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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: 7-MAR-2013

SUBJECT: Imidacloprid: Section 3 Requests for Use on Oyster Beds.

PC Code: 129099 DP Barcode: D400189

Decision No.: 461091 Registration No.: xxx-xxx, xxx-xxx, 264-758

Petition No.: 2E7988 Regulatory Action: Section 3 Registration

Risk Assessment Type: NA Case No.: 7605

TXR No.: NA CAS No.: 138261-41-3

MRID No.: 48741901 40 CFR: §180. 472

FROM: Jennifer R. Tyler, Chemist

Risk Assessment Branch 1 (RAB1)

Health Effects Division (HED; 7509P)

THROUGH: George F. Kramer, Ph.D., Branch Senior Chemist

RAB1/HED (7509P)

TO: Sidney Jackson/Barbara Madden, RM Team 05

Registration Division (RD; 7505P)

Executive Summary

The Interregional Research Project No. 4 (IR-4) has submitted a petition (PP# 2E7988) for the 

use of imidacloprid (1-[(6-chloro-3-pyridinyl)methyl]-N-nitro-2-imidazolidinimine) on oyster 

beds to control burrowing shrimp. IR-4 has requested to add this use to the following labels: 

Protector 0.5G [a granular (G) product containing 0.5% imidacloprid as the active ingredient 

(ai); EPA Reg. No. xxx-xxx], and Protector 2F [a flowable concentrate (F) formulation 

containing 21.4% imidacloprid as the ai; EPA Reg. No. xxx-xxx). In conjunction with this 

petition, tolerances have been requested for the combined residues of imidacloprid and its 

metabolites containing the 6-chloropyridinyl moiety, all expressed as the parent, in/on fish at 

0.05 ppm, and fish-shellfish, mollusc at 0.05 ppm.

The nature of imidacloprid residues in plants and livestock is adequately understood. The 

residue of concern in plants and livestock is imidacloprid and its metabolites containing the 6-

chloropyridinyl moiety, all expressed as the parent, as specified in 40 CFR §180.472.
Imidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

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Adequate enforcement methods are available for determination of imidacloprid residues of 

concern in plant [Bayer gas chromatography/mass spectrometry (GC/MS) Method 00200] and 

livestock commodities (Bayer GC/MS Method 00191). These methods have undergone 

successful EPA petition method validations (PMVs), and the registrant has fulfilled the 

remaining requirements for additional raw data, method validation, independent laboratory

validation (ILV), and an acceptable confirmatory method [high-performance liquid 

chromatography/ultraviolet (HPLC/UV) Method 00357] (Memos, F. Griffith, 6/18/93, D187911; 

6/1/94, D202113; 6/8/94, D200233; 6/8/95, D213252; and 12/18/95, D221591). In the 

magnitude of the residue in oyster study, oyster meat samples were analyzed for residues of 

imidacloprid using a GC/MS method that is derived from the tolerance-enforcement method. 

The method was verified on oyster meat prior to and concurrent with sample analysis and is 

considered adequate based on acceptable recovery data. The fortification levels used in method 

validation and concurrent method recovery are adequate to bracket residues found in the 

submitted crop field trials.

Bayer Corporation previously submitted adequate multiresidue (MRM) recovery data for 

imidacloprid and the metabolites 5-hydroxy imidacloprid, imidacloprid olefin, des nitro 

imidacloprid, and 6-chloronicotinic acid (6-CNA) through Food and Drug Administration (FDA) 

Protocols A through E (Memos, F. Griffith, 6/18/93, D187911; 7/15/93, D193027; 6/8/94, 

D200233; and 6/22/94, D194206). Imidacloprid and its metabolites were not recoverable by 

these methods. The results of the MRM testing for imidacloprid were forwarded to FDA for 

inclusion in the Pesticide Analytical Method Volume I (PAM I) (Memo, F. Griffith, 7/15/93, 

D193005).

The available storage stability data are adequate to support the submitted magnitude of residue in 

oyster meat study. The maximum storage interval from collection to extraction was 112 days 

(3.7 months) from collection to analysis; including 8 days between extraction and analysis. 

Adequate storage stability data are available indicating that residues of imidacloprid and 6-CNA 

are stable in oyster meat at -15C for at least 112 days and 119 days, respectively. Residues of 

imidacloprid have been shown to be stable in a variety of raw agricultural commodities (RACs)

for up to 2 years (~728 days) of storage (Memo, F. Griffith, 6/8/95, PP#5F4480). Analysis of 

samples from the 14C-imidacloprid plant metabolism studies for corn, cotton, apples, and 

potatoes showed no loss of imidacloprid and its major metabolites during a period of 2 years of 

frozen storage (Memo, F. Griffith, 9/21/93, D185148).

No magnitude of the residue in fish or nature of the residue in fish studies were submitted in 

support of the proposed use. However, the registrant recently submitted a waiver request for 

both studies. The request was presented to the HED Science Advisory Council for Chemistry

(ChemSAC) on 23-FEB-2011, and the ChemSAC agreed with the rationale for the waiver 

(ChemSAC Minutes). Therefore, data demonstrating the magnitude of the residue or nature of 

the residue in fish are not necessary to support of the proposed use on oyster beds. The 

ChemSAC determined that the proposed tolerance for residues of imidacloprid and its metabolites 

containing the 6-chloropyridinyl moiety, all expressed as the parent, in/on fish at 0.05 ppm is 

appropriate.
Imidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

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The submitted magnitude of the residue study in oysters was conducted in accordance with 

OPPTS Guideline 860.1400, and the data are adequate to support the proposed use. Total 

residues of imidacloprid were less than limit of quantitation [LOQ, defined as the lowest level of 

method validation, LLMV (0.05 ppm)] in/on oyster meat harvested 26-86 days following either a 

single application of Mallot®0.5G at an application rate of 0.50 lb ai/A; or Mallot 2F®at an 

application rate of 2.0 lb ai/A. Samples were analyzed for total imidacloprid residues using an 

acceptable method, and the study is supported by adequate storage stability data. For oysters, the 

Organization for Economic Co-operation and Development (OECD) tolerance-calculation 

procedures could not be used to calculate a possible tolerance as residues of imidacloprid were 

<LOQ in/on all samples of oyster meat. Therefore, the tolerance of 0.05 ppm for fish-shellfish, 

mollusc is appropriate (see Section 860.1550 Proposed Tolerances).

Regulatory Recommendations and Residue Chemistry Deficiencies

HED concludes that the residue chemistry database is sufficient for unconditional registration 

and establishment of permanent tolerances for imidacloprid in or on the commodities listed 

below.

a) General. Tolerances are established for residues of the insecticide imidacloprid, including its 

metabolites and degradates, in or on the commodities in the table below. Compliance with the 

tolerance levels specified below is to be determined by measuring only the sum of imidacloprid

(1-[6-chloro-3-pyridinyl)methyl]-N-nitro-2-imidazolidinimine) and its metabolites containing the 

6-chloropyridinyl moiety, calculated as the stoichiometric equivalent of imidacloprid, in or on 

the following commodities:

Fish.................................................................................0.05 ppm

Fish-shellfish, mollusc ...................................................0.05 ppm

A human-health risk assessment for imidacloprid is forthcoming.

Background

Imidacloprid is an insecticide registered for uses on a variety of crops for the control of aphids, 

cucumber beetles, and whiteflies (including sweet potato or silverleaf whitefly). Imidacloprid is 

a member of the pyridylmethylamine class of compounds. Its mode of action is the disruption of 

the nervous system by acting as an inhibitor at nicotinic acetylcholine receptors. Imidacloprid 

blocks the signals that are induced by acetylcholine at the post-synaptic membrane, resulting in 

normal nerve function impairment.

Tolerances are currently established for the combined residues of imidacloprid and its 

metabolites containing the 6-chloropyridinyl moiety, all expressed as the parent, under 40 CFR 

§180.472 in/on various plant and livestock commodities. Indirect or inadvertent tolerances are 

established as a result of application of the pesticide to growing crops and other non-food crops 

under 40 CFR §180.472(d). The nomenclature and physicochemical properties of imidacloprid 

are presented below in Tables 1 and 2.
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Table 1. Test Compound Nomenclature.

Chemical Structure

Common Name Imidacloprid

Company experimental name Imidacloprid

IUPAC name (EZ)-1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine

CAS name 1-[(6-chloro-3-pyridinyl)methyl]-N-nitro-2-imidazolidinimine

CAS # 138261-41-3

End-use products/(EP) Protector 2F (EPA Reg. No. xxx-xxx)

Protector 0.5G (EPA Reg. No. xxx-xxx) 

Table 2. Physicochemical Properties of the Technical Grade Test Compound. 

Parameter Value Reference

Melting point 144oC

The Pesticide 

Manual

Twelfth Edition 

(2000)

pH 5 to 11

Specific gravity 1.54 (@ 23oC)

Water solubility (g/L at 20oC) 0.61

Solvent solubility (g/L at 20oC) Dichloromethane: 55, Isopropanol: 1.2, 

Toluene: 0.68, n-hexane: < 0.1

Vapor pressure (mPa at 20oC) 4 x 10-7

Octanol/water partition coefficient [Log(KOW)] 0.57 (21oC)

UV/visible absorption spectrum Not provided.

860.1200 Directions for Use

The petitioner has submitted draft labels for the Protector 0.5G (EPA Reg. No. xxx-xxx), and 

Protector 2G (EPA Reg. No. xxx-xxx). A summary of the proposed use patterns is detailed in 

Table 3.

N

N

N

Cl

C

H2

N

O2N

H
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Table 3. Summary of Proposed Directions for Use of Imidacloprid.

Use 

Site

Trade Name 

(EPA Reg. 

No.)

Application 

Equipment

App. 

Rate

(lb ai/A)

Max.

Seasonal 

App. 

Rate

(lb ai/A)

PHI1

(days)

Max.

# 

App.

Min.

GPA2

RTI3

(days)

Oyster 

beds

Protector 0.5G 

(xxxxx-xx)

Drop/rotary spreader

Tractor-drawn 

spreader

Belly grinder

Helicopter

0.5 0.5 30 1 NA NA

(only 1 

treatment 

per acre 

Protector 0.5F per year)

(xxxxx-xx)

Groundboom

Helicopter

Backpack

0.5 0.5 30 1

ground: 5

air: 2

Restrictions:

 Not for sale to any persons other than a member of the Willapa-Greys Harbor Oyster Growers Association.

 A single application/year is allowed.

 No adjuvants or surfactants allowed.

 Aerial applications must be made on beds exposed at low tide.

 Applications from a floating platform or boat may be made under water using a calibrated granular applicator.

 All application must be made between April 15 and December 15. Do not apply aerially during Federal Holidays.

 During aerial applications, all public access areas and public boat launches within 1⁄4 mile radius of bed shall be 

posted.

1. PHI = pre-harvest interval.

2. GPA = gallons of water per acre.

3. RTI = retreatment interval.

HED Conclusions: The use directions provided by the petitioner are adequate to allow 

evaluation of the residue data relative to the proposed use of imidacloprid on oyster beds to 

control ghost shrimp.

860.1300 Nature of the Residue - Plants and Livestock

Data concerning the metabolism of imidacloprid in apples, potatoes, tomatoes, eggplant, 

cottonseed, field corn, tobacco, ruminants, and poultry have been submitted and reviewed 

(Memos, F. Griffith, 9/20/93, DP# 185148; 6/8/94, DP# 200233; and 2/29/96, DP# 217632). 

The results of the aforementioned plant and livestock metabolism studies were presented to the 

HED Metabolism Assessment Review Committee (MARC) on 6/22/93 (Memo, F. Griffith, 

6/25/93, TXR#: 0050886). The nature of imidacloprid residues in plants and livestock is 

adequately understood. The residue of concern in plants and livestock is imidacloprid and its 

metabolites containing the 6-chloropyridinyl moiety, all expressed as the parent, as specified in 

40 CFR §180.472.

860.1340 Residue Analytical Methods

Adequate enforcement methods are available for determination of imidacloprid residues of 

concern in plant (Bayer GC/MS Method 00200) and livestock commodities (Bayer GC/MS 

Method 00191). These methods have undergone successful EPA PMVs, and the registrant has 

fulfilled the remaining requirements for additional raw data, method validation, ILV, and an 

acceptable confirmatory method (HPLC/UV Method 00357) (Memos, F. Griffith, 6/18/93, 

D187911; 6/1/94, D202113; 6/8/94, D200233; 6/8/95, D213252; and 12/18/95, D221591). The 
Imidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

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limit of detection (LOD) and LOQ for the GC/MS Method 00200 are 0.01 and 0.05 ppm, 

respectively, in plant commodities.

In the magnitude of the residue in oyster study, oyster meat samples were analyzed for residues 

of imidacloprid using a GC/MS method entitled “Working Analytical Method for the 

Determination of Total Residues of Imidacloprid in Oysters,” which is a modification of Bayer 

Method 00191 M001-Reformatted. In the method, imidacloprid and all metabolites containing 

chloropyridine moiety are oxidized into 6-CNA, which is then converted into trimethylsilyl ester 

prior to quantitation using GC/MS. For imidacloprid, based on the recoveries of samples 

fortified at the lowest LLMV, the LOD and LOQ were calculated as 0.014 ppm and 0.042 pm, 

respectively. For 6-CNA, the LOD and LOQ were calculated as 0.0048 ppm and 0.014 

respectively. The method was verified on oyster meat prior to and concurrent with sample 

analysis and is considered adequate based on acceptable recovery data. The fortification levels 

used in method validation and concurrent method recovery are adequate to bracket residues 

found in the submitted crop field trials.

860.1360 MRM

Bayer Corporation previously submitted adequate MRM recovery data for imidacloprid and the 

metabolites 5-hydroxy imidacloprid, imidacloprid olefin, des nitro imidacloprid and 6-CNA 

through FDA Protocols A through E (Memos, F. Griffith, 6/18/93, D187911; 7/15/93, D193027; 

6/8/94, D200233; and 6/22/94, D194206). Imidacloprid and its metabolites were not recoverable 

by these methods. The results of the MRM testing for imidacloprid were forwarded to FDA for 

inclusion in the PAM I (Memo, F. Griffith, 7/15/93, D193005).

`860.1380 Storage Stability

In the magnitude of the residue in oyster study, oyster meat samples were stored for a maximum 

of 112 days (3.7 months) from collection to analysis; including 8 days between extraction and 

analysis. Samples were stored below freezing (<-15°C) at the field sites and at the analytical 

laboratory prior to extraction. Adequate storage stability data are available indicating that 

residues of imidacloprid and 6-CNA are stable in oyster meat at -15C for at least 112 days and 

119 days, respectively. These data support the storage conditions and durations of imidacloprid

for the oyster meat field trial samples. 

In addition, residues of imidacloprid have been shown to be stable in a variety of RACs for up to 

2 years (~728 days) of storage (Memo, F. Griffith, 6/8/95, PP#5F4480). Analysis of samples 

from the 14C-imidacloprid plant metabolism studies for corn, cotton, apples, and potatoes showed 

no loss of imidacloprid and its major metabolites during a period of 2 years of frozen storage 

(Memo, F. Griffith, 9/21/93, D185148).
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860.1400 Water, Fish, and Irrigated Crops

Magnitude of the Residue in Fish and Nature of the Residue in Fish

No magnitude of the residue in fish or nature of the residue in fish studies were submitted in 

support of the proposed use. However, the registrant recently submitted a waiver request for 

both studies. The rationale in support of the waiver request was based on both the projected lack 

of significant uptake by fish, and the projected low dietary risk to sensitive populations in cases 

where residues of imidacloprid are found in fish (using the FISH model).

HED Conclusions: The waiver request was presented to the HED ChemSAC on 23-FEB-2011, 

and the ChemSAC concluded the following (ChemSAC Minutes):

ChemSAC agreed that no fish metabolism or magnitude of the residue data are needed to support 

this use. However, it was suggested that risk assessment team contact EFED to see if their KOWbased Aquatic Bioaccumulation Model (KABAM) model (a comparable model to FISH) has been 

used to project residues of imidacloprid in fish; and if so, were the results similar to the FISH 

model results. The ChemSAC also agreed that tolerances at the LOQ may need to be established 

for residues of imidacloprid in fish. The ChemSAC determined that there is a potential for 

Environmental Justice problems with this use. The risk assessment team should consult the most 

recent carbaryl RED for further guidance on this matter. It was noted that the carbaryl 

assessment should also be used as an example of a swimmer exposure assessment.

Therefore, data demonstrating the magnitude of the residue or nature of the residue in fish are 

not necessary to support of the proposed use on oyster beds. However, the proposed tolerance of 

0.05 ppm (LOQ) for residues of imidacloprid in/on fish is appropriate (see Section 860.1550 

Proposed Tolerances).

It should be noted the EFED was contacted to see if their KABAM model (a comparable model 

to FISH) has been used to project residues of imidacloprid in fish. EFED reported that the 

KABAM model has not been used for imidacloprid (personal communication between J. Tyler 

and M. Barrett, 20-AUG-2012). Due to imidalcoprid’s low Kow (3.7 @21°C) and low toxicity

to fish, accumulation values are expected to be negligible.

Magnitude of the Residue in Oysters

48741901.der.doc

Table 4. Summary of Residue Data from Oyster Field Trials with Imidacloprid.

Commodity Total App. 

Rate (lb ai/A)2

PHI 

(days)

Residue Levels (ppm)1

n

Sample

Min.

Sample

Max. LAFT3 HAFT3 Median Mean Std. Dev.

Oyster Meat

0.525-0.590

28 2 ND ND - - - - -

57 2 ND ND - - - - -

84-86 6 ND <0.05 - - - - -

1.87-2.02

27 2 <0.05 <0.05 - - - - -

56 2 <0.05 <0.05 - - - - -

84-85 6 ND <0.05 - - - - -

1. LLMV= 0.05 ppm.

2. One application of Mallot®0.5B at approximately 0.50 lb ai/A, or one application of Mallet®2F at approximately 2.0 lb ai/A.

3. LAFT = lowest average field trial. HAFT = highest-average field trial.
Imidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

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IR-4 has submitted data from a study examining residues of imidacloprid in oysters. Three 

supervised irrigated crop trials were conducted in Washington [North American Free Trade 

Agreement (NAFTA)] Growing Zone 12 during the 2010 growing season.

Two treated plots were established in each trial, one for the granular formulation (Mallot®0.5G, 

TRT 02), and one for the flowable concentrate formulation (Mallot®2F, TRT 03). In TRT02, a 

single application of imidacloprid was made using either a drop spreader or hand spreader at an 

application rate of approximately 0.50 ai/A. In TRT03, a single application of imidacloprid was 

made using a backpack sprayer at an application rate of 2.0 lb ai/A. All applications were made 

at low tide. In WA44, TRT 02 was overapplied by approximately 18%, and TRT 03 was 

underapplied by approximately 6.5%. Oyster samples were collected from each plot 84-86 days 

following applications; and, additional oyster samples were collected from the treated plots in 

WA43 at approximately 30 and 60 days. Shucked meat was retained as samples.

Total residues of imidacloprid were below the LLMV (0.05 ppm) in oyster meat harvested 26-86 

days following either a single application of Mallot®0.5G (TRT02) at an application rate of 0.50 

lb ai/A; or Mallot®2F (TRT03) at an application rate of 2.0 lb ai/A.

HED Conclusions: The magnitude of the residue study was conducted in accordance with 

OPPTS Guideline 860.1400, and the data are adequate to support the proposed use. Total 

residues of imidacloprid were <LLMV (0.05 ppm) in/on oyster meat harvested 26-86 days 

following either a single application of Mallot®0.5G (TRT02) at an application rate of 0.50 lb 

ai/A; or Mallot 2F®(TRT03) at an application rate of 2.0 lb ai/A. Samples were analyzed for 

total imidacloprid residues using an acceptable method, and the study is supported by adequate 

storage stability data.

For oysters, the OECD tolerance-calculation procedures could not be used to calculate a possible 

tolerance as residues of imidacloprid were <LOQ in/on all samples of oyster meat. Therefore, 

the recommended tolerance is 0.05 ppm for fish-shellfish, mollusc is appropriate (see Section 

860.1550 Proposed Tolerances).

860.1480 Meat, Milk, Poultry, and Eggs

There are no livestock feed items associated with the proposed use; therefore, residue data on 

livestock commodities are not required to support the subject petition.

860.1500 Crop Field Trials

As there are no proposed uses on primary crops associated with the subject petition, crop field 

trial data are not required.

860.1520 Processed Food and Feed

As there are no processed commodities associated with the proposed use, a processing study is 

not required to support the subject petition.
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860.1550 Proposed Tolerances

A summary of the proposed and recommended tolerances for the proposed uses are listed in

Table 5.

Table 5. Tolerance Summary for Imidacloprid.

Commodity

Proposed 

Tolerance 

(ppm)

Currently 

Established 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments

(correct commodity definition)

fish 0.05 - 0.05

fish-shellfish, mollusc 0.05 - 0.05

There are currently no established Codex, Canadian, or Mexican maximum residue limits 

(MRLs) for imidacloprid on fish or molluscs. An International Residue Limit Status Sheet is 

attached in Appendix I.

860.1850 and 860.1900 Confined/Field Accumulation in Rotational Crops

According to the current guidance, rotational crop studies are not required for the subject 

petitions.

Attachment 1: IRLS Sheet.

cc: J. Tyler

RDI: RAB1 Chemists (9/xx/12); G. Kramer (9/7/12)

J. Tyler: S-10943: Potomac Yard 1 (PY1): (703) 305-5564: 7509P: RAB1
Imidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

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Attachment 1: IRLS Sheet.

Imidacloprid (129099; Date of Request: 08/30/2012)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR §180.472:

sum of imidacloprid (1-[6-chloro-3-

pyridinyl)methyl]-N-nitro-2-

imidazolidinimine) and its metabolites 

containing the 6-chloropyridinyl moiety, 

calculated as the stoichiometric equivalent 

of imidacloprid

1-[(6-chloro-3-

pyridinyl)methyl]-N-nitro2-

imidazolidinimine, 

including metabolites 

containing the

6-chloropicolyl moiety

Sum of 

imidacloprid and 

its metabolites 

containing the 6-

chloropyridinyl 

moiety

Commodity1 Tolerance (ppm)/Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex3

fish 0.05

fish, shellfish, mollusc 0.05

Completed: M. Negussie; 08/31/2012

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the 

applicant.

2 Mexico 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. MRLs indicated as proposed 

have not been finalized by the CCPR and the CAC.