E. I. DuPont de Nemours & Company Chlorantraniliprole

Page 1 of 6 **EPA REGISTRATION DIVISION -**  **COMPANY NOTICE OF FILING FOR PESTICIDE PETITION**  **Docket ID Number: EPA -** **HQ -**  **OPP -**  **2012 -**  **0 6**  **35 EPA Registration Division**  **C ontact: 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 tolerance s for residues of chlorantraniliprole, 3 -bromo -N - [4 - chloro - 2 - methyl 6 - [(methylamino)carbonyl]phenyl] - 1 - (3 - chloro - 2 - py ridinyl) - 1 H

-py razole - 5 - c arboxamide 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 may haw; fruit, citrus, group 10; fruit, pome, group 11; corn, field, forage; corn, field, grain; corn, field, milled by

products; 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. L ivestock Metabolism . The metabolism of chlorantraniliprole in ruminants and poultry is adequatel y understood to support the proposed tolerances. L actating goat and laying hen metabolism studies were conducted. The goat and hen rapidly excreted > 9 3 % and > 98% of the dose d radiolabeled residues , respectivel y . 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 b e requested from: Chief, Analy ticalE. I. DuPont de Nemours & Company Chlorantraniliprole

Page 2 of 6 Chemistry

B ranch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755 - 5350; telephone number: (410) 305 - 2905; e - mail address: residuemethods@epa.gov. 4. M agnitude 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 th e 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

P HI) 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

w ere 12.4 ppm, in sorghum stover were 6.9 ppm and in b arley and wheat straw were 15.4 ppm. Processing study . A wheat processing study w as conducted and the processing factors observed as compared to the raw agricultural commodity w ere 33.7X for the aspirated grain fraction, 1.2X for wheat germ, 1.1X for whe at 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 globall y by

the registrant , E. I. du Pont de Nemours & Company, and by o ther organizations including the IR- 4 Project. The relevant U.S. and foreign re sidue 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 action s 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

---------------E. I. DuPont de Nemours & Company Chlorantraniliprole

Page 3 of 6 Formulated products are as equall y non - toxic following acute exposures as is technical chlorantraniliprole. The acute inhalation toxicity for th e 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 , 00 0 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 ly mphocy te s)

 In vivo mouse micronucleus 3. Reproductive and developmental toxicity . In developmental toxicity

studies in rats and rabbits, chlorantraniliprole exhibited no effects on any p arameter 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 dehy drated 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 f or females), 7,000 ppm in mice (1,135 mg/kg bw/day for males and 1,539 mg/kg bw/day f or females) and 40,000 ppm in dogs (1,163 mg/kg bw/day f or males and 1,220 mg/kg bw/day f or 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

f eeding 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

b ased on reductions in body weight gain and food efficiency at 1,000 mg/kg bw/day.E. I. DuPont de Nemours & Company Chlorantraniliprole

Page 4 of 6 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

f or chronic toxicity

in the 18 -month mouse study was 1,2 00 ppm ( 158 mg/kg bw /day in males) and was based on e osinophilic foci accompanied by hepatocellular hy

pertrophy 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 ,0 00 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 [ 14 C ] - 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 14 C residues were readily e liminated 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 s ignificant 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 c onsidered onl y chronic exposure . Chronic dietary exposure assessments w ere 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 l abeled - are treated with chlorantraniliprole and that all crops contain residues at tolerance level or atE. I. DuPont de Nemours & Company Chlorantraniliprole

Page 5 of 6 residue levels equal to tolerance levels for similar crops . In particular all leafy vegetables, including leaves of root and tuber vegetables and le af y 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 1 1% 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 (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 conservativel y 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) greatl y exceed the 100 - f old 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 th ere 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 th ere is a reasonable certainty that no harm will result to the general population from the aggregate exposure to chlorantraniliprole. N o 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. N o additional safety factors are warranted. F. International Tolerances Numerous chlorantraniliprole maximum residue levels (MRL s ) have been established orE. I. DuPont de Nemours & Company Chlorantraniliprole

Page 6 of 6 are expected to be established supporting registrations in 82 countries. Codex MRL s have also been established for chlorantraniliprole on numerous crops.