Chlorantraniliprole Human Health Risk Assessment DP No. 411938 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: May 12, 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Chlorantraniliprole: Human Health Risk Assessment for Proposed Uses on 

Cereal Grains Group 15 (except Rice) and Cereal Grains Forage, Fodder, and Straw Group 16, 

and Conversion of Citrus and Pome Fruit Groups. 

PC Code: 090 I 00 

Decision No.: 4Q7.)21 

Petition No.: 2E8064 

Risk Assessment Type: Single Chemical, Aggregate 

TXR No.: NA 

MRID No.: NA 

FROM: Sheila Healy, Risk Assessor 

Steve Funk, Senior Chemist 

Kristin Rury, Biologist 

Risk Assessment Branch Ill 

Health Effects Division (7509P) 

THROUGH: Christine Olinger, Chief 

Risk Assessment Branch I 

Health Effects Division 50 

DP Barcode: 411938 

Registration No.: 352-728, 352-729,352-730 and 352-

844 

Regulatory Action: Section 3 Registration 

Case No.: NA 

CAS No.: 500008-45-7 

40 CFR: 180.628 

TO: Barbara Madden/Sidney Jackson (RM 05) 

Risk Integration, Minor Use & Emergency Response Branch 

Registration Division (7505P) 

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Chlorantraniliprole Human Health Risk Assessment DP No. 411938 

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

2.0 Regulatory Conclusions and Recommendations .................... ........................................ . 6 

2.1 Data Deficiencies/Conditions of Registration ...................... ... ........ .... ........ .... ............. 6 

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

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

2.2.2 International Harmonization ............. ........... ........ ... ............ ... ................................... 6 

2.2.3 Recommended Tolerances ..... .... .......................................... ........ ... ..... .... .... .... .... ...... 6 

2.2.4 Revisions to Petitioned-For Tolerances .................. .... .... .... ........ ... .... .... ..... .............. 9 

2.3 Label Recommendations ................... .... ........... .... ............ .............................................. 9 

3.0 Introduction ....... ....... ....... ....... .... ... ..... ... ...................................................... ... ......... ... ...... .. 9 

3.1 Chemical Identity ..................................... ............................... ........ .... .... .... .... ............... 9 

3.2 Physical/Chemical Characteristics ................................................................ ............. 1 0 

3.3 Pesticide Use Pattern ............................ ....... ........ .... ............ ............... ................. .... .... . 11 

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

3.5 Consideration of Environmental Justice ................... ........... ..... ........... ................ .... .. 14 

4.0 Hazard Characterization and Dose-Response Assessment .......................................... 14 

4.1 Summary of Toxicological Effects .................................... .... .. .......... ........... .... ........... 14 

4.2 Safety factor for Infants and Children (FQPA Safety Factor) ..... ........ ................... 15 

4.2.1 Completeness of the Toxicology Database ............... ........................................... .... 16 

4.2.2 Evidence of Neurotoxicity .............................. ............... .... .... ........ ........ .... .... ........... 16 

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal.. ...... 16 

4.2.4 Residual Uncertainty in the Exposure Database ................................................... 16 

4.3 Toxicity Endpoint and Point of Departure Selections ... .... ................... .... ............. ... 16 

5.0 Dietary Exposure and Risk Assessment .............. .... ............ ................. ...... ......... ........ ... 17 

5.1 Residues of Concern Summary and Rationale ...................................... ............. ....... 17 

5.2 Food Residue Profile .... ....... .... ........... ............ ........... ............................... ........ ............ 18 

5.3 Water Residue Profile .................................................................................................. 19 

5.4 Dietary Risk Assessment ..... ....... ........... .... .... .... ................... .... .... .... ............ .... .... .... .... 19 

5.4.1 Description of Residue Data Used in Dietary Assessment .................................... 19 

5.4.2 Acute Dietary Risk Assessment ........ ....... .... ........ ............ ........... ........ .... .... ..... .... .... 20 

5.4.3 Chronic Dietary Risk Assessment ........................................................................... 20 

5.4.4 Cancer Dietary Risk Assessment. ..... ... ..... ....... ........ ............... ........................ ......... 20 

5.4.5 Summary Table ..... ................. ............................... .... .... .... ............... .... .... .... .... ........ . 20 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ........ ..................... 21 

6.1 Residential Handler Exposure .................................................................................... 21 

6.2 Post-Application Exposure ... ............... .... .... .... ....................... ........ .... ........... ......... ..... 21 

6.3 Combined Exposure .............. ............ ....... .... ............ ... .... .... .... ........... ..... ... ............ .... .. 21 

6.4 Residential Bystander Postapplication Inhalation Exposure ............................. ...... 21 

6.5 Spray Drift ........ .......... .... ........ .......... ................... .... .... .... .... ........... .... .... .... .... .... .... .... .. 22 

7.0 Aggregate Exposure/Risk Characterization ............................ ...................................... 22 

8.0 Cumulative Exposure/Risk Characterization .. .... .... .... ... .... .... .... .... .... .... .... .... ........ ...... 23 

9.0 Occupational Exposure/Risk Characterization ... .................................. ....................... 23 

10.0 References .. ....... .............. ..................................... ....................... ...................................... 23 

Appendix A. Toxicology Profile ............................... ...................................... ....... ......... .... .... ... 25 

A.l Toxicology Data Requirements ....... ....... .... ............... .... ........ ... ................................... 25 

A.2 Toxicity Profiles ........................................... ....... ........ ........ ... .... .... .... ... .... .... .... ..... .... ... 26 

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Chlorantraniliprole Human Health Risk Assessment DP No. 411938 

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Appendix B. Physical/Chemical Properties............................................................................. 30
Chlorantraniliprole Human Health Risk Assessment DP No. 411938 

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1.0 Executive Summary

Chlorantraniliprole (DPX-E2Y45) is an anthranilic diamide insecticide that belongs to a class of 

compounds that acts on the ryanodine receptor. It is an insecticide that was developed and 

registered by E.I. du Pont de Nemours and Company (DuPont) for control of lepidopteran pests 

and controls many insects primarily via interruption of normal muscle contraction pathways, 

which leads to paralysis and eventual death of the pest. 

On behalf of E.I. du Pont de Nemours and Company (DuPont), the Interregional Research 

Project No. 4 (IR-4) of Rutgers University has submitted a petition for tolerances and a Section 3 

registration of chlorantraniliprole for use on cereal grains group 15 except rice and cereal grain 

forage, fodder, and straw group 16. Updating of the citrus fruit group 10 to 10-10 and the pome 

fruit group 11 except mayhaw to the pome fruit group 11-10 was also requested. Concurrent 

with these changes, the revocation of existing tolerances for field corn commodities, pop corn 

commodities, and sweet corn commodities is requested. These commodities are members of the 

cereal grain group 15. The revocation of the mayhaw tolerance is also requested. The latter 

commodity is covered by group 10-10.

Permanent tolerances are currently established in 40 CFR §180.628 for chlorantraniliprole in/on 

a variety of commodities.

Use Profile

The end-use product (EP) formulations relevant to this registration request for use on cereal 

grains are a 5% active ingredient (ai) suspension concentrate (SC) Prevathon®Insect Control 

(0.43 lb ai per gallon, or 0.053 kg ai/l), EPA Reg. No. 352-844, a 18.4% active ingredient (ai) 

suspension concentrate (SC) Coragen®Insect Control (1.67 lbs ai/gallon or 0.200 kg ai/l), EPA 

Reg. No. 352-729, and a 35.0% active ingredient (ai) water dispersible granular (WDG) 

Altacor® (35 lb ai/100 lb) EPA Reg. No. 352-730. Chlorantraniliprole may be applied via drip 

irrigation, ground, handheld and aerial application methods. There is potential for short- and 

intermediate-term occupational exposure from the uses of chlorantraniliprole on the proposed 

crops. Chlorantraniliprole is also registered for use in residential settings on turf, landscape 

ornamentals and interiorscapes. Chlorantraniliprole may also be used on golf courses and sod 

farms.

Hazard Characterization

HED has concluded that sufficient toxicology information exists for chlorantraniliprole for 

selecting doses and endpoints needed for assessing its risk to humans when used as an 

insecticide. Chlorantraniliprole is not genotoxic, neurotoxic, immunotoxic, carcinogenic, or 

developmentally toxic. Chlorantraniliprole is classified as Acute Toxicity Category IV for oral 

toxicity, dermal toxicity, inhalation toxicity, eye irritation, and primary skin irritation. 

Chlorantraniliprole is not a dermal sensitizer. There was only one animal toxicity study (18-

month carcinogenicity study in mice) in the toxicology database which evidenced any adverse 

effect of chlorantraniliprole exposure. This study was used to establish a point of departure 

(POD), based on hepatocellular effects, for the chronic dietary exposure scenario. Although 

residential and occupational exposure is expected over the short- and intermediate-term (via the 
Chlorantraniliprole Human Health Risk Assessment DP No. 411938 

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dermal and/or incidental oral route), there is no hazard expected via these routes/durations, and,

therefore, no risk associated with these scenarios.

HED recommends that the FQPA SF be reduced to 1X because 1) the toxicology database for 

chlorantraniliprole is complete for the purposes of this risk assessment and the characterization 

of potential pre- and postnatal risks to infants and children is adequate; 2) no susceptibility was 

identified in the toxicological database, and there are no residual uncertainties with respect to

pre-and/or postnatal exposure; 3) there were no treatment-related neurotoxic findings in the acute 

or subchronic oral neurotoxicity studies in rats; and 4) the exposure assessment is protective: the 

dietary food exposure assessment utilizes tolerance level residues for all commodities and

assumes that 100% or the registered and proposed crops are treated with chlorantraniliprole; the 

drinking water assessment utilizes values generated by models and associated modeling 

parameters which are designed to provide conservative, health protective, high-end estimates of 

water concentrations.

Dietary Risk Estimates (Food + water)

An acute assessment was not performed as no acute dietary toxicity endpoint could be identified 

based on the toxicology data currently available for chlorantraniliprole. 

A conservative chronic dietary risk assessment was conducted using the Dietary Exposure 

Evaluation Model software with the Food Commodity Intake Database (DEEM-FCIDTM, Version 

3.16). DEEMTM default processing factors and 100% crop treated (CT), and tolerance-level 

residues were assumed for all commodities. Drinking water was incorporated directly into the 

dietary exposure assessment using the chronic EDWC of 39.87 μg/L for surface water (noncancer, 1 in 10 year annual mean). The chronic dietary risk assessment shows that the chronic 

dietary risk estimates do not exceed HED’s level of concern [i.e., <100% of the chronic 

population-adjusted dose (cPAD)]. For the general U.S. population, the exposure for food and 

water utilized approximately 2% of the cPAD. The chronic dietary risk estimate for the highest 

exposed population subgroup, children 1-2 years old, is 6.3% of the cPAD.

Aggregate Risk

Acute and cancer aggregate risks were not assessed due to the absence of an acute dietary 

endpoint and to the fact that chlorantraniliprole is not likely to be carcinogenic to humans.

The chronic aggregate risk assessment for chlorantraniliprole includes exposure to residues in 

food and water. No risk is expected from residential exposures or from spray drift.

Occupational Risk

There is a potential for occupational short- and intermediate-term inhalation and dermal exposure 

to chlorantraniliprole during mixing, loading, application, and postapplication activities. 

However, the chlorantraniliprole toxicology database indicates there is no systemic hazard 

associated with short- and intermediate-term dermal and inhalation exposure, and therefore, no 

occupational exposure and risk assessment was conducted.

Environmental Justice
Chlorantraniliprole Human Health Risk Assessment DP No. 411938 

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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).

2.0 Regulatory Conclusions and Recommendations

2.1 Data Deficiencies/Conditions of Registration

None

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate methods are available for the enforcement of tolerances for chlorantraniliprole residues 

in/on crops (liquid chromatography with tandem mass spectrometric detection (LC/MS/MS); 

Method DuPont-11374). . The limit of quantification (LOQ) is reported at 0.01 ppm for parent 

chlorantraniliprole. The method for the determination of chlorantraniliprole and its metabolites 

in processed commodities is an LC-MS/MS method, DuPont-14314, which is a slightly modified 

version of DuPont-11374. 

The enforcement method for livestock commodities is an LC-MS/MS method. The LOQ is 

reported at 0.010 ppm for parent and each of the metabolites. The described plant and animal 

methods have been reviewed and accepted by Agency chemists in the Analytical Chemistry 

Branch (ACB) of the Biological and Economic Analysis Division (BEAD) (DP#340358, C. 

Stafford, 02/06/08).

The requirements for multiresidue methods data are fulfilled. Chlorantraniliprole is not 

recovered by the U.S. Food and Drug Administration’s (FDA’s) multiresidue methods. 

2.2.2 International Harmonization

CODEX and Canada have established chlorantraniliprole maximum residue limits (MRLs) for a 

number of crop and animal commodities. There are no Mexican MRLs for chlorantraniliprole as 

Mexico adopts Codex or US standards for its export purposes. Canada does not have MRLs for 

cereal grains, so there is no issue of harmonization relevant to this petition. The Codex MRL for 

cereal grains is significantly lower than the recommended US tolerance for cereal grain. The US 

tolerance cannot be harmonized (lowered), as this would create a possible situation of tolerance 

violation from use according to the the labels. In general US tolerances for livestock 

commodities are not harmonized with Canada or Codex. Again, US values are higher and result 

from the increased exposure in livestock diets from treated cereal grain crops.

2.2.3 Recommended Tolerances
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Tolerances are established under 40 CFR §180.628 for residues of the insecticide

chlorantraniliprole, including its metabolites and degradates, in or on the commodities in Table 

2.2.3 below. Compliance with the tolerance levels specified below is to be determined by 

measuring only chlorantraniliprole, 3-bromo-N-[4-chloro-2-methyl-6-

[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide.

Pending revisions to Section F, HED has no objections to the establishment of tolerances for 

Cereal Grains, Except Rice (Crop Group 15), Cereal Grain Forage (Crop Group 16), Pome Fruit 

(Crop Group 11-10) and citrus (Crop Group 10-10). With the establishment of these subgroup 

tolerances, a number of individual grain forage, fodder, and or/straw tolerances and inadvertent 

tolerances need to be removed. See Table 2.2.3 for a list of recommended tolerances and 

tolerance revocations.

Table 2.2.3. Tolerance Summary for Chlorantraniliprole.

Commodity Existing 

Tolerance 

(ppm)

Proposed 

Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

180.628 (a) General

Grain, cereal, group 15, 

except rice

- 6.0 6.0 Grain, cereal, group15, except 

rice and corn.

Field corn grain, pop corn grain, 

and sweet corn must be excluded 

from the group as their residues

are much lower than 6.0 resulting 

from the barley grain.

Grain, cereal, forage, 

fodder and straw, group 

16

-

30 40 OECD statistical calculation based 

on barley straw.

Fruit, citrus, group 11 1.4 Remove Remove Replaced by group 11-10

Fruit, citrus, group 11-

10

- 1.4 1.4 Crop group conversion.

Fruit, pome, group 11, 

except mayhaw

1.2 Remove Remove Replaced by group 11-10

Mayhaw 1.2 Remove Remove Replaced by group 11-10

Fruit, pome, group 11-

10

- 1.2 1.2 Crop group conversion.

Field corn forage 14 Remove Remove Replaced by crop group 16

Field corn grain 0.04 Remove 0.04 Retain, as 0.04 differs from the 

crop group 15 tolerance by a factor 

>5X.

Field corn milled 

byproducts

0.1 - 0.1 Corn, field, milled byproducts

Retain, in accordance with the 

retention of the field corn grain 

tolerance.

Pop corn grain 0.04 Remove 0.04 Corn, pop, grain

Pop corn grain cannot be included 

in group 15 (see grain, cereal, 

group 15 except rice and corn)
Chlorantraniliprole Human Health Risk Assessment DP No. 411938 

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Table 2.2.3. Tolerance Summary for Chlorantraniliprole.

Commodity Existing 

Tolerance 

(ppm)

Proposed 

Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Pop corn forage 14 Remove Remove Replaced by crop group 16

Pop corn stover 14 Remove Remove Replaced by crop group 16

Sweet corn forage 14 Remove Remove Replaced by crop group 16

Sweet corn kernels plus 

cob with husk removed

0.02 Remove 0.02 Corn, sweet, kernel plus cobs with 

husk removed

Sweet corn cannot be included in 

group 15 (see grain, cereal, group 

15 except rice and corn)

Sweet corn stover 14 Remove Remove Replaced by crop group 16

Cattle, liver 0.3 - Remove Replace with Cattle, meat 

byproducts

Liver is grouped with other meat 

byproducts.

Cattle, meat 

byproducts, except liver

0.2 - 0.5 Cattle, meat byproducts

Cereal grain group 15 and group 

16 elevated the cattle dietary 

exposure.

Milk 0.05 - 0.1 Cereal grain group 15 and group 

16 elevated the cattle dietary 

exposure

Goat, liver 0.3 - Remove Replace with Goat, meat 

byproducts

Liver is grouped with other meat 

byproducts.

Horse, liver 0.3 - Remove Replace with Horse, meat 

byproducts

Liver is grouped with other meat 

byproducts.

Sheep, liver 0.3 - Remove Replace with Sheep, meat 

byproducts

Liver is grouped with other meat 

byproducts.

Hog, meat byproducts 0.02 - 0.05 Cereal grain group 15 elevated the 

hog dietary exposure.

Goat, meat byproducts, 

except liver

0.2 - 0.5 Goat, meat byproducts

Horse, meat 

byproducts, except liver

0.2 - 0.5 Horse, meat byproducts

Sheep, meat 

byproducts, except liver

0.2 - 0.5 Sheep, meat byproducts

Hog, meat - - 0.02 Cereal grain group 15 elevated the 

hog dietary exposure.

Hog, fat 0.02 - 0.05 Cereal grain group 15 elevated the 

hog dietary exposure.

Eggs 0.2 - 1.0 Cereal grain group 15 elevated the 

laying hen dietary exposure.
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Table 2.2.3. Tolerance Summary for Chlorantraniliprole.

Commodity Existing 

Tolerance 

(ppm)

Proposed 

Tolerance 

(ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Poultry, meat 

byproducts

0.02 - 0.2 Cereal grain group 15 elevated the 

laying hen dietary exposure.

Poultry, meat - - 0.05 Cereal grain group 15 elevated the 

laying hen dietary exposure.

Poultry, fat 0.01 - 0.2 Cereal grain group 15 elevated the 

laying hen dietary exposure.

180.628(d) Indirect or inadvertent residues

Grain, cereal, forage, 

fodder and straw, group 

16

0.20 Expires 

04/10/14

Remove Replaced by crop group 16 as a 

primary crop.

2.2.4 Revisions to Petitioned-For Tolerances

The cereal grain group 15 except rice proposal of 6.0 ppm is not acceptable. EPA is 

recommending a tolerance of 6.0 ppm for group 15 except rice and except corn. The existing 

tolerance for pop corn (0.04 ppm), sweet corn (0.02 ppm), and field corn (0.04 ppm) are much 

lower than the 6.0 ppm appropriate for other cereal grains. Therefore the group 15 tolerance will 

exclude corn (including field corn, pop corn, and sweet corn), and the existing tolerances for 

corn grains will remain.

The cereal grain forage, fodder, and straw group 16 proposal of 30 ppm is not acceptable. EPA 

is recommending establishment of a 40 ppm tolerance based on the analysis of the field trial data 

with the OECD tolerance calculation procedure.

The tolerances for certain livestock commodities will need to be created or increased because the 

expansion of use to more cereal grains and cereal grain forages, fodders, and straws increased the 

dietary exposure of livestock to chlorantraniliprole. Additionally, the tolerances for the liver of 

cattle, goat, horse, and sheep are replaced by tolerances for meat byproducts. These are detailed 

in Table 2.2.3

2.3 Label Recommendations

There are no label recommendations for this tolerance petition. 

3.0 Introduction

3.1 Chemical Identity
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Table 3.11. Chlorantraniliprole Nomenclature.

Chemical structure

Common name Chlorantraniliprole

Company experimental name DPX-E2Y45

IUPAC name 3-bromo-4′-chloro-1-(3-chloro-2-pyridyl)-2′-methyl-6′-

(methylcarbamoyl)pyrazole-5-carboxanilide

CAS name 3-bBromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro2-pyridinyl)-1H-pyrazole-5-carboxamide

CAS registry number 500008-45-7

End-use product (EP) Altacor® WG (35%; EPA Reg. No. 352-730)

DuPontTM Coragen® SC Insect Control (1.67 lb ai/gal; EPA Reg. No. 352-729)

3.2 Physical/Chemical Characteristics

The physical/chemical properties of chlorantraniliprole are summarized in Appendix B. Based 

on the low vapor pressure (6.3 x 10-12 Pa) and KOW (~3 at pH ranges 4 to 9), chlorantraniliprole 

is not expected to volatilize, pass lipid barriers (consistent with dermal absorption findings in 

mammals) or bioaccumulate. Environmental fate data indicate chlorantraniliprole is persistent 

and mobile in terrestrial and aquatic environments. Major routes of chlorantraniliprole 

dissipation are expected to be alkaline-catalyzed hydrolysis, photodegradation in water, leaching, 

and runoff. 

N N N

NH

O

Cl

Br

HN

O

Cl
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3.3 Pesticide Use Pattern

For the proposed Section 3 registrations addressed herein there are two end-use products, two 

suspension concentrates and one water dispersible granule. Proposed labels have been provided 

for a 5% active ingredient (ai) suspension concentrate (SC) Prevathon® Insect Control (0.43 lb ai 

per gallon, or 0.053 kg ai/l) EPA Reg. No. 352-844, a 18.4% active ingredient (ai) suspension 

concentrate (SC) Coragen®Insect Control (1.67 lbs ai/gallon or 0.200 kg ai/l) EPA Reg. No. 

352-729, and a 35.0% active ingredient (ai) water dispersible granular (WDG) Altacor® (35 lb 

ai/100 lb) EPA Reg. No. 352-730. Changes to the Altacor® label involve only crop 

conversions. The WDG formulation is not proposed for use on cereal grains. The summary of 

the relevant proposed uses is presented in Table 3.3. 
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. 

Table 3.3: Proposed Use Pattern for (SC) Prevathon® Insect Control and (SC) Coragen®Insect Control

Crop Group Crop Appl. Type Max # of 

Appl.

Volume

(gal/A)

[L/ha]

Rate/Appl.

(lb ai/A)

[kg ai/ha]

Max. 

Rate/Season

(lb ai/A)

[kg ai/ha]

Min.

RTI

(days)

PHI

(days)

Comment

Cereal 

grains 

group 15, 

except rice, 

except corn

Barley

Buckwheat

Pear millet

Proso millet

Oats 

Rye

Sorghum (milo)

Sorghum (grain 

sorghum, 

sudangrass)

Teosinte

Triticale

Wheat

Wild rice

foliar 4 N/S 0.047– 0.067

(0.053 – 0.075)

0.20

(0.22)

7 14 Minimum 5 gpa 

water for aerial 

for Coragen and 2 

gpa water for 

Prevathon, 10 gpa 

for ground 

application.

May be applied 

by ground, aerial, 

overhead 

sprinkler 

irrigation.

Adjuvants 

allowed. 

Corn 

(sweet)1

Corn 

(seed)1

Sweet corn

Seed corn

Soil at 

plantingIn-furrow 

spray

4 N/S 0.067 – 0.098

(0.075 – 0.11)

0.20

(0.22)

1 1 Minimum 5 gpa 

water for aerial 

for Coragen and 2 

gpa water for 

Prevathon, 10 gpa 

for ground 

application.

May be applied 

by ground, aerial, 

overhead 

sprinkler 

irrigation.

Adjuvants 

allowed.

Foliar N/S 0.047 – 0.067

(0.053 – 0.075)

Corn 

(field)1

Corn (pop)1

Field corn

Pop corn

Soil at 

plantingIn-furrow 

spray

4 N/S 0.067 – 0.098

(0.075 – 0.11)

0.20

(0.22)

7 14 Minimum 5 gpa 

water for aerial 

for Coragen and 2 

gpa water for 

Prevathon, 10 gpa 

for ground 

Foliar N/S 0.047 – 0.067

(0.053 – 0.075)
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Table 3.3: Proposed Use Pattern for (SC) Prevathon® Insect Control and (SC) Coragen®Insect Control

Crop Group Crop Appl. Type Max # of 

Appl.

Volume

(gal/A)

[L/ha]

Rate/Appl.

(lb ai/A)

[kg ai/ha]

Max. 

Rate/Season

(lb ai/A)

[kg ai/ha]

Min.

RTI

(days)

PHI

(days)

Comment

application. May 

be applied by 

ground, aerial, 

overhead 

sprinkler 

irrigation.

Adjuvants 

allowed

1Consistent with existing approved labels for Coragan® Registration No. 352-729 (05/15/2011) and for Prevathon® Registration No. 352-844 (11/08/2011).
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3.4 Anticipated Exposure Pathways

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

chlorantraniliprole may be applied directly to growing crops and application may result in 

chlorantraniliprole reaching surface and ground water sources of drinking water. There are 

registered residential uses of chlorantraniliprole, 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 a potential for 

post-application exposure for workers re-entering treated fields.

This risk assessment considers all of the aforementioned exposure pathways based on the 

proposed new uses of chlorantraniliprole, but also considers the existing uses as well, 

particularly for the dietary assessment.

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.epa.gov/environmentaljustice/resources/policy/exec_order_12898.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 U.S. Department of 

Agriculture’s 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 and ethnic group. 

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

No new toxicity and/or metabolism data have been received since the last risk assessment. This 

assessment includes summaries of prior assessments (S. Healy, 05/17/12, D399493).

4.1 Summary of Toxicological Effects
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

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Chlorantraniliprole is an anthranilic diamide insecticide that belongs to a class of compounds 

that acts on the ryanodine receptor (RyR). It controls lepidopteran pests and insects primarily via 

interruption of normal muscle contraction pathways, which leads to paralysis and eventual death. 

The relative absence of mammalian hazard may be due in part to chlorantranilprole’s selectivity 

for insect RyR over mammalian counterparts. In short-term studies, the most consistent effects 

are those associated with non-adverse pharmacological response to the xenobiotic, induction of 

liver enzymes and subsequent increase in liver weights. In a 28-day dermal toxicity study in rats, 

increased microvesiculation of adrenal cortex was observed in males only, with no light or 

electronic microscopic evidence of adrenal cellular degeneration or toxicity. Supporting data 

demonstrated no effect on the capacity of the adrenal gland to produce corticosterone under 

either basal or following ACTH stimulation. Therefore, adrenal cortex effects observed in the 

dermal toxicity study were not considered adverse. Chlorantraniliprole is not genotoxic, 

neurotoxic, immunotoxic, carcinogenic, or developmentally toxic. Furthermore, it does not 

exhibit pre- or postnatal toxicity as there were no maternal or fetal effects in studies conducted in 

rats and rabbits. Based on the results of a 28-day dermal study in rats, as well as the dermal LD50

study, DPX-E2Y45 has relatively low dermal toxicity. Chlorantraniliprole is not acutely toxic

via the oral, dermal, and inhalation routes of exposure. The LD50 for oral and dermal acute 

exposure is ≥5000 mg/kg/day and the LC50 for acute inhalation exposure is ≥5.1 mg/L. 

Chlorantraniliprole is not an eye or skin irritant and does not cause skin sensitization. The acute 

inhalation study did not report any portal of entry effects or acute irritation via the inhalation 

route of exposure. 

Absorption, Distribution, Metabolism, Excretion (ADME)

Chlorantraniliprole metabolism was studied extensively in rats, mice, and dogs. In rats, 

absorption of chlorantraniliprole was rapid with peak concentrations occurring at 5-12 hours 

after low or high (10 or 200 mg/kg) oral single dose administration. The plasma elimination 

half-lives ranged from 38-82 hours. Tissue distribution of the absorbed dose was extensive and 

indicated low potential for accumulation. The tissue residues were higher in female rats than in 

male rats, which is consistent with female rats having a longer elimination half-life and higher 

area under the curve (AUC) in plasma. Excretion in both high- and low-dose groups was 

substantially complete by 48-72 hours after dosing. Fecal excretion was the primary route of 

elimination followed by the urine with no significant excretion occurring by exhalation. 

Metabolism of the absorbed dose was extensive and involved sex differences (greater 

hydroxylation in males). Results also suggest possible species differences in the primary 

metabolites formed in all three species tested. Metabolites represented in the rat metabolism 

cascade were: IN-K9T00, IN-HXH44, IN-KAA24, IN-H2H20, and IN-GAZ70 (chemical 

nomenclature and molecular structures for these compounds can be found in: S. Healy, 

02/28/11, D381810).

Based on studies conducted in rats, dermal penetration of chlorantraniliprole (20SC and 35WG 

formulations) is less than 3%.

4.2 Safety factor for Infants and Children (FQPA Safety Factor)
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

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Based on the hazard and exposure data, the HED chlorantraniliprole risk assessment team 

recommends that the FQPA SF be reduced to 1X. The rationale for this recommendation is 

provided in the following sections.

4.2.1 Completeness of the Toxicology Database

The toxicity database for this chemical is complete for the purposes of this risk assessment and 

considered adequate for the characterization of potential pre- and postnatal risks to infants and 

children. Acceptable developmental toxicity and 2-generation reproduction studies have been 

submitted and reviewed, as well as a complete neurotoxicity screening battery and 

immunotoxicity study.

4.2.2 Evidence of Neurotoxicity

No evidence of neurotoxicity was observed in studies conducted with chlorantraniliprole in rats. 

The NOAEL in an acute, oral gavage neurotoxicity study was 2000 mg/kg, the limit dose. In a 

subchronic neurotoxicity study, the NOAEL was 1313/1586 mg/kg/day (M/F), the maximum 

dietary concentration administered (greater than the limit dose). The NOAELs were based on 

the absence of treatment related effects on systemic toxicity and neurotoxicity parameters, 

including microscopic neuropathology. Neurological assessments conducted in conjunction with 

the 18-month oncogenicity study in mice following 45, 60, and 90 days of dietary administration 

of chlorantraniliprole confirmed the lack of potential neurotoxicity. Further, no treatment related 

clinical signs indicative of potential neurotoxicity were observed in short-term or long-term 

exposure studies in rats, mice, or dogs. 

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

There were no effects on prenatal fetal growth or postnatal development up to the limit dose of 

1000 mg/kg/day in rats or rabbits. There were no treatment related effects on the numbers of 

litters, fetuses (live or dead), resorptions, sex ratio, or post-implantation loss. There were no 

effects on fetal body weights, skeletal ossification, and external, visceral, or skeletal 

malformations or variations. 

4.2.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. Since the dietary and non-dietary 

exposure estimates were based on several conservative assumptions, HED does not believe that 

the exposure estimates are underestimated. The chronic dietary assessment utilized tolerance 

level residues for all crops and assumed that 100% crop of the proposed and registered crops 

were treated with chlorantraniliprole. Default processing factors were used as appropriate. The 

DEEM-FCID analysis also assumed that all drinking water will contain chlorantraniliprole at the 

highest EDWC levels modeled by EFED for ground water or surface water. For these reasons it 

can be concluded that the DEEM-FCID analysis does not underestimate risk from chronic 

exposure to chlorantraniliprole.

4.3 Toxicity Endpoint and Point of Departure Selections
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

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The details for selecting toxicity endpoints and points of departure for various exposure 

scenarios are presented in the original risk assessment for Section 3 Registration (S. Winfield, 

DP336983, 03/07/08). There have been no changes to the prior dose-response assessment or

recommendations for combining routes of exposure and/or cancer classification. Refer to Table 

4.3.1.

Table 4.3.1. Summary of Toxicological Doses and Endpoints for Chlorantraniliprole for Use in Dietary, NonOccupational, and Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(All 

Populations)

N/A N/A N/A

No acute hazard attributable to a single 

dose was identified; therefore, an acute 

dietary endpoint was not selected for 

quantitative risk assessment.

Chronic 

Dietary (All 

Populations)

NOAEL= 

158 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Chronic RfD 

= 1.58 

mg/kg/day

cPAD = 1.58 

mg/kg/day

18-Month Oral (feeding)/mouse

LOAEL = 935 mg/kg/day based on 

eosinophilic foci accompanied by 

hepatocellular hypertrophy and increased 

liver weight (males only).

Incidental Oral 

Short-

/IntermediateTerm 

N/A N/A N/A

There was no hazard identified via the oral 

route over the short- and intermediateterm and, therefore, no endpoint was 

selected for quantitative risk assessment.

Dermal Short-

/IntermediateTerm N/A N/A N/A

There was no hazard identified via the 

dermal route (and no concerns for 

developmental, reproductive or neurotoxic 

effects) and, therefore, no dermal endpoint 

was selected for quantitative risk 

assessment.

Inhalation 

Short-

/IntermediateTerm 

N/A N/A N/A

Based on the lack of hazard identified in 

the acute inhalation study, lack of acute 

irritation, and extremely low oral toxicity,

no inhalation endpoint was selected for 

quantitative risk assessment.

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on weight of evidence of data: 

no treatment-related tumors reported in the submitted chronic and oncogenicity studies in rats and 

mice, subchronic studies in mice, dogs and rats and no mutagenic concern was reported in the 

genotoxicity studies. 

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. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity 

among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern. 

N/A = not applicable.

5.0 Dietary Exposure and Risk Assessment

5.1 Residues of Concern Summary and Rationale
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

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A summary of the residues of concern and rationale can be found in a previous risk assessment 

(D. Rate, DP#361397, 01/12/2010).

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression

Matrix Residues included in 

Risk Assessment

Residues included in 

Tolerance Expression

Plants Primary Crop Chlorantraniliprole Chlorantraniliprole

Rotational Crop Chlorantraniliprole Chlorantraniliprole

Livestock Ruminant Chlorantraniliprole, 

IN-HXH44, INK9T00. 

Chlorantraniliprole

Poultry Chlorantraniliprole

Eggs: 

Chlorantraniliprole, 

IN-H2H20, INK7H29, IN-GAZ70

Chlorantraniliprole

Drinking Water Chlorantraniliprole N/A

5.2 Food Residue Profile

The submitted magnitude of the residue data is adequate for risk assessment and tolerance 

assessment. For all crops, the number and locations of field trials are adequate. Barley, grain 

sorghum and wheat trials reflect the proposed label maximum application rate and other 

conditions, with the exception of the preharvest interval (PHI). The proposed label PHI is 14 

days, whereas the trials were conducted with a 1 day PHI. Residue decline studies on other 

commodities show that chlorantraniliprole residues decline with increasing PHI. Residues at the 

proposed 14 days PHI will be less than residues at the tested 1 day PHI, and therefore the 

tolerance estimate will be adequate. 

The field trial studies are supported by adequate storage stability data.

The wheat processing study is adequate. Residues do not concentrate in wheat processed 

commodities relative to the wheat grain, except aspirated grain fractions. Only one tolerance is 

established for aspirated grain fractions from all commodity sources, and soybeans yields higher 

aspirated grain fraction residues. Therefore, the existing aspirated grain fraction tolerance based 

on soybean remains.

Adequate confined and limited field rotational crop data are available. HED previously 

concluded that the residue of concern in rotational crops is parent only. All necessary rotational 

crop tolerances were established previously or appropriate label restrictions were implemented. 
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

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Extensive primary crop or crop group tolerances have been established, and therefore there are 

few inadvertent tolerances needed.

5.3 Water Residue Profile

For surface water, the EDWCs for the scenarios modeled in this assessment did not exceed the 

previous EDWCs for use on cranberries generated by the Provisional Cranberry Model which is 

a provisional refinement to the Tier I Rice Model (C. Koper, DP#3881819, 12/01/2010)..

Refinements include the addition of simple degradation processes in dry and flooded conditions 

and a water depth of twelve inches, rather than the water depth of four inches used in the rice 

model. The previously reported acute concentration of 55.30 μg/L, annual mean (chronic) 

concentration of 39.87μg/L and the 30 year annual average concentration of 39.87μg/L are 

greater than the reported EDWCs from the proposed uses for all scenarios reported in Table 3.3. 

Table 5.3. Summary of Estimated Surface Water and Ground Water Concentrations for 

Chlorantraniliprole.

Surface Water 

Concentration

(ppb a)

Ground Water 

Concentration 

(ppb b)

Acute 55.30

0.842 Chronic (non-cancer, 1 in 10 year annual 

average)

39.87

Chronic (cancer, 30-year annual average) 39.87

a

Pesticide Root Zone Model (PRZM v3.12.2, May 12, 2005) and Exposure Analysis Modeling System (EXAMS 

v2.98.04.06, April 25, 2005), simulation models, were coupled with the input PE5.pl.shell. The Provisional 

Cranberry Model was used to assess cranberry. The model does incorporate a degradation component. 

b

From the SCI-GROW model, assuming a maximum seasonal use rate of 0.200 lbs ai/acre (2 X 0.100 lb ai/acre), a 

Koc of 153, and a half-life of 410 days from the aerobic soil metabolism study. This is lower than the previous 

estimate of 1.06 ppb. 

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Recommended or established tolerance-level residues and 100% CT were used for all 

commodities included in this assessment and, therefore, this assessment is considered 

conservative. Processed commodity tolerance-level residues were used. DEEM default 

concentration factors for processed commodities were used if available.

The drinking water residues used in the dietary risk assessment were provided by EFED (C. 

Koper, 1/17/2013, D404711; C. Koper, 2/29/2012, D397882; and C. Koper, 12/01/2010, 

D3881819) and incorporated directly into this dietary assessment. Water residues were 

incorporated in the DEEM-FCIDTM into the food categories “water, direct, all sources” and 

“water, indirect, all sources.” The estimated surface water concentration of 39.87 ppb was used 
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

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for this assessment since it is higher than the ground water concentration of 0.842 ppb. This 

value of 39.87 ppb is the one in ten year annual mean.

5.4.2 Acute Dietary Risk Assessment

No acute dietary toxicity endpoint could be identified based on the toxicology data currently 

available for chlorantraniliprole; therefore, an acute assessment was not performed. 

5.4.3 Chronic Dietary Risk Assessment

The chronic dietary (food and drinking water) exposure assessment for chlorantraniliprole 

assumed recommended and/or established tolerance-level residues and 100% crop treated (CT). 

DEEM default processing factors were used. Estimated drinking water concentrations (EDWCs) 

from EFED (39.87 ppb) were also included. The results of this chronic analysis indicate that 

chronic dietary (food and drinking water) exposure and risk does not exceed HED’s level of 

concern for the general U.S. population and all population subgroups. The results of the DEEMFCIDTM analysis indicate that the risks are about 2% of the chronic population-adjusted dose for 

the general U.S. population and 6.3% of the cPAD for children (1-2 years old), the most highly 

exposed subgroup.

5.4.4 Cancer Dietary Risk Assessment

Chlorantraniliprole is classified as “not likely to be carcinogenic to humans”; therefore, a cancer 

assessment was not performed.

5.4.5 Summary Table

Table 5.4.5. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Chlorantraniliprole.

Population Subgroup

Chronic Dietary

Dietary Exposure

(mg/kg/day) % cPAD*

General U.S. Population 0.032474 2.1

All Infants (<1 year old) 0.051597 3.3

Children 1-2 years old* 0.099596 6.3

Children 3-5 years old 0.076426 4.8

Children 6-12 years old 0.042431 2.7

Youth 13-19 years old 0.024386 1.5

Adults 20-49 years old 0.026971 1.7

Adults 50+ years old 0.026545 1.7

Females 13-49 years old 0.025763 1.6

*The subpopulation(s) with the highest risk estimates (Insert an asterisk after the population subgroups with the 

highest risk estimates and highlight the subpopulations in bold print)
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6.0 Residential (Non-Occupational) Exposure/Risk Characterization

6.1 Residential Handler Exposure

Although there are existing residential uses for chlorantraniliprole, residential exposure to 

chlorantraniliprole was not assessed due to the lack of toxicity via inhalation and dermal routes.

No risk is expected from residential handler exposure to chlorantraniliprole.

6.2 Post-Application Exposure

Due to the lack of toxicity via inhalation and dermal routes of exposure, as well as the lack of 

toxicity over the acute, short- and intermediate-term via the oral route, a residential postapplication risk assessment is not required.

6.3 Combined Exposure

Residential postapplication pesticide exposure can occur within a scenario from multiple routes 

of exposure (e.g., dermal, inhalation, and oral). These exposures to pesticides do not occur as 

single, isolated events, but rather as a series of sequential or concurrent events that may overlap 

or be linked in time and space. Based on this, risk estimates resulting from different exposure 

routes may be combined when it is likely that they can occur simultaneously based on the use 

pattern and when the toxicological effects across different routes of exposure are the same. If 

appropriate for an exposure scenario, the recommended routes of exposure for combining 

include dermal, inhalation, and hand-to-mouth.

For the chronic, non-cancer assessment, combined exposures were not necessary to assess for 

chlorantraniliprole since no hazard was identified for the inhalation and dermal routes of 

exposure.

6.4 Residential Bystander Postapplication Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for chlorantraniliprole at this time primarily because of the low 

acute inhalation toxicity (Toxicity Category IV), low vapor pressure (6.3 X10-12 Pa @ 20 ̊C), and 

the low proposed use rate (0.2 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, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify 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 chlorantraniliprole.
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

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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 

chlorantraniliprole. 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 at http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by 

chemical basis, the Agency is now requiring interim mitigation measures for aerial applications 

that must be placed on product labels/labeling. 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 

risks associated with drift.

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.

Aggregate exposure risk assessments were assessed by incorporating the drinking water directly 

into the dietary exposure assessment for the chronic exposure scenario. Due to the lack of 

toxicity over the acute, short- and intermediate-term via the oral route and dermal and inhalation

routes of exposure, no risk is expected from these exposures. Acute and cancer aggregate risk 

assessments were not performed because no appropriate endpoint was available to determine the 

aRfD for the general population or any population subgroup, as well as the fact that 

chlorantraniliprole is not carcinogenic.

An acute aggregate risk assessment was not performed because no appropriate endpoint was 

available to determine the aRfD for the general U.S. population or any population subgroup. 

Short- and intermediate term aggregate risk was not performed because no hazard was identified 

over a short- or intermediate-term duration.

The chronic dietary exposure estimates are not of concern to HED for the general U.S. 

population and all population subgroups (see Table 5.4.5). Therefore, the chronic aggregate risk 

for chlorantraniliprole does not exceed HED’s level of concern for the general U.S. population or 

any population subgroups.
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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 

to chlorantraniliprole and any other substances and chlorantraniliprole 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 chlorantraniliprole 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

There is potential for short- and intermediate-term occupational exposure to chlorantraniliprole 

during both handler [mixing, loading, and application (via the dermal and inhalation routes)] and 

postapplication activities (via the dermal route) based on the proposed uses. However, the 

chlorantraniliprole toxicology database indicates there is no hazard associated with short- and 

intermediate-term dermal and inhalation exposure, and, therefore, no occupational exposure and 

risk assessment was conducted.

10.0 References

Chlorantraniliprole: Chronic Aggregate Dietary (Food plus Drinking Water) Exposure and Risk 

Assessment for the Section 3 Registration Action on Cereal Grains, Except Rice (Crop Group 

15), Cereal Grain Forage (Crop Group 16), Pome Fruit (Crop Group 11-10) and Citrus (Crop 

Group 10-10), Kristin Rury, D411997, 05/29/13

Chlorantraniliprole (DPX-E2Y45). Section 3 Registration for Proposed Uses on Cereal Grains 

Group 15 (except Rice) and Cereal Grains Forage, Fodder, and Straw Group 16. Request for 

Crop Group Conversions for Pome Fruit Group 11-10 and Citrus Fruit Group 10-10. Poultry 

Feeding Study. Summary of Analytical Chemistry and Residue Data, Steve Funk, D 404708, 

3/29/13

Tier II Drinking Water Exposure Assessment to Establish Tolerances of Chlorantraniliprole on 

Bushberries Subgroup 13-07B, Cucurbit Vegetables Group 9, Fruiting Vegetables Group 8, 

Large Shrub/Tree Berries Subgroup 13-07C, Low Growing Berries Subgroup 13-07G, Okra, 

Onion (bulb) Subgroup 3-07A, Peanut (hay, nutmeat), Root and Tuber Vegetables Group 1, 

Sugar Beet Molasses, Ti Palm, Leaves of Root and Tuber Vegetables Group 2, Dried Tea Leaves 

and Corn, Christopher Koper, DP# 381819, 12/01/10

Tier II Drinking Water Exposure Assessment to Establish Tolerances of Chlorantraniliprole on 

Citrus Fruits Group 10-10, Pome Fruits Group 11-10, Cereal Grain Crop Group 15 (except 
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

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Rice), and Cereal Grain Forage, Fodder, and Straw, Crop Group 16, Christopher Koper, 

DP#404711, 1/17/13

Chlorantraniliprole (DPX-E2Y45): Human Health Risk Assessment for Section 3 Registration 

Request to Expand Uses of Coragen®, Altacor®, and DemacorTM X-100 Labels on Various 

Field, Vegetable, and Fruit Crops, Debra Rate, DP#361397, 01/12/2010

Chlorantraniliprole (DPX-E2Y45): Human Health Risk Assessment for Proposed Uses on Pome 

fruit, Stone fruit, Leafy vegetables, Brassica leafy vegetables, Cucurbit vegetables, Fruiting 

vegetables, Cotton, Grapes, Potatoes, Turf and Ornamentals, S. Winfield, DP#336983, 

03/07/08). 
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

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Appendix A. Toxicology Profile 

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for food use for chlorantraniliprole are in Table A.1. Use of the new guideline 

numbers does not imply that the new (1998) guideline protocols were used.

Test 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

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (non-rodent)........................................

870.3200 21-Day Dermal ..............................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

no

no

yes

yes

yes

-

-

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (non-rodent) ...........................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent) ..............................................

870.4100b Chronic Toxicity (non-rodent).......................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse)....................................................

870.4300 Chronic/Oncogenicity....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5385 Mutagenicity—Structural Chromosomal Aberrations...

870.5395 Mutagenicity—Micronucleus........................................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen) .....................................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotox. Screening Battery (rat) .......................

870.6200b 90-Day Neurotox. Screening Battery (rat).....................

870.6300 Develop. Neurotox ........................................................

no

no

yes

yes

no

-

-

yes

yes

-

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration ........................................................

870.7800 Immunotoxicity .............................................................

yes

no

yes

yes 

-

yes
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

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A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile of Chlorantraniliprolea

Guideline No. Study Type MRID(s) Results Toxicity 

Category

870.1100 Acute oral - rat 46889112 LD50 > 5000 mg/kg IV

870.1200 Acute dermal - rat 46889113 LD50 > 5000 mg/kg IV

870.1300 Acute inhalation - rat 46889121 LC50 > 5.1 mg/L IV

870.2400 Acute eye irritation -rabbit 46889115 Iritis score of 1 in 1/3 rabbits, 

conjuctival redness score of 1 

in 2/3 rabbits. All eyes 

returned to normal after 72 

hours.

IV

870.2500 Acute dermal irritation - rabbit 46889114 No dermal irritation, clinical 

signs or body weight loss

IV

870.2600 Skin sensitization - mouse 46889221 Not a dermal sensitizer Negative

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Chlorantraniliprole

STUDY/

SPECIES

DOSES 

(mg/kg/day)

NOAEL 

(mg/kg/day)

LOAEL 

(mg/kg/day) EFFECTS

Non-guideline

14-day Oral 

Gavage/ rat

0, 25, 100, 1000 1000 Not 

established

No adverse effects. Weak inducer of cytochrome 

P450 3A at all dose levels, with statistical 

significance at 100 and 1000 mg/kg/day.

Non-guideline

28-Day Oral 

(feed)/rat

0, 20.7, 106 and 

584 (male); 0, 24, 

128 and 675 

(female)

584 (male) 

and 675 

(female)

Not 

established

No adverse effects. Slight increase in liver weight 

at 128 and 675 mg/kg/day in females and minimal 

hepatocellular hypertrophy at 675 mg/kg that is 

attributed to enzyme induction characterized by 

increased amount of eosinophilic cytoplasm with 

hepatocytes but no histomorphologic evidence of 

hepatocellular damage. In 128 and 675 mg/kg 

females, a statistically significant increase in UDPGT activity was observed in HDT female rats, with 

a similar increase in males. These changes are 

consistent with a pharmacological response and 

were not considered adverse.

Non-guideline

28-Day Oral 

(feed)/mouse

0, 52, 182, 538 

and 1443 (male); 

0, 64, 206, 658 

and 1524 

(female)

1443 (male) 

and 1524 

(female)

Not 

established

No adverse effects. Slight increase in liver wt. in 

658 and 1524 mg/kg/day females corresponded 

with a mild increase in cytochrome P450 enzyme 

activity. No histopathological evidence of liver 

toxicity was observed.

A reduction in body weight gain was observed in 

HDT males (52%) but not in females. No 

statistically significant decrease in absolute body 

weight was observed therefore, this effect was not 

considered adverse. 

Non-guideline

28-day Oral 

(capsule)/

Dog

0, 300, 1000 1000 Not 

established

No adverse effects. Induction of cytochrome P450 

enzyme activity (58%) in both males and females at 

1000 mg/kg/day, specifically 1A1 and 2B1/2 at 300 

and 1000 mg/kg/day.

Non-guideline

28-day Oral 

0, 26, 138, 266, 

797 and 1302 

1302 (male) 

and 1240 

Not 

established

No adverse effects. Food consumption generally 

increased as the study progressed with males 
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

Page 27 of 30

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Chlorantraniliprole

STUDY/

SPECIES

DOSES 

(mg/kg/day)

NOAEL 

(mg/kg/day)

LOAEL 

(mg/kg/day) EFFECTS

(feed)/dog –

Palatability 

study

(male); 0, 28, 

138, 298, 888, 

and 1240 

(female)

(female) generally demonstrating the highest food 

consumption when fed the HDT.

870.3100

90-day Oral 

(feed)/rat

0, 36.9, 120, 359, 

1188 (male); 0, 

47, 157, 460, 

1526 (female)

1188 (male) 

and 1526 

(female)

Not 

established

No adverse effects. A slight increase in liver 

weight at HDT females and reduction in bilirubin 

in females at ≥157 mg/kg/day, with no 

corresponding histopathological evidence of liver 

toxicity.

870.3100

90-day Oral 

(feed)/mouse

0, 32.6, 115, 345, 

1135 (male); 0, 

40.7, 158, 422, 

1529 (female)

1135 (male) 

and 1529 

(female)

Not 

established

No adverse effects. Hyperactivity and 

hyperreactivity in females were observed near the 

end of the study and one male in the upper mid 

dose had convulsions, but these effects were 

considered spurious as they were not reproducible 

in the 18-month mouse study with a FOB.

A slight increase in liver weight at the HDT males 

and females, with no corresponding 

histopathological evidence of liver toxicity.

870.3150

90-day Oral 

(feed)/dog

0, 32.2, 119, 303, 

1163 (male); 0, 

36.5, 133, 318, 

1220 (female)

1163 (male) 

and 1220 

(female)

Not 

established

No adverse effects. A mild increase in liver weight 

was observed in males at 1163 mg/kg/day, with no 

corresponding histopathological evidence of liver 

toxicity.

870.3200

28-day 

Dermal/rat

0, 100, 300 and 

1000

1000 Not 

established

No adverse effects. Reductions in mean body 

weight gain (22% and 19% for males and females) 

and food efficiency (19% and 17% for males and 

females) over the 28-day at the HDT.

Increased microvesiculation of adrenal cortex in 

males only, with no light or electronic microscopic 

evidence of adrenal cellular degeneration or 

toxicity. No effect on the capacity of the adrenal 

gland to produce corticosterone under either basal 

or following ACTH stimulation. Therefore, these 

effects were not considered adverse.

870.4100

52-week Oral 

(feed)/dog

0, 32, 112, 317, 

1164 (male); 0, 

34, 113, 278, 

1233 (female)

1164 (male) 

and 1233 

(female)

Not 

established

No adverse effects. A mild increase in liver weight 

in HDT males and females, and increase in alkaline 

phosphatase in HDT males, with no corresponding 

histopathological evidence of liver toxicity.

Body weight gain increase in HDT males for weeks 

8-9 compared to controls, with an increase in food 

efficiency in week 9.

870.4300

2-Year Oral 

(feeding)/rat

0, 7.71, 39, 156, 

805 (male); 0, 

10.9, 51, 212, 

1076 (female)

805 (male) 

and 1076 

(female)

Not 

established

No evidence of carcinogenicity and no adverse 

findings. Increased adrenal cortical 

microvesiculation due to lipid was present in the 

zona fasciculata region of the adrenal gland of 

some male rats in all dose groups in both the oneyear and main studies. This finding was considered 

test substance related but was not considered 

adverse as the adrenal morphology was generally in 

the range of what was observed in control rats, and 

the finding was not associated with any indication 

of cytotoxicity or other evidence of structural or 

functional impairment of the adrenal gland.

870.4200

18-Month 

0, 2.6, 9.2, 26.1, 

158, 935 (male); 

158 (male) 

and 1155 

935 (male), 

no LOAEL 

No evidence of carcinogenicity. Eosinophilic foci 

accompanied by hepatocellular hypertrophy and 
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

Page 28 of 30

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Chlorantraniliprole

STUDY/

SPECIES

DOSES 

(mg/kg/day)

NOAEL 

(mg/kg/day)

LOAEL 

(mg/kg/day) EFFECTS

Oral 

(feeding)/

Mouse

0, 3.34, 11.6, 

32.9, 196, 1155 

(female)

(female) established 

for female

increased liver weight form the bases for the male 

LOAEL of 935 mg/kg/day.

870.3800

Twogeneration 

oral study/rat

0, 200, 1000, 

4000, 20000 

ppm,

mg/kg bw/d 

equivalents: 

pre-mating:

P1 m: 0, 12, 60, 

238, 1199

F1 m: 0, 18, 89, 

370, 1926

P1 f: 0, 16, 78, 

318, 1594

F1 f: 0, 20, 104, 

406, 2178, 

1199 (male) 

and 1594 

(female)

Not 

established

A slight increase in mean liver weights in P1 

and F1 males and females at 238/318.9 

mg/kg/day and above, slight increase in mean 

adrenal weight at 238/318.9 mg/kg/day and 

1199/1594 mg/kg/day P1 and F1 males and 

females. Mean body weight of 1199/1594 

mg/kg/day F1 pups was slightly reduced on 

lactation days 7, 14 and 21. No effects on F2 

offspring weights during lactation.

Minimal to mild increase in adrenal cortical 

microvesiculation in P1 adult males and F1 

adult males and females. P1 adult at 60.4/77.8 

mg/kg/day and greater. F1 adult males at 12 

mg/kg/day and greater. These effects were not 

observed in weanlings. No cytotoxicity or 

abnormal cellular structures were observed 

under light or electron microscopy.

870.3700

Develop

mental 

study/rat

0, 20, 100, 300, 

1000

1000 Not 

established

No adverse effects.

870.3700

Develop

mental 

study/rabbit

0, 20, 100, 300, 

1000

1000 Not 

established

No adverse effects.

870.6200a

Acute oral 

neurotoxicity/rat

0, 200, 700, 

2000 in 0.5% 

methyl 

cellulose

2000 Not 

established

No evidence of neurotoxicity was observed at 

any dose

870.6200b

Subchronic 

oral neurontoxicity/rat

0, 12.7, 64.2, 

255, 1313 

(male); 0, 15.1, 

77.3, 304, 1586 

(female)

1313 (male) 

and 1586 

(female)

Not 

established

No evidence of neurotoxicity was observed at 

any dose.

870.7485

Metabolism 

and kinetics

The absorption of 14C-chlorantraniliprole was 

rapid with peak concentrations occurring at 5-

12 hours after low or high (10 or 200 mg/kg 

bw) dose administration. The percent 

absorption decreased after high dose 

administration. The plasma elimination halflives ranged from 38-82 hours. Tissue 

distribution of the absorbed dose was 

extensive and indicated low potential for 

accumulation. The tissue residues were 

higher in female than male rats consistent with 

female rats having a longer elimination halflife and higher AUC in plasma. Excretion 

was substantially complete by 48-72 hour 
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

Page 29 of 30

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Chlorantraniliprole

STUDY/

SPECIES

DOSES 

(mg/kg/day)

NOAEL 

(mg/kg/day)

LOAEL 

(mg/kg/day) EFFECTS

after dosing. Faecal excretion was the 

primary route of elimination followed by the 

urine with no significant excretion occurring 

by exhalation. Metabolism of the absorbed 

dose was extensive and involved sex 

differences primarily in initial methylphenyl 

and N-methyl carbon hydroxylations. Further 

metabolism of the hydroxylated metabolites 

included N-demethylation, nitrogen-to-carbon 

cyclisation with loss of a water molecule, 

oxidation of alcohols to carboxylic acids, 

amide bridge cleavage, amine hydrolysis, and 

O-glucuronidation

870.7800

28-day 

Immunotoxicity/rat

0, 74, 363, 1494 

(male); 0, 82, 

397, 1601 

(female)

1494 (male) 

and 1601 

(female)

Not 

established

No evidence of treatment-related effects on 

the sheep red blood cells specific antibody 

(IgM) responses in either male or female rats 

at any dietary concentration tested.

870.7800

28-day 

Immunotoxicity/

Mouse

0, 48, 264, 1144 

(male); 0, 64, 

362, 1566 

(female)

1144 (male) 

and 1566 

(female)

Not 

established

No evidence of treatment-related effect on the 

sheep red blood cells specific antibody (IgM) 

responses in either male or female mice at any 

dietary concentration tested.

a Studies are described and listed, along with MRID numbers, in TXR 0054555
Chlorantraniliprole Human Health Risk Assessment DP No. 411938

Page 30 of 30

Appendix B. Physical/Chemical Properties

Table B. Physicochemical Properties of Technical Grade of Chlorantraniliprole.

Parameter Value Reference

Melting point/range (°C) 200-202 (95.9%)/208 – 210 (99.2%) 46889033

pH 5.77 ± 0.087 at 20°C 46889031

Relative Density 1.5189 (95.9%)/1.507 (99.2%) at 20°C 46889033

Water solubility (20°C) Deionized Water 1.023 mg/L

pH 4 0.972 mg/L

pH 7 0.880 mg/L

pH 9 0.971 mg/L

46889026

Solvent solubility (20°C) Acetone 3.446 ± 0.172 g/L

Acetonitrile 0.711 ± 0.072 g/L

Ethyl Acetate 1.144 ± 0.046 g/L

Dichloromethane 2.476 ± 0.058 g/L

Dimethylformamide 124 ± 4 g/L

n-Octanol 0.386 ± 0.01 g/L

Methanol 1.714 ± 0.057 g/L

n-Hexane <0.0001 g/L

o-Xylene 0.162 ± 0.01 g/L

46889030

Vapor pressure 6.3 x 10-12 Pa @ 20°C, 2.1 x 10-11 Pa @ 25°C 46889130

Dissociation constant, pKa 10.88 ± 0.71 46889034

Octanol/water partition 

coefficient, KOW (20°C)

Deionized Water 589

pH 4 588

pH 7 721

pH 9 654

46889032

UV/visible absorption (max) pH <2 no absorption max >200 nm, at 290 ε = 

3941

pH 7 no absorption max >200 nm, at 290 ε = 4185

pH >10 absorption max at ~320 nm which may be

due to decomposition of DPX-E2Y45, at 290 ε =

6082

46889027