseline 40

0.021

1.40E-04

0.00024

1.60E-05

0.00016 64,000

15

Assail 70WP, Air 

blast, 0.1 lb AI/A Applic. Baseline + 

open cab 40

0.36

2.40E-03

0.0045

3.00-E04

0.0027 3,700
Page 54 of 63

Table A.3 contd .....

Grape

16 Assail 30SG, Aerial, 

0.1 lb AI/A 

M/L Baseline 350

0.066

3.85E-03

0.00077

4.49E-04

0.0043 2,300

17 Assail 30SG, Aerial, 

0.1 lb AI/A 

Applic. same as # 12 -- - - -

18 Assail 30SG, Aerial, 

0.1 lb AI/A 

Flagger same as # 13 -- - - -

19

Assail 30SG, Air 

blast 0.1 lb AI/A M/L Baseline 40

0.066

4.40E-04

0.00077

5.13E-05

0.00049 20,000

20

Assail 30SG 

Air blast, 0.1 lb 

AI/A

Applic. same as # 15 -- - - -

1. All the foot notes are the same as in Table A.2.
Page 55 of 63

Table A.4. Acetamiprid: Short- and Intermediate-term Occupational Risks to Handlers Resulting From the Use of TriStar 30SG Insecticide on 

Tomatoes Grown in Greenhouse.1

Scen.

Nos.1

Formulation, & 

Appl. equipment Handler PPE & Mitigation 2

Total Area ** 

treated/day

Unit exposure (mg AI/lb 

handled) and Exposed dose 

(mg/kg/day) 3 Total exposure 

(mg/kg/ day) 4

MOE 5

Dermal Inhal. Short/Inter. -

term Long-term 

21

TriStar 30SG, 

0.075 lb AI/A 

micro-irrigation

not assessed due to lack of appropriate unit 

exposures

- - - - -

22

TriStar 30SG, 

0.075 lb AI/A, base 

of plant appl., backpack 

M/L/A

Baseline + 

gloves 0.4

2.5

1.25E-4

0.03

1.50E-05

0.00014 71,000 51,000

23

TriStar 30SG, 

0.075 lb AI/A, base 

of plant appl., low

pressure hand wand

M/L/A

Baseline + 

gloves 0.4

0.43

2.15E-5

0.03

1.50E-05

0.00004 270,000 190,000

24

TriStar 30SG, 0.075 

lb AI/A, base of 

plant appl., high 

pressure hand wand

M/L/A

Baseline + 

gloves 10

2.5

3.13E-03

0.12

1.50E-03

0.00463 2,200 1,500

1. All the foot notes are the same as in Table A.2. Note that in Table A.4, the M/L/A unit exposures are for a liquid formulation rather than a soluble granule product.

** The total area (A) treated/day in the greenhouse was derived as follows: the spray volume handled/day was taken as 40 gal for back-pack and low-pressure hand wand and 

1000 gal for high-pressure hand wand sprayer (root zone drench). It is assumed that 100 gal of spray would cover 1.0 A of greenhouse area (L. Venkateshwara, D355232, 

11/21/08). 
Page 56 of 63

Table A.5. Acetamiprid: Short-term Post-application Dermal Risk to Workers From the Use of Assail 70WP and Assail 30SG Insecticides on Grapes. 

Crop 

Max. single 

appl. rate 

(lb Ai/A)

Dislodgeable 

foliar residue 

(μg/cm2)

1

Surrogate 

crop group

Post-treatment 

activity 

Transfer 

coefficient 

(cm2/hr) 2

Dermal 

absorpt. 

(%)

ADD 

(mg/kg/day) 3

MOE 4

Short/Interm.

-term

Longterm

Clover 0.075 0.168 Field and row

crop, forage

irrigation/ 

scouting 1,500

10

0.0034 3,000 NA

Grape 0.1 0.224 Vine, trellis

training, 

scouting 1,000 0.003 3,300 NA

hand 

harvesting,

pruning

5,000 0.015

670

NA

turning and 

tying 10,000 0.0299 330 NA

Tomatoes 

grown in 

greenhouses

0.075 0.168 Fruiting 

vegetables

staking, 

thinning, 

training, tying

1,000 0.00224 4,500 3,200

1. Dislodgeable foliar residue (DFR) = max. single appl. rate for the crop (lb AI/A) * 20% * 4.54 x 108(μg/lb) * 2.47 x 10-8(A/cm2). 

2. TC values are from Science Advisory Council for Exposure Policy No. 3.1. 

3. Average daily dose (ADD) = [DFR * TC for the activity * 8 (hrs/day) * 0.001 mg/μg * dermal absorp.] / BW (60 kg).

4. Short/intermediate-term dermal MOE = ADD/ short/intermediate-term dermal NOAEL (10 mg/kg/day). Long-term dermal MOE = ADD/ long-term dermal 

NOAEL (7.1 mg/kg/day).
Page 57 of 63

Appendix B: Toxicology Assessment

Appendix B. Toxicity Profile for Acetamiprid: Subchronic, Chronic, and

Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. 

(year)/Classification 

/Doses

Results

870.3100

90-Day oral toxicity-rat

(dietary)

44651843 (1997)

Acceptable/guideline

0, 50, 100, 200, 800, 1600 ppm

0/0, 3.1/3.7, 6.0/7.2, 12.4/14.6, 

50.8/56.0, 99.9/117 (M/F) 

mg/kg/day

NOAEL = 12.4/14.6 (M/F) mg/kg/day 

LOAEL = 50.8/56.0 mg/kg/day (M/F) based on 

decreased BW, BW gain and food consumption

870.3100

90-Day feeding – mouse

44988425 (1997)

Acceptable/guideline

0, 400, 800, 1600, 3200 ppm

0/0, 53.2/64.6, 106.1/129.4, 

211.1/249.1, 430.4/466.3 (M/F) 

mg/kg/day

NOAEL = 106.1/129.4 (M/F) mg/kg/day 

LOAEL = 211.1/249.1 (M/F) mg/kg/day based 

on reduced BW and BW gain, decreased glucose 

and cholesterol levels, reduced absolute organ 

weights

870.3150

90-Day oral toxicity-dog

(Dietary)

44988424 (1998)

Acceptable/guideline 

0, 320, 800, 2000 ppm

0/0, 13/14, 32/32, 58/64 (M/F) 

mg/kg/day

NOAEL = 13/14 (M/F) mg/kg/day 

LOAEL = 32 mg/kg/day based on reduced BW 

gain in both sexes

870.3200

21-Day dermal toxicityrabbit

44651844 (1997)

Acceptable/guideline

0, 100, 500, 1000 mg/kg/day

Systemic NOAEL = 1000 mg/kg/day 

LOAEL= not determined

Dermal NOAEL= 1000 mg/kg/day

LOAEL= not determined

870.3700

Developmental toxicity - rat

(gavage)

44651847 (1997)

Acceptable/guideline

0, 5, 16, 50 mg/kg/day

Maternal:

NOAEL = 16 mg/kg/day

LOAEL = 50 mg/kg/day based on reduced BW 

& BW gain and food consumption, increased 

liver weights

Developmental:

NOAEL = 16 mg/kg/day 

LOAEL = 50 mg/kg/day based on increased 

incidence of shortening of the 13th rib
Page 58 of 63

Appendix B. Toxicity Profile for Acetamiprid: Subchronic, Chronic, and

Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. 

(year)/Classification 

/Doses

Results

870.3700

Developmental toxicity –

rabbit

(gavage)

44651848 (1997)

Acceptable/guideline

0, 7.5, 15, 30 mg/kg/day

Maternal:

NOAEL = 15 mg/kg/day

LOAEL = 30 mg/kg/day (BW loss and 

decreased food consumption).

Developmental:

NOAEL = 30 mg/kg/day (HDT) 

LOAEL = not determined

870.3800

Reproduction and fertility 

effects-rats

(dietary)

44988430 (1999)

Acceptable/guideline

0, 100, 280, 800 ppm

Parental animals

0/0, 6.5/7.6, 17.9/21.7, 

51.0/60.1 (M/F) mg/kg/day

F1 animals

0/0, 7.5/8.4, 21.0/23.8, 

63.3/72.6 (M/F) mg/kg/day

Parental/Systemic:

NOAEL = 17.9/21.7 (M/F) mg/kg/day 

LOAEL = 51.0/60.1 (M/F) mg/kg/day based on 

decreased body weight, body weight gain and 

food consumption

Offspring:

NOAEL = 17.9/21.7 (M/F) mg/kg/day 

LOAEL = 51.0/60.1 (M/F ) mg/kg/day based on 

reductions in pup weight, litter size, viability and 

weaning indices; delay in age to attain preputial 

separation and vaginal opening

Reproductive:

NOAEL = 17.9/21.7 (M/F) mg/kg/day 

LOAEL = 51.0/60.1 (M/F) mg/kg/day based on 

reductions in litter weights and individual pup 

weights on day of delivery

870.4100

Chronic toxicity-rat 

Same as Chronic 

Toxicity/Carcinogenicity- rat 

see below (870.4300)

See below (870.4300)

870.4100

Chronic toxicity-dog 

(Dietary)

44651846 (1998)

Acceptable/guideline

0, 240, 600, 1500 ppm

0/0, 9/9, 20/21, 55/61 (M/F) 

mg/kg/day

NOAEL = 20/21 (M/F) mg/kg/day 

LOAEL = 55/61 (M/F) mg/kg/day based on 

initial BW loss and overall reduction in BW gain

870.4200

Carcinogenicity-mouse

(dietary)

44988428, 45245305 (1999) 

Acceptable/guideline

0, 130, 400, 1200 ppm 

(equivalent to 0/0, 20.3/25.2, 

65.6/75.9, 186.3/214.6 

mg/kg/day in males/females)

NOAEL = 20.3/75.9 mg/kg/day (M/F)

LOAEL = 65.6/214.6 (M/F ) mg/kg/day based 

on decreased BW & BW gain and amyloidosis in 

numerous organs (M) and decreased BW and 

BW gain (F)

Not oncogenic under conditions of study
Page 59 of 63

Appendix B. Toxicity Profile for Acetamiprid: Subchronic, Chronic, and

Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. 

(year)/Classification 

/Doses

Results

870.4300

Chronic/

Carcinogenicity-rat 

44988429, 45245304 (1999)

Acceptable/guideline

0, 160, 400, 1000 ppm

(equivalent to 0/0, 7.1/8.8, 

17.5/22.6, 46.4/60.0 (M/F) 

mg/kg/day)

NOAEL = 7.1/8.8 (M/F) mg/kg/day 

LOAEL = 17.5/22.6 mg/kg/day (M/F) based on 

decreases in mean BW & BW gain (F) and 

hepatocellular vacuolation (M)

Evidence of treatment-related increase in 

mammary tumors

870.5100

Salmonella typhimurium/E. 

coli

Reverse gene mutation assay

44651849 (1997)

Acceptable/guideline

313 to 5000 μg a.i./plate 

incubated 65.5 hours with +/-

S9

Not mutagenic under the conditions of the study

870.5300

Mammalian cells in culture

Forward gene mutation 

assay - CHO cells

44651857 (1998)

Acceptable/guideline

500-4000 ug/mL –S9 or 250-

3000ug/mL + S9

Not mutagenic under the conditions of the study.

870.5375

In vitro mammalian 

chromosome aberration testChinese hamster ovary 

(CHO) cells

44651855 (1997)

Acceptable/guideline

175, 350, 700 μg/mL - S9 or 

338, 675, 1350 ug/mL + S9 

(Highest doses slight to 

moderately cytotoxic).

Acetamiprid is a clastogen under the conditions 

of the study.

870.5385

In vivo mammalian 

chromosome aberrations -

rat bone marrow

44651854 (1998)

Acceptable/guideline

250 mk/kg (maximum tolerated 

dose)

Bone marrow analyzed at 6, 24, 

and 48 hours.

Acetamiprid did not induce a significant increase 

in chromosome aberrations in bone marrow cells 

when compared to the vehicle control group.

970.5395

In vivo mammalian 

cytogenetics - micronucleus 

assay in mice

44651852 (1998)

Acceptable/guideline

20, 40, 80 mg/kg

Bone marrow analyzed at 24, 

48, or 72 hours

Acetamiprid is not a clastogen in the mouse bone 

marrow micronucleus test.

870.5550 

Unscheduled DNA synthesis 

in primary rat 

hepatocytes/mammalian cell 

culture

44651856 (1998)

Acceptable/guideline

0.5 to 1000 μg/mL

Acetamiprid tested negatively for UDS in 

mammalian hepatocytes in vivo.
Page 60 of 63

Appendix B. Toxicity Profile for Acetamiprid: Subchronic, Chronic, and

Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. 

(year)/Classification 

/Doses

Results

870.6200a

Acute neurotoxicity 

screening battery-rats

(gavage)

44651842 (1997) 

Acceptable/guideline

0, 10, 30, 100 mg/kg

Neurotoxicity:

NOAEL= 10 mg/kg/day

LOAEL = 30 mg/kg based on reduction in 

locomotor activity

870.6200b

Subchronic neurotoxicity 

screening battery

(dietary)

44651845 (1997)

Acceptable/guideline

0, 100, 200, 800, 1600 ppm

(equivalent to 0/0, 7.4/8.5, 

14.8/16.3, 59.7/67.6, 118/134 

mg/kg/day)

Neurotoxicity:

NOAEL= 14.8/16.3 mg/kg/day (M/F)

LOAEL = 59.7/67.6 (M/F) mg/kg/day based on 

reductions in BW, BW gain, food consumption 

and food efficiency

870.6300

Developmental 

neurotoxicity – rat (gavage)

46255619 (2003)

Acceptable/Non-Guideline

0, 2.5, 10, 45 mg/kg/day 

Volume: 5 mL/kg

Vehicle: 5% gum Arabic with 

0.01% Tween 80 

Maternal:

NOAEL = 10 mg/kg/day

LOAEL = 45 mg/kg/day based on decreased 

body weight and body weight gains during 

gestation only

Offspring:

NOAEL = 10 mg/kg/day. 

LOAEL = 45 mg/kg/day based on decreased 

maximum auditory startle response in males on 

PND 20 and PND 60, and decreased body 

weight and body weight gain, and pup viability

870.7485

Metabolism and 

pharmacokinetics-rats

44988503-7 (1997)

Acceptable/guideline

Single dose study with 1 mg/kg 

(iv), 1 or 50 mg/kg (gavage) 

15-day repeated doses study 

with 1 mg/kg (gavage); Biliary 

excretion study with 1 mg/kg 

(gavage)

Extensively and rapidly metabolized. 

Metabolites 79-86% of administered dose. 

Profiles similar for males and females for both 

oral and intravenous dosing. Thirty-seven 

percent of dose recovered in urine and feces as 

unchanged test article. Urinary and fecal 

metabolites from 15-day repeat dose experiment 

only showed minor differences from single-dose 

test. Initial Phase I biotransformation: 

demethylation of parent. 6-chloronicotinic acid 

was the most prevalent metabolite. Phase II 

metabolism shown by the increase in glycine 

conjugate.
Page 61 of 63

Appendix B. Toxicity Profile for Acetamiprid: Subchronic, Chronic, and

Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. 

(year)/Classification 

/Doses

Results

870.7485

Metabolism - mice, rats, 

rabbits

Special study

Male mice, rats or rabbits were administered 

single doses of acetamiprid by gavage, 

intraperitoneal injection (i.p.) or intravenous 

injection (i.v.) up to 60 mg/kg. The animals 

were assessed for a variety of neurobehavioral 

parameters. In vitro experiments were also done 

using isolated ileum sections from guinea pigs to 

assess contractile responses in the absence and 

presence of agonists (acetylcholine, histamine 

diphosphate, barium chloride and nicotine 

tartrate). Acetamiprid was also assessed via i.v. 

in rabbits for effects on respiratory rate, heart 

rate and blood pressure; via gavage in mice for 

effects on gastrointestinal motility; and via i.p. in 

rats for effects on water and electrolyte balance 

in urine, and blood coagulation, hemolytic 

potential and plasma cholinesterase activity. 

Based on a number of neuromuscular, 

behavioral and physiological effects of 

acetamiprid in male mice, under the 

conditions of this study, an overall NOAEL of 

10 mg/kg (threshold) and LOAEL of 20 

mg/kg could be estimated for a single dose by 

various exposure routes.

870.7600

Dermal penetration

44651844 (1997)

Acceptable/guideline

0, 100, 500, 1000 mg/kg/day

Applied 6 hours/day for 5 

days/week over a 21 day period

NOAEL > 1000 mg/kg/day

Revised dermal absorption rate of 10% (from 

30%) is based upon the dermal absorption study 

with acetamiprid (MRID 44651858) and 

consideration of dermal penetration values from 

other neonicitinoid insecticides (thiamethoxam), 

and consideration of Kow and octanol/water 

coefficient data of other neonicitinoid 

compounds (clothianidin).

44651858 (1997)

Acceptable/non-guideline 

1.09, 9.53, 90.2 ug/cm2

Absorption was highest at the mid-dose and 

increased with duration (4.07% at 10 after 10 

hours and 6.34% after 24 hours). Residue 

remaining in the skin at 24 hours is 25.0%. In 

addition to absorbed dose (6.34%), total 

absorption is estimated at 30%.

N/A

28-Day Range-finding Study

– dog

(dietary)

45245306

Non-guideline

0, 125, 250, 500, 1000 

mg/kg/day

NOAEL = 16.7/19.1 (M/F) mg/kg/day 

LOAEL = 28.0/35.8 (M/F) mg/kg/day based on 

reduced BW gain
Page 62 of 63

Appendix C: Tolerance Summary

Appendix C. Tolerance Summary for Acetamiprid.

Commodity Established/Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Clover, forage 0.10 0.10 Recommended tolerances are for 

Clover, hay regional registration. 0.01 0.01

Fruit, small, vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

0.35 0.35 Pending label revision to prohibit use 

of a spreader, methylated seed oil or 

crop oil. Correct term is Fruit, 

small, vine climbing, except fuzzy 

kiwifruit, subgroup 13-07F

NOTE: The established individual 

tolerance for grape at 0.20 ppm 

should be concomitantly removed 

upon establishment of the 

subgroup 13-07F tolerance.

Grape 0.20 Remove Grapes will be covered under the 

subgroup 13-07F tolerance.

Tea, dried 50.0 50.0 Tolerance without a U.S. 

registration.
Page 63 of 63

Appendix D: INTERNATIONAL RESIDUE LIMIT STATUS

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: Common Name:

Acetamiprid

X Proposed tolerance

 Reevaluated tolerance

 Other

Date: 07/06/2009

Updated: Oct 5, 2009 

with the tea MRL 

information.

Codex Status (Maximum Residue Limits) U. S. Tolerances

X No Codex proposal step 6 or above

 No Codex proposal step 6 or above for the crops 

requested

Petition Number: 9E7544

DP Barcode: D364833

Other Identifier: 

Residue definition (step 8/CXL): N/A Reviewer/Branch: Dennis McNeilly/RAB2

Residue definition: acetamiprid [N1-[(6-chloro-3-

pyridyl)methyl]-N2-cyano-N1-methylacetamidine]

Crop (s) MRL (mg/kg) Crop(s) Tolerance (ppm)

Clover, forage 0.10

Clover, hay 0.01

Fruit, small, vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

0.35

Tea 50.0

Limits for Canada Limits for Mexico

 No Limits

 No Limits for the crops requested

 No Limits

X No Limits for the crops requested

Residue definition: (E )-N-[(6-chloro-3-

pyridinyl)methyl]-N’ -cyano-N-methylethanimidamide

Residue definition: acetamiprid

Crop(s) MRL (mg/kg) Crop(s) MRL (mg/kg)

Grapes 0.2

Notes/Special Instructions:

S. Funk, 07/07/2009. Note: There are no MRLs for acetamiprid in Codex. There is no MRL for 

acetamiprid on tea in Australia. There is no MRL for acetamiprid on tea in Canada. Japan has a 50 

ppm MRL for tea.