Document ID: EPA-HQ-OPP-2009-0261-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-05-06T04:00Z

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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 rice grain, rice straw,
rice hulls and crayfish 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 by establishing 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  the raw agricultural
and processed commodities: Acerola at 2 ppm; Almond, hull at 5 ppm;
Apple, wet pomace at 2.5 ppm; Artichoke at 4 ppm; Asparagus at 13 ppm;
Atemoya at 4 ppm; Avocado at 4 ppm; Banana at 4 ppm; Biriba at 4 ppm;
Black sapote at 4 ppm; Cacao bean, bean at  0.15 ppm; Cacao, roasted
beans at 1.4 ppm; Canistel at 4 ppm;  Cattle, fat at 0.3 ppm; Cattle,
liver at 0.3 ppm; Cattle, meat at 0.05 ppm; Cattle, meat byproducts
except liver at 0.2 ppm; Cherimoya at 4 ppm; Chocolate at 3 ppm; Citrus,
dried pulp at 14 ppm; Cocoa powder at 3 ppm; Coffee, bean, green at 0.5
ppm; Coffee, instant at 2.5 ppm; Corn, sweet at 0.02 ppm; Corn, field,
grain at 0.04 ppm; Corn, pop at 0.04 ppm; Corn, aspirated grain
fractions at 2 ppm; Corn, processed commodities at 0.1 ppm; Crambe at
0.3 ppm; Crayfish at 8 ppm; Custard apple  at 4 ppm; Egg at 0.1 ppm;
Feijoa at 4 ppm; Figs at 4 ppm; Forage, fodder, and straw of cereal
grains, group 16, forage and fodder at 25 ppm; Forage, fodder, and straw
of cereal grains, group 16, hay and straw at 90 ppm; Fruit, caneberry,
subgroup 13-07A at 1.8 ppm; Fruit, citrus, group 10 at 1.4 ppm; Fruit,
pome, group 11 at 1.2 ppm; Fruit, small vine climbing, subgroup 13-07D
at 2.5 ppm; Fruit, stone, group 12 at 4 ppm; Goat, fat at 0.3 ppm; Goat,
liver at 0.3 ppm; Goat, meat at 0.05 ppm; Goat, meat byproducts, except
liver at 0.2 ppm; Grass forage, fodder and hay, group 17, forage and
fodder at 25 ppm; Grass forage, fodder and hay, group 17, hay and straw
at 90 ppm; Guava at 4 ppm; Hare's ear mustard at 0.3 ppm; Herbs and
spices, subgroup 19A, dried at 90 ppm; Herbs and spices, subgroup 19A,
fresh at 25 ppm; Herbs and spices, subgroup 19B, spices at 7 ppm; Hops
at 90 ppm; Horse, fat at 0.3 ppm; Horse, liver at 0.3 ppm; Horse, meat
at 0.05 ppm; Horse, meat byproducts, except liver at 0.2 ppm; Ilama at 4
ppm; Jaboticaba at 2 ppm; Jojoba at 0.3 ppm; Lesquerella at 0.3 ppm;
Longan at 4 ppm; Lunaria at 0.3 ppm; Lychee at 2 ppm; Mango at 4 ppm;
Milk at 0.05 ppm; Milkweed at 0.3 ppm; Mint at 9 ppm; Mustard at 0.3
ppm; Non-grass animal feeds, group 18, forage and fodder at 13 ppm;
Non-grass animal feeds, group 18, hay and straw at 45 ppm; Non-grass
animal feeds, group 18, seeds at 3.5 ppm; Nut, tree, group 14 at 0.04
ppm; Oil radish at 0.3 ppm; Okra at 0.7 ppm; Olive at 4 ppm; Olive, oil
at 40 ppm; Papaya at 2 ppm; Passionfruit at 2 ppm; Peanut at 0.1 ppm;
Peanut hay at 90 ppm; Persimmon at 4 ppm; Pineapple at 1.5 ppm;
Pineapple process residue at 3 ppm; Pistachio at 0.04 ppm; Pomegranate
at 4 ppm; Poppy seed at 0.3 ppm; Poultry, fat at 0.02 ppm; Poultry, meat
at 0.02 ppm; Poultry, meat byproducts at 0.02 ppm; Prickly pear cactus
at 13 ppm; Pulasan at 4 ppm; Raisins at 5 ppm; Rambutan at 4 ppm;
Rapeseed/canola at 0.3 ppm; Rice, grain at 0.15 ppm; Rice, hulls at 0.3
ppm; Rice, straw at 0.3 ppm; Rose hip at 0.3 ppm; Sapodilla at 4 ppm;
Sapote, mamey at 4 ppm; Sesame at 0.3 ppm; Sheep, fat at 0.3 ppm; Sheep,
liver at 0.3 ppm; Sheep, meat at 0.05 ppm; Sheep, meat byproducts,
except liver at 0.2 ppm; Soursop at 4 ppm; Spanish lime at 4 ppm; Star
apple at 4 ppm; Starfruit at 4 ppm; Strawberries at 1 ppm; Sugar apple
at 4 ppm; Sugarcane molasses at 420 ppm; Sugarcane, cane at 14 ppm;
Tallowwood at 0.3 ppm; Tea oil plant at 0.3 ppm; Ti palm, leaves at 13
ppm; Ti palm, roots at 0.1 ppm; Vegetables, Brassica leafy, group 5 at
11 ppm; Vegetables, foliage of legume, group 7, forage/vines at 30 ppm;
Vegetables, foliage of legume, group 7, hay at 90 ppm; Vegetables,
legume, group 6, except soybeans, at 2 ppm; Vegetables, tuberous and
corm, subgroup 1C at 0.01 ppm; Wax jambu at 4 ppm; White sapote
(casimiroa) and other cultivars and/or hybrids at 4 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. 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.  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. 

3. Analytical method.  

Analytical methods were previously submitted which permit determination
of chlorantraniliprole residues in meat, milk, poultry and eggs at
appropriate detection levels.  

4. Magnitude of residues. 

Alfalfa

Fifteen trials (14 MOR, 1 decline) were conducted on alfalfa (Medicago
sativa) at the rate of 0.10 lb ai/A/application for two applications.
Two cuttings were made at each site. A second treated plot was
established at 13 of the 15 trial sites in which a single application
was made at approximately 5 to 7 days before commercial seed harvest.

Maximum residues of chlorantraniliprole found in replicate treated
alfalfa forage, hay, and seed samples collected at 0-day PHI were 11,
47, and 1.8 ppm, respectively. Residues were comparable in forage and
hay following the first application/cutting and the second
application/cutting. These data indicate the first application does not
carryover and impact residues in the raw commodities. By extrapolation,
even though only one application was made in these residue trials prior
to seed harvest, residues in seed would not be impacted by an earlier
application/cutting of alfalfa forage and/or hay prior to a second
application/cutting for seed harvest.

Caneberry

Eight residue field trials were conducted in the US and Canada. 

Two foliar applications of 0.1 lb ai/A was applied to the treated plots.
 Commercially mature raspberries and blackberries were collected 3 days
after the last application. At one site, additional samples were
collected at 1, 7, and 10 days after the last application for a decline
study. The maximum residue in caneberry fruit was 0.543 ppm at the 3-day
PHI. In the decline study, maximum residues in caneberry at 1-, 3-, 7-,
and 10-day PHIs were 0.15, 0.0744, 0.0921, and 0.0671 ppm, respectively.

Coffee

Four MOR tests on coffee in Brazil were conducted with a
chlorantraniliprole 35WG formulation.  Three applications were made at
52.5 g ai/ha 14 days apart with samples collected at 7 and 21 days after
the last application (DALA).  Maximum residues determined in the green
coffee beans (dried coffee beans with hulls removed) at 21 DALA were
0.115 mg/kg.  Since the application rate in the US is proposed to be
110.5 g ai/ha, use of proportionality for the application rate and a
worst-case assumption that all residues are from the last application,
indicates maximum residues in green coffee beans treated according to
the US use pattern would be 0.24 mg/kg.

Dry Soybean

An MOR/decline study on field-grown soybeans was conducted in Japan. 
The study was conducted at 2 sites making 3 applications at 25 g ai/ha
7 days apart and harvested 7 days after the final application.  Maximum
residues determined in the dried shelled soybeans were 0.03 mg/kg. Since
the application rate in the US is proposed to be 109.5 g ai/ha, use of
proportionality for the application rate indicates maximum residues in
dried, shelled beans would be 0.13 mg/kg.

Field Corn

Seven corn trials (5 MOR, 2 MOR/Processing) were conducted with
chlorantraniliprole on corn (Zea mays) as a foliar broadcast spray at
the rate of 0.10 lb ai/A/application.  At two of the seven test
locations, a foliar broadcast spray was applied at the rate of 0.50 lb
ai/A to generate grain samples.  This exaggerated rate corresponds to 5(
the maximum proposed use rate and the grain samples were analyzed to
determine if processing trials were necessary.  Two applications were
made to the treated plots at 7-day intervals with the last application
occurring approximately 14 days before normal grain and stover harvest. 
Maximum residues of chlorantraniliprole found in 1(-treated corn forage
collected 1 day after Application 2 and 1(-treated corn grain and
stover samples collected 14 days (( 1) after Application 2 were 3.1,
0.12, and 5.3 ppm, respectively.  Maximum residues of
chlorantraniliprole found in aspirated grain fractions generated from
1(-treated corn grain collected 14 days (( 1) after Application 2 were
0.34 ppm.  Maximum residues of chlorantraniliprole found in 5(-treated
corn grain collected 14 days (( 1) after Application 2 were 0.004 ppm.  

Green Beans

Field studies with chlorantraniliprole on field and protected green
beans (fresh legume vegetables) with two applications of foliar
broadcast sprays on 7-day intervals at the targeted rate of 40 g 
ai/ha, for a nominal seasonal application rate of 80 g ai/ha.  At the
protected green bean tests, there was a target application rate of 60 g
ai/ha for each of two applications, 7-days apart, for a nominal seasonal
application rate of 120 g ai/ha.

Maximum chlorantraniliprole residues in field and protected green bean
edible pods were 0.25 and 0.30 mg/kg at 1 day after the last
application.

Green Soybean

Field-grown soybeans were treated at 2 sites with 3 applications at 25
g ai/ha 7 days apart with a 3-day PHI for green soybeans (in pods). 
Maximum residues determined in the green soybeans (in pods) were 0.32
mg/kg. Since the application rate in the US is proposed to be 109.5 g
ai/ha, use of proportionality for the application rate indicates maximum
residues in edible-podded beans in the US would be 1.4 ppm.

Japanese radish roots and tops

Turnip roots and tops

Field-grown Japanese radishes and turnips were treated with 3
applications at 50 g ai/ha 7 days apart and harvested 1-day post
application.  Maximum residues determined in the roots and tops were
0.03 and 3.36 ppm, respectively.  Residues were higher in the turnip
roots than in the Japanese radish roots.  Since the application rate in
the US is proposed to be 109.5 g ai/ha, use of proportionality for the
application rate indicates maximum residues in roots and tops in the US
would be 0.07 and 7.4 ppm, respectively.

Mint

Five sites were treated twice with 0.1 lb ai/A chlorantraniliprole.
Commercially mature mint tops (leaves and stems) were collected 3 days
after the final application. Oil was steam distilled from additional
samples.

The maximum residues in mint tops were 6.24 ppm. No residues above the
detection limit (0.01 ppm) were observed in mint oil. 

Polebeans

Polebeans (an edible-podded bean) were treated with 6 applications at 20
g ai/ha 5 days apart and harvested 1 day following the last application.
 Residues determined in the pole beans were 0.057 mg/kg.  Since the
application rate in the US is proposed to be 109.5 g ai/ha, use of
proportionality for the application rate and a worst-case assumption
that all residues are from the last application, indicates residues in
edible-podded beans in the US would be 0.31 mg/kg.

Rice

The active ingredient was applied as a seed treatment at a use rate of
0.10 mg ai/seed (10.3 fl oz fp/100 lb seed) approximately 2x the
maximum proposed seed treatment rate at 16 locations.  The target
seeding rate of 120 lb seed/acre resulted in treatment rates of 560 g
ai/ha (0.50 lb ai/acre) approximately 4x the maximum proposed
application rate.  Rice grain and straw were harvested at maturity with
PHIs ranging from 113 to 148 days.  Average rice grain residues for the
sixteen trials were 0.045 ppm with a maximum residue of 0.087 ppm and a
highest average field trial (HAFT) of 0.086 ppm.  Average rice straw
residues for the sixteen trials were 0.12 ppm with a maximum residue of
0.25 ppm.

Two trials were completed to determine residues in processed rice
commodities.  The active ingredient was applied as a seed treatment at a
use rate of 0.20 mg ai/seed approximately 4x the maximum proposed seed
treatment rate.  The target seeding rate of 120 lb seed/acre resulted in
treatment rates of 1120 g ai/ha (1.0 lb ai/acre) approximately 8x the
maximum proposed ground rate.  Rice grain was harvested at maturity with
PHIs ranging from 120 to 148 days.  Chlorantraniliprole residues in
polished rice produced by mechanical processing with or without
parboiling were reduced (all samples had <0.010 mg/kg residues) relative
to the unprocessed grain with an average processing factor of 0.12. 
Chlorantraniliprole residues in bran and hulls produced by mechanical
processing with or without parboiling concentrated relative to the
unprocessed grain with average processing factors of 1.7 and 3.4,
respectively.

Strawberry

Strawberries were treated at 2 sites with 2 applications at 50 g ai/ha 7
days apart and harvested 1 day post application.  Maximum residues
determined in the strawberries were 0.30 mg/kg.  Since the application
rate in the US is proposed to be 110.5 g ai/ha, use of proportionality
for the application rate, indicates maximum residues in strawberries in
the US would be 0.66 mg/kg.

Sweet Corn

Fourteen sweet corn field trials were treated with four foliar
applications at a rate of approximately 0.1 lb ai/A each, for a total of
approximately 0.4 lb ai/A (one location received a fifth application of
0.1 lb ai/A was made for a total of 0.5 lb ai/A). The first two
applications were made approximately 1 day apart and timed so that corn
could be harvested at the milk stage, in the form of forage and kernels
plus cob with husks removed (K+CWHR) at a 1-day PHI. These samples
represent the sweet corn RACs. 

The last two applications were made 7(±1) days apart so that
commercially mature field corn RACs could be collected in the form of
stover and grain at a 14(±1) day PHI. In one case, the second
application was mistakenly done 12 days after the first; an extra
application was scheduled for two days after the second application and
one day before the first harvest, to correct the oversight. The results
from the trials show that the maximum residues of chlorantraniliprole in
forage and kernels plus cob with husks removed were 6.46 and <0.01 ppm,
respectively.  The maximum residues found on field grain and on stover
were 0.0159 ppm and 14.4 ppm, respectively.

Tea

A tea magnitude of residues study was conducted at 2 sites with 1
application at 200 g ai/ha.  Samples were collected at 3, 7, 14, and 21
days after the application.  The tea plants were covered with
cheesecloth for the final 10 days prior to harvest. Maximum residues
determined in dried tea leaves at the target 3-day PHI were 39 mg/kg. 
Since the seasonal application rate in the US is proposed to be 219 g
ai/ha, use of proportionality for the application rate, indicates
maximum residues in dried tea in the US would be 43 mg/kg at a 3-day
PHI.  Extrapolating these residues based on an average decline rate
indicates maximum residues in dried tea in the US would be 53 mg/kg at
a 1-day PHI.

Turnip roots and tops

Data are summarized above in conjunction with the Japanese radish roots
and tops data.

Crayfish

Estimated chlorantraniliprole residues in whole crayfish farmed in rice
paddies planted with treated rice seed at the maximum rate are
3.75 mg/kg.  These estimated residues support an MRL/tolerance of 8
mg/kg in crayfish.

Livestock

Mammalian: Based on the cattle feeding study and the estimated dietary
burdens for cattle and swine, DuPont proposes MRLs/tolerances for
livestock commodities and provides estimates of residues in livestock
commodities to be used in dietary risk assessment.

The highest cattle and swine dietary burdens are estimated to be 2.1 and
0.078 mg chlorantraniliprole/kg bw/day (54.4 and 2.5 mg/kg feed)
calculated for dairy cows and swine in Canada and the United States.  In
the cattle feeding study, dosing was made at target levels of 1 mg/kg
feed, 3 mg/kg feed, 10 mg/kg feed and 50 mg/kg feed in the animal diet
on a dry weight basis.  The estimated swine dietary burden (2.5 mg/kg
feed) is well represented by the feeding levels studied and the
estimated highest cattle dietary burden (54.4 mg/kg feed) is not
significantly higher than the highest feeding level of 50 mg/kg.  Thus,
these dietary burdens and the residues observed in the cattle feeding
study were used to estimate residues and propose tolerances for cattle,
goat, horse, sheep, and swine commodities.  

No MRLs/tolerances are proposed for swine commodities.

MRLs/tolerances of 0.3, 0.3, 0.2, 0.05, and 0.05 mg/kg are proposed in
cattle fat, liver, kidney, muscle, and milk, respectively. These
MRLs/tolerances should also be applied to goat, horse, and sheep
commodities.

MRLs/tolerances should be used for worst-case dietary risk assessment
for mammalian fat, liver, kidney, and muscle.

Milk residues of 0.15 mg/kg are proposed for worst-case dietary risk
assessment.

Poultry

A poultry feeding study will not provide additional useful information
for dietary risk assessment, MRL/tolerance proposals or residue
definition and, therefore, the poultry feeding study should be waived.

The poultry metabolism study was conducted by dosing laying hens at 0.87
mg/kg body weight (bw)/day (10.311 mg/kg feed equivalents/day),
approximately 5X the estimated dietary burden of 0.17 mg
chlorantraniliprole/kg bw (2.706 mg/kg feed) for 14 consecutive days.
The total radioactive residues in the eggs were at steady state levels
after 7-9 days and major radioactive compounds were identified and
quantified in the eggs and tissues.  The interpolated residue levels for
1X dietary burden using the results from the metabolism study are
adequate for defining the residue for dietary risk assessment, setting
MRLs/tolerances, and estimating residues for use in dietary risk
assessment.

The residue definition for dietary risk assessment for eggs is proposed
to include only chlorantraniliprole and IN-GAZ70.

MRLs/tolerances of 0.1 and 0.02 mg/kg are proposed in eggs and poultry
commodities except eggs, respectively.  Residues for worst-case dietary
risk assessment of 0.25 and 0.02 mg/kg are proposed in eggs and poultry
commodities except eggs, respectively. 

B. Toxicological Profile

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 and GP Maximization)	Category IV

Category IV

Category IV

Category IV

Category IV

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

	Formulated products are as equally low in toxicity 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).  Chlorantraniliprole 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.  Although reductions in body weight gain and
food efficiency occurred at the high dose, overall body weight was
unaffected.  Therefore, the NOAEL for male and female rats was 1000
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 in the liver accompanied by
hepatocellular hypertrophy and increased liver weight.  

	In rats, there were no adverse effects on any 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™, 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 MRLs have been established or are soon expected be established
on other crops in the European Union, Australia and Canada.  Codex MRLs
for chlorantraniliprole on various crops are being sought.

E. I. du Pont de Nemours & Company                                      
             	Chlorantraniliprole

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