Cyantraniliprole Human Health Risk Assessment DP No. 404762 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: March 7, 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: 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 11-1 0), Stone Fruits (Group 12), 

Tree Nuts (Group 14), Tuberous and Corm Vegetables (Subgroup IC); 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). 

PC Code: 090098 

Decision No.: 451670 

DP Barcode: 0404762,0407979 

Registration Nos.: 352-IAE, 352-IAG, 352-IAI, 352-IAL, 

253-IAN, 352-ILA, 352-ILI, 352-ILO, 352-ILT, 100-RUEE, 

100-RUEG, 100-RUEN, 100-RUER, 100-RUEU, 100-RURI 

Petition No.: I F7894 Regulatory Action: Section 3 

Risk Assessment Type: Aggregate Human Health 

TXRNo.: NA 

CaseNo.: NA 

CAS No.: 736994-63-1 

MRIDNo.: NA 40 CFR: to be determined (new active ingredient) 

FROM: Nancy J. Tsaur, Chemist, Risk Assessor t}f~ 

Whang Phang, Senior Toxicologist II . J .. . A., .- ~- 110 ~"'( _ Steve Funk, Senior Chemist ~ ~~ · 'J f 

Meheret Negussie, Chemist Heherd- ,J(j~-e_ 

Risk Assessment Branch 3 (RAB3) 

Health Effects Division (7509P) 

THROUGH: Christine Olinger, Branch Chief tJ / ?/ 

Risk Assessment Branch 3 (RAB3) t,·· :/'0 

and v 

Wade Britton, Industrial Hygienist, Designated Review r 

Ray Kent, Senior Chemist, Designated RevieweY:l_ \: 

Risk Assessment Review Committee '--.)'{) 

Health Effects Division (7509P) 

TO: Thomas Harris/John Hebert, RM #07 

Insecticide Rodenticide Branch (IRB) 

Registration Division (7505P) 

Page I of85 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Table of Contents 

1.0 Executive Summary ............................................. ................................................................ 4 

2.0 HED Recommendations ....................................................................................................... 6 

2.1 Data Deficiencies ....... ........... ........... ....... ........ ............ ............... .... .................................. 6 

2.2 Tolerance Considerations .. ................................................................................................ 6 

2.2.1 Enforcement Analytical Method ............................................................................... 6 

2.2.2 Recommended Tolerances ................................................. ....................................... 6 

2.2.3 Revisions to Petitioned-For Tolerances ..................................... ............................. 10 

2.2.4 International Harmonization ................................................................................... 11 

2.3 Recommendations .......................................................................................................... 11 

2.3 .1 Recommendations from Residue Reviews ....................... .... .................................. 11 

2.3.2 Recommendations from Occupational Assessment ................................................ 11 

2.3.3 Recommendations from Residential Assessment.. ................................................. 12 

3.0 Introduction ........................................................................................................................ 12 

3.1 Chemical Identity ........................................................................................................... 12 

3.2 Physical/Chemical Characteristics ................................................................................. 12 

3.3 Pesticide Use Pattern ...................................................................................................... 13 

3.4 Anticipated Exposure Pathways .................................................... ................................. 14 

3.5 Consideration of Environmental Justice ........................................................................ 15 

4.0 Hazard Characterization and Dose-Response Assessment ...................... .............. ............ 15 

4.1 Toxicology Studies Available for Analysis ................................................................... 16 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME) ................................... 16 

4.3 ·Toxicological Effects ..................................................................................................... 17 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ....................................... 19 

4.4.1 Completeness of the Toxicology Database ............................................................. 20 

4.4.2 Evidence ofNeurotoxicity ...................................................................................... 20 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ......... 20 

4.4.4 Residual Uncertainty in the Exposure Database ..................................................... 20 

4.5 Toxicity Endpoint and Point of Departure Selections .................................................... 20 

4.5.1 Dose-Response Assessment. ................................................................................... 20 

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment ........ 22 

4.5.3 Cancer Classification and Risk Assessment Recommendation .............................. 22 

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment ............................................................................................................................ 22 

5.0 Dietary Exposure and Risk Assessment .................... ................ ........ .... ............................ 25 

5.1 Metabolite/Degradate Residue Profile ........................................................................... 25 

5.1.1 Summary ofPlant and Animal Metabolism Studies ............................................... 25 

5 .1.2 Summary of Environmental Degradation ............................................................... 25 

5 .1.3 Comparison of Metabolic Pathways ....................................................................... 26 

5.1.4 Residues of Concern Summary and Rationale ........................................................ 27 

5.2 Food Residue Profile ...................................................................................................... 28 

5.3 Water Residue Profile ............................... ..................................................................... 29 

5.4 Dietary Risk Assessment ................................................................................................ 30 

5.4.1 Description of Residue Data Used in Dietary Assessment ..................................... 30 

5.4.2 Acute Dietary Risk Assessment ....................... ....................................................... 31 

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Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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5.4.3 Chronic Dietary Risk Assessment .......................................................................... 31

5.4.4 Summary Table....................................................................................................... 31

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... 31

6.1 Residential Handler Exposure........................................................................................ 32

6.2 Post-Application Exposure............................................................................................. 34

6.3 Residential Risk Estimates for Use in Aggregate Assessment ...................................... 36

6.4 Residential Bystander Post-Application Inhalation Exposure ....................................... 37

6.5 Spray Drift...................................................................................................................... 38

7.0 Aggregate Exposure/Risk Characterization....................................................................... 38

7.1 Acute Aggregate Risk .................................................................................................... 38

7.2 Short-Term Aggregate Risk ........................................................................................... 39

7.3 Intermediate-Term Aggregate Risk................................................................................ 39

7.4 Chronic Aggregate Risk................................................................................................. 39

7.5 Cancer Aggregate Risk................................................................................................... 39

8.0 Cumulative Exposure/Risk Characterization..................................................................... 39

9.0 Occupational Exposure/Risk Characterization .................................................................. 40

9.1 Short- and Intermediate-Term Handler Risk.................................................................. 40

9.2 Short- and Intermediate-Term Post-Application Risk ................................................... 42

9.2.1 Dermal Post-Application Risk ................................................................................ 42

9.2.2 Restricted Entry Interval......................................................................................... 42

9.2.3 Inhalation Post-Application Risk............................................................................ 43

10.0 References.......................................................................................................................... 44

Appendix A. Detailed Use Profile Summary............................................................................ 47

Appendix B. Toxicology Profile and Executive Summaries.................................................... 55

B.1 Toxicology Data Requirements...................................................................................... 55

B.2 Toxicity Profiles............................................................................................................. 56

B.3 Hazard Identification and Endpoint Selection ............................................................... 67

B.3.1 Acute Reference Dose (aRfD) - General Population.............................................. 67

B.3.2 Chronic Reference Dose (cRfD)............................................................................. 67

B.3.3 Incidental Oral Exposure (Short- and Intermediate-Term)..................................... 67

B.3.4 Dermal Exposure (Short-, Intermediate- and Long-Term)..................................... 68

B.3.5 Inhalation Exposure (Short- and Intermediate-Term)............................................. 68

B.4 Human Equivalent Concentrations (HEC) and Human Equivalent Dose Calculations. 69

Appendix C. Metabolism Summary Table ............................................................................... 72

Appendix D. Physical/Chemical Properties.............................................................................. 79

Appendix E. Review of Human Research................................................................................ 79

Appendix F. Occupational Exposure/Risk Summary Tables................................................... 80
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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1.0 Executive Summary

Cyantraniliprole is a new second-generation ryanodine receptor (RyR) insecticide currently 

undergoing global joint review. It is a systemic insecticide that is mobile in both the xylem and 

phloem of plants. Cyantraniliprole belongs to the diamide class of chemistry whose pesticidal 

mode of action (MOA) is through unregulated activation of insect RyR channels. This then leads

to internal calcium store depletion and impaired regulation of muscle contraction, causing

paralysis and eventual death of the insect.

Proposed Use Profile

Cyantraniliprole has been jointly developed by DuPont and Syngenta, with a proposal for one 

technical product and 14 U.S. end-use product (EP) registrations, including agricultural food

uses (PP#1F7894). The agricultural uses include foliar, soil, and seed treatment to various crops 

including cotton, fruits, oilseeds, and vegetables. The residential use sites include turfgrass, 

ornamentals, and structural buildings (including indoor crack/crevice and outdoor broadcast).

Exposure Profile

Non-occupational exposures to cyantraniliprole are expected for short- and intermediate-term 

durations. Exposure pathways include dietary (food and drinking water), and residential 

exposure sources. Dietary exposures are also expected for chronic duration. Occupational 

exposures are expected for short- and intermediate-term durations only. The dermal route of 

exposure is not assessed because there is no dermal hazard. The proposed residential uses (turf, 

ornamentals, and indoor crack/crevice) result in inhalation exposures for adults (handlers) and 

post-application incidental oral exposures for children (1 to <2 years old).

Toxicity/Hazard

The risk assessment for cyantraniliprole is based on a well-characterized and complete 

toxicology database. While unregulated activation of RyR channels leads to insect death, the 

insect RyR are shown to be 350 to >2500 times more sensitive than those of mammals. In 

general, cyantraniliprole administration 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. 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. Therefore, the 

data support a reduction of the Food Quality Protection Act (FQPA) safety factor to 1X. There is 

no evidence of an adverse effect attributable to a single dose. The toxicity endpoint and points of 

departure (PODs) for chronic dietary and short-/intermediate-term incidental oral exposure are 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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based on the 1-year and 90-day dog oral toxicity studies, respectively. The toxicity endpoint and 

POD for inhalation exposure are based on the results of a 28-day rat inhalation toxicity study.

Dietary Exposure (Food and Water) and Risk Estimates

An acute dietary assessment was not conducted because there was no indication of an adverse 

effect attributable to a single dose. A somewhat refined chronic (food and drinking water) 

dietary assessment was conducted assuming average field trial residues for all proposed crops 

(except crop subgroup 1A) and that 100% of crops are treated (CT). Tolerance-level residues 

were adequate to cover residues in all livestock commodities except liver and meat byproducts 

for which higher anticipated residue calculations were used. The estimated drinking water 

concentration (EDWC) of 24.45 μg/L derived from the 1-in-10 year annual mean from surface 

water estimates was incorporated directly into the chronic dietary assessment. The results of the 

chronic dietary (food and drinking water) analysis are below the Agency’s level of concern 

(LOC) for the general U.S. population and all population subgroups. The dietary (food and 

drinking water) exposure is estimated at 22% of the chronic Population Adjusted Dose (cPAD) 

for the general U.S. population and 50% of the cPAD for children 1-2 years old, the population 

subgroup with the highest estimated chronic dietary exposure to cyantraniliprole.

Residential Exposure and Risk Estimates

Residential exposure may occur by the dermal, oral, and inhalation routes of exposures. As 

previously noted, cyantraniliprole does not pose a dermal hazard; therefore, only inhalation 

(handler exposure for adults) and oral (post-application incidental oral for children) require 

assessment. The proposed uses do not result in residential handler inhalation (adults) or postapplication incidental oral (children) risk estimates of concern. For the proposed residential uses 

(turf, ornamentals, and crack/crevice), the short-term residential handler inhalation margins of 

exposure (MOEs) range from 22,000 to 220,000,000. Short-term incidental oral post-application 

risk estimates (which are protective of intermediate-term risk estimates) for all scenarios are not

of concern to HED (MOEs range from 290 to 1,000,000).

Residential Aggregate Exposure Risk Estimates

There is potential for short-term aggregate exposure to cyantraniliprole via the dietary and 

residential pathways. For adults, the oral and inhalation routes of exposure should not be 

aggregated since the endpoints of concern are not common. For children, the short-term 

aggregate risk estimate is not of concern; the MOE is 190 which is greater than the LOC of 100.

Occupational Exposure and Risk Estimates

Occupational handler and post-application exposure may occur by the dermal and inhalation 

routes of exposure only. Since there is no dermal hazard, only inhalation exposures were 

quantitatively assessed. The results of the occupational handler exposure and risk assessment

indicate that short- and intermediate-term inhalation risk estimates are not of concern at baseline

(long-sleeved shirt, long pants, shoes plus socks) without mitigation from any personal protective 

equipment (PPE). In general, the labels require PPE of chemical-resistant gloves. The proposed 

level of clothing and PPE are adequate for protection of workers. Short- and intermediate-term 

inhalation MOEs range from 370 to 3,900,000. Based on the Agency's current practices, a 

quantitative non-cancer occupational post-application inhalation exposure assessment was not 

performed for cyantraniliprole at this time. The technical form of cyantraniliprole meets the 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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criteria for a 4-hour REI. However, two of the proposed EPs (EPA Reg. No. 352-ILT and EPA 

Reg. No. 352-ILI) have been identified as dermal sensitizers, so a 12-hour REI is required to 

protect agricultural workers from post-application exposures to cyantraniliprole. Aside from 

these two products, a 4-hour REI is adequate to protect agricultural workers from postapplication exposures to cyantraniliprole.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment. Dietary and non-dietary exposures were considered.

2.0 HED Recommendations

HED has examined the toxicology and residue chemistry databases for cyantraniliprole. Pending 

submission of a revised Section B (label), a revised Section F (tolerances), and submission of

analytical reference standards, there are no toxicology or residue chemistry issues that would 

preclude granting Section 3 registration for the requested crop commodity uses of 

cyantraniliprole (except food/feed establishment uses), or establishment of tolerances for 

residues of cyantraniliprole. The specific tolerance recommendations are discussed in Section 

2.2, and label modifications are discussed in Section 2.3.

2.1 Data Deficiencies

There are no data deficiencies to prohibit tolerance establishments or product registrations.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

The submitted residue analytical method data are adequate. Validation data have been provided 

for the proposed enforcement methods. Methods for measuring cyantraniliprole include the 

European Union (EU) multi-residue method DFG S19 (LC/MS/MS module, Dupont-21328) and 

the North American Free Trade Association (NAFTA) LC/MS/MS 1187 & 1552 methods. 

These methods utilize two mass ion transitions so confirmatory methods are not required. EU 

Method DFG S19 has been independently validated with a limit of quantification (LOQ) of 0.01 

ppm for parent cyantraniliprole in cereals and dry products, matrices with high water content, 

acidic matrices, and fatty products. NAFTA method 1187 has been independently validated with 

an LOQ of 0.01 ppm for parent cyantraniliprole in almonds, onions, tomato paste, and sun dried 

tomatoes. NAFTA method 1552 has been independently validated with an LOQ of 0.01 ppm for 

parent cyantraniliprole in milk, muscle, and kidney. Note that cyantraniliprole is not recovered 

using the FDA multi-residue methods.

2.2.2 Recommended Tolerances

It is recommended that tolerances be established for residues of the insecticide cyantraniliprole 

(3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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pyrazole-5-carboxamide), including its metabolites and degradates, in or on the plant 

commodities and livestock specified below in Table 2.2.2. 

It is recommended that indirect or inadvertent tolerances be established for residues of the 

insecticide 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 commodities specified below in Table 2.2.2. 

Compliance with the tolerance levels specified below is to be determined by measuring only 

cyantraniliprole in or on the commodity.

Table 2.2.2 Tolerance Summary for Cyantraniliprole

Commodity

Proposed Tolerance Recommended 

Tolerance Comments

Correct Commodity Definition

ppm ppm

40CFR §180 Part (a) General: It is recommended that tolerances be established for residues of the insecticide 

cyantraniliprole (3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1Hpyrazole-5-carboxamide), including its metabolites and degradates, in or on the commodities below. Compliance 

with the tolerance levels specified below is to be determined by measuring only cyantraniliprole in or on the 

commodity.

Almond, hulls 30 8.0

A revised Section F must be 

submitted to propose a tolerance 

at 8.0 ppm.

Berries and small fruits, 

bushberries (crop subgroup 13-

07B)

4 4.0 Bushberry subgroup 13-07B

Brassica (Cole) leafy 

vegetables, head and stem 

Brassica (crop subgroup 5A)

2 3.0

Brassica, head and stem, 

subgroup 5A

A revised Section F must be 

submitted to propose a tolerance 

at 3.0 ppm.

Brassica (Cole) leafy 

vegetables, leafy Brassica

greens (crop subgroup 5B)

30 30 Brassica, leafy greens, subgroup 

5B

Bulb vegetables, onion, bulb 

(crop subgroup 3-07A) 0.04 0.04 Onion, bulb, subgroup 3-07A

Bulb vegetables, onion, green 

(crop subgroup 3-07B) 8 8.0 Onion, green, subgroup 3-07B

Cattle, fat 0.01 0.01

Cattle, liver 0.04 None Included under meat byproducts.

Cattle, meat 0.01 0.01

Cattle, meat byproducts, except 

liver 0.01 0.01 Cattle, meat byproducts

Cherries 6 6.0 Cherry subgroup 12-12A

Citrus fruits (crop group 10-

10) 0.7 0.70 Fruit, citrus, group 10-10

Citrus, oil 4 2.4

A revised Section F must be 

submitted to propose a tolerance 

at 2.4 ppm.
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Table 2.2.2 Tolerance Summary for Cyantraniliprole

Commodity

Proposed Tolerance Recommended 

Tolerance Comments

Correct Commodity Definition

ppm ppm

Citrus, raw peel 0.9 None

Cotton, gin byproduct 10 10 Cotton, gin byproducts

Cucurbit vegetables (crop 

group 9) 0.3 0.40

A revised Section F must be 

submitted to propose a tolerance 

at 0.4 ppm.

Vegetable, cucurbit, group 9

Fruiting vegetables (crop 

group 8-10) 2 2.0 Vegetable, fruiting, group 8-10

Goat, fat 0.01 0.01

Goat, liver 0.04 None Included under meat byproducts.

Goat, meat 0.01 0.01

Goat, meat byproducts, except 

liver 0.01 0.01 Goat, meat byproducts

Hog, fat 0.01 None 40CFR§180(a)(3)

Hog, liver 0.04 None 40CFR§180(a)(3)

Hog, meat 0.01 None 40CFR§180(a)(3)

Hog, meat byproducts, except 

liver 0.01 None 40CFR§180(a)(3)

Horse, fat 0.01 0.01

Horse, liver 0.04 None Included under meat byproducts.

Horse, meat 0.01 0.01

Horse, meat byproducts, except 

liver 0.01 0.01 Horse, meat byproducts.

Leafy vegetables (except 

Brassica vegetables) (crop 

group 4)

15 20

A revised Section F must be 

submitted to propose a tolerance 

at 20 ppm.

Vegetable, leafy, except 

Brassica, group 4

Milk 0.01 0.01

Milk fat 0.04 None Covered by milk tolerance.

Oilseeds, except cotton 

byproduct (crop group 20) 1 1.5

A revised Section F must be 

submitted to propose a tolerance 

at 1.5 ppm.

Oilseed group 20

Pome fruits (crop group 11-10) 0.8 1.5

A revised Section F must be 

submitted to propose a tolerance 

at 1.5 ppm.

Fruit, pome, group 11-10

Potato, wet peel 0.3 None

Root and tuber vegetables, 

tuberous and corm vegetables 

(crop subgroup 1C)

0.15 0.15 Vegetable, tuberous and corm, 

subgroup 1C

Sheep, fat 0.01 0.01

Sheep, liver 0.04 None Included under meat byproducts.

Sheep, meat 0.01 0.01
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Table 2.2.2 Tolerance Summary for Cyantraniliprole

Commodity

Proposed Tolerance Recommended 

Tolerance Comments

Correct Commodity Definition

ppm ppm

Sheep, meat byproducts, 

except liver 0.01 0.01 Sheep meat byproducts

Stone fruits, except cherries 

(crop group 12) 1.5

1.5 Peach subgroup 12-12B

0.50 Plum subgroup 12-12C

Tree nuts, except almond hulls 

(crop group 14) 0.06 0.04

A revised Section F must be 

submitted to propose a tolerance 

at 0.04 ppm.

Nut, tree, group 14

40CFR §180 Part (d) Indirect or inadvertent residues: It is recommended that indirect or inadvertent tolerances be 

established for residues of the insecticide 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 commodities below. Compliance with the tolerance levels specified below is to be determined by 

measuring only cyantraniliprole in or on the commodity.

Foliage of legume vegetables 

(crop group 7), forage 0.15 None Only one tolerance per crop group.

Foliage of legume vegetables 

(crop group 7), hay 0.6 0.70

A revised Section F must be 

submitted to propose a tolerance 

at 0.7 ppm.

Vegetable, foliage of legume, 

group 7

Forage, fodder and straw of 

cereal grains (crop group 16), 

forage

0.06 None Only one tolerance per crop 

group.

Forage, fodder and straw of 

cereal grains (crop group 16), 

hay and straw

0.15 0.5

A revised Section F must be 

submitted to propose a tolerance 

at 0.5 ppm.

Grain, cereal, forage, fodder and 

straw, group 16

Grass forage, fodder, and hay 

(crop group 17), forage 0.06 None Only one tolerance per crop group.

Grass forage, fodder, and hay 

(crop group 17), hay 0.15 0.50

A revised Section F must be 

submitted to propose a tolerance 

at 0.5 ppm.

Grass, forage, fodder and hay, 

group 17

Leaves of root and tuber 

vegetables (human food or 

animal feed) (crop group 2)

0.04 0.04 Vegetable, leaves of root and 

tuber, group 2

Nongrass animal feeds (forage, 

fodder, straw, and hay) (crop 

group 18), forage

0.06 None Only one tolerance per crop

group.

Nongrass animal feeds (forage, 

fodder, straw, and hay) (crop 

group 18), hay

0.15 0.20

A revised Section F must be 

submitted to propose a tolerance 

at 0.2 ppm.

Animal feed, nongrass, group 18
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Table 2.2.2 Tolerance Summary for Cyantraniliprole

Commodity

Proposed Tolerance Recommended 

Tolerance Comments

Correct Commodity Definition

ppm ppm

Peanut, hay 0.03 0.01

A revised Section F must be 

submitted to propose a tolerance 

at 0.01 ppm.

Peanut, hay

Root and tuber vegetables, root 

vegetables (crop subgroup 1A) 0.03 0.02

A revised Section F must be 

submitted to propose a tolerance 

at 0.02 ppm.

Vegetable, root, subgroup 1A

2.2.3 Revisions to Petitioned-For Tolerances

The proposed tolerances must be modified for the following plant commodities: almond hulls, 

Brassica vegetables (crop subgroup 5A), cucurbit vegetables (crop group 9), leafy vegetables 

except Brassica (crop group 4), oilseeds (crop group 20), pome fruits (crop group 11-10), stone 

fruits except cherry (crop group 12-12), and tree nuts (crop group 14). The recommended 

primary plant commodity tolerances are derived from use of the Organization of Economic 

Cooperation and Development (OECD) statistical calculation procedures.

The proposed tolerances for processed commodities are not appropriate for citrus raw peel and 

potato wet peel. The processing studies do not show a concentration of residue in these 

commodities relative to the raw agricultural commodities (RAC). The proposed tolerance for 

citrus oil needs to be lowered from 4 ppm to 2.4 ppm, consistent with the results from 

application of the median processing factor to the highest average field trials (HAFT) for

oranges.

The proposed tolerances for livestock commodities are acceptable, except for liver of cattle, goat, 

horse, and sheep; hog fat, liver, meat, and meat byproducts; and milk fat. The livestock 

commodity tolerances are derived from consideration of the maximum reasonably balanced 

livestock diets and the livestock feeding studies. A tolerance value of 0.01 ppm is appropriate 

for liver (of cattle, goat, horse, and sheep), which would be covered by the meat byproducts

tolerance. The dietary exposures of hogs and poultry do not indicate a need for tolerances 

(residues are not anticipated), and there is no indication of significant concentration of 

cyantraniliprole in milk fat relative to milk.

With the exception of the proposed tolerance for leaves of root and tuber vegetables, all of the 

proposed tolerances for inadvertent residues (with a plantback interval (PBI) of 30 days) need to 

be revised. The revisions must reflect the recommended tolerances based on the use of the 

OECD statistical calculation procedures. For some crop groups, more than one tolerance was 

proposed for various components of the group (e.g. crop group 16 which includes forage, fodder, 

and straw of cereal grains); however, only one tolerance is possible per group, and the tolerance 

is based on the member commodity with the highest residue levels.
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2.2.4 International Harmonization

Currently there are no Codex Maximum Residue Limits (MRLs)/tolerances for cyantraniliprole. 

Therefore, there are no issues with harmonization of tolerances. Canadian MRLs are being 

proposed concurrently with US tolerances and are harmonized for primary crop and livestock 

commodities except for fruiting vegetables. The US fruiting vegetables tolerance is harmonized 

with the European Union.

2.3 Recommendations

2.3.1 Recommendations from Residue Reviews

860.1200 Directions for Use

The use in food/feed handling establishments is not supported by the required studies of OCSPP

Guideline 860.1460. Therefore, all uses related to treatment of food and feed handling/storage/ 

transportation are not allowed. This applies specifically to DuPontTM HGW86 SC Insect Control

(EPA Reg. No. 352-IAI).

The rotational crop restrictions must be amended, as follows: 

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

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

860.1650 Submittal of Analytical Reference Standards

Analytical reference standards for cyantraniliprole must be submitted to the Analytical 

Chemistry Lab, which is located at Fort Meade, to the attention of either Theresa Cole or Thuy 

Nguyen at the following address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

2.3.2 Recommendations from Occupational Assessment

The labeled use pattern for EPA Reg. No. 352-IAG must be clarified. The proposed label states 

both: “For vegetable transplants in and around greenhouses,” as well as “Do not apply to 

greenhouse or field grown vegetables, only apply to vegetable transplants grown in enclosed 

structures.” Note that both use patterns have been considered in this risk assessment and neither 

would result in occupational risk estimates of concern.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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2.3.3 Recommendations from Residential Assessment

There are no recommendations based on the residential exposure and risk assessment.

3.0 Introduction

Cyantraniliprole is a new second-generation RyR insecticide currently undergoing global joint 

review. It is a systemic insecticide that is mobile in both the xylem and phloem of plants. 

Cyantraniliprole belongs to the diamide class of chemistry whose pesticidal MOA is through 

unregulated activation of insect RyR channels. This then leads to internal calcium store 

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

the insect.

Cyantraniliprole has been jointly developed by DuPont and Syngenta, with a proposal for one 

technical product and 14 U.S. end-use product (EP) registrations, including several agricultural 

food-uses (PP#1F7894) and various residential use sites.

3.1 Chemical Identity

Table 3.1 Test Compound Nomenclature

Chemical Structure

Br

Cl

O

O

NH

N

N

HN

N

N

CH3

CH3

Empirical Formula C19H14BrClN6O2

Common Name cyantraniliprole

Company experimental name DPX-HGW86; SYN545377

IUPAC name 3-bromo-1-(3-chloro-2-pyridyl)-4’-cyano-2’-methyl-6’-(methylcarbamoyl)-

pyrazole-5-carboxanilide

CAS Name 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-

[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide

CAS Registry Number 736994-63-1

End-use product/EP 352-IAG, 18.66% SX; 352-IAI, 18.66% SC; 352-IAN, 18.66% SC; 352-IAT, 

50% FS; 352-ILT, 50% FS; 352-ILD, 10.2% SE; 352-ILT, 10.26% OD.

Chemical Class Anthranilic diamide

Known Impurities of Concern None

3.2 Physical/Chemical Characteristics
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The physicochemical properties of the technical grade of cyantraniliprole are summarized in 

Appendix D, Table D.1. The log of the octanol/water partition coefficient is 1.9, which indicates 

a lack of fat solubility and, therefore, low propensity to bioaccumulate in fatty tissue or milk. 

The low coefficient also suggests low potential for dermal absorption. At 20°C, the Henry’s 

Law constant was calculated to be 1.7×10-13 Pa/m3/mol (1.7×10-18 atm·m

3

/mol) based on vapor 

pressure and water solubility. Thus, cyantraniliprole is unlikely to volatilize significantly. 

Cyantraniliprole is hydrolytically stable under acid and neutral conditions, and has some water 

solubility (0.014 g/L) which suggests persistence in ground water. However, this is 

counterbalanced by lack of photolytic stability, which would impact surface waters.

3.3 Pesticide Use Pattern

Cyantraniliprole has been jointly developed by DuPont and Syngenta, with a proposal for one 

technical product and 14 U.S. EP registrations, including agricultural food-uses. The agricultural 

uses include foliar, soil, and seed treatment to various crops including cotton, fruits, oilseeds, and 

vegetables. The residential uses include turfgrass, ornamentals, and structural buildings 

(including indoor crack/crevice and outdoor broadcast). The proposed formulations include the 

following: flowable suspension (FS), granular (G), oil dispersion (OD), suspension concentrate

(SC), suspoemulsion (SE), and water dispersible granular (WG). A summary of all proposed

EPs is summarized in Table 3.3, and a detailed use pattern is summarized in Appendix A, Table 

A.1.

Table 3.3 Summary of Proposed Cyantraniliprole Products (DuPont and Syngenta Labels)

Trade Name

EPA Reg. 

File Symbol

Number

% Active 

Ingredient

Formulation 

Typea Target Crop/Use Site

DuPont

DuPontTM HGW86 

fly control bait 352-IAE 0.5% G(ready-to-use)

residential, commercial, and agricultural 

structures (including hotels, kennels, schools, 

food/beverage processing plants, 

poultry/livestock housing, horse stables, and 

food/feed handling establishments)

DuPontTM HGW86 

GH & N insect 

control

352-IAG

18.66%

(1.67 lb 

ai/gallon)

SC

ornamental plants/shrubs/trees and vegetable 

transplants in and around greenhouses, 

nurseries, interior plantscapes, lath and 

shadehouses (trees (including non-fruit 

bearing and nut trees), shrubs, evergreens, 

bedding plants, flowering plants, flowers, 

foliage plants, ground covers, vines (nonbearing), interior plantscape plants, and 

vegetable transplants (including fruiting, 

leafy, and tuberous/corm))

DuPontTM HGW86 

SC insect control 352-IAI

18.66%

(1.67 lb 

ai/gallon)

SC

single and multi-family residential buildings, 

schools, institutional, commercial, agricultural 

and industrial facilities (including 

warehouses, apartments, supermarkets, 

restaurants, motels, hotels, hospitals, 

daycares, and food 

handling/storage/processing establishments, 

animal production facilities, feedlots, broiler 

houses, livestock barns, pet kennels) and 

transportation equipment such as aircraft, 

trains, ships, boats and buses
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table 3.3 Summary of Proposed Cyantraniliprole Products (DuPont and Syngenta Labels)

Trade Name

EPA Reg. 

File Symbol

Number

% Active 

Ingredient

Formulation 

Typea Target Crop/Use Site

DuPontTM HGW86 

T&O insect control 352-IAL

18.66%

(1.67 lb 

ai/gallon)

SC

landscape and recreational turfgrass 

(including golf courses), sod farms, 

ornamental plants and interior plantscapes

DuPontTM 

VerimarkTM insect 

control powered by 

CyazypyrTM

352-IAN

18.66

(1.67 lb 

ai/gallon)

SC

Brassica vegetables, cucurbit vegetables, 

fruiting vegetables, leafy vegetables, tuberous 

and corm vegetables, citrus, potato seed 

pieces

DuPontTM 

CyazypyrTM 

Technical

352-ILA 96.7% white fine 

powder solid all proposed uses

DuPontTM 

Dermacor® Z-103 

insecticide seed 

treatment

352-ILI

50.0%

(5.21 lb 

ai/gallon)

FS rapeseed (canola), mustard seed

DuPontTM ExirelTM 

insect control 

powered by 

CyazypyrTM

352-ILO

10.20%

(0.83 lb 

ai/gallon)

SE

Brassica vegetables, bulb vegetables, cucurbit 

vegetables, fruiting vegetables, leafy 

vegetables, bushberries (subgroup 13-7B), 

citrus fruit, pome fruit, stone fruit, tree nuts, 

commercial greenhouse grown (to harvest: 

eggplant, pepper, tomato)

DuPontTM BeneviaTM 

insect control 

powered by 

CyazypyrTM

352-ILT

10.26%

(0.83 lb 

ai/gallon)

OD bulb vegetables, cotton, oil seed crops, 

tuberous and corm vegetables, tree nuts

Syngenta

Mainspring 

Insecticide (MAI 

with thiamethoxam)

100-RUEE 20.0%

(3.2 oz ai/lb) WG

ornamental plants, fruit and nut trees (nonbearing), and forest seedlings grown in 

greenhouses, lath and shade houses, 

containers, field nurseries and interiorscapes, 

vegetable plants grown for transplant and resale to consumers (fruiting vegetables, 

cucurbit vegetables, Brassica vegetables)

A16901B Residential 

Insecticide 100-RUEG 20.0%(3.2 oz ai/lb) WG residential landscape plants

A17960A ST 

Insecticide 100-RUEN 48.8%(600 g ai/L) FS potato seed pieces, sunflower seeds

A16901B CP 

Insecticide (MAI 

with thiamethoxam)

100-RUER 20.0%

(3.2 lb ai/oz) WG

Brassica vegetables, cucurbit vegetables, 

fruiting vegetables, leafy vegetables, tuberous 

and corm vegetables

A16901B Turf 

Insecticide 100-RUEU 20.0%(3.2 lb ai/oz) WG

turfgrass including golf courses, institutional, 

commercial and residential lawns, sod farms, 

sports fields, parks, municipal grounds and 

cemeteries

A17960B ST 

Insecticide 100-RURI 48.8%(600 g ai/L) FS potato seed pieces, sunflower seeds

a Formulation codes: G = granular, SC = suspension concentrate, SE = suspoemulsion, WG = water dispersible granules, OD = 

oil dispersion, FS = flowable suspension.

3.4 Anticipated Exposure Pathways

Humans may be exposed to cyantraniliprole in food and drinking water, since cyantraniliprole 

may be applied directly to growing crops and application may result in cyantraniliprole reaching 

surface and ground sources of drinking water. There are also residential uses of cyantraniliprole, 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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so there is likely to be exposure in residential or non-occupational settings. In an occupational 

setting, applicators may be exposed while handling the pesticide prior to application, as well as 

during application. There is also a potential for post-application exposure for workers reentering treated fields. 

This is the first aggregate risk assessment prepared for the proposed uses of cyantraniliprole. 

This risk assessment considers all of the exposure pathways based on the proposed new uses of 

cyantraniliprole.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the USDA under the Continuing 

Survey of Food Intake by Individuals (CSFII) and/or the CDC under the National Health and 

Nutrition Examination Survey/What We Eat in America (NHANES/WWEIA), and are used in 

pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and 

categorized by subgroups based on age, season of the year, ethnic group, and region of the 

country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups 

and exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-application are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Cyantraniliprole belongs to the anthranilic diamide class of pesticides. Anthranilic diamides are 

potent activators of RyRs; they control insects through unregulated activation of RyR channels 

leading to internal calcium store depletion that impairs regulation of muscle contraction. Insects 

exposed to anthranilic diamides exhibit general lethargy and muscle paralysis, ultimately

followed by death (Cordova et al., 2006).

RyRs are present across species and their role is similar across species. However, primary 

sequence diversity indicates differences between the isoforms within and across species. Insects 

possess a single form of RyR which is distributed in muscle and neuronal tissue. Whereas 

mammals possess three forms of RyR: (1) RyR1 which is distributed primarily in skeletal, (2) 

RyR2 which is distributed primarily in cardiac muscle, and (3) RyR3 which is heterogeneously 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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distributed. Mammalian RyRs are substantially less sensitive to the effects of anthranilic 

diamides than the insect RyR, ranging from 350 to >2500 times less sensitive (Satelle et al., 

2008; Lahm et al., 2009). This selectivity indicates relatively low mammalian toxicity in 

comparison to other pesticides that act on neuronal receptors. As seen in the cyantraniliprole 

toxicity studies relevant for human health, lethargy or effects on muscle control were not 

observed, supporting the concept that RyRs may not be the primary target in mammals. Instead, 

effects on the liver and thyroid are the most sensitive and are being used to derive PODs.

4.1 Toxicology Studies Available for Analysis

All of the required toxicity studies have been submitted to support the proposed food-use 

registrations for cyantraniliprole and the potential exposure scenarios associated with this action.

Furthermore, subchronic toxicity studies in rats, mice, and dogs contain additional data on liver 

enzymes, thyroid hormones, and metabolite measurements (beyond what is typically required by 

Agency guidelines).

The toxicology database is acceptable for characterizing cyantraniliprole hazard. It includes the

following toxicity studies: 14-day oral, 28-day oral, 90-day oral, 28-day dermal, 28- day 

inhalation, 2-year dietary combined chronic/carcinogenicity, 2-generation reproduction study, 

acute/subchronic neurotoxicity, and metabolism and pharmacokinetic in rats; 28-day oral, 90-day

oral, and carcinogenicity in mice; 28-day-oral, 90-day oral, and 1-year dietary in dogs; 

developmental studies in rats and rabbits; mutagenicity and genotoxicity studies in bacterial & 

mammalian model systems; 28-day dietary immunotoxicity studies in rats and mice; and in vivo

and in vitro dermal absorption factor studies on the SC, SE, and OD formulations.

Several metabolites which were not identified in the rat metabolism studies (IN-JSE-76, INPLT97, IN-F6L99, and IN-N5M09) were tested for mutagenic potential, and a 28-day oral 

toxicity study was conducted with IN-JSE-76. Mechanistic studies on the adrenal and thyroid

glands, and an in vitro thyroid peroxidase inhibition study are also available. Summaries of all 

toxicology studies are presented in the Toxicology Disciplinary Chapter (DP408479, W. Phang, 

11/21/2012).

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

ADME was evaluated in male and female rats following single and repeated low-dose (10 

mg/kg) administration, as well as a single high-dose (150 mg/kg) administration. A bile 

cannulation study was conducted with both single low- and single high-dose administration. All 

of the metabolism studies were conducted with both [Cyano14C]- and [pyrazo-carbonyl14C]-

cyantraniliprole. The data do not show an appreciable difference in ADME between the two 

labeled compounds. Therefore, the following discussion does not reference specific radiolabels.

The data also do not show a significant difference in ADME between single (at the low dose 

level of 10 mg/kg/day) and multiple (at 10 mg/kg/day) dosing and the results following single 

dosing are typical of what was seen following multiple dosing.

Cyantraniliprole is readily absorbed, and the absorption patterns are similar at low and high 

doses. The majority of the absorption occurs during the first 24 hours (85% of the absorbed 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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radioactivity), and the peak plasma concentration is reached approximately 2 hour after dosing, 

regardless of the sex or dose level. The values of Cmax and area-under-the-curve (AUC) 

demonstrate a greater internal dose in female rats than in male rats. With dose-normalized AUC, 

the data suggest a decrease in percent absorption at the high dose in comparison to the low dose. 

Following oral dosing, the majority of the dose is initially associated with the gastrointestinal 

(GI) tract contents followed by uptake and distribution to all tissues. The tissue concentration 

data show the skin, liver, GI content, and muscle to have a higher percent of the administered 

dose. However, each of the four tissues had less than 0.5 % of the administered dose at 168 

hours. The mean half lives in plasma are shorter in males than in females (≈ 42 hours and 129 

hour in males and females, respectively). As expected, female rats contained a greater 

proportion of 14C residues than male rats.

The absorbed cyantraniliprole was readily and extensively metabolized; IN-N7B69 and INMYX98 were initially formed due to respective hydroxylations of methylphenyl and N-methyl 

carbon. During the initial step, cyantraniliprole also underwent nitrogen-to-carbon ring closure 

to yield IN-J9Z38. Further metabolism of the hydroxylated metabolites includes N-methylation, 

nitrogen-to-carbon cyclization with loss of water molecule, oxidation of alcohols to carboxylic 

acids, amide bridge cleavage, amine hydrolysis, and O-glucuronidation. The bile was found to 

be very rich in metabolites, and most of the metabolites were found in both urine and feces.

Rats given a single 10 mg/kg dose eliminated a greater percentage of the dose in urine (22.0 to 

34.6%) than rats dosed with 150 mg/kg (11.8 to 14.8% of the dose). For both dose levels, the 

majority was eliminated by 24 to 48 hours after administration with the feces as the major route 

of elimination. By seven days after dosing, the mean percentage for total recovery ranged from 

88.3 to 96.5% of the administered dose. Furthermore, there was no appreciable tendency for 

bioaccumulation to occur.

4.3 Toxicological Effects

In general, cyantraniliprole administration 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 are observed across multiple species (rats, mice, dogs). The 

increases in liver weights are accompanied by hepatocellular hypertrophy along with increases in 

metabolic liver enzymes (cytochrome P450) and UDP-glucuronyltransferase activity. In rats, the 

liver effects tend to be more pronounced in females than in males, which is consistent with the

pharmacokinetic data that shows a greater internal dose in female rats than in male rats. Most of 

the liver effects seen in the subchronic rat toxicity studies consist of increases in liver weights 

and hepatocellular hypertrophy. These effects are considered adaptive, whereas the liver effects 

in the chronic/carcinogenicity study are considered adverse based on conditions such as foci of 

cellular alteration and focal vacuolation. The data also show that dogs are more sensitive to liver 

effects than rats and mice. The adverse liver effects in rats occur at approximately 85 mg/kg 

with 2-year treatment while comparable effects are seen at 6 mg/kg with 1-year treatment in 

dogs; adverse liver effects in mice occur at even higher dose levels (769 mg/kg with 18-month 

treatment).
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The available data also show thyroid hormone homeostasis is altered in rats following exposure 

to cyantraniliprole after 28 or 90 days. The findings include decreases in T4 (and in some cases,

T3) and increases in TSH. Thyroid follicular cell hypertrophy (graded as minimal) is evident in 

both the 28-day and 90-day studies with rats. However, it does not persist with longer term 

dosing because it is neither present at the one year interim sacrifice nor following the two years 

of exposure in the 2-year chronic toxicity/carcinogenicity study in rats.

A dose-related increase in the incidence of thyroid follicular epithelial cell hypertrophy/

hyperplasia occurred in the P1 and F1 adult parental animals of a reproduction study. Based on 

the submitted mechanistic data, HED proposes an adverse outcome pathway (AOP) by which 

cyantraniliprole disrupts thyroid homeostasis via induction of hepatic metabolizing enzymes 

including UDP glucuronyltransferase (Wolf et al., 2006). However, at this time, HED has not 

conducted a Mode of Action Analysis using the MOA Framework. The PODs selected for risk 

assessment are derived from liver effects in the dog. As such, the limited mechanistic data do 

not inform the PODs. The submitted data do support a conclusion that the effects on the thyroid 

are secondary to effects on the liver. Specifically, the available data in the rats is consistent with

increases in hepatic cytochrome P450 content and UDP-glucuronyltransferase activity, which 

lead to decreases in plasma T4 thyroid hormone level and alteration of thyroid hormone 

homeostasis, resulting in increases in TSH. Increased plasma TSH then stimulates the thyroid 

gland, which results in the thyroid follicular epithelial cell hypertrophy/hyperplasia. 

Effects in the dog studies provide lower NOAELs for use in deriving PODs compared to the rat 

studies. In the 28-day, 90-day, and 1-year dog studies, consistent findings in clinical chemistry 

parameters include: increases in alkaline phosphatase, alanine aminotransferase, and gamma 

glutamyltransferase; and decreases in total protein, albumin, and cholesterol. The liver effects in 

the dog also show progressive severity with increased duration of exposure. For example, in the 

28- day and 90-day dog studies, clinical chemistry parameters indicate liver toxicity; while, in 

the 1-year dog study, similar clinical chemistry changes are observed but are associated with 

hepatocellular histopathological changes. When considered in combination with altered enzyme 

levels, significant increases in absolute and relative liver weights are indicative of adverse liver 

effects. Microscopic observations in the liver include hepatocellular degeneration, inflammation 

of the portal regions with increased fibrous connective tissues and pigment deposition, and/or 

bile duct hyperplasia. 

Although it is not observed in dogs, an increased incidence of adrenal cortical microvesiculation 

is mainly seen in males in both the 90-day rat and mouse studies, and in the 2-generation 

reproduction rat study. The microvesiculation in affected groups is predominantly graded as 

minimal with a few incidences graded as mild. These microvesiculations are not associated with 

changes in gross appearance, adrenal cortical cytotoxicity, hypertrophy, or atrophy. Effects on 

cortical cell function are not associated with the microvesiculation changes as demonstrated by 

studies evaluating corticosterone concentrations in serum and urine with ACTH stimulation. In 

addition, treatment-related neoplastic changes are not observed in the adrenal cortex of rats 

following chronic dietary administration of cyantraniliprole. Rats exposed to cyantraniliprole do

show a slight increase in lipid storage in the adrenal cortex. However, the study report indicates

that the adrenal cortex normally shows a microvesiculation appearance under light microscopes

resulting from the storage of lipid to be used as precursors for steroid hormone synthesis. 
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Although clearly treatment-related, the slight microvesiculation of the adrenal cortex noted 

following exposure to cyantraniliprole is not considered toxicologically relevant.

The results of the chronic/carcinogenicity in rats and the carcinogenicity study in mice do not 

show compound-related increase in tumor incidence. Genotoxic potential is not found in the 

mutagenicity study battery.

Cyantraniliprole does not produce developmental toxicity in either rats or rabbits. In rats, there 

are no maternal or fetal effects up to the limit dose of 1000 mg/kg/day. In rabbits, reduced pup 

weight and late gestation abortions or early deliveries occur as a result of severe maternal 

toxicity. The 2-generation reproduction study in rats shows that cyantraniliprole has no adverse 

effect on any reproductive parameters. In offspring, reductions in body weight and organ

weights (thymus and spleen), as well as clinical signs such as dehydration, are noted at dietary 

concentrations where there is evidence of maternal toxicity. A significant increase in the thyroid 

weights (absolute and relative) is seen in P1 and F1 parental animals at 14 mg/kg or above with a

corresponding dose-related increase in the incidence of the thyroid follicular epithelial cell 

hypertrophy/hyperplasia in the P1 males and females at 136 mg/kg/day or above and in F1 

parental males and females at 14 mg/kg/day or above. In the F1 parental males and females, the 

increased incidence of thyroid follicular epithelial cell hypertrophy/hyperplasia occur at lower 

dose level (14 mg/kg/day) relative to that of the P1 parental males and females (136 mg/kg/day). 

However, a clear NOAEL (1.4 mg/kg/day) is demonstrated for thyroid follicular cell 

hypertrophy/hyperplasia in the F1 parental animals, which were dosed prenatally and postnatally. 

Furthermore, the PODs selected for risk assessment (1 or 3 mg/kg/day) are protective of the 

effects seen in the F1 parental animals.

Acute and subchronic neurotoxicity studies reveal no evidence of neurotoxicity. Similarly, 

cyantraniliprole does not adversely impact the immune system in rats and mice. The decrease in 

thymus and spleen weights seen in the 2-generation reproduction study weights are not observed 

in rat or mice. Based on the results of a 28-day dermal study in rats (as well as the dermal LD50

study), cyantraniliprole does not demonstrate any appreciable toxicity via dermal exposure. The 

28-day inhalation toxicity study in rats does not show any adverse systemic or portal of entry 

effect at the highest concentration tested (100 mg/m

3

, equivalent to 18 mg/kg/day). However, an 

increase in the incidence of minimal laryngeal squamous metaplasia is seen at the highest tested 

concentration. This finding is considered to be treatment related but not adverse because the 

effect is graded as minimal. With longer duration of treatment and higher concentrations, the 

effects seen in the larynx could potentially progress and become adverse.

Cyantraniliprole has no significant acute toxicity via the oral, dermal, and inhalation routes of 

exposure (Toxicity Category IV). Cyantraniliprole is not an eye or skin irritant and does not 

cause skin sensitization. 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

Based on the currently available toxicity and exposure data, the risk assessment team 

recommends that the FQPA Safety Factor be reduced to 1X for the following reasons: there is a 

complete toxicological data base, there is no evidence of neurotoxicity, the PODs based on liver 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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toxicity selected for risk assessment are protective of effects on the thyroid observed in the 

reproductive toxicity study, and there is no uncertainty in the exposure data. The details for 

reducing the FQPA safety factor to 1X are detailed below.

4.4.1 Completeness of the Toxicology Database

The toxicology database is complete for cyantraniliprole.

4.4.2 Evidence of Neurotoxicity

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.

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

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 NOAEL (1.4 mg/kg/day) is 

established for F1 parental animals, and the 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. As such, a comparative thyroid study is not required. The 

FQPA safety factor can be reduced to 1X.

4.4.4 Residual Uncertainty in the Exposure Database

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, and conservative ground and surface drinking water 

modeling estimates. New 2012 Residential 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.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

As discussed in Section 4.3, the thyroid effects in treated animals are a consequence of a series 

of effects in the liver leading to disturbance in thyroid hormone homeostasis and thyroid effects.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Therefore, the liver effects are the most appropriate in selecting the toxicity endpoints and PODs

for risk assessment. The liver effect seen in the 1-year dog study provides the most solid basis 

for a toxicity endpoint and for the POD for chronic dietary exposure risk assessment. In 

addition, the POD is also protective of the thyroid effects seen in all toxicity studies in rats. For 

dermal and inhalation exposure risks, route specific studies are considered.

A dermal POD is not chosen because systemic toxicity is not seen in the 28-day dermal toxicity 

study in rats up to the limit dose (1000 mg/kg/day). The short- and intermediate-term incidental 

oral POD is based on two co-critical studies: the 28-day and 90-day oral toxicity studies in dogs 

(NOAEL = 3.0 mg/kg/day). In the special 28-day study (MRID 48119942) in dog, liver effects 

were observed at the LOAEL of 35 mg/kg/day. As such, the liver findings in the dog are 

relevant for the short-term duration of 1-30 days.

The short- and intermediate-term inhalation PODs are based on the results of a 28-day inhalation 

toxicity study in rats (NOAEL = 10.08 mg/kg/day for occupational exposure, NOAEL = 7.2 

mg/kg/day for residential exposure). To determine the inhalation PODs for residential and 

occupational exposure, the Agency’s Reference Concentration (RfC) methodology was used to 

calculate human equivalent concentrations (HECs). These calculations are detailed in Appendix 

B, Section B.4. The HECs are based on a 28-day rat inhalation study which show no systemic or 

port of entry effects at the highest concentration (NOAEL = 0.1 mg/L). Because the 28-day 

study was conducted 6 hours per day, 5 days per week, the HECs are adjusted to represent both 

residential and occupational exposure scenarios. For residential exposure, the HEC is adjusted to 

represent continual exposure for 24 hours per day, 7 days per week. For occupational exposure, 

the HEC was adjusted to represent an average work week for 8 hours per day, 5 days per week. 

The short-term inhalation HEC of 0.21 mg/L calculated for residential exposures is then 

converted to a human equivalent dose NOAEL of 7.2 mg/kg/day to allow for comparison to 

estimated residential inhalation doses (which are in units mg/kg/day). The short- and 

intermediate-term inhalation HEC of 0.05 mg/L calculated for occupational exposures was also 

converted to a human equivalent dose NOAEL of 10.08 mg/kg/day to allow for comparison to 

estimated occupational inhalation doses (which are in units mg/kg/day).

Although a route specific 28-day inhalation study is used to establish the intermediate-term POD, 

some of the toxicity data indicate a progression in toxicity with time. The data indicate an 

approximate three-fold difference in the LOAEL between a 28-day oral toxicity study in rats (53 

mg/kg/day) and a reproduction study in rats (14 mg/kg/day). Therefore, an uncertainty factor of 

3X is selected to account for using a POD from a short-term 28-day day inhalation study to 

assess intermediate-term exposure (1- 6 months). Given that the 28-day inhalation study does 

not show any adverse effects at the highest concentration, HED acknowledges that the 

application of 3X is a conservative approach. However, given the progression of liver effects 

seen in oral studies, HED cannot rule out the potential for adverse port of entry or systemic 

effects given longer exposures.

The toxicity endpoints and PODs are summarized in Tables 4.5.4a and 4.5.4b, and detailed 

rationale for the selections is presented in Appendix B, Section B.3.
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4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

In accordance with the requirements of the FQPA (1996), HED has considered the potential for 

concurrent cyantraniliprole exposure via oral, dermal, and inhalation routes. HED aggregates 

exposure from different routes for each population if the same toxic effects are seen for that 

duration of exposure by each route. The dermal route of exposure does not need to be combined 

with another route of exposure or included in the aggregate risk assessment because there is no 

identified dermal hazard. For adults, the oral and inhalation routes of exposure should not be

aggregated since the endpoints of concern are not common.

4.5.3 Cancer Classification and Risk Assessment Recommendation

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. For cancer risk assessment, a non-linear approach is recommended and adequately 

accounts for all chronic toxicity.

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk

Assessment

Table 4.5.4a Summary of Toxicological Doses and Endpoints for Cyantraniliprole for Use in NonOccupational/Residential Human Health Risk Assessmentsa

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute 

Dietary 

(General 

Population, 

including

Infants and 

Children 

and 

Females 13-

49 years of 

age)

An effect attributed to a single dose was not identified in the toxicology database. 

Chronic 

Dietary (All 

Populations)

NOAEL = 

1 

mg/kg/day

UFA = 10x

UFH =10x

FQPA SF = 

1x

cRfD = 

0.01 

mg/kg/day

cPAD = 

0.01

mg/kg/day

1-year oral study in dogs.

LOAEL = 6 mg/kg/day based on effects indicative 

of liver toxicity (increased liver weights and 

alkaline phosphatase activity), and significant 

decreases in albumin level.
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Table 4.5.4a Summary of Toxicological Doses and Endpoints for Cyantraniliprole for Use in NonOccupational/Residential Human Health Risk Assessmentsa

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Incidental 

Oral

Short-Term 

(1-30 days)

and 

Intermediate

-Terms (1-6 

months)

NOAEL = 

3 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

LOC = 100

28-day and 90-day oral study in dogs.

28-day LOAEL = 35 mg/kg/day (lowest dose 

tested) based on decreases in body weight, food 

consumption, food efficiency, and changes in 

clinical chemistry (↑ALP, ↓ cholesterol and ↓ 

albumin).

90-day LOAEL = 32 mg/kg/day based on a 

collection of treatment-related effects indicative of 

liver toxicity. 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. 

Dermal 

Short-Term 

(1-30 days)

A toxicity endpoint was not identified.

Systemic toxicity was not seen in 28-day dermal toxicity in rats at the limit dose (1000 

mg/kg/day). There are no concerns for developmental or reproductive toxicity or neurotoxicity.

Inhalation 

Short-Term 

(1-30 days)

NOAEL = 

0.1 mg/L UFA = 3Xb

UFH = 10X

FQPA SF = 

1X

LOC = 30

28-day inhalation toxicity study in rats.

A LOAEL was not established because the highest 

concentration tested (0.1 mg/L) did not demonstrate 

any adverse portal of entry or systemic effects.

HEC = 

0.05 mg/L

HED = 7.2 

mg/kg/day

Cancer (oral, 

dermal, 

inhalation)

Classification: “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.

a Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to 

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. 

NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. HED = human equivalent dose. 

HEC = human equivalent concentration. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). 

UFH = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety 

Factor. LOC = level of concern.

b The magnitude of the UFs applied is dependent on the methodology used to calculate risk. The RfC methodology takes into 

consideration the pharmacokinetic (PK) differences, but not the pharmacodynamic (PD) differences. Consequently, the UF for 

interspecies extrapolation may be reduced to 3X (to account for the PD differences).
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Table 4.5.4b Summary of Toxicological Doses and Endpoints for Cyantraniliprole for Use in Occupational 

Human Health Risk Assessmentsa

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal 

Short-Term 

(1-30 days) 

and 

Intermediate

-Terms (1-6 

months)

A toxicity endpoint was not identified.

Systemic toxicity was not seen in 28-day dermal toxicity in rats at the limit dose (1000 

mg/kg/day). There are no concerns for developmental or reproductive toxicity or neurotoxicity.

Inhalation 

Short-Term 

(1-30 days) 

NOAEL = 

0.1 mg/L

UFA = 3Xb

UFH = 10X LOC = 30

28-day inhalation toxicity study in rats.

A LOAEL was not established because the highest 

concentration tested (0.1 mg/L) did not demonstrate 

any adverse portal of entry or systemic effects.

HEC = 

0.05 mg/L

HED = 

10.08 

mg/kg/day

Inhalation 

Intermediate

-Term (1-6 

months)

NOAEL = 

0.1 mg/L

UFA = 3X

UFH = 10X

UFDB = 3Xc

LOC = 100

28-day inhalation toxicity study in rats.

A LOAEL was not established because the highest 

concentration tested (0.1 mg/L) did not demonstrate 

any adverse portal of entry or systemic effects.

HEC = 

0.05 mg/L

HED = 

10.08

mg/kg/day

Cancer (oral, 

dermal, 

inhalation)

Classification: “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.

a Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to 

mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. 

NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. HED = human equivalent dose. 

HEC = human equivalent concentration. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). 

UFH = potential variation in sensitivity among members of the human population (intraspecies). UFDB = database uncertainty 

factor: use of a short-term study for intermediate-term risk assessment. FQPA SF = FQPA Safety Factor. LOC = level of 

concern.

b The magnitude of the UFs applied is dependent on the methodology used to calculate risk. The RfC methodology takes into 

consideration the pharmacokinetic (PK) differences, but not the pharmacodynamic (PD) differences. Consequently, the UF for 

interspecies extrapolation may be reduced to 3X (to account for the PD differences).

c A route specific 28-day inhalation study is used to establish the intermediate term exposure toxicity endpoint and point of 

departure. Some of the toxicity data on cyantraniliprole indicate that there was a progression in toxicity with time. The data 

indicate a ~three-fold difference in the LOAEL between a 28-day oral toxicity study in rats (53 mg/kg/day) and a reproduction 

study in rats (14 mg/kg/day). Therefore, an uncertainty factor of 3X was selected to account for using a POD from a short-term 

28-day day inhalation study to assess intermediate-term exposure (1- 6 months).
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5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

The plant metabolism studies are adequate. Studies indicate that metabolism of cyantraniliprole 

is similar following foliar and soil application to the following crops: rice, lettuce, cotton, and 

tomato (respectively representing cereal, leafy vegetables, oilseeds, and fruit groups). The 

metabolic fate of this insecticide is complex with the formation of many low level metabolites. 

However, cyantraniliprole is the major component in rice, lettuce, cotton, and tomato; results in 

crop field trials confirm that the parent compound is the predominant residue in all crop fractions 

at various sampling points up to crop maturity. Numerous metabolites were detected in various 

crop matrices.

In plants, metabolism of cyantraniliprole appears to proceed via loss of water leading to the 

formation of the quinazolinone ring, oxidation of the cyano group, and hydroxylation of the Nmethyl and/or tolyl methyl group. Immature and mature samples taken of four different crop 

groups covering a wide range of agro-climatic conditions show very similar metabolic pathways. 

The formation of a new metabolite soon after application would be very unlikely. The chemical 

names and structures of each metabolite are summarized in Appendix C, Table C.1.

The nature of the residues in livestock is adequately understood. The metabolism of 

cyantraniliprole in poultry and ruminants was found to be similar. The metabolism in livestock 

is extensive and the amount of unchanged parent present in milk, eggs, and tissues is matrixdependent. The major components present in various tissues include a combination of the parent

compound, IN-N7B69, IN-J9Z38, IN-MLA-84, and/or IN-MYX98.

In rotational crops, the parent compound is the major residue present in soybean, wheat grain, 

lettuce, and beet root. As in primary crops, many minor metabolites exist. In livestock 

feedstuffs such as wheat (forage, hay, and straw) and soybean (foliage), parent plus a few

metabolites (IN-J9Z38, IN-JSE76, and/or IN-MLA84) are present as major residues.

5.1.2 Summary of Environmental Degradation

Since cyantraniliprole is soluble in water (14.2 mg/L at 20oC), it may move from the treated 

fields to surface water through run-off occurring shortly after application (i.e. rainfall events). 

Mobility and persistence of cyantraniliprole degradates may be of concern. Due to the stability 

and mobility of the degradates, some compounds may move from the treated field to 

groundwater through leaching. Batch equilibrium studies on cyantraniliprole and its degradates 

characterize cyantraniliprole as being moderately mobile (Koc = 157 to 376 mL/goc) in test soils. 

Cyantraniliprole degradates have measured Koc values ranging from 14 to 32,152 mL/g,

indicating that some degradates are more mobile than the parent and some are less mobile than 

the parent. 
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Major routes of dissipation include alkaline-based hydrolysis, photodegradation in aqueous and 

moist soil environments, and aerobic and anaerobic biotransformation in terrestrial and aquatic 

environments. Considering abiotic degradation, hydrolytic degradation appears to be pH 

dependent, with degradation increasing with increasing pH. Photodegradation appears to be a 

major degradation pathway in aqueous and moist soil environments. The aqueous photolysis 

study shows a phototransformation half-life of about 7.9 hours or 0.33 days. Biodegradation is 

an effective dissipation pathway for cyantraniliprole, with anaerobic biotransformation occurring 

at a faster rate than aerobic biotransformation in terrestrial and aquatic environments. It is 

important to note that all aerobic soil metabolism degradation half-life values are significantly 

longer than that of the parent cyantraniliprole.

Based on laboratory studies, the major environmental degradates of cyantraniliprole include INJ9Z38, IN-NXX69, IN-QKV54, IN-RNU71, IN-JSE76, IN-JCZ38, IN-PLT97, and IN-K5A78, 

IN-K5A78 and IN-PLT97. The majority of these degradates formed under both microbialmediated and abiotic processes. Major degradates that continued to increase over time to the 

study termination in various fate studies include IN-J9Z38, IN-RNU71, IN-JSE76, IN-JCZ38, 

IN-K5A78 and IN-PLT97. In addition, IN-K5A77, IN-K5A79, and IN-PLT97 were also 

detected in the terrestrial field studies. 

5.1.3 Comparison of Metabolic Pathways

The metabolism/degradation in plant, livestock, rat, rotational crops, and processed commodities 

is similar. The cyantraniliprole parent compound along with the same minor metabolites is the 

common theme (see Appendix C, Table C.1).

The nature of the residues in processing studies indicates that cyantraniliprole degrades under

simulated conditions of pasteurization and sterilization. Further degradation of cyantraniliprole 

occurs under hydrolytic conditions representative of baking, brewing, or boiling at 100 C for 60 

minutes in a pH 5 solution. In actual processing studies, the formation of these degradates was 

very minor, except for a few processed commodities (such as cooked spinach, tomato 

puree/paste, and apple sauce).

Rotational crop metabolism is similar to primary crop metabolism. Cyantraniliprole was the 

major component of the residue at all PBIs (30, 120, 365 days). Transfer of cyantraniliprole and 

its metabolites to animal feed items was higher than observed in the commodities for human 

consumption. Inadvertent tolerances for various livestock feed items were necessary and were 

established based on a PBI of 30 days. Residues are not anticipated in food commodities from a 

30-day PBI or are covered by primary crop commodity tolerances (with the exceptions of root 

and tuber vegetables subgroup 1A and leaves of root and tuber vegetables group 2).

Metabolism in lactating goats and laying hens is similar. Transfer of residues to poultry 

commodities was low, and cyantraniliprole was generally the major component of the total 

radioactive residue approach (TRR) in all consumable matrices. The available feedstuffs with 

cyantraniliprole residues produced a relatively low dietary burden for livestock. Residues are 

expected in poultry and hog commodities; low levels are anticipated in ruminant commodities. 
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In the feeding studies, there was no indication of significant concentration of cyantraniliprole in 

milk fat or fat tissue.

5.1.4 Residues of Concern Summary and Rationale

Parent cyantraniliprole was detected as a main residue in the metabolism studies, crop field trials,

and livestock feeding studies. Based on this, it is considered an appropriate marker for primary 

crops, rotational crops, and livestock commodities. Thus, parent cyantraniliprole is 

recommended as the residue of concern (ROC) for tolerance enforcement. Due to structural 

similarity and lack of toxicity data for the associate metabolites, hazard is expected to be similar.

Primary Crops: Metabolism studies show parent cyantraniliprole as a major residue in rice, 

lettuce, cotton, and tomato; and IN-J9Z38 as a major residue in rice and lettuce. However, in 

lettuce field trials, IN-J9Z38 was generally absent. The crop field trials show the presence of 

several metabolites at levels below the LOQ or at significantly lower amounts than parent 

cyantraniliprole.

Rotational Crops: Parent cyantraniliprole was the main residue in all the commodities for 

human consumption. Other metabolites were present at similar or lower levels than parent 

cyantraniliprole in feedstuff commodities only. Since the metabolites will not be significant 

contributors to the overall livestock dietary burden, inclusion of the metabolites in the residue of 

concern will not significantly affect the dietary risk assessment.

Processed Commodities: Although metabolites IN-J9Z38, IN-N5M09, and IN-F6L99 were 

formed under conditions of heat and/or hydrolysis, only IN-J9Z38 was generally observed at 

significant concentrations in a few processed commodities (e.g. cooked spinach, apple sauce). 

IN-N5M09 and IN-F6L99 were found at low levels in apple sauce and cooked spinach, but were 

absent (<LOQ) in a variety of other processed commodities. In addition to parent 

cyantraniliprole, metabolite IN-J9Z38 is included as a residue of concern for risk assessment.

Livestock: Feeding studies show that parent cyantraniliprole, IN-N7B69, IN-MLA84, INMYX98, and/or IN-J9Z38 are likely to be present in significant amounts in some commodities. 

These metabolites are assumed to have similar toxicity to parent cyantraniliprole. In addition to 

parent cyantraniliprole, metabolites IN-N7B69, IN-MLA84, IN-MYX98, and IN-J9Z38 are 

included as residues of concern for risk assessment.

Water: Cyantraniliprole is likely to extensively degrade in the environment through several 

degradation routes to form IN-J9Z38, IN-NXX69, IN-QKV54, IN-RNU71, IN-JSE76, INJCZ38, IN-K5A78, IN-K5A77, IN-K5A79, and IN-PLT97. These degradates were major 

degradates in relevant laboratory studies, formed in the field, or both. In the absence of toxicity 

data and similar analogs, these degradates are considered no more toxic than the parent 

compound.
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Table 5.1.4 Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression

Matrix Residues included in Risk 

Assessmenta

Residues included in 

Tolerance Expression

Plants

Primary Crop Cyantraniliprole Cyantraniliprole

Rotational Crop Cyantraniliprole Cyantraniliprole

Processed 

Commodities

Cyantraniliprole and INJ9Z38Cyantraniliprole

Livestock

Ruminant Cyantraniliprole, IN-N7B69, 

IN-MLA84, IN-MYX98,

and/or IN-J9Z38b

Cyantraniliprole

Poultry Cyantraniliprole

Drinking Water Cyantraniliprole and the 

degradates listed belowc Not Applicable

a Cyantraniliprole is 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-

carboxamide. The names and chemical structures of the metabolites can be found in Appendix C, Table C.1. 

b Parent cyantraniliprole is recommended as residue of concern in all commodities along with the metabolites that are at 

significant amounts in the commodity under consideration. 

c IN-J9Z38, IN-NXX69, IN-QKV54, IN-RNU71, IN-JSE76, IN-JCZ38, IN-K5A78, IN-K5A77, IN-K5A79, and IN-PLT97. 

5.2 Food Residue Profile

Quantifiable residues of cyantraniliprole from foliar application or a combination of seed 

treatment or at-plant applications and foliar applications were consistently found. The residue 

from foliar applications was primarily a surface residue, as evidenced by distribution of residue 

in peel and pulp.

Adequate field trial data are available to support the proposed uses on Brassica vegetables 

(Group 5), bulb vegetables (Group 3-07), bushberries (Group 13-07B), oilseeds (Group 20), 

citrus fruits (Group 10-10), cucurbit vegetables (Group 9), fruiting vegetables (Group 8-10), 

leafy vegetables (non-Brassica) (Group 4), pome fruits (Group 11-10), stone fruits (Group 12-

12), tree nuts (Group 14), and tuberous and corm vegetables (Subgroup 1C). However, there are 

no data to support use in food/feed handling, storage, and transport facilities.

Processing studies have been submitted for several crops including potato, tomato, orange, apple, 

plum, and cottonseed. Tolerances are not needed for most processed commodities, as parent

cyantraniliprole did not increase from the RAC to the processed commodity. Cyantraniliprole 

did concentrate in tomato dry pomace, sundried tomatoes, orange oil, apple puree, apple dry 

pomace (but not wet), and dried plums. Citrus oil is recognized as a processed commodity for 

tolerance purposes.

Storage stability data have been submitted for residues of cyantraniliprole and various 

metabolites in five categories of plant commodity matrices, in milk, and in eggs. The storage 

stability intervals cover the actual intervals of frozen storage of plant and livestock commodity 

samples from the crop field trials, processing studies, and livestock feeding studies. Corrections 

for loss during storage are not needed for any plant or livestock commodity for purposes of 

tolerance considerations.
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Based on the livestock metabolism studies, HED concludes that storage stability data for the 

livestock matrices are unnecessary. This is mainly due to the fact that there was no change in the 

metabolic profile after 10 months of frozen storage for eggs, muscle, and fat of hens nor after 6 

months of frozen storage for milk, fat, kidney and liver of goats. Furthermore, the egg, milk, and 

tissue samples from the livestock feeding studies were stored frozen and analyzed within 30 days 

of collection.

Adequate cattle and poultry feeding studies have been submitted. The data indicate that 

tolerances for milk and the fat, meat, and meat byproducts of cattle, goat, horse, and sheep are 

needed to support the proposed cyantraniliprole uses, but tolerances are not required for hog and 

poultry commodities. 

The confined rotational crop studies are adequate. Adequate limited and extended field 

rotational crop studies have been submitted. The studies indicate the presence of nonquantifiable levels of parent residues in/on cereal grains, soybean seed, and legumes, and 

quantifiable levels in leafy vegetables, foliage of legume vegetables, and some root commodities,

at a PBI of 30 days. The studies also indicate the presence of quantifiable levels of parent 

residues in livestock feed stuffs such as alfalfa, grass hay, and soybean hay. Inadvertent or 

indirect tolerances for these rotational crops are needed at a PBI of 30 days. 

5.3 Water Residue Profile

Since cyantraniliprole is a new chemical, there is no monitoring data regarding the 

concentrations of the parent cyantraniliprole in surface or ground water. The drinking water 

residues used in the dietary risk assessment were provided by EFED (DP403747, C. Koper, 

11/21/2012). This drinking water assessment was conducted on the parent cyantraniliprole and

numerous degradates. The degradates included in the drinking water assessment are the 

following: IN-J9Z38, IN-NXX69, IN-QKV54, IN-RNU71, IN-JSE76, IN-JCZ38, IN-K5A78, 

IN-K5A77, IN-K5A79, and IN-PLT97. In the absence of toxicity data and similar analogs, these 

degradates are considered no more toxic than the parent compound and the TRR was 

recommended for risk assessment purposes.

The EDWCs for use in the human health risk assessment are based on the maximum proposed 

application rates specified in the product labels. EDWCs for the chronic assessments were 

estimated using two EFED Tier I screening models. For surface water, the FIRST (FQPA Index 

Reservoir Screening Tool) Version1.1.1 model was used to estimate drinking water 

concentrations. For ground water, the SCI-GROW (Screening Concentration in Ground Water)

Version 2.3 model was used to predict the maximum acute concentrations present in shallow 

ground water. The model and its description are available at the EPA internet site: 

http://www.epa.gov/oppefed1/models/water/. Based on FIRST and SCI-GROW modeling, the 

surface and ground water EDWCs for the parent cyantraniliprole for various uses are presented 

in Table 5.3.

For drinking water derived from surface water, the FIRST model estimated the acute and chronic 

(annual average) EDWC at 43.14 μg/L and 24.45 μg/L, respectively. For drinking water derived 

from ground water, the SCI-GROW model estimated the ground water EDWC at 6.33 μg/L. The 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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EDWC chosen for chronic dietary assessment is the 1-in-10 year annual mean of 24.45 μg/L 

from surface water estimates.

Table 5.3 Maximum Estimated Drinking Water Concentrations (EDWCs) Resulting from Applications of

Cyantraniliprole for Various Usesa

Drinking 

Water Source 

(Model)

Label Use Method

Application 

Rate

(interval 

between 

applications)b

PCA 

Adjustment 

Factor c

Peak Day 

(acute) 

Conc.

Annual 

Average

(chronic) 

Conc.

μg/L μg/L

Surface Water 

(FIRST)

352-ILT

352-ILO

Various 

Crops Aerial 3 app @ 0.133 ai/acre (5 days)

1

40.77 23.11

352-IAN Citrus

Vegetables Chemigation 1 app @ 0.4 ai/acre (NA) 40.75 23.09

352-ILI Canola

Mustard

Seed 

Treatment

1 app @ 0.4 

ai/acre (NA) 40.75 23.09

352-IAE Fly Control Bait

Broadcast

5 app @ 0.087 

ai/acre (7 days) 43.14 24.45

100-RUEN

100-RURI Potato Seed Treatment

1 app @ 0.468 

ai/acre (NA) 23.84 13.51

Ground Water

(SCI-GROW)

352-ILT

352-ILO

Various 

Crops Aerial 3 app @ 0.133 ai/acre (5 days)

--- 5.40 5.40

100-RUEN

100-RURI Potato Seed Treatment

1 app @ 0.468 

ai/acre (NA)

--- 6.33 6.33

a Bold values denote maximum EDWCs.

b NA = Not Applicable.

c Percent Cropped Area (PCA) Adjustment Factor = 1 following updated PCA guidance document (2012).

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

A somewhat refined chronic (food and drinking water) dietary assessment was conducted 

assuming average field trial residues for all proposed crops (except crop subgroup 1A) and that 

100% CT. Tolerance-level residues were adequate to cover residues in all livestock commodities 

except liver and meat byproducts for which a higher anticipated residue calculations were used. 

For processed commodities, input values included combined average residues of parent and the 

metabolite with relevant processing factors. The chronic assessment incorporated empirical 

processing factors if available or (Dietary Exposure Evaluation Model) DEEM Version 7.81 

default processing factors as appropriate. Empirical processing factors were used for potato 

flakes and chips, tomatoes (paste, puree, dried, and juice), orange juice, apple juice, cottonseed 

oil, citrus oil, and dried plums. The processing factors for these commodities were set at 1 

because the input values included combined residues of the parent and the metabolite with 

relevant processing factors. Crop field trial data depicting residues in/on citrus fruit peels (lemon

and orange) were available and included into the assessment. The EDWC of 24.45 μg/L was 

incorporated directly into the dietary assessment.
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5.4.2 Acute Dietary Risk Assessment

An acute dietary endpoint was not selected for quantitative risk assessment because acute hazard

attributable to a single dose was not identified. 

5.4.3 Chronic Dietary Risk Assessment

The results indicate that chronic dietary (food and drinking water) exposure and risk estimates do

not exceed HED’s LOC for the U.S. population and all population subgroups. The risk estimates

are not underestimated at 22% of the cPAD for the general U.S. population and 50% of the 

cPAD for children (1-2 years old), the most highly exposed subgroup. Table 5.4.4 summarizes 

the dietary exposure and risk estimates for cyantraniliprole.

The dietary exposure and risk estimates are somewhat refined since they assume average 

residues for most crops and include empirical processing factors. Additional refinements may be 

implemented such as the incorporation of %CT data.

5.4.4 Summary Table

Table 5.4.4 Summary of Dietary (Food and Drinking Water) Exposure and Risk for Cyantraniliprolea

Population Subgroup cPAD

Chronic Dietary

Dietary Exposure cPAD

mg/kg/day mg/kg/day %

General U.S. Population

0.010

0.002223 22

All Infants (< 1 year old) 0.004378 44

Children 1-2 years old 0.005027 50

Children 3-5 years old 0.003738 37

Children 6-12 years old 0.002205 22

Youth 13-19 years old 0.001484 15

Adults 20-49 years old 0.001977 20

Adults 50+ years old 0.002244 22

Females 13-49 years old 0.002053 21

a The values for the highest exposed population is bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

Residential exposure may occur by the dermal, oral, and inhalation routes of exposures. 

However, since dermal hazard has not been identified for cyantraniliprole, the only exposures of 

concern are handler inhalation (for adults), and post-application incidental oral (for children). 

These exposures have been assessed with current policies which include updates to HED’s 2012 

Residential SOPs1along with policy changes for body weight assumptions (N. Tsaur, DP407964, 

02/26/2013).

The end use products that may lead to residential exposures (handler and/or post-application 

exposures) include the following EPs:

1. EPA Reg. No. 352-IAE (fly bait for use in and around residential structures);

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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2. EPA Reg. No. 352-IAG (foliar and systemic insect control on ornamental 

plants/shrubs/trees, and interior plantscapes);

3. EPA Reg. No. 352-IAI (for indoor use as a crack/crevice and for outdoor broadcast in 

single and multi-family residential buildings, schools, apartments, and daycares);

4. EPA Reg. No. 352-IAL (foliar and systemic insect control in landscape and recreational 

turfgrass, including golf courses and interior plantscapes);

5. EPA Reg. No. 100-RUEG (outdoor applications to residential landscape plants); and

6. EPA Reg. No. 100-RUEU (foliar and systemic insect control in turfgrass including golf 

courses, residential lawns, and recreational turfgrass).

6.1 Residential Handler Exposure

Of all proposed residential uses, only one WG product is intended for homeowner use: A16901B 

Residential (EPA Reg. No. 100-RUEG: outdoor applications to residential landscape plants). 

However, since the other labels include residential use sites, use by homeowners is possible, and 

prohibition of use by homeowners is not enforceable. Thus, residential handler exposure and 

risk estimates have been calculated for all possible residential exposure scenarios. Including all 

possible residential exposure scenarios provides a conservative and health protective assessment 

for the potential for homeowners to use the professionally labeled products on residential use 

sites. The formulations for the other labels include G and SC.

Residential handler exposure is expected to be short-term in duration. The turf and ornamental 

labels indicate that a maximum of two applications are allowed per season. Thus, intermediateterm exposures are not likely because of the intermittent nature of applications by homeowners. 

Unit exposure values and estimates for area treated or amount handled were taken from HED’s 

2012 Residential SOPs2(Lawns/Turf; Gardens and Trees; Indoor Environments). The 

algorithms used to estimate exposure and dose for residential handlers can be found in the 2012 

Residential SOPs2(Lawns/Turf; Gardens and Trees; Indoor Environments).

Handler risk estimates were assessed for all possible residential handler scenarios in which 

homeowners may be exposed to cyantraniliprole. Risk estimates of all possible scenarios are not 

of concern. Short-term inhalation MOEs range from 22,000 to 220,000,000 as summarized in 

Table 6.1. Furthermore, these calculated risk estimates are highly conservative because the 

inhalation exposure POD is based on an exposure duration of 24 hours per day.

 

2 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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Table 6.1 Residential Handler Non-Cancer Exposure and Risk Estimates for Cyantraniliprole

Application 

Equipment Crop or Target

Inhalation 

Unit 

Exposure

Maximum 

Application 

Ratea

Amount 

Handled 

Dailyb

Inhalation

Dosec

MOEd

mg/lb ai mg/kg/day

Mixer/Loader/Applicator for Granular Formulations

Push-Type 

Rotary Spreader

Outdoor areas used for storage of 

waste around commercial 

establishments, commercial 

operations, and agricultural animal 

production facilities

0.0026 0.0871

lb ai/A

0.5

acres

0.00000142 5,100,000

Belly Grinder 0.039

0.00000200

lb ai/sq ft

1200

sq ft 0.00000117 6,200,000

Spoon 0.087

100

sq ft

0.000000218 33,000,000

Cup 0.013 0.0000000325 220,000,000

Hand Dispersal 0.38 0.000000950 7,600,000

Shaker Can 0.013 0.0000000325 220,000,000

Bait 

Station/Trap

Indoor areas of residential, 

institutional, public, agricultural 

buildings/structures, or food/feed 

handling establishments (including 

restaurants, warehouses, 

supermarkets, hospitals, nursing 

homes, motels, hotels, schools, 

daycares, laboratories, computer 

facilities, aircraft, buses, boats/ships, 

trains, pet shops and zoos)

Exposure is considered negligible.

Mixer/Loader/Applicator for Liquid Formulations

ManuallyPressurized 

Handwand

Indoor Spot and Crack/Crevice 1.1 0.00887

lb ai/gal

0.5

gal 0.0000610 120,000

Outdoor Broadcast: Gardens/Trees

0.018

0.00000719

lb ai/sq ft

1200

sq ft 0.00000194 3,700,000

0.00418

lb ai/gal

5

gal 0.00000470 1,500,000

Outdoor Broadcast: Lawns/Turf

Hose-End 

Sprayer

Outdoor Broadcast: Gardens/Trees 0.0014

0.00000719

lb ai/sq ft

1200

sq ft 0.000000151 48,000,000

0.00418

lb ai/gal

11

gal 0.000000804 9,000,000

Outdoor Broadcast: Lawns/Turf 0.022 0.313

lb ai/A

0.5

acres

0.0000431 170,000

Backpack

Outdoor Broadcast: Gardens/Trees

0.14

0.00000719

lb ai/sq ft

1200

sq ft 0.0000151 480,000

0.00418

lb ai/gal

5

gal 0.0000365 200,000

Outdoor Broadcast: Lawns/Turf

Sprinkler Can

Outdoor Broadcast: Gardens/Trees

0.0014 0.00000719

lb ai/sq ft

1200

sq ft 0.000000151 48,000,000

0.0014 0.00418

lb ai/gal

5

gal 0.000000365 20,000,000

Outdoor Broadcast: Lawns/Turf 0.022 0.00000719

lb ai/sq ft

1000

sq ft 0.00000198 3,600,000
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table 6.1 Residential Handler Non-Cancer Exposure and Risk Estimates for Cyantraniliprole

Application 

Equipment Crop or Target

Inhalation 

Unit 

Exposure

Maximum 

Application 

Ratea

Amount 

Handled 

Dailyb

Inhalation

Dosec

MOEd

mg/lb ai mg/kg/day

Mixer/Loader/Applicator for Dry Flowable Formulations

ManuallyPressurized 

Handwand

Outdoor Broadcast: Gardens/Trees

1.1

0.00000301

lb ai/sq ft

1200

sq ft 0.0000497 140,000

0.00203

lb ai/gal

5

gal 0.000139 52,000 Outdoor Broadcast: Lawns/Turf

Hose-End 

Sprayer

Outdoor Broadcast: Gardens/Trees 0.0014

0.00000301

lb ai/sq ft

1200

sq ft 0.0000000633 110,000,000

0.00475

lb ai/gal

11

gal 0.000000914 7,900,000

Outdoor Broadcast: Lawns/Turf 0.022 0.133

lb ai/A

0.5

acres

0.0000182 400,000

Backpack

Outdoor Broadcast: Gardens/Trees

1.1

0.00000301

lb ai/sq ft

1200

sq ft 0.0000497 140,000

0.00475

lb ai/gal

5

gal 0.000327 22,000

Outdoor Broadcast: Lawns/Turf 0.00203

lb ai/gal

5

gal 0.000139 52,000

Sprinkler Can

Outdoor Broadcast: Gardens/Trees 0.0014

0.00000301

lb ai/sq ft

1200

sq ft 0.0000000633 110,000,000

0.00475

lb ai/gal

5

gal 0.000000416 17,000,000

Outdoor Broadcast: Lawns/Turf 0.022 0.00000304

lb ai/sq ft

1000

sq ft 0.000000836 8,600,000

a Based on maximum application rates on proposed labels:

EPA Reg. No. 352-IAE for granular application to indoor and outdoor areas,

EPA Reg. No. 352-IAI for liquid applications to indoor crack and crevices, 

EPA Reg. No. 352-IAL for liquid applications to ornamentals and turf,

EPA Reg. No. 100-RUEE for dry flowable applications to ornamentals, and

EPA Reg. No. 100-RUEU for dry flowable applications to turf.

b Based on HED’s 2012 Residential SOPs: Lawns/Turf; Gardens and Trees; Indoor Environments

(http://www.epa.gov/pesticides/science/residential-exposure-sop.html).

c Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or lb ai/gal) × Amount Handled (A/day or 

gallons/day) ÷ BW (80 kg adult).

d Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Short-Term Inhalation NOAEL = 7.2

mg/kg/day. Level of concern = 30.

6.2 Post-Application Exposure

Although residential dermal exposure is expected following the treatment of turf or 

cracks/crevices, a quantitative post-application dermal risk assessment was not conducted 

because a dermal hazard was not identified for cyantraniliprole. Furthermore, a risk assessment 

for incidental oral ingestion of granules has not been conducted based on a lack of hazard via the 

acute dietary route of exposure; and an indoor inhalation risk assessment has not been conducted 

because the acute inhalation toxicity is low (Toxicity Category IV), and exposure is expected to 

be negligible based on the low vapor pressure of cyantraniliprole (3.85×10-17 mm Hg at 20oC)

and the low proposed application rate (0.391 lb ai/A). Short-term incidental oral post-application 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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risk estimates for all scenarios are not of concern to HED (MOEs range from 290 to 1,000,000). 

Furthermore, short-term incidental oral post-application risk estimates are protective of 

intermediate-term because the POD is the same.

The lifestage (children 1 to <2 years old) selected for each post-application scenario is based on 

an analysis provided as an Appendix in the 2012 Residential SOPs3. This lifestage is not the 

only lifestage that could be potentially exposed for these post-application scenarios; however, the 

assessment of these lifestages is health protective for the exposures and risk estimates for any 

other potentially exposed lifestages.

The end use products that may lead to residential post-application exposures include the 

following EPs:

1. EPA Reg. No. 352-IAE (G fly bait for use in and around residential structures);

2. EPA Reg. No. 352-IAI (SC crack and crevice use in single and multi-family residential 

buildings, schools, apartments, and daycares);

3. EPA Reg. No. 352-IAL (foliar and systemic insect control in landscape and recreational 

turfgrass, including golf courses and interior plantscapes); and

4. EPA Reg. No. 100-RUEU (foliar and systemic insect control in turfgrass including golf 

courses, residential lawns, and recreational turfgrass).

A series of assumptions and exposure factors served as the basis for completing the residential 

post-application risk assessment. Each assumption and factor is detailed in the 2012 Residential 

SOPs4(Lawns/Turf; Indoor Environments). The algorithms used to estimate residential postapplication exposure and dose can be found in the 2012 Residential SOPs5

(Lawns/Turf; Indoor 

Environments). Based on the SOPs, the deposited residue value for liquid application to indoor 

cracks/crevices was calculated to be 1.74 μg/cm2.

In addition to the SOPs, the registrant has submitted chemical-specific turf transferrable residue 

(TTR) data (DP407965, N. Tsaur, 01/22/2013, Cyantraniliprole. Determination of Transferable 

Residues of Cyantraniliprole from Turf Treated with Water-Dispersible Granule (WG) and 

Granule (GR) Formulations of Cyantraniliprole). The high-end TTR value chosen to be 

protective of all exposure scenarios (regardless of formulation applied), is the predicted Day 0 

residue from the California site of 0.0282 μg/cm2. This value is based on a target application rate 

of 0.20 lb ai/A and must be adjusted for the proposed application rates in quantitative postapplication risk estimate calculations.

Table 6.2 presents the post-application incidental oral MOE values calculated from the following 

application scenarios:

1. liquid application of cyantraniliprole to turf,

2. granular application to cyantraniliprole to turf, and

3. liquid application of cyantraniliprole to indoor cracks/crevices.

 

3 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html

4 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html

5 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Post-application risk estimates for all scenarios are not of concern to HED (MOEs range from 

290 to 1,000,000). The incidental oral scenarios (i.e., hand-to-mouth and object-to-mouth) 

should be considered inter-related and it is likely that they occur interspersed amongst each other 

across time. However, combining these scenarios would be overly-conservative because of the 

conservative nature of each individual assessment. Therefore, the hand-to-mouth postapplication exposure scenario for children 1 < 2 years old should be considered a protective 

estimate of children’s exposure to pesticides used indoors. Furthermore, incidental oral risk 

estimates are highly conservative because the short- and intermediate-term incidental oral POD 

is based on a 90-day exposure duration.

Table 6.2 Residential Post-Application Non-Cancer Exposure and Risk Estimates for Cyantraniliprole

Lifestage

Post-Application Exposure Scenario Application 

Ratea

Doseb

MOEsc

Use Site Route of Exposure mg/kg/day

Children

1 to <2 years old

Liquid Application

to Turf

ST Hand to Mouth

0.313

lb ai/A

0.00604 500

ST Object to Mouth 0.000184 16,000

ST/IT Incidental Soil Ingestion 0.0000106 280,000

Granular Application

to Turf

ST Hand to Mouth

0.0871

lb ai/A

0.000834 3,600

ST Object to Mouth 0.0000511 59,000

ST/IT Incidental Soil Ingestion 0.00000295 1,000,000

Incidental Granular Ingestion Acute dietary hazard not identified.

Liquid Application to 

Cracks/Crevices

(Carpet)

ST/IT Hand to Mouth

0.0000355

lb ai/sq ft

0.0103 290

ST/IT Object to Mouth 0.00137 2,200

Liquid Application to 

Cracks/Crevices

(Hard Surfaces)

ST/IT Hand to Mouth 0.00342 880

ST/IT Object to Mouth 0.000910 3,300

a Based on registered or proposed label (Reg. Nos.352-IAE, 352-IAI, 352-IAL).

EPA Reg. No. 352-IAE for granular application to indoor and outdoor areas,

EPA Reg. No. 352-IAI for liquid applications to indoor crack and crevices, and

EPA Reg. No. 352-IAL for liquid applications to turf.

b Dose (mg/kg/day) equations:

Hand-to-Mouth Dose = hand residue loading (μg/cm2) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm2) 

× exposure time (1.5 hrs/day) × # of replenishment intervals/hr (4 int/hr) × (1-((1-saliva extraction factor (0.5))^(Number of 

hand-to-mouth events per hour (13.9 events/hr) ÷ # of replenishment intervals/hr)) ÷ body weight (11 kg).

Object-to-Mouth Dose = object residue loading (μg/cm2) × unit conversion factor (0.001 mg/μg) × object surface area mouthed 

/ event (10 cm2/event) × exposure time (1.5 hrs/day) × # replenishment intervals/hr (4 int/hr) × (1-((1- saliva extraction factor 

(0.50))^(# Object-to-Mouth Events/hr (8.8 events/hr) ÷ # replenishment intervals/hr)) ÷ body weight (11 kg).

Soil Ingestion = soil residue (μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 g/μg) ÷ body weight (11 kg).

TTR for liquid application rate of 0.313 lb ai/A = 0.0282 μg/cm2× (0.313 lb ai/A ÷ 0.20 lb ai/A) = 0.0441 μg/cm2.

TTR for granular application rate of 0.0871 lb ai/A = 0.0282 μg/cm2× (0.0871 lb ai/A ÷ 0.20 lb ai/A) = 0.0123 μg/cm2.

Deposited residue for liquid application to cracks/crevices = 1.74 μg/cm2.

c MOE = NOAEL ÷ Daily Dose (mg/kg/day). ST/IT Incidental Oral NOAEL = 3.0 mg/kg/day. Level of concern = 100.

6.3 Residential Risk Estimates for Use in Aggregate Assessment

For the purpose of the cyantraniliprole aggregate human health risk assessment, a summary of 

the most protective residential exposure risk estimates for all proposed residential uses are 

provided in Table 6.3. Based on the residential use profile, and the 2012 Revised Residential 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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SOPs, only short-term inhalation residential handler exposures (for adults) and short-term 

incidental oral post-application exposures (for children) should be included in the aggregate risk 

assessment. It is noted that intermediate-term incidental oral post-application exposures are 

possible (i.e. from indoor applications and form soil ingestion due to the persistence of 

cyantraniliprole); however, the short-term incidental oral exposures are protective of the possible 

intermediate-term incidental oral exposures because the POD for both durations is the same.

Although it is possible for residential handlers to have combined exposures from concurrent turf 

and ornamental applications (based on the proposed label for EPA Reg. No. 352-IAL which 

would result in an MOE of 90,000)

6

, the suggested exposure contribution for aggregate risk 

estimate is based on the most protective risk estimate from dry flowable application to 

ornamentals only (based on the proposed label for EPA Reg. No. 100-RUEE which results in an 

MOE of 22,000). The most protective risk estimate for children’s post-application incidental 

oral exposures is based on indoor liquid crack/crevice application to carpets which results in an 

MOE of 290.

Table 6.3 Scenarios Recommended for Aggregate Risk Assessment of Cyantraniliprole

Scenario Daily DoseaMOEb

mg/kg/day

Adults 

Residential Handler Inhalation Exposure

(Applying Dry Flowables to Ornamentals with a Backpack Sprayer) 0.000327 22,000

Children (1 to <2 Years Old)

Post-Application Incidental Oral Exposure: Hand-to-Mouth

(After Liquid Application to Cracks/Crevices on Carpet) 0.0103 290

a Daily Dose = See Table 6.1 for adult handler scenarios and Table 6.2 for post-application incidental oral

scenarios. Adults based on EPA Reg. No. 100-RUEE (WG). Children based on EPA Reg. No. 352-IAI (SC).

b MOE = NOAEL/Daily Dose (mg/kg/day).

ST Inhalation NOAEL = 7.2 mg/kg/day. ST Inhalation LOC = 30.

ST/IT Incidental Oral = 3.0 mg/kg/day. ST/IT Incidental Oral LOC = 100.

6.4 Residential Bystander Post-Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for cyantraniliprole at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV), low vapor pressure (3.85×10-17 mm Hg at 20oC), and 

the low proposed use rate (0.391 lb ai/A). However, volatilization of pesticides may be a source 

of post-application inhalation exposure to individuals nearby pesticide applications. The Agency 

sought expert advice and input on issues related to volatilization of pesticides from its Federal 

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, 

and received the SAP’s final report on March 2, 20107. The Agency is in the process of 

evaluating the SAP report and may, as appropriate, develop policies and procedures to identify 

 

6

 EPA Reg. No. 352-IAL (SC) may lead to concurrent turf and ornamental exposures. A conservative healthprotective calculation of these two exposures results in a daily dose of 0.0000431 mg/kg/day (liquid application to 

lawns/turf) + 0.0000365 mg/kg/day (liquid application to gardens/trees) = 0.0000796 mg/kg/day; thus resulting in a 

combined MOE of 90,000 (NOAEL of 7.2 mg/kg/day ÷ 0.0000796 mg/kg/day).

7 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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the need for and, subsequently, the way to incorporate post-application inhalation exposure into 

the Agency's risk assessments. If new policies or procedures are developed, the Agency may 

revisit the need for a quantitative post-application inhalation exposure assessment for 

cyantraniliprole.

6.5 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for cyantraniliprole. 

The Agency has been working with the Spray Drift Task Force, EPA Regional Offices, and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray drift 

management practices (see the Agency’s Spray Drift website for more information)

8

. The 

Agency has completed its evaluation of the new database submitted by the Spray Drift Task 

Force, a membership of U.S. pesticide registrants, and is developing a policy on how to 

appropriately apply the data and the AgDRIFT computer model to its risk assessments for 

pesticides applied by air, orchard airblast, and ground hydraulic methods. After the policy is in 

place, the Agency may impose further refinements in spray drift management practices to reduce

off-target drift with specific products with significant risk estimates associated with drift.

Although a quantitative residential post-application inhalation exposure assessment was not 

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation 

exposure assessment was performed for flaggers. This exposure scenario is representative of a 

worse case inhalation (drift) exposure and may be considered protective of most outdoor 

agricultural and commercial post-application inhalation exposure scenarios. 

It is noted that the 0.313 lb ai/acre application rate for turf was modeled to estimate postapplication residential exposure of children. As this rate is equal to or higher than many of the 

agricultural application rates, this scenario is protective of any incidental inhalation exposure of 

farm children via spray drift from agricultural cyantraniliprole applications.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g. a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

7.1 Acute Aggregate Risk

An acute aggregate risk assessment was not conducted since adverse effects attributable to a 

single dose were not identified.

 

8 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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7.2 Short-Term Aggregate Risk

There is potential short-term exposure to cyantraniliprole via the dietary (which is considered 

background exposure) and residential (which is considered primary exposure) pathways. For 

adults, the oral and inhalation routes of exposure should not be aggregated since the endpoints of 

concern are not common. For children, the pathways lead to exposure via the dietary oral 

(background) and incidental oral (primary) routes. The children short-term aggregate risk 

estimate (dietary and residential) is not of concern (as presented in Table 7.2). The MOE is 190 

which is greater than the LOC of 100.

Table 7.2 Short-Term Aggregate Risk Calculations

Population

Short-Term Scenario

NOAEL 

mg/kg/day LOCa

Max 

Allowable 

Exposureb

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/dayc

Total 

Exposure 

mg/kg/dayd

Aggregate 

MOE (food, 

water, and 

residential)e

Children

1-2 years old 3.0 100 0.030 0.005027 0.0107 0.0157 190

a Children LOC = 100 (based on inter- and intra- species uncertainty factors, each at 10X).

b Maximum Allowable Exposure (mg/kg/day) = NOAEL ÷ LOC.

c Residential Exposure = Incidental Oral Only for children (See Table 6.3).

d Total Exposure = Average Food and Water Exposure + Residential Exposure.

e Aggregate MOE = NOAEL ÷ Total Exposure. ST Children NOAEL = 3 mg/kg/day. LOC = 100.

7.3 Intermediate-Term Aggregate Risk

For adults, intermediate-term exposure is not expected for the residential exposure pathway. 

Therefore, the intermediate-term aggregate risk would be equivalent to the chronic dietary 

exposure estimate. Refer to Section 5.4.3. For children, the incidental oral POD is the same for 

both short- and intermediate-term durations. Thus, the short-term aggregate risk estimate is 

protective of potential intermediate-term exposures and risks. Refer to section 7.2.

7.4 Chronic Aggregate Risk

There are no chronic residential exposure scenarios; therefore, the chronic aggregate risk would 

be equivalent to the chronic dietary (food and drinking water) risk estimate. Refer to Section 

5.4.3.

7.5 Cancer Aggregate Risk

Cyantraniliprole is classified as “not likely to be carcinogenic to humans.” Therefore, an 

aggregate cancer assessment was not conducted.

8.0 Cumulative Exposure/Risk Characterization

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

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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to cyantraniliprole and any other substances and cyantraniliprole does not appear to produce a 

toxic metabolite produced by other substances. For the purposes of this tolerance action, 

therefore, EPA has not assumed that cyantraniliprole has a common mechanism of toxicity with 

other substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative.

9.0 Occupational Exposure/Risk Characterization

Occupational handler and post-application exposure may occur by the dermal and inhalation 

routes of exposure only. Since there is no dermal hazard, only inhalation exposures were 

quantitatively assessed. The results of the occupational handler exposure and risk assessment

indicate that short- and intermediate-term inhalation risk estimates are not of concern (N. Tsaur, 

DP407964, 02/26/2013). Appendix F, Tables F.1 and F.2 summarize all assessed occupational 

exposure and risk estimates including those from proposed seed treatment uses.

9.1 Short- and Intermediate-Term Handler Risk

Agricultural Field Uses

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

that can potentially be used, occupational handler exposure is expected from the proposed

agricultural uses. The quantitative exposure/risk assessment developed for occupational handlers 

is based on several scenarios which include mixing/loading/applying various formulations of 

cyantraniliprole, including liquids, dry flowables, and granules. The use sites are summarized in 

Section 3.0. Methods of application include aerial, airblast, chemigation, groundboom, seed 

treatment, and handheld equipment (refer to Appendix F for a detailed list of each scenario).

HED classifies exposures from 1 to 30 days as short-term and exposures 30 days to six months 

as intermediate-term. Exposure duration is determined by many things, including the exposed 

population, the use site, the pest pressure triggering the use of the pesticide, and the cultural 

practices surrounding that use site. For most agricultural uses, it is reasonable to believe that 

occupational handlers will not apply the same chemical every day for more than a one-month 

time frame; however, there may be a large agribusiness and/or commercial applicators who may 

apply a product over a period of weeks (e.g., completing multiple applications for multiple 

clients within a region). The area treated or amount handled is based on HED ExpoSAC Policy

No. 9.1 (refer to Appendix F for these assumptions for each scenario).

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic handler data, used as surrogate data in the absence of chemical-specific data, include 

PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force (ORETF) 

database, or other registrant-submitted occupational exposure studies. Some of these data are 

proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The 

standard values recommended for use in predicting handler exposure that are used in this 

assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 41 of 85

Exposure Surrogate Reference Table9”, which, along with additional information on HED policy 

on use of surrogate data, including descriptions of the various sources, can be found at the 

Agency website10.

In general, the labels require the chemical-resistant gloves as PPE. The results of the 

occupational handler exposure and risk assessment indicate that short- and intermediate-term 

inhalation risks do not exceed HED’s 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 shortand intermediate-term PODs are the same, the inhalation MOEs are also the same, ranging from 

1,200 to 3,900,000. Note that only engineering control (enclosed cockpit) data are available to 

assess risks to handlers operating aircrafts.

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for 

human flaggers when appropriate, agricultural aviation has changed dramatically over the past 

two decades. According to the 2012 National Agricultural Aviation Association (NAAA) survey 

of their membership, the use of GPS for swath guidance in agricultural aviation has grown 

steadily from the mid 1990’s. Over the same time period, the use of human flaggers for aerial 

pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the 

most recent (2012) NAAA survey. The Agency will continue to monitor all available 

information sources to best assess and characterize the exposure potential for human flaggers in 

agricultural aerial applications.

HED 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. With this 

level of protection, there are no risk estimates of concern for applicators.

Agricultural Seed Treatment Uses

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

that can potentially be used, 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: 

1. Mixing/loading liquids for potato seed piece treatment,

2. Planting potato seed pieces,

3. Mixing/loading liquids for commercial seed treatment, and

4. Planting treated seed.

Occupational seed treatment handlers may experience short- and intermediate-term exposure to

cyantraniliprole while performing seed treatment activities in commercial settings. In addition, 

occupational secondary handlers may experience short- and intermediate-term exposure while 

planting cyantraniliprole-treated seeds. No chemical-specific handler exposure data were 

 

9 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

10 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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submitted in support of this use pattern. For assessing commercial seed treatment and seed 

planting activities, unit exposure data were taken from HED ExpoSAC Policy 14: SOPs for Seed 

Treatment. The amount of active ingredient handled depends on the application rate (lb ai/lb 

seed) and the pounds of seed treated in a day (or the pounds of seed that can be planted in a day), 

all of which vary depending upon the seed type. Values for the amount of seed treated and 

planted per day were obtained from HED ExpoSAC Policy 15.

The results of the occupational handler exposure and risk assessment indicate that short-term 

inhalation risk estimates do not exceed HED’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 HED’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).

9.2 Short- and Intermediate-Term Post-Application Risk

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

9.2.1 Dermal Post-Application Risk

An occupational post-application exposure and risk assessment was not conducted because a 

dermal hazard was not identified for cyantraniliprole.

9.2.2 Restricted Entry Interval

Cyantraniliprole is classified as Toxicity Category IV via the dermal route. It is not irritating to 

the skin and it is not a skin sensitizer. Typically, the REI specified on the proposed label is 

based on the acute toxicity of the active ingredient. Under 40 CFR 156.208 (c) (2) (iii), active 

ingredients classified as Acute III or IV for acute dermal, eye irritation and primary skin 

irrigation are assigned a 12-hour REI. However, REIs may be further reduced from 12 hours if 

certain criteria are met for both the technical material and the different end-use products in 

accordance with the Pesticide Registration (PR) Notice 95-3 [Reduction of Worker Protection 

Standard (WPS) Interim Restricted Entry Intervals (REIs) for Certain Low Risk Pesticides].11 

The criteria for reducing REIs include the following:

(1) The active ingredient is in Toxicity Category III or IV based upon data for acute dermal 

 

11 Available: http://www.epa.gov/PR_Notices/pr95-3.html
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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toxicity, acute inhalation toxicity, primary skin irritation, and primary eye irritation.

(2) The active ingredient is not a dermal sensitizer.

(3) The active ingredient is not a cholinesterase inhibitor.

(4) The active ingredient is not associated with known reproductive, developmental, 

carcinogenic, or neurotoxic effects.

(5) EPA does not possess incident information that are “definitely” or “probably” related to 

the post-application exposures to the active ingredient.

With respect to the active ingredient, cyantraniliprole, these criteria have been met for the 

technical and all but two of the proposed EPs. Since the two products, EPA Reg. No. 352-ILT 

and EPA Reg. No. 352-ILI, have been identified as dermal sensitizers, a 12-hour REI is required 

to protect agricultural workers from post-application exposures to cyantraniliprole. Aside from 

these two products, the 4-hour REIs listed on all other proposed labels are adequate. Table 9.2.2 

shows the acute toxicity results for each proposed label and formulation.

Table 9.2.2 Acute Toxicity Results of All Proposed U.S. Registrations for Cyantraniliprole

Reg. No. Formulation Oral Dermal Inhalation Skin Irritation Eye Irritation Sensitization

352-ILA 96.7% technical IV IV IV IV IV -ve

352-ILT 100 g/l OD IV IV IV IV III +ve

352-ILO 100 g/l SE IV IV IV III III +ve

352-IAN 200 g/l SC IV IV IV IV IV -ve

352-ILI 625 g/l FS IV IV IV IV IV -ve

352-IAE 0.5% RB IV IV waivedaIV IV -ve

352-IAI 200 g/l SC IV IV IV IV IV -ve

352-IAL 200 g/l SC IV IV IV IV IV -ve

352-IAG 200 g/l SC IV IV IV IV IV -ve

100-RUER 200 +200 g/kg WG IV IV IV IV III -ve

100-RUEE 200 +200 g/kg WG IV IV IV IV III -ve

100-RUEG 200 +200 g/kg WG IV IV IV IV III -ve

100-RUEU 200 +200 g/kg WG IV IV IV IV III -ve

100-RUEN 600 g/l FS IV IV IV IV IV -ve

100-RURI 600 g/l FS IV IV IV IV III -ve

a Waiver request granted (Technical = Tox Cat IV; Bait station, no potential for inhalation exposure, etc.)

9.2.3 Inhalation Post-Application Risk

Agricultural/Commercial Outdoor Uses

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for cyantraniliprole at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV), low vapor pressure (3.85×10-17 mm Hg at 20oC), and 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 44 of 85

the low proposed use rate (0.391 lb ai/A). However, there are multiple potential sources of postapplication inhalation exposure to individuals performing post-application activities in 

previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert 

advice and input on issues related to volatilization of pesticides from its Federal Insecticide, 

Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and 

received the SAP’s final report on March 2, 201012. The Agency is in the process of evaluating 

the SAP report as well as available post-application inhalation exposure data generated by the 

ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, 

subsequently, the way to incorporate occupational post-application inhalation exposure into the 

Agency's risk assessments. If new policies or procedures are put into place, the Agency may 

revisit the need for a quantitative occupational post-application inhalation exposure assessment 

for cyantraniliprole.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

Greenhouse Uses

The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting 

workers from inhalation exposures during and after greenhouse applications through the use of 

ventilation requirements.13

Indoor Commercial Uses

Commercial applicators do not typically return to the treated areas after an indoor commercial 

pesticide application (sites such as warehouses, food handling establishments, and hotels, etc.) 

and thus an occupational post-application inhalation exposure assessment was not performed for 

commercial applicators.

Seed Treatment Uses

A post-application inhalation exposure assessment is not required as exposure is expected to be 

negligible. Seed treatment assessments provide quantitative inhalation exposure assessments for 

seed treaters and secondary handlers (i.e. planters). It is expected that these exposure estimates 

would be protective of most post-application inhalation exposure scenarios.

10.0 References

D. Cordova, E.A. Benner, M.D. Sacher, J.J. Rauh, J.S. Spoa, G.P. Lahm, T.P. Selby, T.M. 

Stevenson, L. Flexner, S. Gutteridge, D.F. Rhoades, L. Wu, R.M. Smith, Y. Tao. (2006).

anthranilic diamides: a new class of insecticides with a novel mode of action, ryanodine 

receptor activation. Pesticide Biochemistry and physiology 84 (2006) 196-214.

 

12 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

13 40 CFR 170.110, (3) (Restrictions associated with pesticide applications)
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 45 of 85

I. Encarnacion, 09/25/2012, DP404411, “Cyantraniliprole: Report of the Residues of Concern 

Knowledgebase Subcommittee (ROCKS).”

S. Funk, 01/25/2013, DP407961, “Cyantraniliprole. Petition for the Establishment of Permanent 

Tolerances and Registration for Use on Brassica (Cole) Leafy Vegetables (Group 5), Bulb 

Vegetables (Group 3-07), Bushberries (Group 13-07B), Oilseed (Group 20), Citrus Fruit 

(Group 10-10), Cucurbit Vegetables (Group 9), Fruiting Vegetables (Group 8-10), Leafy 

Vegetables (non-Brassica) (Group 4), Pome Fruit (Group 11-10), Stone Fruit (Group 12), 

Tree Nuts (Group 14), Tuberous and Corm Vegetables (Subgroup 1C), and Food/Feed 

Handling Establishments. Summary of Analytical Chemistry and Residue Data.”

S. Funk, 01/25/2013, DP407962, “Cyantraniliprole. Application (Syngenta) for Section 3 

Registration for Use of WG Formulation on Brassica (Cole) Leafy Vegetables (Group 5), 

Cucurbit Vegetables (Group 9), Fruiting Vegetables (Group 8-10), Leafy Vegetables (nonBrassica) (Group 4), and for Use of FS Formulation on Sunflower and Tuberous and Corm 

Vegetables (Subgroup 1C). Summary of Analytical Chemistry and Residue Data.”

J. Kidwell, 09/27/2012, ToxSAC Report PC Code 090098, “Cyantraniliprole- Summary of 

Toxicology Science Advisory Council (ToxSAC) Meeting of July 19, 2012.”

C. Koper, 11/21/2012, DP403747, “Tier I Drinking Water Exposure Assessment for 

Cyantraniliprole in Support of New Chemical Registration on Various Crops.”

G.P. Lahm, D. Cordova, J.D. Barry. (2009). New and selective ryanodine receptor activators for 

insect control. Bioorganic & Medicinal Chemistry (2009) 17 (12): 4127-4133.

M. Negussie,01/29/2013, DP407963, “Cyantraniliprole: Chronic Aggregate Dietary (Food plus 

Drinking Water) Exposure and Risk Assessments for the First Food Uses in Support of a 

Section 3 Registration Action on Brassica (Cole) Leafy Vegetables (Group 5), Bulb 

Vegetables (Group 3-07), Bushberries (Group 13-07B), Canola (Rapeseed), Citrus Fruit 

(Group 10-10), Cotton, Cucurbit Vegetables (Group 9), Fruiting Vegetables (Group 8-10), 

Leafy Vegetables (non-Brassica) (Group 4), Mustard Seed, Oil Seed Crops (Group 20), 

Pome Fruit (Group 11-10), Stone Fruits (Group 12), Tree Nuts (Group 14) and Pistachio, and 

Tuberous and Corm Vegetables (Subgroup 1C).”

D.B. Sattelle, D. Cordova, T.R Cheek. (2008). Insect ryanodine receptors: molecular targets for 

novel pest control chemical. Invert Neurosci (2008) 8:107-119.

P.W. Snyder, E.A. Kazacos, J.C. Scott-Moncrieff, H. HogenEsch, W.W. Carlton, L.T. Glickman, 

P.J. Felsburg. (1995). Pathologic features of naturally occurring Juvenile polyarteritis in 

Beagle dogs. Vet Path (1995) 32:337-345.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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N. Tsaur, 02/28/2013, DP407964, “Cyantraniliprole. Occupational and Residential Exposure 

and 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, 

Mustard Seed, Sunflowers, and Potatoes; and Residential, Commercial, and Agricultural 

Uses on Ornamentals, Turfgrass (including Sod Farms), and Structural Buildings (including 

Indoor Crack/Crevice and Outdoor Broadcast).”

D.C. Wolf, J.W. Allen, M.H. George, et al. (2006). Toxicity Profiles in Rats Treated with 

Tumorigenic and Nontumorigenic Triazole Conazole Fungicides: Propiconazole, 

Triadimefon, and Myclobutanil. Toxicologic Pathology (2006) 34:895–902.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Appendix A. Detailed Use Profile Summary

Table A.1 Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application 

Timing, Type, and 

Equipment

Formulation

[EPA Reg. No.]

Trade Namea

Maximum 

Application 

Rate

Max. No. 

of

Apps per

Season

Max. 

Seasonal 

Application 

Rate

RTI Use Directions and Limitations

days

Brassica (Cole) Leafy Vegetables (Group 5)

Soil at Planting

(in-furrow spray, 

transplant water 

treatment, hill drench, 

surface band, soil 

shank injection)

18.66% SC

[352-IAN]

VerimarkTM

0.176

lb ai/A

0.00202

lb ai/gal

1

0.176

lb ai/A N/A

Only to be applied to the soil by ground or drip 

chemigation application equipment. Must be 

applied uniformly in the root zone. Do not make 

aerial or airblast applications. Do not treat plants 

being grown for transplanting in nurseries. Use 

this product only in commercial and farm 

plantings. May be used on crops grown for seed 

production.

Foliar

(ground, aerial)

10.20% SE

[352-ILO]

ExirelTM

0.133

lb ai/A

0.00443

lb ai/gal

N/S

0.4

lb ai/A

5

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates; non-ionics; organosilicones/

organosilicates). Use a minimum of 10 gallons 

per acre for all vegetable crops.

Soil

(in-furrow spray at 

seeding or 

transplanting; post 

seeding, post 

transplant, hill 

drench; drip 

(trickle) 

chemigation; 

shanked into root 

zone)

20.0% WG

[100-RUER]

A16901B CP

0.175

lb ai/A

0.0175

lb ai/gal

1 NA

Use this product only in commercial and farm 

plantings. Do not use in greenhouses. Do not 

treat plants grown for transplanting. Apply 

within 21 days of planting or transplanting. 

Make only one soil application per growing 

season.

Foliar

(ground, aerial, 

chemigation)

20.0% WG

[100-RUER]

A16901B CP

0.0875

lb ai/A

0.00875

lb ai/gal

N/S 7

Use this product only in commercial and farm 

plantings. Do not use in greenhouses. Do not 

treat plants grown for transplanting. Apply 

within 21 days of planting or transplanting. Use 

a minimum of 10 gal water per acre for ground 

application.

Bulb Vegetables (Group 3-07)

Foliar

(ground, aerial)

10.20% SE

[352-ILO]

ExirelTM

0.133

lb ai/A

0.00443

lb ai/gal

N/S 0.4

lb ai/A 5

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates; non-ionics; organosilicones/

organosilicates). Use a minimum of 10 gallons 

per acre for all vegetable crops.

Foliar

(ground, aerial, 

chemigation)

10.26% OD

[352-ILT]

BeneviaTM

0.133

lb ai/A

0.0133

lb ai/gal

N/S 0.4

lb ai/A 5

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates; non-ionics; organosilicones/

organosilicates). Use a minimum of 10 gallons 

per acre for bulb vegetables.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table A.1 Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application 

Timing, Type, and 

Equipment

Formulation

[EPA Reg. No.]

Trade Namea

Maximum 

Application 

Rate

Max. No. 

of

Apps per

Season

Max. 

Seasonal 

Application 

Rate

RTI Use Directions and Limitations

days

Bushberries (Group 13-07B)

Foliar

(ground, aerial)

10.20% SE

[352-ILO]

ExirelTM

0.133

lb ai/A

0.00443

lb ai/gal

N/S 0.4

lb ai/A 5

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates; non-ionics; organosilicones/

organosilicates). Use a minimum of 30 gallons 

per acre for all fruit and nut crops.

Citrus Fruits (Group 10-10)

Soil drench or 

microsprinkler 

chemigation

18.66% SC

[352-IAN]

VerimarkTM

0.391

lb ai/A

0.00449

lb ai/gal

1

0.4

lb ai/A N/A

For use on citrus nursery stock (trees less than 4 

years old). Only to be applied to the soil by 

ground or drip chemigation application 

equipment. Must be applied uniformly in the 

root zone. Do not make aerial or airblast 

applications. Do not treat plants being grown 

for transplanting in nurseries. Use this product 

only in commercial and farm plantings. May be 

used on crops grown for seed production.

Foliar

(ground, aerial)

10.20% SE

[352-ILO]

ExirelTM

0.133

lb ai/A

0.00443

lb ai/gal

N/S 0.4

lb ai/A 7

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates; non-ionics; organosilicones/

organosilicates). Use a minimum of 30 gallons 

per acre for all fruit and nut crops.

Cotton

Foliar

(ground, aerial)

10.26% OD

[352-ILT]

BeneviaTM

0.133

lb ai/A

0.0133

lb ai/gal

N/S 0.4

lb ai/A 7

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates; non-ionics; organosilicones/

organosilicates). Use a minimum of 10 gallons 

per acre for cotton.

Cucurbit Vegetables (Group 9)

Soil at Planting

(in-furrow spray, 

transplant water 

treatment, hill drench, 

surface band, soil 

shank injection)

18.66% SC

[352-IAN]

VerimarkTM

0.176

lb ai/A

0.00202

lb ai/gal

1

0.176

lb ai/A N/A Only to be applied to the soil by ground or drip 

chemigation application equipment. Must be 

applied uniformly in the root zone. Do not

make aerial or airblast applications. Do not treat 

plants being grown for transplanting in 

nurseries. Use this product only in commercial 

and farm plantings. May be used on crops 

Drip chemigation grown for seed production.

18.66% SC 

[352-IAN]

VerimarkTM

0.130

lb ai/A

0.00149

lb ai/gal

2

(1 if atplant 

app is 

made)

0.260

lb ai/A 10
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table A.1 Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application 

Timing, Type, and 

Equipment

Formulation

[EPA Reg. No.]

Trade Namea

Maximum 

Application 

Rate

Max. No. 

of

Apps per

Season

Max. 

Seasonal 

Application 

Rate

RTI Use Directions and Limitations

days

Foliar

(ground, aerial)

10.20% SE

[352-ILO]

ExirelTM

0.133

lb ai/A

0.00443

lb ai/gal

N/S 0.4

lb ai/A 1

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates; non-ionics; organosilicones/

organosilicates). Use a minimum of 10 gallons 

per acre for all vegetable crops.

Soil

(in-furrow spray at 

seeding or 

transplanting; post 

seeding, post 

transplant, hill 

drench; drip 

(trickle) 

chemigation; 

shanked into root 

zone)

20.0% WG

[100-RUER]

A16901B CP

0.175

lb ai/A

0.0175

lb ai/gal

1

0.4

lb ai/A NA

Use this product only in commercial and farm 

plantings. Do not use in greenhouses. Do not 

treat plants grown for transplanting. Apply 

within 21 days of planting or transplanting. 

Make only one soil application per growing 

season.

Foliar

(ground, aerial, 

chemigation)

20.0% WG

[100-RUER]

A16901B CP

0.0875

lb ai/A

0.00875

lb ai/gal

N/S 0.4

lb ai/A 7

Use this product only in commercial and farm 

plantings. Do not use in greenhouses. Do not 

treat plants grown for transplanting. Apply 

within 21 days of planting or transplanting. 

Use a minimum of 10 gal water per acre for 

ground application.

Fruiting Vegetables (Group 8-10)

Soil at Planting (infurrow spray, 

transplant water 

treatment, hill drench, 

surface band, soil 

shank injection)

18.66% SC

[352-IAN]

VerimarkTM

0.176

lb ai/A

0.00202

lb ai/gal

1

0.176

lb ai/A N/A Only to be applied to the soil by ground or drip 

chemigation application equipment. Must be 

applied uniformly in the root zone. Do not

make aerial or airblast applications. Do not treat 

plants being grown for transplanting in 

nurseries. Use this product only in commercial 

and farm plantings. May be used on crops 

Drip chemigation grown for seed production.

18.66% SC

[352-IAN]

VerimarkTM

0.130

lb ai/A

0.00149

lb ai/gal

2

(1 if atplant 

app is 

made)

0.260

lb ai/A 10

Foliar

(ground, aerial)

Foliar

(greenhouse)

10.20% SE

[352-ILO]

ExirelTM

0.133

lb ai/A

0.00443

lb ai/gal

N/S 0.4

lb ai/A 1

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates: non-ionics; organosilicones/

organosilicates). Use a minimum of 10 gallons 

per acre for all vegetable crops.

Soil

(in-furrow spray at 

seeding or 

transplanting; post 

seeding, post 

transplant, hill 

drench; drip 

(trickle) 

chemigation; 

shanked into root 

zone)

20.0% WG

[100-RUER]

A16901B CP

0.175

lb ai/A

0.0175

lb ai/gal

1

0.4

lb ai/A NA

Use this product only in commercial and farm 

plantings. Do not use in greenhouses. Do not 

treat plants grown for transplanting. Apply 

within 21 days of planting or transplanting. 

Make only one soil application per growing 

season.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 50 of 85

Table A.1 Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application 

Timing, Type, and 

Equipment

Formulation

[EPA Reg. No.]

Trade Namea

Maximum 

Application 

Rate

Max. No. 

of

Apps per

Season

Max. 

Seasonal 

Application 

Rate

RTI Use Directions and Limitations

days

Foliar

(ground, aerial, 

chemigation)

20.0% WG

[100-RUER]

A16901B CP

0.0875

lb ai/A

0.00875

lb ai/gal

N/S 0.4

lb ai/A 7

Use this product only in commercial and farm 

plantings. Do not use in greenhouses. Do not 

treat plants grown for transplanting. Apply 

within 21 days of planting or transplanting. 

Use a minimum of 10 gal water per acre for 

ground application.

Leafy Vegetables (non-Brassica) (Group 4)

Soil at Planting

(in-furrow spray, 

transplant water 

treatment, hill drench, 

surface band, soil 

shank injection)

18.66% SC

[352-IAN]

VerimarkTM

0.176

lb ai/A

0.00202

lb ai/gal

1

0.176

lb ai/A N/A

Only to be applied to the soil by ground or drip 

chemigation application equipment. Must be 

applied uniformly in the root zone. Do not

make aerial or airblast applications. Do not treat 

plants being grown for transplanting in 

nurseries.

Use this product only in commercial and farm 

plantings. May be used on crops grown for seed 

production.

Foliar

(ground, aerial)

10.20% SE

[352-ILO]

ExirelTM

0.133

lb ai/A

0.00443

lb ai/gal

N/S 0.4

lb ai/A 1

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates: non-ionics; organosilicones/

organosilicates). Use a minimum of 10 gallons 

per acre for all vegetable crops.

Soil

(in-furrow spray at 

seeding or 

transplanting; post 

seeding, post 

transplant, hill 

drench; drip 

(trickle) 

chemigation; 

shanked into root 

zone)

20.0% WG

[100-RUER]

A16901B CP

0.175

lb ai/A

0.0175

lb ai/gal

1

0.4

lb ai/A NA

Use this product only in commercial and farm 

plantings. Do not use in greenhouses. Do not 

treat plants grown for transplanting. Apply 

within 21 days of planting or transplanting. 

Make only one soil application per growing 

season.

Foliar

(ground, aerial, 

chemigation)

20.0% WG

[100-RUER]

A16901B CP

0.0875

lb ai/A

0.00875

lb ai/gal

N/S 0.4

lb ai/A 7

Use this product only in commercial and farm 

plantings. Do not use in greenhouses. Do not 

treat plants grown for transplanting. Apply 

within 21 days of planting or transplanting. 

Use a minimum of 10 gal water per acre for 

ground application.

Mustard Seed

Seed treatmentb

50% FS

[352-ILI]

Dermacor®

Z-103

1.0

lb ai/cwt 1

0.4

lb ai/A 7

Apply as a water-based slurry prior to planting. 

May be applied with other registered seed 

treatment fungicides and insecticides. Use EPAapproved dye or colorant to ensure that seed 

pieces are dyed an unnatural color.

Oilseed Crops (Group 20) (see also rapeseed)

Foliar

(ground, aerial)

10.26% OD

[352-ILT]

BeneviaTM

0.133

lb ai/A

0.0133

lb ai/gal

N/S 0.4

lb ai/A 7

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates: non-ionics; organosilicones/

organosilicates). Use a minimum of 10 gallons 

per acre for oilseed crops.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 51 of 85

Table A.1 Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application 

Timing, Type, and 

Equipment

Formulation

[EPA Reg. No.]

Trade Namea

Maximum 

Application 

Rate

Max. No. 

of

Apps per

Season

Max. 

Seasonal 

Application 

Rate

RTI Use Directions and Limitations

days

Pome Fruits (Group 11-10)

Foliar

(ground, aerial)

10.20% SE

[352-ILO]

ExirelTM

0.133

lb ai/A

0.00443

lb ai/gal

N/S 0.4

lb ai/A 7

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates: non-ionics; organosilicones/

organosilicates). Use a minimum of 30 gallons 

per acre for all fruit and nut crops.

Potato

Seed piece 

treatmentb

18.66% SC

[352-IAN]

VerimarkTM

0.176

lb ai/A

0.010

lb ai/ cwt

1

0.176

lb ai/A N/A

Apply as a water-based slurry prior to planting. 

May be applied with other registered seed 

treatment fungicides and insecticides. Use 

EPA-approved dye or colorant to ensure that 

seed pieces are dyed an unnatural color. Treat 

seed pieces as close to planting as possible. If 

planting is delayed, do not cover seed pieces as 

rotting can be accelerated. Best results are 

obtained if treated potatoes are allowed to dry 

during transit and planted the same day of 

treatment.

Seed piece 

treatmentb

48.8% FS

[100-RUEN]

A17960A ST

0.000135 lb 

ai/lb seed 1

0.000135 

lb ai/lb 

seed

N/A

Seed piece 

treatmentb

48.8% FS

[100-RURI]

A17960B ST

0.000135 lb 

ai/lb seed 1

0.000135 

lb ai/lb 

seed

N/A

Rapeseed (Canola)

Seed treatmentb

50% FS

[352-ILI]

Dermacor®

Z-103

1.0

lb ai/cwt 1

0.4

lb ai/A N/A

Apply as a water-based slurry prior to planting. 

May be applied with other registered seed 

treatment fungicides and insecticides. Use EPAapproved dye or colorant to ensure that seed 

pieces are dyed an unnatural color.

Stone Fruits (Group 12)

Foliar

(ground, aerial)

10.20% SE

[352-ILO]

ExirelTM

0.133

lb ai/A

0.00443

lb ai/gal

N/S 0.4

lb ai/A 7

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates: non-ionics; organosilicones/

organosilicates). Use a minimum of 30 gallons 

per acre for all fruit and nut crops.

Sunflower

Seed treatmentb

48.8% FS

[100-RUEN]

A17960A ST

0.2

mg ai/seed

0.00397

lb ai/lb seed

1

0.2 mg

ai/seed 

0.00397 

lb ai/lb 

seed

N/A Apply as a water-based slurry prior to planting. 

May be applied with other registered seed 

treatment fungicides and insecticides. Use EPAapproved dye or colorant to ensure that seed 

Seed treatment pieces are dyed an unnatural color. b

48.8% FS

[100-RURI]

A17960B ST

1 N/A
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 52 of 85

Table A.1 Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application 

Timing, Type, and 

Equipment

Formulation

[EPA Reg. No.]

Trade Namea

Maximum 

Application 

Rate

Max. No. 

of

Apps per

Season

Max. 

Seasonal 

Application 

Rate

RTI Use Directions and Limitations

days

Tree Nuts (Group 14) and Pistachio

Foliar

(ground, aerial)

10.20% SE

[352-ILO]

ExirelTM

0.133

lb ai/A

0.00443

lb ai/gal

N/S 0.4

lb ai/A 7

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates: non-ionics; organosilicones/

organosilicates). Use a minimum of 30 gallons 

per acre for all fruit and nut crops.

Foliar

(ground, aerial)

10.26% OD

[352-ILT]

BeneviaTM

0.133

lb ai/A

0.000443

lb ai/gal

N/S 0.4

lb ai/A 7

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates: non-ionics; organosilicones/

organosilicates). Use a minimum of 30 gallons 

per acre for tree nuts.

Tuberous and Corm Vegetables (Subgroup 1C)

Soil at Planting

(in-furrow spray, 

transplant water 

treatment, hill drench, 

surface band, soil 

shank injection)

18.66% SC

[352-IAN]

VerimarkTM

0.176

lb ai/A

0.010

lb ai/ cwt

1

0.176

lb ai/A N/A

Only to be applied to the soil by ground or drip 

chemigation application equipment. Must be 

applied uniformly in the root zone. Do not

make aerial or airblast applications. Do not treat 

plants being grown for transplanting in 

nurseries. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production.

Foliar

(ground, aerial)

Chemigation 

(overhead only)

10.26% OD

[352-ILT]

BeneviaTM

0.133

lb ai/A

0.0133

lb ai/gal

N/S 0.4

lb ai/A 5

Do not treat plants grown for transplanting. Do 

not apply to the soil or through drip irrigation 

systems. Use this product only in commercial 

and farm plantings. May be used on crops 

grown for seed production. Adjuvants may be 

used (methylated seed oils; petroleum oil 

concentrates: non-ionics; organosilicones/

organosilicates). Use a minimum of 10 gallons 

per acre for tuberous and corm vegetables.

Soil

(in-furrow spray 

during planting; 

apply impregnated 

on dry granular

fertilizer before or 

during planting; at 

plant emergence 

by direct spray to 

the soil near base 

of plant and 

incorporate with 

irrigation; at plant 

emergence with 

overhead 

chemigation after 

hilling)

20.0% WG

[100-RUER]

A16901B CP

0.125

lb ai/A

0.0125

lb ai/gal

1

0.4

lb ai/A NA

Use this product only in commercial and farm 

plantings. Do not use in greenhouses. Do not 

treat plants grown for transplanting. Apply 

within 21 days of planting or transplanting. 

Make only one soil application per growing 

season.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 53 of 85

Table A.1 Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application 

Timing, Type, and 

Equipment

Formulation

[EPA Reg. No.]

Trade Namea

Maximum 

Application 

Rate

Max. No. 

of

Apps per

Season

Max. 

Seasonal 

Application 

Rate

RTI Use Directions and Limitations

days

Residential, Commercial, Agricultural Structures

(Single and multi-family residential buildings, schools, institutional, commercial, agricultural and industrial facilities (including warehouses, apartments, 

supermarkets, restaurants, motels, hotels, hospitals, daycares, and food handling/storage/processing establishments, animal production facilities, feedlots, 

broiler houses, livestock barns, pet kennels) and transportation equipment such as aircraft, trains, ships, boats and buses).

Broadcast or 

bait station

0.5% G

[352-IAE]

HGW86

Fly Control Bait

0.0871

lb ai/A

0.00000200

lb ai/sq ft

As 

needed

Not 

specified 7

INTENDED FOR USE BY COMMERCIAL 

APPLICATORS ONLY.

Broadcast or scatter HGW86 fly control bait 

using suitable granular spreader equipment or

directly from the container evenly to the target 

areas. Use in indoor areas at all the above 

described use sites only if HGW86 fly control 

bait is placed in bait stations. Use commercially 

available bait stations that are designed to hold 

granular baits. When bait stations are being 

used, place them where the stations are 

inaccessible to children or pets.

Outdoor: broadcast

Indoor: crack and 

crevice, including 

indoor areas with 

exposed food/feed 

present

18.66% SC

[352-IAI]

HGW86 SC 

Insect Control

0.0355

lb ai/1000 sq ft

0.00887 lb 

ai/gallon

As 

needed

Not 

specified 7

INTENDED FOR USE BY COMMERCIAL 

APPLICATORS ONLY.

Avoid spraying food and feed handling 

equipment. Do not apply to areas that are 

routinely washed such as cracks and crevices in 

tops of tables, food/feed preparation and 

prepared food holding surfaces. Do not apply a 

broadcast or general surface application to

interior surfaces of residential or commercial 

structures. Do not apply this product to pets, 

edible crops, or sources of electricity. Do not 

make applications to structures while occupied 

by livestock, poultry or companion animals. Do 

not apply to milk rooms or feed rooms. Do not 

make applications to any animal feedstuffs, 

water, or watering equipment. Do not 

contaminate any animal food, feed, or water in 

and around livestock, poultry, or companion 

animal housing when making applications.

Ornamentals

(Ornamental plants/shrubs/trees and vegetable transplants in and around greenhouses, nurseries, interior plantscapes, lath and shadehouses (grassy, weedy, 

mulched, bare soil areas in and around), trees (including non-fruit bearing and nut trees), shrubs, evergreens, bedding plants, flowering plants, flowers, 

foliage plants, ground covers, vines (non-bearing), interior plantscape plants, vegetable transplants (including fruiting, leafy, and tuberous/corm)).

Foliar spray, soil 

broadcast spray, soil 

drench, soil injection, 

or chemigation

18.66% SC

[352-IAG]

HGW86 GH&N 

Insect Control

0.261

lb ai/A

0.00326

lb ai/gal

2

0.418

lb ai/A 7

Do not apply this product with aerial application 

equipment. Do not apply to greenhouse or field 

grown vegetables, only apply to vegetable 

transplants grown in enclosed structures.

Foliar

18.66% SC

[352-IAL]

HGW86 T&O 

Insect Control

0.313

lb ai/A

0.00418

lb ai/gal

2

0.418

lb ai/A 7

Do not apply this product through any type of 

irrigation system. Do not apply this product 

with aerial application equipment. Do not use 

on plants being grown for sale or other 

commercial use; or for commercial seed 

production. Do not apply this product in 

commercial nurseries and greenhouses.

Foliar, soil, 

chemigation, or 

handheld equipment

20% WG

[100-RUEE]

Mainspring 

Insecticide

0.131

lb ai/A

0.00131

lb ai/gal

2

0.263

lb ai/A 14 Do not apply with aerial equipment.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 54 of 85

Table A.1 Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application 

Timing, Type, and 

Equipment

Formulation

[EPA Reg. No.]

Trade Namea

Maximum 

Application 

Rate

Max. No. 

of

Apps per

Season

Max. 

Seasonal 

Application 

Rate

RTI Use Directions and Limitations

days

Soil (individual fire 

ant mound treatment)

20% WG

[100-RUEE]

Mainspring 

Insecticide

0.00475

lb ai/gal NA NA NA

For small mounds (<6 inch in diameter) apply 1 

gal of water per mound and for larger mounds 

apply 2-3 gal of dilute solution per mound for 

optimum control. Direct the application to the 

center of the mound, including a 6-inch diameter 

circle.

Foliar

20% WG

[100-RUEG]

A16901B 

Residential

0.000781

lb ai/gal 2

0.00156

lb ai/gal 7

Mix 1 teaspoon in 1 gallon of water.

Apply as a thorough cover spray.

1 gallon treats plants in a 400 square feet area.

Turfgrass

(including golf courses, institutional, commercial and residential lawns, landscape, recreational, sod farms, sports fields, parks, municipal grounds and 

cemeteries).

Foliar

18.66% SC

[352-IAL]

HGW86 T&O 

Insect Control

0.313

lb ai/A

0.00418

lb ai/gal

2

0.418

lb ai/A 7

Do not apply this product through any type of 

irrigation system. Do not apply this product 

with aerial application equipment. Do not use 

on plants being grown for sale or other 

commercial use; or for commercial seed 

production. Do not apply this product in 

commercial nurseries and greenhouses.

Foliar

20% WG

[100-RUEU]

A16901B Turf 

Insecticide

0.133

lb ai/A

0.00203

lb ai/gal

2

0.265

lb ai/A 30 Do not apply this product through any type of irrigation system.

a Formulation codes: G = granular, SC = suspension concentrate, SE = suspoemulsion, WG = water dispersible granules, OD = 

oil dispersion, FS = flowable suspension.

b cwt = hundredweight (100 lb seed).

Seed treatment rate calculations are based on the following assumptions:

Mustard seed: 90,000 to 115,000 seeds per lb (assumed to be equivalent to rapeseed/canola).

Potato seed pieces: 5 to 11 seed pieces per lb.

Rapeseed (canola): 90,000 to 115,000 seeds per lb.

Sunflowers: 2,000 to 9,000 seeds per lb.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 55 of 85

Appendix B. Toxicology Profile and Executive Summaries

B.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food and non food uses for cyantraniliprole are in Table 

1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols 

were used.

Table B.1 Summary of Toxicology Data Requirements

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation ..............................................

870.2600 Dermal Sensitization......................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3050 28-Day Oral (rodent) .....................................................

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent) .........................................

870.3200 21-Day Dermal ..............................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation (28-Day Inhalation) .........................

no

yes

yes

CRb

CRb

yes

yes

yes

yes

yes

-

yes

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (nonrodent).............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100b Chronic Toxicity (nonrodent-dog).................................

870.4200b Carcinogenicity (mouse)................................................

870.4300 Chronic Toxicity/Oncogenicity (rodent-rat)..................

no

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)...............................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotoxicity Screening Battery (rat) .................

870.6200b 90-Day Neurotoxicity Screening Battery (rat)...............

870.6300 Develop. Neurotoxicity .................................................

no

no

yes

yes

CRb

-

-

yes

yes

-

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration ........................................................

870.7800 Immunotoxicity .............................................................

yes

CRb

yes

yes

-

a

yes

a A dermal penetration study on the technical grade is not available; however, both in-vivo and in-vitro dermal penetration 

studies on four formulations are available. A human dermal absorption factor was calculated based on these studies.

b CR = conditionally required.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 56 of 85

B.2 Toxicity Profiles

Table B.2.1 Acute Toxicity Profile – Technical Cyantraniliprole

Guideline No. Study Type MRID Results Toxicity Category

870.1100 Acute oral (mouse) 48119957 LD50 >5000 mg/kg IV

Acute oral (rat) 48119952 LD50 >5000 mg/kg IV

870.1200 Acute dermal (rat) 48119953 LD50 >5000 mg/kg IV

870.1300 Acute inhalation—4 hour (rat) 48119958 LC50 >5.2 mg/L IV

870.2400 Acute oral (mouse) 48119957 LD50 >5000 mg/kg IV

870.2500

Skin irritation (rabbit) 48119954 Not irritating

NA

Eye irritation (rabbit) 48119955 Slightly irritating; 

clearing by 72 hours

Eye irritation (rabbit) 48208421 Not irritating

870.2600

Skin sensitization (mouse)

local lymph node assay 48208422 Not sensitizing

Skin sensitization (mouse)

local lymph node assay 48208423 Not sensitizing

Skin sensitization (guinea pig)

maximization test 48119984 Not Sensitizing

Table B.2.2 Acute Toxicity Profile – Cyantraniliprole Metabolites

Test Substance Study Type MRID Results Toxicity Category

IN-JSE76-005 Acute oral (rat) 48119978 LD50 >5000 mg/kg IV

IN-PLT97-003 Acute oral (mouse) 48122579 LD50 >5000 mg/kg IV

IN-F6L99-004 Acute oral (mouse) 46979929 LD50 >2000 mg/kg IV

IN-N5M09-003 Acute oral (mouse) 48119939 LD50 >5000 mg/kg IV

Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

Subchronic Toxicity Studies

870.3050

2-Week oral 

study—gavage with 

metabolism 

information (rats)

48119938 (2010)

Acceptable/non-guideline

25, 300, and 1,000 

mg/kg/day

NOAEL =1,000 mg/kg/day (HDT). Treatment 

related effects were not found at any dose levels.

Supplemental data:

The kinetic data indicate that the plasma T1/2 = 3.84, 

6.41, and 5.44 hours for the 25, 300, and 1,000 

mg/kg/day, respectively. Tmax = 2.00, 2.33, and 1.67 

hours in the 25, 300, and 1,000 mg/kg/day groups, 

respectively. The tissue concentration in peripheral 

fat was <0.1% at 24 hrs after dosing. Total 

cytochrome P-450 content in male or female rats was 

minimally elevated. In male rats, cyantraniliprole is 

an inducer of cytochrome P-450 isozyme CYP1A1 

and CYP2B1. In female rats, cyantraniliprole is an 

inducer of cytochrome P-450 isozyme CYP2B1.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 57 of 85

Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

870.3050 28-Day feeding 

study (mice)

48119940 (2009)

Acceptable/guideline

0, 300, 1,000, 3,000, and

7,000 ppm

M: 0, 53, 175, 528, and 1,261 

mg/kg/day

F: 0, 63, 212, 664, and 

1,476 mg/kg/day

NOAEL = 528/664 (M/F).

LOAEL = 1,261/1,476 mg/kg/day (M/F) (highest 

dose tested). Adverse effects were not found at any 

dietary concentrations.

Supplemental data:

Cyantraniliprole does not induce hepatic -oxidation 

in male or female mice. In male mice, the total 

cytochrome P-450 content significantly increased at 

dietary concentrations of 3,000 and 7,000 ppm. In 

female mice, total cytochrome P-450 content 

significantly increased at dietary concentrations of 

300, 1,000, 3,000, and 7,000 ppm. At 3,000 and 

7,000 ppm, both male and female mice show 

adaptive liver responses such as increased liver 

weight and liver enzyme.

870.3050 28-Day feeding 

study (rats)

48119941 (2009)

Acceptable/guideline

0, 600, 2000, 6000, and

20,000 ppm

M: 0, 53, 175, 528, and 

1,776 mg/kg/day

F: 0, 62, 188, 595, and 

1,953 mg/kg/day

NOAEL for males cannot be established due to 

treated-related increase in the incidence of thyroid 

follicular hypertrophy at 53 mg/kg/day (LOAEL) 

(lowest dose tested).

For females: NOAEL = 62 mg/kg/ day. LOAEL = 

188 mg/kg/day based on thyroid follicular cell 

hypertrophy.

Supplemental data:

In male rats, cyantraniliprole is a mild inducer of 

hepatic UDP- glucuronyltransferase activity (range 

from ↑39% at low dose to ↑132% at high dose) while 

inducing only a minimal effect on cytochrome P-450 

content. In female rats, cyantraniliprole causes a 

slight increase in total hepatic cytochrome P-450 

content while inducing a somewhat lesser effect on 

hepatic UDP-glucuronyltransferase activity. 

Cyantraniliprole does not induce hepatic -oxidation, 

a measure of peroxisome proliferation, in male or 

female rats.

870.3050

28-Day palatability 

study—dietary 

(dogs)

48119942 (2007)

Acceptable/non-guideline

0, 1000, 10,000, and 

40,000 ppm 

M: 0, 35, 311, and 

1,043 mg/kg/day

F: 0, 35, 335, and 

1,240 mg/kg/day)

NOAEL for male and female dogs could not be 

determined. LOAEL = 35 mg/kg/day (lowest dose 

tested) based on decreases in body weight, food 

consumption, food efficiency, and changes in clinical 

chemistry (↑ALP, ↓ cholesterol and ↓ albumin). 

Supplemental data:

Increases in hepatic cytochrome P-450 (total and 

2B1, 3A2, and 4A1/2/3 isozymes) were observed in 

all male and female dose groups but the increase did 

not demonstrate a dose related response. 
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 58 of 85

Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

870.3100 90-Day feeding 

toxicity study 

(mice)

48119943 (2007)

Acceptable/ guideline

48119944 (2007)

supplement to 48119943 

Provide information about 

metabolites

0, 50, 300, 1,000, and 7,000 

ppm

M: 0, 7, 47, 150, and 1,092 

mg/kg /day.

F: 0, 10, 58, 204, & 

1,344 mg/kg/day.

NOAEL = 150/204 (M/F)

LOAEL =1,092/1,344 (M/F) based on increased

incidence of focal necrosis of the liver, and liver 

weight increase.

Supplemental data:

Metabolite analyses showed that IN-MLA84 was the 

most prevalent analyte present in male and female 

mice, followed by cyantraniliprole. Plasma values 

for all the evaluated metabolites were similar

between males and females at comparable dose 

levels.

870.3100

90-Day feeding 

study (rats)

[Interim sacrifice

was also conducted 

on 5/sex/dose on 

29th (♂) day and

30th day(♀)]

48119945 (2007)

Acceptable/ guideline

48119946 (2007)

Supplement to 48119945

0, 100, 400, 3,000, and 

20,000 ppm

M: 0, 6, 22, 168, and 1,147 

mg/kg /day

F: 0, 7, 27, 202, or 

1,346 mg/kg/day

Females: NOAEL = 7 mg/kg/day.

LOAEL = 27 mg/kg/day) based on thyroid follicular 

cell hypertrophy, increased thyroid weights, and 

alterations in thyroid hormone homeostasis.

Males: NOAEL =168 mg/kg/day.

LOAEL= 1,147 mg/kg/day) based on thyroid 

follicular cell hypertrophy, increased thyroid 

weights, and alterations in thyroid hormone 

homeostasis in male rats.

Supplemental data:

IN-MLA84 was the major metabolite present in the 

plasma of male and female rats followed by parent 

cyantraniliprole and IN-J9Z38.

870.3150

90-Day oral study—

dietary (dogs)

[T3, T4, TSH, and 

cytochrome P450 

were also measured]

48119948 (2007)

Acceptable/guideline

48119947 (2007)

Supplement to 48119948

0, 30, 100, 1,000, and 10,000 

ppm

M: 0, 1, 3, 32, and 281 

mg/kg/day

F: 0, 1, 3. 34, and 294 

mg/kg/day)

NOAEL = 3 mg/kg/day.

LOAEL = 32 mg/kg/day based on based on a 

collection of treatment-related effects indicative of 

hepatotoxicity. The effects included decreases in 

total protein, albumin, and cholesterol in males and 

females; increases in alkaline phosphatase in males 

and females, and increases in alanine 

aminotransferase in females, and increase liver 

weights in males and females.

Supplemental data indicated the major analyte in the 

plasma was the parent cyantraniliprole. Thyroid 

hormone levels were not consistently changed.

870.3200 28-Day dermal

study (rats)

48119970 (2009)

Acceptable/guideline

0, 100, 300, and 1,000 mg/kg 

/day (6 hours/day)

NOAEL ≥ 1,000 mg/kg/day (highest dose tested). 

Systemic toxicity was not found.

870.3465 28-Day inhalation

study (rats)

48663602 (2011)

Acceptable non guideline 

0, 1, 10, and 100 mg/m3

NOAEL = 100 mg/m3(0.1 mg/L). Systemic or 

portal of entry effects were not seen at the highest 

concentration. However, at 100 mg/m3, an increase 

in the incidence of minimal laryngeal squamous 

metaplasia was found; it was considered to be 

treatment-related and non adverse.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 59 of 85

Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

Developmental and Reproductive Toxicity Studies

870.3700a

Prenatal 

developmental

study—gavage (rats)

48119968 (2009)

Acceptable/guideline

0, 20, 100, 300, and 

1,000 mg/kg/day (GD 6 to 

20)

Both maternal and developmental NOAELs = 1,000 

mg/kg/day, the highest dosage tested. LOAELs were 

not established.

870.3700b

Prenatal 

developmental 

study—gavage 

(rabbits)

48119969 (2009)

Acceptable/guideline

0, 25, 100, 250, and 500 

mg/kg /day (GD 7-28)

Maternal: NOAEL = 25 mg/kg/day.

LOAEL = 100 mg/kg/day based on increased 

mortality, increased incidences of diarrhea and 

reduced and/or absent of feces, decreased body 

weights, and reduced food consumption.

Developmental: NOAEL=100 mg/kg /day. LOAEL 

was 250 mg/kg/day based on reductions in mean 

fetal body weights.

870.3800 2-Generation 

reproduction

study—dietary (rats)

48119967 (2011)

Acceptable/guideline

0, 20, 200, 2,000, and 20,000 

ppm

0, 1.4, 14, 136, and 1,344 

mg/kg/day based on 

premating compound intake 

in P1 females

Parental NOAEL = 1.4 mg/kg/day.

LOAEL= 14 mg/kg/day based on thyroid weight 

increase and corresponding dose-related increase in 

the incidence of thyroid follicular epithelial cell 

hypertrophy/ hyperplasia.

Reproductive: NOAEL = 1344 mg/kg/day (the 

highest dose tested) based on the lack of adverse test 

substance-related effects on fertility and reproductive 

parameters at any dose levels in the study.

Offspring: NOAEL = 14 mg/kg/day. LOAEL=136 

mg/kg/day based on dose-related decreases in organ 

weights (thymus and spleen), and pup body weight 

in the F2 generation pups.

Chronic Toxicity Studies

870.4100

Combined chronic/ 

carcinogenicity 

study (rats)

48122577 (2011)

Acceptable/guideline

0, 20, 200, 2,000, and 

20,000 ppm

M: 0, 0.8, 8.3, 84.8, and 

906.6 mg/kg /day

F: 0, 1.1, 10.5, 106.6, and

1,160.8 mg/kg/day

NOAEL = 8.3 mg/kg/day

LOAEL = 84.8 mg/kg/day based on microscopic 

liver pathology characterized by foci of cellular 

alteration (clear, eosinophilic, and basophilic) and 

focal vacuolation.

Cyantraniliprole did not produce compound-related 

or dose-related increase in tumor incidence.

870.4100b

1-Year oral study—

dietart with active 

ingredient (dogs) 

[a recovery period 

was also included]

48119960 (2010)

Acceptable/guideline

48208427 (2010)

Supplement to 48119960.

0, 40, 200, 1,000, and 5,000 

ppm

M: 0, 1, 6, 27, and 144 

mg/kg/day

F: 0, 1, 6, 27, and 133 

mg/kg/day

NOAEL = 1 mg/kg/day

LOAEL = 6 mg/kg/day based on decreases in 

albumin levels, statistically significant increases in 

liver weight and alkaline phosphatase. At the next 

dose level (1,000 ppm, or 27 mg/kg bw/day) 

histopathological changes characterized by 

hepatocellular degeneration and inflammatory 

process with associated increases in alkaline 

phosphatase (ALP) and alanine aminotransferase 

(ALT), and decreases in total protein and albumin 

were found.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 60 of 85

Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

870.4200b

18-Month 

carcinogenicity 

study (mice)

48122578 (2011)

Acceptable/guideline

0, 20, 150, 1,000, and 

7,000 ppm

M: 0, 2, 16, 104, and 769 

mg/kg/day

F: 0, 2, 19, 131, and 904 

mg/kg/day

NOAEL = 104/131 (M/F)

LOAEL = 769/904 (M/F)

Based on the finding that cyantraniliprole induced a 

statistically significant increase in food consumption 

and a decrease in food efficiency with very little 

changes in body weights. These changes suggest that 

the high dose animals were unable to adequately 

utilize food, and it was a compound-related effect 

and was considered to be adverse.

Cyantraniliprole did not produce compound-related 

increase in tumor incidence.

Genotoxicity Toxicity Studies

870.5100

Bacterial reverse 

mutation test (S. 

typhimurium and E. 

coli)

48122587 (2010)

Acceptable/guideline 

Negative.

0, 50, 150, 500, 1,500, and 5,000 g/plate were 

tested (+/- S9). Precipitate was observed at 5,000 

g/plate.

48119980 (2009)

Acceptable/guideline

Negative.

The dose levels tested were 0, 50, 150, 500, 1,500, 

and 5,000 μg/plate (+/- S9); precipitate was observed 

at 5,000 g/plate.

48208424 (2009)

Acceptable/guideline

Negative.

The dose levels tested were 0, 50, 150, 500, 1,500, 

and 5,000 μg/plate. (+/- S9). Precipitation was 

observed at 5,000μg/ plate.

870.5300

In vitro

mammalian cell 

gene mutation test 

(CHO/HGPRT 

assay)

48122589 (2010)

Acceptable/guideline

Negative.

of 0, 50.0, 100, 150, 250, and 500 μg/ml (+/- S9). 

Ethyl methanesulfonate (EMS) and benzo(a)pyrene 

(BaP) were used as positive controls.

870.5300

In vitro

CHO/HPRT

forward mutation 

assay

48208443 (2011)

Acceptable/guideline

Negative.

0, 10.0, 25.0, 50.0, 100, 250, 500, 750, and 1,000 

μg/mL were tested. Ethyl methanesulfonate (EMS)

and methylcholanthrene (MCA) were used as 

positive controls. Compound precipitation was 

observed at concentrations in treatment medium 

≥250 g/mL.

870.5375

In vitro

Mammalian 

chromosome 

aberration test with 

human lymphocytes

48208425 (2009)

Acceptable/guideline

Negative.

0, 62.5, 125, 250, 500, 600, 700, 800, and 900 

g/mL for the 4-hour non-activated and activated 

treatment conditions, and 0, 31.3, 62.5, 125, 250, 

400, 500, 600, 700, and 800 g/mL for the 20-hour 

non-activated treatment condition. 

870.5375

In vitro

Mammalian 

chromosome 

aberration test with 

human lymphocytes

48208426 (2009)

Acceptable/guideline

Negative .

Doses ranged from 125 to 3,500 μg/mL for the nonactivated and S9-activated 4-hour exposure groups, 

and from 15.7 to 1,500 μg/mL for the non-activated 

20-hour exposure group. Compound precipitation 

was recorded at ≥1,000 μg/mL.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 61 of 85

Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

870.5375

In vitro

Mammalian 

chromosome 

aberration test with 

human peripheral 

blood lymphocytes 

(HPBL)

48122588 (2010)

Acceptable/guideline

Negative.

0, 62.5, 125, 250, 500, 600, 700, 800, and 

1,000 g/mL for non-activated 4-hour; 0, 62.5, 125, 

250, 500, 600, 700, 800, and 900 g/mL for 

activated 4-hour; and 0, 7.8, 15.6, 31.3, 62.5, 125, 

250, 500, and 1,000 g/mL for non-activated 20-

hour. Visible precipitate was observed in treatment 

medium at 500 g/mL.

870.5395

(Other Genotoxic 

Effects)

In vivo 

Mouse bone marrow 

micronucleus—

gavage

48208444 (2011)

Acceptable/guideline

Negative.

Doses were 0, 500, 1,000 and 2,000 mg/kg by singledose oral gavage (10 Crl:CD1(ICR) mice/sex/dose).

Neurotoxicity Studies

870.6200a Acute neurotoxicity

study—gavage (rats)

48119950 (2006)

Acceptable/guideline

0, 250, 1,000, and

2,000 mg/kg

NOAEL = 2,000 mg/kg (HDT). Adverse effects 

were not observed at any tested dose levels.

870.6200b

90-Day 

neurotoxicity

study—dietary (rats)

48119966 (2009)

Acceptable/guideline

0, 200, 2,000, and

20,000 ppm

M: 0, 11, 116, and 1,195 

mg/kg/day

F: 0, 14, 137, and 1,404 

mg/kg/day

NOAEL = 1,195/1,404 mg/kg/day (M/F) (HDT). 

Adverse effects were not observed at any tested dose 

levels.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 62 of 85

Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

Metabolism Studies

870.7485 Metabolism study—

ADME (rats)

48119949 (2010)

Acceptable/guideline

Single gavage dose of 10 or 

150 mg/kg/day (low- and 

high-dose, respectively) of 

either [CN14C]-

cyantraniliprole or [PC14C]-

cyantraniliprole

Cyantraniliprole was absorbed readily either at low 

(10 mg/kg/day) or high (150 mg/kg/day) dose with 

oral dosing (62-80% of the administered dose was 

absorbed). The majority of the absorption occurred 

during the first 48 hours, and the peak plasma 

concentration was reached at approximately 2 hour 

after dosing irrespective of the position of label, sex 

of the test animal, and dose level.

Male low dose half-lives: CN T1/2 = 42 hrs; PC T1/2 = 

54 hrs;

Female low dose half-lives: CN T1/2 = 129 hrs; PC 

T1/2 = 117 hrs;

Male high dose half-lives: CN T1/2 = 62 hrs; PC T1/2 

= 55 hrs;

Females high dose half-lives: CN T1/2 = 65 hrs; 

PC T1/2 = 80 hrs.

The distribution data showed that the majority of the 

dose was initially associated with the GI tract 

contents and subsequently showed uptake and 

distribution to all tissues. Female rats retained a 

greater proportion of 14C residues than male rats.

Cyantraniliprole was readily hydroxylated to form 

IN-N7B69 and IN-MYX98. IN-N7B69 was further 

metabolized to a glucuronide. Cyantraniliprole also 

underwent ring closure to generate IN-J9Z38. The 

metabolites which were found to be greater than 5% 

of the administered dose were bis-hydroxycyantraniliprole, IN-N7B69, IN-MYX98, INDBC80, 

and the parent compound.

There was very little difference in elimination 

between rats administered [CN14C]-cyantraniliprole 

or [PC14C]-cyantraniliprole. Majority of the 

administered dose was eliminated during the first 24 

to 48 hour after administration. The major route of 

elimination was via feces (approximately 80% of the 

administered dose). The data show no 

bioaccumulation).

870.7485

Disposition during 

and after multiple 

dosing—kinetics

and metabolism

study (male and 

female rats)

48119951 (2009)

Acceptable/non-guideline

A mixture of [CN14C]-

cyantraniliprole and [PC14C]-cyantraniliprole at a 1:1 

mg ratio: 10 mg/kg /day 

multiple doses by gavage

The data on the tissue concentrations and the tissue 

percent recovery showed that tissue concentration 

fell rapidly following the end of dosing. The tissue 

concentration half-lives ranged from 2.6 days in fat 

to approximately 6 days in whole blood. Very little 

tissue accumulation was found.

The total percent of the administered dose eliminated 

via urine was 29% in males and 20% in females and 

that eliminated via feces was approximately 60% in 

males and females.

Metabolites found in this study were similar to those 

in the single dose study (MRID 48119949).

Dermal Absorption Toxicity Studies

870.7600 Dermal penetration No dermal penetration study on technical grade is available, but several in vivo and in 

vitro dermal penetration studies on three formulations are available.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 63 of 85

Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

In vivo

dermal absorption—

SC formulation

(rats)

48120313 (2009)

Acceptable

200 g/L and 1 g/L

Maximum absorption 

200 g/L = 0.34% at 498 

hrs

1 g/L = 0.93% at 498 

hrs 

DAF

200 g/L = 0.02%

1 g/L = 0.43%

Nearly all the applied 

dose was readily 

removed from the skin 

surface with gentle skin 

washing.

In vitro

dermal penetration 

study—SC 

formulation (rat and 

human skin)

48120314 (2009)

Acceptable

200 g/L & 1g/L

Maximum Dermal 

penetration at 24 hrs:

Human skin: 

200 g/L = 0.24% 

1 g/L = 5.28%

Rat skin:

200 g/L = 3.69% 

1 g/L = 11.5%

In vivo

dermal absorption—

SE formulation

(rats)

48120413 (2009)

Acceptable

100 g/L and 1 g/L

Maximum absorption:

100 g/L = 1.25% at 498 

hrs

1 g/L = 1.47% at 498 

hrs 

DAF

100 g/L = 0.25%

1 g/L = 0.83%

Nearly all the applied 

dose was readily 

removed from the skin 

surface with gentle skin 

washing.

In vitro

dermal penetration 

study—SE 

formulation (rat and 

human skin)

48120412 (2009)

Acceptable

100 g/L and 1 g/L

Maximum Dermal 

penetration at 24 hrs:

Human skin:

100 g/L = 2.7 % 

1 g/L = 6.1 %

Rat skin:

100 g/L =13.4 % 

1 g/L = 10.7 %

In vivo

dermal absorption—

OD formulation

(rats)

48120209 (2008)

Acceptable

100 g/L and 1 g/L

Maximum absorption 

100 g/L = 1.36% at 498 

hrs

1g/L = 0.74% at 498 hrs DAF

100 g/L = 0.06%

1 g/L = 0.03%

Nearly all the applied 

dose was readily 

removed from the skin 

surface with gentle skin 

washing.

In vitro

dermal penetration 

study—OD 

formulation (rat and 

human skin)

48120210 (2008)

Acceptable

100 g/L and 1 g/L

Maximum Dermal 

penetration at 24 hrs:

Human skin:

100 g/L = 0.25 % 

1 g/L = 0.86%

Rat skin:

100 g/L = 10.5% 

1 g/L = 20.2 %

In vivo

dermal absorption—

cyantraniliprole/

thiamethoxam WG 

formulation 

(A16901B)

formulation (rat

skin)

48432611 (2011)

Acceptable

Slurry concentrate, 1/20 and

1/267 dilution, correspond to 

10.0, 1.0, and 0.75 mg/rat 

respectively

At 24 hours after 

dosing: 0.08%, 0.92%, 

and 1.23% of the 

applied dose were 

absorbed with slurry 

concentrate, 1/20 

dilution and 1/267 

dilution, respectively.

DAF for WG 

formulation:

Slurry concentrate 1/20 

dilution = 0.005%

Slurry concentrate 1/267 

dilution = 0.07%
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 64 of 85

Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

In vitro

dermal penetration 

study—

cyantraniliprole/

thiamethoxam WG 

formulation 

(A16901B)

formulation (rat

skin)

48432513 (2011)

Acceptable

Slurry concentrate, 1/20 

dilution and 1/267 dilution 

At 24 hours after 

dosing, the total 

absorbable dose were 

0.133%, 2.57%, and 

15.78% of the applied 

dose for slurry 

concentrate, 1/20 

dilution and 1/267 

dilution, respectively.

Nearly all the applied 

dose was readily 

removed from the skin 

surface with gentle skin 

washing.

In vivo

dermal absorption—

cyantraniliprole/

thiamethoxam WG 

formulation 

(A16901B)

formulation (human 

skin)

48432512 (2011)

Acceptable

Slurry concentrate, 1/20 

dilution and 1/267 dilution

At 24 hours after 

dosing, the total 

absorbable dose were 

0.008%, 0.128% and

0.92% of the applied 

dose for slurry 

concentrate, 1/20 

dilution and 1/267 

dilution, respectively.

In vitro

dermal penetration 

study—

cyantraniliprole/

thiamethoxam WG 

formulation 

(A16901B)

formulation (human 

skin)

48432412 (2011)

Acceptable

Slurry concentrate, 1/534 

dilution and 1/1,600 dilution

The total absorbable dose expressed as percent of the 

applied dose over 24 hours was 0.010, 1.597, and 

0.561% for concentrate slurry, 1/534 w/w dilution, 

and 1/167 w/w dilution, respectively. Irrespective of 

the applied dose, greater than 97% of the applied 

dose remained on the skin surface after a 24 hour 

exposure period and was readily removed by gentle 

skin washing. Very low proportions of the dose 

were associated with the stratum corneum and the 

remaining epidermal membrane.

Immunotoxicity Toxicity Studies

870.7800

28-Day 

immunotoxicity 

study—dietary (rats)

[assess primary 

humoral response to 

sheep red blood 

cells (sRBC)]

48119971 (2009)

Acceptable/guideline

0, 20, 200, 2,000, and

20,000 ppm

M: 0, 1.7 , 17, 166, and 1,699 

mg/kg/day

F: 0, 1.8 , 18, 172, and 1,703 

mg/kg/day

Systemic toxicity NOAEL = 1,699/1,703 mg/kg/day 

(M/F) (highest dose tested). A LOAEL was not

established.

The SRBC-specific IgM ELISA results did not 

indicate any treatment-related immunosuppressive 

effects. Therefore, the immunotoxicity NOAEL = 

1,699/1,703 mg/kg/day (M/F).

870.7800

28-Day 

immunotoxicity 

study—dietary 

(mice) 

[assess primary 

humoral response to 

sheep red blood 

cells (sRBC)]

48119972 (2009)

Acceptable/guideline

0, 20, 150, 1,000, or 

7,000 ppm

M: 0, 3.0, 23, 154, or 1,065 

mg/kg/day

F: 0, 4.1, 32, 224, or 1,386 

mg/kg/day

The systemic toxicity NOAEL = 1,065/1,386 

mg/kg/day (M/F) (highest dose tested). The LOAEL 

was not established.

The SRBC-specific IgM ELISA results did not 

indicate any treatment-related immunosuppressive 

effects. There were no statistical differences in 

quantity of SRBC-specific IgM in any treatment 

group when compared with the vehicle controls. 

Evaluation of individual animal data did not show 

any trend or distribution that would demonstrate 

significant suppression of SRBC-specific antibody 

response. Therefore, the immunotoxicity NOAEL = 

1,065/1,386 mg/kg/day (M/F) (highest dose tested).
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

Page 65 of 85

Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

Metabolite: IN-JSE76 Toxicity Studies

870.3050

28-Day feeding 

study with INJSE76 (up to 

20,000ppm)

48119983 (2010)

Acceptable/guideline

48208474 (2010)

Supplemental study to 

48119983

0, 100, 400, 3,000, and 

20,000ppm

M: 0, 7, 29, 212, and 1,445 

mg/kg/day

F: 0, 8, 31, 232, and 1,471 

mg/kg/day

NOAEL = 1,445/1,471 mg/kg /day (M/F) (highest 

dose tested).

A LOAEL was not established because toxicity was 

not seen at any tested dose level.

870.5100

Bacterial reverse 

mutation test (S. 

typhimurium & E. 

coli)

48119976 (2009)

Acceptable/guideline 

Negative.

Toxicity test: 1.5, 5.0, 15, 50, 150, 500, 1,500, and 

5,000 g/plate. 

Confirmatory assay, 50, 150, 500, 1,500, and 

5,000 g/plate.

870.5300

In vitro

mammalian cell 

gene mutation test 

(CHO/HGPRT 

assay)

48119974 (2009)

Acceptable/guideline

Negative.

Test concentrations: 0, 100, 150, 500, 1,000, and 

1,500 g/mL.

870.5375

In vitro

mammalian 

chromosome 

aberration test with 

human lymphocytes

48119975 (2009)

Acceptable/guideline

Negative.

-S9: 0, 313, 625,1,250, and 2,500 g/mL-4-hr 

exposure; 

-S9 156, 313, 625, 1,000, 1,500, and 2,000 g/mL 

20-hr exposure; and

+S9: 156, 313, 625, 1,250, and 2,500 g/mL-4-hr 

exposure.

Metabolite: IN-PLT97 Toxicity Studies

870.5100

Bacterial reverse 

mutation test (S. 

typhimurium & E. 

coli)

48122580 (2009)

Acceptable/guideline

Negative.

0, 50, 150, 500, 1,500, and 5,000 g/plate were 

tested in the confirmatory test. The test substance 

was administered as a workable suspension in 

DMSO.

870.5300

In vitro

mammalian cell 

gene mutation test 

(CHO/HGPRT 

assay)

48122582 (2010)

Acceptable/guideline

Negative.

Test concentrations: 10, 25, 50, 100, and 150 μg/ml. 

Exposure time = 5 hours. Precipitation occurred at ≥ 

150 μg/ml.

870.5375

In vitro

mammalian 

chromosome 

aberration test with 

human lymphocytes

48122581 (2011)

Acceptable/guideline

Negative.

-S9 &+S9: 50, 100, 200, 400, 800, and 1,550 g/mL 

-4 hr exposure.

-S9: 25, 50, 100, 200, 500, 1000, and 1,550 g/mL -

20-hr exposure.
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Table B.2.3 Subchronic, Chronic, and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

Metabolite: IN-F6L99 Toxicity Studies

870.5100

Bacterial reverse 

mutation test (S. 

typhimurium & E. 

coli)

46979931 (2006)

Acceptable/guideline

Negative.

Initial toxicity (Trial I): 33.3, 66.7, 100, 333, 667, 

1,000, 3,333, and 5,000 g/plate.

Confirmatory test (Trail II): 333, 667, 1,000, 3,333, 

and 50,00 g/plate .

Metabolite: IN-N5M09 Toxicity Studies

870.5100

Bacterial reverse 

mutation test (S. 

typhimurium & E. 

coli)

48119982 (2009)

Acceptable/guideline

Negative.

Toxicity test (Trial I):1.5, 5.0, 15, 50, 150, 500 

1,500, and 5,000 g/plate.

Confirmatory assay(Trial II): 50, 150, 500, 1,500,

and 5,000 g/plate.

Other (Non-Guideline) Studies (Mechanistic Studies)

Adrenal and thyroid 

mechanistic study 

(rats)

48119973 (2010)

Acceptable/non-guideline

For thyroid effect (female 

rats): 20,000 ppm (1,903 

mg/kg/day) for 29 days

For adrenal effect (male 

rats): 20,000 ppm 

(1,230 mg/kg/day) for 93 

days

In 20,000 ppm females, increased liver and thyroid 

weights and minimal thyroid follicular cell 

hypertrophy were seen. These effects were 

associated with increased hepatic UDPglucuronyltransferase (UDPGT) activity and reduced 

serum T4 and increased TSH levels.

90-Day adrenal 

mechanistic study—

feeding (male mice)

48119985 (2010)

Acceptable/non-guideline

7,000 ppm (1,120 

mg/kg/day) for 93 days

Cyantraniliprole at 1,120 mg/kg/day did not 

adversely affect the following parameters: survival, 

clinical signs of toxicity, body weight, food 

consumption, or food efficiency. No gross or 

microscopic pathology effects were attributed to test 

substance exposure. No adverse effects on adrenal 

cortical structure or function were found. Basal 

urinary corticosterone was comparable between the 

control and treated groups. The electron microscopy 

results showed that cyantraniliprole did not affect 

adrenal cortical cell structure. The finding of the 

microvesiculation of the adrenal cortex in male mice 

at ≥ 50 ppm in the 90-day study (MRID 48119943) 

was not duplicated in this study where male mice 

were fed dietary concentration of 7,000 ppm (1,120 

mg/kg/day) of cyantraniliprole for 93 days.

In vitro

thyroid peroxidase 

inhibition

[thyroid preparation 

derived from 

Yucatan pig, 

microswine]

48119979 (2010)

Acceptable/non-guideline

2, 5, 10, 20, 50, 100, 200, 

and 400 M

Positive control: 

Propylthiouracil (PTU)

Cyantraniliprole did not cause inhibition of thyroid 

peroxidase at any concentration tested; therefore, an 

IC50 value for cyantraniliprole was unable to be 

determined. The positive control, PTU at 7.2 M 

caused a 50% reduction in enzyme activity.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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B.3 Hazard Identification and Endpoint Selection

B.3.1 Acute Reference Dose (aRfD) - General Population

Not established. An endpoint attributable to a single dose was not seen in the database 

(including the pre-natal toxicity studies in rats and rabbits). 

B.3.2 Chronic Reference Dose (cRfD)

Study Selected

One-Year Oral Toxicity Study in Dogs

MRID No.

48119960

Dose and Endpoint for Establishing cRfD

NOAEL = 1 mg/kg/day. LOAEL = 6 mg/kg/day based on effects indicative of liver toxicity 

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

levels).

Uncertainty Factor (UF)

100X (10X intraspecies, 10X interspecies, 1X FQPA).

Comments about Study/Endpoint/Uncertainty Factor

The one-year dog study is appropriate for both the duration and population of concern. The dogs 

appear to be more sensitive to the liver effects than rats. The results of the one-year dog study 

provide the most sensitive LOAEL (6 mg/kg/day) for liver effects. The POD is also protective 

of the thyroid effects seen in all toxicity studies in rats, including the 2-generation reproduction 

study (LOAEL = 14 mg/kg/day). 

cRfD = 1 mg/kg/day = 0.01 mg/kg/day

 100

cPAD = 0.01 mg/kg/day = 0.01 mg/kg/day

1

B.3.3 Incidental Oral Exposure (Short- and Intermediate-Term)

Selected Study

90-Day Oral Toxicity Study in Dogs

MRID No.

48119947, 48119948

Dose and Endpoint for Risk Assessment

NOAEL = 3 mg/kg/day. LOAEL = 32 mg/kg/day based on a collection of treatment-related 

effects indicative of liver toxicity. The effects include decreases in total protein, albumin, and 

cholesterol in males and females; increases in alkaline phosphatase in males and females;
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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increases in alanine aminotransferase in females; and increased liver weights in males and 

females.

Uncertainty Factor (UF)

100X (10X intraspecies, 10X interspecies, 1X FQPA).

Comments about Study/Endpoint/Margins of Exposure

This study is appropriate for the duration of exposure. While the population of concern is for 

children engaged in hand-to-mouth behavior, the POD (NOAEL of 3 mg/kg/day) selected from 

the 90-day study is protective of the effects seen in the 2-generation reproduction study in rats. 

B.3.4 Dermal Exposure (Short-, Intermediate- and Long-Term)

Systemic toxicity was not seen in the 28-day dermal toxicity in rats up to the limit dose (1000 

mg/kg/day). The target organs of toxicity were looked at in this study. In addition, there are no 

concerns for developmental, reproductive, or neurotoxicity. The lack of effects in the dermal 

study is consistent with the low dermal absorption factor of 1%.

B.3.5 Inhalation Exposure (Short- and Intermediate-Term) 

Selected Study

28-Day Inhalation Toxicity Study - Rats

MRID No.

48663602

Dose and Endpoint for Risk Assessment

NOAEL =0.1 mg/L. A LOAEL was not established since the highest concentration (0.1 mg/L) 

tested did not demonstrate any adverse effects.

Uncertainty Factor (UF)

Short-term = 30X (10X intraspecies, 3X interspecies, 1X FQPA for residential only).

Intermediate-term = 100X (10X intraspecies, 3X interspecies, 3X database uncertainty).

The UF is reduced from the default 100X because the RfC methodology was used to calculate 

inhalation risk. The RfC methodology accounts for the pharmacokinetic (PK) differences 

between rats and humans, but does not account for the pharmacodynamic (PD) differences. 

Consequently, the UF for interspecies extrapolation may be reduced to 3X (to account for the PD 

differences) while the UF for intraspecies variation is retained at 10X. Thus, the UF when using 

the RfC methodology is customarily 30X. For intermediate-term exposures, the occupational 

and residential LOC for MOE = 100. An additional 3X UF was added to the intermediate-term 

exposure scenarios. This was based on a number of factors:

The database indicates a progression in the severity of toxicity with time;

The chemical has a low vapor pressure, and;

The 28-day inhalation study is protective of critical effects.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Although a 10X UF is typically applied for extrapolating for durations of exposure, a 3X UF is 

sufficient for cyantraniliprole. This conclusion is supported by the observation that the LOAEL 

for the multigeneration reproduction toxicity study in rats (a long-term study) is ≈3X lower than 

the LOAEL for the 28-day oral toxicity study in rats (14 versus 53 mg/kg/day, based on thyroid 

toxicity). In addition, the lack of toxicity in the acute inhalation toxicity study at a dose 50X

higher than the 28-day inhalation study supports that a 3X UF for duration of exposure 

extrapolation is sufficiently protective.

Comments about Study/Endpoint/Margins of Exposure

The route-specific 28-day inhalation toxicity study is appropriate to use for this assessment. 

Although this 28-day inhalation toxicity study in rats could be tested14 at higher concentrations 

and adverse effects were not identified in the study, it is appropriate for risk assessment. This 

conclusion is based on a weight of evidence (WOE) approach that takes into consideration the 

overall toxicity profile for this chemical. Liver and thyroid toxicity are the critical effects 

identified in the cyantraniliprole database, with thyroid toxicity being most likely the result of 

liver enzyme activation. Although the inhalation study did not measure thyroid hormones, it 

does provide histopathology data on the thyroid; clinical chemistry observations for liver 

enzymes; liver histopathology; and liver weights (all of the endpoints of concern). Since the 

thyroid effect is secondary to liver effect and the liver is not affected in this study, the inhalation 

study provides a conservative NOAEL. While the POD selected for the inhalation risk 

assessment may be artificially low (i.e. resulting in an overestimation of risk) due to dose 

selection, the inhalation study is selected because it is route-specific and protective of the effects 

seen throughout the database.

B.4 Human Equivalent Concentrations (HEC) and Human Equivalent Dose 

Calculations

The HEC and human equivalent dose calculations were based on the results of a 28-day rat 

inhalation study in rats (MRID 48697401). In this study, cyantraniliprole was administered (as 

an aerosol) to Crl:CD(SD) rats (10/sex/dose) for 6 hours/day, 5 days/week, for 4-weeks. The test 

animals were exposed nose-only to target concentrations of 0 (air control), 1, 10, or 100 mg/m3 

of cyantraniliprole (equivalent to 0.001, 0.01, and 0.1 mg/L, respectively). Adverse effects were

not seen at any concentration tested, although laryngeal metaplasia was considered treatment 

related but not adverse at 0.1 mg/L. The NOAEL was 0.1 mg/L.

RDDR for Cyantraniliprole

Calculations used to estimate the inhalation risk to humans from aerosols are dependent not on 

the regional gas dose ratio (RGDR) as for gases, but on the regional deposited dose ratio 

(RDDR). Inhalation studies using aerosols characterize particulate exposure by defining the 

particulate diameter [mass median aerodynamic diameter (MMAD)] and the geometric standard 

deviation (σg), which is then used to determine the RDDR. The RDDR is a multiplicative factor 

used to adjust an observed inhalation particulate exposure concentration of an animal (A) to the 

predicted inhalation particulate exposure concentration for a human (H) that would be associated 

with the same dose delivered to the affected region (r) or target tissue.

 

14

 An acute inhalation toxicity study tested concentrations 50-fold higher than the highest concentration in the 28-

day inhalation study.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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RDDRr = (RDDr/Normalizing Factor)A / (RDDr/Normalizing Factor)H

As with calculations for gases, the affected regions and potential target tissues are the three 

respiratory regions (extrathoracic, tracheobronchial, and pulmonary). The RDDR is easily 

calculated by using a software program designed specifically for computing the RDDR from the 

MMAD and σg defined from an aerosol inhalation study. The values for the species-specific 

parameters used to calculate the RDDR are provided in the EPA document “Methods for 

Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry.” 

The magnitude of the UFs applied is dependent on the methodology used to calculate risk. The 

RfC methodology takes into consideration the PK differences, but not the PD differences. 

Consequently, the UF for interspecies extrapolation may be reduced to 3X (to account for the PD 

differences) while the UF for intraspecies variation is retained at 10X. Thus, the UF when using 

the RfC methodology is customarily 30X.

Regional Deposited Dose Ratio (RDDR) 

MMAD = 3.00

Sigma g = 2.30

SPECIES Body Weight (g) Minute Ventilation (VE, ml) deposited fraction

rat 236 171.5 0.587

human 70000 13800.0 0.759

RATIO 0.734

RDDR = (VE/SA)animal ÷ (VE/SA)human × deposited fractionanimal ÷ deposited fractionhuman

= (171.5/236)animal ÷ (13800/70000)human × 0.587 ÷ 0.759

= 2.8

Example for HEC calculations for short-term occupational exposure:

Assume workers will be in the greenhouse for 8 hrs/day and 5 days/week:

HEC = NOAELstudy × (daily duration of exposureanimal ÷ daily duration of exposurehuman) × (days/week of 

exposureanimal ÷ days/week of exposurehuman) × RDDR

HEC = 0.1 mg/L × (6 ÷ 8) × (5 ÷ 5) × 2.8 = 0.21 mg/L

Table B.4. HEC Array for Non-Occupational and Occupational Risk Assessment

Relevant Study LOAEL

(mg/L)

NOAEL

(mg/L) Da Dh Wa Wh RDDR HEC (mg/L) inter intra UF

Short-& Intermediate-Term Occupational Exposure

Inhalation – Rat

(MRID 48697401 ) 28-day Not Obs. 0.1 6 8 5 5 2.8 0.21 3 10 NA

Short-& Intermediate-Term Non-Occupational (Residential) Exposure

Inhalation – Rat

(MRID 48697401 ) 28-day Not Obs. 0.1 6 24 5 7 2.8 0.05 3 10 NA
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table B.4. HEC Array for Non-Occupational and Occupational Risk Assessment

Long Term Exposure: Not Appropriate

Key:

LOAEL: Lowest observed adverse effect level

Da: Daily animal exposure (hrs/day)

Wa: Weekly animal exposure (days/week)

RRDR: Regional Deposited Dose Ratio

inter: interspecies extrapolation uncertainty factor

Dh: Anticipated daily human exposure (hrs/day)

Wh: Anticipated weekly human exposure (days/week)

HC: Human Concentration

HEC: Human Equivalent Concentration

intra: intraspecies variation uncertainty factor

UF: Other uncertainty factor(s)

Summary of Human Equivalent Concentrations

Occupational Short-Term

Study NOAEL (m/L)

systemic RDDR

Daily Duration

(6 hrs rat/8 hrs 

human)

Weekly (days/week)

Duration (rat 5 days/human 5 days)

HEC 

(mg/L) UF

28-day rat 0.1 2.8 0.75 1 0.21 30

Non-Occupational Short-Term

Study NOAEL (m/L)

systemic RDDR

Daily Duration

(6 hrs rat/24 hrs 

human)

Weekly (days/week)

Duration (rat 5 days/human 7 days)

HEC 

(mg/L) UF

28-day rat 0.1 2.8 0.25 0.714 0.05 30

Human Equivalent Doses

The HEC is in mg/L but exposure data are in mg/kg/day. Therefore, conversion of the human 

mg/L value to human mg/kg/day was conducted as follows: 

Inhalation to Oral Equation:

dose (systemic HEC value) mg/L × A × CF (L/hr/kg) × D (hours) × AF = mg/kg;

Occupational: (0.21 mg/L) × 1 × 6 × 8 × 1 = 10.08 mg/kg/day 

Residential: (0.05 mg/L) × 1 × 6 × 24 × 1 = 7.2 mg/kg/day 

Where:

A absorption: ratio of deposition and absorption in respiratory tract compared to absorption by the oral route. A 

default A of 1 was used.

CF Conversion Factor: A L/hr/kg factor which accounts for respiratory volume and body weight for a given 

species and strain (A human conversion factor of 6 for ages 10-30 yrs was used for both occupational and nonoccupational calculations).

D Duration: Duration of daily animal or human exposure (hours). The default assumption for occupational is 8 

hrs while non-occupational could potentially be 24 hrs.

AF Activity Factor: The default human activity factor is 1.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Appendix C. Metabolism Summary Table

Table C.1 Tabular Summary of Metabolites and Degradates

Chemical Name (other names in 

parenthesis) and Structure Matrix

Percent TRR (ppm)

Matrices - Major Residue 

(>10%TRR)

Matrices - Minor 

Residue (<10%TRR)

Cyantraniliprole

DPX-HGW86

SYN545377

CAS Name: 3-Bromo-1-(3-chloro-2-

pyridinyl)-N-[4-cyano-2-methyl-6 

[(methylamino)carbonyl]phenyl]-1Hpyrazole-5-carboxamide

Br

Cl

O

O

NH

N

N

HN

N

N

CH3

CH3

Rice

Foliage: 57.4 (0.232) [CN]

48.7 (0.205) [PC]

Grain: 62.7 (0.007) [CN]

46.2 (0.014) [PC]

Straw: 44.9 (0.125) [CN]

42.1 (0.125) [PC]

Lettuce Leaves: 37.1 (0.004) [CN]

69.0 (0.039) [PC]

Cotton

Gin byproducts:

25.6 (0.025) [CN]

46.8 (0.011) [PC]

Tomato Leaves: 43.4 (0.562) [CN/PC]

Rotational Crops

Ruminant

Milk: 39.5 (0.030) [CN]

49.6 (0.070) [PC]

Liver: 17.1 (0.073) [CN]

27.3 (0.136) [PC]

Kidney: 12.7 (0.017) [CN]

18.9 (0.0.040) [PC]

Muscle: 30.3 (0.009) [CN]

15.3 (0.006) [PC]

Fat: 30.8 (0.016) [CN]

45.4 (0.054) [PC]

Poultry

Egg white: 32.5 (0.084) [CN]

41.7 (0.085) [PC]

Egg yolk: 10.3 (0.009) [CN]

9.3 (0.008) [PC]

Rat

Water

IN-J9Z38 

CAS Name: 2-[3-Bromo-1-(3-chloro-2-

pyridinyl)-1H-pyrazol-5-yl]-3,4-dihydro-3,8-

dimethyl-4-oxo-6-quinazolinecarbonitrile

N

N

N N

O

Br

N

Cl

CH3

N

CH3

Rice

Foliage: 16.2 (0.066) [CN]

22.1 (0.093) [PC]

Grain: 10.2 (0.001) [CN]

Straw: 18.4 (0.051) [CN]

14.3 (0.042) [PC]

Lettuce Leaves: 10.0 (0.005) [PC]

Cotton Gin byproducts

Tomato Leaves

Rotational Crops

Ruminant

Poultry

Egg white: 29.2 (0.075) [CN]

17.1 (0.034) [PC]

Egg yolk: 13.1 (0.011) [PC]

Liver

Rat

Water

IN-JCZ38

Rice Foliage, grain, straw
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table C.1 Tabular Summary of Metabolites and Degradates

Chemical Name (other names in 

parenthesis) and Structure Matrix

Percent TRR (ppm)

Matrices - Major Residue 

(>10%TRR)

Matrices - Minor 

Residue (<10%TRR)

CAS Name: 4-[[[3-Bromo-1-(3-chloro-2-

pyridinyl)-1H-pyrazol-5-yl]carbonyl]amino]-

N’3’,5-dimethyl-1,3-benzenedicarboxamide

Br

Cl

O

O

NH

N

N

NH

N

CH3

H3C

H2N

O

Cotton Gin byproducts

Tomato Leaves

Rotational Crops

Ruminant Milk, liver

Poultry

Rat

Water

IN-JSE76

CAS Name: 3-(Methylaminocarbonyl)-4-

[[[3-bromo-1-(3-chloro-2-pyridinyl)-1Hpyrazol-5-yl]carbonyl]amino]-5-

methylbenzoic acid

Br

Cl

O

O

NH

N

N

NH

N

CH3

H3C

HO

O

Rice Foliage, grain, straw

Cotton Gin byproducts

Tomato

Rotational Crops

Ruminant

Poultry Egg yolk

Rat

Water

IN-K7H19

CAS Name: 4-[[[3-Bromo-1-(3-chloro-2-

pyridinyl)-1H-pyrazol-5-yl]carbonyl]amino]-

5-methyl-1,3-benzenedicarboxamide

Br

Cl

O

O

NH

N

N

H2N

N

CH3

H2N

O

Rice Straw

Cotton Gin byproducts

Tomato Leaves

Rotational Crops

Ruminant Milk, liver, kidney, muscle, 

fat

Poultry

Rat

Water

IN-MLA84

CAS Name: 2-[3-Bromo-1-(3-chloro-2-

Rice Foliage, straw

Lettuce Leaves (+ IN-NXX70)
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table C.1 Tabular Summary of Metabolites and Degradates

Chemical Name (other names in 

parenthesis) and Structure Matrix

Percent TRR (ppm)

Matrices - Major Residue 

(>10%TRR)

Matrices - Minor 

Residue (<10%TRR)

pyridinyl)-1H-pyrazol-5-yl]-1,4-dihydro-8-

methyl-4-oxo-6-quinazolinecarbonitrile

N

NH

N

N

O

Br

N

Cl

CH3

N

Cotton Gin byproducts

Tomato Leaves (+ IN-NXX70)

Rotational Crops

Ruminant

Poultry

Egg white: 18.7 (0.049) [CN]

18.2 (0.037) [PC]

Egg yolk: 11.6 (0.011) [CN]

16.8 (0.015) [PC]

Liver

Rat

Water

IN-DBC80

CAS Name: 3-Bromo-1-(3-chloro-2-

pyridinyl)-1H-pyrazole-5-carboxylic acid

Br

Cl O

OH

N

N

N

Rice Foliage, grain, straw

Cotton

Tomato Leaves

Rotational Crops

Ruminant

Poultry

Rat

Water

IN-N7B69

CAS Name: 3-Bromo-1-(3-chloro-2-

pyridinyl)-N-[4-cyano-2-(hydroxymethyl)-6-

[(methylamino)carbonyl]phenyl]-1Hpyrazole-5-carbonitrile

Br

Cl

O

O

NH

N

N

HN

N

N

CH3

HO

Rice Foliage, grain

Cotton Gin byproducts

Tomato Leaves

Rotational Crops

Ruminant Milk: 11.8 (0.008) [CN]

Poultry Liver

Rat

Water

IN-K5A77

CAS Name: 2-[3-Bromo-1-(3-chloro-2-

pyridinyl)-1H-pyrazol-5-yl]-3,4-dihydro-3,8-

Rice Foliage, straw

Cotton
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table C.1 Tabular Summary of Metabolites and Degradates

Chemical Name (other names in 

parenthesis) and Structure Matrix

Percent TRR (ppm)

Matrices - Major Residue 

(>10%TRR)

Matrices - Minor 

Residue (<10%TRR)

dimethyl-4-oxo-6-quinazolinecarboxamide

N

N

N N

O

Br

N

Cl

CH3

CH3

H2N

O

Tomato

Rotational Crops

Ruminant

Poultry

Rat

Water

IN-K5A78

CAS Name: 2-[3-Bromo-1-(3-chloro-2-

pyridinyl)-1H-pyrazol-5-yl]-3,4-dihydro-3,8-

dimethyl-4-oxo-6-quinazolinecarboxylic acid

N

N

N N

O

Br

N

Cl

CH3

CH3

HO

O

Rice Foliage, grain, straw

Cotton

Tomato

Rotational Crops

Ruminant

Poultry Liver

Rat

Water

IN-K5A79

CAS Name: 3-(Aminocarbonyl)-4-[[[3-

bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol5-yl]carbonyl]amino]-5-methylbenzoic acid

Br

Cl

O

O

NH

N

N

NH2

N

CH3

HO

O

Rice

Cotton

Tomato

Rotational Crops

Ruminant

Poultry Egg white, yolk, liver

Rat

Water

IN-HGW87

Rice
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table C.1 Tabular Summary of Metabolites and Degradates

Chemical Name (other names in 

parenthesis) and Structure Matrix

Percent TRR (ppm)

Matrices - Major Residue 

(>10%TRR)

Matrices - Minor 

Residue (<10%TRR)

CAS Name: N-[2-(Aminocarbonyl)-4-cyano6-methylphenyl]-3-bromo-1-(3-chloro-2-

pyridinyl)-1H-pyrazole-5-carboxamide

Br

Cl

O

O

NH

N

N

H2N

N

N

CH3

Lettuce Leaves

Cotton

Tomato

Rotational Crops

Ruminant

Poultry Egg yolk: 12.0 (0.011) [CN] Egg white

Rat

Water

IN-QKV54

CAS Name: 2-[3-Bromo-1H-pyrazol-5-yl]-

3,4-dihydro-3,8-dimethyl-4-oxo-6-

quinazolinecarbonitrile

N

N

N

NH

O

Br

CH3

N

CH3

Rice

Lettuce Leaves

Cotton Gin byproducts

Tomato Leaves

Rotational Crops

Ruminant

Poultry

Rat

Water

IN-MYX98

Rice
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Table C.1 Tabular Summary of Metabolites and Degradates

Chemical Name (other names in 

parenthesis) and Structure Matrix

Percent TRR (ppm)

Matrices - Major Residue 

(>10%TRR)

Matrices - Minor 

Residue (<10%TRR)

CAS Name: 3-Bromo-1-(3-chloro-2-

pyridinyl)-N-[4-cyano-2-[[(hydroxymethyl) 

amino]carbonyl]-6-[(methylphenyl]-1Hpyrazole-5-carboxamide

Br

Cl

O

O

NH

N

N

NH

N

N

CH3

HO

Cotton

Tomato Leaves

Rotational Crops

Ruminant Milk: 15.1 (0.011) [CN]

18.3 (0.026) [PC] Liver, kidney

Poultry Egg white, yolk, liver

Rat

Water

IN-NBC94

CAS Name: 2-[3-Bromo-1-(3-chloro-2-

pyridinyl)-1H-pyrazol-5-yl]-3,4-dihydro-3-

methyl-4-oxo-8-hydroxymethyl-6-

quinazolinecarbonitrile

N

N

N N

O

Br

N

Cl

N

CH3

HO

Rice

Cotton

Tomato

Rotational Crops

Ruminant Fat

Poultry Egg white, yolk, liver

Rat

Water

IN-N5M09

N

N

O

CH3 Cl

N

Processing Conditions
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table C.1 Tabular Summary of Metabolites and Degradates

Chemical Name (other names in 

parenthesis) and Structure Matrix

Percent TRR (ppm)

Matrices - Major Residue 

(>10%TRR)

Matrices - Minor 

Residue (<10%TRR)

IN-F6L99

HN

N

Br

HN

CH3

O

Processing Conditions

a Cyantraniliprole is labeled with carbon-14 either in the cyano group [CN] or in the carbonyl next to the pyrazole 

ring [PC]. The label positions are depicted below.

 

1. [CN14C]-cyantraniliprole

2. [PC14C]-cyantraniliprole

NH

O

HN

O N

N

Br

N

Cl

NC

1

2
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Appendix D. Physical/Chemical Properties

Table D.1 Physicochemical Properties of the Technical Grade of Cyantraniliprole

Parameter Value Reference

Molecular Weight 473.72 g/mol

MRID 48208438

Physical state White fine powder solid

Melting point 224 oC

Density 1.4965 g/cm3at 20 oC

pH pH 4: Stable

pH 7: Stable

Water solubility (20°C) 14.24 mg/L

Solvent solubility (g/L at 20°C)

Acetone 6.54

Ethyl acetate 1.96

Dichloromethane 5.05

Toluene 0.576

n-Octanol 0.79

Methanol 4.73

o-Xylene 0.29

Acetonitrile 2.45

Vapor pressure (20°C) 5.13 x 10-15 Pa

3.85×10-17 mm Hg

Henry’s Law Constant (20 °C) at pH7 = 1.7 x 10-18 atmosphere.m3/mole

Dissociation constant, pKa (20°C) 8.80 + 1.38

Octanol/water partition 

coefficient, log KOW (20°C) Log Kow = 1.94 + 0.11

Hydrolysis and photolysis

pH 9: Hydrolyzed very rapidly with a half-life of <1 

day. One major metabolite was observed: IN-J9Z38.

Photolysis: 0.233 days at 40o latitude in the summer to 

4.12 days at 60o latitude in the winter.

Appendix E. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include Pesticide 

Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler Exposure Task 

Force (AHETF) database; the Outdoor Residential Exposure Task Force (ORETF) database;

ExpoSAC Policy 14 and 15.1 (SOPs for Seed Treatment); and the Residential SOPs 

(Lawns/Turf; Gardens and Trees; Indoor Environments), are (1) subject to ethics review pursuant 

to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics 

requirements. For certain studies, the ethics review may have included review by the Human 

Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be 

found at the Agency website15.

 

15 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Appendix F. Occupational Exposure/Risk Summary Tables

Table F.1 Occupational Handler Non-Cancer Exposure and Risk Estimates for Cyantraniliprole

Exposure Scenario Crop or Targeta

Baseline 

Inhalation 

Unit 

Exposureb

Maximum

Application 

Ratec

Area 

Treated or 

Amount 

Handled 

Dailyd

Baseline Inhalation

Dosee MOEf

μg/lb ai lb ai/A Acres mg/kg/day ST LOC = 30

IT LOC = 100

Mixer/Loader

Mixing/Loading Dry 

Flowables for Aerial 

Application

Sod Farms

8.96

0.133

350

0.00520 1,900

Typical Field Crops 0.175 0.00686 1,500

Mixing/Loading Dry 

Flowables for Airblast 

Application

Nursery Plants 0.131 20 0.000294 34,000

Mixing/Loading Dry 

Flowables for 

Chemigation 

Application Only

Typical Field Crops 0.175 350 0.00686 1,500

Greenhouse Plants

0.131 60 0.000883 11,000

Nursery Plants

Mixing/Loading Dry 

Flowables for 

Groundboom 

Application

Golf Courses

(tees and greens only) 0.133 5 0.0000743 140,000

Golf Courses

(fairways, tees, and greens) 0.133 40 0.000594 17,000

Field-Grown Ornamentals 0.131 40 0.000588 17,000

Nursery Plants 0.131 60 0.000883 11,000 Greenhouse Plants

Sod Farms 0.133 80 0.00119 8,500

Typical Field Crops 0.175 80 0.00156 6,500

Mixing/Loading 

Liquids for Aerial 

Application

Orchard Crops

0.219

0.133 350 0.000128 79,000

Sod Farms 0.313 350 0.000300 34,000

Typical Field Crops 0.133 350 0.000128 79,000

High-Acreage Field Crops 0.133 1200 0.000436 23,000

Mixing/Loading 

Liquids for Airblast 

Application

Nursery Plants 0.261 20 0.0000143 700,000

Orchard Crops 0.133 40 0.0000145 700,000

Mixing/Loading 

Liquids for 

Chemigation

Orchard Crops 0.391 350 0.000375 27,000

Sod Farms 0.313 350 0.000300 34,000

Typical Field Crops 0.133 350 0.000128 79,000

High-Acreage Field Crops 0.133 350 0.000128 79,000

Greenhouse Plants 0.261 60 0.0000429 230,000

Nursery Plants 0.391 60 0.0000643 160,000

Mixing/Loading 

Liquids for 

Groundboom 

Application

Golf Courses

(tees and greens only) 0.313 5 0.00000429 2,300,000

Golf Courses

(fairways, tees, and greens) 0.313 40 0.0000343 290,000

Field-Grown Ornamentals 0.261 40 0.0000286 350,000

Nursery Plants 0.391 60 0.0000643 160,000

Greenhouse Plants 0.261 60 0.0000429 230,000

Sod Farms 0.313 80 0.0000686 150,000

Typical Field Crops 0.133 80 0.0000291 350,000

High-Acreage Field Crops 0.133 200 0.0000728 140,000

Applicator
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Table F.1 Occupational Handler Non-Cancer Exposure and Risk Estimates for Cyantraniliprole

Exposure Scenario Crop or Targeta

Baseline 

Inhalation 

Unit 

Exposureb

Maximum

Application 

Ratec

Area 

Treated or 

Amount 

Handled 

Dailyd

Baseline Inhalation

Dosee MOEf

μg/lb ai lb ai/A Acres mg/kg/day ST LOC = 30

IT LOC = 100

Applying Sprays for 

Aerial Application

Orchard Crops

0.068

0.133 350 0.0000395 260,000

Sod Farms 0.133 350 0.0000394 260,000

Typical Field Crops 0.175 350 0.0000521 190,000

High-Acreage Field Crops 0.133 1200 0.000135 75,000

Applying Sprays for 

Airblast Application

Nursery Plants 4.71 0.131 20 0.000155 65,000

Orchard Crops 0.133 40 0.000313 32,000

Applying Sprays for 

Groundboom 

Application

Golf Courses

(tees and greens only)

0.34

0.133 5 0.00000281 3,600,000

Golf Courses

(fairways, tees, and greens) 0.133 40 0.0000225 450,000

Field-Grown Ornamentals 0.131 40 0.0000224 450,000

Nursery Plants 0.131 60 0.0000335 300,000 Greenhouse Plants

Sod Farms 0.133 80 0.0000450 220,000

Typical Field Crops 0.175 80 0.0000595 170,000

High-Acreage Field Crops 0.133 200 0.000113 89,000

Applying Granules via 

Hand Dispersal

Poultry/Livestock 

Houses/Horse Barns/Feedlots 470 0.0871 1 0.000511 20,000

Flagger

Flagging for Aerial 

Applications

Orchard Crops

0.35

0.133 350 0.000204 49,000

Sod Farms 0.133 350 0.000203 50,000

Typical Field Crops 0.175 350 0.000268 38,000

High-Acreage Field Crops 0.133 350 0.000204 49,000

Mixer/Loader/Applicator

M/L/A Dry Flowables 

for Backpack Sprayers

Greenhouse Plants (Foliar)

140 0.00131

lb ai/gal

40

gallons

0.0000919 110,000

Nursery Plants (Foliar)

Nursery Plants (Ground/Soil) 2.58 0.00475

lb ai/gal 0.00000613 1,600,000

Landscaping 

(trees/shrubs/bushes) 140 0.00131

lb ai/gal 0.0000919 110,000 Landscaping

(plants/flowers)

Landscaping

(turf, lawns, athletic fields, 

parks, etc)

2.58 0.00203

lb ai/gal 0.00000261 3,900,000

M/L/A Dry Flowables 

for ManuallyPressurized Handwand 

Sprayers

Greenhouse Plants (Foliar)

30 0.00131

lb ai/gal 40

gallons

0.0000198 510,000

Nursery Plants (Foliar)

Landscaping 

(trees/shrubs/bushes)

Landscaping

(plants/flowers)

Interior Landscaping

Landscaping

(turf, lawns, athletic fields, 

parks, etc)

30 0.00203

lb ai/gal 0.0000304 330,000

M/L/A Dry Flowables 

for MechanicallyGreenhouse Plants (Foliar) 120 0.00131lb ai/gal

1000

gallons 0.00198 5,100
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table F.1 Occupational Handler Non-Cancer Exposure and Risk Estimates for Cyantraniliprole

Exposure Scenario Crop or Targeta

Baseline 

Inhalation 

Unit 

Exposureb

Maximum

Application 

Ratec

Area 

Treated or 

Amount 

Handled 

Dailyd

Baseline Inhalation

Dosee MOEf

μg/lb ai lb ai/A Acres mg/kg/day ST LOC = 30

IT LOC = 100

Pressurized Handgun 

Sprayers

Greenhouse Plants 

(Ground/Soil)

0.00475

lb ai/gal 0.00713 1,400

Nursery Plants (Foliar)

3.9

0.00131

lb ai/gal 0.0000640 160,000

Nursery Plants (Ground/Soil) 0.00475

lb ai/gal 0.000231 44,000

Landscaping

(trees/shrubs/bushes)

0.00131

lb ai/gal 0.0000640 160,000

Typical Field Crops (Foliar) 3.9 0.00875

lb ai/gal 0.000426 24,000

Typical Field Crops 

(Ground/Soil) 3.9 0.0175lb ai/gal 0.000854 12,000

Golf Courses

(tees and greens only)

42 0.133 5

acres

0.000348 29,000

Golf Courses

(fairways, tees, and greens)

Landscaping

(turf, lawns, athletic fields, 

parks, etc)

M/L/A Liquids for 

Backpack Sprayers

Orchard (Ground/Soil) 2.58 0.00443

lb ai/gal

40

gallons

0.00000571 1,800,000

Greenhouse Plants (Foliar)

140 0.00326

lb ai/gal

0.000229 44,000

Nursery Plants (Foliar)

Nursery Plants (Ground/Soil) 2.58 0.00000421 2,400,000

Landscaping 

(trees/shrubs/bushes) 140

0.00418

lb ai/gal

0.000293 34,000 Landscaping

(plants/flowers)

Landscaping

(turf, lawns, athletic fields, 

parks, etc)

2.58 0.00000539 1,900,000

Industrial/Commercial Areas 

(tires, rail yards, junk yards, 

etc) 30 0.00887

lb ai/gal

0.000133 76,000 Poultry/Livestock 

Houses/Horse Barns/Feed 

Lots

Foundations/Perimeters 2.58 0.0000115 880,000

M/L/A Liquids for 

Manually-Pressurized 

Handwand Sprayers

Greenhouse Plants (Foliar)

30

0.00326

lb ai/gal

40

gallons

0.0000489 210,000 Nursery Plants (Foliar)

Landscaping 

(trees/shrubs/bushes) 0.00418

lb ai/gal 0.0000626 160,000 Landscaping

(plants/flowers)

Landscaping

(turf, lawns, athletic fields, 

parks, etc) 30 0.00418

lb ai/gal 0.0000626 160,000

Interior Landscaping
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table F.1 Occupational Handler Non-Cancer Exposure and Risk Estimates for Cyantraniliprole

Exposure Scenario Crop or Targeta

Baseline 

Inhalation 

Unit 

Exposureb

Maximum

Application 

Ratec

Area 

Treated or 

Amount 

Handled 

Dailyd

Baseline Inhalation

Dosee MOEf

μg/lb ai lb ai/A Acres mg/kg/day ST LOC = 30

IT LOC = 100

Industrial/Commercial Areas 

(tires, rail yards, junk yards, 

etc)

30

0.00887

lb ai/gal

0.000133 76,000

Poultry/Livestock 

Houses/Horse Barns/Feedlots

Foundations/Perimeters

Structural Areas (bridges, 

shipyards, home decks, 

foundations)

Warehouses

1100 0.00448 2,100

Residential Living Spaces 

(homes, apartments)

Childcare 

Center/Schools/Institutions

M/L/A Liquids for 

MechanicallyPressurized Handgun 

Sprayers

Orchard Crops (Foliar) 3.9 0.00443

lb ai/gal

1000

gallons

0.000216 47,000

Orchard Crops (Ground/Soil) 3.9 0.00449

lb ai/gal 0.000219 46,000

Greenhouse Plants (Foliar)

120 0.00326

lb ai/gal

Greenhouse Plants 0.00489 2,100

(Ground/Soil)

Nursery Plants (Foliar) 3.9 0.000159 63,000 Nursery Plants (Ground/Soil)

Landscaping 

(trees/shrubs/bushes) 3.9 0.00418lb ai/gal

0.0000626 160,000

Industrial/Commercial Areas 

(tires, rail yards, junk yards, 

etc)

3.9

0.00887

lb ai/gal

0.000433 23,000

Warehouses

79 0.00876 1,200

Poultry/Livestock 

Houses/Horse Barns/Feedlots

Structural (bridges, shipyards, 

home decks, foundations, etc)

Typical Field Crops (Foliar)

3.9 0.00202

lb ai/gal Typical Field Crops 0.0000985 100,000

(Ground/Soil)

Golf Courses

(tees and greens only)

1.9 0.313 5

acres

0.0000371 270,000

Golf Courses

(fairways, tees, and greens)

Landscaping

(turf, lawns, athletic fields, 

parks, etc)

Loader/Applicator

L/A Granules for Belly 

Grinders

Orchard Crops

62 0.0871 1

acre

Greenhouse Plants 0.0000675 150,000

Nursery Plants
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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Table F.1 Occupational Handler Non-Cancer Exposure and Risk Estimates for Cyantraniliprole

Exposure Scenario Crop or Targeta

Baseline 

Inhalation 

Unit 

Exposureb

Maximum

Application 

Ratec

Area 

Treated or 

Amount 

Handled 

Dailyd

Baseline Inhalation

Dosee MOEf

μg/lb ai lb ai/A Acres mg/kg/day ST LOC = 30

IT LOC = 100

Landscaping 

(trees/shrubs/bushes)

Landscaping

(plants/flowers)

Landscaping

(turf, lawns, athletic fields, 

parks, etc)

Industrial/Commercial Areas 

(tires, rail yards, junk yards, 

etc)

Poultry/Livestock 

Houses/Horse Barns/Feedlots

Foundations/Perimeters

L/A Granules for 

Rotary Spreaders

Orchard Crops

10 0.0871 5

acres

0.0000545 180,000

Greenhouse Plants

Nursery Plants

Golf Courses

(tees and greens only)

Golf Courses

(fairways, tees, and greens)

Landscaping

(turf, lawns, athletic fields, 

parks, etc)

Industrial/Commercial Areas 

(tires, rail yards, junk yards, 

etc)

Poultry/Livestock 

Houses/Horse Barns/Feed 

Lots

10 0.0871 1

acre

0.0000109 920,000

L/A Granules for 

Backpack Sprayers

Nursery Plants

23.8 0.0871 1

acre

0.0000259 390,000 Industrial/Commercial Areas 

(tires, rail yards, junk yards, 

etc)

L/A Granules for Cups

Poultry/Livestock 

Houses/Horse Barns/Feed 

Lots

12.5 0.0871 1

acre

0.0000136 740,000

L/A Granules for 

Spoons

Poultry/Livestock 

Houses/Horse Barns/Feed 

Lots

121 0.0871 1

acre

0.000131 77,000

Hand Dispersal of 

Granules

Poultry/Livestock 

Houses/Horse Barns/Feed 

Lots

470 0.0871 1

acre

0.000511 20,000

a “Typical Field Crops” include Brassica (Cole) leafy vegetables (Group 5), bulb vegetables (Group 3-07), bushberries (Group 13-07B), citrus 

fruits (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), potatoes, stone fruits (Group 12), sunflowers, tree nuts (Group 14), tuberous and corm 

vegetables (Subgroup 1C).

“High-Acreage Field Crops” includes cotton.

“Nursery Plants” include ornamentals, vegetables, trees, container stock.

“Greenhouse Plants” include ornamentals, roses, cut flowers, container stock, vegetables grown for re-sale to consumers.

b Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012); Level of mitigation = Baseline.
Cyantraniliprole Human Health Risk Assessment DP No. 404762 

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c Based on the maximum application rates on the proposed labels (Reg. Nos. 352-IAE, 352-IAG, 352-IAI, 352-IAL, 253-IAN, 352-ILA, 352-

ILI, 352-ILO, 352-ILT, 100-RUEE, 100-RUEG, 100-RUEN, 100-RUER, 100-RUEU, and 100-RURI).

d Exposure Science Advisory Council Policy #9.1.

e Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or 

Amount Handled Daily (A or gal/day) ÷ BW (80 kg adult).

f Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

Table F.2 Summary of Short-Term Handler Exposures and Risks for Cyantraniliprole (Seed Treatment 

Only)a

Seed Type

Max 

Application 

Rateb

Inhalation 

UEc

Amount of 

Seed Treated 

or Planted

Per Dayd

Inhalation 

Dosee

Inhalation 

MOEf

lb ai/lb seed mg/lb lb seed/day mg/kg/day ST LOC = 30

Loader/Applicator

Potato Seed Pieces 0.000135 0.0064*

800,000 0.00864002 1,200

Rapeseed/Canola 0.0100

0.00034

125,000 0.00531939 1,900

Mustard Seed 0.0100 125,000 0.00531939 1,900

Sunflowers 0.00397 339,500 0.00572580 1,800

Sewer

Rapeseed/Canola 0.0100

0.00023

125,000 0.00359841 2,800

Mustard Seed 0.0100 125,000 0.00359841 2,800

Sunflowers 0.00397 339,500 0.00387333 2,600

Bagger

Rapeseed/Canola 0.0100

0.00016

125,000 0.00250324 4,000

Mustard Seed 0.0100 125,000 0.00250324 4,000

Sunflowers 0.00397 339,500 0.00269449 3,700

Multiple Activities

Rapeseed/Canola 0.0100

0.0016

125,000 0.02503242 400

Mustard Seed 0.0100 125,000 0.02503242 400

Sunflowers 0.00397 339,500 0.02694492 370

Planter

Potato Seed Pieces 0.000135

0.0034

800,000 0.0045900 2,200

Rapeseed/Canola 0.0100 400 0.0001702 59,000

Mustard Seed 0.0100 560 0.0002383 42,000

Sunflowers 0.00397 320 0.0000540 190,000

a Seed treatment rate calculations are based on the following assumptions:

Mustard seed: 90,000 to 115,000 seeds per lb; 7 lbs of seed planted per day, 80 acres planted per day.

Potato seed pieces: 5 to 11 seed pieces per lb; 800,000 seed pieces planted per day.

Rapeseed (canola): 90,000 to 115,000 seeds per lb; 5 lbs of seed planted per day, 80 acres planted per day.

Sunflowers: 2,000 to 9,000 seeds per lb; 4 lbs of seed planted per day, 80 acres planted per day.

b Application Rates based on proposed label uses for cyantraniliprole (EPA Reg. Nos. 352-IAN, 100-RUEN, and 100-RURI).

c Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment (baseline 

inhalation = no respirator).

* The inhalation unit exposure for potato seed pieces comes from D378750.

d HED default for lb seed treated/planted per day from HED Exposure Science Advisory Council Interim Policy 15.1 and the BEAD memo 

“Acres Planted Per Day and Seeding Rates of Crops Grown in the United States” (J. Becker, March 2011).

e Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) 

÷ body weight (80 kg adult).

f Inhalation MOE = NOAEL (10.08 mg/kg/day for short-term exposure) ÷ Inhalation Dose (mg/kg/day). Short-term level of concern = 30.