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http://www.epa.gov/fedrgstr/EPA-PEST/2005/June/Day-30/p12950.htm

[Federal Register: June 30, 2005 (Volume 70, Number 125)]
[Notices]
[Page 37852-37856]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr30jn05-93]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2005-0149; FRL-7718-9]

Indoxacarb; Notice of Filing a Pesticide Petition to Establish a
Tolerance for a Certain Pesticide Chemical in or on Food
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket identification (ID) number OPP-
2005-0149, must be received on or before August 1, 2005.
ADDRESSES: Comments may be submitted electronically, by mail, or
through hand delivery/courier. Follow the detailed instructions as
provided in Unit I. of the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: Shaja R. Brothers, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 308-3194; e-mail address:
brothers.shaja@epa.gov .

SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
• Crop production (NAICS 111)
• Animal production (NAICS 112)
• Food manufacturing (NAICS 311)
• Pesticide manufacturing (NAICS 32532)
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

1. Docket. EPA has established an official public docket for this
action under docket ID number OPP-2005-0149. The official public docket
consists of the documents specifically referenced in this action, any
public comments received, and other information related to this action.
Although a part of the official docket, the public docket does not
include Confidential Business Information (CBI) or other information
whose disclosure is restricted by statute. The official public docket
is the collection of materials that is available for public viewing at
the Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall #2, 1801 S. Bell St., Arlington, VA. This docket
facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The docket telephone number is (703) 305-5805.

2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/ .
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although not all docket materials may be
available electronically, you may still access any of the publicly
available docket materials through the docket facility identified in
Unit I.B.1. Once in the system, select ``search,'' then key in the
appropriate docket ID number.
Certain types of information will not be placed in the EPA Dockets.
Information claimed as CBI and other information whose disclosure is
restricted by statute, which is not included in the official public
docket, will not be available for public viewing in EPA's electronic
public docket. EPA's policy is that copyrighted material will not be
placed in EPA's electronic public docket but will be available only in
printed, paper form in the official public docket. To the extent
feasible, publicly available docket materials will be made available in
EPA's electronic public docket. When a document is selected from the
index list in EPA Dockets, the system will identify whether the
document is available for viewing in EPA's electronic public docket.
Although not all docket materials may be available electronically, you
may still access any of the publicly available docket materials through
the docket facility identified in Unit I.B. EPA intends to work towards
providing electronic access to all of the publicly available docket
materials through EPA's electronic public docket.

For public commenters, it is important to note that EPA's policy is
that public comments, whether submitted electronically or in paper,
will be made available for public viewing in EPA's electronic public
docket as EPA receives them and without change, unless the comment
contains copyrighted material, CBI, or other information whose
disclosure is restricted by statute. When EPA identifies a comment
containing copyrighted material, EPA will provide a reference to that
material in the version of the comment that is placed in EPA's
electronic public docket. The entire printed comment, including the
copyrighted material, will be available in the public docket.
Public comments submitted on computer disks that are mailed or
delivered to the docket will be transferred to EPA's electronic public
docket. Public comments that are mailed or delivered to the docket will
be scanned and placed in EPA's electronic public docket. Where
practical, physical objects will be photographed, and the photograph
will be placed in EPA's electronic public docket along with a brief
description written by the docket staff.

C. How and To Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through hand
delivery/courier. To ensure proper receipt by EPA, identify the
appropriate docket ID number in the subject line on the first page of
your comment. Please ensure that your comments are submitted within the
specified comment period. Comments received after the close of the
comment period will be marked ``late.'' EPA is not required to consider
these late comments. If you wish to submit CBI or information that is
otherwise protected by statute, please follow the instructions in Unit
I.D. Do not use EPA Dockets or e-mail to submit CBI or information
protected by statute.

1. Electronically. If you submit an electronic comment as
prescribed in this unit, EPA recommends that you include your name,
mailing address, and an e-mail address or other contact information in
the body of your comment. Also, include this contact information on the
outside of any disk or CD ROM you submit, and in any

[[Page 37853]]

cover letter accompanying the disk or CD ROM. This ensures that you can
be identified as the submitter of the comment and allows EPA to contact
you in case EPA cannot read your comment due to technical difficulties
or needs further information on the substance of your comment. EPA's
policy is that EPA will not edit your comment, and any identifying or
contact information provided in the body of a comment will be included
as part of the comment that is placed in the official public docket,
and made available in EPA's electronic public docket. If EPA cannot
read your comment due to technical difficulties and cannot contact you
for clarification, EPA may not be able to consider your comment.

i. EPA Dockets. Your use of EPA's electronic public docket to
submit comments to EPA electronically is EPA's preferred method for
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/
edocket/ , and follow the online instructions for submitting comments.
Once in the system, select ``search,'' and then key in docket ID number
OPP-2005-0149. The system is an ``anonymous access'' system, which
means EPA will not know your identity, e-mail address, or other contact
information unless you provide it in the body of your comment.
ii. E-mail. Comments may be sent by e-mail to opp-docket@epa.gov ,
Attention: Docket ID Number OPP-2005-0149. In contrast to EPA's
electronic public docket, EPA's e-mail system is not an ``anonymous
access'' system. If you send an e-mail comment directly to the docket
without going through EPA's electronic public docket, EPA's e-mail
system automatically captures your e-mail address. E-mail addresses
that are automatically captured by EPA's e-mail system are included as
part of the comment that is placed in the official public docket, and
made available in EPA's electronic public docket.

iii. Disk or CD ROM. You may submit comments on a disk or CD ROM
that you mail to the mailing address identified in Unit I.C.2. These
electronic submissions will be accepted in WordPerfect or ASCII file
format. Avoid the use of special characters and any form of encryption.

2. By mail. Send your comments to: Public Information and Records
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001, Attention: Docket ID Number OPP-2005-0149.

3. By hand delivery or courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Office of Pesticide
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall
#2, 1801 S. Bell St., Arlington, VA, Attention: Docket ID
Number OPP-2005-0149. Such deliveries are only accepted during the
docket's normal hours of operation as identified in Unit I.B.1.

D. How Should I Submit CBI to the Agency?
Do not submit information that you consider to be CBI
electronically through EPA's electronic public docket or by e-mail. You
may claim information that you submit to EPA as CBI by marking any part
or all of that information as CBI (if you submit CBI on disk or CD ROM,
mark the outside of the disk or CD ROM as CBI and then identify
electronically within the disk or CD ROM the specific information that
is CBI). Information so marked will not be disclosed except in
accordance with procedures set forth in 40 CFR part 2.
In addition to one complete version of the comment that includes
any information claimed as CBI, a copy of the comment that does not
contain the information claimed as CBI must be submitted for inclusion
in the public docket and EPA's electronic public docket. If you submit
the copy that does not contain CBI on disk or CD ROM, mark the outside
of the disk or CD ROM clearly that it does not contain CBI. Information
not marked as CBI will be included in the public docket and EPA's
electronic public docket without prior notice. If you have any
questions about CBI or the procedures for claiming CBI, please consult
the person listed under FOR FURTHER INFORMATION CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing your
comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide copies of any technical information and/or data you
used that support your views.
4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
5. Provide specific examples to illustrate your concerns.
6. Make sure to submit your comments by the deadline in this notice.
7. To ensure proper receipt by EPA, be sure to identify the docket
ID number assigned to this action in the subject line on the first page
of your response. You may also provide the name, date, and Federal
Register citation.

II. What Action is the Agency Taking?
EPA has received pesticide petitions as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical in or on various food commodities under section 408
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that these petitions contain data or information
regarding the elements set forth in FFDCA section 408(d)(2); however,
EPA has not fully evaluated the sufficiency of the submitted data at
this time or whether the data support granting of the petitions.
Additional data may be needed before EPA rules on the petitions.
List of Subjects
Environmental protection, Agricultural commodities, Feed
additives, Food additives, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: June 21, 2005.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petitions
The petitioner summary of the pesticide petitions is printed below
as required by FFDCA section 408(d)(3). The summary of the petitions
was prepared by the petitioner and represents the view of the
petitioner. The petition summary announces the availability of a
description of the analytical methods available to EPA for the
detection and measurement of the pesticide chemical residues or an
explanation of why no such method is needed.

Interregional Research Project No. 4
PP 5E6911 and PP 5E6926

EPA has received pesticide petitions (PP) 5E6911 and 5E6926 from
Interregional Research Project No. 4 (IR-4), 681 U.S. Highway
#1 South, North Brunswick, NJ 08902-3390 proposing, pursuant to
section 408(d) of the (FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part
180 by establishing tolerances for residues of indoxacarb, (S)-methyl
7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl]
amino]carbonyl]indeno[1,2e] [1,3,4]oxadiazine-4a(3H)-carboxylate] and
its R-enantiomer [(R)-methyl 7-chloro-2,5-dihydro-2-
[[(methoxycarbonyl)[4-(trifluoromethoxy) phenyl]

[[Page 37854]]

amino]carbonyl]indeno [1,2-e] [1,3,4] oxadiazine-4a(3H)-carboxylate] in
or on the following raw agricultural commodities:

1. PP 5E6911 proposes the establishment of tolerances for leafy
greens, except spinach, subgroup 4A at 10 parts per million (ppm),
spinach at 3.0 ppm, leafy petioles subgroup 4B at 1.5 ppm, fruit, pome,
except pear, group 11 at 1.0 ppm, vegetable, tuberous and corm,
subgroup 1C at 0.01 ppm, and okra at 0.5 ppm.

2. PP 5E6929 proposes the establishment of tolerances for pea,
southern at 0.1 ppm; peppermint, tops at 10 ppm; and spearmint, tops at
10 ppm.

EPA has determined that the petitions contain 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
petitions. Additional data may be needed before EPA rules on the petitions.

A. Residue Chemistry

The active ingredient in the end-use formulation, DuPont\TM\
Avaunt[reg] insecticide, is a 75:25 mixture of two isomers, indoxacarb
(DPX-KN128) and IN-KN127. Only one of the isomers, indoxacarb (DPX-
KN128), has insecticidal activity. Since the insecticidal efficacy is
based on the concentration of indoxacarb (DPX-KN128), the application
rates have been normalized on an indoxacarb (DPX-KN128) basis. The
proposed tolerance expression includes both indoxacarb (DPX-KN128) and
IN-KN127, and the residue method does not distinguish between the
enantiomers. Therefore, residues are reported as the sum of indoxacarb
(DPX-KN128) combined with IN-KN127. Residues of indoxacarb (DPX-KN128)
combined with IN-KN127 will be referred to as KN128/KN127.

1. Plant metabolism. The metabolism of indoxacarb in plants is
adequately understood to support these tolerances. The only significant
residue is the parent compound.

2. Analytical method. The plant residue enforcement method detects
and quanitates indoxacarb in various matrices including sweet corn,
lettuce, tomato, broccoli, apple, grape, cottonseed, tomato, peanut and
soybean commodity samples by high performance liquid chromotography
using ultra-violet detection (HPLC-UV). The limit of quanitation in the
method allows monitoring of crops with indoxacarb residues at or above
the levels proposed in these tolerances.

3. Magnitude of residues. The magnitude of residues for the
proposed tolerances is adequately understood.

B. Toxicological Profile

Formulated products are slightly less acutely toxic than indoxacarb.

1. Acute neurotoxicity study. In an acute neurotoxicity study,
indoxacarb exhibited decreased forelimb grip strength, decreased foot
splay, and some evidence of slightly reduced motor activity, but only
at the highest doses tested. The no observed adverse effect level
(NOAEL) was 100 milligrams/kilogram (mg/kg) for males, and 12.5 mg/kg
for females, based on body weight effects in females 50 mg/kg.

2. Genotoxicty. Indoxacarb, has shown no genotoxic activity in the
following listed in vitro and in vivo tests: Ames-negative; in vitro
mammalian gene mutation Chinese hampster ovary/hypoxanthine quanine
phopphoribosyl transferase (CHO/HGPRT)-negative; in vitro unscheduled
DNA synthesis-negative; in vitro chromosomal aberration-negative; and
in vivo mouse micronucleus-negative.

3. Reproductive and developmental toxicity. The results of a series
of studies indicated that there were no reproductive, developmental or
reproductive hazards associated with the use of indoxacarb. In a 2-
generation rat reproduction study, the parental NOAEL was 1.5 mg/kg/
day. The parental NOAEL was based on observations of reduced weight
gain and food consumption for the higher concentration groups of the
F 0 generation and potential treatment-related changes in
spleen weights for the higher groups of the F 1 generation.
There was no effect on mating or fertility. The NOAEL for fertility and
reproduction was 6.4 mg/kg/day. The offspring NOAEL was 1.5 mg/kg/day,
and was based on the reduced mean pup weights noted for the
F 1 litters of the higher concentration groups. The effects
on pup weights occurred only at a maternal effect level and may have
been due to altered growth and nutrition in the dams. In studies
conducted to evaluate developmental toxicity potential, indoxacarb was
neither reproductive nor uniquely toxic to the conceptus (i.e., not
considered a developmental toxin). Developmental studies conducted in
rats and rabbits demonstrated that the rat was more susceptible than
the rabbit to the maternal and fetal effects of DPX- MP062.
Developmental toxicity was observed only in the presence of maternal
toxicity. The NOAEL for maternal and fetal effects in rats was 2 mg/kg/
day based on body weight effects and decreased food consumption at 4
mg/kg/day. The NOAEL for developmental effects in fetuses was >4 mg/kg/
day. In rabbits, the maternal and fetal NOAELS were 500 mg/kg/day based
on body weight effects, decreased food consumption in dams and
decreased weight and delayed ossification in fetuses at 1,000 mg/kg/day.

4. Subchronic toxicity. Subchronic 90-day feeding studies were
conducted with rats, mice, and dogs. In a 90-day feeding study in rats,
the NOAEL was

[[Page 37855]]

3.1 and 2.1 mg/kg/day for males and females, respectively. In male
rats, the NOAEL was based on decreased body weight and nutritional
parameters, mild hemolytic anemia and decreased total protein and
globulin concentration. In female rats, the NOAEL was based on
decreased body weight and food efficiency. In a subchronic
neurotoxicity study in rats, there was no evidence of neurotoxicity at
11.9 and 6.09 mg/kg/day, the highest dose tested for males and females,
respectively. The subchronic NOAEL in dogs (5.0 mg/kg/day, M/F) was
based on hemolytic anemia. Erythrocyte values for most dogs were within
a range that would be considered normal for dogs in a clinical setting.
Mice were less sensitive to indoxacarb than the rats or dogs. NOAELs
(23 mg/kg/day, males, 16 mg/kg/day, females) were based on mortality
(males only); increased reticulocytes and Heinz bodies and decreased
body weight, weight gain, food consumption, food efficiency; and
increased clinical signs (leaning to one side and/or with abnormal gait
or mobility) (females only). In a 28-day repeated dose dermal study,
the NOAEL was 50 mg/kg/day based on decreased body weights, body weight
gains, food consumption, and food efficiency in females, and changes in
hematology parameters, the spleen and clinical signs of toxicity in
both sexes in rats.

5.Chronic toxicity. Chronic studies with indoxacarb were conducted
on rats, mice, and dogs to determine carcinogenic potential and/or
chronic toxicity of the compound. Effects generally similar to those
observed in the 90-day studies were seen in the chronic studies.
Indoxacarb, was not carcinogenic in rats or mice. The chronic NOAEL in
male rats was 5 mg/kg/day based on body weight and nutritional effects.
In females, the NOAEL of 2.1 mg/kg/day was based on body weight and
nutritional changes, as well as biologically significant hematologic
changes at 3.6 mg/kg/day and above. Hemolytic effects were present only
through the 6-month evaluation and only in females. The regenerative
nature of indoxacarb-induced hemolytic anemia was demonstrated by the
absence of significant changes in indicators of circulating erythrocyte
mass at later evaluations. In mice, the chronic NOAEL of 2.6 mg/kg/day
for males was based on deceased body weight and weight gain effects and
food efficiency at 13.8 mg/kg/day and above. The NOAEL for females was
4.0 mg/kg/day based on body weight nutritional effects, neurotoxicity,
and clinical signs at 20 mg/kg/day. In dogs, the chronic NOAEL was
about 2.3 and 2.4 mg/kg/day in males and females, respectively based on
hemolytic effects similar to those seen in the subchronic dog study.

6. Animal metabolism. Animal metabolism has been studied in the
rat, hen, and cow and is well understood. In contrast to crops,
indoxacarb is extensively metabolized in animals.

i. Poultry. In poultry, hens were fed at 10 ppm/day for 5 days, 87-
88% of the total administered dose was excreted; parent comprised 51-
54% of the total dose in excreta. Concentrations of residues in eggs
were low, 0.3-0.4 of the total dose, as were the concentrations of
residues in muscle, 0.2% of the total dose. Parent and metabolite IN-
JT333 were not detected in egg whites; only insecticidally inactive
metabolites were identified. Parent and IN-JT333 were found in egg
yolks; however, their concentrations were very low-0.01-0.02 ppm.
Concentrations of parent and IN-JT333 in muscle were at or below the
limit of quantitation, (LOQ) 0.01 ppm.

ii. Poultry feeding study. A poultry feeding study was not
conducted for the initial section 3 registration because finite
concentrations of residues would not be expected based on the low
concentration of residues in the metabolism study. However, the Agency
has required a poultry feeding study as a condition of registration for
indoxacarb. The study was submitted on October 31, 2003. Once the
Agency has determined the components of the tolerance expression,
poultry meat, fat, by-products and egg tolerances will be proposed.

iii. Cattle. For the cow study, the cattle were fed at 10 ppm/day
for 5-days; approximately 20% of the total administered dose was
excreted in urine and 53-60% was excreted in feces in 5-days. Four-
tenths to 1.2% of the total dose in urine was parent indicating
extensive metabolism; parent represented 46-68% of the fecal activity.
Thus, most residues were not absorbed; those residues that were
absorbed were extensively metabolized. Less than 1% of the total
administered dose was in milk, most of which was parent compound. The
insecticidally active metabolite IN-JT333 was not found in milk.
Residues in muscle represented less than 0.01% of the total
administered dose most of which was parent. IN-JT333 was not detected
in muscle. No other metabolites were seen above 10% of the dose, thus
only parent and IN-JT333 were monitored in the cattle feeding study.

iv. Cattle feeding study. A cattle feeding study was conducted with
indoxacarb at doses of 7.5 ppm, 22.5 and 75 ppm. The mean KN128/KN127
concentrations were proportional to the dosing level in whole milk,
skim milk, cream, muscle, fat, liver and kidney. Based on final residue
values for the respective commodities contributing to the cattle diet,
the anticipated dietary burden in dairy cattle is 51.7 ppm and the
anticipated dietary burden in beef cattle is 49.1 ppm. The proposed
grape use will not increase the animal dietary burden. Based on
standard curves constructed from data in the cattle feeding study,
KN128/KN127 concentrations at the 51.7 ppm feeding level are 0.123 ppm
for whole milk, 0.033 ppm for skim milk, and 1.46 ppm for cream. The
KN128/KN127 concentrations at the 49.1 ppm feeding level are 0.046 ppm
for muscle, 1.37 ppm for fat, 0.012 ppm for liver, and 0.026 ppm for
kidney. Tolerances have been established at 1.5 ppm in fat (cattle,
goat, horse, sheep and hog), 0.05 ppm in meat, 0.03 ppm in meat by-
products, 0.15 ppm in milk, and 4.0 ppm in milk fat.\

7. Metabolite toxicology. In rats, indoxacarb was readily absorbed
at the low dose 5 mg/kg, but saturated at the high dose 150 mg/kg.
Indoxacarb, was metabolized extensively, based on very low excretion of
parent compound in bile and extensive excretion of metabolized dose in
the urine and feces. Some parent compound remained unabsorbed and was
excreted in the feces. No parent compound was excreted in the urine.
The retention and elimination of the metabolite IN-JT333 from fat
appeared to be the overall rate determining process for elimination of
radioactive residues from the body. Metabolites in urine were cleaved
products containing only one radiolabel, while the major metabolites in
the feces retained both radiolabels. Major metabolic reactions included
hydroxylation of the indanone ring, hydrolysis of the carboxylmethyl
group from the amino nitrogen and the opening of the oxadiazine ring,
which gave rise to cleaved products. Metabolites were identified by
mass spectral analysis, NMR, UV and/or by comparison to standards
chemically synthesized or produced by microsomal enzymes.

8. Endocrine disruption. Lifespan, and multi-generational bioassays
in mammals, acute, and subchronic studies on aquatic organisms and
wildlife did not reveal endocrine effects. Any endocrine related
effects would have been detected in this definitive array of required
tests. The probability of any such effect due to agricultural uses of
indoxacarb is negligible.

[[Page 37856]]

C. Aggregate Exposure

1. Dietary exposure--i.Food. The chronic, and acute dietary
exposure resulting from the currently approved use of indoxacarb on
apples, crop group 5 brassica vegetables, cotton, pears, peppers, sweet
corn, tomatoes, eggplant, alfalfa, head and leaf lettuce, peanuts,
potatoes, soybeans, cranberries current section 18 use and the proposed
uses on grapes, leafy brassica, leafy greens crop subgroup 4A except
spinach, spinach, leaf petioles crop subgroup 4B, tuberous and corm
vegetables crop subgroup 1C, pome fruits crop group 11 except pear,
okra, pea southern and mint are well within acceptable limits for all
sectors of the population.

Chronic dietary exposure. The Dietary Exposure Evaluation Model
(DEEM), Exponent, Inc., formerly Novigen Sciences, Inc., Version 7.87,
was used to conduct the chronic dietary exposure assessment for the
U.S. general population with the RfD of 0.02 mg/kg/day based on a NOAEL
of 2.0 mg/kg/day from the subchronic rat feeding study, the subchronic
rat neurotoxicity study, and the chronic/carcinogenicity study and
using an uncertainty factor of 100.
The analysis used overall mean field trial values, processing
factors and projected peak percent crop treated values. Secondary
residues in milk, meat and poultry products were also included in the
analysis. The chronic dietary exposure to indoxacarb for the U.S.
population is 0.000185 mg/kg/day. The exposure of the most highly
exposed subgroup in the population, children age 1-2 years, is 0.000347
mg/kg/day. The exposure for all infants and females 20+ not pregnant
and nursing is 0.000126 mg/kg/day and 0.000179 mg/kg/day respectively.
The results of this analysis indicate large margins of safety for each
population subgroup, and very low probability of effects resulting from
chronic exposure to indoxacarb.

Acute dietary exposure. DEEM, Exponent, Inc., formerly Novigen
Sciences, Inc., Version 7.87, was used to conduct the acute dietary
exposure assessment for the U.S. general population with the RfD of
0.12 mg/kg/day based on the NOAEL of 12.5 mg/kg in the acute
neurotoxicity study and an uncertainty factor of 100. The acute RfD for
females 13-50 years of age is 0.02 mg/kg/day, based on the NOAEL of 2
mg/kg/day observed in the developmental rat toxicity study and using an
uncertainty factor of 100.
The Tier 3, analysis used distributions of field trial residue data
adjusted for projected peak percent crop treated. Secondary residues in
milk, meat and poultry products were also included in the analysis. The
acute dietary exposure to indoxacarb for the U.S. population is
0.020267 mg/kg/day. The exposure of the most highly exposed subgroup in
the population, children age 3-5 years, is 0.005358 mg/kg/day, and the
exposure for all infants is 0.018458 mg/kg/day. The results of this
analysis indicate large margins of safety for each population subgroup,
and very low probability of effects resulting from acute exposure to
indoxacarb.

ii. Drinking water. Indoxacarb, is highly unlikely to contaminate
groundwater resources due to its immobility in soil, low water
solubility, high soil sorption, and moderate soil half-life. Based on
the PRZM/EXAMS and SCI-GROW models the estimated environmental
concentrations (EECs) of indoxacarb and its R-enantiomer for acute
exposures are estimated to be 6.84 parts per billion (ppb) for surface
water and 0.0025 ppb for groundwater. The EECs for chronic exposures
are estimated to be 0.316 ppb for surface water and 0.0025 ppb for
groundwater. Drinking water levels of comparison (DWLOCs), theoretical
upper allowable limits on the pesticides concentration in drinking
water, were calculated to be much higher than the EECs. The chronic
DWLOCs ranged from 198 to 697 ppb. The acute DWLOCs ranged from 440 to
3,890 ppb. Thus, exposure via drinking water is acceptable.

2. Non-dietary exposure. Indoxacarb, product registrations for
residential non-food uses have been approved. Non-occupational, non-
dietary exposure for DPX-MP062 has been estimated to be extremely
small. Therefore, the potential for non-dietary exposure is insignificant.

D. Cumulative Effects

EPA's consideration of a common mechanism of toxicity is not
necessary at this time because there is no indication that toxic
effects of indoxacarb would be cumulative with those of any other
chemical compounds. Oxadiazine chemistry is new, and indoxacarb has a
novel mode of action compared to currently registered active ingredients.

E. Safety Determination

1. U.S. population. Dietary and occupational exposure will be the
major routes of exposure to the U.S. population. The chronic dietary
exposure to indoxacarb utilized 1% of the RfD for the U.S. general
population. The acute dietary exposure to indoxacarb will utilize 17%
of the aPAD acute population adjusted dose for the overall U.S. general
population.
Using only Pesticide Handler Exposure Database levels A and B those
with a high level of confidence, margin of exposures (MOEs) for
occupational exposure are 650 for mixer/loaders, and 1,351 for airblast
applicators worst-case. Based on the completeness and reliability of
the toxicity data and the conservative exposure assessments, there is a
reasonable certainty that no harm will result from the chronic and
acute aggregate exposure of residues of indoxacarb, including all
anticipated dietary exposure and all othernon-occupational exposures
for the U.S. general population.

2. Infants and children. The chronic dietary exposure to
indoxacarb for the most highly exposed population subgroup, children
ages 1-2 and 3-5, utilized 2% of the RfD. For all infants, the chronic
exposure accounts for 1% of the RfD. For acute exposure at the 99.9th
percentile, children ages 3-5 utilized 30% aPAD, and all infants
utilized and 15% aPAD.

Residential uses of indoxacarb/DPX-MP062 have been approved and
exposure is calculated to be extremely minimal. The estimated levels of
indoxacarb in drinking water are well below the DWLOC. Based on (a) the
completeness and reliability of the toxicity data; (b) the lack of
toxicological endpoints of special concern; (c) the lack of any
indication that children are more sensitive than adults to indoxacarb;
and (d) the conservative exposure assessment, there is a reasonable
certainty that no harm will result to infants and children from the
aggregate exposure of residues of indoxacarb, including all anticipated
dietary exposure and all other non-occupational exposures. Accordingly,
there is no need to apply an additional safety factor for infants and
children.

F. International Tolerances

To date, numerous tolerances exist for indoxacarb residues in
various food and feed crops, and foods of animal origin in at least 25
countries.
[FR Doc. 05-12950 Filed 6-29-05; 8:45 am]
BILLING CODE 6560-50-S