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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.

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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: By mail: [EPA Product Manager], Product
Manager (PM), Registration Division, (7505), Office of Pesticide
Programs, Environmental Protection Agency, Ariel Rios Building 1200
Pennsylvania Avenue, N. W., Washington, DC 20460.  Office location and
telephone number:                   , Arlington, VA., (703) 306-0415. 
Email: manager.product@epa.gov.

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 tree nuts, group 14;
almond hulls and pistachios 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. 

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 Company, DuPont Crop Protection, 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-chlor
o-2-pyridinyl)-1H-pyrazole-5-carboxamide in or on tree nuts, group 14 at
0.07 ppm; on almond hulls at 5 ppm and on pistachios at 0.07 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. Field residue trials were conducted on tree
nuts (almonds and pecans) at 12 locations.  The treated plots received 2
applications of chlorantraniliprole at the maximum proposed labeled rate
7 days apart with the last application occurring 10 days before harvest.
 Residues in almond nutmeats ranged from 0.003 to 0.009 ppm, in almond
hulls from 0.37 to 1.7 ppm and in pecan nutmeats from <0.003 to 0.016
ppm.

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 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.  

Evaluation Model (DEEM-FCID™, 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

 

Ȇ

B*

B*

, including tree nuts, are being sought and are expected to be
established in 2009.

E. I. DuPont de Nemours & Company                                       
            	Chlorantraniliprole

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