Acequinocyl Human - Health Risk Assessment D 38 9519

Page 1 of 35 **UNITED STA TES ENVIRONMENTA**  **L PROTECTION A GENCY** 

**WA SHINGTON, D.C. 20460**  **OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION**  **MEMORANDUM Date:**  30 -NOV - 201 1 **SUBJECT: Acequinocyl;**  Human - Health Risk Assessment for Proposed Section 3 Uses on

Succulent Soy

bean Vegetable; Succulent Shelled Beans; Cowpea Forage; Caneberry

Subgroup 13 - 07A; Melon Subgroup 9A; Cucumber, Cherry ; Low Growing Berry

Subgroup 13 - 07G; and Small Fruit Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13 - 07F. **PC Code:** 006329 **DP Barcode:** D 38 9519 **Decision No.:** 4 48205 **Registration No. :**  66330 - 38 **Petition No.:** 1 E 7864 **Regulatory Action:** Section 3 **Risk Assessment Type:** Single Chemical/Aggregate **Case No.:** 7621 **T XR No.:**  NA **CAS No.:** 57960 - 19 - 7 **MRID No.:** NA **40 CFR:** §180.599 **FROM:** Sarah J. L ev y, Chemist

Anwar Y. Dunbar , Ph.D., Pharmacologist Kelly M. Lowe , Environmental Scientist Risk Assessment Branch 1 (RAB1) Health Effects Division (HED) (7509P) **THROUGH:** Dana M. Vogel, Branch Chief

George F. Kramer, Ph.D., Branch Senior Chemist RAB1/HED (7509P) **TO:** B. Madden/ L. Nollen , Risk Manager ( RM0 5)

Registration Division (RD) (7505 P ) The HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard and exposure data and conduct dietary , occupational/residential and aggregate exposure assessments, as needed, to estimate the risk to human health that will result from the registered and proposed uses for acequinocyl o n succulent soy bean vegetables, succulent shelled beans, cowpea forage, caneberry subgroup 13 - 07A, melon subgroup 9A, cucumber, cherry ; low - growing berry subgroup 13 - 07G, and small fruit vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F . Note that th e cucumber and caneberry field trial data were a joint - review with Canada. A summary

of the estimated human health risks resulting from the registered and proposed uses for acequinocyl are provided in this document. The risk assessment, residue chemistry data review, and dietary

exposure assessment were provided by Sarah Lev y (RAB1), the hazard characterization was provided by Anwar Dunbar, the occupational/residential exposureAcequinocyl Human - Health Risk Assessment D 38 9519

Page 2 of 35 assessment was provided by Kelly L owe (RAB1), and the drinking water exposure assessment was provided by M ichael Lo wit of the Environmental Fate and Effects Division (EFED). Recommendation for Tolerances and Registration Pending submission of revised Sections B and F, there are no toxicological, residue chemistry , or occupational/residential issues that would preclude granting a conditional registration for the requested uses of acequinocyl . Permanent tolerances should be established for residues of acequinocyl, including its metabolites and degradates, in or on the c ommodities listed below. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of acequinocyl [ 2 - (acet yl oxy) - 3 - dodecyl - 1,4 - naphthalenedione] and its metabolite, 2 - dodecyl - 3 - hydroxy - 1,4 - naphthoquinone , calculate d as the stoichiometric equivalent of acequinocyl, in or on the commodity : Soy bean, vegetable, succulent

....................................................... 0.25 ppm Low growing berry

subgroup 13 - 07G 1

.............................................. 0.50 ppm Small fruit vine climbing subgroup 13 - 07F, except fuzzy kiwifruit 1

... 1.6 ppm Bean, succulent shelled

................................................................................. 0.30 ppm Cowpea, forage

........................................................................... 6.0 ppm Cowpea, hay

................................................................................. 18 ppm Caneberry

subgroup 13 - 07A ......... ................................................... 4.0 ppm Melon subgroup 9A

........................................................................ 0.15 ppm Cucumber

...................................................................................... 0.15 ppm Cherry , tart ................................................................................. 1.0 ppm Cherry , sweet .............................................................................. 0.50 ppm Meat by products of cattle, goat, horse and sheep 1

........................... 0.02 ppm 1 Note to RD: With the establishment of these tolerances, the following tolerances should be removed: strawberry; grape; and liver of cattle, goat, horse, and sheep. Registration should be conditional pending resolution of the following deficienc ies : **Toxicology**  An Immunotoxicity

Study .  Acute and Subchronic Neurotoxicity Stud ies.  A 28 - Day

Inhalation Study .Acequinocyl Human - Health Risk Assessment D 38 9519

Page 3 of 35 

### TABLE OF CONTENTS **1.0 EXECUTIVE SUMMARY** ................................ ................................ ................................ ... 4 **2.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION** ............................... 8 **2.1 Identification of Active Ingredient** ................................ ................................ ........... 8 **2.2 Structural Formula of Acequinocyl and Acequinocyl -**  **OH** ................................ .... 8 **2.3 Physical and Chemical Properties of Acequinocyl**  ................................ ................. 8 **3.0 HAZARD CHARACTERIZATION/FQPA CONSIDERATIONS** ................................ ... 9 **3 .1 Hazard Profile**  ................................ ................................ ................................ ........... 9 . **3.2 FQPA Considerations** ................................ ................................ .............................. 11 **3.3 Dose -**  **Response Assessment** ................................ ................................ ..................... 12 **3.4 Recommendation for Aggregate Exposure Risk Assessments** ............................. 14 **4.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION** ................................ ........ 15 **4.1 Summary of Uses** ................................ ................................ ................................ ...... 16 **4.2 Dietary Exposure/Risk Pathway** ................................ ................................ ............. 17 **4.2.1 Residue Profile** ................................ ................................ .......................... 17 **4.3 Water Exposure/Risk Pathway** ................................ ................................ ............... 20 **4.4 Dietary Exposure Analyses** ................................ ................................ ..................... 21 **4.4.1 Chronic Dietary Exposure Analysis** ................................ ........................ 22 **4.5 Residential/Non -**  **Occupational Exposure Pathway** ................................ ............... 23 **4.5.1 Short -**  **term Residential Handler Risk** ................................ ..................... 23 **4.5.2 Short -**  **term Residential Post -**  **application Risk** ................................ ........ 23 **4.5.3 Spray Drift** ................................ ................................ ................................ . 23 **4.5.4 Residential Bystander Post -**  **applicat ion Inhalation Exposure**  **..............** 24 **5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION** ............. 24 **5.1 Acute Aggregate Risk**  ................................ ................................ .............................. 24 **5.2 Short -**  **Term Aggregate Risk** ................................ ................................ .................... 24 **5.3 Intermediate -**  **Term Aggregate Risk** ................................ ................................ ....... 26 **5.4 Long -**  **Term Aggregate Risk** ................................ ................................ .................... 26 **5.5 Cancer Risk** ................................ ................................ ................................ .............. 26 **6.0 CUMULATIVE RISK** ................................ ................................ ................................ ......... 26 **7.0 OCCUPATIONAL EXPOSURE AND RISK ASSESSMENT** ................................ ........ 26 **7.1 Short**  **- and Intermediate**  **- term Occupational Handler Risk**  ................................ . 27 **7.2 Short -**  **and Intermediate -**  **term Occupational Post -**  **application Risk** ................... 29 **8.0 RESIDUE CHEMISTRY AND TOXICOLOGY DEFICIENCIES** ............................... 31 **8.1 Residue Chemistry** ................................ ................................ ................................ ... 31 **8.2 Toxicology** ................................ ................................ ................................ ................. 31 **8.3 Occupational and Residential Exposure** ................................ ................................ 31 **APPENDIX: Toxicity Profile Tables and Metabolites.**  ................................ .......................... 32Acequinocyl Human - Health Risk Assessment D 38 9519

Page 4 of 35 **1.0 EXECUTIVE SUMMARY**  Acequinocyl is a quinoline - ty pe miticide that is currentl y registered for the use in the U.S. on a number of raw agricultural commodities (RACs) for the control of various phy tophagous mite species. Acequinocyl is also registered for use in/ on greenhouse s , shadehouse s , ornamental, floral, foliage, nursery

crops , landscape ornamentals in and around residences, businesses, public propert y, schools, interiorscapes, and other non - production areas b y commercial applicators and homeowners . Acequinocyl is currently registered to Ary sta Li fescience North America Corporation as a 15% soluble - concentrate (SC) formulation. Under PP#1E7864, the Interregional Research Project No.4 (IR - 4), on behalf of the Agricultural Experiment Station of TX, CA, OR, PA, GA, NM, OK, TN, UT, MI, FL, and AZ, is requesting for the establishment of tolerances for combined residues of the insecticide acequinocyl, 2 - (acet yl oxy) - 3 - dodecyl - 1,4 - naphthalenedione, and its metabolite, 2 - dodecyl - 3 - hydrox y - 1,4 - naphthoquinone (acequinocyl - OH), expressed as acequinocyl equivalents in/on the following commodities: Soy bean, vegetable, succulent ................................ ................................ .. 0.25 ppm Lo w growing berry

subgroup 13 - 07G ................................ ...................... 0.4 ppm Small fruit vine climbing subgroup 13 - 07F, except fuzzy kiwifruit ........ 1.6 ppm Bean, succulent shelled ................................ ................................ ............. 0.15 ppm Cowpea, forage ................................ ................................ ......................... 9.0 ppm Caneberry

subgroup 13 - 07A ................................ ................................ ..... 4.5 ppm Melon subgroup 9A ................................ ................................ .................. 0.06 ppm Cucumber ................................ ................................ ................................ .. 0.15 ppm Cherry ................................ ................................ ................................ ....... 0.8 ppm The end - use product proposed for use on the aforementioned proposed crops is Kanemite TM 15 SC Miticide a 1.25 pounds (lb)/gallon (gal) SC formulation (alternate brand names: ShuttleTM 15 SC Miticide, and ShuttleTM O Miticide). Up to two foliar, postemergent, ground app lications are proposed for a maximum seasonal rate of 0.6 lb active ingredient (ai)/acre (A), with a 1 - day preharvest interval (PHI), except for succulent shelled beans and cherries for which a 7 - day PHI is proposed. **Hazard Assessment:** Acequinocyl has lo w acute toxicity via the oral, dermal, and inhalation routes ( T oxicity C ategories III and IV). No ocular or dermal irritation was noted. Acequinocyl is not a dermal sensitizer. Acequinocyl is a known Vitamin K antagonist; therefore, it is thought to pro duce its adverse effects by disrupting the blood coagulation sy stem , as indicated by increased prothrombin time, increased activated partial thromboplastin time, and internal hemorrhages. In a subchronic oral toxicity study , a 28 - day

dermal toxicity

stu dy , and a chronic feeding/oncogenicity

study (all in the rat), acequinocyl increased prothrombin and activated partial thromboplastin times. Although clotting factors were not measured in some studies ( i. e., rat/rabbit developmental toxicity study , mouse subchronic/chronic toxicity study , and 2 - generation reproduction rat study), internal hemorrhages were observed. In the combined chronic toxicity

/oncogenicity

study in rats, enlarged eyeballs were observed. Hepatotoxicity in the mouse was evidenced by hi stopathology

and increased liver enz ym es.Acequinocyl Human - Health Risk Assessment D 38 9519

Page 5 of 35 In both rat and rabbit developmental toxicity studies, acequinocyl increased the number of resorptions. Developmental effects (i.e., resorptions) occurred at a dose that was higher than or the same as the dose that caused maternal toxicity . In the 2 - generation reproduction toxicity study in the rat, there was no evidence of reproductive toxicity , though there were notable toxic effects observed in offspring that were n o t observed in adults including swollen body parts, protruding eyes, clinical signs, delay s in pupil development and increased mortality occurring mainly after weaning. A clear no - observable - adverse - effect level (NOAEL ) was observed for these effects. There was no evidence of carcinogenic potential in either the rat or mouse carcinogenicity study , indicating that acequinocyl is "not likel y" to be carcinogenic to humans. There was no concern for mutagenic activity

as indicated by

several mutagenicity studies. **Dose -**  **Response Assessment and F**  **ood Quality Protection Act (FQPA) Decision:**  The HED Hazard Identification Assessment Review Committee (HIARC) met on October 14, 2003, to select endpoints for risk assessments and to evaluate the potential for increased susceptibility of infants and children. The Committee recommended the FQPA S afet y F actor (SF) for increased susceptibility

of infants and children be reduced to 1 X because there are no residual uncertainties for pre - and/or post - natal toxicity . In April 2010, HED’s RAB1 toxicology team re - evaluated the previously

determined endpoints to incorporate any newly submitted data, changes in use patterns, and changes in exposure scenarios. For a detailed explanation of the endpoints and rationale, see Section 3.3. **Dietary Exposure (Food +**  **Drink ing**  **Water) :**  A chronic aggregate dietary (food + drinking water) exposure and risk assessment was conducted for acequinocyl using the Dietary Exposure Evaluation Model (DEEM - FCID TM ), Version 2.03 , which use s food consumption data from the U.S. Department of Agriculture’s (USDA’s) Continuing Survey s of Food Intakes by Individuals (CSFII) from 1994 - 1996 and 1998 . Tolerance - level residues, DEEM  ver. 7.76 default processing factors, and 100 percent crop treated (%CT) data were used in the chronic dietary assessment . An acute dietary assessment was not conducted for acequinocyl because an endpoint of concern attributable to a single dose was not identified; therefore, an acute reference dose (aRfD ) was not estab lished. A cancer dietary assessment was not conducted because acequinocyl was classified as not likely to be carcinogenic to humans. For the chronic dietary

assessment, the general U.S. population and all population subgroups have risk estimates that wer e not of concern to HED. The chronic dietary risk assessment shows that the chronic dietary

risk estimates do not exceed HED ’s level of concern [(L OC) ; i.e., <100% of the chronic population - adjusted dose (cPAD)]. For the general U.S. population, the expo sure for food + drinking water utilized 1 3 % of the cPAD. The chronic dietary risk estimate for the highest exposed population subgroup, children 1 - 2 years old, is 5 5% of the cPAD. **Residential Exposure**

**/Risk :**  Acequinocyl is currently registered for use on landscape ornamentals in and around residences, businesses, public property, schools, interiorscapes, and other non - production areas by commercial applicators and homeowners. The last residential exposure risk assessment was conducted in June 2010 ( Memo, A. Nowotarski ; D369099) . All risks for residential handlers were above the target margin of exposure ( MOE ) of 100 and did not exceed the LOC. Post - application residential exposure was not anticipated for the registered uses, and, therefore, a quantitati ve residential post - application assessment was not conducted. HED has determined that the proposed uses will result in negligible residential exposure.Acequinocyl Human - Health Risk Assessment D 38 9519

Page 6 of 35 **Occupational Exposure Estimates:** The occupational handler assessment was completed assuming the maxi mum label application rate for each crop. Based on the activity use pattern, the duration of exposure is expected to be short - term (1 to 30 day s) and intermediate - term (1 to 6 months) for occupational scenarios; long - term exposures (greater than 6 months) are not anticipated based on the proposed use pattern. For the dermal route of exposure, the same points of departure (PODs) were chosen for short - term and intermediate - term exposures; therefore, risks are the same for all durations of exposure. For the inhalation route of exposure, different PODs were chosen for short - term and intermediate - term exposure durations. The proposed label requires a long - sleeved shirt, long pants, shoes plus socks, and chemical - resistant gloves as dermal personal - protective equipment (PPE) for all applicators and other handlers. Occupational handler dermal and inhalation risk estimates were calculated. For occupational handlers, dermal and inhalation MOEs above 100 do not exceed HED’s LOC. All risk estimates for occupational handlers are above the target MOE of 100 with the use of gloves, and do not exceed the LOC as the proposed labels already require the use of gloves as PPE . Occupational dermal post - application risk estimates were calculated using available chemical specific dislodgeable foliar residue (DFR) data. There were no risks of concern for all occupational post - application activities associated with the proposed uses . Since no risks of concern were identified, the restricted - entry interval (REI) is based on the acute toxicity of the active ingredient. Acequinocyl is classified in Toxicity Category I II for acute dermal and acute inhalation. It is classified in Toxic ity Category I V for primary

eye irritation and primary skin irritation and it is not a dermal sensitizer. Therefore, the Worker Protection Standard (WPS) interim REIof 12 hours is adequate to protect agricultural workers from post - application exposures t o acequinocyl. **Aggregate Exposure Assessment:** Acute and cancer aggregate - risk assessments were not performed because no appropriate endpoint was available to determine the aRfD for the general population or any

population subgroup, and acequinocyl is cl assified as “Not likely to be Carcinogenic to Humans,” respectivel y. Intermediate - and long - term aggregate assessments were not performed since the use pattern is not expected to result in residential handler or post application exposure of more than 30 - d ay duration. A chronic aggregate exposure risk assessment was assessed b y incorporating the drinking water directly into the dietary - exposure assessment. As the chronic dietary exposure estimates are not of concern to HED for the general U.S. populatio n or an y population subgroup, the chronic aggregate risk is not of concern for these populations. An aggregate risk assessment was performed for short - term aggregate exposure (food + drinking water + residential exposure) because there are residential use s. Short - term aggregate exposures and risk estimates were calculated for the general U.S. population and females 13 - 49 years old (this sub - population is the highest exposed adult population and can be considered protective of the other adult populations groups) . T he aggregate MOEs are > 100, therefore, they do not exceed HED’s level of concern. **E nvironmental Justice Considerations:**  Potential areas of environmental justice concerns, to the extent possible, were considered in this human - health risk asses sment, in accordance with U.S. Executive Order 12898, “Federal Actions to Address Environmental Justice in Minority Populations and L ow - Income Populations,” http://www.hss.energy .gov/nuclearsafet y/ env/guidance/justice/eo12898.pdf ).Acequinocyl Human - Health Risk Assessment D 38 9519

Page 7 of 35 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 exposures 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 the USDA under 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 . Additionally , OPP is able to assess dietary exposure to smaller, spe cialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non - dietary exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, an d 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 lifest yle 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 p esticide or other chemical. These data, which include studies from the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force (ORETF) database ; the Agricultural Re - entry Task Force (ARTF) database; and MRIDs 454286 - 19, 456516 - 11, are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements. Descriptions of data sources as w ell as guidance on their use can be found at http://www.epa.gov/pesticides/science/handler - exposure - data.html and http://www.epa.gov/pesticides/science/post - app - exposure - data.html . **Recommendation for Tolerances and Registration:** Pending submission of rev ised Sections B and F, there are no toxicological, residue chemistry , or occupational/residential exposure issues that would preclude granting a conditional registration for the requested uses of acequinocyl. Permanent tolerances should be established for residues of acequinocyl, including its metabolites and degradates, in or on the commodities listed below. Compliance with the tolerance levels specified below is to be determined b y measuring only the sum of acequinocyl [ 2 - (acet yl oxy) - 3 - dodecyl - 1,4 - naphthalenedione] and its metabolite, 2 - dodecyl - 3 - hydrox y - 1,4 - naphthoquinone , calculated as the stoichiometric equivalent of acequinocyl, in or on the commodity : Soy bean, vegetable, succulent

...................................................... ... 0.25 ppm Berry , low growing, subgroup 13 - 07G 1

........................................... .. 0.50 ppm F ruit , small vine climbing , except fuzzy kiwifruit , subgroup 13 - 07F 1

... 1.6 ppm Bean, succulent shelled

................................................................................. 0.30 ppm Cowpea, forage

........................................................................ ... ... 6.0 ppm Cowpea, hay

................................................................................. 18 ppm Caneberry

subgroup 13 - 07A ............................................................ 4.0 ppm Melon subgroup 9A

........................................................................ 0.15 ppm Cucumber

...................................................................................... 0.15 ppm Cherry , tart ................................................................................. ... 1.0 ppm Cherry , sweet ........................................................................... ...... 0.50 ppm Meat by products of cattle, goat, horse and sheep 1

........................... ... 0.02 ppm Note to RD: With the establishment of these tolerances, the following tolerances should be removed: strawberry; grape; and liver of cattle, goat, horse, and sheep.Acequinocyl Human - Health Risk Assessment D 38 9519

Page 8 of 35 Registration should be conditional pending resolution of the following deficiencies: **To xicology**   An Immunotoxicity

Study .  Acute and Subchronic Neurotoxicity Stud ies .  A 28 - Day

Inhalation Study . **2.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION**  Provided below are the phy sical/chemical properties for acequinocyl. Most of this information was obtained from the acequinocyl “Pesticide Fact Sheet;” 9/26 / 03 (http://www.epa.gov/opprd0 01/factsheets/acequinocyl.pdf ). **2.1 Identification of Active Ingredient** 

Registrant: Ary sta L ifescience North America Corporation Trade Names: Kanemite  (EPA Reg.#: 66330 - 38) CAS Chemical Name: 2 - (acet yl oxy) - 3 - dodecyl - 1,4 - naphthalenedione CAS Registry

No.: 57960 - 19 - 7 Common Name: Acequinocyl PC Code: 006329 Pesticide Ty

pe: Miticide Chemical Famil y: Quinoline Target Pests: Tetranychus, Panonychus and Eutetranychus spp of mites Formulation: Product - Kanemite TM 15 SC; 1.25 lb ai/gal Ty pes of Formulations: Technical (96.8% ai); End - Use Product (15.8%) Empirical Formula: C 24 H 32 O 4 Molecular Weight: 384.5 **2.2 Structural Formula of Acequinocyl and Acequinocyl -**  **OH**

Acequinocyl Acequinocyl - OH **2.3 Physical and Chemical Properties**  **of Acequinocyl** These ph ys ical and chemical properties are for the end - use product unless otherwise noted. Appearance: Pale yellow Phy sical State: Liquid Suspension Vapor Pressure: 1.69 x 10 - 9 pascals at 25 0 C (technical) Water Solubility : 6.69 μg/L at 20 0 C (technical) Octanol/Water Partition Coefficient (Log Kow):  6.2 (technical) O

O C H 2 ( C H 2 ) 1 0 C H 3 O C O C H 3 O

O C H 2 ( C H 2 ) 1 0 C H 3

O HAcequinocyl Human - Health Risk Assessment D 38 9519

Page 9 of 35 Melting Point: 59.6  C (technical) Density : 1.13 g/cm 3 Acequinocyl is a liquid at room temperature , thus, any losses due to volatilization/ sublimation are expected to be minimal. **3.0 HAZARD CHARACTERIZATION/FQPA CONSIDERATIONS** The existing toxicological database for acequinocyl is complete and supports the establishment of permanent tolerances for residues of acequinocyl in/on the RACs resulting from the proposed uses. The toxicity

profile tables also may

be found in the Appendix, Tables A - 1 and A - 2. The following documents support the hazard characterization of acequinocyl:

 Acequinocyl. 2 nd Report of the HIARC. Meeting Date: October 14, 2003. P. Terse , 13 -NO V - 20 04 ; TXR No. 0052234.  Acequinocyl. Report of the HIARC . Meeting Date: July 15, 2003. R. Fricke , 14 - AUG - 20 03 ; TXR No. 0052075. **3.1 Hazard Profile** Acequinocyl binds to the Qo center at Complex III in the mitochondria of mite cells and, thereb y, exerts its miticidal action b y inhibiting electron transfer. Acequinocyl possesses moderate activity

against plant mitochondrial complex III, in contrast to much higher activity against an insect mitochondrial complex III. There is a lack of information regarding whether or not acequinocyl inhibits the mammalian mitochondrial electron transfer s ys tem. Acequinocyl exhibits marginal absorption into the plasm a (13 - 16% for the 10 mg/kg low dose and 8 - 9% for the 500mg/kg high dose) and relatively rapid and complete excretion (24 hours for the low dose and 72 hours for the high dose), primarily via the bile and feces (82.6%) in rat . Absorption is saturated at th e high dose. Plasma kinetic data revealed peak plasma concentrations occurring at 2 - 6 hours following a single or 14 - day repeated low dose and at approximately

24 hours for the high dose group. The elimination half - life is about 4.4 - 6.5 hours for the sin gle day

low dose group. Acequinocyl undergoes nearl y complete metabolism to hydrol ys is products and a glucuronide conjugate. There was no evidence for selective tissue accumulation or sequestration. Acequinocyl has low acute toxicity via the oral, der

mal, and inhalation routes. No ocular or dermal irritation was noted. Acequinocyl is not a dermal sensitizer. Acequinocyl is a known Vitamin K antagonist and, therefore, is thought to disrupt blood coagulation. This mechanism is supported by

effects ob served in the database. In the rat subchronic oral toxicity study , the primary

effects included pallor, swelling of the eyes and limbs, decreased motor activity , piloerection, reddish urine, increased activated partial thromboplastin time, increased pro thrombin time, and internal hemorrhages. In the mouse subchronic oral toxicity

study , effects included pallor, sunken eyes, labored/irregular breathing, hunched posture, piloerection, weight loss, and hepatic vacuolization (blood coagulation profile was n ot evaluated in this study). In the dog subchronic oral toxicity study , toxic effects included reduced body - weight gain s, reduced food efficiency , decreased total protein, increased trigl yceride levels, elevated platelet counts, elevated reticulocytes, in creased prothrombin time, and decreased liver and heart weights (absolute). In the rat 28 - day dermal toxicity

study , theAcequinocyl Human - Health Risk Assessment D 38 9519

Page 10 of 35 primary effects were red - stained treated skin area, increased prothrombin time, increased activated partial prothromboplastin time, in creased fibrinogen levels, and increased heart weights (absolute and relative to the body weight) . In the rat chronic oral studies, toxic effects included enlarged eyeballs, increased prothrombin time, and increased activated partial thromboplastin time. Inthe mouse chronic oral toxicity study , hepatotoxicity

was indicated by

increased liver enzy

me levels (alanine and aspartate aminotransferase), increased liver weight, hepatocy te vacuolization, and hepatocy te fatt y deposition (blood clotting was not eva luated in this study). In the dog chronic toxicity study , effects included elevated prothrombin time, increased reticulocy te/platelet count, reduced body weight gain , and reduced food efficiency . In the rat prenatal developmental toxicity study , mater

nal toxicity

resulted in pale eyes, piloerection, red vaginal discharge, and internal hemorrhage at the lowest - observable adverse effects level (L OAEL ; 500 mg/kg/day), whereas developmental toxicity was indicated by increased resorptions and fetal variatio ns (750 mg/kg/day). In the rabbit, maternal toxicity produced body - weight loss , reduced fecal output, reduced food consumption, pale lungs/liver, internal hemorrhaging, hair loss, and blood - stained urine (120 mg/kg/day). The developmental toxicity study in rabbits identified an increased number of complete resorptions (120 mg/kg/day). In the rat two - generation reproductive toxicity study , both the maternal and reproductive toxicity LOAELs were not observed ; however , the LOAEL for parental males was 58.9 /69.2 mg/kg/day based on hemorrhagic effects. The offspring s ys temic L OAEL was also 58.9 mg/kg/day . Though the offspring LOAELwas similar to that of parental male’s, there were effects specific to the pups which , in addition to the hemorrhagic effects n oted in both generations, included swollen body

parts, protruding eyes, clinical signs, delays in pupil development , and increased mortality occurring mainly

after weaning. Previously , HED’s HIARC concluded that exposure to acequinocyl does not pose a neurotoxicity concern. First, acequinocyl is a known Vitamin K antagonist; neurotoxic compounds of similar structure were not identified. Second, although two studies showed effects that could be indicative of neurotoxicity , HIARC considered these as sec ondary because they

were observed at very high doses. In the 2 - generation reproduction study , significant reduction in startle response in F 2 pups was observed in the mid - and high - dose groups (58.9/69.2 mg/kg/day and 111.2/133.5 mg/kg/day). However, oth er functional development tests (such as a pupillary reflex test at 21 day s post partum, an open field exploration test at 35 - 48 day s post partum and a water maze test with a learning phase and a memory phase at 35 - 48 day s post partum) that were performed on pups did not show significant differences as compared to control values even at the highest dosage level. In the rat subchronic oral toxicity study , neurotoxicity

signs, such as decreased motor activity , piloerection , and hunched posture, were observed at the high dose (252.7/286.0 mg/kg/day), but in the presence of clinical signs including wasting, swelling of the orbit and limbs, pallor, and reddish urine. Furthermore, all rats in this 252.7/286.0 mg/kg/day (3200 ppm) group died or were sacrificed mo ribund in the first three weeks of treatment. There was no evidence of carcinogenic potential in either the rat or mouse carcinogenicity study , indicating that acequinocyl is "not likel y" to be carcinogenic to humans. There was no concern for mutagenic a ctivity as indicated by

several mutagenicity

studies, including a bacterial (Salmonella, E. coli ) reverse - mutation assay , an in vitro mammalianAcequinocyl Human - Health Risk Assessment D 38 9519

Page 11 of 35 chromosomal - aberration assay , an in vivo mouse bone marrow micronucleus assay , and a bacterial DNA damage or repair assay . **3.2 FQPA Considerations** HED’s RAB1 risk assessment team concluded that based on toxicological considerations and the residue assumptions used in the dietary and residenti al exposure analy ses, the FQPA SF may be reduced to 1 X . This recommendation is based on the following considerations:

 There are no residual uncertainties for pre - and post - natal toxicity .  There is potential evidence of neurotoxicity or neuropathology

in the 2 - generation reproduction study as well as the rat subchronic neurotoxicity study , however these toxicities are not considered to be primary effects since they

occur in the presence of more severe s ys temic effects in both studies. Therefore, although an acute and subchronic neurotoxicity

studies are now required as a part of new data requirements in the 40CFR §158 for conventional pesticide registration, the agency does not believe that conducting these studies will result in a lower POD than that curr ently used for overall risk assessment, and therefore, a database uncertainty factor (UF DB ) is not needed to account for lack of these studies.  There is no evidence of increased susceptibility of rat or rabbit fetuses to in utero exposure to acequinocyl. Inthe 2 - generation reproduction study , more severe effects were observed in the offspring, however these effects were observed at the same doses as parental effects, and a clear NOAEL was established which is being used in endpoint selection.  The toxico logy

database for a cequinocyl does not show any evidence of treatment - related effects on the immune system. The overall weight of evidence suggests that this chemical does not directly target the immune s ys tem. An immunotoxicity study is required as a part of new data requirements in the 40 CFR Part 158 for conventional pesticide registration; however, the Agency does not believe that conducting a functional immunotoxicity

study will result in a lower POD than that currently in use for overall risk assess ment, and therefore, a UF DB is not needed to account for the lack of this study .  A 28 - day

inhalation study

is not available; however, the EPA has determined that the additional FQPA SF is not needed. Residential inhalation risk was estimated by calculatin g exposure using the Agency 's Residential Standard Operating Procedures (SOPs) . For chemicals with low vapor pressure (7.5 x 10 - 5 mmHg or below for outdoor uses at 20 - 30 0 C) , these standard assumptions are expected to overestimate the exposure via the inha lation route. Acequinocyl is such a compound ( 1.69 x 10 - 11 mmHg at 25 0 C) and exposure through the inhalation route is expected to be minimal. Therefore, the risk estimate is conservative and is considered protective and the additional FQPA SF is not need ed.  Since all calculated inhalation MOEs for residential handlers are significantly greater than HED’s LOC (MOE >100), the lack of an inhalation study will not affect the FQPA SF.  The dietary

food (tolerance - level residues, 100% crop treated) and drinking water exposure (modeled) assessments will not underestimate the potential exposures for infants and children; and the residential use (ornamentals) is not expected to result in post - application exposure to infants and children.  The dietary

dri nking water assessment utilizes model - generated water concentration values and associated modeling parameters that are designed to provide conservative,Acequinocyl Human - Health Risk Assessment D 38 9519

Page 12 of 35 health - protective, high - end estimates of water concentrations that will not likely be exceeded. **3. 3**  **Dose -**  **Response Assessment** Table 3. 3 .1 provide s the toxicity endpoints used in this risk assessment. **Table 3.3.1. Summary of Toxicological Doses and Endpoints for Acequinocyl for Use in Dietary, Occupational, and Residential Exposure Risk**  **Assessments. 1**  **E xp**  **osure/ Scenario**  **POD Uncertainty/FQPA SF**  **RfD, PAD, LOC Study and Toxicological Effects**  Acute Dietary (General Population, including Infants and Children) N/A N/A N/A An endpoint of concern (effect) attributable to a single dose was not identified in the database. Quantification of acute risk to general population including infants and children is not required. Chronic Dietary (All Populations) NOAEL = 2.7

mg/kg/day UF A = 10x

UF H =10x FQPA SF = 1X cPAD = cRfD = 0.027 mg/kg/day 18 - month carcinogenicity study in mice; LOAEL = 7.0 mg/kg/day based on clinical chemistry and microscopic nonneoplastic lesions (brown pigmented cells and perivascular inflammatory cells in liver). Short - term (1 - 30 days) incidental oral NOAEL=60

mg/kg/day UF A = 10x

UF H =10x LOC (residential) = MOE <100 Developmental toxicity study in rabbits; Maternal LOAEL = 120 mg/kg/day based on clinical signs (hematuria, reduced fecal output, body weight loss, and reduced food consumption) and gross ne cropsy findings (pale lungs and liver, hemorrhaging uterus, fluid in the cecum, fur in the stomach, blood stained vaginal opening, blood - stained urinary bladder contents/urine). Intermediate term (1 - 6 months) incidental oral NOAEL = 16

mg/kg/day UF A = 10x

UF H =10x LOC (residential) = MOE <100 Subchronic toxicity in mice; LOAEL = 81 mg/kg/day based on hepatocyte vacuolization. Short - (1 - 30 days) and Intermediate term (1 - 6 months) Dermal Dermal NOAEL

= 200 mg/kg/day UF A = 10x

UF H =10x LOC (occupational/ residential) = MOE <100 28 - day dermal study in rats; LOAEL = 1000 mg/kg/day based on increased clotting factor times. Short - term (1 - 30 days) Inhalation Oral

NOAEL=60 mg/kg/day (inhalation absorption rate=100%) UF A= 10x

UF H =10x LOC (occupational/ residential) = MOE <100 Developmental toxicity study in rabbits; Maternal LOAEL = 120 mg/kg/day based on clinical signs (hematuria, reduced fecal output, body weight loss, and reduced food consumption) and gross necropsy findings (pa le lungs and liver, hemorrhaging uterus, fluid in the cecum, fur in the stomach, blood stained vaginal opening, blood - stained urinary bladder contents/urine).Acequinocyl Human - Health Risk Assessment D 38 9519

Page 13 of 35 **Table 3.3.1. Summary of Toxicological Doses and Endpoints for Acequinocyl for Use in Dietary, Occupational, and Residential Exposure Risk**  **Assessments. 1**  **E xp**  **osure/ Scenario**  **POD Uncertainty/FQPA SF**  **RfD, PAD, LOC Study and Toxicological Effects**  Intermediate - (1 - 6 months) Term Inhalation Oral NOAEL =

16 mg/kg/day (inhalation absorption rate=100%) UF A = 10x

UF H = 10x LOC (occupational/ residential) = MOE <100 Subchronic toxicity in mice; LOAEL = 81 mg/kg/day based on hepatocyte vacuolization. Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans.” 1 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. 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, NOAEL = no - observed - adverse - effect level, LOAEL = lowest - observed - adverse - effect level, RfD = reference dose (a = acute, c = chronic), PAD = population - adjusted dose, MOE = margin of exposure, LOC = level of concern, N/A = Not Applicable. Acute Dietary Endpoint : The aRfD for the general population, inc luding infants and children, was not established because an endpoint of concern attributable to a single dose was not identified. Therefore, this assessment is not necessary . Chronic Dietary Endpoint : The chronic reference dose (cRfD) of 0.027 mg/kg/day was derived from the chronic carcinogenicity study in mice. An UF of 100 (10 - fold for interspecies extrapolation and 10 - fold for intraspecies variability) was applied to the NOAEL of 2.7 mg/kg/day

to generate the cRfD. The LOAEL of 7.0 mg/kg/day is base d on clinical chemistry and microscopic non - neoplastic lesions (brown - pigmented cells and perivascular inflammatory cells) in the liver. The FQPA SF of 1X is applicable for chronic dietary risk assessment. Therefore, the cPAD is equal to the RfD and is 0 .027 mg/kg/day . The lowest NOAEL in the database was derived from this study , and this study is thus appropriate for the chronic reference dose. It is also appropriate for both the expected duration of exposure and the route of exposure. Short- Term Inci dental Oral Endpoint: The short - term incidental endpoint was derived from the development rabbit study where the maternal NOAEL was 60 mg/kg bw/day . The maternal LOAEL was 120 mg/kg bw/day based on treatment - related clinical signs leading to premature sa crifice (hematuria, reduced fecal output, body weight loss, and reduced food consumption) and gross necrops y findings (pale lungs and liver, hemorrhaging uterus, fluid in the cecum, fur in the stomach, blood stained vaginal opening, blood - stained urinary b ladder contents/urine). This study is relevant for the duration of exposure, and is protective of the populations of concern. Intermediate - Term Incidental Oral Endpoint: The intermediate - term incidental or endpoint is based on hepatocy

te vacuolization seen in the 90 - day oral study

in mice observed at the LOAEL of 81 mg/kg/day

(NOAEL = 16 mg/kg/day). based upon hepatocy te vacuolization observed in male and female mice at the L OAEL of 81/ 100 mg/kg/day . The endpoint is appropriate for the route, duration of exposure (1 - 6 months) and populations of concern. Corneal effects seen in rats at 800 ppm (36.41 mg/kg/day and 46.20 mg/kg/day

for male and female, respectively) would also be protected b y this dose (NOAEL, 16 mg/kg/day). Dermal Absorption: No dermal - absorption factor was necessary for the short - and intermediate term dermal assessments since the endpoint was based on a dermal study. However, HIARC selected a dermal - absorption rate of 15% for the long - term dermal assessment. The dermal penetration study yi elded absorptions of 12.23%, 19.75% and 14.77% at 168 hours (doses wereAcequinocyl Human - Health Risk Assessment D 38 9519

Page 14 of 35 0.1, 0.01, and 0.001 mg/cm 2 , respectively). Because a higher dermal absorption value (20%) was observed at the mid - dose than observed at the lowest dose (15%), HIARC selected a 15% dermal - absorption value that was based on the average absorption values at the three doses at 168 hours (7 day s). Short- and Intermediate - Term Dermal Endpoints: The s hort - and intermediate - term dermal endpoints are based on increased clotting factor times seen in the rat 28 - day dermal toxicity study at the LOAEL of 1000 mg/kg/day (NOAEL = 200 mg/kg/day). This study is ideal for this exposure scenario because it is the route specific study , it matches the durations of exposure (1 - 30 day s and 1 - 6 months) , and it is consistent with the mechanism of action for this active ingredient. The LOC for occupational exposure is for a MOE of <100. Short- Term Inhalation Endpoint: The s hort - term inhalation endpoint is based on the maternal NOAEL of 60 mg/kg/day in the developmental study in rabbits. The NOAELof 60 mg/kg/day was based on clinical signs (hematuria, reduced fecal output, body - weight loss , and reduced food consumpti on) and gross necrops y findings (pale lungs and liver, hemorrhaging uterus, fluid in the cecum, fur in the stomach, blood stained vaginal opening, blood - stained urinary bladder contents/urine) at the LOAELof 120 mg/kg/day . Because H IARC selected an oral NOAEL for short - term inhalation exposure assessment, a conservative 100% oral equivalent inhalation absorption factor is assumed. This study is relevant for the duration of exposure and is protective of pregnant females from the above - mentioned effects , which are consistent with mechanism of action for this active ingredient . Intermediate - Term Inhalation Endpoint: The i ntermediate - term inhalation endpoint is based on hepatocy te vacuol iz ation seen in the 90 - day oral study

in mice observed at the LOAEL o f 81 mg/kg/day (NOAEL = 16 mg/kg/day). Because HIARC selected an oral NOAEL for intermediate - term inhalation exposure assessment, a conservative 100% oral equivalent inhalation absorption factor is assumed. This study is relevant for the duration of exposure (90 - day s). The LOC for occupational exposure is for a MOE of < 100. Long- Term Dermal and Inhalation Endpoint s : Since the uses under consideration in the current risk assessment do not include long - ter m dermal or inhalation exposure s , long - term dermal and inhalation risk assessment s w ere not performed. Based on the available toxicity database and the Agency 's current practices, the inhalation risk for acequinocyl was assessed using an oral toxicity stu dy . The Agency

sought expert advice and input on issues related to this route - to - route extrapolation approach (i.e., the use of oral toxicity studies for inhalation risk assessment) from its Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scie ntific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may , as appropriate , re - examine and develop new policies and procedures for conducting inhalation risk assessments, including route - to - route extrapolation of toxicity

data. If any

new policies or procedures are developed, then the Agency may revisit the need for an inhalati on toxicity study for acequinocyl and/or a re - examination of the inhalation toxicity

risk assessment. **3. 4**  **Recommendation for Aggregate Exposure Risk Assessments** S ince short - and intermediate - term inhalation endpoints are based on oral studies, dietaryAcequinocyl Human - Health Risk Assessment D 38 9519

Page 15 of 35 e xposure will be aggregated to inhalation exposure for all populations/durations. **4.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION**  Please refer to the following documents for detailed considerations of the material summarized in this section:

 PP#: 1E7864 . Petition for Use on Succulent Soybean Vegetable; Succulent Shelled Beans; Cow pea Forage; Caneberry Subgroup 13 - 07A; Melon Subgroup 9A; Cucumber, Cherry; Low - Growing Berry Subgroup 13 - 07G; and Small Fruit Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13 - 07F. Summary of Analytical Chemistry and Residue Data . S. Levy, 30 -NOV - 2011; D389989 .  PP#: 1E7864. Acequinocyl. Chronic Aggregate Dietary (Food + Drinking Water) Exposure and Risk Assessment for the Section 3 Registration Action Use on Succulent Soy bean Vegetable; Succulent Shelled Beans; Cowpea Forage; Caneberry Subgroup 13 - 07A; Melon Subgroup 9A; Cucumber; Cherry; Low Growing Berry Subgroup 13 - 07G; and Small Fruit Vine Climbing, Except Fuzzy Kiwifruit, Subgroup 13 - 07F. S. L e vy , 30 - NOV - 2011 ; D38 9990.  Acequinocyl: Occupational and Residential Exposure/Risk Assessment for Proposed Use on Succulent soy bean; Low growing berry subgroup 13 - 07G; Small fruit vine climbing (except fuzzy kiwifruit, subgroup 13 - 07F); Succulent bean; Cow pea forage; Caneberry (subgroup 13 - 07A); Melon (subgroup 9A); Cucumber (greenhouse and field), and Cherry. K. Lowe, 30 -NOV - 2011; D 389991 .  A cequinocyl : Drinking Water Assessment to Support Proposed New IR - 4 Uses (Succulent Soybean Vegetable, Low Growing Berry, Small Fruit Vine Climbing - Except Fuzzy Kiwifruit, Succulent Shelled Beans, Cow

pea Forage, Caneberry, Melon, Cucumber, and Cherry) . M. Lowit et al . , 07 - SEP - 2011 ; D389520. Acequinocyl is a quinoline - ty pe miticide registered for use in the U.S. on a number of RACs for the control of various phytophagous mite species. Under PP#1E7864, the IR - 4, on behalf of the Agricultural Experiment Station of TX, CA, OR, PA, GA, NM, OK, TN, UT, MI, FL, and AZ, is requesting for the establishment of tolerances for combined resi dues of the insecticide acequinocyl and its metabolite, 2 - dodecyl - 3 - hydrox y - 1,4 - naphthoquinone (acequinocyl - OH), expressed as acequinocyl equivalents in/on the following commodities: Soy bean, vegetable, succulent ................................ ................................ .. 0.25 ppm Lo w growing berry

subgroup 13 - 07G ................................ ...................... 0.4 ppm Small fruit vine climbing subgroup 13 - 07F, except fuzzy kiwifruit ........ 1.6 ppm Bean, succulent shelled ................................ ................................ ............. 0.15 ppm Cowpea, forage ................................ ................................ ......................... 9.0 ppm Caneberry

subgroup 13 - 07A ................................ ................................ ..... 4.5 ppm Melon subgroup 9A ................................ ................................ .................. 0.06 ppm Cucumber ................................ ................................ ................................ .. 0.15 ppm Cherry ................................ ................................ ................................ ....... 0.8 ppm No new data were submitted to support tolerances on succulent so ybean vegetables, low - growing berry 13 - 07G crop subgroup, or small fruit vine climbing subgroup 13 - 07F, except fuzzy kiwifruit. The petitioner has requested that existing tolerances be e xpanded to their respective crops or crop groups.Acequinocyl Human - Health Risk Assessment D 38 9519

Page 16 of 35 **4.1 Summary of Uses**  The petitioner provided a draft label for Kanemite TM 15 SC Miticide (EPA Reg. No. 66330 - 38), a 1.25 lb/gal SC formulation of acequinocyl. This acequinocyl formul ation is currentl y registered for use on several fruit and nut crops, fruiting vegetables, okra, edible - podded beans, and hops. Table 4.1.1 provides a summary of the proposed use patterns. **Table 4.1.1. Summary of Proposed Directions for Use of Acequinocyl.**  Applic. Timing, T ype, and Equip. Form

ulation [EPA Reg. No.] Applic.

Rate (lb ai/A) Max. No.

Applic. per Season Max. Seasonal

Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations 1 Bean, succulent shelled Postemergence, foliar; Ground only ; Groundboom 1.25 lb/gal

SC [66330 - 38] 0.3 2 0.6 7 Minimum spray volume of 30 gal/A; minimum RTI of 14 days. Do not allow grazing on cow

pea forage within 7 days of last treatment. Caneberry subgroup 13 - 07A Postemergence, foliar; Ground only ; Groundboom 1.25 lb/gal

SC [66330 - 38] 0.3 2 0.6 1 Minimum spray volume of 50 gal/A; minimum RTI of 21 days. Melon subgroup 9A Postemergence, foliar; Ground only ; Groundboom 1.25 lb/gal

SC [66330 - 38] 0.3 2 0.6 1 Minimum spray volume of 30 gal/A; minimum RTI of 21 days. Cucumber Postemergence, foliar; Ground only ; Groundboom (field); Handheld sprayers (greenhouse) 1.25 lb/gal

SC [66330 - 38] 0.3 or 0.1 2 2 0.6 1 Minimum spray volume of 3 0 gal/A; minimum RTI of 21 days. The use of an adjuvant or surfactant is prohibited. Cherry Postemergence, foliar; Ground only ; Airblast 1.25 lb/gal

SC [66330 - 38] 0.3 2 0.6 7 Minimum spray volume of 40 gal/A; for optimal control, use a minimum of 150 gal/A; minimum RTI of 14 days. Do not use in alternate row middle applications. 1 RTI = retreatment interval. 2 Label indicates a minimum of 30 gal/A. Application rate = 0.3 lb ai/A ÷ 30 gal/A = 0.01 lb ai/gal. General label restrictions include : (i) do not appl y through an y typ e of irrigation sy stem; (ii) do not apply by air; (iii) do not apply

within 75 feet of aquatic areas; and (iv) not for indoor residential use. The product may be combined with most commonly used pesticides with the excep tion of strongl y alkaline material, which can reduce activity; combination with Phos - ethyl (foset yl ) is prohibited. Broad - spectrum insect control may be obtained by

tank - mixing the SCAcequinocyl Human - Health Risk Assessment D 38 9519

Page 17 of 35 acequinocyl product with other miticide/insecticide products; a spray m ix compatibility

and phy totoxicity trial under local conditions should first be conducted. A 12 - hour REIis specified. The label requires applicators and other handlers to wear a long - sleeved shirt and long pants and shoes plus socks, plus chemical - resis tant gloves. Rotational crop restrictions are as follows: food and feed crops not listed on the proposed label must not be planted within 30 day s of the last Kanemite TM 15 SC application. Conclusions: The proposed use directions are adequate to allow for evaluation of the submitted residue data relative to the proposed uses. The proposed uses are supported by the submitted field trial data. Furthermore, the submitted field trial data reflect applicati ons made without the use of a spray

adjuvant. **A revised Section B should be submitted incorporating an adjuvant**   ** use restriction.** An adequate confined rotational crop study was previousl y submitted, reflecting the maximum proposed use pattern for rotated crops. The available data support a 30 - day PBI for all non - labeled crops, which is reflected on the proposed label. **4.2 Dietary Exposure/Risk Pathway**  **4.2.1 Residue Profile**  **Nature of the Residue:** The nature of acequinocyl residues in apples, oranges, and eggplants is understood based on the previously submitted and reviewed metabolism studies. In these crops, the metabolism of acequinocyl involves the loss of the acetyl oxy moiet y to form acequinocyl OH, the opening of the quinone ring to form AKM - 18, and the subsequent degradation of the quinone ring to yi eld polar metabolites that degrade to phthalic acid. For purposes of risk assessment and the tolerance expression, the HED Metabolism Assessment Review Committee (MARC) has determined that the resid ues of concern in these commodities include parent and acequinocyl - OH (Memo, S. L ev y, et al ., 07 - JAN - 2004; D 297872). The qualitative nature of acequinocyl residues in ruminants is understood based on an adequate goat metabolism study

(Memo, S. L ev y, 10 - MA R - 2004; D284757). The metabolism of acequinocyl in goats appears to involve the loss of the acetyloxyl moiet y t o form acequinocyl OH and partial cleavage of the dodecyl side chain to form AKM - 15. Opening and degradation of the quinone ring was also evide nced b y the presence of AKM - 18 and phthalic acid. The MARC concluded that for tolerance expression, the residues of concern in livestock commodities include parent and acequinocyl - OH. For risk assessment purposes, the residues of concern in livestock commodities are parent and acequinocyl - OH (for liver and kidney , metabolite AKM - 15 is to be included as well (Memo, S. L ev y, et al ., 07 - JAN - 2004; D297872). Metabolism data on poultry are not required at the present time as none of the proposed or existing uses of acequinocyl are on crops having regulated poultry feedstuffs. **Magnitude of the Residue -**  **Plants :**  IR - 4 submitted adequate field trial data in support of the proposed uses on succulent shelled beans, caneberry , cantaloupe, cherry , and cucumber. The field trials reflect the proposed use patterns and an adequate number of field trials were conducted in major crop growing regions. The submitted field trial data reflect applications made without the use of a spray adjuvant. **A revised Section B should b e submitted**  **prohibiting the addition of adjuvants to the spray solution.** The Organization for Economic Co - operation and Development (OECD) maximum residue limit (MRL) calculator was used toAcequinocyl Human - Health Risk Assessment D 38 9519

Page 18 of 35 determine the appropriate tolerance levels. The field trial data will support tolerances of: 0.30 ppm for residues in/on bean, succulent shelled; 6.0 ppm for residues in/on cowpea, forage; 18 ppm for residues in/on cowpea, hay ; 4.0 ppm for residues in/on caneberry subgroup 13 - 07A; 0.15 ppm for residues in/on melon sub group 9A; 1.0 ppm for residues in/on cherry , tart; 0.50 ppm for residues in/on cherry , sweet; and 0.15 ppm for residues in/on cucumber. **A revised Section F should be submitted.**  No new data were submitted to support tolerances on succulent so ybean vegeta bles, low - growing berry 13 - 07G crop subgroup, or small fruit climbing vine subgroup 13 - 07F, except fuzzy kiwifruit. However, existing established tolerances in 40 CFR §180.599 should be extended to support these crop group tolerances. HED recommends that that the tolerance for residues at in/on edible - podded beans should be extended to soy bean, vegetable, succulent; the tolerance for residues in/on strawberries should be extended to the low - growing berry 13 - 07G subgroup; and the tolerance for residues in/ on grapes should be extended to small fruit vine climbing subgroup 13 - 07F, except fuzzy

kiwifruit. See Table 4.2.1.1 for details. There are no processed food/feed items associated with the proposed uses. Therefore, data requirements for this guideline are not relevant to this tolerance petition. **Magnitude of the Residue -**  **Livestock:** Based on the potential dietary exposure of livestock to acequinocyl residues from the current and proposed uses, the dietary burden was re - evaluated. The re - evaluated dietary burden indicates that the currentl y established tolerance level of 0.02 ppm for residues in cattle, goat, horse, and sheep fat are appropriate. Furthermore, the 0.02 - ppm residue level is sufficient to cover residues of the additional metabolite (AKM - 15) of concern in ruminant liver and kidney . The established 0.02 - ppm residue level in cattle, goat, horse, and sheep liver is appropriate; however , the commodity definition should be changed to “meat by products” rather than “liver.” With the establishment of the cattle, goat, horse, and sheep tolerance in meat b yproducts, RD should remove the tolerance (40 CFR §180.599) for liver. Furthermore, the meat byproducts tolerance of 0.02 ppm is adequate to cover residues in the kidney of cattle, goats, horses, and sheep. **A revised Section F should be submitted. Resi** **due Analytical Method for Crops:** There are adequate residue anal yt ical methods for enforcing tolerances for acequinocyl residues of concern in/on the proposed/registered commodities. These methods include two high - performance liquid chromatography methods with tandem mass - spectroscopy detection (HPLC/MS/MS) for determining residues in/on plant commodities (Morse Methods Meth - 135 and #Meth - 133, revision #3 ). For each of these methods, residues are extracted with hexane or acetonitrile (ACN)/water and cleaned up b y solvent partitioning, gel - permeation chromatography (GPC) and/or silica - gel solid - phase extraction (SPE). In the current field trials, residues of acequinocyl and acequinocyl - OH were determined using a modified version of Morse Method #Meth - 133, revision #3. The method limit of quantitation (LOQ; based on the lowest level of method validation (LLMV)) for succulent shelled beans was 0.02 ppm for each analy te . The LOQs (based on the LLMV) for cantaloupe were 0.015 ppm for acequinocyl, and 0.01 ppm for acequinocyl - OH. For cherries, cucumbers, and caneberries, th e LOQ (based on the LLMV) was 0.01 for each anal yt e. The method was adequatel y validated in conjunction with the analysis of field trial samples. Analy tical reference standards for acequinocyl and acequinocyl - OH are currentl y available at the EPA National Pesticide Standards Repository (electronic communication with Theresa Cole, 31 - OCT - 2011) with expiration dates of June, 2012.Acequinocyl Human - Health Risk Assessment D 38 9519

Page 19 of 35 The data requirem ents for multiresidue (MRM) methods are fulfilled. Certain MRM protocols resulted in acceptable recoveries. The MRM testing data have been forwarded to the U.S. Food and Drug Administration (FDA) for further evaluation (Memo, S. L ev y, 18 - FEB - 20 04; D29891 7). **Storage Stability in Plants:** The submitted concurrent storage stability data for the subject crops are adequate to support the storage intervals and conditions incurred by the field trial studies. **Confined Accumulation in Rotational Crops:** An adequate confined rotational crop study was previously

submitted. These data reflect the maximum proposed use pattern for rotated crops (fruiting vegetables and edible - podded beans); the results indicate that residues of acequinocyl do not accumulate in rotat ed crops. These data support a 30 - day PBI for all non - labeled crops , which is reflected on the proposed label . **Proposed and Recommended Tolerances:** There are currentl y no established Codex, Canadian, or Mexican MRL s for acequinocyl residues in/on cucumb ers or caneberries. Data for these crops were jointly

reviewed by

the U.S. and Canada. The data support tolerance levels of 0.15 ppm and 0.40 ppm, respectively . These levels are harmonized between the U.S. and Canada. Canada has a MRLof 0.5 ppm for residues in/on strawberries. The OECD Calculator shows that the data support a tolerance of 0.40 ppm for residues in/on the low - growing berry subgroup 13 - 07G (which includes strawberries); however, in order to harmonize with Canada, HED recommends establi shing a tolerance of 0.50 ppm for residues in this subgroup. Canada also has a MRLfor residues of 0.02 ppm in/on meat by products of cattle, goat, horse, and sheep . HED is recommending for the same tolerance level as Canada; therefore, harmonization will not be an issue. The proposed and HED - recommended tolerances are listed in Table 4.2.1.1 . The petitioner should submit a revised Section F with the appropriate commodity definitions and/or HED - recommended tolerance levels listed in Table 4.2.1.1 . Furthermore, the Section F should state the following (as it appears in 40 CFR §180.599): “Tolerances are established for residues of acequinocyl, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined b y measuring only

the sum of acequinocyl [ 2 - (acetyloxy ) - 3 - dodecyl - 1,4 - naphthalenedione] and its metabolite, 2 - dodecyl - 3 - hydrox y - 1,4 - naphthoquinone , calculated as the stoichiometric equivalent of acequino cy l, in or on the commodity.” **A revised Section F should be submitted. Table 4.2.1.1. Tolerance Summary for Acequinocyl.**  Commodity Proposed Tolerance (ppm) HED Recommended Tolerance (ppm) Comments;

Correct Commodity Definition Soy bean, vegetable, succulent 0.25 0.25 Established edible - podded bean tolerance extended to soy bean, vegetable, succulent. Lo w - growing berry subgroup 13 - 07G 0.4 0.50 Established straw berry tolerance extended for a subgroup tolerance. With establishment of this subgroup tolerance, the strawberry tolerance should be removed. Berry, low growing, subgroup 13 - 07GAcequinocyl Human - Health Risk Assessment D 38 9519

Page 20 of 35 **Table 4.2.1.1. Tolerance Summary for Acequinocyl.** Commodity Proposed Tolerance (ppm) HED Recommended Tolerance (ppm) Comments;

Correct Commodity Definition Small fruit vine climbing subgroup 13 - 07F, except fuzzy kiwifruit 1.6 1.6 Established grape tolerance extended for a subgroup tolerance. With establishment of this subgroup tolerance, the grape tolerance should be removed. Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F Bean, succulent shelled 0.15 0.30 Cow pea, forage 9.0 6.0 Cow pea, hay -- 18 Caneberry subgroup 13 - 07A 4.5 4.0 Melon subgroup 9A 0.06 0.15 Cucumber 0.15 0.15 Cherry 0.8 1.0 Cherry, tart

-- 0.50 Cherry, sweet Liver of cattle, goat, horse, and sheep 1

-- 0.02 Meat byproducts of cattle, goat, horse and sheep 1 A tolerance of 0.02 ppm is already established under 40 CFR §180.599; however, the commodity definition should be changed to meat byproducts to cover residues in liver and kidney. **4.3 Water Exposure/Risk Pathway Environmental Fate Assessment:**  Acequinocyl appears to undergo fairl y rapid transformation in mos t aquatic and terrestrial environments. Itundergoes hydrol ys is with a half - life of a few hours to less than 2 day s under neutral and alkaline pH conditions. However, it is stable at acidic pH conditions. Photodegradation in water appears to be the main route of degradation in aquatic environments, with half

- lives occurring in less than 15 minutes in sterile lab and river water. Acequinocyl also undergoes fast degradation in terrestrial environments. The half - lives for aerobic biotransformation on soil are less than 2 day s under laboratory conditions and under field conditions, acequinocyl applied to bare plots dissipated with half - lives ranging from 2 hrs in California to 14 hours in New York. Acequinocyl can reach surface water via spray drift and less likely

via runoff. Due to its high Kd values it is expected to exhibit low mobility in soil and low potential to leach into groundwater. Once acequinocyl has entered surface water, it is not lik ely to persist as it will hydrol yz e to form hydrox y - acequinocyl (also known as R - 1). **Surface and Ground Water Estimated Drinking Water Concentrations (**  **EDWC s**  **) :**  For the aquatic exposure modeling, both parent and metabolite (acequinocyl - OH) concentrations w ere estimated in the surface and ground water to address the toxicity concerns associated with the acequinocyl - OH degradate. There are no drinking water monitoring data available f or either acequinocyl or acequinocyl - OH. Groundwater EDWCs were generated for acequinocyl using the Screening Concentration in Ground Water (SCI - GROW) Model. Surface water EDWCs were generated using the Pesticide Root Zone Model/Exposure Analy sis Modeling S ys tem (PRZM/EXAMS) model for all proposed uses except cranberry (cranberries are part of the lowAcequinocyl Human - Health Risk Assessment D 38 9519

Page 21 of 35 growing berries subgroup, 13 - 07G). Cranberry harvesting may

involve field flooding and PRZM/EXAMS is not currentl y parameterized to assess this ty pe of scenario; therefore, cranberry was assessed using the provisional cranberry mo del (note that since the provisional cranberry model onl y uses a one year simulation, the highest 30 - year annual average concentration is not available for the cranberry scenario). Similar to previous drinking water assessments provided by EFED, two appro aches were used in performing the drinking water assessment for proposed acequinocyl uses. In Approach #1 , acequinocyl was conservatively assumed to be stable to all routes of degradation to account for the uncertainties associated with the environmental fate data. In Approach #2 , total (acequinocyl + acequinocyl - OH) residues were modeled with the assumption that the half - lives of acequinocyl and R1 are valid and the total toxic residues were modeled to address toxicity concerns with R1. The EDWCs are summarized below in Table 4. 3 .1 . Surface water EDWCs for the proposed uses are higher than those previously reported for both approaches. The ground water EDWC for the current assessment is the same as the last assessment. **Table 4.3.1. Recommended EDWCs of Acequinocyl Derived from the Previous Uses.**  Drinking water source (model) Proposed

Use/Scenario 3 EDWCs from Surface Water Sources (ug/L ) 1,2 Approach 1 (assume no acequinocyl degradation) Approach 2 (combined acequinocyl and R1) 1 - in - 10 - year acute 1 - in - 10 - year

chronic 30 - year

mean 1 - in - 10 -

year acute 1 - in - 10 - year

chronic 30 - year

mean Surface water (PRZM/EXAMS) Cherry/MI cherry **6.69** (25.89) 4 **6.69**

(17.84) 4 **6.69**

(10.19) 4 **5.59** 0.42 0.26 Surface water (PRZM/EXAMS) Small fruit (vine

climbing, except fuzzy kiwifruit, 13 - 07F)/NY grape **6.69** (23.12) 4 **6.69**

(15.34) 4 **6.69**

(9.57) 4 4.22 0.38 **0.27** Surface water (Provisional Cranberry Model) Cranberry/Provisional

Cranberry Model 4.24 3.75 -- 3.81 5 **1.36** 5

-- Groundwater (SCIGROW) All proposed uses 3.6 x 10 - 3 < 3.6 x 10 - 3 < 3.6 x 10 - 3 3.6 x 10 - 3 < 3.6 x 10 - 3 < 3.6 x 10 - 3 1 Bolded values are the recommended EDWCs by EFED. 2 A default PCA of 0.87 was applied. 3 Maximum of 2 applications of 0.3 lb ai/A for all proposed uses. 4 EDWC (shown in parentheses ) exceeds the solubility limit of acequinocyl (6.69 μg/L at 20°C); therefore, the recommended EDWC is 6.69 ppb. 5 Based on a one - year simulation; 1 - 10 - year calculation is not applicable. Since the surface water EDWCs are higher than the groundwater ED WC, HED selected the surface water value for use in the chronic dietary assessment. The EDWC derived via Approach #1 represents the upper - bound value (6.69 ppb) while that derived via Approach #2 represents the lower - bound value (1.36 ppb). The 6.69 ppb value was used in this dietary assessment as this value assures a conservative assessment. **4.4 Dietary Exposure Analyses**  An acute dietary

assessment was not conducted for acequinocyl because an endpoint of concern attributable to a single dose was not identified; therefore, an aRfD was not established and an acute dietary

assessment is not necessary . A cancer dietary assessment was not conducted because acequinocyl was classified as not likel y to be carcinogenic to humans.Acequinocyl Human - Health Risk Assessment D 38 9519

Page 22 of 35 An acequinocyl chronic dietary exposure assessment was conducted using the DEEM - FCID TM , Version 2.03 , which incorporates consumption data from USDA’s CSFII, 1994 - 1996 and 1998. The 1994 - 96, 98 data are based on the reported consumption of more than 20,000 individuals over two no n - consecutive survey day s. Foods “as consumed” ( i.e. , apple pie) are linked to EPA defined food commodities ( i. e., apples, peeled fruit - cooked; fresh or N/S; baked; or wheat flour

- cooked; fresh or N/S, baked) using publicl y available recipe translatio n files developed jointly by USDA/ARS and EPA. For chronic exposure assessment, consumption data are averaged for the entire U.S. population and within population subgroups. Based on analysis of the 1994 - 96, 98 CSFII consumption data, which took into acc ount dietary patterns and survey

respondents, HED concluded that it is most appropriate to report risk for the following population subgroups: the general U.S. population, all infants (<1 ye ar old), children 1 - 2, children 3 - 5, children 6 - 12, yo uth 13 - 19, a dults 20 - 49, females 13 - 49, and adults 50+ years old. For chronic dietary

exposure assessment, an estimate of the residue level in each food or food form ( i. e., orange or orange juice) on the food commodity residue list is multiplied by the average dail y consumption estimate for that food/food form to produce a residue intake estimate. The resulting residue intake estimate for each food/food form is summed with the residue intake estimates for all other food/food forms on the commodity residue list to arrive at the total average estimated exposure. Exposure is expressed in mg/kg body weight/day and as a percent of the cPAD. This procedure is performed for each population subgroup. **4.4.1 Chronic Dietary Exposure Analysis**  The DEEM - FCID TM analy sis estimat es the dietary exposure of the U.S. population and various population subgroups. The chronic dietary exposure assessment (using tolerance level residues and 100% CT information for all registered and proposed uses) was conducted for the general U.S. popul ation and various population subgroups. DEEM  ver. 7.81 default processing factors were used with the exception of those for grape juice and raisins. As residues were reduced in both grape juice (<0.02x) and raisin (0.15x), separate tolerances are not re quired for these commodities. The DEEM  ver. 7.81 default processing factors for juice and raisin were set to 1 as concentration was shown not to occur (Memo, S. L ev y, 05 - SEP - 2007; DP#: 342805). Drinking water was incorporated directly into the dietary

assessment using the chronic concentration for surface water generated b y the PRZM/EXAMS model. The highest chronic surface water value (i.e., most conservative) of 6.69 ppb was used for this asses sment. This assessment concludes that the chronic dietary exposure estimates are not of concern to HED for the general U.S. population ( 13 % cPAD) and all population subgroups. The most highl y exposed population subgroup is children 1 - 2 years old at 5 5% of the cPAD. The use of anticipated residues ( ARs ) , empirical processing factors, and %CT data would refine further HED’s exposure and risk estimates; however, refinement is not needed at this time. **Table 4.4.1.1. Summ ary of Dietary (Food + Drinking**  **Water) Exposure and Risk for Acequinocyl. Population Subgroup**  **Chronic Dietary 1**  **Dietary Exposure (m**  **g/kg/day) % cPAD**  U.S. Population (total) 0.003627 13 All Infants (<1 year old) 0.006513 24 **Children 1 -**  **2 years old 0.014761**  **55** Children 3 - 5 years old 0.010370 38 Children 6 - 12 years old 0.005172 19Acequinocyl Human - Health Risk Assessment D 38 9519

Page 23 of 35 **Table 4.4.1.1. Summ ary of Dietary (Food + Drinking**  **Water) Exposure and Risk for Acequinocyl. Population Subgroup**  **Chronic Dietary 1**  **Dietary Exposure (m**  **g/kg/day) % cPAD**  Youth 13 - 19 years old 0.002825 11 Adults 20 - 49 years old 0.002525 9.4 Adults 50+ years old 0.002473 9.2 Females 13 - 49 years old 0.002563 9.5 1 Chronic dietary POD of 0.027 mg/kg/day applies to the general U.S. population and all population subgroups. The values for the highest exposed population are bolded. **4.5 Residential/Non**  **- Occupational Exposure Pathway**  **4.5.1 Short**  **- term**  **Residential Handler Risk** Acequinocyl is currentl y registered for use on landscape ornamentals in and around residences, businesses, public property , schools, interiorscapes, and other non - production areas b y commercial applicators and homeowners. Residential handler exposure from applying acequinocyl to trees and ornamentals with handheld equipment was assessed in June 2010 (A. Nowotarski, D369099). All MOEs were >100 and are not of concern to HED (see Table 4.5.1.1) . **Table 4**  **. 5**  **.1 .1**  **. Summary of Residential Handler Exposure and Risk.**

**Scenario Residential Handler Dose**  **(m g/k** **g/day) Residential Handler MOE**  Mixer/Loader/Applicator

– Liquid Formulation with Low - Pressure Handwand Dermal Baseline: 0.005 Inhalation Baseline: 2.3E - 07 Dermal Baseline: 40,000 Inhalation Baseline: 2.6E+08 Mixer/Loader/Applicator

– Liquid Formulation with Hose - End Sprayer (ORETF -- fruit trees

and ornamentals) Dermal Baseline: 0.07 Inhalation Baseline: 2.9E - 06 Dermal Baseline: 2,900 Inhalation Baseline: 2.1E+07 **4.5.2 Short**  **- term**  **Residential Post -**  **application Risk** Post - application exposure was not anticipated for the registered residential uses; and therefore, a quantitative post - application assessment was not conducted. **4.5.3 Spray Drift** Spray drift is alway s a potential source of exposure to residents nearby to spraying operations. This is particularly

the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application metho d employed for acequinocyl. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the Agency ’s Spray D rift website for more information at http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical - by - chemical basis, 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, a membership of U.S. pesticide registrants, and isAcequinocyl Human - Health Risk Assessment D 38 9519

Page 24 of 35 developing a policy

on how to appropriatel y apply the data and the AgDRIFT ® computer model to its risk a ssessments for pesticides applied b y 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 with specific products with significant risks associated with drift. **4. 5.4**  **Residential Bystander Post -**  **application Inhalation Exposure** Based on the Agency 's current practices, a quantitative residential b ys tander post - application inhalation exposure assessment was not performed for ac equinocyl at this time. However, volatilization of pesticides may be a potential source of post - application inhalation exposure to individuals nearb y to pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pestici des from its FIFRA SAP in December 2009. The Agency received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may , as appropriate, dev elop policies and procedures, to identify

the need for and, subsequently , the way to incorporate post - application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative post - application inhalation exposure assessment for acequinocyl. **5.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION**  In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and risks from three major s ources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard, or the risks themselves can be aggregated. When aggregating exposure s and risks from various sources, HED considers both the route and duration of exposure. **5.1 Acute Aggregate Risk**  An endpoint of concern was not identified to quantify acute - dietary

risk to the general population or to any population subgroup. Since an acute hazard does not exist , an acute aggregate assessment was not performed. **5.2 Short**  **- Term Aggregate Risk**  Short - term aggregate risk is made up of dietary and non - dietary

sources of exposure. Since acequinocyl has a residential use on ornamentals, adult residential handler exposure is expected. Short - term aggregate risk is made up of average dietary exposures from food and drinking water sources, and dermal and inhalation residential exposures. T he females 13 - 49 ye ars old population is the highest exposed adult population and can be considered protective of the other adult populations groups ; therefore, this population subgroup is shown below in Table 5.2.1, as well as the general U.S. population . Dietary (food and drinking water) exposure is based on a Tier 1 (unrefined) chronic dietary exposure assessment (see Table 4. 4 .1.1 ). Residential exposure estimates are conservative estimates due to the standard assumptions that were built into the calculations. Reside ntial exposure estimates were taken from Table 4.5 . 1 .1 . The s hort - term aggregate risk calculations forAcequinocyl Human - Health Risk Assessment D 38 9519

Page 25 of 35 both the general U.S. population and the females 13 - 49 years old sub - population are shown below in Table 5.2.1 and are not of concern to HED .Acequinocyl Human - Health Risk Assessment D 38 9519

Page 26 of 35 **Table 5.**  **2.1. Short**  **- Term** **Aggregate Risk Calculations .**  Population Dietary MOE 1 Residential Dermal MOE 2 Residential Inhalation MOE 2 Aggregate

MOE 3 U.S. Population 17 ,000 2,900 21,000,000 2, 5 00 Females 13 - 49 years old 2 3,000 2,900 21,000,000 2, 6 00 1 Dietary MOE = short - term oral NOAEL (60 mg/kg/day)  chronic dietary exposure . 2 Residential MOEs are from Table 4.5. 1 .1. The “liquid with hose - end sprayer handler” scenario was used as the MOEs for this scenario are lower (i.e., more conservative) than the “liquid with low - pressure handwand handler” scenario. 3 Aggregate MOE (dietary and residential) = 1  ((1  MOE dietary )+(1  MOE dermal)+(1  MOE inhalat io n); LOC = 100 . **5 .3**  **Intermediate -**  **Term Aggregate Risk** Intermediate - term aggregate risk was not calculated since the use pattern is not expected to result in residential handler or post - appli cation exposure of more than 30 - day duration. **5 .4**  **Long -**  **Term Aggregate Risk** Chronic (long - term) aggregate risk is made up only of dietary

sources; therefore, the chronic exposure estimates provided in the chronic dietary exposure anal ys is (see Table 4.4.1.1) represents chronic aggregate exposure. **5 .5**  **Cancer Risk** Aggregate cancer risk was not calculated because acequinocyl is not considered to be a carcinogen. **6.0 CUMULATIVE RISK**  Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common m echanism of toxicity , EPA has not made a common mechanism of toxicity finding as to acequinocyl and any

other substances and acequinocyl does not appear to produce a toxic metabolite produced b y other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that acequinocyl has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of su ch chemicals, see the policy statements released by

EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/. **7.0 OCCUPATIONAL EXPOSURE AND RISK ASSESSMENT**  The proposed uses are on agricultural crops; therefore, there is the potential for occupational handler and post - application exposure. Please refer to the following document for detailed considerations of the material summarized in this section:

 Acequino cyl: Occupational and Residential Exposure/Risk Assessment for Proposed Use on Succulent soy bean; Low growing berry subgroup 13 - 07G; Small fruit vine climbing (except fuzzy kiwifruit, subgroup 13 - 07F); Succulent bean; Cowpea forage; Caneberry (subgroup 13 - 07A); Melon (subgroup 9A); Cucumber (greenhouse and field), and Cherry. K. Lowe, 30 -NOV - 2011; D 389991.Acequinocyl Human - Health Risk Assessment D 38 9519

Page 27 of 35 **7.1 Short**  **- and Intermediate**  **- term Occupational Handler Risk**  Based on the anticipated use patterns and current labeling, typ es of equipment and techniq ues that can potentially

be used, occupational handler exposure is expected from the proposed uses. The quantitative exposure/risk assessment developed for occupational handlers is based on the following scenarios: 1) Mixing/loading liquids in support o f groundboom operations, 2) Applicators using open - cab groundboom equipment, 3) Mixing/loading/appl yi ng liquids via backpack sprayers, 4) Mixing/loading/appl yi ng liquids via mechanically - pressurized handgun, and 5) Mixing/loading/appl yi ng liquids via manuall y pressurized handwand. For pesticide handlers, HED presents estimates of dermal exposure for “baseline” (i.e., workers wearing a single layer of work clothing consisting of a long - sleeved shirt, long pants, shoes plus socks , and no protective gloves), as well as for “baseline” and the use of protective gloves or other PPE, as might be necessary . The acequinocyl product labels direct mixers, loaders, applicators , and other handlers to wear long - sleeved shirt and long pants, c hemical - resistant gloves, and shoes plus socks. It is the policy

of HED to use the best available data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical - specific data, include the PHED ( Versi on 1.1 ) , the A HETF database, the O RETF database, or other registrant - submitted occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended f or use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (http://www.epa.gov/opp00001/science/handler - exposure - table.pdf) , which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at http://www.epa.gov/pesticides/s cience/handler - exposure data.html . Ty pically , HED completes short - and intermediate - term assessments for occupational scenarios in all cases because these kinds of exposures are likely and acceptable use/usage data are not available to justify

deleting intermediate - term scenarios. Based on use data and label instructions, HED believes that occupational exposures may occur over a single day

or up to weeks at a time for man y of the use - patterns and that intermittent exposure over several weeks may also occur. Some applicators may appl y these products over a period of weeks, because they are commercial applicators who are completing multiple pesticide applications for multiple clients. L ong - term exposures are not expected; therefore, a long - term assessment was not conducted. Table 7 .1.1 pr ovides a summary of the estimated exposures and risks to occupational pesticide handlers. An MOE ≥100 is adequate to protect occupational pesticide handlers. Since all the estimated MOEs are >100 with baseline protection, the proposed u ses are not of con cern for HED.Acequinocyl Human - Health Risk Assessment D 38 9519

Page 28 of 35 **Table 7**  **.1.1. Short -**  **/Intermediate -**  **Term Occupational Exposure and Risk Esti mates for Acequinocyl (with baseline protection).**  Exposure Scenario Crop or Target Application Rate 2 Area Treated or

Amount Handled Daily3 Unit Exposure (mg/lb ai) 1 Dose (mg/kg/day) 4 Short - and Intermediate - term MOEs 5 Baseline 6 Dermal Baseline 6

Inhalation Baseline

Dermal Baseline

Inhalation Baseline

Dermal Baseline

Inhalation **Mi xer** **/Loader** Mixing/Loading Liquids for Groundboom Applications soybeans 0.3 lb ai/A 200

acres 0.22 0.000219 0.19 0.00019 1,100 ST: 320,000 IT: 85,000 small fruit and berry, succulent bean, cowpea forage, melon, cucumber (field) 0.3 lb ai/A 80

acres 0.22 0.000219 0.075 0.000075 2,700 ST: 800,000 IT: 210,000 Mixing/Loading Liquids for Airblast Applications cherries 0.3 lb ai/A 40

acres 0.22 0.000219 0.038 0.000038 5,300 ST: 1,600,000 IT: 430,000 **Applicator** Applying Sprays via Groundboom Equipment soybeans 0.3 lb ai/A 200

acres 0.0786 0.00034 0.067 0.00029 3,000 ST: 210,000 IT: 55,000 small fruit and berry, succulent bean, cowpea forage, melon, cucumber (field) 0.3 lb ai/A 80

acres 0.0786 0.00034 0.027 0.00012 7,400 ST: 510,000 IT: 140,000 Applying Sprays via Airblast Equipment cherries 0.3 lb ai/A 40

acres 1.77 0.00471 0.3 0.00081 660 ST: 74,000 IT: 20,000 **Mi xer/Loader/Applicator**  Mixing/Loading/Applying Liquids with Backpack Sprayer Greenhouse cucumbers 0.01 lb ai/gallon 40 gallons 13.2 0.14 0.075 0.0008 2,700 ST: 75,000 IT: 20,000 Mixing/Loading/Applying Liquids with Manually pressurized Handwand 40 gallons 100 0.03 0.57 0.00017 350 ST: 350,000 IT: 93,000 Mixing/Loading/Applying Liquids with Mechanically pressurized Handgun Sprayer 1000 gallons 3.5 0.12 0.5 0.017 400 ST: 3,500 IT: 930 1. Unit Exposures are taken from “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (September 26, 2011) . 2. Applic. Rate. = Maximum rate listed on proposed Kanemite label (Reg. No. 66330 - 38). 3. Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; ExpoSAC SOP No. 9.1. Revised Sept ember 25, 2001. 4. Dose (mg/kg/day) = Unit Exposure (mg/lb ai) * Application Rate * Area treated or Amount ha ndled  Body Weight ( **7** 0 kg). 5. MOE = NOAEL  Dose. NOAEL = 200 (dermal), 60 (short - term inhalation), or 16 (intermediate - term inhalation) mg/kg bw/day. 6. Baseline = Long - sleeve shirt, long pants, and no gloves (dermal); no respirator (inhalation).Acequinocyl Human - Health Risk Assessment D 38 9519

Page 29 of 35 **7.2 Short -**  **and Intermediate -**  **term Occupational Post -**  **application Risk** Dermal HED expects that post - application exposure will occur since acequinocyl is applied post emergence as a foliar spray . Post - application exposure is expected to be s hort - and intermediate term based on information provided on proposed labels (e.g., maximum of two spray s per season at a rate of 0.3 lb ai/A). The POD for the dermal route of exposure is the same for short - and intermediate - term exposure durations, so the risk estimate is protective of both durations of exposure. It is not anticipated that there would be long - term exposure from the greenhouse cucumber use since the label recommends that the proposed product not be used in successive applications to avoid resistance issues. The following inputs and assumptions were used in the post - application exposure calculations:

 Exposure Duration: 8 hours per day  Body Weight: 70 kg  Dermal TCs from the Science Advisory Council for Exposure (ExpoSAC) Policy Number 3.  Chemical - specific DFR data o Chry santhemums in greenhouses (MRID 454286 - 19) o Apples (MRID 456516 - 11) It is the policy

of HED to use the best availab le data to assess post - application exposure. Sources of generic post - application data, used as surrogate data in the absence of chemical specific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting post - application exposure that are used in this assessment, known as “transfer coefficients , ” are presented in the “ExpoSAC Policy 3” (http://www.epa.gov/pesticides/scienc e/exposac_policy 3.pdf), which, along with additional information about the ARTF data, can be found at http://www.epa.gov/pesticides/science/post app - exposure - data.html. Chemical - specific DFR data were available for acequinocyl; however, the data were not for the currentl y proposed crops. Since DFR data are not available for the specific crops currentl y proposed for acequinocyl, the available data were used as surrogates. Based on a review of the available data, it was decided that the DFR data for chry santhemums in greenhouses would be used as a surrogate for cucumbers in greenhouses, and the DFR data for apples would be used for all other proposed field crops. All agricultural crop scenarios resulted in MOEs greater than 100 on day 0 and are not of concern. Table 7 .2. 1 presents the risk estimates for all crops for the highest transfer coefficient associated with that crop; this represents the activities with the high est estimated risk.Acequinocyl Human - Health Risk Assessment D 38 9519

Page 30 of 35 **Table 7**  **.2. 1**  **: Derm al Post**  **- application Exposure and Risk Using Chemical**  **- Specific DFR Data.**  **Crop Group Proposed Crop**  **Highest Transfer Coefficient for Crop (cm**  **2 /hr)**  **and Associated Activity Days after**  **Treat me**  **nt Study** 

**Test Site**  **Che mi**  **cal**  

** specific** **DFR 1**  **(ug/cm 2**  **) Dermal** 

**Dose 2**  **(m g/k** **g/day) MOE**  **3** Field/row crop, low/medium Succulent

soybean, succulent bean, cowpea forage 1,900

(irrigation; hand set) 0 CA 0.217 0.047 4,200 NY 0.613 0.130 1,500 WA 0.435 0.094 2,100 Berry, low Low growing

berries subgroup 13 - 07G 1,900

(irrigation; hand set) 0 CA 0.217 0.047 4,200 NY 0.613 0.130 1,500 WA 0.435 0.094 2,100 Vine trellis Small fruit,

subgroup 13 - 07F, Caneberry crop subgroup 13 - 07A 19,300

(girdling, turning) 0 CA 0.217 0.480 420 NY 0.613 1.4 150 WA 0.435 0.960 210 Vegetable, cucurbit Melon subgroup

9A, Cucumber (field) 1,900

(irrigation; hand set) 0 CA 0.217 0.047 4,200 NY 0.613 0.130 1,500 WA 0.435 0.094 2,100 Vegetable, greenhouse Cucumber

(greenhouse) 1,200

(Hand harvesting, Pinching, Pollination, Hand pruning, Scouting, Turning, Tying/Training, Hand weeding, Propagating) 0 CA 0.617 0.085 2,400 Tree, “fruit,” deciduous Cherry 3,600 (thinning fruit) 0 CA 0.217 0.089 2,200 NY 0.613 0.250 790 WA 0.435 0.180 1,100 1 Chemical - specific DFR = measured chrysanthemum DFR data for greenhouse cucumbers and predicted apple DFR data for all other crops. Application rate in studies = proposed application rate; therefore, no adjustment of the DFR data was necessary. 2 Dermal Dose = [DFR (ug/cm 2 ) x TC (cm2/hr) x 0.001 mg/ug x 8 hrs/day]  body weight (70 kg). 3 MOE = NOAEL (200 mg/kg/day)/ Dermal Dose (mg/kg/day). Inhalation Based on the Agency 's current practices, a quantitative occupational post - application inhal ation exposure assessment was not performed for acequinocyl at this time. However, there are multiple potential sources of post - application inhalation exposure to individuals performing post application activities in previously treated areas. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on issues related to volatilization of pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report as well as available post - application inhalation exposure data generated b y the A gricultural Reentry Task Force and may , as appropriate, develop policies and procedures, to identify the need for and, subsequently , the way to incorporate occupational post - application inhalation exposure into the Agency's risk assessments. If new polici es or procedures are put into place, the Agency may revisit the need for a quantitative occupational post - application inhalation exposure assessment for acequinocyl. REI Acequinocyl is classified in Toxicity Category I II for acute dermal and acute inhal ation. It is classified in Toxicity

Category IV for primary

eye irritation and primary skin irritation and it isAcequinocyl Human - Health Risk Assessment D 38 9519

Page 31 of 35 not a dermal sensitizer. Therefore, the WPS interim REI of 12 hours is adequate to protect agricultural workers from post - application exposur es to acequinocyl. The proposed label lists a REIof 12 hours. **8.0 RESIDUE CHEMISTRY AND TOXICOLOGY DEFICIENCIES**  **8.1 Residue Chemistry**

 Revised Section F.  Revised Section B. **8.2 Toxicology**

 An Immunotoxicity

Study .  Acute and Subchronic Neurotoxicity Stud ies .  A 28 - Day

Inhalation Study . **8.3 Occupational and Residential Exposure** 

 None.

c c: S. Levy (RAB1) ; A. Dunbar (RAB1) ; K. Lowe (RAB1) RDI : RAB1 Branch ( 23 -NOV - 201 1 ); RAB1 Chemists ( 09 -NOV - 201 1 ) S. Levy: S10953 : PY1:703 - 3 05 - 0783 ; 7509P:RAB1Acequinocyl Human - Health Risk Assessment D 38 9519

Page 32 of 35 **APPENDIX :**  **Toxicity Profile Tables and Metabolites .**  **Table A -**  **1. Acute Toxicity of Acequinocyl.**  Guideline No. Study T ype MRID #(s) Results Toxicity Category 870.1100 (81 - 1) Ac ute Oral (rat) 45435011 LD 50 >5000 mg/kg IV 870.1200 (81 - 2) Ac ute Dermal 45435012 LD 50 >2000 mg/kg III 870.1300 (81 - 3) Ac ute Inhalation 45435013 LC 50 >0.84 mg/L III 870.2400 (81 - 4) Primary Eye Irritation 45435014 Not an eye irritant IV 870.2500 (81 - 5 ) Primary Skin Irritation 45435015 Not a dermal irritant IV 87.2600 (81 - 6) Dermal Sensitization 45435016 Not a dermal sensitizer N/A **Table A -**  **2. Toxicity Profile for Acequinocyl**  **. Guideline No.;**  **Study Type MRID (year); Doses; Classification**  **Results** 870.3100 90 - Day Oral Toxicity Rodents - MOUSE 45673701 (1995); 0, 100, 500, 1000 ppm M: 0, 16, 81, 151 mg/kg/day F: 0, 21, 100, 231 mg/kg/day Acceptable/Guideline NOAEL (M/F) = 16/21 mg/kg/day; LOAEL (M/F) = 81/100 mg/kg/day based on hepatocyte vacuolizat ion .

870.3100 90 - Day Oral Toxicity Rodents - RAT 45531904 (1998); 0, 100, 400, 1600, 3200 ppm; M: , 7.6, 30.4, 119.5, 252.7 mg/kg/day F: 0, 8.3, 32.2, 129.2, 286.0 mg/kg/day Acceptable/Guideline NOAEL (M/F) = 30.4/32.2 mg/kg/day; LOAEL (M/F) = 119.5/129.2 mg/kg/day based on increased prothrombin times in males and increased activated partial thromboplastin times in both sexes . 870.3150 90 - Day Oral Toxicity Nonrodents - DOG 45531905 (1995); 0, 40, 160, 640, 1000 mg/kg/day Acceptable/Guideline NOAEL (M/F) = 40/40 mg/kg/day; LOAEL (M/F) = 160/160 mg/kg/day based on decreased body - weight gains and reduced food efficiencies in males and for female beagle dogs based on increased platelet counts . 870.3200 28 - Day Dermal Toxicity RAT 45531906 (1999); 0, 40, 200, 1000 mg/kg/day Acceptable/Guideline Systemic NOAEL = 200 mg/kg/day; LOAEL = 1000 mg/kg/day based on increased clotting factor times (increased prothrombin time, increased activated partial prothromboplastin time, increased fibrinogen levels). Dermal NOAEL = 1000 mg/kg/day; LOAEL = not established . 870.3700a Prenatal Developmental in Rodents - RAT 45531908, 45651706 (1995); 0, 50, 150, 500, 750 mg/kg/day Acceptable/Guideline Maternal NOAEL = 150 mg/kg/day; LOAEL = 500 mg/kg/day based on signs of internal hemorrhage and increased incidence of clinical signs (pale eyes, piloerection, red vaginal discharge) . Developmental NOAEL = 500 mg/kg/day; LOAEL = 750 mg/kg/day based on increased resorptions .Acequinocyl Human - Health Risk Assessment D 38 9519

Page 33 of 35 **Table A -**  **2. Toxicity Profile for Acequinocyl**  **. Guideline No.;**  **Study Type MRID (year); Doses; Classification**  **Results** 870.3700b Prenatal Developmental in Nonrodents - RABBIT 45531907, 45651705 (1995); 0, 30, 60, 120 mg/kg/day Acceptable/Guideline Maternal NOAEL = 60 mg/kg/day; LOAEL

= 120 mg/kg/day based on treatment - related clinical signs leading to premature sacrifice (hematuria, reduced fecal output, body weight loss , and reduced food consumption) and gross necropsy findings (pale lungs and liver, hemorrhaging uterus, fluid in the ce cum, fur in the stomach, blood stained vaginal opening, blood - stained urinary bladder contents/urine, and hair loss) . Developmental NOAEL = 60 mg/kg/day; LOAEL = 120 mg/kg/day based upon increased number of complete resorptions . 870.3800 2 - Generation Reproduction and Fertility - RAT 45531909 (1997); 0, 100, 800, 1500 ppm; M: 0, 7.3, 58.9, 111.2 mg/kg/day F: 0, 8.7, 69.2, 133.5 mg/kg/day Acceptable/Guideline Parental NOAEL (M/F): 111.2/ 133.5 mg/kg/day; LOAEL (M/F) = not established Offspring NOAEL (M/F): 7.3 - 8.2/8.7 mg/kg/day; LOAEL (M/F) = 58.9/69.2 based on hemorrhagic effects, swollen body parts, protruding eyes, clinical signs, delays in pupil development and increased mortality post weaning . Reproductive NOAEL (M/F): 124/13 6 mg/kg/day; LOAEL (M/F) = not established . 870.4100b Chronic Toxicity - DOG 45531910 (1996); 0, 5, 20, 80, 320 mg/kg/day Acceptable/Guideline NOAEL (M/F) = 80/80 mg/kg/day . LOAEL (M/F) = 320/320 mg/kg/day based on premature sacrifice (inappetence, body weight loss) . 870.4300 Chronic/ Carcinogenicity MOUSE 45531911 (1994); 0, 20, 50, 150, 500 ppm ; M: 0, 2.7, 7.0, 20.3, 66.0 mg/kg/day F: 0, 3.5, 8.7, 26.3, 86.00 mg/kg/day Acceptable/Guideline NOAEL (M/F) = 2.7/3.5 mg/kg/day . LOAEL (M/F) = 7.0/8.7 mg/kg/day based on clinical chemistry and microscopic non neoplastic lesions (brown pigmented cells and perivascular inflammatory cells in liver) . 870.4300 Chronic/ Carcinogenicity - RAT 45531912 (1997); 0, 50, 200, 800 or 1600 ppm; M: 0, 2.25, 9.02, 36.41, 74.00 mg/kg/day F: 0, 2.92, 11.61, 46.2, 93.56 mg/kg/day Acceptable/Guideline NOAEL (M/F) = 2.25/46.20 mg/kg/day LOAEL (M/F) = 9.02/93.56 mg/kg/day based on enlarged eyeballs in male an d female rats (coagulopathy). 870.5100 Gene Mutation 45435101 (1998); 19.5, 39.1, 78.1, 156, 313, 625, 1250, 2500 or 5000 μg/plate in the presence and absence of mammalian metabolic activation (S9 - mix) and additionally at 9.77 μg/plate without S9 - mi x. Acceptable/Guideline There was no evidence of induced mutant colonies over background .

870.5300 Gene Mutation 45435102 (1998); 5 - 7 doses ranging from 10 - 320 μg/mL Acceptable/Guideline There was no clear evidence of biologically significant induction of mutant colonies over background .Acequinocyl Human - Health Risk Assessment D 38 9519

Page 34 of 35 **Table A -**  **2. Toxicity Profile for Acequinocyl**  **. Guideline No.;**  **Study Type MRID (year); Doses; Classification**  **Results** 870.5375 Chromosome Aberration 45435103 (1998); 0, 150, 300, 600, or 1200 μg/mL for 24 or 48 hours without metabolic activation (S9 - mix) and to concentrations of 0, 481, 963, 1925 or 3850 μg/mL (highest concentration is equivalent to 10mM) for 6 hours with S9 - mi x. Acceptable/Guideline There was no evidence of chromosome aberrations induced over background .

870.5395 Mammalian Erythrocyte Micronucleus Test in M OUSE 45435104 (1993); 0, 1250, 2500, or 5000 mg/kg body weight Acceptable/Guideline There was no statistically significant increase in the frequency of micronucleated polychromatic erythrocytes in mouse bone marrow at any dose or harvest time . 870.7485 Metabolism - RA T 45435105, 455319 13 (1997); single oral doses of 10 or 500 mg/kg (phenyl label) or 10 mg/kg (dodecyl label), and 14 - day repeated 10 mg/kg dose (phenyl label). Acceptable/Guideline Acequinocyl exhibits marginal absorption, relatively rapid and complete excretion primaril y via the bile and feces, and undergoes nearly complete metabolism to hydrolysis products and a glucuronide conjugate. There was no evidence for selective tissue accumulation or sequestration of 2023 (acequinocyl) or its metabolites in rats . 870.7600 Dermal Penetration - RAT 45435106(2000); 0, 0.001, 0.01, 0.1, 1.0 mg/cm2 Acceptable/Guideline Percent of dose absorbed decreased with exposure concentration indicating that saturation of absorption at/or about the high dose. Absorption at 168 hours was 12.23%, 19.75%, and 14.77% for the 0.1, 0.01 , and 0.001 mg/cm2 dose groups, respectively . **Table A**  **- 3. Structures of Acequinocyl and Its**  **Metabolites .**  **Comm on**  **Nam e/Code**  **Chemical Name Chemical Structure**  Acequinocyl 2 - (acetyloxy) - 3 - dodecyl - 1,4 - naphthalenedione

Acequinocyl - OH (Metabolite R1) 2 - dodecyl - 3 - hydroxy - 1,4 - naphthalenedione

AKM - 18 2 - (1,2 - dioxotetradecyl) - benzoic acid O

O C H 2 ( C H 2 ) 1 0 C H 3 O C O C H 3 O

O C H 2 ( C H 2 ) 1 0 C H 3 O H O

O O O H ( C H 2 ) 1 1 C H 3Acequinocyl Human - Health Risk Assessment D 38 9519

Page 35 of 35 **Table A**  **- 3. Structures of Acequinocyl and Its**  **Metabolites .**  **Comm on**  **Nam e/Code**  **Chemical Name Chemical Structure** 

AKM - 15 2 - hydroxy - 3 - hexanoic acid - 1, 4 naphthalenedione

AKM - 14 2 - hydroxy - 3 - butanoic

acid - 1,4 - naphthalenedions O

O O H C O O H

O O C H 2 O H ( C H 2 ) 9 C H 3 C H O H