Acetamiprid DP No.: 369474

Page 1 of 63 UNITED STATES ENVIRONMENTAL PROTECTI ON AGENCY WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES D ec 1, 2009 MEMORANDUM SUBJECT: Acetamiprid : Human Health Risk Assessment for Proposed Food Use s on Clover

Grown for Seed , Small Vine Climbing Fruits, except Kiwifruit, Subgroup 13 - 07F, Greenhouse Grown Tomatoes and Tea . PC Code: 099050 DP Barcode: D 369474 Decision No.: 408298 Registration No s . : 8033 - 23, 8033 - 36, 8033 - 94 Petition No.: 9E7544 Regulatory Acti on: Amended Section 3 Risk Assessment Type: Single Chemical Aggregate Case No.: N/A T XR No.: N/A CAS No.: 135410 - 20 - 7 MRID No s .: N/A 40 CFR: §180.578 FROM: Dennis McNeill y, Chemist

Suku Oonnithan, Biologist Edward J. Scollon, Ph . D . , Toxico logist Registration Action Branch 2 Health Effects Division (7509 P ) THROUGH: Mike Doherty, Ph.D, Senior Chemist

Alan Lev y, Ph.D., Senior Toxicologist Shih - Chi Wang, Biologist and Christina Swartz, Branch Chief Richard Loranger, Ph . D . , Senior Scienti st Registration Action Branch 2 Health Effects Division (7509 P ) TO: Laura Nollen, Risk Manager Reviewer

Barbara Madden, Team Leader (RM Team 5) RIMUERB/Registration Division (RD) (7505P)Acetamiprid DP No.: 369474

Page 2 of 63 Table of Contents 1.0 Executive Summary ................................ ................................ ................................ ............... 4 1.1 Summary

of Recommendations ................................ ................................ ............................... 7 1.2 Summary

of Proposed Uses ................................ ................................ ................................ ..... 8 2.0 Ingredient Profile ................................ ................................ ................................ ................. 11 3.0 Hazard Characterization/Assessment ................................ ................................ ........... 12 3.1 Hazard and Dose - Res ponse Characterization ................................ ....................... 12 3.1.1 Database Summary ................................ ................................ ................... 12 3.1.1.1 Studies available and considered (animal, human, general literature ) ................................ ................................ ....................... 12 3.1.1.2 Mode of action ................................ ................................ .............. 12 3.1.1.3 Sufficiency

of studies/data ................................ ............................ 13 3.1.2 Toxicological Effects ................................ ................................ ................ 13 3.1.3 Dose - response ................................ ................................ ........................... 15 3.1.4 FQPA 15 3.2 Absorption, Distribution, Metabolism, Excretion (ADME) ................................ . 16 3.3 FQPA Considerations ................................ ................................ ........................... 16 3.3.1 Adequacy

of the Toxicity Database ................................ .......................... 16 3.3.2 Evidence of Neurotoxicity ................................ ................................ ........ 16 3.3.3 Developmental Toxicity Studies ................................ ............................... 17 3.3.4 Reproductive Toxicity Study ................................ ................................ .... 17 3.3.5 Additional Information from L iterature Sources ................................ ...... 17 3.3.6 Pre - and/or Postnatal Toxicity ................................ ................................ ... 17 3.3.6.1 Determination of Susceptibility ................................ .................... 17 3.3.6.2 Degree of Concern Analysis and Residual Uncertainties for Pre and/or Postnatal Susceptibility ................................ ...................... 17 3.3.7 Recommendation for a Developmental Neurotoxicity Study ................... 18 3.4 Safety

Fact or for Infants and Children ................................ ................................ .. 18 3.5 Hazard Identification and Toxicity Endpoint Selection ................................ ........ 19 3.5.1 Acute Reference Dose (aRfD) - Females age 13 - 49 ................................ . 19 3.5.2 Acute Reference Dose (aRfD) - General Population ................................ 19 3.5.3 Chronic Reference Dose (cRfD) ................................ ............................... 19 3.5.4 In cidental Oral Exposure (Short - and Intermediate - Term) ....................... 20 3.5.5 Dermal Absorption ................................ ................................ .................... 20 3.5.6 Dermal Exposure (Short - , Intermediate - and Long - Term) ....................... 21 3.5.7 Inhalation Exposure (Short - , Intermediate - and Lo ng - Term) ................... 22 3.5.8 Level of Concern for Margin of Exposure ................................ ................ 23 3.5.9 Recommendation for Aggregate Exposure Risk Assessments ................. 24 3.5.10 Classification of Carcinogenic Potential ................................ ................... 24 3.5.11 Summary

of Toxicological Doses and Endpoints for Use in Human Risk Assessments ................................ ................................ .............................. 25 3.6 Endocrine disruption ................................ ................................ ............................. 27 4.0 Public Health and Pesticide Epidemiology Data ................................ .......................... 27 4.1 Other Pesticide Epidemiolo gy Published L iterature ................................ ............. 27Acetamiprid DP No.: 369474

Page 3 of 63 5.0 Dietary Exposure/Risk Characterization ................................ ................................ ..... 27 5.1 Pesticide Metabolism and Environmental Degradation ................................ ........ 27 5.1.1 Metabolism in Primary Crops ................................ ................................ ... 27 5.1.2 Metabolism in Rotational Crops ................................ ............................... 27 5.1.3 Metabolism in L ivestock ................................ ................................ ........... 28 5.1.4 Analy

tical Methodology ................................ ................................ ........... 28 5.1.5 Environmental Degradation ................................ ................................ ...... 29 5.1.6 Comparative Metabolic Profile ................................ ................................ . 29 5.1.7 Pesticide Metabolites and Degradates of Concern ................................ .... 30 5.1.8 Drinking Water Residue Profile ................................ ................................ 30 5.1.9 Food Residue Profile ................................ ................................ ................. 31 5.1.10 International Residue Limits ................................ ................................ ..... 37 6.0 Residential (Non - Occupational) Exposure/Risk Characterization ............................ 40 6.1 Residential Handler Exposure ................................ ................................ ............... 41 6.2. Residential Postapplication Exposure ................................ ................................ ... 41 6.3 Other (Spray

Drift, etc .) ................................ ................................ ........................ 43 7.0 Agg regate Risk Assessments and Risk Characterization ................................ ............ 43 7.1 Acute Term Aggregate Risk ................................ ................................ ................. 43 7.2 Short - and Intermediate - Term Aggregate Risk ................................ ..................... 43 7.3 Chronic - Term Aggregate Risk ................................ ................................ .............. 44 8.0 Cumulative Risk Characterization/Assessment ................................ ........................... 45 9.0 Occupational Exposure/Risk Pathway ................................ ................................ .......... 46 9.1 Short - /Intermediate - /L ong - Term Handler Risk ................................ .................... 46 9.2 Handler and Pesticide Control Operator Risk Characterization ........................... 46 9.3 Postapplication Exposure and Risk ................................ ................................ ....... 46 10.0 Data Needs and Lab el Recommendations ................................ ................................ .... 47 References: ................................ ................................ ................................ ................................ ... 48 Appendix A: Occupational Exposure and Risk Tables ................................ .............. 50 Appendix B: Toxicology Assessment ................................ ................................ ........... 57 Appendix C: Tolerance Summary ................................ ................................ ................ 62 Appendix D: International Residu e Limit Status ................................ ....................... 63Page 4 of 63

1.0 E xecutive Summary Acetamiprid { N 1

- [(6 - chloro - 3 - py ridyl )meth yl ] -N 2

- cyano -N 1

- methylacetamidine } is a chloronicotinyl insecticide registered to control sucking type in sects (e.g., aphids, whitefly , etc.) on a wide variety

of crops including cotton, leafy vegetables, fruiting vegetables, and citrus fruits. Tolerances are established for acetamiprid residues in assorted crops and livestock commodities under 40 CFR § 180.5 78. The majority of the agricultural uses are for broadcast foliar spray

(via ground or aerial equipment), but there are also registered seed treatment uses on mustard and canola. R eady- to - use , bait , and water soluble packet formulation s are registered f or residential uses. The Interregional Research Project Number 4 (IR - 4) has submitted amended Section 3 registration requests for new uses of acetamiprid on clover grown for seed, small vine climbing fruits, except kiwifruit, subgroup 13 - 07F (amending the established grape use), greenhouse - grown tomatoes , and tea . Tea was not in cluded in the original petition, but was added in a June 10, 2009 letter from IR - 4 stating that the tolerance was submitted to support both tea grown in South Carolina and tea imp orted into the U.S. The acute toxicity

data indicate that acetamiprid is moderatel y toxic via the oral route and is minimally

toxic via the dermal and inhalation routes . Acetamiprid is not an eye or skin irritant, and it is not a dermal sensitizer . The toxicological database for acetamiprid is not complete. As part of the new 40 CFR Part 158 guidelines, an immunotoxicity study in rats and/or mice is required. However , a database uncertainty factor is not needed because acetamiprid does not show an y evi dence of treatment - related effects on the immune sy stem. The overall weight of evidence suggests that this chemical does not directly target the immune system and the Agency does not believe that conducting a functional immunotoxici ty study will result in a lower point of departure ( POD ) than that currentl y use d for overall risk assessment. Based on subchronic, chronic, developmental and reproductive studies in rats, rabbits, and dogs, a cetamiprid does not appear to have specific target organ toxicity . An acceptable developmental neurotoxicity (DNT) study has been submitted and reviewed. Developmental studies showed no evidence of either quantitative or qualitative susceptibility of the rat or rabbit fetuses from in utero exposure. However, both the DNT study and the multi generation reproduction studies show ed an increas e in qualitative susceptibility of pups; effects in pups consisted of decreased pup viability , and maternal toxicity consisted of decreased body weight and body weight gain. HED has redu ced the FQPA Safety Factor to 1X, because : (i) the endpoints selected for risk assessment are based upon the effects of concern in offspring ; (ii) there is a clear NOAEL for the offspring effects ; and, (iii) HED has n o residual uncertainties with regards t o pre - and postnatal toxicity . HED has determined that acetamiprid is not likely to be carcinogenic to humans. With the exception of chronic dietary , HED has chosen the NOAEL (10 mg/kg/day) from the DNT study

(LOAEL = 45 mg/kg/day) as the endpoint and d ose for dietary , non - occupational and occupational risk assessments for all durations and all routes of exposure. For the chronic dietary assessment, HED has chosen the NOAEL (7.1 mg/kg/day) from the chronic toxicity / carcinogenicity study

(LOAEL = 1 7. 5 m g/kg/day).Page 5 of 63

HED has used the refined dermal penetration value of 10% . The default 100% absorption factor was used for all inhalation exposure scenarios. The nature of the residue is adequatel y understood for both plants and animals, and an acceptable me thod validation has been submitted. Acceptable residue data have been submitted to support the proposed uses as well as the tolerances recommended in Appendix C . T he submitted clover field trial data are not completely adequate to satisfy data requirements. The three clover field trials were all conducted in Zone 11 (OR) at the same location and within a very short time period of each other. As a condition of registration, HED recommends that two additional clover field trials be required, as confirmato ry data. In addition, the submitted reside data included field trial data for onl y the 70WP formulation. However, additional residue chemistry field trial data are not required to support registration of the 30SG formulation. Since the residue chemistry data submitted for clover hay reflect PHIs of between 56 - 63 day s, the PHI for clover should be increased to 56 day s for any crop which will be harvest ed for hay . The submitted grape residue data included field trial data for onl y the 70WP formulation (original field trials also used only a 70WP formulation). Although HED’s residue chemistry review (D364833, 10/14/09) recommended that a s a condition of registration, three side - by- side field trials be conducted and submitted to determine if residues are co mparable for the two different formulations , additional information provided by the registrant has convinced HED such data are not necessary . In addition, the submitted grape field trials were not conducted using an adjuvant . The label for Assail® 30SG ( EPA Reg. No. 8033 - 36) should be revised to remove the use of a spreader, methylated seed oil or crop oil f rom the product label . Furthermore, in line with present OPP policy for a late season foliar use, a statement should be added to both the 30SG and 70 WP labels prohibiting addition of adjuvants for application to grapes. If use of an a djuvant is desired then one should be used in side - by- side testing . Although the greenhouse trials were conducted at a 2x rate and the number of trials is marginal, no a dditional residue data will be required to support the proposed greenhouse use pattern for tomatoes. T he tomato greenhouse data indicate that acetamiprid residues resulting from applications of Assail 70WP formulation of acetamiprid according to the propo sed use pattern would not exceed the established tolerance for residues of acetamiprid in fruiting vegetables, C rop Group 8 (0.20 ppm). Although n o data were provided for the proposed use of Tristar® 30SG on greenhouse tomatoes , HED now concludes the WP d ata support use of this additional formulation. The submitted magnitude of the residue data for tea reflect application of a 20% SP formulation of acetamiprid to green tea grown in Japan at 0.13 lb ai/A (0.15 kg ai/ha) and 0.27 lb ai/A (0.30 kg ai/ha) and to black tea grown in India at 0.022 lb ai/A (0.025 kg ai/ha) and 0.045 lb ai/A (0.050 kg ai/ha). Acceptable methods were used for determination residues of acetamiprid and metabolites determined as acetamiprid. No U.S. residue field trial data were sub mitted and proposed domestic use directions were not provided. At least one U.S. residue field trial study is required to establish a domestic registration for use of acetamiprid on tea. The dietary

assessment is partially

refined, using field trial data , percent crop - treated values , and various empirical processing factors. Estimated drinking water concentrations (EDWCs) , whichPage 6 of 63

are based upon the highest application values of all registered and proposed uses, have been incorporated directl y into the die tary exposure model. A cute and chronic dietary risk estimates for all population subgroups d o not indicate a risk of concern . C hildren 1 - 2 years old are the highest exposed population subgroup for both acute and chronic exposure scenarios. Acute exposur e constitute s 41 % of the acute population adjusted dose (aPAD) , and the chronic exposure constitute s 12 % of the chronic population adjusted dose (cPAD) . Aggregate risk assessment s for acute, short - term , and chronic durations w ere conducted. Residential e xposures incorporat ed into the aggregate assessments are based on currentl y registered residential uses (indoor crack and crevice , and outdoor perimeter treatment) . All aggregate assessments indicate no risks of concern ( aggregate MOEs ≥ 2 90 ) . Occupation al handler (mix er /load ers, appli cators, and flaggers ) assessments were conducted for the proposed agricultural uses of acetamiprid . HED’s assessment indicate s that exposures to occupational handlers are not a risk concern , provided they wear baseline pers onal protective equipment (PPE) c onsisting of long - sleeved shirt, long pants, and shoes with socks plus gloves (MOEs > 280) . HED identified no post - application risk concerns (MOEs > 3 3 0) for the proposed uses on the day of application , and set the restricted entry interval (REI) at 12 hours based upon the acute toxicity categories of acetamiprid. Environmental Justice Considerations Potential areas of environmental justice concerns, to the extent possible, were considered for this human health risk ass essment, in accordance with US Executive Order 12898, Federal Actions to Address Environmental Justice in Minority Populations and L ow - Income Populations, http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf . As a part of every

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well - established procedures. In line with OPP policy , HED estimates risks to population subgroups from pesticide e xposures that are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by USDA under the CSFII, and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are anal yz ed and categorized by subgroups based on age, season of the ye ar, ethnic group, and region of the country . Whenever appropriate, non - dietary exp osures based on home use of pesticide products, associated risks for adult applicators and for toddlers, yo uths, and adults entering or playing on treated areas post - application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to by standers and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups. Review of Human Research This risk assessment relies in part on data from studies in which adult human subjects were intentionally

exposed to a pesticide or other chemical. These studies, which comprise the Pesticide Handlers Exposure Database (PHED), have been determined to require a review ofPage 7 of 63

their ethical conduct, and have received that review. The studies in PHED were considered appropriate (or ethically

conducted) for use in risk assessments . 1.1 Summary of Recommendation s (see also Section 10.0) Directions for Use : No proposed use was submitted for the use on tea in South Carolina. HED cannot evaluate the domestic use without a proposed use, application methods, and a proposed formulation. Good Agricultural Practice ( GAP ) information was provided for Japan and India. The use directions are adequate to establish a tolerance without U.S. registrations (an “import” tolerance). Because the grape field trial data submitted with this petition did not reflect the use of a surfactant in the application spray s, the label directions regarding use of a spreader, methylated seed oil or crop oil should be removed from the product label of Assail® 30SG (EPA Reg. No. 8033 - 36). Furthermore, in line with present OPP policy for a late season foliar us e, a statement should be added to both the 30SG and 70WP labels prohibiting addition of adjuvants for application to grapes. If use of an adjuvant is desired then one should be used in side - by- side testing. The PHI for clover harvested for hay should be increased to 56 day s on the 30SG and 70WP labels. Tolerances : a) HED recommends tolerances for acetamiprid be established as specified in Appendix C . b) Additionally , the tolerance expression in section (a) (1) should be revised to read as follows: Tolerances are established for residues of the insecticide acetamiprid [N 1

- [(6 - chloro - 3 - py ridyl )meth yl ] -N 2

- cyano -N 1

- methylacetamidine ] , including its metabolites and degradates, in or on the commodities in the table below as a result of the application of acetamiprid . Compliance with the tolerance levels specified below is to be determined by measuring only acetamiprid [N 1

- [(6 - chloro - 3 - py ridyl)meth yl ] -N 2

- cyano -N 1

- methylacetamidine ] i n or on the following commodit ies. c) The tolerance expression in section ( a) (2) should be revised to read as follows: Tolerances are established for residues of the insecticide acetamiprid [N 1

- [(6 - chloro - 3 - py ridyl )meth yl ] -N 2

- cyano -N 1

- methylacetamidine ] , including its metabolites and degradates, in or on the commodit ies in the table below as a result of the application of acetamiprid . Compliance with the tolerance levels specified below is to be determined by measuring acetamiprid [N 1

- [(6 - chloro - 3 - py ridyl )methyl] -N 2

- cyano -N 1

- methylacetamidine ] and N 1

- [(6 - chloro - 3 - py ridyl )methyl] -N 2

- cyano - acetamidine in or on the following commodit ies.Page 8 of 63

d) The final tolerances for subgroup 13 - 07F should reflect the correct commodity definition as specified in Appendix C . A revised Section F is no t needed for this minor change. The established individual tolerance for grape at 0.20 ppm should be concomitantly removed with establishment of the subgroup 13 - 07F tolerance. Conditional Data:

 Two clover field trials reflecting the same use pattern utilized in the submitted studies. Submittal of Analytical Reference Standards : Analy tical standard s for the IM - 2 - 1 and IM - 2 - 1 - amide metabolites are not available at the Repository and should be supplied. The reference standards should be sent to the Analy tical Chemi stry

L ab, which is located at Fort Meade, to the attention of Theresa Cole at the following address: USEPA National Pesticide Standards Repository /Anal yt ical Chemistry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 (Note that the mail will be returned if the extended zip code is not used.) 1.2 Summary of Proposed Uses A list of acetamiprid end - use products (EPs) relevant to this registration action is presented below in Table 1.2.1. All listed EPs are registered to Nippon Soda Co., Lt d. (c/o Nisso America, In c.). Table 1.2.1 . List of Acetamiprid E nd - Use Products Associated with PP# 9E7544 . Trade Name Reg. No. ai (% of formulation) Formulation Type Label Date Assail® 30SG Insecticide 8033 - 36 30% by wt Soluble granule 3/4/2009 (draft) Assail® 70WP Insecticide 8033 - 23 70% by wt Wettable powder 3/4/2009 (draft) Tristar® 30SG Insecticide 8033 - 94 30% by wt Soluble granule 3/4/2009 (draft) A summary

of the proposed or amended use patterns is pr esented in Table 1.2.2. For clover, new use is proposed for Assail® 30SG and Assail® 70WP . For grapes, a change to the registered use pattern is proposed. The current labels permit up to two foliar applications on grapes at 0.05 lb ai/A/application for a maximum seasonal rate of 0.1 lb ai/A with a 7 - day preharvest interval (PHI). The requested new use on grapes (and small vine climbing fruits, except kiwifruit, subgroup 13 - 07F ) will permit up to two applications of Assail® 30 SG or Assail® 70WP at 0.1 lb ai/A/application for a seasonal rate of 0.2 lb ai/A with a 3 - day PHI. For tomatoes, new use is proposed for greenhouse - grown tomatoes. The current Assail® 30 SG and Assail® 70WP labels permit up to four foliar applications on field - grown tomatoes at 0.07 5 lb ai/A/application for a maximum seasonal rate of 0.3 lb ai/A with a 7 - day PHI . The requested new use on tomatoesPage 9 of 63

add s a greenhouse use pattern using Tristar® 30 SG , with a maximum of two applications (reduced from four for resistance management) at 0.0 75 lb ai/A/application (based on 10,000 plants per acre) for a maximum seasonal rate of 0.15 lb ai/A, applied via chemigation with a 1 - day PHI . No use directions were proposed for the domestic use of acetamiprid on tea grown in South Carolina. The foll owing GAP information was provided for the 20% SP formulation in Japan: one application at 0.10 - 0.40 kg ai/ha applied in 2000 - 4000 L/ha, with a 14 - day PHI . GAP information was also provided for India: one application at 0.022 lb ai/A (0.025 kg ai/ha) or 0.045 lb ai/A (0.050 kg ai/ha), shoots along with bud are typicall y harvested at a 7 - day PHI. There were no rotational crop restrictions listed on any of the acetamiprid draft labels. Table 1.2.2. Summary of Directions for Use of Acetamiprid. Applic. Timing, Ty pe, and Equip. Trade Name

[EPA Reg. No.] Applic.

Rate (lb ai/A) Max. No.

Applic. per Season 1 Max. Seasonal

Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations Clover 2 Post emergence Broadcast foliar spray Ground/aerial Assail®

30SG; [8033 - 36] Assail® 70WP [8033 - 23] 0.047 -

0.075 1 0.075 28 Proposed use is limited to clover grown in ID, OR, and WA only. Begin applications when treatment thresholds have been reached. Apply in minimum spray volumes of 5 GPA by air or 20 GPA by ground. Grapes and Other Climbing Vine Small Fruits (Except Fuzzy Kiwifruit) (Within Crop Subgroup 13 - 07F): Amur River Grape; Gooseberry; Hardy Kiwifruit; Maypop; Schisandra Berry; and Cultivars, Varieties, and/or Hybrids

Post emergence Broadcast foliar spray Ground/aerial Assail®

30SG; [8033 - 36] Assail® 70WP [8033 - 23] 0.047 - 0.1 2 0.2 3 Begin applications when treatment thresholds have been reached. Do not apply more than once every 14 days. Apply in minimum spray volumes of 5 GPA by air or 20 GPA by ground. Assail® 30SG states that the addition of a spreader, methylated seed oil or crop oil will enhance pest control. 3Page 10 of 63 Table 1.2.2. Summary of Directions for Use of Acetamiprid. Applic. Timing, Ty pe, and Equip. Trade Name

[EPA Reg. No.] Applic.

Rate (lb ai/A) Max. No.

Applic. per Season 1 Max. Seasonal

Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations Greenhouse - Grown Tomatoes

Post emergence Drip or micro Irrigation Tristar®

30SG [8033 - 94] 0.075 lb

ai/A of crop (based on 10,000 plants /A) 2 0.15 1 For use in greenhouse grown tomato production. May be applied by injection into drip irrigation or micro irrigation (spaghetti tube or emitter) systems, soil drenching, or by hand held or motorized calibrated irrigation equipment direc ted to the plant roots. Application should be made only to mature tomato plants grown in non - soil media such as rock wool, vermiculite, perlite, or other soil - less media. Some cultivars may exhibit sensitivity and therefore treatment of a few plants is re commended prior to treating an entire greenhouse. Begin applications when treatment thresholds have been reached. 1 The number of treatments allowed per season when the EP is applied at the maximum single application rate. 2 Section G of the petiti on specifies that the EP is proposed for use on red clover grown for seed. The draft label does not specify that use is for clover grown for seed. 3 HED recommends that this be removed from the label until side - by - side residue data are submitted. Furthermore, in line with present OPP policy for a late season foliar use, a statement should be added to both the 30SG and 70WP labels prohibiting addition of adjuvants for application to grapes. If use of an adjuvant is desired then one should be used in side - by - side testing. Conclusions . The submitted labels are adequate to allow evaluation of the residue data relative to the proposed use , except for the use on tea in South Carolina for which directions were not proposed. The available fiel d trial data reflect the proposed use patterns for all of the submitted field trials except those submitted for grapes and clover hay . Because the grape field trial data submitted with this petition did not reflect the use of a surfactant in the applicati on spray s, the label directions regarding use of a spreader, methylated seed oil or crop oil should be removed from the product label of Assail® 30SG (EPA Reg. No. 8033 - 36). Furthermore, in line with present OPP policy

for a late season foliar use, a stat ement should be added to both the 30SG andPage 11 of 63

70WP labels prohibiting addition of adjuvants for application to grapes. If use of an adjuvant is desired then one should be used in side - by- side testing. The PHI for clover harvested for hay should be increased to 56 day s on the 30SG and 70 WP labels. 2.0 Ingredient Profile Acetamiprid is an insecticide in the chloronicotinyl class of compounds. It has a molecular weight of 222.68 Daltons and is not volatile (vapor pressure = 7.5  10 - 9 Torr at 25  C; Henry ’s Law Constant = 5.17 x10 - 11 atm M 3 /mole at 25  C). Acetamiprid is quite soluble in water (4.25 g/ L) as well as organic solvents (>200 g/Lin ethanol, acetone, and dichloromethane). The log KOW of acetamiprid is 0.8. Based o n these data, acetamiprid vapors should not present a significant inhalation risk and this compound is not expected to concentrate in fatty tissues. Technical - grade acetamiprid does not contain impurities of known or potential toxicological concern. The nomenclature and phy siochemical properties of acetamiprid are presented below in Tables 2 .a and 2 . b. T able 2 . a. Test Compound Nomenclature Compound

Chemical Structure Comm on Name Acetamiprid Company Experimental Name EXP - 61842A, AEF124370, NI - 25 IUPAC Name ( E ) - N 1 - [(6 - chloro - 3 - pyridyl)methyl] - N 2 - cyano -

N 1 - me thylacetamidine CAS Name (1 E ) - N - [(6 - chloro - 3 - pyridinyl)m ethyl] - N' - cyano - N - me thylethanimidamide CAS # 135410 - 20 - 7 End - Use Product Assail ® 70WP , Assail® 30SG, F4688 50WSP Chemic al Name of Acetamiprid Me tabolite IM - 2 - 1 N 1 - [(6 - chloro - 3 - pyridyl)m ethyl] - N 2 - cyano - acetamidine Chemical Name of Acetamiprid Me tabolite IM - 2 - 1 - amide (also referred to as IM - 2 - 2) N 2 - aminocarbonyl - N 1 - [(6 - chloro - 3 - pyridyl)m ethyl]acetamidinePage 12 of 63 Tab le 2 . b. Physicochemical Properties of Acetamiprid Param eter Value Melting Point/Range (  C) 98.9 pH (20  C) 6.08 (Aqueous Solution) Density (20  C) 1.33 g/cm3 Water Solubility (25  C) 4.25 g/L Solvent Solubility (25  C) in:

Acetone E thanol Dichloromethane n - Hexane >20 g/100 g >20 g/100 g >20 g/100 g 6.54 ppm Vapor Pressure (mm Hg) 7.5 x 10 - 9 Dissociation Constant (pKa) 0.7 Octanol/Water Partition Coefficient, Log KOW (20  C) 0.8 UV/Visible Absorption Spectrum Not Availabl e . 3.0 Hazard Characterization/Assessment 3.1 Hazard and Dose - Response Characterization 3.1.1 Database Summary 3 .1.1.1 Studies available and considered (animal, human, general literature) The toxicity

data base contains : 1) subchronic oral toxicity studies in rats, mice, and dog s; 2) a chronic oral toxicity

study in dogs and carcinogenicity stu di es in rats and mice; 3) developmental and reproduction studies in rats and a developmental study in rabbits; 4) acute, subchronic, and developmental neurotoxicity studies in rats; and, 5) subchronic dermal toxicity and dermal penetration studies in rats. There is also a complete mutagenicity battery , as well as metabolism studies in the rat . 3.1.1.2 Mode of action Acetamiprid is a chloronicotinyl insect icide registered to control sucking type insects (e.g., aphids, whitefly , etc.) on a wide variety of crops including cotton, leafy vegetables, fruiting vegetables, and citrus fruits. Acetamiprid acts as an agonist of the nicotinic acetyl choline receptor, a ffecting the s ynapses in the insect central nervous s ys tem.Page 13 of 63

3.1.1.3 Sufficiency of studies/data The toxicological database for acetamiprid is not complete. As part of the new 40 CFR Part 158 guidelines, an immunotoxicity study in rats and/or mice is required. However , acetamiprid does not show any

evidence of treatment - related effects on the immune sy stem. The overall weight of evidence suggests that this chemical does not directly target the immune syst em and the Agency does not believe that conducting a functional immunotoxici ty study will result in a lower point of departure ( POD ) than that currentl y use d for overall risk assessment. Therefore, a database uncertainty factor (UF DB ) is not needed to acc ount for lack of this study. The scientific quality of the available studies is relatively high and the toxicity

profile of acetamiprid can be characterized for most effects, including potential carcinogenicity, mutagenicity , developmental toxicity and neurotoxicity . 3.1.2 Toxicological Effects The acute toxicity

data indicate that acetamiprid is moderatel y toxic via the oral route of exposure (Toxicity

Category I I) and is minimally

toxic via the dermal and inhalatio n routes of exposure (Toxicity

Category I II). Acetamiprid is not an eye or skin irritant, nor is it a dermal sensitizer. Acetamiprid does not appear to have specific target organ toxicity . In all species tested, generalized nonspecific toxicity was obse rved as decreases in body weight, body

weight gain, food consumption and food efficiency . Generalized effects were also observed in the liver in the form of hepatocellular h ypertroph y in both mice and rats and hepatocellular vacuolation in the rat. Hepat ocellular hy

pertrophy was observed in the rat subchronic feeding study at doses of 50 mg/kg/day

and above, and in the rat chronic feeding study at doses of 17.5 mg/kg/day and above at both the 12 - month sacrifice and study termination. In mouse studies, he patocellular hy pertrophy was observed at 430 mg/kg/day at 90 day s and at 186 mg/kg/day at 12 and 18 months. These effects are considered to be adaptive. Hepatocellular vacuolation was observed at 17.5 mg/kg/day

in the rat chronic study . In light of the lack of major liver effects in the rat studies, it is likely

that the vacuolization is more related to liver activity in response to the presence of the chemical rather than frank toxicity . Other effects observed in the oral studies include am yl oidosis of multiple organs in the mouse oncogenicity study, tremors in high dose females in the mouse subchronic study, and microconcretions in the kidney papilla and mammary

hy perplasia in the rat chronic feeding/oncogenicity study. No effects were observed in the 21 - day dermal study

in the rabbit and no inhalation studies were conducted. A dermal absorption study with acetamiprid was conducted using male rats with exposure durations of 0.5, 1, 2, 4, 10 and 24 hours. Measured absorption was small and increased wi th duration of exposure. The quantity absorbed also generall y increased with dose. In the previous acetamiprid risk assessment, the highest dermal absorption value (6.34% at 24 hours) was added to the residue remaining on the skin at 24 hours (25%) to estimate a 30% dermal absorption value. However, HED has refined the dermal absorption value (to 10%) based upon comparison to clothianidin, which is structurally related. HED believes that a refined dermal penetrationPage 14 of 63

value for acetamiprid of 10% is reason able and protective. See Section 3.5.3 for more details. There is no quantitative or qualitative evidence of increased susceptibility of rat or rabbit fetuses to in utero exposure in the developmental studies. In the rat, an increase in the incidence of shortening of the 13 th rib was observed in fetuses at the same LOAEL as the dams. Maternal effects included reduced mean body weight, body weight gain and food consumption and increased liver weights. No developmental toxicity was observed in the rabbit fetuses at dose levels that induced maternal effects including body weight loss and decreased food consumption. In the 2 - generation reproduction study , qualitative evidence of increased susceptibility of rat pups was observed. The parental and offsprin g s ystemic L OAELs were 51.0/60.1 (M/F) mg/kg/day

based on a decrease in mean body weight, body weight gain, and food consumption in the parents and significant reductions in pup weights in both generations. Also observed w ere reduction in litter size, and viability and weaning indices among F 2 offspring as well as significant delay s in the age to attain vaginal opening and preputial separation in the offspring. These offspring effects were considered to be more severe than the parental effects. In the DN T study

there was evidence of increased qualitative susceptibility . The purpose of the DNT study

is to evaluate the potential functional and morphological effects to the nervous sy stem which may

arise in the offspring from exposure of the mother during pr egnancy and lactation. It provides data on sensorimotor function and on habituation which is considered to be a simple form of learning. In the acetamiprid DNT, the offspring L OAEL was 45 mg/kg/day based on decreased body weights and body weight gains in males and females, decreased pre weaning survival (PND 0 - 1), and decreased maximum auditory startle response in males on PND 20 and PND 60 . This was observed in the presence of decreased maternal body weight and body weight gains during gestation. Altho ugh there were reductions in the maximum auditory startle response in the 10 mg/kg/day in males on PND 20 and PND 60, the mean response was within the range of historical control means and standard deviations among other DNT studies conducted (b y the same laboratory) within a 5 - ye ar span of the a cetamiprid DNT study . HED noted that statistical significance could onl y be achieved b y combining data for both sexes at both time points (PND 20, and PND 60). Agency scientists agreed that it was appropriate to c ombine the data for the sexes, but there was no definitive consensus regarding combining the data from the different time points. The discussion regarding the combining of data from the two time points cent e red around the equipment used to measure the auditory startle reflex, and how it is calibrated differentl y t o account for increases in body weight as the animals grow. Based upon the anal ys is of the DNT, technical arguments submitted by the registrant, and consideration of all other data in the acetami prid toxicity profile, HED believes that the decrease in maximum startle response in males is only treatment related at the high - dose level of 45 mg/kg/day . The decreased auditory

startle response in males in conjunction with the decreases in pup body wei ght and body weight gains and decreased pup viability lead the Agency to a weight - ofevidence LOAEL determination of 45 mg/kg/day . For a more detailed discussion of the DNT study refer to the DNT DER (MRID 46255619) and cover memo entitled Acetamiprid: Data Evaluation Record for Acetamiprid Developmental Neurotoxicity Study and EPA Response to Rebuttals Submitted by Nisso America, (TXR 0054508). In an acute rat neurotoxicity study , a decrease in locomotor activity was observed in both sexesPage 15 of 63

on the day of dosing. A slight decrease in the duration of movements persisted in some males on day s 7 and 14. Functional observational battery evaluations revealed several treatment - related observations on the day

of dosing. High - dose males exhibited tremors, di fficulty in handling, walking on toes, dilated pupils and coldness to the touch. High - dose males also had decreased forelimb grip strength and hind limb foot splay . High - dose females displayed tremors, chewing, coldness to the touch, and dilated pupils. High - dose females had decreased hind limb foot splay and were seen to have abnormal gaits and/or posture, including walking on toes and hunched posture. However, in a subchronic rat neurotoxicity study , the onl y effects observed were related to decreases in body

weight/body

weight gain, food consumption and food efficiency . No neuropathology

was observed in any

of the three neurotoxicity studies. Tremors in high dose female mice in the subchronic feeding study were the only other potentially neurotoxic e ffects observed in an y other studies. Acetamiprid tested negative in a Salmonella typhimurium (Ames) assay , a forward mutation assay in Chinese hamster ovary cells, an in vivo chromosome aberration assay in Sprague Dawley (CD) rats, a mouse micronucleus assay , and in repeat assay s for unscheduled DNA sy nthesis (UDS) in rat liver primary cell cultures. Acetamiprid tested positive as a clastogen in an in vitro mammalian chromosome aberration assay in Chinese hamster ovary (CHO) cells. However, the in vivo chromosomal aberration study does not support the results of the in vitro study . All acetamiprid metabolites tested were negative for mutagenicity . 3.1.3 Dose - response Since HED’s last hazard assessment of acetamiprid in 2007, endpoints have been selected to account for occupational long - term oral, dermal, and inhalation exposure s . For acute dietary exposure, the DNT and acute neurotoxicity studies were co - critical for determining the acute reference dose (aRfD) of 0.1 mg/kg/day for all populations. These studies share a NOAEL of 10 mg/kg/day . In the DNT, the maternal LOAEL (45 mg/kg/day) is based on decreased body weight and body weight gain during gestation and the offspring LOAEL (45 mg/kg/day) is based on decreased b ody

weights and body

weight gains in males and females, decreased pre - weaning survival (PND 0 - 1), and decreased maximum auditory startle response in males on PND 20 and PND 60 . The LOAEL in the acute neurotoxicity study , 30 mg/kg, is based on reduction in locomotor activity

in males. For the chronic dietary exposure, the chronic/oncogenicity study was used to calculate the chronic reference dose (cRfD) of 0.071 mg/kg/day for all populations. The NOAEL, 7.1 mg/kg/day , is based on reduced body weight and bo dy

weight gains for females and hepatocellular vacuolation for males. The L OAEL is 17.5 mg/kg/day . For the incidental - oral (short - and intermediate - term), as well as short - and intermediate - term dermal and inhalation exposures, the DNT was used. For l ong - term inhalation and dermal exposures, the chronic/carcinogenicity study in rats was used for endpoint selection. 3.1.4 FQ PA See Section 3.3.Page 16 of 63

3.2 Absorption, Distribution, Metabolism, Excretion (ADME) Several studies have examined the in vivo metabolism and distribution of acetamiprid in the rat including single dose, 15 - day repeated dose, biliary

excretion, and metabolite characterization studies. Acetamip rid is rapidl y absorbed and eliminated. Metabolite studies indicate 96 - 99% absorption following an oral administration. Peak blood concentrations in the rat occur within 1 - 2 hours, with nearl y complete clearance from the blood b y 48 hours. Acetamiprid d istributes widely in the body but tissue burdens rarel y exceed 1% of the administered dose. Acetamiprid is extensively metabolized with metabolites accounting for 79 - 86%of the administered radioactivity . 6 - Chloronicotinic acid is the most abundant metabo lite, accounting for 24 - 28% of the dose in single - dose studies and 8 - 10% in repeated - dose studies. Urinary excretion was the major route of elimination, accounting for 79 - 97% of the administered dose within 24 hours in single oral dose groups. Fecal excretion accounted for 21 - 35% of the administered radioactivity , with males being slightly higher. Excretion rates for the IV and repeated dose studies were similar. As a result of the rapid absorption, metabolism, and clearance of acetamiprid in the rat, the pharmacokinetic parameters derived from the 15 - day repeated dose study

were similar to the single dose study . Therefore, the potential for acetamiprid to bioaccumulate is minimal. A dermal absorption factor of 10% is proposed for risk assessment. The factor is based on an acetamiprid dermal absorption study in rats, a dermal absorption study in monkey s, and a comparison of structurally similar neonicotinoid pesticides. 3.3 FQ PA Considerations 3.3.1 Adequacy of t he Toxicity Database Acceptable guideline studies for developmental and reproductive toxicity are available for FQPA assessment , including an acceptable DNT study . However, an immunotoxicity study is requ ired as a part of new data requirements in the 40 CFR Part 158 for conventional pesticide registration. Therefore, the lack of an immunotoxicity study is considered to be a data gap. (Note: An immunotoxicity

study was previously requested in D352925, W. Drew , 11/25/2008 .) 3.3.2 Evidence of Neurotoxicity Acetamiprid produced signs of neurotoxicity in the high dose groups in the acute and developmental neurotoxicity studies in rats. In the acute neurotoxicity study , male and female rats displayed decreased motor activity , tremors, walking and posture abnormalities, dilated pupils, coldness to the touch, and decreased grip strength and foot splay . There was a decrease in the auditory

startle response in male rats in the DNT. Tremors in the high dose female mice in the subchronic feeding study were the only

other potentially

neurotoxic effects observed in the other studies.Page 17 of 63

3.3.3 Developmental Toxicity Studies In th e gavage developmental studies, fetal effects were observed at the doses associated with maternal effects. In the rat developmental study, fetal shortening of the 13 th rib and reduced maternal body weight and body weight gain were observed at the same LOAEL . No developmental effects were observed in the rabbit at doses that reduced maternal body weight and food consumption. In the DNT, parental and offspring s ys temic LOAEL s were the same, 51.0/60.1 (M/F) mg/kg/day . Offspring and parental L OAELs were bas ed on decreased auditory startle response in male pups and decreased body weight and body weight gain during gestation, respectivel y. 3.3.4 Reproductive Toxicity Study In the 2 - generation reproduction study , th e LOAEL for the parental and offspring s ys temic effects, 17.9/21.7 (M/F) mg/kg/day , were based on a decrease in mean body weight, body

weight gain, and food consumption in the parents, and reductions in pup weights, litter size, viability , and weanling indices, as well as age to attain vaginal opening and preputial separation in the offspring. 3.3.5 Additional Information from Literature Sources A literature search did not reveal information that would impact the risk assessment. 3.3.6 Pre - and/or Postnatal Toxicity 3.3.6.1 Determination of Susceptibility HED determined that neither quantitative no r qualitative evidence of increased susceptibility of fetuses to in utero exposure to acetamiprid was observed in either the developmental toxicity study in rat, or in rabbit. However, in the 2 - generation reproduction study , qualitative evidence of increa sed susceptibility of rat pups was observed. While parental and offspring NOAELs and LOAELs are set at the same doses (17.9 and 51.0 mg/kg/day , respectivel y), the effects in the offspring are considered to be more severe than the parental effects. Likewi se, in the DNT study maternal and offspring effects were observed at the same dose (45 mg/kg/day). However, the offspring effects included decreased pup viability which is considered to be more severe than the maternal body weight effects. Therefore, HED concluded that there was evidence of increased qualitative susceptibility

to fetuses exposed in utero and/or during lactation in the DNT study . Quantitative evidence of increased susceptibility was not observed in any

study . 3.3.6.2 Degree of Concern Analysis and Residual Uncertainties for Pre - and/or Postnatal Susceptibility Since there is evidence of increased qualitative susceptibility of the young following in utero exposure to acetamiprid in the rat reproduction study , and increased qualitative susceptibility to pups in the DNT study , HED performed a degree of concern analy sis to: 1) determine the levelPage 18 of 63

of concern for the effects obser ved when considered in the context of all available toxicity data; and, 2) identify

an y residual uncertainties after establishing toxicity endpoints and traditional uncertainty factors to be used in the acetamiprid risk assessment. If residual uncertainti es are identified, HED examines whether the residual uncertainties can be addressed by a FQPA safety factor, and if so, what factors should be retained. Considering the overall toxicity profile and the endpoints and doses selected for the acetamiprid risk assessment, HED characterized the degree of concern for the effects observed in the acetamiprid DNT study

as low , noting that there is a clear NOAEL for the offspring effect s and regulatory

doses were selected to be protective of these effects. No other residual uncertainties were identified. Based on the available data, HED determined that changes in motor activity , auditory startle reflex, learning and memory assessments, and even changes in the brain morphometrics can occur as the result of a single e xposure at a critical junction during pregnancy or from multiple exposures throughout pregnancy and lactation. Therefore, the NOAEL for offspring effects observed in the DNT was selected as the dose for acute dietary exposures (co critical with the acute neurotoxicity study), as well as short - term and long - term non - dietary risk assessment. The chronic dietary study in rats yielded a lower long - term NOAEL (7.1 mg/kg/day) and will be used for assessing chronic dietary risk. HED believes that the endpoints and doses selected for acetamiprid are protective of adverse effects in both offspring and adults. 3.3.7 Recommendation for a Developmental Neurotoxicity Study A developmental neuroto xicity study has been requested, received, and reviewed by the Agency (see Section 3.3.2). 3.4 FQ PA Safety Factor for Infants and Children HED recommends the FQPA SF be reduced to 1X for the following rea sons: (1) HED is regulating based upon the effects of concern, i.e., developmental effects in pups following pre and/or post - natal exposure; (2) the rat appears to be the most sensitive species tested, and the NOAEL and LOAEL selected from the DNT study i n rats are protective of effects observed in other species throughout the toxicology database; and, (3) there are no residual uncertainties for pre - and/or post - natal toxicity . The recommended FQPA safety factor also reflects HED’s conclusion that the exp osure databases (dietary food, drinking water, and residential) are complete and that the risk assessment for each potential exposure scenario includes all metabolites and/or degradates of concern and does not underestimate the potential risk to infants or children. The lack of an immunotoxicity study is considered a data gap. However, because there was no indication in any

of the submitted toxicity studies that there was an effect on the immune sy stem, a 10x safety

factor for a data gap is not required at this time . (Note: An immunotoxicity study was requested in: D352925, W. Drew; Nov 25, 2008.)Page 19 of 63

3.5 Hazard Identification and Toxicity Endpoint Selection 3.5.1 Acute Reference Dose ( aRfD) - Females age 13 - 49 A separate aRFD is not being used for females age 13 - 49. Females in this age group will be assessed using the aRFD for the general population (see 3.5.2). 3.5.2 A cute Reference Dose (aRfD) - General Population Co - Critical Studies Selected : Developmental Neurotoxicity Study in Rats ( MRID 46255619) Acute Neurotoxicity

Study in Rats ( MRID 44651842) Dose and Endpoint for Risk Assessment : NOAEL = 10 mg/kg/day based on offspring decreased body weights and body

weight gains, decreased pre - weaning survival (PND 0 - 1), and decreased maximum auditory

startle response in males on PND 20 and PND 60 of the DNT study at 45 mg/kg/day , as well as decreased locomotor activity in males in the ACN study at 30 mg/kg bw. The DNT and acute neurotoxicity studies are considered co - critical due to similar L OAE Ls and signs of toxicity . mg/kg 0.1 RfD Acute 

 (UF) 100 mg/kg 10 C omments about Study

/Endpoint/Uncertainty Factors : These endpoints and dose were selected because : 1) the oral route of exposure is relevant to dietary risk assessment, 2) the duration of exposure is relevant to acute dietary risk (both endpoints can be c onsidered the result of a single dose), and 3) they

are protective of potential offspring effects. Based on the available data, HED determined that changes in motor activity , auditory startle reflex, learning and memory assessments, and changes in the brain morphometrics can occur as the result of a single exposure at a critical junction during pregnancy or from multiple exposures throughout pregnancy and lactation. The standard uncertainty factors (100x) were applied to all dietary exposure scenarios (10 x for intraspecies variability and 10x for interspecies extrapolation). 3.5.3 Chronic Reference Dose (cRfD ) Studies Selected : Chronic/ Carcinogenicity Study in the Rat MRID Nos .: 44988429, 45245304 Dose and Endpoint for Risk Assessment : NOAEL = 7.1 mg/kg/day based on decreased body weights and body weight gains in females and hepatocellular vacuolation in males observed at the L OAEL of 17.5 mg/kg/day . mg/kg/day 0.071 RfD Chronic 

 (UF) 100 mg/kg/day 7.1Page 20 of 63

Comments about Study

/Endpoint/Uncertainty Factors : This endpoint and dose was selected because: 1) the oral route of exposure is relevant to dietary risk assessment, 2) the duration of exposure is relevant to chronic risk scenarios, and 3) it is the lowest endpoint in the toxicology d atabase and is therefore protective of both chronic effects and potential qualitative sensitivity of offspring . The standard uncertainty factors were applied to all dietary exposure scenarios (10x for intraspecies variability and 10x for interspecies extrapolation). 3.5.4 Incidental Oral Exposure (Short - and Intermediate - Term) Short - and Intermediate- Term Incidental Exposure (1 -30 days and 1 - 6 months ) Study Selected : Developmental Neurotoxicity Study in Rats ( MRID 46255619) Dose and Endpoint for Risk Assessment : NOAEL = 10 mg/kg/day based on offspring decreased body weights and body

weight gains, decreased pre - weaning survival (PND 0 - 1), and decreased maximum auditory

startle resp onse in males on PND 20 and PND 60 o f the DNT study at 45 mg/kg/day . Comments about Study

/Endpoint/Uncertainty Factors : The NOAE L and LOAEL from the DNT study were selected for the short - and intermediate - term dermal risk assessment because they are prot ective of developmental effects present in rat pups observed in the presence of less severe maternal effects at similar doses. The standard uncertainty factors (100x) were applied (10x for intraspecies variability

and 10x for interspecies extrapolation). 3.5.5 Dermal Absorption In the previous risk assessment ( D303171; Tom Moriarty ; 25 October 2007), HED used a 30% dermal penetration value derived from an acetamiprid dermal penetration study in rats (MRID 44651858), in which multiple doses were tested for durations ranging from 0.5 to 24 hours. To arrive at the 30% value, HED added the highest dermal absorption value (6.34%) to the amount sequestered in the skin at 24 hours (approximately 25%). To validate this estimate and determine whether further refinement was needed, HED reexamined the dermal penetration study with acetamiprid, and reviewed the dermal penetration information of several other neonicotinoid insecticides. To refine its assumption regarding treatment of sequestered acetamiprid on the skin, HED looked at the amount of radioactivity remaining at the application site. The amount of radiolabeled material remaining at the application site at various intervals varied between 0

– 5% percent between time points. If the radioactivity remaining at the application site is added to that which is absorbed, a maximum penetration value for acetamiprid would be 11%. However, since the duration of the acetamiprid study was onl y 24 hours, HED examined the thiamethoxam der mal penetration study, another neonicotinoid, which was terminated after 336 hours (14 days). Results from that study

indicate little additional absorption (1

– 3%) occurred between 24 hours post dosing and 14 day s post dosing.Page 21 of 63

HED also considered the Kow and octanol/water coefficient data of other neonicotinoid compounds, and found acetamiprid is most closely related to clothianidin with respect to its log Kow and octanol/water coefficient, and therefore would likely act most similarly

to clothianidin when applied to the skin. The dermal penetration value for clothianidin (1%) is based upon dermal penetration study

with monkey s (s ee Table 3.5.5. below ) . Table 3.5.5. Absorption Param eters for Selected Neonicitinoids. Compound Log Kow Octanol/Water C oefficient Derm al Penetration Value Acetamiprid 0.8 6.3 30% (dermal penetration study with rat) Clothianidin 0.9 8 1% (dermal penetration study in monkeys) Adjustment of the monkey dermal penetration value for clothianidin to account for the 2 - 10 fol d increased dermal sensitivity of rats compared to humans (dermal penetration of monkey is considered equivalent to human) would yield a comparative rat dermal penetration value for acetamiprid of 2

– 10%. Likewise, if the current dermal penetration value for acetamiprid is adjusted downward to account for the increased sensitivity of rats to humans, then a value of 10 - 15% results. Since the acetamiprid study shows 6% dermal penetration at 24 hours, a refined dermal penetration value reflecting a longer dermal exposure would likely be greater than 6%, and may lie between 10 - 15 %. Based upon its reconsideration of the acetamiprid dermal penetration study , and on comparison of acetamiprid to the structurally related clothianidin, HED determined that a refined dermal penetration value for acetamiprid of 10% is reasonable and protective. Based upon this, HED would not require an y additional dermal penetration data for acetamiprid. 3.5.6 Dermal Exposure (Short - , Intermediate - and Long - Term) Short - and Intermediate- Term Dermal Exposures (1 -30 days and 1 - 6 months) Study Selected : Developmental Neurotoxicity Study in Rats MRID No. : 46255619 Dose and Endpoint for Risk Assessment: NOAEL = 10 mg/kg/day based on decreased body weights and body weight gains in males and females, decreased pre - weaning survival (PND 0 - 1), and decreased maximum auditory startle response in males on PND 20 and PND 60 of the DNT study at 45 mg/kg/day , as well as decreased locomotor activity in males in the ACN study at 30 mg/kg bw. Comments about Study

/Endpoint/Uncertainty Factors : The NOAE L and LOAEL from the DNT study were selected for the short - and intermediate - term dermal risk assessment because they are p rotective of developmental effects present in rat pups observed in the presence of less severe maternal effects at similar doses. Although a dermal (route specific) toxicity study in rabbits was submitted, no effects were seenPage 22 of 63

at the highest dose tested o f 1000 mg/kg/day . Use of the route - specific study for dermal risk assessment would not be protective of the offspring effects observed in both the DNT and the 2 - generation reproduction studies because the effects seen could occur as a result of a single e xposure at a critical junction during pregnancy or from multiple exposures throughout pregnancy

lactation. Therefore, the NOAEL for offspring effects observed in the DNT was selected as the dose for both short - term and intermediate - term dermal exposure sc enarios. Since the dermal endpoint is based on an oral study, a 10% dermal absorption factor is used to determine dermal exposure and risk. The standard uncertainty factors were applied to all exposure scenarios (10x for intraspecies variability and 10x f or interspecies extrapolation). Long - Term Dermal Exposure (> 6 months) Study Selected : Chronic/Carcinogenicity Study in Rats MRID No. : 44988429, 45245304 Dose and Endpoint for Risk Assessment: NOAEL = 7.1 mg/kg/day based on decreases in mean body weight and body

weight gain in females and hepatocellular vacuolation in males. Comments about Study

/Endpoint/Uncertainty Factors : The NOAE L and LOAEL from the chronic/carcinogenicity s tudy were selected for the long - term dermal risk assessment because the y are protective of developmental effects seen in the 2 - generation and DNT studies and the study is of an appropriate duration. Although a dermal (route specific) toxicity study in rabbits was submitted, no effects were seen at the highest dose tested of 1000 mg/kg/day . Use of the route - specific study for dermal risk assessment would not be protective of the offspring effects observed in both the DNT and the 2 - generation reproduction studies because the effects seen could occur as a result of a single exp osure at a critical junction during pregnancy or from multiple exposures throughout pregnancy

lactation. Since the dermal endpoint is based on an oral study , a 10% dermal absorption factor (DAF) is used to determine dermal exposure and risk. The standard uncertainty factors were applied to all exposure scenarios (10x for intraspecies variability and 10x for interspecies extrapolation). 3.5.7 Inhalation Exposure (Short - , Intermediate - and Long - Term) Short - and Intermediate- Term Inhalation Exposures (1 -30 days and 1 - 6 months) Study Selected : Developmental Neurotoxicity Study in Rats MRID No. : 46255619 Dose and Endpoint for Risk Assessment: NOAEL = 10 mg/kg/day based on decreased b ody weights and body weight gains in males and females, decreased pre - weaning survival (PND 0 - 1), and decreased maximum auditory startle response in males on PND 20 and PND 60 of the DNT study at 45 mg/kg/day . Comments about Study

/Endpoint/Uncertainty Fac tors : No route - specific information isPage 23 of 63

available for the inhalation toxicity of acetamiprid. In the absence of a route - specific study, the NOAEL and LOAEL from an oral study , along with an inhalation absorption factor (IAF, 100%), are used to estimate inhalation exposure and the associated risk. In this case, the NOAEL and LOAEL from the DNT study were selected because the duration is appropriate for short - and intermediate - term exposures and it is protective of potential effects in offspring. Because e ffects seen in the DNT can occur as the result of a single exposure at a critical junction during pregnancy

or from multiple exposures throughout pregnancy and lactation, the NOAEL for offspring effects observed in the DNT was selected as the dose for shor t - and intermediate term inhalation exposure scenarios. The standard uncertainty factors were applied to all exposure scenarios (10x for intraspecies variability and 10x for interspecies extrapolation). Long - Term Inhalation Exposures (> 6 months) Study S elected : Chronic/Carcinogenicity Study in Rats MRID No. : 44988429, 45245304 Dose and Endpoint for Risk Assessment: NOAEL = 7.1 mg/kg/day based on decreases in mean body weight and body

weight gain in females and hepatocellular vacuolation in males. C omments about Study

/Endpoint/Uncertainty Factors : No route - specific information is available for the inhalation toxicity of acetamiprid. In the absence of a route - specific study, the NOAEL and LOAEL from an oral study , along with an IAF (100%), are used to estimate inhalation exposure and the associated risk. In this case, the NOAEL and LOAEL from the chronic/carcinogenic study were selected because the duration is appropriate for long - term exposures and it is protective of potential effects in offspring observed in the DNT and 2 - generation study in rats. The standard uncertainty factors were applied to all exposure scenarios (10x for intraspecies variability and 10x for interspecies extrapolation). 3.5.8 Level of Concern for Margin of Exposure Table 3.5.8. Summary of Levels of Concern for Risk Assessment. Route Short - Term (1 - 30 Day s) Intermediate - Term

(1 - 6 Months) Long - Term

(> 6 Months) Occupational (Worker) Exposure Dermal 100 100 100 Inhalation 100 100 100 Residential Exposure Dermal 100 100 100 Inhalation 100 100 100 In cidental Oral 100 100 100Page 24 of 63

3.5.9 Recommendation for Aggregate Exposure Risk Assessments The FQPA requires that HED aggregate pesticide exposures from the three major exposure routes (oral, dermal, and inhalation) when there is potential residential exposure to a pesticide. HED has chosen a single endpoint and dose from the DNT study for short - and intermediate term exposure scenarios. Therefore, the short - and intermediate dermal, oral, and inhalation exposure can be combined and aggregated with the dietary (food + water) exposures. 3.5.10 Classification of Carcinogenic Potential HED has determined that acetamiprid is “ not like ly to be carcinogenic to humans.” The classification is based on the absence of a dose - response and the lack of a statistically significant increase in the mammary adenocarcinoma incidence b y pair - wise comparison of the mid - and high - dose groups with the controls; although the incidence exceeded the historical control data from the same laboratory, it was within the range of values from the supplier.Page 25 of 63

3.5.11 Summary of Toxicological Doses and Endpoints for Use in Human Risk Assessments Table 3.5.11a . Summary of Toxicological Doses and Endpoints of Acetamiprid for Use i n Dietary and Non - Occupational Hum an Health Risk Assessment Exposure Scenario Dose Used in Risk Assessment Uncertainty

Factors/FQPA Safety Factors RfD, PAD Level

of Concern for Risk Assessment Study and Toxicological Effect Ac ute Dietary (All populations ) NOAEL = 10 mg/kg/day UF A = 10x

UF H = 10x FQPA SF = 1x aPAD = 0.10

mg/kg/day Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspring, decreased early pup survival on PND 0 - 1, and decrease d startle response on PND 20/60 in males. Ac ute Neurotoxicity Study in rat LOAEL = 30 mg/kg/day based on decreased locomotor activity Chronic Dietary all populations NOAEL = 7.1 mg/kg/day UF A = 10x

UF H = 10x FQPA SF = 1x cPAD = 0.071

mg/kg/day Chronic To xicity/Oncogenicity Study in rats

LOAEL = 17.5 mg/kg/day based on decreased body weight and body weight gains in females and hepatocellular vacuolation in males. Short - and Intermediate Term Incidental Oral (1 - 30 days and 1 - 6 mo.) NOAEL = 10 mg/kg/day UF A = 10x

UF H = 10x FQPA SF = 1x LOC for MOE =

100 Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspring, decreased early pup survival on PND 0 - 1, and decreased startle response on PND 20/60 in males. Short - and Intermediate term Dermal (1 - 30 days, 1

– 6 mo.) NOAEL = 10 mg/kg/day DAF = 10% UF A = 10x

UF H = 10x FQPA SF = 1x LOC for MOE =

100 Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspring, decreased early pup survival on PND 0 - 1, and decreased startle response on PND 20/60 in males. Short - and Intermediate term Inhalation (1 - 30 days, 1

– 6 mo.) NOAEL = 10 mg/kg/day IAF = 100% UF A = 10x

UF H = 10x FQPA SF = 1x LO C for MOE =

100 Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspring, decreased early pup survival on PND 0 - 1, and decreased startle response on PND 20/60 in males. Cancer (oral, derma l, inhalation) - not likely to be carcinogenic to humans. DAF = dermal absorption factor. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose - response data and used to mark the beginning of extrapolation to d etermine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOA EL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PA D = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.Page 26 of 63

Table 3.5.11b . Summary of Toxicological Doses and Endpoints of Acetamiprid for Use in Occupational Hum an Health Risk Assessment Exposure Scenario Dose Used in Risk Assessment Uncertainty

Factors Level of Concern

for Risk Assessme nt Study and Toxicological Effect Short - , Intermediate - term Dermal (1 - 30 days, 1 - 6 mo.) oral study NOAEL= 10 mg/kg/day dermal absorption rate = 10% UF A = 10x

UF H = 10x LOC for MOE =

100 Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspring, decreased early pup survival on PND 0 - 1, and decreased startle response on PND 20/60 in males. Long - term

Dermal (> 6 mo.) NOAEL = 7.1 mg/kg/day UF A = 10x

UF H = 10x FQPA SF = 1x dermal absorption rate = 10% LOC for MOE =

100 Chronic Toxicity/Oncogenicity Study in rats

LOAEL = 17.5 mg/kg/day based on decreased body weight and body weight gains in females and hepatocellular vacuolation in males. Short - and Intermediate term Inhalation (1 - 30 days, 1 - 6 mo.) Oral study NOAEL= 10 mg/kg/day inhalation absorption rate = 100% UF A = 10x

UF H = 10x LOC for MOE =

100 Developmental Neurotoxicity in rat

LOAEL = 45 mg/kg/day based on decreased body weight and body weight gains in offspri ng, decreased early pup survival on PND 0 - 1, and decreased startle response on PND 20/60 in males. Long - term

Inhalation (1 - 30 days, 1

– 6 mo.) NOAEL = 7.1 mg/kg/day inhalation absorption rate = 100% UF A = 10x

UF H = 10x FQPA SF = 1x LOC for MOE =

100 Chronic Toxicity/Oncogenicity Study in rats

LOAEL = 17.5 mg/kg/day based on decreased body weight and body weight gains in females and hepatocellular vacuolation in males. Cancer (oral, dermal, inhalation) - not likely to be carcinogenic to humans. Point of Departure (POD) = A data point or an estimated point that is derived from observed dose - response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observ ed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. UF S = use of a short - term study for long - term risk assessment. UF DB = to account for the absence of key date (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = a cute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.Page 27 of 63

3.6 Endocrine disruption EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) “may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administra tor may designate.” Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA determined that there were scientific bases for including, as part of the program, androgen and thy roid hormone s ys tems, in addition to the estrogen hormone sy stem. EPA also adopted EDSTAC’s recommendation that the Program include evaluations of potential effects in wildlife. When the appropriate screening and/or testing protocols being considered under the Agency ’s Endocrin e Disrupter Screening Program (EDSP) have been developed and vetted, acetamiprid may

be subjected to additional screening and/or testing to better characterize effects related to endocrine disruption. 4.0 Public Health and Pesticide Epidemiology Data No public health data were considered at this time. 4.1 O ther Pesticide Epidemiology Published Literature A literature search did not reveal information that would impact the risk assessment. 5.0 Dietary Exposure/Risk Characterization 5.1 Pesticide Metabolism and Environmental Degradation 5.1.1 Metabolism in Primary Crops Residue Chemistry Memo D 264154, 12 /31/2001, M . Doherty (PP#0F6082) MARC Decision Memo, D278652, 11/13/2001, M. Doherty The nature of acetamiprid residue in plants has been adequatel y delineated and is based on radiolabeled studies with carrot, cabbage, cotton, apple, and eggplant. In plants, there appears to be little translocation of acetamiprid following foliar application. In cabb age, there was significant uptake and translocation of acetamiprid to the above - ground portions of the plant following a soil application. However, d ue to the rapid dissipation of acetamiprid in the field, root uptake is not a likely source of residues in plants. 5.1.2 Metabolism in Rotational Crops Residue Chemistry Memo D 328216 , 1 0 /2 3/200 7 , W. Drew (PP#6F7051 and PP#6E7163) Resi due Chemistry Memo D 264154, 1 2 /31/2 001, M . Doherty (PP#0F6082) No new confined rotational crop data were submitted with this petition ; the nature of the residue in rotational crops is understood . A confined rotational crop study was reviewed in conjunctionPage 28 of 63

with PP#0F 6082. In the study , acetamiprid was not detected in any rotational crop matrix (mustard greens, radish, and grain crops) at an y of the plantback interval s (PBIs), which were 30 - , 58 - , 120 - and 365 day s after treatment (DAT) following application to bare s oil at 0.66 lb ai/A . The major metabolite identified in rotational crops was IM - 1 - 4, at 2.94 - 56.65% TRR (<0.001 - 0.040 ppm). Two other metabolites were identified in most rotational crops: IM - 0 - Glc, at 1.11 - 15.23% TRR (<0.001 - 0.010 ppm) , and IC - 0, at 2.7 5 - 24.19% TRR (<0.001 - 0.014 ppm). Storage stability data, required as a condition of registration in the original petition PP#0F6082, have been submitted and determined to rectify deficiencies under PP#6F7051. HED has determined that the residue of concer n in rotational crops for enforcement purposes is the parent onl y, and that tolerances would not be needed on rotational crops. The available rotational crop data are adequate to support the uses proposed in this petition. 5.1.3 Metabolism in Livestock Residue Chemistry Memo D 264154, 12 /31/2001, M . Doherty (PP#0F6082) MARC Decision Memo, D278652, 11/13/2001, M. Doherty The qualitative nature of acetamiprid residue in livestock is also adequat ely understood based upon metabolism studies in ruminants (lactating goat) and laying hens. HED has determined that for risk assessment purposes, the residues of concern in livestock tissue (except ruminant muscle) are acetamiprid, plus its IM - 2 - 1 metabol ite. In ruminant muscle, the residues of concern for risk assessment are acetamiprid plus IM - 2 - 1 plus IM - 2 - 1 - amide. Residues of IM - 2 - 1 - amide in ruminant muscle tissue can be estimated b y applying a 10 - fold factor to residues of IM - 2 - 1 in muscle. 5.1.4 A nalytical Methodology Residue Chemistry Memo D 342549 , 1 1 / 05 /200 8 , W. Drew Residue Chemistry Memo D 328216 , 1 0 /2 3/200 7 , W. Drew (PP#6F7051 and PP#6E7163) Residue Chemistry Me mo D303623, 11/05/2004, W. Drew (PP#4F6833) Residue Chemistry Memo D 264154, 1 2 /31/2001, M . Doherty (PP#0F6082) Adequate gas chromatograph y with electron capture detection (GC/ECD) and high performance liquid chromatograph y with ultraviolet detection (HPL C/UV) residue anal ytical methods are available for the enforcement of established tolerances on plant commodities. The method limits of quantitation (LOQ) are 0.01 ppm for vegetables and non - citrus fruits (GC/ECD), and 0.050 ppm for c itrus fruits (HPLC/UV). A secondary liquid chromatography

with tandem mass spectrometric detection (LC/MS/MS) method, designated b y the petitioner as an alternative to the established GC/ECD tolerance enforcement method, has been determined suitable for t olerance enforcement, and confirmatory anal ys is of vegetables and non - citrus fruits. The GC/ECD method or LC /MS/MS Method #KP - 216R1 (or its modification) was used for the anal ys is of samples from the clover, grape, and tomato field trials. A cceptable rec overies were obtained in method validation efforts conducted prior to the anal ys is of field trial samples . Samples of dried green tea leaves and brewed tea from the Japan study were anal yz ed for residues of acetamiprid and its metabolites convertible to 6 - chloronicotinic acid (Metabolite IC -Page 29 of 63

0) using a common moiety gas chromatograph y method with electron capture detection (GC/ECD) . Using this method, acetamiprid and metabolites are converted to Metabolite I C - 0 and methylated prior to determination by GC/E CD; residues are expressed as acetamiprid. The reported method limit of detection (LOD) is 0.05 ppm as acetamiprid. Samples of green shoots, dried black tea leaves, brewed tea, and spent leaves from the India study were anal yz ed for residues of acetamiprid using a high performance liquid chromatography method with ultraviolet detection (HPL C/UV) similar to the HPL C/UV method discussed above. Regarding the common moiety method used in the Japan study , it was noted that, although Metabolite I C - 0 is not a r esidue of concern for tolerance enforcement or risk assessment, based on the available plant metabolism studies, it may constitute a significant portion of the total residues (e.g., up to 24% total radioactive residues (TRR) in cotton seed and 31% TRR in c arrot flesh; refer to D278652, 11/13/01, H. Bietlot and M. Doherty). Therefore, the residues reported for the Japan study

may reflect an overestimation of expected residues of acetamiprid per se in green tea. Adequate multiresidue methods testing data have been submitted. These data indicate that the multiresidue methods are not appropriate for determining residues of acetamiprid. 5.1.5 Environmental Degradation Acetamiprid is a mobile, rapidly biodegradable compound in most soils. The primary degradation pathway

is aerobic soil metabolism. Acetamiprid is stable to hydrol ys is at environmental temperatures, and photo degrades relatively slowl y in water. Acetamiprid is metabolized moderatel y rapidly in aerobic aquatic sy stems, but is only slowly metabolized in anaerobic aquatic s ys tems. Acetamiprid is expected to be moderatel y to highly mobile in most soils and aquatic sediments; however, based on guideline study data, it is not expected to be persistent in the envi ronment. Inenvironmental fate studies, residues of acetamiprid, IB - 1 - 1, IC O, IM - 1 - 2, IM - 1 - 3, IM - 1 - 4, and IM - 1 - 5 were identified. 5.1.6 Comparative Metabolic Profile Radiolabeled metabolism studies are availa ble for carrot, cabbage, cotton, apple, eggplant, lactating goat, laying hen , and rat . In plants, there appears to be little translocation of acetamiprid following foliar application. In cabbage, there was uptake and translocation of acetamiprid to the abo ve - ground portions of the plant following a soil application. Due to the rapid dissipation of acetamiprid in the field, root uptake is not considered to be a likel y source of residues in plants. Parent acetamiprid is the predominant residue (>90% TRR) in three of the five metabolism studies. Confined rotational crop studies showed no residues of acetamiprid at the 30 - day plant back interval. Acetamiprid and metabolite IM - 2 - 1 are the major residues in all ruminant tissues except muscle, where IM - 2 - 1 - amide accounts for nearl y 50% of the TRR. IM - 2 - 1 - amide was not found in any other ruminant tissue. Metabolite IM - 2 - 1 is the major residue in poultry tissues and eggs (50 - 80% TRR). IM - 2 - 5 is also a major residue in eggs (~20% TRR). Parent acetamiprid was notPage 30 of 63

detected in poultry

tissues or eggs. The metabolism of acetamiprid in lactating goat was similar to the profile observed in laying hen and rat. The initial transformation appears to be demethylation of the parent compound. The most abundant metabolite i dentified (both sexes) resulted from the removal of the cyanoacetamide group from demethyl ated parent. This removal (and direct removal of the group from the parent) resulted in cyanoacetamide metabolites. 5.1. 7 Pesticide Metabolites and Degradates of Con cern A comparison of the available acute toxicity data for the parent versus the metabolites indicates that the metabolites I C - 0, IM - 0, IM - 2 - 1, IM - 1 - 4, IM - 1 - 2, are either similar, or less acut el y toxic than the parent. In subchronic feeding and mutagenicity studies the tested metabolites were shown to be either equivalent to, or less toxic than the parent. The acute toxicity and mutagenicity

data indicate that the metabolite of concern in liv estock, IM - 2 - 1, is less toxic than the parent and is of similar mutagenic potential to the parent. Subchronic studies were not submitted to address the long - term toxicity of the IM - 2 - 1 metabolite. T able 5.1.2 summarize s the residues of concern (parent an d metabolites) that will be considered for regulation . Table 5.1. 7 Summary of Metabolites and Degradates to be included in th e Risk Assessment and Tolerance Expression Matrix Residues included in Risk Assessm ent Residues included in Tolerance Expression Plants Primary Crop Acetamiprid Acetamiprid

Rotational Crop Not applicable None at this time Livestock Ruminant Acetamiprid and IM - 2 - 1 (and IM - 2 - 1 - amide in ruminant muscle only) Acetamiprid and IM - 2 - 1 Poultry Acetamiprid and IM - 2 - 1 Acetamiprid and IM - 2 - 1 Drinking Water Acetamiprid Not Applicable 5.1. 8 Drinking Water Residue Profile D364248, D. Lieu 6/10/09. Tier I Drinking Water Assessment for Acetamiprid Proposed Uses on Red Clover (Grow n for Seed Only), Grape, and Tomato (Greenhouse). In a memo dated 6/10/09 [D364248 , D. L ieu], EFED notified RD that new drinking water estimates would not be provided for the proposed use on red clover (grown for see d onl y), grape, and tomato (greenhouse) because the drinking water estimates derived from the uses on citrus and tree nuts reflect the maximum use patterns for acetamiprid. (Note: No proposed use information has been submitted for U.S. - grown tea.) In con junction with the uses on citrus and tree nuts, the Environmental Fate and Effects Division (EFED) prepared an estimate of potential residues in drinking water [G. Orrick, Tier I DrinkingPage 31 of 63

Water Exposure Assessment for Acetamiprid on Cucurbit, Stone Fruit a nd Tree Nut Crop Groups, 6/21/05, D303582]. Estimated drinking water concentrations for acetamiprid in surface water were generated using the FIRST ( F QPA I ndex R eservoir S

creening T

ool, v. 1.0) model. The results of the model reflect potential residues i n a small drinking water reservoir surrounded by a runoff - prone watershed, assuming maximum pesticide application rates and no buffer between the reservoir and treated fields. Acetamiprid residues in ground water sources of drinking water were estimated u sing the screening regression model SCI - GROW ( S creening C oncentration In Gro und W ater, v. 2.3). The SCI - GROW residue estimate is based on environmental fate properties of the pesticide, maximum application rates, and existing data from small - scale prospec tive ground - water monitoring studies in vulnerable sites. For surface water, the maximum application rate for the existing use of acetamiprid on citrus was used to provide model estimates of drinking water concentrations; for ground water, the proposed us e on tree nut crops was used. However, since modeled surface water residues were considerabl y higher than ground water residues (Table 5.1.8) , onl y the surface water residues were used quantitativel y in the dietary (food + water) assessment. Table 5.1. 8 . Tier I Analysis 1 - in - 10 - year EDWCs in surface water and ground water for acetamiprid. Drinking Water Source Maximum Use Pattern Exposure EDWC Surface water Citrus fruit Peak 20.1 ppb Annual average 4.9 ppb Ground water Tree nut Peak & annual average 0.0016 pp b For the acute assessment, an estimated drinking water concentration of 20.1 ppb was entered into the DEEMTM - FCID model for “water, direct, all sources” and “water, indirect, all sources.” For the chronic assessment, the value of 4.9 ppb was used. The ground water estimate of 1.6 ppt was much lower than surface water residues; therefore, dietary exposure and risk calculated using surface water residues are considered protective of potential exposure through ground water. 5. 1. 9 Food Residue Profile D364833 , Acetamiprid. Request for Label Amendments for New Uses on Clover; Small Vine Climbing Fruits, except Kiwifruit, Subgroup 13 - 07F (amending grape use); Greenhouse - grown Tomatoes; and a Regional Registration for Tea. Summary of Analytical Chemistry and Residue Data. D. McNeilly, 10/1 4 /2009. IR - 4 has submitted magnitude of the residue data for acetamiprid on red clover, grapes, and tomato to support the new uses on clover and greenhouse tomatoes, and amended use on grapes (also expanded to small vine climbing fruits, except fuzzy kiwifruit, subgroup 13 - 07F). A s ummary of the residue data is presented in Table 5.1. 9 a. Residue data for tea, dried leaves; black brewed tea, green brewed te a, and spent leaves (for mass balance purposes only) are summarized in Table 5.1. 9 b .Page 32 of 63

Table 5.1. 9 a . Summary of Residue Data from Tea Crop Field Trials with Acetamiprid. Crop M atrix Total Applic.

Rate (lb ai/A) PHI

(days) Residue Levels (ppm)

n Min. Max. HAFT 1 Median Mean Std. Dev. Clover ( P roposed use = One broadcast foliar spray treatment at a m aximum of 0.075 lb ai/A; 28 - day PHI ) Clover forage 0.074 - 0.079 28 - 34 6 < 0.01 0.05 0.05 0.0 5 0.0 4 0.0 2 Clover hay 56 - 63 6 <0.01 <0.01 <0.01 0.01 0.01 -- Grapes and Other Climbing Vine Small Fruits (Except Fuzzy Kiwifruit) (Within Crop Subgroup 13 - 07F)

(Current registered use on Grapes = 0.1 lb ai/A total application rate; 7 - day PHI) (Proposed am ended use = 0.2 lb ai/A total application rate; 3 - day PHI) Grape 0.195 - 0.206 2 - 3 36 0.01 0.25 0.2 5 0.08 0.11 0.07

Tom atoes (Current registered field use = 0.3 lb ai/A total application rate; 7 - day PHI)

(Proposed greenhouse use = 0.15 lb ai/A total application rate; 1 - day PHI) To mato 0.300 - 0.324 1 6 < 0.01 0.052 0.0 50 0.027 0.02 9 0.01 8 1 HAFT = Highest average field trial result. TABLE 5.1. 9 b. Summary of Residue Data from Crop Field Trials with Acetamiprid. Commodity Total Applic.

Rate, lb ai/A [kg ai/ha] PHI

(days) Residue Levels (ppm)

n Min. Max. HAFT 1 Median (STMdR) Mean

(STMR) Std. Dev. Japan Study - Combined residues of acetamiprid and residues convertible to Metabolite IC - 0 Gr een tea - dried leaves 0.13 - 0.27

[0.15 - 0.30] 6 - 7 8 13.6 40.9 39.3 23.9 25.3 9.82

13 - 14 8 8.15 17.2 16.6 1 3.1 12.8 4.19 20 - 21 8 2.30 5.44 5.44 3.64 3.75 1.19 Gr een tea - brewed tea* 0.13 - 0.27

[0.15 - 0.30 6 - 7 8 7.74 27.7 27.0 17.3 17.4 7.29

13 - 14 8 5.17 12.7 12.6 9.21 9.07 3.38 20 - 21 8 1.57 3.30 3.27 1.87 2.15 0.70 India Study (wet and dry season tea) - Residues of acetamiprid per se (only mean values reported) 2 Black tea - green shoots 0.022 - 0.045

[0.025 - 0.050] 0 12 3.96 9.53 9.53 NC 3 6.54 NC

7 12 0.20 0.51 0.51 NC 0.33 NC 15 12 0.03 0.11 0.11 NC 0.06 NC 21 12 <0.05 <0.05 < 0.05 < 0.05 < 0.05 0 Black tea - dried leaves 0.022 - 0.045

[0.025 - 0.050] 0 12 11.2 26.4 26.4 NC 18.5 NC

7 12 0.54 1.47 1.47 NC 0.95 NC 15 12 <0.05 0.26 0.26 NC 0.11 NC 21 12 <0.05 <0.05 < 0.05 < 0.05 < 0.05 0 Black tea - brewed tea* 0.022 - 0.045

[0.025 - 0.050] 0 12 5.4 1 2.6 12.6 NC 8.92 NC

7 12 0.24 0.61 0.61 NC 0.41 NC 15 12 <0.05 0.13 0.13 NC 0.07 NC 21 12 <0.05 <0.05 < 0.05 < 0.05 < 0.05 0 Black tea - spent leaves 0.022 - 0.045

[0.025 - 0.050] 0 12 4.6 10.2 10.2 NC 7.5 NC

7 12 0.20 0.51 0.51 NC 0.36 NC 15 12 < 0.05 0.09 0.09 NC 0.06 NC 21 12 <0.05 <0.05 < 0.05 < 0.05 < 0.05 0 HAFT = Highest Average Field Trial. 2 The reported LOD (0.05 ppm) was used for calculation of median, mean, and standard deviation where appropriate. Only the 0 - day PHI and PHIs relevant for comparison to the Japan trials were included in the summary. 3 NC = Not calculated. Median and standard deviation could not be calculated because only mean values were reported for each sample set. * The relatively high residues in the brewed te a, which HED expected to be much lower than the residues in or on the dried tea leaves, may reflect a back calculation of what the residues would have been on the dried tea leaves. Otherwise, HED can not account for why the residues were not diluted by th e water used for making the tea.Page 33 of 63

Clover Three red clover field trials were conducted in the U.S. in Zone 11 (OR) during the 2006 growing season. Each trial site consisted of one untreated plot and one treated plot. Red clover was treated with a single b roadcast foliar application of Assail® 30SG, a 30% SG formulation of acetamiprid, at a rate of 0.074 - 0.079 lb ai/A (ca. 1x the maximum proposed seasonal rate on clover). Application was made when the crop was in the vegetative stage to blooming stage usin g ground equipment in 23 - 25 GPA spray volumes, without an adjuvant. Samples of clover forage were harvested 28 to 34 day s following application. Additionally , hay samples were cut at a normal harvest time (coinciding with preharvest intervals of 56 - 63 days) and allowed to dry in the field prior to collection. Residues of acetamiprid were <0.01 - 0.05 ppm in/on red clover forage harvested 28 - 34 day s following a single broadcast foliar application of the 30% SG at 0.074 - 0.079 lb ai/A. Residues were below th e LLMV (<0.01 ppm) in/on clover hay harvested 56 - 63 day s following treatment. Conclusions : The use pattern of the clover field trials adequatel y reflects the proposed label use pattern with the exception of the PHI for hay . The available field trial dat a indicate a regional tolerances for residues of acetamiprid in clover forage at 0.10 ppm and clover hay at 0.01 ppm , are appropriate . However, the submitted clover field trial data are not completely adequate to satisfy data requirements. The three clov er field trials were all conducted in Zone 11 (OR) during the 2006 growing season, at the same location and within a very short time period of each other. The number of trials are adequate to support restricted use on clover in ID, OR and WA (Zones 11 and 12) according to OPPTS Guideline 860.1500, Attachment 11; however the guidelines state that for crops requiring 8 or more trials nationally (12 are required for clover), the trials for regional registrations must be conducted in multiple years to account for variability due to climate conditions. As a condition of registration, HED recommends that two additional clover field trials be required, as confirmatory data. In addition, the submitted reside data included field trial data for only the 30SG formul ation. However, additional residue chemistry field trial data are not required to support registration of the 70 WP formulation. U se on clover grown for seed is to be limited to clover grown in ID, OR, and WA. Since the residue chemistry data submitted for clover hay reflect PHIs of between 56 - 63 day s, the PHI for acetamiprid use on clover should be increased to 56 day s for any clover crop which will be harvested for hay . No residue decline data were included in the clover field trials. However, r esidu e decline studies on cotton, head lettuce, oranges, pears, and peppers were submitted in conjunction with PP#0F6082 ( D 264154 , 12/31/2001, M. Doherty). These data indicated that residues of acetamiprid did not increase in the subject crops with increasing harvest intervals. Given the long PHI (28 - day s) for clover and available residue decline data on other crops, residue decline data will not be required to support the clover field trials. The available field trial data will support tolerances with region al registration for residues of acetamiprid in clover forage at 0.10 ppm (with a 28 - day

PHI) and clover hay

at 0.01 ppm (with a 56 - day PHI).Page 34 of 63

Grape; Fruit, Small Vine Climbing, Subgroup 13 - 07F, Except Fuzzy Kiwifruit Eighteen grape field trials were con ducted in the U.S. and Canada in Zones 1 (NY; 1 trial), 2 (NJ; 2 trials), 5 (ON; 4 trials), 5A (MI; 1 trial), 10 (CA; 8 trials), 11 (BC; 1 trial), and 11/12 (WA; 1 trial) during the 2005 growing season. Mature grape vines in established orchards were treated with two directed foliar applications of Assail® 70WP, a 70% WP formulation of acetamiprid, at 0.096 - 0.103 lb ai/A/application, with a 13 - to 14 - day retreatment interval, for a total rate of 0.195 - 0.206 lb ai/A (ca. 1x the maximum proposed seasonal rat e on grapes and other climbing vine small fruits . Residues of acetamiprid were 0.01 - 0.25 ppm in/on grapes harvested 2 - 3 day s following the last of two directed foliar applications of the 70% WP for a total rate of 0.195 - 0.206 lb ai/A. No residue decline data were included in the field study. Conclusions : The submitted grape residue data included field trial data for only the 70WP formulation (the original field trials also used a 70WP formulation). Although HED’s residue chemistry review (D364833, 10/1 4/09) recommended that additional residue chemistry field trial data are needed to support registration of the 30SG formulation , additional information provided by the registrant has convinced HE D that such data are not necessary . HED agrees that both pro ducts are likel y to produce a solution of acetamiprid due to its high water solubility . The submitted grape field trial data are adequate for the 70 WP formulation pending label revision. Because the grape field trial data did not reflect the use of a surfactant in the application spray s, the label directions regarding use of a spreader, methylated seed oil or crop oil should be removed from the product label of Assail® 30SG (EPA Reg. No. 8033 - 36). Furthermore, in line with present OPP policy for a late season foliar use, a statement should be added to both the 30SG and 70WP labels prohibiting addition of adjuvants for application to grapes. If use of an adjuvant is desired then one should be used in side - by- side testing. The number and locations of the field trials are in accordance with OPPTS Guideline 860.1500 for grapes, and the use pattern of the field trials reflects the use pattern proposed for grapes ( and o ther c limbing v ine s mall f ruits , e xcept f

uzzy kiwifruit , within s ubgroup 13 - 07F) , except f or the adjuvant use. No residue decline data were included in the grape field trials. The r esidue decline studies from PP#0F6082 ( D 264154 , M. Doherty , 12/31/2001 ) , which indicated that residues of acetamiprid did not increase in various crops with increasing harvest intervals , will be used to fulfill the requirements for residue decline data . The available field trial data from the current submission, which reflect a higher seasonal rate and a shortened PHI from that which is currentl y registered for grape, will support a tolerance for residues of acetamiprid at 0.35 ppm . Grape is the representative crop of the fruit, small vine climbing, subgroup 13 - 07F, except f uzzy kiwifruit , and the available grape data will support a subgroup tolerance at 0.35 ppm. The established individual tolerance for grape at 0.20 ppm should be deleted when the subgroup 13 - 07F tolerance is established .Page 35 of 63

Tomatoes (Greenhouse Study) Three trials were conducted on tomatoes in the U.S. and Canada in Zones 4 (TN), 5 (ON), and 6 (TX) during the 2002 and 2003 growing seasons. Each trial site included one untreated plot and one treated plot. Tomato plants grown in rock wool substrate under greenhouse conditions were treated at the fruiting stage with four simulated drip - irrigatio n (chemigation) treatments of Assail® 70WP, a 70% WP formulation of acetamiprid, at rates equivalent to 0.074 - 0.081 lb ai/A/application. Applications were made with 7 - day retreatment intervals, for a total rate of 0.300 - 0.324 lb ai/A (ca. 2x the maximum p roposed seasonal rate for greenhouse - grown tomato); no adjuvant was used. Samples of mature tomato were harvested one day after the last application. At the TX trial, additional treated samples were harvested 3, 5, and 7 day s after the last application t o generate residue decline data. Residues of acetamiprid ranged from below the LLMV (<0.01 ppm) to 0.052 ppm in/on greenhouse - grown tomatoes harvested one day following the last of four drip - irrigation (chemigation) treatments of the 70% WP for a total rate equivalent to 0.300 - 0.324 lb ai/A. The decline data show that residues accumulated slightly , from an average of 0.027 ppm at the 1 - day PHIto an average of 0.037 ppm at the 7 - day PHI. Conclusions: Although the greenhouse trials were conducted at a 2x rate and the number of trials is marginal, no additional residue data will be required to support the proposed greenhouse use pattern for tomatoes. T he tomato greenhouse data indicate that acetamiprid residues resulting from applications of Assail 70WP f ormulation of acetamiprid according to the proposed use pattern would not exceed the established tolerance for residues of acetamiprid in fruiting vegetables, crop group 8 (0.20 ppm). Although n o data were provided for the proposed use of Tristar® 30SG on greenhouse tomatoes , HED now concludes the WP data support use of this additional formulation based on the water solubility of the active ingredient and the application being made to the roots of the plants by soil drench or irrigation water. Tea The Interregional Research Project No. 4 (IR - 4) has submitted a report summarizing the results of two studies on tea conducted in Japan (by Nippon Soda Co., Ltd.) and In dia (by the Institute of Himalayan Bioresource Technology ; IHBT). No raw data were included in the submission, all data presented herein are as reported in the original studies. Nippon Soda Co, Ltd. conducted two trials in the Mie Prefecture and the Fukuoka Prefecture of Japan investigating the magnitude of the residue in dried green tea leaves and brewed tea following a single foliar application of a 20% w ater - soluble powder (SP) formulation of acetamiprid made to green tea in separate plots at 0.13 lb ai/A (0.15 kg ai/ha) and 0.27 lb ai/A (0.30 kg ai/ha). Applications were made in spray volume s of 321 gal/A (3000 L/ha). The following Good Agricultural Practice (GAP) information was provided for the 20% SP formulation in Japan: one foliar application at 0.10 - 0.40 kg ai/ha applied in 2000 - 4000 L/ha, with a 14 - day

preharvest interval (PHI). In a separate study , the Institute of Himalayan Bioresource Technology

(IHBT) conducted two sets of trials in Palampur (Himachal Pradesh,Page 36 of 63

India) investigating the magnitude of the residue in black tea for green shoots, dried tea leaves, brewed tea, and spent leaves after brewing. Acetamiprid was applied to black tea in separate plots as a single foliar application of a 20% SP formulation of acetamiprid at 0.022 lb ai/A (0.025 kg ai/ha) and 0.045 lb ai/A (0.050 kg ai/ha) in spray volumes of 43 gal/A (400 L/ha) . The application rates were reported to be 1x and 2x the recommended application rate for acetamiprid on tea. Two sets of trials were conducted, one during the dry season (June) and the second during the wet season (August). The following GAP informati on was provided for India: shoots along with bud are typic ally harvested at a 7 - day

PHI . Samples of dried green tea leaves and brewed tea from the Japan study were anal yz ed for residues of acetamiprid and its metabolites convertible to 6 - chloronicotinic acid (Metabolite IC 0) using a common moiety gas chromatograph y method with electron capture detection (GC/ECD) . Using this method, acetamiprid and metabolites are converted to Metabolite I C - 0 and methylated prior to determination by GC/ECD; residues are expressed as acetamiprid. The reported method limit of detection (LOD) is 0.05 ppm as acetamiprid. Samples of green shoots, dried black tea leaves, brewed tea, and spent leaves from the India study were anal yz ed for residues of acetamiprid using a high p erformance liquid chromatography method with ultraviolet detection (HPL C/UV). The reported LOD was 0.05 ppm. Both methods are adequate for data collection based on the submitted concurrent recovery data . Regarding the common moiety method used in the Jap an study , we note that, although Metabolite I C - 0 is not a residue of concern for tolerance enforcement or risk assessment, based on the available plant metabolism studies, it may constitute a significant portion of the total residues (e.g., up to 24% total radioactive residues (TRR) in cotton seed and 31% TRR in carrot flesh; refer to D278652, 11/13/01, H. Bietlot and M. Doherty). Therefore, the residues reported for the Japan study

may reflect an overestimation of expected residues of acetamiprid per se i n green tea. Samples of dried green tea leaves and brewed tea from the Japan study were stored frozen from collection to anal ys is for up to 3.5 and 1.7 months, respectivel y. HED believes there are sufficient storage stability data available for acetamiprid, demonstrating that residues are stable in crop commodities stored frozen for up to 12 months and crop commodities stored at ambient temperatures for up to 7 day s, to support both studies (refer to D264154, M. Doherty, 12/31/01). The study report also contained a list of multiresidue method anal ys is results for residues of acetamiprid in tea received in commercial shipments from various countries. Although residues were nondetectable in the majority of green and black tea samples received from Argentin a, Bangladesh, Burundi, China, Ecuador, Ethiopia, India, Indonesia, Iran, Kenya, Malawi, Mozambique, Rwanda, Sri Lanka, South Africa, Tanzania, Turkey , Uganda, Vietnam, Zimbabwe, detectable residues of acetamiprid were found in tea samples from China (0.03 - 0.04 ppm; n=3), Indonesia (0.03 ppm; n=1), and Vietnam (0.03 - 0.12 ppm; n=7). The source of these data was not identified. Conclusions: No use was proposed for domestically grown tea. The acetamiprid data for tea grown in Japan and India consist ed of f ield trial data representing application rates of 0.022 - 0.27Page 37 of 63

lb ai/A (1 foliar application) with a 6 - to 14 - day PHI and were entered into the tolerance spreadsheet as it matched the global GAP of 7 - 14 day PHI s . All 38 field trial sample results were equal to or greater than the LOD (LOD = 0.0 5 ppm ). HED believes that the 50.0 ppm tolerance (without U.S. registrations, i.e., an import tolerance) is adequate to cover residues in or on tea and instant tea and hence is not recommending for a separate instant tea tolerance. HED notes that the 50.0 ppm tolerance harmonizes with Japan. The residue data from Japan included the I C - 0 metabolite, which is not in the U.S. tolerance expression and is considered conservative. A summary

table of proposed and recommen ded tolerances for acetamiprid associated with all th e proposed commodities and uses can be found in Appendix C . 5.1.1 0 International Residue Limits There are no Codex maximum residue limits ( MRLs ) establish ed for residues of acetamiprid o n crop or animal commodities; no Mexican MRL s are established on crops associated with this petition. Canada has established an MRLfor acetamiprid residues in grapes at 0.20 ppm. The recommended U.S. tolerance for Subgroup 13 - 07F tolerance at 0.35 ppm is not harmonized with the Canadian MRL, presumably because of differences in good agricultural practices. Japan has a 50 ppm MRLfor tea and HED recommends setting the tolerance at the same level. An International Residue Li mit Status (IRL S ) sheet is appended to this document . 5.2 Dietary Exposure/Risk Pathway Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For acute and chronic dietary

risk assessments, the risk is expressed as a perc entage of the population adjusted dose (PAD). The acute PAD (aPAD) is d erived by dividing the selected acute dietary dose (NOAEL) b y the appropriate uncertainty and FQPA safety factors. The chronic PAD (cPAD) is derived by

dividing the selected chronic dietary dose (NOAEL) by

the appropriate uncertainty and FQPA safety factors. Ty picall y, HED has dietary

risk concerns when the estimated exposure exceeds 100% of the aPAD and/or cPAD . 5.2.1 Dietary Exposure and Risk Acute and chronic dietary risk assess ments were conducted for acetamiprid using the Dietary Exposure Evaluation Model (DEEM - FCID  , Version 2 . 0 3) which use s food consumption data from the USDA’s Continuing Survey s of Food Intakes by Individuals (CSFII, 1994 - 1996 and 1998). The acute and chron ic dietary analy s e s are considered partially refined by

the inclusion of percent crop treated values and processing data. The full dietary anal ys is for the subject peitions can be found in the HED memorandum : Acetamiprid . Acute and Chronic Dietary Expos ure Assessments to Support Section 3 Registration of Uses on Clover, Small Vine Climbing Fruits, except Kiwifruit, Subgroup 13 - 07F, Greenhouse Grown Tomatoes and Tea. D 369019, 12 / 01 /09 . The current acute and chronic dietary exposure assessments include e xisting uses and the tolerances proposed b y the Interregional Research Project Number 4 (IR - 4) for new uses of acetamiprid on clover grown for seed, small vine climbing fruits, except kiwifruit, subgroup 13 -Page 38 of 63

07F (amending established grape uses), greenhouse - grown tomatoes , and tea. For the acute dietary

assessment, f

ield trial residues were refined when possible . If field trial residues were reported below the limit of quantification (LOQ), HED assumed 1⁄2 LOQ (i.e., 0.005 ppm). In certain cases where it wa s appropriate, HED translated field trial data from one commodity

to another (e.g., peaches to nectarines, or plum to apricots). Percent crop treated estimates, which exist for only several of the subject crops (apples, broccoli, celery , lettuce, pears, grapefruit, grapes, oranges, peppers, spinach, and tomatoes), were incorporated into the dietary assessment s as a refinement. Average percent crop treated values for commodities were applied to the chronic dietary assessment, and maximum percent crop treat ed values were applied to the acute dietary assessment (see Table 5.2. 1 ) . Processing factors based on submitted studies were incorporated into the acute dietary analy s e s for the following commodities: apple juice, orange juice, grape juice, raisins, drie d prunes, tomato paste, and tomato puree. For all other commodities included in the acute assessment, the DEEMTM Version 7.87 default processing factors were used. Those default factors were used for all processed commodities in the chronic assessment except for dried prunes. Finally , t olerance level residues were also used for livestock commodities. Usa ge Data In order to refine the dietary exposure estimates for acetamiprid, HED requested a Screening Level Usage Anal ys is (SLUA), which was conducted by the Biological and Economic Anal ys is Division (BEAD), 6/11/09. The SLUA includes estimates of maximum %CT for the acute assessment and average %CT for determining chronic exposure (Table 5.2.1.) . Commodities with the most significant acetamiprid usage in terms of maximum %CT include pears (60%), apples (30%), celery

(45%), and lettuce (20%). Commodities with the most significant usage in terms of lbs ai applied include apples (10,000), cotton (20,000), and pears (5,000). Table 5.2.1 . Percent Crop Treated Data Used in DEEM Comm odity Avg Max Apples 20 30 Broccoli 5 1 5 Cabbage 5 10 Cauliflower 10 1 5 Celery 25 45 Cotton 5 5 Grapefruit 2.5 2.5 Grapes 5 10 Lemons 5 5 Lettuce 10 20 Oranges 2.5 5Page 39 of 63

Table 5.2.1 . Percent Crop Treated Data Used in DEEM Comm odity Avg Max Peaches 1 2.5 Pears 35 60 Peppers 2.5 5 Potatoes 2.5 2. 5 Pum pkins 1 2.5 Spinach 5 15 Squash 2.5 2.5 Tomatoes 5 10 For the acute anal ys is, %CT w as incorporated into RDFs. For the chronic analy sis, average %CT was included for the commodities listed in the table above. As mentioned above, under Section 5.1. 8 , HED incorporated EDWCs directly into the DEEMTM FCID model for “water, direct, all source s” and “water, indirect, all sources. ” For the acute assessment, an EDWC of 20.1 ppb was entered into the model , and for the chronic assessment, the value of 4.9 ppb was used. 5.2.2 Exposure and Risk Characterization The dietary

anal ys es reflect all currently registered and proposed acetamiprid uses and indicate that both the acute and chronic dietary exposure do not present a risk concern for HED for the general U.S. population o r an y of population subgroup (Table 5.2.2) . Acute Dietary

(Food and Drinki ng Water) Exposure Results and Characterization The probabilistic acute dietary exposure assessment included anticipated residues from field residue trials, processing factors, maximum %CT estimates (for existing uses only) generated by the Biological and Economic Analy sis Division (BEAD), and the modeled peak concentration of acetamiprid residues in surface water sources of drinking water. 100 %CT was assumed for crops where % crop treated information was not available. Although the acute assessment has been refined, the resulting exposure estimates are still considered conservative since field trial data were the basis for the anticipated residues, and because a lower tier drinking water model (FIRST) was used to estimate residues in drinking water. Ac ute dietary

exposure estimates at the 99.9 th percentile are below HED’s level of concern for the general US population and all other population subgroups. For the US population, the estimated exposure of 0.0 20 mg/kg/day corresponds to 20 % aPAD; for children 1 - 2 years old, the estimated exposure of 0.0 41 mg/kg/day corresponds to an acute dietary risk of 41 % aPAD.Page 40 of 63

Chronic Dietary (Food and Drinking Water) Exposure Results and Characterization For the chronic anal ys is, tolerance - level residues were assum ed for all food commodities with existing and proposed acetamiprid tolerances. Percent crop treated was used for man y commodities as detailed in Table 5.2. 1 . The chronic anal ys is also included the modeled surface water annual average residue in drinking water. Even though %CT information was used in the chronic analy sis, the exposure and risk estimates are still conservative since tolerance level residues were used, because 100 %CT was assumed for crops where % crop treated information was not available, and because a lower tier drinking water model (FIRST) was used. Chronic dietary

exposure to acetamiprid, including existing and proposed uses, is below HED’s level of concern for the US population and all other population subgroups. For the general US p opulation, an estimated exposure of 0.00 24 mg/kg/day corresponds to 3 % of the chronic population adjusted dose (cPAD); children 1 - 2 years old were the highest exposed population subgroup, with an estimate of 0.0 087 mg/kg/day , or 12 % cPAD. Risks for all po pulation subgroups are less than 100% cPAD, and are not of concern.

Table 5.2.2. Summary of Dietary (Food + Water) Exposure and Risk for Acetamiprid Population Subgroup Ac ute Dietary (99.9 th Percentile) Chronic Dietary Dietary Exposure (mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD General U.S. Population 0.0 20190 20 0.00 2375 3.3 All Infants (< 1 year old) 0.0 26336 26 0.0 04780 6.7 Children 1 - 2 years old 0.04 0892 41 0.0 08693 12 Children 3 - 5 years old 0.02 9647 30 0.0 06066 8.5 Children 6 - 12 years old 0.01 6429 16 0.00 3396 4.8 Youth 13 - 19 years old 0.01 3137 13 0.00 1739 2.5 Adults 20 - 49 years old 0.01 3988 1 4 0.00 1683 2 .4 Adults 50+ years old 0.0 12372 12 0.00 1808 2.5 Females 13 - 49 years old 0.0 11917 12 0.00 1 7 08 2.4 5.2.3 Cancer Dietary Risk HED has classified acetamiprid as “not likely to be carcinogenic to humans.” Based upon this classification, HED has determined there is no cancer risk associated with the existing and proposed uses. 6.0 Residential (Non - Occupational) Exposure/Risk Ch aracterization The registrant has not proposed new or revised residential use s . Therefore, new residential handler and postapplication exposure assessments were not conducted . Acetamiprid isPage 41 of 63

registered for controlling a wide variety of indoor and outdoor insect pests in residential settings. The MOEs for residents applying bait and gel products were 1500 - 3500 (D303171, T. Moriarity , 10/25/07). In a more recent assessment of exposures t o residential handlers from products used on indoor and outdoor residential settings, the risks were found to be not of concern for all scenarios identified ( D353040, Z. Figueroa, 12/1/08). An anal ys is of the postapplication risks to adults and c hildren from contacting treated areas ha s also been performed recentl y (D353012, C. Swartz, 12/12/08) . Inthe tables below, only the risk to children are shown since as noted in the 12/12/08 memo they

are the worse case versus those for adults. Table 6a . Acetamiprid: Short - and Intermediate - Term Postapplication Exposures and Risks to Toddlers Following Turf Treatments in Residential Settings. 1 Exposure Scenario Application Rate (lb AI/acre) Expo sure (mg/kg/day) MOE 2

Short - term Interm. term Short - term Interm. term Residential turf (dermal) 0.187 0.0072 0.0036 1,400 2,800 Hand to mouth (oral) 0.0028 0.0013 3,600 7,600 Object to mouth (oral) 0.00069 NA 14,500 NA Incidental s oil i nges tion (oral) 0.0000093 NA 1,100,000 NA Total e xposure (dermal & oral) N/A 0.0107 0.0049 900 2,000 1. From C . Swartz, D353012, 12/12/08. 2. Short - & intermediate - term dermal or oral NOAEL (10 mg/kg/day)/exposure (mg/kg/day). TABLE 6b : Acetamiprid: S hort - term Postapplication Exposure and Risk to Toddlers Following Indoor Crack and Crevice Treatments 1 Exposure Scenario Descriptor Exposure (mg/kg/day) MOE 2 Dermal exposure Carpet and hard surfaces 0.0195 510 Incidental oral exposure 0.0065 1500 Total dermal & oral exposures 0.026 380 1. From C . Sw artz, D353012, 12/12/08. 2. Short - & intermediate - term dermal or oral NOAEL (10 mg/kg/day)/exposure (mg/kg/day). Aggregate e xposures of acetamiprid include the short - and intermediate - term postapplication exposures following turf treatment and the short - term postapplication exposure following indoor crack and crevice treatment. 6.1 Residential Handler Exposure The MOEs for residents applying bait and gel products were 1500 - 3500 (D303171, T. Moriarity , 10/25/07). Ina recent assessment of exposures to residential handlers from products used on indoor and outdoor residential settings, the risks are not of concern for all applicable scenarios identified (D353040, Z. Figueroa, 12/1/08). 6.2. Residential Postapplication Exposure An evaluation of postapplication exposure resulting from the proposed use and label change wasPage 42 of 63

completed (D353040, Z. Figueroa, 12/1/08 and D366701, S . Oonnithan , 10/ 9 /09 ); risks were not of concern for an y of the scenarios identified and assessed. Detailed discussions of the assumptions and methods used for asses sing residential exposure from the proposed use are provided in the 12/1/08 memorandum. The postapplication scenarios assessed for toddlers’ exposure following perimeter treatment include:

 Dermal e xposure from treated l awns due to h igh c ontact l awn activ ities;  H and - to - mouth transfer of p esticide residues on l awns ;  O bject - to - mouth transfer of p esticide residues on lawns; and  Incidental i ngestion of s oil from p esticide - treated r esidential areas. Risks for these scenarios are provided in Table 6.2a. Tab le 6.2a . Short - and Intermediate - Term Dermal & Indirect Ingestion - Toddler Residential Risk Estimates for Postapplication Exposure on Turf Exposure Scenario Route of

Exposure Application

Rate (lb ai/acre) Dermal Transfer

Coefficient (μg/cm 2 ) Absorbed Dos e (m g/kg/day) MOE Residential Turf Dermal 0.187 5,200 (Short - term) 0.0072

(Short - term) 1,400 2,600 (Intermediate - term) 0.0036

(Intermediate - term) 2,800 Hand to Mouth Oral NA 0.0028 (Short - term) 3,600 0.0013 (Intermediate - term) 7,600 Object to Mouth Oral NA 0.00069 14,500 Incidental Soil Ingestion Oral NA 0.0000093 1,100,000 Combined Exposure 1 N/A N/A N/A 0.0107 1 (Short - term) 900 1 0.00 49 1 (Intermediate - term) 2 , 00 0 1 1 - Com bined exposure is the sum of dermal and oral exposures. Table 6.2b summarizes the postapplication exposure and risk for toddlers resulting from contact with carpet and hard surfaces following c rack and crevice application of F4688 50 W P Insecticide/Termiticide on indoor surfaces. The bolded values represent the expo sure to be aggregated with exposure from food and drinking water. TABLE 6.2b : Postapplication Exposure and Risk Following Indoor Crack / Crevice Treatm ent . Scenario Descriptor Daily Dose (m g/kg/day) MOE Dermal Exposure Carpet and Hard Surfaces 0.0195 510Page 43 of 63

Incidental Oral Exposure Carpet and Hard Surfaces 0.0065 1500 Combined Dermal Incidental Oral Exposure Carpet and Hard Surfaces 0.0260 380 6.3 Other (Spray Drift, etc .) Spray drift is a potential source of expo sure for residents living in close proximity to spraying operations. This situation is particularl y the case with aerial application. However, to a lesser extent, spray

drift resulting from the ground application of acetamiprid could also be a potential source of exposure. The Agency has been working with the Spray Drift Task Force (a membership of US pesticide registrants), EPA Regional Offices, State l ead Agencies for pesticide regulation, and other parties to develop the best spray drift management practices. The Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling. The Agency has completed its evaluation of the new database submitted by

the Spray

Drift Task Force, and is developin g a policy on how to appropriatel y apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast, and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off - target drift and risks associated with pesticide application . 7.0 Aggregate Risk Assessments and Risk Characterization Consistent with F QPA, HED consider s aggregate risk to a pesticide from the three major routes (dermal, oral, and inhalation) when potential residential exposures exist . In its acetamiprid aggregate assessment, HED combined dietary (food + water) and non - dietary (residenti al) exposure sources to obtain an estimated aggregate exposure. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure. Based upon the residential use pattern of acetamiprid products, HED has dete rmined that acute, short - term, intermediate - term and chronic aggregate risk assessments are appropriate. 7.1 Acute Term Aggregate Risk The acute aggregate risk is equal to the acute dietary exposure via food and drinking water , and therefore is identical to the exposure and risk characterization found in Section 5.2.2 . The a cute aggregate risks for acetamiprid are less than 100 % of the aPAD for all population subgroups and , therefore , do not pose a risk concern fo r HED. 7.2 Short - and Intermediate - Term Aggregate Risk Short - term aggregate risk is based on the chronic (average) dietary exposure (food + water) combined with short - term residential exposure. Intermediate - term aggregate risk is based on the chronic (average) dietary exposure combined with intermediate - term residential exposure.Page 44 of 63

Short - and intermediate - term aggregate risks for residential handlers were assessed previously by T. Moriarity

(see Tab le 15, D303171, 10/25/07). The aggregate MOEs for two adult populations (20 - 49 years; 50+ ye ars) were 900 to 930. Since the dietary exposure estimates are now more refined due to the greater use of percent crop treated, these aggregate risks would be even lower and are not of concern. For short - term and intermediate - term aggregate risks, the combined chronic dietary (food + water) exposure is combined with short - and intermediate - term residential postapplication exposures for toddlers. The combined fo od, water and residential exposures are then compared to the dose for risk assessment to determine the resulting margin of exposure (MOE). HED has updated the dietary

component (food and water) in this assessment. Inthe case of acetamiprid, all short - and intermediate - term risk assessments are based on the effects observed in the DNT study , and therefore exposures from dermal and oral routes have been combined. See Table 7.2 for a summary

of short - and intermediate - term aggregate risks for toddlers. TA BLE 7.2 : Acetamiprid Short - and Interm ediate - Term Aggregate Exposure and Risk for Toddlers . Scenario Combined

Dermal/Oral Exposure (mg/kg/day) 1 Chronic Food Exposure Food (mg/kg/day) 2 Aggregate Exposur e (mg/kg/day) 3 MOE 4 Indoor Exposure Crack and Crevice Treatment (short - term) 0.0260 0.0 08693 0.0 347 290 Turf Exposure (short - term) 0.0107 0.0 08693 0.0194 520 Turf Exposure (intermediate - term) 0.00 49 0.0 08693 0.0136 740 1. Com bined d ermal and oral exposure s were taken from D3 66701 , S . Oonnithan , 10/9 /0 9 . 2. Chronic food exposure does not change with each scenario; see Table 5.2.2 . 3. Aggregate exposure = Combined dermal/oral exposure + chronic food exposure. 4. MOE = NOAEL/Aggregate Exposure = 10 (mg/kg/day)/aggregate exposure (mg/kg/day). Short - and intermediate - term aggregate risks (MOEs) are not of concern . HED notes that the lowest aggregate MOE of 29 0 is based on the indoor use. The MOEs calculated for exposure from turf are higher, but are considered to be more conservative, because the intended use pattern does not include broadcast treatment of lawns, but has been assessed as such in order to be protective. Adult aggregate risks due to postapplication exposure have not been assessed since the toddler risk s are the worst case. 7.3 Chronic - Term Aggregate Risk The dietary

exposure pathway (food and drinking water) is the onl y source of chronic exposure to acetamiprid ( i.e., 180 consecutive day s or more ). Therefore, the chronic aggregate exposurePage 45 of 63

and risk estimates are equivalent to the chronic di e tary exposure and risk estimate s discussed in Section 5.2.2 above . The chronic aggregate risks for acetamiprid are less than 100% of the cPAD for all population subgroups and , do not pose a risk concern for HED. 8.0 Cumulative Risk Characterization/Assessment FQPA (1996) stipulates that when determi n ing the safety of a pesticide chemical, EPA shall base its assessm ent of the risk posed by the chemical on, among other things, available information concerning the cumulative effects to human health that may result from dietary , residential, or other non - occupational exposure to other substances that have a common mecha nism of toxicity . The reason for consideration of other substances is due to the possibility that low - level exposures to multiple chemical substances that cause a common toxic effect by a common mechanism could lead to the same adverse health effect as wo uld a higher level of exposure to any of the other substances individually . A person exposed to a pesticide at a level that is considered safe may , in fact , experience harm if that person is also exposed to other substances that cause a common toxic effec t by

a mechanism common with that of the subject pesticide, even if the individual exposure levels to the other substances are also considered safe. Acetamiprid is a member of the neonicotinoid class of pesticides which also includes thiamethoxam, clothianidin, imidacloprid and several other active ingredients. Structural similarities or common effects do not constitute a common mechanism of toxicity . Evidence is needed to establish that the chemicals operate b y the same, or essentially the same sequence of major b iochemical events (EPA, 2002). Although the neonicotinoids bind selectivel y to insect nicotinic acetyl choline receptors (nAChR), the specific binding site(s)/receptor(s) are unknown at this time. Additionally, the commonality of the binding ac tivity itself is uncertain, as preliminary

evidence suggests that clothianidin operates by direct competitive inhibition, while thiamethoxam i s a non - competitive inhibitor. Furthermore, even if future research shows that neonicotinoids share a common binding activity to a specific site on insect nicotinic acetyl choline receptors, there is not necessaril y a relationship between this pesticidal action and a mechanism of toxicity

in mammals. Structural variations between the insect and mammalian nAChRs produ ce quantitative differences in the binding affinity of the neonicotinoids towards these receptors, which, in turn, confers the notabl y greater selective toxicity of this class towards insects, including aphids and leafhoppers, compared to mammals. Additio nally , the most sensitive toxicological effect in mammals differs across the neonicotinoids ( e.g., testicular tubular atroph y with thiamethoxam; mineralized particles in thyroid colloid with imidaclop rid). Thus, there is currentl y no evidence to indicate that neonicotinoids share common mechanisms of toxicity , and EPA is not following a cumulative risk approach based on a common mechanism of toxicity

for the neonicotinoid s. In addition, acetamiprid does not appear to produce a toxic metabolite produced b y other substances. Therefore, f or the purposes of this tolerance action, EPA has not assumed that acetamiprid has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mec hanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism released b y EPA’s Offic e of Pesticide Programs on EPA’s website at http://www.epa.gov/pesticides/cumulative/ .Page 46 of 63

9.0 Occupational Exposure/Risk Pathway 9.1 Short -/Intermedi ate -/Long - Term Handler Risk No chemical - specific data for assessing handler exposures were submitted to the Agency in support of the proposed uses associated with the three subject petitions. T herefore, when estimating occupational exposure s , HED used : 1) surrogate data from the Pesticide Handlers Exposure Data Base (PHED v 1.1 ; 2) Outdoor Residential Exposure Task Force ( ORETF) data; 3) standard assessment variables established b y the Health Effec ts Division Science Advisory Council for Exposure (e.g. maximum application rates, standard acres treated per day , 70 kg body weight for workers ) ; and, 4) standard protection factors assumed with specified personal protective equipment). The estimated exp osures are believed to be reasonable high - end estimates . The proposed use patterns of acetamiprid indicate that the Assail ® 70WP and Assail ® 30SG are applied 1 - 2 times per season at 1 - 14 day intervals on clover and grapes resulting in short - term exposure to mixers, loaders, and applicators. R epeated use of these products by commercial handlers on several farms growing clover and/or grapes would also result in intermediate - term exposure to handlers as well. In the case of greenhouse grown tomatoes using TriStar ® 30SG , the handlers are subjected to short - , intermediate, and long - term exposures due to the year - round growing operations. 9.2 Handler and P esticide C ontrol O perator (PCO) Risk Characterization Since both dermal (short - and intermediate - term) and inhalation (short - and intermediate - term) endpoints for occupational exposures were the same , the route specific exposure values were combined to calculate a total exposure whi ch was compared to the NOAEL (10 mg/kg/day from the DNT study) to determine the MOEs. Estimated exposures for all scenarios of the three product labels do not present a risk concern to HED when the PPE stated on the proposed label is assumed . E xposures t o agricultural handlers associated with the proposed uses on Assail® 70WP, and Assail® 3 0S G are not a risk concern to HED , provided handlers obey the personal protection directions specified on the proposed label s . Inaddition , exposures to PCO’s from the proposed labeled uses are not a risk concern to HED provided PCO’s comply with the personal protection directions specified on the label . MOEs for handlers are attached in Appendix A . 9.3 Postapplication Exposure and Risk The registrant has not submitted a chemical - specific postapplication exposure study to quantify postapplication exposure for proposed crops of clover, grape, and tomatoes. In the absence of chemical - specific data, dermal exposures were estimated using default dislodgeable foliar residue (DFR) and surrogate transfer coefficient (TC) values. In Appendix A , Table A .5 is a summary of the short - and intermediate - term risk to workers who enter treated fields of clover, grape, and tomatoes on day "0". The estimated postapplication risk for all crop - related activities is MOE ≥ 330 ( the LOC=100); therefore, not of concern. Long -Page 47 of 63

term risk to workers performing scouting, irrigation, and harvesting of tomatoes grown in greenhouses also is not of conce rn. The use of acetamiprid in the greenhouse as a soil drench and micro - irrigation is also not of concern with regard to postapplication exposure to workers. Restricted Entry Interval (REI) All three labels, Assail ® 70WP, Assail ® 30SG, and TriStar® 30SG have CAUTION as the SI GNAL WORD. An REI of 12 hours is set based on the acute toxicity of acetamiprid technical , which is classified as Category III and IV for acute dermal toxicity , dermal irritation, and eye irritation. Acetamiprid is not a dermal sen sitizer. Acute toxicity Category III and IV chemicals are assigned a 12 - hour REI . The current assessment of postapplication exposures and risks for the proposed uses on clover, grapes, and greenhouse grown tomatoes indicates that the 12 - hour REIset fo r acetamiprid is adequate to protect the workers who may enter treated fields to do any crop - related agricultural activities. 10.0 Data Needs and Label Recommendations Directions for Use : No proposed use was submitted for the use on tea in S outh Carolina. HED cannot evaluate the domestic use without a proposed use, application methods, and a proposed formulation. GAP information was provided for Japan and India. The use directions are adequate to e stablish a tolerance without U.S. registrations (an “import” tolerance). Because the grape field trial data submitted with this petition did not reflect the use of a surfactant in the application spray s, the label directions regarding use of a spreader, m eth yl ated seed oil or crop oil should be removed from the product label of Assail® 30SG (EPA Reg. No. 8033 - 36). Furthermore, in line with present OPP policy for a late season foliar use, a statement should be added to both the 30SG and 70WP labels prohibi ting addition of adjuvants for application to grapes. If use of an adjuvant is desired then one should be used in side - by- side testing. The PHI for clover harvested for hay should be increased to 56 day s on the 30SG and 70WP labels. Tolerances : HED rec ommends tolerances for acetamiprid be established as specified in Appendix C . The tolerance expression should be revised as stated in Section 1.1. The final tolerances for subgroup 13 - 07F should reflect the correct commodity definition as specified in Ap pendix C . A revised Section F is no t needed for this minor change. The established individual tolerance for grape at 0.20 ppm should be concomitantly removed with establishment of the subgroup 13 - 07F tolerance.Page 48 of 63

Conditional Data:

 Two clover field trials reflecting the same use pattern utilized in the submitted studies. Submittal of Analytical Reference Standards : Analy tical standard s for the IM - 2 - 1 and IM - 2 - 1 - amide metabolites are not available at the Repository and should be supp lied. The reference standards should be sent to the Analy tical Chemistry

L ab, which is located at Fort Meade, to the attention of Theresa Cole at the following address: USEPA National Pesticide Standards Repository /Anal yt ical Chemistry

Branch/OPP 701 Mapes Road Fort George G. Meade, MD 20755 - 5350 (Note that the mail will be returned if the extended zip code is not used.) References: Acetamiprid. Request for Label Amendments for New Uses on Clover; Small Vine Climbing Fruits, except Kiwi f

ruit, Subgroup 13 - 07F (amending grape use) ; Greenhouse - grown Tomatoes; and a Regional Registration for Tea . Summary of Analy tical Chemistry

and Residue Data. D364833, 10/ 14 / 09, D. McNeilly . Acetamiprid. Acute and Chronic Dietary Exposure As sessments to Support Section 3 Registration of Uses on Clover, Small Vine Climbing Fruits, except Kiwifruit, Subgroup 13 - 07F, Greenhouse Grown Tomatoes and Tea. D369019, D. McNeill y, Dec 1, 2009. Acetamiprid : Occupational and Residential Exposure Assessm ent for the New Uses on Clover and Greenhouse Grown Tomatoes and for Increasing the Application Rate on Grapes . D366701, S. Oonnithan , 10/9/09 . Acetamiprid : Occupational/Residential Exposure and Risk Assessment for Proposed Use on Indoor/Outdoor Househol d Pest Control. 12/1/08, Z. Figueroa. Tier I Drinking Water Assessment for Acetamiprid Proposed Uses on R ed Clover (Grown for Seed Only), Grape and Tomato (Greenhouse). David L ieu, June 10 , 2009 . Acetamiprid New Uses (Bulb Vegetables, Succulent Legumes , Strawberries, and Other Berries): Transmittal of Tier I Drinking Water Exposure Assessment. July 24, 2007; D331596, and D336256. Acetamiprid. Human Health Risk Assessment for a Proposed Label Amendment Allowing Food/Feed Use on Vegetable Transplants. D352925 , 11/2 5 / 08, W. Drew .Page 49 of 63

Acetamiprid: Occupational and Residential Exposure Assessment for Proposed Section 3 Registration for General Pest Control Uses. 02/17/05; D304214. Acetamiprid : Aggregate Risk Assessment Associated with the Proposed Use on Indoor/Outdoor Household Pest Control. 12/12/08, Christina Swartz. Acetamiprid: Human Health Risk Assessment for Proposed Food Uses on Stone Fruits, Cucurbit Vegetables, Tree Nuts, Berries, Strawberries, Bulb Vegetables, Legumes (Peas and Beans) and for Residential/Commercial Insecticide/Termiticide Uses. 10/25/07, T. Moriarity . Acetamiprid. Petitions Requesting the Establishment of Permanent Tolerances (Associated with Section 3 Registration) for New Food/Feed Uses of the Insecticide on Berries ( Crop Group 13), Bulb Vegetables (Crop Group 3), Edible Podded Legume Vegetables (Crop Subgroup 6A), Succulent Shelled Pea and Bean (Crop Subgroup 6B), and Strawberry and Other Low - growing Berries. Summary

of Analy tical Chemistry

and Residue Data. Petitio n Numbers 6F7051 (Various Crops) and 6E7163 (Strawberry). 10/23/2007; W. Drew; D328216.Page 50 of 63

Appendix A : Occupational Exposure and Risk Table s Table A .1 . Acetamiprid: Potential Short - termE xposure Scenarios Resulting fromIts Use on Clover, Grape, and Greenhouse G rown Tom atoes. Crop Form

ulation 1 Scen. No. Appl . equipment Handler Comments 2 Clover Assail ® 70WP

and WP/WSB 1 foliar/ aerial, fixed wing M/L

2 " " applicator 3 " " flagger 4 foliar/gr ound boom M/L 5 " " applicator Assail ® 30SG 6 foliar/ aerial, fixed wing M/L

7 " " applicator same as # 2 8 " " flagger same as # 3 9 foliar/gr ound boom M/L 1 0 " " applicator same as # 5 Grape Assail ® 70WP

and WP/WSB 11 foliar/ aerial, fixed wing M/L

1 2 " " applicator 1 3 " " flagger 1 4 foliar/air blast M/L 1 5 " " applicator Assail ® 3 0SG 16 foliar/ aerial, fixed wing M/L

17 " " applicator same as # 12 18 " " flagger same as # 13 19 foliar/air blast M/L 20 " " applicator same as # 15 T omato es grown in green house Tri S tar ® 30SG 21 drip/micro irrigation M/L/A no unit exposures 22 back - pack sprayer M/L/A root zone spray 23 low - pr. Hand wand M/L/A root zo ne spray 24 high pr. Hand wand M/L/A soil drench 1. Assail 70WP is sold as WP (powder) and as water soluble bags (WSB). 2. Duplicate scenarios (indicated) having identical inputs were not assessed.Page 51 of 63

Table A .2. Acetamiprid: Short - and Interm ediate - termOccupational Risks to Handlers Resulting Fromthe Use of Assail 70WP Assail 30SG Insecticides on Clover. Crop Scen.

No. 1 Form

ulation, Appl. method & Rate (AI/A) Handler PPE & Mitigation 2 Acres

treated/ d ay Unit exposure (mg/lb AI handled)

and Exposed dose mg/kg/day) 3 Total exp, (mg/kg/ day) 4 Short/Interm.

term MOE 5 Dermal Inhal.

Clover 1A Assail 70WP,

Aerial, 0.075 M/L Baseline 350 3.7 1.62E - 01 0.04342

1.90E - 02 0.18087 55 1B " M/L Baseline + gloves 350 0.17 7.44E - 03 0.04342

1.90E - 02 0.02643 380 1C Assail 70WP/WSB Aerial, 0.075 M/L Baseline 350 0.021 9.19E - 04 0.00024

1.05E - 04 0.00102 9,800 2 Assail 70WP Aerial, 0.075 Applic. Baseline + cl. C ockpit 350 0.005 2. 19E - 04 0.00007

3.06E - 05 0.00025 40,000 3 Assail 70WP, Aerial, 0.075 Flagger Baseline 350 0.011 4.81E - 04 0.00035

1.53E - 04 0.00063 16,000 4A Assail 70WP Ground boom , 0.075 M/L Baseline 80 3.7 3.70E - 02 0.04342

4.34E - 03 0.04134 240 4B " M/L Baseline + gloves 80 0.17 1.70E - 03 0.04342

4.34E - 03 0.00604 1,700 4C Assail 70WP/WSB Aerial, 0.075 M/L Baseline 80 0.021 2.10E - 04 0.00024

2.40E - 05 0.00023 43,000 5 Assail 70WP, Ground boom , 0.075 Applic. Baseline + open cab 80 0.014 1.40E - 04 0.00074

7.40E - 05 0 .00021 47,000 6 Assail 30SG Aerial, 0.075 M/L Baseline 350 0.066 2.89E - 03 0.00077

3.37E - 04 0.00322 3,100Page 52 of 63

Table A .2 contd ...

Clover 7 Assail 30SG

Aerial, 0.075 Applic. same as # 2 - - - - - 8 Assail 30SG Aerial, 0.075 Flagger same as # 3 - - - - - 9 Assail 30SG Ground boom , 0.075 M/L Baseline 80 0.066 6.60E - 04 0.00077

7.70E - 05 0.00074 14,000 10 Assail 30SG Ground boom , 0.075 Applic. same as # 5 - - - - - 1. The scenario numbers are from Table A .1 . The Assail 70WP may be sold as free flowing powder and as water soluble bags (WSB); therefore, both products were included in the exposure evaluations. 2. Baseline PPE includes long sleeved shirt, long pants and shoes with socks. Additional PPE such as gloves, respirators and engineering controls (open/closed cab/cockpit, etc.) are added if the exposure exceeds the Agency's LOC (MOE = ≤ 100). 3. Dermal exposure/day = (appl. rate * area treated/day * dermal unit exp. * dermal absorption (10%) / body wt (60 kg). Inhalatio n exposure/day = (appl. rate * area treated/day * inhalation unit exp. * inhalation absorption rate (100%) / body wt (60 kg). 4. Since the dermal and inhalation endpoints are the same; the dermal and inhalation exposures were combined. 5. Short - and int ermediate - term MOE = short - and intermediate - term POD (10 mg/kg/day) / combined exposure (mg/kg/day). Since the short - and intermediate term dermal and inhalation PODs are the same the short - and intermediate - term dermal and inhalation MOEs also are the same. The bolded MOE is of concern and adding gloves to the baseline clothing reduces the exposure.Page 53 of 63

Table A .3. Acetamiprid: Short - and Interm ediate - termOccupational Risks to Handlers Resulting Fromthe Use of Assail 70WP and Assail 30SG Insecticides on Grapes. 1 Crop Scen.N

os. 1 Form

ulation, Appl. equipment & App. rate Handler PPE & Mitigation 2 Acres

Treated/ d ay Unit exposure (mg AI/lb handled)

and Exposed dose (mg/kg/day) 3 Total exposure. (mg/kg/day) 4 Short/Interm.

term MOE 5 Dermal I nhal.

Grape 11A Assail 70WP

Aerial, 0.1 lb AI/A M/L Baseline 350 3.7 2.16E - 01 0.04342

2.53E - 02 0.2416 41 11B Assail 70WP Aerial, 0.1 lb AI/A M/L Baseline + gloves 350 0.17 9.92E - 03 0.04342

2.53E - 02 0.03505 280 11C Assail 70WP/WSB Aerial, 0.1 lb AI/A M/L Baseline 350 0.021 1.23E - 03 0.00024

1.40E - 04 0.00137 7,300 12 Assail 70WP, Aerial (fixed wing), 0.1 lb AI/A Applic. Baseline + closed cockpit 350 0.005 2.92E - 04 0.00007

4.08E - 05 0.00033 30,000 13 Assail 70WP Aerial, 0.1 lb AI/A Flagger Baseline 350 0.011 6.42E - 04 0.00035

2.04E - 04 0.00085 12,000 14A Assail 70WP Air blast, 0.1 lb AI/A M/L Baseline 40 3.7 2.47E - 02 0.04342

2.89E - 03 0.02756 360 14B Assail 70WP Air blast, 0.1 lb AI/A M/L Baseline + gloves 40 0.17 1.13E - 03 0.04342

2.89E - 03 0.00403 2,500 14C Assail 70WP/WSB Air blast, 0.1 lb AI/A M/L Baseline 40 0.021 1.40E - 04 0.00024

1.60E - 05 0.00016 64,000 15 Assail 70WP, Air blast, 0.1 lb AI/A Applic. Baseline + open cab 40 0.36 2.40E - 03 0.0045

3.00 - E04 0.0027 3,700Page 54 of 63

Table A .3 contd .....

Grape 16 Assail 30SG, Aerial,

0.1 lb AI/A M/L Baseline 350 0.066 3.85E - 03 0.00077

4.49E - 04 0.0043 2,300 17 Assail 30SG, Aerial, 0.1 lb AI/A Applic . same as # 12 - - - - - 18 Assail 30SG, Aerial, 0.1 lb AI/A Flagger same as # 13 - - - - - 19 Assail 30SG, Air blast 0.1 lb AI/A M/L Baseline 40 0.066 4.40E - 04 0.00077

5.13E - 05 0.00049 20,000 20 Assail 30SG Air blast, 0.1 lb AI/A Applic. same as # 15 - - - - - 1. All the foot notes are the same as in Table A .2 .Page 55 of 63

Table A .4. Acetamiprid: Short - and Interm ediate - termOccupational Risks to Handlers Resulting Fromthe Use of TriStar 30SG Insecticide on Tom atoes Grown in Greenhou se. 1 Scen. Nos. 1 Form

ulation, & Appl. equipment Handler PPE & Mitigation 2 Total Area **

treated/d ay Unit exposure (mg AI/lb

handled) and Exposed dose (mg/kg/day) 3 Total exposure

(mg/kg/ day) 4 MOE 5 Dermal Inhal. Short/Inter. - term Lo ng - term 21 TriStar 30SG, 0.075 lb AI/A micro - irrigation not assessed due to lack of appropriate unit

exposures - - - - - 22 TriStar 30SG, 0.075 lb AI/A, base of plant appl., back pack M/L/A Baseline + gloves 0.4 2.5 1.25E - 4 0. 03

1.50E - 05 0.00014 71,000 51,000

23 TriStar 30SG, 0.075 lb AI/A , base of plant appl., low pressure hand wand M/L/A Baseline + gloves 0.4 0.43 2.15E - 5 0.03

1.50E - 05 0.00004 270,000 190,000

24 TriStar 30SG, 0.075 lb AI/A, base of plant appl., hig h pressure hand wand M/L/A Baseline + gloves 10 2.5 3.13E - 03 0.12

1.50E - 03 0.00463 2,200 1,500 1. All the foot notes are the same as in Table A .2 . Note that in Table A .4 , the M/L/A unit exposures are for a liquid formulation rather than a soluble granule product. ** The total area (A) treated/day in the greenhouse w as derived as follows: the spray volume handled/day was taken as 40 gal for back- pack and low - pressure hand wand and 1000 gal for high - pressure hand wand sprayer (root zone drench). It is a ssumed that 100 gal of spray would cover 1.0 A of greenhouse area (L. Venkateshwara, D355232, 11/21/08).Page 56 of 63

Table A .5. Acetamiprid: Short - termPost - application Derm al Risk to Workers From the Use of Assail 70WP and Assail 30SG Insecticides on Grapes. Crop Max. single

appl. rate (lb Ai/A) Dislodgeable

foliar residue (μg/cm

2 ) 1 Surrogate crop group Post - treatment

activity

Transfer coefficient (cm 2 /hr) 2 Dermal

absorpt. ( %) ADD

(mg/kg/day) 3 MOE 4

Short/Interm.

- term Long term Clover 0.075 0.168 Field and row crop, forage irrigation/

scouting 1,500

10 0.0034 3,000 NA

Grape 0.1 0.224 Vine, trellis training, scouting 1,000 0.003 3,300 NA hand harvesting, pruning 5,000 0.015 670 NA turning and tying 10,000 0.0299 330 NA Tomatoes grown in greenhouses 0.075 0.168 Fruiting vegetables staking,

thinning, training, tying 1,000 0.00224 4,500 3,200 1. Dislodgeable foliar residue (DFR) = max. single appl . rate for the crop (lb AI/A) * 20% * 4.54 x 10 8 ( μg/lb) * 2.47 x 10 - 8 ( A/cm 2 ) . 2. TC values are from Science Advisory Council for Exposure Policy No. 3.1 . 3. Average daily dose (ADD) = [DFR * TC for the activity * 8 (hrs/day) * 0.001 mg/μg * dermal ab sorp.] / BW (60 kg). 4. Short/intermediate - term dermal MOE = ADD/ short/intermediate - term dermal NOAEL (10 mg/kg/day). Long - term dermal MOE = ADD/ long - term dermal NOAEL (7.1 mg/kg/day).Page 57 of 63

Appendix B : Toxicology Assessment Appendix B . Toxic ity Profile for Acetamiprid: Subchronic, Chronic, and Other Toxicity Studies Guideline No./ Study Type MRID No.

(year)/Classification /Doses Results 870.3100 90 - Day oral toxicity - rat (dietary) 44651843 (1997) Acceptabl e/guideline 0, 50, 100, 200, 800, 1600 ppm 0/0, 3.1/3.7, 6.0/7.2, 12.4/14.6, 50.8/ 56.0, 99.9/117 (M/F) mg/kg/day NOAEL = 12.4/14.6 (M/F) mg/kg/day LOAEL = 50.8/56.0 mg/kg/day (M/F) based on decreased BW, BW gain and food consumption

870.3100 90 - Day fe eding

– mo use 44988425 (1997)

Acceptable/guideline 0, 400, 800, 1600, 3200 ppm 0/0, 53.2/64.6, 106.1/129.4, 211.1/249.1, 430.4/466.3 (M/F) mg/kg/day NOAEL = 106.1/129.4 (M/F) mg/kg/day LOAEL = 211.1/249.1 (M/F) mg/kg/day based on reduced BW and BW gain , decreased glucose and cholesterol levels, reduced absolute organ weights 870.3150 90 - Day oral toxicity - dog (Dietary) 44988424 (1998) Acceptable/guideline 0, 320, 800, 2000 ppm 0/0, 13/14, 32/32, 58/64 (M/F) mg/kg/day NOAEL = 13/14 (M/F) mg/kg/day LOAEL = 32 mg/kg/day based on reduced BW gain in both sexes 870.3200 21 - Day dermal toxicity rabbit 44651844 (1997) Acceptable/guideline 0, 100, 500, 1000 mg/kg/day Systemic NOAEL = 1000 mg/kg/day LOAEL= not determined Derm al NOAEL = 1000 mg/kg/day LOAEL = not determined 870.3700 Developmental toxicity - rat (gavage) 44651847 (1997) Acceptable/guideline 0, 5, 16, 50 mg/kg/day Maternal: NOAEL = 16 mg/kg/day LOAEL = 50 mg/kg/day based on reduced BW & BW gain and food consumption, increased liver weights Developm ental: NOAEL = 16 mg/kg/day LOAEL = 50 mg/kg/day based on increased incidence of shortening of the 13 th ribPage 58 of 63

Appendix B . Toxic ity Profile for Acetamiprid: Subchronic, Chronic, and Other Toxicity Studies Guideline No./ Study Type MRID No.

(year)/Classification /Doses Results 870.3700 Developmental toxicity

– rabbit (gavage) 44651848 (1997) Acceptable/guideline 0, 7.5, 15, 30 mg/kg/day Maternal: NOAEL = 15 mg/kg/day LOAEL = 30 mg/kg/day (BW loss and decreased food consumption). Developm ental: NOAEL = 30 mg/kg/day (HDT) LOAEL = not determined 870.3800 Reproduction and fertility effects - rats (dietary) 44988430 (1999) Acceptable/guideline 0, 100, 280, 800 ppm Parental animals 0/0, 6.5/7.6, 17.9/21.7, 51.0/60.1 (M/F) mg/kg/day F 1 animals 0/0, 7.5/8.4, 21.0/23.8, 63.3/72.6 (M/F) mg/kg/day Parental/Systemic: NOAEL = 17.9/21.7 (M/F) mg/kg/day LOAEL = 51.0/60.1 (M/F) mg/kg/day based on decreased body weight, bo dy weight gain and food consumption Offspring: NOAEL = 17.9/21.7 (M/F) mg/kg/day LOAEL = 51.0/60.1 (M/F ) mg/kg/day based on reductions in pup weight, litter size, viability and weaning indices; delay in age to attain preputial separation and vaginal ope ning Reproductive: NOAEL = 17.9/21.7 (M/F) mg/kg/day LOAEL = 51.0/60.1 (M/F) mg/kg/day based on reductions in litter weights and individual pup weights on day of delivery 870.4100 Chronic toxicity - rat Same as Chronic Toxicity/Carcinogenicity - rat see b elow (870.4300) See below (870.4300) 870.4100 Chronic toxicity - dog (Dietary) 44651846 (1998) Acceptable/guideline 0, 240, 600, 1500 ppm 0/0, 9/9, 20/21, 55/61 (M/F) mg/kg/day NOAEL = 20/21 (M/F) mg/kg/day LOAEL = 55/61 (M/F) mg/kg/day based on initial BW loss and overall reduction in BW gain 870.4200 Carcinogenicity - mouse (dietary) 44988428, 45245305 (1999) Acceptable/guideline 0, 130, 400, 1200 ppm (equivalent to 0/0, 20.3/25.2, 65.6/75.9, 186.3/214.6 mg/kg/day in males/females) NOAEL = 20.3/75.9 mg/kg/day (M/F) LOAEL = 65.6/214.6 (M/F ) mg/kg/day based on decreased BW & BW gain and amyloidosis in numerous organs (M) and decreased BW and BW gain (F) Not oncogenic under conditions of studyPage 59 of 63

Appendix B . Toxic ity Profile for Acetamiprid: Subchronic, Chronic, and Other Toxicity Studies Guideline No./ Study Type MRID No.

(year)/Classification /Doses Results 870.4300 Chronic/ Carcinogenicity - rat 44988429, 4524530 4 (1999) Acceptable/guideline 0, 160, 400, 1000 ppm (equivalent to 0/0, 7.1/8.8, 17.5/22.6, 46.4/60.0 (M/F) mg/kg/day) NOAEL = 7.1/8.8 (M/F) mg/kg/day LOAEL = 17.5/22.6 mg/kg/day (M/F) based on decreases in mean BW & BW gain (F) and hepatocellular va cuolation (M) Evidence of treatment - related increase in mammary tumors 870.5100 Salmonella typhimurium/E. coli Reverse gene mutation assay 44651849 (1997) Acceptable/guideline 313 to 5000 μg a.i./plate incubated 65.5 hours with +/ - S9 Not mutagenic unde r the conditions of the study

870.5300 Mammalian cells in culture Forward gene mutation assay - CHO cells 44651857 (1998) Acceptable/guideline 500 - 4000 ug/mL

– S9 or 250 - 3000ug/mL + S9 Not mutagenic under the conditions of the study.

870.5375 In vitro mammalian chromosome aberration test Chinese hamster ovary (CHO) cells 44651855 (1997) Acceptable/guideline 175, 350, 700 μg/mL - S9 or 338, 675, 1350 ug/mL + S9 (Highest doses slight to mo derately cytotoxic). Acetamiprid is a clastogen under the conditions of the study.

870.5385 In vivo mammalian chromosome aberrations - rat bone marrow 44651854 (1998) Acceptable/guideline 250 mk/kg (maximum tolerated dose) Bone marrow

analyzed at 6, 24, and 48 hours. Acetamiprid did not induce a significant increase in chromosome aberrations in bone marrow cells when compared to the vehicle control group.

970.5395 In vivo mammalian cy to genetics - micronucleus assay in mice 44651852 (1998) Acceptable/guideline 20, 40, 80 mg/kg Bone marrow

analyzed at 24, 48, or 72 hours Acetamiprid is not a clastogen in the mouse bone marrow micronucleus test.

870.5550 Unscheduled DNA synthesis in pri mary rat hepatocytes/mammalian cell culture 44651856 (1998) Acceptable/guideline 0.5 to 1000 μg/mL Acetamiprid tested negatively for UDS in mammalian hepatocytes in vivo.Page 60 of 63

Appendix B . Toxic ity Profile for Acetamiprid: Subchronic, Chronic, and Other Toxicity Studies Guideline No./ Study Type MRID No.

(year)/Classification /Doses Results 870.6200a Ac ute neurotoxicity screening battery - rats (gavage) 44651842 (1997) Acc eptable/guideline 0, 10, 30, 100 mg/kg Neurotoxicity: NOAEL= 10 mg/kg/day LOAEL = 30 mg/kg based on reduction in locomotor activity 870.6200b Subchronic neurotoxicity screening battery (dietary) 44651845 (1997) Acceptable/guideline 0, 100, 200, 800, 160 0 ppm (equivalent to 0/0, 7.4/8.5, 14.8/16.3, 59.7/67.6, 118/134 mg/kg/day) Neurotoxicity: NOAEL= 14.8/16.3 mg/kg/day (M/F) LOAEL = 59.7/67.6 (M/F) mg/kg/day based on reductions in BW, BW gain, food consumption and food efficiency 870.6300 Developmenta l neurotoxicity

– rat (gavage) 46255619 (2003) Ac ceptable/Non - Guideline 0, 2.5, 10, 45 mg/kg/day Volume: 5 mL/kg Vehicle: 5% gum Arabic with 0.01% Tween 80 Maternal: NOAEL = 10 mg/kg/day LOAEL = 45 mg/kg/day based on decreased body weight and body wei ght gains during gestation only Offspring: NOAEL = 10 mg/kg/day . LOAEL = 45 mg/kg/day based on decreased maximum auditory startle response in males on PND 20 and PND 60, and decreased body weight and body weight gain, and pup viability 870.7485 Metaboli sm

and pharmacokinetics - rats 44988503 - 7 (1997) Acceptable/guideline Single dose study with 1 mg/kg (iv), 1 or 50 mg/kg (gavage) 15 - day repeated doses study with 1 mg/kg (gavage); Biliary excretion study with 1 mg/kg (gavage) Extensively and rapidly met abolized. Metabolites 79 - 86% of administered dose. Profiles similar for males and females for both oral and intravenous dosing. Thirty - seven percent of dose recovered in urine and feces as unchanged test article. Urinary and fecal metabolites from 15 - d ay

repeat dose experiment only showed minor differences from single - dose test. Initial Phase I biotransformation: demethylation of parent. 6 - chloronicotinic acid wa s the most prevalent metabolite. Phase II metabolism shown by the increase in glycine con jugate.Page 61 of 63

Appendix B . Toxic ity Profile for Acetamiprid: Subchronic, Chronic, and Other Toxicity Studies Guideline No./ Study Type MRID No.

(year)/Classification /Doses Results 870.7485 Metabolism - mice, rats, rabbits Special study Male mice, rats or rabbits were administered single doses of acetamiprid by gavage, intraperitoneal injection (i.p.) or intravenous injection (i.v.) up to 60 mg/kg. The animals were assesse d for a variety of neurobehavioral parameters. In vitro experiments were also done using isolated ileum sections from guinea pigs to assess contractile responses in the absence and presence of agonists (acetylcholine, histamine diphosphate, barium chlorid e and nicotine tartrate). Acetamiprid was also assessed via i.v. in rabbits for effects on respiratory rate, heart rate and blood pressure; via gavage in mice for effects on gastrointestinal motility; and via i.p. in rats for effects on water and electrolyte balance in urine, and blood coagulation, hemolytic potential and plasma cholinesterase activity. Based on a number of neuromuscular, behavioral and physiological effects of acetamiprid in male mice, under the conditions of this study, a n overall NOAE L of 10 m g/kg (threshold) and LOAEL of 20 mg/kg could be estimated for a single dose by various exposure routes. 870.7600 Dermal penetration 44651844 (1997) Acceptable/guideline 0, 100, 500, 1000 mg/kg/day Applied 6 hours/day for 5 days/week over a 21 day period NOAEL > 1000 mg/kg/day Revised dermal absorption rate of 10% (from 30%) is based upon the dermal absorption study with acetamiprid (MRID 44651858) and consideration of dermal penetration values from other neonicitinoid insecticides (thiamethoxam) , and consideration of Kow and octanol/water coefficient data of other neonicitinoid compounds (clothianidin). 44651858 (1997) Acceptable/non - guideline 1.09, 9.53, 90.2 ug/cm2 Absorption was highest at the mid - dose and increased with duration (4.07% at 10 after 10 hours and 6.34% after 24 hours). Residue remaining in the skin at 24 hours is 25.0%. In addition to absorbed dose (6.34%), total absorption is estimated at 30%. N/A 28 - Day Range - f

inding Study

– dog (dietary) 45245306 Non - guideline 0, 125, 250, 500, 1000 mg/kg/day NOAEL = 16.7/19.1 (M/F) mg/kg/day LOAEL = 28.0/35.8 (M/F) mg/kg/day based on reduced BW gainPage 62 of 63

Appendix C : Tolerance Summary Appendix C . Tolerance Summary for Acetamiprid. Commodity Established/Proposed Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity

Definition Clover, forage 0.10 0.10 Recommended tolerances are for regional registration. Clover, hay 0.01 0.01 Fruit, small, vine climbing, except fuzzy kiwif

ruit, subgroup 13 - 07F 0.35 0.35 Pending label revision to prohibit use of a spreader, methylated seed oil or crop oil. Correct term

is Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F NOTE: T he established individual tolerance for g rape at 0.20 ppm should be concomitantly removed upon establishment of the subgroup 13 - 07F tolerance. Grape 0.20 Remove Grapes will be covered under the subgroup 13 - 07F tolerance. Tea, dried 50.0 50.0 Tolerance without a U.S. registration.Page 63 of 63

Appendix D : INTERNATIONAL RESIDUE LIMIT STATUS 

## INTERNATIONAL RESIDUE LIMIT STATUS Chemical Name: Common Name: Acetamiprid X Proposed tolerance  Reevaluated tolerance  Other Date: 07/06/2009 Updated: Oct 5, 2009 with the tea MRL information. Codex Status (Maximum Residue Limits) U. S. Tolerances X No Codex proposal step 6 or above  No Codex proposal step 6 or above for the crops requested Petition Number: 9E7544 DP Barcode: D364833 Other Identifier: Residue definition (step 8/CXL): N/A Revie wer/Branch: Dennis McNeilly /RAB2 Residue definition: acetamiprid [N1 - [(6 - chloro - 3 - pyridyl)methyl] - N2 - cyano -N1 - methylacetamidine] Crop (s) MRL (mg/kg) Crop(s) Tolerance (ppm) Clover, fora ge 0.10 Clover, hay 0.01 Fruit, small, vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F 0.35 Tea 50.0 Limits for Canada Limits for Mexico  No Limits  No Limits for the crops requested  No Limits X No Limits for the crops requested Residue definition: (E ) -N - [(6 - chloro - 3 - pyridinyl)methyl] -N’ - cyano -N - methylethanimidamide Residue definition: acetamiprid Crop(s) MRL (mg/kg) Crop(s) MRL (mg/kg) Grapes 0.2 Notes/Special Instructions: S. Funk, 07/07/200 9. Note: There are no MRLs for acetamiprid in Codex. There is no MRL for acetamiprid on tea in Australia. There is no MRL for acetamiprid on tea in Canada. Japan has a 50 ppm MRL for tea.