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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: December 9, 2013

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

Green Onion Subgroup 3-07b, and Peanut; for the Requests to Update the Crop 

Groups of Stone Fruit, Tree Nut, and Spices; to Shorten the Pre-Harvest Intervals 

for Papaya, Passionfruit, and Mayhaw; and Evaluation of Condition of 

Registration Data on Rice, Coffee, Strawberry, and Tropical Fruits.

PC Code: 090100 DP Barcodes: D410513, D412173, D412170, 

D412171, D412169

Decision Nos.: 476038; 477960; 477964; 477967; 

477972; 477962 ; 477952; 477965; 477970; 

477963; 477954; 477966; 477971; 417413

Registration Nos.: 352-728; 352-729; 352-730; 352-

820; 352-841; 352-838; 352-844

Petition Nos.: 3E8170; 3F8158 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical, Aggregate Case No.: NA

TXR No.: NA CAS No.: 500008-45-7

MRID No.: NA 40 CFR: 180.628

FROM: Kristin Rury, Risk Assessor

Steve Funk, Senior Chemist

Minerva Mercado, Toxicologist

Risk Assessment Branch III

Health Effects Division (7509P)

THROUGH: Christine Olinger, Branch Chief

Risk Assessment Branch III

Health Effects Division (7509P)

TO: Venus Eagle/Jennifer Urbanski, RM 01

Insecticide-Rodenticide Branch

Registration Division (RD; 7505P)

And

Barbara Madden/Laura Nollen, RM 05

Risk Integration Minor Use, and Emergency Response Branch 

Registration Division (RD; 7505P)
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1.0 Executive Summary........................................................................................................... 3

2.0 Regulatory Conclusions and Recommendations............................................................. 5

2.1 Data Deficiencies/Conditions of Registration .............................................................. 5

2.2 Tolerance Considerations.............................................................................................. 5

2.2.1 Enforcement Analytical Method ............................................................................... 5

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

2.2.3 Recommended Tolerances......................................................................................... 7

2.2.4 Revisions to Petitioned-For Tolerances.................................................................... 7

2.3 Label Recommendations................................................................................................ 8

3.0 Introduction........................................................................................................................ 8

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

3.2 Physical/Chemical Characteristics ............................................................................... 9

3.3 Pesticide Use Pattern...................................................................................................... 9

3.4 Anticipated Exposure Pathways................................................................................. 12

3.5 Consideration of Environmental Justice.................................................................... 12

4.0 Hazard Characterization and Dose-Response Assessment.......................................... 13

4.1 Summary of Toxicological Effects.............................................................................. 13

4.2 Safety factor for Infants and Children (FQPA Safety Factor) ................................ 14

4.2.1 Completeness of the Toxicology Database.............................................................. 14

4.2.2 Evidence of Neurotoxicity........................................................................................ 14

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 15

4.2.4 Residual Uncertainty in the Exposure Database ................................................... 15

4.3 Toxicity Endpoint and Point of Departure Selections.............................................. 15

5.0 Dietary Exposure and Risk Assessment......................................................................... 16

5.1 Residues of Concern Summary and Rationale.......................................................... 16

5.2 Food Residue Profile .................................................................................................... 17

5.3 Water Residue Profile.................................................................................................. 18

5.4 Dietary Risk Assessment.............................................................................................. 18

5.4.1 Description of Residue Data Used in Dietary Assessment.................................... 18

5.4.2 Acute Dietary Risk Assessment............................................................................... 19

5.4.3 Chronic Dietary Risk Assessment........................................................................... 19

5.4.4 Cancer Dietary Risk Assessment............................................................................. 19

5.4.5 Summary Table......................................................................................................... 19

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 19

6.1 Residential Handler Exposure .................................................................................... 19

6.2 Post-Application Exposure.......................................................................................... 20

6.3 Residential Bystander Post-Application Inhalation Exposure ................................ 20

6.4 Spray Drift.................................................................................................................... 20

7.0 Aggregate Exposure/Risk Characterization.................................................................. 20

8.0 Cumulative Exposure/Risk Characterization ............................................................... 21

9.0 Occupational Exposure/Risk Characterization ............................................................ 21

10.0 References......................................................................................................................... 21

Appendix A. Toxicology Profile................................................................................................ 23

A.1 Toxicology Data Requirements................................................................................... 23

A.2 Toxicity Profiles............................................................................................................ 24

Appendix B. Physical/Chemical Properties............................................................................. 30
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1.0 Executive Summary

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

that acts on the ryanodine receptor (RyR). It was developed and registered by E.I. du Pont de 

Nemours and Company (DuPont) to control lepidopteran pests and insects primarily via 

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

However, the relative absence of mammalian hazard following chlorantraniliprole exposure may

be due in part to chlorantranilprole’s selectivity for insect RyR over mammalian counterparts. 

There are five proposed chlorantraniliprole registration actions evaluated in this risk assessment:

1. D410513 - E.I. du Pont de Nemours and Company (DuPont) has requested a Section 3 

registration and tolerances of chlorantraniliprole on peanuts.

2. D412169 – The Interregional Research Project No. 4 (IR-4) of Rutgers University has 

requested crop group conversions for existing tolerances on the stone fruit and tree nut 

crop groups to correspond with the crop group commodities update in 2012. 

3. D412173 – The IR-4 has requested to shorten the existing pre-harvest intervals (PHIs) for 

papaya, passionfruit, and mayhaw. Additionally, IR-4 has requested to delete the existing 

separate mayhaw tolerance because mayhaw will be supported by the existing pome fruit

tolerance (crop group 11-10). 

4. D412170 –The IR-4 requested to add greenhouse use directions to the existing 

chlorantraniliprole labels for fruiting vegetables and cucurbits. The existing cucumber 

and tomato data will support the addition of greenhouse use directions on the labels for 

greenhouse tomato, pepper, and cucumber; there is no request for tolerances. 

5. D412717 – The IR-4 has requested chlorantraniliprole use and tolerances on green onion 

(crop subgroup 3-07B) and requested to raise the existing tolerance for spice subgroup 

19B based on data on green onion and dill. 

Concomitant with these petitions, condition of registration field trial data were submitted for 

rice, coffee, and strawberry; these data confirm the existing tolerances. Additionally, a study

submitted as confirmatory data for crayfish supports lowering the current crayfish tolerance. 

Condition of registration residue decline data on cherry, papaya, and lychee were also submitted 

to support existing tolerances for certain tropical fruits and to propose lowering the PHIs from 10 

days to 1 day, with a tolerance increase of 2 ppm to 4 ppm for papaya and passionfruit. The new 

data for dried onions combined with previous data for alfalfa hay translated to dried basil support 

retention of the 90 ppm tolerance for herb subgroup 19A. 

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 these requests 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% ai SC, Coragen®Insect Control (1.67 lb ai/gallon or 0.200 kg 

ai/l), EPA Reg. No. 352-729; a 35.0% ai water dispersible granular (WDG), Altacor® (35 lb 

ai/100 lb) EPA Reg. No. 352-730; and a 50% ai Flowable Concentrate (FC), Dermacor® X-100 
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Seed Treatment (FS, 5.210 lb ai/gal), EPA Reg No. 352-820). Chlorantraniliprole may be 

applied via drip irrigation, ground, handheld, seed treatment, and aerial application methods. 

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.

Exposure Profile 

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

to chlorantraniliprole during mixing, loading, application, and post-application activities. There 

is potential for short-term exposure from the registered residential uses on turf, golf courses 

landscape ornamentals, and interiorscapes. There is also exposure expected through food and 

drinking water from the proposed and registered uses of chlorantraniliprole.

Hazard Characterization

There is sufficient toxicology information for selecting doses and endpoints for 

chlorantraniliprole risk assessment. In short-term studies, the most consistent effects are those 

associated with non-adverse induction of liver enzymes and subsequent increase in liver weights. 

Increased microvesiculation of the adrenal cortex was observed in several rat studies; however

detailed histopathology and a special adrenal function study found no adverse adrenal effects in 

the rat. There was only one animal toxicity study (18-month carcinogenicity study in mice) in 

the database that produced adverse effects following chlorantraniliprole exposure.

Chlorantraniliprole is not considered developmentally toxic, genotoxic, neurotoxic, 

immunotoxic, or carcinogenic. A subchronic inhalation toxicity study is not required for 

chlorantraniliprole at this time. Chlorantraniliprole is classified as Acute Toxicity Category IV 

for acute oral, dermal, and inhalation toxicity; acute eye irritation; and primary skin irritation. 

Chlorantraniliprole is not a dermal sensitizer. Based on the available hazard and exposure data, 

the Food Quality Protection Act (FQPA) Safety Factor (SF) is reduced to 1x for all population 

subgroups and exposure scenarios. 

Dietary Risk Estimates (Food and water)

An acute dietary risk assessment was not performed because there was no acute hazard 

attributable to a single dose identified in the chlorantraniliprole toxicity database. 

The chronic dietary (food and drinking water) exposure assessment is considered conservative 

and assumed tolerance-level residues and that 100% of the proposed and registered crops were

treated with chlorantraniliprole (100%CT). Where processing data indicated a reduction (or no 

increase) in residue upon processing, the residue level of the raw agricultural commodity (RAC) 

was used without reduction. Where processing data indicated an increase in residue in the 

processed commodity, a tolerance was established and used, e.g., raisins from grapes. Where 

adequate processing data did not exist, default concentration factors were used if available. 

Estimated drinking water concentrations (EDWCs) from ground water from the Environmental 

Fate and Effects Division (EFED) were also included. The results of the chronic analysis 

indicate that the chronic dietary (food and drinking water) risk estimates utilized 2.3% of the 

chronic population adjusted dose (cPAD) for the general U.S. population and utilized 6.7% of 

the cPAD for children 1-2 years old, the most highly exposed population subgroup. Therefore, 

the chronic dietary risk is not of concern (i.e., <100% of the cPAD). 
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Aggregate Risk

Short- and intermediate-term aggregate risk assessments were not performed because there was 

no hazard identified over short- or intermediate-term durations. Therefore, the aggregate risk 

assessment for chlorantraniliprole only includes chronic exposures to residues in food and 

drinking water. The chronic dietary risk assessments for the U.S. population and all population 

subgroups are not of concern to HED (<100% cPAD).

Occupational Risk

Although there is potential for occupational handler and post-application exposure, the 

chlorantraniliprole toxicology database indicates there is no systemic hazard associated with 

short- and intermediate-term dermal and inhalation exposure, and therefore, no quantitative 

occupational exposure and risk assessment was conducted.

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).

2.0 Regulatory Conclusions and Recommendations

HED has examined the residue chemistry, toxicity, and exposure databases for 

chlorantraniliprole and concluded that, provided a revised Section F is submitted, there are no 

deficiencies that would preclude granting a Section 3 registration on peanuts and green onion 

subgroup 3-07B; adding the greenhouse use directions for fruiting vegetables and cucurbits; and 

granting the requested crop group conversions. A crayfish tolerance of 8 ppm was previously 

established based on a fish bioconcentration study and the estimated residues in water, sediment, 

and rice straw. The present crayfish study showed no residues (<0.01 ppm) at various sampling 

intervals from the use of chlorantraniliprole as a seed treatment on rice. This reflects the actual 

use pattern. Therefore, a tolerance of 0.01 ppm is more appropriate and a modified Section F is 

required.

The specific tolerance recommendations are discussed in Section 2.2.3. 

2.1 Data Deficiencies/Conditions of Registration

There are no data deficiencies associated with the proposed uses of chlorantraniliprole.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate enforcement method (liquid chromatography/tandem mass spectrometry

(LC/MS/MS), DuPont-11374) is available for the determination of chlorantraniliprole residues 

in/on plant commodities. The limit of quantitation (LOQ) is reported at 0.01 ppm for parent 
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chlorantraniliprole. The method for the determination of chlorantraniliprole and its metabolites 

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

version of DuPont-11374. These methods have been accepted by the Analytical Chemistry

Branch (ACB)/Biological and Economical Analysis Division (BEAD; C. Stafford, D340358, 

02/06/2008).

An adequate enforcement method (LC/MS/MS) is available for the determination of residues of 

chlorantraniliprole and its metabolites in/on animal commodities. Atmospheric pressure 

chemical ionization (APCI) MS/MS detection operated in the positive ion mode is used. The 

LOQ is reported at 0.010 ppm for the parent and each of the metabolites. The method has been 

accepted by ACB/BEAD (C. Stafford, D340358, 02/06/2008).

2.2.2 International Harmonization

Residue definitions are harmonized among the US, Canada, and Codex, with the common 

definition chlorantraniliprole. 

The existing US tolerance for the tree nut group is 0.04 ppm, whereas the tolerance in both 

Canada and Codex is 0.02 mg/kg. The US tolerance is based upon the evaluation of field trial 

data for pecans and almonds with the use of the North American Free Trade Agreement 

(NAFTA) statistical spreadsheet (N. Tsaur, D357727, 03/03/2009). The data were reevaluated 

using the Organization for Economic Cooperation and Development (OECD) tolerance 

calculation procedures. The new tolerance estimate is 0.02 ppm. Therefore, the tolerance for 

tree nuts, including pistachio, is lowered to 0.02 ppm, and harmonization with Canada and 

Codex is achieved.

The existing US tolerance for the pome fruit group is 1.2 ppm. The Codex maximum residue 

limit (MRL) for pome fruit is 0.4 ppm, and the Canada MRL for various pome fruits (apple, 

pear, mayhaw, and quince) is 0.4 ppm. The original US tolerance for pome fruits was 0.3 ppm, 

but it was adjusted upwards to 1.2 ppm to accommodate the use of adjuvants and a shortened 

PHI (D. Rate, D361791, 01/08/2010). Therefore, the 1.2 ppm value cannot be lowered to 

harmonize with Codex and/or Canada.

The existing US tolerance for the stone fruit group (except cherry, chickasaw plum, and damson 

plum) is 4.0 ppm. The Codex MRL for stone fruits is 1 mg/kg and the Canada MRL for various 

stone fruits (apricot, nectarine, peach, plum, plumcots, and cherries) is 2.5 mg/kg. The original 

US tolerance for stone fruits was 1.0 ppm, but it was adjusted upwards to 4.0 ppm to 

accommodate the use of adjuvants and a shortened PHI (D. Rate, D361791, 01/08/2010). 

Therefore, the 4.0 ppm value cannot be lowered to harmonize with Codex and/or Canada.

Codex has not established MRLs for passionfruit, papaya, peanuts, green onions, herbs, or 

spices. Therefore, there is no harmonization issue with Codex. Canada does not have MRLs for 

these same commodities, with the exception of green onions and peanuts. Canada and the US 

are conducting a joint review for green onions and peanuts and will work to harmonize the 

MRLs.
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2.2.3 Recommended Tolerances

The current tolerance definition is found at 40CFR§180.628. Compliance with the tolerance is 

based on measuring only chlorantraniliprole for both plant and animal commodities.

Table 2.2.3. Tolerance Summary for Chlorantraniliprole

Commodity Established 

Tolerance 

(ppm)

Proposed 

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Comments 

(correct commodity definition)

Papaya 2.0 4.0 4.0

Passionfruit 2.0 4.0 4.0

Peanut, nutmeat - 0.06 0.06

Peanut, hay 0.20 

(exp 04/10/14)

90 90 Translation from alfalfa hay

Onion, green, subgroup 

3-07B

- 3.0 3.0

Spice subgroup 19B 14140 90

Nut, tree, group 14-12 0.04 - 0.02 Crop group conversion.

International harmonization.

Nut, tree, group 14 0.04 - Remove Replaced by crop group 14-12

Pistachio 0.04 - Remove Replaced by crop group 14-12

Fruit, pome, group 11-

10

1.2 - 1.2 Crop group conversion

Fruit, pome, group 11, 

except mayhaw

1.2 - Remove Replaced by crop group 11-10

Mayhaw 0.6 - Remove Replaced by crop group 11-10

Fruit, stone group 12-

12, except cherry, 

Chickasaw plum, and 

damson plum

4.0 - 4.0 Crop group conversion

Fruit, stone group 12, 

except cherry, 

Chickasaw plum, and 

damson plum

4.0 - Remove Replaced by crop group 12-12

Crayfish 8.0 - 0.01

Onion, green 0.20 (exp 

04/10/14)

- Remove Replaced by Onion, green, 

subgroup 3-07B

Onion, welsh 0.20 (exp 

04/10/14)

- Remove Replaced by Onion, green, 

subgroup 3-07B

Shallots, fresh leaves 0.20 (exp 

04/10/14)

- Remove Replaced by Onion, green, 

subgroup 3-07B

Leek 0.20 (exp 

04/10/14)

- Remove Replaced by Onion, green, 

subgroup 3-07B

1 A tolerance of 14 ppm was recommended (D361791, D. Rate, 01/08/2010), but is not listed in 40CFR§180.628. 

This was based on the translation of alfalfa seed data, with adjustments for adjuvant use (2x) and application rate 

(2x).

2.2.4 Revisions to Petitioned-For Tolerances

The petitioned tolerances are the same as the recommended tolerances, except for spice subgroup 

19B, crayfish, and increased/decreased tolerances for the crop group conversions due to 

international harmonization. 
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Residue data on dill seed was presented in support of a spice subgroup 19B tolerance. HED had 

previously recommended for a spice subgroup 19B tolerance of 14 ppm. The petitioner 

requested 40 ppm, but evaluation of the dill seed data indicates that 90 ppm is appropriate. 

Condition of registration data on field trial residue decline for cherry, papaya, and leechee 

support existing tolerances for certain tropical fruits and allow for lowering of the PHIs from 10 

days to 1 day, with an increase in tolerance from 2 ppm to 4 ppm, for papaya and passionfruit.

A crayfish tolerance of 8 ppm was previously established based on a fish bioconcentration study

and the estimated residues in water, sediment, and rice straw. The present crayfish study showed 

no residues (<0.01 ppm) at various sampling intervals from the use of chlorantraniliprole as a 

seed treatment on rice. This reflects the actual use pattern. A tolerance of 0.01 ppm is 

appropriate. A modified Section F is required.

A crop group conversion for tree nut group 14 to tree nut group 14-2 was requested. This is 

acceptable, but the tolerance will be changed from 0.04 ppm to 0.02 ppm to harmonize with 

Canada and Codex.

The registrant must submit a revised Section F requesting tolerances of 90 ppm and 0.01 ppm for 

the spice subgroup 19B and crayfish, respectively.

2.3 Label Recommendations

There are no label recommendations for this petition. 

3.0 Introduction

The ai, chlorantraniliprole, is an anthranilic diamide insecticide that belongs to a class of 

compounds that acts on the RyR. It was developed and registered by E.I. du Pont de Nemours 

and Company (DuPont) to control lepidopteran pests and insects primarily via interruption of 

normal muscle contraction pathways, leading to paralysis and eventual death.
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3.1 Chemical Identity

Table 3.1. 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-bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-

pyridinyl)-1H-pyrazole-5-carboxamide

CAS registry number 500008-45-7

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

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

DuPontTM Prevathon® Insect Control (0.43 lb ai/gal; EPA Reg No. 352-844)

DuPontTM Dermacor® X-100 Seed Treatment (FS, 5.210 lb ai/gal; EPA Reg No. 352-820)

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 at 20o C) 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. 

3.3 Pesticide Use Pattern

For the proposed Section 3 registrations addressed herein there are four EPs, two SCs, one FC,

and one WDG. The proposed changes will also apply to the technical product label (EPA Reg. 

No. 352-728). Proposed labels have been provided for a 5% ai SC, Prevathon® Insect Control 

(0.43 lb ai per gallon, or 0.053 kg ai/l) EPA Reg. No. 352-844; a 18.4% ai SC, Coragen®Insect 

Control (1.67 lb ai/gallon or 0.200 kg ai/l) EPA Reg. No. 352-729; a 35% ai WDG, Altacor® 

(35 lb ai/100 lb) EPA Reg. No. 352-730; and a 50% ai Flowable Concentrate (FC) Dermacor® 

X-100 Seed Treatment (FS, 5.210 lb ai/gal), EPA Reg No. 352-820). Changes to the Altacor® 

label involve only crop conversions, and changes to Dermacor® only involves the conditional 

data related to seed treatment use on rice. The WDG formulation is not proposed for use on 

cereal grains. The summary of the relevant proposed uses is presented in Table 3.3. 

N

N N

NH

O

Cl

Br

HN

O

Cl
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Table 3.3. Summary of Proposed/Relevant Existing Chlorantraniliprole Use Directions 

Applic. 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Proposed Use: Peanut

Foliar

(ground; 

aerial)

18.4% SC

1.67 lb 

ai/gal

Coragen

[352-729]

0.045 –

0.065

4

0.2 (from all 

chlorantraniliprole sources)1

Minimum interval 

between treatments is 3 

days. Foliar

(ground; 

aerial)

5% SC

0.43 lb 

ai/gal

Prevathon

[352-844]

0.047-

0.067

Proposed Use: Bulb Vegetables (including green onion subgroup)

Foliar

(ground; 

aerial)

18.4% SC

1.67 lb 

ai/gal

Coragen

[352-729]

0.045 –

0.065 4

0.2 per crop

0.6 per year

(from all 

chloroantranili

-prole sources)

1

Minimum interval 

between treatments is 4 

days.

Proposed Use: Greenhouse Cucumbers, Greenhouse Peppers, Greenhouse Tomatoes

Foliar

18.4% SC

1.67 lb 

ai/gal

Coragen

[352-729]

0.031 

tomato

0.045 

pepper, 

cucumber

3 (per 

crop 

cycle)

0.134 per crop 

cycle 1

Minimum interval 

between treatments is 7 

days.

Mix 1.6 fl oz per 100 gal 

spray volume (0.0209 lb 

ai/100 gal)

Maximum application is 

150 gal spray solution 

per acre for tomato and 

214 gal spray solution 

per acre for cucumber 

and pepper.

Updated Use: Tropical Fruits (Papaya, Passionfruit, Lychee)

1, 2

Foliar

35.0% 

WDG

Altacor

[352-730]

0.066-

0.099 3

0.2

(from all 

chloroantraniliprole sources)

1

2

10 

(acerola, 

jaboticaba, 

and 

lychee)

Minimum interval 

between treatments is 7 

days.

Do not apply dilute 

solutions of more than 

200 gal water per acre.

Do not apply less than 

30 gal water per acre.

Updated Use: Low growing berry (subgroup 13-07G)

1

Foliar

35.0% 

WDG

Altacor

[352-730]

0.066-

0.099 3

0.2

(from all 

chloroantranilprole sources)

1

Minimum interval 

between treatments is 7 

days.

Do not apply dilute 
Page 11 of 33

Table 3.3. Summary of Proposed/Relevant Existing Chlorantraniliprole Use Directions 

Applic. 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

solutions of more than 

200 gal water per acre.

Do not apply less than 

30 gal water per acre.

Do not apply to 

strawberry or cranberry.

Foliar

18.4% SC

1.67 lb 

ai/gal

Coragen

[352-729]

0.045-

0.065 4

0.2 per crop 

(from all 

chloroantranili

-prole sources)

0.4 per year 

(from all 

chloroantranili

-prole sources)

1

Minimum interval 

between treatments is 7 

days.

Updated Use: Rice1

Seed treatment

50% FS

5.21 lb 

ai/gal

Dermacor 

[352-820]

0.084 1 N/S N/S

Do not use 

DERMACOR® X-100 

treated rice field

for the aquaculture of 

edible fish or Crustacea

(including crawfish) 

during the rice 

production cycle

(planting through 

harvest).

Updated Use: Coffee1

Foliar

35.0% 

WDG

Altacor

[352-730]

0.066-

0.099 3

0.2 (from all 

chloroantranili

-prole sources)

7

Minimum interval 

between treatments is 

14days.

Do not apply dilute 

solutions of more than 

200 gal water per acre.

Do not apply less than 

30 gal water per acre.

Updated Use: Herb Subgroup 19A1

Foliar

18.4% SC

1.67 lb 

ai/gal

Coragen

[352-729]

0.045 –

0.065 4

0.2 per crop 

(from all 

chloroantranili

-prole sources)

0.8 per year 

(from all 

chloroantranili

-prole sources)

1

Minimum interval 

between treatments is 3 

days.

Updated Use: Spices Subgroup 19B1

Foliar 18.4% SC 0.045 – 4 0.2 per crop 1 Minimum interval 
Page 12 of 33

Table 3.3. Summary of Proposed/Relevant Existing Chlorantraniliprole Use Directions 

Applic. 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

1.67 lb 

ai/gal

Coragen

[352-729]

0.065 (from all 

chloroantraniliprole sources)

0.8 per year 

(from all 

chloroantraniliprole sources)

between treatments is 3 

days.

1Uses associated with condition of registration data evaluated in association with the Section 3 and crop group

conversion requests.

2The PHI for papaya and passionfruit has been reduced from 10 days to 1 day.

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 children 1-2 years, youths, and adults entering or playing on treated 
Page 13 of 33

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, D399493, 05/17/2012). The 

Hazard and Science Policy council waived the required subchronic inhalation toxicity study

(TXR#0056851). 

4.1 Summary of Toxicological Effects

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

that acts on the 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 mammalian studies, the most consistent 

effects are increased liver weights and mild induction of liver enzymes. In oral and dermal 

toxicity studies in rats, increased incidence of adrenal cortex microvesiculation was observed 

(usually in males only). However, an additional special study to assess the capacity of the 

adrenal gland to produce corticosterone found no effects in male rats (with or without 

microvesiculation) following ACTH stimulation. Therefore, adrenal cortex microvesiculation 

observed in rat studies was not considered adverse. Chlorantraniliprole does not exhibit pre- or 

postnatal toxicity as there were no maternal or fetal effects in studies conducted in rats and 

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

developmentally toxic. Chlorantraniliprole is classified as “Not likely to be Carcinogenic to 

Humans”. No treatment-related tumors were reported in the submitted chronic and oncogenicity

studies in rats and mice (18-month carcinogenicity study) or in the subchronic studies in mice, 

dogs and rats.

Based on the results of short-term and acute dermal studies, chlorantraniliprole has relatively low 

dermal toxicity. Chlorantraniliprole is not acutely toxic via the oral, or inhalation routes of 

exposure. The LD50 for both 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 after single dose ranged from 41 hours in males to 79 hours in female rats. 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 
Page 14 of 33

rats having a longer elimination half-life. Rapid excretion was observed via bile (49-53%) 

within 48 hours and 88-97% total excretion was observed within 7 days after single or multiple 

doses. Fecal excretion was the primary route of elimination followed by excretion in 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, D381810, 02/28/2011).

Based on studies conducted in rats, dermal penetration of chlorantraniliprole formulations is 

approximately ≤ 1.09% for undiluted concentrates and 2.10-2.79% for 0.75 g/L aqueous 

dilutions of the concentrates.

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

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 post-natal risks to infants and 

children. Acceptable developmental toxicity, 2-generation reproduction toxicity, acute 

neurotoxicity, subchronic neurotoxicity, and immunotoxicity studies have been submitted and 

reviewed. The Hazard and Science Policy council waived the required subchronic inhalation 

toxicity study based on chlorantraniliprole’s physical chemical properties, including low vapor 

pressure; low acute inhalation toxicity (Toxicity Category IV); and the use of a conservative, 

chronic oral POD that results in screening-level MOEs >12,000 (TXR#0056851). 

4.2.2 Evidence of Neurotoxicity

There is no indication that chlorantraniliprole is a neurotoxic chemical and there is no need for a 

developmental neurotoxicity study or additional uncertainty factors (UFs) to account for 

neurotoxicity. The no observed adverse effect level (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. 
Page 15 of 33

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

There is no evidence that chlorantraniliprole results in increased susceptibility in in utero rats or 

rabbits in the prenatal developmental studies or in young rats in the 2-generation reproduction 

study. 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 identified in the exposure databases. The chronic dietary 

assessment utilized tolerance-level residues for all crops and assumed 100% CT of the proposed 

and registered crops were treated with chlorantraniliprole. Where processing data indicated a 

reduction (or no increase) in residue upon processing, the residue level of the RAC was used 

without reduction. Where processing data indicated an increase in residue in the processed 

commodity, a tolerance was established and used, e.g., raisins from grapes. Where adequate 

processing data did not exist, default concentration factors were used if available. EPA made 

conservative (protective) assumptions in the ground and surface water modeling used to assess 

exposure to chlorantraniliprole in drinking water. Moreover, there is a lack of toxicity via the 

dermal route, as well as the lack of toxicity over the acute-, short- and intermediate-term via the 

oral route. These assessments will not underestimate the exposure and risks posed by

chlorantraniliprole.

4.3 Toxicity Endpoint and Point of Departure Selections

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, 03/07/2008). 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.
Page 16 of 33

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-

/IntermediateTermN/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. RfD = Reference Dose. PAD = Population Adjusted Dose. 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

The residues of concern for tolerance enforcement and risk assessment in plants, livestock, and 

water are summarized below in Table 5.1. See Appendix B for names and structures. HED also 

recalculated the dietary burdens for beef and dairy cattle (S. Funk, D416101, 11/12/2013). The

resulting residue estimates were below the established tolerances for ruminants; therefore, 

tolerance-levels were used in the dietary risk assessment for cattle.
Page 17 of 33

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, INHXH44, IN-K9T00. 

Chlorantraniliprole

Poultry Chlorantraniliprole

Eggs: Chlorantraniliprole, 

IN-H2H20, IN-K7H29, INGAZ70, IN-F9N04

Chlorantraniliprole

Drinking Water Chlorantraniliprole N/A

5.2 Food Residue Profile

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

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

tomato, greenhouse pepper, greenhouse cucumber, rice, coffee, and strawberry trials reflect the 

proposed label maximum application rate and other conditions and demonstrate that the existing 

tolerances are adequate. The crayfish trials show that the existing tolerance may be reduced. 

Residues in passionfruit, papaya, and mayhaw will increase with decreased PHIs, but the existing 

respective group tolerances are protective. Trials for proposed uses on green onions and peanuts 

are adequate both in number of trials and geographic distribution and are conducted under 

conditions reflective of the proposed labels. The new feed item, peanut hay, does not increase 

the calculated dietary exposure of ruminants and therefore does not change the existing 

tolerances for ruminant commodities. The dill seed trials provide a tolerance estimate of 90 ppm 

for the spices subgroup 19B. This is an increase from the previous recommendation of 14 ppm, 

and the registrant request for 40 ppm. The new data for dried onions combined with previous 

data for alfalfa hay translated to dried basil support retention of the 90 ppm for herb subgroup 

19A. The field trial studies are supported by adequate storage stability data.

The existing cotton seed processing study is translated to peanut, and no concentration of residue 

occurs in the oil or meal. 

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. 

Several inadvertent tolerances will now be replaced with primary crop commodity tolerances. 

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

very few inadvertent tolerances needed.
Page 18 of 33

5.3 Water Residue Profile

The EDWC for groundwater from the assessment evaluating the proposed uses is greater than the 

surface and groundwater estimates from the previous assessment. Thus, the groundwater 

concentration of 207 ppb (one-in-ten-year annual mean) based on the Wisconsin corn scenario 

was used in the dietary exposure assessment (C. Koper, D414839, 09/23/2013). 

 

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

Chronic (non-cancer, 1 in 10 year annual average) 39.87 207

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 PRZM-GW model

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

HED used tolerance-level residues for the proposed and registered crops and 100% crop treated 

was assumed for all commodities included in this assessment; therefore, this assessment is 

considered conservative. Where processing data indicated a reduction (or no increase) in residue 

upon processing, the residue level of the RAC was used without reduction, for example mint oil 

from spearmint. Where processing data indicated an increase in residue in the processed 

commodity, a tolerance was established and used, e.g., raisins from grapes. Where adequate 

processing data did not exist, default concentration factors were used if available. Default 

concentration factors were used for the following: dried apple, apple juice, dried apricot, dried 

banana, dried beef meat, cherry juice, field corn syrup, cranberry juice, grape juice, grapefruit

juice, lemon juice, lime juice, dried lychee, dried (dehydrated) bulb onion, orange juice, dried 

peach, dried pear, peanut butter, dried pineapple, pineapple juice, dried plantain, dried plum 

prune, plum juice, dried potato (flakes, granules), potato flour, tangerine juice, tomato paste, 

tomato puree, dried tomato, and tomato juice. 

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

Koper, D414839, 09/23/2013) and incorporated directly into this dietary assessment. Water 

residues were incorporated in the Dietary Exposure Evaluation Model software with the Food 

Commodity Intake Database (DEEM-FCIDTM) into the food categories “water, direct, all 

sources” and “water, indirect, all sources.” The estimated groundwater concentration of 207 ppb

was used for this assessment. 
Page 19 of 33

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 results of the chronic analysis indicate that the chronic dietary (food and drinking water) risk 

estimates utilized 2.3% of the cPAD for the general U.S. population and utilized 6.7% of the 

cPAD for children 1-2 years old, the most highly exposed population subgroup. Therefore, the 

chronic dietary risk is not of concern (i.e., <100% of the cPAD). A summary of these results is 

shown in Table 5.4.5.

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 0.036207 2.3

All Infants (<1 year old) 0.060811 3.8

Children 1-2 years old* 0.105269 6.7

Children 3-5 years old 0.081499 5.2

Children 6-12 years old 0.046110 2.9

Youth 13-19 years old 0.027234 1.7

Adults 20-49 years old 0.030559 1.9

Adults 50+ years old 0.030166 1.9

Females 13-49 years old 0.029398 1.9

*The subpopulation with the highest risk estimate.

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 quantitatively assessed due to the lack of toxicity via inhalation and 

dermal routes. No risk is expected from residential handler exposure to chlorantraniliprole.
Page 20 of 33

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 Residential Bystander Post-Application 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 x 10-12 Pa @ 20 ̊C), and 

the low proposed use rate (0.099 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, 20101. 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.

6.4 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for chlorantraniliprole. The Agency has been working with the Spray Drift 

Task Force (a task force composed of various registrants which was developed as a result of a 

Data Call-In issued by EPA), 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).2 The Agency is also taking means to 

qualitatively and qualitatively address spray drift as a potential source of exposure in risk 

assessments for pesticides through existing programs such as Ag Drift and chemical specific 

properties of pesticides. The potential for spray drift will be quantitatively evaluated for each 

pesticide during the Registration Review process which ensures that all uses for that pesticide 

will be considered concurrently. 

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 

 

1 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Page 21 of 33

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

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 short- or intermediate-term durations.

Therefore, the aggregate risk assessment for chlorantraniliprole only includes chronic exposures 

to residues in food and drinking water. The chronic dietary risk assessments for the U.S. 

population and all population subgroups are not of concern to HED (<100% cPAD). The results 

of the chronic analysis indicate that the chronic dietary (food and water) risk estimates utilized 

2.3% of the cPAD for the general U.S. population and utilized 6.7% of the cPAD for children 1-

2 years old, the most highly exposed population subgroup. 

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 

post-application 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 quantitative occupational 

exposure and risk assessment was conducted.

10.0 References

Kristin Rury, D416093, 12/03/2013. Chlorantraniliprole: Chronic Dietary (Food and Drinking 

Water) Exposure and Risk Assessment for the Section (3) Registration Actions on Green Onion 

Subgroup 3-07b, and Peanut; and for the Requests to Update the Crop Groups of Stone Fruit, 

Tree Nut, and Spices; and to Shorten the Pre-Harvest Intervals for Papaya, Passionfruit, and 

Mayhaw. 
Page 22 of 33

Christopher Koper, D414839, 09/23/2013. Tier II Drinking Water Assessment to Establish 

Tolerances of Chlorantraniliprole on Various Crops with Multiple Seasons. 

Steve Funk, D416101, 11/12/2013. Chlorantraniliprole. Petition for the Establishment of 

Permanent Tolerances and Registration for Use on Peanuts and on Green Onion, Addition of Use 

on Greenhouse Tomato and Greenhouse Pepper and Greenhouse Cucumber, Crop Group 

Conversions for Stone Fruit and Tree Nuts, and Label Amendment to Shorten the PHI for 

Passionfruit, Papaya, and Mayhaw. Condition of Registration Data for Rice, Crayfish, Coffee, 

Strawberry, and Livestock Analytical Methods. Summary of Analytical Chemistry and Residue 

Data.
Page 23 of 33

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

no

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

* Based on a weight of evidence approach a subchronic inhalation toxicity study is not required for the current uses 

(TXR#0056851).

** Submittal of 870.4300 fulfills the requirement for 870.4100a and 870.4200a.
Page 24 of 33

A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile of Chlorantraniliprole

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

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3050 28–Day oral toxicity

(rat)

46979941, 46979942 

(2006)

Acceptable–Nonguideline

0, 300, 1500, 8000 ppm

(M: 0, 20.7, 106, 584 

mg/kg/d; F: 24, 128, 675 

mg/kg/d)

NOAEL = 584/675 (M/F) mg/kg/d

LOAEL not established. F had dose-dependent 

increase in liver weight and hepatocellular 

hypertrophy without corresponding 

histopathological evidence of adverse liver 

effects.

870.3050 28–Day oral toxicity

(mouse)

46979303 (2003)

Acceptable–Nonguideline

0, 300, 1000, 3000, 7000 

ppm (M: 0, 52, 182, 538, 

and 1443 mg/kg/d; F: 0,

64, 206, 658, and 1524 

mg/kg/d)

NOAEL = 1443/1524 (M/F) mg/kg/d

LOAEL not established. F had dose-dependent 

increase in liver weight; M and F had dosedependent increase in CYP content and 

decreased hepatic β-oxidation at HDT; these 

effects occurred without corresponding 

histopathological evidence of adverse liver 

effects.

870.3100 90-Day oral toxicity 

(rat)

46889010 (2005) 

Acceptable–Guideline 

0, 600, 2000, 6000, or 

20,000 ppm (M: 0, 36.9, 

120, 359, 1188 mg/kg/d; 

F: 0, 47, 157, 460, 1526 

mg/kg/d) 

NOAEL = 1188/1526 (M/F) mg/kg/d

LOAEL not established. F had slight increase 

in liver weight at HDT and dose-dependent 

decreased bilirubin without corresponding 

histopathological evidence of adverse liver 

effects.
Page 25 of 33

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

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral toxicity 

(mouse)

46889013 (2006)

Acceptable–Guideline 

0, 200, 700, 2000, or 7000 

ppm (M: 0, 32.6, 115, 

345, 1135 mg/kg/d; F: 0, 

40.7, 158, 422, 1529 

mg/kg/d)

NOAEL = 1135/1529 (M/F) mg/kg/d

LOAEL not established. M and F had slight 

increase in liver weight at HDT but no 

corresponding histopathological evidence of 

adverse liver effects. Hyperactivity/ 

hyperreactivity seen in 1529 mg/kg/d F near 

end of study and convulsions in one male were 

not reproducible in 18-month mouse study 

with FOB (MRID 46979720).

870.3150 90-Day oral toxicity 

(dog)

46889012 (2004)

Acceptable–Guideline 

0, 1000, 4000, 10,000, 

and 40,000 ppm (M: 0, 

32.2, 119, 303, 1163 

mg/kg/d; F: 0, 36.5, 133, 

318, 1220 mg/kg/d)

NOAEL = 1163/1220 (M/F) mg/kg/d

LOAEL not established. M had slight increase 

in liver weight at HDT but no corresponding 

histopathological evidence of adverse liver 

effects.

870.3200 21/28-Day dermal 

toxicity (rat)

46889128 (2006)

Acceptable–Guideline 

0, 100, 300, 1000 mg/kg/d

Systemic NOAEL = 1000 mg/kg/d

LOAEL not established. Increased incidence 

of adrenal cortex microvesiculation in males 

was not associated with changes in adrenal 

function (MRID 48889214) and is not 

considered adverse.

Dermal irritation NOAEL= 1000 mg/kg/d

LOAEL not established. 

870.3700a Prenatal 

developmental in rat

46889108 (2004)

Acceptable–Guideline 

0, 20, 100, 300, 1000 

mg/kg/d

Maternal NOAEL = 1000 mg/kg/d

LOAEL not established due to the absence of 

maternal effects at any dose.

Developmental NOAEL = 1000 mg/kg/d

LOAEL not established due to the absence of

developmental effects at any dose.

870.3700b Prenatal 

developmental in 

rabbit

46889109 (2005)

Acceptable–Guideline 

0, 20, 100, 300, 1000 

mg/kg/d

Maternal NOAEL = 1000 mg/kg/d

LOAEL not established due to the absence of 

maternal effects at any dose.

Developmental NOAEL = 1000 mg/kg/d

LOAEL not established due to the absence of

developmental effects at any dose.
Page 26 of 33

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

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3800 Reproduction and 

fertility effects –

2 generation (rat)

46889107, 46979722

(2006)

Acceptable–Guideline 

0, 200, 1000, 4000, or 

20,000 ppm (M: 0, 12.0, 

60.4, 238, 1199 mg/kg/d; 

F: 0, 15.5, 77.8, 319, 1594

mg/kg/d)

Parental/Systemic NOAEL = 1199/1594 

(M/F) mg/kg/d

LOAEL not established. Increase in adrenal 

weights and microvesiculation incidence 

(M/F) was not associated with changes in 

adrenal function (MRID 48889214) and is not 

considered adverse. Increase in liver weight 

(F) was not associated with adverse effects 

(MRID 46889010). 

Reproductive NOAEL = 1000 mg/kg/day

LOAEL not established due to the absence of 

reproductive effects at any dose.

Offspring NOAEL = 1199/1594 (M/F)

mg/kg/day

LOAEL not established due to absence of 

adverse effects in pups during lactation.

870.4100a Chronic toxicity

(rodents)

Combined chronic / carcinogenicity study available (see below)

870.4100b Chronic toxicity 

(dog)

46979718 (2006)

Acceptable–Guideline 

0, 1000, 4000, 10000, or 

40000 ppm (M: 0, 32, 

112, 317, 1164 mg/kg/d; 

F: 0, 34, 113, 278, 1233 

mg/kg/d)

NOAEL = 1164/1233 (M/F) mg/kg/day

LOAEL not established. M and F had slight 

increase in liver weight at HDT but no 

corresponding histopathological evidence of 

adverse liver effects.

870.4300a Chronic / 

Carcinogenicity

(rat)

46979719 (2006)

Acceptable–Guideline 

0, 200, 1000, 4000, 20000 

ppm (M: 0, 7.71, 39.0, 

156, 805 mg/kg/d; F: 0, 

10.9, 51.0, 212, 1076 

mg/kg/d)

NOAEL = 805/1076 (M/F) mg/kg/d

LOAEL not established. Increase incidence of

adrenal microvesiculation (M) was not 

associated with changes in adrenal function 

(MRID 48889214) and is not considered 

adverse. Increase in relative liver weight (F) 

without corresponding histopathological 

evidence of adverse liver effects. 

No evidence of carcinogenicity

870.4200 Carcinogenicity

(mouse)

46979720 (2006)

Acceptable–Guideline 

0, 20, 70, 200, 1200, 7000 

ppm (M: 0, 2.60, 9.20, 

26.1, 158, 935 mg/kg/d; 

F: 0, 3.34, 11.6, 32.9, 196, 

1155 mg/kg/d)

NOAEL = 158/1155 (M/F) mg/kg/d

LOAEL = 935 (M) mg/kg/d based on mild 

eosinophilic foci in 5/70. A LOAEL in F was 

not established. M and F (≥ 158/196 mg/kg/d) 

had increase in absolute and relative liver 

weight and minimal-mild hepatocellular 

hypertrophy.

No evidence of carcinogenicity
Page 27 of 33

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

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.5100 Bacterial Reverse 

Mutation Test 

46889103 (2004)

Acceptable–Guideline 

Initial assay: 8 concs. (2.5 

to 5000 μg/plate)

Confirmatory assay: 5

concs. (50 to 5000 μg 

/plate)

Negative with and without metabolic 

activation (S9) in Salmonella strains TA98, 

TA100, TA 1535 and TA 1537, and in E. Coli

WP2 uvrA strain.

870.5100 Bacterial Reverse 

Mutation Test 

46979921 (2006)

Acceptable–Guideline 

Initial assay: 8 concs.

(33.3 to 5000 μg/plate)

Confirmatory assay: 5

concs. (333 to 5000 μg 

/plate)

Negative with and without metabolic 

activation (S9) in Salmonella strains TA98, 

TA100, TA 1535 and TA 1537, and in E. Coli

WP2 uvrA strain.

870.5300 In vitro Chinese 

Hamster Ovarian Cell 

Gene Mutations at 

HGPRT Locus Test

46889106 (2004)

Acceptable–Guideline 

0, 15.6, 31.3, 62.5, 125,

250 g/mL

Negative with and without metabolic 

activation (S9).

870.5375 In vitro Human 

Lymphocyte 

Chromosome 

Aberration Test

46979922 (2006)

Acceptable–Guideline 

0, 50, 100, 500 μg/mL (no 

S9); 1, 10, 25 μg/mL (w/ 

S9)

Negative with and without metabolic 

activation (S9).

870. 5375 In vitro Human 

Lymphocytes

Chromosome 

Aberration Test 

46889105 (2004)

Acceptable–Guideline 

0, 125, 250, 500 μg/mL 

Negative with and without metabolic 

activation (S9).

870. 5375 In vitro Human 

Lymphocytes

Chromosome 

Aberration Test 

46979922 (2006)

Acceptable–Guideline 

0, 1, 10, 25, 50, 100, 500, 

1000, 2000, 4831.5

μg/mL 

Negative with and without metabolic 

activation (S9).

870.5395 Mouse Erythrocyte 

Micronucleus Assay

46889104 (2006)

Acceptable–Guideline 

0, 500, 1000, or 2000 

mg/kg/d

Negative in the bone marrow of M and F

Crl:CD-1

®

(ICR)BR mice.

870.6200a Acute neurotoxicity 

screening battery (rat)

46979312 (2004)

Acceptable–Guideline 

0, 200, 700, 2000 mg/kg/d

NOAEL = 2000 mg/kg/day

LOAEL not established due to absence of 

adverse systemic or neurological effects.
Page 28 of 33

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

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.6200b Subchronic 

neurotoxicity 

screening battery (rat)

46979721 (2006)

Acceptable–Guideline 

0, 200, 1000, 4000, 

20,000 ppm (M: 0, 12.7, 

64.2, 255, and 1313 

mg/kg/d; F: 0, 15.1, 77.3, 

304, 1586 mg/kg/d)

NOAEL = 1313/1586 (M/F) mg/kg/d 

LOAEL not established due to absence of 

adverse systemic or neurological effects.

870.7485 Metabolism and 

pharmacokinetics 

(rat)

46979330 (2006)

Acceptable–Guideline 

10 or 200 mg/kg single 

dose

Readily absorbed after low (10 mg/kg bw) or

high (200 mg/kg bw) single oral gavage. 

Plasma levels peak 5-12 hours after dosing.

Extensive tissue distribution and low

tissue:plasma ratios (<1) show low potential 

for accumulation. Tissue levels slightly greater 

in F than M. Distribution 7 days after low

dose: 24-29% urine, 62-64% feces, 0.8-3.3% 

tissues; after high dose, 3.8-5.2% urine, 91-

92% feces, 0.2-0.5% tissues. Urinary 

excretion slightly greater in M than F. 

Extensive metabolism characterized by 

methylphenyl and N-methyl hydroxylation, 

followed by N-demethylation, nitrogen-tocarbon cyclisation, alcohols oxidation to 

carboxylic acids, amide bridge cleavage, 

amine hydrolysis, and O-glucuronidation.

870.7485 Metabolism and 

pharmacokinetics 

(rat)

46979331 (2006)

Acceptable–Guideline 

10 mg/kg/d for 4, 8, 11, or 

14 days

Tmax 14 days administration in male rats; 

female rats were near steady state. After 

cessation of dosing, readily eliminated from 

the plasma and tissues. Tissue distribution at 

1 and 7 days similar to that found after single 

dose and confirmed minimal accumulation 

potential. Feces was the predominate route of 

elimination. Extensive metabolism consistent 

with that observed for the single dose study.

870.7800 Immunotoxicity (rat) 46979343 (2006)

0, 1000, 5000, or 20,000 

ppm (M: 0, 74, 363, 1494 

mg/kg/d; F: 0, 82, 397, 

1601 mg/kg/d)

NOAEL = 1494/1601 (M/F) mg/kg/d

LOAEL not established due to absence of 

adverse systemic or immune effects.

870.7800 Immunotoxicity 

(mice)

47231202 (2007)

0, 300, 1700, or 7000 ppm

(M: 0, 48, 264, 1144

mg/kg/d; F: 0, 64, 362, 

1566 mg/kg/d)

NOAEL = 1494/1601 (M/F) mg/kg/d

LOAEL not established due to absence of 

adverse systemic or immune effects.
Page 29 of 33

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

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

Special 

Study

28-day repeated-dose 

dermal mechanistic 

study in males (rat)

46889214 (2006)

Acceptable–NonGuideline

1000 mg/kg/d

Chlorantraniliprole had no effect on adrenal 

function after ACTH challenge in male rats at 

a dermal dose that resulted in an increase 

incidence of adrenal cortical 

microvesiculation. 

Special 

Study

Development of 

methods for 

evaluation of adrenal 

cortex (rat)

46979749, 46979927

(2006)

Acceptable–NonGuideline

Method was able to detect a reduction of 

ACTH-stimulated serum corticosterone level

at a positive control dose that did not alter 

basal serum corticosterone. In some rats from 

several studies (28-day dermal, 90-day oral, 

multigeneration reproduction, 2-year chronic) 

a slight, treatment-related increased in

microvesiculation was observed in zona 

fasciculata cells of the adrenal cortex.

Special 

Study

14-day toxicity, 

metabolism and 

pharmacokinetics 

(rat)

46979935 (2006)

Acceptable–NonGuideline

0, 25, 100, 1000 mg/kg/d

NOAEL = 1000 mg/kg/day

LOAEL not established due to absence of 

adverse effects.

Decreased absorption was observed at higher 

doses. Estimated T1/2 was 3.4 - 4.0 hr. Tmax

was 0.25 - 2.75 hr. Cmax was similar at all 

dose levels. 

Weak induction of CYP3A in F only. Total 

CYP in M and β-oxidation in M or F were not 

altered.

Special 

Study

28–Day oral (capsule) 

toxicity (dog)

46979711 (2003)

Acceptable–Nonguideline

0, 300 or 1000 mg/kg/d

NOAEL = 1000 mg/kg/d

LOAEL not established. An increase in 

hepatic CYP content at HDT without 

corresponding histopathological evidence of 

adverse liver effects.

T1/2 = 8.1-9.3/13.3-17.2 hr (M/F). Cmax = 2.5-

3.0 μg/mL (M and F)

Special 

Study

28–Day oral (feed) 

toxicity (dog)

46979713 (2003)

Acceptable–Nonguideline

Group 1: 1000 (Wk 1), 

5000 (Wk 2), 10,000 (Wk 

3-4) ppm; 

Group 2: 30,000 (Wk 1-2) 

40,000 (Wk 3-4) ppm 

(M: 0, 26, 138, 266, 797, 

1302 mg/kg/d; F: 0, 28, 

138, 298, 888, 1240 

mg/kg/d)

NOAEL = 1302/1240 (M/F) mg/kg/d

LOAEL not established due to absence of 

adverse effects.

Palatability of the diet was not affected by 

inclusion of the test material

F = females; M = males; HDT = highest dose tested; dose-dependent = a change was observed in at least 

the two highest doses; CYP = cytochrome P450 enzymes; CYP3A = CYP isoenzyme 3A; Cmax = 

maximum (i.e. steady-state) serum concentration; Tmax = time at maximum serum concentration; T1/2 = 

half-life in serum, i.e. time at half of maximum serum concentration. Wk = week
Page 30 of 33

Appendix B. Physical/Chemical Properties

Table B. Physicochemical Properties of Technical Grade of Chlorantraniliprole.

Parameter Value Reference (MRID)

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

Structures of Chlorantraniliprole and Possible Metabolites

Structures of Chlorantraniliprole and Possible Metabolites.

Chemical Name; Company Code Structure

3-Bromo-N-[4-chloro-2-methyl-6-

[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-

pyridinyl)-1H-pyrazole-5-carboxamide

Chlorantraniliprole

DPX-E2Y45

N

N N

NH

O

Cl

Br

HN

O

Cl
Page 31 of 33

Structures of Chlorantraniliprole and Possible Metabolites.

Chemical Name; Company Code Structure

3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-

carboxylic acid

IN-DBC80

2-[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-

6-chloro-3, 8-dimethyl-4(3H)-quinazolinone

IN-EQW78

5-Bromo-N-methyl-1H-pyrazole-3-carboxamide

IN-F6L99

N-[2-(Aminocarbonyl)-4-chloro-6-methylphenyl]-3-

bromo-1-(3-chloro-2-pyridinyl)1H-pyrazole-5-

carboxamide

IN-F9N04

2-[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-

6-chloro-8-methyl-4(3H)-quinazolinone

IN-GAZ70

3-Bromo-N-[4-chloro-2-

[[(hydroxymethyl)amino]carbonyl]-6-methylphenyl]-1-

(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

IN-H2H20

N

N N

O

Cl

Br

OH

N

N

N

N N

Br

O

Cl

Cl

N

H

HN

O

N

Br

N

N N

NH

O

Cl

Br

O

Cl

NH2

N

NH

N

N N

Br

O

Cl

Cl

N

N N

NH

O

Cl

Br

HN

O

Cl

OH
Page 32 of 33

Structures of Chlorantraniliprole and Possible Metabolites.

Chemical Name; Company Code Structure

N-[2-Aminocarbonyl]-4-chloro-6-

(hydroxymethyl)phenyl]-3-bromo-1-(3-chloro-2-

pyridinyl)-1H-pyrazole-5-carboxamide

IN-HXH40

3-Bromo-N-[4-chloro-2-(hydroxymethyl)-6-

[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-

pyridinyl)-1H-pyrazole-5-carboxamide

IN-HXH44

2-[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-

6-chloro-8-(hydroxymethyl)-4(3H)-quinazolinone

IN-K7H29

3-Bromo-N-[4-chloro-2-(hydroxymethyl)-6-

[[(hydroxymethyl)amino)carbonyl]phenyl]-1-(3-

chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide

IN-K9T00

6-Chloro-1, 2, 3, 4-tetrahydro-2, 4-dioxo-8-

quinazolinecarboxylic acid

IN-K9X71

N N N

NH

O

Cl

Br

NH2

O

Cl

HO

N

N N

NH

O

Cl

Br

HN

O

Cl

HO

N

NH

N

N N

Br

O

Cl

Cl

HO

N

N N

NH

O

Cl

Br

HN

O

Cl

HO

OH

N

H

NH

O

O

Cl

HO O
Page 33 of 33

Structures of Chlorantraniliprole and Possible Metabolites.

Chemical Name; Company Code Structure

2-[[[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-

yl]carbonyl]amino]-5-chloro-3-

[(methylamino)carbonyl]benzoic acid

IN-KAA24

2-Amino-5-chloro-3-[(methylamino)carbonyl]benzoic 

acid

IN-L8F56

IN-E5F18 Not provided

N

N N

NH

O

Cl

Br

HN

O

Cl

HO

O

O

Cl

HO O

N

NH2