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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Laura Nollen, (703) 305-7390

Interregional Project No. 4 (IR-4)

Petition Number (PP# 1E7919)

EPA has received a pesticide petition, PP# 1E7919, from IR-4, IR-4 Project 

Headquarters, 500 College Road East, Suite 201W, Princeton, NJ, 08540 proposing, 

pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 

U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of

acetamiprid, N 1-[(6-chloro-3-pyridyl)methyl]- N 2-cyano- N 1-methylacetamidine, in or 

on the raw agricultural commodities asparagus at 0.8 parts per million (ppm); brassica, 

leafy greens, subgroup 5B at 15 ppm; turnip greens at 15 ppm; corn, sweet, kernel plus 

cob with husks removed at 0.01 ppm; corn, sweet, forage at 10 ppm; corn, sweet, stover 

at 30 ppm; vegetable, fruiting, group 8-10 at 0.20 ppm; fruit, citrus, group 10-10 at 0.50 

ppm; fruit, pome, group 11-10 at 1.0 ppm; and brassica, head and stem, subgroup 5A at 

1.20 ppm. 

Upon approval of the aforementioned tolerances, the petition additionally

proposes to remove the following established tolerances of acetamiprid from 40 CFR 

180.578: fruit, citrus, group 10 at 0.50 ppm; fruit, pome, group 11 at 1.0 ppm; vegetable, 

fruiting, group 8 at 0.20 ppm; and vegetable, brassica, leafy, group 5 at 1.20 ppm. The 

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

will be superseded by the updated crop group tolerances. The vegetable, brassica, leafy

group 5 tolerance will be superseded by the brassica, leafy greens, subgroup 5B and 

brassica, head and stem, subgroup 5A tolerances. EPA has determined that the petition 

contains data or information regarding the elements set forth in section 408 (d)(2) of 

FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at 

this time or whether the data supports granting of the petition. Additional data may be 

needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism of acetamiprid in plants is well understood, 

having been investigated in eggplant, apples, cabbage, carrots, and cotton.

2. Analytical method. Based upon the metabolism of acetamiprid in plants and the 

toxicology of the parent and metabolites, quantification of the parent acetamiprid is 

sufficient to determine toxic residues. As a result a method was developed that involves 
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extraction of acetamiprid from crop matrices with a solvent followed by a decantation 

and filtration and finally analysis by a LC/MS/MS method. For asparagus, the LOD for 

the method was calculated to be 0.00142 ppm and the LOQ was calculated to be 0.00425 

ppm. The lowest level of method validation (LLMV) for asparagus was 0.01 ppm for 

acetamiprid. For mustard greens the LOD for the method was calculated to be 0.0040 

ppm and the LOQ was calculated to be 0.0119 ppm. The lowest level of method 

validation (LLMV) for greens (mustard) was 0.01 ppm for acetamiprid. For sweet corn 

matrices, the respective LODs and LOQs were: KCHR—0.0029 and 0.0088, forage—

0.0028 and 0.0084, stover-0.0017 and 0.0051. The lowest level of method validation 

(LLMV) for each sweet corn matrix was 0.01 ppm for acetamiprid. Based on acceptable 

recoveries, the analytical method was reliable for the tested matrices.

3. Magnitude of residues. Magnitude of residue was determined in a tests

designed to simulate a representative worst-case exposure. The trials were conducted as 

specified in the Residue Chemistry Guidelines. 

For asparagus, magnitude of residue data were collected from eight field trials located in 

appropriate NAFTA Regions where asparagus is grown. At each trial, two foliar 

applications of the test substance 10-14 days apart were made to the treated plot. The 

application rates were in the range 0.099-0.103 lb ai/A per application for a total rate 

range of 0.200-0.204 lb ai/A per season. A non-ionic surfactant was included in the tank 

mix in California, Idaho, and Michigan trials and in the second application at a trial in 

Washington. All applications were made using appropriate spray equipment, and the 

spray volume was sufficient to provide adequate dispersal of the test substance. 

Sampling started in the untreated control plot and ended in the treated plot. At all the 

field trials, samples were harvested one day after the last application. Additionally, at 

one California trial, duplicate samples were collected 0, 4, 8, and 11 days after the last 

application. 

For mustard greens, magnitude of residue data were collected from eight field trials 

located in NAFTA Regions where leafy brassica crops are grown. At each trial, four 

foliar applications of the test substance 6-8 days apart were made to the treated plots, 

except in a Georgia trial a fifth application was needed because the crop was not mature 

after four applications. A nonionic surfactant was included in the tank mix for each 

application. The first application was made in the range 0.074-0.080 lb ai/A per 

application, and subsequent applications were made in the range 0.097-0.104 lb ai/A, for 

a total rate range of 0.374-0.476 lb ai/A per season. (Although an exception was made in 

a Georgia trial, the plan was for four applications with a maximum of 0.375 lb ai/A per 

season.) All applications were made using appropriate spray equipment, and the spray

volume was sufficient to provide adequate dispersal of the test substance. Sampling 

started in the untreated control plot and ended in the treated plot. At all the field trials, 

samples were harvested 2-4 days after the last application.

For sweet corn, magnitude of residue data were collected from seven field trials located 

in NAFTA Regions where the crop is grown. At each trial, the Trt 01 plot was the 

untreated control. The Trt 02 plot received four foliar applications of the test substance 

6-8 days apart, except in a Georgia trial in which the intervals were as short as 4 days. 
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The application rates were in the range 0.053-0.057 lb ai/A per application for a total rate 

range of 0.212-0.220 lb ai/A per season. The Trt 03 plot received two foliar applications 

of the test substance 12-16 days apart. The application rates were in the range 0.094-

0.109 lb ai/A per application for a total rate range of 0.195-0.214 lb ai/A per season. All 

applications were made using appropriate spray equipment, and the spray volume was 

sufficient to provide adequate dispersal of the test substance. Sampling started in the 

untreated control plot and ended in the treated plots. At all the field trials, samples were 

harvested from the Trt 02 plot one day after the last application and from the Trt 03 plot 

5-8 days after the last application. Samples were collected from each plot of kernel plus 

cob with husks removed, forage, and stover. Stover was dried after harvest as needed 

prior to sample collection. (In the New York trial, stalks for stover samples were not cut 

{harvested} until the sampling date.)

Magnitude of residue data were also collected in 2006 from a total of eight Canadian field trials, 

which were conducted in Ontario (Crop Zone 5, four trials), Quebec (Crop Zone 5B, two trials), 

Alberta (Zone 7A, one trial), and British Columbia (Crop Zone 12, one trial).

Each field trial site consisted of one untreated control plot and one treated plot. It was

proposed that four foliar broadcast applications of Assail 70 WP (acetamiprid), at a target rate of 

60.2 g a.i./ha, should be applied to the treated plots at a pre-harvest interval (PHI) of 1+1 days for 

sweet corn kernel plus cob with husk removed ("K+CWHR") and forage, and at normal harvest 

for stover. The actual rate of application ranged from 59 to 63 g a.i./ha/application (total, 239 to 

245 g a.i./ha/season), with the exception of Trial ID#138 where the first three applications were 

made at 83 to 87 g a.i./ha, due to an oversight by field personnel. The fourth spray application 

was made at 59.5 g a.i./ha (making the total, 315 g a.i./ha/season); which resulted in sweet corn 

residues that were comparable to samples obtained from the other trials with the exception of the 

stover fraction which resulted in higher residues. The actual PHI was 1 or 2 days for the harvest 

of K+CWHR and forage, and 38 to 89 days for stover. There was a 6 to 8 day re-treatment 

interval between applications. 

The crop samples were shipped to Trace Analytical Laboratory, University of California in Davis, 

CA, to be analyzed for the presence of acetamiprid residues of concern (ROC). The limit of 

quantification (LOQ) was determined to be 0.01 ppm for acetamiprid and the limit of detection 

(LOD) was estimated to be 0.005 ppm. The overall method validation recoveries for acetamiprid 

were 89% ± 3 for K+CWHR, 85% ± 12 for forage, and 82% ± 9 for stover. The overall 

concurrent method recoveries were 90% ± 5, 83% ±5, and 81% ±4 for K+CWHR, forage, and 

stover, respectively. 

Residues of acetamiprid were below the limit of quantification (<0.01 ppm, or <LOQ) in all 

sweet corn K+CWHR samples and were 0.23-1.1 ppm in the forage samples, each harvested at a 

1 or 2 day PHI. For forage, the HAFT, mean, and median residue values were 1.05 ppm, 0.60 

ppm ± 0.23, and 0.60 ppm, respectively. Residues of acetamiprid were <0.01 ppm to 0.16 ppm in 

the stover samples collected at normal harvest, 38 to 89 days after the last application.

The HAFT, mean and median residue values in stover were 0.16 ppm, 0.05 ppm ± 0.05, and 0.04 

ppm, respectively. When normalized to ~83% dry matter, the acetamiprid residues in the stover 

samples were <0.01 to 0.22 ppm. The residue results, unless otherwise stated, were not corrected 

for moisture content, apparent residues in controls, or procedural recoveries.
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Residues of acetamiprid in sweet corn K+CWHR were below the limit of quantification

(<0.01 ppm) in all samples collected at the site investigating residue decline; therefore,

residue decline could not be determined. The data for forage and stover indicate that

acetamiprid residues decrease as post-harvest intervals increase.

B. Toxicological Profile

1. Acute toxicity. Acute Toxicity for Technical Acetamiprid- The acute oral LD50 for acetamiprid was 146 mg/kg for female Sprague-Dawley rats and 217 for male rats. 

The acute dermal LD-50 for acetamiprid was greater than 2000 mg/kg in rats. The acute 

4 hour inhalation LC-50 for acetamiprid was greater than 1.15 mg/L, the highest 

attainable concentration. Acetamiprid was not irritating to the eyes or skin and was not 

considered to be a sensitizing agent. The NOEL for acute neurotoxicity was 10mg/kg and 

no evidence of neuropathy was noted. 

Acute Toxicity for Formulated Acetamiprid 70WP-The acute oral LD-50 for Acetamiprid 

70WP was 944 mg/kg for female Sprague-Dawley rats and 1107 mg/kg for male rats. 

The acute dermal LD-50 for formulated acetamiprid was greater than 2000 mg/kg in rats. 

The acute inhalation LC-50 (four hour) for Acetamiprid 70WP was determined to be 

greater than 2.88 mg/L, the highest attainable concentration. Acetamiprid 70WP was 

concluded to be a mild eye irritant and slight skin irritant. There were no indications of 

skin sensitization for the formulated product.

Acute Toxicity for Formulated Acetamiprid 30 SG – The acute oral LD-50 for 

Acetamiprid 30 SG was 805 mg/kg for female Sprague-Dawley rats and 886 mg/kg for 

male rats. The acute dermal LD-50 for the formulation was greater than 200 mg/kg in 

rats. An acute inhalation toxicity test was waived for the formulation due to the nonrespirable particle size of the formulation. Acetamiprid 30 SG was found to be a 

moderate eye irritant and mild skin irritant. There were no indications of skin 

sensitization for the formulated product.

2. Genotoxicty. Based on the weight of the evidence provided by a complete test 

battery, acetamiprid is neither mutagenic nor genotoxic. The compound was found to be 

devoid of mutagenic activity (with and without metabolic activation) in Salmonella 

typhimurium and Escherichia coli (Ames assay). Acetamiprid was also not mutagenic in 

an in vitro mammalian cell gene mutation assay on Chinese hamster ovary (CHO) cells 

(HPRT locus, with and without metabolic activation). Acetamiprid did not induce 

unscheduled DNA synthesis (UDS) in either rat liver primary cell cultures or in 

mammalian liver cells in vivo. In an in vitro chromosomal aberration study using CHO 

cells, acetamiprid was positive when tested under metabolic activation at cytotoxic dose 

levels; no effect was detected without metabolic activation. Acetamiprid was nonclastogenic in an in vivo chromosomal aberration study in rat bone marrow. It also was 

negative in an in vivo mouse bone marrow micronucleus assay.

3. Reproductive and developmental toxicity. In the multi-generation rat 

reproduction study a NOEL of 100 ppm was established based on decreased body weight 

gains and a reproduction NOEL of 800 ppm (highest dose tested) was established for 

reproductive performance and fertility. In the rat teratology study the developmental 
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NOEL was 50 mg/kg/day (maternal NOEL of 16 mg/kg/day based on decreased body 

weight and food consumption) and in the rabbit teratology study the developmental 

NOEL was 30 mg/kg/day (maternal NOEL of 15 mg/kg/day based on decreased body 

weight and food consumption). In both the rat and rabbit studies there were no fetotoxic 

or teratogenic findings.

A developmental neurotoxicity study in rats with acetamiprid was conducted. The test 

article was administered orally by gavage to Crl:CD(SD)IGS BR rats once daily from 

gestation day 6 through lactation day 21 inclusive at dosage levels of 2.5, 10, and 45 

mg/kg/day. One female in the 45 mg/kg/day group died during parturition on gestation 

day 23, following delivery of one pup. All other females survived to the scheduled 

necropsies. No adverse clinical signs were noted. F0 maternal toxicity was expressed at 

a dose level of 45 mg/kg/day by a single mortality and reductions in body weight gain 

and food consumption. No maternal toxicity was exhibited at dose levels of 2.5 and 10 

mg/kg/day. F1 developmental toxicity was expressed at a dose level of 45 mg/kg/day by

early postnatal mortality and reduced post-weaning body weights. No developmental 

toxicity was exhibited at dose levels of 2.5 and 10 mg/kg/day. Deficits in auditory startle 

response occurred in the 45 mg/kg/day group F1 males and females without concomitant 

effects in other functional endpoints (FOB), neuropathology or brain morphometry. 

Based on the results of this study, the NOAEL for maternal toxicity, developmental 

toxicity and developmental neurotoxicity is considered to be 10 mg/kg/day.

4. Subchronic toxicity. In the 3-month dog feeding study a NOEL of 800 ppm (32 

mg/kg/day for both males and females) was established based on growth retardation and 

decreased food consumption. 

In the 3-month rat feeding study a NOEL of 200 ppm (12.4 and 14.6 mg/kg/day

respectively for male and female rats) was established based on liver cell hypertrophy at a 

dose of 800 ppm.

In the 3-month mouse feeding study a NOEL of 400 ppm (53.2 and 64.6 mg/kg/day 

respectively for male and female mice) was established based on increased liver/body 

weight ratio and decreased cholesterol in females at 800 ppm. 

A 13 week dietary neurotoxicity study for acetamiprid established a NOEL of 200 ppm 

(14.8 and 16.3 mg/kg for male and female rats) based on reduced body weight and food 

consumption decreases at 800 ppm. There was no evidence of neurotoxicity. 

A 21 day dermal study in rabbits at dose levels up to 1000 mg/kg/day caused no systemic 

toxicity, dermal irritation or histomorphological lesions in either sex tested.

5. Chronic toxicity. In the 1-year dog study, the NOEL was established at 600 

ppm (20 and 21 mg/kg/day for male and female dogs, respectively) based on growth 

retardation and decreased food consumption at a dose of 1500 ppm. 

In the 18-month mouse study the NOEL was established at 130 ppm (20.3 and 25.2 

mg/kg/day for male and female mice) based on growth retardation and hepatic toxicity at 

400 ppm.

In the 2-year rat study the NOEL was 160 ppm (7.1 and 8.8 mg/kg/day for male and 

female rats) based on growth retardation and hepatic toxicity. There were no indications 
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of carcinogenicity in either the rat or mouse chronic studies.

6. Animal metabolism. The metabolism of acetamiprid is well understood and the 

primary animal metabolite is IM-2-1.

7. Metabolite toxicology. Testing of IM-2-1 demonstrated that it is significantly

less toxic than the parent acetamiprid and it is not being considered as part of the total 

toxic residue in plants, therefore no tolerance is being requested by the registrant. The 

acute oral LD50 of IM-2-1 is 2543 mg/kg for male rats and 1762 mg/kg for female rats.

8. Endocrine disruption. Acetamiprid does not belong to a class of chemicals 

known or suspected of having adverse effects on the endocrine system. Developmental 

toxicity studies in rats and rabbits and a reproductive study in rats gave no indication that 

acetamiprid has any effects on endocrine function. The chronic feeding studies also did 

not show any long-term effects related to endocrine systems.

9. Immunotoxicity. Dietary administration of acetamiprid to CD-1 mice at 

concentrations up to 900 ppm for four weeks caused a non-specific toxic response at 300 

ppm in females and 900 ppm in both sexes but there was no effect on the immune 

function, as assessed by the measurement of antigen-specific, T-cell dependent antibody

formation. The no-observed-effect level in mice for immunotoxicity by acetamiprid was 

therefore greater than 900 ppm (i.e., >128 mg/kg/day in males and > 157 mg/kg/day in 

females). Dietary administration of acetamiprid to Sprague Dawley rats at concentrations 

up to 900 ppm for four weeks caused a non-specific toxic response at 300 ppm in males 

and 900 ppm in both sexes but there was no effect on the immune function, as assessed 

by the measurement of antigen-specific, T-cell dependent antibody formation. The noobserved-effect level in rats for immunotoxicity by acetamiprid was therefore greater 

than 900 ppm (i.e., >62.9 mg/kg/day in males and > 67.7 mg/kg/day in females).

C. Aggregate Exposure

1. Dietary exposure. Acute and chronic dietary analyses were conducted to 

estimate exposure to potential acetamiprid residues in/on the following crops: asparagus,

leafy and head cole crop groups and turnip greens, sweet corn, citrus crop group, fruiting 

vegetable crop group, pome fruit crop group, grapes, leafy vegetables, canola oil, mustard 

seed, cotton, tuberous and corm vegetable crop group, cucurbit crop group, stone fruit 

crop group, tree nut crop group (including pistachio), berries, bulb vegetables, succulent 

legumes (excluding soybeans), clover, tea, soybeans (pending tolerance), and food 

handling establishments (pending tolerance). The assessment also included anticipated 

residues in meat, milk, poultry, and eggs. Exposure estimates from drinking water were 

made based on conservative FIRST and SCI-GROW modeling. The additional dietary

exposure from the use of acetamiprid on asparagus and sweet corn and the revised use on 

leafy vegetables is expected to remain within acceptable levels.

i. Food. Residue data from field trial studies conducted at maximum label 

application rates and the shortest pre-harvest interval (PHI) were used to estimate chronic 

and acute dietary exposure to potential residue of acetamiprid in food. For the chronic 
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analysis, tolerance-level residues were assumed, resulting in a conservative estimate of 

potential residues. For the acute analysis, EPA policy permits the use of mean residues in 

acute assessments only for blended foods (i.e., oils, grains, beans, etc.) and distributions 

of residue data from field trial studies were used for non-blended and partially blended 

foods. 

Chemical-specific processing factors were used for processed commodities. In the 

absence of chemical-specific processing factors, DEEM default processing factors were 

used where appropriate.

Percent crop treated estimates were obtained from the most recent EPA dietary exposure 

assessment for acetamiprid. Following EPA convention, 100% crop treated was assumed 

for the pending and proposed uses.

Tolerance-level residues were assumed for all livestock tissues in the acute and chronic 

dietary exposure assessments.

Chronic dietary exposures to acetamiprid were compared against a chronic population 

adjusted dose (cPAD) of 0.071 mg/kg bw/day. The cPAD is based on the chronic no 

observed adverse effect level (NOAEL) of 7.1 mg/kg bw/day from a chronic 

toxicity/oncogenicity study in rats and an uncertainty factor of 100. No FQPA safety 

factor is necessary, so the cPAD is identical to the cRfD.

Chronic exposure (food + water) was estimated for the overall US population and select 

population subgroups. Chronic exposure for the overall US population was estimated to 

be 0.003036 mg/kg bw/day, representing 4.3% of the cPAD. Exposure for the most 

highly exposed population subgroup, children 1-2 years old, was calculated to be 

0.009952 mg/kg bw/day, or 14% of the cPAD. 

Acute dietary exposure to potential acetamiprid residues in food was compared against

the NOAEL of 10 mg/kg bw/day from the developmental neurotoxicity study in rats. 

Based on the acute NOAEL and an uncertainty factor of 100, the acute RfD (aRfD) is 0.1 

mg/kg bw/day. No FQPA safety factor is necessary so the acute population adjusted dose 

(aPAD) is identical to the aRfD.

Results of the acute dietary (food + water) exposure analysis demonstrate that exposure at 

the 99.9th percentile is less than the aPAD for all population groups. For the general US 

population, the 99.9th percentile exposure is 0.026021 mg/kg/day or 26.02% of the aPAD. 

For the most highly exposed population subgroup, children 1-2 years old, acute dietary

exposure at the 99.9th percentile of exposure was calculated to be 0.046017 mg/kg/day

which represents 46.02% of the aPAD.

ii. Drinking water. Residues in surface water were estimated by EPA (Internal 

EPA Memorandum, D. McNeilly to L. Nollen, January 14, 2010) using the FIRST model 

and were 20.1 ppb for acute exposure and 4.9 ppb for chronic exposure. The ground 

water concentration was estimated to be 1.6 ppt using the SCI-GROW model. The 
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surface and ground water estimates were based on the registered uses on citrus and tree 

nuts, for which the maximum use pattern applies, and it was assumed that the proposed 

uses would not be associated with higher concentrations in water (i.e., lower rates). The 

surface water estimate was used in the dietary assessments because they provide the most 

conservative estimate of dietary exposure via acetamiprid residues in water.

The proposed use of acetamiprid on asparagus, leafy brassicas, and sweet corn is not 

expected to increase the Estimated Drinking Water Concentration (EDWC) values.

2. Non-dietary exposure. Residential post-application exposures and margins of 

exposure (MOEs) for toddlers contacting acetamiprid residues on treated turf or 

following indoor crack & crevice application were estimated by EPA in 2008 and carried 

forward to through to the most recent EPA assessment in 2010. Aggregate MOEs for 

toddlers were estimated to be 278 for the short-term indoor crack & crevice scenario, 484 

for the short-term turf scenario, and 673 for the intermediate-term turf scenario. MOEs 

greater than 100 indicate that aggregate exposures for toddlers are not of concern.

D. Cumulative Effects

[A determination has not been made that acetamiprid has a common mechanism 

of toxicity with other substances. Acetamiprid does not appear to produce a common 

toxic metabolite with other substances. A cumulative risk assessment was therefore not 

performed for this analysis.

E. Safety Determination

1. U.S. population. Based on assessments estimating the aggregate risk from the 

current uses of acetamiprid and the potential exposure from asparagus, sweet corn, and 

modified use pattern on leafy brassica crops, there is a reasonable certainty that no harm 

will result to the U.S. general population from aggregate exposure to acetamiprid 

residues.

2. Infants and children. Based on assessments estimating the aggregate risk from 

the current uses of acetamiprid and the potential exposure from asparagus, sweet corn, 

and modified use pattern on leafy brassica crops, there is a reasonable certainty that no 

harm will result to infants and children from aggregate exposure to acetamiprid residues.

F. International Tolerances

Acetamiprid is registered for use on food crops in several countries outside the 

United States. There is a MRL established at 1.2 ppm for leafy brassicas in Canada and a 

pending MRL for sweet corn at 0.01 ppm. No Canadian MRL exists for asparagus. There 

are no Codex MRLs for acetamiprid.