E. I. DuPont de Nemours & Company Chlorantraniliprole

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EPA REGISTRATION DIVISION - COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITION 

Docket ID Number: EPA-HQ-OPP-2012-0635

EPA Registration Division Contact: Sidney Jackson (703) 305-7610 

Interregional Research Project Number 4 

Pesticide Petition Number: PP 2E8064

EPA has received a pesticide petition (PP 2E8064) 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-methyl6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide 

in or on grain, cereal, group 15, except rice at 6.0 parts per million (ppm); grain, cereal, 

forage, fodder and straw, group 16 at 30.0 ppm; fruit, citrus, group 10-10 at 1.4 ppm; 

fruit, pome, group 11-10 at 1.2 ppm; and concurrent deletion of tolerances for mayhaw; 

fruit, citrus, group 10; fruit, pome, group 11; corn, field, forage; corn, field, grain; corn, 

field, milled byproducts; corn, field, stover; corn, pop, forage; corn, pop, grain; corn, pop, 

stover; corn, sweet, forage; corn, sweet, kernel plus cobs with husk removed; and corn, 

sweet, stover. 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 

support 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 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 proposed 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 is understood.

3. Analytical method. Adequate enforcement methodology (liquid 

chromatography mass spectrometry (LC/MS/MS)) is available to enforce the 

tolerance expression. The method may be requested from: Chief, Analytical 
E. I. DuPont de Nemours & Company Chlorantraniliprole

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Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, 

MD 20755-5350; telephone number: (410) 305-2905; e-mail address: 

residuemethods@epa.gov.

4. Magnitude of residues. Field residue trials were conducted with 

chlorantraniliprole on raw agricultural commodities of barley, grain sorghum 

(milo) and wheat. Eleven MOR trials were conducted. The locations of the field 

trials were selected to represent the regions with most production per crop. A 

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

ai/A/application. The treated plots received two applications targeted at 1 day 

before harvest (1-day PHI) of mature grain. Maximum residue levels in barley 

grain were 2.17 ppm, in sorghum grain were 1.52 ppm and in wheat grain were 

0.428. The maximum residue levels in wheat and sorghum forage were 5.0 ppm, 

in barley and wheat hay were 12.4 ppm, in sorghum stover were 6.9 ppm and in 

barley and wheat straw were 15.4 ppm.

Processing study. A wheat processing study was conducted and the processing 

factors observed as compared to the raw agricultural commodity were 33.7X for 

the aspirated grain fraction, 1.2X for wheat germ, 1.1X for wheat bran, 0.7X for

shorts, 0.4X for flour and 0.3X for middlings.

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

States and globally by the registrant, E. I. du Pont de Nemours & Company, and 

by other organizations including 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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E. I. DuPont de Nemours & Company Chlorantraniliprole

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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 milligram per liter (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: 

 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/kilogram body weight per day (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 no-observed-adverse-effects-level (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.
E. I. DuPont de Nemours & Company Chlorantraniliprole

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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 

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 
E. I. DuPont de Nemours & Company Chlorantraniliprole

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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 chronic population-adjusted 

dose (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 Pesticide Root Zone Model/Exposure Analysis Modeling System

(PRZM/EXAMS), was used to calculate the surface water estimated drinking water 

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 maximum residue levels (MRLs) have been established or 
E. I. DuPont de Nemours & Company Chlorantraniliprole

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are expected to be established supporting registrations in 82 countries. Codex MRLs 

have also been established for chlorantraniliprole on numerous crops.