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Indoxacarb (DuPont). April 16,
2003.
Proposed 3-year temporary pesticide tolerance
for residues in or on peaches at 10 ppm. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/2003/April/Day-16/p9340.htm
[Federal Register: April 16, 2003 (Volume 68, Number 73)]
[Proposed Rules]
[Page 18582-18592]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr16ap03-24]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2003-0125; FRL-7302-3]
Indoxacarb; Proposed Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: This document proposes to establish a temporary tolerance for
combined residues of Indoxacarb, (S)-methyl 7-chloro-2,5-dihydro-2-
[[(methoxy carbonyl) [4-(trifluor omethoxy)phenyl]amino]carbonyl]
indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate + its R-enantiomer
[(R)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoro
methoxy)phenyl]amino]carbonyl]indeno [1,2-e][1,3,4]oxadiazine-4a(3H)-
carboxylate in or on peaches under the Federal Food, Drug, and Cosmetic
Act (FFDCA), as amended by the Food Quality Protection Act of 1996
(FQPA). This action is in response to university extension specialists,
DuPont Crop Protection, and EPA's combined efforts to generate the
information necessary for use of the reduced risk pesticide,
Indoxacarb, on peaches for control of oriental fruit moth and plum
cuculio. This proposed temporary tolerance supports a non-crop destruct
experimental use permit (EUP) under section 5 of the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) authorizing use of
Indoxacarb on peaches in Georgia, Michigan, New Jersey, Pennsylvania,
South Carolina, and West Virginia. This regulation proposes to
establish a maximum permissible level for residues of Indoxacarb in
this food commodity pursuant to section 408(e) of FFDCA, as amended by
FQPA.
DATES: Comments, identified by docket ID number OPP-2003-0125, must be
received on or before May 1, 2003.
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: Rita Kumar, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave, NW., Washington, DC 20460-0001; telephone
number: (703) 308-8291; e-mail address: kumar.rita@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 Code 111)
¥ Animal production (NAICS Code 112)
¥ Food manufacturing (NAICS Code 311)
¥ Pesticide manufacturing (NAICS Code 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 identification (ID) number OPP-2003-0125. 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,
1921 Jefferson Davis Hwy., 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/. A frequently updated
electronic version of 40 CFR part 180 is available at http://www.access.
gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfr180_00.html, 
a beta site currently under development. To access the OPPTS Harmonized
Guidelines referenced in this document, go directly to the guidelines
at http://www.epa.gov/opptsfrs/home/guidelin.htm.
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. 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
[[Page 18583]]
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 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-2003-0125. 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-2003-0125. 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-2003-0125.
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, 1921 Jefferson Davis Hwy., Arlington, VA., Attention:
Docket ID Number OPP-2003-0125. 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.
[[Page 18584]]
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. Offer alternative ways to improve the proposed rule or
collection activity.
7. Make sure to submit your comments by the deadline in this
document.
8. 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. Background and Statutory Findings
EPA, in cooperation with DuPont Crop Protection and university
extension specialists, under section 408(e) of the FFDCA, 21 U.S.C.
346a, is proposing to establish a tolerance for combined residues of
the insecticide Indoxacarb, in or on peaches at 10.0 parts per million
(ppm). This action is in response to university extension specialists,
DuPont, and EPA's combined efforts to generate the information
necessary for registration of the reduced risk pesticide, Indoxacarb,
on peaches for control of oriental fruit moth and plum cuculio. This
proposed temporary tolerance supports a non-crop destruct experimental
use permit (EUP) under section 5 of FIFRA authorizing use of Indoxacarb
on peaches in Georgia, Michigan, New Jersey, Pennsylvania, South
Carolina, and West Virginia. Section 5 of FIFRA authorizes EPA to issue
an experimental use permit for a pesticide. This provision was not
amended by FQPA. EPA has established regulations governing such
experimental use permits in 40 CFR part 172. Section 408(r) of FFDCA
authorizes EPA to issue temporary tolerances for pesticide residues
from FIFRA experimental use permits.
Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) of the FFDCA defines ``safe'' to mean that ``there is
a reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) of the FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical residue * *
*''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 of the FFDCA and a complete
description of the risk assessment process, see the final rule on
Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).
III. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed
the available scientific data and other relevant information in support
of this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure, consistent with section
408(b)(2) of the FFDCA, for a tolerance for combined residues of
Indoxacarb on peaches at 10.0 ppm. EPA's assessment of exposures and
risks associated with establishing the tolerance follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by Indoxacarb are
discussed in Table 1 of this unit as well as the no-observed-adverse-
effect-level (NOAEL) and the lowest-observed-adverse-effect-level
(LOAEL) from the toxicity studies reviewed.
Table 1.-- Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
Guideline No. Study Type Results
----------------------------------------------------------------------------------------------------------------
870.3100 90-Day oral toxicity DPX-MP062
rodents NOAEL = M 3.1 mg/kg/day
F 2.1 mg/kg/day
LOAEL = M 6.0 mg/kg/day, F 3.8 mg/kg/day
based on decreased body weight, body
weight gain, food consumption and food
efficiency.
----------------------------------------------------------------------------------------------------------------
870.3150 90-Day oral toxicity in DPX-JW062
nonrodents NOAEL = 5.0 mg/kg/day
LOAEL = 19 mg/kg/day based on hemolytic
anemia, as indicated by decrease in HGB,
RBCs; increases in platelets, increased
reticulocytes; and secondary
histopathologic findings indicative of
blood breakdown (pigment in Kupffer cells,
renal tubular epithelium, and spleen and
bone marrow macrophages); increase in
splenic EMH; and RBC hyperplasia in bone
marrow in dogs.
----------------------------------------------------------------------------------------------------------------
870.3200 21/28-Day dermal toxicity DPX-MP062
NOAEL = 2,000 mg/kg/day
LOAEL = >2,000 mg/kg/day in rats.
DPX-MP062
NOAEL = 50 mg/kg/day
LOAEL = 500 mg/kg/day based on decreased
body weights, body weight gains, food
consumption, and food efficiency in F*,
and changes in hematology parameters
(increased reticulocytes), the spleen
(increased absolute and relative weight M*
only, gross discoloration), clinical signs
of toxicity in both sexes in rats.
----------------------------------------------------------------------------------------------------------------
[[Page 18585]]
870.3700 Prenatal developmental in DPX-MP062
rodents Maternal NOAEL = 2.0 mg/kg/day
LOAEL = 4.0 mg/kg/day based on decreased
mean body weights, body weight gains, food
consumption.
Developmental NOAEL = 2.0 mg/kg/day
LOAEL = 4.0 mg/kg/day based on decreased
fetal weights.
DPX-JW062
Maternal NOAEL = 10 mg/kg/day
LOAEL = 100 mg/kg/day based on mortality,
clinical signs, and decreased mean body
weights, body weight gains, and food
consumption.
Developmental NOAEL = 10 mg/kg/day
LOAEL = 100 mg/kg/day based on decreased
numbers of live fetuses/litter.
DPX-JW062
Maternal NOAEL = 1.1 mg/kg/day
LOAEL = 2.2 mg/kg/day based on decreased
mean body weights, body weight gains, food
consumption, and food efficiency.
Developmental NOAEL = 1.1 kg/day
LOAEL = 2.2 mg/kg/day based on decreased
fetal body weights.
----------------------------------------------------------------------------------------------------------------
870.3700 Prenatal developmental in DPX-JW062 - rabbits
nonrodents Maternal NOAEL = 500 mg/kg/day
LOAEL = 1,000 mg/kg/day based on slight
decreases in maternal body weight gain and
food consumption.
Developmental NOAEL = 500 mg/kg/day
LOAEL = 1,000 mg/kg/day based on decreased
fetal body weights and reduced
ossification of the sternebrae.
----------------------------------------------------------------------------------------------------------------
870.3800 Reproduction and fertility DPX-JW062
effects Parental/Systemic NOAEL = 1.5 mg/kg/day
LOAEL = 4.4 mg/kg/day based on decreased
body weights, body weight gains, and food
consumption of F0 females, and increased
spleen weights in the F0 and F1 females
Reproductive NOAEL = 6.4 mg/kg/day
LOAEL = 6.4 mg/kg/day
Offspring NOAEL = 1.5 mg/kg/day
LOAEL = 4.4 mg/kg/day based on decrease in
the body weights of the F1 pups during
lactation.
----------------------------------------------------------------------------------------------------------------
870.4100 Chronic toxicity rodents DPX-JW062
NOAEL = M 5, F 2.1 mg/kg/day
LOAEL = M 10, F 3.6 mg/kg/day based on
decr. body weight, body weight gain, and
food consumption and food efficiency;
decreased HCT, HGB and RBC at 6 months in
F only.
no evidence of carcinogenic potential
----------------------------------------------------------------------------------------------------------------
870.4100 Chronic toxicity dogs DPX-JW062
NOAEL = M 2.3, F 2.4 mg/kg/day
LOAEL = M 18, F 19 mg/kg/day based on decr.
HCT, HGB and RBC; increased Heinz bodies
and reticulocytes and associated secondary
microscopic changes in the liver, kidneys,
spleen, and bone marrow; increased
absolute and relative liver weights.
----------------------------------------------------------------------------------------------------------------
870.4200 Carcinogenicity rats DPX-JW062 see 870.4100. No evidence of
carcinogenicity
----------------------------------------------------------------------------------------------------------------
870.4300 Carcinogenicity mice DPX-JW062
NOAEL = M 2.6, F4.0 mg/kg/day
LOAEL = M 14, F 20 mg/kg/day based on
decreased body weight, body weight gain,
and food efficiency and clinical signs
indicative of neurotoxicity.
No evidence of carcinogenicity
----------------------------------------------------------------------------------------------------------------
870.5100 Gene Mutation DPX-MP062 strains TA97a, TA98, TA100 and
TA1535 of S. typhimurium and strain
WP2(uvrA) of E. coli were negative for
mutagenic activity both with and without
S9 activation for the concentration range
10-5,000 [mu]g/plate
DPX-JW062 strains TA97a, TA98, TA100 and
TA1535 of S. typhimurium and strain
WP2(uvrA) of E. coli were negative for
mutagenic activity both with and without
S9 activation for the concentration range
10-5,000 [mu]g/plate.
----------------------------------------------------------------------------------------------------------------
[[Page 18586]]
870.5300 Gene Mutation DPX-MP062 negative for mutagenic activity
for the following concentration ranges:
3.1-250 [mu]g/mL (-S9); 3.1-250 [mu]g/mL
(+S9)
DPX-JW062
negative for mutagenic activity for the
following concentration ranges:
Negative;100-1,000 [mu]g/mL (-S9); 100-
1,000 [mu]g/mL (+S9), precipitate >=1,000
[mu]g/mL
----------------------------------------------------------------------------------------------------------------
870.5375 Cytogenetics DPX-MP062
no evidence of chromosomal aberrations
induced by the test article over
background for the following concentration
ranges: 15.7-1,000 [mu]g/mL (+/-S9)
DPX-JW062
no evidence of chromosomal aberrations
induced by the test article over
background for the following concentration
ranges: 19-300 [mu]g/mL (- S9), 19-150
[mu]g/mL (+S9); partial insoluble and
cytotoxicity >=150 [mu]g/mL
----------------------------------------------------------------------------------------------------------------
870.5395 Cytogenetics DPX-MP062
no evidence of mutagenicity for the
following dose ranges: 3,000-4,000 mg/kg -
males; 1,000-2,000 mg/kg - females
DPX-JW062
no evidence of mutagenicity at 2,500 or
5,000 mg/kg
----------------------------------------------------------------------------------------------------------------
870.5550 Other Effects DPX-MP062
no evidence of mutagenic activity at the
following concentration range: 1.56-200
[mu]g/mL; cytotoxicity was seen at
concentrations of >=100 [mu]g/mL
DPX-JW062
No evidence of mutagenic activity at the
following concentration range: 0.1-50
[mu]g/mL, cytotoxicity observed at >=50
[mu]g/mL
----------------------------------------------------------------------------------------------------------------
870.6200 Acute neurotoxicity DPX-MP062
screening battery NOAEL = M 100, F 12.5 mg/kg
LOAEL = M 200 mg/kg based on decreased body
weight gain, decreased food consumption,
decreased forelimb grip strength, and
decreased foot splay. F 50 mg/kg based on
decreased body weight, body weight gain,
and food consumption
DPX-JW062
NOAEL= M > 2,000 mg/kg
= F < 500 mg/kg
LOAEL > M 2,000 mg/kg
F < 500 mg/kg based on clinical signs,
decreased body weight gains and food
consumption, and FOB effects
----------------------------------------------------------------------------------------------------------------
870.6200 Subchronic neurotoxicity DPX-MP062
screening battery NOAEL = M 0.57, F 0.68 mg/kg/day
LOAEL = M 5.6, F 3.3 mg/kg/day based on
decreased body weight and alopecia
----------------------------------------------------------------------------------------------------------------
870.7485 Metabolism and Both DPX-MP062 and DPX-JW062 were
pharmacokinetics extensively metabolized and the
metabolites were eliminated in urine,
feces, and bile. The metabolite profile
for DPX-JW062 was dose dependent and
varied quantitatively between males and
females. Differences in metabolite
profiles were also observed for the
different label positions (indanone and
trifluoromethoxyphenyl rings). All biliary
metabolites undergo further
biotransformation in the gut. The proposed
metabolic pathway for both DPX-MP062 and
DPX-JW062 has multiple metabolites bearing
one of the two ring structures (see 870-
4100 chronic toxicity rodents above).
----------------------------------------------------------------------------------------------------------------
B. Toxicological Endpoints
The dose at which no adverse effects are observed (the NOAEL) from
the toxicology study identified as appropriate for use in risk
assessment is used to estimate the toxicological level of concern
(LOC). However, the lowest dose at which adverse effects of concern are
identified (the LOAEL) is sometimes used for risk assessment if no
NOAEL was achieved in the toxicology study selected. An uncertainty
factor (UF) is applied to reflect uncertainties inherent in the
extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns. An UF of 100 is routinely used, 10X to account for
interspecies differences and 10X for intra species differences.
For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by the
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor is
retained due to concerns unique to the FQPA, this additional factor is
applied to the RfD by dividing the RfD by such additional factor. The
acute or chronic Population Adjusted Dose (aPAD or cPAD) is a
modification of the RfD to accommodate this type of FQPA Safety Factor
(SF).
For non-dietary risk assessments (other than cancer) the UF is used
to determine the LOC. For example, when 100 is the appropriate UF (10X
to account for interspecies differences and 10X for intraspecies
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and
compared to the LOC.
The linear default risk methodology (Q*) is the primary method
currently
[[Page 18587]]
used by the Agency to quantify carcinogenic risk. The Q* approach
assumes that any amount of exposure will lead to some degree of cancer
risk. A Q* is calculated and used to estimate risk which represents a
probability of occurrence of additional cancer cases (e.g., risk is
expressed as 1 x 10-6 or one in a million). Under certain
specific circumstances, MOE calculations will be used for the
carcinogenic risk assessment. In this non-linear approach, a ``point of
departure'' is identified below which carcinogenic effects are not
expected. The point of departure is typically a NOAEL based on an
endpoint related to cancer effects though it may be a different value
derived from the dose response curve. To estimate risk, a ratio of the
point of departure to exposure (MOEcancer = point of
departure/exposures) is calculated. A summary of the toxicological
endpoints for Indoxacarb used for human risk assessment is shown in
Table 2 of this unit:
Table 2.-- Summary of Toxicological Dose and Endpoints for Indoxacarb for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
FQPA SF* and Level of
Exposure Scenario Dose Used in Risk Concern for Risk Study and Toxicological
Assessment, UF Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary (females 13-50 years of NOAEL = 2.0 mg/kg/day FQPA SF = 1 Developmental rat
age) UF = 100............... aPAD = acute RfD/FQPA toxicity study.
Acute RfD = 0.02 mg/kg. SF = 0.02 mg/kg/day. developmental LOAEL =
4.0 mg/kg/day based on
decreased fetal body
weight.
----------------------------------------------------------------------------------------------------------------
Acute Dietary general population NOAEL = 12.5 mg/kg FQPA SF = 1 Acute oral rat
including infants and children UF = 100............... aPAD = acute RfD/FQPA neurotoxicity study.
Acute RfD = 0.12 mg/kg. SF = 0.12 mg/kg/day. LOAEL = 50 mg/kg based
on decreased body
weight and body weight
gain in females.
----------------------------------------------------------------------------------------------------------------
Chronic Dietary all populations NOAEL = 2.0 mg/kg/day FQPA SF = 1 90-day rat subchronic
UF = 100............... cPAD = chronic RfD/FQPA toxicity study, 90-day
Chronic RfD = 0.02 mg/ SF = 0.02 mg/kg/day. rat neurotoxicity
kg/day. study, chronic/
carcinogenicity rat
study.
LOAEL = 3.3 mg/kg/day
based on decreased
body weight, alopecia,
body weight gain, food
consumption and food
efficiency; decreased
hematocrit, hemoglobin
and red blood cells
only at 6 months. 3.3
mg/kg/day is the
lowest LOAEL of the
three studies.
----------------------------------------------------------------------------------------------------------------
Short-Term Oral (1-7 days) oral study NOAEL= 2.0 LOC for MOE = 100 Developmental rat
(Residential) mg/kg/day (Residential, includes toxicity study.
the FQPA SF) Maternal LOAEL = 4.0 mg/
kg/day based on
decreased mean
maternal body weights,
body weight gains, and
food consumption.
----------------------------------------------------------------------------------------------------------------
Intermediate-Term Oral (1 week - oral study NOAEL= 2.0 LOC for MOE = 100 90-day rat subchronic
several months) (Residential) mg/kg/day (Residential, includes toxicity study.
the FQPA SF) LOAEL = 3.8 mg/kg/day
based on decreased
body weight, body
weight gain, food
consumption and food
efficiency.
----------------------------------------------------------------------------------------------------------------
Short- (1-7 days), Intermediate- (1 dermal study NOAEL= 50 LOC for MOE = 100 28-day rat dermal
week - several months), and Long- mg/kg/day (Occupational) toxicity study.
(several months - lifetime) Term LOC for MOE = 100 LOAEL = 500 mg/kg/day
Dermal (Occupational/Residential) (Residential, includes based on decreased
the FQPA SF). body weights, body
weight gains, food
consumption, and food
efficiency in females,
and changes in
hematology parameters
(increased
reticulocytes), the
spleen (increased
absolute and relative
weight males only,
gross discoloration),
and clinical signs of
toxicity in both
sexes.
----------------------------------------------------------------------------------------------------------------
Short-Term Inhalation (1-7 days) oral study NOAEL= 2.0 LOC for MOE = 100 Rat developmental
(Occupational/Residential) mg/kg/day (inhalation (Occupational) toxicity study.
absorption rate = LOC for MOE = 100 Maternal LOAEL = 4.0 mg/
100%) (Residential, includes kg/day based on
the FQPA SF). decreased mean
maternal body weights,
body weight gains, and
food consumption.
----------------------------------------------------------------------------------------------------------------
Intermediate-Term Inhalation (1 week - oral study NOAEL= 2.0 LOC for MOE = 100 90-day rat subchronic
several months) (Occupational/ mg/kg/day (inhalation (Occupational) toxicity study.
Residential) absorption rate = LOC for MOE = 100 LOAEL = 3.8 mg/kg/day
100%) (Residential, includes based on decreased
the FQPA SF). body weight, body
weight gain, food
consumption and food
efficiency.
----------------------------------------------------------------------------------------------------------------
Long-Term Inhalation (several months - oral study NOAEL= 2.0 LOC for MOE = 100 90-day rat subchronic
lifetime) (Occupational/ mg/kg/day (inhalation (Occupational) toxicity study, 90-day
Residential) absorption rate =100%) LOC for MOE = 100 rat neurotoxicity
(Residential, includes study, chronic/
the FQPA SF). carcinogenicity rat
study.
LOAEL = 3.3 mg/kg/day
based on decreased
body weight, body
weight gain, food
consumption and food
efficiency; decreased
hematocrit, hemoglobin
and red blood cells
only at 6 months.
----------------------------------------------------------------------------------------------------------------
[[Page 18588]]
Cancer (oral, dermal, inhalation) ``not likely'' to be N/A no evidence of
carcinogenic to humans carcinogenicity in
either the rat or
mouse in acceptable
carcinogenicity
studies and no
evidence of
mutagenicity.
----------------------------------------------------------------------------------------------------------------
* The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique
to the FQPA.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. Tolerances have been
established (40 CFR 180.564) for the combined residues of Indoxacarb,
in or on a variety of raw agricultural commodities. Including
tolerances already established for: alfalfa, forage at 10 ppm; alfalfa,
hay at 50 ppm; apple at 1.0 ppm; apple, wet pomace at 3.0 ppm;
brassica, head and stem, subgroup at 5.0 ppm; cattle, goat, horse,
sheep, and hog fat at 1.5 ppm; cattle, goat, horse, sheep, and hog meat
at 0.05 ppm; cattle, goat, horse, sheep , and hog meat byproducts at
0.03 ppm; corn, sweet, forage at 10 ppm; corn, sweet, kernel plus cob
with husk removed at 0.02 ppm; corn, sweet stover at 15 ppm; cotton gin
byproducts at 15 ppm; cotton, undelinted seed at 2.0 ppm; lettuce, head
at 4.0 ppm; lettuce, head at 5.0 ppm; lettuce, leaf at 10.0 ppm; milk
at 0.15 ppm; and milk, fat at 4.0 ppm; peanut at 0.01 ppm; peanut, hay
at 40 ppm; pear at 0.20 ppm; potato at 0.01 ppm; soybean, seed at 0.8
ppm; soybean, aspirated grain fractions at 45 ppm; and vegetables,
fruiting, group at 0.50 ppm. Risk assessments were conducted by EPA to
assess dietary exposures from Indoxacarb in food as follows:
i. Acute exposure. Acute dietary risk assessments are performed for
a food-use pesticide if a toxicological study has indicated the
possibility of an effect of concern occurring as a result of a one day
or single exposure. The Dietary Exposure Evaluation Model (DEEM[reg])
analysis evaluated the individual food consumption as reported by
respondents in the USDA 1989-1992 nationwide Continuing Surveys of Food
Intake by Individuals (CSFII) and accumulated exposure to the chemical
for each commodity. The following assumptions were made for the acute
exposure assessments: An acute Tier 2 (partially refined analysis)
dietary assessment was performed with use of anticipated residues (ARs)
from field trial data, processing factors (where applicable), and
assumed 100% crop treated (CT) for all crops. ARs for meat, milk,
poultry, and eggs (MMPE) raw agricultural commodities (RACs) were
calculated also.
ii. Chronic exposure. In conducting this chronic dietary risk
assessment the DEEM[reg]
analysis evaluated the individual food
consumption as reported by respondents in the USDA1989-1992 nationwide
CSFII and accumulated exposure to the chemical for each commodity. The
following assumptions were made for the chronic exposure assessments:
Chronic exposure estimates are expressed in mg/kg bw/day and as a
percent of the cPAD. The chronic dietary assessment assumed tolerance
level residues, DEEM[reg]
default processing factors, assumed 100% CT
for all crops other than peaches, and 1% CT for the peach EUP (300
acres)(Tier 1).
iii. Cancer. There is no evidence for mutagenicity and there is no
evidence of carcinogenicity in either the rat or mouse. Indoxacarb has
been classified as ``not likely to be carcinogenic in humans'' by the
Agency; therefore, no carcinogenic dietary risk analysis was performed.
iv. Anticipated residue and percent crop treated (PCT) information.
Section 408(b)(2)(E) of the FFDCA authorizes EPA to use available data
and information on the anticipated residue levels of pesticide residues
in food and the actual levels of pesticide chemicals that have been
measured in food. If EPA relies on such information, EPA must require
that data be provided 5 years after the tolerance is established,
modified, or left in effect, demonstrating that the levels in food are
not above the levels anticipated. Following the initial data
submission, EPA is authorized to require similar data on a time frame
it deems appropriate. As required by section 408(b)(2)(E) of the FFDCA,
EPA will issue a data call-in for information relating to anticipated
residues to be submitted no later than 5 years from the date of
issuance of this tolerance.
Section 408(b)(2)(F) of the FFDCA states that the Agency may use
data on the actual percent of food treated for assessing chronic
dietary risk only if the Agency can make the following findings:
Condition 1, that the data used are reliable and provide a valid basis
to show what percentage of the food derived from such crop is likely to
contain such pesticide residue; Condition 2, that the exposure estimate
does not underestimate exposure for any significant subpopulation
group; and Condition 3, if data are available on pesticide use and food
consumption in a particular area, the exposure estimate does not
understate exposure for the population in such area. In addition, the
Agency must provide for periodic evaluation of any estimates used. To
provide for the periodic evaluation of the estimate of PCT as required
by section 408(b)(2)(F) of the FFDCA, EPA may require registrants to
submit data on PCT.
The Agency used PCT information as follows:
Dietary exposure estimates were based on 1% PCT for peaches. This
PCT of 1% was based on the fact that the 2-year experimental use permit
was issued for only 300 acres of peaches to be treated annually, which
amounts to 0.2% of the total peach acreage in the United States. The
reason for using 1% instead of 0.2% is to allow for any uncertainties
in the residue evaluation. Before making this tolerance permanent,
reevaluation of dietary exposure will be performed using all available
information. Other commodities were assumed to be 100% treated.
The Agency believes that the three conditions previously discussed
have been met. With respect to Condition 1, EPA finds that the PCT
information described 1% for Indoxacarb used on peaches is reliable and
has a valid basis. A 2-year EUP has been issued for this use, which
will allow for use of Indoxacarb on 300 acres of peaches in some
eastern states. Before the use can be expanded for treatment of greater
than 300 acres per year, permission from the Agency must be obtained.
As to Conditions 2 and 3, regional consumption information and
consumption information for significant subpopulations is taken into
account through EPA's computer-based model for evaluating the exposure
of significant subpopulations including several regional groups. Use of
this consumption information in EPA's risk
[[Page 18589]]
assessment process ensures that EPA's exposure estimate does not
understate exposure for any significant subpopulation group and allows
the Agency to be reasonably certain that no regional population is
exposed to residue levels higher than those estimated by the Agency.
Other than the data available through national food consumption
surveys, EPA does not have available information on the regional
consumption of food to which Indoxacarb may be applied in a particular
area.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for Indoxacarb in drinking water.
Because the Agency does not have comprehensive monitoring data,
drinking water concentration estimates are made by reliance on
simulation or modeling taking into account data on the physical
characteristics of Indoxacarb.
The Agency uses the Generic Estimated Environmental Concentration
(GENEEC) or the Pesticide Root Zone/Exposure Analysis Modeling System
(PRZM/EXAMS) to estimate pesticide concentrations in surface water and
SCI-GROW (screening concentration in ground water), which predicts
pesticide concentrations in groundwater. In general, EPA will use
GENEEC (a tier 1 model) before using PRZM/EXAMS (a tier 2 model) for a
screening-level assessment for surface water. The GENEEC model is a
subset of the PRZM/EXAMS model that uses a specific high-end runoff
scenario for pesticides. GENEEC incorporates a farm pond scenario,
while PRZM/EXAMS incorporate an index reservoir environment in place of
the previous pond scenario. The PRZM/EXAMS model includes a percent
crop area factor as an adjustment to account for the maximum percent
crop coverage within a watershed or drainage basin.
None of these models include consideration of the impact processing
(mixing, dilution, or treatment) of raw water for distribution as
drinking water would likely have on the removal of pesticides from the
source water. The primary use of these models by the Agency at this
stage is to provide a coarse screen for sorting out pesticides for
which it is highly unlikely that drinking water concentrations would
ever exceed human health levels of concern.
Since the models used are considered to be screening tools in the
risk assessment process, the Agency does not use estimated
environmental concentrations (EECs) from these models to quantify
drinking water exposure and risk as a percent reference dose (%RfD) or
percent population adjusted dose (%PAD). Instead, drinking water levels
of comparison (DWLOCs) are calculated and used as a point of comparison
against the model estimates of a pesticide's concentration in water.
DWLOCs are theoretical upper limits on a pesticide's concentration in
drinking water in light of total aggregate exposure to a pesticide in
food, and from residential uses. Since DWLOCs address total aggregate
exposure to Indoxacarb they are further discussed in the aggregate risk
sections below.
Based on the PRZM/EXAMS and SCI-GROW models the estimated
environmental concentrations (EECs) of Indoxacarb for acute exposures
are estimated to be 13.7 parts per billion (ppb) for surface water and
0.02 ppb for ground water. The EECs for chronic exposures are estimated
to be 3.7 ppb for surface water and 0.02 ppb for ground water.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets). Indoxacarb is not
registered for use on any sites that would result in residential
exposure.
4. Cumulative exposure to substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of the FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
EPA does not have, at this time, available data to determine
whether Indoxacarb has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
Indoxacarb does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that Indoxacarb has a common mechanism of toxicity
with other substances. For information regarding EPA's efforts to
determine which chemicals have a common mechanism of toxicity and to
evaluate the cumulative effects of such chemicals, see the final rule
for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).
D. Safety Factor for Infants and Children
1. In general. Section 408 of the FFDCA provides that EPA shall
apply an additional tenfold margin of safety for infants and children
in the case of threshold effects to account for prenatal and postnatal
toxicity and the completeness of the data base on toxicity and exposure
unless EPA determines that a different margin of safety will be safe
for infants and children. Margins of safety are incorporated into EPA
risk assessments either directly through use of a MOE analysis or
through using uncertainty (safety) factors in calculating a dose level
that poses no appreciable risk to humans.
2. Prenatal and postnatal sensitivity. There is no evidence for
either qualitative or quantitative susceptibility. In all developmental
studies, the developmental endpoint occurs at the maternal LOAEL or
above. Although there is no rabbit developmental toxicity study with
indoxacarb, a study is not required since: (1) studies both using
methyl cellulose comparing JW062 in the rabbit and rat demonstrate that
the toxicity profiles for the rat and rabbit are similar and that the
rat is the more sensitive species; (2) range finding studies in the rat
comparing indoxacarb and JW062 indicate that the maternal and external
developmental toxicity are comparable; (3) a dietary developmental
toxicity study in the rat with JW062 had comparable toxicity to the
gavage indoxacarb rat developmental toxicity study. Developmental
toxicity only occurred at levels at or above maternal toxicity.
The reproduction toxicity study with JW062 can be used to satisfy
the requirement for an indoxacarb study because: 1) systemic toxicity
is at similar doses and of similar magnitude to that observed in
subchronic feeding studies with both indoxacarb and JW062; 2) based on
the data base, the HIARC determined that there was support for using
data from dietary studies conducted with JW062 to satisfy the data
requirements for indoxacarb.
The Agency has required a developmental neurotoxicity study as
confirmatory data due to:
¥ Clinical signs of neurotoxicity in several studies, males
and females, mice and rats, at some doses that do not cause mortality;
¥ Signs of neurotoxicity in the acute neurotoxicity study rat
with indoxacarb (males and females), no mortality in males at
neurotoxic doses;
[[Page 18590]]
¥ Clinical signs of neurotoxicity in the 90-day toxicity
study rat indoxacarb (females), mortality;
¥ Clinical signs of neurotoxicity in the 90-day toxicity
study mouse with the racemic mixture, JW062 (males and females), no
mortality in females at neurotoxic doses, mortality in males;
¥ Clinical signs of neurotoxicity in the 18 month
carcinogenicity study mouse with JW062 (males and females) high and mid
dose, mortality at the high but no mortality at the mid dose; and
¥ Clinical signs of neurotoxicity in the developmental
toxicity study rat with JW062 (using methyl cellulose as the vehicle),
at doses causing mortality.
3. Conclusion. The Agency concluded that the FQPA safety factor
could be reducecd to 1X for Indoxacarb because:
¥ There is no indication of quantitative or qualitative
increased susceptibility of rats or rabbits to in utero and/or
postnatal exposure;
¥ The requirement of a developmental neurotoxicity study is
not based on the criteria reflecting special concern for the developing
fetuses or young which are generally used for requiring a DNT study -
and a safety factor (e.g.: neuropathy in adult animals; CNS
malformations following prenatal exposure; brain weight or sexual
maturation changes in offspring; and/or functional changes in
offspring) - and therefore does not warrant an FQPA safety factor; and
¥ The dietary (food and drinking water) exposure assessments
will not underestimate the potential exposures for infants and children
¥ There are no registered residential uses at the current
time.
E. Aggregate Risks and Determination of Safety
To estimate total aggregate exposure to a pesticide from food,
drinking water, and residential uses, the Agency calculates drinking
water level of comparison (DWLOCs) which are used as a point of
comparison against the model estimates of a pesticide's concentration
in water (EECs). DWLOC values are not regulatory standards for drinking
water. DWLOCs are theoretical upper limits on a pesticide's
concentration in drinking water in light of total aggregate exposure to
a pesticide in food and residential uses. In calculating a DWLOC, the
Agency determines how much of the acceptable exposure (i.e., the PAD)
is available for exposure through drinking water [e.g., allowable
chronic water exposure (mg/kg/day) = cPAD - (average food + residential
exposure)]. This allowable exposure through drinking water is used to
calculate a DWLOC.
A DWLOC will vary depending on the toxic endpoint, drinking water
consumption, and body weights. Default body weights and consumption
values as used by the USEPA Office of Water are used to calculate
DWLOCs: 2 liter (L)/70 kg (adult male), 2L/60 kg (adult female), and
1L/10 kg (child). Default body weights and drinking water consumption
values vary on an individual basis. This variation will be taken into
account in more refined screening-level and quantitative drinking water
exposure assessments. Different populations will have different DWLOCs.
Generally, a DWLOC is calculated for each type of risk assessment used:
acute, short-term, intermediate-term, chronic, and cancer.
When EECs for surface water and groundwater are less than the
calculated DWLOCs, EPA concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which EPA has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because EPA considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses are added in the future, EPA will reassess the potential impacts
of residues of the pesticide in drinking water as a part of the
aggregate risk assessment process.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food to
Indoxacarb will occupy 12% of the aPAD for the U.S. population, 69% of
the aPAD for females 13 years and older, 67% of the aPAD for infants
less than 1 year old and 36% of the aPAD for children 1 to 2 years old.
In addition, there is potential for acute dietary exposure to
Indoxacarb in drinking water. After calculating DWLOCs and comparing
them to the EECs for surface and ground water, EPA does not expect the
aggregate exposure to exceed 100% of the aPad, as shown in Table 3 of
this unit:
Table 3.-- Aggregate Risk Assessment for Acute Exposure to Indoxacarb
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population Subgroup aPAD (mg/ % aPAD Water EEC Water EEC Acute DWLOC
kg) (Food) (ppb) (ppb) (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population 0.12 7 13.7 0.02 3,700
----------------------------------------------------------------------------------------------------------------
Females 13 + 0.02 69 13.7 0.02 180
----------------------------------------------------------------------------------------------------------------
All infants less than 1 year 0.12 67 13.7 0.02 400
----------------------------------------------------------------------------------------------------------------
Children 1 to 2 0.12 36 13.7 0.02 760
----------------------------------------------------------------------------------------------------------------
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
Indoxacarb from food will utilize 30% of the cPAD for the U.S.
population, 29% of the cPAD for infants less than 1 year old and 79% of
the cPAD for children 1 to 2 years old. There are no residential uses
for Indoxacarb that result in chronic residential exposure to
Indoxacarb. Based the use pattern, chronic residential exposure to
residues of Indoxacarb is not expected. In addition, there is potential
for chronic dietary exposure to Indoxacarb in drinking water. After
calculating DWLOCs and comparing them to the EECs for surface and
ground water, EPA does not expect the aggregate exposure to exceed 100%
of the cPAD, as shown in Table 4 of this unit:
[[Page 18591]]
Table 4.-- Aggregate Risk Assessment for Chronic (Non- Cancer) Exposure to Indoxacarb
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population Subgroup cPAD mg/kg/ % cPAD Water EEC Water EEC Chronic
day (Food) (ppb) (ppb) DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population 0.02 30 3.7 0.02 490
---------------------------------------------------------------------------
All infants less than 1 year old 0.02 29 3.7 0.02 140
---------------------------------------------------------------------------
Children 1 to 2 0.02 79 3.7 0.02 43
----------------------------------------------------------------------------------------------------------------
3. Short-term risk. Short-term aggregate exposure takes into
account residential exposure plus chronic exposure to food and water
(considered to be a background exposure level). Indoxacarb is not
registered for use on any sites that would result in residential
exposure. Therefore, the aggregate risk is the sum of the risk from
food and water, which do not exceed the Agency's level of concern.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account residential exposure plus chronic exposure to food
and water (considered to be a background exposure level). Indoxacarb is
not registered for use on any sites that would result in residential
exposure. Therefore, the aggregate risk is the sum of the risk from
food and water, which do not exceed the Agency's level of concern.
5. Aggregate cancer risk for U.S. population. There is no evidence
for mutagenicity and there is no evidence of carcinogenicity in either
the rat or mouse. Indoxacarb has been classified as ``not likely to be
carcinogenic in humans'' by the Agency; therefore, Indoxacarb is not
expected to pose carcinogenic risk when used as directed.
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, and to infants and children from aggregate
exposure to Indoxacarb residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology ( high performance liquid
chromatography HPLC/UV Method AMR 2712-93) is available to enforce the
tolerance expression. The method may be requested from: Calvin Furlow,
PRRIB, IRSD (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20460;
telephone number: (703) 305-5229; e-mail address:
furlow.calvin@epa.gov.
B. International Residue Limits
There are no established or proposed Codex, Canadian, or Mexican
maximum residue limits (MRLs) for residues of indoxacarb; therefore,
international harmonization is not an issue at this time.
V. Conclusion
A 15-day comment period is being allowed for this proposed rule
because of the speed of growth and the pest pressure, and the Agency's
desire to be suportive of efforts by peach growers and researchers to
find alternatives to organophosphates for control of oriental fruit
moth and plum curculio in peaches. Additionally, the Agency feels that
there is strong evidence in support of the safety of this proposed
action.
Therefore, a temporary tolerance for 3 years is proposed for
combined residues of Indoxacarb, (S)-methyl 7-chloro-2,5-dihydro-2-
[[(methoxy carbonyl) [4-(trifluoromethoxy)phenyl]
amino]carbonyl]
indeno[1,2-e][1,3,4]oxadiazine-4a(3H)- carboxylate + its R-enantiomer]
(R)-methyl 7-chloro-2,5-dihydro-2- [[(methoxycarbonyl)[4-(trifluoro
methoxy)phenyl]amino]carbonyl]indeno [1,2-e][1,3,4]oxadiazine-4a(3H)-
carboxylate in peaches at 10.0 ppm.
VI. Statutory and Executive Order Reviews
This proposed rule is establishing a tolerance under section 408(d)
of the FFDCA. EPA is proposing this regulation in cooperation with
Research Extension Specialists at the University of Georgia, Rutgers
University, Clemson University, Pennsylvania State University, Michigan
State University, University of West Virginia, and DuPont de Nemours
and Company. The Office of Management and Budget (OMB) has exempted
these types of actions from review under Executive Order 12866,
entitled Regulatory Planning and Review (58 FR 51735, October 4, 1993).
Because this proposed rule has been exempted from review under
Executive Order 12866 due to its lack of significance, this proposed
rule is not subject to Executive Order 13211, Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use (66 FR 28355, May 22, 2001). This proposed rule does not contain
any information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable
duty or contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor
does it require any special considerations under Executive Order 12898,
entitled Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations (59 FR 7629, February 16, 1994);
or OMB review or any Agency action under Executive Order 13045,
entitled Protection of Children from Environmental Health Risks and
Safety Risks (62 FR 19885, April 23, 1997). This action does not
involve any technical standards that would require Agency consideration
of voluntary consensus standards pursuant to section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (NTTAA),
Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since
tolerances and exemptions that are established on the basis of a
petition under section 408(d) of the FFDCA, such as the tolerance in
this proposed rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply. In addition, the Agency has determined that this
action will not have a substantial direct effect on States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government, as specified in Executive Order 13132, entitled Federalism
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to
develop an accountable process to ensure ``meaningful and timely input
by State and local officials in the development of regulatory policies
that have federalism implications.'' ``Policies that have federalism
implications'' is
[[Page 18592]]
defined in the Executive order to include regulations that have
``substantial direct effects on the States, on the relationship between
the national government and the States, or on the distribution of power
and responsibilities among the various levels of government.'' This
proposed rule directly regulates growers, food processors, food
handlers and food retailers, not States. This action does not alter the
relationships or distribution of power and responsibilities established
by Congress in the preemption provisions of section 408(n)(4) of the
FFDCA. For these same reasons, the Agency has determined that this
proposed rule does not have any ``tribal implications'' as described in
Executive Order 13175, entitled Consultation and Coordination with
Indian Tribal Governments (59 FR 22951, November 6, 2000). Executive
Order 13175, requires EPA to develop an accountable process to ensure
``meaningful and timely input by tribal officials in the development of
regulatory policies that have tribal implications.'' ``Policies that
have tribal implications'' is defined in the Executive order to include
regulations that have ``substantial direct effects on one or more
Indian tribes, on the relationship between the Federal Government and
the Indian tribes, or on the distribution of power and responsibilities
between the Federal Government and Indian tribes.'' This proposed rule
will not have substantial direct effects on tribal governments, on the
relationship between the Federal Government and Indian tribes, or on
the distribution of power and responsibilities between the Federal
Government and Indian tribes, as specified in Executive Order 13175.
Thus, Executive Order 13175 does not apply to this proposed rule.
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: April 10, 2003.
Debra Edwards,
Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 03-9340 Filed 4-15-03; 8:45 a.m.]
BILLING CODE 6560-50-S