IR-4 Chlorantraniliprole

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ENVIRONMENTAL PROTECTION AGENCY

Notice of Filing of a Pesticide Petition for the Establishment of Tolerances for

Residues of Chlorantraniliprole in or on Food Commodities 

AGENCY: Environmental Protection Agency (EPA). 

ACTION: Notice.

Interregional Research Project Number 4 (IR-4)

Pesticide Petition (PP#) 3E8170

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SUMMARY: This notice announces the initial filing of a pesticide petition 

proposing the establishment of tolerances for residues of chlorantraniliprole in or 

on food commodities under the Federal Food, Drug, and Cosmetic Act (FFDCA), 

as amended by the Food Quality Protection Act of 1996 (FQPA).

FOR FURTHER INFORMATION CONTACT: Laura Nollen, (703) 305-7390, 

nollen.laura@epa.gov . Registration Division, (7505), Office of Pesticide Programs, 

Environmental Protection Agency, 1200 Pennsylvania Avenue, N.W., Washington, DC 

20460. 

SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition

#3E8170, proposing the establishment and/or amendment of regulations for

residues of certain pesticide chemicals in or on onion, green, subgroup 3-

07B; fruit, stone, group 12-12, except cherry, chickasaw plum, and damson plum; 

papaya; passionfruit; nut, tree, group 14-12; and spice, subgroup 19B under

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

346a (d). EPA has determined that this petition contains data or information

regarding the elements set forth in section 408(d)(2); however, EPA has not fully 

evaluated the sufficiency of the submitted data at this time or whether the data

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

rules on the petition.

List of Subjects

Environmental Protection, Agricultural Commodities, Food Additives, Feed

Additives, Pesticides and Pests, Reporting and Recordkeeping Requirements. 

Summary of Petition

A summary of the pesticide petition is given below. The petitioner prepared the summary 
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of the petition.

PP# 3E8170

EPA has received a pesticide petition, PP# 3E8170, from the Interregional

Research Project Number 4 (IR-4), IR-4 Project Headquarters, 500 College Road East,

Suite 201 W, Princeton, New Jersey, 08540, proposing, pursuant to section

408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to 

amend 40 CFR part 180 to establish tolerances for residues of chlorantraniliprole, 3-

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

pyridinyl)-1H-pyrazole-5-carboxamide in or on onion, green, subgroup 3-07B at 3.0 

ppm; fruit, stone, group 12-12, except cherry, chickasaw plum, and damson plum at 4.0 

ppm; papaya at 4.0 ppm; passionfruit at 4.0 ppm; nut, tree, group 14-12 at 0.04 ppm; and 

spice subgroup 19B at 40 ppm. Concurrently, IR-4 is requesting removal of the 

following existing time-limited tolerances: leek; onion, green; onion, Welsh; and shallots, 

fresh leaves at 0.2 ppm.IR-4 is finally requesting remove of the following permanent

tolerances: fruit, stone, group 12, except cherry, chickasaw plum, and damson plum at

4.0 ppm; mayhaw at 0.6 ppm; papaya and passionfruit at 2.0 ppm; nut, tree, group 14

at 0.04 ppm; pistachio at 0.04 ppm and spice, subgroup 19B at 14 ppm. EPA has

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

in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated the sufficiency 

of the submitted data at this time or whether the data supports granting of the petition. 

Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism of chlorantraniliprole is adequately

understood to support the proposed exemption from the requirement of tolerances. 

Studies in apple, lettuce, rice, tomato, and cotton when treated at proposed label 

rates showed no significant metabolites. The only significant residue is the parent 

compound.

2. Livestock Metabolism. The metabolism of chlorantraniliprole in ruminants and 

poultry is adequately understood to support the exemption from the requirement 

of tolerances. Lactating goat and laying hen metabolism studies were conducted. 

The goat and hen rapidly excreted >93% and >98% of the dosed radiolabeled 

residues, respectively.

The metabolic pathway in poultry and ruminant (goat) animals was consistent. 

There is no reasonable expectation of transfer of finite residues of 

chlorantraniliprole and its metabolites to fat, meat, milk, and eggs.

3. Analytical method. Since chlorantraniliprole and its metabolic degradates are 

not of toxicological concern, analytical methods are not applicable.
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4. Magnitude of residues. Greenhouse residue trials were conducted with 

chlorantraniliprole on the raw agricultural commodity cucumbers. Three MOR 

trials were conducted. The locations of the field trials were selected to represent 

the regions with most greenhouse cucumber production. A foliar broadcast spray 

of chlorantraniliprole was applied at the rate of 0.1 lb ai/A/application. The 

cucumber plants received two applications targeted at 1 day before harvest (1-day 

PHI) of mature crop. Concurrent recoveries from control samples fortified at

0.010 to 5.0 mg/kg of chlorantraniliprole ranged from 96 to 100%. The maximum 

residue level in cucumbers was 0.0738 ppm which is below the currently 

established tolerance of 0.5 ppm for cucurbits.

Greenhouse residue trials were conducted with chlorantraniliprole on the raw 

agricultural commodity tomatoes. Four MOR trials were conducted. The 

locations of the field trials were selected to represent the regions with most 

greenhouse tomato production. A foliar broadcast spray of chlorantraniliprole was 

applied at the rate of 0.1 lb ai/A/application. The tomato plants received two 

applications targeted at 1 day before harvest (1-day PHI) of mature crop. 

Concurrent recoveries from control samples fortified at 0.010 to 5.0 mg/kg of 

chlorantraniliprole ranged from 98 to 102%. The maximum residue level in 

tomatoes was 0.102 ppm which is below the currently established tolerance of 1.4 

ppm for fruiting vegetables.

Field residue trials were conducted with chlorantraniliprole on the raw 

agricultural commodities cherry, papaya and lychee. Two MOR trials were 

conducted for each commodity. A foliar broadcast spray of chlorantraniliprole 

was applied at the rate of 0.1 lb ai/A/application. The test plants received two 

applications targeted at 1, 3, 6-7, 9-10 and 13-15 days before harvest of mature 

crop. Concurrent recoveries from control samples fortified at 0.010 to 5.0 mg/kg 

of chlorantraniliprole ranged from 97 to 123%. In cherry samples, the total 

residues of chlorantraniliprole ranged from 0.151 to 0.192 ppm in samples taken 

at 1 day PHI, 0.135 to 0.162 ppm in samples taken at 3 days PHI, 0.105 to 0.120 

ppm in samples taken at 6 days PHI, 0.132 to 0.151 ppm in samples taken at 10 

days PHI and 0.0994 to 0.129 ppm in samples taken at 15 days PHI. In lychee 

samples, the total residues of chlorantraniliprole ranged from 0.402 to 0.500 ppm 

in samples taken at 1 day PHI, 0.306 to 0.442 ppm in samples taken at 3 days 

PHI, 0.363 to 0.386 ppm in samples taken at 6 days PHI, 0.239 to 0.313 ppm in 

samples taken at 9 days PHI and 0.308 to 0.337 ppm in samples taken at 13 days 

PHI. In papaya samples, the total residues of chlorantraniliprole ranged from

0.284 to 0.292 ppm in samples taken at 1 day PHI, 0.204 to 0.224 ppm in samples 

taken at 3 days PHI, 0.196 to 0.211 ppm in samples taken at 7 days PHI, 0.164 to

0.196 ppm in samples taken at 10 days PHI and 0.137 to 0.142 ppm in samples 

taken at 14 days PHI.

Field residue trials were conducted with chlorantraniliprole on the raw 

agricultural commodities onions and dill. Five MOR trials were conducted with 

onions and two MOR trials were conducted with dill. The locations of the field
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trials were selected to represent the regions with most onion and spice production. 

A foliar broadcast spray of chlorantraniliprole was applied at the rate of 0.1 lb 

ai/A/application. The onion and dill crops received two applications targeted at 1 

day before harvest (1-day PHI) of mature crop. Concurrent recoveries from 

control samples fortified at 0.010 to 5.0 mg/kg of chlorantraniliprole ranged from

81 to 117%. The total residues of chlorantraniliprole ranged from 0.371 to 1.50 

ppm in fresh green onion samples taken at 1 day PHI. The total residues of 

chlorantraniliprole ranged from 0.900 to 11.1 ppm in dried green onion samples 

taken at 1 day PHI. The total residues of chlorantraniliprole ranged from 15.4 to

24.3 ppm in dill seed samples taken at 1 day PHI.

Numerous residue studies have been conducted on many crops in the United

States and globally by the registrant and by other organizations such as the IR-4

Project. The relevant U.S. and foreign residue study reports required to support 

use of chlorantraniliprole and existing tolerances in the United States have been 

submitted to EPA and reviewed as part of prior registration actions for this active 

ingredient.

B. Toxicological Profile

1. Acute toxicity. Based on EPA criteria, chlorantraniliprole is classified 

as follows for Toxicity Categories:

Guideline Title Results Category

870.1100

870.1200

870.1300

870.2400

870.2500

870.2600

Acute Oral Toxicity

Acute Dermal Toxicity 

Acute Inhalation Toxicity 

Primary Eye Irritation 

Primary Dermal Irritation 

Skin Sensitization

LD50: >5,000 mg/kg (Rat)

LD50: >5,000 mg/kg (Rat) 

LC50: >5.1 mg/L (Rat) 

Mild irritation (Rabbit)

No irritation (Rabbit)

Not a sensitizer (Mouse LLNA)

Category IV

Category IV 

Category IV 

Category IV 

Category IV

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Formulated products are as equally non-toxic following acute exposures as is 

technical chlorantraniliprole. The acute inhalation toxicity for the suspension concentrate 

formulation could not be determined above the maximum practically attainable 

atmospheric aerosol concentration of 2 mg/L.

There was no evidence of neurotoxicity in rats following a single limit dose of 2,000 

mg/kg

2. Genotoxicty. Chlorantraniliprole has shown no genotoxic activity in the following 

listed in vitro and in vivo tests:
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− Bacterial reverse mutation

− In vitro mammalian gene mutation (CHO/HGPRT)

− In vitro chromosomal aberration (human lymphocytes)

− In vivo mouse micronucleus

3. Reproductive and developmental toxicity. In developmental toxicity studies in 

rats and rabbits, chlorantraniliprole exhibited no effects on any parameter in pregnant 

females or their offspring at levels up to and including the maximum tested dose of 1,000 

mg/kg bw/day.

No reproductive toxicity was observed in a two-generation reproduction study with 

chlorantraniliprole in rats. No adverse effects were observed on reproduction, fertility, 

sperm parameters, estrous cycle, litter size, pup survival and developmental landmarks up to 

the maximum tested dose of 20,000 ppm in the diet. There were no adverse histological 

findings indicative of reproductive toxicity. There was a slight reduction in the F1 pup (but 

not F2 pup) weight during lactation at the highest dose level (mean maternal intake during 

lactation equal to 3,118 mg/kg bw/day); this was attributed, in part, to weight loss in one 

dehydrated dam during lactation which had a litter with some of the lowest pup weights. 

The slight change in pup weight was without subsequent effects since overall body weight, 

weight gain and development in F1 rats fed 20,000 ppm were similar to control animals.

4. Subchronic toxicity.

Subchronic (90-day) feeding studies were conducted with rats, mice and dogs. No 

adverse effects were observed at the highest dietary concentrations tested of 20,000 ppm in 

rats (1,188 mg/kg bw/day for males and 1,526 mg/kg bw/day for females), 7,000 ppm in 

mice (1,135 mg/kg bw/day for males and 1,539 mg/kg bw/day for females) and 40,000 ppm 

in dogs (1,163 mg/kg bw/day for males and 1,220 mg/kg bw/day for females). 

Chlorantraniloprole showed no evidence of immunotoxicity in 28-day feeding studies in rats 

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

concentrations greater than the limit dose of 1,000 mg/kg bw/day.

A 28-day dermal toxicity study in rats was conducted at doses of 100, 300 and 1,000 

mg/kg bw/day. The NOAEL for male and female rats was 300 mg/kg bw/day based on 

reductions in body weight gain and food efficiency at 1,000 mg/kg bw/day.

No adverse target organ effects were observed in any subchronic toxicity study.

5. Chronic toxicity.

Chlorantraniliprole was not carcinogenic in either a 2-year study in rats or an 18-

month study in mice. The NOAEL for chronic toxicity in the 18-month mouse study was

1,200 ppm (158 mg/kg bw/day in males) and was based on eosinophilic foci accompanied 

by hepatocellular hypertrophy and increased liver weight.

In rats, there were no adverse effects on any in-life parameter in either males or 

females administered chlorantraniliprole up to and including a maximum dietary 

concentration of 20,000 ppm for 2 years (805 and 1,076 mg/kg bw/day, respectively).

In a one-year feeding study in dogs, the NOAEL was the highest dose tested, 40,000
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ppm (1,164 and 1,233 mg/kg/day in males and females, respectively).

6. Rat metabolism.

The absorption of [

14C]-chlorantraniliprole in rats was rapid with peak concentrations 

occurring at 5-12 hours after single dose administration. Tissue distribution of the absorbed 

dose was extensive and indicated low potential for accumulation. Excretion was 

substantially complete by 48-72 hours after dosing (>90%).

Following 14 days of oral administration

14C residues were readily eliminated from

the plasma and tissues and confirmed minimal potential for accumulation. The profile of 

metabolites in urine and feces indicated extensive metabolism consistent with that observed 

for the single dose study.

7. Metabolite toxicology. Due to the extremely low toxicity of the parent compound 

and the extensive metabolism observed in mammalian systems, chlorantraniliprole 

metabolites are not expected to result in any significant toxicity. Toxicology studies 

conducted with metabolites support this conclusion.

8. Endocrine disruption. No adverse effects were observed on any endocrine tissue 

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

C. Aggregate Exposure

1. Dietary exposure -- i. Food. Because an endpoint attributable to a single dose 

was not identified, the dietary exposure assessment considered only chronic exposure.

Chronic dietary exposure assessments were conducted using the Dietary Exposure 

Evaluation Model (DEEM-FCIDTM, Version 2.03) which uses food consumption data 

from the U.S. Department of Agriculture’s Continuing Surveys of Food Intakes by 

Individuals (CSFII) from 1994-1996 and 1998. The chronic dietary exposure assessment 

was conducted using a chronic reference dose of 1.58 mg/kg bw/day based on the 

NOAEL established in the 18-month study in mice. DuPont has conducted chronic 

assessments which assume that 100% of all crops – including those not labeled - are 

treated with chlorantraniliprole and that all crops contain residues at tolerance level or at 

residue levels equal to tolerance levels for similar crops. In particular all leafy 

vegetables, including leaves of root and tuber vegetables and leafy vegetables including 

brassica vegetables, are assumed to have residues of 15 parts per million. All other 

human foods (including plant and animal commodities) are assumed to have residues of 2 

parts per million.

These assumptions result in conservative, health-protective estimates of exposure which 

are well below the Agency’s level of concern (100% of the cPAD). The maximum 

estimate is less than 11% of the cPAD for all population subgroups.

ii. Drinking water. A drinking water assessment for chlorantraniliprole, 

conducted based on PRZM/EXAMS (Pesticide Root Zone Model/Exposure Analysis 

Modeling System), was used to calculate the surface water estimated drinking water
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concentrations (EDWCs) and the Screening Concentration in Ground Water (SCIGROW) model was used to calculate the groundwater EDWC. The EDWCs do not 

exceed the Agency’s level of concern.

2. Non-dietary exposure. Residential exposure (non-occupational, non-dietary 

exposure to consumers) was conservatively assessed for dermal post-application 

exposure (children and adults), and for children the oral exposures via hand-to-mouth, 

object-to-mouth, and incidental ingestion of soil were also assessed. The margins of 

exposure (MOE) greatly exceed the 100-fold MOE required for these routes and from the 

combined children’s incidental oral ingestion. Therefore, residential non-dietary 

exposure is not a concern.

D. Cumulative Effects

It is not necessary at this time to consider cumulative effects because there is no 

indication that toxic effects of chlorantraniliprole have a common mechanism with those 

of any other chemical compounds.

E. Safety Determination

1. U.S. population. Based on risk assessments performed using worst-case 

exposure assumptions there is a reasonable certainty that no harm will result to the 

general population from the aggregate exposure to chlorantraniliprole. No additional 

safety factors are warranted.

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

exposure assumptions there is a reasonable certainty that no harm will result to the infants 

and children from the aggregate exposure to chlorantraniliprole. No additional safety 

factors are warranted.

F. International Tolerances

Numerous chlorantraniliprole MRLs have been established or are expected to be 

established supporting registrations in 92 countries. Codex MRLs have also been 

established for chlorantraniliprole on numerous crops.