## Registration of the New Active Ingredient Cyantraniliprole

An Insecticide for Use on Multiple Commodities, Ornamentals, Turfgrass, and in

Commercial or Residential Buildings

Approved by:

# ~**~~**

Date: Steven P. Bradbury, Director

Office of Pesticide ProgramsPage 2 of 18 

### Registration of the New Active Ingredient Cyantraniliprole

Summary of the Regulatory Decision

The Agency is granting an unconditi onal registration under section 3(c)(5 ) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIF RA) of the new active ingredient cyantraniliprole formulated as a technical product and fourteen end- use products. The registered uses for this new insecticide include agricultural crops (bushberry (subgr oup 13-07B), citrus (group 10-10), pome fruit (group 11-10), stone fruit (group 12-12), tree nuts (group 14-12), oilseed (group 20), Brassica, Cole and leafy vegetables (group 5), bulb vegetables (group 3-07) cucurbits (group 9), fruiting vegetables (gr oup 8-10), leafy vegetables (except Brassica) (group 4), and tuberous and corm vegetabl es (subgroup 1C)), ornamentals and turf (ornamental plants, shrubs, trees in and around greenhouses, nurserie s, lath- and shade-houses, and interior plantscapes, landscape and recreational turfgrass (i ncluding golf courses), and sod fa rms), as well as structures and equipment (in and around agri cultural, commercial, and residential st ructures (excluding food/feed handling establishments), and transportation equipment.

Product formulations include liquid, granular, and granul ar bait. Methods of application include broadcast sprays for aerial and ground applications, soil dren ch, chemigation, and seed treatment. Maximum single application rates are 0.4 lb. a.i./A for liquid, granular , or seed treatments. The maximum annual application rate is 0.4 lb. a.i./A/year fo r all application methods.

The Agency’s Reduced Risk Committee approved cyantr aniliprole as a "reduced risk" candidate for the proposed uses. Based on the committee's evaluation of the information provided, the mammalian toxicity and ecotoxicity risk profiles for cyantran iliprole are favorable compared to re gistered alternatives, which include organophosphates, pyrethroids, carbamates and neonicotinoids. The novel mode of action for cyantraniliprole fits in well with resistance management strategies.

The evaluation of cyantraniliprole wa s conducted as a “Global Joint Review ” project. EPA scientists worked in collaboration with their colleague s in the Regulatory Authorities of France, the United Kingdom, Canada, and Australia. In the course of this analysis, the agenci es considered a robust databa se that included over 800 studies. Scientists in each partne ring authority conducted primary revi ews, peer reviewed evaluations conducted by their counterparts and participated in technical committee meetings to coordinate and

harmonize scientific conclusions.

After review and consideration of all of the data pr ovided by the 800+ studies, the determinations made by the multiple scientists involved in the project, and the outcome of the human health and ecological risk assessments, the Agency supports the decision of its Re duced Risk Committee; cyantraniliprole is therefore

classified as a Reduced Risk Pesticide.

Cyantraniliprole is a broad spectrum in secticide, with activity on a wide va riety of target pests. While it is the third compound registered in the Insecticide Resistance Action Committee (IRAC) Mode of Action Classification Group 28, ryanodine recepto r modulators, it has a broader sp ectrum of activity than the other two compounds. It is expected to fit well in IPM programs.Page 3 of 18 

### I. Chemical Information

Chemical Name: cyantraniliprole, 3-bromo-1-(3-chloro-2-pyridinyl)- N -[4-cyano-2-methyl-6- [(methylamino)carbonyl]phenyl]-1 H -pyrazole-5-carboxamide

EPA PC Code: 090098

Chemical Abstracts Servi ce (CAS) Number: 736994-63-1

IRAC MoA Classification: Group 28 - Ryanodine receptor modulators

Mode of Action: Insecticide Re sistance Action Committee (IRAC) Mode of Action Classification Group 28: ryanodine receptor modulators (RyR). The mode of ac tion is through unregulated activation of insect RyR channels leading to internal calcium store depletion and impaired regulation of muscle contraction, causing paralysis and eventual death.

Registrants: E.I. du Pont de Nem ours & Company and Syngenta Crop Protection



### II. Human Health Risk

A summary of the human health eff ects and risk of cyantraniliprole as assessed in the Agency document entitled “Cyantraniliprole. Aggreg ate Human Health Risk Assessment for the Proposed New Uses of the New Active Insecticide, including Ag ricultural 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 Treatm ent Uses on Canola (Rapeseed), Mustard Seed, Sunflowers, and Potatoes; and Residential, Commercial , and Agricultural Uses on Ornamentals, Turfgrass (including Sod Farms and Golf Courses), and Struct ural Buildings (including Indoor Crack/Crevice and Outdoor Broadcast)" is provided below.

A. Summary of Toxicological Effects

Cyantraniliprole is a second-generation ryanodine recep tor (RyR) insecticide belonging to the diamide class of chemistry whose pesticidal mode of action (MOA) is through unregulated activation of insect RyR

channels. This leads to internal calcium store depletion and impaired regulation of muscle contraction, causing paralysis and eventual death of the insect. Mammalian RyR ar e shown to be 350 to >2500 times less sensitive than those of insects. In general, cyantran iliprole administration in mammals produces both adverse and adaptive changes in the liver, thyroid gland, a nd adrenal cortex. With repeated dosing, consistent findings of mild to moderate increases in liver weights across multiple species (rats, mice, dogs) are observed. Dogs appear to be more sensitive than rats and mice; cyantraniliprole produces adverse liver effects (increases in alkalin e phosphatase, decreases in cholesterol, and decreases in albumin) in dogs at

lower dose levels than in rats. In addition, the liver effects in the dog show progressive severity with increased duration of exposure. The available data also show thyroid hormone homeostasis is altered in rats following exposure to cyantranilipro le after 28 or 90 days due to e nhanced metabolism of the thyroid hormones by the liver. However, cyantraniliprole is not a direct thyroid toxicant. Cyantraniliprole is classified as “Not Likely to be Carcinogenic to Humans” based on the ab sence of increased tumor incidence in acceptable/guideline carcinogenicity studies in rats and mice. In addition, there are no genotoxicity,Page 4 of 18 mutagenicity, neurotoxicity, or imm unotoxicity concerns. There are also no developmental or reproductive toxicity concerns. There is no evidence of an adverse effect attributable to a single dose.

B. Food Quality Protection Act Safety Factor (FQPA SF)

EPA has determined that reliable data show the safety of infants and children woul d be adequately protected. EPA believes that the appropriate Food Quality Protecti on Act Safety Factor (FQPA SF) for cyantraniliprole

should be reduced to 1X fo r the following reasons:

• The toxicity database for cyantraniliprole is complete.

• There are no indications in any of the available studies that the nervous system is a target for cyantraniliprole. Effects indicative of neurotoxicity are not seen in the neurotoxicity screening battery at or above the limit dose levels in acute (2,000 mg/kg) and 90-day (1,000 mg/kg) neurotoxicity

studies.

• There is no evidence of susceptibility in developm ental toxicity studies in rats and rabbits. The developmental toxicity study in rats is tested up to the limit dose (1,000 mg/kg/day). In the rabbit developmental toxicity study decrease in fetal body weight is seen at a dose higher than that resulting in maternal effects. In the reproductive toxic ity study, increased incidence of thyroid follicular epithelium hypertrophy/hyperpla sia occurs in fetal 1 (F 1 ) parental animals at a dose lower than that for the parental (P) generation. A clear No-O bserved Adverse Effect Level (NOAEL) (1.4 mg/kg/day) is established for F 1 parental animals, and the Point of Departures (PODs) selected for risk assessment from the dog studies (1 or 3 mg/kg/da y) are protective of the effect (thyroid effect)

seen in the F 1 parental animals. In addition the submitted data support the conclusion that the effects on the thyroid are secondary to effects on the liver.

• The exposure databases are complete or are estim ated based on data that reasonably account for potential exposures. The chronic dietary food e xposure assessment was conservatively based on 100% crop treated (CT) assumptions, average residue levels from field trials, and conservative ground and surface drinking water modeling estimates. New 2012 Residential Standard Operating Procedures (SOPs) are used to assess post-applica tion exposure to children including incidental oral exposure. The residential post-appl ication assessment assumes that maximum application rates are applied and that hand-to-mouth activities occur on the day of application. All of the exposure estimates are based on conservative, health-p rotective assumptions and are not likely to

underestimate risk.

C. Toxicological End Points and Doses Us ed in the Human Heal th Risk Assessment

1. Acute

No acute dietary toxicity endpoint was selected as an effect because no eff ect attributed to a single dose was identified in the mammalian toxicology database.

2. Chronic Dietary (all populations)

EPA established a chronic reference dose (cRfD) a nd a Chronic Population Adjusted Dose (cPAD) for cyantraniliprole of 0.01 mg/kg body wt/day, based on the NOAEL of 1 mg/kg body wt/day from a 1-year oral study in dogs and an FQPA Safe ty Factor of 1X. In this study, e ffects indicative of liver toxicity (increased liver weights and alkalin e phosphatase activity), an d significant decreases in albumin level were

observed at the Lowest Observed Adverse E ffect Level (LOAEL) of 6 mg/kg body wt/day.Page 5 of 18 3. Short- and Intermediate-Term Oral

EPA selected the NOAEL of 3 mg/kg body wt/day from the 90-day oral study in dogs, based on effects observed in the co-critical 28-day an d 90-day toxicity studies in dogs. In the 90-day study, a collection of

treatment-related effects indicative of liver toxicity were obser ved at the LOAEL = 32 mg/kg body wt/day.

The effects included decreases in tota l protein, albumin, and cholesterol in males and females; increases in alkaline phosphatase in males and fema les; increases in alanine aminotransferase in females; and increases in liver weights in males and females. In the co-c ritical 28-day study, decrea ses in body weight, food consumption, food efficiency, and change s in clinical chemistry (increased ALP, decreased cholesterol, and decreased albumin) were observed at the LOAEL = 35 mg/kg body wt/day (l owest dose tested). The level of concern for assessing short- and inte rmediate-term occupational exposure to cyantraniliprole is a margin of exposure (MOE) that is less than 100.

4. Short-Term Dermal

No short-term dermal toxicity endpoint was selected because systemic toxicity was not seen in 28-day dermal toxicity in rats at the limit dose (1,000 mg/ kg/day). There are no concerns for developmental or reproductive toxicity or neurotoxicity.

5. Short-Term Inhalation

EPA selected the NOAEL of 0.1 mg/L from the 28- day inhalation study in rats. A LOAEL was not established because the highest concentration tested (0.1 mg/L) did not demonstrate any adverse effects.

6. Cancer

EPA has classified cyantraniliprole as “Not likely to be Carcinogeni c to Humans” based on data showing

lack of treatment-related increase in tumor incidence in th e rat and mouse carcinogenicity studies. Mutagenic concern was not reported in th e mutagenicity studies.

D. Cumulative Effects

Unlike other pesticides for which EPA has followe d a cumulative risk approach based on a common mechanism of toxicity, EPA has not found cyantranilipro le to share a common mech anism of toxicity with any other substances, and cyantrani liprole does not appear to produce a toxic metabolite produced by other substances. For the purposes of this action, therefore, EPA has assumed that cyantraniliprole does not have a common mechanism of toxicity with other substances.

E. Aggregate Risk Assessment

1. Acute Dietary Risk

An acute aggregate risk assessment ta kes into account acute exposure estimates from dietary consumption of food and drinking water. No adverse e ffect resulting from a single oral exposure was identified and therefore no acute dietary endpoint was selected. Cyantranilip role is not expected to pose an acute risk.Page 6 of 18 2. Chronic dietary risk

EPA has concluded that chronic exposure to cyantran iliprole from food and water will utilize 50% of the cPAD for children 1-2 years old (the population group receiving the grea test exposure) and 22% of the general U.S. population.

3. Short-term risk

Short-term aggregate exposure takes into account short- term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Cyantranilip role is proposed for uses that

could result in short-term residentia l exposure, and the Agency has determined that it is appropriate to aggregate chronic exposure through food and water with short-term residen tial exposures to cyantraniliprole. Residential exposure estimates of a ll possible scenarios are not of conc ern. Short-term inhalation MOEs range from 22,000 to 220,000,000. Furthermore, these calcul ated risk estimates are highly conservative because the inhalation exposure POD is based on an exposure duration of 24 hours per day.

Using the exposure assumptions desc ribed in this unit for short-term exposures, EPA has concluded the combined short-term food, water, and residential expos ures result in aggregate MO Es of 290 for children 1-2 years old (the population group receiving the greatest exposure) and 22,000 for adults. Because EPA’s level of concern for cyantraniliprole is a MOE of 100 or below, these MOEs are not of concern.

4. Intermediate-term risk

Intermediate-term aggregate exposure takes into account intermediate-term residential exposure plus chronic exposure to food and water (considered to be a bac kground exposure level). For adults, intermediate-term exposure is not expected for the re sidential exposure pathway. The inte rmediate-term aggregate risk would be equivalent to the chronic diet ary exposure estimate. For children 1 to <2 years old, the short-term aggregate risk is protective of the intermediate-term duration.

5. Aggregate cancer risk for U.S. population

Based on the lack of evidence of carcinogenicity in two adequate rodent carcinogenicity studies, cyantraniliprole is not expected to pose a cancer risk to humans.

F. Occupational Risk Assessment

1. Handler Exposure and Risk

Occupational handler and post-appli cation exposure may occur by the de rmal and inhalation routes of exposure only. Since there is no dermal hazard from cyantraniliprole, only inhalation exposures were quantitatively assessed. Also, since no acute toxicity effects were found fo r cyantraniliprole, only short- and

intermediate-term inhalation risk estimates were calculated.

a. Agricultural Field Uses

The results of the occupational handler exposure and ri sk assessment indicate that short- and intermediateterm inhalation risks do not exceed EPA’s Level of Concern (LOC) (i.e. an MOE < 30 for short-term exposures and an MOE < 100 for intermediate-term expos ures) at baseline mitigation (no PPE). Since the short- and intermediate-term PODs are the same, th e inhalation MOEs are al so the same, ranging from 1,200 to 3,900,000.Page 7 of 18 EPA has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed cockpits. Therefore, risks to pilo ts are assessed using the e ngineering control (enclosed cockpits) and baseline attire (long-s leeve shirt, long pants, shoes, a nd socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, pilots are not required to wear protective gloves for the duration of the application. Th ere are no risk estimates of c oncern for aerial applicators.

b. Agricultural Seed Treatment Uses

Based on the anticipated use patter ns and current labeling, types of equipment and techniques that can potentially be used, some occupational handler exposur e is expected from the pr oposed seed treatment uses. The quantitative exposure/risk assess ment developed for occupational ha ndlers is based on the following

scenarios: Mixing/loading liquids for pot ato seed piece treatment, Planting potato seed pieces, Mixing/loading liquids for commer cial seed treatment, and Planting treated seed.

The results of the occupational handler exposure and risk assessment indicate that short-term inhalation risk estimates do not exceed EPA's LOC (i.e. an MOE < 30 for short-term exposures) at baseline, without mitigation from PPE. Short-term exposure risk estimates are protective of intermediate-term exposure risk estimates because the throughput (amount of seed treated) is greater th an, or equal to, the throughput of intermediate-term exposure. The calculated inha lation risk estimates do not exceed EPA's LOC for intermediate-term exposures (i.e. an MOE < 100) at ba seline, without mitigation from PPE. The inhalation MOEs range from 370 to 4,000 for primary handlers (treaters) and 2,200 to 190,000 for secondary handlers (planters).

2. Occupational Postapplication Exposure and Risk

An occupational post-application exposure and risk assessment was not conducted because a dermal hazard was not identified for cyantraniliprole.



### III. Environmental Risk

A summary of the environmental fate and ecological effect s and risks of cyantraniliprole as assessed in the Agency document entitled “Environmental Risk Assessment of Proposed New Global Chemical Cyantraniliprole on Bushberries, Citr us, Cotton, Oil Seeds, Pome Fruit, Stone Fruit, Tree Nuts, Vegetables (Bulb, Corm and Tuberous, Cucurbit , Fruiting, Leafy Brassica, and L eafy-Non-Brassica), and Professional Products (Fly Bait, Indoor and Outdoor Insect Control for Public Health Pests Such as Cockroaches, Ants, Flies, Termites, Nuisance Insect Pests, Turfgr ass and Ornamentals, Tree Injection, and Production Greenhouse and Nursery Ornamentals)" is provided below. Additional information and points of clarification

not included in the risk assessment are included in the document, dated January 24, 2014, entitled

“ADDENDUM – EFED Environmental Risk As sessment of Proposed New Global Chemical Cyantraniliprole on Bushberries, Citr us, Cotton, Oil Seeds, Pome Fruit, Stone Fruit, Tree Nuts, Vegetables (Bulb, Corm and Tuberous, Cucurbit , Fruiting, Leafy Brassica, and L eafy-Non-Brassica), and Professional Products (Fly Bait, Indoor and Outdoor Insect Control for Public Health Pests Such as Cockroaches, Ants, Flies, Termites, Nuisance Insect Pests, Turfgr ass and Ornamentals, Tree Injection, and Production Greenhouse and Nursery Ornamentals) .” This addendum includes a revision of the chronic mammalianPage 8 of 18 endpoint, characterizatio n of potential risk concerns to monocots, and presents a comparison of acute honey bee toxicity data for cyantran iliprole and other insecticides.

A. Environmental Fate

Cyantraniliprole is a systemic insect icide. It is soluble at neutral pH and given its low vapor pressure (3.85 x 10-17 mm Hg) and Henry’s Law constants (1.70 x 10- 18 atm*m 3 /mol), is not consider ed volatile and is not likely prone to atmospheric transport. While cyantraniliprole is subject to both abiotic alkaline hydrolysis (half-life = 21 hrs) and photodegrad ation in aqueous (half-life = 8 hrs) and moist soil environments and biotic (aerobic and anaerobi c biotransformation in terrestrial and aqua tic environments, half-lives range from 2 days to 3 months) degradation, the chemical degrad es into a total of 13 degradation products. Of these degradates, eight are major and fi ve are minor. Based on degradate aerobic soil metabolism and mobility studies, six of the eight major degradat es had longer dissip ation half-life (DT 50 ) values (more persistent) and three of the eight degradates were more mobile than the parent cyantraniliprole. According to the Food and Agriculture Organization (FAO) cla ssification system, based on organi c carbon partitioning coefficients, cyantraniliprole is characterized as moderately mobile. Bioconcentration f actor data (BCF value <1 in whole fish) indicate that cyantraniliprole is not likely to bioaccumulate.

Given the uncertainty of the behavior and toxicity of these degradates, their toxicity is assumed to be equivalent to the parent compound, cyantraniliprole. Fo r the aquatic exposure mode ling, a total toxic residue approach (considers the parent compound and eight major degradates including two degradates from terrestrial field studies) was utili zed. For surface water, peak estimated environmental concentrations (EECs) ranged from 0.23 μg/L from cyantraniliprole use on trees using the Oregon Christmas tree scenario to 38 μg/L from cyantraniliprole use on cotton using the No rth Carolina cotton scenario. For pore water, peak EECs ranged from 0.22 μg/L from cyantraniliprole use on trees using the Oregon Chri stmas tree scenario to 37 μg/L from cyantraniliprole use on rapeseed using the North Dakota wheat scenario.

B. Ecological Risk

Ecological risk characterizat ion integrates the results of the exposur e and ecotoxicity data to evaluate the likelihood of adverse ecological effect s. The means of integrating the re sults of exposure and ecotoxicity data is called the risk quotient method. For this me thod, risk quotients (RQs) are calculated by dividing exposure estimates by ecotoxicity values, both acute a nd chronic (RQ = Exposure/Toxicity). RQs are then compared to EPA's levels of concern (LOCs). The LOCs are criteria used by the Agency to indicate potential risk to non-target organisms. The criteria indicate wh ether a pesticide, when used as directed, has the potential to cause adverse effects to non-target organisms. The ecological risk profile is described in detail

below.

Risks to Aquatic Organisms

Fish Cyantraniliprole is classified as “sli ghtly to moderately toxic” to freshwat er fish on an acute exposure basis. A conservative calculation using the peak aquati c EEC (37.97 μg ai/L) and the typical end product LC 50 (2,400 μg ai/L) resulted in an RQ of 0.016. This is well below the acute risk to listed species LOC of 0.05. Consequently, direct acute risks to freshwater fish a nd aquatic-phase amphibians, for which fish serve as surrogates, from the proposed uses of cyan traniliprole are not considered likely.

Risk quotients calculated for chroni c exposures to cyantran iliprole ranged from <0.001 to 0.003 and were all

well below the chronic risk to list ed and non-listed species LOC of 1. Th e risk quotient analysis indicatedPage 9 of 18 that direct chronic effects to freshwater fish are not expected; none of the risk quot ients exceeded the chronic

risk LOC of 1.

Risk quotients could not be calculated for direct acute e ffects to estuarine/marine fish because the toxicity value was non-definitive. In lieu of this, the most se nsitive toxicity va lue can be compared with the peak

EEC. The most sensitive LC 50 (>12,000 μg total ai/L), a lthough non-definitive, is much larger than the peak aquatic EEC of 37.97 μg ai/L. There was precipitate in this toxicity test and measured concentrations were not centrifuged or filtered; therefore, the amount of dissolved cyantranilipro le is uncertain, lending uncertainty to the study’s results. No mortality or sub-lethal effects were observed in any treatment group in the test. Furthermore, the LC 50 would need to be 16 times more sens itive (759 μg ai/L) to even reach the acute risk to listed species LOC of 0.05. Thus, the likelihood of adverse eff ects on estuarine/marine fish from direct acute exposure from th e proposed uses of cyantranil iprole is considered low.

Risk quotients could not be calcula ted for chronic effects to estuar ine/marine fish because only nondefinitive toxicity data we re available. Given that the No Observ ed Adverse Effect Concentration (NOAEC) was a less than value (NOAEC <750 μg ai/L), it is not possible to preclude the possibility of direct chronic risks to estuarine/marine fish. Growth parameters (length and weight) were affected at the lowest concentration tested. Although the absolute value of the NOAEC (750 μg total ai/L) is one order of magnitude higher than the highest 60-d ay aquatic EEC of 37.42 μg ai/L, ri sk concerns cannot be eliminated on this alone. Risk mitigation language is include d on the labels (refer to section IV. E.).

Invertebrates Cyantraniliprole ranged in toxicity from slightly to very highly toxic to freshwater invertebrates on an acute exposure basis. Risk quotients for acute exposures to freshwater invertebrates ranged from 0.011 to 1.9. Most

uses exceeded the acute risk to listed species LOC of 0.05 and some exceeded the acute risk to non-listed species LOC of 0.5.

Risk quotients for chronic exposures to freshwater invertebrates ranged from 0.035 to 5.8 with some uses exceeding the listed and non-listed sp ecies chronic risk LOC of 1.

Cyantraniliprole is moderately to hi ghly toxic to estuarine/marine inve rtebrates on an acute exposure basis. Acute risk quotients for estuarin e/marine invertebrates ranged from <0.001 to 0.073 showing a slight

exceedance of the acute risk to lis ted species LOC of 0.05. Chronic risk quotients ranged from 0.001 to 0.23 (oyster) and < 0.001 to 0.12 (mysid shrimp). No scenar ios exceeded the listed a nd non-listed species chronic risk LOC of 1. Thus, while mortality (direct) of estu arine/marine invertebrates is possible following acute exposure for eight of the proposed us es, the likelihood of (dir ect) adverse effects from chronic exposure is

considered low.

Cyantraniliprole is highly toxic to benthic invertebrates on an acute exposure basis. Acute risk quotients for benthic invertebrates ranged from <0.001 to 0.051 but only one use exceeded the acute risk to listed species LOC of 0.05. Chronic risk quotients ranged from 0.022 to 3.7 with some us es exceeding the listed and nonlisted species chronic risk LOC of 1.

To reduce the potential risk to aquatic invertebrates, risk mitigation langua ge is included on the labels (refer to section IV.D.).

Aquatic Plants Toxicity data for technical-grade cyantraniliprole wa s non-definitive for aquatic vascular and non-vascular plants. Thus, risk quotients were not calculated. Given the lines of evidence, it is unlikely that there will be direct adverse effects to aquatic plants based on exposure from the pr oposed uses of cyantraniliprole.Page 10 of 18 Risks to Terrestrial Organisms

Birds Cyantraniliprole is classified as ‘practically nontoxic’ to birds on an acute oral and sub-acute dietary exposure basis. Since all of the endpoints from the acute oral and sub-acute dietary to xicity studies with birds are non-definitive ( i.e ., they are ‘greater than’ values), they were not used to calculate RQs. Instead, the nondefinitive toxicity values were directly compared to the EECs. The most sensitive TGAI studies were selected (in two cases, there were more sensitive re sults for the typical end-use product (TEP) studies, but these were also non-definitive and the lower toxicity va lue is probably an artifact of the largest dose of product that was given to the bird rath er than the active ingredient itself). In all cases, none of the EECs were larger than the non-definitive toxicity values for the mo st sensitive avian species. No sub-lethal effects were

observed in either the acute oral or sub-acute dietary studies for any of the species tested. Acute effects to

listed and non-listed bird species are not expected.

The chronic dietary-based RQs range from <0.01 to 0.45, and are below the LOC of 1.0. Therefore, the

likelihood of chronic adverse effects for listed and non-listed birds, reptile s, and terrestrial-phase amphibians from exposure to residues from the proposed cyantraniliprole uses is expected to be low.

Mammals Cyantraniliprole is classified as ‘practically nontoxic’ to mammals on an acute oral exposure basis. Nondefinitive toxicity values were directly compared to the EECs. In all cases, none of the EECs were larger than the non-definitive toxicity valu es. Furthermore, no sub-lethal effect s were observed in the acute oral toxicity study. Therefore, acute effects on listed and non-listed mammalian sp ecies are not expected.

There were no LOC exceedances of th e listed and non-listed sp ecies chronic risk LOC (1), except for the following uses/application type s: soil injection/drench fo r hardwood trees (RQ of 1.3) , soil drench for citrus (RQ of 1.2), and drip irrigation applications for cucurbits (RQ of 3.2). These risk quotients were conservatively calculated by estimating th e concentration of cyantraniliprole in the leaf biomass of the plant, where for the screening-level risk assessment the risk quotients above we re calculated assuming 100% of the animal’s diet comes from the treated site ( e.g., citrus leaves). It is important to note that it is unlikely that these use sites make up 100% of a non-target mammalian diet; therefore th e actual potential for risk is low considering the variability of non-target mammalian diets.

Terrestrial Invertebrates Toxicity data for parasitic wasps, beetles, spiders, lacewings, predatory mites, a nd collembola indicated that cyantraniliprole is toxic to some terrestrial invertebrates at very low application rates (48-hr LR 50 = 0.00008 lb ai/A – parasitic wasp), consiste nt with its insecticidal mode of action. Conversely, collembola, which are exposed to cyantraniliprole through direct contact with the soil, were insensitive to applications of cyantraniliprole (EC 50 > 1,200 mg ai/kg-soil. Likewise, earthworm s demonstrated a low toxic effect to cyantraniliprole (EC 50 > 102.6 mg ai/kg-soil – based on the TEP).

While there is some uncertainty in honeybee toxicity data for cyantran iliprole, due to some non-definitive endpoints, it is highly toxic on an acute oral and contact basis; howev er, this compound is generally less toxic to honey bees than organophosphate, pyrethroid, neonicotinoid, an d carbamate insecticides (Table 1). Refined acute oral RQs for adult honeybees using em pirically-based maximum reported concentrations in nectar and pollen were determined as the ratio of cyan traniliprole consumed in pollen/nectar (i.e., dose) to

the acute LD 50 for cyantraniliprole-only TEP (0.116 μ g ai/bee) and ranged from 0.017 to 0.066 and are below

the LOC of 0.4. The LOC of 0.4 was established for acute risks to honeybees. If an RQ is less than LOC, the chemical being assessed does not pose a risk concern to insect pollinators on an acute exposure basis andPage 11 of 18 higher tier studies are not required. Th e registration packet included semi-f ield and field data for honeybees,

which were used to confirm this conclusion. The LOC of 0.4, and framework for assessing risk to pollinators – used in the cyantraniliprole ecological risk asse ssment – is outlined in the Agency’s White Paper for assessing potential risks to polli nators and was evaluated by the FI FRA Scientific Advisory Panel 1

.

Table 1 below is a comparison of the relative hon eybee acute toxicity for cyantraniliprole to organophosphates, carbamates, pyrethroi ds and neonicotinoids, which have similar uses to cyantraniliprole. The table below includes honeybee acute contact and acute oral toxicity ranges for organophosphates, carbamates, pyrethroids, and neonicotinoids, as well as the toxicity values for cyantraniliprole and cyantraniliprole/thiamethoxam TEP. The comparativel y low toxicity of the dua l a.i. product containing cyantraniliprole/thiamethoxam is largely reflective of the toxicity of thiamethoxam, although less toxic than

thiamethoxam alone. This table illustra tes that cyantraniliprole is typica lly less toxic to honeybees compared

to these chemical classes.

Table 1. Comparison of relative honeybee acute toxicity *

Chemical Honeybee acute contact

LC 50 (μg ai/bee) Honeybee acute oral LD 50 (μg ai/bee)

Carbamates 0.1600 to 35 0.094 to 3.01

Neonics 0.024 to <12.5 0.0037 to >10.21 Organophosphates 0.059 to 58.9 0.056 to 0.44 Pyrethroids 0.0015 to 0.52 0.172 to 0.909 Cyantraniliprole 0.55 0.116 Cyantraniliprole/thiamethoxam TEP 0.058 0.0062

* Additional comparisons to individual chemicals are included in the Addendum to the Ecological Risk Assessment.

The semi-field studies indicated tr ansient effects on behavior, foraging activity and mortality. Observations of brood health and colony strength (up to 28 days) suggested no significa nt lethal or sub-lethal adverse effects on larvae or colony strength from cyantran iliprole applications. The field studies provide in situ information about the effects of cy antraniliprole applications to br ood development and longer-term colony

health. If the larvae in a hive are undergoing adverse toxicological effects to a significant degree, a decrease in hive population or other colony-level effects will be seen over time – especially during the overwintering period; which was not observed in the cyantraniliprole studies.

Non-target Terrestrial and Semi-Aquatic Plants Based on the risk quotient analysis, the LOC for risk to listed terrestrial pl ants was not exceeded for monocots or dicots. There is some uncertainty re garding the analysis for monocots because seedling emergence data were available for only one monocot sp ecies. However, available data indicate that onion

was the most sensitive monocot usin g a vegetative vigor study, where it is approximately 2X more sensitive than the available monocot (corn) species data. Theref ore it would be reasonable to expect the seedling emergence endpoint for onion to be lower than the monocot and dicot observed endpoints. Taking into account this uncertainty, the analysis suggests risks are not of concern for non-listed monocot or dicot plant species, nor for listed animal species that do not possess an obligate rela tionship with a particular monocot. Risk was identified for listed monocot species within a short distance of the tr eated field and for listed animal species with an obligate re lationship with a partic ular monocot plant. Fu rther, the registration package includes uses on monocots (s pecifically bulb vegetables, onion); therefore it is unlikely that the potential impact on onions is sign ificant. Additionally, exceedance of the Agency’s LOC is lowered

1 Regulations.gov docket for the FIFRA SAP: http://www.regulations.gov/#!docketBro wser;rpp=25;po=0;dct=SR;D=EPA-HQOPP-2012-0543 ; and the Agency’s White paper: http://www.regula tions.gov/#!documentDeta il;D=EPA-HQ-OP P-2012-0543-

0004Page 12 of 18 significantly as distance increases from the treated fiel d; therefore the implemented buffers on the labels are intended to mitigate this potential risk.



### IV. Regulatory Decision

The Agency is unconditionally granting the registrati on of the new active ingredient, cyantraniliprole, formulated as a technical product and fourteen en d use products, under section 3(c)(5) of the Federal Insecticide, Fungicide, and R odenticide Act for the following uses (a complete list of all registered products is included in the attachment):

Agricultural crops bushberry (crop subgroup 13-07B); fr uit, citrus (crop group 10-10); fruit, pome (crop group 11-10); fruit, stone (crop group 12-12); nut, tree (crop group 14-12); oilseed (cr op group 20); vegetable, Brassica (Cole) leafy (crop group 5); vegetable, bulb (crop group 3- 07); vegetable, cucurbit (crop group 9); vegetable, fruiting (crop group 8-10); vegeta ble, leafy (except Brassica) (crop group 4); and vegetable, tuberous and corm (crop subgroup 1C).

Ornamentals and turf ornamental plants, shrubs, trees in and around gr eenhouses, nurseries, lath- and shade-houses, and interior plantscapes; landscape and recreational turfgr ass (including golf courses); sod farms.

Structures and equipment in and around agricultural, comm ercial, and residential structur es (excluding food/feed handling establishments); and transportation equipment.

For the food uses, Canadian Maximum Residue Levels (MRLs) and U.S. tolerances are harmonized for primary crop commodities and livestock commodities. A few items are not harmonized: a) Canada will establish import tolerances for grapes and olives; th e US does not have this re quest. b) Canada does not establish MRLs for livestock only commodities whereas th e US does. c) Canada is setting MRLs for poultry commodities at the level of quantif ication (LOQ) of the analytical method (0.01 ppm) in accord with Canadian policy for situations of no residues anticipated in the livestock commodities where there are feed items with residues. The US is not establishing tolerances for poultry commodities as no significant accumulation in poultry tissues or eggs is expected, i.e., category 40CFR §180.6(a)(3).

U.S. and Canadian tolerances are not entirely harm onized with European Union (EU) MRLs. This is due both to differences in regional use pa tterns and climate as well as how the maximum levels are calculated. Examples of different maximum leve ls include: citrus ( 0.70 ppm US/CA vs. 0.9 ppm EU ); leafy vegetables (20 ppm US/CA vs. 15 ppm EU); pom e fruit (1.5 ppm US/CA vs. 0.8 ppm EU); plums (0.5 ppm US/CA vs. 1.5 ppm EU); tree nuts (0.04 ppm US /CA vs. 0.03 ppm EU). Fruiting vege tables (including peppers) are harmonized at 2 ppm except tomatoes (2 ppm US/C A vs. 1.5 ppm EU) and eggplant (2 ppm US/CA vs. 0.4 ppm EU).

Codex maximum residue levels (MRLs) for cyantranilip role were proposed in September, 2013 but have not been adopted to date.

A. Public Comments

Notice of ReceiptPage 13 of 18 On April 26, 2012, EPA published a Noti ce of Receipt in the Federal Re gister of an application for registration of cyantraniliprole and announced a public comment period of 30 days. Only two comments were received, one from the San Francisco Bay Regi onal Water Quality Control Board and the other from the California Stormwater Quality Association. The commen ts were similar in that they requested that EPA consider adverse impacts to aquati c systems from urban use sites.

EPA addressed these comments during the risk asse ssment process by employing the Total Toxic Residue approach (i.e. including parent chemi cal and all potential degradates) in its evaluation of cyantraniliprole and its degradates in aquatic systems. The Total Toxic Re sidue approach essentially extends the duration of the predicted EECs to account for the time it would take for both the parent and degradates of concern to dissipate in the environment. It assumes that the degrad ates have equivalent fate and ecotoxicity properties as the parent which is a co nservative assumption.

Notice of Filing On May 23, 2012, EPA published a Notice of Filing in th e Federal Register; no co mments were received.

Proposed Registration Decision On June 6, 2013 EPA posted a Proposed Registration of Cyantraniliprole to the public docket (EPA-HQOPP-2011-0668). Twenty three public comments were rece ived. A detailed review of the public comments can be found in Cyantraniliprole - Response to Pub lic Comments on EPA’s “Proposed Registration of the New Active Ingredient Cyantraniliprole: An Insect icide for Use on Multiple Commodities, Ornamentals, Turfgrass, and in Commercial or Reside ntial Buildings" posted to the docket.

B. Regulatory Rationale

Cyantraniliprole is a broad spectrum in secticide, with activity on a wide va riety of target pests. While it is the third compound registered in the Insecticide Resistance Action Committee (IRAC) Mode of Action Classification Group 28; ryanodine recep tor modulators, it has a broader sp ectrum of activity than the other two compounds. It is expected to fit well in IPM programs.

As an efficacious insecticide, cyantraniliprole is exp ected to have invertebrate biological activity and therefore it may pose a risk to pollinators, as is the base for insectic ides in general. Cyantraniliprole was granted classification as a Reduced Risk pesticide. This means that compared to existing conventional pesticides such as the organophosphates, carbamates and pyrethroids, it pres ents characteristics that include lower impact on human health, lower toxicity to non-target organisms, low potential for groundwater contamination, and compatibility with IPM practices. Based on the committee's evaluation of the information provided, the mammalian toxicity and ecot oxicity risk profiles for cyantranil iprole are favorable compared to registered alternatives, which include organophosphate s, pyrethroids and abamectin. The novel mode of action for cyantraniliprole fits in well with resistance management strategies. After review and consideration of all of the data provided by the 800+ studies, the determinations made by the multiple scientists and international partners involved in the project, and the outcome of th e human health and ecological risk assessments, the Agency supports the decision to regist er cyantraniliprole as a reduced risk compound.

In light of this determination, the Agency considered the potential risks posed by cyantraniliprole. The risks were found not to be unreasonable when weighed against the benefits it provides. Cyantraniliprole controls lepidoptera, whiteflies, leafminers, psyllids, leaf-feeding beetles, fruit flies, and sawflies. Cyantraniliprole is effective at controlling the establishment and populat ion growth of aphids, w eevils and thrips. In a comparative qualitative analysis of efficacy, cyantranilip role is considered to be more efficacious than current registrations of more toxic compounds for control of citrus psylla, citrus leaf miner, citrus aphid, beetPage 14 of 18 armyworm, cotton bollworm, Silverleaf whitefly, co tton thrips, oriental fruit moth, and obliquebanded

leafroller.

Cyantraniliprole is expected to be an essential tool to citrus grower s and blueberry growers. The citrus industry is under serious threat from citrus greening disease (HLB). Once a tree becomes infected, there is no cure and it will die. The only way to protect citrus trees from HLB is through prevention by control of the Asian Citrus Psyllid and there are very few effective al ternatives; cyantraniliprole is one of the least toxic

alternatives that would be available for citrus growers. Florida and California growers need cyantraniliprole to provide an additional mode of action to combat this psyllid. Deaths of trees resu lting in serious losses to the citrus industry will also affect beekeepers that rely on citrus for honey production and as a resource for

their bees.

The Agency is also aware of the threat to numerous crops from the invasive fruit fly, the spotted wing Drosophila (SWD). This pest has already seriously injured the US blueberry crop. On July 29, 2013, the Washington Post wrote an ar ticle about the concern that Maine’s wild blueberry growers have for the threat posed by SWD. There is a zero tolerance standard for SW D in blueberries, a load of harvested blueberries will be rejected no matter the level of infestation. Ex tension agents in blueberry growing states have recommended carbaryl, diazinon, malathion, methomyl , phosmet, bifenthrin, es fenvalerate and other conventional chemicals, however pre- harvest intervals for these compoun ds are long and SWD infestations occur when fruit is ripe therefore growers are in need of tools with short PHIs. Michigan and New Jersey State Lead Agencies have made crisis declar ations under FIFRA Section 18 Emergency Exemption provisions on behalf of blueberry growers for the use of malathion to combat SWD. Registration of cyantraniliprole will provide the growers with an eff ective tool that has a shor t PHI and a more favorable toxicological profile co mpared to currently registered alternatives.

Cyantraniliprole is expected to be an alternative to a number of insecticide classes (organophosphates, carbamates, pyrethroids and some neoni cotinoids). Compared to these alternatives cyantraniliprole generally presented a more favorable environmental fate prof ile including its low volatility, low accumulation and leaching potential in addition to microbial-mediated a nd abiotic dissipation pathways. Additionally, it is generally less toxic towards mammals, birds and fish than the leading alte rnatives, and also honey bees (see Section III.B., Table 1). In critical pest situations, cyantraniliprole may also replace multiple or repeated applications of these other compounds, which expose non-target organisms many times and present greater risks to a wider range of non- target species. Registration of cyantraniliprole should therefore serve to reduce overall risks to such species, including listed species, when users substitute this product for the majority of the available registered alternatives.

C. Data Requirements

No additional studies required, the cyantraniliprole database is complete for the proposed uses.

D. Labeling Requirements

As noted in section III. B., aquatic invertebrates may be affected by cyantraniliprole. To mitigate the potential risk, cyantranilipro le labels will state:

“Do not make ground applications within 25’ or aerial applications w ithin 50’ of lakes, rivers, reservoirs, permanent streams, marshe s, natural ponds, estuarie s or coastal areas.

Do not cultivate within 25’ of these aquatic areas to allow gr owth of a vegetative filter strip.”Page 15 of 18 Additionally, an extens ive “Spray Drift Management” section is included on the labels, which provides applicators with information intended to decrease drift potential. The information addresses droplet size, boom length, application height, wind speed and other weather conditions.

While a potential chronic risk to mammals was identified for three specific application/use scenarios (soil injection/drench for hardwood trees, so il drench for citrus, and drip irriga tion applications for cucurbits), it was based on a screening-level risk assessment that assu mes that 100% of the animal’s diet has been treated with cyantraniliprole from these three specific applic ation sites. Thus, the potential risk is based on conservative assumptions where it is unlikely that thes e sites make up 100% of a non-target mammalian diet; therefore the actual potential for risk is low consider ing the variability of non-target mammalian diets. Additionally, cyantraniliprole is e xpected to be an alternative to compounds in the organophosphate and carbamate chemical classes, which adversely affect mammals.

Since cyantraniliprole is an insec ticide, and as with other insecticid es (see Table 1) it was not unexpected

that the data indicate that it is highly toxic on an acu te oral and contact basis to honeybees and other insect pollinators. However, it is ranked lower compared to neonicotinoids, carbamates and pyrethroids. In order to reduce exposure to these organisms, and to alert applic ators, cyantraniliprole labels must include pollinator protective labeling, as follows:

1. A “Pollinator Protection Box” that contains in formation regarding routes of exposure, a web site resource for Best Management Pract ices, and contacts for reporting beekills.

2. Use of a “Bee Icon” to call attention to the protective text

3. Prohibition of applications to crops during bl oom, except under certai n specific conditions

4. Restrictions for ornamentals that prohibit application during bloom.Page 16 of 18 ATTACHMENT A

Complete List of Registered Products:

EPA Registration

# product name formulation use sites (with crop group #)

352-856 DuPont Cyazypyr

Technical 96.7%

technical - Agricultural crops bushberry (subgroup 13-07B); fruit, citrus (group 10-10); fruit, pome (group 11-10); fruit, stone (group 12-12); nut, tree (group 14-12); oilseed (group 20); vegetable, Brassi ca (Cole) leafy (group 5); vegetable, bulb (group 3-07); vegetable, cucurbit (group 9); vegetable, fruiting (group 8-10); vegetable, leafy (except Brassica), (group 4) vegetable, tuberous and corm (subgroup 1C) - industrial, public, & residential: turf,

ornamentals - commercial production: ornamentals, sod

farms - in & around residential, public, commercial, agricultural structures; transportation vehicles (excluding food/feed handling establishments): indoors - spot or crack & crevice only outdoors - spot; crack & crevice; band - in & around residential, commercial, agricultural structures: scatterbait and bait

stations

352-857 DuPont Benevia

Insect Control 10.26% OD

0.83 lb ai/gal - nut, tree 14-12 - oilseed 20 (inc ludes cotton) - vegetable, bulb 3-07 - vegetable, tuberous & corm 1C

352-858 DuPont

Lumiderm

Insecticide Seed

Treatment 50% FS

5.21 lb ai/gal - rapeseed (canola)

- mustard seedPage 17 of 18 EPA Registration

# product name formulation use sites (with crop group #)

352-859 DuPont Exirel

Insect Control 10.20% SE

0.83 lb ai/gal - bushberry 13-07B - fruit, citrus 10-10 - fruit, pome 11-10 - fruit, stone 12-12 - nut, tree 14-12 - vegetable Brassica (Cole) leafy 5 - vegetable, bulb 3-07 - vegetable, cucurbit 9 - vegetable, fruiting 8-10 including eggplant, pepper, tomato in commercial greenhouses - vegetable, leafy except Brassica 4

352-860 DuPont Verimark

Insect Control 18.66% SC

1.67 lb ai/gal - fruit, citrus 10-10 - vegetable Brassica (Cole) leafy 5 - vegetable, cucurbit 9 - vegetable, fruiting 8-10 - vegetable, leafy except Brassica 4 - vegetable, tuberous & corm 1C

352-862 HGW86 Fly

Control Bait 0.5% RB - in & around residential, commercial, agricultural structures: scatterbait and bait

stations

352-863 HGW86 GH & N

Insect Control 18.66% SC

1.67 lb ai/gal - ornamentals and "grassy, weedy, mulched,

or bare soil areas" in & around greenhouses, nurseries, shadehouses, lathhouses - ornamentals in interior plantscapes

352-865 HGW86 T & O

Insect Control 18.66% SC

1.67 lb ai/gal - outdoor turfgrass & ornamentals (residential & public incl. golf courses) - interior plantscapes

- sod farms

352-868 HGW86 SC

Insect Control 18.66% SC

1.67 lb ai/gal - in & around residential, public, commercial, agricultural structures; transportation vehicles (excluding food/feed handling establishments): indoors - spot or crack & crevice only' outdoors - spot; crack & crevice; band

100-1418 Fortenza Red

Insecticide [seed treatment] 48.8% FS 600 g/l - potato
- sunflowerPage 18 of 18 EPA Registration

# product name formulation use sites (with crop group #)

100-1420 Fortenza

Insecticide [seed treatment] 48.8% FS 600 g/l - potato
- sunflower

100-1421 Minecto Duo

Insecticide 20% + 20%

WG vegetable Bra ssica (Cole) leafy 5 vegetable, cucurbit 9 vegetable, fruiting 8-10 vegetable, leafy except Brassica 4 vegetable, tuberous & corm 1C

100-1422 A16901B

Ornamental

Insecticide 20% + 20%

WG - ornamentals, non-bearing fruit and nut trees, and forest seedlings in commercial greenhouse, nurseries, and interiorscapes - certain crop plants grown for sale as transplants to consumers (only): .vegetable, Brassica leafy 5 .vegetable, cucurbit 9 .vegetable, fruiting 8-10

100-1423 A16901B

Residential

Insecticide 20% + 20%

WG - outdoor residential ornamentals

100-1424 Spinner

Insecticide 20% + 20%

WG - turfgrass (residential & public including golf courses)

- sod farms - ornamentals, non-bearing fruit and nut trees, and forest seedlings in commercial greenhouse, nurseries, and interiorscapes - certain crop plants grown for sale as transplants to consumers (only): .vegetable, Brassica leafy 5 .vegetable, cucurbit 9 .vegetable, fruiting 8-10