EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Andrew Ertman; 703-308-9367

Inter-Regional Project No. 4 (IR-4)

PP #3E8147

EPA has received a pesticide petition (3E8147) from 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 including 

its metabolites and degradates in or on the raw agricultural commodities corn, sweet, 

kernel plus cob with husks removed at 0.01 ppm; corn, sweet, forage at 15 ppm; and 

corn, sweet, stover at 30 ppm. The petition also proposes to increase the existing 

tolerances for acetamiprid including its metabolites and degradates in meat, meat 

byproducts, and milk. Tolerances for cattle, goat, horse, and sheep meat are proposed at 

0.30 ppm; cattle, goat, horse, and sheep fat at 0.20 ppm; cattle, goat, horse, and sheep 

meat byproducts at 0.70 ppm; and milk at 0.30 ppm. 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 residues of concern for enforcement purposes. As a result a 

method was developed that involves 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 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. 

Separate magnitude of the residue studies with sweet corn were conducted by the IR-4 

Project in the U.S. and AAFC in Canada.
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In the IR-4 study, magnitude-of-residue data were collected from seven field trials. 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 the GA*14 trial in which the 

intervals were as short as 4 days. 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 (KCHR), 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.)

No residues above the LLMV were found in samples of KCHR from the Trt 02 plots (4 

applications at 0.054 lb ai/acre, PHI=1 day) or from the Trt 03 plots (2 applications at 

0.10 lb ai/acre, PHI=5-8 days). Forage samples from the Trt 02 plots had residues in the 

range 0.42-8.1 ppm, whereas forage samples from the Trt 03 plots had residues in the 

range 0.39-10 ppm. Stover samples from the Trt 02 plots had residues in the range 0.12-

16 ppm, whereas stover samples from the Trt 03 plots had residues in the range 0.21-21 

ppm. 

In the Canadian study, magnitude-of-residue data were collected from eight field trials. 

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

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

target rate of 60.2 grams a.i./ha, should be applied to the treated plots at a preharvest 

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. 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 retreatment interval 

between applications.

Residues of acetamiprid were below the limit of quantification 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. 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 Trt 02 plots in the U.S. study were treated at a rate and timing similar to the 

Canadian treated plots. The Trt 03 plots in the U.S. study were treated at a different rate 

and timing, and the data are intended to show that this alternate use pattern will not 

produce residues above the proposed tolerances based on the data from the samples in the 
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Trt 02 plots (U.S.) and the Canadian treated plots.

The sweet corn reports were submitted to EPA in 2011 and assigned the respective 

MRID’s 48590103 and 48590103. The Agency’s residue chemistry review dated March 

6, 2012, stated that:

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

sweet corn. Although there is evidence to support residue equivalency for the 70% WP 

formulation and the 30% SG formulation and the combination of trials conducted with 

these two formulations provide for an adequate number of trials with sufficient 

geographic variation, it is not possible to combine the two sets due to the significant 

differences in the stover PHIs between the U.S. and Canadian trials. These differences 

are reflected in the residue data for stover. In the U.S. trials, residues (and per trial 

averages) of acetamiprid were <0.01 (<0.01) in K+CWHR, 0.39-10 (0.41-9.1) in forage, 

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

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

0.35 (0.011-0.285) ppm in stover. Furthermore, although the use patterns were similar 

between the U.S. and Canadian trials for K+CWHR and forage (four applications, 1- to 

2-day PHI), the U.S. trials performed with the 30% SG formulation included an adjuvant, 

whereas the Canadian trials using the 70% WP formulation did not include an adjuvant. 

Additional crop field trial data are required to support the proposed uses.

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

restrictive for stover (1- or 7-day PHI in the U.S. vs. harvest at maturity in Canada); 

therefore, to support the proposed uses on sweet corn, five additional crop field trials 

must be conducted in the U.S. with the 30% SG formulation and an adjuvant in Zones 1 

(1 trial), 5 (3 trials), and 12 (1 trial) to provide a full set of field trial data for this 

formulation. Each trial should include an additional side-by-side treated plot reflecting 

application of the 70% WP formulation with an adjuvant. Although the available data 

suggest that residues are similar following application according to the fourapplication/1-day PHI use pattern and the two-application/7-day PHI use pattern, HED 

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

After receiving this review, the IR-4 Project planned on conducting the additional field 

trials; however, following further consultation with the Agency, it was determined that 

“...no additional data are needed to support the sweet corn use given the recent change in 

policy [i.e., August 13, 2012, ChemSAC memo] regarding adjuvants.” 

The nature of the residues of acetamiprid is adequately understood, and an acceptable 

analytical method is available for enforcement purposes. Based on these results, the 

establishment of the proposed tolerances is appropriate. EPA’s Health Effects Division 

indicated that a 30 ppm tolerance for stover, a 0.01 ppm for K+CWHR, and a 15 ppm 

tolerance for forage would be acceptable. They also indicated that the existing livestock 

tolerances would need to be increased as follows: milk at 0.30 ppm, fat of cattle, goat, 

horse, and sheep at 0.20 ppm, meat of cattle, goat, horse, and sheep at 0.30 ppm and meat 

byproducts of cattle, goat, horse, and sheep at 0.70 ppm.
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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 

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.
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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 

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.
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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 exposure analyses were conducted 

by the Agency (HED memo, February 14, 2012) to estimate exposure to potential 

acetamiprid residues in/on the following crops: asparagus, leafy and head cole crop 

groups and turnip greens, 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, food handling establishments, and sweet corn. The assessment also 

included residues in meat, milk, poultry, and eggs using the currently established 

tolerance levels for these commodities. Exposure estimates from drinking water were 

made based on conservative FIRST and SCI-GROW modeling. 

Even when considering the proposed increases to meat, meat byproducts, and milk 

tolerances the additional dietary exposure from the use of acetamiprid on sweet corn is

expected to remain within acceptable levels since the dietary assessment was unrefined 

with assumptions of 100% crop treated and tolerance-level crop residues for all existing 

and proposed uses.

i. Food. Tolerance-level and 100% crop treated values were used to estimate 

chronic and acute dietary exposure to potential residue of acetamiprid in food. 

Chemical-specific processing factors were used for processed commodities. In the 
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absence of chemical-specific processing factors, DEEMTM Version 7.81 default 

processing factors were used where appropriate.

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 + drinking water) was conservatively estimated for the overall 

US population and select population subgroups. Chronic exposure for the overall US 

population was estimated to be 0.007145 mg/kg bw/day, representing 10% of the cPAD. 

Exposure for the most highly exposed population subgroup, children 1-2 years old, was 

calculated to be 0.023734 mg/kg bw/day, or 33% of the cPAD. 

Acute dietary exposure to potential acetamiprid residues 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 conservative acute dietary (food + water) exposure analysis demonstrate 

that exposure at the 95th percentile is less than the aPAD for all population groups. For 

the general US population, the 95th percentile exposure is 0.020582 mg/kg/day or 21% of 

the aPAD. For the most highly exposed population subgroup, children 1-2 years old, 

acute dietary exposure at the 95th percentile of exposure was calculated to be 0.051942 

mg/kg/day and represents 52% of the aPAD.

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

memo, February 14, 2012) using the FIRST model and were 95.2 ppb for acute exposure 

and 26.6 ppb for chronic exposure. The ground water concentration was estimated to be 

0.035 ppb using the SCI-GROW model. The surface and ground water estimates were 

based on a pending use for acetamiprid as a scatter bait for fly control (i.e. maximum use 

pattern) and it is assumed that the proposed sweet corn use would not be associated with 

higher concentrations in water. The surface water estimates of 26.6 ppb and 95.2 ppb 

were used in the chronic and acute dietary assessments, respectively, because they

provide the most conservative estimates of dietary exposure via acetamiprid residues in 

water. 

The proposed use of acetamiprid on 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 through to the most recent EPA assessment in 2010. Aggregate MOEs for 
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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 sweet corn 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 sweet corn 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 Canadian MRL established for sweet corn (KCHR) at 0.01 

ppm. There are no Codex MRLs for acetamiprid.