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EPA REGISTRATION DIVISION CO MPANY 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 Ma rket Street, Wilmington, Delaware requesting, pursuant to secti on 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 tole rance for residues of

chlorantraniliprole,3- bromo-N-[4-chloro-2-methyl-6-[(methylamino)- carbonyl]phenyl]-1-(3-chl oro-2-pyridinyl)-1H-p yrazole-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, cottons eed subgroup 20C at 0.3 ppm; soybean aspirated grain fractions at 300 ppm; vegetabl e, 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 c ontains 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 significan t 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. Lactatin g 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 c onsistent. There is no reasonable expectation of transfer of finite residues of ch lorantraniliprole and its2

metabolites to fat, meat, milk, and eggs

.

3. Analytical method. An analytical residue method has been submitted to EPA which permits determination of tra ce 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 th e rate of 0.1 lb ai/A/application. The canola and sunf lower treated plots received two applications targeted at 1 day before harvest (1-day PHI) of mature seed.

Concurrent recoveries from control sa mples 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 chlorantranilipro le on soybeans to

determine the residue level which would occur in the aspirated grain fraction. Chlorantraniliprole was applied as a folia r broadcast spray at the rate of 0.1 lb ai/A for two separate app lications 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 samp les 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 aspira ted grain fraction were 60 ppm.

Numerous residue studie s have been conducted on many crops in the United States and globally by the registrant a nd by other organizations such as the IR-4 Project. The relevant U.S. and foreign residue study re ports required to support use of chlorantranili prole 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 IV3

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 vitr o and in vivo tests:

− Bacterial reverse mutation

− In vitro mammalian gene mutation (CHO/HGPRT)

− In vitro chromosomal aberra tion (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 paramete rs, 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 a dverse histological findings indicative of reproductive toxicity. There was a sl ight reduction in the F1 pup (but not F2 pup) weight during lactation at th e highest dose level (mean maternal intake during lactation equa l 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 ove rall 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 st udies were conducted with rats, mice and dogs. No adverse effects we re observed at th e 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 a nd 1,220 mg/kg bw/day for females). Chlorantraniloprole showed no evidence of immunotoxicity in 28-day feeding4

studies in rats or mice and no evidence of neurotoxicity in a 90-day feeding study in rats at dietary concentrati ons greater than th e 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 ef ficiency at 1,000 mg/kg bw/day.

No adverse target organ effects were observed in any su bchronic 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 ma les 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 accumula tion. Excretion was substantially complete by 48-72 hours after dosing (>90%).

Following 14 days of oral administrati on 14C residues were readily eliminated from the plasma and tissues a nd confirmed minimal potential for accumulation. The profile of metabolit es in urine and feces indicated

extensive metabolism consistent with th at 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 e xpected to result in any significant toxicity. Toxicology studies conducted with me tabolites 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.5

C. Aggregate Exposure

1. Dietary exposure.

i. Food. Because an endpoint attr ibutable to a single dos e was not identified, the dietary exposure assessment consid ered only chronic exposure.

Chronic dietary exposure assessments were conducted using the Dietary Exposure Evaluation Model (DEEM-FCI DTM, 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 ba sed on the NOAEL established in the 18-month study in mice. DuPont has conducted chronic assessments which assume that 100% of all crops – includi ng those not labeled - are treated with chlorantraniliprole and that all crops c ontain residues at tole rance 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 assume d 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 (Pesti cide Root Zone Model/Exposure Analysis Modeling System), was used to calculate the surf ace water estimated drinking water concentrations (EDWCs) and the Screening Concentration in Ground Water (SCI-GROW) model was us ed 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 conservativel y assessed for dermal post-application exposure (children and adults), and for children the oral exposures via hand-tomouth, object-to-mouth, and incidental ingest ion of soil were also assessed. The margins of exposure (MOE) greatly exce ed the 100-fold MOE required for these

routes and from the combined children’s incidental oral inge stion. Therefore, residential non-dietary e xposure 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 chlora ntraniliprole have a common mechanism with those of any other chemical compounds.6

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 chlora ntraniliprole. No additional safety factors are warranted.

2. Infants and children

. Based on the risk assessment s performed using worst-case exposure assumptions there is a reasonable certainty that no harm will result to the infants and children from the aggregat e exposure to chlorantraniliprole. No additional safety factors are warranted.

F. International Tolerances

Numerous chlorantraniliprole MRLs have b een established or ar e expected to be established supporting registrations in 82 c ountries. Codex MRLs have also been

established for chlorantrani liprole on numerous crops.