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Novaluron (Makhteshim-Agan of North America, Inc.). February 25, 2004.
Pesticide tolerance petition. Federal Register.

http://www.epa.gov/fedrgstr/EPA-PEST/2004/February/Day-25/p3937.htm

[Federal Register: February 25, 2004 (Volume 69, Number 37)]
[Notices]
[Page 8649-8654]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25fe04-61]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2004-0030; FRL-7344-6]

Novaluron; Notice of Filing a Pesticide Petition to Establish a
Tolerance for a Certain Pesticide Chemical in or on Food
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of a pesticide
petition 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-
2004-0030, must be received on or before March 26, 2004.
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: Daniel C. Kenny, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-7546; e-mail address: <:kenny.dan@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-2004-0030. 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/>.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at <http://www.epa.gov/edocket/> to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although not all docket materials may be
available electronically, you may still access any of the publicly
available docket materials through the docket
[[Page 8650]]
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 EPA's 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.1. 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-2004-0030. 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-2004-0030. 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-2004-0030.

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-2004-0030. 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.
[[Page 8651]]

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 a pesticide petition 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 this petition contains 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 petition.
Additional data may be needed before EPA rules on the petition.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: February 12, 2004.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

The petitioner's summary of the pesticide petition is printed below
as required by FFDCA section 408(d)(3). The summary of the petition 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.

Makhteshim-Agan of North America, Inc.
PP 2F6430
EPA has received a pesticide petition (2F6430) from Makhteshim-Agan
of North America, Inc. (MANA), 551 Fifth Avenue, Suite 1100, New York,
NY 10176 proposing, pursuant to section 408(d) of the FFDCA, 21 U.S.C.
346a(d), to amend 40 CFR part 180 by establishing a tolerance for
residues of novaluron in or on the raw agricultural commodity pome
fruits (excluding pears) at 1.0 parts per million (ppm), apple pomace
at 6.0 ppm, pears at 2 ppm, cottonseed at 0.3 ppm, cotton gin by-
products at 17 ppm, tuberous and corm vegetables (Crop Subgroup 1-C) at
0.05 ppm, cattle meat at 0.3 ppm, cattle meat-by-products at 6.0 ppm,
cattle fat at 6.0 ppm, cattle liver at 0.4 ppm, cattle kidney at 0.4
ppm, and milk at 0.4 ppm. EPA has determined that the petition contains
data or information regarding the elements set forth in section
408(d)(2) of the FFDCA; however, EPA has not fully evaluated the
sufficiency of the submitted data at this time or whether the data
support granting of the petition. Additional data may be needed before
EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The qualitative nature of the residue of
novaluron in plants is adequately understood based on acceptable apple,
cabbage, cotton, and potato metabolism studies. These plant metabolism
studies have demonstrated that novaluron does not metabolize and is
non-systemic (does not translocate within the plant). The results
observed in the plant and livestock metabolism studies show similar
metabolic pathways. The residue of concern, which should be regulated,
is the parent compound, novaluron, only.

2. Analytical method. An adequate analytical method, gas
chromatography/electron capture detector (GC/ECD), is available for
enforcing tolerances of novaluron residues in or on plant and animal
commodities. The amount of novaluron in most crop matrices is
determined using GC with ECD. GC is also used to determine residues of
novaluron in milk, bovine fat, kidney, liver, and meat.

3. Magnitude of residues--i. Pome fruits. Field residue trials were
conducted on pome fruits (total of 23 trials on apples including a
processing study, and 10 trials on pears), in several locations in the
U.S. and Canada (2000-2002). In view of the proposed use directions
(maximum seasonal rate of 1 lb active ingredient per acre, up to 4
applications, pre-harvest-interval of 14 days), the maximum novaluron
residue found on apples was 0.876 ppm, which is below the proposed
tolerance of 1.0 ppm for pome fruit (excluding pears). The highest
residues measured on pears following 6 applications at a seasonal rate
of 2 lb active ingredient per acre were 1.9 ppm, which is below the
proposed tolerance of 2 ppm. Residues in juice from apple processing
were below 0.05 ppm, demonstrating that there was no concentration in
juice and therefore no need for proposing a tolerance. The proposed
tolerance for apple pomace of 6 ppm is supported by using the highest
average residues measured in the field (0.774 ppm) multiplied by the
established concentration factor of 7.2 from the available apple
processing study.

ii. Cotton. Seventeen residue trials were conducted in the U.S.
over a 2-year period (2000-2002). The novaluron residues in cottonseed
ranged from less than 0.05 to 0.23 ppm, and in cotton gin by-products
the residues ranged from 3.5 ppm to 14.8 ppm, following the proposed
use directions. Therefore, tolerances of 0.3 ppm for cottonseed and 17
ppm for cotton gin by-products are being requested.

iii. Tuberous and corm vegetable subgroup (Crop Subgroup 1-C). A
series of potato residue trials in support of the tuberous and corm
vegetable subgroup was conducted over a 2-year period (1999-2000) in
Europe (Germany, France, Spain, and Italy). Treatments were made twice
at 0.022 lb active ingredient per acre with the last application 21
days before harvest, in addition to residue decline studies with
sampling dates of 0, 3, 7, 14, and 21 days after the last application.
No residues were detected above 0.01 ppm limit of quantitation (LOQ),
even at sampling dates right after the last application. Data from
field trials conducted in Oregon and Pennsylvania (2002), using an
exaggerated rate of 0.25 lb active ingredient per acre at 21 and 7 days
before harvest, also indicate that no measurable residues were detected
(LOQ = 0.05 ppm). Therefore, the generated data set is in full support
of the proposed tolerance of 0.05 ppm.

B. Toxicological Profile

1. Acute toxicity. In an acute oral toxicity study in rats,
novaluron had a lethal dose (LD)50 ≤5,000 mg/kg. A
dermal toxicity study in rats resulted in an LD50 greater
than 2,000 mg/kg. The lethal concentration (LC)50 for acute
[[Page 8652]]
inhalation in rats was greater than 5.15 milligrams/Liter (mg/L). In
rabbits, novaluron is not a skin irritant but it is a mild eye
irritant. Novaluron is not a sensitizer in guinea pigs.

2. Genotoxcity. The mutagenic potential of novaluron was
investigated in several in vivo and in vitro studies. Results in two
Ames assays, an in vivo mouse micronucleus assay, an in vitro
unscheduled DNA synthesis (UDS) assay, an in vitro cell mutation assay,
and an in vitro human lymphocyte clastogenicity test were negative.
Novaluron is therefore considered to have no potential to induce
mutagenicity.

3. Reproductive and developmental toxicity--i. A 2-generation rat
reproduction study was conducted with dose levels of 1,000, 4,000, and
12,000 ppm (74.2, 297.5, 894.9 mg/kg/day, and 84, 336.7, 1009.8 mg/kg/
day for males and females, respectively). There were no effects on
fertility or pregnancy at any dose. The no observed adverse effect
level (NOAEL) was determined to be 12,000 ppm (894.9 and 1009.8 mg/kg/
day for males and females, respectively).

ii. Teratology studies were conducted in the rat and rabbit. No
treatment-related mortalities were observed in either study. No effect
on survival, development or growth of fetuses was noted in either
species in either study. The maternal and fetal NOAEL was determined to
be 1,000 mg/kg/day (highest dose tested (HDT)) in the rat study. In the
rabbit study the maternal and fetal NOAEL was 1,000 mg/kg/day. The
fetal effect in the rabbit study was weight gain at 1,000 mg/kg/day.
These two studies demonstrate that novaluron was not teratogenic in
either rats or rabbits based on the study results.

4. Subchronic toxicity. Rats, mice, and dogs all show the same
toxicologic response. Generally, novaluron induces small increases in
methemoglobin; red cells are sequestered; and, compensatory
hematopoiesis occurs. The severity of these changes is well within the
physiological capacity of the animals and is judged not adverse.
Rats treated topically with novaluron in a 28-day study at 0, 75,
400, and 1,000 mg/kg/day did not show signs of systemic toxicity. Small
treatment-related increases in methemoglobin were seen in both sexes at
1,000 mg/kg/day and in females at 400 mg/kg/day. The highest
methemoglobin value seen in females was 1.28% compared with 0.86% in
controls. Organ weights, macroscopic and microscopic examination of
organs and tissues did not reveal any treatment-related changes.

i. Two 13-week rat studies were conducted. In one study, doses were
administered at 50, 100, 200, 400 ppm (3.52, 6.93, 13.83, 27.77 mg/kg/
day and 4.38, 8.64, 17.54, and 34.39 mg/kg/day for males and females,
respectively). The NOAEL was 400 ppm, the HDT (27.77 and 34.39 mg/kg/
day for males and females, respectively). In the second 13-week rat
study, doses were administered at 50, 100, 10,000, and 20,000 ppm (4.2,
8.3, 818.5, 1666.9 mg/kg/day and 4.7, 8.9, 871, 1820.6 mg/kg/day for
males and females, respectively). The NOAEL was determined to be 8.3
mg/kg/day. The lowest observed adverse effect level (LOAEL) of 818.5
mg/kg/day, is based on histopathological parameters in the spleen.

ii. A 13-week mouse study was conducted with dose levels of 30,
100, 1,000, 10,000 ppm (4.2, 12.8, 135.9, 1391.9 mg/kg/day and 4.7,
15.2, 135.6, 1493.1 mg/kg/day, for males and females, respectively).
The NOAEL was determined to be 100 ppm (12.8 and 15.2 mg/kg/day, male
and females, respectively). The LOAEL was 1,000 ppm (135.9 and 135.6
mg/kg/day, males and females, respectively) based on increased body
weight gain, low erythrocyte counts, and secondary splenic changes.
There were no clinical treatment-related signs noted.

iii. Two 13-week dog studies were conducted. One study resulted in
an NOAEL of 100 mg/kg/day and a LOAEL of 300 mg/kg/day based on low
erythrocyte counts and secondary splenic and liver changes. No clinical
treatment-related signs were noted. Another study, was conducted using
only one dose level of 10 mg/kg/day. There were no clinical or
histopathological treatment-related signs and the NOAEL was determined
to be 10 mg/kg/day.

5. Chronic toxicity--i. Chronic toxicity and oncogenicity was
evaluated in the rat, mouse and dog. The rat chronic toxicity and
oncogenicity was conducted with dose levels of 25, 700, 20,000 ppm
(1.25, 35, 1,000 mg/kg/day). The no observed effect level (NOEL) was 25
ppm (1.25 mg/kg/day) based on methemoglobin. There was no evidence of
carcinogenicity in this study. A mouse chronic toxicity study was
conducted with dose levels of 30, 450, 7,000 ppm (4.5, 67.5, 1,050 mg/
kg/day). The NOEL was 30 ppm (4.5 mg/kg/day) based on methemoglobin.
There was also no evidence of carcinogenicity in this study. Chronic
toxicity was investigated in dogs using dose levels of 10, 100, 1,000
mg/kg/day. The NOEL of 100 mg/kg/day was based on methemoglobin.

ii. A reference dose (RfD) of 0.083 mg/kg/day has been established
for novaluron. The RfD is based on a subchronic rat study with a NOAEL
of 8.3 mg/kg/day, based on histopathological parameters in the spleen.
An uncertainty factor (UF) of 100 is used.

iii. The proposed classification of novaluron is Group E (not
likely human carcinogen) due to results of oncogenicity studies that
show no evidence of carcinogenicity.

6. Animal metabolism. Metabolism studies in rats and goats were
conducted with the parent material labeled in both the difluorophenyl
and chlorophenyl moieties.
Rats absorb little novaluron when it is administered orally. More
than 90% of the dietary administered chlorophenyl \14\C(U) novaluron is
recovered in the feces. When the diflurophenyl ring of the molecule is
labeled, the recovered \14\C activity in the feces is lower but still
above 75%. The difference is thought to reflect intestinal metabolism
by microbial flora and the higher absorption of the diflurophenyl
metabolites.
The parent molecule as well as its degradates are absorbed from the
gastrointestinal tract (GI). All parent material is metabolized either
upon initial entry into the systemic circulation or, if sequestered to
the fat, upon its depuration back to the systemic circulation. There is
no intact novaluron found in the urine. Novaluron's high octanol-water
partition coefficient is responsible for its preferential movement to
fat. The half-life in fat calculated from the rat metabolism study is
approximately 55 hours.
Two groups of metabolites are formed after oral administration of
novaluron. One group is typified by the aniline metabolite 3-chloro-4-
(1,1,2-trifluoro-2-trifluoromethoxyethoxy) aniline, referred to as 3-
TFA. The other group of metabolites is typified by 2,6-difluorobenzoic
acid is from the diflurophenyl moiety of the molecule. Nearly all the
metabolites are formed at a level of 1% or less of the applied dose.
They are rapidly excreted.
The metabolism in goats mimics that seen in rats.

7. Metabolite toxicology. Makhteshim-Agan of North America Inc.,
has determined that there are no metabolites of toxicological concern
and therefore, no metabolites need to be included in the tolerance
expression and require regulation.

8. Endocrine disruption. No special studies investigating potential
estrogenic or other endocrine effects of novaluron have been conducted.
[[Page 8653]]
However, inspection of in-life data from toxicology studies does not
indicate that novaluron is an endocrine disruptor. Specifically,
endocrine organ weights (e.g., thyroid, testes, ovaries, pituitary from
the 2-generation study) were not adversely affected by novaluron.
Milestones of sexual development were not affected by novaluron; and,
reproduction was not adversely affected. Based on these observations,
there is no evidence to suggest that novaluron has an adverse effect on
the endocrine system.

C. Aggregate Exposure

Dietary exposure. Tolerances are proposed for residues of novaluron
in or on pome fruit (excluding pears), apple pomace, pears, cottonseed,
cotton gin by-products, tuberous, and corm vegetables, cattle meat,
fat, liver, kidney, meat by-products, and milk. For the purpose of
assessing the potential dietary exposure for these proposed tolerances,
an exposure assessment was conducted using Exponent's Dietary Exposure
Evaluation Model (DEEM) software, consumption data derived from the
1994-1998 United States Department of Agriculture (USDA) Continuing
Surveys of Food Intake by Individuals (CSFII), residue levels at
proposed tolerance levels, and projected percent crop treated for
cotton and pome fruit at market maturity, and assuming 100% crop
treated for potatoes.

1. Food--i. Acute dietary exposure. No acute dietary assessments
were conducted since no toxicological endpoint attributable to a single
exposure was identified in the available toxicology studies, including
the rat and rabbit developmental studies.

ii. Chronic dietary exposure. The appropriate RfD value for
novaluron is 0.083 mg/kg/day, based upon the NOAEL of 8.3 mg/kg/day
from the 13-week oral rat study and an UF of 100. The chronic dietary
exposure estimate for the overall U.S. population is 1.5% of the RfD of
0.083 mg/kg/day. Children 1 to 2 years old, the most exposed population
subgroup, utilize 7.6% of the RfD. The chronic exposure estimates for
the overall U.S. population and 32 population subgroups, including
infants and children, were less than 8% of the RfD. Based on these
exposure estimates, Makhteshim-Agan of North America, Inc., concludes
that there is reasonable certainty of no harm for the use of novaluron
on pome fruit, cotton, tuberous, and corm vegetables.

2. Drinking water. A comparison of the calculated drinking water
level of concern (DWLOC) value to the drinking water estimated
concentration (DWEC) is made. If the DWLOC exceeds the DWEC value then
there is reasonable certainty that no harm will result from the short-
term or the intermediate-term aggregate exposure. There are no
monitoring data for novaluron, so the Food Quality Protection Act
(FQPA) Index Reservoir Screening Tool (FIRST) model was used to
estimate a surface water residue. Estimated DWLOC values are 767 parts
per billion (ppb) for children (1 to 2 years old), 2,470 ppb for adult
females, and 2,861 ppb for the U.S. population. Since the calculated
DWLOC values for the U.S. population and all its subgroups considerably
exceed the modeled DWEC of 0.14 ppb in surface water, Makhteskim-Agan
of North America Inc., concludes that there is reasonable certainty
that no harm will result from aggregate (food and water) exposure to
novaluron residues.

D. Cumulative Effects
To Makhteskim-Agan of North America's Inc., knowledge, there are
currently no available data or other reliable information indicating
that any toxic effects produced by novaluron would be cumulative with
those of other chemical compounds; thus only the potential risks of
novaluron have been considered in this assessment of its aggregate
exposure.

E. Safety Determination

1. U.S. population. No acute dietary assessment was conducted
because there is no toxicological endpoint attributable to a single
exposure. A conservative chronic exposure analysis was conducted, using
tolerance level residues, with adjustments for percent crop treated at
product maturity (cotton and pome fruits), and no adjustment for
potatoes (100% treated). The chronic novaluron exposure is low,
accounting for 0.8% to 7.6% of the RfD, depending on the population
subgroup. The chronic exposure for the U.S. population is 0.001243 mg/
kg/day, which uses 1.5% of the RfD. The most sensitive population
subgroup, children 1 to 2 years old, has a chronic exposure of 0.006339
mg/kg/day, which utilizes only 7.6% of the RfD. Based on the lack of
acute toxicity and the chronic exposure analyses, Makhteskim-Agan of
North America Inc., concludes that there is reasonable certainty that
no harm will result from acute and chronic exposure to novaluron.

2. Infants and children--i. General. Data from rat and rabbit
developmental toxicity studies and a 2-generation rat reproduction
study have been used to assess the potential for increased sensitivity
of infants and children. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from pesticide exposure during prenatal development.
Reproduction studies provide information relating to reproductive and
other effects on adults and offspring from prenatal and postnatal
exposure to the pesticide. FFDCA section 408 provides that EPA may
apply an additional safety factor for infants and children to account
for prenatal and postnatal toxicity and the completeness of the data
base. Makhteskim-Agan of North America Inc., concludes that the
toxicology data base for novaluron regarding potential prenatal and
postnatal effects in children is complete according to existing Agency
data requirements and does not indicate any developmental or
reproductive concerns.

ii. Developmental toxicity studies. In the rat developmental study,
the maternal NOAEL was determined to be 1,000 mg/kg/day based on slight
increase in body weight gain and food consumption and the fetal NOAEL
was determined to be 1,000 mg/kg/day, the HDT. There was no effect on
survival, development or growth of the fetuses. There were no
developmental effects noted in the rabbit study, even at the limit dose
level (1,000 mg/kg/day), however, slight maternal toxicity (body weight
effects) was observed at the limit dose level.

iii. Reproductive toxicity studies. There was no evidence of
adverse effects on reproductive capability, fertility or pregnancy,
observed at any dose level in the rat 2-generation reproductive study.
However, there was increased bodyweight and spleen weight, and
hemosiderosis of the spleen at the high dose. The NOAEL was 894.9 in
males and 1009.8 mg/kg/day in females, the HDT.

iv. Conclusion. Based on the absence of fetal effects and pup
toxicity in any of the reference studies, Makhteskim-Agan of North
America Inc., concludes that reliable data support the use of the
standard 100-fold UF, and that an additional UF is not needed to
protect the safety of infants and children. In addition, the RfD is
based on a NOAEL of 8.3 mg/kg/day (from a 13-week rat study), which is
already more than 120-fold lower than the NOAEL in the rabbit
developmental toxicity study. Thus, the proposed RfD of 0.083 mg/kg/day
is considered to be appropriate for assessing potential risks to
infants and children and an additional FQPA safety factor is not
warranted. As noted previously, the aggregate chronic exposure
assessment utilizes less than 8% of the RfD for the entire U.S.
[[Page 8654]]
population and various population subgroups, including the most
sensitive subgroup, children 1 to 2 years old. Therefore, Makhteskim-
Agan of North America Inc., concludes that there is reasonable
certainty that no harm will result to infants and children from
aggregate exposure to novaluron residues.

F. International Tolerances

There are no Canadian, Mexican, or Codex maximum residue limits
established for novaluron. Therefore, international harmonization is
not an issue at this time.
[FR Doc. 04-3937 Filed 2-24-04; 8:45 am]
BILLING CODE 6560-50-S