Document ID: EPA-HQ-OPP-2013-0235-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-06-05T04:00Z

----------------------------------------------------------------------- ENVIRONMENTAL PROTECTION AGENCY
 Notice of Filing of a Pesticide Petition for the Establishment of Tolerances for
 Residues of Chlorantraniliprole in or on Food Commodities AGENCY: Environmental Protection Agency (EPA). ACTION: Notice.
 Interregional Research Project Number 4 (IR-4)
 Pesticide Petition (PP#) 3E8170
 -----------------------------------------------------------------------

 SUMMARY: This notice announces the initial 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   INFORMATION   CONTACT:   Laura Nollen, (703) 305-7390, nollen.laura@epa.gov . Registration Division, (7505), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Avenue, N.W., Washington, DC 20460. 

 SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition #3E8170, proposing the establishment and/or amendment of regulations for residues of certain pesticide chemicals in or on onion,  green,  subgroup  3-07B;  fruit, stone, group 12-12, except cherry, chickasaw plum, and damson plum; papaya; passionfruit; nut, tree, group 14-12; and spice, subgroup 19B 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 elements 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.  Additional data may be needed before EPA rules on the petition.

 List of Subjects

 Environmental  Protection,  Agricultural  Commodities,  Food  Additives,  Feed
 Additives, Pesticides and Pests, Reporting and Recordkeeping Requirements. Summary of Petition
 A summary of the pesticide petition is given below. The petitioner prepared the summary of the petition.

 PP# 3E8170

 EPA has received a pesticide petition, PP# 3E8170, 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-methyl-6-[(methylamino)-carbonyl]phenyl]-1-(3-chloro-2- pyridinyl)-1H-pyrazole-5-carboxamide in  or on  onion,  green,  subgroup  3-07B  at  3.0 ppm; fruit, stone, group 12-12, except cherry, chickasaw plum, and damson plum at 4.0 ppm; papaya at 4.0 ppm; passionfruit at 4.0 ppm; nut, tree, group 14-12 at 0.04 ppm; and spice subgroup 19B at 40 ppm. Concurrently, IR-4 is requesting removal of the following existing time-limited tolerances: leek; onion, green; onion, Welsh; and shallots, fresh leaves at 0.2 ppm.IR-4 is finally requesting remove of the following permanent tolerances: fruit, stone, group 12, except cherry, chickasaw plum, and damson plum at 4.0 ppm; mayhaw at 0.6 ppm; papaya and passionfruit at 2.0 ppm; nut, tree, group 14 at 0.04 ppm; pistachio at 0.04 ppm and spice, subgroup 19B at 14 ppm.  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 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 metabolites to fat, meat, milk, and eggs.

       3. Analytical method.  Since chlorantraniliprole and its metabolic degradates are not of toxicological concern, analytical methods are not applicable.

       4. Magnitude of residues. Greenhouse residue trials were conducted with chlorantraniliprole on the raw agricultural commodity cucumbers.   Three MOR trials were conducted. The locations of the field trials were selected to represent the regions with most greenhouse cucumber production. A foliar broadcast spray of chlorantraniliprole was applied at the rate of 0.1 lb ai/A/application. The cucumber plants received two applications targeted at 1 day before harvest (1-day PHI) of mature crop.   Concurrent recoveries from control samples fortified at
       0.010 to 5.0 mg/kg of chlorantraniliprole ranged from 96 to 100%.  The maximum residue level in cucumbers was 0.0738 ppm which is below the currently established tolerance of 0.5 ppm for cucurbits.

       Greenhouse residue trials were conducted with chlorantraniliprole on the raw agricultural  commodity  tomatoes.     Four  MOR  trials  were  conducted.  The locations of the field trials were selected to represent the regions with most greenhouse tomato production. A foliar broadcast spray of chlorantraniliprole was applied at the rate of 0.1 lb ai/A/application. The tomato plants received two applications targeted at 1 day before harvest (1-day PHI) of mature crop. Concurrent recoveries from control samples fortified at 0.010 to 5.0 mg/kg of chlorantraniliprole ranged from 98 to 102%.  The maximum residue level in tomatoes was 0.102 ppm which is below the currently established tolerance of 1.4 ppm for fruiting vegetables.

       Field   residue   trials   were   conducted   with   chlorantraniliprole   on   the   raw agricultural commodities cherry, papaya and lychee.   Two MOR trials were conducted for each commodity. A foliar broadcast spray of chlorantraniliprole was applied at the rate of 0.1 lb ai/A/application. The test plants received two applications targeted at 1, 3, 6-7, 9-10 and 13-15 days before harvest of mature crop.  Concurrent recoveries from control samples fortified at 0.010 to 5.0 mg/kg of chlorantraniliprole ranged from 97 to 123%.   In cherry samples, the total residues of chlorantraniliprole ranged from 0.151 to 0.192 ppm in samples taken at 1 day PHI, 0.135 to 0.162 ppm in samples taken at 3 days PHI, 0.105 to 0.120 ppm in samples taken at 6 days PHI, 0.132 to 0.151 ppm in samples taken at 10 days PHI and 0.0994 to 0.129 ppm in samples taken at 15 days PHI. In lychee samples, the total residues of chlorantraniliprole ranged from 0.402 to 0.500 ppm in samples taken at 1 day PHI, 0.306 to 0.442 ppm in samples taken at 3 days PHI, 0.363 to 0.386 ppm in samples taken at 6 days PHI, 0.239 to 0.313 ppm in samples taken at 9 days PHI and 0.308 to 0.337 ppm in samples taken at 13 days PHI. In papaya samples, the total residues of chlorantraniliprole ranged from
       0.284 to 0.292 ppm in samples taken at 1 day PHI, 0.204 to 0.224 ppm in samples taken at 3 days PHI, 0.196 to 0.211 ppm in samples taken at 7 days PHI, 0.164 to
       0.196 ppm in samples taken at 10 days PHI and 0.137 to 0.142 ppm in samples taken at 14 days PHI.

       Field   residue   trials   were   conducted   with   chlorantraniliprole   on   the   raw agricultural commodities onions and dill.  Five MOR trials were conducted with onions and two MOR trials were conducted with dill. The locations of the field

       trials were selected to represent the regions with most onion and spice production. A foliar broadcast spray of chlorantraniliprole was applied at the rate of 0.1 lb ai/A/application. The onion and dill crops received two applications targeted at 1 day before harvest (1-day PHI) of mature crop.   Concurrent recoveries from control samples fortified at 0.010 to 5.0 mg/kg of chlorantraniliprole ranged from
       81 to 117%.  The total residues of chlorantraniliprole ranged from 0.371 to 1.50 ppm in fresh green onion samples taken at 1 day PHI. The total residues of chlorantraniliprole ranged from 0.900 to 11.1 ppm in dried green onion samples taken at 1 day PHI. The total residues of chlorantraniliprole ranged from 15.4 to
       24.3 ppm in dill seed samples taken at 1 day PHI.

       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

 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
 ---------------

 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 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.

 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-FCID(TM), 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-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 MRLs have been established or are expected to be established supporting registrations in 92 countries.   Codex MRLs have also been established for chlorantraniliprole on numerous crops.