Page 3 of 29

In conjunction with HED’s conclusion that the 21/28 day inhalation study is required to support 

registration review, HED retained the 10X uncertainty factor for the inhalation route of exposure 

in its most recent new use risk assessment. (E. Holman et al., 04/19/2012). During registration 

review, the endpoints, doses, and safety factors used in the most recent human health risk 

assessments should be reconsidered based on current HED policy, as well as any new data 

received.

The current endpoint selection for acute dietary and short-and intermediate term incidental oral, 

dermal, and inhalation assessments are based on the point of departure (POD) and endpoints (i.e., 

body weight changes, decreased pup survival, and decreased startle response) from the 

developmental neurotoxicity study in rats. Chronic dietary and long-term dermal and inhalation 

assessments are based on the body weight changes and liver effects (hepatocellular vacuolation)

observed in the combined chronic/carcinogenicity study in rats. 

The dietary exposure database is adequate to support the registration review of acetamiprid. 

However, if the acute and chronic dietary endpoints change, an updated dietary risk assessment 

may be needed. Any updated dietary assessment would include any updated drinking water 

estimates. Currently, there are no dietary risk estimates of concern for the existing uses of 

acetamiprid. 

The residential exposure database is adequate to support registration review for acetamiprid. All 

of the residential handler and postapplication risk estimates are below the Agency’s level of 

concern. An updated residential exposure assessment may be needed during registration review 

as a result of the revisions to HED’s Residential Exposure Standard Operating Procedures 

(SOPs). Furthermore, because of the potential for residential bystander exposure to acetamiprid

from aerial and airblast applications, volatilization, and/or transport from treated areas (drift), 

HED will evaluate the need for a bystander assessment during registration review.

For acetamiprid, residential exposures are aggregated with dietary exposures. In the most recent 

human health risk assessment, there were no aggregate risk estimates of concern (Memo, 

D394322, E. Holman et al., 04/19/2012). During registration review, updated aggregate risk 

assessments may be needed. 

The occupational exposure database is adequate to support registration review for acetamiprid. 

There are no occupational handler and postapplication risk estimates of concern. Although no 

chemical-specific dislodgeable foliar residue (DFR) data are available, these data are not 

required for the current uses based on weight of evidence considerations. This conclusion may 

change if new uses and/or higher application rates are proposed. HED will consider the need for 

an updated occupational exposure assessment during registration review, pending the receipt of 

the inhalation toxicity study; until the data from that study are reviewed, and regulatory 

determinations based on that review are implemented, interim mitigation may be needed to 

ensure inhalation exposures are not of concern. These interim mitigation measures will need to 

be considered particularly for handlers mixing/loading acetamiprid formulations for aerial 

application, or multiple activities workers conducting seed treatments, as these scenarios are 

where inhalation exposure is anticipated to be greatest.
Page 4 of 29

Introduction

HED evaluated the most recent human health risk assessments for acetamiprid in association 

with the available toxicity, exposure, and usage information to determine if sufficient data are 

available and if further updates are needed to support registration review. Recent human health 

risk assessments include a 2012 assessment for the use of acetamiprid on asparagus, leafy greens, 

turnip greens, and sweet corn (Memo, D394322, E. Holman et al., 04/19/2012) and the 2011 

assessment for the use of acetamiprid in food handling establishments and on soybean (Memo, 

D385260, M. Doherty et al., 11/30/2011). In addition, HED considered the latest Agency 

science policies and risk assessment methodologies. 

The structure of acetamiprid, as well as the chemical names and other identifiers can be found in 

the chemical identity table attached to this document (Attachment 1).

Acetamiprid is registered for use on a wide variety of crops, and permanent tolerances have been 

established (40 CFR §180.578) ranging from 0.01 ppm to 50 ppm in plant commodities and from 

0.010 ppm to 0.20 ppm in livestock commodities. These tolerances are summarized in 

Attachment 2, along with International Residue Limits. Acceptable analytical methods are 

available to enforce tolerances for residues of acetamiprid in plant and livestock commodities.

The registered formulations, active ingredient levels, use sites, application methods, and uses that 

were evaluated in previous assessments are summarized in Attachment 3.

Hazard Identification/Toxicology

The toxicology database for acetamiprid is mostly complete, with the exception of a 28 day 

subchronic inhalation toxicity study, 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. 

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 were 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.

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, 
Page 5 of 29

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.

No effects were observed in the 21-day dermal study in the rabbit. 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, for more recent assessments, HED determined that a refined dermal 

penetration value for acetamiprid of 10% is reasonable and protective after reexamining the 

acetamiprid dermal penetration study and reviewing the dermal penetration information for 

several other neonicotinoid insecticides. No inhalation toxicity studies were conducted. 

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

fetuses to in utero exposure in the developmental studies. However, increased qualitative 

susceptibility was observed in a 2-generation reproduction study and a developmental 

neurotoxicity, both in rats. In the reproduction study, decreased body weight, body weight gain, 

and food consumption were observed in parental animals while significant reductions in pup 

weights were seen in the offspring in both generations. Also observed were reduction in litter 

size, and viability and weaning indices among F2 offspring as well as significant delays in the 

age to attain vaginal opening and preputial separation. In the 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 pre-weaning survival (post-natal days 

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

Despite the increase in qualitative susceptibility observed in rats, HED recommended that 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. 

However, in the absence of the required inhalation toxicity study, HED recommended that the 

10X FQPA factor be retained as a database uncertainty factor for assessing exposure and risk via 

the inhalation route.
Page 6 of 29

Acetamiprid is classified as “not likely to be carcinogenic to humans.” The classification is 

based on (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.

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.

In the most recent human health risk assessment for acetamiprid (E. Holman, D394322), the 

endpoint selection for acute dietary, short-and intermediate term incidental oral, dermal, and 

inhalation assessments are based on the POD and endpoints from the developmental 

neurotoxicity study in rats. Chronic dietary and long-term dermal and inhalation assessments are 

based on the body weight changes and liver effects (hepatocellular vacuolation) observed in the 

combined chronic/carcinogenicity study in rats. 

Conclusions for Hazard Identification/Toxicology

The toxicology database for acetamiprid is mostly complete. However, a 28 day inhalation 

toxicity study is not available. This study is required based on weight of evidence 

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

via the inhalation route. This data gap was identified in a recent new use registration risk 

assessment (Memo, D394322, E. Holman et al., 04/19/2012). There is uncertainty about 

potential portal of entry effects occurring via the inhalation route of exposure. Therefore, in the 

absence of the study, HED has retained the 10X FQPA factor as a database uncertainty factor for

the inhalation route of exposure only, pending submission of the required study. The selected 

toxicological endpoints from the most recent human health risk assessment are summarized in 

Attachment 4. 

During registration review, the endpoints, doses, and safety factors used in the most recent 

human health risk assessments should be reconsidered based on current HED policy, as well as 

any new data received. 

Dietary Exposure

As stated above, acetamiprid is registered for use on a wide variety of crops, and permanent 

tolerances have been established (40 CFR §180.578) ranging from 0.01 ppm to 50 ppm in plant 

commodities and from 0.010 ppm to 0.20 ppm in livestock commodities. The residue definition 

for risk assessment and tolerance enforcement is the parent compound for plant commodities, 

and combined residues of the parent compound and Metabolite IM-2-1 for livestock 

commodities (plus Metabolite IM-2-1-amide in ruminant muscle for risk assessment purposes 
Page 7 of 29

only). Acceptable analytical methods are available to enforce tolerances for residues of 

acetamiprid in plant and livestock commodities.

HED used the Dietary Exposure Evaluation Model (DEEM-FCIDTM Version 2.03) to conduct the 

most recent acute and chronic aggregate dietary (food and drinking water) risk assessments for

acetamiprid. This model incorporates consumption data from the USDA’s Continuing Survey of 

Food Intakes by Individuals taken between 1994 and 1996 along with a supplemental children’s 

survey taken in 1998. Both the acute and chronic analyses are based on tolerance-level residues, 

assume 100% crop treated, and utilize both empirical and default processing factors. In order to 

estimate food handling establishment residues in the chronic analysis, a residue value of 0.01 

ppm has been used for all food forms not already accounted for by existing/proposed uses. Note 

that per HED policy, residue estimates associated with the food-handling establishment uses are 

not included in the acute dietary assessment.

The most recent acute dietary exposure resulted in an estimated risk equivalent to 21% of the 

aPAD (acute population adjusted dose) for the general U.S. population at the 95

th percentile of 

exposure. The most highly exposed population subgroup was Children 1-2 years old, which used

52% of the aPAD at the 95

th percentile of exposure. Chronic dietary exposure to acetamiprid 

resulted in an estimated risk equivalent to 10% of the cPAD (chronic population adjusted dose) 

for the general U.S. population. The most highly exposed population subgroup was Children 1-

2, which used 33% of the cPAD. 

EFED recommended that modeled estimates of residues in drinking water be used in the most 

recent dietary risk assessment. During registration review, HED will evaluate whether updated 

drinking water estimates are available and whether these revised estimates make it necessary to 

complete a new dietary assessment. Depending on the magnitude of any updates, a new dietary 

assessment may be required to appropriately estimate risks associated with drinking water 

exposure. 

Conclusions for Dietary Exposure

The dietary exposure database is adequate to support the existing registrations and tolerances. 

No new residue chemistry data are required. However, a new dietary assessment may be needed 

if one or more of the following occur: new data are identified which impact dietary exposure 

estimates, including those from drinking water; new toxicological points of departure are 

identified, including revisions to the FQPA SF; Office of Pesticide Programs (OPP) dietary 

exposure policies and procedures are revised. HED is in the process of updating its dietary 

model to incorporate more recent consumption data from the National Health and Nutrition 

Examination Survey (NHANES). The newer version of the model will be used during 

registration review if a new dietary assessment is needed. 

Residential Exposure

Acetamiprid is registered for controlling a number of indoor and outdoor household and 

ornamental insect pests in residential settings, but there are no registered turf uses. Some of the 

acetamiprid products are formulated, packaged, and registered for use by homeowners and they 
Page 8 of 29

include baits and bait stations, WSP, ECs, and ready-to-use (RTU) sprays. The most recent 

residential exposure assessments also included structural insect control products that are 

designed for use by commercial and professional applicators. Unless these products are labeled 

for “Restricted Use Only” they are assumed to be available for purchase and use by homeowners,

resulting in residential handler exposures. The recommended application equipment for 

household and commercial labels includes hose-end sprayers, manually pressurized handwands, 

and either pump or electric hand-held sprayers. The cockroach baits and fly strips are applied by 

hand, but very little homeowner exposure is expected due to lack of dermal contact and vapor 

generation. Acetamiprid uses in both indoor and outdoor areas result in short- (1-30 days) and 

intermediate-term (1-6 months) exposures for residential handlers. For handler exposure via the 

dermal route, and postapplication exposure via the dermal and oral routes, HED’s level of 

concern (LOC) is 100, and therefore if the estimated margin of exposure (MOE) is ≥100, the risk 

is not of concern. However, for inhalation exposures, an additional 10X factor was retained for 

the missing inhalation toxicity study, and therefore the LOC for inhalation exposure is an MOE 

of 1000.

Residential Handler Exposure

Most of the residential uses of acetamiprid have been evaluated for residential handler exposures 

(Attachment 3). There were no risks of concern identified for the assessed residential handler 

scenarios. Some scenarios corresponding to registered uses of acetamiprid have not been 

assessed quantitatively at this time for residential handler risks--these scenarios are either similar 

to scenarios assessed previously that did not show risks of concern or they represent potentially 

lower exposures; we consider the risks associated with these scenarios not to be of concern. 

During registration review, HED will reassess representative residential handler scenarios, taking 

into account any new information such as revised toxicological endpoints and uncertainty factors 

for risk assessment. 

Recently, HED has updated the Residential Standard Operating Occupational Pesticide Handler 

Unit Exposure (OPHED) Surrogate Data (June 21, 2011) and Human Body weight Data; 

therefore, new assessments may be required during registration review to update the risk 

estimates.

Residential Postapplication Exposure

Use of structural insect control products containing acetamiprid in indoor and outdoor settings by 

homeowners and professional applicators results in short- and intermediate-term postapplication 

dermal and inhalation exposure to adults and children, and incidental oral exposure to children.

No postapplication dermal exposure to acetamiprid is anticipated for either adults or children 

following the use of cockroach/ant baits and fly strips in homes, due to the way these products 

are packaged and applied. Use of acetamiprid as crack and crevice, mattress, and outdoor 

perimeter treatments results in estimated dermal MOEs of ≥300 for adults and children, and 

incidental oral MOEs ≥900 for children; since all assessed dermal and oral postapplication 

scenarios resulted in MOEs greater than the LOC of 100, the risk estimates are not of concern. 
Page 9 of 29

Postapplication inhalation exposure to adults and children may occur by breathing indoor air 

after surface and crack and crevice treatments with acetamiprid sprays. Pesticide vapor may be 

produced from surface applications and by vaporization of the active ingredient. A Tier 1 (Air 

Saturation Concentration) analysis of the indoor uses indicated that the exposure and risk 

resulted in MOEs significantly greater than 100 (the inhalation LOC at the time) and were 

therefore not of concern (M. Collantes, D383325, 7/22/2011). In addition, HED recently 

updated the exposure and risk estimates via the inhalation route; relative to the new LOC of 1000 

for inhalation exposure, the risks were not of concern (MOEs ≥ 1000).

Residential bystander exposures to acetamiprid may result from the off-site transport of spray 

droplets applied to agricultural sites and for public health insect control. Pesticide drift to nearby 

residential areas may be more typically associated with aerial applications, but it could also be a 

potential source of exposure from ground-based applications of 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 may require specific mitigation measures to address pesticide drift. Other potential 

sources of residential bystander postapplication exposure include volatilization of pesticides and 

re-suspension of dusts and/or particulates that contain pesticides.

Although a quantitative residential bystander postapplication inhalation exposure assessment was 

not performed for pesticide drift from treated agricultural fields, an inhalation exposure 

assessment was performed for flaggers who assist in aerial applications of acetamiprid at 0.039 

lb ai/A on soybean fields resulted in an MOE of 8,800 (not of concern based on the LOC of 1000 

for inhalation exposure). The flagger scenario is considered to be representative of a worst case 

inhalation (drift) exposure (S. Oonnithan, D389062, 11/16/2011), thus all other inhalation drift 

exposures are not considered to pose risks of concern.

Combined Residential Exposure 

HED combines residential handler and postapplication exposures for adults, and combines 

postapplication exposures for children, resulting from residential exposure scenarios when it is 

likely they can occur simultaneously based on the use-pattern and the behavior associated with 

the exposed population. Such an analysis performed for all residential uses of acetamiprid 

indicated combined postapplication MOEs of 430 for adults and 220 for children. The combined 

MOEs are greater than 100, so these combined exposures are not considered to be of concern (M. 

Collantes, D383325, 7/22, 2011). Dermal, oral, and inhalation risks for short-term exposures 

were combined in the most recent risk assessment, since the toxicological endpoints were the 

same for the relevant routes of exposure (Memo, D394322, E. Holman et al., 04/19/2012). 

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 were combined using the 

aggregate risk index (ARI) approach. In HED’s most recent risk assessment, residential

exposure and risk were recalculated using the ARI) approach to account for the new LOC of 

1000 for inhalation exposures, and there were no combined risks of concern (i.e., ARI>1).
Page 10 of 29

Conclusions for Residential Exposure

All residential handler (adults) and postapplication exposure scenarios (children and adults) 

resulted in dermal and oral MOEs greater than the LOC of 100 and are not of concern. Even 

when the revised LOC of 1000 is considered for the inhalation route of exposure, there are no 

risks of concern identified. For these assessments, HED used default assumptions from the 

Residential Standard Operating Procedures (SOP), April 5, 2000. However, as a result of the 

recent revisions made to HED’s Residential SOPs, the parameters and algorithms for dermal, 

inhalation, and oral exposure calculations will likely change. These changes could result in a 

different residential handler/postapplication exposure estimates and therefore, during registration 

review, HED may conduct a new residential exposure assessment that incorporates any potential 

new methods or policies for estimating exposure associated with residential use patterns. 

Furthermore, residential bystander exposures might occur as a result of aerial application if 

acetamiprid, volatilization of active ingredient from treated surfaces, and/or transport from 

treated areas. HED will evaluate the need for a bystander assessment during registration review. 

Additionally, refinements to residential inhalation exposure assessments may be required during 

registration review when the 28-day inhalation study is submitted per the Hazard and Science 

Policy Council (HASPOC) recommendations and a route endpoint and dose are selected.

Aggregate Risk Assessment

In the most recent risk assessment (Memo, D394322, E. Holman, 04/19/2012), aggregate risk 

assessments for acetamiprid exposures were conducted as follows: acute and chronic aggregate 

assessments were conducted based on food and water exposures, and short-term aggregate 

assessments were conducted based on food, water, and residential exposures. No long-term 

aggregate risk assessment was conducted because no long-term exposure scenarios are expected 

from residential uses of acetamiprid. There were no aggregate risk estimates of concern

associated with the existing uses.

Conclusions for Aggregate Assessment

During registration review, updated aggregate assessments may be conducted to include changes 

in toxicological endpoints, updated dietary exposure estimates, and updated residential exposure 

estimates. However, these updates may occur in conjunction with new use risk assessments, and 

therefore would not be needed during registration review.

Occupational Exposure and Risk

Section 3 and Section 24(c) registrations of acetamiprid are listed in Attachment 3. These 

formulations may be applied using aerial, groundboom, airblast, and handheld spray equipment. 

For seed treatment, on-farm and commercial treatment methods may be used. The personal 

protective equipment (PPE) required for handlers and is single layer clothing (long sleeve shirt, 

long pants, and socks plus shoes) and chemical resistant gloves. For seed treatment, PPE 

consists of single layer clothing, chemical resistant gloves and dust/mist respirator. The

restricted entry interval (REI) for acetamiprid formulations is 12 hours.
Page 11 of 29

The agricultural, ornamental, and structural pest control uses of acetamiprid result in short-term 

(1 - 30 days) and intermediate-term (1 - 6 months) occupational exposures. For evaluating 

occupational handler and postapplication risks resulting from use of acetamiprid, the Health 

Effects Division (HED) has set a level of concern (LOC) of 100 for the dermal route and 1000 

for the inhalation route; when estimated MOEs exceed these LOCs for the respective routes of 

exposure, the MOEs are not of concern (i.e., ≥100 for dermal and ≥1000 for inhalation).

Occupational Handler Exposure

The registrant has not submitted chemical-specific exposure data to estimate handler exposures. 

In the absence of chemical-specific data, it is HED policy to use the best available data to assess 

handler exposures. Sources of such generic (surrogate) handler data include Pesticide Handlers 

Exposure Database Version 1.1 (PHED 1.1), and the Agricultural Handler Exposure Task Force 

(AHETF) database, or other registrant-submitted occupational exposure studies. Some of these 

data are proprietary (e.g., AHETF data), and subject to the data protection provisions of Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA). Default assumptions established by the 

HED's Exposure Science Advisory Council for Exposure (ExpoSAC) were used for parameters 

such as body weight, acres treated per day and amount of active ingredient handled per day. 

Most of the handler exposures resulting from agricultural, structural, and seed treatment uses of 

acetamiprid have been evaluated (Attachment 3). All the estimated dermal risks resulted in 

MOEs greater than 100 either at baseline (single layer clothing) or with additional PPE (i.e., 

gloves and/or dust-mist respirator or engineering controls). For exposure scenarios that have not 

previously been assessed, they are believed to be similar to those already assessed and therefore 

are not likely to pose risks of concern; these exposure scenarios will be considered during 

registration review as appropriate. 

However, an additional 10x database uncertainty factor has been retained for inhalation risk 

assessments (only) due to the absence of an inhalation toxicity study, as recommended by the 

HASPOC (TXR 52354, 3/15/2012). Therefore, for inhalation exposure the LOC is an MOE of 

1000; based on the previous assessments for use of acetamiprid in aerial applications to stone 

fruits and seed treatment of canola and mustard, additional inhalation mitigation measures may 

be needed, including additional PPE or reduced application rates.

A few new formulations and/or new uses may have been registered without occupational 

exposure assessment and these will be assessed during registration review. A quick evaluation 

of these previously unassessed scenarios indicate that previously completed assessments would 

be protective because the uses to be assessed either have lower application rates and/or 

formulations types that have lower exposure potential. HED has also updated the Occupational 

Pesticide Handler Unit Exposure (OPHED) Database (June 21, 2011) resulting in small 

variations in MOEs from those previously estimated, and HED will consider the need for 

reassessing these scenarios during registration review.

Occupational Postapplication Exposure
Page 12 of 29

Use of acetamiprid on agricultural crops, for seed treatment, and for structural insect control 

results in potential postapplication dermal and inhalation exposures to workers when they enter 

treated areas to perform crop/site specific post-treatment activities. The registrant did not submit 

a chemical specific postapplication exposure study for a quantitative evaluation of risks resulting 

from use of registered acetamiprid products. 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 nonproprietary data. All the estimated dermal risks for agricultural and commercial postapplication 

scenarios are not of concern if workers enter treated areas after the REI period of 12 hours has 

expired. HED is not requesting a chemical-specific dislodgeable foliar residue (DFR) study for 

acetamiprid at this time because of the following: 1) No toxicity was observed up to the limit 

dose tested in the acetamiprid dermal toxicity study; 2) The dermal toxicity endpoint has been 

conservatively estimated using results from the oral developmental neurotoxicity study; 3) A 

dermal absorption factor has been derived using a combination of chemical-specific data and 

data from structurally similar chemicals, but is still considered to provide an upper-bound 

estimate of absorption; 4) No risks of concern have been identified for postapplication exposures 

using these conservative assumptions. If the foliar application use pattern were to change prior 

to the preliminary risk assessment for registration review, including new uses and/or increased 

application rates, the registrant should consider submitting a DFR study.

A quantitative postapplication inhalation exposure assessment was not performed for acetamiprid 

based on the Agency's current practices. However, there are multiple potential sources of 

inhalation exposure to workers performing postapplication activities in previously treated fields. 

These potential sources include volatilization of pesticides and re-suspension of dusts and/or 

particulates that contain pesticides. The Agency sought expert advice and input on issues related 

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

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

March 2, 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 postapplication 

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 postapplication inhalation exposure assessment was not performed for 

acetamiprid, an inhalation exposure assessment was performed for occupational handlers. 

Exposure to mixers, loaders, applicators, and flaggers resulting from handling of pesticides for 

agricultural and structural pest control uses is likely to result in higher inhalation exposure than 

routine postapplication exposures encountered by workers. The assessment of occupational 

handler exposure results in MOEs greater than or equal to the LOC (MOEs ≥ 1000); these 

exposures are considered not to be of concern. Since inhalation postapplication exposures are 

expected to be lower than occupational handler inhalation exposures, we can infer that those

risks also are not of concern.
Page 13 of 29

Conclusions for Occupational Exposure and Risk

The registered uses of acetamiprid have been assessed for occupational handler and 

postapplication exposure scenarios using the 1998 version of PHED and 2004 version of Seed 

Treatment SOPs 14 and 15 (2004). All assessed handler exposure scenarios resulted in dermal 

MOEs greater than 100 either at baseline or with the additional PPE such as gloves or mitigation. 

All of the estimated dermal risks for postapplication scenarios are not of concern if workers enter 

treated area after the REI period of 12 hours. 

Inhalation exposure and risk estimates may be of concern for certain handler scenarios, including 

seed treatments, based on the inhalation MOE of 1000. The results of the requested inhalation 

toxicity study may impact these conclusions. The need for mitigation of these scenarios will be 

considered during registration review, and pending receipt of the new study. 

During registration review, revised occupational handler and postapplication assessments may be 

required if there are any new exposure scenarios or toxicological endpoints, or if the Agency 

receives new data that impact dermal or inhalation exposure estimates. In addition, updated 

occupational handler exposure assessments might be required based upon revisions to the 

Agency’s scenario-specific surrogate handler exposure data 

(http://www.epa.gov/pesticides/science/handler-exposure-table.pdf). Updated occupational 

postapplication exposure assessments might also be required under registration review based on 

revisions to the dermal transfer coefficients from the Science Advisory Council for Exposure 

Policy Number 3 (http://www.epa.gov/pesticides/science/ exposac_policy3.pdf). 

Public Health and Pesticide Epidemiology Data

D401173, S. Recore, May 3, 2012

For this evaluation, the OPP Incident Data System (IDS) was utilized to retrieve pesticide 

incident data on the active ingredient acetamiprid (PC Code 099050). Main IDS incidents 

involving only one pesticide are considered to provide more certain information about the 

potential effects of exposure from the pesticide. When an incident involves more than one 

pesticide, it is difficult to determine which effects are attributed to the pesticide being 

considered. The less severe human incidents (minor, unknown, or no effects outcomes) are

reported by registrants as counts called aggregate summaries and are recorded in a separate 

module called Aggregate IDS.

For the main IDS, from January 1, 2007 to February 22, 2012, there were 13 incidents reported 

involving for the single chemical only in the database and 10 more incidents reported that 

involved more than one chemical. All of the single chemical incidents were classified as 

moderate severity. Overall, there are few incidents involving acetamiprid reported to IDS. 

In Aggregate IDS, from January 1, 2007 to February 22, 2012, there were 79 reported incidents

involving acetamiprid. 
Page 14 of 29

Acetamiprid is not included in the Agricultural Health Survey (AHS), and therefore does not 

provide information for this report.

Based on the low frequency and generally low severity of incident cases reported for 

acetamiprid, there does not appear to be a concern at this time that would warrant further 

investigation. The Agency will continue to monitor the incident information and if a concern is 

triggered, additional analysis will be included in the risk assessment.

Tolerance Assessment and International Harmonization

As stated above, acetamiprid is registered for use on a wide variety of crops and permanent 

tolerances have been established (40 CFR §180.578) ranging from 0.01 ppm to 50 ppm in plant 

commodities and from 0.010 ppm to 0.20 ppm in livestock commodities. The residue definition 

for risk assessment and tolerance enforcement is the parent compound for plant commodities, 

and combined residues of the parent compound and Metabolite IM-2-1 for livestock 

commodities (plus Metabolite IM-2-1-amide in ruminant muscle for risk assessment purposes 

only). Acceptable analytical methods are available to enforce tolerances for residues of 

acetamiprid in plant and livestock commodities. The current tolerance definition for acetamiprid 

(40 CFR 180.578) is appropriate regarding scope and compliance. 

Codex has established maximum residue limits (MRLs) for acetamiprid, defined as the parent 

compound for plant commodities, and combined residues of the parent compound and 

Metabolite IM-2-1 for livestock commodities. 

For acetamiprid, Mexico adopts U.S. tolerances and/or Codex MRLs for its export purposes. 

Canada has established MRLs for acetamiprid, using the same residue definition as the U.S. and 

Codex. The Canadian MRLs are equivalent to the U.S. tolerances, with only a few exceptions. 

Specifically, Canadian MRLs are lower for bushberry subgroup 13-07B, grapes, and stone fruit, 

whereas they are higher for gooseberries and meat byproducts). For plant commodities, in most 

cases, the Codex MRLs generally differ from the Canadian and U.S. tolerances, with some 

values higher and some lower. For livestock commodities, the Codex MRLs are either equal or 

lower than the U.S. tolerances. 

The international residue limit status sheet can be found in Attachment 2. 

During registration review, HED will reconsider the U.S. tolerances and will harmonize them 

with Codex MRLs to the extent possible.

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 
Page 15 of 29

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.

Endocrine Disruptor Screening Program 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of acetamiprid’s most recent registration decision, EPA reviewed 

these data and selected the most sensitive endpoints for relevant risk assessment scenarios from 

the existing hazard database. However, as required by FFDCA section 408(p), acetamiprid is 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 
Page 16 of 29

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for acetamiprid. For further information 

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the 

test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/.

Cumulative Risk Assessments 

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/.

Human Studies

Past acetamiprid risk assessments rely in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. 

These data, which include studies from the Pesticide Handlers Exposure Database Version 1.1 

(PHED 1.1); the Outdoor Residential Exposure Task Force (ORETF) database; the Agricultural 

Re-entry Task Force (ARTF) database; and other registrant-submitted exposure monitoring 

studies, are subject to ethics review pursuant to 40 CFR 26, have received that review, and are 

compliant with applicable ethics requirements. For certain studies that review may have 

included review by the Human Studies Review Board. Descriptions of data sources as well as 

guidance on their use can be found at http://www.epa.gov/pesticides/science/handler-exposuredata.html and http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

Data Requirements

At this time, the Agency has identified only one data gap for information needed to conduct 

a comprehensive assessment of health risks:

Toxicology: 28 day inhalation Toxicity Study in Rats

References

Bangs, G., D283286, 10/15/2002: Response to Assessment of Handler Exposure Resulting From the Commercial 

Application of Acetamiprid to Canola and Mustard Seed.

Collantes, M., D264160, 3/11/2002: EPA and PMRA Joint Review of Occupational and Residential Exposure 

Assessment for Section 3 Registration of Acetamiprid on Cotton, Leafy Vegetables, Cole Crops, Fruiting 

Vegetables, Citrus Fruits, Pome Fruits, Grapes, and Canola and Mustard Seed Treatment.
Page 17 of 29

Figueroa, Z., D295704, 9/29/2004: Occupational and Residential Exposure Assessment for Proposed Section 3 

Registration for Use on Tobacco, Stone Fruits, Cucurbits, Tree Nuts, Tuberous and Corm Vegetables, Termiticide 

Perimeter Treatment and General Pest Control Uses.

Figueroa, Z., D304214, D310760, 2/17/2005: Occupational and Residential Exposure Assessment for Proposed 

Section 3 Registration for General Pest Control Uses.

Dow, M., D343132, 9/11/2007: Occupational Human Exposure/Risk Assessment for the Proposed Use of 

Acetamiprid for Commercial Treatment of Potato Seed Pieces.

Figueroa, Z., D345240 and D310760: 10/24/2007: Occupational/Residential Exposure Assessment for Proposed 

Use on Stone Fruits, Cucurbit Vegetables, Tree Nuts, Berries, Bulb Vegetables, Edible Podded Legumes and 

Succulent Shelled Peas and Beans and Insecticide/Termiticide Uses.

Figueroa, Z., D355774, 9/11/2008: Occupational/Residential Exposure Assessment for Proposed Use on 

Ornamentals and Vegetable Transplants (leafy and fruiting vegetables, cole crops, cucurbits, onions and other bulbs.

Figueroa, Z., D353040, 12/1/2008: Occupational/Residential Exposure Assessment for Proposed Use on 

Indoor/Outdoor Household Pest Control.

Wang, S-C., D35709, 12/27/2008: Occupational/Residential Exposure Assessment for Amendment of Acetamiprid 

Use to Include Basal Bark Treatment and Direct Injection on Trees. 

Oonnithan, S., D36670, 10/9/2009: Occupational and Residential Exposure Assessment for the New Uses on 

Clover Grown for Seeds and Tomatoes Grown in Greenhouses and for Increasing the Application Rate on Grapes. 

Collantes, M., D383325, 7/22/2011: Occupational/Residential Exposure Assessment for Use to Control Bed Bugs.

Oonnithan, S., D389062 and D389097, 11/16/2011: Occupational and Residential Exposure Assessment for the 

New Uses in Food/Feed Handling Establishments and on Soybeans.

Oonnithan, S., D 395470, 2/15/2012. Occupational and Residential Exposure Assessment for the Proposed New 

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

Rury, K., TXR 52354, 3/15/2012. Summary of Hazard and Science Policy Council (HASPOC) Meeting: 

Recommendation on the need for a 28-day inhalation study. 

Holman, E. D394322, 04/19/2012. 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. 

Attachments

Attachment 1. Chemical Identity Table

Attachment 2. International Residue Limit Status

Attachment 3. Acetamiprid Products and Use Sites

Attachment 4. Acetamiprid Endpoint Selection Tables
Page 18 of 29

Attachment 1. Chemical Identity Table

Chemical Identity

Common Name Acetamiprid

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

2

-cyano-N 1-methylacetamidine

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

PC Codes 099050

Chemical Abstracts Numbers 135410-20-7

Registration Review Case No. 7617

Chemical Class neonicotinoid

Vapor Pressure 7.5 x 10-9

(at 25 C)

Chemical Structure (Acetamiprid)

Chemical Structure of 

Acetamiprid Metabolite 

IM-2-1

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

2

-cyano-acetamidine

Chemical Structure of 

Acetamiprid Metabolite 

IM-2-1-amide 

(also referred to as IM-2-2)

N

2

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

N N

H

Cl

CH3

N

O

NH2

N N

H

C

l

CH3

N

CN

N N

CH3

C

l

CH3

N

CN
Page 19 of 29

Attachment 2. International Residue Limit (IRL) Status

Acetamiprid (PC Code 099050)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3,4

Plant: acetamiprid (1 E )-

N -[(6-chloro-3-

pyridinyl)methyl]- N' -

cyano- N –

methylethanimidamide

Livestock: acetamiprid and 

(1 E )- N -[(6-chloro-3-

pyridinyl)methyl]- N' -

cyano- N -ethanimidamide 

Plant: (E)-N-[(6-chloro-3-

pyridinyl)methyl]-N'-cyano-Nmethylethanimidamide

Livestock:(E)-N-[(6-chloro-3-

pyridinyl)methyl]-N'-cyano-Nmethylethanimidamide, including the 

metabolite (E)-N-[(6-chloro-3-

pyridinyl)methyl]-N'-

cyanoethanimidamide

Plant: Acetamiprid. 

Livestock:

Sum of acetamiprid 

and its desmethyl 

(IM-2-1) metabolite, 

expressed as 

acetamiprid. The 

residue is not fatsoluble.

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

US Canada Mexico1 Codex2

Almond, hulls 5.0

Berry, low growing 

subgroups 13–07G

0.60 0.6 lowbush blueberries, 

lingonberries

2 berries and other 

small fruits (except 

grapes and 

strawberries)

0.5 strawberry 

Bushberry subgroup 13–

07B

1.6 0.6 aronia berries, buffalo 

currants, Chilean guavas, 

currants, elderberries, European 

barberries, gooseberries, 

highbush blueberries highbush 

cranberries honeysuckle, 

huckleberries, jostaberries, 

lingonberries, lowbush 

blueberries, native currants, 

salal berries, saskatoon berries 

(juneberries), sea buckthorn

2 berries and other 

small fruits (except 

grapes and 

strawberries)

Caneberry subgroup 13–

07A

1.6 2 berries and other 

small fruits (except 

grapes and 

strawberries)

Canola, seed 0.010 0.01 rapeseeds (canola)

Citrus, dried pulp 1.20 1.2 dried citrus fruit pulp

Cotton, gin byproducts 20.0

Cotton, undelinted seed 0.60 0.6 0.7 cotton seed

Fruit, citrus, group 10 0.50 0.5 calamondin, citrus citron, 

citrus hybrids, grapefruits, 

kumquats, lemons, limes, 

oranges, pummelos, tangerines, 

Satsuma mandarins

0.8 citrus fruits
Page 20 of 29

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3,4

Fruit, pome, group 11 1.0 1.0 apples, Asian pears, 

crabapples, loquats, mayhaws, 

pears, quinces

0.8 pome fruits

Fruit, small, vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

0.35 0.6 gooseberries

0.2 grapes

2 berries and other 

small fruits (except 

grapes and 

strawberries)

0.5 grapes

Fruit, stone, group 12, 

except plum, prune

1.20 0.7 apricots, nectarines, 

peaches, sweet cherries, tart 

cherries

0.2 plumcots, plums, prune 

plums

1.5 cherries

0.7 nectarine

0.7 peach

0.2 plums (including 

prunes)

0.6 prunes

Grain, aspirated fractions 5.0

Mustard, seed 0.010 0.01

Nut, tree, group 14 0.10 0.06 tree nuts

Onion, bulb, subgroup 3–

07A

0.02 0.02 garlic, onion 

bulb

Onion, green, subgroup 3–

07B

4.5 5 spring onion

Pea and bean, succulent 

shelled, subgroup 6B

0.40 0.4 beans, except 

broad bean and soya 

bean

0.3 beans, shelled

0.3 peas, shelled 

(succulent seeds)

Pistachio 0.10 0.06 tree nuts

Plum, prune, dried 0.40 0.4 dried prune plums

Plum, prune, fresh 0.20 0.2 plumcots, plums, prune 

plums

0.2 plums (including 

prunes)

0.6 prunes

Soybean, hulls 0.04

Soybean, seed 0.03 0.3 beans, shelled

Tea, dried150.0

Tomato, paste 0.40 0.4 

Vegetable, brassica, leafy, 

group 5

1.20 1.2 bok choy Chinese cabbages, 

broccoli, broccoli raab, Brussels 

sprouts, cabbages, cauliflower, 

Chinese broccoli, Chinese 

mustard cabbages, collards, kale, 

kohlrabi, mustard greens, 

mustard spinach, napa Chinese 

cabbages, rape greens

0.7 cabbages, head

0.4 flowerhead 

brassicas (includes 

broccoli: broccoli, 

Chinese and 

cauliflower)

Vegetable, cucurbit, group 

9

0.50 0.2 fruiting 

vegetables, cucurbits 

(except sweet corn 

and mushrooms)
Page 21 of 29

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3,4

Vegetable, fruiting, group 

8

0.20 0.2 bell peppers, eggplants. 

ground cherries, non-bell 

peppers, pepinos, pepper 

hybrids, tomatillos, tomatoes

0.2 fruiting 

vegetables other than 

cucurbits

2 peppers chili, dried

Vegetable, leafy, except 

brassica, group 4

3.00 3.0 amaranth, arugula, cardoon, 

celery, celtuce, Chinese celery, 

corn salad, dandelion leaves, 

dock, edible leaved 

chrysanthemum, endives, fresh 

chervil leaves, fresh Florence 

fennel leaves and stalks, fresh 

parsley leaves, garden cress, 

garden pursiane , garland 

chrysanthemum, head lettuce, 

leaf lettuce, New Zealand 

spinach, orach leaves, radicchio, 

rhubarb, spinach, Swiss chard, 

upland cress, vine spinach, 

winter purslane

1.5 celery 

3 leafy vegetables 

(except spinach)

5 spinach

Vegetable, legume, edible 

podded, subgroup 6A

0.60 0.4 beans, except

broad bean and 

soyabean

0.3 beans, shelled

0.3 peas, shelled 

(succulent seeds)

Vegetable, tuberous and 

corm, group 1

0.01 0.01 potatoes

US [40 CFR 

§180.505(a)(2)]

Canada Mexico1 Codex2

Livestock: acetamiprid and 

(1 E )- N -[(6-chloro-3-

pyridinyl)methyl]- N' -

cyano- N -ethanimidamide 

in or on the following 

commodities.

Livestock/Daily commodities: (1E)-N-

[(6-chloro-3-pyridinyl)methyl]-N'-cyanoNmethylethanimidamide, including the 

metabolite

(1E)-N-[(6-chloro-3-pyridinyl)methyl]-

N'-

cyanoethanimidamide

Animal

commodities): sum 

of acetamiprid and 

its desmethyl (IM-2-

1) metabolite, 

expressed as 

acetamiprid. The 

residue is not fatsoluble.

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

US Canada Mexico2 Codex3

Cattle, fat 0.10 0. 1 fat of cattle 0.02 mammalian fats 

(except milk fats)

Cattle, meat 0.10 0. 1 meat of cattle 0.02 (fat) meat (from 

mammals other than 

marine mammals)

Cattle, meat byproducts 0.20 0.3 meat byproducts of cattle 0.05 edible offal 

(mammalian)

Egg 0.010 0.01 0.01

Goat, fat 0.10 0.1 fat of goats 0.02 mammalian fats 

(except milk fats)
Page 22 of 29

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3,4

Goat, meat 0.10 0.1 meat of goats 0.02 (fat) meat (from 

mammals other than 

marine mammals)

Goat, meat byproducts 0.20 0.3 meat byproducts of goats 0.05 edible offal 

(mammalian)

Hog, fat 0.10 0.1 fat of hogs 0.02 mammalian fats 

(except milk fats)

Hog, meat 0.10 0.1 meat of hogs 0.02 (fat) meat (from 

mammals other than 

marine mammals)

Hog, meat byproducts 0.20 0.3 meat byproducts of hogs 0.05 edible offal 

(mammalian)

Horse, fat 0.10 0.1 fat of horses 0.02 mammalian fats 

(except milk fats)

Horse, meat 0.10 0.1 meat of horses 0.02 (fat) meat (from 

mammals other than 

marine mammals)

Horse, meat byproducts 0.20 0.3 meat byproducts of horses 0.05 edible offal 

(mammalian)

Milk 0.10 0.1 0.02 milks

Poultry, fat 0.010 0.01 fat of poultry

Poultry, liver 0.050 0.05 (*) poultry 

edible offal

Poultry, meat 0.010 0.01 meat of poultry 0.01 (*) poultry meat

Sheep, fat 0.10 0.1 fat of sheep 0.02 mammalian fats 

(except milk fats)

Sheep, meat 0.10 0.1 meat of sheep 0.02 (fat) meat (from 

mammals other than 

marine mammals)

Sheep, meat byproducts 0.20 0.3 meat byproducts of sheep 0.05 edible offal 

(mammalian)

MRLs with no US equivalent

None None

Completed: : M. Negussie; 04/30/2012

1There are no U.S. registrations as of February 10, 2010, for the use of acetamiprid on dried tea.

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

3

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

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

fat portion of the sample. 

4 All Codex MRLs are proposed (have not been finalized by the CCPR and the CAC).

3) A tolerance of 0.01 ppm is established for residues of the insecticide acetamiprid, including its 

metabolites and degradates, in or on all food/feed items (other than those covered by a higher tolerance in 

paragraph (a)(1) or (a)(2) of this section as a result of the use on growing crops) as a result of the 

application of acetamiprid in food/feed handling establishments. Compliance with the 0.01 ppm tolerance 
Page 23 of 29

level is to be determined by measuring only acetamiprid (1 E )- N -[(6-chloro-3-pyridinyl)methyl]- N' -

cyano- N -methylethanimidamide in or on the commodities.

(c) Tolerances with regional registrations. Tolerances with regional registrations are established for 

residues of the insecticide acetamiprid (1 E )- N -[(6-chloro-3-pyridinyl)methyl]- N' -cyano- N -

methylethanimidamide, including its metabolites and degradates, in or on the commodities in the table 

below as a result of the application of acetamiprid. Compliance with the tolerance levels specified below 

is to be determined by measuring only acetamiprid in or on the following commodities.

Commodity Parts per million

Clover, forage 0.10

Clover, hay 0.01
Page 24 of 29

Attachment 3 – Acetamiprid Products and Use Sites

FIFRA Sec. 3 Registrations

Table 1. Use Patterns of Sec. 3 End-use Product Formulations of Acetamiprid Insecticide.

Registered

products & 

Formul. Types 

% AI Use Sites and 

Applicable ORE Reviews 

Application 

equipment Comments 

8033-20

Technical 99.5 NA NA

8033-21

Liquid, RTU 0.006

- flowers and ornamental and house plants, leafy 

vegetables, cole crops, fruiting vegetables, citrus 

and pome fruits (Collantes, D264160, 3/11/2002).

Battery operated 

hand sprayer

8033-22, WSP 70

- bedding-, foliage-, and potted flowering plants, 

and plants grown in greenhouses, flowers grown 

for cutting, ornamental trees, non-bearing fruit and 

nut trees (Collantes, D264160, 3/11/2002). 

Handwand, 

backpack, 

handgun

8033-23, WP 70

- stone fruits, cucurbits, tree nuts, strawberries and 

other low growing berries, blueberries and other 

bush berries, bulb vegetables, edible podded 

legumes and succulent shelled peas and beans 

(Figueroa, D345240 and D310760: 10/24/2007). 

- grapes & climbing vine small fruits and clover 

grown for seeds (Oonnithan, D36670, 10/9/2009).

- tuberous and corm vegetables, tobacco, stone 

fruits, cucurbits, tree nuts (Figueroa, D295704, 

9/29/2004).

- cotton, leafy vegetables, cole crops, fruiting 

vegetables, citrus, pome fruits, and grapes 

(Collantes, D264160, 3/11/2002).

- asparagus and turnip greens (Oonnithan, 

D395470,2/15/2012).

- canola and mustard (Collantes, D264160, 

3/11/2002 and Bangs, D283286, 10/15/2002).

Air, ground 

broadcast, 

airblast, 

chemigation

Seed treatment, 

commercial 

8

8033-24, DF 70 Cotton Air and ground 1

8033-25 WSP

8033-26 WSP 70 - termite and indoor/outdoor treatment (Figueroa, D295704, 9/29/2004).

Handwand, 

backpack, 

handgun

8033-28, -29,

-30, and -31

Bait

0.15 - indoor/outdoor of homes and other structures 

(Figueroa, D304214, D310760, 2/17/2005). By hand

8033-32, -33,

-34, and -35

Bait

0.35

- indoor/outdoor of homes and other structures, 

and food/feed handling establishments (Figueroa, 

D304214, D310760, 2/17/2005).

Handwand, 

backpack, 

handgun

8033-36 SG 30

- stone fruits, cucurbits, tree nuts, berries, bulb 

vegetables, edible podded legumes and succulent 

shelled peas and beans (Figueroa, D345240 and 

D310760: 10/24/2007). 

- grape & climbing vine small fruits and clover 

grown for seeds (Oonnithan, D36670, 10/9/2009).

Air, ground 

broadcast, airblast 2
Page 25 of 29

Table 1. Use Patterns of Sec. 3 End-use Product Formulations of Acetamiprid Insecticide.

Registered

products & 

Formul. Types 

% AI Use Sites and 

Applicable ORE Reviews 

Application 

equipment Comments 

- cotton, leafy vegetables, cole crops, fruiting 

vegetables, citrus, pome fruits, tuberous and corm 

vegetables, tobacco.

8033-90, -91,

-92, and -93

Gel/bait

0.35

- indoor/outdoor of homes and other structures and 

food handling establishments (Figueroa, D304214, 

D310760, 2/17/2005).

By hand

8033-94, SG 30

- ornamentals and vegetable transplants (Figueroa, 

D355774, 9/11/2008). 

- basal bark and tree injection (Wang, D35709, 

12/27/2008), and

- tomatoes grown in greenhouse (Oonnithan, 

D36670, 10/9/2009). 

Handwand, 

backpack, 

handgun, Tree 

injector

8033-95, EC 40 - potato seed pieces Dow (D343132, 9/11/2007).

Seed piece 

treatment

On-farm/ 

commercial

8033-96, WSP 22.73

- termite, outdoor perimeter, indoor C&C 

(Figueroa, D345240, D310760: 10/24/2007, and 

Figueroa, D353040, 12/1/2008).

Handwand, 

backpack, 

handgun

8033-97, -98,

-99, -100, and

-105 Gel/ baits

0.075 - indoor and/or outdoor of homes, apartments, 

food handling establishments. By hand 3

8033-101, EC 8.5 - cotton Air and ground 

broadcast 1

8033-106, EC 8.5

- ornamentals and vegetable transplants (Figueroa, 

- basal bark and tree injection 

- tomatoes grown in greenhouse 

Handwand, 

backpack, 

handgun, tree 

injector

4

8033-107

Liquid, Ready

to Use (RTU)

0.5 - indoor/outdoor residential ornamentals (annuals, 

shrubs and trees), vegetables, and fruits. 

Hand sprayer, 

hose-end, tank 

sprayer

5

8033-108

Liquid, RTU 0.26 - indoor and outdoor residential ornamentals (annuals, shrubs and trees). 

Hand sprayer, 

hose-end, tank 

sprayer

5

8033-109, EC 5

- termite, indoor and outdoor pests in residential, 

public and commercial structures. 

Handwand, 

backpack, 

handgun

6

8033-114, and

-115, Fly Bait 

stations

4.4 - indoor/outdoor; industrial and commercial trash 

areas.

By hand 7

Abbreviations used: AI = active ingredient, C&C = crack and crevice, DF = dry flowable, EC = emulsifiable 

concentrate, NA = not applicable, RTU = ready to use, SG = soluble granule, WP = wettable powder, WSP = water 

soluble package.

1. SG and EC formulations were not assessed; but, the dermal and inhalation unit exposures being lower than that of 

WP for the same use patterns, the WP MOEs is expected to be protective. 

2. Exposure from SG on some sites was not assessed. WP MOEs would be protective if use of WP is registered. 

3. The 0.075% bait gel was not assessed; a 0.35% gel was assessed and would be protective (Figueroa, D304214, 

D310760, 2/17/2005). 

4. The 8.5% EC was not assessed; a 30% SG was assessed and would be protective (Figueroa, D355774, 9/11/2008, 

Wang, D35709, 12/27/2008, and Oonnithan, D36670, 10/9/2009).
Page 26 of 29

5. Not assessed, but the application rate is expected to be lower than WP and SG formulations applied on 

ornamentals in residential settings.

6. The EC formulation was not assessed, but a 70% WSP was assessed for the same uses and rates and risks are not 

of concern (Figueroa, D295704, 9/29/2004).

7. Not assessed, but exposures are expected to be insignificant due to incorporation of acetamiprid in the glue. 

However, in case of bleeding of acetamiprid/glue mix (due to higher temperature when used indoors and outdoors), 

applying by hand would result in dermal exposure. 

8. Due to inhalation LOC of 1000, crops with aerial applications ≥0.1 lb ai/A may require PF5 respirator for 

mixer/loader, in order to be protective. 

FIFRA Sec. 24(c) Registrations

There are a number of Special Local Need (SLN) also known as FIFRA Sec. (24c) registrations 

for acetamiprid insecticide (Table 2). These SLN sites may not have been reviewed for 

occupational exposures; however, ORE reviews conducted for the same or similar sites would 

support the SLN uses. These comparable ORE reviews are discussed below. 

Table 2. Use Patterns of SLN Registrations of Acetamiprid Insecticide.

SLN No. and

Parent Reg. No.

% AI of 

Parent Use Site Single Appl. Rateand Method Comments 1

ID070011 (8033-23) 70 WP

Alfalfa seed crop 0.075 lb ai/A

Foliar ground and aerial 

Aerial 

application 

may require 

re-evaluation

ID090014 (8033-36) 30 SG

NV070004 (8033-23) 70 WP

OR070017 (8033-23) 70 WP

UT090001(8033-23) 70 WP

WA070006 (8033-23) 70 WP

WY080010 (8033-23) 70 WP

OK100001 (8033-96) 22.73 WSP Post-construction, subconcrete treatment 

using piping, injector, 

reticulation etc. for 

termite control 

0.00184 lb ai/gal per linear ft.

A higher rate 

(0.0043 lb 

ai/gal) has

been assessed

OK100003 (8033-96-279) 22.73 WSP

OK110002 (8033-109) 5 EC

OR090005 (8033-23) 70 WP Hybrid poplar grown 

for wood 

1.2 mg ai/A plus pheromone

Spot, trap attached to trees to 

attract & kill carpenter worm

Not assessed 

but not of 

concern due 

to very low 

appl. rate

WA060009 (8033-94) 30 SG

Apples, pears, etc. 0.15 lb ai/A 

Foliar ground 

Spraying in 

residential 

areas requires

re-evaluation

WA060011 (8033-22) 70 WSP

WA110010 (8033-106) 8.5 EC

1. Rationale used to support ORE assessment for the SLN site is described in the text. 

Alfalfa seed crop: Several Western States have registered WP and SG formulations of 

acetamiprid for controlling lygus bug infestations on alfalfa. No occupational handler exposure 

was evaluated for this use. However, an ORE assessment conducted for the same products (70% 

WP and 30% SG) on clover grown for seed applied at a maximum single application rate of 

0.075 lb ai/A would be protective of handler and postapplication exposures (S. Oonnithan, 

D366701, 10/9/2009). A re-evaluation of handler exposure may be required when the WP 

formulation of acetamiprid is applied on 1,200 acres/day using aerial equipment because treating 

350 A of clover per day resulted in an MOE of 380 with a LOC of 100 at baseline PPE plus 
Page 27 of 29

gloves (the re-evaluation would be needed for inhalation exposure only, based on the LOC of 

1000 for that route of exposure).

Termite treatment: The State of Oklahoma has two SLNs for treating new and post-construction 

sub-concrete slabs for termite control. The application methods used are piping, injector, 

reticulation (tubes placed under slabs for future treatments), or similar sub-concrete slab delivery 

systems. No occupational handler exposure was evaluated for this use. However, a comparable 

ORE assessment (Z. Figueroa, D345240, 10/24/2007), where a 22.73% acetamiprid WSP

formulation applied with a hand gun and low-pressure handwand at 0.0043 lb ai/gal at 1,000 

gal/day (as compared with SLN’s 0.00184 lb ai/gal/linear ft.) is expected to be protective of 

piping and reticulation systems allowed for under the OK SLNs.

Apple maggot control: The State of Oregon has registered three SLNs as a quarantine and pest 

free program to control apple maggots on apples, crabapples, pears, ornamental plants and trees 

and non-bearing fruit and nut trees growing in non-agricultural and residential areas. No 

occupational (handler) and likely residential postapplication exposure (to adults and children) 

were evaluated for this use. However, a comparable ORE assessment (M. Collantes, D264160, 

3/11/2002) consisting of aerial application using the 70% WP (Reg. No. 8033-23) on pome fruits 

applied at 0.15 lb ai/A (same application rate as in SLNs) would be protective of ground 

applications of all the three SLNs used on apple and other trees.
Page 28 of 29

Attachment 4. Acetamiprid Endpoint Selection Table

Summary of Toxicological Doses and Endpoints of Acetamiprid for Use in Dietary and Non-Occupational Human 

Health Risk Assessment

Exposure Scenario Dose Used in 

Risk 

Assessment

Uncertainty 

Factors/FQPA 

Safety Factors

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

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 

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

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).

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. 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.
Page 29 of 29

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.

Long-term Dermal

(> 6 mo.)

NOAEL = 7.1 

mg/kg/day 

DAF = 10%

UFA = 10x

UFH = 10x

FQPA SF = 1x

LOC for MOE 

= 100

Chronic Toxicity/Oncogenicity Study in 

rats

LOAEL = 17.5 mg/kg/day based on 

decreased body weight and body weight 

gains in females and hepatocellular 

vacuolation in males.

Short- and 

Intermediate-term 

Inhalation 

(1 - 30 days, 1 - 6 

mo.)

NOAEL=

10 mg/kg/day UFA = 10x

UFH = 10x

LOC for MOE 

= 100 

Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on 

decreased body weight and body weight 

gains in offspring, decreased early pup 

survival on PND 0-1, and decreased 

startle response on PND 20/60 in males.

Long-term 

Inhalation

(1-30 days, 1 – 6 

mo.)

NOAEL = 7.1 

mg/kg/day

UFA = 10x

UFH = 10x

UFDB = 10X

LOC for MOE 

= 1000

Chronic Toxicity/Oncogenicity Study in 

rats

LOAEL = 17.5 mg/kg/day based on 

decreased body weight and body weight 

gains in females and hepatocellular 

vacuolation in males.

Cancer (oral, dermal, inhalation) - not likely to be carcinogenic to humans (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. DAF = dermal absorption factor. MOE = margin of exposure. 

LOC = level of concern. N/A = not applicable.