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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Jennifer Urbanski (703) 347-0156 

TEMPLATE: 

E. I. DuPont de Nemours and Company, DuPont Crop Protection

1F7954

 EPA has received a pesticide petition 1F7954 from E. I. DuPont de Nemours and 

Company, DuPont Crop Protection, 1007 Market Street, Wilmington, Delaware

requesting, 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

 by establishing a tolerance 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 the raw 

agricultural commodity oilseed, rapeseed subgroup 20A at 2.0 ppm; oilseed, sunflower 

subgroup 20B at 2.0 ppm; oilseed, cottonseed subgroup 20C at 0.3 ppm; soybean 

aspirated grain fractions at 300 ppm; vegetable, legume, group 6 at 2.0 ppm; vegetable, 

foliage of legume, group 7 at 30 ppm and forage, vegetable, foliage of legume, group 7 at 

90 ppm. EPA has determined that the petition contains data or information regarding the 

elements set forth in section 408 (d)(2) of FDDCA; 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 
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metabolites to fat, meat, milk, and eggs.

3. Analytical method. An analytical residue method has been submitted to EPA 

which permits determination of trace residues of the parent compound on 

numerous and various food and feed commodities.

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

chlorantraniliprole on raw agricultural commodities of canola and sunflower 

seed. Twelve 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 canola and sunflower treated plots received two 

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

Concurrent recoveries from control samples fortified at 0.010 to 3 mg/kg of 

chlorantraniliprole ranged from 92 to 105%. Residue levels in canola seed 

averaged 0.47 ppm and ranged from 0.12 to 1.2 ppm whereas residue levels in 

sunflower seed averaged 0.36 ppm and ranged from 0.27 to 0.85 ppm. 

A field residue trial was conducted with chlorantraniliprole on soybeans to 

determine the residue level which would occur in the aspirated grain fraction. 

Chlorantraniliprole was applied as a foliar broadcast spray at the rate of 0.1 lb 

ai/A for two separate applications with the second application made one day 

prior to harvest. Samples from treated and untreated plots were analyzed by 

LC-MS/MS to determine residues of chlorantraniliprole in/on the samples. 

Concurrent recoveries from control samples fortified at 0.010 to 100 mg/kg of 

chlorantraniliprole ranged from 92 to 108%. Residues in the raw seed were at 

0.19 ppm and residues in the aspirated grain fraction were 60 ppm. 

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 

Acute Oral Toxicity 

Acute Dermal Toxicity 

Acute Inhalation Toxicity 

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

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

LC50: >5.1 mg/L (Rat) 

Category IV 

Category IV 

Category IV 
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870.2400 

870.2500 

870.2600 

Primary Eye Irritation 

Primary Dermal Irritation 

Skin Sensitization 

Mild irritation (Rabbit) 

No irritation (Rabbit) 

Not a sensitizer (Mouse LLNA) 

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: 

− 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 
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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 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.
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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 concentrations (EDWCs) and the Screening Concentration in 

Ground Water (SCI-GROW) 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-tomouth, 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.
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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 82 countries. Codex MRLs have also been 

established for chlorantraniliprole on numerous crops.