EPA REGISTRATION DIVISION - COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITION

Docket ID Number: EPA-HQ-OPP-2012-0204

EPA Registration Division contact: Sidney Jackson, (703) 305-7610

Interregional Research Project Number 4 (IR-4)

Pesticide Petition Number (PP#): 2E7988

EPA has received a pesticide petition (PP), 2E7988 from IR-4, 500 College 

Road East, Suite 201W, Princeton, New Jersey, 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 the combined 

residues of the insecticide imidacloprid, including its metabolites and degradates, in 

or on the following commodities: Fish at 0.05 parts per million (ppm) and fishshellfish, mollusc at 0.05 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 support granting of the petition. Additional data may be needed before EPA 

rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The nature of the imidacloprid residue in plants and 

livestock is adequately understood. The residues of concern are combined residues 

of imidacloprid and it metabolites containing the 6-chloropyridinyl moiety, all 

calculated as imidacloprid.

2. Analytical method. Adequate enforcement methodologies, Bayer Gas 

Chromatography/Mass Spectrometry (GC/MS) Method 00200 and Bayer GC/MS

Method 00191, is available to enforce the tolerance expression. The methods may be 

requested from: Chief, Analytical Chemistry Branch, Environmental Science 

Center, 701 Mapes Rd., Ft. Meade, MD 20755–5350; telephone number: (410) 305–

2905; e-mail address: residuemethods@epa.gov.
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3. Magnitude of residues. Three residue field trials were conducted in 

Washington. Approximately 0.5 lb ai/A (TRT 02, granular formulation) or 2.0 lb 

ai/A (TRT 03, flowable formulation) was applied to the treated plots in one 

broadcast application of either Mallet 0.5G (TRT 02) or Mallet 2F (TRT 03). 

Oyster meat samples were collected 84 to 86 days following the application. 

Additional samples were collected from WA43 at approximately 30 and 60 days. A

storage stability analysis demonstrated that the analytes remained stable in frozen 

oyster meat. No residues above the LLMV of 0.05 ppm were observed 

B. Toxicological Profile

1. A summary of the toxicological endpoints for imidacloprid used for human 

risk assessment can be found at http://www.regulations.gov in document 

‘‘Imidacloprid: Human-Health Risk Assessment,’’ pages 16 - 17 in docket ID 

number EPA–HQ–OPP–2008–0772.

C. Aggregate Exposure

1. Dietary exposure. In the Federal Register of April 28, 2010 (FRL-8818-5), 

EPA evaluated the dietary exposure to imidacloprid. EPA considered exposure 

under the petitioned-for tolerances as well as all existing imidacloprid tolerances in 

(40CFR 180.472). EPA assessed dietary exposures from imidacloprid in food as 

follows: 

i. Acute exposure. Quantitative acute dietary exposure and risk assessments 

are performed for a food-use pesticide, if a toxicological study has indicated the 

possibility of an effect of concern occurring as a result of a 1–day or single exposure. 

In estimating acute dietary exposure, EPA used food consumption information from 

the United States Department of Agriculture (USDA) 1994–1996 and 1998 

Nationwide Continuing Surveys of Food Intake by Individuals (CSFII). As to 

residue levels in food, EPA conducted an unrefined, acute dietary exposure 

assessment using tolerance-level residues and assuming 100% crop treated (CT) for 

all registered and proposed commodities for the general U.S. population and 

various population subgroups. 

ii. Chronic exposure. In conducting the chronic dietary exposure assessment 

EPA used the food consumption data from the USDA 1994–1996 and 1998 CSFII. 

As to residue levels in food, EPA conducted a partially refined, chronic dietary 

exposure assessment using tolerance-level residues for all registered and proposed 

commodities and percent crop treated (PCT) for some registered commodities.

iii. Cancer. A cancer exposure assessment was not performed because 

imidacloprid is not carcinogenic. On November 11, 1993, the Agency classified 

imidacloprid as a Group E chemical, ‘‘Evidence of non- carcinogenicity for 

humans,’’ by all routes of exposure based upon lack of evidence of carcinogenicity 

in rats and mice.
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i. Percent crop treated (PCT) Information. Section 408(b)(2)(F) of FFDCA 

states that the Agency may use data on the actual percent of food treated for 

assessing chronic dietary risk only if:

• Condition a: The data used are reliable and provide a valid basis to show 

what percentage of the food derived from such crop is likely to contain the pesticide 

residue.

• Condition b: The exposure estimate does not underestimate exposure for 

any significant subpopulation group.

• Condition c: Data are available on pesticide use and food consumption in a 

particular area, the exposure estimate does not understate exposure for the 

population in such area.

In addition, the Agency must provide for periodic evaluation of any estimates 

used. To provide for the periodic evaluation of the estimate of PCT as required by 

FFDCA section 408(b)(2)(F), EPA may require registrants to submit data on PCT.

The Agency used PCT information as follows:

Commodity Average percent Crop 

Treated Data

Almonds..................... <1

Apples....................... 25

Artichoke................... 5

Avocados................... <1

Blueberry................... 10

Broccoli..................... 50

Cabbage.................... 20

Cantaloupe................ 40

Cauliflower................ 50

Celery....................... 10

Cherries..................... 10

Cotton...................... 10

Cucumbers................ 5

Eggplant................... 35

Field corn.................. <2.5

Filberts (hazelnuts)...... <1

Grapefruit................. 10

Grapes...................... 30

Honeydew.................. 30

Lemons..................... 5

Lettuce...................... 65

Oranges..................... 10

Peaches...................... 5

Pears......................... 5

Pecans........................ 10

Peppers...................... 30

Commodity Average percent Crop 
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Treated Data

Potatoes..................... 35

Prunes....................... <1

Pumpkin................... 10

Soybeans................... <1

Spinach..................... 20

Squash...................... 10

Strawberries............... 10

Sugar beets................ <1

Sweet corn................. <1

Tangerines................. 5

Tobacco.................... 20

Tomatoes................... 15

Walnuts..................... <1

Watermelon................ 15

In most cases, EPA uses available data from the United States Department of 

Agriculture/National Agricultural Statistics Service (USDA/NASS), proprietary 

market surveys, and the National Pesticide Use Database for the chemical/crop 

combination for the most recent 6 years. EPA uses an average PCT for chronic 

dietary risk analysis. The average PCT figure for each existing use is derived by 

combining available public and private market survey data for that use, averaging 

across all observations, and rounding to the nearest 5%, except for those situations 

in which the average PCT is less than one. In those cases, 1% is used as the average 

PCT and 2.5% is used as the maximum PCT. EPA uses a maximum PCT for acute 

dietary risk analysis. The maximum PCT figure is the highest observed maximum 

value reported within the recent 6 years of available public and private market 

survey data for the existing use and rounded up to the nearest multiple of 5%.

The Agency believes that the three conditions discussed in Unit III.C.1.iv. 

have been met. With respect to Condition a, PCT estimates are derived from

Federal and private market survey data, which are reliable and have a valid basis. 

The Agency is reasonably certain that the percentage of the food treated is not likely 

to be an underestimation. As to Conditions b and c, regional consumption 

information and consumption information for significant subpopulations is taken 

into account through EPA’s computer-based model for evaluating the exposure of 

significant subpopulations including several regional groups. Use of this 

consumption information in EPA’s risk assessment process ensures that EPA’s 

exposure estimate does not understate exposure for any significant subpopulation 

group and allows the Agency to be reasonably certain that no regional population is 

exposed to residue levels higher than those estimated by the Agency. Other than the 

data available through national food consumption surveys, EPA does not have 

available reliable information on the regional consumption of food to which 

imidacloprid may be applied in a particular area.

ii. Drinking water. The Agency used screening level water exposure models in 
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the dietary exposure analysis and risk assessment for imidacloprid in drinking 

water. These simulation models take into account data on the physical, chemical, 

and fate/transport characteristics of imidacloprid. Further information regarding 

EPA drinking water models used in pesticide exposure assessment can be found at 

http://www.epa.gov/ oppefed1/models/water/index.htm. Based on the First Index 

Reservoir Screening Tool (FIRST) and Screening Concentration in Ground Water 

(SCI- GROW) models, the estimated drinking water concentrations (EDWCs) of 

imidacloprid for acute exposures are estimated to be 36.0 parts per billion (ppb) for 

surface water and 2.09 ppb for ground water. Modeled estimates of drinking water 

concentrations were directly entered into the dietary exposure model. For acute 

dietary risk assessment, the water concentration value of 36.0 ppb was used to assess 

the contribution to drinking water. For chronic dietary risk assessment, the water 

concentration of value 17.2 ppb was used to assess the contribution to drinking 

water.

2. Non-dietary exposure. The term ‘‘residential exposure’’ is used in this 

document to refer to non- occupational, non-dietary exposure (e.g., for lawn and 

garden pest control, indoor pest control, termiticides, and flea and tick control on 

pets). Imidacloprid is currently registered for the following uses that could result in 

residential exposures: Indoor and outdoor ornamental plantings, ornamental lawns 

and turf, pre- and post-construction termiticide applications, spot-on treatments for 

dogs and cats, and crack and crevice treatments. Additionally, it is registered for 

use on mattresses for bed bug control. EPA assessed residential exposure using the 

assumption that residential pesticide handlers (i.e., persons who might mix, load 

and, or apply a pesticide material) could be exposed to several formulations that 

contain imidacloprid. The Agency also assessed post-application exposure for 

adults and children contacting surfaces, foliage, or pets that were treated with 

imidacloprid. Residential exposures are expected to be short-term (i.e., 1 to 30 days) 

or intermediate-term (1 to 6 months) based upon the pest spectra, sites of 

application, methods of application, formulations and the retreatment intervals. 

Since the indoor crack and crevice and mattress scenarios resulted in the highest 

potential exposures, these assessments are protective of all residential exposures 

from imidacloprid. 

3. Cumulative Effects EPA has not found imidacloprid to share a common 

mechanism of toxicity with any other substances, and imidacloprid does not appear 

to produce a toxic metabolite produced by other substances. For the purposes of 

this tolerance action, therefore, EPA has assumed that imidacloprid does not have 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 EPA’s website at http:// 

www.epa.gov/pesticides/cumulative.
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D. Safety Determination

1. Infants and Children.

1. In general. In the Federal Register of April 28, 2010 (FRL-8818-5), the 

EPA specified that Section 408(b)(2)(C) of FFDCA provides that EPA shall apply 

an additional tenfold (10X) margin of safety for infants and children in the case of 

threshold effects to account for prenatal and postnatal toxicity and the 

completeness of the database on toxicity and exposure unless EPA determines based 

on reliable data that a different margin of safety will be safe for infants and 

children. This additional margin of safety is commonly referred to as the FQPA SF. 

In applying this provision, EPA either retains the default value of 10X, or uses a 

different additional safety factor when reliable data available to EPA support the 

choice of a different factor. 

2. Prenatal and postnatal sensitivity. There was no quantitative or qualitative 

evidence of increased susceptibility of rat and rabbit fetuses to in utero exposure in 

developmental studies. There was no quantitative or qualitative evidence of 

increased susceptibility of rat offspring in the multi-generation reproduction study. 

There was evidence of increased qualitative susceptibility in the rat developmental 

neurotoxicity study; however, the concern is low for the following reasons: 

i. The effects in pups are well characterized with a clear NOAEL;

ii. The pup effects occur in the presence of maternal toxicity with the same 

NOAEL for effects in both pups and dams; and

iii. The doses and endpoints selected for regulatory purposes are protective of 

the pup effects noted at higher doses in the developmental neurotoxicity study. 

Therefore, there are no residual uncertainties for prenatal/postnatal toxicity in this 

study.

3. Conclusion. EPA has determined that reliable data show the safety of 

infants and children would be adequately protected if the FQPA SF were reduced to 

1X for all exposure scenarios, except acute dietary (all populations). That decision 

is based on the following findings:

i. The toxicological database for imidacloprid is complete, with the exception 

of an immunotoxicity study.

ii. The toxicology database for imidacloprid does not show any evidence of 

treatment-related effects on the immune system. The overall weight of evidence 

suggests that this chemical does not directly target the immune system. An 

immunotoxicity study is required as a part of new data requirements in 40 CFR 

part 158 for conventional pesticide registration; however, the Agency does not 

believe that conducting a functional immunotoxicity study will result in a lower 

POD than that currently used for overall risk assessment. Therefore, a database 

uncertainty factor (UFDB) is not needed to account for lack of this study.

iii. There is no evidence that imidacloprid results in increased susceptibility 

in utero to rats or rabbits in the prenatal developmental studies or in offspring in 

the 2–generation reproduction study.

iv. A developmental neurotoxicity study was performed with imidacloprid 

and well-defined NOAELs were achieved in the study.

v. There was evidence of increased qualitative susceptibility in the rat 
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developmental neurotoxicity study; however, the concern is low for reasons stated 

above.

vi. There are no residual uncertainties for prenatal/postnatal toxicity.

vii. The acute dietary food exposure assessment utilizes existing and 

proposed tolerance-level residues and 100% CT information for all commodities. 

By using these screening- level assessments, actual exposures/ risks will not be 

underestimated.

viii. The chronic food exposure assessment utilizes and proposed tolerancelevel residues and %CT data for several existing uses. For all proposed uses, 100% 

CT is assumed. The chronic assessment is somewhat refined and based on reliable 

data and will not underestimate exposure/risk.

ix. The dietary drinking water assessment utilizes water concentration values 

generated by model and associated modeling parameters which are designed to 

provide estimates of water concentrations which will not likely be exceeded.

x. The residential handler assessment is based upon the residential standard 

operating procedures (SOPs) in conjunction with chemical-specific study data in

some cases and Pesticide Handler Exposure Database (PHED) unit exposures in 

other cases. The majority of the residential post-application assessment is based 

upon chemical-specific Turf Transfer Residue (TTR) data or other chemical-specific 

post-application exposure study data. The chemical-specific study data as well as 

the surrogate study data used are reliable and also are not expected to 

underestimate risk to adults as well as to children. In a few cases where chemicalspecific data were not available, the SOPs were used alone. The residential SOPs 

are based upon reasonable ‘‘worst-case’’ assumptions and are not expected to 

underestimate risk. These assessments of exposure are not likely to underestimate 

the resulting estimates of risk from exposure to imidacloprid.

A 3X FQPA SF was retained in the form of a UFL (uncertainty factor due to 

extrapolation from a LOAEL in the absence of a NOAEL) for the acute dietary (all 

populations) exposure scenario only, since a NOAEL was not observed in the 

relevant study for that exposure scenario (acute neurotoxicity study in rats). A 3X 

uncertainty factor was judged to be adequate (as opposed to a 10X) for the following 

reasons:

1. The LOAEL (42 mg/kg) is comparable to the LOAELs seen in adults in the 

developmental rat study (30 mg/kg/day) and the 2–generation reproduction study 

[47/52 milligrams/ kilograms/day (mg/kg/day) (male/ female)] and in the offspring in 

the DNT study (55 mg/kg/day);

2. The extrapolated NOAEL of 14 mg/kg (42/3 = 14) is comparable to the 

NOAEL of 20 mg/kg/day established in the offspring in the DNT; and,

3. The neurotoxic effects in this study showed a good dose response which 

resulted in minimal effects on motor activity and locomotor activity at the LOAEL.
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E. Safety Determination

In the Federal Register of April 28, 2010 (FRL-8818-5), the EPA specified 

that EPA determines whether acute and chronic pesticide exposures are safe by 

comparing aggregate exposure estimates to the aPAD and cPAD. The aPAD and 

cPAD represent the highest safe exposures, taking into account all appropriate SFs. 

EPA calculates the aPAD and cPAD by dividing the POD by all applicable UFs. For 

linear cancer risks, EPA calculates the probability of additional cancer cases given 

the estimated aggregate exposure. Short-, intermediate, and chronic-term risks are 

evaluated by comparing the estimated aggregate food, water, and residential 

exposure to the POD to ensure that the MOE called for by the product of all 

applicable UFs is not exceeded.

1. Acute risk. An acute aggregate risk assessment takes into account 

exposure estimates from acute dietary consumption of food and drinking water. No 

adverse effect resulting from a single-oral exposure was identified and no acute 

dietary endpoint was selected. Therefore, imidacloprid is not expected to pose an 

acute risk. Using the exposure assumptions discussed in this unit for acute 

exposure, the acute dietary exposure from food and water to imidacloprid will 

occupy 70% of the aPAD for (children 1 to 2 years old) the population group 

receiving the greatest exposure.

2. Chronic risk. Using the exposure assumptions described in this unit for 

chronic exposure, EPA has concluded that chronic exposure to imidacloprid from 

food and water will utilize 32% of the cPAD for (children 1 to 2 years old) the 

population group receiving the greatest exposure. Based on the explanation in Unit 

III.C.3., regarding residential use patterns, chronic residential exposure to residues 

of imidacloprid is not expected.

3. Short-term risk. Short-term aggregate exposure takes into account shortterm residential exposure plus chronic exposure to food and water (considered to 

be a background exposure level). Imidacloprid is currently registered for crack and 

crevice uses and bed bug uses that could result in short-term residential exposure 

and the Agency has determined that it is appropriate to aggregate chronic 

exposure through food and water with short-term residential exposures to 

imidacloprid. Using the exposure assumptions described in Unit III.C.3. for shortterm exposures, EPA has concluded the combined short-term food, water, and 

residential exposures aggregated result in aggregate MOEs of 430 for adults and 170 

for children. Toddlers’ residential short-term aggregate exposure includes dermal 

and inhalation exposure from the crack and crevice uses, dermal exposure from the 

bed-bug uses, and incidental oral exposure from hand-to-mouth contact with 

treated surfaces. Adult short-term aggregate exposure includes dermal and 

inhalation exposure from indoor crack and crevice uses, and dermal exposure from 

the bed-bug uses. These exposures were higher than those calculated for all other 

residential uses of imidacloprid. Therefore, the crack and crevice and bed bug 

treatment exposure estimates were aggregated with the chronic dietary to provide a 

worst-case estimate of short- term aggregate risk for the U.S. population and 

children 1 to 2 years old. The combined short-term residential MOEs for these 

scenarios were 580 for adults and 240 for children.
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4. Intermediate-term risk. Intermediate-term aggregate exposure takes into 

account intermediate-term residential exposure plus chronic exposure to food and 

water (considered to be a background exposure level). 

Imidacloprid is currently registered for crack and crevice uses and bed 

bug uses that could result in intermediate- term residential exposure and the 

Agency has determined that it is appropriate to aggregate chronic exposure 

through food and water with intermediate-term residential exposures to 

imidacloprid.

Using the exposure assumptions described in Unit III.C.3. for short-term 

exposures, EPA has concluded the combined short-term food, water, and 

residential exposures aggregated result in aggregate MOEs of 400 for adults and 150 

for children. Toddlers’ residential intermediate-term aggregate exposure includes 

dermal and inhalation exposure from the crack and crevice uses, dermal exposure 

from the bed-bug uses, and incidental oral exposure from hand-to-mouth contact 

with treated surfaces. Adult intermediate-term aggregate exposure includes dermal 

and inhalation exposure from indoor crack and crevice uses, and dermal exposure 

from the bed-bug uses. These exposures were higher than those calculated for all 

other residential uses of imidacloprid. Therefore, the crack and crevice and bed 

bug treatment exposure estimates were aggregated with the chronic dietary 

exposure to provide a worst-case estimate of intermediate-term aggregate risk for 

the U.S. population and children 1 to 2 years old. The combined intermediate-term 

residential MOEs for these scenarios were 540 for adults and 260 for children.

5. Aggregate cancer risk for U.S. population. Based on the lack of evidence of 

carcinogenicity in mice and rats at doses that were judged to be adequate to assess 

the carcinogenic potential, imidacloprid was classified as ‘‘not likely to be 

carcinogenic to humans,’’ and is not expected to pose a cancer risk to humans. 

Therefore, a quantitative cancer risk assessment is not needed.

6. Determination of safety. Based on these risk assessments, EPA concludes 

that there is a reasonable certainty that no harm will result to the general

population, or to infants and children from aggregate exposure to imidacloprid 

residues.

F. International Tolerances

There are no established Mexican, Canadian or Codex maximum residue 

limits (MRLs) for the proposed new uses.