Acetamiprid Human Health Risk Assessment DP No. D394322 

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION

MEMORANDUM

Date: April 19, 2012

SUBJECT: Acetamiprid: Human Health Risk Assessment for New Uses on Asparagus; 

Brassica, Leafy Greens, Subgroup 5B, and Turnip Greens; and Sweet Corn; and 

Updated Crop Group Definitions for Fruiting Vegetables, Citrus, and Pome Fruit. 

 

PC Code: 099050 DP Barcode: D394322 

Decision Nos.: 454284 Registration Nos.: 8033-23, 8033-36 

Petition Nos.: 1E7919 Regulatory Action: Section 3 

Assessment Type: Single Chemical Aggregate Registration Case No.: 7617 

TXR No.: None CAS No.: 135410-20-7 

MRID Nos.: 48590101, 48590102, 48590103, 48590104 40 CFR 180.578 

FROM: Elizabeth Holman, Chemist 

 Suku Oonnithan, Biologist 

 Zaida Figueroa, Industrial Hygienist 

 Risk Assessment Branch II 

 Health Effects Division (7509P) 

THROUGH: Christina Swartz, Chief 

 Risk Assessment Branch II 

 Health Effects Division (7509P) 

TO: Laura Nollen, Chemical Review Manager 

 Risk Integration Minor Use, and Emergency Response Branch 

 Registration Division (7508P) 

 
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Table of Contents 

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

2.0 HED Recommendations....................................................................................................... 5

2.1 Data Deficiencies/Conditions of Registration .................................................................. 5

2.2 Tolerance Considerations ................................................................................................. 5

2.2.1 Enforcement Analytical Method ............................................................................... 5

2.2.2 International Harmonization ..................................................................................... 5

2.2.3 Recommended Tolerances ........................................................................................ 6

2.2.4 Revisions to Petitioned-For Tolerances .................................................................... 6

2.3 Label Recommendations .................................................................................................. 7

3.0 Introduction .......................................................................................................................... 7

3.1 Chemical Identity ............................................................................................................. 8

3.2 Physical/Chemical Characteristics ................................................................................... 8

3.3 Pesticide Use Pattern ........................................................................................................ 9

3.4 Anticipated Exposure Pathways ..................................................................................... 10

3.5 Consideration of Environmental Justice ........................................................................ 10

4.0 Hazard Characterization and Dose-Response Assessment ................................................ 10

4.1 Toxicology Studies Available for Analysis ................................................................... 10

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME) ................................... 11

4.2.1 Dermal Absorption.................................................................................................. 11

4.3 Toxicological Effects ..................................................................................................... 11

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ....................................... 13

4.4.1 Completeness of the Toxicology Database ............................................................. 13

4.4.2 Evidence of Neurotoxicity ...................................................................................... 13

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ......... 13

4.4.4 Residual Uncertainty in the Exposure Database ..................................................... 14

4.5 Toxicity Endpoint and Point of Departure Selections .................................................... 14

4.5.1 Dose-Response Assessment .................................................................................... 14

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment ........ 18

4.5.3 Cancer Classification and Risk Assessment Recommendation .............................. 18

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment ............................................................................................................................ 18

5.0 Dietary Exposure and Risk Assessment ............................................................................ 20

5.1 Metabolite/Degradate Residue Profile ........................................................................... 20

5.2 Food Residue Profile ...................................................................................................... 21

5.3 Water Residue Profile .................................................................................................... 23

5.4 Dietary Risk Assessment ................................................................................................ 24

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... 25

6.2 Spray Drift ...................................................................................................................... 26

7.0 Aggregate Exposure/Risk Characterization ....................................................................... 27

7.1 Acute Aggregate Risk .................................................................................................... 27

7.2 Short- and Intermediate-Term Aggregate Risk .............................................................. 27

7.3 Chronic Aggregate Risk ................................................................................................. 28

7.4 Cancer Aggregate Risk ................................................................................................... 28

8.0 Cumulative Exposure/Risk Characterization ..................................................................... 28

9.0 Occupational Exposure/Risk Characterization .................................................................. 28
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9.1 Short- and Intermediate-Term Handler Risk .................................................................. 29

9.2 Short- and Intermediate-Term Postapplication Risk ...................................................... 31

9.2.1 Dermal Postapplication Risk................................................................................... 31

9.2.2 Inhalation Postapplication Risk .............................................................................. 31

10.0 References .......................................................................................................................... 32

Appendix A. Toxicology Profile and Executive Summaries ....................................................... 34
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1.0 Executive Summary 

The Agency has received a petition from the Interregional Research Project No. 4 (IR-4) to 

register the insecticide acetamiprid {(1E)-N-[(6-chloro-3-pyridinyl)methyl]-N'-cyano-Nmethylethanimidamide} for post-emergent foliar use on asparagus; Brassica leafy greens, 

subgroup 5B, and turnip greens; and sweet corn. In addition, IR-4 is proposing to update crop 

group definitions for established tolerances for vegetable, fruiting, group 8-10; fruit, citrus, group 

10-10; and fruit, pome, group 11-10. The end-use products under consideration for the new uses 

are the 70% wettable powder (WP) formulation, Assail® 70 WP Insecticide (EPA Reg. No. 

8033-23), and the 30% water soluble granule (SG) formulation, Assail® 30 SG Insecticide (EPA 

Reg. No. 8033-36). 

The proposed maximum single application rate for both product formulations on the proposed 

commodities is 0.1 lb ai/A. These formulations may be applied using aerial and ground 

equipment. The maximum number of applications is 2 per season for asparagus with a 10-day 

re-treatment interval (RTI). For sweet corn, Brassica leafy greens (subgroup 5B), and turnip 

greens, the maximum number of applications is 4 per season with a 7-day RTI. The pre-harvest 

intervals (PHIs) are 1 day for asparagus and sweet corn, and 3 days for turnip greens and 

Brassica leafy greens (subgroup 5B). There are no changes in the existing acetamiprid use 

pattern for cole crops, fruiting vegetables, citrus and pome fruit. The updated crop group 

definitions didn’t require a new occupational exposure and risk assessment since the use patterns 

were previously assessed, and no risks of concern were identified. To reflect the updated crop 

group definitions, the dietary exposure assessment has been updated to include all appropriate 

commodities. 

HED has evaluated the hazard information, proposed labels and residue data for these uses, and 

assessed risk associated with occupational, residential, dietary, and aggregate exposures. Risk 

estimates based on screening level, health protective inputs are well below HED’s level of 

concern for all scenarios and population subgroups, including those of infants and children. 

This risk assessment has taken into consideration potential environmental justice issues. Based 

on the existing and proposed uses for acetamiprid, and on current Office of Pesticide Programs 

(OPP) assessment policies, there are no environmental justice concerns associated with 

acetamiprid. 

There are no human health risk concerns that would preclude granting the requested uses and 

establishing new tolerances for residues of acetamiprid. However, at this time, HED concludes 

that the available data are insufficient for establishing the proposed tolerances associated with 

the requested registration on sweet corn. 

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 

Occupational Pesticide Handlers Exposure Database (OPHED; 

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

http://www.epa.gov/pesticides/science/post-app-exposure-data.html), have been determined to 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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

have been ethically conducted. 

2.0 HED Recommendations 

HED recommends granting the requested registrations for use of acetamiprid on asparagus, 

turnip greens, and Brassica leafy greens, subgroup 5B and establishing tolerances as described in 

Section 2.2.3. Revisions to petitioned-for tolerances (Section 2.2) and label modifications 

(Section 2.3) should be made by the petitioner prior to registration. At this time, HED concludes 

that the available data are insufficient for establishing tolerances associated with the requested 

registration on sweet corn. As outlined in Section 2.1, five additional field trials are required to 

fill this data gap. 

2.1 Data Deficiencies/Conditions of Registration 

The toxicological database lacks a 21/28 day inhalation study in rats, which is a required study. 

HED has determined that the required inhalation study cannot be waived, based on weight of 

evidence considerations, including the available toxicity data and the potential for exposure to 

acetamiprid via the inhalation route. 

To support the proposed uses on sweet corn, five additional crop field trials must be conducted in 

the U.S. with the 30% SG formulation and an adjuvant in Zones 1 (1 trial), 5 (3 trials), and 12 (1 

trial) to provide a full set of field trial data for this formulation. Each trial should include an 

additional side-by-side treated plot reflecting application of the 70% WP formulation with an 

adjuvant. Although the available data suggest that residues are similar following application 

according to the four-application/1-day PHI use pattern and the two-application/7-day PHI use 

pattern, HED recommends that each use pattern be represented in at least two of the required 

trials. The registrant has been made aware of these issues and intends to complete the required 

trials during the 2012 growing season. Until these data have been received and the sweet corn 

dataset re-evaluated, the proposed use and associated tolerances for sweet corn cannot be 

established. 

2.2 Tolerance Considerations 

2.2.1 Enforcement Analytical Method 

An approved LC-MS/MS tolerance enforcement method, with an LOQ of 0.01 ppm, is available 

for vegetables and non-citrus crops. An approved HPLC/UV tolerance enforcement method, 

with an LOQ of 0.05 ppm, is available for citrus fruits. These methods are adequate for 

enforcing the proposed tolerances associated with this petition. 

2.2.2 International Harmonization 

There are currently no established Codex, Canadian, or Mexican maximum residue limits 

(MRLs) for acetamiprid on asparagus and no established Codex MRLs on any Brassica

vegetables; therefore, there are no issues of harmonization. Canadian MRLs are established for 
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residues of acetamiprid at 1.2 ppm in/on Chinese cabbage (Bok choy), cabbages, broccoli raab, 

collards, kale, mustard greens, mustard spinach, and rape greens. With the establishment of 

separate tolerances in leafy greens, subgroup 5B, and Brassica head and stem, subgroup 5A, the 

Canadian MRLs for Bok choy Chinese cabbages, broccoli raab, collards, kale, mustard greens, 

mustard spinach, and rape greens will no longer be harmonized with U.S. tolerances. This 

petition requests a revised use pattern for subgroup 5B commodities, specifically a shorter PHI; 

therefore, a higher U.S. tolerance of 15 ppm is required. (Subgroup 5B includes bok choy 

Chinese cabbage, broccoli raab, collards, kale, mustard greens, mustard spinach, and rape 

greens.) 

2.2.3 Recommended Tolerances 

The current tolerance definition for acetamiprid (40 CFR 180.578) is appropriate regarding scope 

and compliance. 

Table 2.2.3. Tolerance Summary for Acetamiprid. 

Commodity Established/Propo

sed Tolerance 

(ppm) 

Recommended 

Tolerance (ppm) 

Comments (Correct Commodity Definition) 

Asparagus 0.8 0.80 

Brassica, leafy greens, 

subgroup 5B 

15 15 

Turnip greens 15 15 Turnip, greens 

Vegetable, brassica, leafy, 

group 5 

1.20 None With the establishment of the separate 5B 

tolerance, the group 5 tolerance should be 

removed. 

Brassica, head and stem, 

subgroup 5A 

-- 1.2 Using the existing group 5 tolerance and 

available data, this separate 5A tolerance 

can be established without additional data. 

Corn, sweet, kernel plus 

cob with husks removed 

0.01 To be determined Insufficient data are available to support the 

proposed use/tolerances for sweet corn at 

Corn, sweet, forage 10 this time. 

Corn, sweet, stover 30 

Vegetable, fruiting, group 8 0.20 None 

Fruit, citrus, group 10 0.50 None 

Fruit, pome, group 11 1.0 None 

Vegetable, fruiting, group 

8-10 

 0.20 0.20 

Fruit, citrus, group 10-10 0.50 0.50 

Fruit, pome, group 11-10 1.0 1.0 

2.2.4 Revisions to Petitioned-For Tolerances 

Requested and recommended tolerances are in agreement for residues in/on asparagus; Brassica, 

leafy greens, subgroup 5B; or turnip greens. No revisions are necessary relative to the 

petitioned-for tolerances updating the crop group definitions for vegetable, fruiting, group 8-10; 

fruit, citrus, group 10-10; and fruit, pome, group 11-10. 
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In keeping with HED conventions for tolerance rounding and significant figures, the proposed 

tolerance for asparagus was changed from 0.8 ppm to 0.80 ppm. 

With the establishment of a tolerance in Brassica leafy greens, subgroup 5B, the established 

tolerance in vegetable, Brassica, leafy, group 5, should be removed, and a new tolerance should 

be established in Brassica, head and stem, subgroup 5A, at 1.2 ppm. 

Insufficient data are available to support the proposed tolerances in corn, sweet, kernel plus cob 

with husks removed; corn, sweet, forage; and corn, sweet, stover. Until the outstanding field 

trial data are received, no tolerances will be established. 

The petitioner should submit a revised Section F, specifying the recommended tolerances in 

Table 2.2.3. 

2.3 Label Recommendations 

HED has concluded that insufficient data have been submitted to support the use of either the 

70% WP or the 30% SG formulation on sweet corn. Until the requested crop field trial data have 

been submitted, use on sweet corn should be removed from both labels. 

In support of the proposed use on turnip greens, the labels should be revised to prohibit the 

harvest of turnip root for food/feed purposes because use on turnip root is not supported by 

residue data or an established tolerance. 

In support of the proposed use on Brassica leafy greens, subgroup 5B, the labels should be 

revised to include Chinese Bok Choy with the subgroup 5B commodities. Chinese Bok Choy is 

currently misplaced on the labels with subgroup 5A commodities. 

Because other adjuvant types were not tested, the labels should specify use of an NIS as adjuvant 

for the asparagus, Brassica leafy greens and turnip greens uses. 

It was noted that the draft label for the 30% SG formulation includes the following error in the 

“Site” column: “Pome Fruit (within Crop Group 11)” instead of “Pome Fruit (within Crop 

Group 11-10)”. This error should be corrected on the label. 

3.0 Introduction 

Acetamiprid is a selective insecticide intended for use against various sucking/chewing insect 

pests that feed upon fruit and vegetable crops. It is a member of the chloronicotinyl 

(neonicotinoid) class of insecticides, which function by binding to nicotinic acetylcholine 

receptors in the post-synaptic neurons of the insect’s central nervous system. This binding 

results in the opening of ion pores, causing a subsequent overload of sodium ions in the neurons 

which leads to nervous system hyper-excitation, and eventual death of the insect. 
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3.1 Chemical Identity 

Table 3.1. Acetamiprid Nomenclature. 

Chemical Structure 

Common Name Acetamiprid 

Molecular Formula C10H11ClN4

Molecular Weight 222.68 

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

IUPAC Name (E)-N 1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N 1-methylacetamidine 

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

CAS Registry Number 135410-20-7 

End-use Product (EP) Assail® 70 WP Insecticide (EPA Reg. No. 8033-23) 

Assail® 30 SG Insecticide; EPA Reg. No. 8033-36) 

3.2 Physical/Chemical Characteristics 

The physicochemical properties of technical-grade acetamiprid are summarized in Table 3.2. 

The values in the table suggest that there are not any exposure scenarios that are likely to require 

special consideration. The vapor pressure for acetamiprid is quite low and as such, inhalation 

exposure via volatilization is expected to be negligible. The octanol/water partitioning 

coefficient indicates that partitioning into fatty tissues is unlikely and that there is low potential 

for bioaccumulation. 

Table 3.2. Physicochemical Properties of Technical-Grade Acetamiprid. 

Parameter Value Reference1

Melting Point/Range (C) 98.9 PP#6F7051 

pH 6.08 (Aqueous solution at 20C) 

Density (g/cm3) 1.33 (at 20C)

Water Solubility (g/L) 4.25 (at 25C) 

Solvent Solubility (at 25C) Acetone >20 g/100 g 

Methanol >20 g/100 g 

Ethanol >20 g/100 g 

Dichloromethane >20 g/100 g 

Chloroform >20 g/100 g 

Acetonitrile >20 g/100 g 

Tetrahydrofuran >20 g/100 g 

Benzene 2.44 g/100 g 

Xylene 4.01 g/100 g 

n-Hexane 6.54 ppm 

Carbon disulfide 507 ppm 

Vapor Pressure (mm Hg) 7.5 x 10-9 (at 25C) M. Doherty, D264154, 31 December 2001 

Dissociation Constant, pKa 0.7 (at 25C) PP#6F7051 

Octanol/Water Partition Coefficient, 

Log KOW

0.8 (at 25C) 

N N

CH3

Cl

CH3

N

CN
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Table 3.2. Physicochemical Properties of Technical-Grade Acetamiprid. 

Parameter Value Reference1

UV/Visible Absorption Spectrum Not available 1

From D328216; W. Drew; 10/23/07 

3.3 Pesticide Use Pattern 

Table 3.3. Summary of Proposed Directions for Use of Acetamiprid.1

Applic. Timing, 

Type, and Equip. 

Formulation 

[EPA Reg. 

No.] 

Applic. 

Rate 

(lb ai/A) 

Max. No. 

Applic. per 

Season 

Max. Seasonal 

Applic. Rate 

(lb ai/A) 

PHI 

(days) 

Use Directions and 

Limitations2 

Asparagus 

Post-emergence, 

Broadcast, 

Aerial (≥5 

gal/A) or 

ground, (≥20 

gal/A) 

Assail® 

70 WP

[8033-23] 

0.05-0.1 2 0.2 1 Minimum RTI = 10 days 

Assail® 

30 SG 

[8033-36] 

0.047-0.1 

Head and Stem Cole Crops (Crop Subgroup 5A) 

No change from established use pattern for Cole Crops (within Group 5)3

Leafy Cole Crops (Crop Subgroup 5B) and Turnip Greens 

Post-emergence, 

Broadcast, 

Aerial (≥5 

gal/A) or 

ground, (≥30 

gal/A) 

Assail® 

70 WP

[8033-23] 

0.035-0.1 4 0.375 3 Minimum RTI = 7 days 

Assail® 

30SG 

[8033-36] 

0.038-0.1

Sweet corn 

Post-emergence, 

Broadcast, 

Aerial (≥5 

gal/A) or 

ground, (≥20 

gal/A) 

Assail® 

70 WP

[8033-23] 

Assail® 

 30 SG 

[8033-36] 

0.04-0.1 4 0.21 7 Minimum RTI = 14 days 

0.04-0.1 4 1 Minimum RTI = 7 days 

(if applied in a rotation or 

tank mixture with another 

insecticide) 

Fruiting Vegetables (within Crop Group 8-10): 

No change from established use pattern for Fruiting Vegetables (within Crop Group 8)3

Citrus (within Crop Group 10-10) 

No change from established use pattern for Citrus (within Crop Group 10)3 

Pome Fruit (within Crop Group 11-10) 

No change from established use pattern for Pome Fruit (within Crop group 11)3 

1

 From draft labels dated 8/25/11 for Assail® 70 WP and 8/24/11 for Assail® 30 SG 

2

 RTI = Re-treatment interval 

3

 Refer to accepted labels dated 6/29/11 for both Assail® 70 WP and Assail® 30 SG. 

Personal Protective Equipment (PPE): Both proposed labels have the following PPE 

statements: “Applicators and other handlers must wear long-sleeved shirt and long pants, 

waterproof gloves, shoes plus socks and headgear for overhead chemical exposure”. 
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3.4 Anticipated Exposure Pathways 

Acetamiprid is registered for use on growing crops as well as in and around the home. As a 

result of the uses on crops, as well as a recently proposed and assessed use in food/feed handling 

establishments, humans may be exposed to acetamiprid in food and drinking water. In addition, 

exposure may occur in residential or non-occupational settings. In an occupational setting, 

applicators may be exposed while handling the pesticide prior to application, as well as during 

application. There is a potential for post-application exposure for workers re-entering treated 

fields. 

Risk assessments have been previously prepared for the existing uses of acetamiprid. This risk 

assessment considers all of the aforementioned exposure pathways based on the proposed new 

uses of acetamiprid, and also considers the existing uses, particularly for dietary exposure.

3.5 Consideration of Environmental Justice 

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

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

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

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to 

assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures and risks based on home use of pesticide products for adult applicators and 

postapplication activities for toddlers, youths, and adults entering or playing on treated areas are 

evaluated. Further considerations are currently in development as OPP has committed resources 

and expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups. 

4.0 Hazard Characterization and Dose-Response Assessment 

4.1 Toxicology Studies Available for Analysis 

The toxicity database 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; 5) immunotoxicity studies in rats and mice; and, 6) 

subchronic dermal toxicity and dermal penetration studies in rats. There is also a complete 
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mutagenicity battery, as well as metabolism studies in the rat. The lack of a 21/28 day inhalation 

study in rats is considered to be a data gap; the HED HASPOC has determined that the study 

cannot be waived (TXR 0052354, K.Rury, 03/15/2012). No literature information is available 

that would have an impact upon risk assessment. Metabolites were only examined in some 

mutagenicity studies.

4.2 Absorption, Distribution, Metabolism, & Elimination (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. Metabolism 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. Biliary excretion did not vary between genders and, by 48 hours, accounted for about 

19% of the administered radioactivity. 

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. 

 4.2.1 Dermal Absorption

A dermal absorption factor of 10% is being used 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 neonicotinoids. The derivation of this factor is fully discussed 

in the 2009 risk assessment for acetamiprid (D369474, D. McNeilly et al., 1 December 2009). 

4.3 Toxicological Effects 

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. These effects are considered to be adaptive. 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/oncogenicity study. 
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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 up to 24 hours. In some earlier acetamiprid risk assessments, a 30% dermal absorption 

value was estimated from this study. However, as noted above, HED has refined the dermal 

absorption value (to 10%) based upon comparison to clothianidin, which is structurally related. 

There was no quantitative or qualitative evidence of increased susceptibility of rat or rabbit 

fetuses to in utero exposure in the developmental studies. 

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

pups was observed. The parental and offspring systemic effects were 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. These offspring observations were considered to be 

more severe than the parental effects. 

In the developmental neurotoxicity study there was also evidence of increased qualitative 

susceptibility. In this study, the offspring LOAEL was based on decreased body weights and 

body weight gains in males and females, decreased pre-weaning survival [post-natal days 

(PNDs) 0-1], and decreased maximum auditory startle response in males on PNDs 20 and 60. 

This was observed in the presence of decreased maternal body weight and body weight gains 

during gestation. 

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

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

during later observations. Functional observational battery evaluations revealed several 

treatment-related observations on the day of dosing. At the high dose only, males exhibited 

tremors, difficulty in handling, walking on toes, dilated pupils, coldness to the touch as well as 

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

chewing, coldness to the touch, dilated pupils, decreased hind limb foot splay, and abnormal 

gaits and/or posture, including walking on toes and hunched posture. This was not noted in a 

subchronic rat neurotoxicity study. No neuropathology was observed in any of the 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. 

Four week immunotoxicity studies were performed in both sexes in rats and mice. No effects on 

the immune system were observed in either species up to the highest dose tested. Significant 

reductions in body weight and body weight gain were noted at that dose. 

Acetamiprid did not show clear evidence of genotoxic potential. It was 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 
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study. Acetamiprid metabolites IC-0, IM-1-2, IM-1-4, IM-2-1, and IM-0 tested negative for 

mutagenicity. 

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

HED recommends the FQPA SF of 10X be reduced to 1X for dermal and oral exposure 

pathways based on the following reasons: (1) the toxicology data base is complete (with the 

exception of an inhalation study); (2) HED is regulating the use of acetamiprid based upon the 

effects of concern, i.e., developmental effects in pups following pre-and/or post-natal exposure; 

(3) the rat is 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; (4) there are no residual uncertainties for pre- and/or post-natal toxicity; (5) the 

exposure databases (dietary food, drinking water, and residential) are complete; and (6) 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. In the absence of the 

required inhalation toxicity study, HED is recommending the 10X FQPA factor be retained as a 

database uncertainty factor only for assessing inhalation exposure and risk. 

4.4.1 Completeness of the Toxicology Database 

Acceptable guideline studies for developmental, reproductive toxicity and neurotoxicity 

(including DNT) are available for FQPA assessment. Immunotoxicity studies in rats and mice 

have also been submitted and reviewed. A subchronic inhalation study remains outstanding and 

is considered a data deficiency. 

4.4.2 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. However, no 

neurotoxic findings were reported in the subchronic neurotoxicity study. 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. 

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

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 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, the effects in the offspring (including decreased viability) are 

considered to be more severe than those observed in the parents (decreased body weight and 

body weight gain). In the DNT study, maternal and offspring effects were observed at the same 

dose. However, the offspring effects included decreased pup viability which is considered to be 
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 14 of 43 

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. 

4.4.4 Residual Uncertainty in the Exposure Database 

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 

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 with respect to susceptibility. HED believes that the endpoints and doses 

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

In the absence of the 28-day inhalation study, there is uncertainty about potential portal of entry 

effects occurring via the inhalation route of exposure, and HED is recommending retaining the 

10X FQPA factor as a database uncertainty factor for the inhalation route of exposure only, 

pending submission of the required study. 

HED has used conservative assumptions in the exposure assessment, including the use of 100% 

crop treated assumptions, tolerance-level residue values, and upper-bound estimates of potential 

exposure through drinking water. In addition, the residential exposure assessment was 

conducted such that residential exposure and risk will not be underestimated. The aggregate 

exposure and risk estimates presented in this assessment are expected to over-estimate actual 

exposure and risk expected based on the current and proposed use patterns, and no risk estimates 

of concern were identified. 

4.5 Toxicity Endpoint and Point of Departure Selections 

4.5.1 Dose-Response Assessment 

4.5.1.1 Acute Reference Dose (aRfD) - All Populations 

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

 Acute Neurotoxicity Study in Rats (MRID 44651842) 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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Dose and Endpoint for Risk Assessment: NOAEL = 10 mg/kg/day (both studies) based on 

decreased pre-weaning survival (PND 0-1), 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). 

4.5.1.2 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)

7.1 mg/kg/day

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). 

4.5.1.3 Incidental Oral Exposure 

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

Study Selected: Developmental Neurotoxicity Study in Rats (MRID 46255619) 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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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 incidental oral 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). 

4.5.1.4 Dermal Exposure 

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 

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 
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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). 

4.5.1.5 Inhalation Exposure 

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 

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

NOAEL and LOAEL from an oral study are used to estimate inhalation exposure and the 

associated risk (i.e., inhalation toxicity is assumed to be equivalent to oral toxicity). 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). In the absence 

of the required inhalation toxicity study, HED is recommending the 10X FQPA factor be 

retained as a database uncertainty factor only for assessing inhalation exposure and risk. 

Long-Term Inhalation Exposures (> 6 months) 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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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 are used to estimate inhalation exposure and the 

associated risk (i.e., inhalation toxicity is assumed to be equivalent to oral toxicity). 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). In the absence of the required inhalation toxicity study, HED is recommending 

the 10X FQPA factor be retained as a database uncertainty factor only for assessing inhalation 

exposure and risk. However, HED notes that no long-term exposure via the inhalation route is 

expected based on existing and proposed uses. 

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment 

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-term dermal, oral, and 

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

4.5.3 Cancer Classification and Risk Assessment Recommendation 

The CARC report, Dec. 11, 2001 (TXR No. 0050331) stated that acetamiprid is, “not likely to be 

carcinogenic to humans.” The classification is based on the following: (1) the absence of an 

increase in the incidence of tumors in a mouse carcinogenicity study; and (2) in a rat 

chronic/carcinogenicity study, 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). There 

was no clear evidence of a mutagenic effect. Acetamiprid tested positive as a clastogen in an in 

vitro study but not in an in vivo study. 

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment 

Table 4.5.4a. Summary of Toxicological Doses and Endpoints of Acetamiprid for Use in Dietary and NonOccupational Human Health Risk Assessment 
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 19 of 43 

Exposure Scenario Dose Used in 

Risk 

Assessment 

Uncertainty 

Factors/FQPA 

Safety Factors 

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 

Co-critical studies 

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on 

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 

Intermediate-Term 

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 

Intermediate-term 

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 

Intermediate-term 

Inhalation 

(1-30 days, 1–6 

mo.) 

NOAEL = 10 

mg/kg/day 

Inhalation 

toxicity 

assumed to be 

equivalent to 

oral toxicity 

UFA = 10x 

UFH = 10x 

FQPA SF = 1x 

UFDB = 10X 

LOC for MOE 

= 1000 

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 (2005 revised Agency cancer guidelines). 

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. UFDB = Database uncertainty factor retained for missing data, in this case the 28-day inhalation toxicity study. PAD = 

population adjusted dose (a = acute, c = chronic) = reference dose/all uncertainty factors. MOE = margin of exposure. LOC = level of concern. 

N/A = not applicable. 

 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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Table 4.5.4b. 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.) 

NOAEL= 

10 mg/kg/day 

DAF = 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. 

Short- and 

Intermediate-term 

Inhalation 

(1 - 30 days, 1 - 6 

mo.) 

NOAEL= 

 10 mg/kg/day 

Inhalation 

toxicity 

assumed to be 

equivalent to 

oral toxicity 

UFA = 10x 

UFH = 10x 

UFDB = 10x 

LOC for MOE 

= 1000 

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 (2005 revised Agency cancer guidelines). 

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). UFDB = Database uncertainty factor retained for missing data, in this case the 28-day inhalation 

toxicity study. DAF = dermal absorption factor. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. 

5.0 Dietary Exposure and Risk Assessment 

E. Holman, D394779, 6 March 2012 

E. Holman, D395331, 14 February 2012 

5.1 Metabolite/Degradate Residue Profile 

The nature of the residue for acetamiprid has been adequately delineated based on acceptable 

plant and livestock metabolism studies, as well as confined rotational crop studies. The residue 

definitions for tolerance enforcement and risk assessment are summarized in Table 5.1. For 

further details on these metabolism studies, please refer to M. Doherty et al (D278352, 

10/16/2001). 

Table 5.1. Risk Assessment and Tolerance Enforcement Residue Definitions for Acetamiprid. 

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 + IM-2-1+ IM-2-1-amide 

(ruminant muscle only) 

Acetamiprid and IM-2-1 

Poultry Acetamiprid and IM-2-1 Acetamiprid and IM-2-1 
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 21 of 43 

Table 5.1. Risk Assessment and Tolerance Enforcement Residue Definitions for Acetamiprid. 

Matrix Residues included in Risk Assessment Residues included in 

Tolerance Expression 

Drinking Water Acetamiprid Not Applicable 

5.2 Food Residue Profile 

The established tolerances in vegetable, fruiting, group 8; fruit, citrus, group 10; and fruit, pome, 

group 11, can be updated to the current crop group definitions (with no accompanying data) to 

vegetable, fruiting, group 8-10; fruit, citrus, group 10-10; and fruit, pome, group 11-10. 

To support the proposed uses, the petitioner has submitted studies depicting residues of 

acetamiprid following broadcast foliar or directed application treatment in/on sweet corn 

commodities, asparagus, and mustard greens. Applications were made in accordance with the 

proposed labeling and the residue data are supported by appropriate analytical method and 

storage stability data. The proposed preharvest intervals (PHI) are acceptable for asparagus, 

Brassica leafy greens, and turnip greens. Tables 5.2.1.-5.2.3 summarize the submitted field trial 

data for the proposed commodities. 

The submitted residue data for asparagus are acceptable. The submitted study reflects the 

maximum proposed use pattern for the 70% WP formulation for asparagus; however, owing to 

the designation of one pair of residue trials as a single trial with replicate samples, geographic 

representation is inadequate from NAFTA Zone 10 per OCSPP 860.1500. However, given the 

requested PHI of 1 day, the maximum anticipated residues are going to be driven by application 

parameters and not meteorological or cultural practices. Furthermore, the available residue data 

is tightly grouped around the mean, with a small observed standard deviation. Therefore, it is 

highly unlikely that additional residue data from Zone 10 would have a significant impact on the 

recommended tolerance. Consequently HED is not requesting additional field trials for 

asparagus. 

The submitted residue data for mustard greens are also acceptable. The study reflects the 

maximum proposed use pattern for the 70% WP formulation for Brassica leafy greens, subgroup 

5B and turnip greens, and the number and location of the field trials are in accordance with 

OCSPP 860.1500 for mustard greens 

For asparagus and mustard greens, it is noted that all of the submitted field trials used the 70% 

WP formulation. The registrant is requesting the use of both the 70% WP and the 30% SG 

formulation. Normally, consistent with OCSPP and OECD Crop Field Trial Guidance, 

additional bridging data would be required to support the use of the 30% SG formulation. 

However, during a previous assessment, a similar situation was encountered and the registrant 

provided additional information on the SG formulation. As a result, HED concluded that such 

data were not necessary, agreeing that due to high water solubility both products are likely to 

produce a similar solution of acetamiprid (D369474, 12/1/09). Therefore bridging data to 

support the use of the 30% SG formulation on these commodities are not required. The data are 

sufficient for establishing tolerances on these commodities associated with the requested 

registration of the 70% WP and 30% SG formulations. 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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HED has concluded that insufficient data have been submitted to support the use on sweet corn. 

Although there is evidence to support residue equivalency for the 70% WP formulation and the 

30% SG formulation and the combination of trials conducted with these two formulations 

provide for an adequate number of trials with sufficient geographic variation, it is not possible to 

combine the two sets due to the significant differences in the stover PHIs between the U.S. and 

Canadian trials. These differences are reflected in the residue data for stover. In the U.S. trials, 

residues (and per trial averages) of acetamiprid were <0.01 (<0.01) in K+CWHR, 0.39-10 (0.41-

9.1) in forage, and 0.12-21 (0.19-20) ppm in stover. In the Canadian trials, residues (and per trial 

averages) were <0.01 (<0.01) in K+CWHR, 0.23-1.1 (0.43-0.82) in forage, and <0.01-0.35 

(0.011-0.285) ppm in stover. Furthermore, although the use patterns were similar between the 

U.S. and Canadian trials for K+CWHR and forage (four applications, 1- to 2-day PHI), the U.S. 

trials performed with the 30% SG formulation included an adjuvant, whereas the Canadian trials 

using the 70% WP formulation did not include an adjuvant. Additional crop field trial data are 

required to support the proposed uses. 

Based on the crop field trial study designs, the U.S. use pattern appears to be less restrictive for 

stover (1- or 7-day PHI in the U.S. vs. harvest at maturity in Canada); therefore, to support the 

proposed uses on sweet corn, five additional crop field trials must be conducted in the U.S. with 

the 30% SG formulation and an adjuvant in Zones 1 (1 trial), 5 (3 trials), and 12 (1 trial) to 

provide a full set of field trial data for this formulation. Each trial should include an additional 

side-by-side treated plot reflecting application of the 70% WP formulation with an adjuvant. 

Although the available data suggest that residues are similar following application according to 

the four-application/1-day PHI use pattern and the two-application/7-day PHI use pattern, HED 

recommends that each use pattern be represented in at least two of the required trials. The 

registrant has been made aware of these issues and intends to complete the required trials during 

the 2012 growing season. 

At this time, HED concludes that the available data are insufficient for establishing tolerances 

associated with the requested registration on sweet corn. The available residue chemistry data 

for acetamiprid are sufficient for purposes of assessing risk and establishing tolerances on 

asparagus, Brassica leafy greens, and turnip greens. 

The proposed use of acetamiprid on sweet corn will result in a significant increase in the 

maximum reasonable dietary burden to ruminants as a result of dietary contributions from sweet 

corn forage and cannery waste. When the results of the dairy cattle feeding study are adjusted 

for the increased dietary burden, the maximum expected combined residues of acetamiprid and 

IM-2-1 increase in milk and all tissues. Based on the data currently available, the tolerance in 

milk should be increased from 0.10 to 0.30 ppm, and the tolerances in the fat, meat, and meat 

byproducts of cattle, goat, horse, and sheep should be increased from 0.10 to 0.20 ppm in fat; 

from 0.10 to 0.30 ppm in meat; and from 0.20 to 0.70 ppm in meat byproducts. The tolerances 

need not be revised at this time, but should be re-evaluated when the outstanding data for sweet 

corn have been submitted and reviewed. 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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Table 5.2.1. Summary of Residue Data from Asparagus Crop Field Trials with Acetamiprid.

Commodity Total 

Applic. Rate 

 (lb ai/A) 

PHI 

(days) 

Residue Levels 

 (ppm)1

n Sample 

Min. 

Sample 

Max. 

LAFT2 HAFT2 Median Mean Std. 

Dev. 

ASPARAGUS (proposed use = 0.2 lb ai/A total application rate, 1-day PHI) 

Asparagus 0.200-0.204 1 7 0.11 0.43 0.12 0.41 0.26 0.25 0.09 

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. 2

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

Table 5.2.2. Summary of Residue Data from Mustard Greens Crop Field Trials with Acetamiprid. 

Commodity Total 

Applic. Rate 

 (lb ai/A) 

PHI 

(days) 

Residue Levels 

 (ppm)1

n Sample 

Min. 

Sample 

Max. 

LAFT2 HAFT2 Median Mean Std. 

Dev. 

BRASSICA, LEAFY GREENS, SUBGROUP 5B and TURNIP GREENS 

(proposed use = 0.375 lb ai/A total application rate, 3-day PHI) 

Mustard greens 0.374-0.476 2-4 8 0.20 10 0.30 9.2 1.9 2.6 2.8 

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. 2

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

Table 5.2.3. Summary of Residue Data from Sweet Corn Crop Field Trials with Acetamiprid. 

Commodity No. 

Apps. 

Total Applic. 

Rate 

 (lb ai/A) 

PHI 

(days)

Residue Levels (ppm)1

n Sampl

e Min.

Sample 

Max. 

LAFT2 HAFT2 Median Mean Std. 

Dev. 

SWEET CORN (proposed use = 0.21 lb ai/A total application rate; 

4 applications with a 1-day PHI or 2 applications with a 7-day PHI)

U.S. Trials (30% SG formulation) 

K+CWHR 4 0.212-0.220 1 7 <0.01 <0.01 0.01 0.01 0.01 0.01 N/A 

2 0.195-0.214 5-8 7 <0.01 <0.01 0.01 0.01 0.01 0.01 N/A 

Forage 4 0.212-0.220 1 7 0.42 8.1 0.54 7.3 1.3 3.0 2.8 

2 0.195-0.214 5-8 7 0.39 10 0.41 9.1 1.4 2.9 3.1 

Stover 4 0.212-0.220 13 7 0.12 16 0.19 15.5 4.1 5.7 5.7 

2 0.195-0.214 5-83 7 0.21 21 0.21 20 2.8 5.3 7.0 

Canada Trials (70% WP formulation) 

K+CWHR 4 0.213-0.281 

(238.5-314.7) 

1-2 5 <0.01 <0.01 0.01 0.01 0.01 0.01 N/A 

Forage 4 5 0.23 1.1 0.43 0.82 0.61 0.60 0.15 

Stover 4 0.213-0.219 

(238.5-245.4) 

41-89 4 <0.01 0.35 0.011 0.285 0.050 0.082 0.095

1

 Except for sample min/max, values reflect per trial averages; n = no. of field trials. N/A = Not applicable 2

 LAFT = lowest average field trial; HAFT = highest average field trial. 3

 Including PHIs of 28 and 35 days for stover from plots 2 and 3 of the NY trial, respectively. Although the PHIs 

from this trial differed by >25%, this data was included in the summary results because the residues were within the 

range of those in the other trials, and the use pattern was consistent with typical stover harvest. 

5.3 Water Residue Profile 

K. White, D394234/D394479, 11 October 2011 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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In a memo dated 11 October 2011 (K. White, D394234/D394479), the Environmental Fate and 

Effects Division (EFED) provided estimated residues of acetamiprid in drinking water from the 

use of acetamiprid as a scatter bait as well as on tree nuts. The bait use results in the highest 

estimated drinking water concentrations (EDWCs) for all assessed use scenarios. The EDWCs 

used in this dietary assessment are summarized in Table 5.3. The surface water EDWCs were 

generated using the FQPA Index Reservoir Screening Tool (FIRST) Model and the ground water 

estimates are from the Screening Concentration In GROund Water (SCI-GroW) Model. The 

models and their descriptions are available at the EPA internet site: 

http://www.epa.gov/oppefed1/models/water/. 

No monitoring data are currently available to further characterize potential drinking water 

exposure. In the dietary risk assessment conducted to support the proposed uses and label 

changes, HED incorporated the surface water EDWCs directly into the dietary model, since 

surface water estimates were higher than those provided for ground water. The use of the 

surface water values in the dietary assessment is therefore protective of potential exposure 

through ground water sources of drinking water. 

Table 5.3. Tier I Analysis - 1-in-10-year EDWCs in surface water and ground water for acetamiprid. 

Drinking Water Source Maximum Use Pattern Exposure EDWC (ppb) 

Surface water Scatter Bait Peak (acute) 95.2 

Annual average (chronic) 26.6 

Ground water Scatter Bait Peak & annual average 0.035 

5.4 Dietary Risk Assessment 

Acute and chronic dietary (food+drinking water) exposure and risk assessments were conducted 

using the Dietary Exposure Evaluation Model DEEM-FCIDTM, Version 2.03 which uses food 

consumption data from the U.S. Department of Agriculture’s Continuing Surveys of Food 

Intakes by Individuals (CSFII) from 1994-1996 and 1998. Per HED policy, residue estimates 

associated with the food-handling establishment use are not included in the acute dietary 

assessment. 

Both the acute and chronic analyses are based on tolerance-level residues and assume 100% crop 

treated. Acute and chronic dietary risk estimates are below HED’s level of concern for all 

population subgroups (Table 5.4). For acute exposures, the dietary risk for the U.S. population is 

estimated to be 21% of the population-adjusted dose (PAD). Acute risk for children 1-2 years 

old, the highest-exposed population subgroup, is estimated to be 52% of the PAD. Chronic risk 

estimates are 10% of the PAD for the U.S. population and 33% of the PAD for children 1-2 years 

old. Acetamiprid is classified as “not likely to be carcinogenic to humans,” and therefore cancer 

risk is not an issue for this chemical. 

There are no dietary exposure or risk concerns that would preclude granting the requested uses of 

acetamiprid and establishing tolerances associated with these uses. 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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Table 5.4. Summary of Dietary Exposure and Risk Estimates for Acetamiprid. 

Population Subgroup Acute (95th Percentile) Chronic 

Exposure (mg/kg/day) % PAD Exposure (mg/kg/day) % PAD 

U.S. Population (total) 0.020582 21 0.007145 10 

All infants (< 1 year) 0.049933 50 0.014333 20 

Children 1-2 yrs 0.051942 52 0.023734 33 

Children 3-5 yrs 0.037549 38 0.017226 24 

Children 6-12 yrs 0.021678 22 0.009434 13 

Youth 13-19 yrs 0.013955 14 0.005705 8 

Adults 20-49 yrs 0.013804 14 0.005229 7 

Adults 50+ yrs 0.014640 15 0.005836 8 

Females 13-49 yrs 0.014121 14 0.005424 8 

Populations with the highest exposure estimates are bolded. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization 

M. Collantes, D383325, 22 July 2011 

Acetamiprid is registered for controlling a wide variety of indoor and outdoor insect pests in 

residential settings. The registrant is not proposing any new residential uses with this 

submission, and therefore a new residential exposure assessment was not conducted. For 

acetamiprid, HED’s level of concern (LOC) is 100. In the most recent residential handler and 

postapplication exposure assessment, all scenarios resulted in margins of exposure (MOEs) 

greater than 100 and are not of concern (M. Collantes, D383325, 22 July 2011). 

The applicable combined residential risk estimates to adults (handler and postapplication) and 

children (3-6 years; postapplication only) are summarized in Table 6. All scenarios resulted in 

an aggregate risk index (ARI) greater than 1 and are not of concern. Although there is the 

potential for co-occurrence of adult exposure resulting from applying and entering treated areas 

(postapplication), the risks from both exposures are not combined because HED believes that this 

would result in an over-estimation of exposures. 

The risk estimates presented in Table 6 do not reflect the most recent (Feb. 2011) updates to the 

SOPs for residential exposure assessment, or the updated assumptions for body weights, in 

accordance with the October 2011 Exposure Factors Handbook. However, HED has determined 

that the updated SOPs and body weights will not result in significantly different exposure and 

risk estimates, and therefore would not significantly impact this aggregate risk assessment. The 

impact of the SOPs and body weights will be assessed in conjunction with registration review 

(docket opening scheduled for FY2013). Due to the lack of the required inhalation toxicity 

study, HED has determined that an additional 10X FQPA factor must be retained as a database 

uncertainty factor, raising the level of concern (LOC) to 1000 for inhalation scenarios. The ARI 

results presented in Table 6 were not included in the July 2011 assessment and are calculated 

here for the purposes of assessing this increased LOC, with these risks not being of concern as 

indicated above. 

 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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 Table 6. Combined Residential Exposure and Risk Estimates from the Indoor Crack and Crevice and Bed Bug 

Mattress Use1

Scenarios Daily Dose 

(mg/kg/day) 

MOE 2 ARI3

Adult Handler 

Mattress Treatment - Dermal 0.00088 11,000 26.1 

Mattress Treatment - Inhalation 0.000039 260,000 

Crack & Crevice - Dermal 0.00178 5,600 

Crack & Crevice - Inhalation 0.000078 130,000 

Adult Postapplication 

Dermal –Crack & Crevice 0.0232 430 4.2 

Inhalation– Crack & Crevice 0.000018 560,000 

Dermal - Mattress Treatment 0.00015 66,000 

Child Postapplication 

Dermal – Crack & Crevice 0.0333 300 2.2 

Inhalation – Crack & Crevice 0.000046 220,000 

Hand-To-Mouth – Crack and Crevice 0.011 900 

Dermal - Mattress Treatment 0.000323 31,000 1 With the exception of the Aggregate Risk Index (ARI), all information from this table is taken from D383325, M. 

Collantes, 22 July 2011. 2

 MOE = NOAEL (10 mg/kg/day) / Daily Dose. 

3

 Adult Handler ARI = 1/[(1/dermal MOE/100)+(1/inhalation MOE/1000)] 

Adult Postapplication ARI = 1/[(1/dermal MOE/100)+(1/inhalation MOE/1000)] 

Child Postapplication ARI = 1/[(1/dermal MOE/100)+(1/inhalation MOE/1000) + (1/Hand-to-Mouth MOE/100)] 

6.2 Spray Drift 

Spray drift is always a potential source of exposure to residents nearby spraying operations. This 

is particularly the case with aerial application, but, to a lesser extent, could also be a potential 

source of exposure from the ground application method employed for acetamiprid. The Agency 

has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead 

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

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

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

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

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

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

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

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

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

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

associated with drift. 

Although a quantitative residential postapplication inhalation exposure assessment was not 

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

exposure assessment was performed for flaggers who assist with aerial applications of 

acetamiprid on field crops. This exposure scenario is representative of a worse case inhalation 

(drift) exposure and may be considered protective of most outdoor agricultural and commercial 

postapplication inhalation exposure scenarios. 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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7.0 Aggregate Exposure/Risk Characterization 

In accordance with the FQPA, HED must consider and aggregate (add) pesticide risks from three 

major sources: food, drinking water, and residential exposures. When aggregating exposures and 

risks from various sources, HED considers toxicological endpoints as well as the route and 

duration of exposure.

7.1 Acute Aggregate Risk 

Typically, HED does not consider residential exposures when assessing acute aggregate risk 

unless such exposures can be characterized as a series of single-day exposures. For acetamiprid, 

residential exposures are assessed as short- and intermediate-term exposures. Therefore, acute 

aggregate risk estimates for acetamiprid are equivalent to the acute dietary risk estimates 

(Section 5.4) and are below HED’s level of concern. 

7.2 Short- and Intermediate-Term Aggregate Risk 

Toxicological endpoints and points of departure for assessing short- (1 to 30 days) and 

intermediate-term (1 to 6 months) risks associated with exposure to acetamiprid are identical; 

therefore, separate assessments are not being conducted for these durations. Short- and 

intermediate-term residential exposures to acetamiprid may occur from uses of this chemical 

around the home (Section 6) as well as from acetamiprid residues in food and drinking water 

(Section 5). For assessing aggregate risk, the chronic dietary exposure estimate is used since it 

represents a background exposure level from food and drinking water that may co-occur with 

residential exposures. Dermal, oral, and inhalation risks for short- and intermediate-term 

exposures were combined in this assessment, since the toxicological endpoints and points of 

departure were the same. However, the level of concern (LOC) values were different (i.e. 

dermal and oral LOC = 100, while inhalation LOC = 1000); therefore, the respective risk 

estimates are combined using the ARI approach. This approach reflects risk estimates resulting 

from exposure via the dermal, inhalation, and oral routes. The results of these calculations are 

presented in Table 7.2. All ARI’s are greater than 1 and indicate that risks are not of concern. 

 

Table 7.2 Short-Term and Intermediate Term Aggregate Risk Calculations1 

Population 

Short- or Intermediate-Term Scenario 

Dietary 

Exposure2 

Oral 

Residential 

Exposure3 

Dermal 

Residential 

Exposure4

Inhalation 

Residential 

Exposure5 

Aggregate 

ARI (food, 

water, and 

residential)6 MOE ARI MOE ARI MOE ARI MOE ARI 

Adult 1714 17.14 NA 428 4.28 555556 556 3.41 

Child 909 9.1 900 9 297 2.97 217391 217 1.45 

1

 HED is concerned if the ARI is less than 1. (ARI = Aggregate Risk Index.) 

2

 MOE dietary = [(short- or intermediate-term oral NOAEL of 10 mg/kg-day)/(chronic dietary exposure)]. ARI 

dietary = [(MOE dietary)/(MOE target)]. MOE target = 100. 

From Table 5.4, Child Chronic Dietary Exposure = Children 1-2 years (maximum exposure) = 0.023734 mg/kg-day; 

and Adult Chronic Dietary Exposure = Adult 50+ years (maximum exposure) = 0.005836 mg/kg-day 3

 MOE oral = [(10 mg/kg-day)/(hand-to-mouth residential exposure)]. ARI oral = [(MOE oral)/(MOE target)]. 

Hand-to-mouth residential exposure (from Table 6) = 0.011 mg/kg-day (child only). MOE target = 100. 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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4

 MOE dermal = [(10 mg/kg-day)/(high end dermal residential exposure)]. ARI dermal = [(MOE dermal)/(MOE 

target)]. From Table 6, High end dermal residential exposure = 0.02335 (adult) and 0.0033623 (child). 

MOE target = 100. 

5

 MOE inhalation = [(10 mg/kg-day)/(high end inhalation residential exposure)]. ARI inhalation = [(MOE 

inhalation)/(MOE target)]. From Table 6, High end inhalation residential exposure = 0.000018 (adult) and 

0.000046 (child). MOE target = 1000. 

6

 ARI Aggregate = 1/[(1/ARI dietary) + (1/ARI oral) + (1/ARI dermal) + (1/ARI inhalation)] 

7.3 Chronic Aggregate Risk 

There are no long-term residential exposures expected for acetamiprid. Therefore, chronic 

aggregate risk estimates are equivalent to the chronic dietary risk estimates (Section 5.4) and are 

below HED’s level of concern. 

7.4 Cancer Aggregate Risk 

Acetamiprid has been classified as “not likely to be carcinogenic to human;” therefore, cancer 

risk is not of concern for this chemical. 

8.0 Cumulative Exposure/Risk Characterization 

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

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to acetamiprid and any other substances and acetamiprid does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that 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 released by EPA’s OPP concerning common mechanism determinations and 

procedures for cumulating effects from substances found to have a common mechanism on 

EPA’s website at http://www.epa.gov/pesticides/cumulative/. 

9.0 Occupational Exposure/Risk Characterization 

S. Oonnithan, D395464/D395468/D395470, 15 February 2012 

The Health Effects Division (HED) has conducted an occupational and residential exposure 

(ORE) assessment for the proposed new uses of acetamiprid insecticide on asparagus, and sweet 

corn, and for the proposed increased maximum single application rate on turnip greens. 

Assessed scenarios include workers handling and/or applying end-use products as well as 

workers re-entering treated areas/fields. Occupational exposure to acetamiprid from the 

requested uses are expected to be of short-term (1-30 days) or intermediate-term (1-6 months) 

duration. As the short- and intermediate-term points of departure are the same, separate shortand intermediate-term assessments were not conducted. Long-term exposures are not expected. 

In addition to the new uses, the proposed labels have been amended to include the Agency’s 

updated crop group definitions for cole crops, fruiting vegetables, citrus and pome fruit. The 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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updated crop group definitions don’t require a new occupational exposure and risk assessment 

since the use patterns have been previously assessed, and no risks of concern were identified. 

9.1 Short- and Intermediate-Term Handler Risk 

Estimates of handler exposure to acetamiprid associated with the requested uses were assessed 

using surrogate study data available in the Pesticide Handlers Exposure Database Version 1.1 

(PHED 1.1), and the Agricultural Handler Exposure Task Force (AHETF) database. For all 

crops, assessed activities include mixers/loaders and applicators for ground-based and aerial 

applications, as well as flaggers. All of the proposed uses are on crops with the same use pattern 

(i.e., application rates and methods). Therefore, sweet corn was selected as a representative crop 

because it is the crop with the highest acreage treated. The exposures from dermal and 

inhalation routes were added together to calculate an ARI since the endpoints were the same (i.e., 

the same toxic effects), but with different levels of concern. All MOEs assume a baseline level 

of personal protective equipment (PPE) plus chemical resistant gloves, with the exception of the 

mixer/loader scenario for aerial applications of the WP formulation. With the exception of this 

mixer/loader aerial application scenario (using only baseline PPE), use of acetamiprid on 

assessed crops resulted in ARIs greater than 1 (Table 9.1) are not of concern. With the addition 

of a PF5 respirator to the mixer/loader scenario, the ARI is increased to 1.7 and is not of concern. 

Due to the lack of an inhalation study, HED determined that an additional 10X FQPA must be 

retained as a database uncertainty factor, raising the level of concern (LOC) to 1000 for 

inhalation scenarios. The ARI results presented in Table 9.1 were not included in the February 

2012 occupational assessment and are calculated here for the purpose of assessing this increased 

LOC, with these risks not being of concern as indicated above. 

 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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Table 9.1. Occupational Handler Exposure and Aggregate Risk Estimates From the Use of Acetamiprid 1. 

Exposure 

Scenario 2 Handler Miti

gation 

Level 3

Single 

Appl. Rate 

(lb ai/A) 

Acres 

Treated 

Unit exposures 

(μg/lb ai) 4 Dermal Dose (mg/kg/ 

day) 5

Inhal. Dose

(mg/kg/ 

day) 6

Derm

MO

Dermal Inhal. 

All crops WP for aerial appl. M/L B + G 0.1 350 170 (PHED) 43.4 (PHED) 0.00992 0.02532 1,00All crops WP for aerial appl. M/L B + G+ R (PF5) 0.1 350 170 (PHED) 8.68 (PHED) 0.00992 0.00506 1,00All crops  DF for aerial appl. M/L B + G 0.1 350 51.6 (AHETF) 8.96 (AHETF) 0.00301 3322 0.00523 3,32All crops, spray with fixed wing aircraft Applicator Encl. Cockpit 0.1 350 5.0 (PHED) 0.068 (PHED) 0.00029 0.00004 34,2All crops, Groundboom sprayer Applicator B + G, Open Cab 0.1 80 16.1 (AHETF) 0.34 (AHETF) 0.00021 0.00005 46,5All crops, aerial Flagger B+G 0.1 350 12.0 (PHED) 0.35 (PHED) 0.0007 0.0002 14,2

Abbreviations used: AHETF = Agricultural Handler Exposure Task Force, ARI = Aggregate risk index, B = Baseline personal protect

see # 3 below), DF = Dry flowable, G = Gloves, LOC= Level of concern, MOE = Margin of exposure, PHED = Pesticide Handler Exp

respirator, WP = Wettable powder. 1. Table (S. Oonnithan/D395470/2/15/2012) modified to estimate Aggregate risk index. 2. All crops are asparagus, sweet corn, and turnip greens. The use pattern is same for all crops. 3. Baseline PPE includes long-sleeved shirt, long pants and shoes with socks. Label recommended PPE is baseline plus chemical resis4. Unit exposures are surrogate values selected from AHETF and PHED data bases. 

5. Dermal dose (mg/kg/day) = [Appl. rate (lb ai/A) * Acres treated/day * Dermal unit exposure (μg/lb ai handled/day /1000) * Dermal 

 Body wt (60 kg).; LOC = 100. 6. Inhalation dose (mg/kg/day) = [Appl. rate (lb ai/A) * Acres treated/day * Inhal. unit exposure (μg/lb ai handled/day /1000)] * Inhal. 

 Body wt (60 kg); LOC = 1,000. 7. Aggregate risk index = 1/[(1/dermal MOE/100) + (1/inhalation MOE/1000)]. 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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9.2 Short- and Intermediate-Term Postapplication Risk 

The proposed labels for Assail® 70 Wettable Powder (WP) and Assail® 30 Soluble Granule 

(SG) Insecticides have a 12-hour REI and are in compliance with the Worker Protection 

Standard because acetamiprid is Toxicity Category III via the dermal route and is not an eye or 

skin irritant, and is not a skin sensitizer. 

9.2.1 Dermal Postapplication Risk 

The registrant did not submit a chemical specific postapplication exposure study for a 

quantitative evaluation of risks resulting from use of Assail® WP and SG products on the 

proposed crops. Dermal exposures during postapplication activities were estimated using 

standard default values for dermal transfer coefficients from the Science Advisory Council for 

Exposure Policy Number 3.2: Agricultural Transfer Coefficients, June 3, 2011 and based on 

proprietary data (from the Agricultural Reentry Task Force [ARTF]) and non-proprietary data. 

Farm workers who enter treated fields after the REI period to perform postapplication activities 

such as irrigation, weeding, scouting and harvesting may be exposed to residues of acetamiprid. 

These activities result in short-and intermediate-term postapplication dermal MOEs of 190 to 

1,800 and are not of concern (Table 9.2). 

Table 9.2. Risk Estimates to Workers Resulting from Postapplication Activities Performed in Fields 

Treated with Acetamiprid.

Crop High Contact 

Activity 

Appl. Rate 

(lb ai/A) 

DFR 

(ug/cm2)

1

Transfer 

Coefficient 

 (cm2/hr) 2

Short-term 

Dermal Dose 3 

(mg/kg/day) 

Short-term 

Dermal 

MOE 4

Asparagus Irrigation (hand 

weeding) 

0.1 0.224 

1,900 

(MRID No. 

45726301) 

0.00567 1,800 

Sweet corn 

Detasseling and 

Harvesting Hand 

17,600 

(MRID No. 

45005905) 

0.05256 190 

Turnip 

greens 

Irrigation (hand 

set) 1,900 0.00567 1,800 

1. Dislodgeable Foliar Residue (DFR) = Appl. Rate (lb ai/A) * (1- Daily Dissipation Rate)t * Conv. Factor 1 

(4.54E+8 μg/lb) * Conv. Factor 2 (2.47E-8 A/cm2

) * Residue Transfer Rate (20% default) after treatment. 

2. Transfer coefficient is a surrogate value for workers having low-high contact with field crops foliage during 

postapplication activities (ExpoSAC Policy #3, June 3, 2011). 

3. Daily Dose (mg/kg/day) = [DFR * Transfer Coefficient * Conv. Factor (0.001 mg/μg) * Dermal Absorption (10 

%) * 8 hrs/day] / Body Weight (60 kg). 

4: Short-term Margin of Exposure (MOE) = Short-term Dermal NOAEL (10 mg/kg/day) / Daily Dose (mg/kg/day). 

9.2.2 Inhalation Postapplication Risk 

Based on the Agency's current practices, a quantitative postapplication inhalation exposure 

assessment was not performed for acetamiprid at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III), low vapor pressure (7.5×10-9 mm Hg), and the low 

proposed application rate (0.1 lb ai/A). However, there are multiple potential sources of 

postapplication inhalation exposure to individuals performing postapplication activities in 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

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

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

received the SAP’s final report on 2 March 2 2010 

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

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

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate occupational 

postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

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

postapplication inhalation exposure assessment for acetamiprid. 

Although a quantitative occupational postapplication inhalation exposure assessment was not 

performed, HED has assessed inhalation exposure and risk for occupational/commercial flaggers 

for aerial applications of acetamiprid on sweet corn and the risk was not of concern. Inhalation 

exposure of flaggers resulting from aerial application of pesticides is likely to result in higher 

exposure than the exposure resulting from postapplication activities. Therefore, it is expected 

that the flagger inhalation risk estimate conducted for sweet corn would be protective of all 

postapplication inhalation exposure scenarios. 

10.0 References 

K. White. D394234/D394479. 11 October 2011. Tier I Drinking Water Exposure Assessment 

for the Section 3 New Use of Acetamiprid on Various Agricultural Crops and as a Scatter 

Bait to Control Insects 

M. Collantes. D383325. 22 July 2011. Acetamiprid: Occupational and Residential Exposure 

Assessment for Use to Control Bed Bugs 

M. Doherty. D278352. 16 October 2001. Acetamiprid - Metabolism Assessment Review 

 Committee Briefing Memorandum. 

M. Doherty. D264154. 31 December 2001. Section 3 Registration for Use of Acetamiprid on 

Cotton, Leafy Vegetables, Cole Vegetables, Fruiting Vegetables, Citrus Fruits, Pome Fruits, 

Grapes, and Canola and Mustard Seed. Summary of Analytical Methods and Residue 

Chemistry DERs. 

E. Holman. D394779. 6 March 2012. Acetamiprid. Petition for the Establishment of Permanent 

Tolerances and Registration for Use on Asparagus; Brassica, Leafy Greens, Subgroup 5B, 

and Turnip Greens; and Sweet Corn; and Update of Crop Group Definitions for Established 

Tolerances for Vegetable, Fruiting, Group 8-10; Fruit, Citrus, Group 10-10; and Fruit, 

Pome, Group 11-10. Summary of Analytical Chemistry and Residue Data. 

E. Holman. D395331. 14 February 2012. Acetamiprid Acute and Chronic Dietary (Food and 

Drinking Water) Exposure and Risk Assessment – Uses on Asparagus, Brassica Leafy 

Greens (Subgroup 5B), Sweet Corn, and Updated Crop Groups for Pome, Citrus Fruit, and 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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Fruiting Vegetables. 

S. Oonnithan. D395464, D395468, and D395470. 15 February 2012. Acetamiprid: 

Occupational and Residential Exposure Assessment for the Proposed New Uses on 

Asparagus and Sweet Corn, and for an Increased Application Rate for Turnip Greens. 

K. Rury. TXR 0052354. 15 March 2012. Acetamiprid: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting of March 12, 2012. Recommendations on the need for a 28-

day inhalation study. 

 
Acetamiprid Human Health Risk Assessment DP No. D394322 

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Appendix A. Toxicology Profile and Executive Summaries 

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for based on food uses of acetamiprid are in Table 1. Use of the new guideline 

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

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity 

870.1200 Acute Dermal Toxicity 

870.1300 Acute Inhalation Toxicity 

870.2400 Primary Eye Irritation 

870.2500 Primary Dermal Irritation 

870.2600 Dermal Sensitization 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

870.3100 Oral Subchronic (rodent) 

870.3150 Oral Subchronic (nonrodent) 

870.3200 21-Day Dermal 

870.3250 90-Day Dermal 

870.3465 21/28-Day Inhalation 

Yes 

Yes 

Yes 

No 

Yes 

Yes 

Yes 

Yes 

-- 

No 

870.3700a Developmental Toxicity (rodent) 

870.3700b Developmental Toxicity (nonrodent) 

870.3800 Reproduction 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

870.4100a Chronic Toxicity (rodent) 

870.4100b Chronic Toxicity (nonrodent) 

870.4200a Oncogenicity (rat) 

870.4200b Oncogenicity (mouse) 

870.4300 Chronic/Oncogenicity 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

870.5100 Mutagenicity—Gene Mutation - bacterial 

870.5300 Mutagenicity—Gene Mutation - mammalian 

870.5xxx Mutagenicity—Structural Chromosomal Aberrations 

870.5xxx Mutagenicity—Other Genotoxic Effects 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 

870.6100a Acute Delayed Neurotoxicity (hen) 

870.6100b 90-Day Neurotoxicity (hen) 

870.6200a Acute Neurotoxicity Screening Battery (rat) 

870.6200b 90-Day Neurotoxicity Screening Battery (rat) 

870.6300 Develop. Neurotoxicity 

No 

No 

Yes 

Yes 

Yes 

-- 

-- 

Yes 

Yes 

Yes 

870.7485 General Metabolism 

870.7600 Dermal Penetration 

870.7800 Immunotoxicity 

Yes 

Yes 

Yes 

Yes 

Yes 

Yes 
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 35 of 43 

A.2 Toxicity Profiles

Acute Toxicity of Technical Acetamiprid 

GDLN Study Type MRID Results Tox Category 

870.1100 Acute Oral - rat 44651833 LD50: 217 mg/kg (M) 

LD50: 146 mg/kg (F) 

II 

870.1200 Acute Dermal - rat 44651836 LD50 > 2000 mg/kg III 

870.1300 Acute Inhalation - rat 44651837 LC50: > 1.15 mg/L (~) 

> 1.15 mg/L (~) 

III 

870.2400 Primary Eye Irritation - rabbit 44651838 Not irritating to the eye IV 

870.2500 Primary Skin Irritation - rabbit 44651839 Not irritating to the skin IV 

870.2600 Dermal Sensitization - Guinea pig 44651840 Is not a sensitizer under 

conditions of study. 

N/A 

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 
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 36 of 43 

Toxicity Profile for Acetamiprid: Subchronic, Chronic, and Other Toxicity Studies 

Guideline No./ Study 

Type 

MRID No. 

(year)/Classification /Doses

Results 

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 

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 
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 37 of 43 

Toxicity Profile for Acetamiprid: Subchronic, Chronic, and Other Toxicity Studies 

Guideline No./ Study 

Type 

MRID No. 

(year)/Classification /Doses

Results 

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 

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, not considered treatmentrelated 

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. 

870.5395 

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. 
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 38 of 43 

Toxicity Profile for Acetamiprid: Subchronic, Chronic, and Other Toxicity Studies 

Guideline No./ Study 

Type 

MRID No. 

(year)/Classification /Doses

Results 

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.

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 - rats 

(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. 
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 39 of 43 

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 - rat 

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%. Discuss revised 

dermal absorption briefly here or refer to dermal 

abs. section 

870.7800 

Immunotoxicity – rat 

(dietary) 

48113402 (2010) 

acceptable/guideline 

0, 100, 300, 900 ppm 

Equivalent to 0/0, 7.4/8.6, 

21.6/24.3, 62.9/67.7 (M/F) 

mg/kg/day 

Systemic: 

NOAEL = 21.6/24.3 (M/F) mg/kg/day 

LOAEL = 62.9/67.7 (M/F) mg/kg/day based on 

decreases in body weight, body weight gain, food 

consumption and water consumption (males 

only). 

Immunotoxicity: 

NOAEL = 62.9/67.7 (M/F) mg/kg/day 

LOAEL = not attained 

870.7800 

Immunotoxicity – mouse 

(dietary) 

48113401 (2010) 

acceptable/guideline 

0, 100,300, 900 ppm 

Equivalent to 0/0, 15.3/20.2, 

47.0/54.4, 128/157 (M/F) 

mg/kg/day 

Systemic: 

NOAEL = 47.0/54.4 (M/F) mg/kg/day 

LOAEL = 128/157 (M/F) mg/kg/day based on 

decreases in body weight (slight), body weight 

gain, food consumption and water consumption 

(males only) 

Immunotoxicity: 

NOAEL = 128/157 (M/F) mg/kg/day 

LOAEL = not attained 
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 40 of 43 

Toxicity Profile for Acetamiprid: Subchronic, Chronic, and Other Toxicity Studies 

Guideline No./ Study 

Type 

MRID No. 

(year)/Classification /Doses

Results 

N/A 

28-Day Range-finding Study 

– dog 

(dietary) 

45245306 (1998) 

Acceptable/Non-guideline 

0, 125/3000, 250, 500, 1000 ppm 

mg/kg/day: M= 0, 4.1/42.5, 8.4, 

16.7, 28.0; F= 0, 4.8/46.2, 8.7, 

19.1, 35.8 [ppm: 125/3000 = 125 

for 2 weeks, 3000 for 2 weeks] 

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 

 
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 41 of 43 

A3. Executive Summaries – Immunotoxicity Studies 

STUDY TYPE: 4-Week Dietary Immunotoxicity Study – Mouse; 

 OPPTS 870.7800 

EXECUTIVE SUMMARY:

In a 4-week dietary immunotoxicity study (MRID 48113401) Acetamiprid (99.9% a.i., Lot 

No.NFG-02) was administered to 10 Crl:CD-1 (ICR) mice/sex/dose in the diet at dose levels of 0 

(control and positive control groups), 100, 300, or 900 ppm (equivalent to 0, 15.3, 47.0, or 128 

mg/kg/day in males; 0, 20.2, 54.1, or 157 mg/kg/day in females). On Day 25, animals received a 

0.2 mL intravenous injection of sheep red blood cells (SRBCs) in 0.9% saline (2 x 109

SRBCs)/mL). Cyclophosphamide in water (20 mg/kg body weight/day) was administered to the 

positive control group (8 mice/sex) by oral gavage on Days 22-26. 

A significant decrease in mean body weight gain over the 4-week treatment period was seen in 

males in the 900 ppm treatment group when compared with the control (reduction of 56%, 

p<0.01); female mean body weight also was reduced over this period (reduction of 52%, not 

statistically significant). The effect upon mean body weight gain was greatest during the first 

week of treatment, with a mean weight loss seen in both sexes (p<0.01 in males, p<0.05 in 

females). A slight decrease in body weight gain seen in females in the 300 ppm group (reduction 

of 12%, not statistically significant) was also attributed to treatment. Mean food consumption in 

the 900 ppm treatment group was significantly reduced in both sexes during the first two weeks 

of treatment (p<0.01 in males, p<0.05 in females). Overall weeks 1-4 mean water consumption 

was significantly reduced in males in the 900 ppm treatment group (25% reduction compared 

with control, p<0.01). The decreases in mean body weight gain, food consumption, and water 

consumption were considered to be non-specific toxic effects of treatment with Acetamiprid. 

Rales, observed in the 900 ppm group in 2/10 males and 3/10 females during Week 4, also was 

attributed to treatment although the cause was not determined. There were no mortalities during 

the treatment period. 

The systemic NOAEL was 47.0 mg/kg/day for males and 54.4 mg/kg/day for females with 

the LOAEL being 128 mg/kg/day for males and 157 mg/kg/day for females based on 

decreases in body weight (slight), body weight gain, food consumption and water 

consumption (males only). 

There was no effect on immune function associated with exposure of mice to dietary 

concentrations of Acetamiprid of up to 900 ppm. Although females in the 900 ppm group had a 

significant decrease in the mean number of plaque forming cells (PFC)/spleen (p<0.05); this 

finding correlated with a significant decrease in the mean number of cells/spleen (p<0.05) and 

was attributed to a decrease in spleen size and cell numbers, rather than a decrease in immune 

function. The NOAEL is 128 mg/kg/day in males and 157 mg/kg/day in females (highest 

tested dose), based on antigen-specific, T-cell dependent antibody formation. The LOAEL 

for immunotoxicity could not be determined (i.e., greater than the highest dose tested).
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 42 of 43 

This 4-week dietary immunotoxicity study in the mouse is ACCEPTABLE/GUIDELINE and 

satisfies the guideline requirement for a 4-week dietary immunotoxicity study (OPPTS 

870.7800) in mice.

STUDY TYPE: 4-Week Dietary Immunotoxicity Study – Rat; 

 OPPTS 870.7800 

EXECUTIVE SUMMARY:

In a 4-week dietary immunotoxicity study (MRID 48113402) Acetamiprid (99.9% a.i., Lot 

No.NFG-02) was administered to 10 Crl:CD (SD) rats/sex/dose in the diet at dose levels of 0 

(control and positive control groups), 100, 300, or 900 ppm (equivalent to 0, 7.4, 21.6, or 62.9 

mg/kg/day in males; 0, 8.6, 24.3, or 67.7 mg/kg/day in females). On Day 25, animals received a 

1 mL intravenous injection of sheep red blood cells (SRBCs) in 0.9% saline (2 x 108

SRBCs)/mL). Cyclophosphamide in water (50 mg/kg body weight) was administered to the 

positive control group (8 rats/sex) by intraperitoneal injection on Day 27. 

A significant decrease in mean body weight gain over the 4-week treatment period was seen in 

both sexes in the 900 ppm treatment group when compared with the control (reduction of 33% in 

males, 52% in females; p<0.01, both sexes). The effect upon mean body weight gain was 

greatest during the first few days (Days 1-4) of treatment (p<0.01, both sexes). Mean body 

weight gain in males in the 300 ppm treatment group also was significantly lower than the 

control (p<0.05) during Days 1-4. Mean food consumption during the treatment period was 

reduced in males and females in the 900 ppm treatment group (85% of control, both sexes). 

Weekly mean water consumption was decreased in males in the 900 ppm group (71 to 85% of 

mean control values). Food and water consumption data were not statistically analyzed. The 

decreases in mean body weight gain, food consumption, and water consumption were considered 

to be non-specific toxic effects of treatment. There were no clinical signs considered to be 

treatment-related. No mortalities occurred during the treatment period. No treatment-related 

affects were associated with exposure to 100 ppm. 

The systemic NOAEL was 21.6 mg/kg/day for males and 24.3 mg/kg/day for females with 

the LOAEL being 62.9 mg/kg/day for males and 67.7 mg/kg/day for females based on 

decreases in body weight, body weight gain, food consumption and water consumption 

(males only). 

There were no effects on immune function, as assessed by measuring antigen-specific, T-cell 

dependent antibody formation. No significant differences were seen in the number of 

cells/spleen, plaque forming cells (PFC)/106

 cells, or PFC/spleen at dietary concentrations of 

Acetamiprid of up to 900 ppm. The NOAEL is 62.9 mg/kg/day in males and 67.7 mg/kg/day 

in females (highest tested dose), based on antigen-specific, T-cell dependent antibody 

formation. The LOAEL for immunotoxicity could not be determined (i.e., greater than the 

highest dose tested).
Acetamiprid Human Health Risk Assessment DP No. D394322 

Page 43 of 43 

This 4-week dietary immunotoxicity study in the rat is ACCEPTABLE/GUIDELINE and 

satisfies the guideline requirement for a 4-week dietary immunotoxicity study (OPPTS 

870.7800) in rats.