**EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR**

**PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA**  **Registration Division contact:**  **Tom Harris , 703**  **- 308**  **- 9423**  **TEMPLATE: Syngenta Crop Protection, LLC**  **, P.O. Box 18300, Greensboro, NC 27419**  **- 8300**  **P etition**  **No. ( XXX** **)** EPA has received a pesticide petition **( P**  **etition No.**  **XXX )**  from **Syngenta Crop Protection**  **, LLC.,**  **P.O. Box 18300, Greensboro, NC 27419**  **- 8300**  proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of **cyantraniliprole, 3 -**  **bromo -**  **1 -**  **(3 -**  **chloro -**  **2 -**  **pyridinyl) -** **N -**  **[4 -**  **cyano -**  **2 -**  **methyl -**  **6 -**  **[(methylamino)carbonyl]phenyl] -**  **1H -**  **pyrazole -**  **5 -**  **carboxamide (CAS Reg. No.**  **736994 -**  **63 -**  **1) ,**  **including its metabolites and degradates,** in or on the raw agricultural commodity **corn, field and pop**  **, forage** at **0.04** p arts per million (ppm) ; **corn, field and**  **pop , grain**  at **0.01** ppm; **corn, field and pop**  **, stover** at **0.015** ppm; **corn, sweet, forage** at **0.02** ppm ; **corn, sweet, kernel plus cob with husks removed** at **0.01** ppm; **corn, sweet, stover**  at **0.08** ppm; . EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plant metabolism. **The metabolism of cyantra niliprole is adequately**  **understood to support the proposed tolerances. Studies in lettuce, rice, tomato, and cotton when treated at proposed label rates showed no significant metabolites. The**  **metabolism of cyantraniliprole in plants was similar regardless of the crop or the**  **treatment regime. Cyantraniliprole was the principal residue in most crop fractions at various sampling points up to crop maturity. The overall metabolism of**  **cyantraniliprole in rotated crops (wheat, red beets, lettuce, and soybeans) was consistent with metabolism seen in the primary crops.**  2. Analytical method. **Adequate analytical methodology, high -**  **pressure liquid chromatography with ESI**  **- MS/MS detection, is available for enforcement purposes.**  3. Magnitude of residues. **Field trial s were conducted on**  **field corn, pop corn and**  **sweet corn under OPPTS 860.1500 to support the requested uses of**  **cyantraniliprole .**  **The results of the field trials substantiate cyantraniliprole as the ma** **jor residue in harvested raw agricultural commodities.**2

**These residue trials satisfy the requested tolerance on corn (field, pop and sweet).**

B. Toxicological Profile 1. Acute toxicity. **Based on EPA criteria, technical cyantraniliprole is classified as acute toxicology category IV based on overall resul** **ts from several studies. This compound is considered acute toxicology category IV for acute oral,**  **dermal and inhalation toxicity and eye and skin irritation. Technical cyantraniliprole is not a dermal sensitizer.**  **No evidence of neurotoxicity was observed in studies conducted with**  **cyantraniliprole in rats. The NOAEL in an acute neurotoxicity study was 2000 mg/kg bw and was the highest dose administered in the study.**  2. Genotoxicty. **Cyantraniliprole was evaluated in a battery of in vitro and in vivo gen**  **etic toxicology studies. Negative results were obtained in all studies indicating that cyantraniliprole does not cause genetic damage and, therefore, does**  **not pose a mutagenic hazard.** 3. Reproductive and developmental toxicity. **Based on the results of a two**  **** **generation reproduction study in rats and a developmental toxicity studies in rats and rabbits, cyantraniliprole does not pose a specific concern for effects on**  **reproduction or development.** 4. Subchronic toxicity. **The primary toxicological findin gs in short** **- term,**  **repeated -**  **dose feeding toxicity studies included non -**  **adverse increases in liver weight in rats, mice, and dogs due to a pharmacological response to liver metabolism, an**  **effect on thyroid hormones and associated thyroid gland histopathology in rats, a**  **non -**  **adverse increase in the degree of lipid in adrenal cortical cells in both rats and mice, and changes in body weight, nutritional parameters, clinical pathology and**  **liver histopathology in dogs. Dermal application of cyantraniliprole to rat**  **s for 28 days did not result in any treatment related findings up to and including a maximum dose of 1000 mg/kg**  **bw/day. Cyantraniloprole showed no evidence of immunotoxicity in 28**  **- day feeding studies in**  **rats or mice and no evidence of neurotoxicity in a 9 0**  **- day feeding study in rats.**  **No treatment related clinical signs indicative of potential neurotoxicity were observed in short** **- term and long**  **- term exposure studies in rats, mice, or dogs.**  5. Chronic toxicity. **Based on the results of chronic feeding stud ies in rats and**  **mice, cyantraniliprole is not a carcinogen. The lowest NOAEL following chronic,**3

**long -**  **term feeding is 5.7 mg/kg/day is based on liver enzyme changes, liver histopathology and arteritis in the one**  **- dog study.**  **No treatment related clinical sig ns indicative of potential neurotoxicity were**  **observed in long -**  **term exposure studies in rats, mice, or dogs.** 6. Animal metabolism. **The absorption of 14C -**  **cyantraniliprole in rats was rapid with peak concentrations occurring at 1**  **- 2.5 hours after low or h**  **igh (10 or 150 mg/kg bw) dose administration. Tissue distribution of the absorbed dose was**  **extensive and indicated low potential for accumulation. Excretion was substantially complete by 24**  **- 48 hours after dosing.**  **Following 14 days of dose administration t he 14C residues were readily eliminated**  **from the plasma and tissues and confirmed minimal potential for accumulation. The profile of metabolites in urine and**  **f eces**  **indicated extensive metabolism consistent with that observed for the single dose study.**  7. Metabolite toxicology

. **Cyantraniliprole is considered to be the only molecule of toxicological relevance. Toxicology studies conducted with metabolites**  **support this conclusion.** 8. Endocrine disruption

. **No relevant effects were observed on any endocr ine**  **tissue in short -**  **and long -**  **term studies in rats, mice and dogs to suggest an adverse impact on estrogen or androgen pathways or on steroid biosynthesis. Effects on**  **thyroid hormone homeosta s**  **is were observed in rats following dietary exposure and demonstr**  **ated to be due to increased clearance of thyroid hormone as a result of enzyme induction**  C. Aggregate Exposure 1. Dietary exposure. **Short -**  **term and chronic dietary exposure evaluations were completed for cyantraniliprole using the Dietary Exposure Eval**  **uation Model software with the Food Commodity Intake Database (DEEM** **- FCID, version 3.16).**  **DEEM -**  **FCID software incorporates food consumption data from the National Health and Nutrition Examination Survey)/“What We Eat in America”**  **(NHANES/WWEIA) dietary surve y conducted in 2003**  **- 2008**  **. In addition to all uses**  **of cyantraniliprole (agricultural uses on Brassica (Cole) leafy vegetables (Group 5), bulb vegetables (Group 3**  **- 07), bushberries (Group 13**  **- 07b), citrus fruit (Group 10**  **- 10), cotton, cucurbit vegetables (Group**  **9), fruiting vegetables (Group 8 -**  **10), leafy vegetables (non**  **- Brassica) (Group 4), oilseeds (Group 20), pome fruits (Group 11**  **- 10), stone fruits (Group 12), tree nuts (Group 14), tuberous and corm vegetables**  **(Subgroup 1c); seed treatment uses on sunflowers, and potatoes, this exposure**  **assessment included pending seed treatment uses on oilseed crops and**  **proposed seed treatment uses on corn. Drinking water estimates were incorporated directly**  **into the dietary exposure assessment using the higher of the estimate d drinking**  **water concentrations (EDWCs) for surface and ground water.**4 i. Food. **Acute Exposure. Cyantraniliprole is not considered to be acutely toxic and an acute toxicological endpoint was not selected by the Agency.**  **Chronic Exposure: The cyantran iliprole chronic dietary (food only) risk assessment**  **was performed for all population subgroups with a chronic reference dose of 0.01 mg/kg**  **- bw/day based on an oral study in dogs with a No Observable Adverse Effect**  **Level (NOAEL) of 1.0 mg/kg -**  **bw/day and an u ncertainty factor of 100X. The 100**  **- fold safety factor includes intra**  **- and interspecies variations (100X) and the FQPA**  **safety factor was reduced to 1X (complete toxicological database). For the purpose of the aggregate risk assessment, exposure values wer**  **e expressed in terms of margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure**  **for each population subgroup. In addition, exposure was also expressed as a percent of the reference dose (%RfD). Chronic (food only) exposure to**  **the U.S. population resulted in a MOE of 582 (17.2% of the chronic RfD of 0.01 mg/kg**  **** **bw/day). The most sensitive sub -**  **population was children (1 -**  **2 years old) with a MOE of 232 (43.1% of the chronic RfD). Since the benchmark MOE for this**  **assessment was 10 0 and since the EPA generally has no concern for exposures below**  **100% of the RfD, Syngenta believes that there is a reasonable certainty that no harm will result from dietary (food only) exposure to residues arising from all**  **registered, pending and propose**  **d uses for cyantraniliprole.** ii. Drinking water

. **The Estimated Drinking Water Concentrations (EDWCs) of cyantraniliprole and its degradates were determined using Tier l models, FIRST**  **FQ PA Index Reservoir Screening Tool and SCI**  **- GROW (Screening Concentr**  **ation in Ground Water), to estimate pesticide concentration in ground water and surface**  **water, respectively. All registered and**  **pending uses**  **plus pr oposed uses on corn**  **were assessed. Based on the FIRST modeling, the use in bait stations for fly control p**  **rovided a surface water chronic EDWC of 24.45 parts per billion (ppb). Based on the SCI**  **- GROW modeling, the seed treatment use on potatoes provided a ground**  **water chronic EDWC of 6.33 ppb. Since the surface water EDWC exceeds the ground water EDWC, the su**  **rface water value was used for risk assessment purposes and will be considered protective for any ground water exposure concerns.**  **Chronic Exposure from Drinking Water. The chronic surface water EDWC of 24.45 ppb was input directly into the DEEM** **- FCID so**  **ftware as “water, direct and indirect, all sources” to model the chronic drinking water exposures. Chronic**  **drinking water exposure to the U.S. population resulted in a MOE of 1,953 (5.1% of the cRfD of 0.01 mg/kg**  **- bw/day). Chronic drinking water exposure**  **to the most exposed sub**  **- population (all infants, <1 year old) resulted in a MOE of 758 (13.2% of**  **the cRfD of 0.01 mg/kg -**  **bw/day). Since the Benchmark MOE for this assessment was 100 and since EPA generally has no concern for exposures below 100% of the**  **cRf D, Syngenta believes that there is a reasonable certainty that no harm will result**  **from chronic drinking water exposure to residues arising from all registered,**  **pending and proposed uses for cyantraniliprole.** 2. Non

- dietary exposure

. **Three formulation types of cyantraniliprole are** 5

**currently registered**  **at EPA. They are soluble concentrate formulations containing 1.67 lb a.i./gallon, wettable granulars containing 20% a.i. by weight, and fly bait**  **granules containing 0.5% a.i. by weight. These formulation s may be used on**  **turfgrasses on golf courses, sod farms, and residential lawns, on ornamental landscape plants and as crack, crevice and spot treatments in and around homes.**  **Other than one wettable granule product, all products are labeled as intended for professional use only, however, the EPA has determined that use by homeowners is**  **possible, and prohibition of use by homeowners is not enforceable, therefore, residential handler application scenarios were assessed. Residential (non**  **** **occupational) risk as sessments were also conducted for potential post** **- application**  **exposure to children on treated lawns and in treated homes. Because no dermal endpoint of concern was identified, assessments were limited to**  **inhalation and incidental oral exposures. The resid ential handler exposures include**  **mixer/loader/applicator inhalation exposures to granules, liquids and dry flowables from handheld treatment equipment during application to turf, to ornamentals, or**  **as indoor crack/crevice and spot treatments. The post -**  **app lication exposures on**  **treated turf and indoor areas include oral exposures due to hand -**  **to -**  **mouth and object** **- to**  **- mouth activities and soil ingestion. Negligible**  **post application exposure is**  **expected to fly bait granules as the only residential use site is in door bait stations.**  **Risks due to short -**  **term exposures (1 -** **30 days) were assessed using the Margin of Exposure (MOE) approach. Based on the use pattern of cyantraniliprole,**  **intermediate -**  **term exposures (1 to 6 months) are unlikely and long -**  **term exposures (g**  **reater than six months) are not expected. Therefore, intermediate -**  **term and long**   ** term risks were not assessed.** **Residential handler risks were assessed for cyantraniliprole assuming a one -**  **time application at the maximum rate for each product label for gr**  **anular fly bait; liquid concentrate on turf, on ornamentals and as an indoor crack/crevice and spot**  **treatment; and water dispersible granules on turf and ornamentals. The short -**  **term MOEs ranged from 22,048 (manually** **- pressurized handwand and backpack**  **spray er, water** **- dispersible granule on ornamentals) to 221,122,751 (cup and shaker**  **can, granular fly bait). Since the calculated residential hander exposures were found to be well above the EPA’s level of concern (MOEs>30), there are acceptable**  **residential hand ler risks from applications of granular cyantraniliprole products.**  **Post application incidental oral exposure risks for children due to hand -**  **to -**  **mouth and object** **- to**  **- mouth activities on treated turf and indoor carpeted and hard**  **surfaces were calculated for cyantraniliprole. Post application incidental oral**  **exposure risks for children due to soil ingestion were also calculated. The lowest short** **- term MOE for incidental oral exposure was 496 for hand**  **- to**  **- mo**  **uth exposure from turf. This MOE was calculated usin**  **g the transferable turf residue value from a chemical specific study on cyantraniliprole, adjusted the label application rate of**  **0.313 lb a.i./A. The turf object**

**– to**  **- mouth and soil ingestion MOEs were 16,332 and**  **283,036, respectively. The MOEs for hand**

**– to**  **- mouth exposure on indoor carpet and**  **hard surfaces were 1,170 and 3,510. These values were calculated based on an**6

**application rate of 1 gallon of 0.10% solution per square foot. The MOEs for object** 

**– to**  **- mouth exposure on indoor carpet and hard surfaces were**  **8,793 and 13,190. Since the calculated post** **- application exposures were found to be well above**  **the EPA’s level of concern (MOEs>100), there are acceptable post -**  **application risks to children from applications of cyantraniliprole products.**  D. Cumulative Effects **Cumulative Exposure to Substances with a Common Mechanism of Toxicity. Section 408(b)(2)(D)(v) requires that, when considering whether to establish,**  **modify, or revoke a tolerance, the Agency consider “available information” concerning the cumu**  **lative effects of a particular pesticide’s residues and “other substances that have a common mechanism of toxicity”. The EPA does not have, at**  **this time, available data to determine whether cyantraniliprole has a common mechanism of toxicity with other su**  **bstances or how to include this pesticide in a cumulative risk assessment. For the purposes of this tolerance action, the EPA has**  **not assumed that cyantraniliprole has a common mechanism of toxicity with other substances.**  E. Safety Determination 1

. U.S. population. **The chronic dietary exposure analysis (food plus water) showed that exposure from all registered, pending and proposed cyantraniliprole**  **crop uses result in a MOE of 448 (22.3% of the chronic RfD) for the general U.S. population. Based**  **on the completeness and reliability of the toxicity data supporting these petitions, Since all aggregate MOEs exceed the benchmark MOE**  **of 100, Syngenta believes that there is a reasonable certainty that no harm will occur to the general U.S. population fro**  **m aggregate exposure to residues arising from all registered,**  **pending and proposed cyantraniliprole uses, including anticipated dietary exposure from food, water, and all other types of non**  **- occupational**  **exposures.** 2. Infants and children

. **The chronic d ietary exposure analysis (food plus**  **water) showed that exposure from all registered,**  **pending and proposed cyantraniliprole uses would result in a MOE of 198 (50.5% of the chronic RfD) for**  **the most sensitive population subgroup, children (1 -**  **2 years old). A short** **- term**  **aggregate MOE of 270 (LOC = 100) was determined for children (1 -**  **2 years old). Since all aggregate MOEs exceed the benchmark MOE of 100, Syngenta believes**  **that there is a reasonable certainty that no harm will occur to infants and children from**  **aggregate exposure to residues arising from all registered,**  **pending, and proposed cyantraniliprole uses, including anticipated dietary exposure from food,**  **water and all other types of non -**  **occupational exposures.** F. International Tolerances **A number of international tolerances (or Maximum Residue Levels, MRL's)**  **have been established for cyantraniliprole.**