Acetamiprid Human Health Risk Assessment DP No. D410182

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: March 20, 2013

SUBJECT: Acetamiprid: Revised Human Health Risk Assessment for the New Use on Sweet 

Corn and Increased Tolerance on Citrus. 

PC Code: 099050 DP Barcode: D410182

Decision Nos.: 474870, 467044 Registration Nos.: 8033-23, 8033-36

Petition Nos.: 3E8147, 2F8060 Regulatory Action: Section 3 and Amended 

Tolerance

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

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

MRID Nos.: 40 CFR 180.578

FROM: Elizabeth Holman, Physical Scientist

William Drew, Chemist

Risk Assessment Branch II

Health Effects Division (7509P)

THROUGH: Christina Swartz, Chief

Risk Assessment Branch II

Health Effects Division (7509P)

TO: Andrew Ertman, Chemical Review Manager

 Risk Integration Minor Use, and Emergency Response Branch

 Registration Division (7505P)

And

Jennifer Urbanski/Venus Eagle (Team 01)

Insecticide/Rodenticide Branch

Registration Division (7505P)

This revised risk assessment has been issued in order to address inconsistencies regarding 

exposure durations in the residential handler assessment. The earlier risk assessment (D409185, 

E. Holman, 03/07/2013) did not specifically address the inclusion of the intermediate-term 

exposure scenario, with this revision making it clear that such an assessment has been completed. 

No risks of concern were identified in this assessment, and the risk estimates have not changed 

from those presented in the previous assessment. 
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Table of Contents

1.0 Executive Summary ..................................................................................................................3

2.0 HED Recommendations ...........................................................................................................3

2.1 Data Deficiencies/Conditions of Registration .....................................................................4

2.2 Tolerance Considerations......................................................................................................4

2.2.1 Enforcement Analytical Method...................................................................................4

2.2.2 International Harmonization .........................................................................................4

2.2.3 Recommended Tolerances ............................................................................................5

2.2.4 Revisions to Petitioned-For Tolerances........................................................................5

2.3 Label Recommendations.......................................................................................................6

3.0 Introduction ...............................................................................................................................6

3.1 Chemical Identity ..................................................................................................................6

3.2 Physical/Chemical Characteristics.......................................................................................6

3.3 Pesticide Use Pattern.............................................................................................................7

3.4 Anticipated Exposure Pathways...........................................................................................7

3.5 Consideration of Environmental Justice ..............................................................................8

4.0 Hazard Characterization and Dose-Response Assessment.....................................................8

4.1 Summary of Toxicological Effects.......................................................................................8

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) .................................10

4.2.1 Completeness of the Toxicology Database ................................................................10

4.2.2 Evidence of Neurotoxicity ..........................................................................................11

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ..........11

4.2.4 Residual Uncertainty in the Exposure Database........................................................11

4.3 Toxicity Endpoint and Point of Departure Selections.......................................................12

5.0 Dietary Exposure and Risk Assessment ................................................................................14

5.1 Metabolite/Degradate Residue Profile ...............................................................................14

5.2 Food Residue Profile...........................................................................................................15

5.3 Water Residue Profile .........................................................................................................16

5.4 Dietary Risk Assessment ....................................................................................................17

6.0 Residential (Non-Occupational) Exposure/Risk Characterization.......................................17

7.0 Aggregate Exposure/Risk Characterization...........................................................................19

7.1 Acute Aggregate Risk .........................................................................................................19

7.2 Short- and Intermediate-Term Aggregate Risk .................................................................20

7.3 Chronic Aggregate Risk......................................................................................................20

7.4 Cancer Aggregate Risk .......................................................................................................20

8.0 Cumulative Exposure/Risk Characterization ........................................................................20

9.0 Occupational Exposure/Risk Characterization......................................................................21

9.1 Short- and Intermediate-Term Handler Risk .....................................................................21

9.2 Short- and Intermediate-Term Postapplication Risk .........................................................23

9.2.1 Dermal Postapplication Risk.......................................................................................23

9.2.2 Inhalation Postapplication Risk ..................................................................................23

10.0 References................................................................................................................................24

Appendix A. Toxicology Profile and Executive Summaries..........................................................26
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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 sweet corn. In addition, under a 

separate petition, Nisso America Incorporated (Nisso), representing Nippon Soda Company 

Limited, has requested that the existing tolerance on citrus (group 10-10) be increased in order to 

harmonize with European and Codex Maximum Residue Limits (MRLs), and to allow for the 

higher residues expected based on the European use pattern. There has been no change in the US 

use pattern for citrus. The end-use products under consideration for the new use on sweet corn

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 sweet corn is 

0.1 lb ai/A. These formulations may be applied using aerial and ground equipment. For sweet 

corn, the maximum number of applications is 4 per season with a 7-day RTI and a 1-day preharvest interval (PHI).

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. 

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 

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 sweet corn 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. 
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2.1 Data Deficiencies/Conditions of Registration

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

based on the registered use pattern. HED previously determined that the required inhalation 

study was needed, based on weight of evidence considerations, including the available toxicity 

data and the potential for exposure to acetamiprid via the inhalation route. However, the 

registrant recently requested that this conclusion be re-evaluated, with the registrant indicating 

their willingness to implement risk mitigation on registered labels in order to address low 

occupational margins of exposure (MOEs) associated with aerial application mixing/loading 

scenarios of the wettable powder (WP) formulation. Therefore, HED re-considered the need for 

the study, and now finds that a subchronic inhalation toxicity study is not required for 

acetamiprid. This determination considered all of the available hazard and exposure information 

for acetamiprid, including: (1) the registrant’s agreement to provide additional risk mitigation 

for the use of the WP for mixing/loading; (2) the WP formulation is no longer used as a seed 

treatment; and (3) the use of an oral point of departure (POD) that results in MOEs greater than 

1300 for all occupational and residential exposures. However, if the exposure profile for 

acetamiprid changes, the HASPOC will reevaluate the need for a subchronic inhalation toxicity 

study. 

In an earlier risk assessment, HED concluded that additional field trial residue data were required 

for the use on sweet corn (DP394322, E. Holman, 04/19/2012). However, recent changes in 

HED’s policy related to adjuvant use have sufficiently resolved these deficiencies. Therefore, no 

additional field trial data are required to support the proposed use on sweet corn and the 

recommended tolerances have been determined using the previously submitted data. 

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 MRLs for acetamiprid on sweet 

corn; therefore, there are no issues of harmonization. There are Codex and Canadian MRLs on 

livestock commodities, with the revised livestock tolerances for the U.S. being higher than both 

the Codex and Canadian values. Given the revised use pattern including sweet corn, these higher 

U.S. livestock commodity tolerances are warranted. However, this is not considered to be a 

significant trade irritant, as livestock commodities are rarely shipped internationally. With the 

citrus (crop group 10-10) tolerance increase to 1.0 ppm, the U.S. will be harmonized with both 

Codex and the European Union MRLs. However, the Canadian tolerance for citrus is currently 
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at 0.5 ppm; HED has made Canada (PMRA) aware of these impending revisions and they intend 

to harmonize their tolerances when possible at a future date. 

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/Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments (Correct 

Commodity Definition)

Corn, sweet, kernel plus cob with 

husks removed

0.01 0.01

Corn, sweet, forage 15 15

Corn, sweet, stover 30 30

Milk 0.30 0.30

Cattle, fat 0.20 0.20

Cattle, meat 0.30 0.30

Cattle, meat byproducts 0.70 0.70

Goat, fat 0.20 0.20

Goat, meat 0.30 0.30

Goat, meat byproducts 0.70 0.70

Horse, fat 0.20 0.20

Horse, meat 0.30 0.30

Horse, meat byproducts 0.70 0.70

Sheep, fat 0.20 0.20

Sheep, meat 0.30 0.30

Sheep, meat byproducts 0.70 0.70

Fruit, citrus, group 10-10 1.0 1.0 Existing tolerance is at 0.5 

ppm

Citrus, dried pulp 2.4 1.2 Existing tolerance is at 1.2 

ppm and should be maintained

In addition, an error has been identified with a commodity definition listing in the existing 40 

CFR §180.578, which currently lists “vegetable, tuberous and corm, group 1.” In a future action 

associated with acetamiprid, this listing should be revised to read “Vegetable, tuberous and corm, 

subgroup 1C.” 

2.2.4 Revisions to Petitioned-For Tolerances

Requested and recommended tolerances are in agreement for residues in/on sweet corn and 

livestock commodities summarized in Table 2.2.3. Therefore, no revisions are necessary for 

these commodities.
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For citrus fruit (group 10-10), the proposed and recommended tolerance are also in agreement. 

However, for citrus, dried pulp, HED has determined that a revised citrus pulp tolerance is not 

needed and that the existing tolerance of 1.2 ppm is adequate (D404596, W. Drew, 01/04/2013). 

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

Table 2.2.3. 

 

2.3 Label Recommendations

It is noted that sweet corn is one of the crops that has been identified as requiring risk mitigation 

for the mixing/loading scenarios for aerial application on the WP formulation label (D407373, E. 

Holman, 02/07/2012). HED recommends that risk mitigation measures be undertaken to address 

this issue, such as the addition of a PF5 respirator, with appropriate label revisions as needed. 

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. 

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]-N 2-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 Appendix 

Table B1. The values in the table suggest that there are no exposure scenarios that are likely to 

N N

CH3

Cl

CH3

N

CN
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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.

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

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)

Citrus (within Crop Group 10-10)

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

3 for the registered U.S. formulations, 

with a maximum annual use rate of 0.55 lb ai/A. 

In the European Union, there is a higher maximum annual use rate of 0.62 lb ai/A. 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”. As noted 

previously, in the absence of a subchronic inhalation study, sweet corn is one of the crops that 

has been identified as requiring risk mitigation for the mixing/loading scenarios for aerial 

application on the WP formulation label (D407373, E. Holman, 02/07/2012). HED recommends 

that risk mitigation measures be undertaken to address this issue, such as the addition of a PF5 

respirator, with appropriate label revisions as needed. 

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. 
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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 from the U.S. Department of 

Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a 

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

year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary 

exposure to smaller, specialized subgroups and exposure assessments are performed when 

conditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on 

home use of pesticide products and associated risks for adult applicators and for toddlers, youths, 

and adults entering or playing on treated areas postapplication are evaluated. Further 

considerations are currently in development as OPP has committed resources and expertise to the 

development of specialized software and models that consider exposure to bystanders and farm 

workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Comprehensive risk assessments for acetamiprid were conducted in 2012 (D394322; E. 

Holman). There are no changes to the endpoints or points of departure (PODs) for dietary 

assessment for acute, chronic or cancer risk used in the previous evaluations. However, the HED 

HASPOC recently re-evaluated the need for a subchronic inhalation study and determined that it 

is not needed at this time (TXR 0056556, K.Rury, 02/20/2013). Consequently, the 10X database 

uncertainty factor retained in the 2012 assessment for inhalation scenarios has been removed, 

with the level of concern being lowered to 100 for these scenarios. 

 

4.1 Summary of Toxicological Effects

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 

mutagenicity battery, as well as metabolism studies in the rat. The lack of a 21/28 day inhalation 

study in rats is not considered to be a data gap; the HED HASPOC has determined that the study 
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is not needed at this time (TXR 0056556, K.Rury, 02/20/2013). No literature information is 

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

some mutagenicity studies.

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.

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, HED has refined the dermal 

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

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.

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 (DNT) study there was also evidence of increased qualitative 

susceptibility. In this study, the offspring lowest observed adverse effect level (LOAEL) was 

based on decreased body weights and body weight gains in males and females, decreased preweaning survival [post-natal days (PNDs) 0-1], and decreased maximum auditory startle 
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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. Although offspring and maternal effects 

were observed at the same doses, the offspring effects were considered to be more severe.

In a rat acute 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 

study. Acetamiprid metabolites IC-0, IM-1-2, IM-1-4, IM-2-1, and IM-0 tested negative for 

mutagenicity.

Acute lethality studies conducted with acetamiprid indicated that it is moderately toxic via the 

acute oral route (Category II); however, it has low toxicity via the acute dermal or inhalation 

routes (Categories III). It is non-irritating to the eyes and skin and is not a dermal sensitizer.

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

HED recommends the FQPA SF of 10X be reduced to 1X for the following reasons: (1) the 

toxicology data base is complete; (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 no observed adverse effect level (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. 

4.2.1 Completeness of the Toxicology Database
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As summarized in Appendix Table A1, the toxicology database is considered adequate for the 

purpose of assessing pre- and postnatal susceptibility, including an immunotoxicity study. 

Acceptable developmental toxicity studies in the rat and rabbit and a rat reproductive toxicity 

study have been submitted. Based on a WOE approach considering all the available hazard and 

exposure information and proposed addition of a respirator for mixing/loading WP acetamiprid 

for aerial application, or other appropriate mitigation, HED’s HASPOC concluded that a 

subchronic inhalation toxicity study is not required for acetamiprid at this time (TXR# 0056556).

4.2.2 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.

4.2.3 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 

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. 

4.2.4 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.
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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.

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.

4.3 Toxicity Endpoint and Point of Departure Selections

The toxicological endpoints and points of departure selected for dietary and occupational 

exposure and risk assessment are presented below in Tables 4.3.1 and 4.3.2. The complete 

toxicological profile for acetamiprid is summarized in Appendix A.2. There have been no 

changes to the dietary dose-response assessment or endpoints, the cancer classification/risk 

quantification or the occupational dermal assessment. 

A revised occupational exposure and risk assessment has not been conducted for this assessment 

since the use pattern for sweet corn was previously assessed under an earlier petition. Currently, 

occupational exposure of only short- or intermediate-term durations is anticipated. A 28- or 90-

day inhalation study is not required. Since long-term occupational exposure is not anticipated, 

the oral studies of short or subchronic duration (rat, dog and mouse 90-day dietary; rat 

reproductive toxicity; rat and rabbit developmental toxicity) were considered for inhalation risk 

assessment. For inhalation exposure scenarios, as the subchronic inhalation study is no longer 

required as it was in the 2012 assessment (D394322), the level of concern has been lowered to 

100 and the 10X database uncertainty factor has no longer been retained. 

For short- and intermediate-term inhalation exposure, the developmental neurotoxicity (DNT) 

NOAEL of 10 mg/kg/day was selected, with a LOAEL of 45 mg/kg/day. In this DNT study, 

parental effects were limited to decreased body weight and body weight gains, while the 

offspring effects noted were decreased body weights and body weight gains, decreased preweaning survival (post-natal days (PNDs) 0-1), and decreased maximum auditory startle 

response in males on PNDs 20 and 60. Since an oral study was selected for assessing the 

inhalation route, toxicity via this route was considered to be equivalent to toxicity via the oral 

route, for the purpose of risk assessment.

For all of the relevant routes and durations of exposure, clear NOAELs and LOAELs were 

identified. In addition, the toxicity database is considered to be largely complete, and no 

database uncertainty factors (UFs) were needed to account for missing data. With the reduction 

of the FQPA SF to 1X, the standard uncertainty factors of 100X (based on 10X for intraspecies 
Acetamiprid Human Health Risk Assessment DP No. D410182

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variability and 10X for interspecies extrapolation) were applied. For dermal and inhalation risk 

assessment, the level of concern (LOC) is a margin of exposure (MOE) of 100. For dietary 

assessments, the combined UF of 100X was incorporated into the relevant reference doses 

(RfDs) and population adjusted doses (PADs).

Table 4.3.1. Summary of Toxicological Doses and Endpoints of Acetamiprid for Use in Dietary and NonOccupational Human Health Risk Assessment

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; 1-6 

months)

NOAEL = 10 

mg/kg/day

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 

Dermal

(1-30 days; 1-6 

months)

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 

months)

NOAEL = 10 

mg/kg/day

Inhalation 

toxicity 

assumed to be 

equivalent to 

oral toxicity

UFA = 10x

UFH = 10x

FQPA SF = 1x

LOC for MOE 

= 100

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on 

decreased body weight and body weight 

gains in offspring, decreased early pup 

survival on PND 0-1, and decreased 

startle response on PND 20/60 in males.

Cancer (oral, dermal, inhalation) - not likely to be carcinogenic to humans (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. 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.
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Table 4.3.2. 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- and

Intermediate-term

Dermal 

(1 - 30 days; 1 - 6 

months)

NOAEL= 

10 mg/kg/day

DAF = 10%

UFA = 10x

UFH = 10x

LOC for MOE 

= 100

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on 

decreased body weight and body weight 

gains in offspring, decreased early pup 

survival on PND 0-1, and decreased 

startle response on PND 20/60 in males.

Short- and 

Intermediate-term 

Inhalation 

(1 - 30 days, 1 - 6 

months)

NOAEL=

10 mg/kg/day

Inhalation 

toxicity 

assumed to be 

equivalent to 

oral toxicity

UFA = 10x

UFH = 10x

LOC for MOE 

= 100

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on 

decreased body weight and body weight 

gains in offspring, decreased early pup 

survival on PND 0-1, and decreased 

startle response on PND 20/60 in males.

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. UF A = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human 

population (intraspecies). 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, D409726, 07 March 2013 

E. Holman, D409727, 07 March 2013 

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

Drinking Water Acetamiprid Not Applicable
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5.2 Food Residue Profile

The established tolerances in fruit, citrus, group 10-10 can be increased as proposed from 0.5 

ppm to 1.0 ppm. There is no change in the US use pattern associated with citrus; however, the 

European Union maximum annual use rate on citrus is higher at 0.62 lb ai/A vs. 0.55 lb ai/A in 

the U.S. Therefore, these tolerance revisions are being made to harmonize with Codex and 

European Union MRLs and to accommodate the higher EU use rates on imported citrus 

commodities. 

To support the proposed use on sweet corn, the petitioner has submitted studies depicting 

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

corn commodities. 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 sweet corn. Table 5.2.1. summarizes the 

submitted field trial data for the proposed commodities. 

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

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. As noted previously, there are

significant differences in the stover PHIs between the U.S. and Canadian trials (D394779, E. 

Holman, 03/06/2012). These differences are reflected in the residue data for stover and forage. 

In both the U.S. and Canadian trials, residues of acetamiprid were <0.01in K+CWHR, whereas 

residues in forage and stover appeared to be higher in the U.S. trials (up to ~10X higher in forage 

and ~30X higher 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. However, the HED ChemSAC 

recently concluded that the inherent variability in field trials, coupled with the characteristics and 

conservative nature of the OECD tolerance calculation method exceeds the variability seen with 

the use of adjuvants. Therefore, the adjuvant differences observed in the U.S. and Canadian field 

trials are no longer considered to be an issue. Consequently, additional crop field trial data are 

not required to support the proposed use on sweet corn. 

The available residue chemistry data for acetamiprid are sufficient for purposes of assessing risk 

and establishing tolerances on sweet corn. The existing dataset is sufficient for assessing risk 

and establishing an increased tolerance on citrus, with no change in the existing use pattern. 

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 potential increased dietary burden, the maximum expected combined residues of 

acetamiprid and IM-2-1 increase in milk and all tissues. Based on the data 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. 
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Table 5.2.1. Summary of Residue Data from Sweet Corn Crop Field Trials with Acetamiprid.

CommodityNo. 

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 0.213-0.281

(238.5-314.7)

38-89 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

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.
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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 aggregate dietary [food and drinking water] exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model software with the Food 

Commodity Intake Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 food 

consumption data from the U.S. Department of Agriculture’s (USDA’s) National Health and 

Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). 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 25% of the population-adjusted dose (PAD). Acute risk for children 1-2 years 

old, the highest-exposed population subgroup, is estimated to be 68% of the PAD. Chronic risk 

estimates are 14% of the PAD for the U.S. population and 60% 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.

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) 0.024916 25 0.009604 14

All infants (< 1 year) 0.051557 52 0.017618 25

Children 1-2 yrs 0.067723 68 0.042610 60

Children 3-5 yrs 0.045932 46 0.027686 39

Children 6-12 yrs 0.026282 26 0.013626 19

Youth 13-19 yrs 0.015610 16 0.007393 10

Adults 20-49 yrs 0.016009 16 0.006717 10

Adults 50-99 yrs 0.015813 16 0.007152 10

Females 13-49 yrs 0.016260 16 0.006916 10

Populations with the highest exposure estimates are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

M. Collantes, D383325, 22 July 2011
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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. Exposure 

to acetamiprid in residential settings is expected to be short- (1 to 30 days) and intermediate-term 

(1 to 6 months) in duration. For acetamiprid, HED’s level of concern (LOC) is a margin of 

exposure (MOE) of 100. In the most recent residential handler and postapplication exposure 

assessment, all scenarios resulted in 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. 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. 2012) 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). 

In the most recently completed risk assessment, HED had concluded that a subchronic inhalation 

study was required, and an additional 10X FQPA factor was retained as a database uncertainty 

factor, which raised the level of concern (LOC) to 1000 for inhalation scenarios. Therefore, the 

risk estimates were expressed using an aggregate risk index (ARI) in this most recent 2012 

assessment (D394322, E. Holman, 04/20/2012). However, this conclusion was reevaluated 

based on a request from the registrant, and HED has now concluded that this study is not 

required (TXR 0056556, K.Rury, 02/20/2013). Therefore, the risk estimates presented below in 

Table 6 utilize the combined MOE approach, with these risks not being of concern as indicated 

above. 

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 Combined

MOE

Adult Handler

Mattress Treatment - Dermal 0.00088 11,000 3,600

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 430 430

Inhalation– Crack & Crevice 0.000018 560,000

Dermal - Mattress Treatment 0.00015 66,000

Child Postapplication

Dermal – Crack & Crevice 0.0333 300 220
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Table 6. Combined Residential Exposure and Risk Estimates from the Indoor Crack and Crevice and Bed Bug 

Mattress Use1

Inhalation – Crack & Crevice 0.000046 220,000

Dermal - Mattress Treatment 0.000323 31,000

Hand-To-Mouth 0.011 900 1 Table and all values taken from D383325, M. Collantes, 22 July 2011. 2 MOE = NOAEL (10 mg/kg/day) / Daily Dose.

6.2 Spray Drift

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

This is particularly the case with aerial applications allowed on acetamiprid labels, but, to a 

lesser extent, could also be a potential source of exposure from ground application methods

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 post-application inhalation exposure assessment was not 

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

exposure assessment was performed for flaggers. This exposure scenario is representative of a 

worse case inhalation (drift) exposure and may be considered protective of most outdoor 

agricultural and commercial post-application inhalation exposure scenarios. 

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.
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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); in addition, dietary exposure is possible 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. The toxicological endpoints, points of 

departure, and level of concern are the same across oral, dermal, and inhalation routes of 

exposure for acetamiprid; therefore, aggregate risk can be estimated by combining the various 

exposure estimates and comparing the resulting aggregate exposure estimates (Table 7.2) against 

the short- and intermediate-term point of departure. 

All aggregate MOEs are greater than 100 and indicate that risks are not of concern. It is noted 

that the chronic dietary exposure estimates are highly conservative, assuming tolerance-level 

residues and 100% crop treated for all commodities. Therefore, HED also considers the 

aggregate MOEs to be conservative estimates, with the actual exposures likely being much lower 

than those characterized here. 

Table 7.2. Short- and Intermediate-Term Aggregate Risk Estimates for Acetamiprid.

Population NOAEL 

mg/kg/day LOC1 Average Food and Water 

Exposure mg/kg/day2

Residential 

Exposure 

mg/kg/day3

Aggregate 

Exposure 

mg/kg/day4

Aggregate 

MOE5

Adult 10 100 0.007152 0.023368 0.030520 330

Child 10 100 0.042610 0.044669 0.087279 120 1 The LOC is based on the standard inter- and intra- species uncertainty factors totaling 100. 2 From Section 5. Adult = 50+ years group (maximum exposure). Child = Children 1-2 years. 3 Combined residential exposure estimate from Section 6.

4 Aggregate Exposure = Avg Food and Water Exposure + Residential Exposure 5 Aggregate MOE = NOAEL ÷ Aggregate Exposure. Values rounded to two significant figures.

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 
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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 sweet corn. 

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.

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. This assessment was originally conducted for proposed new 

uses on sweet corn, turnip greens, and asparagus; the new uses on turnip greens and asparagus 

were approved under an earlier risk assessment (D394322, E. Holman, 04/19/2012). 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 a combined MOE since the endpoints were the same (i.e., the same toxic effects) with 

the same level 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. 

Use of acetamiprid on assessed crops resulted in combined MOEs greater than 100 (Table 9.1) 

and are not of concern. It is noted that the mixing/loading scenario for aerial application of the 

WP formulation yields an MOE of 280 with baseline PPE. Although this MOE is above the

LOC of 100, in the absence of a subchronic inhalation study a PF5 respirator is required to obtain 

an MOE greater than 1000. HED recommends that appropriate risk mitigation, such as the 

addition of a respirator, be added to the WP label for this application scenario. 
Acetamiprid Human Health Risk Assessment DP No. D410182

Page 22 of 33

Table 9.1. Occupational Exposure and Risk Estimates for Handlers From Use of Acetamiprid.

Exposure Scenario Crop or 

Target1

Mitigation 

Level 2

Max. Single 

Appl.

Rate

(lb ai/A)

Area

Treated 

(Acres)

Dermal

UE 

(μg/lb ai)

Dermal Dose

(mg/kg/day) 3

Inhalation

UE

(μg/lb ai)

Inhalation 

Dose

(mg/kg/day) 4

Total Dose

(mg/kg/day) 5 Total MOE 6

Mixer/Loader

1. WP (assessed for 

highest acreage using 

aerial equipment)

All crops B + G

0.1 350

170

(PHED) 0.00992 43.4

(PHED) 0.02532 0.03523 280

2. DF assessed for 

highest acreage using 

aerial equipment) (DF 

surrogate for SG)

All crops B + G 51.6 

(AHETF) 0.00301 8.96

(AHETF) 0.00523 0.00824 1,200

Applicator 

3. Aerial spray with 

fixed wing aircraft (DF 

surrogate for SG)

All crops Encl. 

Cockpit 0.1

350 5.0

(PHED) 0.00029 0.068

(PHED) 0.00004 0.00033 30,000

4. Groundboom 

sprayer All crops B + G, Open Cab 80 16.1(AHETF) 0.00021 0.34(AHETF) 0.00005 0.00026 38,000

Flagger 

5. Flagger All crops B + G 0.1 350 12

(PHED) 0.00070 0.35(PHED) 0.0002 0.0009 11,000

Abbreviations used: B = baseline PPE, G = gloves, MOE = margin of exposure, PPE = personal protective equipment, UE = unit exposure. 

1. All crops (asparagus, sweet corn, and turnip greens) have the same use pattern. Therefore, sweet corn was selected as a representative crop because it is the 

crop with the highest acreage treated. 

2. Baseline PPE includes long-sleeved shirt, long pants and shoes with socks. Label recommended PPE is baseline plus chemical resistant gloves.

3. Dermal Dose (mg/kg/day) = [Appl. Rate (lb ai/A) * Acres Treated/Day * Dermal Unit Exposure (μg/lb ai handled/day /1000) * Dermal Absorption Factor 

(10%)] / Body wt (60 kg).

4. Inhalation Dose (mg/kg/day) = [Appl. Rate (lb ai/A) * Acres Treated/Day * Inhalation Unit Exposure (μg/lb ai handled/day /1000)] / Body wt (60 kg).

5. Total Dose is the total exposure from dermal and inhalation routes for the day. Total Dose (mg/kg/day) = Dermal Dose + Inhalation Dose.

6. Short-term Total MOE = Short-term NOAEL (10 mg/kg/day) / Total Dose (mg/kg/day). Intermediate-term MOEs were not assessed separately, since the 

same endpoint/study and dose were selected to assess both short-term and intermediate-term durations. The short-term MOEs are protective of risks associated 

with intermediate-term durations of exposure.
Acetamiprid Human Health Risk Assessment DP No. D410182

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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 post-application exposure study for a 

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

corn. Therefore, dermal exposures during post-application 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 post-application dermal MOEs of 190 to 1,800 and are not of concern 

(Table 9.2). The lowest MOE of 190 was associated with detasseling sweet corn and harvesting 

it by hand.

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 post-application 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 post-
Acetamiprid Human Health Risk Assessment DP No. D410182

Page 24 of 33

application inhalation exposure to individuals performing post-application activities in 

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

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

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

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

post-application inhalation exposure into the Agency's risk assessments. If new policies or 

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

post-application inhalation exposure assessment for acetamiprid.

Although a quantitative occupational post-application 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 post-application 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. D394322. 19 April 2012. Acetamiprid: Human Health Risk Assessment for New 

Uses on Asparagus; Brassica, Leafy Greens, Subgroup 5B, and Turnip Greens; and Sweet 
Acetamiprid Human Health Risk Assessment DP No. D410182

Page 25 of 33

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

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 

Fruiting Vegetables.

E. Holman. D409726. 7 March 2013. Acetamiprid Acute and Chronic Dietary Exposure and 

Risk Assessment – Use on Sweet Corn and Increased Citrus (Crop Group 10-10) Tolerance.

E. Holman. D409727. 7 March 2013. Acetamiprid. Petition for the Establishment of 

Permanent Tolerances and Registration for Use on Sweet Corn. Summary of Analytical 

Chemistry and Residue Data.

E. Holman. D407373. 7 February 2013. Acetamiprid. HED’s Response to Comments on the 

Human Health Assessment Scoping Document in Support of Registration Review.

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. D410182

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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

No

Yes

Yes

Yes

--

--

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. D410182

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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. D410182

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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. D410182

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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. D410182

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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. D410182

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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. D410182

Page 32 of 33

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. D410182

Page 33 of 33

Appendix B1.

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-Hexane6.54 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)

UV/Visible Absorption Spectrum Not available 1

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