Document ID: EPA-HQ-OPP-2012-0204-0008
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-06-05T04:00Z

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.

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 -15C 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 [14]C-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.

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[(R)] 0.5G at an application rate of 0.50 lb ai/A; or Mallot 2F[(R)] 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.

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
144[o]C
                             The Pesticide Manual
                            Twelfth Edition (2000)
pH
5 to 11

Specific gravity
1.54 (@ 23[o]C)

Water solubility (g/L at 20[o]C)
0.61

Solvent solubility (g/L at 20[o]C)
Dichloromethane: 55, Isopropanol: 1.2, Toluene: 0.68, n-hexane: < 0.1

Vapor pressure (mPa at 20[o]C)
4 x 10[-7]

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

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.

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)
                                    PHI[1]
                                    (days)
                                  Max. # App.
                                     Min.
                                    GPA[2]
                                    RTI[3]
                                    (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 per year)
                                       
                           Protector 0.5F (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 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 -15C 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 [14]C-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).

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 KOW-based 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.
                                    LAFT[3]
                                    HAFT[3]
                                    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[(R)] 0.5B at approximately 0.50 lb ai/A, or one application of Mallet[(R)] 2F at approximately 2.0 lb ai/A.
3.  LAFT = lowest average field trial.  HAFT = highest-average field trial.

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[(R)] 0.5G, TRT 02), and one for the flowable concentrate formulation (Mallot[(R)] 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[(R)] 0.5G (TRT02) at an application rate of 0.50 lb ai/A; or Mallot[(R)] 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[(R)] 0.5G (TRT02) at an application rate of 0.50 lb ai/A; or Mallot 2F[(R)] (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.
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
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
Mexico[2]
Codex[3]
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-nitro-2-
imidazolidinimine, including metabolites containing the
6-chloropicolyl moiety

Sum of imidacloprid and its metabolites containing the 6-chloropyridinyl moiety
Commodity[1]
Tolerance (ppm)/Maximum Residue Limit (mg/kg)

US
Canada
Mexico[2]
Codex[3]
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.