EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Tom Harris, 703-308-9423

TEMPLATE:

Syngenta Crop Protection, LLC, P.O. Box 18300, Greensboro, NC 27419-8300

Petition No. (XXX)

EPA has received a pesticide petition (Petition No. XXX) from Syngenta Crop 

Protection, LLC., P.O. Box 18300, Greensboro, NC 27419-8300 proposing, pursuant 

to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 

346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of

cyantraniliprole, 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-

[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide (CAS Reg. No. 

736994-63-1), including its metabolites and degradates, in or on the raw agricultural 

commodity corn, field and pop, forage at 0.04 parts per million (ppm); corn, field and 

pop, grain at 0.01 ppm; corn, field and pop, stover at 0.015 ppm; corn, sweet, forage

at 0.02 ppm; corn, sweet, kernel plus cob with husks removed at 0.01 ppm; corn, 

sweet, stover at 0.08 ppm;. EPA has determined that the petition contains data or

information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, 

EPA has not fully evaluated the sufficiency of the submitted data at this time or whether 

the data supports granting of the petition. Additional data may be needed before EPA 

rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism of cyantraniliprole is adequately 

understood to support the proposed tolerances. Studies in lettuce, rice, tomato, and 

cotton when treated at proposed label rates showed no significant metabolites. The 

metabolism of cyantraniliprole in plants was similar regardless of the crop or the 

treatment regime. Cyantraniliprole was the principal residue in most crop fractions 

at various sampling points up to crop maturity. The overall metabolism of 

cyantraniliprole in rotated crops (wheat, red beets, lettuce, and soybeans) was

consistent with metabolism seen in the primary crops.

2. Analytical method. Adequate analytical methodology, high-pressure liquid 

chromatography with ESI-MS/MS detection, is available for enforcement purposes.

3. Magnitude of residues. Field trials were conducted on field corn, pop corn

and sweet corn under OPPTS 860.1500 to support the requested uses of 

cyantraniliprole. The results of the field trials substantiate cyantraniliprole as the 

major residue in harvested raw agricultural commodities.
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These residue trials satisfy the requested tolerance on corn (field, pop and sweet).

B. Toxicological Profile

1. Acute toxicity. Based on EPA criteria, technical cyantraniliprole is 

classified as acute toxicology category IV based on overall results from several 

studies. This compound is considered acute toxicology category IV for acute oral, 

dermal and inhalation toxicity and eye and skin irritation. Technical

cyantraniliprole is not a dermal sensitizer.

No evidence of neurotoxicity was observed in studies conducted with 

cyantraniliprole in rats. The NOAEL in an acute neurotoxicity study was 2000 

mg/kg bw and was the highest dose administered in the study.

2. Genotoxicty. Cyantraniliprole was evaluated in a battery of in vitro and in 

vivo genetic toxicology studies. Negative results were obtained in all studies 

indicating that cyantraniliprole does not cause genetic damage and, therefore, does 

not pose a mutagenic hazard.

3. Reproductive and developmental toxicity. Based on the results of a twogeneration reproduction study in rats and a developmental toxicity studies in rats 

and rabbits, cyantraniliprole does not pose a specific concern for effects on 

reproduction or development.

4. Subchronic toxicity. The primary toxicological findings in short-term, 

repeated-dose feeding toxicity studies included non-adverse increases in liver weight 

in rats, mice, and dogs due to a pharmacological response to liver metabolism, an 

effect on thyroid hormones and associated thyroid gland histopathology in rats, a 

non-adverse increase in the degree of lipid in adrenal cortical cells in both rats and 

mice, and changes in body weight, nutritional parameters, clinical pathology and 

liver histopathology in dogs.

Dermal application of cyantraniliprole to rats for 28 days did not result in any 

treatment related findings up to and including a maximum dose of 1000 mg/kg 

bw/day.

Cyantraniloprole showed no evidence of immunotoxicity in 28-day feeding studies in 

rats or mice and no evidence of neurotoxicity in a 90-day feeding study in rats.

No treatment related clinical signs indicative of potential neurotoxicity were 

observed in short-term and long-term exposure studies in rats, mice, or dogs.

5. Chronic toxicity. Based on the results of chronic feeding studies in rats and 

mice, cyantraniliprole is not a carcinogen. The lowest NOAEL following chronic, 
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long-term feeding is 5.7 mg/kg/day is based on liver enzyme changes, liver 

histopathology and arteritis in the one-dog study.

No treatment related clinical signs indicative of potential neurotoxicity were 

observed in long-term exposure studies in rats, mice, or dogs.

6. Animal metabolism. The absorption of 14C-cyantraniliprole in rats was 

rapid with peak concentrations occurring at 1-2.5 hours after low or high (10 or 150 

mg/kg bw) dose administration. Tissue distribution of the absorbed dose was 

extensive and indicated low potential for accumulation. Excretion was substantially 

complete by 24-48 hours after dosing.

Following 14 days of dose administration the 14C residues were readily eliminated 

from the plasma and tissues and confirmed minimal potential for accumulation. The 

profile of metabolites in urine and feces indicated extensive metabolism consistent 

with that observed for the single dose study.

7. Metabolite toxicology. Cyantraniliprole is considered to be the only 

molecule of toxicological relevance. Toxicology studies conducted with metabolites 

support this conclusion.

8. Endocrine disruption. No relevant effects were observed on any endocrine 

tissue in short- and long-term studies in rats, mice and dogs to suggest an adverse 

impact on estrogen or androgen pathways or on steroid biosynthesis. Effects on 

thyroid hormone homeostasis were observed in rats following dietary exposure and 

demonstrated to be due to increased clearance of thyroid hormone as a result of 

enzyme induction

C. Aggregate Exposure

1. Dietary exposure. Short-term and chronic dietary exposure evaluations 

were completed for cyantraniliprole using the Dietary Exposure Evaluation Model 

software with the Food Commodity Intake Database (DEEM-FCID, version 3.16). 

DEEM-FCID software incorporates food consumption data from the National 

Health and Nutrition Examination Survey)/“What We Eat in America” 

(NHANES/WWEIA) dietary survey conducted in 2003-2008. In addition to all uses 

of cyantraniliprole (agricultural uses on Brassica (Cole) leafy vegetables (Group 5), 

bulb vegetables (Group 3-07), bushberries (Group 13-07b), citrus fruit (Group 10-

10), cotton, cucurbit vegetables (Group 9), fruiting vegetables (Group 8-10), leafy 

vegetables (non-Brassica) (Group 4), oilseeds (Group 20), pome fruits (Group 11-

10), stone fruits (Group 12), tree nuts (Group 14), tuberous and corm vegetables 

(Subgroup 1c); seed treatment uses on sunflowers, and potatoes, this exposure 

assessment included pending seed treatment uses on oilseed crops and proposed 

seed treatment uses on corn. Drinking water estimates were incorporated directly 

into the dietary exposure assessment using the higher of the estimated drinking 

water concentrations (EDWCs) for surface and ground water.
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i. Food. Acute Exposure. Cyantraniliprole is not considered to be acutely 

toxic and an acute toxicological endpoint was not selected by the Agency.

Chronic Exposure: The cyantraniliprole chronic dietary (food only) risk assessment 

was performed for all population subgroups with a chronic reference dose of 0.01 

mg/kg-bw/day based on an oral study in dogs with a No Observable Adverse Effect 

Level (NOAEL) of 1.0 mg/kg-bw/day and an uncertainty factor of 100X. The 100-

fold safety factor includes intra- and interspecies variations (100X) and the FQPA 

safety factor was reduced to 1X (complete toxicological database). For the purpose 

of the aggregate risk assessment, exposure values were expressed in terms of margin 

of exposure (MOE), which was calculated by dividing the NOAEL by the exposure 

for each population subgroup. In addition, exposure was also expressed as a 

percent of the reference dose (%RfD). Chronic (food only) exposure to the U.S. 

population resulted in a MOE of 582 (17.2% of the chronic RfD of 0.01 mg/kgbw/day). The most sensitive sub-population was children (1-2 years old) with a 

MOE of 232 (43.1% of the chronic RfD). Since the benchmark MOE for this 

assessment was 100 and since the EPA generally has no concern for exposures below 

100% of the RfD, Syngenta believes that there is a reasonable certainty that no 

harm will result from dietary (food only) exposure to residues arising from all 

registered, pending and proposed uses for cyantraniliprole.

ii. Drinking water. The Estimated Drinking Water Concentrations (EDWCs) 

of cyantraniliprole and its degradates were determined using Tier l models, FIRST 

FQPA Index Reservoir Screening Tool and SCI-GROW (Screening Concentration 

in Ground Water), to estimate pesticide concentration in ground water and surface 

water, respectively. All registered and pending uses plus proposed uses on corn 

were assessed. Based on the FIRST modeling, the use in bait stations for fly control 

provided a surface water chronic EDWC of 24.45 parts per billion (ppb). Based on 

the SCI-GROW modeling, the seed treatment use on potatoes provided a ground 

water chronic EDWC of 6.33 ppb. Since the surface water EDWC exceeds the 

ground water EDWC, the surface water value was used for risk assessment 

purposes and will be considered protective for any ground water exposure concerns. 

Chronic Exposure from Drinking Water. The chronic surface water EDWC of 

24.45 ppb was input directly into the DEEM-FCID software as “water, direct and 

indirect, all sources” to model the chronic drinking water exposures. Chronic 

drinking water exposure to the U.S. population resulted in a MOE of 1,953 (5.1% of 

the cRfD of 0.01 mg/kg-bw/day). Chronic drinking water exposure to the most 

exposed sub-population (all infants, <1 year old) resulted in a MOE of 758 (13.2% of 

the cRfD of 0.01 mg/kg-bw/day). Since the Benchmark MOE for this assessment 

was 100 and since EPA generally has no concern for exposures below 100% of the 

cRfD, Syngenta believes that there is a reasonable certainty that no harm will result 

from chronic drinking water exposure to residues arising from all registered,

pending and proposed uses for cyantraniliprole.

2. Non-dietary exposure. Three formulation types of cyantraniliprole are 
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currently registered at EPA. They are soluble concentrate formulations containing 

1.67 lb a.i./gallon, wettable granulars containing 20% a.i. by weight, and fly bait 

granules containing 0.5% a.i. by weight. These formulations may be used on 

turfgrasses on golf courses, sod farms, and residential lawns, on ornamental 

landscape plants and as crack, crevice and spot treatments in and around homes. 

Other than one wettable granule product, all products are labeled as intended for

professional use only, however, the EPA has determined that use by homeowners is 

possible, and prohibition of use by homeowners is not enforceable, therefore, 

residential handler application scenarios were assessed. Residential (nonoccupational) risk assessments were also conducted for potential post-application 

exposure to children on treated lawns and in treated homes.

Because no dermal endpoint of concern was identified, assessments were limited to 

inhalation and incidental oral exposures. The residential handler exposures include 

mixer/loader/applicator inhalation exposures to granules, liquids and dry flowables 

from handheld treatment equipment during application to turf, to ornamentals, or 

as indoor crack/crevice and spot treatments. The post-application exposures on 

treated turf and indoor areas include oral exposures due to hand-to-mouth and 

object-to-mouth activities and soil ingestion. Negligible post application exposure is 

expected to fly bait granules as the only residential use site is indoor bait stations. 

Risks due to short-term exposures (1-30 days) were assessed using the Margin of 

Exposure (MOE) approach. Based on the use pattern of cyantraniliprole, 

intermediate-term exposures (1 to 6 months) are unlikely and long-term exposures 

(greater than six months) are not expected. Therefore, intermediate-term and longterm risks were not assessed. 

Residential handler risks were assessed for cyantraniliprole assuming a one-time 

application at the maximum rate for each product label for granular fly bait; liquid 

concentrate on turf, on ornamentals and as an indoor crack/crevice and spot 

treatment; and water dispersible granules on turf and ornamentals. The short-term 

MOEs ranged from 22,048 (manually-pressurized handwand and backpack 

sprayer, water-dispersible granule on ornamentals) to 221,122,751 (cup and shaker 

can, granular fly bait). Since the calculated residential hander exposures were 

found to be well above the EPA’s level of concern (MOEs>30), there are acceptable 

residential handler risks from applications of granular cyantraniliprole products. 

Post application incidental oral exposure risks for children due to hand-to-mouth 

and object-to-mouth activities on treated turf and indoor carpeted and hard 

surfaces were calculated for cyantraniliprole. Post application incidental oral 

exposure risks for children due to soil ingestion were also calculated. The lowest 

short-term MOE for incidental oral exposure was 496 for hand-to-mouth exposure 

from turf. This MOE was calculated using the transferable turf residue value from 

a chemical specific study on cyantraniliprole, adjusted the label application rate of 

0.313 lb a.i./A. The turf object–to-mouth and soil ingestion MOEs were 16,332 and 

283,036, respectively. The MOEs for hand–to-mouth exposure on indoor carpet and 

hard surfaces were 1,170 and 3,510. These values were calculated based on an 
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application rate of 1 gallon of 0.10% solution per square foot. The MOEs for 

object–to-mouth exposure on indoor carpet and hard surfaces were 8,793 and 

13,190. Since the calculated post-application exposures were found to be well above 

the EPA’s level of concern (MOEs>100), there are acceptable post-application risks 

to children from applications of cyantraniliprole products.

D. Cumulative Effects

Cumulative Exposure to Substances with a Common Mechanism of Toxicity. 

Section 408(b)(2)(D)(v) requires that, when considering whether to establish, 

modify, or revoke a tolerance, the Agency consider “available information” 

concerning the cumulative effects of a particular pesticide’s residues and “other 

substances that have a common mechanism of toxicity”. The EPA does not have, at 

this time, available data to determine whether cyantraniliprole has a common 

mechanism of toxicity with other substances or how to include this pesticide in a 

cumulative risk assessment. For the purposes of this tolerance action, the EPA has 

not assumed that cyantraniliprole has a common mechanism of toxicity with other 

substances.

E. Safety Determination

1. U.S. population. The chronic dietary exposure analysis (food plus water) 

showed that exposure from all registered, pending and proposed cyantraniliprole 

crop uses result in a MOE of 448 (22.3% of the chronic RfD) for the general U.S. 

population. Based on the completeness and reliability of the toxicity data 

supporting these petitions, Since all aggregate MOEs exceed the benchmark MOE 

of 100, Syngenta believes that there is a reasonable certainty that no harm will occur 

to the general U.S. population from aggregate exposure to residues arising from all

registered, pending and proposed cyantraniliprole uses, including anticipated 

dietary exposure from food, water, and all other types of non-occupational 

exposures.

2. Infants and children. The chronic dietary exposure analysis (food plus 

water) showed that exposure from all registered, pending and proposed 

cyantraniliprole uses would result in a MOE of 198 (50.5% of the chronic RfD) for 

the most sensitive population subgroup, children (1-2 years old). A short-term 

aggregate MOE of 270 (LOC = 100) was determined for children (1-2 years old). 

Since all aggregate MOEs exceed the benchmark MOE of 100, Syngenta believes 

that there is a reasonable certainty that no harm will occur to infants and children 

from aggregate exposure to residues arising from all registered, pending, and 

proposed cyantraniliprole uses, including anticipated dietary exposure from food, 

water and all other types of non-occupational exposures.

F. International Tolerances

A number of international tolerances (or Maximum Residue Levels, MRL's) 

have been established for cyantraniliprole.