Pesticide Petition to Establish Tolerances for Cyantraniliprole 

I. E.I. du Pont de Nemours and Company 

PP No. (1F7894) 

EPA has received a pesticide petition (PP No. 1F7894) from E.I. du Pont de Nemours & Company 

(“DuPont”), 1007 Market Street, Wilmington, DE 19898, proposing pursuant to section 408 (d) of the 

Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 346a (d), to amend 40 CFR part 180 to establish 

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

[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide, including its metabolites and degradates, 

in or on the following commodities: almond hulls at 30 ppm; berries and small fruits, bushberries (crop 

subgroup 13-07B) at 4 ppm; Brassica (cole) leafy vegetables, head and stem Brassica (crop subgroup 5A) 

at 2 ppm; Brassica (cole) leafy vegetables, leafy Brassica greens (crop subgroup 5B) at 30 ppm; bulb 

vegetables, onion, bulb (crop subgroup 3-07A) at 0.04 ppm; bulb vegetables, onion, green (crop subgroup 

3-07B) at 8 ppm; cattle, fat at 0.01 ppm; cattle, liver at 0.04 ppm; cattle, meat at 0.01 ppm; cattle, meat 

byproducts, except liver at 0.01 ppm; cherries at 6 ppm; citrus fruits (crop group 10-10) at 0.7 ppm; 

cotton gin byproduct at 10 ppm; cucurbit vegetables (crop group 9) at 0.3 ppm; fruiting vegetables (crop 

group 8-10) at 2 ppm; goat, fat at 0.01 ppm; goat, liver at 0.04 ppm; goat, meat at 0.01 ppm; goat, meat 

byproducts, except liver at 0.01 ppm; hog, fat at 0.01 ppm; hog, liver at 0.04 ppm; hog, meat at 0.01 ppm; 

hog, meat byproducts, except liver at 0.01 ppm; horse, fat at 0.01 ppm; horse, liver at 0.04 ppm; horse, 

meat at 0.01 ppm; horse, meat byproducts, except liver at 0.01 ppm; leafy vegetables (except Brassica

vegetables) (crop group 4) at 15 ppm; milk at 0.01 ppm; milk, fat at 0.04 ppm; oilseeds, except cotton gin 

byproduct (crop group 20) at 1 ppm; pome fruits (crop group 11-10) at 0.8 ppm; root and tuber 

vegetables, tuberous and corm vegetables (crop subgroup 1C) at 0.15 ppm; sheep, fat at 0.01 ppm; sheep, 

liver at 0.04 ppm; sheep, meat at 0.01 ppm; sheep, meat byproducts, except liver at 0.01 ppm; stone fruits, 

except cherries (crop group 12) at 1.5 ppm; tree nuts, except almond hulls (crop group 14) at 0.06 ppm; 

citrus, oil at 6 ppm; citrus, raw peel at 2 ppm; and potato, wet peel at 0.3 ppm. 

In addition, DuPont is proposing pursuant to section 408 (d) of the Federal Food, Drug, and Cosmetic 

Act, 21 U.S.C. 346a (d), to amend 40 CFR part 180 to establish indirect or inadvertent tolerances for 

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

[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide, including its metabolites and degradates, 

in or on the following commodities: foliage of legume vegetables (crop group 7), forage at 0.15 ppm, hay 

at 0.6 ppm; forage, fodder and straw of cereal grains (crop group 16), forage at 0.06 ppm, hay and straw 

at 0.15 ppm; grass forage, fodder, and hay (crop group 17), forage at 0.06 ppm, hay at 0.15 ppm; leaves 

of root and tuber vegetables (human food or animal feed) (crop group 2) at 0.04 ppm; nongrass animal 

feeds (forage, fodder, straw, and hay) (crop group 18), forage at 0.06 ppm, hay at 0.15 ppm; peanut hay at 

0.03 ppm; and root and tuber vegetables, root vegetables (crop subgroup 1A) at 0.03 ppm. 

EPA has determined that the petition contains data or information regarding the elements set forth in 

section 408 (d) (2) of the FFDCA; 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 
Pesticide Petition to Establish Tolerances for Cyantraniliprole 

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. Livestock Metabolism. The metabolism of cyantraniliprole in ruminants and poultry is adequately 

understood to support the proposed tolerances. Lactating goat and laying hen metabolism studies were 

conducted. The metabolism of cyantraniliprole in the rat was consistent with that of the lactating goat 

(ruminant) and laying hen.

3. Analytical method. Adequate analytical methodology, high-pressure liquid chromatography with ESIMS/MS detection, is available for enforcement purposes. 

4. Magnitude of residues. Field trials were conducted on corm vegetables (potatoes), bulb vegetables, 

leafy vegetables, brassica vegetables, legume vegetables, cucurbits vegetables, fruiting vegetables, citrus 

fruit, pome fruit, stone fruit, bushberries, tree nuts, and oilseeds with formulations containing 

cyantraniliprole. The trials covered a wide range of locations, climates, and soil types globally and the 

data obtained reflect the commercial use of the cyantraniliprole-containing products in the major crop 

growing regions. 

The results of the field trials substantiate cyantraniliprole as the major residue in harvested raw 

agricultural commodities. For instances of residue in processing factions, the relevant residue was found 

to be cyantraniliprole parent plus the metabolite IN-J9Z38. Residues in commodities of animal origin 

were relevant only for cattle. 

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 two-generation reproduction study in 

rats and a developmental toxicity studies in rats and rabbits, cyantraniliprole does not pose a specific 

concern for effects on reproduction or development. 

4. Subchronic toxicity. The primary toxicological 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. 
Pesticide Petition to Establish Tolerances for Cyantraniliprole 

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, 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. Rat 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 faeces 

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 homeostatis 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 

The residue of concern is parent cyantraniliprole only. 

No acute dietary risk assessment was needed since there is no acute tox endpoint. 

The chronic reference dose (cRfD) 0.057 mg/kg/day is based on the NOEL of 5.7 mg/kg/day from a oneyear dog tox study and a 100X safety factor. 

1. Dietary exposure

i. Food. There is no population in the chronic risk assessment for cyantraniliprole with an exposure 

greater than 5% of the chronic reference dose.

ii. Drinking water. No acute dietary endpoint was identified. Therefore, an acute drinking water risk 

assessment is not considered necessary. One can conclude with reasonable certainty that residues of 

cyantraniliprole in drinking water do not contribute significantly to the aggregate acute human health risk. 
Pesticide Petition to Establish Tolerances for Cyantraniliprole 

Chronic drinking water exposure analyses were calculated for cyantraniliprole using EPA screening 

concentration models for ground water SCI-GROW and surface water FIRST. The groundwater 

concentrations for cyantraniliprole were less than those in surface water, so surface water values were 

used in the dietary risk assessment. 

When the surface water concentration of 1.1 ppb was included for drinking water in the chronic aggregate 

assessment to evaluate chronic exposure and risk from food and drinking water, no population including 

the general U.S. population and all subpopulations had an exposure greater 5% of the chronic reference 

dose (cRfD), indicating a significant margin of safety. These results indicate that a reasonable certainty 

exists that cyantraniliprole residues in drinking water will not contribute significantly to the aggregate 

human risk. 

2. Non-dietary exposure. Residential exposure (non-occupational, non-dietary exposure to consumers) 

was conservatively assessed for dermal post-application exposure (children and adults), and for children 

the oral exposures via hand-to-mouth, object-to-mouth, and incidental ingestion of soil were also 

assessed. The margins of exposure (MOE) greatly exceed the 100-fold MOE required for these routes 

and from the combined children’s incidental oral ingestion. Therefore, residential non-dietary exposure is 

not a concern. 

D. Cumulative Effects

A determination has not been made that cyantraniliprole has a common mechanism of toxicity with other 

substances. Cyantraniliprole does not appear to produce a common toxic metabolite with other 

substances. A cumulative risk assessment was, therefore, not performed for this analysis. 

E. Safety Determination

1. U.S. population. Based on risk assessments performed using worst-case exposure assumptions there is 

a reasonable certainty that no harm will result to the general population from the aggregate exposure to 

cyantraniliprole. No additional safety factors are warranted.

2. Infants and children. Based on the risk assessments performed using worst-case exposure assumptions 

there is a reasonable certainty that no harm will result to the infants and children from the aggregate 

exposure to cyantraniliprole. No additional safety factors are warranted. 

F. INTERNATIONAL TOLERANCES 

No tolerances have been established to date for cyantraniliprole.