Indoxacarb; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food, 37851-37856 [05-12950]
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Federal Register / Vol. 70, No. 125 / Thursday, June 30, 2005 / Notices
after an oral dose of 1 mg/kg. The
mentioned metabolite is a minor
component in the serum of all 3 species
with 5, 4, and 7% of the total
radioactivity in serum in the guinea pig,
rat and mouse respectively.
Measurement of the concentration of
PP796 in the serum of rats and dogs
after prolonged dosing showed:
i. No difference in the levels between
sexes.
ii. A linear dose - peak serum level
response and a linear dose - area under
the curve response in dogs throughout
the range of doses tested (i.e. 0.15-1.5
mg/kg/day) with slopes of 0.26 ug/ml
per 1 mg/kg dose and 1.18 ug.hr/ml per
1 mg/kg dose, respectively. Similar
effects were noted in rats in the dose
range up to 1.25 mg/kg with slopes of
0.11 ug/ml and 0.52 ug.hr/ml per 1 mg/
kg dose, i.e. about half the response seen
in dogs.
iii. A biological half-life of < 3 hours
in the dog.
There was no evidence to suggest that
serum concentration significantly
increased or decreased after prolonged
administration, hence PP796 is unlikely
to be cumulative.
7. Metabolite toxicology. The toxicity
of metabolites of PP796 has not been
studied. Given the level of anticipated
exposure and the available animal
metabolism data, it is unlikely
metabolites of this inert will be of
concern.
8. Endocrine disruption. There is no
evidence that PP796 has hormone
disrupting activity.
C. Aggregate Exposure
1. Dietary exposure. The residues of
PP796 on raw agricultural commodities,
due to application in paraquat
dichloride formulations, are expected to
be negligible. This is due to the low
concentration in end use formulations
(< 0.2% w/w) and the use pattern for
paraquat dichloride, a nonselective
herbicide. In the 1997 RED for paraquat
dichloride the Theoretical Maximum
Residue Concentrations (TMRC) were
calculated for the then existing
tolerances for paraquat dichloride.
Based on the conservative approach
(Tier 1), the chronic exposure of the
U.S. population, and of the most highly
exposed population subgroup (nonnursing infants less than 1-year old), to
paraquat was calculated to be 0.000442
and 0.001398 mg/kg body weight/day,
respectively (pg. 55 of RED Paraquat
Dichloride).
A formulation that contained the
maximum proposed amount of PP796
(0.3% w/w) would contain 110 times
more paraquat ion than PP796
(assuming a technical containing 33.0%
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w/w paraquat ion). Therefore, the
theoretical chronic exposure can be
estimated by dividing the paraquat
exposure numbers by 110, resulting in
0.00000402 mg/kg body weight/day for
the U.S. population and 0.0000127 mg/
kg body weight/day for the most
exposed population (non-nursing
infants (<1 years old).
i. Food. Exposures to PP796 from food
are expected to be negligible.
ii. Drinking water. Exposures to PP796
from drinking water are expected to be
negligible due to the low concentration
in the end-use products. There are no
aquatic uses of products containing
paraquat dichloride.
2. Non-dietary exposure. End use
products containing paraquat dichloride
are restricted use pesticides. There are
no residential or homeowner uses. Nondietary exposure is expected to be
negligible.
D. Cumulative Effects
PP796 is only approved for use in
paraquat dichloride formulations. There
is no evidence for a common
mechanism of toxicity with other
substances. Therefore, there is no
expectation that the use of PP796 as an
inert ingredient in paraquat
formulations (up to 0.3 % w/w) would
contribute to any cumulative toxicity
arising from exposure to other
substances having a common
mechanism of toxicity.
E. Safety Determination
1. U.S. population. Based on the
toxicity data presented and the very low
level of exposure, Syngenta Crop
Protection, Inc. believes that there is
reasonable certainty that no harm will
result to the general U.S. population by
increasing the emetic level in paraquat
dichloride formulations. PP796 is
included in paraquat dichloride
formulations as an added safety factor as
required by USEPA. The 1987 Guidance
for the Reregistration of Pesticide
Products Containing Paraquat
Dichloride as the Active Ingredient
states on page 27 that ‘‘The Agency is
continuing to require that an emetic
cleared under 40 CFR 180.1001(b) and
(c) be incorporated into all
manufacturing use and end use
products containing paraquat. Rationale:
Based on the history of poisoning by
accidental ingestion of paraquat and
partial effectiveness of therapeutic
treatment after exposure, the Agency
determined that an emetic is needed in
formulations to induce rapid vomiting
thereby reducing absorption of
paraquat.’’ Syngenta Crop Protection,
Inc. has developed a novel formulation
which significantly improves acute oral
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37851
toxicity of paraquat dichloride
formulations in vomiting species. This
novel formulation improvement is
largely accomplished by adding a
gelling agent which slows the
movement of paraquat into the intestine
where most absorption occurs.
Improving human safety is the primary
reason for this request, as the emetic
level is being increased to ensure
adequate absorption from the gel in the
stomach.
2. Infants and children. Based on the
toxicity data presented and the very low
level of exposure, Syngenta Crop
Protection, Inc. believes that there is
reasonable certainty that no harm will
result to infants and children by
increasing the emetic level in paraquat
formulations. PP796 is included in
paraquat dichloride formulations as an
added safety factor as required by U.S.
EPA.
F. International Tolerances
Import tolerances are not required for
this inert ingredient. It is listed as a
requirement in FAO Specification
56.302/TK (2003). The FAO
specification requires that ‘‘An effective
emetic, having the following
characteristics, be incorporated into the
technical. It must be rapidly absorbed
(more rapidly than paraquat) and be
quick acting. Emesis must occur in
about half an hour in at least 50% of
cases. It must be an effective (strong)
stimulant of the emetic center of the
brain, to produce effective emesis. The
emetic effect should have a limited
‘action period’, of about two to three
hours, to allow effective treatment of
poisoning. It must act centrally on the
emetic center in the brain. It must not
be a gastric irritant because, as paraquat
itself is an irritant, this could potentiate
the toxicity of paraquat. It must be
toxicologically acceptable. It must have
a short half-life in the body (to comply
with the need for a limited action
period). It must be compatible with, and
stable in, the paraquat formulation and
not affect the herbicidal efficacy or
occupational use of the product. To
date, the only compound found to meet
these requirements is 2-amino-4,5dihydro-6-methyl-4-propyl-s-triazole(1,5a)pyrimidin-5-one (PP796). PP796
must be present in the technical at not
less than 0.8 g/l. The method for
determination of PP796 content is
available from the Plant Protection
Officer, FAO Plant Production and
Protection Division.’’
[FR Doc. 05–12922 Filed 6–29–05; 8:45 am]
BILLING CODE 6560–50–S
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Federal Register / Vol. 70, No. 125 / Thursday, June 30, 2005 / Notices
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
Environmental Protection
Agency (EPA).
ACTION: Notice.
AGENCY:
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.
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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
https://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 https://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
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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 email 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
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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 https://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
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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.
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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 (IR4), 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 7chloro-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 7chloro-2,5-dihydro-2[[(methoxycarbonyl)[4(trifluoromethoxy) phenyl]
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petitions. Additional data may be
needed before EPA rules on the
petitions.
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
Guideline
A. Residue Chemistry
The active ingredient in the end-use
formulation, DuPontTM Avaunt
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 (DPXKN128), the application rates have been
normalized on an indoxacarb (DPXKN128) 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
Title
(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
Results
Category
870.1100
Acute oral toxicity
Lethal Dose LD50:1,730 mg/kg (male
rat) LD50: 268 mg/kg/ (female rat)
Category II
870.1200
Acute dermal toxicity
LD50: >5,000 mg/kg (rat)
Category IV
870.1300
Acute inhalation toxicity
Lethal Concentration LC50: >5.5 mg/
L (male rat) (70% MUP)
Category IV
870.2400
Primary eye irritation
Effects reversed within 72 hours
(rabbit)
Category III
870.2500
Primary dermal irritation
No irritation (rabbit)
Category IV
870.2600
Skin sensitization
Sensitizer (guinea pig)
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
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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
F0generation and potential treatmentrelated changes in spleen weights for
the higher groups of the F1 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 F1 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
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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 DPXMP062. 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
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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 indoxacarbinduced 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
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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 INJT333 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 5days; 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
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Fmt 4703
Sfmt 4703
37855
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 byproducts, 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.
E:\FR\FM\30JNN1.SGM
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37856
Federal Register / Vol. 70, No. 125 / Thursday, June 30, 2005 / Notices
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
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16:26 Jun 29, 2005
Jkt 205001
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 nonfood uses have been approved. Nonoccupational, 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.
PO 00000
Frm 00112
Fmt 4703
Sfmt 4703
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 othernonoccupational 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/DPXMP062 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 nonoccupational 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
ENVIRONMENTAL PROTECTION
AGENCY
[IN–162–1; FRL–7930–8]
Adequacy Status of Evansville,
Indiana, 8-Hour Ozone Redesignation
and Maintenance Plan for
Transportation Conformity Purposes
Environmental Protection
Agency (EPA).
AGENCY:
E:\FR\FM\30JNN1.SGM
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]]>Agencies
[Federal Register Volume 70, Number 125 (Thursday, June 30, 2005)]
[Notices]
[Pages 37851-37856]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-12950]
[[Page 37852]]
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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.
-----------------------------------------------------------------------
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 https://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 https://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 https://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
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Guideline Title Results Category
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.1100 Acute oral toxicity Lethal Dose LD50:1,730 mg/kg (male Category II
rat) LD50: 268 mg/kg/ (female rat)
---------------------------------------------
870.1200 Acute dermal toxicity LD50: >5,000 mg/kg (rat) Category IV
---------------------------------------------
870.1300 Acute inhalation toxicity Lethal Concentration LC50: >5.5 mg/ Category IV
L (male rat) (70% MUP)
---------------------------------------------
870.2400 Primary eye irritation Effects reversed within 72 hours Category III
(rabbit)
---------------------------------------------
870.2500 Primary dermal irritation No irritation (rabbit) Category IV
---------------------------------------------
870.2600 Skin sensitization Sensitizer (guinea pig)
--------------------------------------------------------------------------------------------------------------------------------------------------------
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
F0generation and potential treatment-related changes in
spleen weights for the higher groups of the F1 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
F1 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
