Page 1 of 10 **UNITED STA TES ENVIRONMENTA**  **L PROTECTION A GENCY**  WA SHINGTON, D.C. 20460 **OFFICE OF CHEMICAL SAFETY AND**  **POLLUTION PREVENTION MEMORANDUM**  **Date:** 7 - MAR - 2013 **SUBJECT: Imidacloprid:**  Section 3 Requests for Use on Oy ster 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 **T XR 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 - py ridinyl)methyl] -N

- nitro - 2 - imidazolidinimine) on oy ster 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 in gredient (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 reque sted for the combined residues of imidacloprid and its metabolites containing the 6 - chlorop yridin yl 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 liv estock is adequatel y understood. The residue of concern in plants and livestock is imidacloprid and its metabolites containing the 6 - chloropy ridinyl moiet y, all expressed as the parent, as specified in 40 CFR §180.472.Imidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

Page 2 of 10 Adequate enforcement methods are av ailable for determination of imidacloprid residues of concern in plant [Bayer gas chromatograph y/mass spectrometry (GC/MS) Method 00200] and livestock commodities (Bayer GC/MS Method 00191). These methods have undergone successful EPA petition method vali dations (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 chromatograph y/ultraviolet (HPL C /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 oy ster stud y, o ys ter meat samples were anal yz ed for residues of imidacloprid using a GC /MS method that is derived from the tolerance - enforcement method. The method was verified on oy ster meat prior to and concurrent with sample anal ys is and is considered adequate based on acceptable recovery data. The fortification levels used in method va lidation and concurrent method recovery are adequate to bracket residues found in the submitted crop field trials. Ba ye r 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). Imidaclopri d and its metabolites were not recoverable b y these methods. The results of the MRM testing for imidacloprid were forwarded to FDA for inclusion in the Pesticide Analy tical Method Volume I(PAM I) (Memo, F. Griffith, 7/15/93, D193005). The available stor age stability data are adequate to support the submitted magnitude of residue in oy ster meat study . The maximum storage interval from collection to extraction was 112 day s (3.7 months) from collection to analy sis; including 8 day s between extraction and anal ys is. Adequate storage stability data are available indicating that residues of imidacloprid and 6 - CNA are stable in o ys ter meat at - 15  C for at least 112 day s and 119 day s, respectively . R esidues of imidacloprid have been shown to be stable in a variety of raw agricultural commodities (RACs) for up to 2 y ears (~728 day s) of storage ( Memo, F. Griffith, 6/8/95, PP#5F4480). Anal ys is of samples from the 14 C - imidacloprid plant metabolism studie s for corn, cotton, apples, and potatoes showed no loss of imidacloprid and its major metabolites during a period of 2 ye ars of frozen storage (Memo, F. Griffith, 9/21/93, D185148). No magnitude of the residue in fish or nature of the residue in fish stud ies were submitted in support of the proposed use. However, the registrant recentl y 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 o ys ter beds. The ChemSAC determined that the proposed tol erance for residues of imidacloprid and its metabolites containing the 6 - chloropy ridinyl 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

Page 3 of 10 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 [ LO Q, defined as the lowest level of method validation, LLMV (0.05 ppm)] in/on oy ster meat harvested 26 - 86 day s 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 b y adequate storage stability data. For oy sters, the Organization for Economic Co - operation and Development (OECD) tolerance - calculation procedures could not b e used to calculate a possible to lerance as residues of imidacloprid were <LOQ in/on all samples of oy ster 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 be low. 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 spec ified below is to be determined by measuring only

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

ridinyl)methyl] -N

- nitro - 2 - imidazolidinimine) and its metabolites containing the 6 - chlorop yridin yl moiet y, calculated as the stoichiometric equivalent of imidacloprid , in or on the following commodities:

Fish ................................ ................................ ................. 0. 0 5 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 variet y of crops for the control of aphids, cucumber beetles, and whiteflies (including sweet potato or silverleaf whitefly). Imidacloprid is a member of the p yrid yl methylamine class of compounds. Its mode of action is the disruption of the nervous s ys tem by

acting as an inhibitor at nicot inic acet yl choline receptors. Imidacloprid blocks the signals that are induced b y acet yl choline at the post - sy naptic membrane, resulting in normal nerve function impairment. Tolerances are currentl y established for the combined residues of imidacloprid and its metabolites containing the 6 - chlorop yridin yl 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 phy sicochemical properties of imidacloprid are presented below in Tables 1 and 2.Imidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

Page 4 of 10 **Table 1. Test Compound Nomenclature.** Chemical Structure

Common Name Imidacloprid Com pany experimental name Imidacloprid IUPAC name (EZ ) - 1 - (6 - chloro - 3 - py

ridylmethyl) -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. Param**  **eter 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(K OW )] 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. N

N N C l C

H 2 N O 2N

HImidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

Page 5 of 10 **Tab le 3**  **. Summary of Proposed Dir ections for Use of Imidacloprid.**  **Use Site**  **Trade Name**

**(EPA Reg. No.)**  **Application**

**Equipment App.** 

**Rate (lb**  **ai/A) Ma** **x.**

**Seasonal App.**  **Rate (lb ai/A)**  **PHI 1** 

**(days) Ma** **x.**

**# App.**  **Min.**

**GPA 2**  **RTI 3** 

**(days)**

Oy ster 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. RT I = 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 oy ster 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; 6/8/9 4, 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 o f imidacloprid residues in plants and livestock is adequatel y understood. The residue of concern in plants and livestock is imidacloprid and its metabolites containing the 6 - chlorop yridin yl 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 underg one successful EPA PMVs, and the registrant has fulfilled the remaining requirements for additional raw data, method validation, ILV, and an acceptable confirmatory

method (HPL C/UV Method 00357) (Memos, F. Griffith, 6/18/93, D187911; 6/1/94, D202113; 6/8/9 4, D200233; 6/8/95, D213252; and 12/18/95, D221591). TheImidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

Page 6 of 10 limit of detection (L OD) and LOQ for the GC/MS Method 00200 are 0.01 and 0.05 ppm, respectivel y, in plant commodities. In the magnitude of the residue in oy ster study , oyster meat samples were anal yz ed for residues of imidacloprid using a GC/MS method entitled “Working Analy tical Method for the Determination of Total Residues of Imidacloprid in Oy sters,” which is a modification of Bay er Method 00191 M001 - Reformatted. In the method, imidacloprid and all metabolites containing chloropy ridine moiet y are oxidized into 6 - CNA, which is then converted into trimethylsil yl 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, respectivel y. For 6 - CNA, the L OD and LOQ were calculated as 0.0048 ppm and 0.014 respectivel y. The method was verified on o ys ter meat prior to and concurrent with sample anal ys is and is considered adequate b ased 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** Ba ye r 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, D1 94206). 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 m agnitude of the residue in oy ster study , oyster meat samples were stored for a maximum of 112 day s (3.7 months) from collection to anal ys is; including 8 day s between extraction and anal ys is. Samples were stored below freezing (< - 15°C) at the field sites and at the anal yt ical laboratory

prior to extraction. Adequate storage stability data are available indicating that residues of imidacloprid and 6 - CNA are stable in oy ster meat at - 15  C for at least 112 day s and 119 day s, respectively . These data support the storage conditions and durations of imidacloprid for the oy ster meat field trial samples. In addition, r esidues of imidacloprid have been shown to be stable in a variety of RACs for up to 2 y ears (~728 day s) 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 ye ars of frozen storage (Memo, F. Griffith, 9/21/93, D185 148).Imidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

Page 7 of 10 **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 recentl y 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 b y fish, and the projected low dietary risk to sensitive populations in cases where residues of imidacloprid are found in fish (using the FI SH 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 K OW based Aquatic Bioaccumulation Model (KABAM) model (a comparable model to FISH) has been used to project res idues 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 expo sure 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 oy ster beds. However, the proposed tolerance of 0.05 ppm (L OQ) for residues of imidacloprid i n/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 FI SH) has been used to project residues of imidacloprid in fish. EFED reported that the KABA M 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 Resi due in Oy sters 48741901.der.doc **Table 4 . Summary of Residue Data from Oyster Field Trials with**  **Im idacloprid.**  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. Oy ster 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

Page 8 of 10 IR - 4 has submitted data from a study examining residues of imidacloprid in oy sters. 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 h and spreader at an application rate of approximately 0.50 ai/A. In TRT03, a single application of imidacloprid was made using a backpack spray er at an application rate of 2.0 lb ai/A. All applications were made at low tide. In WA44, TRT 02 was overappli ed by approximately

18%, and TRT 03 was underapplied b y approximately 6.5%. Oy ster samples were collected from each plot 84 - 86 day s following applications; and, additional oy ster samples were collected from the treated plots in WA43 at approximately

30 an d 60 day s. Shucked meat was retained as samples. Total residues of imidacloprid were below the LLMV (0.05 ppm) in oy ster meat harvested 26 - 86 day s following either a single application of Mallot ® 0.5G (TRT02) at an application rate of 0.50 lb ai/A; or Ma llot ® 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 oy ster meat harvested 26 - 86 day s 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 anal yz ed for total imidacloprid residues using an acceptable method, and the study is supported b y adequate storage stability

data. For o ys ters, the OECD tolerance - calculation procedures could not be used to calculate a possible to lerance as residues of imidacloprid were < LOQ in/on all samples of oy ster 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 associ ated 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 tria l 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.Imidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

Page 9 of 10 **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 (MRL s) 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: RAB1Imidacloprid Summary of Analytical Chemistry and Residue Data DP#: 400189

Page 10 of 10 **Attachment 1: IRLS Sheet.**

**Imidacloprid** (129099; Date of Request: 08/30/2012) Summary of US and International Toleran ces 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 mo iety 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 In cludes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those prop osed 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 indica te d as proposed have not been finalized by the CCPR and the CAC.