E. I. DuPont de Nemours & Company Chlorantraniliprole

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ENVIRONMENTAL PROTECTION AGENCY

Notice of Filing of a Pesticide Petition for the Establishment of Tolerances for Residues of Chlorantranilipro le in or on Food Commodities

AGENCY: Environmental Pr otection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the init ial 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 INFORMATI ON CONTACT: By mail: [EPA Product Manager] , Product Manager (PM), Registra tion Division, (7505), Office of Pesticide Programs, Environmental Prot ection Agency, Ariel Rios Building 1200 Pennsylvania Avenue, N. W., Wash ington, DC 20460. Office location and telephone number: , Arlington, VA., (703) 306-0415. Email: manager.product@epa.gov

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SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as follows proposing the establishment and/or amendment of regulations for residues of certain pesticide chemicals in or on bushberries, subgroup 13-07B; cucurbit vegetables, group 9; fruiti ng vegetables, group 8; la rge shrub/tree berries, subgroup 13-07C; low growing berries , subgroup 13-07G; okra; onion, bulb, subgroup 3-07A; peanut, hay; peanut, nutm eat; root and tuber vegetables, group 1; sugar beet molasses; ti palm; leaves of root and tuber vegetables, group 2; and dried tea leaves 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 elem ents 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. Add itional data may be needed before EPA rules on the petition.

List of Subjects

Environmental Protection, Agricultural Commodities, Food Additives, Feed Additives, Pesticides and Pests, Repo rting and Recordkeeping Requirements.

Summary of PetitionE. I. DuPont de Nemours & Company Chlorantraniliprole

Page 2 of 7 A summary of the pesticide pe tition is given below. The petitioner prepared the summary of the petition.

EPA Registration Division contact: Product Manager , (703) XXX-XXXX

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

[Insert petition number]

EPA has received a pesticide petition ( [insert petition number] ) from E. I. DuPont de Nemours and Comp any, DuPont Crop Protectio n, Wilmington, Delaware, 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)-1 H -pyrazole-5-carboxamide in or on bushberry, subgroup 13-07B at 2.5 ppm; la rge shrub/tree berry, subgroup 13-07G at 2.5 ppm; low growing berry, subgroup 13-07G at 2.5 ppm; ti palm, roots at 0.35 ppm; ti palm, leaves at 13 ppm; root and tuber vegeta bles, group 1 at 0.35 ppm; leaves of root and tuber vegetables, group 2 at 40 ppm; sugar beet molasses at 11 ppm; onion, bulb, subgroup 3-07A at 0.35 ppm; peanut, nutmeat at 0.35 ppm; peanut, hay at 90 ppm; tea, dried leaves at 50 ppm and to increase tolera nces in or on fruiting vegetables (except cucurbits), group 8 from 0.70 ppm to 0.90 ppm; cucurbit vegetables, group 9 from 0.25 ppm to 0.30 ppm; and okra from 0.70 ppm to 0.90 ppm . EPA has determined that the petition contains data or info rmation 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 suppor ts granting of the peti tion. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism

. The metabolism of chlorantra niliprole is adequately understood to support the proposed exempt ion from the requireme nt of tolerances. Studies in apple, lettuce, ri ce, tomato, and cotto n when treated at proposed label rates showed no signif icant metabolites. Th e only significant residue is the parent compound.

2. Livestock Metabolism

. The metabolism of chlorantraniliprole in ruminants and poultry is adequately unde rstood 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 rumi nant (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.E. I. DuPont de Nemours & Company Chlorantraniliprole

Page 3 of 7 3. Analytical method

. Since chlorantranilip role and its metabolic degradates are not of toxicological concern, analytic al methods are not applicable.

4. Magnitude of residues . Field residue trials were conducted on cucumber, summer squash, melon, bell pepper, non-bell pepper, tomato, celery, head lettuce, leaf lettuce and spinach with and without adjuvants. Residues of chlorantraniliprole found in replicate tria ls in fruiting vegetables treated with adjuvants may result in higher residues on average by a factor of 1.1-1.3× as compared to the same crops that were not treated with adjuva nts. Residues of chlorantraniliprole found in replicate tr ials in leafy, cucurbit and non-cucurbit vegetables treated with adjuvants may result in higher residues on average by a

factor of 1.0-1.3×.

Six residue trials were conducted with radishes which were treated at the proposed maximum labeled rate and harvested at the minimum pre-harvest interval. Residues of chlorantranilipro le found in replicate treated samples collected 1 day after last application ra nged from 3.6 to 22 mg/kg with an average 11 ± 5.6 mg/kg for radish tops and from 0.021 to 0.26 mg/kg with an average 0.076 ± 0.075 mg/kg for radish roots.

In eleven field trials, two foliar broa dcast or directed applications of chlorantraniliprole were made to blueberrie s at a rate of approximately 0.1 lb ai/A each, for a total of approximately 0.2 lb ai /A. No adjuvant was added to the spray mixtures. The applications were made 7±1 days apart and timed so that commercially mature blueberries could be collected 1 day after the final application. The maximum residue in bl ueberry following a total application of approximately 0.2 lb ai/A and a pre-ha rvest interval (PHI) of 1 day was 0.908

ppm.

In six field trials, two foliar applicati ons of chlorantraniliprole were made to cranberries at a rate of approximate ly 0.1 lb ai/A each, for a total of approximately 0.2 lb ai/A. No adjuvant was added to the spray mixtures. The applications were made 7±1 days apart and timed so that commercially mature

cranberries could be collect ed 1 day after the final application. The maximum residue in cranberry following a total appl ication of approximately 0.2 lb ai/A and a pre-harvest interval (PHI) of 1 day was 0.211 ppm.

Numerous residue studies have been conducted on many crops in the United States and globally by the re gistrant and by othe r organizations such as the IR-4 Project. The relevant U.S. and forei gn residue study reports required to support use of chlorantraniliprole and existing tole rances in the United States have been submitted to EPA and reviewed as part of prior registration actions for this active ingredient.E. I. DuPont de Nemours & Company Chlorantraniliprole

Page 4 of 7 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 inhala tion toxicity for the suspension concentrate

formulation could not be determined a bove 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 ab erration (human lymphocytes)

 In vivo mouse micronucleus

3. Reproductive and developmental toxicity . In developmental toxicity studies in rats and rabbits, chlorantraniliprole exhib ited 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 eff ects were observed on reproduction, fertility, sperm parameters, estrous cycle, litter size, pup survival and de velopmental 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 th e F1 pup (but not F2 pup) weight duri ng lactation at the highest dose le vel (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 weig ht was without subsequent effects since overall body weight,E. I. DuPont de Nemours & Company Chlorantraniliprole

Page 5 of 7 weight gain and developm ent in F1 rats fe d 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 di etary concentrations tested of 20,000 ppm in rats (1,188 mg/kg bw/day fo r males and 1,526 mg/kg bw/day for females), 7,000 ppm in mice (1,135 mg/kg bw/d ay for males and 1,539 mg/kg bw/d ay for females) and 40,000 ppm in dogs (1,163 mg/kg bw/d ay for males and 1,220 mg/k g bw/day for females). Chlorantraniloprole showed no evidence of imm unotoxicity 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 ob served in any subchr onic 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 NOAE L for chronic toxicity in the 18-month mouse study was 1,200 ppm (158 mg/kg bw/d ay in males) and was based on eosinophilic foci accompanied by hepatocellular hypertrophy an d increased liver weight. In rats, there were no adve rse effects on any in-life pa rameter in either males or females administered chlorantraniliprol e 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 stu dy in dogs, the NOAEL was the hi ghest dose tested, 40,000 ppm (1,164 and 1,233 mg/kg/day in males and females, respectively).

6. Rat metabolism

. The absorption of [ 14 C]-chlorantraniliprole in rats was rapid with peak concentrations occurring at 5-12 hours after single dose admini stration. Tissue distri bution of the absorbed

dose was extensive and indi cated low potential for accu mulation. Excretion was substantially complete by 48-72 hours after dosing (>90%).

Following 14 days of oral administration 14 C residues were readily eliminated from the plasma and tissues and confirmed minimal po tential for accumulati on. The profile of

metabolites in urine and feces indicated extensiv e metabolism consistent with that observed for the single dose study.

7. Metabolite toxicology

. Due to the extremely low toxi city of the parent compound

and the extensive metabolism observed in mammalian systems, chlorantraniliprole metabolites are not expected to result in any significant toxi city. Toxicology studies

conducted with metabolites support this conclusion.E. I. DuPont de Nemours & Company Chlorantraniliprole

Page 6 of 7 8. Endocrine disruption

. No adverse effects were obs erved on any endocrine tissue in short- and long-term studi es 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 we re 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 diet ary 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 resi dues 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 an d leafy vegetables including brassica vegetables, are assumed to have residues of 15 parts per million. All other human foods (including plant and animal commo dities) are assumed to have residues of 2 parts per million.

These assumptions result in conservative, he alth-protective estimates of exposure which are well below the Agency’s level of c oncern (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) a nd 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-o ccupational, non-dietary exposure to consumers) was conservative ly assessed for dermal post-application exposure (children and adults), and for ch ildren 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 MO E required for these routes and from the combined children’s incidental oral inges tion. 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 chlorantran iliprole have a common mechanism with those of any other chemical compounds.E. I. DuPont de Nemours & Company Chlorantraniliprole

Page 7 of 7 E. Safety Determination

1. U.S. population . Based on risk assessment s performed using worst-case exposure assumptions there is a reasonable ce rtainty that no harm will result to the general population from the aggregate exposur e 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 cert ainty 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 in 61 countries. Codex MR Ls have also been established for chlorantraniliprole on numerous crops.