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 Programs 
Page 2 of 18 

Registration of the New Active Ingredient Cyantraniliprole 

Summary of the Regulatory Decision 

The Agency is granting an unconditional registration under section 3(c)(5) of the Federal Insecticide, 

Fungicide, and Rodenticide Act (FIFRA) 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 (subgroup 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 (group 8-10), leafy vegetables (except 

Brassica) (group 4), and tuberous and corm vegetables (subgroup 1C)), ornamentals and turf (ornamental 

plants, shrubs, trees in and around greenhouses, nurseries, lath- and shade-houses, and interior plantscapes, 

landscape and recreational turfgrass (including golf courses), and sod farms), as well as structures and 

equipment (in and around agricultural, commercial, and residential structures (excluding food/feed handling 

establishments), and transportation equipment. 

Product formulations include liquid, granular, and granular bait. Methods of application include broadcast 

sprays for aerial and ground applications, soil drench, 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 for all application methods. 

The Agency’s Reduced Risk Committee approved cyantraniliprole 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 cyantraniliprole are favorable compared to registered 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 was conducted as a “Global Joint Review” project. EPA scientists worked 

in collaboration with their colleagues in the Regulatory Authorities of France, the United Kingdom, Canada, 

and Australia. In the course of this analysis, the agencies considered a robust database that included over 800 

studies. Scientists in each partnering authority conducted primary reviews, 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 provided 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 Reduced Risk Committee; cyantraniliprole is therefore 

classified as a Reduced Risk Pesticide. 

Cyantraniliprole is a broad spectrum insecticide, with activity on a wide variety of target pests. While it is 

the third compound registered in the Insecticide Resistance Action Committee (IRAC) Mode of Action 

Classification Group 28, ryanodine receptor modulators, it has a broader spectrum 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]-1H-pyrazole-5-carboxamide 

EPA PC Code: 090098 

Chemical Abstracts Service (CAS) Number: 736994-63-1 

IRAC MoA Classification: Group 28 - Ryanodine receptor modulators 

Mode of Action: Insecticide Resistance Action Committee (IRAC) Mode of Action Classification Group 28: 

ryanodine receptor modulators (RyR). The mode of action 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 Nemours & Company and Syngenta Crop Protection 

II. Human Health Risk

A summary of the human health effects and risk of cyantraniliprole as assessed in the Agency document 

entitled “Cyantraniliprole. Aggregate Human Health Risk Assessment for the Proposed New Uses of the 

New Active Insecticide, including 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 Canola (Rapeseed), Mustard Seed, 

Sunflowers, and Potatoes; and Residential, Commercial, and Agricultural Uses on Ornamentals, Turfgrass 

(including Sod Farms and Golf Courses), and Structural Buildings (including Indoor Crack/Crevice and 

Outdoor Broadcast)" is provided below. 

A. Summary of Toxicological Effects

Cyantraniliprole is a second-generation ryanodine receptor (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 are shown to be 350 to >2500 times less 

sensitive than those of insects. In general, cyantraniliprole administration in mammals produces both adverse 

and adaptive changes in the liver, thyroid gland, and 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 alkaline 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 cyantraniliprole after 28 or 90 days due to enhanced 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 absence 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 immunotoxicity 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 would be adequately protected. 

EPA believes that the appropriate Food Quality Protection Act Safety Factor (FQPA SF) for cyantraniliprole 

should be reduced to 1X for 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 developmental 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 toxicity study, increased incidence of thyroid follicular 

epithelium hypertrophy/hyperplasia occurs in fetal 1 (F1) parental animals at a dose lower than that 

for the parental (P) generation. A clear No-Observed Adverse Effect Level (NOAEL) (1.4 

mg/kg/day) is established for F1 parental animals, and the Point of Departures (PODs) selected for 

risk assessment from the dog studies (1 or 3 mg/kg/day) are protective of the effect (thyroid effect) 

seen in the F1 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 estimated based on data that reasonably account for 

potential exposures. The chronic dietary food exposure 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-application exposure to children including incidental oral 

exposure. The residential post-application 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-protective assumptions and are not likely to 

underestimate risk. 

C. Toxicological End Points and Doses Used in the Human Health Risk Assessment 

1. Acute 

No acute dietary toxicity endpoint was selected as an effect because no effect attributed to a single dose was 

identified in the mammalian toxicology database. 

2. Chronic Dietary (all populations) 

EPA established a chronic reference dose (cRfD) and 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 Safety Factor of 1X. In this study, effects indicative of liver toxicity 

(increased liver weights and alkaline phosphatase activity), and significant decreases in albumin level were 

observed at the Lowest Observed Adverse Effect 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 and 90-day toxicity studies in dogs. In the 90-day study, a collection of 

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

The effects included decreases in total protein, albumin, and cholesterol in males and females; increases in 

alkaline phosphatase in males and females; increases in alanine aminotransferase in females; and increases in 

liver weights in males and females. In the co-critical 28-day study, decreases in body weight, food 

consumption, food efficiency, and changes in clinical chemistry (increased ALP, decreased cholesterol, and 

decreased albumin) were observed at the LOAEL = 35 mg/kg body wt/day (lowest dose tested). The level of 

concern for assessing short- and intermediate-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 Carcinogenic to Humans” based on data showing 

lack of treatment-related increase in tumor incidence in the rat and mouse carcinogenicity studies. Mutagenic 

concern was not reported in the mutagenicity studies. 

D. Cumulative Effects 

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common 

mechanism of toxicity, EPA has not found cyantraniliprole to share a common mechanism of toxicity with 

any other substances, and cyantraniliprole 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 takes into account acute exposure estimates from dietary consumption of 

food and drinking water. No adverse effect resulting from a single oral exposure was identified and therefore 

no acute dietary endpoint was selected. Cyantraniliprole is not expected to pose an acute risk. 
Page 6 of 18 

2. Chronic dietary risk 

EPA has concluded that chronic exposure to cyantraniliprole from food and water will utilize 50% of the 

cPAD for children 1-2 years old (the population group receiving the greatest 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). Cyantraniliprole is proposed for uses that 

could result in short-term residential exposure, and the Agency has determined that it is appropriate to 

aggregate chronic exposure through food and water with short-term residential exposures to cyantraniliprole. 

Residential exposure estimates of all possible scenarios are not of concern. Short-term inhalation MOEs 

range from 22,000 to 220,000,000. Furthermore, these calculated 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 described in this unit for short-term exposures, EPA has concluded the 

combined short-term food, water, and residential exposures result in aggregate MOEs 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 background exposure level). For adults, intermediate-term 

exposure is not expected for the residential exposure pathway. The intermediate-term aggregate risk would 

be equivalent to the chronic dietary 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-application exposure may occur by the dermal 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 for cyantraniliprole, only short- and 

intermediate-term inhalation risk estimates were calculated. 

a. Agricultural Field Uses 

The results of the occupational handler exposure and risk 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 exposures) at baseline mitigation (no PPE). Since the 

short- and intermediate-term PODs are the same, the inhalation MOEs are also 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 pilots are assessed using the engineering control (enclosed 

cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, and 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. There are no risk estimates of concern for aerial applicators. 

b. Agricultural Seed Treatment Uses 

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can 

potentially be used, some occupational handler exposure is expected from the proposed seed treatment uses. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the following 

scenarios: 

Mixing/loading liquids for potato seed piece treatment, 

Planting potato seed pieces, 

Mixing/loading liquids for commercial 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 than, or equal to, the throughput of 

intermediate-term exposure. The calculated inhalation risk estimates do not exceed EPA's LOC for 

intermediate-term exposures (i.e. an MOE < 100) at baseline, 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 effects and risks of cyantraniliprole as assessed in the 

Agency document entitled “Environmental Risk Assessment of Proposed New Global Chemical 

Cyantraniliprole on Bushberries, Citrus, Cotton, Oil Seeds, Pome Fruit, Stone Fruit, Tree Nuts, Vegetables 

(Bulb, Corm and Tuberous, Cucurbit, Fruiting, Leafy Brassica, and Leafy-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, Turfgrass 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 Assessment of Proposed New Global Chemical 

Cyantraniliprole on Bushberries, Citrus, Cotton, Oil Seeds, Pome Fruit, Stone Fruit, Tree Nuts, Vegetables 

(Bulb, Corm and Tuberous, Cucurbit, Fruiting, Leafy Brassica, and Leafy-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, Turfgrass and Ornamentals, Tree Injection, and Production 

Greenhouse and Nursery Ornamentals).” This addendum includes a revision of the chronic mammalian 
Page 8 of 18 

endpoint, characterization of potential risk concerns to monocots, and presents a comparison of acute honey 

bee toxicity data for cyantraniliprole and other insecticides. 

A. Environmental Fate 

Cyantraniliprole is a systemic insecticide. 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 10-18atm*m3

/mol), is not considered volatile and is not 

likely prone to atmospheric transport. While cyantraniliprole is subject to both abiotic alkaline hydrolysis 

(half-life = 21 hrs) and photodegradation in aqueous (half-life = 8 hrs) and moist soil environments and 

biotic (aerobic and anaerobic biotransformation in terrestrial and aquatic environments, half-lives range from 

2 days to 3 months) degradation, the chemical degrades into a total of 13 degradation products. Of these 

degradates, eight are major and five are minor. Based on degradate aerobic soil metabolism and mobility 

studies, six of the eight major degradates had longer dissipation half-life (DT50) values (more persistent) and 

three of the eight degradates were more mobile than the parent cyantraniliprole. According to the Food and 

Agriculture Organization (FAO) classification system, based on organic carbon partitioning coefficients, 

cyantraniliprole is characterized as moderately mobile. Bioconcentration factor 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. For the aquatic exposure modeling, a total toxic residue 

approach (considers the parent compound and eight major degradates including two degradates from 

terrestrial field studies) was utilized. 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 North Carolina cotton scenario. For pore water, peak 

EECs ranged from 0.22 μg/L from cyantraniliprole use on trees using the Oregon Christmas tree scenario to 

37 μg/L from cyantraniliprole use on rapeseed using the North Dakota wheat scenario. 

B. Ecological Risk 

Ecological risk characterization integrates the results of the exposure and ecotoxicity data to evaluate the 

likelihood of adverse ecological effects. The means of integrating the results of exposure and ecotoxicity 

data is called the risk quotient method. For this method, risk quotients (RQs) are calculated by dividing 

exposure estimates by ecotoxicity values, both acute and 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 whether 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 “slightly to moderately toxic” to freshwater fish on an acute exposure basis. 

A conservative calculation using the peak aquatic EEC (37.97 μg ai/L) and the typical end product LC50

(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 and aquatic-phase amphibians, for which fish serve as 

surrogates, from the proposed uses of cyantraniliprole are not considered likely. 

Risk quotients calculated for chronic exposures to cyantraniliprole ranged from <0.001 to 0.003 and were all 

well below the chronic risk to listed and non-listed species LOC of 1. The risk quotient analysis indicated 
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that direct chronic effects to freshwater fish are not expected; none of the risk quotients exceeded the chronic 

risk LOC of 1. 

Risk quotients could not be calculated for direct acute effects to estuarine/marine fish because the toxicity 

value was non-definitive. In lieu of this, the most sensitive toxicity value can be compared with the peak 

EEC. The most sensitive LC50 (>12,000 μg total ai/L), although 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 cyantraniliprole 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 LC50 would need to be 16 times more sensitive (759 μg ai/L) to even reach the 

acute risk to listed species LOC of 0.05. Thus, the likelihood of adverse effects on estuarine/marine fish from 

direct acute exposure from the proposed uses of cyantraniliprole is considered low. 

Risk quotients could not be calculated for chronic effects to estuarine/marine fish because only nondefinitive toxicity data were available. Given that the No Observed 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-day aquatic EEC of 37.42 μg ai/L, risk concerns cannot be eliminated 

on this alone. Risk mitigation language is included 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 species chronic risk LOC of 1. 

Cyantraniliprole is moderately to highly toxic to estuarine/marine invertebrates on an acute exposure basis. 

Acute risk quotients for estuarine/marine invertebrates ranged from <0.001 to 0.073 showing a slight 

exceedance of the acute risk to listed 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 scenarios exceeded the listed and non-listed species chronic 

risk LOC of 1. Thus, while mortality (direct) of estuarine/marine invertebrates is possible following acute 

exposure for eight of the proposed uses, the likelihood of (direct) 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 uses exceeding the listed and nonlisted species chronic risk LOC of 1. 

To reduce the potential risk to aquatic invertebrates, risk mitigation language is included on the labels (refer 

to section IV.D.). 

Aquatic Plants 

Toxicity data for technical-grade cyantraniliprole was 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 proposed uses of cyantraniliprole. 
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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 toxicity 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 results for the typical end-use product (TEP) studies, but 

these were also non-definitive and the lower toxicity value is probably an artifact of the largest dose of 

product that was given to the bird rather than the active ingredient itself). In all cases, none of the EECs were 

larger than the non-definitive toxicity values for the most 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, reptiles, 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 values. Furthermore, no sub-lethal effects were observed in the acute oral 

toxicity study. Therefore, acute effects on listed and non-listed mammalian species are not expected. 

There were no LOC exceedances of the listed and non-listed species chronic risk LOC (1), except for the 

following uses/application types: soil injection/drench for 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 the concentration of cyantraniliprole in the leaf biomass of the plant, 

where for the screening-level risk assessment the risk quotients above were 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 the 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, and collembola indicated that 

cyantraniliprole is toxic to some terrestrial invertebrates at very low application rates (48-hr LR50 = 0.00008 

lb ai/A – parasitic wasp), consistent 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 (EC50 > 1,200 mg ai/kg-soil. Likewise, earthworms demonstrated a low toxic effect to 

cyantraniliprole (EC50 > 102.6 mg ai/kg-soil – based on the TEP). 

While there is some uncertainty in honeybee toxicity data for cyantraniliprole, due to some non-definitive 

endpoints, it is highly toxic on an acute oral and contact basis; however, this compound is generally less 

toxic to honey bees than organophosphate, pyrethroid, neonicotinoid, and carbamate insecticides (Table 1). 

Refined acute oral RQs for adult honeybees using empirically-based maximum reported concentrations in 

nectar and pollen were determined as the ratio of cyantraniliprole consumed in pollen/nectar (i.e., dose) to 

the acute LD50 for cyantraniliprole-only TEP (0.116 μg 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 and 
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higher tier studies are not required. The registration packet included semi-field 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 assessment – is outlined in the Agency’s White Paper for 

assessing potential risks to pollinators and was evaluated by the FIFRA Scientific Advisory Panel1

. 

Table 1 below is a comparison of the relative honeybee acute toxicity for cyantraniliprole to 

organophosphates, carbamates, pyrethroids 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 comparatively low toxicity of the dual a.i. product containing 

cyantraniliprole/thiamethoxam is largely reflective of the toxicity of thiamethoxam, although less toxic than 

thiamethoxam alone. This table illustrates that cyantraniliprole is typically less toxic to honeybees compared 

to these chemical classes. 

Table 1. Comparison of relative honeybee acute toxicity* 

Chemical Honeybee acute contact 

LC50 (μg ai/bee)

Honeybee acute oral LD50 

(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 transient effects on behavior, foraging activity and mortality. Observations 

of brood health and colony strength (up to 28 days) suggested no significant lethal or sub-lethal adverse 

effects on larvae or colony strength from cyantraniliprole applications. The field studies provide in situ

information about the effects of cyantraniliprole applications to brood 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 plants was not exceeded for 

monocots or dicots. There is some uncertainty regarding the analysis for monocots because seedling 

emergence data were available for only one monocot species. However, available data indicate that onion 

was the most sensitive monocot using a vegetative vigor study, where it is approximately 2X more sensitive 

than the available monocot (corn) species data. Therefore 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 relationship with a particular monocot. 

Risk was identified for listed monocot species within a short distance of the treated field and for listed 

animal species with an obligate relationship with a particular monocot plant. Further, the registration 

package includes uses on monocots (specifically bulb vegetables, onion); therefore it is unlikely that the 

potential impact on onions is significant. Additionally, exceedance of the Agency’s LOC is lowered 

 

1

Regulations.gov docket for the FIFRA SAP: http://www.regulations.gov/#!docketBrowser;rpp=25;po=0;dct=SR;D=EPA-HQOPP-2012-0543; and the Agency’s White paper: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2012-0543-

0004 
Page 12 of 18 

significantly as distance increases from the treated field; therefore the implemented buffers on the labels are 

intended to mitigate this potential risk. 

IV. Regulatory Decision 

The Agency is unconditionally granting the registration of the new active ingredient, cyantraniliprole, 

formulated as a technical product and fourteen end use products, under section 3(c)(5) of the Federal 

Insecticide, Fungicide, and Rodenticide Act for the following uses (a complete list of all registered products 

is included in the attachment): 

Agricultural crops

bushberry (crop subgroup 13-07B); fruit, citrus (crop group 10-10); fruit, pome (crop group 11-10); 

fruit, stone (crop group 12-12); nut, tree (crop group 14-12); oilseed (crop 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); vegetable, leafy (except Brassica) (crop group 4); and 

vegetable, tuberous and corm (crop subgroup 1C). 

Ornamentals and turf

ornamental plants, shrubs, trees in and around greenhouses, nurseries, lath- and shade-houses, and 

interior plantscapes; landscape and recreational turfgrass (including golf courses); sod farms. 

Structures and equipment

in and around agricultural, commercial, and residential structures (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; the US does not have this request. b) Canada does not 

establish MRLs for livestock only commodities whereas the US does. c) Canada is setting MRLs for poultry 

commodities at the level of quantification (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 harmonized with European Union (EU) MRLs. This is due 

both to differences in regional use patterns and climate as well as how the maximum levels are calculated. 

Examples of different maximum levels include: citrus (0.70 ppm US/CA vs. 0.9 ppm EU); leafy vegetables 

(20 ppm US/CA vs. 15 ppm EU); pome 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 vegetables (including peppers) are 

harmonized at 2 ppm except tomatoes (2 ppm US/CA vs. 1.5 ppm EU) and eggplant (2 ppm US/CA vs. 0.4 

ppm EU). 

Codex maximum residue levels (MRLs) for cyantraniliprole were proposed in September, 2013 but have not 

been adopted to date. 

A. Public Comments 

Notice of Receipt
Page 13 of 18 

On April 26, 2012, EPA published a Notice of Receipt in the Federal Register 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 Regional Water Quality Control Board and the other from 

the California Stormwater Quality Association. The comments were similar in that they requested that EPA 

consider adverse impacts to aquatic systems from urban use sites. 

EPA addressed these comments during the risk assessment process by employing the Total Toxic Residue 

approach (i.e. including parent chemical and all potential degradates) in its evaluation of cyantraniliprole and 

its degradates in aquatic systems. The Total Toxic Residue 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 degradates have equivalent fate and ecotoxicity properties as 

the parent which is a conservative assumption. 

Notice of Filing

On May 23, 2012, EPA published a Notice of Filing in the Federal Register; no comments 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 received. A detailed review of the public comments 

can be found in Cyantraniliprole - Response to Public Comments on EPA’s “Proposed Registration of the 

New Active Ingredient Cyantraniliprole: An Insecticide for Use on Multiple Commodities, Ornamentals, 

Turfgrass, and in Commercial or Residential Buildings" posted to the docket. 

B. Regulatory Rationale 

Cyantraniliprole is a broad spectrum insecticide, with activity on a wide variety of target pests. While it is 

the third compound registered in the Insecticide Resistance Action Committee (IRAC) Mode of Action 

Classification Group 28; ryanodine receptor modulators, it has a broader spectrum of activity than the other 

two compounds. It is expected to fit well in IPM programs. 

As an efficacious insecticide, cyantraniliprole is expected to have invertebrate biological activity and 

therefore it may pose a risk to pollinators, as is the base for insecticides 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 presents 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 ecotoxicity risk profiles for cyantraniliprole are favorable compared to 

registered alternatives, which include organophosphates, 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 the human health and ecological risk 

assessments, the Agency supports the decision to register 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 population growth of aphids, weevils and thrips. In a 

comparative qualitative analysis of efficacy, cyantraniliprole is considered to be more efficacious than 

current registrations of more toxic compounds for control of citrus psylla, citrus leafminer, citrus aphid, beet 
Page 14 of 18 

armyworm, cotton bollworm, Silverleaf whitefly, cotton thrips, oriental fruit moth, and obliquebanded 

leafroller. 

Cyantraniliprole is expected to be an essential tool to citrus growers 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 alternatives; 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 resulting 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 article about the concern that Maine’s wild blueberry growers have for the threat 

posed by SWD. There is a zero tolerance standard for SWD in blueberries, a load of harvested blueberries 

will be rejected no matter the level of infestation. Extension agents in blueberry growing states have 

recommended carbaryl, diazinon, malathion, methomyl, phosmet, bifenthrin, esfenvalerate and other 

conventional chemicals, however pre-harvest intervals for these compounds 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 declarations 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 effective tool that has a short PHI and a more favorable 

toxicological profile compared to currently registered alternatives. 

Cyantraniliprole is expected to be an alternative to a number of insecticide classes (organophosphates, 

carbamates, pyrethroids and some neonicotinoids). Compared to these alternatives cyantraniliprole generally 

presented a more favorable environmental fate profile including its low volatility, low accumulation and 

leaching potential in addition to microbial-mediated and abiotic dissipation pathways. Additionally, it is 

generally less toxic towards mammals, birds and fish than the leading alternatives, 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, cyantraniliprole labels will state: 

“Do not make ground applications within 25’ or aerial applications within 50’ of lakes, 

rivers, reservoirs, permanent streams, marshes, natural ponds, estuaries or coastal areas. 

Do not cultivate within 25’ of these aquatic areas to allow growth of a vegetative filter 

strip.” 
Page 15 of 18 

Additionally, an extensive “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, soil drench for citrus, and drip irrigation applications for cucurbits), it 

was based on a screening-level risk assessment that assumes that 100% of the animal’s diet has been treated 

with cyantraniliprole from these three specific application sites. Thus, the potential risk is based on 

conservative assumptions where it is unlikely that these sites make up 100% of a non-target mammalian diet; 

therefore the actual potential for risk is low considering the variability of non-target mammalian diets. 

Additionally, cyantraniliprole is expected to be an alternative to compounds in the organophosphate and 

carbamate chemical classes, which adversely affect mammals.

 

Since cyantraniliprole is an insecticide, and as with other insecticides (see Table 1) it was not unexpected 

that the data indicate that it is highly toxic on an acute 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 applicators, cyantraniliprole labels must include pollinator 

protective labeling, as follows: 

1. A “Pollinator Protection Box” that contains information regarding routes of exposure, a web 

site resource for Best Management Practices, 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 bloom, except under certain 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, Brassica (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 (includes 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 seed 
Page 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 

- sunflower 
Page 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 Brassica (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