Proposed Registration of the New Active Ingredient Cyantraniliprole 

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

Commercial or Residential Buildings 

Approved by: ~th ~ 

Date: 

Lois Rossi, Director 

Registration Division 

Office of Pesticide Programs 
2

Proposed Registration of the New Active Ingredient Cyantraniliprole 

Regulatory Rationale 

The Agency is proposing to grant 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 proposed new uses for this insecticide are: 

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 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) 

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) 

transportation equipment 

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

include aerial and ground broadcast; soil application; chemigation; and seed treatment. Maximum single 

application rates are 0.42 lb. a.i./A for liquid or granular applications; 0.69 lb. a.i./A for seed treatments. The 

maximum annual application rate is 0.42 lb. a.i./A/year for liquid or granular applications. 

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: unregulated activation of insect RyR channels leading to internal calcium store depletion 

and impaired regulation of muscle contraction, causing paralysis and eventual death 
3

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

Proposed Products: 

File 

Symbol 

product name formulation use sites (with crop group #) 

352-ILA Cyantraniliprole 

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 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: 

 indoors - spot or crack & crevice only 

 outdoors - spot; crack & crevice; band 

- in & around residential, commercial, 

agricultural structures: scatterbait and bait 

stations 

352-ILT Benevia 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-ILO Exirel 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 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 
4

352-IAN Verimark 18.66% SC 

1.67 lb 

ai/gal 

- fruit, citrus 10-10 

- vegetable Brassica leafy 5 

- vegetable, cucurbit 9 

- vegetable, fruiting 8-10 

- vegetable, leafy except Brassica 4 

- vegetable, tuberous & corm 1C 

352-ILI Dermacor Z-103 

seed treatment 

50% FS 

5.21 lb 

ai/gal 

- rapeseed (canola) 

- mustard seed 

352-IAE Fly Control Bait 0.5% RB - in & around residential, commercial, 

agricultural structures: scatterbait and bait 

stations 

352-IAI SC Insect Control 18.66% SC 

1.67 lb 

ai/gal 

- in & around residential, public, commercial, 

agricultural structures; transportation vehicles: 

 indoors - spot or crack & crevice only' 

 outdoors - spot; crack & crevice; band 

352-IAL 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-IAG 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 

100-

RUER 

A169101B CP 20% + 20% 

WG 

 vegetable Brassica leafy 5 

 vegetable, cucurbit 9 

 vegetable, fruiting 8-10 

 vegetable, leafy except Brassica 4 

 vegetable, tuberous & corm 1C 

100-

RUEE 

Mainspring 20% + 20% 

WG 

- ornamentals in commercial greenhouse & 

nurseries 

- certain crops in commercial greenhouse & 

nurseries: 

 .vegetable, Brassica leafy 5 

 .vegetable, cucurbit 9 

 .vegetable, fruiting 8-10 

100-

RUEG 

A16901B 

Residential 

20% + 20% 

WG 

- outdoor residential ornamentals 

100-

RUEU 

A16901B Turf 20% + 20% 

WG 

- turfgrass (residential & public including golf 

courses) 

- sod farms 
5

100-

RUEN 

A17960A ST 

seed treatment 

48.8% FS 

600 g/l 

- potato 

- sunflower 

100-RURI A17960B ST 

seed treatment 

48.8% FS 

600 g/l 

- potato 

- sunflower 

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, 

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 

if the Food Quality Protection Act Safety Factor (FQPA SF) for cyantraniliprole were reduced to 1x. That 

decision is based on the following findings: 

• The toxicity database for cyantraniliprole is complete. 
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• 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 1. 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. 

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. 
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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. 

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 
8

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. 

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). 
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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. 

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 

(t1⁄2 = 21 hrs) and photodegradation in aqueous (t1⁄2= 8 hrs) and moist soil environments and biotic (aerobic 

and anaerobic biotransformation in terrestrial and aquatic environments, t1⁄2 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 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. 
10

In some cases, toxicity is noted as non-definitive since testing was either not high enough or not low enough 

and an exact value was not determined. Although an actual value can’t be noted, a bound can be put on the 

toxicity as information is known. 

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 

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 and risk concerns cannot be 

eliminated on this alone. The risks will be reduced by mitigation (see Proposed Labeling Changes, below). 

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 nonlisted 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 
11

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. 

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. 

Risks to Terrestrial Animals 

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 

non-definitive toxicity values were directly compared to the Expected Environmental Concentrations 

(EECs). The most sensitive TGAI studies were selected (in two cases, there were more sensitive results for 

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

 The chronic dietary-based RQs range from <0.01 to 0.45. The likelihood of chronic adverse effects in 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. Acute 

dose-based and dietary-based risk quotients could not be calculated to evaluate the risks to mammals because 

only non-definitive acute toxicity data were available. Instead, the non-definitive 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. 

Seed and fruits/pods were the only food items where RQs did not exceed the listed and non-listed species 

chronic risk LOC (1); all other food items (short grass, tall grass, broadleaf plants, and arthropods) exceeded. 

Chronic risk quotients for the proposed foliar spray, bark spray, and seed treatment uses ranged from 0.18 to 

5.48. 

 

Chronic risk quotients for soil injection, soil drench, drip irrigation, and applications to potted ornamentals 

were derived by estimating the concentration of cyantraniliprole in the leaf biomass of the plant. Based on 

the screening-level RQ analysis, risk quotients ranged from 0.23 to 31.8. The proposed use on potted 

ornamentals was the only proposed use that did not exceed the chronic risk LOC of 1. A screening level risk 

assessment assumes that 100% of the animal’s diet has been treated with cyantraniliprole. 
12

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). Conversely, collembola, which are exposed to cyantraniliprole through direct 

contact with the soil, were not found to be very sensitive 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 TEP). 

Honeybee toxicity data for cyantraniliprole indicated that it is highly toxic on an acute oral and contact basis, 

but the endpoints were non-definitive and the true toxicity classification is uncertain. Refined acute oral RQs 

for adult honeybees using 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 level of concern of 0.4. 

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 adverse effects from cyantraniliprole 

applications. The results of longer-term studies must be considered in the context of some uncertainties. 

Namely, the health of all colonies (controls and treatment) was in decline well before overwintering 

reductions in colony size should have occurred. However, of the three studies that followed the hives 

through the overwintering period, most of the data suggest no long-term effects to honeybees that would 

differentiate treated colonies from control colonies. 

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. Onion was the most sensitive monocot in the 

vegetative vigor test, but data from this species were found to be unacceptable in the seedling emergence 

study because of control performance problems. If the seedling emergence NOAEC for onion is ≤0.100, risk 

quotients would exceed the LOC for some uses. Currently, the most sensitive monocot seedling emergence 

NOAEC is 0.134 lb ai/A. Risk quotients could not be calculated for non-listed monocots and dicots because 

only non-definitive data were available for these endpoints. The listed species risk quotients are based on the 

NOAEC, which is more sensitive than the EC25. Thus, the risk quotients for listed species are expected to be 

protective of non-listed species as well. No direct effects are anticipated for terrestrial dicots; however direct 

effects to listed monocots cannot be precluded because of an absence of data. 

IV. Proposed Regulatory Decision 

The Agency is proposing to unconditionally grant 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: 

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 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). 
13

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. 

The Agency has determined that the registration of these uses will not cause any unreasonable adverse effect 

on the environment. In addition, EPA has granted cyantraniliprole reduced risk status compared to the 

currently registered pesticides for these uses. 

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, both requested that EPA: 

“...carefully evaluate all cyantraniliprole product registration applications. Specifically, we request a 

full evaluation of the potential for cyantraniliprole products to cause adverse impacts in the water 

column and/or sediments in California’s urban waterways. We request that EPA consider all urban 

application locations and evaluate potential pathways to receiving waters under conditions consistent 

with label instructions. The evaluation should include stable degradates and the time required for the 

active ingredient to become non-toxic in the environment. If use of the pesticide consistent with the 

label instructions can result in toxicity in the receiving water, further restrictions on use must be 

evaluated. We encourage EPA to pay special attention to application types – like control of insects 

around buildings and pre-construction termiticide applications – that are being addressed in EPA’s 

pyrethroid Registration Reviews.” 

EPA addressed these comments during the risk assessment 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. 

A. Data Requirements 

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

B. Global Joint Review and Reduced Risk Status 

EPA conducted an extensive analysis of cyantraniliprole in collaboration with counterpart agencies in 

France, United Kingdom, Canada, and Australia. In this process, the agencies analyzed data on such aspects 

of cyantraniliprole as its impact on human and animal health, fate and behavior in the environment, and its 

effects on non-target organisms, i.e., on animals and plants other than the pests it is intended to control. In 

the course of this analysis, the agencies considered over 700 published and unpublished studies. 

 

After the conclusion of the joint agency review of data, EPA conducted its own risk assessment of 

cyantraniliprole including a comprehensive analysis of the pesticide’s human health risk, as well as an 

analysis of its environmental fate and ecological risk. The risk assessment considered cyantraniliprole's 

potential effects on animals, plants, soil, and water, and included detailed calculations of the pesticide’s 

potential effects. 
14

 

In addition, on September 20, 2011, EPA'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 and abamectin. The novel mode of action for 

cyantraniliprole fits in well with resistance management strategies. 

As is expected with insecticides, aquatic invertebrates may be affected by cyantraniliprole. To mitigate risks 

to these and nontarget terrestrial invertebrates, cyantraniliprole labels for foliar applications include a section 

on spray drift management, see below, which is intended to keep the pesticide on the treatment area. 

C. Proposed Labeling Changes 

 

1. For end use products used outdoors, EPA proposes to require the labeling include the following in 

the Environmental Hazards section: 

"Drift and runoff may be hazardous to aquatic organisms in water adjacent to treated areas. This 

pesticide is toxic to aquatic invertebrates. This product is highly toxic to bees exposed to direct 

treatment or residues on blooming crops or weeds. Do not apply this product or allow it to drift to 

blooming crops or weeds if bees are visiting the treatment area.” 

2. To address potential risks to aquatic organisms, for end use products used outdoors, EPA 

proposes to require the labeling include the following in the Directions for Use: 

“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.” 

3. Review of the submitted residue data indicates that the following rotational crop restrictions must 

be added to the Directions for Use for the agricultural products: 

• “Cereal grains (crop group 15) may not be planted immediately after use of 

cyantraniliprole. Cereal grains (crop group 15) must have a 30-day plant back interval 

(PBI). This is to be consistent with the 30-day PBI for crop group 16 (forage, fodder, and 

straw of cereal grains).” 

• “Legume vegetables (crop group 6) may not be planted immediately after use of 

cyantraniliprole. Legume vegetables (crop group 6) must have a 30-day PBI. This is to 

be consistent with the 30 day PBI for crop group 7 (foliage of legume vegetables).” 

• “Tuberous and corm vegetables (subgroup 1C) may not be planted immediately after use 

of cyantraniliprole. Subgroup 1C must have a 30-day PBI. This is to be consistent with 

the 30-day PBI for crop group 2 (leaves of root and tuber vegetables).” 

4. Residue data was not submitted to support use in food and feed handling sites, therefore, these 

sites must be deleted from the label for pending product 352-IAI, “SC Insect Control.”